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Biomedical subjects

M Rajasekaran

Publications and source records attributed to M Rajasekaran.

At least 19 recordsLinked to original sources
PubMed2002

A comparative study of the knowledge, beliefs, and practices of diabetic patients cared for at a teaching hospital (free service) and those cared for by private practitioners (paid service).

The aim of this study was to determine and compare the knowledge, beliefs, and practices of diabetics receiving free medical care and those paying for medical care in Tamilnadu, India. A questionnaire was administered to elicit diabetic patients' knowledge regarding diet, exercise, adverse effects, habits, and other matters; their beliefs about diabetes; and their practices regarding diet, medication, and self-monitoring. The results showed a large gap between knowledge and action in both groups and a need for increased efforts toward patient education regarding diabetes.

Age of Onset↗
PubMed2001

Role of genitourinary inflammation in infertility: synergistic effect of lipopolysaccharide and interferon-gamma on human spermatozoa.

Pro-inflammatory cytokines are elevated in the semen of patients with genitourinary inflammation (GUI). Whether this increase in cytokines in GUI patients plays any critical role in male factor infertility is not clear. The present study investigated the in vitro effects of two important pro-inflammatory cytokines, lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), on sperm motility, viability, membrane integrity and motion parameters. Washed spermatozoa from healthy donors were incubated with LPS (0.1 mg/mL) or IFN-gamma (0.1 mg/mL) alone or in combination. Sperm motility, viability, membrane integrity and computer-assisted motion were evaluated at various time intervals (0, 30, 60 and 180 min) after treatment. Sperm membrane integrity was analysed using the hypo-osmotic swelling test (HOST). LPS and IFN-gamma individually did not alter sperm viability or motility, but their combination showed a significant time-dependent decrease (p < 0.05) in sperm motility, viability and membrane integrity. Sperm motion parameters (straight-line velocity, curvilinear velocity, mean linearity, or amplitude of lateral head displacement) were not affected by LPS or IFN-gamma at the concentrations used in this study. These data suggest that the combination of LPS and IFN-gamma is detrimental to human spermatozoa and may contribute to male factor infertility in patients with chronic GUI.

Cell Membrane↗
PubMed2001

Characterization of ultrastructural and metabolic abnormalities in semen from men with spinal cord injury.

BACKGROUND: In men with spinal cord injury (SCI), fertility is impaired because of a combination of ejaculatory dysfunction and poor semen quality. We hypothesized that ultrastructural and metabolic abnormalities of sperm could be an underlying factor in infertility in these men. METHODS: To investigate mechanisms contributing to the abnormal sperm parameters, we analyzed seminal constituents and sperm ultrastructure in ejaculates from 7 men with SCI and compared them with 5 control subjects. Sperm adenosine triphosphate (ATP) content was measured using a firefly luciferase bioluminescent assay kit, and ultrastructure was evaluated by electron microscopy. Seminal oxidative stress (8-iso-prostaglandin F-2alpha [8-iso-PGF2alpha]) and transforming growth factor-beta1 (TGF-beta1) levels were measured by specific enzyme-linked immunoabsorbent assay kits. RESULTS: Semen samples from men with SCI showed azoospermia (3) and severe asthenospermia (2; motility 0-5%). A majority (65%) of sperm from asthenospermic samples showed degenerative changes and significant axonemal defects. Incubation of normal sperm with SCI seminal plasma induced a concentration-dependent decrease in sperm motility (43%) accompanied by a significant drop in intracellular ATP content (33%). Semen samples from men with SCI exhibited levels of 8-iso-PGF2alpha 3.5-fold higher than those from controls and levels of TGF-beta1 that were 10% higher than those from controls. CONCLUSION: Our results suggest that seminal constituents of men with SCI are detrimental to sperm movement and that ultrastructural degenerative changes may contribute to the impaired sperm motility and viability seen in these patients. These preliminary results must be confirmed in larger patient populations and longitudinal studies.

Adult↗
PubMed1999

Male infertility and erectile dysfunction in spinal cord injury: a review.

