Distinct dependence on size of Pt and Rh nanoclusters on graphene/Pt(111) in the decomposition of methanol-d4.

Pt and Rh nanoclusters, grown on deposition of Pt and Rh vapors onto graphene/Pt(111), show separate reactivity toward the decomposition of methanol-d4. The Pt (Rh) clusters had a mean diameter 2.0-3.5 nm (2.1-4.0 nm) and height 0.45-0.94 nm (0.41-0.9 nm) evolving with the coverage; they were structurally ordered, having an fcc phase and growing in (111) orientation, and had lattice constants similar to their bulk values. Methanol-d4 on the Pt clusters did not decompose but desorbed mostly, disparate from that on Pt(111) surface; the disparity arose as the adsorption energies of methanol-d4 on most surface sites of the Pt clusters became smaller than their single crystal counterpart. This size effect, nevertheless, did not apply on the Rh clusters, despite their similar atomic stacking; the Rh clusters showed a reactivity similar to that of the Rh(111) surface because the adsorption energies of methanol-d4 on both Rh clusters and Rh(111) are comparable. The distinct size dependence was rationalized through their electronic structures and charge distribution of Fukui function mapping. Our results suggest that reactive transition metals do not necessarily become more reactive while they are scaled down to nanoscale; their reactivity evolves with their size in a manner largely dependent on their electronic nature.

Indian folklore medicine in managing men's health and wellness.

India is a home for a large variety of plants with remarkable medicinal and pharmacological value. Traditional medicine in the form of Ayurveda, Siddha and Unani has used many of these plants since ancient days for treating and curing various ailments of the body. When it comes to issues related to reproductive health, people still hesitate to discuss and/or accept it openly and hence look for alternate and natural remedies. The various tribal populations distributed across different parts of the country still use these plant extracts in various formulations for maintenance of good health. The medical utilities of several of these plants have been documented; however, there are many more, whose potential is yet to be explored. This review discusses the role of various plants grown in the Indian subcontinent that have been widely used in maintaining various aspects of reproductive health in men such as infertility, aphrodisiac, contraception, libido, sexually transmitted infections and reproductive tract cancers as well as in treating chronic disorders.

Management of Acute Pulmonary Embolism: Consensus Statement for Indian Patients.

Pulmonary embolism (PE) is an important cause of morbidity and mortality among hospitalized patients. Although the exact epidemiology of PE is not known in India, Some of the studies show that more frequently it is missed and not managed appropriately leading to significant cardiovascular morbidity and mortality. Justification and purpose: Indian guidelines for the diagnosis and treatment of acute PE are not yet formulated. The objective of this consensus statement is to propose a diagnostic and management approach for acute PE in India. PROCESS: A working group of 15 experts in the management of acute PE (cardiologists, pulmonologist, haematologist, emergency specialist and intensivists). This consensus statement makes recommendations for diagnosis and management for PE based on literature review, including Indian data.

RISUG: an intravasal injectable male contraceptive.

Over the last two decades RISUG has been drawing attention in the field of male contraception. It promises to sterile men for a period of up to 10-15 years. According to recent studies in animal models, it proves to be completely reversible. Practically, there are no better options available that can assure complete sterility and precise reversibility. Regardless of so much of information available, RISUG is still holding up for many reasons, firstly, the available information engender bewilderment such as what is this copolymer, how does it work and is reversal really possible? Secondly, advancement of this outstanding invention is drastically slow and thirdly, effects of long-term contraception with RISUG and reports on evaluation of anomalies (if any) in F 1 , F 2 progenies, are lacking. In this review the lacunae as well as advances in the development of RISUG in the light of published work and available resources are pointed out. Formulation of the RISUG, its mode of action and clinical trials have been addressed with particular emphasis.

Sperm characteristics and teratology in rats following vas deferens occlusion with RISUG and its reversal.

