Effect of estradiol on expression of cytoskeletal proteins during spermatogenesis in testis of sexually mature rats.

Earlier studies had shown that long term treatment with estradiol arrests spermatogenesis in adult male rats, at a dose of 0.1 mg/kg/day. The present study was therefore undertaken to ascertain the causes underlying the reduction in sperm counts by administering estradiol for a short term, at the dose of 0.1 mg/kg/day. Estradiol valerate was injected at a dose of 0.1 mg/kg/day, for a period of 10 days to one group of adult male rats, which were administered saline for 12 days prior to estradiol injection, and sacrificed after 22 days. The control group was administered saline for 22 days. The sera were analyzed for testosterone and FSH levels. One testis of each male was immersion fixed for histology, and for immunohistochemistry of two testicular cytoskeletal proteins, vimentin and vinculin. The contralateral testes were used for analysis of vimentin and vinculin gene expression by reverse transcriptase polymerase chain reaction (RTPCR) and western blotting. Another group exposed to estradiol for 10 days was injected with bromodeoxyuridine (BrdU), at a dose of 100 mg/kg/day, to ascertain the effect on germ cell proliferation, and sacrificed 12 days later, while estradiol treatment was continued till sacrifice. BrdU, at a dose of 100 mg/kg/day was injected i.p. to a group of control rats treated with saline for 10 days, and sacrificed 12 days later. The testes from both groups were immersion fixed for immunohistochemical detection of BrdU. Histology of estradiol treated testis showed predominance of tubules with round spermatids with accumulation of lipid droplets in Sertoli cell cytoplasm and decreased cell height, whereas controls showed elongating spermatids. BrdU immunolocalization in the testis, irrespective of treatment, indicated its incorporation in deoxyribonucleic acid (DNA) suggesting that estradiol sustained germ cell proliferation. Both vimentin and vinculin could be immunolocalized to the testis. The testicular levels of vimentin and vinculin, quantified after western blotting, were unaffected. The testicular expression of vimentin and vinculin seen by RTPCR was also unaffected. The study suggested that estradiol induced reduction in sperm counts was not due to adverse effects on proliferation. The observed predominance of seminiferous tubules showing round spermatids, accumulation of lipid droplets as compared to controls suggested that reduction in elongated spermatids occurred through reduced spermiation and phagocytosis. The study also suggested that reduction in Sertoli cell height after short-term estradiol treatment was not due to reduced expression of vimentin and vinculin, which could be maintained by estradiol. However, reduction in Sertoli cell height could have been due to suppression of FSH and testosterone, implicated in the polymerization of vimentin and organization of vinculin, two cytoskeletal proteins involved in inter-Sertoli or Sertoli-germ cell junctions. The study suggested that disorganization of Sertoli cell cytoskeleton and reduction in the volume of Sertoli cells could be an important factor for reduced efficiency of spermatogenesis after exposure to estrogenic molecules.

Post-marketing surveillance of arteether in malaria.

OBJECTIVE: To undertake post-marketing surveillance (PMS) of arteether (E-Mal) with the aim of obtaining feedback from clinicians regarding its safety, tolerability, efficacy and adverse event profile in patients of P. falciparum malaria. METHOD: Post-marketing surveillance proforma to collect data from clinicians using arteether (E-Mal) was provided to institutions/nursing homes and hospitals where Arteether (E-Mal) was available for use in treatment of P. falciparum malaria. These clinicians were informed about the need and relevance of providing this feedback regarding their reexperience on E-Mal therapy on predesigned proforma. Duly filled proformas were received by Central Drug Research Institute, Lucknow for data analysis, documentation and conclusions regarding E-Mal therapy. RESULT: A total of 300 reports were received for analysis from states of Bihar, Gujarat, Madhya Pradesh, Maharashtra, Rajasthan and Uttar Pradesh. The results show that 294 cases (98%) were cured, five cases improved and one patient did not show any change in the clinical status. The side effects (headache, nausea, vomiting and giddiness) reported in the proforma of 14 cases were mild in nature and no causal relationship with arteether could be ascertained. CONCLUSION: An indepth analysis of these 300 reports confirmed the safety, highlighted excellent tolerability and further proved the efficacy of three-day schedule of arteether (IMI) for treatment of malaria. Arteether should not be used in P. Vivax malaria (E-Mal) except when smear is positive for both (P. falciparum and P. vivax). In such a situation risk-benefit should be carefully evaluated before advocating the use of E-Mal therapy. The post-marketing surveillance is continuing and it is hoped that with more feedback from the clinicians from various parts of the country PMS data on this novel antimalarial drug (E-Mal) would further be documented.

Assessment of cardio-pulmonary efficiency in athletes and non-athletes.

Cardiopulmonary efficiency was studied in 18 Indian medical students and 19 state level athletes by estimating maximal oxygen uptake (VO2 max), and other parameters related to oxygen transport i.e., heart rate, O2 pulse, respiratory quotient, ventilation volume, breathing reserve and dysponoeic index, following graded exercise on a treadmill. Higher VO2 max observed in athletes, was due to higher stroke volume and arterio-venous O2 difference. Though athletes had higher breathing reserve at VO2 max work load, their dysponoeic index and ventilation volume at VO2 max did not differ significantly from non-athletes suggesting that athletes were economical in expending energy for work of breathing during exercise.

A comparison of ventilatory pulmonary functions between the National Cadet Corps (N.C.C.) of hilly and plain areas.

National Cadet Corps (N.C.C.) were tested for assessing their physical efficiency level with special reference to respiratory performances. The height and weight of the cadets from hilly and plain areas were noted to be similar indicating alike attainment of growth. The mean values of all pulmonary function tests (FVC, IC, ERV+TV, FEV1, MEFR) except MVV were observed to be similar in both the group of subjects. The mean value of MVV was significantly higher in subjects from hilly area than that in those from plain area.

Respiratory performance and grip strength tests on the basketball players of inter-university competition.

The participants of Basketball in the Inter-University competition were tested for assessing the physical efficiency level with special reference to respiratory and strength performances. The simple anthropometric measurements like height and weight of these subjects were noted to be higher than those of average healthy nonathlete populations of India. The socio-economic status of these subjects was assessed by standard questionnaire method and they were from families having income range between Rs. 85/-165/ per capita per month. The respiratory performances viz. FVC, FEV1, MVV, MEFR, PEFR were all noted to be high in these sportsmen in comparison to those of age-matched healthy Indians. The grip strength test values were similar to those of hockey and soccer players. This study, therefore, indicated more efficiency in basketball players than in the age-matched average non-athlete healthy Indians.

Monoamine oxidase activity in the pituitary of mice after estrogen, progesterone and centchroman treatment.

Monoamine oxidase activity (MAO) was estimated in the pituitary of ovariectomized mice after a single administration of estradiol-dipropionate (0.01 mg/kg; im), progesterone (1 mg/kg; im) and centchroman (1.25 mg/kg ip). Estrogen and progesterone were found to decrease the enzymic level, as compared to control, while centchroman remarkably increased it. The significance of dissimilarity in the pituitary threshold for steroidal and nonsteroidal molecule is discussed.