OBJECTIVE: To review the pathophysiology, evaluation, and management of erectile dysfunction and infertility in spinal cord injury (SCI). STUDY SELECTIONS: Studies that covered various treatment options and their contraindications, complications, or side effects, including sildenafil (Viagra), intracavernosal injection therapy, topical medications and a urethral delivery system, a vacuum erection device, and penile prostheses. Other studies covered the effects of SCI on reproduction: spermatogenesis and testicular function, and seminal constituents. In addition, assisted reproductive techniques were compared: external vibratory stimulation, electroejaculation, testicular sperm aspiration, and intracytoplasmic sperm injection. CONCLUSION: Goal-directed therapy is the mainstay of treatment of erectile dysfunction in men with or without SCI. The choice of therapy is often defined more by the needs of the patient's sexual relationship than by his erectile dysfunction. The majority of men with SCI are infertile because of a combination of ejaculatory dysfunction, impaired spermatogenesis, and poor semen quality. Although many technological advances have evolved to overcome ejaculatory dysfunction, the sperm density, motility, and function remain poor. Until these parameters are improved, men with SCI will have to pursue more financially and emotionally taxing procedures. Further studies to elucidate the cellular and molecular mechanisms of diminished sperm quality are needed. Addressing the issues of erectile dysfunction and male infertility may help to preserve the relationship between the patient and his partner.

Erectile Dysfunction↗
PubMed1999

Characterization of reactive oxygen species induced effects on human spermatozoa movement and energy metabolism.

Reactive oxygen species (ROS) inhibit sperm movement and have been implicated in male infertility. In this study, we determined the effects of specific ROS produced by activated leukocytes on human spermatozoa and investigated their metabolic site of action. We used chemiluminescence and electron paramagnetic resonance (EPR) to characterize the ROS generated by both blood and seminal leukocytes. We also determined the effects of these ROS on sperm energy metabolism using biochemical analyses and flow cytometry. Both blood and seminal leukocytes produced the same characteristic ROS which were determined to be hydrogen peroxide (H2O2) and superoxide radicals (O2*-). EPR using the spin trapping technique indicated that superoxide radical-dependent hydroxyl radicals (HO.) were also generated. ROS generated by PMA-stimulated blood leukocytes (2-5 x 10(6)/ml) caused inhibition of sperm movement in 2 h (p < .01). Using the hypoxanthine/ xanthine oxidase (0.5 U/ml) system to generate ROS, we determined that spermatozoa ATP levels, after ROS treatment, were reduced approximately eight-fold in 30 min (0.10 x 10(10) moles/10(6) sperm cells) compared to control (0.84 X 10(-10) moles/10(6) sperm cells) (p < .01). Sperm ATP reduction paralleled the inhibition of sperm forward progression. Neither superoxide dismutase (100 U/ml) nor dimethyl sulfoxide (100 mM) reversed these effects; however, protection was observed with catalase (4 X 10(3) U/ml). Flow cytometric analyses of sperm treated with various doses of H2O2 (0.3 mM-20.0 mM) showed a dose-dependent decrease in sperm mitochondrial membrane potential (MMP); however, at low concentrations of H2O2, sperm MMP was not significantly inhibited. Also, sperm MMP uncoupling with CCClP had no effect on either sperm ATP levels or forward progression. These results indicate that H2O2 is the toxic ROS produced by activated leukocytes causing the inhibition of both sperm movement and ATP production. O2*- and HO. do not play a significant role in these processes. Low concentrations of H2O2 causing complete inhibition of sperm movement and ATP levels inhibit sperm energy metabolism at a site independent of mitochondrial oxidative phosphorylation.

Adenosine Triphosphate↗
PubMed1999

Potentiation of erectile response and cAMP accumulation by combination of prostaglandin E1 and rolipram, a selective inhibitor of the type 4 phosphodiesterase (PDE 4).

