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Biomedical subjects

S Dutta

Publications and source records attributed to S Dutta.

At least 199 records · Page 11Linked to original sources
PubMed1981

Possible formation of nitrosamine in guinea pigs following exposure to nitrogen dioxide and dimethylamine.

The possibility of formation of nitrosamine was investigated in animals exposed to a combination of dimethylamine (DMA) and NO2. First, the distribution and covalent binding of DMA and dimethylnitrosamine (DMN) in rats and guinea pigs were determined. The apparent volume of distribution and biological half-life for [14C]-DMA or [14C]DMN did not reveal any species difference. In general, there were no marked differences in accumulation of radioactivity in tissues of guinea pigs and rats 4 h after the administration of DMA, while the guinea pig tissues showed higher accumulation after DMN administration. Nucleic acid fractions prepared from liver and lungs of both species following administration of DMN or DMA in vivo showed much higher covalent binding with DMN than with DMA. Furthermore, the covalent binding of DMN was found to be due to bioactivation, whereas the DMA binding was nonspecific. Since guinea pig liver showed a higher degree of covalent binding than rat liver, this species was used to investigate the possible increase in covalent binding in the presence of NO2 and DMA as a reflection of DMN formation. There was no evidence of enhancement of covalent binding when animals pretreated with [14C]-DMA were exposed for various lengths of time to different concentrations of NO2.

Animals↗
PubMed1979

Peroxidase activity in the rat breast tissue as a marker of estrogen action.

Peroxidase activity and its inducibility by estrogen in the uterine and breast tissues of Holtzman rats varied with the age of animals. Basal proxidase level of the two tissues was low in immature and high in older animals. Estrogen induced significant peroxidase activity in the uteri of rats up to 56 days of age and thereafter the uterine response was poor. Though the breast tissue peroxidase response to estrogen was significant in 20-160 days old female rats, greater inducibility being noted between 40-90 days of age. Among the sex steroids, only estrogen could induce the enzyme in the breast tissue in a dose dependent way. Peroxidase was also induced appreciably in the male breast tissue to an extent observed in age-matched females. It is suggested that this enzyme could be regarded as a diagnostic end point of estrogen action in the rat breast tissue.

Aging↗
PubMed1979

Stereochemical and dynamic aspects of genetic recombination.

The conformational features of three key intermediates in the gene conversion pathway are described. We have found that the dimensions of the trans turned structure involved in crossover are incompatible with normal H-bond formation occurring in opposing strands within the confines of 23 A axially separated double helices. However, if the separation is reduced to 18 A, slight rotation around the axis can give rise to crossover. A mechanism is proposed in which the crossover junction for short sequences migrates by torsional oscillations. This process is rapid enough to permit strand exchange of 100 bases in less than a millisecond. It is shown that the rotational diffusion mechanism becomes rate limiting for the crossover processes involving longer sequences.

Kinetics↗
PubMed1977

The relationship between Na+, K+-ATPase inhibition and cardiac glycoside-induced arrhythmia in dogs.

In order to determine if there is a relationship between Na+, K+-ATPase inhibition and cardiac glycoside-induced arrhythmia, the time course of the onset and offset of the arrhythmia induced by the semi-synthetic glycoside, actodigin, and the enzyme activity during arrhythmia and following reversion to normal sinus rhythm was studied in the intact, anethetized dog. An infusion of actodigin(AY22,241) at the rate of 0.1 micronmol/kg/min for 30 min induced a severe and persistent arrhythmia within 13.1 +/- 192 min of 9 dogs. Upon termination of the actodigin infusion, the arrhythmia spontaneously converted to sinus rhythm within 17.5 +/- 2.3 min. Left ventricular tissue was taken from dogs sacrificed at the peak of the actodigin-induced arrhythmic periods or from the dogs that were allowed to recover from the actodigin-induced arrhythmia. These samples were homogenized and the membrane-containing fraction was passed through a Millipore filter. The membrane fraction trapped in the filter was then assayed for Na+ + K+ stimulated, Mg2+ dependent ATPase acctivity. The results showed that, in comparison to the time matched control dogs, the cardiac microsomes prepared from the arrhythmic dogs had a markedly reduced Na+, K+-ATPase activity. On the other hand, actodigin-treated dogs that were allowed to recover from the arrhythmic episode had Na+, K+-ATPase activity that was not significantly different from the control values. The amount of 3H-actodigin bound by the cardiac muscle microsomal fraction was also investigated. The microsomes from left ventricle were isolated with a slight modification of the method of Dutta et al. (1968). The microsomal binding of 3H-actodigin was maximum at 30 min (26.6 mol/mg protein) when the sample was prepared from the dogs at the peak of the arrhythmic effect. However, the binding was significantly reduced (11.5pmol/mg protein) in the microsomal fraction from hearts that had returned to sinus rhythm. These data provide direct evidence that inhibition of Na+, K+-ATPase and cardiac glycosideinduced arrhythmia may have some cause and effect relationship.

