Nil Ratan Sircar Medical College and Hospital

In the last few years, a lot of publications suggested that disabling cerebellar ataxias may develop through immune-mediated mechanisms. In this consensus paper, we discuss the clinical features of the main described immune-mediated cerebellar ataxias and address their presumed pathogenesis. Immune-mediated cerebellar ataxias include cerebellar ataxia associated with anti-GAD antibodies, the cerebellar type of Hashimoto's encephalopathy, primary autoimmune cerebellar ataxia, gluten ataxia, Miller Fisher syndrome, ataxia associated with systemic lupus erythematosus, and paraneoplastic cerebellar degeneration. Humoral mechanisms, cell-mediated immunity, inflammation, and vascular injuries contribute to the cerebellar deficits in immune-mediated cerebellar ataxias.

Importance: Calcineurin inhibitors are an established first-line corticosteroid-sparing therapy for patients with corticosteroid-dependent nephrotic syndrome (CDNS), whereas B-lymphocyte-depleting therapy is mostly used as a rescue for calcineurin inhibitor-resistant cases. The positive efficacy and safety profile of rituximab raises the question of whether it could be used as a first-line alternative to calcineurin inhibitor therapy. Objective: To compare the efficacy of rituximab and tacrolimus in maintaining relapse-free survival among children with CDNS. Design, Setting, and Participants: A parallel-arm, open-label, randomized clinical trial was performed from May 8, 2015, to September 20, 2016, with 1-year follow-up in a single-center, tertiary care unit. A total of 176 consecutive children aged 3 to 16 years with CDNS not previously treated with corticosteroid-sparing agents were screened for eligibility. Interventions: The children received either tacrolimus (along with tapering alternate-day prednisolone) for 12 months or a single course of rituximab (2 infusions of 375 mg/m2). Main Outcomes and Measures: Twelve-month relapse-free survival in the intention-to-treat population. Results: Of the 176 children screened for eligibility, 120 were randomized and all but 3 patients completed 1 year of follow-up. The groups were comparable, with mean (SD) age of 7.2 (2.8) years, 32 boys (53.3%) in each group, mean (SD) disease duration of 2.5 (1.5) years and 2.3 (1.7) in the tacrolimus and rituximab groups, respectively, disease duration less than 1 year among 15 children (25.0%) in each group, median (interquartile range) of 4 (3-5) relapses in each group, and mean (SD) cumulative prednisolone dose of 246 (48) mg/kg and 239 (52) mg/kg in the prestudy year in the tacrolimus and rituximab groups, respectively. Rituximab therapy was associated with a higher 12-month relapse-free survival rate than tacrolimus (54 [90.0%] vs 38 [63.3%] children; P < .001; odds ratio, 5.21; 95% CI, 1.93-14.07). Among the patients who experienced relapse, median time to first relapse was 40 weeks in the rituximab group and 29 weeks in the tacrolimus group. Only 2 patients in the rituximab group had more than 1 relapse during the study period compared with 10 patients in the tacrolimus group. The cumulative corticosteroid dose during the 12-month study period was lower with rituximab compared with tacrolimus (mean [SD], 25.8 [27.8] vs 86.3 [58.0] mg/kg). Although both treatments were well tolerated, mild to moderate infections were twice as common in the tacrolimus group (26 [43.3%] vs 13 [21.7%] events). Conclusions and Relevance: In children with CDNS, rituximab appears to be more effective than tacrolimus in maintaining disease remission and minimizing corticosteroid exposure and, given its good tolerability and lack of nephrotoxic effects, may be considered as first-line corticosteroid-sparing therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02438982; Clinical Trial Registry of India: CTRI/2014/01/004355.

