Band 42, Heft 3

Objectives Insulin resistance is the most common metabolic change associated with obesity. The present study aimed to investigate the relationship between insulin resistance and body composition especially adipose tissue in a randomized Tehrani population. Methods This study used data of 2,160 individuals registered in a cross-sectional study on were randomly selected from among subjects who were referred to nutrition counseling clinic in Tehran, from April 2016 to September 2017. Insulin resistance was calculated by homeostasis model assessment formula. The odds ratio (95% CI) was calculated using logistic regression models. Results The mean age of the men was 39 (±10) and women were 41 (±11) (the age ranged from 20 to 50 years). The risk of increased HOMA-IR was 1.03 (95% CI: 1.01–1.04) for an increase in one percent of Body fat, and 1.03 (95% CI: 1.00–1.05) for an increase in one percent of Trunk fat. Moreover, the odds ratio of FBS for an increase in one unit of Body fat percent and Trunk fat percent increased by 1.05 (adjusted odds ratio [95% CI: 1.03, 1.06]) and 1.05 (95% CI: 1.02, 1.08). Also, the risk of increased Fasting Insulin was 1.05 (95% CI: 1.03–1.07) for an increase in one unit of Body fat percent, and 1.05 (95% CI: 1.02–1.08) for an increase in one unit of Trunk fat percent. Conclusions The findings of the present study showed that there was a significant relationship between HOMA-IR, Fasting blood sugar, Fasting Insulin, and 2 h Insulin with percent of Body fat, percent of Trunk fat.

Objectives Breast cancer is a common malignant tumor in women with limited treatment options and multiple side effects. Today, the anti-cancer properties of natural compounds have attracted widespread attention from researchers worldwide. Methods In this study, we treated 4T1 tumor-bearing Balb/c mice with intraperitoneal injection of Auraptene, paraffin oil, and saline as two control groups. Body weight and tumor volume were measured before and after treatment. Hematoxylin and eosin (H & E) staining and immunohistochemistry of Ki-67 were used as markers of proliferation. In addition, ELISA assays were performed to assess serum IFN-γ and IL-4 levels. Results There was no significant change in body weight in all animal groups before and after treatment. 10 days after the last treatment, Auraptene showed its anti-cancer effect, which was confirmed by the smaller tumor volume and H & E staining. In addition, Ki-67 expression levels were significantly reduced in tumor samples from the Auraptene-treated group compared to the paraffin oil and saline-treated groups. In addition, in tumor-bearing and normal mice receiving Auraptene treatment, IL-4 serum production levels were reduced, while serum levels of IFN-γ were significantly up-regulated in tumor-bearing mice after Auraptene treatment. Conclusions In the case of inhibition of tumor volume and Ki-67 proliferation markers, Auraptene can effectively inhibit tumor growth in breast cancer animal models. In addition, it might increases Th1 and CD8 + T cell responses after reducing IL-4 serum levels and IFN-γ upregulation, respectively. However, further research is needed to clarify its mechanism of action.

Objectives High fat diet can lead to testicular structural and functional disturbances, spermatogenesis disorders as well as infertility. So, the present investigation was proposed to clarify whether voluntary exercise could prevent high fat diet induced reproductive complications in rats through testicular stress oxidative and apoptosis. Methods Forty male Wistar rats were randomly divided into four groups; control (C), voluntary exercise (VE), high fat diet (HFD) and high fat diet and voluntary exercise (VE + HFD) groups. The rats in the VE and VE + HFD groups were accommodated in apart cages that had running wheels and the running distance was assessed daily for 10 weeks. In VE + HFD group, animals were fed with HFD for five weeks before commencing exercise. The sperm parameters, the expressions of testicular miR-34a gene, and P53 and SIRT1 proteins as well as testicular apoptosis were analyzed in all groups. Results The results indicated that voluntary exercise in VE + HFD group led to significantly increased GPX and SOD activities, SIRT1 protein expression, sperm parameters, and decreased the expression of miR34a gene and Acp53 protein, and cellular apoptosis index compared to HFD group (p<0.001 to p<0.05). The SOD and catalase activities, SIRT1 protein expression, sperm parameters in VE + HFD group were lower than of those of VE group, however, MDA content, expression of Acp53 protein, apoptosis indexes in VE + HFD group was higher than that of VE group (p<0.001 to p<0.05). Conclusion This study revealed that voluntary exercise improved spermatogenesis, in part by decreasing the testicular oxidative stress status, apoptosis through alteration in miR-34a/SIRT1/p53 pathway.

