There are literally thousands of references on bee venom. Check many of them in PUBMED.

Here below we are offering you only those references which are directly related to Apitherapy.

For more details on these sources you can contact us too through our Contact page.

BEE VENOM BIBLIOGRAPHY (A-Z)

Legend: (***) means that more information about the article/abstract/book can be obtained directly from Dr. Stefan Stangaciu (drstangaciu@gmail.com + drstangaciu@apitherapy.com)

*** (1976, 1980, 1981, 1989) (Romania) – Apitherapy today. On the composition and utilisation of bee products and preparations in nutrition and therapeutics with regard to their biological value.
Apimondia Publishing House, Bucharest, Romania.
English edition, 1976, 107 pp. (***);
French edition, 1976, 105 pp (***);
German edition, 1980, 103 pp. (***);
Romanian second edition, 1981;
Romanian third edition, 1989, 103 pp. (***).

*** Apitherapy in Romania (1994) (Romanian).
Apimondia Publishing House, Bucharest, Romania, 174 pp. ISBN 973-605-016-5 (***).

*** (1999) – Abstract of Papers – Pacific Northwest Apitherapy Conference, Vancouver, Canada, June, 12-14, 1998.
Apitherapy Education Service – Apitronic Services, pp. 25.

Agache Iulia (1992) (Romania) – Considerations on bee venom (Romanian),
in Romania apicolã, # 6.

Ali, A.F.; Fateen, B.; Ezzet, A.; Badawy, H.; Ramadan, A.; El-tobge, A. (2000) (Egypt) – Laparoscopic intraovarian injection of bee venom in the treatment of polycystic ovarian disease: a new modality[1],
in Infertility Research Center, Cairo, Egypt: Obstet Gynecol, April 1;95(4 Suppl 1):S15.

Anisimova L.M., Smirnov A.A., Troshin,V.D., Krylov,V.N. (1995) (Russia) – The use of Solapiven in reflexotherapy of humans with nervous system diseases,
in the XXXIV-Th. Apimondia Congress, Lausanne, Switzerland, 135 (***-abstract).

Artemov, M. N. (1958) (Russia) – The physiological proofs of apitherapy. Bee venom acts as a cholinolytic agent,
in the XVII-Th. International Apicultural Congress, Rome, Italy.

Artemov, M. N. (1965) (USSR) – On bee venom and propolis problems,
in the XX-Th. Apimondia Congress, Bucharest, Romania, pp.415-425 (***).

Artemov, N. M. (1965) (USSR) – Bee venom as a product of apiculture,
in the XX-Th. Apimondia Congress, Bucharest, Romania, p.467-469 (***).

Artemov,N.M., Kireeva V.F., Poberejskaia T.I. (1969) (U.S.S.R.) – Effect of apitoxin on permeability of capillaries and albumin content in blood,
in the XXII-Nd. Apimondia Congress, Munich, Germany, pp.361-365 (***).

Artemov, N. M.; Orlov, B. N.; Korneva N. V.; Krylov, V. N. (1973) (USSR) – Physiological analysis of the cardiotoxic action of the bee venom,
in the XXIV-Th. Apimondia Congress, Buenos Aires, Argentine, pp.415-17 (***). [2]

Arthus,M. (1919) – Recherche expérimental sur le venin des abeilles,
in Compte rendues Sce. Bid., 182, pp.414-415.

Asafova N. Natalia (1997) (Russia) – To the question about mechanisms of bee venom influence on cardio-vascular system,
in the XXXV-Th. Apimondia Congress, Antwerp, Belgium.

Asis, Moises (1988) (Cuba) – Los productos de la colmena. Composicion y uso de la miel, cera, polen, jalea real, propoleo y veneno de las abejas (Spanish).
Centro de Informacion y Documentacion Agropecuaria (CIDA), Ciudad de la Habana, 65 pp.

Asis, Moises (1988) – Les produits de la ruche: composition et utilisations du miel, de la cire, du pollen, de la gélée royale, de la propolis et du venin d’abeille.
Centro de Informacion y Documentacion Agropecuario. Havana. Cuba. 65 pp. 1303L/90.

Baltaceanu, C. V.; Armand, H. (1941) (Romania) – Action sur le coeur du venin des abeilles,
in Bull. Inst. de Balneologie de Bucarest, # 12, pp.5-19.

Baltushkiavichius, A.; Vaivadiene, N.; Driziene, J. (1988) – The Treatment of Degenerative Diseases of the Spine using Apiphoroelectrophoresis,
in the VI-th International Symposium on Apitherapy. Apimondia Publishing House – Romania, Abstracts of Scientific Papers, Portoroz, Yugoslavia, p. 27.

Banks,B.E.C., Hanson M. Jennifer, Sinclair,N.M. (1976) – The isolation and identification of noradrenaline and dopamine from the venom of the honey bee (Apis mellifera),
in Toxicon 14, p.117.

Banks, B. E. C. (1976) – Possible Therapeutic Use of a Peptide from Bee Venom,
in Bulletin de l’Institut Pasteur, 74, pp.137-144.

Banks, B. E. C.; Shipolini, R. A. (1986) – Chemistry and pharmacology of honey-bee venom,
in “Venoms of the Hymenoptera” (T. Pick, ed.). pp.329-416;
London: Academic Press.

Barravieira, Benedito (1994) – Venenos Animais, Uma visão Integrada.
Editora de Publicações Científicas Ltda. Rio de Janeiro, RJ. Brasil. 411 páginas.

Basic,I., Curic,S., Tadic,Z., Orsolic,N., Sulimanovic,D. (1995) (Croatia) – Antimetastatic activity of bee venom and water soluble derivatives of propolis in mice,
in the XXXIV-Th. Apimondia Congress, Lausanne, Switzerland, pp.135-136 (***-abstract).

Bänziger Erica (1997) (Switzerland) – Genuss und Gesundheit aus dem Bienenstock.
Midena Verlag GmbH, ISBN 3-310-00395-7, 125 pp. (bee venom page 59) (***).

Beaudet, M. (1990) – Les piqures d’abeille,
in Revue Française d’Apiculture, Nov, pp.513-517.

Beck, F. Bodog (1935, 1997) (USA) – Bee Venom Therapy. Bee Venom, Its Nature, and its effect on Arthritic and Rheumatoid Conditions.
D. Appleton-Century Co., Incorporated. New York. London, 1935 238 pp.; references, bibliography and two indices (***);
Health Resources Press, 1997 (under the name: The Bible of Bee Venom Therapy).

Becova I.; Marcova O. (1963) – Chemiska characterisacia nicktorych zlosyck veeliche jelu,
in Cheur. Svesti, 17, # 12, pp.884-890.

Belliveau, J. (1992) – The effectiveness of bee venom and adjuvant induced colon cancer of the rats,
in the Second American Apitherapy Society Conference, Boston, USA.

Benton, A. W.; Morse, R. A.; Stewart, J. D. (1963) – Venom collection from honey bees,
in Science 142, pp.228-230.

Benton,A.W., Morse,R.A., Rosikowski (1963) – Bioassay and standardization of the venom of honeybees,
in Nature 198 (4877), 295-296.

Bertea, V. (1974) – Bee venom and rheumatism (Romanian),
in Apicultura, # 10, p.10.

Billingham,M.E.J., Morley,J., Hanson,J.M., Shipolini,R.A., Vernon,C.A. (1973) – Letter: An anti-inflammatory peptide from bee venom,
in Nature 245 (5421), pp.163-164.

Bomalaski, J. S.[3] (1995) – Phospholipase A2-activating protein induces the synthesis of IL-1 and TNF in human monocytes,
in Journal of Immunology, Apr 15;154(8), 4027-31 (***-abstract). [4]

Bourgain, C.; Pauti, M. D.; Fillastre, J. P.; Godin, M.; Francois, A.; Leroy, J. P.; Droy, J. M.; Klotz, F.[5] (1998) (France) – Massive poisoning by African bee stings (original article in French),
in Presse Méd, Jun 20;27(22), 1099-101 (***-abstract). [6]

Bousquet, J. (1981) (France) – Allergie chez les apiculteurs,
in the XXVIII-Th. Apimondia Congress, Acapulco, Mexico, 443-445 (***).

Boutin, Y.; Jobin, M.; Bedard, P. M.; Hebert, M.; Hebert, J. (1994) (Canada) – Possible dual role of anti-idiotypic antibodies in combined passive and active immunotherapy in honeybee sting allergy,
in Journal of Allergy and Clinical Immunology, Jun;93(6), 1039-46 (***-abstract). [7]

Broadman, Joseph [8] (1962, 1997) – Bee Venom – The Natural Curative for Arthritis and Rheumatism.
New York: Putnam and Sons (1962);
Health Resources Press, 224 pages, References, Index, Glossary, Bibliography (1997). ISBN – 1-890708-01-1.

Brooks, R.; Vick, J. A.; Shipman, W.; Mraz Charles; Warren, G. B. (1989) (USA) – Studies of the venom of the honeybee,
in the XXXII-Nd. Apimondia Congress, Rio de Janeiro, Brazil, pp.506-516 (French, German and Spanish abstracts included) (***). [9]

Bugescu, D. (1973) – Rheumatism treatment with bee venom (Romanian),
in Apicultura, # 9, p.25.

Calin, A. (1983) – Diagnosis and Management of Rheumatoid Arthritis.
Menlo Park, Calif.: Addison-Wesley.

Cerrato, P.L. (1998) (USA) – A therapeutic bee sting?
in RN, Aug;61(8), pp.57-8.

Chang,Y.-H., Bliven,M.L. (1979) – Anti-arthritic effect of bee venom,
Agents and Actions 9, p.205-211.

Chauvin, R. (1968) (France) – Traité de biologie de l’abeille. Les produits de la ruche. Tome III.
Masson et Cie, Paris. 400 pp. ……..397/68

Choong-Hee Won; Seong-Sun Hong; Kim Christopher, M.-M. (2000) (Korea, USA) – Efficacy of Apitox (Bee venom) for Osteoarthritis: a randomized active-controlled trial, Part I,
in Bee Informed, volume 7, no. 3, Fall, pp.11-15 (***).

Choong-Hee Won; Seong-Sun Hong; Kim Christopher, M.-M. (2000) (Korea, USA) – Efficacy of Apitox (Bee venom) for Osteoarthritis: a randomized active-controlled trial, Part II,
in Bee Informed, volume 7, no. 4, Winter, pp.10-12 (***).

Choong-Hee Won; Seong-Sun Hong; Kim Christopher, M.-M. (2000) (Korea, USA) – Efficacy of Apitox (Bee venom) for Osteoarthritis: a randomized active-controlled trial, Part III,
in the Journal of the American Apitherapy Society (Bee Informed), volume 8, no. 1, Winter, pp.11-18 (***).

Cherbuliez, Theodore (1997) (USA) – Bee Venom Therapy and Safety,
in Bee Informed # 3, volume 4, Autumn, p.10-11 (***).

Chkenderov, S.; Kobourova, K. (1981) (Bulgaria) – Mécanisme de l’action antiinflammatoire du venin d’abeille,
in the XXVIII-Th. Apimondia Congress, Acapulco, Mexico, p.446 (***-abstract).

Cohen,A., Pearah,J.B., Dubbs,A.W., Best,C.J. (1942) – Bee venom in the treatment of chronic arthritis: a comparative study,
in Trans. Med. Soc. State Pennsylvania 45, p.957-959.

Connell, Patrick (1997) (Canada) – Apitherapy aproach (One),
in Bee sCene, June, # 3, vol. 13, p.16 (***).

Contessi Alberto (1983) (Italy) – Le Api. Biologia, allevamento, prodotti.
Edagricole. Bologna. Italy. ISBN 88-206-2263-7

Croft, L. R. (1988) – Allergy to Bee Stings and Its Prevention.
Elmwood Medical Monographs, ISBN 0-946019-03-7.

Derevici Adelina, Popescu,A., Nuca, C. (1967) – Methode d’identification du venin d’abeille par l’etude de ses propriétés antibiotiques, proteolytiques, hemolytiques et anticoagulantes,
in Bulletin Apicole I (1), 63-73.

Derevici Adelina, Popescu,Al., Nuca Olga (1967) (Romania) – Methods for the identification of bee venom by a study of its antibiotic, proteolytic, haemolytic and anticoagulant properties,
in the XXI-St. Apimondia Congress, Maryland, USA, p.474 (***-abstract).

Derevici Adelina, Dima,V. (1967) (Romania) – Action of bee venom on the development of epithelial cell cultures of monkey kidneys,
in the XXI-St. Apimondia Congress, Maryland, USA, p.491 (***-abstract).

Derevici Adelina, Dima,V. (1967) (Romania) – Comparative research work about the haemolytic action of natural and deproteinized bee venom,
in the XXI-St. Apimondia Congress, Maryland, USA, p.478 (***-abstract).

Derevici Adelina, Boeru,V. (1979) (Romania) – Biologically tests of bee venom (Romanian),
in Apicultura in Romania, # 8, p.12.

Derevici Adelina (1978) (Romania) – Constatãri experimentale privind efectele provocate de cãtre veninul de albine în sângele iepurilor (Romanian),
in Apicultura in Romania, # 9, p.24.

Derevici Adelina (1977) (Romania) – Scientific basis of bee venom therapy (Romanian),
in Apicultura in Romania, # 12, p.14.

Dobrovoda I.(1986) (Slovakia) – Vcelie Produkty (Hive products and health) (Slovak),
in Priroda, Bratislava, p.263-302.

Dobrovoda I. (1989) (Czechoslovakia) – New combined method of acu– and api-puncture,
in the XXXII-Nd. Apimondia Congress, Rio de Janeiro, Brazil, p.520 (***-abstract). [10]

Donald Mac Sue (1983) (USA) – A new hope for the people allergic to bee venom,
in American Bee Journal, August, p.578.

dos Reis, M. A.; Costa, R. S.; Coimbra, T. M.; Teixeira, V. P. [11] (1998) (Brazil) – Acute renal failure in experimental envenomation with Africanized bee venom,
in Ren Fail, Jan; 20(1), 39-51 (*** – abstract). [12]

Doyle,L.A. (1983) – “Bees and arthritis” – an interview with Dr. L.A. Doyle, D.O.,
in American Bee Journal 113, pp.352-355.

Echigo, T.; Matsuka, Mitsuo (1987) (Japan) – Les produits des abeilles,
in Fragrance Journal 15(2), pp.13-19. 972L/89

Eiseman,J.L., von Bredow,J., Alvares,A.P. (1982) – Effect of honeybee (Apis mellifera, L. ) venom on the course of adjuvant-induced arthritis and depression of drug metabolism in the rat,
in Biochem. Pharm. 31, pp.1139-1146.

Egner, W.; Ward, C.; Brown, D. L.; Ewan, P. W. [13](1998) (UK) – The frequency and clinical significance of specific IgE to both wasp (Vespula) and honey-bee (Apis) venoms in the same patient,
in Clin Exp Allergy, Jan;28(1), 26-34 (***-abstract). [14]

Ena, L. M. (1974) – Treatment with bee venom,
in Med Sestra 33(3), 39-44.

Fakhim-Zadeh, Kamran (1998) – Improved device for venom Collection,
in Bee World 79 (1). International Bee Research Association.

Fakhim-Zadeh, Kamran (1990) (Suomi) – Uusi suomalainen keksintö ratkaisemaan myrkynkeruun ongelmat,
in Mehiläinen 7(5): 144-147.

Fakhim-Zadeh, Kamran (1990) (Finland) – A new device for venom collection and apicultural research,
in American Bee Journal 130(12), 785-787.

Faux, J. A.; Moffatt, M. F.; Lalvani, A.; Dekker, J.; Warrell, D. A.; Cookson, W. O. (1997) (U.K.) – Sensitivity to bee and wasp venoms: association with specific IgE responses to the bee and wasp venom and HLA DRB1 and DPB1,
in Clin Exp Allergy, May;27(5), 578-83 (***-abstract). [15]

Fernandez,M.A., Muino (1992) – Le venin d’abeille. Composition et propriétés thérapeutiques,
in Journal Suisse d’Apiculture, # 11-12, 377-383.

Fierro Morales, Walter (1991) (Uruguay) – Accidentes provocados por picaduras de abejas,
in XII congreso de la Asociacion Latinoamericana de Farmacologia Montevideo, Diciembre.

Fierro Morales, Walter (1993) (Uruguay) – Reacciones producidas por picaduras de abejas,
in X Congreso Argentino de Alergia e Inmunologia, Buenos Aires,

Fierro Morales, Walter (1993) (Uruguay) – Reacciones alergicas a las picaduras de abejas. 25 Encuentro de pediatras alergistas Argentinos y 2 Encuentro pediatras alergista uruguayos
Solis, Diciembre.

Fierro Morales, Walter (1994) (Uruguay) – Utilizacion de la apitoxina con fines terapeuticos,
in I Bienal de apicultura INTA Ascasubi. Abril.

Fierro Morales, Walter (1995) (Uruguay) – Alergia a picadura de insectos,
in VI Congreso de Alergia e Imunologia del cono Sur. Punta del Este, Marzo.

Fierro Morales, Walter (1996) (Uruguay) – Prevalence of Systemic Adverse Reaction to Hymenoptera Sting in a General Population in Uruguay,
in the 52-nd Annual Meeting of the American Academy of Allergy, Asthma & Immunology. New Orleans, LA, Marzo.

Fierro Morales, Walter (1996) (Uruguay) – Anafilaxia por picadura de insectos,
in I Jornada de Actualizacion en Alergia e Imunologia Infantil, Junio.

Fisher, R. B. (1986) – Bee venom and chronic inflammatory disease. Letter,
in New Zealand Medical Journal, August 27, 99 (808), 639.

Ford, R. M. (1980) – Honeybee venom immunotherapy. Letter,
in Med J Aust, 1(10), 500.

Ford, R. M. (1984) – Bee venom immunotherapy and bee-sting mortality. Letter,
in Med J Aust, 140(9), 563-4.

Forestier,François (1983) (France) – L’abeille et l’arthritique (venin),
in Revue Française d’Apiculture, Mars, 125-27.

Forestier,François, Palmer M. (1983, 1984) (France) – Bee venom in rheumatology. An experiment performed with 1600 cases (English, French, German, Spanish, Russian),
in the XXIX-Th. Apimondia Congress, Budapest, Hungary, 387-391 (1983) (***);
in Apiacta 19, pp.19-22 (1984).

Forestier, François; Palmer, M. (1983) (France) – Le venin d’abeille en rhumatologie. Aspects d’une experience de 1.600 cas,
in the XXIX-Th. Apimondia Congress, Budapest, Hungary, 408-412 (***).

Forestier, François (1986) (France) – Une experience dans les maladies rhumatismales (venin),
in Revue Française d’Apiculture, Nov, 507.

Forestier, François; Palmer, M. (1986) (France) – Une thérapeutique toujours jeune,
in Revue Française d’Apiculture, Aug -Sept, pp.407-09.

Forestier, François (1993) (France) – Can Bee Venom (BV) Therapy Still Be Practiced in Western Europe ? Management of Chronic Pain,
in The First East-West International Conference on Pain Management, Seoul, Korea, pp.367-369.

Forestier, François (1995) (France) – Apivenintherapie (AVT) du rhumatisme: etat des lieux,
in Revue Française d’Apiculture, Mars, pp.110-15.

Forster, K. A. (1969) (Germany) – Chemistry, pharmacology and therapeutically effectiveness of bee venom,
in the XXII-Nd. Apimondia Congress, Munich, Germany, pp.405-407 (***).

Frankland, A. W. (1976) – Bee sting allergy.
in Bee World 57(4), p.145-50;
IBRA Reprint M88, 6 pp. (***).

Franklin, R.; Baer, H. (1975) – Comparison of Honeybee Venoms and their Components from Various Sources,
in Journal of Allergy and Clinical Immunology, Vol. 55, No. 5, pp.285-298.

Fredholm, B. (1966) – Studies on mast cell degranulating factor in bee venom,
in Biochem. Pharmacol. 15, pp.2037-2042.

Frenkel, M. M. (1983, 1984) – Bee venom products,
in Pcelovodstvo, # 5;
in L’Abeille de France, Mars 1984, p.108 (abstract).

Fry-Welch, D.; Pfalzer, L. (1996) (USA) – Effect of Bee Venom Therapy on Isometric Knee Strength in People with Multiple Sclerosis, [16]
in Neurology Report, vol. 20, # 4, p.13 (***).

Fry-Welch, D.; Pfalzer, L. (1996) (USA) – Effect of Bee Venom Therapy on Gait in People with Multiple Sclerosis [17],
in Neurology Report, vol. 20, # 4, pp.13-14 (***).

Fukazawa, K. (1985) (Japan) – Acuponcture avec abeilles au Japon,
in the XXX-Th. Apimondia Congress, Nagoya, Japan, pp.456-459 (***). [18]

Gauldie,J., Hanson,J.M., Rumianek,F.D., Shipolini,R.A., Vernon,C.A. (1976) – The peptide components of bee venom,
in Eur. J. Biochem 61, pp.369-376.

