Organophosphorus poisoning-induced delayed neuropathy hen model induced by triorthocresyl phosphate and phenylmethylsulfonyl fluoride intervention / 中国组织工程研究

BACKGROUND:Although incidents of organophosphorus poisoning-induced delayed neuropathy (OPIDN) have been documented for over a century, the molecular mechanisms underlying the axonopathy remain poorly understood. Therefore, OPIDN treatment has been increasingly concerned. OBJECTIVE:To construct the OPIDN hen model induced by triorthocresyl phosphate (TOCP) and to explore the effect of phenylmethylsulfonyl fluoride (PMSF) intervention. METHODS:Adult hens were randomly divided into four groups: two TOCP groups, a PMSF group and a control group. TOCP groups were treated with TOCP by gavage at a single dosage of 1 000 mg/kg and 750 mg/kg respectively; control group was given an equivalent volume of saline by gavage while hens in the PMSF group were subcutaneously injected with 40 mg/kg PMSF 24 hours after 1 000 mg/kg TOCP injection. OPIDN neurological signs were assessed by a six-point graded scale. The changes of the hen weight were recorded. The hens were kiled on day 5 and 21 post-dosing. The samples were cut into 50 nm thick sections and examined by transmission electron microscopy. RESULTS AND CONCLUSION:OPIDN neurological signs such as abnormal gaits progressed in severity with time (P < 0.05), and the hen weight was significantly decreased in TOCP groups (P < 0.05). However, no clinical signs of delayed neurotoxicity were observed in hens of the PMSF group and the control group during the experiment period. The mild mitochondrial sweling and the fragmentation of microfilament and microtubule arrangement in axons were observed on day 5 post-dosing, leaving the other organeles remained unchanged. On day 21, neuronal degeneration was apparent, including sweling of endoplasmic reticulum, abnormal change of mitochondria, and disordered arrangement of cytoskeleton. The optimal dose of TOCP was 1 000 mg/kg. Experimental findings indicate that, OPIDN hen model induced by TOCP and PMSF intervention hen model were successfuly constructed. PMSF intervention significantly improved the pathologic changes and clinical symptoms of OPIDN induced by TOCP in hens.

Management of organophosphorus compound poisoning -A one year experience in a tertiary care hospital.

This study was undertaken to assess the distribution pattern, outcome and possible predictors affecting the mortality and the need for ventilator support in patients who had consumed organophosphorus compound pesticides. 91 patients who were admitted to the ICU between April 2009 and March 2010 with history of ingestion of organophosphorus pesticide, were studied. Baseline clinical assessment and investigations were undertaken and SOFA and APACHE II scores were calculated. Out of 91 patients, 39 required ventilator support. Of these 39 patients, 2 died, one due to severe sepsis and multiorgan dysfunction, and the other, a chronic alcoholic with chronic liver disease, due to hepatic encephalopathy and multiorgan dysfunction. The time elapsed since ingestion of poison, SOFA and APACHE II scores were significantly associated with patients requiring ventilator support. However with logistic regression analysis, none of these variables were able to either predict mortality or the need for ventilator support. The overall outcome in these cases was favourable as the mortality rate was 2.3%. Though the time elapsed since ingestion of the pesticide and the APACHE II score were found to predict the need for ventilation in many earlier studies, they failed to predict either the need for ventilation or mortality in the present study. The improved mortality rate could be attributed to an organized approach through protocols between the emergency department and the ICU in order to successfully manage patients with organophosphorus compound poisoning.

Recurrent Hypoglycaemia in Organophosphorus Compound Poisoning - An Unusual Complication.

Organophosphorus compound poisoning commonly presents with muscarinic, nicotinic and central nervous system manifestations. Endocrinal complications of various organophosphorus compounds are rare and cannot be explained by commonly known mechanisms. We report a clinically proven case of organophosphorus compound poisoning in a young male, in whom at least 22 episodes of hypoglycaemia (blood sugar levels in the range of 47–80 mg %) were observed over 2 weeks during his hospi-talization. Hypoglycaemic episodes completely disappeared upon recovery from poisoning. The exact mechanism for such recurrent hypoglycaemia requires detailed evaluation. This report emphasizes the need to observe blood sugar levels in patients with organophosphorus compound poisoning, so as to detect and promptly treat this rare yet important and correctable complication.

