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Peripheral neurotoxicity in human viper bite envenomations
S120
Abstracts / Toxicology Letters 164S (2006) S1–S324
P5-12 Peripheral neurotoxicity in human viper bite envenomations
P5-13 In vitro comparison of eight acetylcholinesterase reactivators to reactivate VX inhibited ACHE
D. Lonati, A. Giampreti, C. Locatelli, R. Butera, V. Petrolini, L. Manzo
Daniel Jun, Jiri Bajgar, Kamil Kuca
Poison Centre and National Toxicology Information Centre, Toxicology Unit, IRCCS Maugeri Foundation and University of Pavia, Italy In the last years, cases involving peripheral neurological symptoms (PNS) after European Vipera species envenomation have been reported both in Italy and South-Eastern France. PNS can be related to the presynaptic toxicity of phospholipases A2 (PLA2), viper venom neurotoxins that cause neuromuscular paralysis. PNS involve mostly cranial nerves and have always been observed in patients with moderate to severe nonneurological systemic symptoms. Objective: To identify and describe the characteristics of PNS observed in patients referred to Pavia Poison Center after viper bite. Methods: Patients observed over a 2 years period were reviewed. Cases were assessed for presence, severity and time course of local, neurological and non-neurological associated signs, overall management and outcome. Results: Six adult patients with PNS were observed. PNS included bilateral (3/6 patients) or monolateral (1/6) ptosis, diplopia (3/6), dysphagia (1/6) and bilateral deficit of masseter muscles (1/6). All patients showed local signs from mild (2/6), to moderate (3/6), to massive limb edema (1/6). Systemic non-neurotoxic effects (vomiting, diarrhea) occurred in 4/6 patients; 2 patients showed local signs and PNS in absence of any other systemic symptoms. PNS were observed 4–30 h after the bite, while systemic non-neurotoxic effects occurred earlier (40 min–17 h). Antivenom was administered in 3/6 patients as soon as PNS were observed. In treated patients, PNS started to improve between 6 and 11 h, and resolved between 24 and 26 h after the onset. In untreated patients PNS improved and resolved later (between 7 and 44, and between 55 and 64 h after the onset, respectively). Conclusion: PNS observed seems to be strictly connected with the mechanism of action of PLA2; PNS can occur with a delayed onset and even in patients presenting only with local effects so a thorough clinical evaluation also for these patients is advisable. Antivenom administration seems to be beneficial in shortening the persistence of PNS, but its efficacy needs to be further investigated in a larger series. doi:10.1016/j.toxlet.2006.06.252
Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic A comparison of one mono-(pralidoxime) and seven bis-(methoxime, obidoxime, K027, K074, K075, HI-6 and HS-6) quaternary acetylcholinesterase reactivators inhibited by VX agent was performed. As a source of the acetylcholinesterase, a rat brain homogenate was taken. There were significant differences in reactivation potency of all tested oximes. The oxime K075 seems to be the most efficacious followed by K074, HI-6, HS6, K027, obidoxime, MMC and 2-PAM. In addition, the results of this study showed, that the reactivation potency of the tested reactivators depends on their structural factors—such as the number of pyridinium rings (two are better than one), the position of functional oxime groups (position four is preferred), as well as the length of the linker bridge between two pyridinium rings (three and four membered chain is preferred). This work was supported by the Ministry of Defence (Czech Republic), Grant No. FVZ0000604. doi:10.1016/j.toxlet.2006.06.253 P5-14 Effects of low dose methylmercury administration during postnatal brain spurt in rats Pietro Borracci 1 , Addolorata Coluccia 1 , Michele 1 Giustino 1 , Mineshi Persichella , Arcangela 2 1 Sakamoto , Maria Rosaria Carrat`u 1 Department
of Pharmacol. and Human PhysiologyMedical School-University of Bari, Italy; 2 National Institute for Minamata Disease, Minamata, Japan Rapid brain growth occurs primarily during the third trimester of pregnancy in humans, whereas in rats it occurs mainly after parturition. In particular, the rat cerebellum is vulnerable to methylmercury during late brain spurt. In the present experiments the effects of low dose methylmercury treatment were studied during the postnatal developing phase in rats. Male Sprague–Dawley rats were orally administered 0.75 mg/kg/day methylmercury chloride (MMC) on postnatal day 14 for 10 consecutive days. This dose level, resulting in MMC brain concentration of 0.82 ± 0.05 g/g tissue, did not cause the typical symp-
