Treatment with Metformin and Combination of Metformin Plus Pioglitazone on Serum Levels of IL-6 and IL-8 in Polycystic Ovary Syndrome: A Randomized Clinical Trial.

Elevated serum levels of inflammatory mediators in conditions such as PCOS reflect a low-grade chronic inflammation and this has been attributed to be associated with insulin-resistance in PCOS. Therefore, insulin-sensitizing agents are suggested to improve both reproductive as well as metabolic aspects of PCOS. This study aimed to compare the effects of metformin taken alone with that of a combination of metformin and pioglitazone on menstrual cycle, hormonal parameters, insulin resistance, and inflammatory biomarkers in women with PCOS. One hundred and six women with PCOS participated in the study. All subjects were randomized into two-arm intervention groups (Arm 1 and 2). Participants in Arm-1 received metformin (500 mg BD) daily while those in Arm-2 a combination of metformin (500 mg BD) and pioglitazone (15 mg BD) for 12 wks. Serum levels of IL-6 and IL-8 were measured using ELISA whereas insulin resistance was assessed using HOMA-IR. At baseline women with PCOS had significantly elevated circulating concentrations of IL-6 and IL-8. Treatment decreased IL-6 in both the groups, however, only the combination group showed a significant decrease (p=0.005). Serum IL-8 level had a significant decrease after treatment in both groups (p <0.001). HOMA-IR and insulin levels also decreased in both the groups (both p <0.001). Testosterone, FSH, and prolactin significantly decreased in both groups. LH also decreased in both groups, however, the change was significant only in the combination group (p=0.013). Combination of metformin and pioglitazone therapy was more effective as compared to metformin alone in reducing the levels of IL-6 and IL-8 as well as insulin resistance in PCOS.

Correlation of plasma kisspeptin with total testosterone levels in smokeless tobacco and smoking tobacco users in a healthy cohort: A cross-sectional study.

Human infertility is a worldwide health issue and is the inability to conceive following twelve months of unprotected sexual intercourse. Consistent studies reiterated tobacco abuse to be an important risk factor which adversely effects male fertility. This study aims to determine the correlation of kisspeptin and total testosterone levels in smokeless tobacco, smoking tobacco users and healthy controls. A total of 180 subjects were selected using random sampling technique. Non-fasting blood samples (5 ml) were drawn, and ELISA technique was used for the evaluation of plasma levels of kisspeptin and total testosterone. Total testosterone was found to be significantly high in smokers and smokeless tobacco users, while the level of kisspeptin was found to be significantly high in smokeless tobacco users only as compared to control group. Furthermore, the level of cholesterol was found to be significantly low, whereas HDL and triglycerides were found to be significantly high in smokeless tobacco users relative to control subjects. Findings of this study suggest that tobacco use has impact on HPG axis by affecting kisspeptin level. The increase in kisspeptin level can affect hypothalamic function leading to pituitary and gonadal dysfunction along with impairment of reproduction. The finding that smokeless tobacco significantly raises kisspeptin strengthens the idea that smokeless tobacco use has more potent effects centrally compared to smoking.

Endostatin Concentration In Plasma Of Healthy Human Volunteers.

BACKGROUND: Angiogenesis is involved in many cardiovascular and cancerous diseases, including atherosclerosis and is controlled by a fine balance between angiogenic and angiostatic mediators. Endostatin is one of the main angiostatic mediators, and inhibits angiogenesis and prevents progression of atherosclerosis. The available literature shows a broad range of concentrations in relatively small samples of healthy controls and is calculated by using different techniques. This study was aimed to determine the basal endostatin concentration in plasma of healthy volunteers, to fully understand its physiological role. METHODS: Fifty healthy adult volunteers were recruited to the study. Participants were advised not to participate in any physical activity on the day before the blood sampling. The volunteers' physical activity, height, weight, heart rate and blood pressure were recorded. The samples were analysed for plasma endostatin concentration, using ELISA. The participants were divided by gender and ethnic groups to calculate any difference. RESULTS: Endostatin and other variables were normally distributed. Most of the participants had a moderate level of physical activity with no gender related difference (p=0.370). The mean value for plasma endostatin in all samples was 105±12 ng/ml with range of 81-132 ng/ml. For males, it was 107±13 ng/ml, while for females; 102±12 ng/ml. There were no significant gender or ethnicity related differences in endostatin concentration. Moreover, endostatin was not significantly related with any anthropometric and physical variable. CONCLUSIONS: This study gives endostatin levels in normal healthy people and show no gender and ethnicity related differences in endostatin levels. Endostatin was not related with any anthropometric and physical variable.