Adenosine Triphosphatases↗
PubMed1977

Accumulation of radioactive cardiac glycosides by various brain regions in relation to the dysrhythmogenic effect.

Ouabain was administered at a loading dose of 3 mug/kg followed by an infusion at a rate of 1 mug/kg-1 min-1 in order to produce severe dysrhythmia in dogs within 60 minutes. Similarly, digitoxin at a loading dose of 9 mug/kg followed by an infusion at a rate of 3 mug kg-1 min-1 was administered to compare its effect with that of ouabain. 2 During the 60 min experimental period, the plasma concentrations gradually rose with the continuous infusion of these drugs. However, in comparison to the 60 min plasma value of 119+/-20 pmol/ml for ouabain and 177+/-68 pmol/ml for digitoxin, the cerebrospinal fluid (CSF) concentrations for these drugs at this time were less than 5 pmol/ml. 3 Upon termination of the experiment at 60 min it was found that kidney, liver, heart, adrenal, and the non-neural tissue in the brain such as pituitary and choroid plexus concentrated ouabain and digitoxin to give high tissue to plasma ratios. However, various neural areas of the brain (cerebellum, mesencephalon, hypothalamus, pons, and medulla) showed no preferential localization or uptake of these two glycosides. 4 Concentration of ouabain and digitoxin by the choroid plexus does not seem to affect the ionic composition of the CSF. 5 It was concluded that sampling the large areas of neural tissue above could provide no evidence for local accumulation of digitalis glycosides that might account for a central nervous system origin of digitalis-induced cardiac arrhythmias.

Animals↗
PubMed1976

The uptake and subcellular distribution of radio-labeled metabolites of digoxin in the isolated perfused guinea-pig heart.

Cardiac glycosides like digitoxin and digoxin with three digitoxoside sugar residues have been reported to undergo step-wise degradation to yield the corresponding genins, and the importance of the digitoxoside side-chain for the pharmaco-dynamics property of cardiac glycosides has also been suggested. A sytematic study was therefore undertaken on the cleavage products of digoxin. Digoxigenin-bis-digiitoxoside (with two sugar residues) digoxigenin-monodigitoxoside (with one sugar residue) and digoxigenin (with no sugar) were compared with the parent compound, digoxin. The radio-labeled compounds were perfused through isolated guinea pig hearts using 10-7 M concentration in the perfusion medium for a fixed period of 64 min followed by an 8 min period of wash-out with normal medium. The uptake and sub-cellular distribution of the drugs were thereafter measured scintillation counting. All the compounds produced postive inotropic responses, the mondigitoxoside producing the greatest effect, digoxigenin next in order of inotropic response magnitude, the bis-digitoxoside produced the least effect, and digoxin was intermediate between the genin and bis-digitoxoside. The uptake of the monodigitoxoside was the highest, and in general, the quantitative uptake was related to the inotropic response. The greatest binding of each digitoxoside was found in the microsomal fraction. Both mechanical activity and uptake of all four drugs were uniformly reduced by an increase in potassium concentration in the perfusion medium.

Animals↗
PubMed1976

Cardiac NaK ATPase activity during positive inotropic and toxic actions of ouabain.