Gallesio Maria Teresa (1986) (Italy) – Diagnosis and therapy of allergy to hymenoptera venom,
in Apiacta, # 3.

Gencheva G., Shkenderov,S.V. (1986) – Inhibition of complement activity by certain bee venom components,
in Doklady Bolgarskoi Akad. Nauk 39, pp.137-139.

Gerst, J. E.; Salomon, Y. [19] (1987) (Israel) – Inhibition by melittin and fluphenazine of melanotropin receptor function and adenylate cyclase in M2R melanoma cell membranes,
in Endocrinology Nov;121(5), 1766-1772 (***). [20]

Ghosh, A. K.; Rukmini, R.; Chattopadhyay, A.[21] (1997) (India) – Modulation of tryptophan environment in membrane-bound melittin by negatively charged phospholipids: implications in membrane organization and function,
in Biochemistry, Nov 25;36(47), 14291-14305. [22]

Ginsberg, N. J.; Dauer, M.; Slotta, K. H. (1968) – Melittin used as a protective agent against X-irradiation,
in Nature 220, 1334.

Giza, J. (1987) – Apitoxitherapy associated with Acupuncture in Rheumatology.
in the XXXI-St Apimondia Congress – Warsaw, Apimondia Publishing House, Romania, pp. 497-500.

Goddle, K. (1985) – The bee stings,
in Bee Craft, Jan., 12-13.

Goodman, Harold (1997) (USA) – Apitherapy: Practice and Safety. How to Monitor Your Treatment Response,
in Bee Informed # 3, volume 4, Autumn, 6-7 (about BVT) (***).

Goullon, H. (1880) (Germany) – Das Bienengift im Dienste der Homoeopathie. Leipzig-Dr. Willmar Schwabe, 1880. pp. 84 (Letter size)

Guseva, M. P.; Kupriianov, V. A.; Golubchik, N. I. (1984) – Ambulatory apitherapy of lumbosacral radiculitis and sciatic neuritis,
in Feldsher Akush, 49(9), 55-6.

Gustov,A.V., Antipenko,E.A., Anisimova L.M., Krylov,N.Vasily (1997) (Russia) – “Solapiven” efficiency at infringements of cognitive functions at discirculatory encephalopathy patients,
in the XXXV-Th. Apimondia Congress, Antwerp, Belgium.

Gustov,A.V., Dudkina O.V., Smirnova A.V., Krylov,N.Vasily (1997) (Russia) – Solapiven in the treatment of patients with vertebro-genetical lumboischialgesis,
in the XXXV-Th. Apimondia Congress, Antwerp, Belgium.

Guyton, F. E. (1974) – Bee sting therapy for arthritis and neuritis,
in Econ. Entomol. 40, pp.469-472.

Habermann,E., Neumann,W.P. (1957) – Reinigung der Phospholipase A des Bienengiftes,
in Biochem. Z. 328, pp.465-473.

Habermann, E.; Reiz, K. G. (1965) – Ein neues Verfahren zur Gewinnung der Komponenten von Bienengift, insbesondere des zentral wirksamen Peptids Apamin,
in Biochem. Zeitschr. 341, pp.451-466.

Habermann, E. (1971) – Chemistry, pharmacology and toxicology of bee, wasp and hornet venoms,
in Venomous Animals and their Venoms, W. Bucherl and E.E. Buckely, eds., Vol. 4, Academic Press, NY.

Habermann, E. (1972) – Bee and Wasp Venom,
in Science 177, p.314.

Habermehl, G. G. (1981) – Venomous Animals and Their Toxins,
in Springer Verlag, Berlin.

Hadjipetrou-Kourounakis, L.; Yiangou, M. (1988) – Bee venom, adjuvant induced disease and interleukin production,
in J. Rheum. 15, pp.1126-1128.

Hanson,M.Jennifer; Moley,J.; Soria-Herrera,C. (1972, 1974) – Anti-inflammatory property of 401 (MCD-peptide), a peptide from the venom of the bee (Apis mellifera L.),
in Br J Pharmacol, 46(3), pp.537-538;
in Brit. J. Pharm. 50, pp.383-392.

Hauser, R.A. (1998) (USA) – Multiple Sclerosis,
in Alternative Medicine Digest, March, Issue 22, pp. 33-34.

Hauser, R. A., et al. (2001) (USA) – Bee-Venom Therapy for Treating Multiple Sclerosis,
in Alternative & Complementary Therapies, Vol. 7, No. 1, pp. 37-45.

Herold, Edmund; Leibold, Gerhard (1991) (Germany) – Heilwerte aus dem Bienenvolk. Honig, Pollen, Gelee Royale, Wachs, Propolis und Bienengift – Ihre Bedeutung für die Gesundheit und Behandlung von Krankheiten.
Ehrenwirth Verlag Gmbh, Munich, 242 pages; ISBN 3-431-03162-5 (***).

Higuchi, M. [23] (1992) (Japan) – Damage to mitochondrial respiration chain is related to phospholipase A2 activation caused by tumor necrosis factor (TNF),
in Journal of Immunotherapy, Jul;12(1), 41-49. [24]

Hoffman, D. R.; Shipman, W. H.; Babin, D. (1977) – Allergens in bee venom. Two new high molecular weight allergenic specifities,
in Journal of Allergology and Clinical Immunology 59, p.147.

Hollander, J. L. (1941) – Bee venom in the treatment of chronic arthritis,
in J. Med. Sci. 201, pp.796-801.

Hommel, D.; Bollandard, F.; Hulin, A. (1998) – Multiple African honeybee stings and acute renal failure,
in Nephron, 78(2), 235-6.

Höffel Ingrid (1983) (Germany) – Residues of heavy metals in bee colonies,
in the XXIX-Th. Apimondia Congress, Budapest, Hungary, 233 (***-abstract).

Hristea, L. Constantin; Ialomiteanu, Mircea (1966, 1969, 1972) (Romania) – The bee products for human health (Romanian).
Asociatia Crescatorilor de albine. Biblioteca Apicultorului, nr. 5/1966, 116 pages (Propolis pages: 74-82) (***); nr. 8/1969; the Third edition, in Apimondia Publishing House, 1972.

Hristea, L. Constantin (1974) (Romania) – Apipuncture with bee venom (Romanian),
in Apicultura, # 12, 10.

Hyre, H. M.; Smith, R. A. (1986) – Immunological effects of honeybee venom using barb/c mice,
in Toxicon 24 (5), 435-440.

Ingold Labs, Christopher; Buku A.; Blandina P.; Birr C.; Gazis D. (1989) – Solid-phase synthesis and biological activity of Mast Cell Degranulating (MCD) peptide, a component of bee venom,
in J. Peptide Protein Res. 33(2), pp.86-93; 58 ref. Cuny Mt. Sinai Sch. Med., Dept Physiol & Biophys, NY.

Inoue, H.; Nakajima, T. (1985) (Japonia) – Une comparaison de la composition du venin d’abeilles d’Apis cerana Japonica et d’Apis mellifera,
in the XXX-Th. Apimondia Congress, Nagoya, Japan, pp.461-464 (***).

Ioyrish, Petrovich Naum (1958, 1984) (USSR) – Veninul de albine si tratamentul reumatismului (Romanian),
in Apicultura, nr. 3, 1958; republished in 1984, nr. 4 (***).

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Rose Amber (1998) (USA) – Which Came First, the Needle or the Bee?
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Rose Amber (1999) (USA) – Progress in Bee Venom Therapy for HIV/AIDS,
in the XXXVI-th. Apimondia Congress, Vancouver, Canada, pp.73-75 (***).

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in American Bee Journal 94, pp.424-425.

Sabbah, A.; Plassais, R.; Grenapin, S.; Drouet, M.; Lauret, M. G.; Loiry, M.; Sainte-Laudy, J.[59] (1998) (France) – Testing basophil activation by flow cytometry in the diagnosis of allergy to hymenopteran venom,
in Allerg Immunol (Paris), Feb;30(2), 44-48. [60]

Saine, J. (1965) (Canada) – Is bee venom a panacea for the treatment of arthritis ?
in the XX-Th. Apimondia Congress, Bucharest, Romania, pp.443-445 (***). [61]

Saine, J. (1981) (Canada) – Prevenir l’arthrite,
in the XXVIII-Th. Apimondia Congress, Acapulco, Mexico, pp.493-501 (***).

Saini, S. S.; Chopra, A. K.; Peterson, J. W.[62] (1999) (USA) – Melittin activates endogenous phospholipase D during cytolysis of human monocytic leukemia cells,
in Toxicon 1999 Nov; 37(11), pp.1605-19 (***). [63]

Santilli, J.; Rockwell, W.J.; Wallerstedt, D.B. and Bellanti, J.A. (1999) (USA) – The Use of Bee Venom Therapy for Chronic Progressive Multiple Sclerosis – A Case Report.
in Bee Informed, Journal of the AAS, Winter, 1999, Vol. 5, No. 4, pp. 1 & 6-7.

Schlüter, H.; Mücke, H. W.; Pietrzik, E. (1981) – Heilkraft aus der Biene für die Medizin (Bee Healing Power for Medicine) (German),
Heinrich Mack Nachf. Illertissen.

Schmidt, D. K. (1978) – The Nature of the Response of Prostaglandins and Cyclic AMP to a Bee Sting.
PhD Diss. University of Georgia.

Schmidt, D. K.; Destephano, D. B.; Brady, U. E. (1978) – Effect of honey bee venom on prostaglandin levels in mouse skin,
in Prostaglandins 16, pp.233-238.

Schmidt, J. (1992 ) (USA) – Allergy to venemous insects,
in The Hive and the Honey Bee, Ch 27. Published by Dadant and Sons, Hamilton, Illinois (***).

Schmidt, J. (1982) (USA) – Biochemistry of insect venoms,
in Annual Rev. Entomology 27, 339-368.

Schumacher, M. J.; Schmidt, J. O.; Egen, N. B. (1989) – Lethality of “killer” bee stings,
in Nature 337, 413.

Schumacher, M. J. et al. (1990) – Quantity, Analysis and Lethality of European and Africanized Honeybee Venoms,
in Journal of Tropical Medicine and Hygiene 43 (1), pp.79-86.

Schumacher, M. J. et al. (1992) – Biochemical Variability of Venoms from Individual European and Africanized Honeybees,
in Journal of Allergy and Clinical Immunology 90, pp.59-65.

Serban, E. (1976) (Romania) – Considerations on Bee Venom Ultrasonophoresis used in the Treatment of Painful Gonarthrosis,
in the II-Nd. International Symposium on Apitherapy, Bucharest, Romania. Apimondia Publishing House, pp. 101-102 (***).

Serban, E. (1981) (Romania) – Utilisation du venin d’abeille injectable dans le traitement de la spondylarthrite ankylosante,
in the XXVIII-Th. Apimondia Congress, Acapulco, Mexico, p.501 (***).

Serban, E. (1983) (Romania) – Le traitement de la meralgie paresthesique essentielle au venin d’abeille,
in the XXIX-Th. Apimondia Congress, Budapest, Hungary.

Serban, E. (1983) (Romania) – Considerations on bee venom treatment in paresis,
in the XXIX-Th. Apimondia Congress, Budapest, Hungary, p.420 (***-abstract).

Sharma, S. V. [64] (1992) (USA) – Melittin resistance: a counterselection for ras transformation,
in Oncogene, Feb;7(2), 193-201. [65]

Shipman, W. H.; Cole, L. J. (1967) – Increased resistance of mice to X-irradiation after injection of bee venom,
in Nature 215, pp.311-312.

Shkenderov, S. (1973) (Bulgaria) – A protease inhibitor in bee venom. Identification, partial purification and some properties,
in FEBS Lett. 33, pp.343-347.

Shkenderov, S. (1976) (Bulgaria) – New pharmacobiochemical data on the anti-inflammatory effect of bee venom.
in “Animal, Plant, and Microbial Toxins”, Vol. 2 (A. Ohsada, K. Hayashi and Y. Sawai, eds), pp.319-336. New York: Plenum.

Shkenderov, S.; Ivanova I.; Grigorova K. (1979) (Bulgaria) – An acid monophosphatase and alpha-glucosidase enzymes newly isolated from bee venom,
in Toxicon 17 (Suppl. 1), pp.169-170.

Shkenderov, S.; Koburova K. (1982) (Bulgaria) – Adolapin, a newly isolated analgesic and anti-inflammatory polypeptide from bee venom,
in Toxicon 20 (1), pp.317-321.

Shkenderov,S., Ivanov,Ts. (1983) (Bulgaria) – Les produits de l’abeille.
Zemizdat, 238 pages (***-abstract in Honey bibliography).

Sikora,J., Muszynska,J., Rybak-Chmielewska,H., Wasik,A. (1987) (Poland) – Use of protozoan Paramecium bursaria in honey bee venom activity assay,
in the XXXI-St. Apimondia Congress, Warsaw, Poland, pp.474-477 (***).

Simics, Mihály; Fogarassy, C. (1993) (Canada) – Extra Income from Bee Venom Collecting,
in Alberta Bee News, May, p.7.

Simics, Mihály (1993) (Canada) – Venom Collecting Extra Income Source for Beekeepers,
in The Speedy Bee, Vol 22, No. 12, December, p.14 (reprint from the Alberta Bee News).

Simics, Mihály (1993, 1995) (Canada) – A Review of Bee Venom Collecting and more.
Apitronic Services, Calgary, Alberta, p.44, first, second and third edition, booklet (***-second edition).

Simics, Mihály (1993-1995) (Canada) – Bee Venom Collector Devices,
in Apitronic Services, Calgary, pp.20, 1st., 2^nd. and 3^rd. editions; photos; booklet.

Simics, Mihály (1994) (Canada) – Bee Venom Collecting around Calgary,
in BeesCene, Vol 10, No. 12, April, p.4 (***).

Simics, Mihály (1994) (Canada) – Bee Venom: Exploring the Healing Power. Age-Old Remedies for Arthritis, Rheumatism and other Ailments. Plus: First Aid for Accidental Bee Stings.
Apitronic Publishing, Calgary, AB, Canada, 77 pp. ISBN 0-9697654-0-1 (***).

Simics, Mihály (1994) (Canada) – The Effect of Bee Stings on the Human Body,
in Bee Informed Vol. 1, No. 4, p.6, Special Edition.

Simics, Mihály (1994) (Canada) – Bee Venom Collection for Medical Use,
in Canadian Beekeeping, Vol. 18, No. 6, p.140 (***).

Simics, Mihály (1995) (Canada) – First Aid for Bee and Wasp Stings.
Apitronic Publishing. Calgary. Alberta, Canada, ISBN 0-9697654-1-X, 32 pages (***).

Simics, Mihály (1995) (Canada) – Bee Venom Collection – Past, Present and Future,
in American Bee Journal, Vol. 135, No. 7, p.489-491 (presented also at the Toronto American Apitherapy Society Convention, April 1995).

Simics, Mihály (1995, 1999) (Canada) – Bee Venom – Frequently Asked Questions,
in American Bee Journal, Vol. 36, No. 2, pp.107-109; personal manuscript (***);
Apitronic Services, Reprint, No. AP003, booklet, pp. 12 (1999).

Simics, Mihály (1996) (Canada) – Changes in Bee Venom Therapy,
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Simics, Michael (1999) (Canada) – Bee Venom Collector Devices.
Apitronic Services, booklet, drawings, pp. 28.

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Apitronic Services, Reprint, No. AP001, booklet, pp. 8.

Simics, Michael (1999) (Canada) – Commercial Bee Venom Collection.
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Simics, Michael (1999) (Canada) – Bee Venom Products – Excerpts from “Apis Venenum Purum.”
Apitherapy Education Service – Apitronic Services, booklet, tables, pp. 10.

Simics, M. (2000) (Canada) – Bee Venom Therapy – Making an Informed Decision. Apitherapy Education Service – Apitronic Services, Richmond, BC, Canada, 10 pp.

Simics, M. (2003) (Canada) – Bee Venom Therapy – Making an Informed Decision. Pocket book edition. Apitherapy Education Service – Apitronic Services, pp. 28.

Simics, M. (2006-2018)(Canada) – Bee Venom Products Preparation Guide – A Supplement to Bee Venom Collector Devices. Apitronic Publishing, Apitronic Services. Richmond, BC, Canada. Good Apitherapy Practice Series, 4th printing, pp. 16.

Simics, M. (2006-2010)(Canada) – Comments on a Randomized Crossover Study of Bee Sting therapy for Multiple Sclerosis. Apitronic Publishing, Apitronic Services. Richmond, BC, Canada. Good Apitherapy Practice Series, 4th updated edition, pp. 20.
Description: It is a how to make products guide on honey and bee venom blend, bee venom cream, liniment and ointment.

BVT Protocols
Simics, M. (2002-2010) – Home Bee Venom Therapy Protocol for Multiple Sclerosis – A good starter protocol for those with multiple sclerosis. A contemporary publication. It will be replaced with BK035. 24 pp., TRP040

Simics, M. (2010) – Methodology of Injectable Bee Venom Therapy with Apixin 3X – Based on the protocol: Methodology for Injectable Bee Venom Therapy, but expanded to the use of Apixin 3X venom solution to treat a variety of health conditions. Neural Therapy protocol practiced by Dr. Klinghardt also included. 24 pp., spiral bound. TRP050

Simics, M. (2010) – Home Bee Venom Therapy Protocol for Chronic Fatigue Syndrome. A basic treatment protocol using Injectable bee venom. 32 pp. TRP060

Simics, M. (2010) – Bee Venom Allergy Treatment Protocol. This is a detailed bee venom allergy desensitization protocol using VeneX-10 or VeneX-20s. 28 pp., See: Starter Packagesfor more details. Available to MD, ND, DO only. Highly restricted! TRP070

Simics, M. (2011) – Homeopathic Bee Venom Therapy with VeneX-HC. Bee venom therapy with ready to use VeneX-HC, or dilute: 5X-6X (D5-D6) venom solutions. 28 pp. TRP080

Simics, M. (2011) – Bee Venom Therapy Protocol – Sensitive Areas. A Supplement, -to treat sensitive affected areas like hand and wrist, foot and ankle. 12 pp. TRP090

Simics, M. (2012) – HomeoAcupuncture with Honeybee Venom. Homeoacupuncture protocol with VeneX-AP and VeneX-10s. 12 pp. TRP100

Simics, M. (2013) – Bee Venom Allergy Tests. An allergy test protocol with VeneX-AL before starting bee sting, or bee venom therapy. One vial is enough for 80 allergy tests, 24 pp. TRP110 – Available as parts of ALK010 KIT only.

Simics, M. (2013) – Homeopathic Bee Venom Therapy with VeneX 4X. Bee venom therapy with a ready to use VeneX 4X venom solution. 28 pp. (contemporary product and protocol). TRP120

Simics, M. (2014) – Postherpetic Neuralgia Protocol. A shingles and PHN protocol with VeneX-10 venom solution. 24 pp. TRP130

Simics, M. (2016) – Korean Bee Venom Acupuncture Protocol. This is a detailed treatment protocol with the therapy dedicated VeneX-AP venom solution. 24 pp. TRP140

Veterinary Apitherapy Protocols
Simics, M. (2011) – Equine Veterinary Apitherapy Protocol. Apitronic Publishing, Apitronic Services. Richmond, BC, Canada. Good Apitherapy Practice Series. 2nd. Ed., 68 pp. TRP300

Simics, M. (2009) – A Case Study: Bee Venom Therapy Used to Treat Equine Arthritis. Apitronic Publishing, Apitronic Services. Richmond, BC, Good Apitherapy Practice Series. 8 pp. TRP310

Simics, M. (2009) – Canine Veterinary Apitherapy Protocol. Apitronic Publishing, Apitronic Services. Richmond, BC, Canada. Good Apitherapy Practice Series. 16 pp. TRP320

Other BVT Protocols:
Marinelli & Klinghardt (2002-2010) – Methodology for Injectable Bee Venom Therapy^ A general protocol for arthritis, scar, joint inflammation, low back pain, etc. treatment. 24 pp. TRP010 –

Klinghardt, D. (2001-2010) – Neural Therapy: Treatment Protocol for Bee Venom Therapy^ It is for those who practice Neural Therapy. 16 pp. TRP020

Klinghardt, D. (2001-2010) – The Treatment of Lyme Disease with Bee Venom^ A summary of treatment of over 500 patients with Lyme disease. Available in English or German languages. 24 pp. TRP030

Simics, M. (1999-2010) – Basic Bee Venom in Products. The processing principles of bee venom in different forms. Apitherapy Education Service – Apitronic Services, 2nd Edition, pp. 24.