Ethnicity and risk of cardiovascular disease (CVD): 4.8 year follow-up of patients with type 2 diabetes living in Scotland.

AIMS/HYPOTHESIS: Potential differences in cardiovascular risk by ethnicity remain uncertain. We evaluated the association of ethnicity with cardiovascular disease (CVD) incidence in a large cohort of people with type 2 diabetes living in Scotland. METHODS: Data from Scottish Care Information-Diabetes (SCI-Diabetes) were linked to Scottish Morbidity Records (SMR01) and National Records of Scotland data for mortality for dates between 2005 and 2011. Of 156,991 people with type 2 diabetes with coded ethnicity, 121,535 (77.4%) had no CVD at baseline (White: 114,461; Multiple Ethnic: 2,554; Indian: 797; Other Asian: 319; Pakistani: 2,250; Chinese: 387; African-Caribbean: 301 and Other: 466) and were followed up (mean ± SD: 4.8 ± 2.3 years) for the development of fatal and non-fatal CVD. RESULTS: During follow-up, 16,265 (13.4%) patients developed CVD (ischaemic heart or cerebrovascular diseases). At baseline, Pakistanis were younger and had developed diabetes earlier, had higher HbA1c and longer duration of diabetes, but had lower BP, BMI, creatinine, proportion of smokers and proportion on antihypertensive therapy than whites. The age and sex adjusted HRs for CVD were HR 1.31 (CI 1.17, 1.47), p < 0.001 in Pakistanis and HR 0.66 (CI 0.47, 0.92), p = 0.014 in Chinese compared with whites. Adjusting additionally for an area measure of deprivation, duration of diabetes, conventional CVD and other risk factors, the HR for Pakistanis (HR 1.45 [CI 1.14, 1.85], p = 0.002) was significantly higher, and that for Chinese (HR = 0.58 [CI 0.24, 1.40], p = 0.228) lower, compared with whites. CONCLUSIONS/INTERPRETATION: Compared with whites with type 2 diabetes, those of Pakistani ethnicity in Scotland were at increased risk of CVD, whereas Chinese were at lower risk, with these differences unexplained by known risk factors.

Treatment with combined resveratrol and myoinositol ameliorates endocrine, metabolic alterations and perceived stress response in women with PCOS: a double-blind randomized clinical trial.

PURPOSE: The present study aimed to assess whether treatment with combined resveratrol and myoinositol is more effective in ameliorating the altered parameters associated with PCOS when compared to the combined metformin and pioglitazone therapy. METHOD: One hundred and ten obese, oligo-anovulatory PCOS women, aged 20-35 years were randomly assigned into two treatment arms. Participants in arm-1 (n = 55), received combination of metformin and pioglitazone (500 mg and 15 mg, respectively), twice daily, while those in arm-2 (n = 55) received combination of resveratrol and myoinositol (1000 mg and 1000 mg, respectively) twice daily for 12 weeks. Evaluations performed at baseline were repeated after 3 months of therapy. The endocrine and metabolic derangements were assessed by measuring serum levels of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), adiponectin and insulin using ELISA. Cohen's perceived stress scale (PSS) was employed as a subjective measure of stress. RESULTS: Pre-treatment PCOS women in both the arms (arm-1 and arm-2) had remarkably elevated serum testosterone and insulin concentrations, low serum adiponectin and high perceived stress response scores. The treatment reduced the altered endocrine indices in arm-2 (resveratrol and myoinositol) participants, manifested by statistically significant reduction in serum testosterone level (p = 0.001) and notably increased serum adiponectin level (p = 0.001). Interestingly, the hormonal profile, including serum LH and FSH levels also decreased (p < 0.001) along with a marked reduction in the ovarian volume (p = 0.001) in arm-2 participants. There was a significant reduction in weight (<0.001), BMI (p < 0.001) and an improvement in waist-hip ratio (p < 0.001) in arm-2 participants compared to arm-1 group. The PSS scores of the arm-2 subjects improved significantly (p < 0.001) whereas, the Ferrimen-Gallwey score was improved in both the arms (arm-1 and arm-2; p = 0.010 and 0.008 respectively) however, the change was highly significant in arm-2. Interestingly, the menstrual regularity was 81.4% in arm-2 while 18.2% in arm-1. We conclude that the therapeutic intervention with combined resveratrol and myoinositol is more effective in ameliorating altered endocrine, metabolic indices and stress burden and could be of clinical importance in high risk group of obese, oligo-anovulatory married PCOS affected women. TRIAL REGISTRATION: ClinicalTials.gov Trial No: NCT04867252. Registered 24 April, 2021, https://clinicaltrials.gov/ct2/show/NCT04867252.

