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Coagulopathy following Papua New Guinean taipan (Oxyuranus scutellatus canni) envenoming
528
Tenth World Congress
Neutralization of haemorrhagic and lethal activities of Crotalus adamenteus venom by natural products. U. R. KUPPUSAMY and N.P. DAS (Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore 051 I). SEVERALnatural products such as the flavonoids (apigenin, kaempferol and luteolin) and tannic acid were tested for their ability to neutralize the haemorrhagic and lethal activities of Crotalus adamenteus venom. The venom alone or the venom plus test compound was administered s.c. into male Swiss mice (body wt. 20 + 2 g). The extent of haemorrhagic activity was determined by measuring the diameters of the haemorrhagic area. The four test compounds inhibited the haemorrhagic activity of the venom dose-dependently. Flavonoids (0.1/z mole) or tannic acid (6/~g) when present in the 50/~1 of venom solution (50 tz g/ml) could almost completely inhibit the haemorrhagic activity. Similar amounts of flavonoids or tannic acid when present in 5 x LOs0venom solution (s.c. LDS0= 27.0 # g/g body wt.) could significantly prolong the survival time(s) of the mice. The order of potency of the test compounds on their ability to antagonize the lethal activity of the venom is as follows: tannic acid >> luteolin = kaempferol)apigenin.
Coagulopathyfollowing Papua New Guinean taipan (Oxyuranus scutellatus canni) envenoming. D. LALLOO,1'2 J. BLACK,2 S. NARAQI,2 D. OWENS,3 A. CHITOLIE,3 R. A. HUTTON,3 R. D. G. THEAKSTON4 and D. A. WARRELL1'4 ('Centre for Tropical Medicine, University of Oxford, U.K.; 2University of Papua New Guinea, Boroko; 3Royal Free Hospital, London, U.K.; 4Liverpool School of Tropical Medicine, U.K.). MECHANISMS of coagulopathy were studied in 13 patients with incoagulable blood after taipan bites. Six had spontaneous bleeding, 11 local lymphadenopathy and seven neurotoxicity. Standard coagulation assays were used to compare the patients with nine healthy PNG controls and 20 normal London blood donors. All patients were severely defibrinated (fibrinogen levels 0-0.6 g/l), and as anticipated from the known prothrombin activator in taipan venom, Factor II levels were reduced (mean 47, range 8-88 u/d0. The labile factors (V and VIII) were very low (ranges 1-13 and 1-28du/l, respectively), partly due to activation of their physiological natural inhibitor, Protein C, which was also low (range 25-59 u/dl). Moderate deficiencies of factors IX, XI and XII were also seen.' Reduction in Factor XIII subunits, plasminogen and alpha-2 antiplasmin, together with elevated cross-linked FDPs (5-250/,g/ml) indicated activated fibrinolysis, although the much higher total FDP (1280-5120/tg/ml) suggested some fibrinogenolysis. The results indicate that a consumption coagulopathy, due in part to the action of the prothrombin activator, is induced by taipan envenoming, but suggest that other haemostatically active components, as yet unidentified, are also contributing to the clinical picture.
Scorpion antivenom production in Iran. M. LATIFI and M. TABATABA!(Razi Institute, P.O. Box 11365-1558 Tehran, Iran). LITTLE is known about the venom of the Iranian scorpion, of which there are more than 20 species. The medically important scorpions are found mostly in the warmer areas of Iran. The polyspecific antivenom was prepared by immunization of horses. The crude serum was purified and concentrated by enzyme digestion and salt fractionation. The venom was obtained either by electrical stimulation or by extraction of the macerated telson and was freeze-dried. Studies on the venom indicated that there were differences in the yields and lethalities of the species. Scorpion venoms of Iran were compared with regard to lethalities (i.v. LD50in mice) and rates of neutralization tests (i.v. mg/ml in mice). This paper describes neutralizattion tests conducted to determine the effectiveness of polyspecific available antivenoms, in the neutralization of homologous and heterologous scorpion venoms. During the studies described, several instances of cross-protection were found, and in some tests heterologous antivenom was more effective than homologous antivenom in protecting white mice against the effects of venom injection.
