Biomedical subjects
Publications and source records attributed to M Rajasekaran.
IDPH-791, a novel centrally acting muscle relaxant, in doses up to 500 mg/kg (po) for 14 days did not result in any appreciable adverse effect on body weight gain, food or water consumption including biochemical and haematologica parameters in rats. Variations observed in the biochemistry and haematology were either comparable to controls or were within normal limits.
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The antifertility activity of oleanolic acid (C30H48O3), isolated from the flowers of Eugenia jambolana, was evaluated in male albino rats. The administration of the compound for 60 days decreased the fertilizing capacity of the animals without any significant changes in body weight or reproductive organ weights. The compound produced arrest of spermatogenesis but did not cause any abnormality to spermatogenic cells, Leydig interstitial cells and Sertoli cells. Oleanolic acid may prove to be a promising antifertility agent devoid of undesirable side effects.
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The effect of calcium chloride and nifedipine on prolactin-(PRL) induced analgesia was studied by chemical assay and compared with other analgesics like morphine, thyrotrophin-releasing hormone (TRH) and clonidine. Nifedipine potentiated the analgesic effect of PRL similar to morphine while that of clonidine and TRH remained unaltered. Further, calcium chloride administration antagonized the analgesic effect of PRL and of morphine. These data suggest that PRL, similar to morphine, may alter calcium movements across the membrane to produce analgesia.
The generation of reactive oxygen species (ROS) and sperm damage was evaluated in (a) samples obtained during electroejaculation (EE) of men with spinal cord injury and (b) in electrolyzed HAM's F-10 medium subjected to electric current in vitro. Chemiluminescence data showed a significant increase in ROS in the ejaculates (6 x 10(7) photons/ml) collected immediately after EE and in the electrolyzed medium (3 to 7 x 10(6) photons/ml) when compared to the control (4 to 7 x 10(4) photons/ml). Incubation of normal human sperm with the electrolyzed medium resulted in a significant threefold decrease in percent motility and a twofold decrease in percent viability. Sperm subjected to direct electric stimulation in vitro exhibited a significant twofold decrease in percent motility and percent viability. Superoxide dismutase (SOD) activity decreased significantly in sperm subjected to direct electric current in comparison to the control or the sample incubated with electrolyzed medium. These studies indicate that in vitro and in vivo electrical stimulation generate reactive oxygen species and affect SOD activity, which in part are responsible for decreased sperm motion and viability.
Major advances in science and medicine have led to improved understanding of the pathophysiology of erectile dysfunction. The development of reliable pharmacological therapy for erectile dysfunction has led to heightened awareness in the public and medical communities. This article reviews recent clinical advances and future research directions.
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Nitric oxide (NO) is a product of nitric oxide synthase (NOS) activity and is recognized as the main mediator of penile erection by induction of cavernosal smooth muscle relaxation. Although excessive NO can be generated via inducible NOS activation under certain inflammatory and noninflammatory conditions, for example, in response to TGF-beta and gamma-IFN (the proinflammatory cytokines), the effect of excessive NO produced as reactive nitrogen radical (NO.-) in the corpora cavernosa is not known. The present study was designed to evaluate whether the effect of NO.- on human cavernosal cells in primary culture is via oxidative stress. Cell growth was monitored by DNA synthesis, and mitochondrial function was evaluated by adenosine triphosphate (ATP) production. Primary culture was initiated with explants from human corpora cavernosa, and the monolayer cavernosal cells (passage 2-3) were plated on 12-well tissue culture plates. At 70%-80% confluency, the cells were incubated with varying concentrations of sodium nitroprusside (SNP) for 16 hours. The cell growth (DNA synthesis) was monitored by measuring [3H] thymidine incorporation, ATP levels (nanomoles per 10(4) cells) were measured by chemiluminescence assay using a luminometer, the total oxidative stress was monitored by measuring the levels of 8-iso PGF2alpha (picograms per milliliter) by using an enzyme-linked immunosorbent assay kit, and NO production was monitored by accumulation of nitrite levels (micrometer per 10(4) cells). Human cavernosal smooth muscle cells (HCSMC) exposed to SNP (0 to 0.8 mM) exhibited a dose-dependent (two- to fivefold) decrease in DNA and ATP synthesis, accompanied by a two- to threefold increase in the levels of 8-iso PGF2alpha and about an eightfold increase in nitrite accumulation. These findings suggest that the NO released by SNP (>0.8 mM) exhibited a significant cytotoxicity to HCSMC, mediated by increased oxidative stress to these cells.
