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Biomedical subjects

P Bhatia

Publications and source records attributed to P Bhatia.

At least 55 records · Page 3Linked to original sources

Dose-dependent radiation effect on microvasculature and repair.

It has been postulated that the damage to microvasculature may be a major factor in the manifestation of late radiation damage to organized tissue. In this study, the radiation damage to microvasculature was investigated in a rabbit model during the early phases of irradiation with the use of vascular permeability as a marker. By means of a triple isotopic technique, the vascular, extravascular, and intracellular spaces could be defined. A forelimb and hindlimb of New Zealand White rabbits were irradiated with single doses of 2-30 Gy. 125I- and 131I-labeled bioscreened albumin were used to determine the changes in vascular permeability due to irradiation. The rabbits were sacrificed at various intervals post irradiation. Vascular and extravascular spaces and the respective albumin concentrations in tissue samples from irradiated limbs were compared with control values from the unirradiated contralateral limbs in each animal. The results indicated a definite increase in the vascular permeability of albumin secondary to irradiation. The increase in vascular permeability was apparent instantaneously with irradiation, even at 2 Gy. The microvascular compromise appear to be dose related. When examined at 16-24 hours post irradiation, the excess extravasation of albumin was significant at and beyond 8 Gy. At 10-30 days post irradiation, injury was not apparent up to 15 Gy. Thus there appeared to be an instantaneous injury at the capillary level due to irradiation, which appeared to be dose related. A repair process became evident as early as 16-24 hours and appeared to be dose related as well as related to elapsed time post irradiation.

Animals↗

Catechol O-methyltransferase. 12. Affinity labeling the active site with the oxidation products of 5,6-dihydroxyindole.

5,6-Dihydroxyindole (5,6-DHI) and a series of 4- and/or 7-methylated analogues of 5,6-DHI have been synthesized and evaluated for their ability to inactivate purified rat liver catechol O-methyltransferase (COMT). The inactivation of COMT by these agents could be prevented by excluding oxygen from the incubation of mixtures, indicating the necessity for their oxidation to the corresponding aminochromes. Substrate protection studies and kinetic studies suggested that the loss of enzyme activity resulted from the modification of a crucial amino acid residue at the active site of COMT through reaction with the quinoid oxidation products. The COMT inhibitory activity of the 4- and/or 7-methylated analogues of 5,6-DHI argue against a mechanism involving a 1,4 Michael addition reaction at positions 4 or 7 on the aminochrome. Considering the number of potential electrophilic centers on the basic aminochrome structure, the site of the reaction might change depending on the aromatic substitution pattern. The preferred pathway of reaction may be determined in part by the juxtaposition of the protein nucleophile to the possible sites of attack on the electrophilic ligand but also in part on the reactivity of the electrophilic site which might change with substitution on the aromatic ring.

Aerobiosis↗

Mucin producing islet cell adenoma.

A well granulated beta cell adenoma of the pancreas was found incidentally at autopsy in a patient with a ruptured aortic aneurysm. The tumor was studied by histochemical an immunocytochemical methods. It consisted of a trabecular arrangement of insulin storing cells intermingled with small ducts. Both components were tightly contiguous. Goblet cells were also present within the tumor cell nests. The implication of the growth of the different types of cells is discussed in relation to the concept of an APUD system.

Adenoma↗

Metabolism of azulene in rats.

1. Azulene was rapidly metabolized in the rat and excreted in the urine as the sulphate conjugate of 1-hydroxyazulene; 45% of the dose was recovered as pure metabolite from the 0-24 h urine. 2. [1,3(-2)H2]Azulene was converted in vivo to 1-hydroxyazulene sulphate which was shown by 1H-n.m.r. spectroscopy to contain one deuterium at C-3 and essentially no detectable deuterium at C-2. This result suggests that, if a 1,2-oxide of azulene was an intermediate in the 1-hydroxylation, it rearranged with direct loss of deuterium from C-1 rather than an NIH shift to C-2.

Animals↗

Effect of hydrazine sulfate on glucose-regulating enzymes in the normal and cancerous rat.

Glucokinase, hexokinase, fructose 1,6-bisphosphatase and phosphoenolpyruvate carboxykinase specific activities were monitored in liver cytosol from rats that had been made cancerous with 1,2-dimethylhydrazine and then treated with hydrazine sulfate. The presence of intestinal cancer, specifically, was confirmed by laparotomy and by histological analysis. Sustained changes in hexokinase and glucokinase specific activities were first evident during the latter weeks that the carcinogen was being administered. Upon subsequent treatment with hydrazine sulfate, glucokinase activity further decreased, and liver cytosolic phosphoenolpyruvate carboxykinase activity increased. Liver cytosolic hexokinase and fructose 1,6-bisphosphatase specific activities were not appreciably affected by the hydrazine sulfate treatment. These results indicate that hydrazine sulfate may influence carbohydrate metabolism at the level of selected liver enzymes not only with respect to gluconeogenesis, but also in terms of glucose uptake.

1,2-Dimethylhydrazine↗