Gopi Krishna - Academia.edu (original) (raw)
Papers by Gopi Krishna
Mutation Research/genetic Toxicology, 1985
The pesticide, ethylene dibromide (EDB), was evaluated with in vivo cytogenetic assays to determi... more The pesticide, ethylene dibromide (EDB), was evaluated with in vivo cytogenetic assays to determine its genotoxicity. CD1 male mice were exposed to EDB through intraperitoneal injections. Bone marrow cells isolated from femora were analyzed for sister-chromatid exchange (SCE), chromosome aberration and micronucleus formation. The results showed that only certain concentrations of EDB tested caused a slight but significant increase in SCEs and chromosome aberrations. However, these increases were not dose-related. No increase in the polychromatic erythrocytes with micronuclei was observed following EDB exposure. Also, EDB did not cause cell-cycle delay in comparison with controls. Thus, it appears that EDB is not an effective genotoxic agent in vivo in mice.
Clinics in Endocrinology and Metabolism, 1984
Biochemical Pharmacology, 1969
Absbnct-Epididymal fat pads from fasting rats were more sensitive to the lipolytic effects of the... more Absbnct-Epididymal fat pads from fasting rats were more sensitive to the lipolytic effects of theophylline than fat pads from fed animals, but the maximum response to this agent was the same in both groups. From these results it may be inferred that fasting did not change the amount of adipose tissue lipase. Tbe amount of activatable adenyl cyclase in adipose tissue was increased about 2-fold by fasting, as shown by direct assay of the enzyme as well as by the increase in the maximum lipolytic response to norepinephrine (NE) in vitro. However, in vivo the adenyl cyclase appears to be activated by a nonadrenergic system, since the rise in free fatty acids (WA) is not inhibited by propranolol, a beta adrenergic blocking drug, though it is inhibited by nicotinic acid. Kinetic analysis of the inhibitory effects of propranolol on lipolytic responses to NE in vitro suggest that characteristics of the receptor, presumably adenyl cyclase, are similar in fasting and fed animals.
Pharmacology, 1971
Treatment of rats with Phenobarbital stimulates the metabolism of bromobenzene and potentiates th... more Treatment of rats with Phenobarbital stimulates the metabolism of bromobenzene and potentiates the hepatic necrosis elicited by the hydrocarbon. In contrast, administration of SKF 525-A or of piperonyl butoxide blocks bromobenzene metabolism and prevents the damage to the ...
Annals of The New York Academy of Sciences, 1971
Dr. Shannon neglected to state that he is really the father of clinical pharmacology. During the ... more Dr. Shannon neglected to state that he is really the father of clinical pharmacology. During the war, I had the privilege of working on the clinical screening of antimalarials a t Goldwater Memorial Hospital, New York, headed by this gifted investigator. I advise clinical pharmacologists to read his concepts on clinical pharmacology, published in the Harvey Lectures, 1945-46, Vol. 42. Despite the emergency nature of the antimalarial project, Dr. Shannon realized how quickly a screening program could become sterile unless it was associated with problems of a fundamental nature. As a matter of fact, the important discoveries in this program were not the development of new compounds, but the development of new principles in drug screening. Actually, the most important single finding was the development of an effective dosage schedule for an old drug, atabrine.
Proceedings of The National Academy of Sciences, 1968
Some signs of hyperthyroidism, including enhanced responses to external stimulation and elevation... more Some signs of hyperthyroidism, including enhanced responses to external stimulation and elevation of basal metabolic rate, are reminiscent of increased sympathetic activity. The possibility has been raised that the action of thyroid hormones is mediated through catecholamines.1 2 Furthermore, hypothyroidism is associated with depressed sympathetic responses to catecholamines.3 The possibility that the thyroid hormones increase the rate of norepinephrine (NE) synthesis is not supported by a recent study from this laboratory showing that the turnover rate of cardiac NE is the same in normal and hyperthyroid mice.4
Biochimica Et Biophysica Acta-general Subjects, 1970
... Reaction blanks containing heatdenatured fat cell homogenate were carried through the procedu... more ... Reaction blanks containing heatdenatured fat cell homogenate were carried through the procedure. Activities of adenyl cyclase were expressed as mymoles Of cyclic 3',5'-AMP formed per z - zoe cells per zo min. ... 3 J. HiMMs-HAGEN, Pharmacol. Rev., I9 (1967) 367. ...
