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Biomedical subjects

S K Roy

Publications and source records attributed to S K Roy.

At least 73 records · Page 4Linked to original sources
PubMed1998

Impact of zinc supplementation on persistent diarrhoea in malnourished Bangladeshi children.

To evaluate the impact of zinc supplementation on the clinical recovery and body weight of children with persistent diarrhoea, a randomized, double-blind, controlled trial was conducted in 190 children with persistent diarrhoea aged between 3 and 24 months. Children were randomly allocated to receive either zinc (20 mg d(-1)) syrup with multivitamin (2 x RDA) or multivitamin alone in three divided daily doses for 2 weeks. The trial was conducted in a diarrhoeal disease hospital in Dhaka, Bangladesh. Duration until clinical recovery (d), impact on body weight and serum zinc level after 2 weeks of zinc supplementation were recorded. The duration of illness was significantly reduced (33%) with zinc supplementation among children who were underweight (< or =70% wt/age, p = 0.03). Supplemented male children also had a significant reduction (27%) in duration for recovery compared with unsupplemented children (p = 0.05). From baseline to convalescence, zinc-supplemented children maintained their serum zinc concentration (13.4 vs 13.6 micromol l(-1)), whereas unsupplemented children had a decrease in serum zinc after the 2 weeks of diarrhoea (13.6 vs 11.8 micromol l(-1),p < 0.03). The mean body weight of the children in the supplemented group was maintained (5.72 vs 5.70 kg, p = 0.62) during hospitalization, unlike that of the control group, in which there was a reduction in body weight (5.75 vs 5.67 kg, p = 0.05). Five children in the unsupplemented group and one child in the zinc-supplemented group died during the 2 weeks of supplementation (p = 0.06). Zinc supplementation in persistent diarrhoea significantly reduced the length of the recovery period in malnourished children and prevented a fall in body weight and serum zinc concentration, indicating that zinc is a beneficial therapeutic strategy in this high-risk childhood illness.

Bangladesh↗
PubMed1998

Ovarian transforming growth factor-beta (TGF-beta) receptors: in-vitro effects of follicle stimulating hormone, epidermal growth factor and TGF-beta on receptor expression in human preantral follicles.

The expression patterns of transforming growth factor (TGF)-beta receptor type I (TbetaRI) and -II (TbetaRII) in pre- and post-menopausal human ovaries, and the in-vitro effects of follicle stimulating hormone (FSH), epidermal growth factor (EGF) and transforming growth factor-beta1 (TGF-beta1) on receptor expression in preantral follicles were evaluated using immunohistochemistry and immunoblotting. Both types of receptor were present in granulosa, theca and interstitial cells; however, more mural than antral granulosa cells were TbetaRII positive. Overall, more cells expressed TbetaRI than TbetaRII. TbetaRI and TbetaRII expressions were detected in the membrane as well as in the soluble fractions. However, marked increases in TbetaRII and TbetaRI expression in the soluble fraction and corresponding decreases in the membrane fraction were noted in the post-menopausal ovary. Preantral follicles in class 1 and 2 responded in vitro to FSH and EGF with increased growth and a corresponding increase in TbetaRII expression in granulosa cells; however, TGF-beta did not influence follicular growth or receptor expression. There was no apparent change in follicular TbetaRI immunoreactivity regardless of test factors or follicular growth status. These results suggest that TbetaRI and TbetaRII are expressed differentially in human ovarian cells, particularly in the granulosa cells. The shift in TbetaR-I and -II from transmembrane to soluble fraction after menopause indicates that the endocrine milieu provided by the granulosa cells positively influences receptor induction in the membrane and, hence, the biological action of TGF-beta. FSH- and EGF-induced preantral follicular development is associated with a selective induction of TbetaRII and may indicate a mechanism whereby gonadotrophins and growth factor(s) regulate preantral folliculogenesis.

Activin Receptors, Type I↗
PubMed1998

In vitro culture of hamster ovarian primary interstitial cells: effect of serum.

