Kirandip Gill

Cytochrome-C oxidase inhibition in 26 aluminum phosphide poisoned patients

Introduction. Aluminum phosphide (ALP) is used worldwide to fumigate grain. ALP poisoning, though reported from different parts of world, is most common in north, northwest and central India. In the presence of moisture, ALP liberates phosphine, which is highly toxic. The mechanism of action of phosphine is not known though experimental studies show that it inhibits cytochrome-c oxidase leading to inhibition of mitochondrial oxidative phosphorylation. Patients and Methods. We estimated cytochrome-c oxidase activity in platelets of patients who had ingested ALP and compared them with those in healthy controls and in patients with shock due to other causes (cardiogenic shock, septic shock and hemorrhagic shock). Results. After analysis of variance using Kruskal-Wallis test followed by Mann Whitney U test, significant inhibition of cytochrome-c oxidase activity could be found in ALP-poisoned patients compared to healthy controls (z = −5.513, p < 0.001) and in patients with shock due to other causes (z = −2.344; p < 0.05). There was no significant difference in inhibition in those who survived ALP poisoning compared to those who died from ALP poisoning (t = 0.02768; p > 0.05). Conclusion. Though inhibition of cytochrome-c oxidase in platelets does not have prognostic value, it suggests that interruption of mitochondrial oxidative phosphorylation as a result of cytochrome-c oxidase inhibition may lead to multi-organ dysfunction and therapeutic strategies to maintain enzyme activity may help in managing these patients.

Hyperamylasemia and acute pancreatitis following anticholinesterase poisoning

A prospective study was undertaken to find the incidence of hyperamylasemia and acute pancreatitis in patients with anticholinesterase poisoning. This was done by serial estimation of total serum amylase and pancreatic imaging by ultrasonography and confirmed, if necessary, by computerized tomography. Anticholinesterase poisoning was caused by either ingestion or accidental exposure to organophosphates or carbamates; it was diagnosed when patients presented with features of cholinergic crisis, depressed serum butrylcholinesterase activity of >50% and showed improvement following administration of atropine alone or atropine and 2-PAM. All the patients admitted with anticholinesterase poisoning between July 2001 and June 2005 were prospectively studied for elevated serum amylase. The serum amylase levels were estimated daily up to 10 days in survivors and in nonsurvivors till they survived. Ultrasonography of the abdomen was carried out in all to find swelling of the pancreas. Computerized tomography was undertaken in those who had a swollen pancreas or whose serum amylase levels were elevated significantly (≥800 S.U). Of the 86 patients enrolled, 79 were taken up for analysis as data were incomplete in 7. Of the 79 patients, serum amylase was found to be elevated that is, >200 S.U. in 37 patients (46.95%). In three patients it was 800 S.U. One of them showed swollen pancreas on ultrasonography, which was confirmed by computerized tomography. This patient had ingested propoxyfur. In the other two patients, evidence of acute pancreatitis was not observed (on autopsy in one who died and on imaging in the other who survived). They had ingested chlorpyriphos. There was no significant correlation between the nature of the compounds (organophosphate or carbamates), inhibition of serum BUChE at admission, duration and severity of cholinergic syndrome and increase and time course of increase in serum amylase. Except for fenthion, significant persistent increase in serum amylase was not observed with individual compounds. The other associated abnormalities were polymorphonuclear leukocytosis (TLC >11 000/cumm) in all 37 patients who had elevated amylase, hyperglycemia (6/37) and, elevated transaminases (6/37). Mild elevation of serum amylase is common in patients with anticholinesterase poisoning. However, acute pancreatitis is rare. Human & Experimental Toxicology (2007) 26 , 467—471

Lead-induced peripheral neuropathy following Ayurvedic medication.

Lead poisoning following intake of Ayurvedic medication is one of the recent areas of concern. We report a case of a 58-year-old type II diabetic man who was stable with diet control and 30 mg pioglitazone per day. He took Ayurvedic medication for generalized weakness and developed peripheral neuropathy following its intake. He was found to have high blood and urinary lead levels and was diagnosed to have subacute lead poisoning. He was treated with d-Penicillamine for 8 weeks, following which his lead levels became normal. The use of d-Penicillamine was proved highly effective in treating a case of lead poisoning.

Letter to the Editor: “Reply to “Comment on ‘Cytochrome-C Oxidase Inhibition in 26 Aluminum Phosphide Poisoned Patients’””

INTRODUCTION Aluminum phosphide (ALP) is used worldwide to fumigate grain. ALP poisoning, though reported from different parts of world, is most common in north, northwest and central India. In the presence of moisture, ALP liberates phosphine, which is highly toxic. The mechanism of action of phosphine is not known though experimental studies show that it inhibits cytochrome-c oxidase leading to inhibition of mitochondrial oxidative phosphorylation. PATIENTS AND METHODS We estimated cytochrome-c oxidase activity in platelets of patients who had ingested ALP and compared them with those in healthy controls and in patients with shock due to other causes (cardiogenic shock, septic shock and hemorrhagic shock). RESULTS After analysis of variance using Kruskal-Wallis test followed by Mann Whitney U test, significant inhibition of cytochrome-c oxidase activity could be found in ALP-poisoned patients compared to healthy controls (z = -5.513, p < 0.001) and in patients with shock due to other causes (z = -2.344; p < 0.05). There was no significant difference in inhibition in those who survived ALP poisoning compared to those who died from ALP poisoning (t = 0.02768; p > 0.05). CONCLUSION Though inhibition of cytochrome-c oxidase in platelets does not have prognostic value, it suggests that interruption of mitochondrial oxidative phosphorylation as a result of cytochrome-c oxidase inhibition may lead to multi-organ dysfunction and therapeutic strategies to maintain enzyme activity may help in managing these patients.