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Biomedical subjects

R S Mathur

Publications and source records attributed to R S Mathur.

At least 19 recordsLinked to original sources

Effect of hemodialysis on serum progesterone level in pregnant women.

The objective of this study is to evaluate the effect of chronic hemodialysis on serum progesterone level in pregnancy. Serum progesterone levels were measured predialysis and postdialysis using the radioimmunoassay technique in seven gravid women with renal failure requiring hemodialysis. Uterine contractions were measured before and after hemodialysis using home uterine activity monitoring (HUAM) in two patients. Thirty-three paired serum samples were obtained between 14 and 39 weeks' gestation. The mean change in serum progesterone level postdialysis throughout pregnancy ranged from -52.0% to +8.7% for each individual patient. The change in serum progesterone level was unrelated to gestational age. The woman experiencing the most significant decrease in serum progesterone level with dialysis continued her pregnancy to greater than 39 weeks. No significant increase in uterine contraction frequency was noted on HUAM postdialysis (P = 0.22), although both monitored patients experienced a small increase in serum progesterone levels. In conclusion, serum progesterone values showed a variable patient-specific response when measured predialysis and postdialysis in pregnancies complicated by renal failure. There was no significant increase in uterine activity noted postdialysis. Progesterone withdrawal does not appear to explain the increased frequency of preterm delivery in women after dialysis.

Female

Presence of platelet-activating factor in squirrel monkey (Saimiri boliviensis) spermatozoa: seasonal differences.

Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphoryl-choline) (PAF) is a potent signaling phospholipid which has pleiotropic biological properties in addition to platelet activation. PAF has been detected in the spermatozoa in a number of species. The concentration of PAF is inversely related to human spermatozoa quality. There are no reports on the presence of PAF in nonhuman primate spermatozoa. Therefore, the primary objective of this study was to determine if PAF is present in the spermatozoa from the squirrel monkey (which is a seasonal breeder). A second objective was to determine if PAF levels change from the breeding to the nonbreeding season. Endogenous lipids were extracted from mature Bolivian squirrel monkeys (Saimiri boliviensis) spermatozoa and assayed for the presence of PAF by [125I] radioimmunoassay. PAF was detected in all samples assayed. PAF levels were significantly higher (P < 0.01) during the breeding season (mean: 3.58 ng/10(6) spermatozoa) than the nonbreeding season (mean: 0.76 ng/10(6) spermatozoa). The data demonstrate that PAF is present in squirrel monkey spermatozoa, with higher levels found during the breeding season. Additional studies are warranted to elucidate the role of PAF in spermatozoa function.

Animals

Diagnostic role of Mantoux test site biopsy in neurosarcoidosis.

We discuss a patient with sarcoidosis presenting with cranial neuropathy and a cerebral mass lesion evident on imaging. Also, we review from the literature six patients with sarcoidosis presenting with cerebral mass lesion. We emphasize the diagnostic role of Mantoux test site biopsy in patients with dominant or isolated neurologic presentation because the involved sites are not easily accessible and Kveim's test antigen is not commercially available.

Biopsy

Zinc, copper and hydrolytic enzymes in epididymis of hydrocortisone treated rat.

Administration of glucocorticoid (1, 2 and 4 mg) in excess leads to degeneration of epididymides as supported by cellular degeneration, sperm density and morphometric measurements. Zinc level increased statistically after 1, 2 and 4 mg hydrocortisone treatment while copper increased after 1 and 2 mg treatment. Cholesterol, protein and leucine aminopeptidase levels increased and decreased significantly in caput and cauda respectively. Activity of alkaline phosphatase reduced significantly while the treatment of hydrocortisone at different doses elevated acid phosphatase, aryl sulphatase and lactate dehydrogenase activities. Evidently, these changes are as a result of onset of cellular degeneration leading to impairment of metabolic/secretory activity of epididymal cells. The possible involvement of pituitary-testis axis in hydrocortisone induced epididymal degeneration and functional inhibition has been discussed.

Acid Phosphatase

Intrauterine insemination: is it an effective treatment for male factor infertility?