The function of ovarian interstitial cells has been largely addressed using rat theca-interstitial cell culture. However, this preparation is primarily enriched with theca and secondary interstitial cells, which make it difficult to address selectively the function of the primary interstitial cells. We have developed an in vitro culture of hamster ovarian primary interstitial cells. Cells were isolated from postnatal hamster ovaries by collagenase digestion and purified over a Percoll gradient. The preparation contained 90% viable, pure interstitial cells, which anchored to the plastic and glass culture surface in the presence of fetal bovine serum. Cell proliferation was noted in the presence of serum dosages higher than 0.2%; however, reduction of serum concentration to 0.1% or complete serum starvation did not affect cell viability but almost completely abolished cell proliferation as determined by [3H]thymidine incorporation, labeling index, and DNA content of the culture. All cells exhibited active 3beta-hydroxysteroid dehydrogenase and P450 side chain cleavage immunoreactivity, which corresponded to basal progesterone and androstenedione accumulation. Replacement of serum to starving cells resulted in the induction of the "S" phase and "M" phase specific cyclins, and resumption of cell proliferation. Our results indicate that hamster primary interstitial cells can be cultured in vitro as a monolayer, and the anchorage and proliferation of these cells depend on serum supplement; however, a viable monolayer can be maintained for several days without serum. This model will be useful for addressing the mechanisms of differentiation of ovarian interstitial cells.

3-Hydroxysteroid Dehydrogenases↗
PubMed1998

Transforming growth factor beta receptor expression in hyperstimulated human granulosa cells and cleavage potential of the zygotes.

A possible relationship between transforming growth factor beta receptor type I (TbetaRI) and type II (TbetaRII) protein expression in human granulosa cells and the quality of preimplantation embryo development in vitro was studied using immunoblot analysis of TbetaRI and TbetaRII in hyperstimulated granulosa cells and morphological assessment of the cleavage potential of the zygotes in vitro. Washed granulosa cells were collected from </= 35-yr-old women with either tubal defects or mild endometriosis who were undergoing controlled ovarian hyperstimulation prior to oocyte retrieval for in vitro fertilization. TbetaRI and TbetaRII were immunoprecipitated from 100 000 g soluble and crude membrane fractions using receptor-specific antibodies and analyzed by Western immunoblotting, and the relative expression was quantitated from the luminographs. The gross morphology (embryo grade) of the preimplantation embryos developed in vitro was determined using a stereomicroscope. Both TbetaRI and TbetaRII are expressed in the soluble and membrane fractions of granulosa cells. Most notably, the zygote always developed into a grade 1 quality preimplantation embryo when the oocyte originated from a follicle that expressed a low amount of TbetaR protein in the granulosa cell membrane. Reduced expression of TbetaR in the granulosa cell membrane may form a mechanism critically regulating TGFbeta action on granulosa cells, and the latter in turn precisely control oocyte development, hence, the subsequent cleavage potential.

Blastomeres↗
PubMed1998

Cloning, characterization, and transcriptional analysis of a gene encoding an alpha-crystallin-related, small heat shock protein from the thermophilic cyanobacterium Synechococcus vulcanus.

hspA, a gene encoding a 16-kDa heat-induced protein from the thermophilic cyanobacterium Synechococcus vulcanus, has been cloned and sequenced. The deduced amino acid sequence of the gene product showed significant homology to sequences of the family of alpha-crystallin-related, small heat shock proteins. A monocistronic mRNA of hspA increased transiently in response to heat shock. The heat shock induction occurred at a vegetative promoter but without the CIRCE (controlling inverted repeat of chaperone expression) element.

Amino Acid Sequence↗
PubMed1998

O6-benzylguanine in humans: metabolic, pharmacokinetic, and pharmacodynamic findings.