Journal of Neurochemistry, 1971
Cyclic AMP and dibutyryl-cyclic AMP, a derivative of cyclic AMP resistant to phosphodiesterase in... more Cyclic AMP and dibutyryl-cyclic AMP, a derivative of cyclic AMP resistant to phosphodiesterase inactivation, were injected into the lateral ventricles of rats. These nucleotides did not change the level of brain 5-HT but increased the brain level of its principal metabolite, 5-hydroxyindoleacetic acid. Cyclic AMP was less potent than dibutyryl-cyclic AMP. Butyrate and 5′-AMP were inactive. The effect of dibutyryl cyclic AMP on 5-HT metabolism was studied both in vivo and in vitro. The rate of synthesis of 5-HT was measured by the rate of accumulation of 5-hydroxyindoleacetic acid after the transport of this acid out of the brain was blocked with probenecid. The rate of synthesis of brain 5-HT increased from 0-38 μg/g/h in control rats to 0-65 μg/g/h after dibutyryl-cyclic AMP. In addition cyclic AMP and dibutyryl-cyclic AMP markedly increased brain tryptophan, while AMP was inactive. Since brain tryptophan hydroxylase has a Km for its substrate that is much higher than the concentrations of tryptophan normally present in the brain, it is likely that the increase in the rate of synthesis of brain 5-HT is secondary to the cyclic AMP induced increase in the levels of brain tryptophan. In vitro studies revealed that dibutyryl-cyclic AMP increased the uptake of radioactive labelled tryptophan into slices of rat brain stem and the formation of 5-HT and 5-hydroxyindoleacetic acid.
Mutation Research/genetic Toxicology, 1985
The pesticide, ethylene dibromide (EDB), was evaluated with in vivo cytogenetic assays to determi... more The pesticide, ethylene dibromide (EDB), was evaluated with in vivo cytogenetic assays to determine its genotoxicity. CD1 male mice were exposed to EDB through intraperitoneal injections. Bone marrow cells isolated from femora were analyzed for sister-chromatid exchange (SCE), chromosome aberration and micronucleus formation. The results showed that only certain concentrations of EDB tested caused a slight but significant increase in SCEs and chromosome aberrations. However, these increases were not dose-related. No increase in the polychromatic erythrocytes with micronuclei was observed following EDB exposure. Also, EDB did not cause cell-cycle delay in comparison with controls. Thus, it appears that EDB is not an effective genotoxic agent in vivo in mice.
Clinics in Endocrinology and Metabolism, 1984
Biochemical Pharmacology, 1969
Absbnct-Epididymal fat pads from fasting rats were more sensitive to the lipolytic effects of the... more Absbnct-Epididymal fat pads from fasting rats were more sensitive to the lipolytic effects of theophylline than fat pads from fed animals, but the maximum response to this agent was the same in both groups. From these results it may be inferred that fasting did not change the amount of adipose tissue lipase. Tbe amount of activatable adenyl cyclase in adipose tissue was increased about 2-fold by fasting, as shown by direct assay of the enzyme as well as by the increase in the maximum lipolytic response to norepinephrine (NE) in vitro. However, in vivo the adenyl cyclase appears to be activated by a nonadrenergic system, since the rise in free fatty acids (WA) is not inhibited by propranolol, a beta adrenergic blocking drug, though it is inhibited by nicotinic acid. Kinetic analysis of the inhibitory effects of propranolol on lipolytic responses to NE in vitro suggest that characteristics of the receptor, presumably adenyl cyclase, are similar in fasting and fed animals.
