Objective: To study the antioxidant status and the extent of oxidative stress in patients with organophosphorus insecticide (OPI) poisoning before and after specific treatment. Material and Methods: The study was conducted in eighty-four OPI poisoned patients. Superoxide dismutase (SOD) and malonyl aldehyde (MDA) levels were estimated as an index of antioxidant status and oxidative stress respectively and comparisons were made (a) between different grades of poisoning based on clinical features and anticholinesterase (AChE) levels, (b) before and after therapy with atropine sulfate plus pralidoxime (PAM) and (c) between healthy control subjects and OPI poisoned patients. Results: There was a progressive fall in both the RBC and plasma AChE levels which correlated with the severity of poisoning. Upon therapy, profound improvement in the AChE levels was observed (an increase by 20.5% and 20.9% in RBC and plasma AChE levels respectively). There was also an increase in the MDA levels which nearly doubled in OPI poisoned patients who failed to survive (3.6 + 0.92 to 6.7 + 2.3 nM/ml). SOD levels increased parallel to the severity of poisoning, but did not normalize after therapy. Conclusion: The increased level of MDA in OPI poisoned patients who failed to survive was probably reflective of accelerated lipid peroxidation, cell damage and death (oxidative stress). Significant improvement was noticed in the AChE (serum and RBC) levels of patients with specific treatment but without much change in the antioxidant status as reflected by the SOD and MDA levels.

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Echinocandins are a new option for fungal infections. They are fungicidal and less toxic to the host by virtue of their novel mechanism of action. They are b-1, 3-glucan synthase inhibitors. FDA, USA has approved caspofungin for treatment of invasive aspergillosis in patients who fail to respond or are unable to tolerate other antifungals. Two other agents are in phase III clinical trials – micafungin and anidulafungin. Caspofungin among echinocandins has been studied vastly and offers apparent exciting advantages of a broad spectrum of activity including strains of fungi resistant to other antifungal agents, tolerability profile, with no nephrotoxicity and hepatotoxicity as compared to azole and macrolide antifungals. It may be effective in AIDS-related candidal esophagitis, oropharyngeal candidiasis, fungal pneumonia and nonmeningeal coccidioidomycosis. Clinical trials are required to ascertain their safety in special groups—pediatric, pregnant and nursing mothers. Echinocandins provide an exciting option for combination therapy with other antifungals in fulminant fungal infections.

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Objective: To study the pharmacokinetics of ofloxacin using salivary drug concentration when administered alone or in combination with rifampicin (R), isoniazid (H) and pyrazinamide (Z) and also to assess the saliva to plasma concentration ratio. Material and Methods: Twelve healthy male volunteers were investigated on four different occasions with an interval of at least one week between occasions. They were administered ofloxacin, either alone or in combination with R, H and Z. A partially balanced incomplete block design was adopted and the subjects were randomly allocated to each group. Salivary and plasma concentrations of ofloxacin were measured at 1, 2, 3, 6 and 8 h after drug(s) administration using validated methods. Results: There were no significant differences between various pharmacokinetic parameters when ofloxacin was administered alone or in combination with R, H and Z. The mean saliva to plasma ratio of ofloxacin concentration was around 0.6. The bioavailability indices of ofloxacin in the saliva and plasma were similar in all the groups. Conclusion: Several pharmacokinetic parameters could be calculated using salivary concentrations of ofloxacin. The determination of ofloxacin levels in saliva may be useful in therapeutic drug monitoring and pharmacokinetic studies.

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Objective: To evaluate the protective efficacy of certain chemoprotectants against cyclic peptide hepatotoxic microcystin-LR in mice. Material and Methods: Swiss albino female mice were used in all experiments for screening antidotes against the lethal dose of microcystin-LR (100 mg/kg body weight, i.p.). The agents, D-glucose, mannitol, dihydroxyacetone, Trolox®, L-cysteine, N-acetylcysteine, amifostine, glutathione, silymarin, naringin, rifampin and cyclosporin-a were administered as either pre-treatment (1, 3 and 24 h), co-administration or post-treatment. Percent survival and time to death were monitored. The biochemical profile of protected animals was monitored 24 h post-treatment. Results: D-glucose, mannitol, L-cysteine, naringin and amifostine extended the survival time of animals but offered no protection against lethality. N-acetylcysteine, glutathione and Trolox® gave partial protection (25-50%) on pretreatment or co-administration. Complete protection was observed with rifampin (25 mg/kg), cyclosporin-A (10 mg/kg) and silymarin (400 mg/kg) when given as pre-treatment. In addition, rifampin and cyclosprin-A gave complete protection when co-administered with microcystin-LR. Rifampin was the only agent which gave protection at 15 min post-treatment. The biochemical profile of surviving animals 24 h after treatment showed increased liver body weight index and levels of hepatic enzymes viz. LDH, ALT, SDH in serum. Conclusion: Chemoprotectants that can inhibit the specific uptake of toxin into the liver can be promising antidotes against lethal poisoning by microcystin-LR in mice.

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Objective: This study was conducted to compare the potential inhibitory effect of ATP-dependent K+ channel blockers, glibenclamide and chlorpropamide on diazoxide-induced relaxation of isolated rat ileum. Material and Methods: The study was performed on rat ileum connected to an isotonic transducer and the contractions were recorded on one-channel MD2 recorder. In this study the relaxant effect of diazoxide on KCl-induced precontracted rat ileum, and its inhibition by different concentrations of glibenclamide and chlorpropamide were studied. Results: Diazoxide (10-5-10-3M) produced dose-dependent relaxation. EC50 for diazoxide-induced relaxation was 8 x 10-5M. Neither glibenclamide nor chlorpropamide had any effect on the resting tension of the rat ileum preparation. Both glibenclamide and chlorpropamide reversed diazoxide-induced relaxation. The pA2 values for glibenclamide and chlorpropamide reversal of diazoxide induced- relaxation were 6.3 and 5 respectively. Conclusion: The results confirm that the inhibitory effect of glibenclamide on diazoxide-induced relaxation in rat ileum is higher than that of chlorpropamide.

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Objective: To characterize nicotinic cholinergic receptors (cholinoceptors) in frog rectus abdominis and mouse esophagus. Material and Methods: Isolated preparations of mouse esophagus and frog rectus abdominis were separately mounted in organ baths filled with Krebs and Ringer solutions respectively. The organ bath medium was continuously gassed with 95% O2 and 5% CO2 and the temperature was maintained at 370C and 250C for mouse esophagus and frog rectus abdominis respectively. Changes in muscle length were recorded by isotonic transducers. The effects of neuromuscular blocking agents were investigated on contractions mediated by nicotinic cholinoceptors in both the preparations. Results: The contractions induced by carbachol (Cch) (5x10-6-5x10-5 M) were significantly inhibited by pancuronium (10-9-5x10-8) in mouse esophagus and frog rectus abdominis. Gallamine inhibited the contractions in the frog rectus abdominis but it failed to reduce the Cch responses in the mouse esophagus. On the other hand, d-tubocurarine caused irreversible contractions in the basal tonus of frog rectus abdominis, but it reduced the contractions evoked by Cch in mouse esophagus. Conclusion: The different effects of the neuromuscular blocking agents on contractions mediated by nicotinic cholinoceptors in frog rectus abdominis and mouse esophagus indicated that the nicotinic cholinoceptors in two different tissues may not be identical and these differences may be attributed to the different nicotinic cholinoceptor subtypes.

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