PURPOSE: O6-Benzylguanine is a potent inactivator of the DNA-repair protein, O6-alkylguanine-DNA alkyl-transferase (AGT), that enhances sensitivity to nitrosoureas in tumor-cell lines and tumor-bearing animals. The objective of this study was to determine the pharmacokinetics and metabolic fate of O6-Benzylguanine in humans and its effect on AGT activity in peripheral-blood mononuclear cells (PBMCs). PATIENTS AND METHODS: Twenty-five cancer patients were treated with O6-Benzylguanine at a dose level of 10, 20, 40, and 80 mg/m2 intravenously (IV) over 1 hour. Plasma and urine samples were collected and analyzed for O6-Benzylguanine and O6-Benzyl-8-oxoguanine concentrations. AGT activity in PBMCs was determined up to 2 weeks postinfusion. RESULTS: There was no toxicity attributable to O6-Benzylguanine alone at all doses tested. O6-Benzylguanine rapidly disappeared from plasma and was converted to a major metabolite, O6-Benzyl-8-oxoguanine. The half-life of O6-Benzyl-8-oxoguanine increased with dose from 2.8 to 9.2 hours at doses of 10 and 80 mg/m2, respectively. The maximum concentration Cmax and area under the concentration-time curve (AUC) for O6-Benzyl-8-oxoguanine were, respectively, 2.2- and 12- to 29-fold greater than those of O6-Benzylguanine. At all doses, depletion of AGT activity was observed in lymphocytes with a return to baseline by 1 week posttreatment. CONCLUSION: This study demonstrates that administration of O6-Benzylguanine to humans results in a rapid conversion to O6-Benzyl-8-oxoguanine, which follows nonlinear kinetics. Both compounds contribute to an effective depletion of AGT activity in lymphocytes; however, prolonged depletion of AGT activity is likely due primarily to the effect of O6-Benzyl-8-oxoguanine.

Alkyl and Aryl Transferases↗
PubMed1998

Influence of alpha-tocopherol and ascorbic acid on pan masala induced genomic damage. An in vitro experiment.

Pan masala is a dry complex mixture of areca nut, catechu, lime, cardamon, unspecified flavouring agents etc., with (PMT) or without tobacco (pm). We have previously reported genotoxic potential of tobacco, areca nut and pan masala per se. An antigenotoxic effect of alpha-tocopherol (AT) and ascorbic acid (AA) against the PM/PMT induced genotoxic on Chinese hamster ovary (CHO) cells have been studied using chromosone aberration (CA) assay. AT and AA, per se, had no effect on CA frequency at the concentrations used in the present study. The short-term treatment of AT with aqueous extracts of PM/PMT yielded lower frequencies of CA as compared to the cultures treated with aqueous extracts of PM/PMT alone. However, a statistically significant reduction in CA frequency was observed with continuous treatment only. AA had no statistically significant protective effect except for continuous treatment with 10 ug/ml AA against the aqueous extract of PMT. The results indicate the possible use of AT to reduce the risk of oral cancer among PM/PMT chewers.

Animals↗
PubMed1998

Smoking status and its effect on cardiorespiratory system, body dimension and plucking performance of Oraon tea garden labourers.

Oraon tea leaf pluckers were examined in terms of their cardiorespiratory functions which include blood pressure measurements and a number of lung function tests. Anthropometric measurements and information on smoking history were obtained. It is known from earlier studies that the individuals studied belong to more or less similar economic and nutritional background. The results suggest that smoking has an effect on cardiorespiratory functions, and may have an indirect effect an anthropometric traits, but no effect of smoking on work performance could be established from the present study.

Adult↗
PubMed1997

Impact of a single megadose of vitamin A at delivery on breastmilk of mothers and morbidity of their infants.

OBJECTIVES: To evaluate the effect of vitamin A supplementation 24 h after delivery on breastmilk retinol concentration. METHODS: Fifty low income women were randomly assigned to a single oral dose of 209 micromol of Vitamin A or none at delivery. Maternal serum and breastmilk retinol levels and infant morbidity and anthropometry were serially assessed. RESULTS: Mean (95% CI) serum retinol levels increased in the supplemented mothers at 2.77 (2.3, 3.2) compared to 1.15 (0.9, 1.4) micromol/l in controls (P < 0.05) and remained at a significantly higher level of 1.59 (1.4, 1.8) micromol/l compared to 1.33 (1.8, 1.5) micromol/l in the control group (P < 0.001) up to a period of three months. Breastmilk retinol concentration was also greater at 24 h after supplementation, mean (CI) 11.34 (9.0, 13.7) micromol/l, compared to 2.95 (2.3, 3.6) micromol/l in the control group (P < 0.0001), and remained higher for the next six months at 1.06 (0.9, , 1.3) micromol/l compared to 0.73 (0.6, 0.8) micromol/l in the control group (P < 0.02). Infants of the supplemented mothers had reduced mean duration of respiratory tract infection of 3.1 (2.7, 3.5) days compared to 3.7 (3.3, 4.2) days (P < 0.03) and mean incidence of febrile illness 0.1 (0.1, 0.1) compared to control infants 0.3 (0.3, 0.3) days, (P < 0.002). CONCLUSION: Vitamin A supplementation of malnourished mothers maintains higher breastmilk retinol concentration for at least six months and reduces the duration of respiratory tract infection and febrile illness in their breastfed infants.