The functional success of the reversal of vas occlusion by styrene maleic anhydride (RISUG), using the solvent vehicle, Dimethyl Sulphoxide (DMSO), has been investigated. Reversal with DMSO was carried out in Wistar albino rats 90 days after bilateral vas occlusion. The body weight, organ weight, sperm characteristics, fertility test and teratology, including skeletal morphology were evaluated in vas occlusion and reversal animals and in F(1) progenies to assess the functional success of the occlusion and reversal. Body weight, organ weight and the cauda epididymal sperm characteristics of vas occlusion and reversal animals and of F(1) progenies were comparable to control. Ejaculated spermatozoa in the vaginal smear showed detached head/tail, acrosomal damage, bent midpiece, bent tail and morphological aberrations in sperm head after vas occlusion, which returned to normal, 90 days after reversal. Monthly fertility test, post-injection showed 0% fertility, which improved gradually and 100% fertility was achieved 90 days after reversal. The fertility/pregnancy/implantation record and skeletal morphology of the offspring were comparable to control. The results suggest functional success and safety of vas occlusion reversal by DMSO.

Safety evaluation through genotoxicity and apoptotic markers following RISUG® induced contraception and its reversal in male rabbits.

The safety evaluation following vas occlusion with RISUG® and its reversal with DMSO and NaHCO3, using genotoxicity tests and apoptotic marker assays, was carried out in rabbits. Animals were divided into groups of sham operated control, vas occlusion with RISUG® for 3 & 12 months, reversal with DMSO and NaHCO3 after 3 & 12 months, respectively. Minimum incidences of micronuclei in erythrocytes and frequency of aberrant chromosomes were observed. Caspase-3 and TUNEL positive cells in testis and cauda epididymis sections were observed within control limits. Comet assay in leukocytes and testicular cells revealed damaged cell range at the control level. DNA damage in cauda epididymal spermatozoa was observed between 2-3 % by in vitro study and annexin V assay indicated a significant enhancement (p < 0.05) of positive cells in 3 months vas occlusion group. In conclusion, RISUG® induced occlusion and its reversal has not been correlated with any toxicity.

Relative suitability of DMSO and NaHCO3 for reversal of RISUG® induced long-term contraception.

Among the vas-based methods on trial, reversible inhibition of sperm under guidance (RISUG(®) ), a co-polymer of styrene and maleic anhydride is being projected as an effective alternative to No Scalpel Vasectomy. RISUG offers long-term contraception with safety, efficacy in human trials and can be delivered by no-scalpel injection. Currently, the procedure is under phase-III clinical trial. However, reversal of this vas-based drug-induced contraception needs to be established in animal models prior to clinical trials to ensure its claim as an effective alternative for vasectomy. In the present investigation, the relative suitability of dimethyl sulphoxide (DMSO) and NaHCO3 for RISUG induced long-term vas occlusion reversal was carried out in albino rats. Animals were allocated into four groups (n = 10), viz., sham-operated control (group-I), vas occlusion with RISUG for 360 days (group-II), vas occlusion with RISUG for 360 days and reversal with DMSO (group-III) and vas occlusion with RISUG for 360 days and reversal with NaHCO3 (group-IV). A variable response in fertility was observed in different groups. Absolute sterility in group III at all mating intervals, while, zero percent fertility in groups II and IV following 90 days of occlusion was observed. Following reversal restoration of fertility with DMSO at 45 days, whereas, reversal by NaHCO3 at 30 days was noticed. Ejaculated spermatozoa of RISUG injected and initial intervals of reversed animals exhibited various degrees of abnormalities. The testes exhibited focal degeneration in vas occluded animals. The occluded lumen of the vas deferens contained an eosinated polymer with exfoliated epithelium. Following vas occlusion reversal, a complete regeneration in the vas epithelium was seen. All other parameters remained unaltered. The reversal with NaHCO3 resulted into an early resumption of fertility when compared with DMSO and the procedure found to be successful, feasible and safe up to F1 generation. Thus, RISUG provides a hope for reversible male contraceptives.

Antispermatogenic effects of tolnidamine in langur (Presbytis entellus).

Tolnidamine (50 mg/kg body weight; twice a week; oral) was administered for 90 days to adult male langur monkeys (Presbytis entellus entellus Dufresne) to assess its contraceptive potential. Semen weight, volume, seminal fluid volume, colour, pH and libido remained unchanged. Sperm motility, vitality and morphology were impaired with the advancement of treatment. Sperm density reduced to severe oligospermia following 75-90 days of treatment. Increased number of immature germ cells were also noticed. Resumption of changes to pretreatment range was observed following 90 days of cessation of treatment. However, sperm density remained low all through the recovery period of 150 days. Seminal fructose, ACP, LDH and citric acid concentrations did not change markedly. A significant depletion in GPC and magnesium levels was recorded during treatment and early recovery periods. Alterations in germ cells and Sertoli cells were also observed. A progressive but reversible rise in serum creatinine was evident. Other clinical parameters and body weight response revealed no drug-related alterations. In conclusion, tolnidamine medication induced irreversible inhibition of spermatogenesis.

