In vitro effects of organophosphate pesticides on rat erythrocytes

In vitro effects of various organophosphate pesticides (dimethoate, chlorpyrifos, ethion and monocrotophos) were studied on hemolysis, K+ leakage and lipid peroxidation in rat erythrocytes. All the four pesticides increased hemolysis and K+ leakage from erythrocytes, that was concentration and time dependent. On the contrary, there was decrease in lipid peroxidation in erythrocyte membrane. Effect of pesticides on lipid peroxidation could be due to pesticide itself abstracting protons or interacting with free radicals rather than polyunsaturated fatty acids (PUFA), thereby protecting the latter against peroxidation.     

Cerebrovascular effects of intravenous dopamine infusions in fetal sheep.

Preterm infants are often treated with intravenous dopamine to increase mean arterial blood pressure (MAP). However, there are few data regarding cerebrovascular responses of developing animals to dopamine infusions. We studied eight near-term and eight preterm chronically catheterized unanesthetized fetal sheep. We measured cerebral blood flow and calculated cerebral vascular resistance (CVR) at baseline and during dopamine infusion at 2.5, 7.5, 25, and 75 microg x kg(-1) x min(-1). In preterm fetuses, MAP increased only at 75 microg x kg(-1) x min(-1) (25 +/- 5%), whereas in near-term fetuses MAP increased at 25 microg x kg(-1) x min(-1) (28 +/- 4%) and further at 75 microg x kg(-1) x min(-1) (51 +/- 3%). Dopamine infusion was associated with cerebral vasoconstriction in both groups. At 25 microg x kg(-1) x min(-1), CVR increased 77 +/- 51% in preterm fetuses and 41 +/- 11% in near-term fetuses, and at 75 microg x kg(-1) x min(-1), CVR increased 80 +/- 33% in preterm fetuses and 83 +/- 21% in near-term fetuses. We tested these responses to dopamine in 11 additional near-term fetuses under alpha-adrenergic blockade (phenoxybenzamine, n = 5) and under dopaminergic D(1)-receptor blockade (SCH-23390, n = 6). Phenoxybenzamine completely blocked dopamine's pressor and cerebral vasoconstrictive effects, while D(1)-receptor blockade had no effect. Therefore, in unanesthetized developing fetuses, dopamine infusion is associated with cerebral vasoconstriction, which is likely an autoregulatory, alpha-adrenergic response to an increase in blood pressure.     

Treatment of organophosphate poisoning. Experience of nerve agents and acute pesticide poisoning on the effects of oximes

Organophosphate (OP) compounds have been used as pesticides and in chemical warfare (nerve agents). Two nerve agents, tabun and sarine, were used by the Iraqi army against Iranian troops and innocent people. Hundreds of the exposed combatants died in the field. Atropine sulphate has been used successfully in large doses to counteract the muscarinic effects of OP poisoning. The effects of oximes in human OP poisoning have not been well studied. Our aim was to study the effects of obidoxime and pralidoxime in OP pesticide poisoning. The patients were divided into three groups: atropine (A), obidoxime + atropine (OA) and pralidoxime + atropine (PA). Sixty-three patients (33 males, 30 females) with a mean age of 25 years were studied in different groups (43 A, 22 OA and 8 PA). There were no statistical significant differences in major clinical findings and acetylcholinesterase (AChE) activity on admission between the groups. Significant changes were observed during the treatment. Notwithstanding the severity of intoxication — particularly respiratory complications were more observed in the OA and PA groups — there were no fatalities in the PA group, whereas 4 (9%) and 6 (50%) patients in the A and OA groups died, respectively. AChE reactivation was only observed in the PA group, although it was not statistically significant (r = 0.4747). There was a good relationship between the AChE reactivation and outcome of the patients. High doses of obidoxime (8 mg/kg followed by 2 mg/kg/h) were found to be hepatotoxic and should be avoided. High doses of pralidoxime (30 mg/kg followed by 8 mg/kg/h) did not induce serious side effects and may be effective in some OP pesticides poisoning.

