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This study was aimed to examine the influence of acclimatization on the change of concentration of stress hormones in men's serum exposed to heat stress during physical training. The study included a total of 40 men, aged 19-21 years, divided randomly into four groups: CTRL group: control, exposed to the Exercise Tolerance Testing in comfortable conditions; O group: exposed to Exercise Tolerance Testing in a warm environment; P group: exposed to passive acclimation to heat for 10 days, followed by Exercise Tolerance Testing in a warm environment; A group: exposed to active acclimation to heat for 10 days, followed by Exercise Tolerance Testing in a warm environment. All participants were tested for thermoregulation and acclimatization, skin and tympanic temperature, heart rate (HR), hormonal status and sweating. The mean skin temperature was the lowest in the control group of subjects exposed to physical exertion under comfortable conditions, and at each point of measurement it was statistically significantly different from that of the other study groups (p < 0.001). Sweating intensity was statistically significantly the lowest in the CTRL group (0.32 ± 0.04 l/m 2 /h; p < 0.001), compared to all other groups. Cortisol was significantly altered in O group (632.2 ± 92.3; 467.2 ± 89.7), testosterone levels were significantly altered in P (19.2 ± 9.3; 16.4 ± 7.3) and in A groups (22.1 ± 12.4; 14.9 ± 9.9), while prolactin was changed in O (392.1 ± 51.3; 181.4 ± 42.3), P (595.1 ± 191.1; 191.2 ± 52.5), and A group (407.4 ± 189.3; 173.4 ± 43.9) after the experimental period. The impact of acclimatization on hormonal indicators emphasizes its importance in the response of the endocrine system of soldiers to perform military activities in warm climates., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Non-obstructive azoospermia (NOA) is one of the leading causes of male factor infertility, which results from impaired spermatogenesis. Currently, the sole feasible therapeutic option for men with NOA to father their biologic children is sperm retrieval by testicular sperm extraction (TESE) approaches followed by an intracytoplasmic sperm injection program. Nevertheless, the rate of sperm retrieval from NOA men following TESE has remained as low as 50%, leading to a significant number of unsuccessful TESE operations. Given that TESE is associated with multiple side effects, the prediction of TESE outcome preoperatively can abolish unnecessary operations and thereby prevent NOA patients from sustaining adverse side effects. As the process of spermatogenesis is under the regulation of hormones, the hormonal profile of serum and/or seminal plasma may contain useful information about spermatogenesis status and can potentially predict the chance of sperm retrieval from NOA patients. A large body of literature is available on the predictive capability of different serum and seminal plasma hormones such as FSH, LH, testosterone, inhibin B, AMH, estradiol, prolactin, and leptin in a stand-alone basis or combinational fashion with respect to the TESE outcome. The present review aimed to evaluate the potential of these hormonal markers as noninvasive predictors of sperm retrieval in men with NOA., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Males are more likely to develop autism as a neurodevelopmental disorder than females, but the mechanisms underlying male susceptibility are not fully understood. In this paper, we used a well-characterized propionic acid (PPA) rodent model of autism to study sex differences in stress hormones, antioxidants' status, and the neuroimmune response that may contribute to the preponderance of autism in males. Sprague Dawley rats of both sexes were divided into a saline-treated group as controls and PPA-treated groups, receiving 250 mg/kg of PPA per day for three days. Animals' social behavior was examined using the three-chamber social test. Hormones (ACTH, corticosterone, melatonin, and oxytocin), oxidative stress biomarkers (glutathione, glutathione-S-transferase, and ascorbic acid), and cytokines (IL-6, IL-1α, IL-10, and IFNγ) were measured in the brain tissue of all the animals. The results showed a sex dimorphic social response to PPA treatment, where males were more susceptible to the PPA treatment and exhibited a significant reduction in social behavior with no effects observed in females. Also, sex differences were observed in the levels of hormones, antioxidants, and cytokines. Female rats showed significantly higher corticosterone and lower oxytocin, antioxidants, and cytokine levels than males. The PPA treatment later modulated these baseline differences. Our study indicates that the behavioral manifestation of autism in PPA-treated males and not females could be linked to neural biochemical differences between the sexes at baseline, which might play a protective role in females. Our results can contribute to early intervention strategies and treatments used to control autism, an increasingly prevalent disorder., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Herbal products with an antioxidant capacity can boost male reproductive functions. The empiric use of Ceratonia siliqua (carob) for its antioxidant properties is common among infertile men in Iran and Turkey. The objective of this study is to investigate the effects of C. siliqua (carob) on semen parameters, oxidative stress markers, and pregnancy rate in a parallel randomized, controlled study. A total of 60 infertile men with oligozoospermia, asthenospermia, and teratospermia were recruited from April 2018 to March 2019. Participants were divided randomly into the following two groups: carob syrup twice a day or vitamin E 100 mg twice a day for 3 months. Semen analysis was performed and hormonal levels and stress oxidative markers were measured in each treatment arm after 3 months. The quality of semen parameters improved in the carob group compared with Vit E semen count (p = 0.04 Cohen's d = .51), morphology (p = 0.001 Cohen's d = .93) and motility parameters (p = 0.002 Cohen's d = .90) were significantly higher in the carob group. No significant difference can be detected in post-treatment hormonal parameters and oxidative markers between groups, except for total antioxidant capacity(TAC) which was higher after post-treatment in carob group. A significantly higher pregnancy rate was found among the carob group. The administration of carob may be an effective agent for the improvement of semen parameters, probably related both to its involvement in the changing of testosterone level and to its antioxidant properties. Nevertheless, additional studies to evaluate the optimal dose and duration of treatment are needed. The trial has been registered in the Iranian Registry of Clinical Trials (Registration number: IRCT20171209037794N1.

The aim of the present study was to assess the effects of plantain herb (Plantago lanceolata L.) supplementation on growth, plasma metabolites, liver enzymatic activity, hormonal status, gastrointestinal parasites, and carcass characteristics of lambs. A total of 24 lambs, aged 6 months weighing 8.0 ± 0.5 kg were randomly allocated to one of two dietary treatments: (1) CL diet-roadside grass and concentrate mixture; (2) PL diet-CL diet + 5% fresh plantain supplementation on a DM basis. The PL diet group exhibited 23% higher (P = 0.01) average daily gain and 15% improved (P = 0.03) feed conversion efficiency. Circulating cholesterol concentrations were suppressed by 9% (P = 0.03), and liver enzyme activity was improved by 5-25% (P < 0.05) in the lamb fed PL diet, compared with CL diet only. The inclusion of plantain in the diet was highly effective at suppressing the parasites, Paramphistomum spp. (P = 0.003) and coccidial parasites (P = 0.04), but not stomach worms. Moreover, plantain supplementation increased growth hormone and insulin concentrations in plasma level, whereas decreased carcass fat by 32.7%. Therefore, supplementation of the lambs' diet with plantain showed some beneficial effects on productivity and parasitic infection, while it led to a leaner carcass.