The effects of tobacco and cannabis use on semen and endocrine parameters in infertile males.

Substances such as tobacco and cannabis can negatively modulate seminal parameters and sex hormones and lead to fertility problems in males. The present study aimed to determine the effect of cigarettes, dipping tobacco, and cannabis on semen parameters and sex hormones in infertile males. A total of 160 infertile healthy participants (cigarette smokers n = 40, dipping tobacco users n = 40, cannabis users n = 40 and infertile controls n = 40) were included in the study. Fasting blood samples were collected from all the participants using the aseptic technique, and semen samples were collected by masturbation following sexual abstinence of 2-7 days. The levels of serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined using ELISA. The serum level of FSH was significantly higher in cannabis users relative to the control group (p = 0.043). A mild non-significant decrease in sperm count, serum LH and testosterone levels were observed in all drug users compared to controls. In conclusion, chronic use of tobacco and cannabis mildly modulates semen and hormonal parameters in infertile males.

T3 is linked to stress-associated reduction of prolactin in lactating women.

The relationship between stress responses and lactation is bidirectional. Breastfeeding confers many benefits to maternal health, including attenuated hypothalamic-pituitary-adrenal axis responsiveness to stress. However, increased stress burden can impair lactation. The mechanisms that underlie these relationships are poorly understood. The present study aimed to compare breastfeeding habits, as well as subjective and objective measures of stress, in employed and non-employed lactating women and assess the relationships between these measures and prolactin (PRL), thyroid hormones (thyroid-stimulating hormone, triiodothyronine [T3] and thyroxine), vasopressin and cortisol levels. A dexamethasone suppression test was also administered to determine the sensitivity of the hypothalamic-pituitary-adrenal axis to negative-feedback. We report that lactating employed women had lower breastfeeding rates and lower PRL than lactating non-employed women. They also had a significantly higher stress burden, indicated by elevations in blood pressure and evening cortisol, relative to lactating non-employed women. In regression analyses that controlled for feeding modality and breastfeeding duration, we found these factors differentially affected PRL in the two groups and there were significant differences in PRL across groups that were not accounted for by these factors. A mediation regression analysis suggested that group differences in PRL were best explained by differences in T3 and income levels, rather than breastfeeding duration or other variables. Our data fit a speculative model in which elevated maternal stress increases cortisol, which suppresses T3, leading to decreased PRL. The decreases in PRL are associated with higher rates of bottlefeeding, which may further contribute to decreased PRL.

