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Biomedical subjects

N R Kalla

Publications and source records attributed to N R Kalla.

At least 19 recordsLinked to original sources
PubMed2006

Effect of monensin on the enzymes of oxidative stress, thiamine pyrophosphatase and DNA integrity in rat testicular cells in vitro.

Monensin, a sodium specific ionophore was evaluated for its in vitro effects on rat testis by studying changes at biochemical parameters as well as at the DNA level. It was observed that monensin produced marked alterations in the activities of various enzymes associated with the testicular functions. The significant inhibition of different enzymes of oxidative defense system points toward the generation of reactive oxygen species (ROS) by monensin treatment. The significant depletion of reduced glutathione and elevation in the level of lipid peroxidation further support the above findings. The significant inhibition of the activities of lactate dehydrogenase and adenosine triphosphatase shows the interference of monensin with the normal energy supply in spermatogenesis. Moreover, the significant increase in the activities of acid phosphatase and thiamine pyrophosphatase demonstrates the interference of monensin with the Golgi-lysosomal complex of the rat testis. Induced DNA fragmentation indicates towards the impact of monensin on the DNA integrity and apoptosis. Further studies are needed to understand the important molecular mechanisms responsible for these effects.

Adenosine Triphosphatases↗
PubMed2001

I. The modulatory effect in genotoxic responses due to age and duration of PHT-therapy in epileptic patients.

Sister chromatid exchange (SCE) frequency has been studied from the peripheral blood lymphocyte cultures of 42 epileptic patients on the anticonvulsant drug phenytoin (PHT) for 3 months and their follow-up (6 and 9 months), of 33 epileptics who had not started therapy (PHT-untreated), and of 40 normal healthy controls, all in the same age group, i.e., 10-30 years. PHT-treated epileptic patients at all three durations of therapy (3, 6, and 9 months) showed higher SCE frequency (P < 0.001) than healthy controls and PHT-untreated patients. There was no significant difference in SCE frequency between control and PHT-untreated patients, suggesting that disease is not associated with an increased frequency of SCEs. The frequency of SCEs seems to be influenced by an age factor, when older treated patients (21-30 years) showed higher SCE frequencies at 3 and 6 months (P < 0.001) and 9 months (P < 0.05) than the younger age group (10-20 years). SCE frequency increased linearly with the duration of therapy, i.e., from 3 months to 9 months. No correlation was found between SCE frequency and sex with respect to controls, PHT-untreated, and PHT-treated subjects. In conclusion, the modulating effect on SCE frequencies elicited by age and duration of therapy has been clearly demonstrated by SCE mean analysis. Teratogenesis Carcinog. Mutagen. 21:135-149, 2001.

Adolescent↗
PubMed2001

II. An altered proliferation response due to the anticonvulsant phenytoin (PHT) in epileptic patients.

Lymphocyte proliferation kinetics (LPK) is an end point used in genetic toxicology that was proposed as an alternative for the screening of anticonvulsant drugs. The effect of phenytoin (PHT) was investigated on the mitotic and proliferation indices in cultured blood lymphocytes of 33 sporadically collected untreated and 42 PHT-treated epileptics, where the duration of treatment was 3, 6, and 9 months, and 40 control subjects (age range 10-30 years). PHT induced mitotic delays and decreased the mitotic index. A significant heterogeneity of the first, second and the third metaphases between treated and untreated groups was revealed. A reduction of the proliferation index (P < 0.001) and proliferation delay per cycle (P < 0.001) was also observed. There was little variation between the controls and untreated patients (P > 0.05). The results have confirmed that PHT can affect responses leading to genotoxicity. Teratogenesis Carcinog. Mutagen. 21:151-164, 2001.

Adolescent↗
PubMed1997

Regulation of male fertility by pyrimethamine in adult mice.

Studies were carried out to determine the antifertility and reversibility effect of pyrimethamine (PYR) in adult male mice. The parameters mainly included sperm count and motility, fertility, histoarchitecture of testis and testicular cell kinetics quantitatively following oral administration of PYR (50 mg/kg body weight per day) for 30 days. The same parameters were also studied in PYR-treated animals which were allowed to recover for 45 days (recovery group). The results suggest that sperm motility as well as counts were significantly decreased in PYR-treated animals, and the fertility rate fell to zero. Testicular histology as well as germ cell kinetics were altered. However, in the animals of the recovery group, all the parameters studied were more or less similar to those of control animals. The study demonstrates the antifertility as well as reversible efficacy of PYR.

Animals↗
PubMed1997

alpha-Glucosidase activity in the rat epididymis under different physiological conditions.