There is a growing evidence for the public health hazards associated with waterpipe tobacco smoking (WTS). While the adverse effects of WTS exposure during pregnancy on the offspring are widely reported, its impact during breastfeeding remains less understood. The effects of WTS exposure during lactation on the reproductive hormones and oxidative stress biomarkers of adult male progeny were examined. Lactating rats received either fresh air (controls) or mainstream WTS for 1 h twice/day from day 4 to day 21 of lactation. The offspring was then followed up until week 20. The data indicated that WTS exposure in the lactating animals reduced the levels of follicle-stimulating hormone (FSH), prolactin (P < 0.05), luteinizing hormone (LH) (P = 0.1146), and estradiol (P = 0.0773) in the blood in male progeny. While the activities of testicular superoxide dismutase (SOD), glutathione peroxidase (GPx) and the levels of thiobarbituric acid reactive substances (TBARS) and blood levels of testosterone (P >0.05) remained unaltered, the activity of catalase increased significantly indicating an increased oxidant load in the WTS exposed rats compared to the controls. WTS exposure during lactation impairs male reproductive hormonal profile, augments oxidative damage, and potentially affects male fertility in male offspring rats.

The use of hypnosis can generate hallucinatory phenomena, which ranged from vivid/auditory imagery to fully developed "hallucinations" in selected people. The aim of this pilot trial was investigating the acute effects of a hypnosis-induced hallucinated breakfast (HB) compared to those of a real breakfast (RB) on subjective appetite and appetite-regulating hormones in highly hypnotizable individuals. Eight healthy post-menopausal women were recruited to consume two meals: the HB and the RB in a randomized crossover design. Participants underwent appetite sensations measurements (before meal and each 30-min until 270-min) and blood sample collection (at 0, 20, 60, 90, 180-min). A 3-day food-record was filled after each meal. The adjusted repeated measures ANCOVA did not show any meal×time interactions on subjective appetite postprandially. As expected, significantly higher glucose (p < 0.001), insulin (p < 0.001), and lower free fatty acid (p < 0.001) concentrations were found after the RB, but not following HB. Furthermore, RB significantly increased postprandial levels of glucagon-like-peptide-1 and peptide-YY at 20, 60, 90 and 180-min, whereas acylated-ghrelin and leptin levels did not differ. Postprandial neuropeptide-Y and orexin-A values significantly increased at different time-points after RB, but not following HB, while α-melanocyte-stimulating hormone levels enhanced after HB only. Energy intakes were significantly lower after HB on the test-day only (HB = 1146.6 ± 343.8 vs RB = 1634.7 ± 274.2 kcal/d; p = 0.003). Appetite sensation might be modulated by fully developed meal "hallucination" induced by hypnosis, likely affecting brain-peptides implicated in the appetite regulation. However, further studies are needed to verify these results obtained in a highly selected group of individuals. NCT03934580.

Ageing is associated with reduced appetite and energy intakes. However, the mechanisms underlying this phenomenon are not fully understood. This systematic review and meta-analysis quantified differences in circulating concentrations of appetite-related hormones between healthy older and younger adults. Six databases were searched through 12th June 2018 for studies that compared appetite-related hormone concentrations between older and younger adults. Data were pooled using random-effects meta-analysis and are presented as standardised mean difference (Hedges' g) with 95% confidence intervals (95% CI). Thirty-five studies were included involving 710 older adults (mean ± SD; age: 73 ± 5 years) and 713 younger adults (age: 28 ± 7 years). Compared with younger adults, older adults exhibited higher fasted and postprandial concentrations of the anorectic hormones cholecystokinin (Fasted: SMD 0.41 (95% CI 0.24, 0.57); p < 0.001. Postprandial: SMD 0.41 (0.20, 0.62); p < 0.001), leptin [Fasted: SMD 1.23 (0.15, 2.30); p = 0.025. Postprandial: SMD 0.62 (0.23, 1.01); p = 0.002] and insulin [Fasted: SMD 0.24 (- 0.02, 0.50); p = 0.073. Postprandial: SMD 0.16 (0.01, 0.32); p = 0.043]. Higher postprandial concentrations of peptide-YY were also observed in older adults compared with younger adults [SMD 0.31 (- 0.03, 0.65); p = 0.075]. Compared with younger adults, older adults had lower energy intakes [SMD - 0.98 (- 1.74, - 0.22); p = 0.011], and lower hunger perceptions in the fasted [SMD - 1.00 (- 1.54, - 0.46); p < 0.001] and postprandial states [SMD - 0.31, (- 0.64, 0.02); p = 0.064]. Higher circulating concentrations of insulin, leptin, cholecystokinin and peptide-YY accord with reduced appetite and energy intakes in healthy older adults. Interventions to reduce circulating levels of these hormones may be beneficial for combatting the anorexia of ageing.

In this study, we sought to evaluate the effects of dietary Bacillus amyloliquefaciens (B. amyloliquefaciens) BLCC1-0238 supplementation on laying performance, egg quality, antioxidant enzyme activities, reproductive hormone, and immunity of laying hens. A total of 240 Hy-Line Brown laying hens (28 weeks old) were randomly divided into four groups, and three replicates per group (n = 20 per replicate). The control group was fed a standard basal diet, and the three treatment groups were provided the basal diet supplemented with either 0.01%, 0.03%, or 0.06% B. amyloliquefaciens BLCC1-0238 (2 × 10 10  CFU/g), respectively. Hens were allowed 2 weeks to acclimate prior to initiation of the 8-week experiment. It was observed that dietary supplementation with 0.01% or 0.03% B. amyloliquefaciens BLCC1-0238 significantly increased egg production and egg mass. However, no significant differences in feed intake, egg weight, and feed conversion ratio among the four groups were observed. Different levels of B. amyloliquefaciens BLCC1-0238 supplementation also significantly increased egg shell strength and thickness. With respect to the levels of reproductive hormones in the hens, B. amyloliquefaciens BLCC1-0238 supplementation significantly reduced serum adrenal cortical hormone (ACTH) levels, while increasing estradiol (E2) and follicle-stimulating hormone (FSH) secretion in the treatment groups compared to the control group. Relative to the control group, supplementation with 0.03% and 0.06% B. amyloliquefaciens BLCC1-0238 was observed to significantly increase serum glutathione S-transferase (GST) concentration, and supplementation significantly reduced serum IL-1 and IL-6 levels, whereas IL-4 levels increased for all concentrations tested. In conclusion, supplementation of a basal chicken diet with B. amyloliquefaciens BLCC1-0238 can improve laying performance and egg quality through the reduction of stress responses, up-regulation of growth hormones, and supporting immunity in laying hens.

An experiment was conducted to evaluate the effects of supplementing feed additives of Barodon®, effective microorganism® (Bacillus (B.) subtilis), and Ampbio® on the growth performance, blood metabolites, stress, and reproductive hormone levels of Korean native heifers. A total of 48 Korean native heifers were assigned to four groups with 6 heifers in each group. The groups were control, Barodon (0.2%), beneficial microorganism (1%), and Ampbio (1%). Animals in all groups were fed a basal diet composed of selected feed additives and water ad libitum for 99 days. Results showed that there are significant changes in body weight and daily gain in the Ampbio-supplemented group as compared with the control and other feed additives groups (p < 0.05). The increased level of feed intake (7.30 ± 0.03 kg) and feed requirements (10.81 ± 0.52 kg) was observed in the Ampbio-fed group followed by the effective microorganism (EM), Barodon, and control groups. There were no significant changes in albumin, glucose, glutamic oxaloacetic transaminase (SGOT), serum pyruvic transaminase (SGPT), and total protein level, but the decreased levels of total cholesterol and triglycerides and the increased level of blood urea nitrogen were noted in the Ampbio-fed group as compared with the control and other feed additive groups. The reduced level of cortisol (p < 0.05) and elevated levels of progesterone and estradiol (p > 0.05) were noted in the Ampbio-fed group as compared to the other feed additive groups. It is therefore concluded that incorporation of Barodon, EM (B. subtilis), and Ampbio in the recommended diet improved the growth and health performance of Korean native heifers.