BACKGROUND: Arsenic is a natural drinking water contaminant affecting 26 million people in West Bengal, India. Chronic arsenic exposure causes cancer, cardiovascular disease, liver disease, neuropathies and ocular diseases. The aims of the present study were to assess bioindicators of hepatocellular injury as indicated by the levels of liver enzymes, to determine the auto immune status, as indicated by the amounts of anti-nuclear antibodies (ANA) and anti-dsDNA antibodies in their serum, and to predict cardiovascular risk in the arsenic exposed population. METHODS: Effect of chronic arsenic exposure on liver was determined by liver function tests. Autoimmune status was measured by measuring ANA and anti-dsDNA in serum. Inflammatory cytokines associated with increased cardiovascular disease risk, IL6, IL8 and MCP-1 were determined. RESULTS: Our results indicated that serum levels of bilirubin, alanine transaminase, aspartate transaminase, alkaline phosphatase and ANA were increased in the arsenic exposed population. Serum levels of IL6 and IL8 also increased in the arsenic exposed group. CONCLUSIONS: Chronic arsenic exposure causes liver injury, increases the serum levels of autoimmune markers and imparts increased cardiovascular risk.

CONTEXT: Polycystic ovarian syndrome (PCOS), the most common endocrinopathy of women in the reproductive age group seems to be adversely affected by associated thyroid dysfunction. Both pose independent risks of ovarian failure and pregnancy related complications. AIMS: The present study from Eastern India is, therefore, aimed to investigate the prevalence and etiology of different thyroid disorders in PCOS subjects. SETTINGS AND DESIGN: Cross-sectional hospital based survey-single centre observational case-control study. MATERIALS AND METHODS: This prospective single-center study recruited 106 female patients with hypertrichosis and menstrual abnormality among which 80 patients were defined as having PCOS according to the revised 2003 Rotterdam criteria and comprised the study population. Another 80 age-matched female subjects were studied as the control population. Thyroid function and morphology were evaluated by measurement of serum thyroid stimulating hormone (TSH), free thyroxine levels (free T3 and free T4), anti-thyroperoxidase antibody (anti-TPO Ab), clinical examination and ultrasound (USG) of thyroid gland. STATISTICAL ANALYSIS USED: It was done by Student's t-test and Chi-square test using appropriate software (SPSS version 19). RESULTS: This case-control study revealed statistically significant higher prevalence of autoimmune thyroiditis, detected in 18 patients (22.5% vs. 1.25% of control) as evidenced by raised anti-TPO antibody levels (means 28.037 ± 9.138 and 25.72 ± 8.27 respectively; P = 0.035). PCOS patients were found to have higher mean TSH level than that of the control group (4.547 ± 2.66 and 2.67 ± 3.11 respectively; P value < 0.05). There was high prevalence of goiter among PCOS patients (27.5% vs. 7.5% of control, P value > 0.001). On thyroid USG a significantly higher percentage of PCOS patients (12.5%; controls 2.5%) had hypoechoic USG pattern also compatible with the diagnosis of autoimmune thyroiditis. CONCLUSIONS: High prevalence of thyroid disorders in PCOS patients thus points towards the importance of early correction of hypothyroidism in the management of infertility associated with PCOS.

Cases of the steroid-resistant nephrotic syndrome that are resistant to rituximab can be difficult to treat. In this report, ofatumumab, an anti-CD20 monoclonal antibody, showed some benefit in five young patients.

(1967). Surgery of the Paralysed and Flail Shoulder. Acta Orthopaedica Scandinavica: Vol. 38, No. sup97, pp. 3-90.