Adult↗
PubMed1997

Aflatoxin B1 epoxidation catalysed by partially purified human liver lipoxygenase.

(1) This study demonstrates for the first time the human liver lipoxygenase-mediated co-oxidation of aflatoxin B1 to the reactive metabolite, aflatoxin B1-8,9-epoxide, which rapidly hydrolyzes to dihydrodiol and preferentially binds to Tris. (2) The Tris-diol complex formed was quantitated fluorimetrically, based on its characteristic excitation at lambda ex = 395 nm and emission at lambda em = 435 nm. (3) The incubation of partially purified human liver lipoxygenase for 30 min under optimum assay conditions (3.5 mM linoleic acid and 50 microM aflatoxin B1 in Tris buffer at pH 7.2) resulted in the formation of 10.6 +/- 1.7 nmol Tris-diol/mg protein. (4) In addition to linoleic acid, other unsaturated fatty acids namely gamma-linolenic acid, cis-11, 14-eicosadienoic acid and arachidonic acid also supported the lipoxygenase mediated epoxidation of aflatoxin B1. (5) The enzymatic Tris-diol formation was significantly inhibited by all the lipoxygenase inhibitors tested in a concentration-dependent manner. (6) These results strongly suggest that lipoxygenase is capable of aflatoxin B1 metabolism and this may represent yet another pathway for the bioactivation of this hepatocarcinogen in the human liver.

Aflatoxin B1↗
PubMed1997

Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea.

OBJECTIVE: To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea. DESIGN: Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks. SETTING: A diarrhoeal disease hospital in Dhaka, Bangladesh. PATIENTS: 111 children, 3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded. MAIN OUTCOME MEASURES: Total diarrhoeal stool output, duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation. RESULTS: Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239 v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v 329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v 6.2 days, p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v -0.3 mumol/l, p < 0.001) during two weeks of supplementation, and better mean weight gain (120 v 30 g, p < 0.03) at the time of discharge from hospital. CONCLUSIONS: Zinc supplementation is a simple, acceptable, and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished.

Acute Disease↗
PubMed1996

Isolation and some properties of dioxygenase and co-oxidase activities of adult human liver cytosolic lipoxygenase.

The evidence presented here constitutes the first report on the occurrence of lipoxygenase (LO) activity in the adult human liver. LO activity was isolated free of hemoglobin from the whole liver cytosol by affinity chromatography using a concanavalin-A sepharose 4B column, and some properties of its dioxygenase and co-oxidase activities were examined. High-pressure liquid chromatography (HPLC) analyses of arachidonic acid metabolites suggested the presence of 5-, 12-, and 15-LO activities in the human liver. Linoleic acid was converted into 13-hydroperoxyoctadecadienoic acid. The dioxygenase activity with a Vmax value of 1.74 mumoles/min/mg protein and a Km value of 0.48 mM was noted in the presence of different concentrations of linoleic acid at pH 10. The activity was markedly stimulated by the presence of calcium, ATP, hydrogen peroxide, and KCl in the assay medium. Under optimum conditions, all the xenobiotics tested were cooxidized by the enzyme preparations in the presence of linoleic acid. Kinetic data obtained for benzidine oxidation yielded a Km value of 0.53 mM and a Vmax value of 90.9 nmoles/min/mg protein. At present, the significance of these findings in in vivo toxicity of benzidine is unknown. The linoleic acid-dependent dioxygenase and co-oxidase activities were thermolabile and inhibited by micromolar concentrations of several classical LO inhibitors, further confirming the involvement of LO in these reactions.

