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Genetic and biochemical studies on deltamethrin (a synthetic pyrethroid) resistance in anopheles stephensi — A malaria mosquito
Poster Session 2H. Chemical Weapons the clinicians should pay attention to treating the benzene poisoning while treating acute organophosphorus pesticides poisoning (AOPP) so as to improve greatly the success in the treatment of AOPP in future.
IP2G223I GENETIC ANDBIOCHEMICAL STUDIES ON DELTAMETHRIN (A SYNTHETIC PYRETHROID) RESISTANCE IN ANOPHELES STEPHENSI- A MALARIA MOSQUITO
N.J. Shetty *, B.H. Rajasree. Centre for Applied Genetics, Bangalore University; J. B. Campus, Bangalore 560 056, India An.stephensi is one of the important urban malaria vectors in the Indian subcontinent. The present investigation deals with the establishment of resistant and susceptible strains of An. stephensi to deltarnethrin for the dosage of 0.004 ppm using W.H.O. standard procedure. From the data of various genetic crosses, LC 50 values and variances of resistant, susceptible and F I hybrid, the degree of dominance was found to be I indicati ng that deltarnethrin resistance was incompletely dominant and autosomal . There is an increase of 10.34 percent total proteins, 4-34 percent soluble proteins, and 5.36 percent general esterase levels in resistant individuals during different stages of development. A marked difference has also been noticed in protein and esterase isozyme profiles during electrophoresis.
IP2G224I PROBLEMS OF BIOLOGICAL VARIABILITY
PRESERVATION IN CONNECTION WITHTHE USE OF PESTICIDES
V.N. Rakitsky,Erisman Institute of Hygiene, Moscow, Russia Analysis of acute peroral toxicity effects of more than 100 pesticides belonging to various chemical classes is performed taking into account species, intraspecie s (age, sex) and interspecies differences. The following order of the increase in differences in toxicity at the level of letal pesticide doses is established intraspecies ~ species ~ interspecies. The mechanism of this rule is due to the differences in toxicokinelics, toxicodynarnics and detoxication systems. Thi s rule indicates the necessity to study the pesticide toxicity at a larger scale of organisms species) and to assess on this basis the risk of individual species disappearance. The goal of such a study will be the biological variability preservation. Classifications of species and intraspecies differences are suggested.
IP2G22S1
LONG-TERM EFFECTS OF CARBAMATES ATTHE MOUSE NEUROMUSCULAR JUNCTION
A.L. Rowbotham , CB. Ferry. Pharmaceutical Sciences Institute, Aston University. Birmingham B4 7ET, UK Carbamate (CB) anti-cholinesterases (anti-Chli) are used as prophylactics against organophosphate poisoning, as pesticides and as therapeutics. Prolonged CB exposure has been associated with myopathy, which is largely uncharacterised. The effects of CBs on skeletal muscle were studied using endplate deformation as a sensitive, quantifiable indicator of early myopathic changes i.e. hypercontractions arising from abnormal intra-cellular concentrations after anti-ChE induced prolonged cholinergic agonism [I]. Male albino mice were continually infused with 11.4 nmol hr-I pyridostigmine or 14 nmol hr- l physostigmine for 14 days (longterm study) or 7 days (recovery study). At intervals during and after treatment, diaphragms were removed and the width (W) and length (L) dimensions of endplates stained for cholinesterase were measured . Both CBs rapidly induced myofibril hypercontractions characterised by the deformation of endplates from an oval to a round
149
morphology as indicated by the WIL ratios in Table 1. These mild myopathic changes persisted after treatment termination and recovery was slow. Table I: Width/length ratios of endplates. (* indicates a significant difference from untreated groups (P < 0.05, MANOVAl Time
Untreated I day 7 days 14 days 7 + 14 days recovery
Pyridostigmine
Physostigmine
0.56 ± 0.04 0.82 ± 0.10' 0.83 ± 0.06' 0.85 ± 0.07' 0.71 ± 0.18'
0.56 ± 0.04 0.92 ± 0.04' 0.81 ± 0.05' 0.88 ± 0.07' 0.70 ± 0.08'
(II (II Ancilewski. A., Crofts. M., Ferry, C.B. and Smith, M.E. (1996) Human & Exp. Toxicol, 14,
IP2G23S1
THE ROLEOF SURFACTANTS IN CARDIOVASCULAR EFFECTS OF A HERBICIDE CONTAINING BIALAPHOS - IN VIVO AND IN VITRO ANALYSIS IN RATS