The estimation of alpha-glucosidase activity in semen is widely used as a marker of epididymal function. In the present studies, glucosidase activity was evaluated in the different segments of the rat epididymis under various physiological conditions. In addition, the effect of two known male antifertility agents, gossypol and alpha-chlorohydrin, on enzyme activity was evaluated. Enzyme activity was absent from the epididymis of rats aged 10 and 20 days but became detectable at 30 days of age when the adult pattern of distribution (highest activity in the caput epididymis) was established. Enzyme activity was reduced significantly in all segments of the epididymis at 7 days after castration and a significant decrease in activity was also observed following the administration of either gossypol or alpha-chlorohydrin. These findings are consistent with a role for alpha-glucosidase in sperm maturation in the epididymis.

Aging↗
PubMed1996

Antifertility effects of an LHRH agonist in male mice.

This study was designed to investigate the effects of repeated high doses of an LHRH agonist on Swiss porton mouse seminiferous epithelium. Seminiferous epithelium showed more pronounced degenerative effects at the higher dose (1000 micrograms/kg wt/day) of the drug, with arrest of spermatogenesis at all stages of differentiation; effects on spermatogenesis become more evident after pachytene spermatocyte stage. The decrease in the testis-specific enzyme LDH-X is accounted for by the decrease in the number of cells of gametogenic origin. Although complete azoospermia was not observed, acute inhibition of motility of spermatozoa may account for severely decreased fertility rates after mating. However, reduced fertility rates due to decreased libido as a consequence of diminished testosterone levels cannot be discounted.

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

Effect of active immunization to luteinizing-hormone-releasing hormone on the fertility and histoarchitecture of the reproductive organs of male rat.

The feasibility of using a vaccine against luteinizing-hormone-releasing factor for suppression of pituitary and gonadal functions has been indicated for some time. Antibody production against this low-molecular-weight, naturally occurring decapeptide, however, requires to be coupled to a carrier protein to enhance its immunogenicity. LHRH was coupled to diphtheria toxoid (DT). Adult male Sprague-Dawley rats with a mean basal body weight of 200 g were immunized with anti-LHRH-DT (20 micrograms/injection/rat) at four-week intervals. An equal number of unexposed animals served as controls. Six animals were killed every two weeks up the end of the week 43. The vaccination schedule did not have any effect on the gain in body weight, nor was any adverse effect of vaccination observed in the course of the investigations. The pituitary, prostate, epididymis, testes, seminal vesicles, adrenal and thyroid were excised for determination of organ weight and histological examination. The adrenal, pituitary and thyroid showed no remarkable weight changes during the observation period, whereas the weights of the reproductive organs demonstrated significant reductions compared to those of the control group. The histopathology revealed marked to significant changes in the gonads and the accessory sex organs including the prostate. A progressive phase of regeneration of spermatogenesis was evident 98 days after vaccination. Total recovery of spermatogenesis was observed 300 days after vaccination. The mating studies showed the return of fertility 300 days after vaccination. The litters borne were normal. Prostate showed recovery after 154 days of vaccination. Our observations lend strong support to the hypothesis that anti-LHRH vaccine can be effectively used on the management of prostate carcinoma. If the vaccination is given together with a suitable dose of long-acting androgen, contained in an adequate delivery system, the regimen may be used for the regulation of male fertility.

Animals↗
PubMed1988

Clinical microdose study of gossypol: effect on sperm motility and renal function.

This study is part of a series designed to identify the smallest effective gossypol dose for male fertility control. Three men, aged 31-35 years, were administered gossypol, 10 mg/day, orally for 3 months. Urinalysis and assays for plasma hormone values, including cortisol, beta 2-microglobulin, potassium, and BUN, showed no changes during treatment. Forward sperm motility, however, was severely affected by the end of the treatment period (less than 4% forward motility). Sperm density also showed a marked decrease. The subjects developed no undue side effects.

Adult↗
PubMed1988

The effect of gossypol acetic acid on the different stages of the spermatogenic cycle in the rat.

The reversibility of the effect of gossypol on testicular histology and fertility was studied in rats. Adult males of proven fertility were treated orally with gossypol acetic acid (15 mg/kg) for 9 or 16 weeks (groups 1 and 2, respectively). Another groups of animals (group 3) was given gossypol (15 mg/kg) for 16 weeks and killed 6 weeks after the end of treatment. Control animals (group 4) were given the vehicle only by oral intubation. In the mating studies, although only 33% of the animals in group 1 were infertile, 100% infertility was observed following 16 weeks of gossypol treatment (group 2). All animals in group 3 regained their fertility 6 weeks after cessation of drug treatment. Damage was observed to 15.7% of the seminiferous tubules after 9 weeks of drug treatment, and to 78% after 16 weeks of treatment. Extensive vacuolization, increased numbers of lipid droplets, degeneration of germ cells, loosening of the epithelium, and a significant decrease in the number of pachytene spermatocytes (stages VII-X) and spermatids (steps 7-10 at stages VII-X) were observed after gossypol treatment. There was a decrease in the diameter of only stage VIII seminiferous tubules after 9 weeks of treatment, whereas a reduction was observed in the tubules of all stages after 16 weeks of gossypol treatment. In the recovery phase, the diameter of seminiferous tubules was similar to that of controls, except for tubules at stage VIII. No change in the area of the lumen of the seminiferous tubules and lipid bodies was observed after 9 weeks of drug treatment, but a marked reduction in the area of the lumen (stages II-X) and an increase in lipid bodies (all stages) was observed after 16 weeks of gossypol treatment. Six weeks after cessation of treatment, the area of the lumen and the number of lipid bodies were comparable to values in controls. A reduction in the area of the epithelium was restricted to just a few stages (VIII-XIV) in treated animals at 9 weeks, whereas after 16 weeks the area of the epithelium was decreased in all tubules. In the recovery phase, except for tubules at stage VIII, the area of the seminiferous epithelium was comparable to that in controls.

