Band 41, Heft 2

Background Fibroblast growth factors (FGFs); FGF-21 and FGF-23, have been proposed to be associated with metabolic syndrome. However, data on the role of these peptides in gestational diabetes mellitus (GDM) are limited. Therefore, this study was designed to assess the association of serum FGF-21 and FGF-23 with the risk of GDM. Furthermore, we evaluated the circulation of these peptides in pregnancy and post-puerperium. Materials and methods Fifty-three pregnant subjects with GDM and 43 normal glucose tolerance (NGT) pregnant women participated in this study. Serum FGF-21 and FGF-23 were measured during pregnancy and post-puerperium. Results FGF-21 and FGF-23 were low in GDM compared to NGT during pregnancy. There were no significant differences in the level of these peptides post-puerperium. Using logistic regression, FGF-23 [odds ratio (OR) 0.70 (95% confidence interval [CI]: 0.50–0.96)] was inversely associated with GDM, so a 1-μg/mL decrease in FGF-23 levels was associated with a 1.4-fold increased risk of developing GDM and this remained statistically significant after adjustment for confounders [adjusted OR (aOR) 0.70 (95% CI: 0.50–0.98)]. There was no association of FGF-21 with the development of GDM risk. Conclusions Lower FGF-23 concentrations could be involved in the pathophysiology of GDM. FGF-21, even though associated with metabolic risk factors in pregnancy, may not be a fundamental factor in GDM.

Background Metabolic syndrome (MetS) continues to be a significant problem globally, affecting nearly 35% of adults in the USA. Whilst there is no ideal biomarker that captures this disorder, high sensitivity C-reactive protein (hsCRP) appears to be most widely accepted. We examined the ratios between neutrophils (PMNs) and monocytes to high-density lipoprotein (HDL)-cholesterol and adiponectin, two anti-inflammatory proteins, in patients with nascent MetS without the confounding of diabetes, atherosclerotic cardiovascular diseases (ASCVD), smoking or lipid therapy to determine if they were also valid biomarkers of MetS. Materials and methods Patients with nascent MetS (n = 58) and matched controls (n = 44) were recruited from Sacramento County. Fasting blood samples were obtained for complete blood counts, basic metabolic panel, lipid profile, insulin and adiponectin. Ratios of PMNs and monocytes to HDL-C and adiponectin were calculated and compared statistically. Results The PMN:HDL-C, monocyte:HDL-C, PMN:adiponectin and monocyte:adiponectin ratios were significantly increased in patients with MetS and increased with increasing severity of MetS. Receiver operating characteristic (ROC) curve analysis showed that both the PMN:HDL-C and monocyte:HDL-C areas under the curve (AUCs) significantly added to the CRP AUC. Also both the ratios correlated with cardio-metabolic features of MetS, hsCRP and insulin resistance. Conclusions Our data indicates that ratios of neutrophils and monocytes to HDL-C are significantly increased in patients with nascent MetS and both ratios appear to be better predictors of MetS than hsCRP alone. These important preliminary findings need to be confirmed in large prospective databases.

Background The increase in soluble suppression of tumorigenicity 2 (sST2) both in the diagnosis and prognosis of heart failure is well established; however, existing data regarding sST2 values as the prognostic marker after myocardial infarction (MI) are limited and have been conflicting. This study aimed to assess the clinical significance of sST2 in predicting 1-year adverse cardiovascular (CV) events in MI patients. Materials and methods In this prospective study, 380 MI patients were included. Participants were grouped into low sST2 (n = 264, mean age: 60.0 ± 12.1 years) and high sST2 groups (n = 116, mean age: 60.5 ± 11.6 years), and all study populations were followed up for major adverse cardiovascular events (MACE) which are composed of CV mortality, target vessel revascularization (TVR), non-fatal reinfarction, stroke and heart failure. Results During a 12-month follow-up, 68 (17.8%) patients had MACE. CV mortality and heart failure were significantly higher in the high sST2 group compared to the low sST2 group (15.5% vs. 4.9%, p = 0.001 and 8.6% vs. 3.4% p = 0.032, respectively). Multivariate Cox regression analysis concluded that high serum sST2 independently predicted 1-year CV mortality [hazard ratio (HR) 2.263, 95% confidence interval (CI) 1.124–4.557, p = 0.022)]. Besides, older age, Killip class >1, left anterior descending (LAD) as the culprit artery and lower systolic blood pressure were the other independent risk factors for 1-year CV mortality. Conclusions High sST2 levels are an important predictor of MACE, including CV mortality and heart failure in a 1-year follow-up period in MI patients.