Simics, M. (2000) – Apis Mellifica Bibliography – 1658-2000. This publication lists honeybees as homeopathic remedy and its related bibliography. Apitherapy Education Service – Apitronic Services, pp. 24. BK032

Simics, M. (2000) – Bee Venom Therapy – Making an Informed Decision. A useful research aid for those considering bee venom therapy for the first time. Apitherapy Education Service – Apitronic Services, pp. 14. BK033

Simics, M. (2002) – Bee Sting & Bee Acupuncture Therapy. A How to Start Bee Sting Therapy Guide with a summary of therapy guidelines for those using bee stings. booklet, pp. 8. Available with product order only. BK041

Simics, M. (2002) – A Summary of Bee Sting Therapy. A general summary of therapy guidelines for those using bee stings. Apitherapy Education Service – Apitronic Services, Booklet, pp. 12 (8.5″x11″). Available with product order only. BK041-B

Simics, M. (2003) – Apis Mellifica Monographs – A Selection From The Homeopathic Literature. Compilation of hard to find information. Apitherapy Education Service, pp. 28. BK038

Simics, M. (2003) – Apium Virus Monographs – A Selection From The Homeopathic Literature. Includes hard to find information on the homeopathic classification of Apium virus (venom sac extract). Apitherapy Education Service – Apitronic Services, pp. 24. BK039

Simics, M. (2003) – Vespa Monographs – A Selection From The Homeopathic Literature. Information about the homeopathic Vespa (Vespa crabro, Vespa vulgaris and Vespa germanica). Apitherapy Education Service – Apitronic Services, pp. 28. BK040

Simics, M. (2003) – A Summary of Bee Venom Therapy. This is a detailed summary for those who use injectable venom solution. Also included is a Consent for Participation in Bee Venom Therapy form, list of available protocols and miscellaneous therapy materials. 3rd Ed., updated. Apitherapy Education Service – Apitronic Services, booklet, physician’s edition, pp. 16. Available with product order only. BK042

Simics, M. (2012) – Bee Venom Therapy – The Healing Crisis. It helps to understand healing crisis and how to minimize its effect. Apitherapy Education Service – Apitronic Services, booklet, pp. 12.

Simics, M. (2014) – VeneX Ointment – Common Application Mistakes and Frequently Asked Questions. It is all about the proper application of the product and answers to questions from users. Apitherapy Education Service – Apitronic Services, booklet, pp. 12.

Sokol, P. T.; Hu, W.; Yi, L.; Toral, J.; Chandra, M.; Ziai, M. R. [66] (1994) – Cloning of an apamin binding protein of vascular smooth muscle,
in J Protein Chem, Jan;13(1), 117-128 (***). [67]

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in Inflammation, Vol. 8, No. 4, pp.385-391.

Somerfield, S. D. (1986) – Bee venom and arthritis: magic, myth or medicine ?
in New Zealand Medical Journal, pp.281-283.

Stangaciu, Stefan (1997) (Romania) – Lecture via the Internet. Answers to Questions from Knowledge Review Course Participants (July 1997, American Apitherapy Society’s Course),
in Bee Informed, #3, volume 4, Autumn, pp.18-19 (***).

Stangaciu, Stefan (1999) (Romania) – Improve Bee Venom’s Efficacy through Integrated, Holistic Apitherapy,
in Bee Informed, Vol. 6, no. 2, pp.1; 16-18 (***).

Stangaciu Stefan (2002) (Romania) – Bee products and their medicinal uses. A Review,
in Honeybee Science 23 (3), 97-104 (***).

Steigerwaldt, F.; Mathies, H.; Damrau, F. (1966) – Standardized bee venom (SBV) therapy of arthritis,
in Industrial Medicine and Surgery 35, pp.1045-1049.

Stoia, I.; Civicã, D. (1965) (Romania) – Consideration on apitherapy and apicotherapy,
in the XX-Th. Apimondia Congress, Bucharest, Romania, pp.569-571 (***).

Tatu Elena (1987) (Romania) – Studies on the antimicrobial and antifungal action of Romanian bee venom,
in the XXXI-St. Apimondia Congress, Warsaw, Poland, pp.478-482 (***).

Tatu Elena (1989) (Romania) – Contributions to the antimicrobial action of bee venom,
in Apiacta XXIV, pp.13-17.

Terč, F. (1888) (Austria) – Über eine merkwürdige Beziehung des Bienenstiches zum Rheumatismus,
in Wiener Medizinische Presse, nr.35.

Terc Phillip (1904, 1962) (Austria) – Lecture in the Monthly Assembly of Beekeepers, February 11, 1904,
in Bee Venom: the natural curative for arthritis and rheumatism. G.P. Putnam’s sons, New York, 1962, Appendix H, pp.183-197.

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Thurnheer, U.; Muller, U.; Stoller, R.; Lanner, A.; Hoigne, R. (1983) – Venom immunotherapy in hymenoptera sting allergy. Comparison of rush and conventional hyposensitization and observations during long-term treatment,
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Tumwine, J. K.; Nkrumah, F. K.[69] (1990) (Zimbabwe) – Acute renal failure and dermal necrosis due to bee stings: report of a case in a child,
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Ariston Verlag, Genf, Germany, 1982, 198 pages; ISBN 3-453-06997-8; 5 Aufl. 1985. 1328/83.

Urtubey, Néstor (2003) (Argentina) – Del veneno de Abejas a la Apitoxina de Uso Medico.
Santiago del Estero, Argentina. 157 paginas. Segunda edicion.
© Néstor Urtubey. ISBN: 987-43-5831-9 (***).

Valiukiene,K., Ceremnych-Aleksejenko,E., Gaigaliene,B., Tamilaitiene,M., Baltuskevicius,A. (1995) (Lithuania) – Local application of the massage cream with bee products in the treatment of systematic sclerodermia and osteoarthrosis,
in the XXXIV-Th. Apimondia Congress, Lausanne, Switzerland, 141 (***-abstract).

van der Brempt, X.; Ledent, C.; Mairesse, M.[71] (1997) (Belgium) – Accelerated desensitization for hymenoptera venom allergy in 30 hours: efficacy and safety in 150 cases (original article in French),
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Varachiu, N.; Luca, N.; Popescu Filofteia; Mateescu Cristina; Pirvu, Gh. (1989, 1991) (Romania) – Experimental and clinical studies concerning the treatment of several forms of periodontal diseases with apitherapeutic products,
in the XXXII-Nd. Apimondia Congress, Rio de Janeiro, Brazil, 1989, p.545 (***-English, French, German [73] , Spanish abstract);
in Kaal, 1991, p.38 (***-abstract).

Varanda A. Eliana; Takahashi S. Catarina; Soares, A. E. E. (1989) (Brazil) – Honeybee venom as a radioprotective agent in Wistar rats irradiated with gamma rays,
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Varanda A. Eliana; Monti, R.; Tavares, D.C. (1999) (Brazil) – Inhibitory effect of propolis and bee venom on the mutagenicity of some direct– and indirect-acting mutagens,
in Teratog Carcinog Mutagen;19(6), 403-13.

Vasiliev,V., Stoianova L., Ninov,V. (1969) (Bulgaria) – Therapy of rheumatism by electrophoretic and phonophoretic methods with lyophilised bee venom,
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Vick, J. A.; Shipman, W. H. (1972) – Effects of whole bee venom and its fractions (apamin and melittin) on plasma cortisol levels in the dog,
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Vick,J.A., Mehlman,B., Brooks,R., Phillips,S.J., Shipman,W. (1972) – Effect of bee venom and melittin on plasma cortisol in the unanesthetized monkey,
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Vick, J. A.; Brooks Robert, B. jr. (1972) (USA) – Pharmacological studies of the major fractions of bee venom,
in American Bee Journal, August, pp.288-89.

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Vick,J.A., Shipman William,H., Brooks Robert,B. (1974) – Beta-adrenergic and anti-arrhythmic effects of cardiopep, a newly isolated substance from whole bee venom,
in Toxicon 12, pp.139-144.

Vick,J.A., Warren Glenn,B., Brooks Robert,B. (1976) (USA) – The effect of treatment with whole bee venom on daily cage activity and plasma cortisol levels in the arthritic dog,
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[1] Mr. Oota is a nice old man; he is the President of the Japanese Api-Puncture Association

[1] Abstract: [Record supplied by publisher]

Background: Based on our previous work, polycystic ovary syndrome represents an autoimmune disease that demonstrates high concentrations of antiovarian antibodies. Bee venom works in an immune mechanism, and its antiinflammatory-like action works 100 times as a hydrocortisone.

Objective: To use for the first time in the literature laparoscopic

intraovarian injection of bee venom in the treatment of polycystic ovarian disease.

Materials and methods: Fifteen patients with polycystic ovarian disease resistant to medical treatment were treated by laparoscopic injection of 0.1 mL of bee venom injected directly into the ovarian stroma.

Results: A statistically significant decrease in luteinizing hormone, androstenedione, and testosterone was observed (P <0.001).
Ovulation occurred in 75% of cases. The pregnancy rate was 50% in those who ovulated.
No complications were observed with this new technique.

Conclusion: Laparoscopic intraovarian injection of bee venom in the treatment of polycystic ovarian disease is a new method for the induction of ovulation in patients with resistant polycystic ovarian disease that is safe, easy to use, and free of complications.

[2] PHYSIOLOGICAL ANALYSIS OF THE CARDIOTOXIC ACTION OF THE BEE VENOM [2]

M. ARTEMOV
N. ORLOV

N.V. KORNEVA

N. KRYLOV

USSR

It is known that a great number of bee sting may cause serious intoxication in man and domestic animals (N. M. ARTEMOV, 1941; S. Z. ANDREEV, 1962, 1963; I. A. ISAEV, 1965; P. I. POKUTA, 1965, A. A. CHERKES, E. V. SVETOV, A. N. AGHEENKO, 1966; KOSZALKA, M. F., 1949 and others). As a symptom of intoxication, various troubles, of the activity of the cardiovascular system are noticed. In order to improve the patient’s condition, the physician has to know the cause of these troubles thoroughly and to take the results of the physiological analysis of the cardiotoxic action of the bee venom into consideration.

We made the first experiments on frog heart preparations, isolated according to the Straub method (N.M. ARTEMOV, O.F. SOLOVIEVA, 1959 ; N.M. ARTEMOV, 1951). We found that the bee venom in a dilution of 1 : 50.000 – 1 :5,000 caused a sudden reduction of the heart contraction amplitude and an increase of the tonus of the ventricle muscle. As a consequence of the bee venom action often arrhythmia and sometimes the heart block have appeared. It is interesting that the bee venom annihilates the hindering effect on the heart of the pneumogastric nerve and renders it insensible to acetylcholine.

For the present paper we synthesized the materials dealing with the cardiotoxic action of the bee venom that we have gathered for 5 years. The experiments were made on warm blooded animals (cats, rabbits).

The investigation on the influence of the bee venom on the heart was carried out on animals nervously and humorally relaxed as well as on untouched animals. In a series of experiments the intoxication with bee venom was performed on sectioned pneumogastric nerves.

The first series was made 15 isolated cat hearts. The isolated heart was fixed on a tube and perfused with Ringer Lock solution according to the Langgedorf method. The rate of perfusion was of 10-15 ml/min. 1 ml of 1 : 2,000 – 1 : l00,000 g/ml bee venom solution was introduced into the aorta through the tube at the same rate as that of the perfused solution. Injections with 1 ml Ringer-Lock solution were used as controls.

The heart of the warm blooded animals reacted a great deal to the bee venom. A 1:5,000 bee venom solution caused the irreversible stop of the heart in 1-10 minutes. The inhibition effect was accompanied by arrhythmia, by Luciani periods, by negative chronotropic and miotropic effects. The administration of a 1:50,000 bee venom solution proved to be efficient. The venom in this dilution had a pronounced negative miotropic effect.

When the bee venom in this dilution was administered several times, a gradual inhibition of the heart contractions appeared after a short period of stimulation. The venom in a 1:100,000 dilution had a weak inhibitory action on the heart ; this was proved by the gradual reduction of the heart contraction amplitude without any pronounced changes in the rhythm of the heart beats.

p.415

We want to point out that the efficient concentration (1 : 1,000 – 1 : 50,000) of bee venom caused a 30-50% reduction of the volume to be perfused and leaving the heart.

The second series of experiments were made on 21 rabbits. The animals were fixed on the operation table on their backs without narcosis. In the distal parts of the extremities needle electrodes were subcutaneously introduced. On a 4 EZG-1 type electrocardiograph the electrocardiogram (EKG) was registered in the first and second standard derivation. Before the experiment was started the bee venom was diluted in one ml physiological serum and was injected into the peripheric vein of the animal’s ear. The doses varied from 0.5 to 2 mg bee venom per kilo of body weight.

No serious heart troubles were noted with an intravenous inoculation of 0.5-1 mg bee venom/kilo of body weight. Only a slackening of the rhythm of the heart beats of a sinusal bradicardy type, having appeared immediately after the inoculation of the venom was noted. Extrasystoles were noted in some experiments. The waves and the duration of the electrocardiogram intervals had not undergone important changes. 5-15 minutes after the bee venom has been injected heart activity became normal and the electrocardiogram had a normal aspect. By the repeated administration of non-lethal doses of bee venom the rhythm of the heart beats did not change to a great extent.

Larger doses of bee venom (1 mg/kilo and more) caused more important troubles of the heart activity. 15-25 minutes from the inoculation of the bee venom a persistent bigeminal type ventricular extrasystole often appeared together with the sinusal bradycardy. In 40-60 minutes the electrocardiogram became partially normalized. Sometimes, at 1-2 minutes from the inoculation of the bee venom the reduction of the number of heart beats was accompanied by a reversible atrium-ventricular blocking.

The repeated inoculations with large doses of bee venom caused a persistent atrium ventricular blocking, a widening of the QRS complex and a sudden reduction of the electrocardiograph voltage (the terminal period of the heart activity).

In a series of experiments when sub-lethal doses of bee venom were repeatedly administered, the atrium-ventricular blocking was accompanied by an alteration of the QRS ventricular complex and the increase of the T wave. Among the other troubles that the administration of sub-lethal and lethal doses of bee venom cause to the heart activity are the appearance of the slow ventricular rhythm and the atrium fibrillation.

According to the experimental results, when the bee venom is internally administered the heart activity is greatly disturbed. The above described changes of the electrocardiogram were recorded during a state of persistent bradycardy and disappeared together with the terminal period of the heart activity. During all experiments the heart contractions could be noted for an additional 10-15 minutes after breathing has completely ceased. During that time the electrocardiogram was that characteristic of a hypoxemia : the voltage of the waves increased for a short time, the atrium-ventricular blocking and the giant wave appeared.

In order to find out the mechanism of the troubles in the heart activity in bee venom intoxication special experiments were carried out on 12 cats. We assumed that the cardio-cardial reflexes played an important part in the evolution of the heart pathology. The experiences have shown that when introducing bee venom (0.7 mg/kilo of body weight) into the right auriculum by means of the catheter, the blood pressure and the rhythm of the heart contractions suddenly drop. When animals with sectioned pneumogastric nerves are inoculated in the heart with the same doses of bee venom their blood pressure goes down very little and no bradycardy is recorded.

We suppose that the reflexes appearing in various reflex generating zones and especially in the heart participate in the organization of the reactions of the cardiovascular system to the penetration, of the toxic doses of bee venom into the blood circulation. The

p.416

heart (especially the ventricles) as compared to the other regions of the cardiovascular system — was known to have most of the receptors ; and that most of the impulses from the heart are transmitted by the pneumogastric nerve (see A. I. KHABAROVA, 1961). The cardiovascular reflexes have obviously a great importance in the mechanism of the heart rhythm slackening as a result of bee venom administration. The multiplication of the afferent signals when the bee venom circulates in the blood system leads to a persistent increase of the tonus in the pneumogastric nerve centers while the further troubles of the heart activity appear on the background of a persistent bradycardia. The slackening of the sinus rhythm is one of the most important factors that increases the activity of the ectopic automatism centers and conditions the various troubles of the heart rhythm (B. M. FEDOROV, 1968).

Nevertheless, apart from the changes of the central-reflexion influences on the heart, the toxic doses of bee venom could disturb the self regulating mechanisms which according to the modern conceptions could greatly modify the functional heart activity without the participation of the central nervous system. Among these mechanisms, the reactions that occur due to the intracardiac nervous system have a great importance (G. I. KOSHITZKI, I.A. CHERNOVA, 1968).

The action of the concentrated bee venom solutions on the isolated heart disturbs the regulating functions of the intracardiac nervous system. Then the other heart troubles and the terminal stage of the heart activity grow worse (Luciani periods, development of transversal blocking, increase of the ventricle muscle tonus etc.).

The lethal doses of bee venom not only seem to disturb the central nervous system and intra-cardiac regulation but may also have a direct influence on the cardiac system and on the automatism centers.

In cases of intoxication this is obvious on the electrocardiogram. Nevertheless, we must point out that when the troubles of the heart activity intensify, these are accompanied by a breathing insufficiency. In the case of hypoxemia, the irreversible troubles of the tissue metabolism of the heart muscle rapidly develop and lead to a pre-terminal period of the heart activity which on its turn aggravates the hypoxemia.

An important feature of the cardiotoxic action of the bee venom is the perturbation of the coronary blood flow which may be appreciated from the reduced volume of the perfusing liquid released from the isolated heart. This is obviously connected with the mellitine content of the bee venom which is capable of contracting the smooth muscles. (NEUMANN W., HABERMANN, E., 1954). In addition to this, we must also consider the histamine content of the bee venom which according to V. I. USPENSKI (1963) and others may cause the spasm of the coronary vessels.

LITERATURE CITED

ANDREEV Z. S., 1962 – in Sov. Med. no. 1. 121-123

ANDREEV Z. S., 1963 – in Vrachebnoe delo no. 1. 145-148

ARTEMOV N. M., 1941 – Pcheinii iad. ego fiziologuicheskie Svoistva o terapevticheskoe primenenie. Izd. ANSSR M-1

ARTEMOV,N.M., 1951 – in Uchi. zap. Gork. gos. un-to. v. 19. 3-16

ARTEMOV,N.M., SOLOVIEV,S.F., 1939 – in Biull. exper. biol. i. med 7. v. 5. 446-449

ISAEV, I. A., 1965 – in Arjiv. patol. no. 11. 65-66

KOSHITZKI, G. I., CHERNOVA, I. A. 1968 – Serdte kak samoreguliruischiaia sistema, M.

POKUTZA, N. N., 1965 – in Vraschebno delo nr. 3. 52

USPENSKI, V. I., 1963 – Guistamin. Gos. iz. med. lit., M

FEDOROV, B. M. – Mejanismi narushenia i vosstanovlenia serdechinoi deiatelnosti. Izd. “Medizzina” M.

HABAROVA A. I. 1961 – Afferetnaia innervatia serdtza Izd. AN SSSR. M-1

CHERKES,A.A., SVETZOV,E.V., AGUEENKO,A.N., 1966 – in Zdravoojr Belorussii, no. 11, 77-78.

27 – The XXIVth international Apicultural Congress p.417

[3] Bomalaski’s Adress – Medical College of Pennsylvania, Philadelphia 19129, USA.
[4] Bomalaski, J. S. (1995) – Phospholipase A2-activating protein induces the synthesis of IL-1 and TNF in human monocytes,
in J Immunol., Apr 15;154(8), pp.4027-31.

Phospholipase A2-activating protein (PLAP) is an important mediator of eicosanoid generation. PLAP can also be found in high concentrations in synovial fluid from patients with rheumatoid arthritis, and injection of PLAP into animal joints results in an inflammatory, rheumatoid-like lesion. We have demonstrated previously that TNF-alpha and IL-1 beta stimulate formation of PLAP before phospholipase A2 (PLA2) enzyme activation and production of eicosanoids. To further explore the mechanisms found in the inflammatory response, we examined the ability of PLAP to stimulate release of TNF and IL-1 from human peripheral blood monocytes. TNF and IL-1 protein levels were measured by ELISA, and IL-1 and TNF mRNA were determined by Northern blotting. PLAP, PLAP peptide, and melittin, a bee venom PLA2 activator with homology with PLAP, all increased IL-1 and TNF production in a time- and dose-dependent manner. Heat-denatured PLAP and actin (an irrelevant protein) failed to exert this effect. PLAP stimulation of TNF and IL-1 could be enhanced with co-treatment of cells with free fatty acids, such as arachidonic or linoleic acid, but it was not blocked completely by PLA2 inhibitors. These results demonstrate not only that synthesis of PLAP can be stimulated by cytokines, but also that PLAP may regulate cytokine synthesis and thus perpetuate an immune or inflammatory response.

[5] Bourgain et al. address: Service de Nephrologie, CHU de Rouen, France.

[6] Bourgain, C.; Pauti, M. D.; Fillastre, J. P.; Godin, M.; Francois, A.; Leroy, J. P.; Droy, J. M.; Klotz, F.[6] (1998) (France) – Massive poisoning by African bee stings (original article in French),
in Presse Med 1998 Jun 20;27(22), pp.1099-101.

BACKGROUND: Bee stings can cause severe toxic effects when envenomation is massive.

CASE REPORT: While touring in Casamance (Southern Senegal) a white male was severely stung by a swarm of African bees. The massive envenomation caused rhabdomyolysis, hemolysis and acute renal failure. Pathology examination of kidney and bladder specimens showed vasculitis affecting both arteries and veins. The patient was treated with several hemodialysis sessions and renal function returned to normal three months after the incident.