In order to define pharmacological actions of ouabain in the dog heart, ouabain uptake and subcellular distribution and its effect on NaK ATPase (MG2+ dependent, Na+-K+-activated adenosinetriphosphate phosphohydrolase, E.C. 3.6.1.3), have been investigated in 21 open-chest dogs. A continuous infusion of ouabain (0.036 mug/kg/min) after a loading dose (20 mug/kg) produced a relatively constant plasma concentration of approximately 10(-8) M (6 ng/ml) ouabain, which induced a sustained positive inotropic response for the 300 min experimental period. In these hearts much greater binding of ouabain was noted in the NaK ATPase and microsomal fractions than in other myocardial fractions. No statistically significant inhibition of NaK ATPase activity was noted. Doubling the loading and infusion doses of ouabain raised the plasma level of ouabain to approximately 3 X 10(-8) M and produced various types of arrhythmia within an hour, which persisted for the rest of the 5 h experimental period. Under this experimental protocol there was a significant inhibition of NaK ATPase activity and increased binding of ouabain to this enzyme. This study does not support the hypothesis that there is a causal relationship between inotropic response to ouabain and NaK ATPase inhibition. It was concluded that NaK ATPase inhibition might be causally related to the development of ouabain toxicity.

Adenosine Triphosphatases↗
PubMed1976

The uptake and subcellular distribution of radio-labelled metabolites of digitoxin in the guinea-pig isolated perfused heart.

1 Comparisons were made of the uptake and inotropic effects of concentrations of 0.1 muM of digitoxin and its cleavage products digitoxigenin-bis-digitoxoside, digitoxigenin-mono-digitoxoside and digitoxigenin in the isolated perfused hearts of guinea-pigs. 2 Digitoxin produced the greatest inotropic responses in this series, while the sequence of cleavage products produced progressively smaller responses. 3 The uptake of digitoxin was significantly higher than that of the three metabolites, and the uptake of metabolites became progressively less with cleavage. The highest binding in each case was found in the microsomal fraction. 4 The uptake of all four digitaloids was reduced when the potassium in the perfusion medium was increased.

Animals↗
PubMed1973

The effects of diphenylhydantoin and potassium on the biological activity of ouabain in the guinea-pig heart.

1. Diphenylhydantoin (DPH) and potassium significantly prevent ouabain intoxication without preventing the inotropic effects of ouabain in the guinea-pig isolated heart.2. The antiarrhythmic effect of DPH and K on ouabain-induced toxicity appears to be related to their ability to reduce ouabain accumulation by the myocardium and thereby prevent the intracellular Na and K changes which lead to the arrhythmic state.

Animals↗
PubMed1972

Species and ionic influences on the accumulation of digitalis glycosides by isolated perfused hearts.

1. The ability of isolated perfused guinea-pig (digitalis-sensitive species) and rat (digitalis-resistant species) hearts to accumulate radio-labelled digitalis glycosides was studied in relation to the ionic composition of the perfusion medium.2. It was observed that in both species much less digoxin was accumulated than was digitoxin or proscillaridin.3. The accumulation of digoxin was markedly inhibited in a low sodium or in high potassium medium. These effects were similar, but relatively less marked, with digitoxin and proscillaridin. Calcium and magnesium removal had relatively smaller effects on the accumulation of both polar and non-polar glycosides.4. The low accumulation of all digitaloids by the rat heart in comparison to the guinea-pig heart may be due to the formation of unstable complexes between the cellular membranes in the rat heart and the various digitaloids used in this study. Although digitaloids have a reduced affinity for rat hearts and rat heart membranes in comparison to guinea-pigs, the order of the accumulation of different glycosides in both species is the same, i.e. much less with polar glycosides than with non-polar glycosides.5. It was concluded that non-polar glycosides such as digitoxin and proscillaridin demonstrate the same ion-dependent accumulation mechanism as do the more polar glycosides such as digoxin and ouabain. In addition, the non-polar glycosides possess high capacity for ion-independent binding presumably due to lipophilic interactions with membranes.

Animals↗