We studied the effect of hormones estriol, ghrelin, kisspeptin, and chorionic gonadotropin in concentrations corresponding to their content in the peripheral blood in each trimester of pregnancy on the expression of membrane molecules on myeloid and plasmacytoid dendritic cells of the thymus. It was found that thymic myeloid dendritic cells are sensitive to the action of estriol and kisspeptin. Estriol in a concentration of the first trimester of pregnancy reduces the number of myeloid dendritic cells expressing receptor for thymic stromal lymphopoietin (CD11c+TSLP-R + ) and inhibitory molecule B7-H3 (CD11c + CD276 + ). In contrast to estriol, kisspeptin regulates the processes of differentiation of thymic myeloid dendritic cells in concentrations typical of the second-third trimesters and reduced their total number (CD11c + ) and the number of cells expressing TSLP-R (CD11c + TSLP-R + ). Estriol and kisspeptin do not affect the total number of plasmacytoid dendritic cells (CD303 + ) and expression of TSLP-R and CD276 by these cells. Ghrelin and chorionic gonadotropin in the studied concentrations had no significant effect on the total number of thymic myeloid and plasmacytoid dendritic cells and on the expression of membrane molecules of TSLP-R and CD276.

Thermal manipulation during embryogenesis has been demonstrated to enhance the thermotolerance capacity of broilers through epigenetic modifications. Heat shock proteins (HSPs) are induced in response to stress for guarding cells against damage. The present study investigates the effect of thermal conditioning during embryogenesis and thermal challenge at 42 days of age on HSP gene and protein expression, DNA methylation and in vitro luciferase assay in brain tissue of Naked Neck (NN) and Punjab Broiler-2 (PB-2) chicken. On the 15th day of incubation, fertile eggs from two breeds, NN and PB-2, were randomly divided in to two groups: control (C)-eggs were incubated under standard incubation conditions, and thermal conditioning (TC)-eggs were exposed to higher incubation temperature (40.5°C) for 3 h on the 15th, 16th, and 17th days of incubation. The chicks obtained from each group were further subdivided and reared under different environmental conditions from the 15th to the 42nd day as normal [N; 25 ± 1 °C, 70% relative humidity (RH)] and heat exposed (HE; 35 ± 1 °C, 50% RH) resulting in four treatment groups (CN, CHE, TCN, and TCHE). The results revealed that HSP promoter activity was stronger in CHE, which had lesser methylation and higher gene expression. The activity of promoter region was lesser in TCHE birds that were thermally manipulated at the embryonic stage, thus reflecting their stress-free condition. This was confirmed by the lower level of mRNA expression of all the HSP genes. In conclusion, thermal conditioning during embryogenesis has a positive impact and improves chicken thermotolerance capacity in postnatal life.

A significant association between fructose corn syrup in sweetened beverages consumption and increased risk of detrimental central nervous system effects has been recently reported. We hypothesized that the aspartame and soft drink induced disturbances in energy production and endocrine function, which play a role in the induction of brain damage. Therefore, we aimed to assess the effect of aspartame and soft drink on brain function and the link between energy status in the brain, oxidative stress and molecular pathways of apoptosis. Thirty rats were randomly assigned to drink water, aspartame (240 mg/kg orally) and cola soft drinks (free access) daily for two months. Subchronic intake of aspartame and soft drink significantly disrupted the brain energy production, as indicated by inhibited serum and brain creatine kinase, specifically in soft drink-received rats. Moreover, they substantially altered serum electrolytes (increased Ca and Na, and depleted Cu, Fe, Zn and K levels), and accordingly the related hormonal status (increased T4 and PTH, and lowered T3 and aldosterone levels), particularly in soft drink-received rats reflecting brain damage. Additionally, significant increment of acetylcholine esterase activity concomitant with the reduction of antioxidant molecules (SOD, CAT, GSH-Px and GSH), and induction of malondialdehyde level are precisely indicative of oxidative brain damage. Brain mRNA transcripts of target genes showed that aspartame and soft drink induced upregulation of BAX, Casp3, P27 and Mdm2 (1.5-fold) and down-regulation of Bcl2, suggesting an activation of cellular apoptosis. Collectively, subchronic aspartame and soft drink-induced brain damage in rats may be driven via a mechanism that involves energy production disruption, electrolytes and hormonal imbalance, increased oxidative stress and activation of molecular pathway of neuronal apoptosis.

This pilot study enrolled 31 women who had breastfed exclusively for 6 months. Lumbar and thoracic BMD increased 4 and 5%, respectively. Femoral neck and total body BMD did not change. Return of menses and progestin-only pill use were two potential signals that predicted a greater increase in BMD., Purpose/introduction: The skeleton is resorbed during lactation to provide much of the calcium content of milk. After lactation ceases, these deficits in skeletal mineral content are largely restored, such that lactation has a neutral or protective effect against the long-term risk of low bone mineral density (BMD), osteoporosis, and fragility fractures. We hypothesized that a large observational study may identify the factors that predict a greater increase in BMD after lactation ceases. A pilot study was first needed to test feasibility and the magnitude of expected BMD change., Methods: We undertook Factors Affecting Bone formation after Breastfeeding Pilot (FABB Pilot), which enrolled women who had breastfed exclusively for 6 months and planned to wean soon. The main outcome was change in BMD between enrolment and 6 months later., Results: Thirty-one women were recruited and completed both time points. Lumbar and thoracic spine BMD increased 4 and 5%, respectively; there was no significant change in femoral neck and total body BMD. Most women did not wean their babies as planned but continued to breastfeed multiple times per day. Despite this, a significant increase in BMD was seen in the subsequent 6 months. Return of spontaneous menses and use of a progestin-only pill at recruitment were two potential signals that predicted a greater increase in BMD during the 6 months after exclusive lactation., Conclusions: Spine BMD increased significantly during 6 months following exclusive lactation and despite continued lactation. The factors that stimulate skeletal recovery remain to be identified.

Purpose: The aim of this study was to assess whether the intrafollicular cytokine profile in naturally developed follicles is different in women with endometriosis, possibly explaining the lower reproductive outcome in endometriosis patients., Methods: A matched case-control study was conducted at a university-based infertility and endometriosis centre. The study population included 17 patients with laparoscopically and histologically confirmed endometriosis (rAFS stages II-IV), each undergoing one natural cycle IVF (NC-IVF) treatment cycle between 2013 and 2015, and 17 age-matched NC-IVF women without diagnosed endometriosis (control group). Follicular fluid and serum was collected at the time of follicle aspiration. The concentrations of inflammatory cytokines (IL-1β, IL-6, IL-8, IL-15, IL-18, TNF-α) and hormones (testosterone, estradiol, AMH) were determined in follicular fluid and serum by single or multiplexed immunoassay and compared between both groups., Results: In the follicular fluid, IL-1β and IL-6 showed significantly (P < 0.001 and 0.01, respectively) higher median concentrations in the endometriosis group than in the control group and a tendency towards endometriosis severity (rAFS stage) dependence. The levels of the interleukins detectable in follicular fluid were significantly higher than those in the serum (P < 0.01). Follicular estradiol concentration was lower in severe endometriosis patients than in the control group (P = 0.036). Follicular fluid IL-1β and IL-6 levels were not correlated with estradiol in the same compartment in neither patient group., Conclusions: In women with moderate and severe endometrioses, some intrafollicular inflammatory cytokines are upregulated and not correlated with intrafollicular hormone concentrations. This might be due to the inflammatory microenvironment in endometriosis women, affecting follicular function and thereby possibly contributing to the reproductive dysfunction in endometriosis.