BACKGROUND: Individual variability in arsenic metabolism may underlie individual susceptibility toward arsenic-induced skin lesions and skin cancer. Metabolism of arsenic proceeds through sequential reduction and oxidative methylation being mediated by the following genes: purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), glutathione S-transferase omega 1 (GSTO1), and omega 2 (GSTO2). PNP functions as arsenate reductase; As3MT methylates inorganic arsenic and its metabolites; and both GSTO1 and GSTO2 reduce the metabolites. Alteration in functions of these gene products may lead to arsenic-specific disease manifestations. OBJECTIVES: To find any probable association between arsenicism and the exonic single nucleotide polymorphisms (SNPs) of the above-mentioned arsenic-metabolizing genes, we screened all the exons in those genes in an arsenic-exposed population. METHODS: Using polymerase chain reaction restriction fragment length polymorphism analysis, we screened the exons in 25 cases (individuals with arsenic-induced skin lesions) and 25 controls (individuals without arsenic-induced skin lesions), both groups drinking similar arsenic-contaminated water. The exonic SNPs identified were further genotyped in a total of 428 genetically unrelated individuals (229 cases and 199 controls) for association study. RESULTS: Among four candidate genes, PNP, As3MT, GSTO1, and GSTO2, we found that distribution of three exonic polymorphisms, His20His, Gly51Ser, and Pro57Pro of PNP, was associated with arsenicism. Genotypes having the minor alleles were significantly overrepresented in the case group: odds ratio (OR) = 1.69 [95% confidence interval (CI), 1.08-2.66] for His20His; OR = 1.66 [95% CI, 1.04-2.64] for Gly51Ser; and OR = 1.67 [95% CI, 1.05-2.66] for Pro57Pro. CONCLUSIONS: The results indicate that the three PNP variants render individuals susceptible toward developing arsenic-induced skin lesions.

Significance Statement Children with frequently relapsing, steroid-dependent nephrotic syndrome (FRSDNS) often require multiple courses of rituximab. However, long-term effects from repeated treatments remain unknown. In this international, multicenter study of 346 children receiving 1149 courses of rituximab, the risk of relapse decreased and relapse-free survival significantly improved with repeated treatments. Important side effects, including hypogammaglobulinemia, neutropenia, and infections, were mostly mild, but significant adverse events could occur. The incidence of side effects did not increase with more treatment courses nor a higher cumulative dose of rituximab. These findings suggest that repeating rituximab therapy is an effective and reasonably safe approach for most children with FRSDNS. Background Long-term outcomes after multiple courses of rituximab among children with frequently relapsing, steroid-dependent nephrotic syndrome (FRSDNS) are unknown. Methods A retrospective cohort study at 16 pediatric nephrology centers from ten countries in Asia, Europe, and North America included children with FRSDNS who received two or more courses of rituximab. Primary outcomes were relapse-free survival and adverse events. Results A total of 346 children (age, 9.8 years; IQR, 6.6–13.5 years; 73% boys) received 1149 courses of rituximab. A total of 145, 83, 50, 28, 22, and 18 children received two, three, four, five, six, and seven or more courses, respectively. Median (IQR) follow-up was 5.9 (4.3–7.7) years. Relapse-free survival differed by treatment courses (clustered log-rank test P &lt;0.001). Compared with the first course (10.0 months; 95% CI, 9.0 to 10.7 months), relapse-free period and relapse risk progressively improved after subsequent courses (12.0–16.0 months; HR adj , 0.03–0.13; 95% CI, 0.01 to 0.18; P &lt;0.001). The duration of B-cell depletion remained similar with repeated treatments (6.1 months; 95% CI, 6.0 to 6.3 months). Adverse events were mostly mild; the most common adverse events were hypogammaglobulinemia (50.9%), infection (4.5%), and neutropenia (3.7%). Side effects did not increase with more treatment courses nor a higher cumulative dose. Only 78 of the 353 episodes of hypogammaglobulinemia were clinically significant. Younger age at presentation (2.8 versus 3.3 years; P =0.05), age at first rituximab treatment (8.0 versus 10.0 years; P= 0.01), and history of steroid resistance (28% versus 18%; P =0.01) were associated with significant hypogammaglobulinemia. All 53 infective episodes resolved, except for one patient with hepatitis B infection and another with EBV infection. There were 42 episodes of neutropenia, associated with history of steroid resistance (30% versus 20%; P =0.04). Upon last follow-up, 332 children (96%) had normal kidney function. Conclusions Children receiving repeated courses of rituximab for FRSDNS experience an improving clinical response. Side effects appear acceptable, but significant complications can occur. These findings support repeated rituximab use in FRSDNS.

