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Biomedical subjects

R S Mathur

Publications and source records attributed to R S Mathur.

At least 37 records · Page 2Linked to original sources
PubMed1996

Inhibition of testosterone 5 alpha-reductase: evidence for tissue-specific regulation of thromboxane A2 receptors.

Testosterone has been implicated as a risk factor for cardiovascular diseases and thromboxane A2 (TXA2) may be an important pathophysiologic mediator for them. Testosterone has been shown to increase TXA2 receptor density in several cell types. Testosterone is reduced at the 5 alpha position to its active metabolite, dihydrotestosterone, by 5 alpha-reductase. We determined the effects of epristeride, a 5 alpha-reductase inhibitor, on the density of TXA2 receptors in rat aortic smooth muscle cells and human erythroleukemia cells, a megakaryocyte-like cell, in vitro, and in rat platelets and aortic membranes in vivo. In rat aortic smooth muscle cells, epristeride significantly (P < .01, n = 5) blocked the effect of testosterone to increase TXA2 receptor density (Bmax: 44 +/- 3, 76 +/- 7, 48 +/- 4 and 46 +/- 4 fmol/mg protein, for control cells, cells treated with testosterone (200 nM), cells treated with testosterone and epristeride (10 nM) and cells treated with epristeride, respectively. Epristeride did not block the effect of testosterone in human erythroleukemia cells. Treatment of male rats with epristeride for 2 weeks significantly (P < .01) decreased TXA2 receptor density in aortic membranes (41 +/- 3 for vehicle, n = 10; 27 +/- 3 fmol/mg protein for epristeride, n = 11) but did not significantly change TXA2 receptor density in platelets. Maximum contractile responses of rat aortas to U46619, a TXA2 mimetic, were significantly (P < .001) lower in epristeride-treated rats than in vehicle-treated rats (4.2 +/- 0.1 for vehicle, n = 16, 3.0 +/- 0.2 g tension for epristeride, n = 15). In conclusion, regulation of expression of TXA2 receptors by testosterone in cells of vascular origin, but not in platelets, appears to be via DHT.

5-alpha Reductase Inhibitors↗
PubMed1995

Testosterone regulation of platelet and vascular thromboxane A2 receptors.

Testosterone has been implicated as a risk factor for cardiovascular diseases and thromboxane A2 (TXA2) plays a role in these diseases. We tested the notion that testosterone regulates the expression of TXA2 receptors in platelets and vascular smooth muscle. Testosterone significantly increased the density of TXA2 receptors in cultured rat aortic smooth muscle and human erythroleukemia cells, a megakaryocyte-like cell. Treatment of rats with testosterone resulted in a significant increase in platelet and aortic TXA2 receptor density and increased responsiveness to TXA2 mimetics. We conclude that testosterone regulates the expression of TXA2 receptors.

Animals↗
PubMed1995

The effect of nicotine on in vitro sperm motion characteristics.

UNLABELLED: PURPOSE AND STUDY PLAN: Men who are habitual smokers tend to have poor semen quality. We studied the effect of nicotine on sperm motility in vitro. Spermatozoa from 13 normal fertile nonsmoking donors, washed free of seminal plasma, were treated with medium alone (control); and, 10 mM, 5 mM, 1 mM and 0.1 mM nicotine (concentrations estimated to approximate residual concentrations of nicotine in the testes of heavy smokers). Computerized sperm motion analysis (CASA) was done at 2, 4, 6 and 24 h after incubation. RESULTS: Sperm motility, beat/cross frequency, linearity and maximum anterior lateral head displacement (ALH max.) were significantly decreased across nominal dosages (P < 0.001 by repeated measures analysis of variance). Of the concentrations tested, 0.1 mM had no effect; 1 mM significantly decreased sperm motility (P = 0.003) and linearity (P = 0.02); 5 mM decreased the beat frequency (P = 0.001) and linearity (0.02); and 10 mM markedly decreased motility (P = 0.0001), beat frequency (P = 0.0002), linearity (P = 0.02) and ALH max. (P = 0.02). The interactions between dose and time were insignificant. CONCLUSION: Nicotine at concentrations of > or = 1 mM significantly decreased sperm motion characteristics after different periods of incubation, whereas 0.1 mM concentration had the least effect.