Isoenzyme Pattern of Creatine Kinase in Acute Organophosphorus Compound Poisoning.

Pesticide poisoning is an important cause of mobidity and mortality in many developing countries. Many organo-phosphorus (OP) pesticide poisoning cases are reported in teaching medical college hospitals of Tamil Nadu every year. Generally, routine biochemical parameters are studied in detail in acute OP poisoning cases. In this study, an attempt was made to study the isoenzyme pattern of serum creatine kinase (CK) in acute OP poisoning. Acute OP cases were classified according to severity of poisoning. Eight cases in each grade (1, 2, 3 & 4) were selected for the study from IMCU and Toxicology ward of Government General Hospital, Chennai between August 2005 and April 2008, and analysed for isoenzyme of CK. Results revealed elevation of 100% CK-MM fraction of CK for Grade 1, 2 & 3 acute OP poisoning cases. Grade 4 cases showed a mild increase in CK-BB and CK-MB fractions along with predominant CK-MM fraction. The increase of CK in acute OP cases is primarily due to respiratory or pulmonary disorder and is not derived from cardiac or skeletal muscles of the body.

Multiple unusual complications in a single patient with combined organophosphate-carbamate pesticide exposure.

Poisoning with organophosphate (OP) or carbamate (CM) pesticides is very common in India. These compounds are powerful inhibitors of acetylcholinesterase, causing accumulation of acetylcholine resulting in muscarinic and nicotinic effects. In addition, there are often direct CNS effects including headache, tremor, delirium, slurred speech, ataxia, and convulsions. Coma supervenes in the later stages. Apart from these, OP poisoning can also induce an “intermediate syndrome” (IMS) characterized by proximal muscle weakness and paralysis; a “delayed syndrome” (organophosphate-induced delayed neuropathy or OPIND) characterized by polyneuropathy and weakness of distal limb muscles; and neuropsychiatric disturbances (chronic organophosphate-induced neuropsychiatric disorder or COPIND). Other disorders have very rarely been reported, such as Guillain-Barre syndrome, Parkin-sonism, transient hepatic dysfunction, pancreatitis, vocal cord paralysis, etc. We report a case of combined organophosphate-carbam-ate poisoning with multiple complications, e.g., intermediate syndrome (IMS), delayed neuropathy (OPIND), and Parkinsonism. These complications are rare, and some of them to the best of our knowledge have not been reported so far.

Organophosphorus compound poisoning deaths in children: An autopsy survey from Manipal.

A 16-year retrospective autopsy-based study (1992–2008) was undertaken by the department of forensic medicine of Kasturba Medical College, Manipal to ascertain the profile of fatal organophosphorus compound poisoning in the paediatric age group. Out of 2532 autopsies performed during the period, twenty-four victims formed the material for the study. The age group of 13–18 years was most commonly affected, with a significant male preponderance. Many of the cases were suicidal in nature. Nearly half of the victims survived for a period of more than a day after consuming poison. A seasonal variation was noticed, with many cases being reported in the summer months.

Study of occupational exposure to insecticides while spraying in cotton farms.

Organophosphorus compounds (OPC) are commonly used in farms and agricultural fields as insecticides. This study deals with manifestations of exposure among 40 workers engaged in the spraying of cotton crops with these insecticides over a period of two months. The compounds used were mostly monocrotophos, acephate, chlorpyriphos, methyl parathion and propanophos. All patients were illiterate males in the range of 15 years to 50 years of age. They showed typical manifestations of OPC poisoning. All of them responded to conventional treatment for OPC poisoning. There was one death. During the course of the survey it was found that none of the farmers were using protective gear as mandated by chapter VIII of Insecticides Rules, 1971 (Insecticides Act, 1968). A few of these workers were exposed to the insecticide for as much as nine hours per day for three days. In practice, in some deaths associated with OPC poisoning, history of inhalation is given. It is important to note that this could change the manner of death from suicidal to accidental. Due precaution must therefore be exercised in such cases before opining on the manner of death. It is imperative that extensive and persistent farmer education is done with regard to the implementation of various provisions under the Insecticides Rules, 1971, especially safety issues.