DISCUSSION: Bees in Africa, known as “killer bees”, are particularly aggressive. They have recently been imported from tropical zones in America where a large number of deaths have been reported. Most cases of massive envenomation have shown acute tubular necrosis or renal involvement with myoglobinuria or hemoglobinuria. The renal pathology observed in our case is not usually described.

[7] Boutin, Y.; Jobin, M.; Bedard, P. M.; Hebert, M.; Hebert, J. (1994) (Canada) – Possible dual role of anti-idiotypic antibodies in combined passive and active immunotherapy in honeybee sting allergy,
in J Allergy Clin Immunol, Jun;93(6), pp.1039-46 (abstract).

Address: Centre de Recherche en Inflammation et Rhumatologie-Immunologie, Centre de Recherche du Centre Hospitalier de l’Universite Laval, Laurier, Ste-Foy, Canada.

BACKGROUND: Passive infusion of beekeepers’ plasma was shown to protect patients against systemic reactions occurring during active immunotherapy by mechanisms still to be clarified. It is tempting to speculate that anti-idiotypic antibodies could play a role because they are found in beekeepers’ plasma and are involved in the regulation of IgE synthesis. METHODS: In this report we studied the effects of passive infusion of a beekeeper’s plasma rich in anti-idiotypic antibodies to a patient who experienced systemic reactions to honeybee venom. RESULTS: We reported, during the days after the infusion, a decrease of clinical sensitivity to the honeybee venom. Indeed, the patient tolerated a cumulative dose of 280 micrograms of venom without adverse reactions. We also observed decreases in skin mast cell and in basophil sensitivity. After the plasma infusion, a modified rush immunotherapy with honeybee venom was initiated in our patient. In the following 76 weeks, increased levels of anti-idiotypic antibodies in the serum of the patient were associated with a diminution of specific antibodies (IgG and IgE) to honeybee venom. CONCLUSION: These results suggest a dual role of anti-id in our combined protocol of passive and active immunotherapy: an immediate action on clinical sensitivity along with a decrease of skin mast cell and basophil sensitivity and an immunoregulatory role on specific antibody production.
PMID: 7516355, UI: 94275034.

[8] Joseph Broadman, M.D. Address: 1359 Alderton Lane, Silver Springs, MD 20906 USA. Tel.: (301) 460-6145.

[9] UNTERSUCHUNG DES BIENENGIFTS DER HONIGBIENEN (Abstrakt)

Brooks
J.A. Vick
W. Shipman
C. Mraz
G.B. Warren

Diese Untersuchung schließt 15 Forschungsjahre ein. Sie befaßt sich eingehend mit den vorlaufenden Arbeiten der Forscher auf dem Gebiete der Pharmakologie und Toxizität des gesamten Bienengifts und seiner Fraktionen. vorgetragen wird eine noch nicht bekannte Arbeit über die allgemeine Förderung des neuro-hormonalen Systems. Die Untersuchung befaßte sich mit den mit integralem Bienengift kombinierten hormonalen Behandlungen, mit dem Verhältnis zwischen Vitamin C und der langandauernden Behandlung der Versuchstiere.

[10] NEW COMBINED METHOD OF ACU- AND API-PUNCTURE

I-DOBROVODA

CZECHOSLOVAKIA

The apipuncture is an acupunctural method in which living bees are applied in the acupunctural points on meridians of the classical Chinese acupuncture. The indication possibilities of the two methods, i.e. acu- and apipuncture are thus higher though it must be said that the majority of indications of the two methods is almost identical. They are applied in various cases regarding the motion apparatus as well as in those treating rheumatological, orthopedic, neurological patients and are well founded also in internal medicine, ophthalmology, etc.

To increase the effectiveness of the method the author introduced a new modified way in which the number of bee sting applications is complemented by acupunctural needles. This technique proves to be very convenient especially at the beginning of the treatment, when the number of stings is limited and the patient – in agreement with acupunctural indications requires a higher number of applications. Nowadays allergies are much spread the estimation gives the figure of 13 per cent of the population – and so the addition of further apipunctural application must be well considered.

[11] dos Reis et. al. address: Department of General Pathology, Faculty of Medicine of Triangulo Mineiro, Uberaba, MG, Brazil.

[12] dos Reis, M. A.; Costa, R. S.; Coimbra, T. M.; Teixeira, V. P. (1998) (Brazil) – Acute renal failure in experimental envenomation with Africanized bee venom,
in Ren Fail, Jan; 20(1), pp.39-51 (*** – abstract).

Human victims of multiple bee or wasp stings have been reported and develop severe clinical signs and symptoms. Acute renal failure (ARF), usually due to acute tubular necrosis (ATN) was a frequent complication. The pathogenetic mechanisms of ATN occurring in these accidents are still unclear. In the present study, female Wistar rats weighing 150-200 g were injected intravenously with Africanized bee venom at a dose of 0.4 microL/100 g body weight, and the kidney was observed under light and transmission electron microscopy and in immunohistochemical studies. The animals were divided into two groups: an Early group studied 3 to 8 hours after inoculation, and a Late group studied 24 to 30 hours after inoculation. The animals showed ATN mainly in the cortex and outer medulla with cast formation. After 24 hours, frequent mitotic figures were found in the tubular epithelium. Immunohistochemical studies revealed the presence of myoglobin and muscle actin in the tubular casts. Under electron microscopy, proximal tubule segments showed increasing intracytoplasmic vacuoles and attenuation of the brush border and of the basolateral infolding. This segment and the thick ascending limb of Henle’s loop showed hydropic degeneration. Dead cells with apoptosis or necrosis due to cellular disintegration resulted in tubular basement membrane denudation. In the Late group, figures of intracytoplasmic myelin could be observed, some of them containing mitochondrial fragments. These changes are likely to be due to interactive effects of venom components, mainly mellitin and enzymes such as phospholipases, both acting on biological membranes. The ATN found was probably due to multiple causes, mainly a direct action of the venom on tubular cells, myoglobinuria, and perhaps ischemic mechanisms.

[13] Address: Department of Clinical Immunology, Addenbrooke’s NHS Trust, Cambridge, UK.

[14] BACKGROUND: Changeover from Phadebas RAST to Pharmacia AutoCAP increased double-positivity to both honey-bee and common wasp (vespula) venom in our patients. OBJECTIVE: We examined the frequency of IgE double-positivity, its clinical relevance and utility in investigating potentially allergic patients.
METHODS: One hundred and eighty-two patients with hymenoptera allergy were tested using RAST (n = 51) and AutoCAP (n = 131) assays over 4 years. Patients had a history of reactions to vespulae (22), honey-bee (10) and unidentified hymenoptera (vespinae) (7). RESULTS: After changing from RAST to AutoCAP double-positivity increased from 10 (5/ 51) to 30% (39/131) (P < 0.01). RAST and CAP assays gave similar median class results (vespula = 3, honey-bee = 2). Thirty-six CAP patients had systemic reactions of Mueller grade II and above.
In vespula-allergic double-positive subjects, high CAP classes (> or = class 3) to honey-bee were common (30%). In 25% the CAP classes were equal. In honey-bee-allergic subjects, all vespula venom CAP IgE was low titre (class 1 or 2) and 20% were equal for both venoms. In 43% of vespinae-allergic patients the CAP class was equal to both (class 2 and 3). In contrast, intradermal skin test double-positivity was uncommon. Double-negative skin test results were common in the CAP double-positive population (22% of honey-bee-allergic, 13% of vespula-allergic and 43% of vespinae-allergic patients). Vespula allergic patients have higher bee-venom IgE than vice versa. Twenty-seven per cent of CAP double-positive patients (representing 8% of all venom allergic patients tested over this period) had equal class IgE to both venoms which was not helpful in diagnosis. Combination of skin testing and CAP is unhelpful in only 5/37 (14%) of patients with double-positive serology. CONCLUSION: If used in isolation CAP may be misleading, especially if only one venom is tested. Identification of the causative venom must utilize both clinical history and skin testing in these double-positive patients, and challenge testing if indicated.
Comments: Comment in: Clin Exp Allergy 1998 Jan;28(1):4-6.

[15] Faux JA, Moffatt MF, Lalvani A, Dekker J, Warrell DA, Cookson WO (1997) (U.K.) – Sensitivity to bee and wasp venoms: association with specific IgE responses to the bee and wasp venom and HLA DRB1 and DPB1,
in Clin Exp Allergy, May;27(5), pp.578-83 (abstract).

Faux et al. address: Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, UK.

BACKGROUND: Stings from bees and wasps can cause systemic reactions which can be fatal in some individuals. In these venom-sensitive patients, specific IgE to the venom is produced and is considered to participate in the adverse reactions. This immune response requires antigen presentation by human leucocyte antigens (HLA) class II molecules, which includes DR and DP, which are present on antigen presenting cells. OBJECTIVE: To test for associations between HLA class II DRB1 and DPB1 alleles and life-threatening sensitivity to both bee and wasp venoms. To establish further whether any associations are independent of the atopy phenotype. METHODS: A total of 33 bee- and 44 wasp-venom-sensitive patients was studied. DRB1 genotypes were determined by single stranded oligonucleotide (SSO) probing of PCR products, and DPB1 genotypes by amplified fragment length polymorphism (AFLP) analysis. Total and specific IgE were measured using the Pharmacia Immunocap, FEIA. Patients with specific IgE to the venom antigens only were termed monosensitive and those with additional specific IgE to HDM and/or GP were termed polysensitive. RESULTS: Allele frequencies were compared to an unrelated control population. The 33 bee-sensitive patients had a greater prevalence of DRB1*07 alleles than the control subjects, 26% vs 14%, with an odds ratio (OR) of 2.1 (95% CI, 1.2-3.7, P = 0.015, corrected for multiple comparisons, Pc = ns). This association was confined to the 15 monosensitive bee patients, who had a 43% DRB1*07 allele frequency when compared with 11% in the 18 polysensitive bee patients, OR 6.1 (95% CI, 1.73-22, P = 0.004, Pc = 0.05), and when compared with a control group of non-venom subjects, 43% vs 16%, OR 3.9 (95% CI, 1.72-9.0, P = 0.002, Pc = 0.02). The 44 wasp-sensitive patients had an increase in the DRB1*11 allele when compared with the control subjects, 13% vs 6%, with an OR 2.2 (95% CI, 1.0-4.6, P = 0.04, Pc = NS), and a decreased prevalence of DRB1*04 alleles, 10% vs 19%, with an OR 0.33 (95% CI, 0.24-0.99, P = 0.04, Pc = NS), but these were not significant when multiple comparisons were taken into account. The DPB1 alleles were not significantly different between the venom sensitive patients and the controls. CONCLUSION: Patients monosensitive to bee venom had a significantly greater prevalence of DRB1*07 alleles than the non-venom, control population suggesting that IgE responses in these patients may, in part be controlled by immune response HLA class II genes. These results are also suggestive of wasp-sensitive patients having a higher prevalence of DRB1*11 and a lower prevalence of DRB1*04 than the control population.
PMID: 9179434, UI: 97322944.

[16] Fry-Welch,D., Pfalzer L. – University of Michigan-Flynt, Flynt, Mich. Supported by a Faculty Development Grant from the University of Michigan-Flynt.

[17] Fry-Welch,D., Pfalzer L. – University of Michigan-Flynt, Flynt, Mich. Supported by a Faculty Development Grant from the University of Michigan-Flynt.

[18]

ACUPONCTURE AVEC ABEILLES AU JAPON

FUKAZAWA, K.

JAPON

L’acuponcture avec abeilles a débuté il y a 65 ans, en 1920, par des apiculteurs enthousiastes. Tout a commencé quand un apiculteur âgé qui était paralysé a essayé de capturer un essaim d’abeilles dans son jardin. Il est tombé et a été piqué par les abeilles sur tout son corps. Les nouvelles de sa miraculeuse guérison se sont répandues et ont servi de bases aux méthodes actuelles.

Autrefois, pour pratiquer l’acuponcture avec abeilles, il y avait besoin seulement d’une demande faite auprès des autorités locales. Quand en 1949 on a modifié les lois, on a adopté un système nationale d’examen ; pour pratiquer l’acuponcture avec abeilles, il y avait besoin de recevoir une approbation sans examen, par un arrangement de faveur avec l’état. Plusieurs personnes qui pratiquaient l’acuponcture et qui sont les témoins de la pratique de l’acuponcture sans approbation vivent encore ; certains pratiquent l’acuponcture à la suite de l’approbation donnée par la Police Métropolitaine de la ville Tokyo.

Binpaku Shiraiwa, l’ancien administrateur de l’Association des Apicultures Japonais s’est occupé de l’acuponcture avec’ abeilles après 1915 et a soutenu la création d’une école d’acuponcture par abeilles dans le cadre du Ministère de la Santé et de la Prospérité en 1939. Pendant ce temps, le journal “Nihon Yoho Shimbun”, est devenu le centre des activités de promotion de l’acuponcture en organisant des séminaires d’acuponcture dans le bâtiment des organisations apicoles, en mettant ainsi les bases de cette discipline qui c’est étendue jusqu’à présent. Au début la méthode spartane avec des piqûres directes a été évitée par le public. L’acuponcture avec abeilles était patronnée, seulement par un secteur des apiculteurs.

En octobre 1979, l’Association japonaise d’études pour l’acuponcture avec abeilles dont le promoteur était “Nihon Yoho Shimbun” a été créé. Il est inutile de mentionner que cela s’est réalisé avec l’aide substantiel des prédécesseurs, comme N. Ohta, Hashimoto, Yamada et Yonekura qui ont fait 20-30 ans de recherches apicoles. On a pu faire de grands progrès car ces prédécesseurs ont dévoilé les secrets de leur art.

Le changement de la méthode des piqûres directes qui donne l’impression que les piqûres des abeilles sont douloureuses, avec la méthode des piqûres sans douleur a contribué à l’utilisation à grande-échelle de l’acuponcture avec abeilles.

Le but de la thérapie de l’acuponcture japonaise avec abeilles est d’établir les bases de l’acuponcture avec abeilles, qui occupe déjà une position primordiale parmi les remèdes domestiques et d’obtenir des connaissances sur la manière avec laquelle l’acuponcture et la moxibustion ont été acceptées par le public. Nous devons à présent réunir les données expérimentales des membres, orienter notre attention vers les chercheurs de prestige et essayer de convaincre la population.

Les séminaires organisés par l’Association ont lieu deux fois par an. En plus, les associations d’apiculteurs préfectorales et les filiales organisent leurs séminaires pour répandre l’acuponcture avec abeilles. On attend de ces séminaires non seulement une augmentation des ventes de miel, mais une promotion aussi des produits apicoles comme la gelée royale, le pollen et le miel, comme nourriture saine et efficace.

Comme au Japon il n’y a pas de possibilités d’obtenir des certificats pour utiliser la thérapie de l’acuponcture avec abeilles, les nouveaux venus ne peuvent pas la pratiquer. L’acuponcture avec abeilles sans approbation est évidemment illégale donc l’association recommande de ne pas le pratiquer.

L’association accorde des permissions de pratiquer l’acuponcture aux personnes qui passent un examen devant des apiculteurs connus et appréciés. Ce système atteste les mérites techniques d’une personne qui pratique l’acuponcture avec abeilles en qualité de “consultant”, une pratique semblable à la qualification des instructeurs qui certifie la qualité de la cérémonie du thé ou de la caligraphie. Le président de la Société Japonaise d’Acuponcture et un membre de la Chambre Supérieure, Kentaro Takagi, ont soutenu récemment la valeur de l’acuponcture avec abeilles. Quand dans sa jeunesse, il y a 30 ans, M. Takagi a commencé l’étude et a soutenu l’acuponcture, il a été calomnié parce qu’on disait qu’il n’était pas normal pour un médecin d’être superstitieux. A présent, remarque-t-il, il y a une différence énorme entre le niveau de l’acuponcture d’aujourd’hui, avec une université spécialisée, et celui d’autrefois.

J’ai entendu que dans d’autres pays également, l’acuponcture avec abeilles est ridiculisée et considérée comme un traitement imaginaire. Pourtant, elle sera reconnue, comme on a reconnu l’acuponcture et la moxibustion. Je croix que le XXIé-e siècle sera une ère brillante pour l’acuponcture avec abeilles.

La raison pour laquelle l’acuponcture avec abeilles a gagné une position de premier ordre parmi les remèdes domestiques est la révélation de leurs effets surprenants. Par exemple, si nous avons une enflure dans la bouche, elle nous ennuyera quelques jours, deviendra purulente, et nécessitera un traitement avec des antibiotiques. Cette plaie sera guérie avec deux ou trois piqûres directes ou aiguillons d’abeilles. Les gencives enflées et douloureuses cesseront de faire mal 30 minutes après la piqûre et l’enfflure se réduira en quelques heures.

Bien que la médecine ait progressé, une meilleure alternative est inimaginable. Le traitement du rhumatisme est difficil et le moyen le plus efficace d’anihiler la douleur est d’employer un analgésique antiflogistique. En accord avec les recherches du Prof. Rangel de l’Université de Prague, les bactéries qui provoquent le rhumatisme cessent leur activité quand elles sont introduites dans une solution de venin d’abeilles diluée mille fois. Il y a beaucoup de cas de guérison radicale de ces maladies réfractaires au traitement.

Parce que la majorité des maladies qui attaquent l’homme sont provoquées par les bactéries et virus, l’histoire de l’humanité peut être considérée comme une lutte contre les bactéries. Dans le cas de la destruction des bactéries par venin d’abeilles, les bacteriés qui provoquent l’affreux cancer ne font pas exception. Les bactéries cancérigènes sont détruites immédiatement après la pénétration du venin d’abeilles. J’attends l’introduction d’une nouvelle thérapie par laquelle le cancer caché dans le corps humain sera attaqué par un injecteur qui puisse y arriver. Les gens souffrant de verrues ou de calvities seront surpris du pouvoir de guérison du venin d’abeilles.

La thérapie de l’acuponcture avec abeilles a la qualité de désinfecter ; il faut accorder de l’attention à son effet purificateur sur le sang. Tout le monde sait qu’une portion bleu à la suite d’une contusion revient à la couleur normale après des piqûres d’abeilles. Quelle autre méthode peut assurer un rétablissement immédiat ?

Les praticiens renommés montrent que dans le cas des patients faisant de l’hypertension qui ont diminué leur tension par acuponcture, une rechute apparaît rarement. On connaît des cas récents de gens qui guérissent de trombose cérébrale ou d’autres maladies. J’espère que l’importance de l’acuponcture avec abeilles sera reconnue. Dans la thérapie de l’acuponcture avec abeilles on suit la voie d’entrée de la maladie dans les points méridiens de la Médecine Orientale et le traitement est concentré sur certains points d’interférence. Dans le cas de la névrite herpétique, une maladie persistante qui se manifeste par zona-zoster et douleurs, 3 ou 4 aiguillons appliqués dans le foyer pathogène sont suffisants pour la guérison; si on ne peut pas localiser les points méridiens, on peut appliquer les aiguillons sur le point douloureux, qui lui démange ou qui est engourdi. Une fois, quand je pêchais dans un ruisseau, l’articulation de mon genou droit est devenue douloureuse et rigide. J’ai capturé trois abeilles qui étaient venues butiner dans un champs de blé et j’ai appliqué leurs aiguillons dans la région douloureuse. Je me suit remis en quelques minutes. Plus tard, quand j’ai affirmé dans une conférence que la où il y a des fleurs, il y a des abeilles, j’ai reçu des plaintes de la part des apiculteurs qui m’ont reproché que ces affirmations faisaient réduire les ventes d’abeilles. J’ai entendu aussi beaucoup d’apiculteurs qui prévoient que les médecins auraient moins de patients si ceux-ci pouvaient se guérir plus vite et avec moins de rechutes par l’acuponcture avec abeilles.

Notre but est de faire des recherches sincères et de répandre la santé en travaillant ensemble avec le monde entier. L’Association japonaise d’études sur la thérapie de l’acuponcture avec abeilles est constituée de médecins, spécialistes en thérapie par acuponcture et moxibustion, spécialistes en thérapie callisthénique, apiculteurs etc. La sixième année de sa création, les médecins spécialisés, ayant à la tête M. Yoshimoto de Kodaira, Tokyo, ont commencé les recherches; la présentation des cas cliniques constituera un grand pas en avant.

Selon les journaux de Chine, un hôpital spécialisé en acuponcture avec abeilles, ouvert ce printemps, a enregistré un taux, de guérison de 70 % pour les névralgies et les rhumatismes.

Récemment, on a posé le problème des praticiens sans licence.
Le Département de la Santé et de la Prospérité affirme que la pratique de l’acuponcture est permise seulement aux médecins et aux personnes qui possèdent une approbation.
C’est le point de vue du Ministère qui ne possède pas de données et ne comprend pas la signification de l’acuponcture avec abeilles. Nous demandons votre support généreux pour des recherches sur l’acuponcture avec abeilles pendant que nous continuons de trouver de nouvelles possibilités par l’instruction correcte de méthodes à remèdes domestiques et le respect des lois.

