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Biomedical subjects

B Sinha

Publications and source records attributed to B Sinha.

At least 55 records · Page 3Linked to original sources
PubMed1994

Enhanced cytotoxicity with interleukin-1 alpha and 5-fluorouracil in HCT116 colon cancer cells.

Recombinant human interleukin-1 alpha (rIL-1 alpha), at concentrations that were not growth-inhibitory when given alone (100-10,000 U/ml), enhanced the growth inhibition resulting from a 72-h fluorouracil (FUra) exposure in HCT116 colon cancer cells. Median-effect analysis of clonogenic assays indicated that rIL-1 alpha, given 24 h prior to and following a 24-h exposure to FUra, increased lethality in a more than additive fashion. rIL-1 alpha did not appear to significantly affect [3H]-FUra metabolism, total [3H]-FUra-RNA incorporation or RNA retention after drug removal, inhibition of thymidylate synthase, or thymidine triphosphate pool depletion. During continuous exposure to rIL-1 alpha, transient stimulation of RNA and DNA synthesis was observed at 72 h, with a return to normal by 96 h. A 24-h exposure to 10 microM FUra altered the elution profile of newly synthesized DNA as monitored by pH step alkaline elution. An accumulation of lower-MW single-stranded DNA species was noted with FUra compared to control, accompanied by a significantly decreased proportion of DNA retained on the polycarbonate filter: 10% retained vs. 32% for control (P = 0.01). A 48-h exposure to rIL-1 alpha alone did not affect the elution profile of nascent DNA species, nor did it enhance the effects of FUra. Although FUra did not appreciably affect pulse [3H]-uridine incorporation into RNA for the initial 8-24 h of FUra exposure, progressive inhibition of net RNA synthesis was observed thereafter. FUra prevented the stimulatory effect of rIL-1 alpha on RNA synthesis, and net RNA synthesis was significantly inhibited (by 64-79% after 72 and 96 h) with the combination compared to rIL-1 alpha alone. Continuous exposure to 10 microM thymidine did not rescue cells from the lethality of FUra alone or the combination of FUra plus rIL-1 alpha, suggesting that depletion of deoxythymidine triphosphate as a consequence of thymidylate synthase inhibition was not the most important component of FUra toxicity. In contrast, 1 mM uridine provided partial protection against the toxicity of FUra alone or with rIL-1 alpha. Although uridine did not affect FUra metabolism, it decreased FUra-RNA incorporation by 42-60%, presumably as a consequence of the 2-fold expansion of UTP pools. [125I]-rIL-1 alpha binding was nonspecific; with a 24-h exposure, however, internalized [125I]-rIL-1 alpha exceeded cell surface-bound material by 2-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Biotransformation↗
PubMed1993

Cross-linking of the beta-glucan receptor on human monocytes results in interleukin-1 receptor antagonist but not interleukin-1 production.

The beta-glucan receptor, found on monocytes and neutrophils, binds glucose polymers derived from fungi. Ligands for the receptor have various immunomodulatory effects, including increased microbicidal killing activity. We have investigated the effect of beta-glucans on the production of interleukin-1 (IL-1) and its naturally occurring inhibitor, the IL-1 receptor antagonist (IL-1Ra). Particulate beta-glucan induced IL-1Ra production from human peripheral blood mononuclear cells (PBMC) but did not stimulate IL-1 beta synthesis or gene expression in these same cells. Monomeric (soluble) beta-glucan did not induce IL-1Ra production. However, when preincubated with PBMC, monomeric beta-glucan significantly (P < .01) reduced particulate beta-glucan induction of IL-1Ra by 40%, suggesting that crosslinking of beta-glucan receptors is required for induction of IL-1Ra. In support of this, monomeric beta-glucan immobilized on plastic surfaces stimulated IL-1Ra production. Vitamin D3, which increases the functional capacity of beta-glucan receptors, increased IL-1Ra production induced by particulate beta-glucan, whereas dexamethasone suppressed IL-1Ra synthesis. Because of their differential effects on cytokine production, beta-glucans may be used to therapeutic advantage in the diseases in which IL-1 is implicated.

Adult↗
PubMed1993

Nitric oxide-releasing agents enhance cytokine-induced tumor necrosis factor synthesis in human mononuclear cells.

In septic shock tumor necrosis factor (TNF) leads to increased nitric oxide (NO) production by induction of NO synthase. An inverse regulatory effect, the influence of NO on cytokine synthesis, has rarely been investigated. The present study assessed the influence of NO-releasing agents on TNF production from interleukin-1 alpha (IL-1 alpha)-stimulated human peripheral blood mononuclear cells (PBMC). 3-Morpholino-sydnonimine (SIN-1) enhanced IL-1 alpha-induced TNF synthesis to a maximum of 272% (mean of n = 5 donors), with 100% set as TNF production by stimulation with IL-1 alpha alone. This finding was confirmed using another NO-donor, i.e., sodium nitroprusside (SNP). The effect was specific for TNF compared to the uninfluenced synthesis of IL-1 beta. Kinetic analysis showed the most pronounced increase in TNF synthesis when SIN-1 was added during the first 60 min after IL-1 alpha addition. These data reveal an enhancing effect of NO on cytokine-induced TNF synthesis. It may contribute to the regulation of TNF synthesis in pathological processes such as microbicidal activity, tumor cell lysis or endothelium-mediated hypotension.

Humans↗
PubMed1991

Cyclic nucleotides differentially regulate the synthesis of tumour necrosis factor-alpha and interleukin-1 beta by human mononuclear cells.