Determination of malathion in blood and urine using thin-layer chromatography.

Malathion is a broad-spectrum Organophosphorus insecticide generally used to control a variety of insects. Routinely it is analysed by Gas Liquid Chromatography & High Performance Liquid Chromatography. Now an attempt has been made to develop a new method for analysis of Malathion in biological samples using Thin Layer Chromatography (TLC) technique, which is inexpensive, accurate and non-destructive. Malathion was extracted from blood and urine using solvent extraction methods and then identified on the TLC plates. For chromatographic separation, various binary and tertiary solvent systems were used to demonstrate in the laboratory. For detection on developed plates, palladium chloride reagent was used which successfully increased the sensitivity without dispensing with the simplicity of the method. For the analysis, a total of 20 solvent systems were chosen. Out of these 20 solvent systems, the three best solvent systems namely Cyclohexane: Chloroform (60:40), Hexane: Acetone (80:20) and Acetone: Hexane: Toluene (40:40:20) were chosen for statistical analysis which included the calculation of mean Rf value, value of standard deviation and coefficient of variance. The method developed is simple, inexpensive, accurate and non-destructive that allows for sensitive and reproducible analysis of Malathion.

Effects of organophosphorus compound, cyanofenphos on the glucose metabolism in rats / 日本農村医学会雑誌

In order to observe the effect of organophosphorus compound, cyanofenphos (0-ethyl 0-4 -cyanophenyl phenylphosphonothioate) (CYP) on the glucose metabolism, 20 mg/kg of CYP was repeatedly administered <I>per</I> os to male Wistar rats, weighing approximately 150g. The supression of the serum and brain cholinesterase activity increased with times of administration, but muscular strength of extremities was not suppressed. The concentration of serum glucose, however, was enhanced in spite of the increase in the concentration of serum insulin. The mechanism of hyperglucosaemia resulted from the supression of the incorporation of glucose into cells in peripheral tissues without the activation of glycogen phosphorylase and suppression of glycogen synthetase activity. It was suggested that the suppression of the incorporation of gulcose into cells resulted from inhibition of insulin receptors or entry sites of glucose in cells by cyanofenphos.<BR>The relation between disturbances of the glucose metabolism and the delayed neurotoxicity was discussed.

Effects of organophosphorus compounds, prothiofos, cyanofenphos and chlorpyrifos on lipid metabolism in rats / 日本農村医学会雑誌

In order to observe the effects of organophosphorus compounds on lipid metabolism, 4mg of prothiofos, cyanofenphos or 1mg of chlorpyrifos were administered per os to different groups of rats, and the results were as follows;<BR>1) Serum cholinesterase activity was significantly suppressed in the experimental group administered these pesticides compared with the control group, administered salad oil only.<BR>2) The lipase activity in the liver was suppressed by administration of prothiofos and that in the kidney was also suppressed by cyanofenphos. There was a close positive correlation between the cholinesterase and lipase activity in epididymal adipose tissues of rats administered prothiofos or cyanofenphos. Furthermore, the positive correlation between the cholinesterase and lipase activity in the kidney was close on day 2 after administration.<BR>3) The acyl CoA synthetase activity in the liver of rats administered cyanofenphos was signifcantly lower than that of the control group, and there was close positive correlation between the cholinesterase and acyl CoA synthetase activity in the rats administered prothiofos.<BR>4) The serum concentration of beta-lipoprotein decreased in the group administered cyanofenphos or chlorpyrifos.<BR>5) The suppression of the lipase and acyl CoA synthetase activity was independent of the serum concentration of immunoreactive insulin.