Objectives The aim of the present study was to investigate the expression of AXL and mTOR genes and their targeting microRNAs (miRNAs) including miR-34a and miR-144 in Medullary Thyroid Carcinoma (MTC) cell line, TT, and determine the effect of these two miRNAs on their target genes to introduce new molecular markers or therapeutics. Methods The expression of miR-34a, miR-144, and their targets genes including AXL and mTOR was evaluated by quantitative Real-time PCR. Luciferase assay was performed to confirm the interaction between miRNAs and their target mRNAs. The expression level of AXL and mTOR was evaluated before and after miRNAs induction in TT cell line compared with Cos7 as control cells. Results The expression of AXL and mTOR were up-regulated significantly, while miR-34a and miR-144 were down-regulated in TT cell line compared to Cos7. After transduction, the overexpression of miR-34a and 144 caused down-regulation of both genes. Luciferase assay results showed that the mTOR is targeted by miR-34a and miR-144 and the intensity of luciferase decreased in the presence of miRNAs. Conclusions Based on the results of the present study and since AXL and mTOR genes play a critical role in variety of human cancers, suppression of these genes by their targeting miRNAs, especially miR-34a and miR-144, can be propose as a new strategy for MTC management. However, more studies are needed to approve the hypothesis.

Objectives Infertility is defined as the absence of pregnancy within the reproductive period despite regular sexual intercourse. Methylarginines are formed as a result of methylation of arginine residues in proteins and formed in three forms as asymmetric dimethyl arginine (ADMA), symmetrical dimethyl arginine (SDMA) and monomethylarginine (L-NMMA). So, here, we aimed to evaluate arginine and their derivatives levels in fertile and infertile individuals. Methods Present study were consist of 30 oligozoospermia patients (proven by spermiogram analysis) and 30 healthy individuals with normozoospermia group who were applied to the urology department. With blood samples taken from individuals, serum methylarginine and its derivatives levels were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Clinic data and demographic characteristics of individuals were also recorded at the same time. Results The serum ADMA level (0.38 ± 0.07) of the oligozoospermia group was found to be significantly higher than the normozoospermia group (0.35 ± 0.05) (p=0.046). A positive correlation were observed between ADMA and SDMA (r=0.686, p=0.000), HArg and SDMA (r=0.611, p=0.001), citrulline and L-NMMA (r=0.595, p=0.001) in patients with oligosospermia. The increase in SDMA, arginine and HArg levels and a decrease in L-NMMA and citrulline levels were not significant as statistically. Also, the ADMA level was found to be high in individuals with low sperm concentration. Conclusions Consequently, serum ADMA levels of individuals with oligozoospermia were statistically significantly higher than those with normozoospermia. As proposal, determination of ADMA levels may be a potential biomarker parameter in terms of early diagnosis of fertility and infertility.

Objectives Chromosome anomalies and Y chromosome microdeletions are one of the reasons that can be seen in infertile patients and affect fertility. In this study, it was aimed to determine the frequencies of chromosomal anomalies and Y chromosome microdeletions in primary infertile male patients. Methods We included 374 patients with primary infertility in this study. Cytogenetic analysis was performed with the GTG banding technique by using trypsin and Giemsa stain. Y microdeletion analysis was studied by multiplex polymerase chain reaction using 28 Y chromosome-specific sequence-tagged sites. Results Chromosomal irregularities were detected in 27 (7.22%) of infertile cases. It was observed that 7 (25.92%) of chromosomal irregularities detected in cases were in autosomal and 20 (%74.08) were in gonosomal chromosomes. The incidence of Y chromosome microdeletion was 1.07% (4/374) and the microdeletions were observed in AZFb, AZFc and AZFd regions. AZFc + AZFd deletion was detected in three patients (0.81%) and AZFb + AZFc + AZFd deletion in one patient (0.26%). Conclusions In conclusion, gonosomal chromosome irregularity was higher than autosomal chromosome irregularity in infertile men. The frequency of Y microdeletion has different rates according to some factors such as ethnic differences of patients, patient selection criteria, differences in the number of cases, and methodological aspects.