Long-term sequelae of tolnidamine on male reproduction and general body metabolism in rabbits.

The long-term effects of tolnidamine on male reproduction and general body metabolism were studied in rabbits (Oryctolagus cuniculus). The study was divided into three groups of 10 animals each. The first group (A) received vehicle alone to serve as controls. The second and third groups (B and C) of animals were administered tolnidamine orally at 50 mg/kg body weight/week and 50 mg/kg body weight/day, respectively, for a period of 150 days. The animals of group B exhibited a sperm density of 23.60 million/mL +/- 4.87 million/mL (vs 453.00 million/mL +/- 65.30 million/mL in group A) after 150 days of treatment. In group C, all animals were azoospermic after 135 days of treatment. A reversible impairment of sperm motility, vitality and morphology was noticed. Semen weight, volume, color, pH, libido, and circulatory levels of testosterone remained unchanged. In group B animals, sperm density did not return to control levels even at 150 days after cessation of treatment (37.40 million/mL +/- 4.46 million/mL, vs 380.00 +/- 40.80 million/mL in group A). However, spermatozoa reappeared in animals treated daily (group C) after 30 days of recovery but remained < 5 million/mL during the entire recovery period. A reversible, significant depletion was recorded in seminal glycerylphosphorylcholine (GPC) levels. Fertility was unimpaired in group B animals when compared with those in group A. In group C, fertility was reduced to zero after 150 days of treatment and at 90 days and 150 days after cessation of treatment. No significant alterations were observed in other semen biochemical, hematologic, or blood/serum biochemical parameters with either dose regimen. It is concluded that tolnidamine administration induced dose dependent, irreversible inhibition of sperm production without altering general body metabolism in male rabbits.

Experience with a potent LH-RH agonist, buserelin, alone and in combination with testosterone for antispermatogenic activity, reversibility and toxicity in langur monkey.

Chronic intermittent treatment of LH-RH superagonist Buserelin alone or in combination with testosterone enanthate were given to adult male langurs for 90 days to evaluate antispermatogenic activity of alone and combination therapy, maintenance of normal androgenicity, possible toxic effects of agonist treatment, related side effects of testosterone supplementation and complete reversibility of the procedure. A gradual decrease in sperm count was recorded in both treatment groups, along with reduced motility and vitality of the spermatozoa. In the combination group, oligospermia was achieved in 4 out of 5 animals, whereas, only 2 animals became oligospermic in the agonist alone group. Significant decrease in serum testosterone levels along with impaired libido and other testosterone withdrawal symptoms were observed in the Buserelin alone group, conversely normal testosterone levels and libido were observed in the combination group. An elevation in haematological variables and serum total protein concomitant with a slight gain in body weight of the animals were recorded in the combination group; these changes were not encountered in the agonist alone group. Reversibility of all the altered parameters to control range was observed in both treatment groups following 75 to 90 days of treatment withdrawal.

Antifertility effect of chronically administered Martynia annua root extract on male rats.

The effects of 50% ethanol extract of Martynia annua L. root on reproduction was studied on male rats. The study was divided into four groups of five animals each. The first group (I) received vehicle alone to serve as control. The second, third and fourth groups (II, III and IV) of animals were administered the root extract daily at 50 mg/kg body weight, po, 100 mg/kg body weight, po, and 200 mg/kg body weight, po, respectively, for a period of 60 days. Significant decreases in the weights of testes, epididymides, seminal vesicle and ventral prostate were observed. A dose related reduction in the testicular sperm count, epididymal sperm count and motility, number of fertile males, ratio between delivered and inseminated females and number of pups were observed. The testis showed a clear correlation between the dose and severity of lesions of seminiferous epithelium. In general, the seminiferous tubules appear reduced in size with a frequently filled eosinophilic material. Spermatogenesis arrested at the secondary spermatocyte stage. Pachytene spermatocytes were undergoing degeneration. Disorganisation and sloughing of immature germ cells were visible. Leydig cells were atrophied. No morphological changes were observed in Sertoli cells. Significant reduction in serum concentration of luteinising hormone and testosterone were observed. No distinct change in serum FSII concentration was recorded. The final body weights of all groups were elevated markedly. No alterations were recorded in any hematological parameters. It is concluded that the 50% ethanol extract of M. annua root produced dose related effects on male reproduction without altering general body metabolism.