Adult↗
PubMed1995

Sex steroid regulation of thromboxane A2 receptors in cultured rat aortic smooth muscle cells.

Thromboxane A2 (TXA2) has been implicated as an important mediator of cardiovascular diseases, and male rat aortas are reported to be more sensitive to it than female aortas. The effects of sex steroids to regulate the expression of TXA2 receptors in cultured male rat aortic smooth muscle cells (RASMC) were determined. TXA2 receptor density (Bmax) and affinity (Kd) were determined via radioligand binding studies with [125I]BOP, a TXA2 receptor agonist. Testosterone increased Bmax in a concentration-dependent manner without any significant change in Kd. Cycloheximide, actinomycin D, and the 5 alpha-reductase inhibitor L645,390 significantly (P < 0.01) blocked the effect of testosterone. Dihydrotestosterone, the active metabolite of testosterone, increased Bmax and was more potent than testosterone. To determine if there is a sex-related difference in response to testosterone, its effect in cultured female RASMC was assessed. Testosterone increased Bmax in female RASMC but the increase was significantly (P < 0.001) less than that seen in male RASMC. These results indicate that androgenic steroids regulate the expression of vascular TXA2 receptors.

Animals↗
PubMed1995

Ovarian hyperstimulation syndrome may be more likely if multiple pregnancy occurs following assisted conception.

Whereas modern assisted conception with such techniques as in vitro fertilisation now helps many subfertile couples to fulfill their ambition to have a child, it has not been without a price. The increased incidence of multiple pregnancies, with their attendant maternal and perinatal sequelae following assisted conception is well known, but perinatologists may be far less familiar with the Ovarian Hyperstimulation Syndrome (OHSS) which is the other major complication when controlled ovarian hyperstimulation is used during assisted conception treatment. Mild forms of OHSS are common and require no more than symptomatic treatment. Severe forms of OHSS are uncommon occurring in 0.6% to 14% of IVF cycles, but are nonetheless very important to identify as they may lead to thrombo-embolic disease, cardiorespiratory dysfunction, renal failure and even death [6]. This review considers whether OHSS may be related to multiple pregnancy by reviewing the available literature and local experience.

Female↗
PubMed1995

Comparison of peak oxygen consumption during cycle and treadmill exercise in severe chronic obstructive pulmonary disease.

BACKGROUND: In normal subjects treadmill exercise usually produces the greatest maximal oxygen consumption (VO2max). This may not be true for patients with severe chronic obstructive pulmonary disease (COPD) in whom bicycle exercise, which offers support for the shoulder girdle, may produce a higher oxygen consumption than treadmill exercise. The aim of this study was to determine which mode of exercise produced the greatest oxygen consumption in patients with severe COPD. METHODS: Eight patients with severe COPD (forced expiratory volume in one second (FEV1) more than three standardised residuals below predicted) exercised to a symptom limited maximum on a bicycle and on a treadmill on separate days. The workload on the bicycle wa increased by 10 watts each minute, and the treadmill gradient was increased by 2.5% alternate minutes whilst the speed remained constant. Measurements of oxygen consumption (VO2), ventilation (VE), heart rate, and oxygen saturation were made, and capillary blood gases were measured before and immediately after exercise. Lactate concentration was measured before and four minutes after exercise. RESULTS: There were no differences at peak exercise between the two forms of exercise for VO2 (median 11.7 and 12.2 ml/min/kg for bicycle and treadmill, respectively), for VE (median 26.6 and 25.0 l/min, respectively), and for heart rate (median 119 and 115 beats/min, respectively). The median lactate levels after bicycle exercise were higher than those after the treadmill (2.42 v 0.94 mmol/l). CONCLUSIONS: Although only a small number of patients was studied and individual variability was large, there was no clear difference between the two forms of exercise. Regular bicycle exercise was unfamiliar to this group of patients and generated the greatest lactate response. The results do not support the hypothesis that bicycle exercise will produce a better performance in patients with severe COPD, but the two modes of exercise cannot be used interchangeably.