Objectives The objective of the study was to determine the level of antibodies (AB) of Ig classes A and G to estradiol (E2), progesterone (P) and benzo [a] pyrene (Bp) in patients with endometriosis of various severity and estimate their threshold values as a risk factor for the development of endometriosis. Methods A retrospective case–control study was performed. The study involved 200 women. Group I: women with endometriosis (n=100), Group II: patients with tubal-peritoneal infertility (n=100). All patients underwent immunological studies of blood serum; and the levels of steroid hormones (P, E2), antibodies to them and Bp were determined. A ROC analysis was carried out to identify threshold values of antibodies levels. Results Women with endometriosis were found to have statistically significantly higher levels of antibodies IgA and IgG to E2, P and benzo [a] pyrene compared to women of Group II. The threshold levels of IgA-Bp, IgA-E2 and IgA-P are >5 CU (conventional unit), IgG-Bp, IgG-E2>9 CU and IgG-P>8 CU. The level of IgG-P in patients with severe forms of endometriosis is statistically significantly higher than in minor forms of the disease. In case of severe forms, there is a tendency to increasing other classes of antibodies. Conclusions Patients with endometriosis usually have a higher level of IgA and IgG to Bp, E2, P. Their threshold values, which are risk factors for the development of the disease, are estimated.

Objectives Thyroid disorders are important risk factor for cardiovascular diseases. Levels of methylarginines such as asymmetric dimethyl arginine (ADMA), L-monomethyl arginine (L-NMMA), symmetric dimethyl arginine (SDMA) are increase in cardiovascular diseases. Multinodular goiter (MNG) is the most common type of goiter in adults. To date, no study has been conducted to determine the levels of methylarginine in euthyroid MNG patients. Our aim in this study is to compare levels of methylarginines and related metabolites in the preoperative, postoperative MNG patients and controls. Methods Serum ADMA, SDMA, L-NMMA, homoarginine (hArg), arginine and citrulline concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results ADMA (p<0.001), L-NMMA (p=0.002), l -arginine (p=0.006) and citrulline (p<0.001) levels were statistically significantly higher in preop group than postop group. ADMA (p=0.003), L-NMMA (p=0.003) levels were statistically significantly higher and SDMA/ADMA (p<0.001), hArg/ADMA (p<0.001) levels were statistically significantly lower in preop group than control group. Conclusions The levels of methylarginines and related metabolites altered in the euthyroid MNG patients compared to the control group, and more importantly, there were significant differences between the preop and postop groups. Therefore, these metabolites can be useful in the diagnosis and prognosis of thyroid disorders, even if thyroid hormone levels are normal.

Objectives To evaluate the effects of an eight week exercise program on the lipid profile in serum, serum levels of adropin, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in male volleyball players. Methods Sixteen healthy male volleyball players participated in this study. Subjects performed eight weeks of aerobic and resistance training, and body mass index (BMI), body fat ratio, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), adropin, SBP, and DBP values were measured at the start (untrained) and end (trained) of training. Non-HDL-C was calculated by subtracting HDL-C from TC. Results Body fat percentage and BMI values decreased significantly after eight weeks of exercise training. There was a statistically significant decrease in the post-test values of LDL-C, TG, non-HDL-C, and DBP compared to pre-test measurements. There was a significant increase in the trained levels of adropin and HDL-C compared to untrained levels. Pearson’s correlation analyses revealed a negative and significant relationship between changes in DBP and adropin levels before and after exercise. Conclusions Eight weeks of exercise training decreased LDL-C, TG, non-HDL-C, and DBP and an increased serum levels of adropin in male volleyball players.

