Effects of inhaled sublethal concentration of methyl isocyanate on lung mechanics in rats.
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Biomedical subjects
Publications and source records attributed to R Vijayaraghavan.
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With a view to ascertaining the possible role of water content of the cells in the reported elevated values for proton spin-lattice relaxation time (T1) in malignant tissues, measurements of percent water content as well as T1 were undertaken in 68 cases of normal and concerous tissues from diverse sites in human patients. T1 values for the uninvolved samples were found to lie in the range of 400-1000 msec while the corresponding range for the involved samples was from 450-1520 msec. Water content of both normal and uninvolved tissues mostly lay in the narrow range of 70-90%. Occasionally samples with large T1 values showed lower water content as well. Data obtained weakens the case for characterization of tumor cells on the basis of their water content alone.
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The effect of sulphur mustard (2,2'-dichlorodiethyl sulphide) exposure through inhalation at 0.5. 1.0 and 2.0 LC50 (21.2, 42.3 and 84.6 mg m(-3) for 1 h) on some urinary variables was studied in female mice at 6, 24 and 48 h and 7 days post-exposure. The urinary excretion and circulatory blood accumulation of uric acid increased significantly. The level of creatine was also elevated significantly as compared to the control at 2 LC50. It is concluded that sulphur mustard alkylates DNA and triggers catabolism of apurinated purine bases in a very short time. The increase in uric acid excretion in urine can be detected only when the exposure concentration is high.
Sulfur mustard (SM), chemically bis (2-chloroethyl) sulfide is a bifunctional alkylating agent that causes serious blisters on contact with human skin. Although several antidotes have been reported for the systemic toxicity of SM in experimental animals none of them are approved so far and decontamination of SM immediately by physical or chemical means is recommended as the best protection. Two compounds amifostine [S-2(3-aminopropylamino) ethyl phosphorothioate] and DRDE-07 [S-2(2-aminoethylamino) ethyl phenyl sulfide] gave very good protection as an oral prophylactic agent against SM the in mouse model, but in the rat model the protection was only moderate. In the search for more effective and less toxic compounds, a number of analogues of DRDE-07 were synthesised and their protective efficacy was evaluated in mouse and rat models. The LD50 of S-aryl substitution was between 1 and 2 g kg(-1) and S-alkyl substitution was more than 2 g kg(-1). In the mouse model, DRDE-07, DRDE-10, DRDE-21, DRDE-30 and DRDE-35 gave about 20 fold protection, and DRDE-23 and DRDE-38 gave less protection of 4.8 and 9.0 fold respectively, against percutaneously administered SM. In the rat model, DRDE-07, DRDE-09, DRDE-10 and DRDE-21 gave about two fold protection. Percutaneously administered SM (19.33 mg kg(-1)) significantly depleted the hepatic GSH content in mice. Pretreatment with DRDE-21 significantly elevated the levels. A 4.4 fold increase in % DNA fragmentation was observed 7 days after SM administration (19.33 mg kg(-1)) in mice. Pretreatment with DRDE-07, DRDE-09, DRDE-10, DRDE-21, DRDE-30 and DRDE-35 significantly protected the mice from SM induced DNA damage. The histopathological lesions in liver and spleen induced by percutaneously administered SM was reduced by pretreatment with DRDE-07, DRDE-09, DRDE-10 and DRDE-21. These analogues may prove as prototypes for the designing of more effective prophylactic drug for SM.
Delayed neurotoxicity of sarin in mice after repeated inhalation exposure has been studied. Female mice exposed to atmospheric sarin (5 mg m-3 for 20 min) daily for 10 days developed muscular weakness of the limbs and slight ataxia on the 14th day after the start of the exposure. These changes were accompanied by significant inhibition of neurotoxic esterase (NTE) activity in the brain, spinal cord and platelets. Histopathology of the spinal cord of exposed animals showed focal axonal degeneration. These changes were comparatively less than in animals treated with the neurotoxic organophosphate, mipafox. Results from this study indicate that sarin may induce delayed neurotoxic effects in mice following repeated inhalation exposure.