Background Inflammation is one of the most important responses of the body against infection or disease, and it protects tissues from injury; however, it causes redness, swelling, pain, fever and loss of function. The aim of this present study was to evaluate the anti-inflammatory activity of emu oil (Eu) formulated nanofibrous scaffold in HFFF2 fibroblast cells. Materials and methods Eu was formulated successfully in nanofibers through the electrospinning method. Besides, the morphological and structural properties of Eu nanofibres were evaluated using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) was performed to evaluate the HFFF2 fibroblast cells’ viability. Also, real-time polymerase chain reaction (PCR) was used to evaluate the anti-inflammatory signaling pathway in treated HFFF2 cells with Eu nanofiber. Results Our study showed that the Eu nanofiber increased the viability of fibroblast HFFF2 cells (p < 0.05). Also, the expression of interleukin1 ( IL1 ), IL6 and tumor necrosis factor- alpha ( TNF-α ) pro-inflammatory cytokines genes were significantly decreased in treated HFFF2 cells with Eu nanofiber (p < 0.05). Conclusions In conclusion, Eu nanofiber scaffold potentially can reduce the inflammation process through downregulation of IL-1, IL-6 and TNF-α cytokines.

Background Physical inactivity is the major risk factor for type 2 diabetes (T2D). The present study was conducted to investigate the effects of resistance training and endurance training on diabetic-related metabolic parameters in diabetic rats. Materials and methods Twenty-four male Wistar rats were randomly assigned to four groups of six rats each: control group (C), diabetic group (D), resistance training group (RES) and endurance training group (END). T2D was induced intraperitoneally using nicotinamide (120 mg/kg) and streptozotocin (STZ, 65 mg/kg). The training period was 70 days. The irisin, betatrophin, insulin, fasting blood glucose (FBG) and lipid profiles were measured in the serum of all rats. Results Diabetes significantly increased serum levels of FBG (p < 0.001), which were decreased significantly after the administration of training (p < 0.001). Training administration had a significant effect in normalizing serum lipid profiles (p < 0.001) and it was shown to increase the serum levels of irisin, betatrophin (p < 0.001) and insulin (END: p < 0.001 and resistance training: p < 0.05). It was also found that the endurance training was more effective in improving this parameters when compared with resistance training (p < 0.05). In addition, the irisin revealed a significant positive association with betatrophin (END: p < 0.01 and resistance training: p < 0.05) and insulin (END: p < 0.01 and RES: p < 0.05) values in diabetic groups. Conclusion This study demonstrated that endurance training was more effective in diabetic related metabolic derangement compared with resistance training. This effect is probably due to better regulation of irisin, betatrophin and insulin relative to resistance training.