[19]Gerst,J.E., Salomon,Y: Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.

[20] Melanotropin (MSH) receptor activity in the M2R mouse melanoma cell line is tightly controlled by calcium by an unknown mechanism. The possibility that calcium regulation is mediated by calmodulin or a calmodulin-related calcium binding protein has been addressed in this report by studying the effects of two known calmodulin antagonists, fluphenazine and melittin, on MSH receptor function. Stimulation of adenylate cyclase (AC) in M2R plasma membranes by beta MSH was strongly inhibited by both antagonists. The concentrations of fluphenazine and melittin yielding half-maximal inhibition (IC50) of AC were 16

microM and 2.4 microM, respectively. Both fluphenazine and melittin also

inhibit prostaglandin E1-, GTP gamma S, and forskolin-stimulated AC activity, as well as that of unstimulated enzyme, although inhibition is shown to occur at significantly higher concentrations of antagonist. We have shown that the calcium-dependent rate-limiting step in MSH stimulation of adenylate cyclase, that of hormone binding, is strongly inhibited by these antagonists at concentrations identical to, if not lower than, those required for the inhibition of AC activity (fluphenazine-IC50, 14 microM; melittin-IC50, 0.7 microM). The actions of these antagonists, furthermore, appear to be calcium insensitive, as melittin affects the stability of both the high affinity (calcium containing) and low affinity (calcium depleted) receptor-MSH complexes. The sensitivity of the MSH receptor to inhibition by calmodulin antagonists resembles that described for purified calmodulin-sensitive enzyme systems, which suggests a possible role for calmodulin in MSH receptor function. Among peptide hormone receptors, this effect by calmodulin antagonists appears to be unique for the MSH receptor.

PMID: 3665846, UI: 88029249.

[21] Centre for Cellular and Molecular Biology, Hyderabad, India.
[22] Melittin is a cationic hemolytic peptide isolated from the European honey bee, Apis mellifera. Since the association of the peptide in the membrane is linked with its physiological effects, a detailed understanding of the interaction of melittin with membranes is crucial. We have investigated the interaction of melittin with membranes of varying surface charge in the context of recent studies which show that the presence of negatively charged lipids in the membrane inhibits membrane lysis by melittin. The sole tryptophan residue in melittin has previously been shown to be critical for its hemolytic activity. The organization and dynamics of the tryptophan residue thus become important to understand the peptide activity in membranes of different charge types. Wavelength-selective fluorescence was utilized to monitor the tryptophan environment of membrane-bound melittin. Melittin exhibits a red edge excitation shift (REES) of 5 nm when bound to zwitterionic membranes while in negatively charged membranes, the magnitude of REES is reduced to 2-3 nm. Further, wavelength dependence of fluorescence polarization and near-UV circular dichroism spectra reveal characteristic differences in the tryptophan environment for melittin bound to zwitterionic and anionic membranes. These studies are supported by time-resolved fluorescence measurements of membrane-bound melittin. Tryptophan penetration depths for melittin bound to zwitterionic and anionic membranes were analyzed by the parallax method [Chattopadhyay, A., and London, E. (1987) Biochemistry 26, 39-45] utilizing differential fluorescence quenching obtained with phospholipids spin-labeled at two different depths. Our results provide further insight into molecular details of membrane lysis by melittin and the modulation of lytic activity by negatively charged lipids.
PMID: 9398147, UI: 98062896.

[23] Higuchi, M. (1992) – Damage to mitochondrial respiration chain is related to phospholipase A2 activation caused by tumor necrosis factor,
in J Immunother Jul;12(1), pp.41-49.

Division of Chemical Toxicology and Immunochemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.

[24] Tumor necrosis factor (TNF) has been shown to be cytotoxic to tumor cell lines in vitro, but the mechanism by which TNF exerts its cell growth-regulatory effects is not known. In this report, we used various inhibitors to investigate the sequence of events that lead to cytotoxic effects of TNF on L.P3 cells, a highly sensitive, murine fibroblast cell line. Our results indicate that mitochondrial respiration chains are damaged by a hydroxyl radical at an early stage of the cell lysis after TNF treatment. This event is followed by the activation of phospholipase A2, and finally leads to cell lysis.

[25] ABSTRACT: The effect of melittin on the release of adrenocorticotropin (ACTH) and beta-endorphin from the corticotropic cells of the rat adenohypophysis was examined in vitro. Anterior pituitary quarters were perifused or incubated in vitro and ACTH- (ACTH-IR) or beta-endorphin-like immunoreactivity (beta-End-IR) in the medium was measured by radioimmunoassays. Melittin stimulated ACTH-IR and beta-End-IR release. This effect was rapid in onset, reversible, and concentration-related (50-5000 ng/ml) and depended on the presence of calcium ions in the incubation medium. Melittin also elevated the tissue content of unesterified 3H-arachidonic acid that had previously been incorporated into lipids. Purported phospholipase A2 inhibitors, mepacrine (up to 1 mM), dexamethasone (0.5 mg/kg in vivo, 50 nM in vitro), or p-bromophenacylbromide (100 microM), did not decrease the melittin (500 ng/ml) – induced beta-End-IR release, although mepacrine and dexamethasone may have inhibited phospholipase A2 activity as indicated by an inhibition of melittin-evoked prostaglandin E2 formation. After stimulation by melittin (500 ng/ml), beta-End-IR release was not affected by the cyclooxygenase inhibitor indomethacin (up to 140 microM), whereas nordihydroguaiaretic acid (100 microM), a lipoxygenase inhibitor, or BW755C (250 microM), an inhibitor of both cyclooxygenase and lipoxygenase, abolished melittin-induced hormone secretion. We conclude that melittin generates a signal in the corticotropic cells of the rat adenohypophysis which induces hormone secretion by exocytosis. This signal may be unrelated to the activation by melittin of phospholipase A2.

CITATION IDS: PMID: 3033749 UI: 87205195.

[26] Knulst’s et al. address: Academisch Ziekenhuis, afd. Dermatologie-Allergologie, Utrecht.

[27] Knulst, A.C.; de Maat-Bleeker, F.; Bruijnzeel-Koomen, C. A. (1998) (Netherlands) – Wasp and bee venom allergy (original article in Dutch),
in Ned Tijdschr Geneeskd, Apr 18;142(16), pp.889-92 (***-abstract).

To diagnose insect venom allergy a good patient history is important. Allergological tests (skin test, specific IgE titre) confirm the diagnosis. Patients are advised on preventive measures (e.g. with respect to clothing and use of perfume). They are also instructed on medical treatment (antihistaminics, epinephrine) in case they are stung again. In patients having had a serious systemic reaction immunotherapy should be considered. Immunotherapy leads to complete protection in more than 98% of patients with wasp (yellow jacket) venom allergy and in 75-80% of patients with bee venom allergy. Serious adverse reactions to immunotherapy are rare. Immunotherapy lasts at least 3 to 5 years. After cessation of immunotherapy the frequency of systemic reactions to the sting of a wasp or bee is in the range of 5-15%. There are insufficient data on the long-term effect of immunotherapy.
PMID: 9623183, UI: 98286386.

[28] Post-herpetic neuralgia (PHN) is the pain that persists for more than four months following the onset of the rash associated with a herpes zoster (shingles) outbreak. PHN pain is generally characterized by severe unrelenting pain described by patients as either deep aching, burning, sharp, jabbing, electrical, lancinating or a combination of these. Frequently allodynia is a disabling sign. The longer the pain persists the longer it is likely to continue, and many of these elderly patients die with their pain never resolving. The current treatment of post-herpetic neuralgia is unsatisfactory to most sufferers and strictly palliative in nature. These treatments involve tedious repetitive procedures or the taking of medications that may have serious side effects. None of these interventions alter the natural history of the condition. They just decrease the symptoms until spontaneous resolution occurs – if it resolves at all.

Treating pain with the venom of the European honeybee, Apis mellifera, dates back several thousand years. Hippocrates and Celsus documented the use of bee venom as a medical treatment. The most frequent use of bee venom today is the treatment of inflammatory arthritis. There are over 20 biologically active peptides in Apis mellifera venom, some of which are anti-inflammatory and others neurotoxic in nature. Animal studies confirm the anti-inflammatory properties of bee venom and it=s ability to suppress adjuvant induced arthritis.

Fourteen PHN patients (average age 72) who suffered pain for an average of 46.1 months (range 5 to 131) were injected at multiple sites (range 3 to 30) with 100 micrograms of dried bee venom in 0.1 cc of 0.5% lidocaine. These sites corresponded to the location of the greatest pain, origins of shooting pain and to areas of cutaneous scarring. The median interval between the first and second visit was three days. Subsequent visits were four days apart. Patients received an average of 14 treatments over a period of 11.7 ” 5.4 weeks.

The mean Visual Analog Scale (VAS) pain score at the beginning of treatment was 7.6 ” 0.39 and at the end was 2.1 ” 1.1, representing a mean decrease of 5.5 ” 1.1 (p < 0.001). As a group there was a significant decrease in VAS score (p<0.02) after the first treatment. Patients noted a significant decrease in the stabbing component of their pain within two treatments (p<0.01). They also reported a significant decrease in allodynia after one treatment (p<0.02). The difference of the VAS score at the fifth visit and the end of treatment was not significant; thus, in most cases, full benefit was achieved following the fourth treatment. At follow-up, which averaged 21 months from completion of treatment, the group had a mean VAS score of 2.6 ” 1.6, with 4 of the patients pain-free. Initially, 6 patients were taking antidepressants and 4 were taking opioids. By the end of treatment, all 6 patients stopped antidepressants and 3 stopped opioids. Sleep quality improved significantly from the beginning to the end of treatment and continued to be good at follow-up (p<0.001). Most patients reported sleeping better after the first treatment.

The results of treatment in these patients suggest that one or more components of honeybee venom are able to decrease the pain of PHN within four treatments on the average by more than 70%, and in some cases completely. These results are maintained long-term. Treatment with bee venom caused positive changes and gave these patients a significantly better quality of life.

[29] Kolecki’s address: Good Samaritan Regional Poison Center, Good Samaritan Regional Medical Center, Phoenix, AZ, USA.
[30] Kolecki, P.[30] (1999) (USA) – Delayed toxic reaction following massive bee envenomation,
in Ann Emerg Med 1999 Jan;33(1), pp.114-16

Massive bee envenomation can produce both immediate and delayed toxic reaction. Signs and symptoms of immediate toxic reaction are fatigue, nausea, vomiting, hemolysis, kidney failure, and disseminated intravascular coagulation. The label “delayed toxic reaction” refers to a patient who is asymptomatic after a massive bee envenomation, with normal initial laboratory results, but later demonstrates laboratory evidence of hemolysis, coagulopathy, thrombocytopenia, rhabdomyolysis, liver dysfunction, and disseminated intravascular coagulation. The subject of this case report, a 66-year-old man, was stung more than 125 times in an attack by Africanized bees. He was initially asymptomatic, except for pain, and his laboratory findings were normal. The first signs of his fatal multi-organ-system failure were not apparent until 18 hours after envenomation. This experience has led the Good Samaritan Regional Poison Center in Phoenix, AZ, to recommend a 24-hour hospitalization for pediatric patients, older patients, and patients with underlying medical problems who are asymptomatic or who are experiencing only pain after an envenomation of 50 or more stings. Such patients have an increased risk of tissue injury, which may be delayed and which may be more effectively treated if identified early rather than on 12- to 24-hour follow-up. All other envenomated, asymptomatic patients or envenomated patients experiencing only pain who become symptomatic or who belatedly exhibit laboratory values consistent with hemolysis, thrombocytopenia, rhabdomyolysis, liver dysfunction, kidney failure, and disseminated intravascular coagulation within a 6-hour emergency department observation period should be admitted. Intravenous fluids, blood products, dialysis, and other intensive measures should be initiated if necessary.

[31] THE THERAPEUTIC EFFECT OF “SOLAPIVEN” ON MODELS OF

BLOOD CIRCULATION PATHOLOGY

222 V. N. KRYLOV, I. V. MUHINA,

A. SABURTZEV (RUSSIA)

The therapeutic effects of “Solapiven” were investigated on animals with various kinds of blood circulation pathology

It was established that “Solapiven” has an antiarrhythmical activity, preventing or eliminating (partially or completely) the troubles of heart rhythm in animals, under the conditions of various experimental models of arrhythmia. This drug does not change the refractory period of the heart; however, it reduces the fast (natrium) and slow (calcium) currents penetrating the cardiomyocyte membranes.

The intravenous introduction of “Solapiven” (0.1 mg/kg) to anaesthetized rats, under the conditions of simulated hypotension, resulted in a hypertensive reaction, precisely expressed by an increase in the arterial pressure and in the shock volume of the left Centre of the heart to 30-40%, in comparison to the initial level of these parameters.

When the animals were reanimated, after a 10-minutes’ period of clinical death, it was proved that, if in the check-up experiments, the reanimation did not result in the restoration of the vegetative functions, the intra-arterial addition of “Solapiven” in a dose of 0.05 – 0.1 mg/kg promoted the restoration of the independent intimate reactions and an increase in the arterial pressure. p.120-121
[32] THE CARDIOPROTECTIVE ACTIVITY OF SOLAPIVEN AND OF UBIQUINONE-10 (Q-10)

225 V.N. KRYLOV,

E.V. YASTREBOVA

(RUSSIA)

The main purpose of this work is to investigate the efficacy of heart protection by means of the bee venom preparation, Solapiven, in comparison to the well known antioxidant preparation Ubiquinone-10 (Q-10). Solapiven efficacy was demonstrated on the model of rats myocarditis induced by adrenaline hydrochloride (in doses of 2.5 mg/kg; single interperitoneal injection).

The functional activity of the heart was determined according to the electrocardiogram data, the POL activity, by analysing the MDA content in the heart muscle and the structure alteration, according to the data obtained from the light microscopy of sections of the papillary heart muscle, in the control and the tested animals.

The experiments have shown a decrease in the bioelectrical activity of the heart, a sharp increase of the MDA level and destructive changes in the morphology of the myocardium, under the influence of the toxic doses of adrenaline. Therapeutical and prophylactic treatments, by means of Solapiven and Q-10 injections, on the myocarditis background, led to a decrease in the toxic alterations of the heart muscle and to a normalisation of the heart function. This process was accompanied by the essential growth of the ORS complex amplitude (especially in prophylactic use), while the POL activity decreased and the myocardium structure alteration became less obvious.

These results indicate an obvious cardioprotective activity of Solapiven, as well as of Q-10 – the mitochondrion enzymatic activity regulator of the warm blooded animals. Thus, this bee venom preparation may be considered an antioxidant. Also, Q-10 is known as a true antioxidant, because of its ability to reconstruct lipid radicals and to decrease the POL activity in the ischemized heart muscle.

p.121

[33] Krylov, V.N.; Deryugina A.V. (1998) – Influence of the bee venom and its components to electrophoretic mobility of erythrocytes,
in The Ukrainian Biochemical Journal.-Vol.70.- ?2, pp.32-37 (abstract).

Summary:
The change of electrophoretic mobility (EPM) of erythrocytes of donor blood caused by their incubation with the bee venom and its major components, melittin and phospholipase A2 was investigated. It was estimated that the bee venom reversibly decreased EPM of erythrocytes to a higher degree than its separate components.
The reaction was completely abolished after preliminary processing of erythrocytes with neuroaminidase and partly after their processing with glutaraldehyde, but the effect of EPM increased under the conditions of the increasing of ATP concentration. Proceeding from the authors’ data it was concluded that the major components of the bee venom successively interacted with glicocalyx elements and membrane of
erythrocytes which evokes the charge redestribution in these blood cells.

[34] Authors address: Department of Veterinary Physiology, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, 441-744, Suwon, South Korea.

[35] Lessof, M. H.; Sobotka, A. K.; Lichtenstein, L. M. (1978) – Effects of passive antibody in bee venom anaphylaxis,
in Johns Hopkins Med J, Jan;142(1), pp.1-7 (abstract).

Twelve patients allergic to honeybees were challenged by injections of bee venom; five responded systemically to the venom, with symptoms ranging from angioedema to respiratory distress. These patients were given intramuscular or intravenous infusions of gamma-globulin obtained from the plasma of hyperimmune beekeepers who had high levels of antibody to an allergen (phospholipase A) in the venom. Post-infusion, all five patients tolerated 1.5 to 5 times the venom dose that previously elicited adverse reactions. The quantity of passive IgG antibody infused did not impair the patient’s own immune response to venom. These results represent the best available evidence for a direct role for IgG blocking antibodies in clinical protection against anaphylaxis occurring as a result of parenteral antigenic challenge as may be observed in penicillin and insect hypersensitivity.
PMID: 75280, UI: 78112042

[36] Address: Rocky Mountain Laboratories Microscopy Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.

[37] Borrelia burgdorferi has demonstrated a capacity to resist the in vitro effects of powerful eukaryotic and prokaryotic metabolic inhibitors. However, treatment of laboratory cultures on Barbour-Stoenner-Kelly medium with melittin, a 26-amino acid peptide contained in honeybee venom, showed immediate and profound inhibitory effects when they were monitored by dark-field microscopy, field emission scanning electron microscopy, and optical density measurements. Furthermore, at melittin concentrations as low as 100 microg/mL, virtually all spirochete motility ceased within seconds of inhibitor addition. Ultrastructural examination of these spirochetes by scanning electron microscopy revealed obvious alterations in the surface envelope of the spirochetes. The extraordinary sensitivity of B. burgdorferi to mellitin may provide both a research reagent useful in the study of selective permeability in microorganisms and important clues to the development of effective new drugs against lyme disease.
PMID: 9233664, UI: 97376893.

[38] Address: Institute of Clinical Chemistry, University Hospital Zurich, Switzerland.
[39] Cross-linking IgE on basophils is known to cause both sulfidoleukotriene (sLT) generation and histamine release. We recently developed an ELISA to determine sulfidoleukotriene generation by blood mononuclear cells which employs pretreatment with IL-3 to enhance leukotriene generation (cellular antigen stimulation test, CAST). Here, we compared the CAST and whole blood histamine release in response to honey bee/yellow jacket venom (BV/YJV) in 23 patients clinically suspected of type-I allergy to these venoms. Of these, 17 were diagnosed as “definitive venom allergics,” defined by a positive skin test at 100 ng/ml of venom or less. The six in whom such skin reactivity was absent were labelled “suspected venom allergics.” Both venoms stimulated sulfidoleukotriene generation and histamine release also from control individuals (n = 10). In patients, insect venoms generally stimulated histamine release and sulfidoleukotriene generation in excess of the mean + 3 SD of values obtained with control individuals. However, about half of the patients reacted predominantly with either histamine release or sulfidoleukotriene generation. No overall correlation was found between threshold doses necessary to stimulate sulfidoleukotriene generation (ThsLT) and histamine release (ThHist). (Linear correlation coefficients between ThsLT and ThHist were -0.02 for honey bee venom and 0.13 for yellow jacket, n = 23). Both findings are in contrast to the concept that these responses occur in parallel. From results with “definitive venom allergics,” CAST sensitivity was calculated as 100% for honey bee venom and 83% for yellow jacket, and that of the histamine release assay as 62.5% for honey bee venom and 50% for yellow jacket. Specificity of the CAST was calculated as 77% for honey bee venom and 100% for yellow jacket, and that of the histamine release assay as 44% for honey bee venom and 60% for yellow jacket. Thus, CAST results are closer to skin test results than to those of the whole blood histamine release assay.
PMID: 9330184, UI: 97471243.

[40] Masterov, G. D. (1995) – Apitherapy in the combined treatment of patients with pulmonary tuberculosis taking into account the hypophyseal-adrenal system indices,
in Lik Sprava(1-2), pp.120-2 (abstract).

Apitherapy (venom of bees and apiculture products) was included into combined treatment of 93 in-patients with pulmonary tuberculosis. Apitherapy had a beneficial effect on the organism of tuberculosis patients, manifested by enhancement of the treatment effectiveness and normalization of indices of endocrine system. It is recommended that the instruction on apitoxinotherapy be amended, in particular, by substantially supplementing the paragraph with indications and contraindications for giving it in active tuberculosis.

[41] Masterov, G. D.; Nersesian, O. N. (1995) – The role of apitherapy in the combined treatment of patients with chronic nonspecific lung diseases,
in Lik Sprava(3-4), pp.155-58 (abstract) .

The authors suggest that apitherapy should be used in the treatment of patients with chronic non-specific pulmonary diseases (ChNPD) in order that it might be more effective. Apitherapeutic complex (bee venom and bee keeping apiculture produce) has been applied to the treatment of 104 ChNPD patients. High effectiveness of apitherapy in a combined treatment of ChNPD patients was demonstrated as was their stimulating and normalizing influence on the function of the adrenals.