Objectives There is a growing evidence indicating an impact of endocrine distrupting chemicals such as bisphenol A (BPA) on human reproduction. Its higher levels in serum or urine have been documented in women with polycystic ovary syndrome (PCOS), however the relationship to ovarian steroidogenesis remains unclear. Aim of the study was to compare urinary BPA (U-BPA) concentrations among PCOS women and control group. Second aim was to assess the relationship of U-BPA to ovarian steroidogenesis in the group with PCOS. Methods Eighty six Caucasian women (age 28.5 ± 5.1 years) diagnosed with PCOS and 32 controls of age 24.9 ± 4.4 years were included in the study. Fasting blood samples were analyzed for biochemical parameters and steroid hormones. U-BPA was measured in the morning urine sample using high pressure liquid chromatography. Results PCOS women had significantly higher U-BPA as compared with control group (p=0.0001). Those with high levels of U-BPA (U-BPA ≥ 2.14 ug/g creatinine) demonstrated higher serum insulin (p=0.029) and HOMA IR (p=0.037), lower serum estrone (p=0.05), estradiol (p=0.0126), FSH (p=0.0056), and FAI (p=0.0088), as compared with low-BPA group (U- BPA <2.14 ug/g creatinine). In PCOS women, U-BPA positively correlated with age (p=0.0026; R 2 =0.17), negatively with estradiol (p=0.0001, R 2 =0.5), testosterone (p=0.0078, R 2 =0.15), free-testosterone (p=0.0094, R 2 =0.12) and FAI (p=0.0003, R 2 =0.32), respectively. Conclusions PCOS women have significantly higher U-BPA concentrations than healthy controls. U-BPA positively correlates with age and negatively with ovarian steroid hormones suggesting a possible suppressive effect of bisphenol A on ovarian steroidogenesis.

Objectives Gestational trophoblastic disease comprises of a spectrum of pregnancy-related tumours which includes complete (CHM) and partial hydatidiform moles (PHM). Accurate diagnosis and subclassification of HM subtypes are crucial as prognosis differs. Histopathological examination using haemotoxylin and eosin (H&E) staining remains the basis for diagnosing HM, with only 80% accuracy. p57kip2 is a cyclin-dependent kinase inhibitor (CDKI) protein and is strongly paternally imprinted, being expressed from maternal allele. Therefore, complete mole (CHM) with only paternal genome has nearly absent expression of p57kip2 compared to partial mole (PHM) having both paternal and maternal genomes. This study is aimed to determine usefulness of p57kip2 immunohistochemistry (IHC) analysis in the diagnosis of HM subtypes. Methods A total of 82 archived paraffin embedded HM tissues with subtypes classified based on H&E staining – 39 (47.5%) CHM, 41 (50.0%) PHM and two (2.43%) unclassified molar pregnancy were retrieved. All tissue samples were subjected for p57kip2 IHC analysis and HM subtypes were then reclassified. Results A total of 66 cases (80.5%) were re-classified as CHM, 14 cases (17.1%) as PHM and two cases (2.4%) were decidual and cystic tissues. Analysis using p57kip2 immunostaining showed a diagnostic discrepancy of 33.0% from routine H&E staining and helps to improve the characterisation of the HM subtypes specifically at early gestations which have less distinctive morphologies. Conclusions IHC using p57kip2 monoclonal antibody should be considered as a routine ancillary test to H&E in improving the diagnosis of HM subtypes particularly in developing countries with limited resources.

Objectives Prader–Willi syndrome (PWS) is a rare genetic syndrome characterized by hyperphagia and early development of morbid obesity. Cardiovascular disease (CVD) and metabolic syndrome (MetS) are major comorbidities in these patients leading to premature death. Inhibitory factor 1 (IF 1 ) works as a regulatory protein, inhibiting the ATP hydrolase activity of mitochondrial ATP synthase and likely playing a role in lipid metabolism. We aimed to assay IF 1 in adult patients with PWS evaluating any relationship with clinical, genetic and biochemical parameters. Methods We recruited 35 adult patients with genetically confirmed PWS. Results IF 1 serum concentration displayed a normal distribution with an average value of 70.7 ± 22.6 pg/mL, a median value of 66.1 pg/mL. It was above the reference range only in one patient. All parameters were compared from both sides of IF 1 median without displaying any significant differences. Patients with normal or low HDL-cholesterol did not present any difference as regards IF 1 levels, which were not different between patients with and without MetS. Non-esterified fatty acids (NEFA) serum levels (r=0.623; p<0.001) showed a statistically significant correlation with IF 1 . Cholesterol and its fractions did not present any correlation with IF 1. Conclusions In this study we do not confirm that HDL-cholesterol and IF 1 are correlated, but we show that in adult PWS patients, NEFA are correlated with serum IF 1. This protein could play a role to some extent in determining the complex metabolic alterations in PWS patients.