Abstracts / Toxicology Letters 164S (2006) S1–S324
P5-12 Peripheral neurotoxicity in human viper bite envenomations
P5-13 In vitro comparison of eight acetylcholinesterase reactivators to reactivate VX inhibited ACHE
D. Lonati, A. Giampreti, C. Locatelli, R. Butera, V. Petrolini, L. Manzo
Daniel Jun, Jiri Bajgar, Kamil Kuca
Poison Centre and National Toxicology Information Centre, Toxicology Unit, IRCCS Maugeri Foundation and University of Pavia, Italy In the last years, cases involving peripheral neurological symptoms (PNS) after European Vipera species envenomation have been reported both in Italy and South-Eastern France. PNS can be related to the presynaptic toxicity of phospholipases A2 (PLA2), viper venom neurotoxins that cause neuromuscular paralysis. PNS involve mostly cranial nerves and have always been observed in patients with moderate to severe nonneurological systemic symptoms. Objective: To identify and describe the characteristics of PNS observed in patients referred to Pavia Poison Center after viper bite. Methods: Patients observed over a 2 years period were reviewed. Cases were assessed for presence, severity and time course of local, neurological and non-neurological associated signs, overall management and outcome. Results: Six adult patients with PNS were observed. PNS included bilateral (3/6 patients) or monolateral (1/6) ptosis, diplopia (3/6), dysphagia (1/6) and bilateral deficit of masseter muscles (1/6). All patients showed local signs from mild (2/6), to moderate (3/6), to massive limb edema (1/6). Systemic non-neurotoxic effects (vomiting, diarrhea) occurred in 4/6 patients; 2 patients showed local signs and PNS in absence of any other systemic symptoms. PNS were observed 4–30 h after the bite, while systemic non-neurotoxic effects occurred earlier (40 min–17 h). Antivenom was administered in 3/6 patients as soon as PNS were observed. In treated patients, PNS started to improve between 6 and 11 h, and resolved between 24 and 26 h after the onset. In untreated patients PNS improved and resolved later (between 7 and 44, and between 55 and 64 h after the onset, respectively). Conclusion: PNS observed seems to be strictly connected with the mechanism of action of PLA2; PNS can occur with a delayed onset and even in patients presenting only with local effects so a thorough clinical evaluation also for these patients is advisable. Antivenom administration seems to be beneficial in shortening the persistence of PNS, but its efficacy needs to be further investigated in a larger series. doi:10.1016/j.toxlet.2006.06.252
Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic A comparison of one mono-(pralidoxime) and seven bis-(methoxime, obidoxime, K027, K074, K075, HI-6 and HS-6) quaternary acetylcholinesterase reactivators inhibited by VX agent was performed. As a source of the acetylcholinesterase, a rat brain homogenate was taken. There were significant differences in reactivation potency of all tested oximes. The oxime K075 seems to be the most efficacious followed by K074, HI-6, HS6, K027, obidoxime, MMC and 2-PAM. In addition, the results of this study showed, that the reactivation potency of the tested reactivators depends on their structural factors—such as the number of pyridinium rings (two are better than one), the position of functional oxime groups (position four is preferred), as well as the length of the linker bridge between two pyridinium rings (three and four membered chain is preferred). This work was supported by the Ministry of Defence (Czech Republic), Grant No. FVZ0000604. doi:10.1016/j.toxlet.2006.06.253 P5-14 Effects of low dose methylmercury administration during postnatal brain spurt in rats Pietro Borracci 1 , Addolorata Coluccia 1 , Michele 1 Giustino 1 , Mineshi Persichella , Arcangela 2 1 Sakamoto , Maria Rosaria Carrat`u 1 Department
of Pharmacol. and Human PhysiologyMedical School-University of Bari, Italy; 2 National Institute for Minamata Disease, Minamata, Japan Rapid brain growth occurs primarily during the third trimester of pregnancy in humans, whereas in rats it occurs mainly after parturition. In particular, the rat cerebellum is vulnerable to methylmercury during late brain spurt. In the present experiments the effects of low dose methylmercury treatment were studied during the postnatal developing phase in rats. Male Sprague–Dawley rats were orally administered 0.75 mg/kg/day methylmercury chloride (MMC) on postnatal day 14 for 10 consecutive days. This dose level, resulting in MMC brain concentration of 0.82 ± 0.05 g/g tissue, did not cause the typical symp-