BACKGROUND: Empathy is a desirable quality in every clinician. It is a crucial determinant of patient-physician communication and relation. There are very few existent Indian studies on empathy of medical students and its correlates. AIM: The aim of the study was to assess empathy level of medical students and its correlates. METHODOLOGY: It was a cross-sectional, hospital-based, analytical observational study conducted from July to November 2017. In total, 249 undergraduate medical students of a medical college of Kolkata were interviewed with a structured schedule. The schedule comprised of the sociodemographic questionnaire, career satisfaction, future career choice, and Jefferson Scale of Empathy. RESULTS: The mean empathy score was 98.5 ± 12.5. Third-semester students had higher empathy scores (102.4 ± 12.4) compared to fifth (97.2 ± 12.9) and seventh semester (95.0 ± 10.9) students. The difference between the mean scores of different semesters was statistically significant. Female students were more empathic than male students. In the multivariable linear regression model, sex, semester, residence, career satisfaction, future career choice, and current place of living were significant predictors of empathy scores. CONCLUSION: Empathy level of medical students of our study was quite low compared to other studies conducted outside India. Empathy eroded with semester, which supports earlier pieces of evidence in this regard.

In West Bengal, India, although more than 6 million people are exposed to arsenic through drinking water, only 15-20% showed arsenic-induced skin lesions, including premalignant hyperkeratosis. This indicates toward some factors that confer susceptibility to arsenic-induced carcinogenicity. In this work, we wanted to explore whether differences in DNA repair capacity could impart arsenic-induced carcinogenicity, through Comet assay, chromosomal aberration (CA) assay and challenge assay. Sixty arsenic exposed (30 individuals with arsenic-induced premalignant hyperkeratosis and 30 without skin lesion, but drinking similar arsenic contaminated water) and 30 arsenic unexposed individuals were recruited as study participants. Alkaline comet assay, and challenge assay were carried out in whole blood and CA study in lymphocytes to find out the DNA damage and DNA repair capacity in both hyperkeratotic and without skin lesion individuals. DNA damage as well as CA were found to be significantly higher in the arsenic-exposed individuals compared to unexposed individuals (p < 0.001). Within the exposed group, there was no significant difference as far as the level of DNA damage is concerned (p > 0.05), but CA was significantly higher in exposed individuals with hyperkeratosis than exposed individuals without hyperkeratosis (p < 0.01). Challenge assay showed that upon induction of DNA damage, the repair capacity in the exposed individuals with premalignant hyperkeratosis is significantly less (p < 0.001) than that of individuals without skin lesion, although the basal level of DNA damage was similar in both. Thus, the deficiency in DNA repair capacities in the hyperkeratotic individuals emerges as a prime contender for arsenic carcinogenicity.

BACKGROUND: Diabetes mellitus (DM) is a frequently encountered chronic metabolic disease with various complications throughout its course, which causes severe restriction and disability in an individual's life. It has been well documented that the incidence of depression is higher in diabetic patients and co-morbid depression causes further deterioration in the quality of life in diabetic patients. AIMS: To study the prevalence of depression and its impact on quality of life in patients with type II DM. SETTINGS AND DESIGN: Single centre, cross-sectional, single interview. MATERIALS AND METHODS: Total 195 type II DM patients are included in this study. To diagnose Depressive Episode Structured Clinical Interview for DSM IV Axis-1 Disorders, Research Version patient edition was applied. All patients were evaluated with a semi-structured socio-demographic proforma to assess socio-demographic characteristics, Hamilton Rating Scale for Depression (HAM-D) and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) SF (Short Form) to measure the quality of life. RESULTS: Among them, 46.15% (N=90; males: 41, females: 49) met the DSM-IV diagnostic criteria for major depressive episodes. Among the depressed group, majority were (36.7%) moderately depressed. QLESQ-SF total and each item scores were significantly lower in the depressed group than in the non-depressed group. Both the HAM-D scores and HbA1c level have significant negative correlations with QLESQ-SF total scores. CONCLUSION: Our study demonstrates that the presence of depression in type II DM further deteriorates the quality of life of the patients. Therefore, treating depression would have a beneficial effect on the quality of life.