Objectives To review non-surgical prevention strategies in women with hereditary breast and ovarian cancer syndromes. Content Women with a g BRCA1 or 2 mutations face a high cumulative breast and ovarian cancer risk. While bilateral mastectomy (PBM) and bilateral salpingo-oophrectomy (PBSO) profoundly reduce the respective cancer risks, they are also associated with considerable side effects. There is therefore an urgent need for alternative and non-surgical risk reduction options. Tamoxifen and aromatase inhibitors have both been evaluated in secondary prevention, but their benefit in primary prevention is currently unknown in BRCA mutation carriers. In addition, their use is compromised by their side effect profile which makes them less appealing for a use in chemoprevention. Summary and outlook Denosumab is a well-tolerated osteoprotective drug, which has been demonstrated to have a potential preventive effect particularly in BRCA1 -deficient models in vitro . The prospectively randomized double-blind BRCA-P trial is currently investigating the preventative effect of denosumab in healthy BRCA1 germ line mutation carriers.

Objectives We compared cases of phenotypic female patients who presented with male karyotype and underwent prophylactic gonadectomy. Case presentation Five patients with female phenotypes presented in early adulthood with primary amenorrhoea with varying degrees of puberty. One was tall with breast development. Another was very short with clitoromegaly and multiple co-morbidities. The other three had no secondary sexual characteristics. They were examined, after which hormonal profile, karyotyping, ultrasound examination and magnetic resonance imaging were done to assess the site of gonads. Gonadectomy was performed once their 46 XY karyotype was confirmed. Results of histopathological examination of their gonads ranged from dysgenetic gonads to having testicular tissues and malignancy. Conclusion Female patients with 46 XY karyotypes require prophylactic gonadectomy performed at different timings depending on diagnosis due to the malignancy risk. Pre-operative assessment is essential to locate the gonads prior to surgery.

The relationship between menopause and the development of metabolic diseases is well established. In postmenopause women, there is an expansion of visceral white adipose tissue (WATv), which highly contributes to the rise of circulating lipids. Meanwhile, muscle glucose uptake decreases and hepatic glucose production increases. Consequently, in the pancreas, lipotoxicity and glycotoxicity lead to deficient insulin production. These factors initiate an energy imbalance and enhance the probability of developing cardiovascular and metabolic diseases. Although the activation of estradiol receptors (ER) has been shown to be beneficial for the WAT stock pattern, leading to the insulin-sensitive phenotype, authors have described the risk of these receptors’ activation, contributing to neoplasia development. The selective activation of beta-type ER (ERβ) seems to be a promising strategy in the treatment of energy imbalance, acting on several tissues of metabolic importance and allowing an intervention with less risk for the development of estrogen-dependent neoplasia. However, the literature on the risks and benefits of selective ERβ activation still needs to increase. In this review, several aspects related to ERβ were considered, such as its physiological role in tissues of energy importance, beneficial effects, and risks of its stimulation during menopause. PubMed, SciELO, Cochrane, and Medline/Bireme databases were used in this study. Highlights – In menopause, the expansion of visceral white adipose tissue contributes to the rise of circulating lipids. – Muscle glucose uptake decreases and hepatic glucose production increases in menopause. – The energy imbalance and the enhanced probability of developing cardiovascular and metabolic diseases. – The activation of estradiol receptors has been shown to be beneficial for the white adipose tissue stock pattern. – It has been described the risk of estradiol receptors’ activation, contributing to neoplasia development. – The selective activation of beta-type estradiol receptor seems to be a promising strategy, allowing an intervention with less risk for estrogen-dependent neoplasia. – The literature on the risks and benefits of selective beta-estradiol receptor activation still needs to increase. – Several physiological aspects related to estradiol beta-receptor need to be more investigated in tissues of energy importance.