PURPOSE: Phosphodiesterases (PDEs) are an important component of the signal transduction pathway during the erectile response. To determine the PDE isoforms in the corpora cavernosa in the cat and to establish the functional presence of PDE 4 in human cavernosal tissue, the erectile response to intracavernosal phosphodiesterase (PDE) inhibitors alone and the combination of PDE inhibitors and prostaglandin E1 (PGE1) was evaluated in the anesthetized cat. The in vitro formation of cAMP and cGMP in human cavernosal smooth muscle cells (HCSMCs) treated with PGE1 and rolipram in primary culture was also measured. MATERIALS AND METHODS: In pentobarbital-anesthetized cats, increases in intracavernosal pressure, penile length, and duration of erectile response were determined after intracavernosal injections of (i) the type 3 cAMP-specific, cGMP-inhibitable PDE inhibitor, milrinone, (ii) the type 4 cAMP-specific PDE inhibitor, rolipram, (iii) the type 5 cGMP-specific PDE inhibitor, zaprinast, and (iv) the combination of rolipram and PGE1. Systemic arterial pressure was concurrently assessed in these experiments. All responses to PDE inhibitors were compared with a control triple-drug combination comprised of papaverine (1.65 mg.), PGE1 (0.5 microg.), and phentolamine (25 microg.). HCSMCs were incubated with PGE1 (3 microM) and rolipram (10 microM) individually or in combination up to 2 hours at 37C. The intracellular cAMP and cGMP was extracted by cold absolute ethanol and measured (pmol./10(6) cells) by a commercially available EIA kit. RESULTS: Milrinone (3 to 100 microg.), rolipram (3 to 100 microg.), and zaprinast (3 to 100 microg.) induced dose-dependent increases in intracavernosal pressure and penile length (p <0.05) when administered intracavernosally. The maximum increase in cavernosal pressure in response to zaprinast was associated with no significant change in systemic arterial pressure. When rolipram was combined with PGE1 (0.1 microg.), the increases in intracavernosal pressure and the duration of erectile response were significantly higher (p <0.05) and longer (p <0.05) than those observed when rolipram alone was injected intracavernosally. PGE1 (3 microM) and rolipram (10 microM) produced significant increases (p <0.05) in the accumulation of intracellular cAMP levels in HCSMCs in primary culture above those of the baseline values while intracellular levels of cGMP did not change. CONCLUSIONS: PDE inhibitors administered intracavernosally caused dose-dependent increases in cavernosal pressure in the cat. When a specific cAMP PDE inhibitor was combined with PGE1, the erectile response was enhanced and intracellular levels of cAMP were increased in HCSMCs in primary culture. These data suggest further exploration of the combination of various PDE inhibitors and PGE1 in the pharmacologic treatment of erectile dysfunction and provide functional evidence for the presence of PDE 4 isoenzyme in human penile cavernosal cells.

Alprostadil↗
PubMed1998

Ex vivo expression of nitric oxide synthase isoforms (eNOS/iNOS) and calmodulin in human penile cavernosal cells.

PURPOSE: Nitric oxide (NO) synthesized by nitric oxide synthase (NOS) is recognized as the central mediator of penile erection. This process appears to be mediated mainly by neuronal NOS (nNOS), which is localized to the nonadrenergic, noncholinergic innervation of the penis. However, the role of non-neuronal penile constituents (specifically the cavernosal smooth muscle), as well as other NOS isoforms in NO production in the human penis is not well understood. The present study evaluates the expression of non-neuronal (inducible and endothelial) isoforms of NOS in human penile cavernosal smooth muscle cells in culture. MATERIALS AND METHODS: Primary culture was initiated with explants of human corpora cavernosa. For gene expression studies, total RNA was extracted from cavernosal cells and subjected to reverse transcriptase polymerase chain reaction (RT-PCR). For NADPH-diaphorase histochemistry, the cells were incubated with 1 mM beta-NADPH and 0.5 mM nitrobluetetrazolium at 37C for 3 hours. For indirect immunofluorescence and electron microscopy, cells were incubated overnight at 4C with specific primary (eNOS; calmodulin) and secondary antibodies. A conventional avidin biotin complex technique was used for electron microscopy. RESULTS: The mRNA expression studies revealed that these cells express both endothelial (eNOS) and inducible (iNOS) forms. Localization studies showed positive signals for NADPH-diaphorase, eNOS, and calmodulin. The electron microscopic evaluation confirmed the localization of eNOS to the cytoplasm and small vesicles in the cells. CONCLUSIONS: These findings support the hypothesis that human cavernosal smooth muscle cells express both endothelial and inducible forms of NOS, which may significantly contribute to NO production in the penile architecture during the erectile process.