CONTEXT: Performance of medical students in developing nations like India is perceived to have largely declined. AIMS: We attempted to assess the reasons behind such trends. SETTINGS AND DESIGN: Students in their third year of medical study were given a predesigned, pretested structured and validated questionnaire that they filled in anonymously. The key areas assessed were concentration, interest and understanding of the subject and other perceived causes of poor performance. Tests for descriptive statistics were applied for evaluation. RESULTS AND CONCLUSIONS: One hundred and fifty students participated in the study. Fifty-five (36.66%) students performed poorly. Male gender, inability to clear the previous professional examination at the first attempt, difficulty in understanding medium of instruction, self-assessed depression, sleep disorders and perceived parental and peer pressure and dissatisfaction with career choice were significantly linked with poor performance (P<0.05 for each factor). Socioeconomic status and regularity in class were not linked to academic performance.

CONTEXT: According to the first population-based cancer registry from eastern part of India, Kolkata and its surrounding areas have the highest prevalence of lung cancer in India. However, there is very limited data from this part of the country. AIMS: The aim of this study is to find out the demographic and clinicoradiological profile of primary bronchogenic carcinoma. SETTINGS AND DESIGN: This is a retrospective review of lung cancer cases diagnosed in two tertiary institutes of Kolkata over a period of 4 years. MATERIALS AND METHODS: We have reviewed the cases with proven histological or cytological diagnosis of primary bronchogenic carcinoma and chi-square test is done to calculate statistical significance. RESULTS: Out of 607 patients, male 489 and female 118, 67.7% are from rural area, 67.2% are smoker and only 9.4% are ≤40 years of age. Smoking is the major risk factor for primary lung cancer (P = 0.000) but no significance could be established with the different histological subtypes (P = 0.207). Though squamous cell carcinoma (SCC) is the most predominant variety (35.1%), adenocarcinoma and undifferentiated type are overrepresented in ≤40 years. SCC occurs at a significantly higher age group (60.84 ± 12.16 years) than other subtypes (P = 0.000). At least 55.2% cases of nonsmall cell lung cancer and 54% of small cell lung cancer presented in very advanced stage. CONCLUSIONS: SCC is the most common histological subtype of primary bronchogenic carcinoma. The relatively increased frequency of adenocarcinoma in our study as compared to other studies from India is probably due to higher proportion of nonsmokers.

BACKGROUND: Vertebrae are the second commonest site among skeletal locations affected by hemangioma, but only about one per cent becomes symptomatic throughout the life. Though surgery, intra vertebral injection of various sclerosing agents have been tried in treating this benign process, no general consensus regarding management has been reached. Radiotherapy is emerging as a low cost, simple, non-invasive but very effective modality of treatment of symptomatic vertebral hemangioma. AIM: This study aims to find out the role of external beam radiotherapy in alleviating the symptoms of symptomatic vertebral hemangiomas without compromising the quality of life. MATERIALS AND METHODS: Seven consecutive patients with symptomatic vertebral hemangioma were treated with a fixed dose of external beam radiotherapy; and muscle power was assessed before, after treatment and during follow-up. RESULTS: All patients showed improvement of muscle power, which increased with the passage of time. Pain relief with improvement of quality of life was obtained in all the patients. CONCLUSION: Effect of radiotherapy on vertebral hemangioma is dose-dependent and the dose limiting factor is the spinal cord tolerance. In the present era of IMRT, greater dose can be delivered to the parts of vertebra affected by the hemangioma without compromising the spinal cord tolerance and expected to give better results.

BACKGROUND: Globally, domestic violence against females is common across culture, religion, class and ethnicity. There are various reasons for domestic violence and it might have serious health outcomes. OBJECTIVES: The study was undertaken to determine the prevalence, characteristics, reasons and the socio-demographic correlates of domestic violence, if any, and to find out the perceptions of the females to cope with the act of violence and to overcome the situation. MATERIALS AND METHODS: A cross-sectional observational study was undertaken by interviewing 141 adult and adolescent females residing in a village of West Bengal, with the help of a pre-designed and pre-tested questionnaire. Data were analyzed statistically by simple proportions and tests of significance (Chi-square test). RESULTS: Out of 141 respondents, 33 (23.4%) adult and adolescent females in this village were exposed to domestic violence in the past year. Among the demographic characteristics, statistically significant maximum prevalence was observed among 30-39 years age group, illiterate and unmarried females. For most of the females who were exposed to domestic violence, their husbands acted as the perpetrators (72.73%) and they reported slapping as the specific act of physical assault (72.73%). Majority of the respondents reported that opportunity of education (31.9%), being economically productive (31.9%) and better family income (23.4%) would help them to overcome the situation. CONCLUSION: This study emphasizes the need for justified female empowerment and this calls for multidisciplinary approach to develop public health measures, which would most effectively address the problem of domestic violence.