Recent reports have shown that phosphodiesterase (PDE) inhibitors suppress production of tumour necrosis factor-alpha (TNF-alpha) in mouse macrophages. In the present study we show that theophylline, pentoxifylline and 3-isobutyl-1-methylxanthine markedly suppress the lipopolysaccharide (LPS)-induced synthesis of TNF-alpha (also) in human mononuclear cells. This effect is selective for TNF-alpha since up to several-fold higher concentrations of these PDE inhibitors do not affect production of interleukin-1 beta (IL-1 beta) in the same system. The observed effect of PDE inhibitors appears to be mediated by accumulation of cAMP since (i) addition of PDE inhibitors increases cAMP while cGMP levels are only marginally elevated; (ii) raising cAMP by another mechanism (enhanced formation induced by prostaglandin E2; PGE2) leads to a similar suppression of TNF-alpha production; and (iii) raising cGMP by activating the soluble guanylate cyclase by 3-morpholinosydnonimine (SIN 1) does not inhibit TNF-alpha synthesis. However, SIN 1 suppressed the synthesis of IL-1 beta. Selective suppression of TNF-alpha synthesis by PDE inhibitors may contribute to their beneficial effects in animal models of septic shock or lung injury and may thus have clinical implications.

Cell Line↗
PubMed1988

Noncardiac side-effects of long-term oral amiodarone in the elderly.

Amiodarone is a powerful anti-arrhythmic drug. However, its use is somewhat limited by side-effects. No study examining side-effects specifically in elderly patients exists. We have reviewed noncardiac side-effects in 61 elderly patients on long-term oral amiodarone treatment (follow-up 3-66 months). The most troublesome side-effect was hypothyroidism (nine patients, 15%). No cases of frank hyperthyroidism were seen. Elevation of aspartate transaminase (AST) was common (16 patients, 26%), but generally mild and transient. Photosensitivity occurred in six patients (10%). Corneal deposits were common but gave rise to symptoms in only one patient. Two patients reported tremor. Hypothyroidism appeared to be more common and photosensitivity less common than in previously reported series in younger adults. Possible reasons for this are discussed. It is our policy to continue to prescribe amiodarone to elderly patients, regulate monitoring for adverse effects is however mandatory.

Administration, Oral↗
PubMed1986

Transurethral resection of the prostate with local anesthesia in 100 patients.

We performed transurethral resections of the prostate in 100 patients under local anesthesia supplemented when appropriate by intravenous medication. In the first part of the study (40 patients) local anesthesia was infiltrated into the prostate transurethrally only, while in the second part (60 patients) infiltration was performed transurethrally and perineally. Prostate sizes ranged from 5 to 50 gm., and pain control was excellent in the majority of the patients, especially when perineal infiltration was added to the procedure. Of the patients 98 per cent said they would do it again, no patient required conversion to general anesthesia and there were no significant complications relating to the anesthesia. Local anesthesia with intravenous supplementation can be performed successfully in the majority of the patients with small to moderately sized prostate glands.

Aged↗
PubMed1986

Does radiolabelled diphosphonate retention reflect bone metabolism in the elderly?

The 24-h whole-body retention of diphosphonates (WBR), a useful measure of bone metabolism in young subjects, was measured in 27 elderly subjects (19 from home and eight in-patients). WBR rose with increasing age (r = 0.55, P less than 0.01) and was negatively correlated with renal function (r = -0.60, P less than 0.01). In five subjects given vitamin D, WBR did not fall. The measurement of WBR in the elderly has to be assessed in the light of an accurate assessment of renal function and so is rarely clinically useful.

Aged↗
PubMed1985

Functional consequences of prenatal exposure to lead in immature rats.

Long-Evans dams were given 0.5% lead acetate as their sole drinking solution two weeks before and throughout pregnancy. Their offspring were transferred to normal surrogate dams on the second day after birth. From days 5 through 30, the rat pups were observed for the appearance of developmental landmarks and given behavioral tests (surface righting, negative geotaxis, eye opening, left-right position discrimination and reversal, ambulation and head dipping). Pups of pair-fed-and-watered as well as normal control dams were also transferred to surrogates and received the same tests. Although the lead-exposed rat pups had markedly elevated blood and brain lead on the day of birth (which were still significantly elevated on day 16), they showed no delay, impairment, or any other change on the various functional measures.

Aging↗
PubMed1984

Pharmacokinetics of meptazinol after single and multiple oral administration to elderly patients.

Oral administration of meptazinol (200 mg Meptid) to male and female geriatric patients (greater than 70 years) resulted in rapid absorption, with peak drug concentrations at 0.5 to 3 h after dosage. Subsequent elimination also proceeded rapidly with a half-life of 3.39 h (+/- 0.26 SEM) after a single dose and 4.97 h (+/- 0.80 SEM) after 13 consecutive 6-h doses. These values were not statistically different. There was no accumulation of meptazinol above that expected from the single-dose kinetics. Plasma protein binding of meptazinol was 33.8% (+/- 0.74 SEM). No sex difference was apparent in any of the pharmacokinetic parameters determined. Comparison of these results with those obtained in an earlier study in young volunteers showed that although the half-life of meptazinol was somewhat longer than the value of 2 h seen in the young, peak plasma concentrations after single and multiple dosing were similar for both age groups, implying that clearance remained largely unaltered. It was concluded that there was no pharmacokinetic basis for recommending a reduction in dosage when treating elderly patients with oral meptazinol.

Age Factors↗