Animals↗
PubMed1988

Effect of high energy shock waves on human spermatozoa in vitro.

We investigated the effect of high energy shock waves on human spermatozoa in vitro. Human semen samples of proven motility, kept in polyethylene tubes, were subjected to shock waves (100, 500, and 1,000) using a HM3 Dornier lithotripter. A progressive decrease in the spermatozoa vitality was observed with increasing doses of shock waves. Spermatozoa decapitation became significant with increasing doses of shock waves. A progressive decrease in sperm motility was observed following exposure to shock waves, but these changes were not significant.

Humans↗
PubMed1986

Ultrastructure of monkey (Macaca radiata) spermatozoa: effect of gossypol in vivo.

The present study examines the ultrastructure of ejaculated spermatoza from bonnet monkey, Macaca radiata under normal conditions, with gossypol treatment and during recovery from such treatment. Monkeys were fed orally with gossypol acetic acid (GAA) for 3 months (4 mg/monkey/5 days a week). Semen samples collected by electro-ejaculation, and the spermatozoa were examined using both light and electron microscopy. The degree of motility was also noted by Kalla et al. Ejaculated spermatoza were immotile 90 days after GAA treatment, but little evidence for any abnormality in the spermatozoa could be seen by light microscopy. Some ultrastructural changes were observed, but not to the extent previously reported in spermatozoa of Macaca fascicularis. After termination of treatment, semen samples were obtained every 5th day until sperm count and motility recovered to the normal level. After 90 days only a small proportion of spermatozoa showed abnormal structure. We conclude that in a subhuman animal model gossypol induced effects on sperm motility and morphology are reversible.

Administration, Oral↗
PubMed1986

Involvement of prostaglandin in the antifertility effects of gossypol.

This study was undertaken to determine the effects of gossypol alone and gossypol in combination with prostaglandin and aspirin. Rats were administered gossypol (40 mg/kg/day), gossypol and prostaglandin (PGF2 alpha-2 mg/kg/day), gossypol and aspirin (300 mg/kg) for 4 weeks. A marked effect of the gossypol-prostaglandin combination was observed on sperm motility and spermatogenesis. The effect of the gossypol-aspirin combination was less pronounced. The ratio of body weight to testicular and epididymal weights between the different groups showed no marked difference. No effect of drug treatment on plasma testosterone, LH and FSH was observed. The data presented in this paper suggest that prostaglandin plays an important role in the antifertility effects of gossypol.

Animals↗
PubMed1984

Effect of gossypol on bull spermatozoa in vitro.

Gossypol acetic acid in a concentration of 1,000 microgram/ml solvent is able to immobilize 1 ml of native bull semen (sperm concentration: 8.5 X 10(8)/ml; motility rate: 87.4%) within 30 min. After GAA treatment the spermatozoa show severe morphological damage on the membrane system, on the acrosomal complex and on the tubular complex of the end piece. The working mechanism of GAA can be assumed to be inactivation of enzyme activities or in direct reactions with plasma membrane material.

Animals↗
PubMed1980

Studies on the mechanism of action of alpha-monochlorohydrin.

After a single oral dose of 100 mg/kg of alpha-chlorohydrine, two distinct phases in the response of the testes to the treatment have been observed: (i) the immediate onset of testicular swelling lasting up to five days, accompanied with a steady increase in the weight of the testes and (ii) thereafter a constant decrease in the testes weight. Changes in the diameter of the seminiferous tubules and the thickness of the basement membrane were observed after the administration of the drug. Multinucleated giant cells were encountered 5 days after drug administration. Alkaline phosphatase, SDH, nucleic acids and proteins showed a fall after treatment with the drug. On the contrary, cholesterol, phospholipids and glycogen showed an increase after its administration. Acid phosphatase showed a fall in the initial stages only, but the activity was higher after 10, 20 and 40 days of the treatment with the drug. The level of plasma and testes testosterone remained normal after chlorohydrin administration. The induction of lesions in hypophysectomised gonadotropin-stimulated animals suggests that the action of chlorohydrin is not mediated through gonadotropins. Alpha-chlorohydrin administered intratesticularly did not evoke any changes in the histo-architecture of the testis.

Animals↗