Calmodulin↗
PubMed1997

Effect of tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on human sperm motility, viability and motion parameters.

Male genital tract infections and non-specific inflammatory conditions may be associated with unexplained infertility. Previous studies have shown the presence of cytokines such as tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the semen of infertile men. However, the mechanism of effect of these cytokines on human sperm function is still controversial. The present study was undertaken to investigate the in-vitro effects of TNF-alpha and IFN-gamma on human sperm motion, viability and the hypoosmotic swelling test (HOST). Washed spermatozoa from normal volunteers (n = 9) were incubated in the presence/absence of TNF-alpha (1 microgram/mL) plus IFN-gamma (0.1 microgram/mL). Sperm motility, viability, HOST, and video sequences were recorded at different time intervals (0, 30, 60 and 180 min). Sperm motion parameters were analysed using computer-assisted semen analysis. There was a time-dependent negative effect of TNF-alpha plus IFN-gamma on sperm motility, viability, HOST, and lateral-head displacement (ALH). The maximum decrease was observed between 60 and 180 min for sperm motility (50.8 +/- 5.6%), viability (52.8 +/- 4.0%), HOST (38 +/- 2%) and ALH (4.7 +/- 0.1 microns) compared to control samples (62.2 +/- 2.8, 62.4 +/- 2.9, 58 +/- 4, and 5.3 +/- 0.4, respectively; All p < 0.05). There was no significant effect on sperm straight-line velocity and mean linearity when compared to control. These data suggest that the common inflammatory cytokines TNF-alpha plus IFN-gamma have only partial detrimental effects on sperm motility, viability, membrane integrity and lateral head displacement, which may contribute to the poor fertilizing potential of human spermatozoa during inflammatory conditions.

Cell Membrane↗
PubMed1997

Effects of luminal nutrients and small bowel transplants on congenital indirect hyperbilirubinemia.

The Gunn rat is an excellent model of Crigler-Najjar syndrome, type 1. In previous studies we demonstrated that heterotopic 15-20-cm jejunal transplants from Wistar rats lowered serum bilirubin levels by 40%, and the reduction was transient (6 weeks). In contrast, orthotopic transplants decreased bilirubin levels by 60% and the effect persisted throughout the 8-week study. This study was initiated to identify the luminal substance(s) which are responsible for the persistent bilirubin-lowering effect of jejunal transplants. Thirty-one Wistar to Gunn 15-20-cm jejunal transplants were randomized to receive daily Thiry-Vella graft irrigation with 5 ml of normal saline (n = 8); bile salts (cholate + deoxycholate, 40 mg/ml, n = 5; fats (Microlipid, 20 mg/ml, n = 5); proteins (Casec caseinate, 40 mg/ml, n = 5); and sugars (Moducal + Polycose, 40 mg/ml, n = 8). Bilirubin levels were measured spectrophotometrically at weekly intervals. At 4 and 8 weeks, enzyme-induced bilirubin conjugation activity was measured using added known amounts of added bilirubin. Irrigation of the transplants with saline, protein, and sugar resulted in moderate (40%) lowering of serum total and indirect bilirubin levels. Fat was significantly more effective, lowering mean total bilirubin levels from 9.6 +/- 0.4 to 1.6 +/- 0.2 mg/dl at 6 weeks. After this time, bilirubin levels increased slightly. Bile salts were slightly less effective, lowering bilirubin levels at 6 weeks by only 75%. However, this effect persisted and at 8 weeks levels averaged 2.4 +/- 0.2 mg/dl. Conjugating enzyme activity in the transplants increased from 1.4 +/- 0.3 to 2.5 +/- 0.5 mg bilirubin conjugated/mg tissue/hr. Luminal fats and bile salts appear to augment enzyme-induced bilirubin conjugation in heterotopic jejunal transplant recipients.

Animal Nutritional Physiological Phenomena↗
PubMed1996

Quantitative assessment of cytokines (GRO alpha and IL-10) in human seminal plasma during genitourinary inflammation.