Introduction Suppressing both androgens and estrogens may circumvent hormone receptor resistance in breast cancer by reducing androgen receptor stimulation. Selective inhibition of the 17, 20-lyase enzyme by orteronel leads to decreased androgen production in men and would be anticipated to reduce estrogen and androgen production in women. Thus, we conducted a phase 1b study of orteronel in postmenopausal women with hormone-receptor positive (HR+) metastatic breast cancer. Methods The primary objective was to identify the recommended phase 2 dose (R2PD) of orteronel in women; escalation was via standard 3 + 3 design. The initial dose was 300 mg BID and escalated to 400 mg BID. Cycle length was 28 days. Enrolled patients had HR+ metastatic breast cancer and were evaluated every 8 weeks for disease progression. Results Eight heavily pre-treated women enrolled [median age: 57 yo (range 47-73)]. Four received 300 mg BID at dose level 1; 4 received 400 mg BID at dose level 2. No dose limiting toxicities (DLTs) were observed. Adverse events (AE) at least possibly related to orteronel included grade 1-2 nausea (n = 4) and bone pain (n = 3), and grade 1 hypokalemia, hot flashes, myalgia and AST elevation (n = 2). The only grade 3 AE was hypertension (n = 2) with 8 patients receiving 34 cycles of treatment. No objective responses were seen; clinical benefit was seen in 2 patients with stable disease for more than 6 months. Serum estrogens and testosterone were suppressed from baseline on both doses of orteronel. Conclusions Orteronel 400 mg BID is well tolerated in postmenopausal women, and significantly suppresses serum estrogens and testosterone. Clinical benefit was seen among heavily pretreated postmenopausal women with HR+ metastatic breast cancer.

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with changes in several hormones and metabolic peptides. Crosstalk between these factors and the immune system may be important for homeostasis during inflammation. Here, we studied the levels of hormones, metabolic peptides, and nutrients in individuals at risk for developing RA (at risk). In total, 18 hormones, metabolic peptides, and nutrients were measured in fasting serum samples from 45 autoantibody-positive individuals at risk, 22 RA patients, and 16 healthy subjects. Triglyceride (TG) levels were also measured in an independent validation cohort of 32 individuals at risk, 20 early arthritis patients, and 20 healthy controls. We found an elevated TG level in individuals at risk and significantly higher TG levels in RA patients compared to healthy controls. These results were confirmed in the validation cohort. Similarly, free fatty acid (FFA) levels showed an increase in individuals at risk and were significantly higher in RA patients compared to healthy controls. In RA patients, FFA levels were positively correlated with disease activity. Pancreatic polypeptide (PP) and norepinephrine levels were highly significantly increased in individuals at risk and RA patients compared to healthy controls. TG and FFA levels are increased in RA patients and positively correlated with disease activity parameters. The results presented here suggest a role for FFAs in the pathogenesis of RA. Furthermore, PP and norepinephrine may be a biomarker that could assist in the identification of individuals at risk., Competing Interests: Compliance with ethical standards Competing Interests All authors do not have financial or other relationships that could give conflicts of interest. Dr. Gerlag and Professor Tak have become employees of GSK after completion of this study; GSK has not been involved in this study. Funding The study was supported by the European Union Seventh Framework Programme (project EuroTEAM; FP7-Health2–2012; grant number 305549). Authors’ Contributions All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version of the article to be published; agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. M.W.T contributed to research design, acquisition of data, and analyzed and interpreted data; F.A.K was involved in research design and acquisition of data; J.P.M.V. contributed to acquisition of data; M.J.H. was involved in analyzing and interpreting data; D.M.G designed the research and analyzed and interpreted data; P.P.T. designed the research and analyzed and interpreted data.

Purpose: To assess female sexual functions in women who were affected by vitamin D 3 deficiency., Methods: A total of 50 women with FSD and 58 healthy women controls were included in the study, according to the Female Sexual Function Index (FSFI) questionnaire using a 26.55 cutoff value. Detailed medical histories were obtained from all sexual active women, and all women were evaluated in terms of possible presence of depression with the Beck Depression Inventory (BDI). Serum 25-hydroxyvitamin D 3 , follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, total and free testosterone, estradiol, dehydroepiandrosterone-SO 4 (DHEA-SO 4 ), sex hormone-binding globulin (SHBG), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) levels were measured., Results: Mean age of premenopausal women was 34.9 ± 6.3 years. The level of serum 25-hydroxyvitamin D 3 was significantly lower in women with FSD compared with the controls (15.9 ± 8.4 and 26.3 ± 11.7 nmol/L, respectively). Desire (p = 0.0001), arousal (p = 0.0001), lubrication (p = 0.002), orgasm (p = 0.0001), satisfaction (p = 0.018), and pain (p = 0.010) domain scores were also correlated with the levels of serum 25-hydroxyvitamin D 3 . The BDI score showed a significant negative correlation with the total FSFI score (r = -0.492, p = 0.0001). The FSFI score not showed a significant correlation with the hormones (p > 0.05)., Conclusion: There is a relationship with FSD and deficiency of vitamin D 3 . Also, increased depressive symptoms were associated with FSD.

Purpose: The effect of growth hormone (GH) on adipose tissue and the role of adipokines in modulating metabolism are documented, but with discordant data. Our aim was to evaluate the impact of GH treatment on a series of selected adipokines known to have a metabolic role and poorly investigated in this setting., Methods: This is a prospective study. Thirty-one prepubertal children (25 M, 6 F; aged 8.5 ± 1.6 years) with isolated GH deficiency treated with GH for at least 12 months and 30 matched controls were evaluated. Auxological and metabolic parameters, insulin sensitivity indexes, leptin, soluble leptin receptor, adiponectin, visfatin, resistin, omentin, adipocyte fatty acid-binding protein and retinol-binding protein-4 were evaluated before and after 12 months of treatment., Results: At baseline, no significant difference in metabolic parameters was found between GHD children and controls, except for higher LDL cholesterol (p = 0.004) in the first group. At multivariate analysis, LDL cholesterol was independently associated with resistin (B 0.531; p = 0.002), while IGF-I was the only variable independently associated with visfatin (B 0.688; p < 0.001). After 12 months, a significant increase in fasting insulin (p = 0.008), Homa-IR (p = 0.007) and visfatin (p < 0.001) was found, with a concomitant decrease in LDL cholesterol (p = 0.015), QUICKI (p = 0.001), ISI Matsuda (p = 0.006), leptin (p = 0.015) and omentin (p = 0.003)]. At multivariate analysis, BMI was the only variable independently associated with leptin (B 0.485; p = 0.040)., Conclusions: GH treatment modifies adipokine secretion and the perturbation of some adipokine levels could contribute to the clinical and metabolic changes observed during the follow-up.

We performed immunophysiological examination of 144 men aged 17-25 years, patients with psychoactive substance dependence, episodic psychoactive drug users, and conditionally healthy individuals. Associations of proinflammatory cytokine production with age, sex, hormone levels, and olfactory and nociceptive indices were revealed in cases of psychoactive drug use and formation of addiction. Predictive models based on the use of androstenone aversion, pressure algometry testing, and immunological parameters were proposed.

