Search PubMed⌕ Search

Biomedical subjects

V K Chadha

Publications and source records attributed to V K Chadha.

7 recordsLinked to original sources

Tuberculin test.

Although tuberculin test is widely used for detection of tuberculous infection among children, there is no clear understanding about its performance and interpretation. This article has been written with the purpose of elucidating the performance and interpretation of standard tuberculin test, based on the experiences gained at the National Tuberculosis Institute, Bangalore and other centres. The standard tuberculin test involves intradermal injection of '1TU PPD RT23 with Tween 80' on the mid-volar aspect of forearm and measurement of the maximum transverse diameter of induration after 3 days. Larger the size of induration, higher is the probability of it being due to tuberculous infection. The majority of reactions with induration size of 15 mm and above are attributable to infection with tubercle bacilli, irrespective of BCG-vaccination status. While indurations of less than 5 mm indicate absence of any kind of tuberculin sensitivity, the majority of indurations in 5-9 mm range are usually of non-tuberculous nature. An induration of 10-14 mm requires more careful interpretation. It is more likely to be attributable to infection with tubercle bacilli in case of history of contact with smear positive case or among children with clinical findings of tuberculosis. However, the size of induration in an infected child may be diminished in the presence of immuno-suppressive conditions. One should also consider the purpose of the test while interpreting the test results.

BCG Vaccine↗

Inhibition of liver alcohol dehydrogenase and ethanol metabolism by 3-substituted thiolane 1-oxides.

3-Substituted thiolane 1-oxides (methyl, n-butyl, n-hexyl, and phenyl) were prepared and tested as inhibitors of horse, monkey, and rat liver alcohol dehydrogenases and of ethanol metabolism in rats. These compounds inhibit alcohol oxidation in an uncompetitive manner with respect to ethanol as a varied substrate. Lengthening the alkyl substituent increased the inhibitory potency because of tighter binding in the hydrophobic substrate binding pocket of the alcohol dehydrogenases. Thus, the 3-hexyl derivative was the most potent inhibitor of the purified rat liver alcohol dehydrogenase, with a Kii value of 0.13 microM. The 3-butyl derivative was the best inhibitor of ethanol metabolism in rats, with a Kii value of 11 mumol/kg. The acute toxicity in mice of the butyl derivative was 1.4 mmol/kg. Since high concentrations of alcohol do not prevent the inhibitory effects of these compounds, they may be particularly useful for preventing poisoning by methanol or ethylene glycol.

Alcohol Dehydrogenase↗

Inactivation of horse liver alcohol dehydrogenase by modification of cysteine residue 174 with 3-bromopropionic acid.

Horse liver alcohol dehydrogenase is inactivated with Michaelis kinetics at pH 7 and 25 degrees C by 3-bromopropionic acid. In the absence of NAD+, the Ki is 2 mM, and the pseudo bimolecular rate constant (k3/Ki) is 0.03 M-1 s-1; in the presence of 1 mM NAD+, Ki is 2.3 mM, and k3/Ki is 0.006 M-1 s-1. 3-Bromopropionic acid is a competitive inhibitor, Ki of 0.4 mM, against ethanol as a substrate. Inactivation was prevented in the ternary complexes with NAD+ X pyrazole and NADH X isobutyramide, was retarded by NAD+, NADH, or bipyridine, and was almost unaffected by imidazole and AMP. Carboxyethylated enzyme did not detectably (as observed spectrophotometrically) bind bipyridine, NAD+, or NADH. Enzyme was inactivated with radioactive 3-bromopropionic acid, aminoethylated, and digested with trypsin and chymotrypsin. Analysis of the labeled peptides showed that Cys-174 was predominantly modified. In the presence of 1 mM NAD+, the reaction was much less specific. The interaction of the carboxyl group of 3-bromopropionic acid with the guanidino group of Arg-369 probably facilitates the selective reaction with Cys-174, which is ligated to the zinc at the active site. Carboxyethylation apparently inactivates by interfering with the proper binding of the pyrophosphate of the coenzyme to the enzyme.

Alcohol Dehydrogenase↗

Inhibition by carboxamides and sulfoxides of liver alcohol dehydrogenase and ethanol metabolism.

Sulfoxides and amides were tested as inhibitors of liver alcohol dehydrogenase and ethanol metabolism in rats. With both series of compounds, increasing the hydrophobicity resulted in better inhibition, and introduction of polar groups reduced inhibition. Of the cyclic sulfoxides, tetramethylene sulfoxide was the best inhibitor as compared to the tri- and pentamethylene analogue and other compounds, and it may be a transition-state analogue. The most promising compounds, tetramethylene sulfoxide and isovaleramide, were essentially uncompetitive inhibitors of purified horse and rat liver alcohol dehydrogenases with respect to ethanol as substrate. These compounds also were uncompetitive inhibitors in vivo, which is advantageous since the inhibition is not overcome at higher concentrations of ethanol, as it is with competitive inhibitors, such as pyrazole. The uncompetitive inhibition constants for tetramethylene sulfoxide and isovaleramide for rat liver alcohol dehydrogenase were 200 and 20 microM, respectively, in vitro, whereas in vivo the values were 340 and 180 mumol/kg. The differences in the values may be due to metabolism or distribution of the compounds. Further studies will be required to determine if isovaleramide or tetramethylene sulfoxide is suitable for therapeutic purposes.

Alcohol Dehydrogenase↗

Effect of gossypol on domestic fowl, Gallus domesticus.

Domestic fowls (Gallus domesticus) were administered gossypol (10 mg/kg body weight/day) by oral intubation for 15 weeks. Drug treatment did not have any effect on body growth rate. The drug treatment, however, caused a marked decrease in the weights of testis and epididymis. Predominant changes in the histoarchitecture of testis (desquamation of germinal epithelium and inhibition of spermatogenesis) were observed following gossypol treatment. Epididymal tubules in gossypol treated animals were devoid of spermatozoa. Gossypol treatment had no effect on hematological parameters (total erythrocyte count, total leucocyte count, hematocrit and hemoglobin) studied in the present investigations.

Animals↗