[42] Dr. Mueller is a professor in Bern, Switzerland.
[43] Address: Medical Division, Zieglerspital Bern, Switzerland.

[44] BACKGROUND: In diagnosis of type I allergy recombinant allergens have potential advantages over conventional allergenic extracts, both regarding specificity and reproducibility. OBJECTIVES: We therefore decided to study honey bee venom (BV) and its major allergen phospholipase A2 (PLA) in native and recombinant form for diagnosis of bee sting allergy. METHOD: We investigated 85 patients with a history of a recent systemic allergic bee sting reaction and positive intracutaneous skin test to BV, and 21 controls with no history of allergic bee sting reaction and negative skin test to BV. Intracutaneous skin tests and determination of specific IgE by ImmunoCAP(R) to BV, native PLA (nPLA) and recombinant PLA (rPLA) were done in all patients and controls. RESULTS: In skin testing 84 (99%) of the 85 patients reacted to nPLA and 81 (95%) to rPLA, while none of the 21 controls was positive with nPLA or rPLA. Specific serum IgE to BV could be detected in 82 of the patients (96%), to nPLA in 73 (86%) and to rPLA in 66 (78%). Four (19%) of the controls had a positive CAP to BV, one (4.8%) to nPLA and none to rPLA. Analysis of discordant results in CAP showed, that most patients with specific IgE to BV, but not to nPLA and rPLA, had positive skin tests to both PLA preparations and low levels of BV specific IgE. Patients with specific IgE to nPLA but not to rPLA were usually sensitized to minor allergens of BV which contaminated the commercial nPLA. CONCLUSIONS: PLA is the major allergen in BV. While diagnostic tests with BV are more sensitive, the specificity of tests with PLA, especially rPLA is clearly increased as compared with BV.
Publication Types:
Clinical trial
Controlled clinical trial
PMID: 9291289, UI: 97435066

[45] Munoz-Arizpe et al. address: Departamento de Nefrologia, Hospital Infantil de Mexico Federico Gomez, D.F., Mexico.

[46] Munoz-Arizpe, R.; Velasquez-Jones, L.; Romero-Navarro, B.; Gomez-Chico, R.[46] (1992) (Mexico) – Acute kidney failure due to stings by Africanized bees (original article in Spanish),
in Bol Med Hosp Infant Mex, Jun; 49(6), pp.388-90.

Africanized bees are unique in their aggressive behavior, characterized by massive attacks during which the victims are injected an important amount of venom. For this reason, Africanized bees are extremely dangerous. Their venom contains biological toxic substances, mainly mellitin, phospholipases, histamine, hyaluronidase and apamin. Non-sensitized persons that survive a massive attack may develop acute renal failure, as a consequence of the severe hemolysis, rhabdomyolysis and shock. These complications may lead to acute renal tubular necrosis. Also, the clinical pattern and treatment of the acute renal failure secondary to bee stings are discussed.

[47] Zoology Department, Faculty of Science, Suez Canal University, Ismailia, Egypt.

[48] 1 The effect of crude honeybee (Apis mellifera) venom on the skeletal, smooth

as well as cardiac muscles were studied in this investigation. 2 Perfusion of

gastrocnemius-sciatic nerve preparation of frogs with 1 microgram/ml venom

solution has weakened the mechanical contraction of the muscle without

recovery. Blocking of nicotinic receptors with 3 micrograms/ml flaxedil before

bee venom application sustained normal contraction of gastrocnemius muscle. 3

The electrical activity of duodenum rabbits was recorded before and after the

application of 1 microgram/ml venom solution. The venom has depressed the

amplitude of the muscle contraction after 15 min pretreatment with atropine

nearly abolished the depressor effect of the venom on smooth muscle. 4 In

concentrations from 0.5-2 micrograms/ml, bee venom caused decrease of heart

rate of isolated perfused toad heart. This bradycardia was accompanied by

elongation in the P-R interval. A gradual and progressive increase in the

R-wave amplitude reflected a positive inotropism of the venom. Application of 5

micrograms/ml verapamil, a calcium channels blocking agent, abolished the

noticed effect of the venom. 5 Marked electrocardiographic changes were

produced within minutes of the venom application on the isolated perfused

hearts, like marked injury current (elevation or depression of the S-T

segment), atrioventricular conduction disturbances and sinus arrhythmias.

Atropine and nicotine could decrease the toxic effect of the venom on the

myocardium. 6 Results of the present work lead to the suggestion that bee venom

is mediated through the peripheral cholinergic neurotransmitter system. General

neurotoxicity of an inhibitory nature involving the autonomic as well as

neuromuscular system are established as a result of the venom, meanwhile a

direct effect on the myocardium membrane stabilization has been suggested.

[49] BIENENGIFT ALS IMKEREIERZEUGNIS

B.N. ORLOV
(USSR)

Als Folge langandauernder Studien wurde eine industrielle Technologie zur Gewinnung von ökologisch reinem Bienengift erarbeitet. Diese Technologie ist bienenharmlos. Es wurden Methoden zur Reinigung des Bienengifts und seiner Qualitätskontrolle festgelegt. Die Einwirkungsmechanismen des Bienengifts und seiner Hauptbestandteile auf die bedeutendsten physiologischen Systeme des Organismus wurden studiert. Die Grundlagen zur Anwendung des Bienengifts in der Behandlung einer Reihe von Krankheiten wurden festgelegt und anhand dieser wurden Modelle pathologischer Zustände aufgestellt.
S. 555
[50] NEURO-ENDOCRINE-METABOLIC BASES OF THE THERAPEUTIC ACTION OF BEE VENOM IN THE DEGENERATIVE VASCULAR DISEASES

Alexandru PARTHENIU

Constantin NEACSU

ROMANIA

The favorable effects of bee venom on the circulation of blood in man have been known as early as in old times. These effects of natural or pharmaceutically processed bee venom were related to the ganglioplegia as well as to effects on the brain.

From a clinical viewpoint the action was considered in relation with rheumatic affections and hypertonic disease (experimented on animals and man).

In connection with the obliterative degenerative vascular diseases, the first clinical observations on the venom were reported only in the 1960’s on the effects of the circulation of blood and some clinical neuro-functional improvements.

Our previous research pointed out neurotic relations existing in both rheumatic affections and the peripheral ischemic syndrome. These relations were characterized on the basis of correlated examinations of the electroencephalographic picture and the indicator of cerebral neurovegetative reactivity, represented by complementary electrophysiological methods of investigation : the electrodermal reflex (EDR) and the cerebral impedance reflex (CIR) explored with the help of the same correlative-integrated technique.

In connection with the mechanism of bee venom action on the nervous system at the cerebral level in man, we could identify in patients showing only a neurosis state (i.e. inhibition or visceral brain neurosis) the acute shutting off effect of bee venom on the neurovegetative component (found in both EDR and CIR dynamics). One can agree that the mechanism of this acute shutting off effect also includes changes in the activity of the reticular formation, taking into account the relations of the EDR and CIR dynamics with this reactivity and the inhibiting influence of the bee venom observed experimentally on animals. We emphasize this aspect in connection with the major implication of the neurotic disorders in the pathogeny of the coronary and peripheral degenerative vascular affections and the mechanisms of bee venom action.

The important neuro-endocrine-metabolic disorders in the vascular degenerative affections are described in the specialized literature but since they are insufficiently characterized, our research included these aspects too. However we considered them correlatively-integrated.

( Graph = Figure 1)

Figure 1. Dynamics of the indicator for cerebral neurovegetative reactivity represented by the electrodermal reflex (EDR).

Explanatory note : m = application of the predominant proprioceptive stimulus (closing and opening of the right fist at examiner’s command ) ; v = application of the predominant interceptive stimulus (a unique, ample breathing at examiner’s command ) ; a = EDR – dynamics in a man presenting a good biological balance (top athlete) ; b = woman patient suffering from ankyl. spondylitis ; c = woman patient suffering from chronical evolutive polyarthritis ; d = woman patient suffering from atherosclerotic arthritis (zero oscillometric index at both shanks) ; e = patient suffering from atherosclerotic arthritis, (oscillometric index 0.5 units at right shank and 1.5 units at left shank) ; f = patient who subsequently (after five months) had a myocardic infarct.
In all cases the EDR registration presented in this figure was made before beginning the treatment with bee venom. This treatment was not applied in the case of myocardic infarct.

According to our experience and view, three groups of aspects seem to be important :

1. Characterizing the correlative neuro-endocrine-metabolic parameters in patients showing these affections.

2. The acute and chronic influence of bee venom on these correlative parameters.

3. The need for a thorough study of the mechanisms in both the etio-pathogenic and prophylactic field as compared to the use of bee venom.

I. Characterizing the correlative, neuro-endocrine, metabolic parameters in degenerative vascular diseases

Cerebral nervous functional aspects

In a group of 92 patients (of both sexes) partly previously mentioned suffering from Bürger disease and atherosclerotic arteritis of the inferior limbs and in several cases of myocardic infarct detected by our investigations prior to and after the appearance of the infarct, we found an electrophysiological picture of neurosis in 100% of the patients.In connection with the electro-encephalogram, the form of ‘irritation” neurosis with the hyperreactivity of the ascending facilitating system of the reticular formation of the brain stem was prevalent (EEG features : a) the average alpha index for the post-rolandic longitudinal leads less than 30%, with reactive picture to the hyperpnea ; b) an obvious disorder of the alpha oscillation trains in terms of both fusiform modulation and regularity as compared to the envelope of the alpha oscillation trains ; c) a high frequency of the cases with a high incidence (over 5%) of the modulation in phase of the alpha activity.But as against the picture of ‘irritation” neurosis in other conditions where the EDR and CIR reactivity shows a normal profile, in our cases of arteritis, both peripheral and coronary, a decrease in the cerebral neurovegetative reactivity of neurotic nature seems to be specific, assuming an aspect of precocity (of months and even years prior to the acute clinical stages), characterized by the fact that EDR and CIR activations are reduced in terms of amplitude and obviously slower as to their dynamics. In addition, according to our casuistry this neurotic neurovegetative aspect detected in beings showing arterial degenerative affections is more marked and earlier than in the case of progressive rheumatic affections such as chronic polyarthritis and ankylopoetic spondilitis (degenerative peripheral and coronary arteritis) as compared to the aspect of the EDR reactivity in men enjoying perfect health (a) and also for the progressive rheumatic affections (b and c). Endocrine metabolic aspectsa) The function of the adrenal gland was watched by determining the urinary elimination of 17 cetosteroids. One could notice that in most cases the value of the elimination of these hormones is inferior to the minimum threshold of normal (less than 7 mg/24 h).b) The thyroid function, watched by determining the P.B.I. in most cases revealed a tendency to a level of hypofunctioning (less than 4 µg%).c) The serical picture of total and complex proteins (glycoproteins, sialic and seromucoid acid) showed :1. Lightly high values of glycoproteins in a reduced number of cases only.
2. Values within the normal limits for sialic acid, some cases showing insignificant rises.

3. Significantly, increased values of seromucoid in all cases studied, the rises reaching
85% as against the highest acceptable physiological limit.

One could notice a higher frequency of the significant increases in the sialic acid in the rheumatic affections as compared to the group suffering from vascular affections.

4. The picture of seric lipids shows increased values of total lipids and cholesterol in both the peripheral vascular and coronary affections these being of the order previously reported in the literature. In the group showing cardiopathies the increase in lipids preceded the clinical detection of the infarct.

The ratio of the 3 categories of the parameters observed namely : nervous, endocrine and metabolic points to an aspect of mutual relation as to the disfunction of both the hypophyso-suprarenal and hypophyso-thyroid axis in case of neurosis, such mutual relations being already reported by the literature quoted. As to the relation between the suprarenal hormones and the metabolism of proteins, the observations performed on the metabolism of glycoproteins also show a correlation.

II. Acute and chronic influence of the bee venom

A. Treatment conditions

Our observations refer to one third of the cases discussed (I.A.) that showed peripheral degenerative vascular affections for both sexes (between 40 and 60 years old) who were treated with natural bee venom administered by bee stings each sting accounting for a dose. According to the technique already reported the stings were applied to the intradermic papulae , the anesthesis being obtained with doses of 0.2 to 0.3 cm³ of a procaine hydrochlor (1-2%) solution.

The two first series of treatment administered during the April-October period included 180 to 200 doses each, applied gradually up to the limit of 12 to 15 doses, at intervals of 5 to 8 days. The next years (3 to 11 years) new series of maintaining treatment were performed in summer, of 80 to 100 doses each.

No specific medication was associated.

The treatment was administered to out-patients.

The diabetes as an associated affection detected in 7 patients resulted in intolerance of the bee venom (even to 5 to 6 doses) causing exaggerated neurovegetative reactions that imposed interruption of the treatment.

The treatment administered to the rest of patients caused no difficulties.

B. Acute effects

1. From the very beginning of the application of bee venom (after administration of about 100 doses) one could notice a systematic decrease of the functional impotence of inferior limbs, with a reduction of the intermittent claudication, a positive evolution, being established after this first series. At the same time the arterial oscillometry of the limbs improved also, even in the case of a null bilateral oscillometry.

2. At the same time an improvement in the cerebral electrophysiological picture (alpha index, EDR and CIR dynamics) as well as in the hypnic function was noticed (the latter aspect being also described in the literature).

C. Chronic effects

The functional improvement noticed as early as the acute stage of the treatment continued over the whole period of observation on the cases including the maintaining stages of treatment (7 to 11 years)

In this situation the circulation and cerebral neurodynamic modifications assumed the aspect of a systematic favorable development. On the contrary, the metabolic picture showed no change in the metabolism of lipids nor in that of proteins.

Our observations on the effect of treatment with natural bee venom on patients under normal habitus conditions show that this effect is specific to the bee venom so much the more that :
on the one hand the patients treated with bee venom had been treated previously with usual medicines, medicinal waters and other physical agents without any result as to the stoppage of the progression of disease ;
on the other hand the bee venom was deliberately applied with neither hormonal treatment nor a severe diet, this being limited to avoid any metabolic excess and provide the balance of the vitamins in the being.To sum up, the observations proved that :The bee venom is able to reduce the neurotic disorders which according to our studies are always present in patients with degenerative arterial affections, which testify to the feature of pathogenic condition of such neurodynamic deformations.2. The treatment with bee venom must be supplemented with therapies adequate to the correction of the endocrine metabolic picture cited.III. The need of further thorough studies of certain mechanisms in both the field of the etiopathogeny and the prophylaxis related to the use of bee venom.a. The effects of bee venom on the neurodynamics and circulation can be considered in connection with peripheral degenerative arterial affections and in the main also with coronary affections, from two view points : curative and prophylactic.b. From the curative view point it is necessary :- to determine the endocrine metabolic regulating therapy compatible with the bee venom action in a synergetic sense as well as to correct the negative effects of the bee venom on certain endocrine glands (the thyroid, the ovaries, a.s.o.). Of paramount importance is the problem of the association of vascular disorders with diabetes ;
– to correct the neurodynamic disfunction by the treatment with bee venom, possibly associated with other adequate therapeutic ways during as early a stage as possible (easy to detect also through the indicators used by us) with a view to preventing the clinic appearance of the syndrome of degenerative arteritis ;

– to study under such conditions the therapeutic patterns for the bee venom;

c. From the prophylactic view point : considering the effects of the bee venom on the cerebral neurodynamic balance of the human being, one can consider the use of bee venom in patients showing neuroses in a preclinical or clinical stage (various forms).

It should be mentioned that treatment with bee venom requires an accurate individualization as to the neuro-endocrine-metabolic condition during the treatment in order to provide a good tolerance and effectiveness.

[51] Patrizzi, R.; Muller, U.; Yman, L.; Hoigne, R. (1979) – Comparison of skin tests and RAST for the diagnosis of bee sting allergy,
in Allergy, Aug;34(4), pp.249-56.

Skin tests and estimation of specific IgE-antibodies by the RAST are evaluated as diagnostic procedures in bee sting hypersensitivity with the following extracts. (2) With bee venom results of skin tests and RAST correspond in 82%, with bee wholebody extracts in 68%. (3) Both with skin tests and the RAST with bee venom a good discrimination between patients with bee sting hypersensitivity and non-allergic controls is observed. Skin tests with bee venom are somewhat more sensitive than bee venom-RAST. (4) With the careful skin test procedure chosen, no adverse reactions were observed.
PMID: 517710, UI: 80085818

[52] Fry-Welch,D., Pfalzer L. – University of Michigan-Flynt, Flynt, Mich. Supported by a Faculty Development Grant from the University of Michigan-Flynt.

[53] Fry-Welch,D., Pfalzer L. – University of Michigan-Flynt, Flynt, Mich. Supported by a Faculty Development Grant from the University of Michigan-Flynt.

[54] ABOUT THE MECHANISM OF THE ACTION OF PHONOPHORESIS OF BEE VENOM BY ULTRASONIC WAVES IN THE TREATMENT OF DEGENERATIVE DISEASES OF JOINTS [54]

POCHINKOVA BULGARIA

The previous experiments showed that the biological activity of bee venom as well as its force of penetration were favoured by the energy of ultrasonic waves.

The portions of the tissues treated show a considerable increase in the number of the active biological mastocytes and their metachromatic granulations as well as an increased amount of the active mucopolysacharides in the basic substance. The same portions show a considerable hydration and a deep active hyperemia. The inhibition of the activity of the tissue cholinesterase is determined histochemically The changes noticed are more marked in the case of longer sittings with smaller doses in terms of both the bee venom concentration and the intensity of the ultrasonic waves.

As is known, the mucopolysacharides constitute a basic part of the cartilage and the intervertebral discs. The former plays a main part in maintaining the latter’s normal function and structure. During the process of degeneration of the articular apparatus the cells of the basic substance cannot produce sufficient mucopolysacharides, particularly acid mucopolysacharides, hence the cartilage of the articulation loses its normal function and possibilities. By applying the phonophoresis with bee venom the increased amount of mastocytes, hence, the acid mucopolysacharides, contributes to the natural physiological restoration of the mucopolysacharides whose deficiencies are specific to such affections. The stimulation of the metabolism of mucopolysacharides under the action of bee venom can be determined by its general simulative effect. The simulative action of bee venom at the cellular and humoral level was pointed out in our experiments on the activation of the hypophyso- suprarenal system (determined after reducing considerably the ascorbic acid in the adrenal gland of the experimental animals) by eosinopeny, a strong enzymatic activity and a marked osteoblastic reaction. In this respect the phonophoresis with bee venom proved to be a substitute therapy, which results in the restoration of the deficiency of mucopolysacharides, but this does not occur by an artificial introduction from the outside (preparations such as “elioparon”, “arteparon” a.s.o.) but from the natural resources of the tissues.

With age and more intense depolymerization of mucopolysacharides in the basic substance, the hydrophile qualities of the cartilaginous tissue are also reduced – the amount of water decreasing from 85 to 65%. This results in microstructural modifications causing a disorder of the articular system. In turn these modifications result in changes in the bony substance and reaction changes in the articular ligamentary system.

Our experimental data showed local changes in the permeability of the capillaries and considerable local hyperemia. The mastocytes releasing the very active substances they contain such as histamines, serotonines, quinines; cathecholamines a.s.o., result in modification of the permeability of blood vessels, all this bringing about edemas. The edemic liquid supplies the tissues with some matter necessary to restore them and also removes the decomposition products from the pathologic focus. In this sense phonophoresis with bee venom is a pathogenetic therapy.

Another main point of the healing process is the inhibition of the tissue cholinesterase in the treated area. The functional innervation results in the cessation of pain and an improvement in the pathologic process. In the spondilo-artroses the pathologic reflexory arc can be detected at the following levels : in the vertebral canal – the seat of the formation of the excitation ; in the vegetative ganglion – the passage of this – and in the peripheral nervous extremities the seat where the energy turns into an answer reaction. By the method of phonophoresis with bee venom the apitoxin is introduced in the vicinity of 3 other seats – positions easily accessible and suitable for the paravertebral, superstellar and peripheral phonophoretic action.

Of paramount importance to the healing process is the presence of venom hyaluronidase which in our experiment showed no modifications in terms of biological activity. Thanks to the action of the antifibrous action of the mechanic ultrasonic waves as well as to the action of the hyaluronidase of the bee, the resistance of the dermal barriers is overcome, thus facilitating the penetration of the other components of the bee venom into the tissue.

[55] DEGENERATIVE SPINE DISEASES TREATED BY ULTRASOUND PHONOPHORESIS WITH BEE VENOM (ELECTROPHYSIOLOGICAL RESEARCH AND CLINICAL OBSERVATIONS)

POCHINKOVA

BULGARIA

Electrophysiological investigation

Materials and methods

Research was conducted on 20 patients suffering from cervical osteocondrosis with unilateral or symmetrical pains. The initial electro-dermic body resistance, in dermatomes C₃ upto D₁ was determined before the treatment was started. After the first, the sixth and the twelfth treatment the electrical resistance was checked in the same dermatomes. The data were included in a system of co-ordinates.