K. Koyama *, Ky. Koyama 1 , K. Goto 1 • Institute of Clinical Medicine. and Institute of Basic Medical SciencesI , University of Tsukuba; Tsukuba, Ibaraki, Japan The suicidal ingestion of the herbicide HARBlE® (bialaphos sodium 18%) causes hypotension and CNS disorders, the latter is suspected to be due to L-glufosinate, the active metabolite of bialaphos. We clarified the exact component that causes direct cardiovascular effects of HARBIE. Methods: In vivo HARBIE , bialaphos, L-glufosinate, and two surfactants contained in HARBIE (Sur l and SurZ) were used. Each drug was injected intravenously to male Wistar rats (8-week-old) under urethane anesthesia The blood pressure (BP) and heart rate (HR) was measured through the femoral artery . In vitro Each drug was cummulatively applied to Ringer' s solution where right atrium (RA) , electrically driven left atrium (LA), or a ring segment of aorta was suspended. The spontaneous beating rate of RA, isometric tension of LA and aorta was recorded. Results: In vivo HARBIE and Surl caused a decrease in BP and HR. Sur Z causes similar but mild effects. The other drugs caused no effects. In vitro In RA, HARBIE caused negative chronotropic efffects, whereas Sur I and SurZ caused similar and more mild effects. In LA, HARBIE and Sur! causes positive inotropic effects, whereas SurZ caused similar but mild effects. In high concentrations, HARBIE. Surl, and SurZ causes negative inotropic effects. In aorta, HARBlE and Sur! causes vasodilative effects, whereas SurZ caused similar but more mild effects. The other drugs caused no effects. Discussion: The direct cardiovascular effects of HARBIE are due essentially to Surl and partly to SueZ, but not due to the main component bialaphos or its metabolite L-glufosinate.
P2H. Chemical Weapons
IP2H226 I
INTERACTION OF MEMANTINE AND PYRIDINIUM OXIMES IN MICELETHALLY INTOXICATED WITH SOMAN
B. Milic *1, M.P. Stojiljkovic'", M. Maksimovicl , M. Nedeljkovic" , M. Dukic 1 , V. Kilibarda 2 . ] Department of Toxicological Chemistry.
School of Pharmacy. University ofBelgrade; 2 Military Poison Control Centre, Military Medical Academy, Belgrade, FR. Yugoslavia Previous experiments have shown that memantine prophylaxis affords good protection in rats lethally poisoned with soman and treated
IP2G223I GENETIC ANDBIOCHEMICAL STUDIES ON DELTAMETHRIN (A SYNTHETIC PYRETHROID) RESISTANCE IN ANOPHELES STEPHENSI- A MALARIA MOSQUITO
N.J. Shetty *, B.H. Rajasree. Centre for Applied Genetics, Bangalore University; J. B. Campus, Bangalore 560 056, India An.stephensi is one of the important urban malaria vectors in the Indian subcontinent. The present investigation deals with the establishment of resistant and susceptible strains of An. stephensi to deltarnethrin for the dosage of 0.004 ppm using W.H.O. standard procedure. From the data of various genetic crosses, LC 50 values and variances of resistant, susceptible and F I hybrid, the degree of dominance was found to be I indicati ng that deltarnethrin resistance was incompletely dominant and autosomal . There is an increase of 10.34 percent total proteins, 4-34 percent soluble proteins, and 5.36 percent general esterase levels in resistant individuals during different stages of development. A marked difference has also been noticed in protein and esterase isozyme profiles during electrophoresis.
IP2G224I PROBLEMS OF BIOLOGICAL VARIABILITY
PRESERVATION IN CONNECTION WITHTHE USE OF PESTICIDES
V.N. Rakitsky,Erisman Institute of Hygiene, Moscow, Russia Analysis of acute peroral toxicity effects of more than 100 pesticides belonging to various chemical classes is performed taking into account species, intraspecie s (age, sex) and interspecies differences. The following order of the increase in differences in toxicity at the level of letal pesticide doses is established intraspecies ~ species ~ interspecies. The mechanism of this rule is due to the differences in toxicokinelics, toxicodynarnics and detoxication systems. Thi s rule indicates the necessity to study the pesticide toxicity at a larger scale of organisms species) and to assess on this basis the risk of individual species disappearance. The goal of such a study will be the biological variability preservation. Classifications of species and intraspecies differences are suggested.