Background Gonadotrophins exert their functions by binding follicle-stimulating hormone receptor (FSHR) or luteinizing hormone and human chorionic gonadotropin receptor (LHCGR) present on endometrium. Within ovaries, FSH induces autophagy and apoptosis of granulosa cells leading to atresia of non-growing follicles, whereas hCG and LH have anti-apoptotic functions. Endometrial cells express functioning gonadotrophin receptors. The objective of this study was to analyze the effect of gonadotrophins on physiology and endometrial cells survival. Materials and methods Collected endometria were incubated for 48 or 72 h with 100 ng/mL of recombinant human FSH (rhFSH), recombinant human LH (rhLH) or highly purified hCG (HPhCG) alone or combined. Controls omitted gonadotrophins. The effect of gonadotrophins on cytochrome P450 family 11 subfamily A polypeptide 1 ( CYP11A1 ), hypoxia inducible factor 1α ( HIF1A ), and cell-death-related genes expression was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Immunohistochemistry for microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) and apoptotic protease activating factor 1 (APAF-1) was performed. Results Gonadotrophins are able to modulate the endometrial cells survival. FSH induced autophagy and apoptosis by increasing the relative expression of MAP1LC3B and FAS receptor . In FSH-treated samples, expression of apoptosis marker APAF-1 was detected and co-localized on autophagic cells. hCG and LH does not modulate the expression of cell-death-related genes while the up-regulation of pro-proliferative epiregulin gene was observed. When combined with FSH, hCG and LH prevent autophagy and apoptosis FSH-induced. Conclusions Different gonadotrophins specifically affect endometrial cells viability differently: FSH promotes autophagy and apoptosis while LH and hCG alone or combined with rhFSH does not.

Background Hyperandrogenemic polycystic ovary syndrome (PCOS) may have occult corticosteroidogenic enzyme abnormalities. The current study compares the activities of 11β-hydroxylase between normoandrogenemic PCOS (NA-PCOS) and hyperandrogenemic PCOS (HA-PCOS) phenotypes. Materials and methods Anthropometric, and biochemical variables were compared between normal cycling women [n = 272] and those with PCOS [n = 453]; either normoandrogenemic [n = 98] or hyperandrogenemic [n = 355]. Univariate and multivariate logistic regression analyses were performed using 11β-hydroxylase enzyme activity as the criterion variable. Results 11β-Hydroxylase enzyme activity tended to be slightly higher in both PCOS subgroups and did not change with ethnicity. Using univariate logistic regression, 11β-hydroxylase activity in controls was associated with dehydroepiandrosterone, insulin, homeostatic model for insulin resistance (HOMA-IR), and high-density lipoprotein cholesterol (HDL-C). In NA-PCOS women the activity of 11β-hydroxylase was associated with estradiol (E 2 ), androstenedione (A4), and androstenedione/dehydroepiandrosterone ratio; in the hyperandrogenemic (HA-PCOS) group, 11β-hydroxylase activity associated with sex-hormone binding globulin (SHBG), 17-hydroxypregnenolone (17-OHPE), fasting glucose, and β-cell activity. After multivariate logistic regression, androstenedione/dehydroepiandrosterone ratio, and β-cell activity were the best predictors of 11β-hydroxylase activity in controls; in NA-PCOS group only androstenedione/dehydroepiandrosterone ratio was confirmed as a significant predictor of 11β-hydroxylase activity, and in HA-PCOS patients, 17-OHPE and β-cell activity demonstrated to be significant predictors. Conclusions 11β-Hydroxylase activity was equal in different ethnicities. The prevalence of decreased 11β-hydroxylase activity was higher in the HA-PCOS phenotype. 17-OHPE, and β-cell function are significant predictors of 11β-hydroxylase activity in HA-PCOS subjects. These findings may help to identify which PCOS patient would have benefit in measuring 11-deoxycortisol (compound S) and 11β-hydroxylase enzyme activity.

Background The aim of this study was to analyze two different polymorphisms, Ser680Asn and -29 (G>A) promoter polymorphism, of the follicle-stimulating hormone receptor ( FSHR ) gene, individually but also in combination, in a sample of Greek women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Materials and methods One hundred and forty-one women undergoing IVF or ICSI and 94 controls were genotyped by real-time polymerase chain reaction (RT-PCR) for the two FSHR polymorphisms. The association of the alleles with the clinical, biochemical and other parameters concerning the controlled ovarian stimulation (COS) protocol and outcome was investigated, as well as the pregnancy rate. Results The study of each polymorphism individually revealed a positive correlation of the SerSer genotype (Ser680Asn polymorphism) with higher luteinizing hormone (LH) levels on the third day of the menstrual cycle. On the other hand, the A allele for the -29 (G>A) promoter polymorphism correlated with the increased number and quality of cumulus-oocyte complexes (COCs). No differences were detected when the different genotypes of the two polymorphisms were combined – the population study was grouped according to the number of polymorphic alleles they carried (0–4 alleles). Women who presented all polymorphic alleles, AsnAsn/AA, exhibited the lowest LH levels (2.62 ± 0.68 mIU/L), but were rarely detected (n = 2, 1.4% of the studied population). Conclusions The data from this study reflect that the investigation of the combination of polymorphisms, such as FSHR -29 and Ser680Asn, could offer a valuable tool in order to evaluate and anticipate the outcome of the ovulation induction protocols, especially in the group of patients with failed attempts.