PROBLEM: Mechanisms involved in infertility due to genitourinary (GU) inflammation are unknown. The production of pro-inflammatory (GRO alpha) and anti-inflammatory (IL-10) cytokines in seminal plasma is monitored in this study. METHOD: GRO alpha, IL-10, and granulocyte elastase were evaluated in semen from I) normal, II) infertile patients, and III) infertile patients with leukocytospermia. RESULTS: GRO alpha in infertile patients with GU inflammation was 1.5-fold higher compared to group II and 2.5-fold higher compared to group I patients. The IL-10 was higher in group III than the other two groups. A positive correlation was observed between granulocyte elastase and GRO alpha in all groups. Group III patients exhibited poor sperm parameters. CONCLUSIONS: A shift towards increased production of pro-inflammatory chemokine GRO alpha may have a potential role in male infertility associated with GU inflammation.

Chemokine CXCL1↗
PubMed1995

Oxidative stress and interleukins in seminal plasma during leukocytospermia.

OBJECTIVE: To quantify the levels of reactive oxygen species, superoxide dismutase (SOD), and interleukins (IL) 2 and 8 in seminal plasma of infertile patients as well as to examine the possible relationship between oxidative stress and proinflammatory cytokines. DESIGN: Semen collected from normal fertile donors, infertile men without symptoms of genitourinary (GU) inflammation, and infertile men with symptoms of infection-inflammation of the GU tract was evaluated for the levels of granulocyte elastase, reactive oxygen species, SOD, IL-2, and IL-8. Any correlation between the levels of reactive oxygen species and other parameters in these population was analyzed statistically. RESULTS: Significantly high levels of granulocyte elastase (18.32 +/- 1.52 U/L), reactive oxygen species (6 x 10(5) cpm), IL-8 (3.7 +/- 0.10 microgram/L), and IL-2 (18.32 +/- 1.47 ng/L) were observed in semen of infertile patients with leukocytospermia compared with the other two groups. In leukocytospermic samples, the activity of SOD was significantly lower (624.89 +/- 41.16 NU/mL) compared with nonleukocytospermic samples (787.85 +/- 24.26 NU/mL) or fertile donors (816.29 +/- 50.16 NU/mL). A significant positive correlation was observed between the levels of reactive oxygen species and IL-8. CONCLUSIONS: These findings suggest that increased oxidative stress observed during leukocytospermia may modulate the level of proinflammatory cytokines. The increased oxidative stress may be due to a defect in the reactive oxygen species scavenging system.

Humans↗
PubMed1993

Spermicidal activity of an antifungal saponin obtained from the tropical herb Mollugo pentaphylla.

The ethyl acetate fraction of Mollugo pentaphylla, a tropical herb, contains an antifungal saponin (mollugogenol-A). We report here the spermicidal effects of this saponin. Washed sperm (> 100 x 10(6) with > 50% motility) from normal volunteers were incubated with varying concentrations (0-300 micrograms/ml) of mollugogenol-A at 30 degrees C. Sperm motility, velocity and viability were assessed at 0, 30, 60 minutes both manually and by using computer assisted semen analysis (CASA). Samples collected at 0 and 60 minutes were evaluated for membrane lipid peroxidation, superoxide dismutase (SOD) activity and transmission electron microscopy. A dose- and time-dependent effect of this saponin on sperm motion and viability was observed. The maximal spermicidal effect (4-5 fold decrease in motility and viability) was observed with 300 micrograms/ml dose of saponin. A three-fold increase in sperm membrane lipid peroxidation with corresponding inhibition of SOD activity were observed after 60 minutes incubation with this spermicidal agent. Transmission electron microscopy of saponin-treated samples revealed significant damage to the sperm membrane in both head and tail regions, and the acrosomal membranes were notably swollen and disrupted. These results indicate that this natural saponin has a potential spermicidal effect besides its known antifungal activity. The likely mechanism of its action involves sperm membrane damage by increased lipid peroxidation.

Acrosome↗
PubMed1991

Pre-clinical toxicity of IDPH-791: a new centrally acting muscle relaxant in rats.

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.

Animals↗
PubMed1988

Antifertility effect in male rats of oleanolic acid, a triterpene from Eugenia jambolana flowers.

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.

Animals↗