Aged↗
PubMed1995

Effect of adrenalectomy and adrenalectomy+hydrocortisone treatment on histopathological, biochemical and zinc and copper profiles in rat testes.

Degenerative changes such as decreased seminiferous tubule diameter, Leydig cell nuclear diameter, spermatogenic arrest, oedematous fluid in the interstitium and lumen of seminiferous tubules and increased levels of zinc, copper and enzymes (lactate dehydrogenase, LDH; leucine aminopeptidase, LAP; and aryl sulphatase) in adrenalectomised rats suggest a possible role of adrenal cortex and its hormones in spermatogonial cell proliferation and subsequent differentiation, homeostasis of biological trace elements and behaviour of enzymes. Atrophy of Leydig cells and the degenerative changes in testes of adrenalectomised rats can be attributed to reduced supply of testosterone. Hydrocortisone, administered through a single dose acted as hyperstate of hydrocortisone for a short duration, thereby inhibiting steroidogenesis either directly by affecting Leydig cell testosterone production or indirectly by affecting the release of LH from pituitary gland and thus caused degeneration of germinal epithelium. Once hydrocortisone (half life < 12 hr) was metabolized, the animals returned to adrenalectomised state, the degeneration persisted. Thus, hydrocortisone administered through a single dose was insufficient to sustain spermatogenesis. Chronic administration at physiological dose may renew spermatogenesis. Increased levels of LDH, LAP and arylsulphatase are, probably, necessary for cellular degeneration. Zinc and copper exhibited an increase and the rise can be corroborated to (1) failure of regulatory mechanism(s) that control the flow of the elements across the blood-testes barrier; and (2) increased oedematous fluid formed by cellular deaths of the germinal epithelium.

Adrenal Cortex↗
PubMed1994

Propranolol metabolism in normal subjects: association with sex steroid hormones.

The objective of this study was to determine the potential role of circulating testosterone and estradiol in regulation of the activity of the sex-dependent pathways of propranolol metabolism (i.e., alpha-naphthoxylactic acid and propranolol glucuronide). The pharmacokinetics of a single 80 mg oral dose of propranolol and the plasma levels of the sex steroid hormones were therefore determined in normal volunteers. In 33 young men there was a positive correlation between the testosterone levels and the propranolol clearances through both alpha-naphthoxylactic acid (p < 0.001) and propranolol glucuronide (p < 0.002), as well as the total clearance (p < 0.05), but not through aromatic ring hydroxylation. Testosterone cypionate administration led to an increased clearance of propranolol through alpha-naphthoxylactic acid in nine of the 11 men studied, further supporting a stimulatory effect of testosterone on propranolol metabolism. In 23 young women there was no significant association between the circulating levels of either estradiol or testosterone and any of the clearances of propranolol. These observations may be clinically relevant for propranolol therapy and may provide improved insight into the influence of gender and circulating gonadal hormones on drug metabolism in humans.

Adult↗
PubMed1994

Testosterone treatment enhances thromboxane A2 mimetic induced coronary artery vasoconstriction in guinea pigs.

Thromboxane A2 (TXA2) has been implicated as an important mediator of cardiovascular diseases. There have been several clinical reports of acute myocardial infarctions occurring in young male athletes abusing anabolic steroids. The effects of treatment of male Guinea pigs with testosterone on the responses to U46619, a TXA2 receptor agonist, in the isolated perfused heart were determined. The maximum pressor responses of the isolated perfused Guinea pig heart to U46619 were significantly (P < 0.05) greater in the Guinea pigs treated with testosterone compared to the controls. These results indicate that testosterone can enhance coronary artery vascular reactivity to TXA2.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Testosterone increases thromboxane A2 receptor density and responsiveness in rat aortas and platelets.

