Search PubMed⌕ Search

Biomedical subjects

G Krishna

Publications and source records attributed to G Krishna.

At least 109 records · Page 6Linked to original sources
PubMed1986

Increased sensitivity of the isometric contraction of the neonatal isolated rat atria to halothane, isoflurane, and enflurane.

Isolated atria from neonatal (0-5 day old) and adult (50 +/- 5 day old) rats were perifused in oxygenated Kreb's Henseleit solution at 30 +/- 0.5 degrees C and exposed to four different concentrations of halothane, isoflurane, or enflurane while isometric contractile tension was recorded and compared with control atria. ED50 values (mM of anesthetic required to produce 50% reduction in contractile tension) of neonates for halothane (0.18 +/- 0.01), isoflurane (0.41 +/- 0.05), and enflurane (0.41 +/- 0.04) were significantly lower than those of adults (0.35 +/- 0.02, 0.80 +/- 0.05, and 1.15 +/- 0.05, respectively). Furthermore, neonatal ED50 calculated as per cent of adult ED50 was significantly less for enflurane (35%) than for halothane (54%) or isoflurane (51%).

Action Potentials↗
PubMed1986

Genetic expression of cyclic GMP phosphodiesterase activity defines abnormal photoreceptor differentiation in neurological mutants of inherited retinal degeneration.

We have examined cyclic GMP concentrations, guanylate cyclase activities, and cyclic GMP phosphodiesterase (PDE) activities in developing retinas of congenic mice with different allelic combinations at the retinal degeneration (rd) and retinal degeneration slow (rds) loci. Although guanylate cyclase activities were found to be uniformly low in the mutant retinas, striking differences in PDE activity and cyclic GMP levels were observed in retinas of the various genotypes. Homozygous rds mice, which lack receptor outer segments, showed reduced retinal PDE activity and cyclic GMP concentration in comparison to normal animals. In heterozygous rds/+ mice with abnormal outer segments, the levels were intermediate. In retinas of homozygous rd mice, PDE activity was lower than in rds retinas and cyclic GMP levels were much higher. In mice homozygous for both rd and rds genes, retinal PDE activities were even lower than in single homozygous rd mice; the cyclic GMP level reached the same high value as in the rd animals, persisted for a longer time at this high level, and did not correlate with the rate of photoreceptor cell loss. Thus, a marked variation in PDE activity appears to be the major manifestation of abnormal outer segment differentiation and eventual degeneration of photoreceptor cells in these neurological mutants. An increased cyclic GMP level seems to be an essential corollary in the expression of the rd gene even in the absence of outer segments, but it appears unlikely that an abnormally high nucleotide level in itself causes photoreceptor cell death.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Inhibition of overall protein and RNA synthesis as a mechanism for the tunicamycin induced decrease in cytochrome P-450 in rat hepatocytes.

In rat hepatocytes maintained in culture, cytochrome P-450 and NADPH cytochrome c reductase activities were decreased by tunicamycin in a dose and time dependent fashion. The effect of tunicamycin was mainly due to inhibition of protein synthesis. Tunicamycin decreased L-[35S] methionine incorporation into many proteins, including a 52 kDa cytochrome P-450 isozyme. Tunicamycin also reduced RNA synthesis. These results indicate that tunicamycin decreased cytochrome P-450 levels in hepatocytes by inhibiting protein and RNA synthesis.

Animals↗
PubMed1986

A simple method for the assay of Bordetella pertussis adenylate cyclase employing 31P nuclear magnetic resonance spectroscopy.

A simple method for the simultaneous assay of both substrate utilization and product formation by Bordetella pertussis adenylate cyclase has been developed. This method involves measurement of ATP remaining in the reaction mixture and cyclic 3',5'-AMP (cAMP) formation by 31p-NMR spectroscopy. No separation of the nucleotides is required. The measurement of the rate of cAMP formation compared very well with other methods that require separation of product from the substrate. With this method it has been possible to show calmodulin activation of B. pertussis adenylate cyclase and to demonstrate an inhibition of calmodulin activation by melittin. The inhibition of calmodulin-activated adenylate cyclase by melittin is not permanent and can be overcome by long-term incubation.