Ultrastructure of langur monkey epididymidis prior to and following vasectomy and vasovasostomy.

The ultrastructural changes in langur monkey epididymis prior to and following vasectomy or vasovasostomy were studied. The epididymal epithelium of the intact langur monkey was found to consist mainly of principal cells and basal cells and frequently apical or mitochondria rich cells were found. Besides these cells intraepithelial lymphocytes were also a consistent feature of the epididymal epithelium. Principal cells identified by means of the tuft of the stereocilia on their apical surface, bear well developed Golgi bodies, endoplasmic reticulum, vesicles, vacuoles and multivesicular bodies. This suggests their active involvement in absorption and secretion. Basal cells present at the base of the lamina bear a few cellular organelles and strong interdigitations with the adjacent cells. Apical or mitochondria rich cells were characterized by clusters of mitochondria in the apical region of the cell and few microvilli on their apical surface. Lymphocytes with a large nucleus and a pale rim of cytoplasm were also found at the base of the epithelium. Secretory and absorptive functions of principal cells of the epididymal epithelium were found to be increased after vasectomy, as indicated by bulging of the apical portion of the principal cells and membrane bound structure in the lumen. An extensive increase in the number of lysosomes, vesicles and vacuoles was also observed. An increase in the number of macrophages with spermatozoa remnants in the lumen of epididymis suggests that the principal mechanism for spermatozoa disposal following vasectomy is intraluminal endocytosis by macrophages. Changes following vasectomy persisted in vasovasostomized animals even after 12 months of recanalization, which may contribute to the failure of functional reanastomosis.

Evaluation of genotoxicity in leukocytes and testis following intra-vasal contraception with RISUG and its reversal by DMSO and NaHCO3 in Wistar albino rats.

Evaluation of genotoxicity of RISUG® - a vas based contraceptive, was carried out in the present study. Animals were allotted into groups of sham operated control, vas occlusion with RISUG (5-7 µl) for 360 days and reversal by DMSO (250-500 µl) and 5% NaHCO3 (500 µl). Blood samples and testis were collected at 360 days of vas occlusion and 90 days of vas occlusion reversal for comet analysis. Hydrogen peroxide induced samples were used as positive control. Olive moment, tail length and percentage DNA in tail were recorded with minimum variation in all groups for both leukocytes and testis. When compared with positive control the variation was highly significant for both 20 µM and 50 µM H2O2 (p<0.001). It is concluded that vas occlusion with RISUG at the contraceptive dose regimen is not associated with genotoxicity in leukocytes or the testis of pre- and post-reversal rats.

Gene silencing of A-kinase anchor protein 4 inhibits cervical cancer growth in vitro and in vivo.

Earlier, we reported an association of A-kinase anchor protein 4 (AKAP4) expression in cervical cancer patient specimens, indicating its implications as an immunotherapeutic target. In this study, we investigated the possible role of AKAP4 in cervical carcinogenesis. AKAP4 messenger RNA and protein expression was assessed in four cervical cancer cell line models, C-33A, CaSki, HeLa and SiHa. Gene silencing approach was employed to investigate the potential role of AKAP4 in cellular growth, proliferation, colony-forming ability, migration and invasion in aggressive squamous cell carcinoma cells (SiHa). Further, the effect of downregulation of AKAP4 on tumor growth was examined in the cervical cancer xenograft model in nude mice. Our data clearly indicated that AKAP4 was expressed in all cervical cancer cells at the gene and protein level. We also observed distinct cytoplasmic and surface localization by indirect immunofluorescence and flow cytometry, respectively. Ablation of AKAP4 protein caused significant inhibition in cellular proliferation, colony-forming ability, migration and invasion ability of SiHa cells. Further, gene silencing of AKAP4 also resulted in reduced tumor growth in nude mice in vivo. Collectively, AKAP4 surface localization and its significant association with malignant properties of cervical cancer cells imply its clinical utility as an immunotherapeutic target.