Abstract The potentiality of nano‐enzymes in therapeutic use has directed contemporary research to develop a substitute for natural enzymes, which are suffering from several disadvantages including low stability, high cost, and difficulty in storage. However, inherent toxicity, inefficiency in the physiological milieu, and incompatibility to function in cellular enzyme networks limit the therapeutic use of nanozymes in living systems. Here, it is shown that citrate functionalized manganese‐based biocompatible nanoscale material (C‐Mn 3 O 4 NP) efficiently mimics glutathione peroxidase (GPx) enzyme in the physiological milieu and easily incorporates into the cellular multienzyme cascade for H 2 O 2 scavenging. A detailed computational study reveals the mechanism of the nanozyme action. The in vivo therapeutic efficacy of C‐Mn 3 O 4 nanozyme is further established in a preclinical animal model of Huntington's disease (HD), a prevalent progressive neurodegenerative disorder, which has no effective medication to date. Management of HD in preclinical animal trial using a biocompatible (non‐toxic) nanozyme as a part of the metabolic network may uncover a new paradigm in nanozyme based therapeutic strategy.

India is in the thalassemia belt of the world. Both α- and β-thalassemia (α- and β-thal) are found in West Bengal, a state in the eastern part of India. There was no systematic large published study to investigate the prevalence rates of different hemoglobinopathies in West Bengal. This study was conducted in school and college students, newly married couples and pregnant women after proper counseling in the rural areas of five districts of West Bengal state in eastern India. Thalassemia testing was done using high performance liquid chromatography (HPLC). A total of 35,413 individuals were screened for hemoglobinopathies. β-Thalassemia trait was found in 10.38%, Hb E [β26(B8)Glu→Lys] trait in 4.30%, sickle cell trait in 1.12%, borderline Hb A(2) value 0.73%, low Hb A(2) 0.68% and Hb D trait 0.37%. This is the first study that addresses the prevalence of different hemoglobinopathies in rural areas of West Bengal. The prevalence of β-thal trait is higher in West Bengal than other parts of India. This data is likely to be helpful in planning screening programs in rural areas of West Bengal, India.

Arsenic in drinking water is of critical concern in West Bengal, India, as it results in several physiological symptoms including dermatological lesions and cancers. Impairment of the DNA repair mechanism has been associated with arsenic-induced genetic damage as well as with several cancers. ERCC2 (Excision Repair Cross-Complementing rodent repair, complementation group 2), mediates DNA-repair by interacting with Cdk-activating kinase (CAK) complex, which helps in DNA proof-reading during transcription. Arsenic metabolism alters epigenetic regulation; we tried to elucidate the regulation of ERCC2 in arsenic-exposed humans. Water, urine, nails, hair and blood samples from one hundred and fifty seven exposed and eighty eight unexposed individuals were collected. Dose dependent validation was done in vitro using HepG2 and HEK-293. Arsenic content in the biological samples was higher in the exposed individuals compared with the content in unexposed individuals (p < 0.001). Bisulfite-modified methylation specific PCR showed a significant (p < 0.0001) hypomethylation of the ERCC2 promoter in the arsenic-exposed individuals. Densitometric analysis of immunoblots showed a nearly two-fold increase in expression of ERCC2 in exposed individuals, but there was an enhanced genotoxic insult as measured by micronuclei frequency. Immuno-precipitation and western blotting revealed an increased (p < 0.001) association of Cdk7 with ERCC2 in highly arsenic exposed individuals. The decrease in CAK activity was determined by observing the intensity of Ser(392) phosphorylation in p53, in vitro, which decreased with an increase in arsenic dose. Thus we infer that arsenic biotransformation leads to promoter hypomethylation of ERCC2, which in turn inhibits the normal functioning of the CAK-complex, thus affecting DNA-repair; this effect was highest among the arsenic exposed individuals with dermatological lesions.