Adenosine Triphosphate↗
PubMed1986

Inhibition of cyclophosphamide and mitomycin C-induced sister chromatid exchanges in mice by vitamin C.

Ascorbic acid (vitamin C) is known to act as an antimutagen and anticarcinogen in several test systems. However, there is no report of its effect on carcinogen-induced chromosomal damage in vivo in animals. The present study was performed to determine whether or not ascorbic acid affects sister chromatid exchanges (SCEs) induced by cyclophosphamide (CPA) and mitomycin C (MMC) in bone marrow and spleen cells in mice. The results indicate that ascorbic acid per se did not cause a significant increase in SCEs in mice. However, increasing concentrations of ascorbic acid caused decreasing levels of CPA- and MMC-induced SCEs in both cell types in vivo. At the highest concentration of ascorbic acid, 6.68 g/kg, approximately 75 and 40% SCE inhibition in both cell types was noted for CPA and MMC, respectively. Likewise, under in vivo/in vitro conditions (exposure of animals to experimental chemicals followed by culturing of cells), ascorbic acid caused a dose-related decrease in CPA- and MMC-induced SCEs, up to a dose of 3.34 g/kg At this concentration, approximately 50% CPA- and MMC-induced SCE inhibition was observed in both cell types studied. Thus, ascorbic acid acts as an anti-SCE agent in both in vivo and in vivo/in vitro conditions in mice.

Animals↗
PubMed1985

Inhibition of protein synthesis: a basis for tunicamycin-induced decrease in rat liver cytochrome P-450.

Tunicamycin caused a dose and time dependent decrease in cytochrome P-450 in rat liver. A dose of 50 micrograms/kg caused a decrease of about 50% in 72 hours. A similar decrease in the activities of rat liver microsomal aniline hydroxylase, aminopyrine N-demethylase and ethoxycoumarin O-deethylase were also seen after the tunicamycin treatment. Tunicamycin also suppressed food and water intake but the decrease in cytochrome P-450 was not related to these effects. NADPH cytochrome c reductase was not markedly decreased by tunicamycin. A decrease in cytochrome P-450 was also observed in cultured rat hepatocytes treated with tunicamycin. It decreased incorporation of [35S]-methionine into total proteins as well as into various cytochrome P-450 isozymes of rat hepatocytes. This indicates that a decrease in protein synthesis may be responsible for the tunicamycin-induced decrease in cytochrome P-450 and drug metabolism.

Animals↗
PubMed1985

A simple and sensitive method for monitoring drug-induced cell injury in cultured cells.

A simple, sensitive method has been developed for evaluating cell injury noninvasively in monolayer cells in culture. The cell ATP pool was radiolabeled by incubating the cells with [14C]adenine. The uptake and incorporation of [14C]adenine was shown to proportional to the number of cells. As determined by HPLC, about 65-70% of the incorporated 14C label was in the ATP pool, 15-20% was in the ADP pool, and the rest was in the 5'-AMP pool. When prelabeled cells were exposed to toxic drugs (acetaminophen, calcium ionophore A-23187, or daunomycin) there was a marked decrease in cell ATP with a concomitant increase in leakage of labeled nucleotides, mainly 5'-AMP and 5'IMP. We have shown that leakage of 14C label into the medium from the prelabeled cells may be employed for quantitation of cell injury. This new measure of toxicity was shown to correlate very well with LDH leakage from the cells, which is a well accepted measure of cell injury. The leakage of 5'-[14C]AMP also correlated very well with the reduction of cell ATP in cardiac myocytes. This method has been used for monitoring drug-induced toxicity in liver cells, cardiac myocytes, and LB cells.

Adenine↗
PubMed1985

The calcium ionophore A23187 evokes and potentiates antiviral activity of interferon.

Calcium ionophore A23187, which causes a rapid efflux of Ca2+ from cells, evokes an antiviral response in mouse LB, simian COS-1, Hela, human amniotic (U), baby hamster kidney (BHK), and VERO cells against Sindbis (SBV) and vesicular stomatitis (VSV) viruses. The degree of antiviral activity depends on the type of cell, virus, and the dose of A23187. A23187 inhibits the production of infectious VSV; however, VSV particle production was not significantly inhibited as measured by viral RNA and viral proteins. The VSV released from the A23187-treated cells is deficient in VSV glycoprotein (G) and membrane (M) protein. A23187 potentiates the antiviral activity of interferon (IFN) against SBV and VSV in mouse LB and human U cells. It is possible to postulate that a change in intracellular Ca2+ may play an important role in the antiviral activity of IFN.

