Biomedical subjects

R Nigam

Publications and source records attributed to R Nigam.

27 records · Page 2Linked to original sources

PubMed1992

Inhibition of nitrovasodilator- and acetylcholine-induced relaxation and cyclic GMP accumulation by the cytochrome P-450 substrate, 7-ethoxyresorufin.

We examined the effect of the cytochrome P-450 substrate, 7-ethoxyresorufin (7-ER), and its corresponding product, resorufin, on nitrovasodilator- and endothelium-dependent relaxation of isolated rat aorta. The EC50 value for glyceryl trinitrate (GTN) induced relaxation was increased over 100-fold by 7-ER and less than 3-fold by resorufin. The EC50 value for sodium nitroprusside (SNP) induced relaxation was increased approximately 12-fold by 7-ER, acetylcholine (ACh) induced relaxation was abolished, and relaxation induced by isopropylnorepinephrine was not significantly affected. GTN-, SNP-, and ACh-induced increases in cyclic GMP accumulation were inhibited by 7-ER, as were basal cyclic GMP levels in endothelium-intact, but not endothelium-denuded tissues. 7-ER decreased GTN biotransformation in intact aorta and decreased the regioselective formation of glyceryl-1,2-dinitrate. The activation by GTN and SNP of aortic guanylyl cyclase in broken cell preparations was not affected by 7-ER, indicating that the inhibitory effect of 7-ER is probably not due to a direct interaction with guanylyl cyclase. The inhibitory effect of 7-ER on GTN-induced relaxation was not altered by the addition of superoxide dismutase, suggesting that 7-ER does not act by increasing superoxide anion concentration (which would serve to increase the degradation of nitric oxide (NO) formed during vascular GTN biotransformation). Our data provide further evidence for the role of the cytochrome P-450--cytochrome P-450 reductase system in the biotransformation of GTN to an activator (presumably nitric oxide) of guanylyl cyclase. The data are consistent with a mode of action of 7-ER involving either competitive inhibition of vascular cytochrome P-450 or uncoupling of vascular cytochrome P-450 reductase from cytochrome P-450. The data also suggest that the cytochrome P-450 system facilitates NO release from SNP and that 7-ER has an inhibitory effect on endothelial nitric oxide synthase.

Acetylcholine↗

PubMed1990

Cholesterol: free radical peroxidation and transfer into phospholipid membranes.

Cholesterol, when sequestered in saturated liposomes of dimyristoylphosphatidylcholine (DMPC) or dipalmitoylphosphatidylcholine (DPPC), undergoes peroxidation thermally initiated either by a lipid-soluble or a water-soluble azo initiator and in both cases the reaction is inhibited effectively by the water-soluble antioxidant, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylate (Trolox). Quantitative kinetic methods of autoxidation show that the oxidizability, kp/(2kt)1/2 (where kp and 2kt are the rate constants of radical chain propagation and termination, respectively) of cholesterol in DMPC or DPPC multilamellar liposomes, where kp/(2kt)1/2 is 3.0.10(-3) to 4.3.10(-3) M-1/2 s-1/2 at 37-45 degrees C, is similar to that measured in homogeneous solution in chlorobenzene, where kp/(2kt)1/2 is 3.32.10(-3). However, its oxidizability in smaller unilamellar vesicles of DMPC or DPPC increases by at least 3-times that measured in multilamellar systems. Autoxidation/antioxidant methods show that cholesterol partitions directly from the solid state into DMPC or DPPC liposomes by shaking and this is confirmed by 31P and 2H quadrupole NMR spectra of deuterated cholesterol when membrane bound. Analytical studies indicate that up to 21 mol% cholesterol will partition into the membranes by shaking.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1986

Three times daily or 8-hourly.

The timing of drug ingestion over 24 hours was assessed in 58 outpatients taking drugs three times daily. The mean time between 1st and 2nd dose was 5.7 hours, 2nd and 3rd 6.1 hours and between 3rd and 1st of the next day 12.2 hours. Based on a simulation of hydralazine pharmacokinetics, such irregular administration would increase peak levels by 10% and decrease trough levels by 64% compared with regular 8-hourly doses.

Adult↗

PubMed1976

Chronic myelogenous leukemia presenting in the blastic phase and its association with a 45 XO Ph1 karyotype.

A 58-yr-old male patient presented in the blastic phase of chronic myelogenous leukemia (CML). Cytogenetic studies revealed a 45 XO Ph1 chromosome pattern in bone marrow cells during a short remission and again in the blastic phase of the disease. The patient expired 8 mo following diagnosis. The blastic phase of CML can stimulate acute myelogenous leukemia (AML) clinically and hematologically; CML can be differentiated by the presence of the Ph1 chromosome and the stigmata of CML. Absence of the Y chromosome from the bone marrow in CML is a recently described finding. Previous reports indicating the prevention of the blastic phase in patients with this karyotype could not be confirmed by our or other recently reported cases.

Chromosomes, Human, 21-22 and Y↗

PubMed1974