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Oxygen toxicity is an inherent challenge to aerobic life, including spermatozoa, the cells responsible for propagation of the species. How this toxicity affects the spermatozoan in its interactions with the ovum is still unknown. An increase in oxidative damage to sperm membranes, proteins, and DNA is associated with alterations in signal transduction mechanisms that affect fertility. Recent evidence suggests that spermatozoa and oocytes possess an inherent but limited capacity to generate ROS to aid in the fertilization process. Though a variety of defense mechanisms encompassing antioxidant enzymes (SOD, catalase, and GSH peroxidase and reductase), vitamins (E, C, and carotenoids), and biomolecules (GSH and ubiquinol) are available, a balance of the benefits and risks from ROS and antioxidants appears to be necessary for the survival and functioning of spermatozoa. An assay system for the evaluation of OSS needs to be developed. Such an assay will assist the clinician in the assessment of fertility status of both male and female partners. The determination of this OSS value will also theoretically identify the subgroups of responders and nonresponders to any putative antioxidant therapy. Though the therapeutic use of antioxidants appears attractive, clinicians need to be aware of exaggerated claims of antioxidant benefits by various commercial supplements for fertility purposes until proper multicenter clinical trial have been completed.
Human serum albumin (HSA) is being considered as an alternate media for sperm enrichment in assisted reproductive technology (ART) because of recent concern with the use of Percoll. In this study, we compared HSA and Percoll for 1) sperm recovery, 2) reactive oxygen species scavenging potential, and 3) effects on total oxidative stress to spermatozoa. The spermatozoa-enriched fractions obtained from Percoll (80%:40%) and HSA (12%) were monitored for sperm motility, viability, hypoosmotic swelling test (HOST), and adenosine triphosphate (ATP) levels. The effect of superoxide anions (O2.-) on donor human spermatozoa was observed in the presence of either HSA or Percoll media. A combination of luminol and the Cypridina luciferin analog 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo(1,2-alpha)pyraz in-3-one hydrochloride was used as a highly sensitive chemiluminescence probe in our hypoxanthine and xanthine oxidase-based assay for O2.-. Sperm membrane total oxidative stress was determined by measuring levels of the prostanoid 8-iso-Prostaglandin F2alpha (8-iso-PGF2alpha). Significant differences in sperm parameters between the Percoll-enriched spermatozoa (motility 60%+/-4%, viability 56%+/-6%, and HOST 73%+/-7%) and those enriched with HSA (motility 84%+/-5%, viability 85%+/-4%, and HOST 84%+/-3%; P < 0.01) were observed. Adenosine triphosphate levels were significantly higher, by almost 50%, in samples processed with HSA than with Percoll (P=0.03). The dismutation rate of O2.- in HSA (slope -6.8) was significantly lower than in Percoll (slope -87.0; P < 0.01). Sperm motility and ATP levels decreased at a slower rate after treatment with O2.- in the presence of HSA when compared to Percoll; moreover, spermatozoa in HSA regained partial motility after 2 hours, whereas spermatozoa in Percoll were immobilized. No significant differences in 8-iso-PGF2alpha levels in spermatozoa enriched by either HSA or Percoll were observed. We conclude that the HSA sperm enrichment procedure improves the recovery of higher quality spermatozoa compared to Percoll and, because of its antioxidant properties, may be useful in processing high leukospermia semen samples for ART purposes.
The purpose of this study was to investigate the in vivo effects of intracavernosal injections of adrenomedullin (ADM), calcitonin gene-related peptide (CGRP), nociceptin, vasoactive intestinal polypeptide (VIP), sodium nitroprusside (SNP), and prostaglandin E1 (PGE1) on penile erection in castrated and intact (control) anesthetized cats. Erectile responses to ADM, CGRP, nociceptin, VIP, SNP, and PGE1 were compared with responses to a standard triple-drug combination (1.65 mg of papaverine, 25 microg of phentolamine, and 0.5 microg of PGE1) in both castrated and control cats. In control animals, ADM, CGRP, nociceptin, VIP, SNP, and PGE1 induced penile erections similar to those elicited by the triple-drug combination. However, in castrated animals, there was a significant decrease in erectile response; the response to intracavernosal injection of the standard triple-drug combination in castrated cats was 28% of that of the control group of animals. Serum testosterone levels demonstrated a significant (P < 0.0001) positive correlation (r = 0.52) with intracavernosal pressure in response to the standard combination. A marked reduction in serum testosterone levels was observed in castrated cats when measured by radioimmunoassay (0.34 +/- 0.1 ng/dl in castrated cats, compared with 31.15 +/- 6 ng/dl in control cats). These data suggest that the presence of testosterone is a necessary prerequisite to sustain a pharmacologically induced penile erection in the cat.