Results

According to a therapeutical scheme, the bee venom introduced phonophoretically, into the painful area caused the displacement of the pathological dermatomic curve of the main vegetative axis (by means of the electro-dermic resistance value). In 13 patients this deviation appeared together with the clinical improvement. In 7 patients at the beginning of treatment the vegetative curve deviated towards high pathological values, then towards the end of the treatment it gradually moved downwards and in some patients the electrodermic resistance turned into a vagotonic healing phase when the treatment was finished. As the skin is considered a tactile organ and forms part of the neuro-vegetative system, the electro-dermic changes due to the action of the phonophoretically introduced bee venom show that this has a direct bearing on the functional condition of the vegetative nervous system.

Clinical observations

326 patients suffering from spondyloartrosis were observed. The diagnosis was determined on basis of clinical examinations and X rays. 165 patients had cervical, 38 thoracic, 105 lumber and 18 generalized pains. In order to convey the ultrasounds and collect the medicine a salve with a concentration of 150 mg% bee venom was used in the phonopho- resis. The dosage of ultrasounds depends on the stage, type and location of the disease as well as on the treated area : dosage varied from 0.2 to 1.5 W/cm². A sitting lasted for 5-12 minutes ; 12-15 sittings a day. The patient was first biologically tested for his sensitiveness towards bee venom and then the treatment started. In ill patients the main symptom was pain ; 326 had great pains.

After applying the treatment, 194 patients (59.5%) lost the pains, in 98 (30%) the pains diminished and were less spread or appeared only in certain conditions (fatigue, cold, etc.) ; in the remaining 34 (10.5%) no change was noted. The treatment also had a favorable effect on the patients’ general condition.

276 patients (81.8%) had pronounced muscle and ligament troubles. When the treatment was over, normal muscle tonus recovered in 160 patents (59.9%) improved in 50 (18.7%), and remained unchanged in 57 (21.4%).

97 (29.3%) patients had a reduced muscle force. When treatment was finished half of the patients with ‘limited muscle force” passed into the ‘slightly limited” group and those from the “slightly limited” group into the “without changes” group. Their muscle force increased by an average of 6 kilos.

270 patients (82.7%) suffered from acroosteopathy in various spots. Only 46 patients (17%) were completely healed, in 154 (57.1%) the number of the osteopathic areas decreased, in 70 (28.9%) the treatment had no effect.

In 43 patients (13.5) tactility was confused ; in 11 of them it was diffuse over large areas, with zones of high or low sensitiveness.

26 patients had a higher and 17 a lower tactility. As a result of the treatment in 20 patients (46.5%) the tactility became uniform, in 9 patients (21%) it improved, and in 14 it did not change.

62 patients (19%) suffered from paresthesia. In 19 patients (13.6%) it completely disappeared in 32 (51.6%) weakened and in 11 (17.8%) the treatment had no effect. When the treatment was finished we could not determine the radiological modifications in all the spine zones. Of 40 radiologically examined patients suffering from periartritis of the shoulder joint, the calcifications compact disappeared after the treatment in 36.

At the beginning of the treatment the laboratory examinations were almost normal. During the treatment period and afterwards no changes occurred. 214 patients were anamnestically observed throughout one to three years : they were examined 282 times. The favorable results obtained when the treatment was over lasted a long time as demonstrated with 256 examinations. During the treatment and afterwards no unpleasant secondary phenomena appeared.

Though the radiographs showed no modifications, which meant that the objective situation was still present, the pains and the other clinical symptoms diminished or completely disappeared in most patients. This means that the clinical “arthrosis” is caused by reaction and other modifications and these are removed by the applied treatment.

[56] Ramanathan and Lam’s address: Department of Medicine, General Hospital, Melaka.

[57] Ramanathan, M.; Lam, H. S.[57] (1990) – Acute renal failure due to multiple bee stings — case reports,
in Med J Malaya, Dec;45(4), pp.344-6 (abstract).

This report deals with a father and his son who developed acute renal failure following multiple bee stings. The renal lesion in these patients appears to be due to rhabdomyolysis caused by the bee venom. The other mechanisms are also discussed. The need for clinicians to be aware of acute renal failure as a complication of bee stings is stressed.

[58] Roy, Leo (1978) (Canada) – Sclerolysis,
work presented in the Second Symposium (January 16, 1978) of the North American Apiotherapy Society. University of Maryland, College Park, Maryland, USA.
SCLEROLYSIS

Leo Roy, M. D., Toronto, Ontario, Canada

Sclerolysis, or the dissolving of scar tissue, is a variation of bee venom therapy in which the venom is not the sole agent, but is used in conjunction with other therapy to greatly enhance the effectiveness of this therapy. Bee venom is the greatest source of hyaluronidase, which attacks fibrous tissue in all parts of the body, including scars. Scars themselves sound like simple enough things, perhaps not worth talking about, but on a visit to Germany in 1960 I discovered that there are two hospitals, one in Bonn and one in Stuttgart, all the work of which is the treating of scars. Using therapy based on the work of two brothers, the Doctors Hinecke, the hospitals handle several hundred cases a day, both in- and out-patient, and some of the cases I learned of on this visit gave me a real appreciation of this important adjunct to any medical practice.

For example, the doctors spoke of a soldier who developed gangrene in a leg a couple of years after the war. He went through every available therapy only to ultimately lost the leg. A couple of years after that, the other leg began to develop gangrene. Having already explored every recourse, and being unwilling to start the same thing all over again, he somehow ended up trying Dr. Hinecke. The first thing the doctor noticed was a shrapnel scar on the soldier’s neck. The doctor treated the scar and the gangrene in the leg disappeared.

Upon returning to Toronto, I had a patient crippled by migraine headaches. He had suffered these headaches for fifteen to eighteen years and had spent the last three years visiting doctors all over the United States and Europe to no avail. This man bore a large scar on the neck from an abcessed submaxillary gland. Based on my experiences in Germany, I injected the scar and his migraine cleared. It did, however, keep returning, necessitating further examination of the patient. Therapy with submaxillary gland cell extracts reduced the incidence of the headaches further, and ultimately the discovery and treatment of allergies, in addition to the other treatments cleared the migraines up entirely and permanently.

So thus far sclerolysis may be seen to be sometimes effective by itself and sometimes in conjunction with other therapy. But the third, and most dramatic case which I will present, should illustrate most clearly how far-reaching the effects of abnormal scarring may be.

The patient involved was a woman of 50 or 55 years, who could not recall being well since infancy. She felt terribly sick and just could not enjoy her life, yet could not pinpoint any one thing that was at fault. Many doctors had tried to help her but none had succeeded. My own system for starting work with a patient involves not only a physical examination, but a 3000 to 4000 question form through which I attempt to get every piece of information possible which might shed light on the illness. This woman’s questionnaire and examination turned up all kinds of deficiencies and/or imbalances, toxic conditions, etc., any of which might have been the source of her continuing physical misery and all of which should have yielded to suitable therapy. Treatment was started and absolutely no progress whatsoever was observed. I was forced to conclude that no matter how careful and thorough I thought I had been, something had been overlooked. So we started over again, pretending it was her first visit. Upon being asked what problem was uppermost in her mind, she countered promptly with the complaint of her sore throat. This sore throat had not been so much as mentioned in the initial examination; as it turned out, she had become tired of mentioning it to doctors since they had treated it as a passing affair of no consequence. When asked how long the throat had been sore, I was told it had been so since infancy, when she was operated on four times for her tonsils.
Dr. Hinecke’s scar therapy came immediately to mind. On examination, the entire tonsil fossa was found to be covered with scar. This was only my second attempt at sclerolysis, but using my longest needle, I injected the scar tissue, concluded the interview, and asked the patient to return in three days. On her return, her description of her response to the treatment has remained with me ever since. In effect, she said she felt as though she had been hit by a truck — “No, hold on,” she said. “You know how it is when you’re walking down the street and have a high level of vitality. If you get hit by a truck, your vitality goes down like a stone that’s falling, and then you’re on a low level of vitality until your body can recuperate. I experienced that feeling in reverse. When I got that injection, my life forces went up like that.”

I injected her ten or twelve times and then never saw her again, but her case is truly exemplary. When you get failure cases, cases involving toxic or allergic problems, sometimes even a loss of the desire to live, there can be a scar involved. And that scar will prevent the patient from ever getting any better from any single therapy you may give him. This sounds radical, but I believe it to be so. Cases like the above-mentioned frequently seem to require nearly double the amount of therapy one might give the average patient just to keep them going, and yet get little or no better. There have been times with patients of this type in which I have failed to check for scars, but when I do so, I find that upon completion of treatment of the scar, other medication can usually be reduced by about half, and in a month or two they are hardly taking any treatment at all. It almost appears as though the treatment builds up inside them, but the body is not getting the benefit of it; somehow it is blocked off from the body. As soon as you get rid of the scar, all the effects and benefits of the therapy seem to come to life. A scar doing that may, not appear to make much sense, but when you see these people — and I have seen one to two hundred of them in the last fifteen years — it is hard to interpret it any other way.

Plainly, not everyone has this condition. It might be one out of every ten or twenty adult patients. Children usually heal so beautifully that you get no problems, although I have seen one or two cases. When the situation does occur, however, one must ask oneself why and the most likely reason is as follows.

In healing, tissue fibers grow across the wound like weaving. They consolidate and contract, and the problem lies in the fact that nerve fibers are growing back, too. If each type of fiber grows at a normal rate, you have no difficulties. But if there are abcesses or if you have people with low protein who cannot manufacture good enough fibers to do the weaving job, or have low vitamin C or poor elastic tissue, then you do not get a normal healing process. You are, however, likely to have a normal healing process in the nerve fibers anyway. The nerve tissue therefore grows faster than the surrounding scar tissue, which ends up pinching off the nerves, which in turn has as drastic an overall effect on the body as having a vise pinching a finger. It results in a condition of not being able to think properly, or feeling tired and miserable, of general malaise. The irritation from this pinched nerve appears to build up and in time flood the entire nervous system, which then affects the circulatory system and the glands.

Therefore, if the problem is pinched nerves, as it appears to be, the question becomes how to un-pinch them. This, in line with Dr. Hinecke’s work, is done by stretching the tissue to relieve the pressure by infiltrating the area with sterile water, creating an artificial edema. As sterile water is one of the most painful injections one can give, one percent novocaine is added. After exposure to the work of Charles Mraz and others, I have begun to also add bee venom to the solution, feeling that it reduces the number of injections needed and dissolves more of the fibrous tissue, yielding a better and more long-lasting effect due to its hyaluronidase content. As I have done no controlled research in this area, I must present my findings strictly from the clinical point of view.

It is almost impossible to locate the exact nerve endings involved, so I find the general area of the pinched nerve by running a needle slowly down the length of the scar, with the patient advised to mention any abnormal sensation. If the situation is severe, his pain will be acute as the needle passes over the affected area. Or it may be mild pain, or a tingling sensation running through the body, or a general discomfort. Where the scar is normal, the patient feels nothing, so the difference is very noticeable to him. The sensitive area is marked with crayon to guide the following injection.

Often the appearance of a scar will offer a clue. The abnormal scar may present an “angry” appearance, be red or keloid.. Again, when questioned on the history of the scar, the patient will recall not being in the best of health at the time the wound, burn, or surgery occurred. I look for protein and mineral deficiencies then in other fibrous tissues of the body. Bruising, fallen arches, double-jointedness may indicate these deficiencies. “Phantom pains” following amputations may very well be caused by nerves pinched in the scar from the amputation. Itching of the scar is another common complaint, as is tenderness. The discomfort of the scar-pinched nerve may sometimes be blamed on adhesions. In addition, as may be judged from the description of the general malaise caused by abnormal healing, the patient may be thought to be a hypochondriac. Hypochondriacs should always be very carefully inspected for scars. And not only is the general health often affected by these scars, but the patient may have aches and pains in various parts of the body, and if no logical reason for these can be seen, they may be blamed on arthritis.

The injection itself contains ten minims of novocaine and 500 micrograms of bee venom dissolved in sterile water for a total volume of 10 ml, administered with a small needle, such as a 25 gage, which is 7/8 to one inch long. In a young patient, I may start with only 1/10 ml of bee venom and gradually build up the dosage. I do not use pure hyaluronidase instead of bee venom as I feel that the other constituents of the venom are beneficial.

In a large scar, I may use up the entire 10 ml, on a smaller scar perhaps only 2 or 3 ml. I inject only about 1 ml in each tender area of the scar, starting subcutaneously, that is very close to the surface where most nerve endings are. But I bear in mind that scars may also be deep, so I probe with the needle more and more deeply, in all directions, locating all sensitive spots, and injecting each with 1 ml of the solution. With small or not terribly serious scars, one treatment will frequently solve the problem permanently; with larger or more serious scars repeated injections at intervals or approximately every three days may be needed. When bruising occurs, indicating low vitamin C, the bruises must heal before continuing treatment. A scar problem may appear to be entirely cleared up, only to find a few months later that there are other sensitive areas within it that were initially masked by the stronger effects of the first-treated sections.

An interesting secondary effect of the treatment of these scars points

up the inter-relationship of all parts of the body. Injecting one area of a scar will occasionally cause sensation or cessation of discomfort in another part of the body, as exemplified by acupuncture. This would appear to indicate that the pinched nerve is affecting this other part.

Occasionally a patient will have an allergic reaction, in which case I give them an anti-allergy therapy prior to each injection. A physiological histamine such as “Antronex” or “Antipyronex” can be given over a long period of time without damaging the liver. “Allerplex”, a combination of anti-histamine, vitamine C and adrenal gland cell extract is what I usually use. I have even used it in conjunction with extra vitamin C and niacin to bring a patient out of anaphylactic shock. A common minor reaction to the scar therapy is a feeling of faintness and dizziness about 20 to 30 minutes after the injection, as a result of the novocaine, but it passes quickly. Very occasionally, a patient will call in reporting that he is feeling very upset and miserable, a condition lasting two or three days. The therapy is contraindicated by flu, a fever, and pregnancy.

In conclusion, I would say that while the majority of scars are normal and need no help, the examination of patients for sensitive scars should be standard procedure for all doctors. A great deal of emphasis is placed on the diagnosis and treatment of disease, but insufficient emphasis is placed on the blocks to healing within the body. Abnormal scarring is of great importance in this aspect of medicine.

[59] Laboratoire d’Immuno-Allergologie-CHU, Angers France.
[60] Diagnosis of allergy to hymenoptera venom must be precise and depends on

indisputable bio-clinical criteria, because of specific immunotherapy for indications such as systemic and/or anaphylactic reactions. Until nowadays, diagnosis was by specific IgE, histamine release and skin tests, most often done for the venoms of wasp, honey bee and hornet at the same time since, in 7-8 cases in 10 the patients had not identified the responsible insect. Basophil activation test (TAB) by Flux cytometry and measurement of leukotriene C4 (LTC4) are new techniques of great reliability. The work shows the correlations between the different immunobiological parameters by reference to TAB by CAF and measurement of LTC4. When the overall results for mixed venoms or those for single venoms are considered, the correlation between TAB, LTC4 and the other parameters are highly significant. It can now be considered objectively that TAB by CTF and measurement of LCT4 are the two highest-performing techniques for diagnosis of hymenoptera venom allergy and so validates them.

[61] Saine, J. (1965) (Canada) – Is bee venom a panacea for the treatment of arthritis ?
in the XX-Th. Apimondia Congress, Bucharest, Romania, p.443-445

In the past, we dwelt at sufficient length on the fact that arthritis is curable, particularly if we direct our efforts towards etiological factors and if co-operation can be expected from the patient. We also showed that recovery does not confer immunity: in similar circumstances, the same causes are bound to induce the same effects.

Bee venom is a powerful weapon only if all its natural properties are preserved and if it is manipulated with art and according to the laws resulting from the apitherapist’s experience.

Bee venom, if introduced epidermically – either by using live bees or by injections – is apt, we believe, to remove pain, inflammation and ankylosis in acute and subacute crises, without any recourse to other therapeutic means. If injected into the muscles, the articulations, the synovial glands and the outer covering of the extremities and the hypertrophic articular surfaces of the bones, bee venom seems to induce – when used in stronger concentrations – even more remarkable effects.

If injected into the epidermis or into the lombo-sacral para-vertebral muscular mass, bee venom appears to act upon the arthritis of the articulations of the lower limbs: knees, ankles etc.; when injected around the last cervical articulations and the first two dorsal articulations, it seems to act on deformities and the hypertrophy of the upper limbs : wrists, hands etc.

Introduction of bee venom into the same patient by different ways (epidermic, intradermic, periarticular, intraarticular, intramuscular, intraperiostic and para-vertebral) seems to be a particularly effective method : the results obtained in cases of very advanced arthritis appear to be superior to those reached by each one of the above mentioned ways.

We must remember that bee venom is no holy water endowed with the grace of chasing away the demon of arthritis; in order to derive any profit from it, we must make a thorough investigation of its biological properties and use it in chronic cases, on the same patient for several months, a year, two, three or even more. We should add, however, that results are obtained quite rapidly if the disease is in its initial phase. We have had patients who were successfully treated three or four years for their deforming polyarthritis. They had been previously treated with no results by corticotherapy. Apitherapy enabled us to bring about a regression of the disease. We, can also declare that the latter method is categorically more effective than the former.

Nevertheless, we have a clear impression that bee venom is no panacea for all arthritic cases; when the self-defence of the organism is weakened to such an extent that arthritis deformities become irreversible, we resort, in treating our patients, to the following therapeutic arsenal :

By “d’Arsonvalizing” the articulations we improve local circulation, especially in the capillaries and thus contribute to reducing anoxemia and sub-oxidation. It is superfluous to note that in addition to intensifying the local metabolic activities, this method enables us to obtain a completer elimination of catabolic and articular residues.

“D’Arsonvalization” of the dorsal sympathetic centres and of the lombosacral para-sympathetic ones induces – apart from an excessive vasodilatation throughout the organism – a state of eutony of the neuro- vegetative system and in this way provents vasconstriction of capillaries, which seems to lie at the base of the deformities appearing in these tiny vessels before rheumatoid arthritis or osteo-arthritis sets in. We must first of all recall the sympathetic gangliectomy and ramicotomy operations performed on 16 cases by Rawntree and Adson at Mayo Clinic ; they actually obtained unexpected results in patients with deforming polyarthritis. In addition, after tereo-microscopic observations on synovial biopsies from patients suffering from osteo-arthritis or rheumatoid arthritis, the recent work of Kulka and his collaborators at the Medical Department of Harvard University, entitle the authors to reach the conclusion that the capillaries are the target-organ in arthritis and rheumatic affections. – As a matter of fact, Pemberton, whom we cited in our lecture at Vermont University, came to this conclusion already 30 years ago : “nihil nove sub sole”.

We also resort to ionizing the articulations with anions or cations of magnesium chloride, potassium iodide, sodium or lithium salicylate and of other salts.

We use ultra- and infra-sounds, as well as faradism and direct or interrupted current, in trying to remove contractions, ankylosis or “spasticities” or to correct muscular atrophies due to movement limitations, thus regulating the chronaxy.

Remembering the physiological principle that man is born and lives under the sign of the pituitary gland, ovaries or testicles, and considering it as already established that in cases of chronic polyarthritis, when deformities seem irrever sible, there are always some endocrine deficiencies, we never hesitate to regularly offer those patients who appear to need it, a supplement of either propionate of testosterone or alpha- oestradiol or progesterone, according to the phases of the menstrual cycle or to the patient’s sex. In fact, did not Dr. Wilson M. D. of Brooklyn, New York, write in the “Journal of the American Medical Associations” (27 th October, 1962, vol. 182, pp. 327-331) that for instance alphaoestradiol exerts a protective influence on several vital processes, especially in the cardio-vascular, osseous and protein metabolism ?

We endeavour to eliminate all apparent or existing seats of infection from the organism.

Attack on self-intoxication due either to constipation or to enteritis causing diarrhoea. For a long time, our attention has been attracted by the etiological factor of arthritis, whose paroxysm always coincides with acute or subacute manifestations of rheumatic diseases. We mentioned this in our. Vermont University lecture already in 1962. But in 1963, Dr. M. Kohno of Tokyo informed us at the Fifth European Congress on Rheumatic Diseases, held in Stockholm, that he had succeeded in isolating Streptococcus faecalis from the blood of patients suffering from rheumatoid polyarthritis. It should be noted that Prednison prevents the abundant multiplication of Streptococcus faecalis, in vitro and in vivo in test animals. It is therefore very difficult to isolate this streptococcus in blood taken from patients undergoing corticotherapy. It should also be noted that according to Dr. Kohno, corticotherapy does not bring about the complete destruction of this streptococcus. It is desirable that other laboratories should take up these experiments in order to either invalidate or confirm the opinion of our Japanese colleague.