Poison information system in the management of poisoning. A. A. LATIFF, D. A. RAZAK, R. AWANG, M. B. BAHAm, M. I.A. MAJID, A. B.A. MAJEED, A.H. HUSSlN and S.H. HUSSAIN (Integrated Drug and Poison Information Service, School of Pharmaceutical Sciences, 11800 Penang, Malaysia). A CONSIDERABLEpercentage of cases in hospitals and health centres are those that arise from cases of drug overdoses, accidental poisoning, poisoning due to household products or pesticides, poisoning related to animal or plant toxins and those extending to environmental or occupational hazards. Toxic risks being widespread and escalating in the present decade necessitates efficient and accurate information with regard to poisoning and management of the poisoned patient. It is with this in mind that a Poison Information System was developed as an integral part of special programmes for poison control with capabilities to assist diagnosis, treatment and prevention of poisonings. The system consists of two main sections, namely poison information retrieval and poison epidemological data. A retrieval menu allows accessing of information on the clinical signs and
Tenth World Congress
Neutralization of haemorrhagic and lethal activities of Crotalus adamenteus venom by natural products. U. R. KUPPUSAMY and N.P. DAS (Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore 051 I). SEVERALnatural products such as the flavonoids (apigenin, kaempferol and luteolin) and tannic acid were tested for their ability to neutralize the haemorrhagic and lethal activities of Crotalus adamenteus venom. The venom alone or the venom plus test compound was administered s.c. into male Swiss mice (body wt. 20 + 2 g). The extent of haemorrhagic activity was determined by measuring the diameters of the haemorrhagic area. The four test compounds inhibited the haemorrhagic activity of the venom dose-dependently. Flavonoids (0.1/z mole) or tannic acid (6/~g) when present in the 50/~1 of venom solution (50 tz g/ml) could almost completely inhibit the haemorrhagic activity. Similar amounts of flavonoids or tannic acid when present in 5 x LOs0venom solution (s.c. LDS0= 27.0 # g/g body wt.) could significantly prolong the survival time(s) of the mice. The order of potency of the test compounds on their ability to antagonize the lethal activity of the venom is as follows: tannic acid >> luteolin = kaempferol)apigenin.
Coagulopathyfollowing Papua New Guinean taipan (Oxyuranus scutellatus canni) envenoming. D. LALLOO,1'2 J. BLACK,2 S. NARAQI,2 D. OWENS,3 A. CHITOLIE,3 R. A. HUTTON,3 R. D. G. THEAKSTON4 and D. A. WARRELL1'4 ('Centre for Tropical Medicine, University of Oxford, U.K.; 2University of Papua New Guinea, Boroko; 3Royal Free Hospital, London, U.K.; 4Liverpool School of Tropical Medicine, U.K.). MECHANISMS of coagulopathy were studied in 13 patients with incoagulable blood after taipan bites. Six had spontaneous bleeding, 11 local lymphadenopathy and seven neurotoxicity. Standard coagulation assays were used to compare the patients with nine healthy PNG controls and 20 normal London blood donors. All patients were severely defibrinated (fibrinogen levels 0-0.6 g/l), and as anticipated from the known prothrombin activator in taipan venom, Factor II levels were reduced (mean 47, range 8-88 u/d0. The labile factors (V and VIII) were very low (ranges 1-13 and 1-28du/l, respectively), partly due to activation of their physiological natural inhibitor, Protein C, which was also low (range 25-59 u/dl). Moderate deficiencies of factors IX, XI and XII were also seen.' Reduction in Factor XIII subunits, plasminogen and alpha-2 antiplasmin, together with elevated cross-linked FDPs (5-250/,g/ml) indicated activated fibrinolysis, although the much higher total FDP (1280-5120/tg/ml) suggested some fibrinogenolysis. The results indicate that a consumption coagulopathy, due in part to the action of the prothrombin activator, is induced by taipan envenoming, but suggest that other haemostatically active components, as yet unidentified, are also contributing to the clinical picture.
Scorpion antivenom production in Iran. M. LATIFI and M. TABATABA!(Razi Institute, P.O. Box 11365-1558 Tehran, Iran). LITTLE is known about the venom of the Iranian scorpion, of which there are more than 20 species. The medically important scorpions are found mostly in the warmer areas of Iran. The polyspecific antivenom was prepared by immunization of horses. The crude serum was purified and concentrated by enzyme digestion and salt fractionation. The venom was obtained either by electrical stimulation or by extraction of the macerated telson and was freeze-dried. Studies on the venom indicated that there were differences in the yields and lethalities of the species. Scorpion venoms of Iran were compared with regard to lethalities (i.v. LD50in mice) and rates of neutralization tests (i.v. mg/ml in mice). This paper describes neutralizattion tests conducted to determine the effectiveness of polyspecific available antivenoms, in the neutralization of homologous and heterologous scorpion venoms. During the studies described, several instances of cross-protection were found, and in some tests heterologous antivenom was more effective than homologous antivenom in protecting white mice against the effects of venom injection.
Poison information system in the management of poisoning. A. A. LATIFF, D. A. RAZAK, R. AWANG, M. B. BAHAm, M. I.A. MAJID, A. B.A. MAJEED, A.H. HUSSlN and S.H. HUSSAIN (Integrated Drug and Poison Information Service, School of Pharmaceutical Sciences, 11800 Penang, Malaysia). A CONSIDERABLEpercentage of cases in hospitals and health centres are those that arise from cases of drug overdoses, accidental poisoning, poisoning due to household products or pesticides, poisoning related to animal or plant toxins and those extending to environmental or occupational hazards. Toxic risks being widespread and escalating in the present decade necessitates efficient and accurate information with regard to poisoning and management of the poisoned patient. It is with this in mind that a Poison Information System was developed as an integral part of special programmes for poison control with capabilities to assist diagnosis, treatment and prevention of poisonings. The system consists of two main sections, namely poison information retrieval and poison epidemological data. A retrieval menu allows accessing of information on the clinical signs and