Within the Flemish Environment and Health studies (FLEHS I, 2002-2006, and FLEHS II, 2007-2012), pesticide exposure, hormone levels and degree of sexual maturation were measured in 14-15-year-old adolescents residing in Flanders (Belgium). In FLEHS II, geometric mean concentrations (with 95 % confidence interval (CI)) of 307 (277-341) and 36.5 ng L(-1) (34.0-39.2) were found for p,p'-dichlorophenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB). These values were respectively 26 and 60 % lower than levels in FLEHS I, 5 years earlier. Metabolites of organophosphorus pesticides (OPPs) and of para-dichlorobenzene were measured for the first time in FLEHS II, yielding concentrations of 11.4, 3.27 and 1.57 μg L(-1) for the sum of dimethyl- and diethyl phosphate metabolites and 2,5-dichlorophenol (2,5-DCP), respectively. Data on internal exposure of HCB showed a positive correlation with sexual maturation, testosterone and the aromatase index for boys and with free thyroxine (fT4) and thyroid stimulating hormone (TSH) (both boys and girls). For both p,p'-DDE and HCB, a negative association with sexual development in girls was found. The OPP metabolites were negatively associated with sex hormone levels in the blood of boys and with sexual maturation (both boys and girls). The pesticide metabolite 2,5-DCP was negatively correlated with free T4, while a positive association with TSH was reported (boys and girls). These results show that even exposure to relatively low concentrations of pesticides can have significant influences on hormone levels and the degree of sexual maturation in 14-15-year-old adolescents.

Studies reporting the effects of oxytocin on the health of lactating animals are lacking and still no such data is available on Nili Ravi buffalo, the most prominent Asian buffalo breed. The present study was conducted to investigate the effect of oxytocin on physiological and metabolic parameters of lactating Nili Ravi buffaloes. Healthy lactating buffaloes (n = 40) of recent calving were selected from a commercial dairy farm situated in the peri-urban area of district Faisalabad, Pakistan. These buffaloes were randomly allocated to two equal groups viz experimental and control, comprising 20 animals each. Twice-a-day (morning and evening) milking practice was followed. The experimental and control buffaloes were administered subcutaneously with 3 mL of oxytocin (10 IU/mL) and normal saline respectively, prior to each milking. Serum biochemical profile including glucose, total cholesterol (tChol), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), total proteins (TP), C-reactive protein (CRP), liver enzymes aspartate transaminase (AST), alanine transaminase (ALT), and metabolic hormones triiodothyronine (T₃) and thyroxine (T₄) were studied. Results revealed significantly higher (P ≤ 0.01) levels of glucose, total cholesterol, LDL-C, triglycerides, total proteins, and C-reactive protein in experimental (oxytocin-injected) lactating buffaloes compared to control group. Liver enzymes AST and ALT as well as serum T₄ concentration was significantly higher (P ≤ 0.01) in oxytocin-injected lactating buffaloes as compared to control animals. It was concluded that oxytocin had the key role in increasing the metabolic parameters and hormones, resulting in the optimization of production. But, at the same time, it may pose a threat to the animal health.

MicroRNAs (miRNAs) are class of molecular regulators found to participate in numerous biological processes, such as adipogenesis and obesity in mammals. To determine the roles of miRNAs involved in castration-induced body fatness, we investigated the different miRNA expression patterns in subcutaneous adipose tissue between intact and castrated male pigs. Our results showed that castration led to decrease serum testosterone but increase serum Leptin levels (P < 0.01). Moreover, castration also increased adipocyte size, body fat content and backfat thickness in male pigs (P < 0.01). Meanwhile, miRNA expression profiles in adipose tissue were changed by castration, and 18 miRNAs were considered as the differentially expressed candidates between intact and castrated male pigs. Furthermore, functional analysis indicated that the differential expressed miRNAs and their target genes are involved in the regulation of fatty acid metabolism. In brief, our present study provides a comprehensive view on how miRNAs works in subcutaneous adipose tissue with castration. These results suggested that miRNAs might play an important role in the castration-induced fat deposition in male pigs.

Background: Exogenous estrogens have been shown to affect markers of cardiovascular risk in women., Aim: The objective of this study was to determine the effect of menstrual cycle phase on markers of cardiovascular risk in young, healthy women with regular menstrual cycles., Subjects and Methods: This prospective cohort study examined 20 healthy pre-menopausal women at 2 time-points in the menstrual cycle, in early follicular phase and early luteal phase., Results: In the early luteal phase, levels of estrogen, progesterone, LH, total cholesterol, and HDL were significantly higher, compared with the early follicular phase. In contrast, there were no significant differences in LDL or triglyceride levels between the 2 phases. Furthermore, there were no significant effects of menstrual cycle phase on glycemic indices (fasting blood glucose, glycohemoglobin or homeostatic model assessment of insulin resistance), markers of inflammation (C-reactive protein, soluble CD40 ligand, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, or adiponectin), or vascular function, as measured by brachial artery reactivity., Conclusions: Although menstrual cycle phase affects total cholesterol and HDL levels, it does not affect other markers of cardiovascular risk in young women with regular menstrual cycles.

The objective of the present study was to investigate the changes in a large panel of emergent geriatric biomarkers in long-term trained elderly men to analyze the effects of long-term exercise on an aged population. We collected blood samples from two groups of male volunteers older than 65 years who maintain a measure of functional independence: one group of sedentary subjects without a history of regular physical activity and the other of subjects who have sustained training, starting during adulthood (mean training time = 49 ± 8 years). We studied morbidity, polypharmacy, cellular and serological inflammatory parameters, and endocrine mediators. After adjusting for confounding factors, we observed reduced medication intake per subject and lower number of diseases per subject with statistical differences nearly significant in the long-term exercise group. We showed that long-term training was associated with lower levels of white blood cell counts, neutrophil counts, interleukin-6, interleukin-10, interleukin-1 receptor antagonist, and soluble TNF receptor-I. Furthermore, we noted an increase in the concentrations of insulin-like growth factor-1 and dehydroepiandrosterone in the long-term training group. We concluded that long-term exercise training from adulthood to old age is clearly associated with a healthy profile of emergent geriatric biomarkers. Long-term training could improve the inflammatory-endocrine imbalance associated with disease, frailty, functional decline, and mortality in elderly men. Our results point to the benefits of prolonged exercise from adulthood to old age.

Background: Oxidative stress may play a role in the pathophysiology of polycystic ovary syndrome (PCOS). Insulin resistance (IR) also can be found in young non-obese women with PCOS. Hyperglycemia may increase reactive oxygen species production and decrease antioxidant levels., Aim: To investigate oxidative status and its relation with IR in young non-obese patients with PCOS., Material/subjects and Methods: Thirty-one patients with hyperinsulinemic (no.=13) and normoinsulinemic (no.=18) PCOS and 29 healthy controls were included in this study. Serum levels of glucose, insulin, gonadotropins, total testosterone, DHEAS, SHBG, 2-h plasma glucose on oral glucose tolerance test, malondialdehyde (MDA), protein carbonyl (PC), reduced glutathione (GSH), β carotene, vitamin A, C, E and the enzyme activities of catalase and glutathione S-transferase (GST), IR [by homeostasis model assessment (HOMA)-IR], and β cell function [by HOMA-B] were assessed., Results: Serum glucose, insulin, total testosterone, DHEAS, HOMA-IR levels, and LH/FSH ratios were higher in young non-obese women with PCOS. Serum MDA and PC levels were also higher but GSH, vitamin C and E levels, and GST enzyme activity were lower in these women than in healthy controls, independently of the status of IR (p<0.05)., Conclusions: Oxidative stress characterized by increased oxidants and decreased antioxidant levels which are independent of IR may be involved in the pathogenesis of PCOS in young non-obese women., (© 2012, Editrice Kurtis.)