Adenosine Triphosphate↗
PubMed1996

A fluid dynamics study of the Trac catheter.

A fluid mechanics study of the Trac catheter was done using a 10 x scaled model. Wall pressure distributions and particle and dye flow visualization studies show that a primary vortex develops due to the spinning tip, and a secondary flow recirculates material along the chamber wall to the base of the chamber and back to the tip. Strong, nearly instantaneous mixing occurs throughout the vortex for speeds above 50,000 rpm scaled for the full-scale catheter. Close-contact pressure studies also show that wall pressures of the order of 0.4 MPa may be obtained for a full-scale catheter.

Angioplasty↗
PubMed1996

Pharmacokinetics and metabolism in rats of 2,4-diamino-6-benzyloxy-5- nitrosopyrimidine, an inactivator of O6-alkylguanine-DNA alkyltransferase.

Inactivation of the human DNA repair protein, O6-alkylguanine-DNA-alkyltransferase (AGT), by exposure to O6-benzylguanine leads to a dramatic enhancement in the cytotoxic response of cells to chemotherapeutic alkylnitrosoureas. Benzylated pyrimidines identified as more potent inactivators than O6-benzylguanine in vitro include 2,4-diamino-6-benzyloxy-5-nitrosopyrimidine (5-nitroso-BP) and 2,4-diamino-6-benzyloxy-5-nitropyrimidine (5-nitro-BP). In efforts to determine the clinical usefulness of these benzylated pyrimidines, we examined the metabolism and pharmacokinetics of 5-nitroso-BP in Sprague-Dawley rats, together with its potency as an AGT inactivator in mice. The mean plasma half-life, clearance, and volume of distribution of 5-nitroso-BP in rats were, respectively, 3.8 min, 22 liters/hr/kg, and 2.1 liters/kg. Two metabolites were identified in rat plasma (i.e. 5-nitro-BP and 2,4,5-triamino-6-benzyloxypyrimidine) after intravenous administration of 5-nitroso-BP in rat. Reduction of 5-nitroso-BP (100 microM) occurred primarily in cytosol and was inhibited (> 95%) by 1 mM menadione. Dicumarol (100 microM), a DT-diaphorase inhibitor, did not significantly inhibit this reaction. This indicated a possible role of a dicumarol-resistant quinone reductase. At higher substrate and protein concentration, NADPH-dependent oxidation of 5-nitroso-BP to 5-nitro-BP primarily occurred in microsomes and was completely inhibited by 1-aminobenzotriazole (1 mM), a P450 inhibitor. Unfortunately, neither 5-nitroso-BP nor 5-nitro-BP was as effective as O6-benzylguanine at depleting AGT activity in mouse liver or spleen. At 1 hr after injection of 15 mg/kg O6-benzylguanine, 5-nitroso-BP, or 5-nitro-BP, AGT levels in liver fell to 1%, 66%, and 71% basal activity, respectively. Rapid cytosolic reduction of 5-nitroso-BP may explain the lack of potency of the pyrimidines in vivo.

Animals↗
PubMed1996

Follicular development through preantral stages: signalling via growth factors.

Although gonadotrophins, particularly FSH, are the primary pituitary regulators of ovarian folliculogenesis, the involvement of ovarian-derived growth factors in follicular growth and maturation has become increasingly apparent over the past decade. Regulators of ovarian somatic cells can be broadly divided into (1) mitogenic factors, and (2) differentiation-induction factors, based on two primary cellular requirements, that is, proliferation and differentiation that are fundamental to folliculogenesis and ovarian functions. In this article, direct as well as indirect evidence is presented that highlights the roles of epidermal growth factor--a mitogen, and transforming growth factor beta--a differentiation-induction factor, in modulating gonadotrophin action in the ovary, particularly in the preantral follicles. An exquisitely timed and regionalized expression of these two types of peptide factor, along with their membrane receptors, may determine the differential success of follicle development, hence, allowing selection of the best oocytes for fertilization and subsequent development.

Animals↗