Pharmacology, 1971
Treatment of rats with Phenobarbital stimulates the metabolism of bromobenzene and potentiates th... more Treatment of rats with Phenobarbital stimulates the metabolism of bromobenzene and potentiates the hepatic necrosis elicited by the hydrocarbon. In contrast, administration of SKF 525-A or of piperonyl butoxide blocks bromobenzene metabolism and prevents the damage to the ...
Annals of The New York Academy of Sciences, 1971
Dr. Shannon neglected to state that he is really the father of clinical pharmacology. During the ... more Dr. Shannon neglected to state that he is really the father of clinical pharmacology. During the war, I had the privilege of working on the clinical screening of antimalarials a t Goldwater Memorial Hospital, New York, headed by this gifted investigator. I advise clinical pharmacologists to read his concepts on clinical pharmacology, published in the Harvey Lectures, 1945-46, Vol. 42. Despite the emergency nature of the antimalarial project, Dr. Shannon realized how quickly a screening program could become sterile unless it was associated with problems of a fundamental nature. As a matter of fact, the important discoveries in this program were not the development of new compounds, but the development of new principles in drug screening. Actually, the most important single finding was the development of an effective dosage schedule for an old drug, atabrine.
Proceedings of The National Academy of Sciences, 1968
Some signs of hyperthyroidism, including enhanced responses to external stimulation and elevation... more Some signs of hyperthyroidism, including enhanced responses to external stimulation and elevation of basal metabolic rate, are reminiscent of increased sympathetic activity. The possibility has been raised that the action of thyroid hormones is mediated through catecholamines.1 2 Furthermore, hypothyroidism is associated with depressed sympathetic responses to catecholamines.3 The possibility that the thyroid hormones increase the rate of norepinephrine (NE) synthesis is not supported by a recent study from this laboratory showing that the turnover rate of cardiac NE is the same in normal and hyperthyroid mice.4
Biochimica Et Biophysica Acta-general Subjects, 1970
... Reaction blanks containing heatdenatured fat cell homogenate were carried through the procedu... more ... Reaction blanks containing heatdenatured fat cell homogenate were carried through the procedure. Activities of adenyl cyclase were expressed as mymoles Of cyclic 3',5'-AMP formed per z - zoe cells per zo min. ... 3 J. HiMMs-HAGEN, Pharmacol. Rev., I9 (1967) 367. ...
Journal of Neurochemistry, 1971
Cyclic AMP and dibutyryl-cyclic AMP, a derivative of cyclic AMP resistant to phosphodiesterase in... more Cyclic AMP and dibutyryl-cyclic AMP, a derivative of cyclic AMP resistant to phosphodiesterase inactivation, were injected into the lateral ventricles of rats. These nucleotides did not change the level of brain 5-HT but increased the brain level of its principal metabolite, 5-hydroxyindoleacetic acid. Cyclic AMP was less potent than dibutyryl-cyclic AMP. Butyrate and 5′-AMP were inactive. The effect of dibutyryl cyclic AMP on 5-HT metabolism was studied both in vivo and in vitro. The rate of synthesis of 5-HT was measured by the rate of accumulation of 5-hydroxyindoleacetic acid after the transport of this acid out of the brain was blocked with probenecid. The rate of synthesis of brain 5-HT increased from 0-38 μg/g/h in control rats to 0-65 μg/g/h after dibutyryl-cyclic AMP. In addition cyclic AMP and dibutyryl-cyclic AMP markedly increased brain tryptophan, while AMP was inactive. Since brain tryptophan hydroxylase has a Km for its substrate that is much higher than the concentrations of tryptophan normally present in the brain, it is likely that the increase in the rate of synthesis of brain 5-HT is secondary to the cyclic AMP induced increase in the levels of brain tryptophan. In vitro studies revealed that dibutyryl-cyclic AMP increased the uptake of radioactive labelled tryptophan into slices of rat brain stem and the formation of 5-HT and 5-hydroxyindoleacetic acid.