Testosterone has been implicated as a risk factor for cardiovascular diseases. Thromboxane (Tx) A2 is an important pathophysiological mediator for thrombotic vascular diseases. This study investigated the effects of testosterone on platelet and vascular TxA2 receptors. Male rats were treated with either testosterone cypionate for 2 wk, sham operated, castrated, or castrated and treated with testosterone cypionate for 2 wk. Treatment of intact rats with testosterone significantly (P < 0.001) increased the TxA2 receptor density in platelets from 25.4 +/- 3.2 to 42.9 +/- 4.2 fmol/mg protein (P < 0.005, n = 17) and in aortic membranes from 48.7 +/- 1.7 to 86.1 +/- 6.1 fmol/mg protein, n = 9. The threshold concentration of the TxA2 mimetic, [1S-(1 alpha, 2 beta(5Z),3 alpha(1E,3R*)4 alpha)]-7-[3-(3-hydroxy-4- (4'-iodophenoxy)-1-butenyl)-7-oxabicyclo[2.21]heptan-2-yl]-5 -heptenoic acid (I-BOP), to induce platelet aggregation was significantly (P < 0.01) decreased from 0.45 +/- 0.16 nM, n = 7, in the control rats to 0.07 +/- 0.01 nM, n = 13, in the testosterone-treated rats. Testosterone treatment resulted in a significantly (P < 0.05) greater maximum aortic contractile response to the TxA2 mimetic, U-46619, compared with intact rats. Castration resulted in a significant (P < 0.01) decrease in aortic TxA2 receptor density from 51.7 +/- 3.7 to 27.3 +/- 5.3 fmol/mg protein, which was significantly reversed by testosterone treatment (89.2 +/- 7.1 fmol/mg protein; n = 4). Castration resulted in a significantly (P < 0.05) lower maximal aortic contractile response that was reversed by treatment with testosterone. Castration did not significantly change platelet TxA2 receptor density.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Selenium--its biological perspectives.

Selenium is an essential trace element at lower concentrations and toxic at higher concentration. Animals can metabolize both inorganic and organic forms and convert non methylated Se to mono--or di--or tri--methylated forms, of which, mono-methylated forms are most toxic. Glutathione reductase converts selenoglutathione to H2S in liver and erythrocytes and is ultimately excreted. Se effects the toxicities of xenobiotic agents, provides antagonistic effect to Sulphur and co-administration with Zn increase Se retention in certain organs. At its toxic level (4-8 ppm) it increases Cu contents of heart, liver and kidney and has detoxifying or protecting effect against Cd and Hg. It is a prosthetic group of several seleno metalloenzymes. The concentration of the element is decreased in serum/plasma or erythrocytes of patients of AIDS, trisomy-21, Crohn's and Down's syndrome, phenylketonurea, Keshan's disease and cancer. Rather, the element has antiproliferative and cancer protecting effect. Se content of testes increases considerably during pubertal maturation and, during Se deficiency, the supply to the testes has priority over the other tissues. The element is localized in the mitochondrial capsule protein (MCP) and is involved in biosynthesis of testosterone. Neither the age of mother nor the concentration of Se during pregnancy has any effect on weight of baby or the length of pregnancy. Se levels in human milk is affected by maternal intake and its requirements by infants and young children are higher for their rapid growth. Clinical symptoms of its toxicity include severe irritations of respiratory system, metallic taste in mouth, formication of nose, signs of rhinitis, lung edema and brancho-pneumonia. The typical garlic odour of breath and sweat is due to dimethyl-selenide.

Animals↗
PubMed1993

Androgen regulation of thromboxane A2/prostaglandin H2 receptor expression in human erythroleukemia cells.