Background Thyroid cancer (TC) is known to be the most common endocrine malignancy with an incidence rate which has increased by 2.3-fold over the past 30 years. Approximately, 30% of the thyroid fine-needle aspiration biopsy (FNAB) outcomes are indecisive. Moreover, researchers recognized multiple differentially expressed microRNAs (miRNAs) as candidate diagnostic markers for thyroid nodules. The purpose of this study was to identify thyroid tumor-associated miRNAs in FNAB with the capacity to be developed as unique biomarkers. Materials and methods According to the study design, a quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) was applied to evaluate the expression levels of nine miRNAs ( Let7, miR-34a, miR-146b, miR-221, miR-151, miR-155, miR-181b, miR-222 and miR-375 ) among 224 FNA samples as the training set. Results The findings of this study revealed that miR-181b and miR-146b are the best predictors to diagnose benign thyroid FNA samples from malignant samples. However, the remaining miRNAs were co-expressed and had no significant effect on the predictor model. On the other hand, sensitivity and specificity of miR-181b and miR-146b were reported at 83.0%–83.0% and 83.0%–66.0%, respectively. Conclusions According to the results of this study, miR-146b and miR-181b might be considered as adjunct markers contributing to thyroid FNAB in tumor types. In addition, miR-146b and miR-181b were recognized as biomarkers for discriminating benign thyroid nodules from malignant ones. It is suggested that further prospective clinical trials be conducted to evaluate the accuracy of such findings in a larger cohort and determine the clinical uses.

Background Growth hormone(GH) and epidermal growth factor (EGF) stimulate cell growth and differentiation, and crosstalking between their signaling pathways is important for normal cellular development. Growth hormone transduction defect (GHTD) is characterized by excessive GH receptor (GHR) degradation, due to over-expression of the E3 ubiquitin ligase, cytokine inducible SH2-containing protein (CIS). GH induction of GHTD fibroblasts after silencing of messenger RNA (mRNA) CIS (siCIS) or with higher doses of GH restores normal GH signaling. β-Transducing-repeat-containing protein (β-TrCP), another E3 ubiquitin ligase, also plays a role in GHR endocytosis. We studied the role of β-TrCP in the regulation of the GH/GHR and EGF/EGF receptor (EGFR) pathways in normal and GHTD fibroblasts. Materials and methods Fibroblast cultures were developed from gingival biopsies of a GHTD (P) and a control child (C). Protein expression and cellular localization of β-TrCP were studied by Western immunoblotting and immunofluorescence, respectively, after: (1) GH 200 μg/L human GH (hGH) induction, either with or without silence CIS (siCIS), and (2) inductions with 200 μg/L GH or 1000 μg/L GH or 50 ng/mL EGF. Results After induction with: (1) GH200/siCIS, the protein expression and cytoplasmic-membrane localization of β-TrCP were increased in the patient, (2) GH200 in the control and GH1000 in the patient, the protein and cytoplasmic-membrane localization of β-TrCP were increased and (3) EGF, the protein expression and cytoplasmic-membrane localization of β-TrCP were increased in both the control and the patient. Conclusions (1) β-TrCP appears to be part of the negative regulatory mechanism of the GH/GHR and EGF/EGFR pathways. (2) There appears to be a negative correlation between β-TrCP and CIS. (3) In the control and GHTD patient, β-TrCP increases when CIS is suppressed, possibly as a compensatory inhibitor of the GH/GHR pathway.