Animals↗
PubMed1984

Correlative genotoxicity studies of airborne particles in Salmonella typhimurium and cultured human lymphocytes.

The acetone extracts of ambient air particulates collected locally were tested for their capacity to induce sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) in human lymphocytes, and to induce gene mutations (GMs) in Salmonella typhimurium. The extracts caused dose-related clastogenic/mutagenic responses in all three assay systems. With the same concentration, it seems that the Ames Salmonella/microsomal assay with TA98 gave the highest, and the chromosomal aberration assay with human lymphocytes the lowest, mutagenic/clastogenic responses, respectively. Because high frequencies of SCEs were induced by solvent extracts of airborne particles, this study further indicated the usefulness of SCE assay in human lymphocytes for genotoxicity studies of airborne particles.

Air Pollutants↗
PubMed1984

Dopamine reverses cardiovascular depression of toxic doses of pentobarbitone in dogs.

Pentobarbitone, 20 mg X kg-1 IV followed by infusion of 25 mg X kg-1 X hr-1, produced a progressive decrease in mean arterial pressure in dogs from 113 +/- 17 mmHg (SD) after one hour of infusion to 82 +/- 21 mmHg after 3.5 hours and to 49 +/- 22 mmHg after 5.5 hours. EEG silence occurred at 3.6 +/- 0.6 hours. In dogs similarly treated with pentobarbitone, a two hour infusion of dopamine 5 micrograms X kg-1 X min-1 beginning at the time of EEG silence prevented the further decrease in pressure and restored pressure to 87 +/- 18 mmHg. The mechanism for this effect of dopamine was an increase in cardiac output as systemic vascular resistance was unaffected by dopamine. The cardiac output increase was mainly the result of an increase in stroke volume as heart rate increased only slightly. Since reduced stroke volume was the main reason why pentobarbitone lowered blood pressure, the effect of dopamine on stroke volume and thus on blood pressure makes it an appropriate antagonist to the cardiovascular effects of toxic doses of pentobarbitone.

Animals↗
PubMed1984

Effect of age on epinephrine-induced arrhythmias during halothane anaesthesia in pigs.

The effect of age on the arrhythmogenicity of epinephrine during halothane anaesthesia was studied in pigs of two different age groups. At a stable alveolar concentration of 0.84 volumes per cent halothane, ventricular arrhythmias could not be elicited in one- to three-day-old pigs by a 100 micrograms X kg-1 infusion of epinephrine. PVCs were produced in 50- to 55-day-old pigs at a mean epinephrine dose of 9.55 micrograms X kg-1. Heart rate, systolic blood pressure, and rate-pressure product were significantly higher before and during the epinephrine infusion in the 50- to 55-day-old pigs. It is concluded that there is an age dependent effect upon epinephrine induced arrhythmias during halothane anaesthesia in pigs.

Aging↗
PubMed1984

Deuterated halothane--anesthetic potency, anticonvulsant activity, and effect on cerebellar cyclic guanosine 3',5'-monophosphate.

The effect of substituting deuterium for hydrogen in the halothane molecule on anesthetic potency, motor activity, and cerebellar cyclic guanosine 3',5'-monophosphate (cGMP) content was studied in mice. The concentration of halothane required to abolish the righting reflex in 50% of the mice (ED50RR) was chosen as index of anesthetic potency; cerebellar control of motor activity was evaluated by the incidence of isoniazid-induced convulsions. The ED50RR for deuterated (D)-halothane was similar to that of halothane (0.87 +/- 0.04 and 0.88 +/- 0.03 vol%, respectively). Both D-halothane and halothane (0.15-0.90 vol%) protected the mice against isoniazid-induced convulsions and decreased cerebellar cGMP content in a dose-dependent manner. D-halothane and halothane were equipotent on both parameters. Thus deuteration did not alter the anesthetic potency, the anticonvulsant activity, or the effect on cerebellar cGMP content of the anesthetic. Furthermore, the reactivity of the C-H bond is probably not critical for these actions of halothane.

Animals↗