To investigate the ameliorative potential of sodium selenite and zinc sulfate on intensive-swimming-induced testicular disorders, 48 Wistar male rats (age, 4 months; mass, 146.2 +/- 3.6 g) were randomly divided into 4 groups: the unexercised-control group (n = 12); the exercised group (n = 12); the control supplemented group (n = 12); and the exercised supplemented group (n = 12). For 10 weeks, the exercised rats underwent a protocol that consisted of 4 h.d-1 swimming, for 6 d.week-1; the control rats did not exercise. For 10 weeks, both the supplemented groups received an oral daily dose of a combination of sodium selenite and zinc sulfate (6 and 3 mg.kg body mass-1, respectively). After 10 weeks, a significant reduction (p < 0.05) was seen in rats in the exercised group, compared with rats in both control groups, in paired testicular masses; in epididymal sperm count; in testicular Delta5, 3beta-hydroxysteroid dehydrogenase (HSD) and 17beta-HSD; in plasma levels of testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin; in the numbers of preleptotine spermatocytes, midpachytene spermatocytes, and stage 7 spermatids of the stage VII seminiferous epithelium cycle; and in fertility performance. As well, a significant increase (p < 0.05) was seen in the exercised group, compared with both control groups, in plasma corticosterone levels and in testicular content of malondialdehyde and catalase activity. At the same time, there was a significant reduction (p < 0.05) in the exercised group, compared with both control groups, in plasma concentrations of zinc and selenium; in the testicular content of glutathione (GSH), the glutathione and glutathione disulphide (GSSG) ratio, ascorbic acid, and alpha-tocopherol; and in testicular activities of superoxide dismutase, glutathione-peroxidase, and glutathione-S-transferase in the testes. No significant changes were seen in the number of spermatogonia-A from the stage VII seminiferous epithelium cycle or the testicular content of GSSG among the groups. Sodium selenite and zinc sulfate supplementation significantly protected against exercise-induced testicular gamatogenic and spermatogenic disorders, prevented testicular oxidative stress, and increased antioxidant status. It can be concluded that intensive-swimming-induced oxidative stress causes dysfunctions in the male reproductive system, which can be protected by the coadministration of sodium selenite and zinc sulfate.

Arsenic (As) induces pre-malignant and malignant dermatological lesions, non-dermatological health effects and cancers in humans. Senescence involves telomere length changes and acquisition of senescence-associated secretory phenotype (SASP), which promotes carcinogenesis. Though in vitro studies have shown that As induces senescence, population based studies are lacking. We investigated the arsenic-induced senescence, telomere length alteration and its contribution towards development of As-induced skin cancer. The study participants included 60 each of As-exposed individuals with skin lesion (WSL), without skin lesions (WOSL) and 60 unexposed controls. Exposure assessment of drinking water and urine was done. SA β-gal activity, ELISA, and quantification of senescence proteins, alternative lengthening of telomere (ALT) associated proteins and telomerase activity were performed. Relative telomere length (RTL) was determined by qPCR. A significantly higher number of senescent cells, over-expression of p53 and p21 were observed in the As-exposed individuals when compared to unexposed. SASP markers, MMP-1/MMP-3 were significantly higher in the WSL but not IL-6/IL-8. A significant increase of RTL was observed in the WSL group, which was telomerase-independent but exhibited an over-expression of ALT associated proteins TRF-1 and TRF-2 with higher increase in TRF-2. An increased risk for developing As-induced skin lesions was found for individuals having RTL greater than 0.827 (odds ratio, 13.75; 95% CI: 5.66-33.41; P < 0.0001). Arsenic induces senescence in vivo, but the SASP markers are not strictly over-expressed in the As-induced skin lesion group, whereas telomerase-independent elongation of telomere length might be useful for predicting the risk of development of As-induced skin lesions.