Résumé

Les composés organophosphorés (OP) ont été utilisés comme pesticides et comme gaz de combat (agents neurotoxiques). Deux gaz de combat, appelés tabun et sarin, ont été utilisés par l'armée iraquienne contre les troupes iraniennes et des populations civiles. Des centaines de combattants ont péri sur le champ de bataille. Le sulfate d'atropine à fortes doses a été utilisé avec succès pour supprimer les effets muscariniques des organophosphorés. L'effet des oximes n'a pas été bien étudié dans le cas d'empoisonnements humains pour ces agents. Nous avons donc entrepris d'analyser des effets de l'obidoxime et de la pralidoxime. Les patients ont été divisés en trois groupes, recevant l'atropine seule (A), l'atropine avec l'obidoxime (OA) et la pralidoxime avec l'atropine (PA). Soixante trois patients (33 hommes et 30 femmes) d'âge moyen 25 ans, ont été traités (43 A, 12 OA et 8 PA). Il n'y avait aucune différence statistiquement significative entre les états cliniques et les niveaux d'acétylcholinestérase (AChE) entre les groupes lors de leur admission, mais des différences importantes sont apparues au cours du traitement. Bien que la sévérité de l'intoxication, en particulier les complications respiratoires, ait été plus marquée dans les groupes OA et PA, il n'y a pas eu de décès dans le groupe PA, alors qu'il y en a eu 4 dans le groupe A (9 %) et 6 dans le groupe OA (50%). Nous n'avons observé de réactivation de l'AChE que dans le groupe PA, et elle n'était pas statistiquement significative (r = 0,5). Nous avons observé une bonne corrélation entre la réactivation d'AChE et l'état des patients. De fortes doses d'obidoxime (8 mg/kg, suivi par 2 mg/kg/h) ont produit une hépatoxicité et doivent être évitées. De fortes doses de pralidoxime (30 mg/kg, suivi de 8 mg/kg/h) n'ont pas induit d'effets secondaires sérieux et peuvent être efficaces dans certains cas d'intoxication par les OPs.     

Plasma triiodothyronines in fetal sheep: effects of illness and thyroidectomy.

Plasma 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine concentrations were measured in fetal sheep prior to death in utero and after thyroidectomy. In six fetal sheep who subsequently died in utero, plasma rT3 concentrations were elevated in all for 2 to 13 days prior to death. There were no consistent changes in plasma T4 concentrations. In two thyroidectomized fetal sheep, plasma T4 and rT3 concentrations fell to low levels. Plasma T3 concentrations remained low and there was no increase in plasma T3 in the last week prior to parturition like that which occurs in normal fetal sheep. Parturition was preceded by the normal increase in fetal plasma cortisol concentrations and occurred at the normal time. These data indicate that plasma rT3 concentrations are increased as a result of illness in fetal sheep and that such measurements may be useful as an indicator of fetal distress. The normal increase in plasma T3 late in gestation is not necessary for the late gestational cortisol surge or for normal parturition.     

有机磷生物修复研究进展

目前,有机磷的生物修复还主要是微生物修复。但是植物修复更具优越性,因其花费更少、对环境更安全。然而植物对生长条件的要求相对较高,修复效率较低,应用还非常有限。本文综述了有机磷微生物修复和植物修复的研究进展,总结了已知的有机磷降解酶及其生物来源。结果表明,植物材料的筛选、土壤与OPs作用机理的研究、植物耐受和消除OPs的基因组学研究、植物-微生物联合降解体系的建立以及降解酶的植物根系分泌系统的利用是提高有机磷植物修复效率的重要途径。     

Cardiorespiratory effects of nifedipine in pregnant sheep

Four concentrations of nifedipine (AdalatR, Bayer) were infused into 25 pregnant sheep of 123-140 days of gestation (term, 147 days) and the effects on the ewe and the foetus have been studied. At all doses of nifedipine infused, maternal diastolic pressure fell by about 15% and maternal heart rate increased by 33%. There was no change in blood gases or pH. Uterine activity, as measured by uterine electromyographic recordings, was reduced due to an increase in the interval between periods of activity. The duration of a burst of activity remained unaffected. The effects of nifedipine on the foetus, were similar. Mean foetal arterial pressure fell by 4-5 mmHg and heart rate rose by 15 to 50%, both changes being maintained for the duration of the infusion and the increased heart rate for longer. The electrocorticogram of the foetal sheep was unaffected by nifedipine. The effects on foetal breathing movements were small. At the concentration of 5 micrograms/kg/min for either 2 or 4 hours the breathing pattern changed so that the episodes of breathing were shorter and more frequent. The total amount of breathing per hour was unaffected. Control infusion of ethanol had little effect on the ewe except for a significant increase in lactate production. In the foetus breathing was reduced at the highest concentration used.