Cadmium (Cd), an environmental pollutant, has been shown to be highly toxic to both humans and animals. Its widespread industrial use has led to its accumulation in the environment. Cd has been shown to target multiple organs following acute intoxication, causing nephrotoxicity, immunotoxicity, osteotoxicity, and reproductive toxicity. Cd can cross the placental barrier and cause a wide range of defects during fetal development. The current study was aimed to assess the effect of Cd on the female reproductive system. Female rats were exposed to Cd [50/200 ppm] from embryonic day 9 to 21 through drinking water. Serum steroid hormone concentrations, hematological parameters, antioxidant enzyme levels, and ovarian histopathology were described. Water consumption, gravid uterine/body weight decreased in both the doses of Cd-treated dams. The hematological parameters analyzed in rat pups showed a significant reduction in both doses of Cd studied, while hemoglobin showed a significant reduction in 200 ppm Cd treatment alone. MCHC levels did not show any variation in 50 ppm Cd treatment, while 200 ppm Cd treatment significantly increased. Specific activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and serum testosterone, estradiol, and progesterone were significantly decreased. The levels of hydrogen peroxide and lipid peroxidation were increased in 50 and 200 ppm Cd-treated rats. These changes were accompanied with disrupted ovarian histoarchitecture, an extended estrous cycle, and delayed pubertal onset in Cd-treated rats. The data generated from the present study suggest that gestational Cd treatment induces ovarian toxicity and reproductive dysfunction through increased oxidative stress.

Objective: To determine the safety and efficacy of oral pentoxifylline (PTX) administration in improving semen parameters in infertile men with idiopathic OAT., Patients and Methods: The study included 254 infertile men who underwent double-blind therapy with 400 mg PTX (Apotex Inc., Toronto, Canada) twice daily (group 1, n = 127), or similar regimen of placebo (group 2, n = 127). The study consisted of a 4-week screening phase, a 24-week treatment phase, and a 12-week treatment-free period. The effects of treatment on semen parameters, serum hormones including testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and inhibin B, seminal plasma catalase-like and superoxide dismutase (SOD)-like activity, and acrosome reaction test were evaluated., Results: A significant increase in sperm concentration (mean value, 26.4 ± 4.6 × 10(6)/ml vs. 16.2 ± 3.4 × 10(6)/ml), sperm motility (mean value, 35.8 ± 4.2% vs. 26.4 ± 2.4%), and sperm with normal morphology (mean value, 25.4 ± 4.3% vs. 17.4 ± 4.2%) was observed after PTX administration when compared with baseline (all P = 0.001); in contrast, a subtle decreased values were observed after placebo (median values, 16.4 ± 4.1 × 10(6)/ml vs. 16.7 ± 3.6 × 10(6)/ml, P = 0.1; 25.7 ± 3.6% vs. 26.8 ± 2.5%, P = 0.08; and 16.9 ± 4.1% vs. 17.6 ± 4.4%, P = 0.08, respectively). Mean SOD-like and catalase-like activity in the semen of PTX group was significantly greater than in the semen of placebo group (46.4 ± 2.4 vs. 36.3 ± 1.3 U/ml and 371 ± 44 vs. 301 ± 14 U/ml, respectively, both P = 0.003). The acrosome reaction was observed to be increased in PTX group (P = 0.01). Levels of reproductive hormones were also affected., Conclusions: PTX administration significantly improves semen parameters in infertile men with idiopathic OAT.

Background: Erythropoietin (EPO) is an oxygenregulated hormone promoting the differentiation of erythroid progenitor cells. Apart fromhypoxia, few data is available about release by secretagogues including hormones., Aim: To investigate EPO serum concentration in subjects with endocrine diseases., Material and Methods: A retrospective study evaluating serumEPO concentrations in serumleftovers fromsubjects with various endocrine disorders., Results: EPO is not noticeably influenced by thyroid hormone or cortisol concentrations and the relationship with hemoglobin concentration is preserved. In acromegalic patients, the latter is lost but EPO is neither statistically influenced by GH/IGF-I. This may reflect a dual action of GH and/or IGF-I on erythroid progenitors proliferation as well as on EPO synthesis., Conclusion: EPO is not noticeably modified by endocrine disorders although GH and or IGF-I may alter EPO relationship with blood hemoglobin concentration.

Recent studies have demonstrated that carotenoid-based traits are under the control of testosterone (T) by up-regulation of carotenoid carriers (lipoproteins) and/or tissue-specific uptake of carotenoids. T can be converted to dihydrotestosterone (DHT) and estradiol (E2), and variation in conversion rate may partly explain some contradictory findings in the literature. Moreover, most studies on the effect of T on sexual signals have focused on the male sex only, while in many species females show the same signal, albeit to a lesser extent. We studied the effects of T, DHT, and E2 treatment in male and female diamond doves Geopelia cuneata in which both sexes have an enlarged red eye ring, which is more pronounced in males. We first showed that this periorbital ring contains very high concentration of carotenoids, of which most are lutein esters. Both T and DHT were effective in enhancing hue, UV-chroma and size in both sexes, while E2 was ineffective. However, E2 dramatically increased the concentration of circulating lipoproteins. We conclude that in both sexes both color and size of the secondary sexual trait are androgen dependent. The action of androgens is independent of lipoproteins regulation. Potential mechanisms and their consequences for trade-off are discussed.

Two experiments investigated extinction and blocking of a conditioned inhibitor in a human contingency-learning task. Lotz and Lachnit (2009) and Melchers, Wolff, and Lachnit (2006) reported extinction of inhibition only when participants experienced outcome levels lower than those used in training. In Experiment 1, which used more neutral instructions than the previously mentioned studies, we found that extinction of inhibition occurred, whether or not participants experienced lower outcome levels. In Experiment 2, we applied this outcome manipulation to blocking of a conditioned inhibitor. We found blocking of inhibition both when participants had experience with lower outcomes and when they did not. The results of our two experiments are consistent with Rescorla and Wagner's (1972) associative model, and inconsistent with an inferential account of causal learning (De Houwer, Beckers, & Vandorpe, 2005).

Previous reports have described panhypopituitarism associated with severe cases of hemorrhagic fever with renal syndrome (HFRS), but the prevalence of hormonal deficiencies after nephropathia epidemica (NE), a milder form of HFRS, has not been studied. This study was conducted in order to determine the prevalence of hormonal defects in patients with acute NE and during long-term follow-up. Fifty-four patients with serologically confirmed acute NE were examined by serum hormonal measurements during the acute NE, after 3 months, and after 1 to 10 (median 5) years. Thirty out of 54 (56%) patients had abnormalities of the gonadal and/or thyroid axis during the acute NE. After a median follow-up of 5 years, 9 (17%) patients were diagnosed with a chronic, overt hormonal deficit: hypopituitarism was found in five patients and primary hypothyroidism in five patients. In addition, chronic subclinical testicular failure was found in five men. High creatinine levels and inflammatory markers during NE were associated with the acute central hormone deficiencies, but not with the chronic deficiencies. Hormonal defects are common during acute NE and, surprisingly, many patients develop chronic hormonal deficiencies after NE. The occurrence of long-term hormonal defects cannot be predicted by the severity of acute NE.