Alpha-2-haemogliase, which is still extensively used in his researches by Dr. J. de Larebeyrette (whose work has been awarded a prize by the French Academy of Medicine), is another factor to be fought against in our arthritis patients. We also stop them from consuming white sugar, bread and pastries made of flour whitened with nitrogen peroxide and whose composition is left unbalanced after the extraction of bran, mineral substances, 13 vitamins, a part of its protein and especially of the wheat germen, the source of E vitamin. The characteristics of the white race are due, partially at least, to the nutritive value of integral wheat. This out of balance that we impose on our everyday bread, is it designed to help the finance sharks to put on weight or to make the whole race rachitic, in order to make it receptive for the inculcation of new doctrines or religions ?

In either case, this inert and unbalanced flour should be banished from society; is it not a source of haemogliase which in its turn, can cause capillary thrombosis and, consequently, arthritis ?

The Czechoslovak legislators for example, were remarkably inspired when they listened to their doctors, who advised them to prohibit the use of this lifeless flour which brings about so many evils.

We often employ a well-known physical agent which seems to have, during the first hours, a sympathetic-mimetic and afterwards vagomimetic effect. I am referring to the ultraviolet rays which, apart from the eutony they induce in the organism, help to turn D pre-vitamin into D vitamin and thus contribute towards the fixation of calcium in bones. In fact, osteoporosis preceeds in very many cases, the appearance of arthritic symptoms. Besides, these rays also help to remove capillary contractions.

In certain cases we go on utilizing sodium salicylate in intravenous injections. But in order to prevent the appearance of depression or constipation effects, we add 400 mg ascorbic acid and 200 mg thiamine and pyridoxine per each 6 m3 of salicylate. This compound is still useful against ankylosis or pain, either acute or subacute.

Recourse to all these means might still prove to be insufficient at times, if we do not prescribe general hygiene good mastication and a well-balanced- diet consisting not only of proteins, lipides and glucides, but also of fresh fruit and vegetables. White sugar is replaced by honey ; coffee and tea – which especially when taken in the evening, shorten the sleep and induce a state of vasoconstriction – are replaced by infusions and often acacia honey. Remember that tea constipates.

All these recommendations will only be useful when the patient complies with the first commandment imposed on us by nature ; to eat our. bread with the sweat of our brow. We also recommend daily sports activities, to the extent to which they are possible. Invalids should have their muscles activated with currents provided by a correctly understood and widely utilised electrotherapy. Unfortunately, these cannot be offered to their patients by most of the world’s big hospitals, by reason of their deficiency of adequate equipment and physicians actually accustomed to the discipline of true electrotherapy.

Our therapeutics will be incomplete if we do not encourage our patients, making them self-confident and if we do not eliminate all the causes of anxiety. And particularly, we must make them understand that despite what has been said – groundlessly after all – by many of the world’s greatest rheumatologists, arthritis can be cured. They are able to see that, for themselves in a clinic like ours, where they meet cured or nearly cured patients.

This enumeration of therapeutic procedures forming a complex but altogether logical method, will not enable any rheumatologist to obtain our excellent results; he would need long experience in handling both physical agents and bee venom. In other words, he should have long experience in apitherapy in correctly understood electrotherapy (according to d’Arsonval’s conception) and in psycho-somatic medicine.

C o n c l u s i o n s

If we are to wage total war on arthritis, we must resort to every means at our disposal, including bee venom and physical agents which we must learn to manipulate. No one of these means should be regarded as a panacea for all cases of arthritis.

[62] Saini, S. S. et al address: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555-1070, USA. sssaini@utmb.edu

[63] Saini, S. S.; Chopra, A. K.; Peterson, J. W. (1999) (USA) – Melittin activates endogenous phospholipase D during cytolysis of human monocytic leukemia cells,
in Toxicon 1999 Nov; 37(11), pp.1605-19.

Human monocytic leukemia cells (U937) were challenged with synthetic melittin, and arachidonic acid (AA)/acylated lipids from both cells (pellet) and media (supernatant) were analyzed by thin layer chromatography (TLC). From these data, melittin-mediated activation/inhibition of major phospholipases in U937 cells was related to pore formation, permeabilization and cytolysis as determined by light microscopy. Also, the effect of melittin on acylhydrolase activity in the cell-free sonicated lysates of U937 cells was examined. Here we report that synthetic melittin (1 microM) caused cytolysis of U937 cells within 10-15 min. Cellular hypertrophy (5 min) and aggregation (1 min) preceded cytolysis. TLC analysis of these lipids showed that total levels (cellular + medium) of diacylglycerol (DAG), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) decreased, while that of arachidonic acid (AA) increased continuously (5-30 min). However, levels of phosphatidylethanol (PEt) phosphatidic acid (PA) and phosphatidylserine (PS) were increased transiently at 5-10 min being maximal at 5 min. Taken together, the combined levels of PEt and PA (an end product of phopholipase D, PLD) were about 42-fold higher than the level of AA at 5-10 min. Enhancement of AA levels appeared to result from in vitro reactions of various acylhydrolases and their phospholipid substrates (free/membrane bound) liberated into the medium during pore formation/cell lysis. Incubation of sonicated cell lysates also enhanced release of AA, which decreased upon addition of melittin, indicating that melittin inhibited these acylhydrolases. A consistent decrease in the level of DAG showed that phospholipase C was unaffected. Hence, transient activation of PLD bymelittin at the point of initiation of cytolysis, suggested a role for PLD in melittin-mediated membrane disruption/cytolysis by an uncharacterized signal transduction mechanism.
PMID: 10482394, UI: 99410120

[64] Address: Department of Microbiology and Immunology, University of Tennessee, Memphis 38163.

[65] Sharma, S. V. (1992) (USA) – Melittin resistance: a counterselection for ras transformation,
in Oncogene, Feb;7(2), pp.193-201.

The prevalence of activated ras oncogenes in human primary tumors suggests a central role for this oncogene in human cancer.
Despite its ubiquitous distribution, the biochemical role of the oncogene remains unclear, and hence attempts to control its activity have been frustrated.
This study demonstrates the ability of melittin, a 26 amino acid, amphipathic peptide from bee venom, to specifically select against cells in culture that express high levels of the ras oncogene.
Acquisition of resistance to increasing concentrations of melittin is accompanied by corresponding decreases in the levels of expression of the ras oncoprotein and the number of copies of the ras gene. This results in a concomitant reversion of transformed cells to a normal morphology in a strict dose-dependent manner.
Melittin is a known activator of cellular phospholipase A2 (PLA2), and these results suggest an interrelationship between ras and PLA2.
In addition these studies indicate that melittin preferentially hyperactivates PLA2 in ras oncogene-transformed cells, resulting in their selective destruction.

[66] Department of Molecular Pharmacology, American Cyanamid Company, Lederle Laboratories, Pearl River, New York 10965.

[67] The receptor for the bee venom derived neurotoxin, apamin, is widely believed

to be an integral component of the small conductance calcium-activated

potassium channel in many excitable cells. By affinity chromatography on

immobilized apamin, a 78 kD apamin binding protein of the bovine brain

synaptosomes was isolated. Antibodies were elicited against this protein and

used to clone a cDNA from a porcine vascular smooth muscle expression library.

This gene (Kcal 1.8) codes for a 438 amino protein with four potential

transmembrane domains, one putative calcium binding site, a protein kinase C

phosphorylation site, and a leucine zipper motif. Kcal 1.8 encoded protein has

no significant sequence homologies with any known ion channels or receptors.

Kcal 1.8 is likely to encode a protein associated with the small conductance

calcium-activated potassium channel in vascular smooth muscle.

PMID: 7912073, UI: 94280514

[68] 42 patients with confirmed hypersensitivity to honey bee (HBV) and/or yellow jacket (YJV) were treated with the respective venoms (7 with HBV, 5 with YJV and 30 with both venoms). Treatment tolerance, skin tests (ST), specific IgE- and specific IgG-antibodies were monitored before, after 3, 6, 12, 24 and 36 months. 21 patients had a rush and 21 a conventional treatment schedule. Maintenance dose was 100 micrograms. Adverse effects occurred as large local (8 patients), slight systemic (12 patients) and moderate to severe systemic reactions (4 patients). Of 24 re-exposed patients 17 had no reaction at all, six a markedly decreased and one an unchanged reaction. After 3 years of treatment ST became negative in nine of 31 patients on HBV and in seven of 26 patients on YJV. RAST became negative in three of 30 patients on HBV and 17 of 29 patients on YJV treatment. Both ST and RAST became negative in five HBV- and 10 YJV-treated patients. Loss of venom hypersensitivity according to diagnostic tests may correspond to actual desensitization and enable discontinuation of immunotherapy.
PMID: 6638413, UI: 84050107

[69] Tumwine and Nkrumah’s address: Department of Paediatrics and Child Health, University of Zimbabwe Medical School, Avondale, Harare.

[70] Tumwine, J. K.; Nkrumah, F. K.[70] (1990) (Zimbabwe) – Acute renal failure and dermal necrosis due to bee stings: report of a case in a child,
in Cent Afr J Med, Aug;36(8), pp.202-4.

Although several cases of reactions to bee venom including acute renal failure have been reported, the literature from Africa is scanty and that concerning children virtually non-existent. We report a child who was stung by over 1,000 bees and developed acute renal failure and extensive scalp necrosis. The pathogenesis of these complications is discussed and the importance of their public awareness stressed.

[71] Departement de Pneumo-allergologie, Clinique Saint-Luc, Bouge, Belgium.
[72] In this study, we performed 150 desensitizations in 139 Hymenoptera venom allergic patients (109 Yellow jacket allergic patients, 19 Honey bee allergic patients and 11 patients sensitized to both insects, who received a dual desensitization). We used a rush protocol, allowing injection of a total cumulated dose of 125,1 (Honey bee) to 175,1 (Yellow jacket) microgram of venom in 30 hours. Patients were hospitalized, with all emergency precautions for treating systemic reactions. The protocol was well tolerated in 147/150 cases; 3 patients had a benign systemic reaction. Patients received monthly maintenance doses of 100 micrograms venom. 39 patients experienced a field sting during immunotherapy; 2 of them (5%) had a benign systemic reaction.
Thus, our rush desensitization protocol seems to be safe and effective.
PMID: 9273600, UI: 97391533.

[73] VERSUCHE ZUR BEHANDLUNG EINIGER PARADONTOPATHIEN

MIT APITHERAPIEPRODUKTEN

VARACHIU
N. LUCA
Filofteia POPESCU
Cristina MATEESCU
Gh. PIRVU

Experimentell und klinisch wird die Wirkung eines neuen Apitherapieprodukts untersucht, u. zwar mit Bienengift und Pollen vermischte Propolis. Dieses produkt wurde bei der Behandlung von Paradontopathien verwendet. Die Untersuchungen erfolgten mit Hunden, vor allem der Beagle-Rasse.

Das Referat bringt die erhaltenen Ergebnisse.
S. 545
[74] DAS BIENENGIFT ALS RADIOSCHÜTZENDES ELEMENT BEI

GAMMABESTRAHLUNGEN VON WISTARRATTEN

Eliana A. VARANDA
Catarina S. TAKAHASHI
A.E.E. SOARES (Brazil)
Viele Untersuchungen bewiesen, daß das Bienengift der Apis mellifera eine Schutzwirkung gegenüber den physikalischen Erregern ausübt und zu dem Überleben der Zellen oder des ganzen Organismus beiträgt. Wir wollten untersuchen, ob das Bienengift eine radioschützende Wirkung hat, u. zwar durch die Herabsetzung der Frequenz von Chromosomanomalien, die in in-vivo-Versuchen bei Wistarratten durch Bestrahlung verursacht worden sind. 100 g schweren Tieren wurde intraperitoneal 1 l Bienengift 1 Stunde und 24 Stunden vor bzw. 30 Minuten nach dem Bestrahlen mit 300 R gespritzt. 24 Stunden nach dem Bestrahlen wurden die Tiere getötet. Die vorliegenden Ergebnisse und die der Fachliteratur lassen uns schlußfolgern, daß das Bienengift eine radioschützende Wirkung ausübt, und daß zwischen Bienengiftbehandlung und Bestrahlung ein gewisses Zeitintervall notwendig ist.
S. 546
[75] Pat Wagner’s Address: 5431 Lucy Drive, Waldorf, MD 10601
Tel.: (301) 843-8350. E-mail: beelady@olg.com

[76] Weeks, Brad (1991) – Which diseases have been helped with bee venom?
in BeeWell, January.

The scientific literature describes bee venom’s effects on a great variety of diseases in humans and animals. In reviewing the reported effects of bee venom, one is suspicious of bee venom claiming panacea status. However, I propose that the action of the bee venom, as described above, is significant for its immune-stimulant activity. Acting, as it might, at this fundamental level, one can easily understand its varied therapeutic effects. Just as good nutrition, sleep and attitude are beneficial (psycho-neuro-immunology teaches us this), so too does bee venom exercise its myriad therapeutic effects through both local and systemic immune stimulation.

For the sake of simplicity, I have organized the following anecdotal (but documented) effects of bee venom into organ systems. The purpose of this list is to encourage bee venom therapists to try BVT on any of the following diseases since they reportedly have been helped by BVT in the past. BVT in many cases ought not be the only drug of choice, but certainly ought to be included in the pharmacological armamentarium.

Immune System:

T cell suppression and B cell enhancement
Systemic lupus erythematosus (SLE), AIDS

Nervous System:

multiple sclerosis, post-herpetic neuralgia, chronic pain syndromes, sciatica, peripheral neuritis, lumbago neuralgia, Dupuytren’s contracture.

Anti-cancer:

malignant melanoma, basal cell carcinoma, lymphoma (increases survival of lymphoma-bearing mice), protective agent against X-irradiation in mice

Rheumatological:

all arthritic conditions: rheumatoid arthritis, osteoarthritis, juvenile arthritis, traumatic arthritis, Schlermann’s disease, polyartritis deformans, psoriatic arthritis
lateral epicondylitis (tennis elbow), acute and chronic bursitis, myalgias (neck, paraspinal spasms), ankylosing spondylitis deformans, scleroderma, systemic lupus erythematosus (SLE), fibrosistis, documented significant lowering of ANA counts.

Dermatological:

topical ulcers, degranulating wounds, eczema, psoriasis, sclerolysis, degranulating wounds, corns, mycosis fungoides, seborrheic dermatitis.

Viral:

post-herpetic neuralgia (shingles), warts (inc. planter’s warts) Epstein Barr Virus (EBV), Mononucleosis, AIDS.

Cardiovascular:

hypertension (chronic and acute), arrhythmias, obliterating endarteritis, atherosclerosis, peripheral vascular disease, Raynaud’s disease, acute rheumatic carditis.

Endocrine:

stimulates endogenous plasma ACTH, cortisol secretion, infertility (increases bull sperm count at U. Penn. – Dr. Alan Benton).
BVT has been associated with MISCARRIAGES (causing and curing them) as well as but also has been associated with achieving pregnancy. Therefore may increase fertility in sterile women and may increase risk of miscarriage in newly pregnant women.
premenstrual syndrome (PMS), menstrual cramps, irregular periods, mood swings, hypoglycemia.

Psychiatry:

depression. This may be due to primary disease improvement or to lessening of depression.
[77] Bavarian Nordic Research Institute, Munich, Germany.

[78] Winder D, Gunzburg WH, Erfle V, Salmons B [78] (1998) (Germany) – Expression of antimicrobial peptides has an antitumour effect in human cells,
in Biochem Biophys Res Commun Jan 26;242(3), pp.608-612.

The antimicrobial peptides cecropin and melittin are known to exhibit

antitumour activity in tumour derived cell lines. To achieve a similar effect in vivo these peptides would have to be given repeatedly to maintain therapeutic levels, which may be pharmacologically unfavourable. The expression of the genes encoding such antimicrobial peptides in the desired cell type may circumvent

these problems. Expression constructs carrying cecropin or melittin have

been introduced into a human bladder carcinoma derived cell line and the resultant cell clones analysed for tumorigenicity in nude mice.

Expression of cecropin resulted in either a complete loss of

tumorigenicity in some clones or reduced tumorigenicity, as measured by latency of tumour formation.

These results suggest that vector mediated delivery of this gene to tumour cells may prove useful for cancer gene therapy.

[79] Allergy Department, School of Medicine, Sao Paulo University, Brazil.

[80] Seventy-eight Brazilian beekeepers who had been stung on average six times per month were studied. Sixty-eight beekeepers (87.1%) showed restricted local clinical reactions; nine individuals (11.5%) had extensive local reactions, and only one (1.2%) suffered anaphylactic shock. The humoral immunologic pattern of these individuals were studied by using immunoenzymatic methods to determine the serum titres of specific IgE and specific IgG4. Three groups of beekeepers presenting different humoral immunologic patterns were identified, in which the predominant pattern was the absence of specific IgE and high levels of specific IgG4 (38.4%). There was a positive correlation between the high levels of specific IgG4 and the number of bee stings. This correlation was not found in either specific or total IgE. The results of the present study suggest: i) the immunologic response to the number of exposures to Africanized honey-bee venom is not related to the number of exposures; and, ii) other nonhumoral and/or nonimmunologic factors may be involved in the reaction to the insect sting, which are responsible for both the clinical symptoms and protection.

[81] Youlten, L. J.; Atkinson, B. A.; Lee, T. H. (1995) (UK) – The incidence and nature of adverse reactions to injection immunotherapy in bee and wasp venom allergy,
in Clin Exp Allergy, Feb;25(2), pp.159-65 (abstract).

Department of Allergy & Respiratory Medicine, UMDS, Guy’s Hospital, London, U. K.

The incidence, time course and nature of systemic reactions to injections of bee and wasp venom during immunotherapy have been estimated in an open, prospective, single centre study. One hundred and nine survivors of moderate to severe systemic reactions to stings from hymenoptera, received courses of bee or wasp venom by monthly subcutaneous injection for up to 3 years. Systemic reactions were recorded after 7.5% of 946 weekly venom injections during the initial phase of treatment, and after 2.1% of 1789 monthly maintenance injections. In both phases of treatment, reactions were more frequent after bee (17% of initial phase, 7.8% of maintenance treatment) than after wasp (3% of initial phase, 0.3% of maintenance treatment) venom injections. The percentage of patients experiencing at least one reaction was also higher for bee (46%) than for wasp (14%) sensitive patients. Over 80% of reactions began within 30 min of injection, over 90% within 1 h and only two (2%), between 1 and 2 h, the remaining six (5.5%) starting more than 2 h after injection. Only 0.47% of venom injections produced a systemic reaction which was severe enough to require adrenaline treatment. The female patients experienced more reactions (21% of the wasp, 60% of the bee, sensitive) than the males (5.5% wasp, 20% bee). Age and atopy did not appear to be significant risk factors for systemic reactions. We conclude that wasp and bee venom immunotherapy in a conventional dosage regimen was generally well tolerated.
PMID: 7750008, UI: 95269160.

[82] BEE STING ACUPUNCTURE USED TO PREVENT AND CURE THE

HYPERSENSITIVITY REACTION CAUSED BY MELLISSOTHERAPY

413 ZHANG Shi-fen, YANG Xiao, YAN Hong

(CHINA)

Hypersensitivity reactions are very popular in clinic treatment in China, being a result of mellissotherapy. After the first 2-3 weeks of treatment, when the patients are administered mellissotherapy again, some of them develop a hypersensitivity reaction. To be able to successfully continue the application of mellissotherapy and to prevent hypersensitivity reactions, in the third week of treatment, we used bee sting to perform acupuncture in the “Chihshin” point (Urinary Bladder 52 = ZHISHI point), which is the projection of the adrenal gland on the skin. 264 patients were observed and we noticed that none of them developed any hypersensitivity reaction to mellissotherapy any more. By this method, we cured many kinds of hypersensitivity reactions, thus contributing to the development of apitherapy.

p.125

[83] BIENENGIFT IN DER BEHANDLUNG VON SEXUALSCHWÄCHE

Li ZHONGPU (China)

Die klassische chinesische Medizin erwähnt schon seit langem, daß die Impotenz mit Bienengift und Waben geheilt werden kann, da in diesen Waben nach dem Migrieren der Bienen etwas Bienengift übrigbleibt. 1960 beobachtete der Verfasser, daß ein zufälliger Bienenstich in den Knöchel einen impotenten Kranken vollständig heilte.

Ab 1966 behandelte der Verfasser 3.015 impotente Patienten durch Stiche lebendiger Bienen in den Punkten Rangu (Kidney 2) und Taixi (Kidney 3) des Fußes. Die erzielte Wirkung war 78,2 %-ig. Wenn täglich auch noch 30 g Acanthopanax (dreimal täglich) zugegeben wird, dann ist die Wirkung 98,5 %-ig. Die schwerkranken Patienten brauchen zusätzlich noch zwei oder mehrere Behandlungen.
S.525

· Mezrina, O. V. (1975) – Oral administration of novocaine solution for treatment of allergic complications of apitherapy,
in Vrach Delo(7), pp.125-7.

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· Mezrina, O. V. (1975) – Oral administration of novocaine solution for treatment of allergic complications of apitherapy, in Vrach Delo(7), pp.125-7.

· Mezrina, O. V. (1975) – Oral administration of novocaine solution for treatment of allergic complications of apitherapy,
in Vrach Delo(7), pp.125-7.