Fertility, developmental toxicity and teratogenicity in albino rats treated with methanol sub-fraction of Carica papaya seeds.

OBJECTIVE: To evaluate the status of fertility, developmental stages during gestation and teratological changes, if any, following oral administration of methanol sub-fraction (MSF) of the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya in rats. MATERIALS AND METHODS: The MSF was administered at the doses of 50 mg contraceptive dose (CD), 100 mg (2× CD), 250 mg (5× CD) and 500 mg (10× CD)/kg body wt/day along with vehicle-treated control using 10 male and 20 female Wistar rats in each group. Necropsies were performed one day before the expected parturition. Status of gravid/non-gravid uterus, the number of corpora lutea in the ovary, implantation status, fetal wellbeing, fetal resorption, fetal body weight, external, visceral and skeletal malformations were recorded. RESULTS: Pregnancies were recorded in vehicle-treated control animals and in the animals treated with 50 mg/kg body wt/day. The animals treated with 2× CD, 5× CD and 10× CD did not get pregnant. The fetuses and the status of the ovary, uterus and implantation, fetal body weight, soft tissues and skeletal structures were recorded normal. Data were comparable to those of control. CONCLUSION: The results suggest that the test substance had no developmental toxicity and teratogenicity which could affect pregnancy, implantation and gestation.

Safety evaluation of long term oral treatment of methanol sub-fraction of the seeds of Carica papaya as a male contraceptive in albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The manuscript is one of the series of attempts in authenticating scientific documentation of the seeds of Carica papaya being traditionally used for contraception. AIMS OF THE STUDY: To establish safety of the methanol sub-fraction (MSF) of the seeds of Carica papaya as a male contraceptive following long term oral treatment. MATERIALS AND METHODS: MSF was administered orally to albino rats at multiples of contraceptive dose (CD) at 50 (1x), 100 (2x), 250 (5x) and 500 (10x)mg/kg body weight daily for 52 weeks. Body weight, organs weight, morbidity, mortality, clinical chemistry, sperm analysis, histopathology and serum testosterone were evaluated to assess the safety and contraceptive efficacy. RESULTS: MSF treatment at various dose regimens, daily for 52 weeks did not show significant changes in body weight, organs weight, food and water intake and pre-terminal deaths compared to those of control animals. Sperm count and viability in 50mg/kg body weight treated animals and the weight of epididymis, seminal vesicle and prostate of all the treated animals showed significant reduction compared to control. Cauda epididymal spermatozoa of 50mg/kg body weight treated animals were immotile. Azoospermia was observed in 100, 250 and 500 mg/kg body weight treated animals. Serum clinical parameters, serum testosterone and histopathology of vital organs were comparable to those of control animals. Histology of testis revealed adverse effects on the process of spermatogenesis, while the histology of epididymis, seminal vesicles and ventral prostate showed no changes compared to control. CONCLUSION: The long term daily oral administration of MSF affects sperm parameters without adverse side effects and is clinically safe as a male contraceptive.

Langur prostate and its hormonal modulation.

The normal histoarchitecture of langur prostate of different growth phases, viz., juvenile, sub-adult, and adult, and the hormonal modulation of adult prostate were studied in order to explore its suitability of a surrogate for human prostate. The histological observations revealed that the langur prostate is histoarchitecturally homogeneous. The volumetric composition of stroma (%) was found to be decreased significantly from juvenile to adult and that of epithelium and lumen was found to be increased significantly. The absolute volume (c.c.) of stroma, epithelium, and lumen increased significantly from juvenile to adult. A marked depletion in the various prostatic fluid biochemical parameters was observed in castration groups, which were recovered to control level following testosterone enanthate administration. The castration induced significant increase in volumetric composition of stroma; conversely that of the epithelium and lumen decreased significantly. The absolute volume of stroma did not show any appreciable variation, while that of epithelium and lumen decreased significantly. The inter acinar stroma decreased from juvenile to adult, while the lumen diameter increased significantly from juvenile to adult. Castration increased the inter acinar and lumen diameter; conversely the epithelial height decreased. The testosterone supplementation restored the prostate. However, the volumetric composition of stroma remained high, while the luminal volume remained low. Various prostatic parameters in normal and under altered hormonal conditions suggest that the langur prostate is similar to the human and therefore could be used as surrogate for the human prostate.