IP2G22S1
LONG-TERM EFFECTS OF CARBAMATES ATTHE MOUSE NEUROMUSCULAR JUNCTION
A.L. Rowbotham , CB. Ferry. Pharmaceutical Sciences Institute, Aston University. Birmingham B4 7ET, UK Carbamate (CB) anti-cholinesterases (anti-Chli) are used as prophylactics against organophosphate poisoning, as pesticides and as therapeutics. Prolonged CB exposure has been associated with myopathy, which is largely uncharacterised. The effects of CBs on skeletal muscle were studied using endplate deformation as a sensitive, quantifiable indicator of early myopathic changes i.e. hypercontractions arising from abnormal intra-cellular concentrations after anti-ChE induced prolonged cholinergic agonism [I]. Male albino mice were continually infused with 11.4 nmol hr-I pyridostigmine or 14 nmol hr- l physostigmine for 14 days (longterm study) or 7 days (recovery study). At intervals during and after treatment, diaphragms were removed and the width (W) and length (L) dimensions of endplates stained for cholinesterase were measured . Both CBs rapidly induced myofibril hypercontractions characterised by the deformation of endplates from an oval to a round
149
morphology as indicated by the WIL ratios in Table 1. These mild myopathic changes persisted after treatment termination and recovery was slow. Table I: Width/length ratios of endplates. (* indicates a significant difference from untreated groups (P < 0.05, MANOVAl Time
Untreated I day 7 days 14 days 7 + 14 days recovery
Pyridostigmine
Physostigmine
0.56 ± 0.04 0.82 ± 0.10' 0.83 ± 0.06' 0.85 ± 0.07' 0.71 ± 0.18'
0.56 ± 0.04 0.92 ± 0.04' 0.81 ± 0.05' 0.88 ± 0.07' 0.70 ± 0.08'
(II (II Ancilewski. A., Crofts. M., Ferry, C.B. and Smith, M.E. (1996) Human & Exp. Toxicol, 14,
IP2G23S1
THE ROLEOF SURFACTANTS IN CARDIOVASCULAR EFFECTS OF A HERBICIDE CONTAINING BIALAPHOS - IN VIVO AND IN VITRO ANALYSIS IN RATS
K. Koyama *, Ky. Koyama 1 , K. Goto 1 • Institute of Clinical Medicine. and Institute of Basic Medical SciencesI , University of Tsukuba; Tsukuba, Ibaraki, Japan The suicidal ingestion of the herbicide HARBlE® (bialaphos sodium 18%) causes hypotension and CNS disorders, the latter is suspected to be due to L-glufosinate, the active metabolite of bialaphos. We clarified the exact component that causes direct cardiovascular effects of HARBIE. Methods: In vivo HARBIE , bialaphos, L-glufosinate, and two surfactants contained in HARBIE (Sur l and SurZ) were used. Each drug was injected intravenously to male Wistar rats (8-week-old) under urethane anesthesia The blood pressure (BP) and heart rate (HR) was measured through the femoral artery . In vitro Each drug was cummulatively applied to Ringer' s solution where right atrium (RA) , electrically driven left atrium (LA), or a ring segment of aorta was suspended. The spontaneous beating rate of RA, isometric tension of LA and aorta was recorded. Results: In vivo HARBIE and Surl caused a decrease in BP and HR. Sur Z causes similar but mild effects. The other drugs caused no effects. In vitro In RA, HARBIE caused negative chronotropic efffects, whereas Sur I and SurZ caused similar and more mild effects. In LA, HARBIE and Sur! causes positive inotropic effects, whereas SurZ caused similar but mild effects. In high concentrations, HARBIE. Surl, and SurZ causes negative inotropic effects. In aorta, HARBlE and Sur! causes vasodilative effects, whereas SurZ caused similar but more mild effects. The other drugs caused no effects. Discussion: The direct cardiovascular effects of HARBIE are due essentially to Surl and partly to SueZ, but not due to the main component bialaphos or its metabolite L-glufosinate.
P2H. Chemical Weapons
IP2H226 I
INTERACTION OF MEMANTINE AND PYRIDINIUM OXIMES IN MICELETHALLY INTOXICATED WITH SOMAN
B. Milic *1, M.P. Stojiljkovic'", M. Maksimovicl , M. Nedeljkovic" , M. Dukic 1 , V. Kilibarda 2 . ] Department of Toxicological Chemistry.
School of Pharmacy. University ofBelgrade; 2 Military Poison Control Centre, Military Medical Academy, Belgrade, FR. Yugoslavia Previous experiments have shown that memantine prophylaxis affords good protection in rats lethally poisoned with soman and treated