Acetyl-L-Carnitine Ameliorates Metabolic and Endocrine Alterations in Women with PCOS: A Double-Blind Randomized Clinical Trial.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder and the main cause of infertility in women of reproductive age. Affected women suffer from insulin resistance and present with an intense stress response. Treatment with insulin sensitizers alone and in combination is used to ameliorate the signs and symptoms associated with the disease. This study was designed to compare the endocrine and metabolic parameters as well as subjective and objective measures of stress in women with PCOS before and after treatment with acetyl-L-carnitine (ALC) and metformin plus pioglitazone. METHODS: A total of 147 women with PCOS were randomly assigned into two groups: the combo group (n = 72) received a combination of metformin, pioglitazone, and ALC (500 mg, 15 mg, and 1500 mg, respectively), twice daily; the Met + Pio group (n = 75) received metformin plus pioglitazone (500 mg, 15 mg, respectively) and placebo (citric acid plus calcium carbonate), twice daily for 12 weeks. Medications were discontinued when pregnancy was confirmed. The Perceived Stress Scale (PSS14) and Profile of Mood States (POMS) were employed as subjective measures of stress. The endocrine and metabolic functions of women with PCOS were assessed by measuring insulin, leutinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and adiponectin levels in fasting blood samples. Insulin resistance was calculated by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). RESULTS: Women at baseline had significantly elevated circulating concentration of insulin and low level of adiponectin. Treatment decreased insulin in both groups; however, the combo group showed a significant decrease (p = 0.001). Serum adiponectin level was raised significantly after treatment in both groups (p < 0.001). HOMA-IR also decreased in both groups (both p < 0.001). Testosterone, FSH, and LH significantly improved in both groups. LH also decreased in both groups; however, the change was significant only in the combo (metformin plus pioglitazone plus ALC) group (p = 0.013). Interestingly, there was a significant improvement in body circumference (p < 0.001) in the combo group. The PSS scores of the patients improved significantly (p < 0.001) in the combo group. Interestingly, regular menstrual cycles were found (97.2%) in the carnitine group, but in only 12.9% of the other group. CONCLUSION: We conclude that addition of ALC therapy is superior to metformin plus pioglitazone in ameliorating insulin resistance, polycystic ovaries, menstrual irregularities, and hypoadiponectinemia in women with PCOS. TRIAL REGISTRATION: Trial registration: clinicalTrial.gov NCT04113889. Registered 3 October, 2019. https://clinicaltrials.gov/ct2/show/NCT04113889 .

Evaluation Of Peer Assisted Learning In Evidence Based Medicine Course: A Pilot Study At University Of Glasgow.

BACKGROUND: Peer Assisted Learning (PAL) is a well-established approach in learning and is increasingly being utilized in the medical education system. It is a process where active help of peer group members is taken for learning. This study aimed to look at the impact of peer assisted learning on the students at the end of the session. METHODS: Sixteen Postgraduate students attending Evidence Based Medicine (EBM) course spanning over two semesters (6 months each) were recruited. It was a cross sectional study and non-probability convenience sampling technique was used for gathering data. All students enrolled in EBM course conducted an hour-long PAL session during the coursework. At the end of the semester a link to an online questionnaire was sent to all the participants. A set of both open and closed ended questions were included in the questionnaire. RESULTS: Response rate was 87.5%, 14 out of the 16 students completed the questionnaire. The results showed an affirmative change in the behaviour and attitude of the participants' after the workshops. Majority of the respondents were of the opinion that it was a valuable experience and they benefitted through involvement in the process. Most of the postgraduate students suggested that it should be implemented in post graduate studies especially medical education. CONCLUSIONS: PAL is more interactive and informal way of teaching and it helps in the professional development, if peers from different specialties are gathered. However, study with a larger sample size are suggested to prove the generalizability of this assertion.

Euglycemic clamp insulin sensitivity and longitudinal systolic blood pressure: role of sex.

Insulin resistance may be an independent risk factor for the development of hypertension, but change in blood pressure (BP) over time has not been adequately studied in healthy individuals fully characterized for insulin sensitivity. In the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study, we measured insulin sensitivity (M/I) using the euglycemic clamp technique in 1073 healthy European adults (587 women, 486 men) aged 30 to 60 years followed up 3 years later. Systolic BP (SBP) at baseline was higher in insulin-resistant women (ie, those in the low sex-specific M/I tertile) compared with those in the intermediate (P<0.001) or high tertiles (P=0.06; mean ± SD: 117 ± 13, 111 ± 12, 114 ± 12 mm Hg, respectively). It did not differ across M/I tertiles in men. After adjustment for age, body mass index, baseline SBP, and other covariates, low insulin sensitivity (M/I) predicted a longitudinal rise in SBP in women but not in men; M/I was not associated with change in diastolic BP. SBP rose over time in both sexes and within all M/I tertiles (P<0.05), except in women with high insulin sensitivity. Therefore, in women (but not in men), low insulin sensitivity was associated with higher SBP at 3 years, and high insulin sensitivity was associated with a lower rise in SBP over time.