Calorie restriction (CR) slows aging and is thought to improve insulin sensitivity in laboratory animals. In contrast, decreased insulin signaling and/or mild insulin resistance paradoxically extends maximal lifespan in various genetic animal models of longevity. Nothing is known regarding the long-term effects of CR on glucose tolerance and insulin action in lean healthy humans. In this study we evaluated body composition, glucose, and insulin responses to an oral glucose tolerance test and serum adipokines levels in 28 volunteers, who had been eating a CR diet for an average of 6.9 +/- 5.5 years, (mean age 53.0 +/- 11 years), in 28 age-, sex-, and body fat-matched endurance runners (EX), and 28 age- and sex-matched sedentary controls eating Western diets (WD). We found that the CR and EX volunteers were significantly leaner than the WD volunteers. Insulin sensitivity, determined according to the HOMA-IR and the Matsuda and DeFronzo insulin sensitivity indexes, was significantly higher in the CR and EX groups than in the WD group (P = 0.001). Nonetheless, despite high serum adiponectin and low inflammation, approximately 40% of CR individuals exhibited an exaggerated hyperglycemic response to a glucose load. This impaired glucose tolerance is associated with lower circulating levels of IGF-1, total testosterone, and triiodothyronine, which are typical adaptations to life-extending CR in rodents.

Objective: To describe serum and urinary hormones, androgens metabolites and testosterone/epitestosterone ratio profiles after testosterone administration in male hypogonadal volunteers, and to evaluate their possible usefulness in detecting doping with testosterone in treated hypogonadal athletes., Design: Controlled open label design vs placebo; pharmacokinetic study., Participants: Ten male volunteers affected by severe hypogonadism (serum testosterone <2.31 ng/ml)., Interventions and Main Outcome Measures: Serum and urinary parameters were evaluated, by radioimmunoassay and gas chromatography-mass spectrometry, before and at different time points for 7/3 weeks after a single administration of testosterone enanthate (250 mg) or placebo, respectively., Results: As partially known, testosterone administration increased, with great individual variability, urinary concentrations of glucuronide testosterone, androsterone, etiocholanolone, 5alpha-androstane- 3alpha,17beta-diol, 5beta-androstane-3alpha,17beta-diol, testosterone/ epitestosterone and testosterone/LH ratios; and decreased epitestosterone and 5alpha-androstane-3beta,17beta-diol/5beta-androstane- 3alpha,17beta-diol ratio. Serum testosterone and dihydrotestosterone increased in all volunteers, and concentrations higher than the upper reference limits were observed in many volunteers until 2 weeks after testosterone administration., Conclusion: Whereas the observed prolonged hyperandrogenism partially limited data interpretation, the report ed characteristics of variation of urinary parameters might be used to suspect testosterone misuse in hypogonadal athletes treated with testosterone enanthate. In this sense, while the actual threshold for tes tos terone/epites tos ter one ratio was confirmed to be of reduced usefulness, we suggest a contemporary evaluation of whole urinary androgen metabolites profile and serum androgens, at specific time points after testosterone enanthate administration. Moreover, an adequate tailoring of treatment, to avoid transitory hyperandrogenism, is highly advisable. Further studies on strategies for detecting doping with testosterone in hypogonadal athletes are warranted.

Individual or combined administration of BCG vaccine and silicon dioxide to male mice induced a nonspecific stress response of the adrenal glands and gonads judging from changes in the concentration of blood cortisol and testosterone. The dynamics of cortisol concentration in the adrenal glands was similar, while changes in progesterone concentration were in antiphase to those in the blood. After combined administration of both inductors of granulomatous inflammation, changes in the concentrations of the studied hormones to a greater extent corresponded to their dynamics after injection of BCG.

Objective: Severe hypoglycemia is an important but uncommon complication of anorexia nervosa. A 35-year-old woman showed severe hypoglycemia after a recovery from severe liver dysfunction due to malnutrition., Methods: To reveal the cause of severe hypoglycemia, we measured plasma hormones and performed a 75g oral glucose loading test., Results: Fasting serum adrenocorticotropic hormone, cortisol, growth hormone, somatostatin, and active ghrelin were elevated. Serum free triiodothyronine, leptin, and adiponectin were reduced. Plasma glucose fluctuated from 67 to 76 mg/dl after a 75g glucose ingestion, without hyperinsulinemia. Serum growth hormone, somatostatin, and active ghrelin levels were decreased after glucose ingestion. Plasma glucagon levels were increased and remained at high levels at 120 min, and glucose-dependent insulinotropic polypeptide (GIP) levels were continuously and remarkably increased after glucose ingestion., Conclusion: We observed a strongly reduced sensitivity in glucagon-induced hepatic glycogenolysis, and significantly elevated fasting and postprandial GIP levels, and a defective GIP-mediated glucagon secretion, in an anorectic patient with severe hypoglycemia.

Purpose: Azoospermia may sometimes be related to the use of androgenic anabolic steroids. We report the case of an azoospermic man who had abused androgenic anabolic steroids and who recovered spermatogenesis six months after cessation of abuse and the administration of hormonal therapy., Methods: An azoospermic 34-year-old man came to Regional Referral Center for Male Infertility. The recovery of spermatogenesis was observed after the cessation of abuse of steroids and the administration of hormonal therapy. Ultrastructural analysis of sperm was carried out by transmission electron microscopy, and the meiotic segregation of chromosomes 1, 9, 18, X, Y was investigated., Results: Mathematically elaborated transmission electron microscopy data highlighted seminal features close to normal fertility. Fluorescence in situ hybridisation showed a high frequency of XY disomy in sperm., Conclusions: Our findings confirm the recovery of spermatogenesis but suggest a possible relationship between altered meiotic segregation and the abuse of androgenic anabolic steroids.

GH and IGF system components are important regulators of bone formation and at the same time pathogenetic factors in functional hyperandrogenism (FH) in lean females. We studied the relationships between bone mineral density (BMD) and serum concentrations of GH, GH-related parameters, androgens and estrogen, in 18 non-obese women of reproductive age with functional hyperandrogenism compared to a group of 10 healthy eumenorrheic age- and weight-matched women. In androgenized women, a significant positive correlation was found between BMD and GH-binding protein (GHBP), whereas BMD did not correlate to GH or other related parameters. It is suggested that higher tissue GH receptor responsiveness in non-obese androgenized women may contribute to their higher BMD.

An adult Caucasian female developed a previously unreported association of pelvic endometriosis (PE) with the triad of alopecia universalis (AU), autoimmune thyroiditis (AT) and multiple sclerosis (MS). Molecular human leukocyte antigen (HLA)-tissue typing of this subject showed the presence of the DR(2) 15 and DR(3) 17 alleles, which are associated to an increased risk of MS and AT, respectively. Clinical onset of AT followed withdrawal of corticosteroid treatment for AU, whereas MS become clinically evident after withdrawal from long-term estroprogestin therapy for PE. This clinical case is presented to discuss the autoimmune origin of PE, its possible association with multiple autoimmune disorders as well as the effect of other factors, such as administration and/ or discontinuation of specific hormonal regimens, on genetic autoimmunity-prone background.