Thromboxane A2 (TxA2), a platelet aggregator and vasoconstrictor, has been implicated as a potential mediator of cardiovascular diseases. Abuse of androgenic steroids has been associated with thrombotic cardiovascular diseases. Human erythroleukemia (HEL) cells, a megakaryocyte-like cell line, express functional TxA2/prostaglandin H2 (PGH2) receptors with characteristics similar to those seen in platelets. This study characterized testosterone regulation of HEL cell TxA2/PGH2 receptors. TxA2/PGH2 receptor affinity (Kd) and density (Bmax) were determined via equilibrium binding experiments using the radiolabeled TxA2 mimetic (1S-[1 alpha,2 beta(5Z),3 alpha(1E,3R*),4 alpha])-7-(3-[3-hydroxy-4-(4'- iodophenoxy)-1-butenyl]-7-oxabicyclo[2.2.1]heptan-2-yl)-5-he ptenoic acid (125I-labeled BOP). Testosterone (200 nM) but not estradiol increased Bmax from 108 +/- 9 fmol/mg protein to 157 +/- 9 fmol/mg protein (n = 7 experiments; P < 0.01) without any significant change in Kd. Testosterone had no significant effect on alpha 2-adrenergic receptor density. The maximum increase in intracellular free calcium induced by the TxA2 agonists I-BOP or U-46619 was significantly (P < 0.005) greater in testosterone-treated cells compared with controls. Hydroxyflutamide (1 microM), an androgen-receptor antagonist, completely blocked the effect of testosterone (P < 0.01). Dihydrotestosterone, the active metabolite of testosterone, also increased Bmax in a concentration-dependent manner and was more potent than testosterone. The effect of testosterone to increase Bmax was significantly (P < 0.01) inhibited by coincubation with cycloheximide (0.1 microgram/ml) or actinomycin D (10 ng/ml). These results indicate that androgenic steroids regulate the expression of functional TxA2/PGH2 receptors in HEL cells. These findings may have relevance to cardiovascular disease.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

3 alpha-Androstanediol and 3 alpha-androstanediol glucuronide. Maternal and umbilical cord plasma concentrations in normal pregnancy.

Concentrations of 3 alpha-androstanediol (A) and 3 alpha-androstanediol glucuronide (AG) were measured with a radioimmunoassay in pregnancy plasma samples collected from the mother in the first trimester (first, n = 18) and second trimester (second, n = 20) and at term (n = 14). At term, along with the maternal samples, matching cord plasma samples were also obtained (n = 14). Throughout pregnancy the levels of A and AG were significantly higher than in normally menstruating women. Although the total concentration of A and AG did not change significantly throughout pregnancy, the levels of A in the second and at term were significantly higher than in the first. In contrast, AG concentrations in the second were significantly lower than in the first and at term. As compared to the maternal concentrations at term, the cord levels of AG and A plus AG were not significantly different. However, the levels of A in the cord were significantly lower than those in the maternal circulation at term. Significant correlations were observed between the term maternal and cord levels of AG and A plus AG. No sex-related differences in the plasma levels of A and AG were noted. The results show that levels of A and AG increase significantly in the first trimester and remain elevated throughout pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstane-3,17-diol↗
PubMed1992

Plasma 3 alpha, 17 beta-androstanediol glucuronide concentrations in normally menstruating Chinese women.

Hirsutism is rare in oriental women. In order to define the androgen metabolism in these women, plasma levels of androstanediol glucuronide (AG) along with testosterone (T), androstenedione (delta 4A), dehydroepiandrosterone sulfate (DHAS) and sex hormone binding globulin (SHBG) were determined in samples collected from 22 normally menstruating Chinese women. Their ages were 37.7 +/- 7.2 years (mean +/- S. D.) with a range of 27 to 46 years. All were born of Chinese parents. None were on any hormonal medication for at least one year. Compared to our local controls, no significant differences were observed in plasma androgens and SHBG concentrations. Comparable levels of AG, delta 4A and T in these two groups suggest that in Chinese women, under basal conditions, the androgen metabolism is comparable to their north american counterparts.

Adult↗