Results were collected from 11 studies comparing intrauterine insemination (IUI) with intracervical insemination (ICI) of frozen donor semen, 10 studies comparing IUI with timed natural intercourse (NI) or ICI in couples with semen defects and seven studies comparing ICI with NI or ICI in couples with unexplained infertility. IUI significantly increased the pregnancy rate relative to favourably timed ICI in donor insemination (DI) with frozen semen both with and without gonadotrophin stimulation of the female partner (odds ratios (95% confidence interval) 1.92 (1.02-3.61) and 2.63 (1.52-4.54) respectively). The benefit of IUI tended to be less when the pregnancy rate for ICI was high and IUI had no benefit with fresh donor semen. Overall IUI was of significant benefit in the male factor couples compared with NI-ICI (odds ratio 2.20 (1.43-3.39) and the advantage appeared to be maintained when comparison was confined to properly timed ICI although the odds ratios were not significantly greater than 1. IUI had no benefit relative to favourably timed NI-ICI for couples with unexplained infertility; an apparent advantage overall was produced by studies where NI was late. None of the studies on male factor used a sperm function test to define male subfertility and three only included couples with good mucus penetration by sperm. The range of semen defects defined was such that many couples would have had a good chance of conceiving naturally given a normal female partner but nevertheless the overall pregnancy rate (4.8%) was considerably less than in the unexplained group (11.6%), suggesting that some sperm dysfunction was present. We conclude that the available evidence suggests that IUI is valuable for DI with cryopreserved semen and for couples with mild to moderately impaired semen quality and postulate that it overcomes failure to fertilize due to impaired mucus penetration and poor survival in the female reproductive tract.

Cryopreservation

The possible role of the immune system in the aetiopathogenesis of ovarian hyperstimulation syndrome.

This review examines recent evidence suggesting a role for the immune system, in particular cytokines, in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). Ovarian tissue is known to contain cells capable of producing a range of immunological mediators and the concentrations of these have been shown to be elevated in serum and ascitic fluid from women with established OHSS. Available evidence points to a role for vascular endothelial growth factor and interleukin-2, possibly acting through other intermediary cytokines, in the pathogenesis of OHSS. However, each individual has a unique cytokine profile and several cytokines may share biological actions, making it difficult to interpret data on isolated cytokine concentrations from relatively small numbers of patients. Improved understanding of the role of the immune system in the development of OHSS may have implications for the prediction, prevention and management of this iatrogenic condition.

Cytokines

Gender-related differences in androgen regulation of thromboxane A2 receptors in rat aortic smooth-muscle cells.

Thromboxane A2 (TXA2) has been implicated as an important mediator of cardiovascular diseases. Aortas obtained from male rats are more sensitive to TXA2 mimetics compared with those obtained from females. A similar phenomenon has been reported in canine coronary arteries. To determine whether there is a gender-related difference in the regulation of TXA2 receptors by androgenic steroids, we determined the effect of testosterone and dihydrotestosterone (DHT) on TXA2 receptor density in cultured rat aortic smooth-muscle (RASM) cells and guinea pig coronary artery smooth-muscle (CASM) cells. TXA2 receptor density (B(max)) and dissociation constant (Kd) were determined by radioligand binding studies with (125)I-BOP, a TXA2 receptor agonist. Testosterone significantly (p < 0.05) increased TXA2 receptor density in cultured RASM cells and guinea pig CASM cells. DHT significantly (p < 0.005) increased the B(max) in male RASM cells (62 +/- 2 vs. 40 +/- 3 fmol/mg protein; n = 7; p < 0.005). DHT increased the B(max) values in both male and female RASM cells, but the increase was significantly (p < 0.05) less in female than in male RASM cells (57 +/- 10% increase for male and 31 +/- 5% for female). Androgen-receptor protein was detected in RASM cells by Western blot and was less in the female RASM cells than in the male. The results indicate that RASM cells possess an androgen receptor and that gender-related differences exist in the regulation of expression of TXA2 receptors by androgens.

Androgens

Androstenedione increases thromboxane A2 receptors in human erythroleukemia cells.

Previous studies have demonstrated an increased thromboxane A2 (TXA2) receptor expression in human erythroleukemia (HEL) cells and rat aortic smooth muscle (RASM) cells in response to testosterone treatment. HEL cells have served as a model for megakaryocytes, the progenitor cell for platelets. Platelets have previously been shown to convert androstenedione to testosterone. This study investigated the effects of androstenedione on the TXA2 receptor density in HEL and cultured RASM cells. Both cell lines were incubated with vehicle, 150 nM testosterone or 250, 500 or 750nM androstenedione for 48 hours. Co-incubation with testosterone or androstenedione significantly (p<0.05) increased the maximum number of TXA2 binding sites (Bmax) in HEL cells compared to controls. There was no significant change in Kd values. In a separate series of experiments, HEL cells were incubated with the androgen receptor antagonist hydroxyflutamide (2.5mM). Treatment with androstenedione (500nM) significantly (p<0.05) increased the Bmax value by 35% compared to control and hydroxyflutamide completely antagonized this effect of androstenedione. Incubation with hydroxyflutamide alone had no effect on the Bmax values compared to control. RASM cells also showed an increase in Bmax values by 25% and 23% over control (95+/-6.6, 118+/-7.2 and 117+/-5.1 fmoles/mg protein, control, testosterone and androstenedione, n=3). Both cell lines converted androstenedione to testosterone. The results raise the possibility that the adrenal androgen, androstenedione can regulate the expression of TXA2 receptors either on its own or via conversion to testosterone and through an androgen receptor.

Androgen Antagonists

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

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

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

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

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