A survey was conducted in 10 districts of northern India. Significant deficiency of zinc was observed in soil, fodders and (cattle) serum samples. The animals showed typical signs of zinc deficiency, namely stiff gait, swelling of hocks and knees, subcutaneous fluid accumulation, rough coat, etc. of variable intensity. A clustered model therapeutic trial was conducted and zinc-deficient cattle were divided into three groups. Group A was provided with mineral mixture containing zinc sulphate. Group B was given mineral mixture without zinc sulphate and group C was given no mineral mixture. Significant improvement (p < 0.01) was observed in the haemoglobin (Hb), total white blood cells (WBC) and total erythrocyte count (TEC) levels at the 7th day of treatment in the animals of group A. Significant improvement in enzyme serum alkaline phosphatase (SAP) was observed in group A animals at the 7th day, while improvement in asparatate aminotransferase (AST), alanine aminotransferase (ALT) and ceruloplasmin (Cp) was observed after 21 days of treatment. Regarding hormones, significant improvement was observed in thyroxine (T3) and triiodothyronine (T4), oestrogen and progesterone in group A animals within 14 days of treatment. The values of vitamin A showed a highly significant (p < 0.01) improvement within 7 days of treatment in group A animals and that of vitamin E on the 21 st day of treatment. The milk yield of lactating cattle and body weight of growing calves in group A showed highly significant (p < 0.01) increases at about 14 and 30 days, respectively. It is concluded that zinc sulphate supplementation is highly effective in alleviating zinc deficiency and improving various biochemical and production parameters in cattle. The clustered model treatment provides a better indicator of the most limiting element under field conditions where simultaneous deficiency of various minerals is prevalent.

Objectives: Coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) causes an acute stress response characterized by changes in the levels of several hormones, which might play a role in the high complication rate experienced by older patients after CABG. Thus, the aim of the study was to investigate changes in the circulating levels of anabolic and catabolic hormones in old people undergoing CABG with CPB., Design: Intervention case study., Methods: 19 patients (12 males, 7 females) aged 70.1 +/- 6.1 yr (age range 62-80) with coronary artery disease and an ejection fraction <40% who underwent cardiac surgery. Cortisol (Cort), DHEA, DHEAS, LH, estradiol (E2), total testosterone (Te), SHBG, IGF-I were measured the day before, on the day of the procedure and 1, 2, 3, 4, and 30 days after CABG., Results: After surgery, serum IGF-I levels decreased (p<0.001), while levels of Cort, DHEAS and E2 significantly increased in both men and women. Alterations in Te levels differed between the two sexes with a significant decline in men and a significant increment in women., Conclusion: CABG with CPB resulted in a dramatic drop in Te levels in old men and a significant decline in IGF-I in both sexes. Serum Cort levels also significantly increased in both sexes. These hormonal changes may, at least partially, explain why the elderly need prolonged rehabilitation after CABG.

Bone mineral density (BMD) is frequently reduced in children and adolescents with Cushing's disease (CD), but there is little follow-up data after cure. BMD was determined by dual energy X-ray absorptiometry (DEXA) in two groups of patients with CD. Group 1 comprised 8 patients, 5 males and 3 females, aged 12.4 yr (8.2-16.8), assessed at diagnosis. Group 2 comprised 11 subjects, 6 males and 5 females, diagnosed at age 13.3 yr (6.4-17.4), cured by transsphenoidal surgery (TSS) (no.=7) or TSS + pituitary irradiation (no.=4). They had measurement of BMD, at mean age of 18.3 yr (11.1-28.5), i.e. 4.5 yr (0.8-11.4) after cure. Four patients, mean age 20.2 yr (17.6-22.4), had repeated DEXA'scans, 1-4 times, for up to 5.8 yr. After cure, GH deficiency was present in 9 patients and treated with hGH in 8. In Group 1, patients' L2-L4 volumetric (v)BMD Z-score was variable with a mean of -1.04 (-3.21-0.11). L2-L4 vBMD Z-score values correlated negatively with midnight cortisol (p < 0.05). In Group 2, mean L2-L4 vBMD was -0.38 (-1.0-0.13); and in 7/11, mean femoral neck (FN) areal (a)BMD Z-score was 0.14 (-1.62-2.46). FN aBMD Z-score was higher than L2-L4 aBMD Z-score (p < 0.05). In patients with repeated scans, mean change in L2-L4 vBMD Z-score was 0.20 (-0.15-0.45), and mean change in FN aBMD Z-score 0.03 (-0.53-0.38). These findings show variability of BMD at diagnosis and near normal BMD after cure of pediatric CD, suggesting that with appropriate replacement of pituitary hormone deficiency normal peak bone mass is achievable.

The aim of this cross-sectional study was to analyze bone mineral density (BMD) and prevalence of osteopenia and osteoporosis in 30 men with prolactinoma, and compare them to 22 control subjects. BMD of lumbar spine and femur was evaluated by dual-energy X-ray absorptiometry. PRL, testosterone, estradiol, sexual hormone-binding globulin and free androgen and estrogen indexes (FAI and FEI, respectively) were measured in all the subjects. In patients with prolactinoma, mean values of PRL and testosterone were calculated for the 12-month period that preceded the study. The mean T-score of the four sites analyzed by bone densitometry was lower in men with prolactinoma than in controls (p-values: lumbar spine=0.015, femoral neck <0.0001, trochanter=0.037, total femur=0.036), and 55.6% of the former presented osteopenia or osteoporosis at one or more sites (p =0.035). The lumbar spine was the most seriously affected site, where 29.6% had osteopenia and 14.8% had osteoporosis. By the time of BMD determination, significant associations were found between BMD and PRL, testosterone, FAI, estradiol, FEI, and duration of hypogonadism. Considering the period of 12 months that preceded BMD evaluation, trochanter BMD was associated with mean PRL levels, while there was an association between lumbar spine BMD and mean testosterone levels. However, the multiple regression analysis showed that estradiol was the main determinant of BMD. In conclusion, men with prolactinoma have high prevalence of osteopenia and osteoporosis. Bone loss in such patients is associated with hyperprolactinemia and hypogonadism, and mainly influenced by estrogen.

Object: The indications for additional radiotherapy (RT) after surgery for non-functioning pituitary adenoma are controversial. The goal of this retrospective study was to evaluate the outcome of surgically treated patients, with or without post- operative irradiation., Methods: Review of cases treated for non-functioning pituitary adenoma. Fifty-one patients were identified, with a mean post-operative follow-up of 6.4+/-3.5 yr. Twenty-nine patients showed residual tumor after surgery and 22 did not. Serial endocrine, visual and radiological evaluations were made after treatment to assess the efficacy and toxicity of surgery and RT. Twenty-seven patients with residual tumor after surgery received RT (22 of them during the post-operative period and 5 after an interval of several yr: 3 because of increased tumor size and 2 with stable residual lesion); tumors in 14 of these patients decreased in size, 11 appeared to be stable on imaging and one patient showed some increase in tumor size (one patient was not followed-up). The residual tumors of the 2 non-irradiated patients remained stable after 5 and 7 yr, respectively. Twenty-two patients without residual disease after surgery (11 with post-operative irradiation, 1 with RT 5 yr after transsphenoidal surgery because of tumor recurrence, and 10 without RT) have shown no evidence of tumor regrowth on serial images., Conclusions: Radiotherapy can be avoided in patients with complete macroscopic resection and absence of residual tumor in post-operative images; they must be carefully followed using imaging techniques and, in the case of recurrence, they should be re-operated and/or irradiated.