Background There is little data regarding the ability of high-intensity interval training (HIIT) to increase of glycolytic capacity and intramuscular metabolic adaptations. The goal of this study was to evaluate the effects of HIIT (8 weeks, 5 times/week) with short (HIIT 1 min : 16 × 1 min work and active recovery at 80–95% and 50–60% VO 2 max, respectively) and long (HIIT 4 min : 4 × 4 min work and active recovery at 80–95% and 50–60% VO 2 max, respectively) duration intervals and 4 weeks detraining on the levels of phosphofructokinase (PFK), glycogen synthase 1 (GYS1), monocarboxylate transporter 4 (MCT4) and lactate dehydrogenase (LDH) activity in the rats’ gastrocnemius muscle. Materials and methods Fifty-four male Wistar rats were assigned into three groups, including HIIT 1 min , HIIT 4 min and control (Ctrl). After 48 h of the last training session and after 4 weeks of detraining, the rats were sacrificed, and the gastrocnemius muscles were isolated. Results The PFK levels in the HIIT 4 min group was significantly higher than in the HIIT 1 min and Ctrl groups, and after the detraining period in the HIIT 4 min DT group significantly decreased compared to the HIIT 4 min group. The LDH activity in the HIIT 4 min and HIIT 1 min groups were significantly higher than the Ctrl group and the increasing trend in the HIIT 4 min group was more than the HIIT 1 min group. There was no significant change in LDH activity after detraining compared to training. No significant changes were observed in the level of GYS1 and MCT4 after HIIT. Conclusions Eight weeks of HIIT with long duration intervals induced more improvements in intramuscular glycolytic capacity than a short duration. After short-term detraining, some of these adaptations have remained.

Background Progranulin (PGRN) is implicated in obesity and insulin resistance (IR). The aim of this study was to evaluate the effects of 8 weeks of circuit resistance training (CRT) on plasma PGRN, IR and body composition in obese men. Materials and methods Twenty-eight healthy obese men [age: 36 ± 7.7 years, body weight (BW): 96.4 ± 15.6 kg, body mass index (BMI): 32.4 ± 4.5 kg/m 2 ] completed the study. Subjects were randomly assigned to two groups of control and training. Subjects in the training group underwent training for 8 weeks, 3 times a week. Blood samples and anthropometric characteristics were taken before the commencement of the exercise protocol and 72 h after the last training session. The homeostatic model assessment of insulin resistance (HOMA-IR) was used to measure IR. Results BW, BF%, BMI, waist-hip ratio (WHR), HOMA-IR and plasma PGRN levels except lean body mass (LBM) were significantly reduced in the training group (p < 0.05). Additionally, except for LBM, subjects in the training group had significantly decreased BW, BF%, BMI, WHR, HOMA-IR and plasma PGRN levels compared to changes in those in the control group (p < 0.05). Significant correlations were found between the changes in plasma PGRN and the changes in insulin, HOMA-IR and BMI (p < 0.05). Conclusions The findings showed that 8 weeks of CRT improved body composition and IR which were accompanied by reduced plasma PGRN levels. This study suggests that CRT has the potential for obese individuals to counteract obesity-associated health impairments.

Background During the past 50 years, motivational studies have evolved from the logical inference of logically required “intervening variables” to explain behavioral change, to electrophysiological and molecular analyses of the mechanisms causing such changes. Aim The purpose of this review article is two-fold: first to describe the logic of sexual motivation in a way that applies to laboratory animals as well as humans, and the second is to address some of the problems of sexual motivation experienced by men. Results When problems of motivational mechanisms are stripped down to their essentials, as performed in the laboratory animal models and are available for reductionistic studies, then the problems can be solved with certainty, as illustrated in the first part of this review. However, with respect to human sexual motivation, the various determinants which include so many behavioral routes and so many brain states come into play, that definite conclusions are harder to come by, as illustrated in the second part of this review. Conclusions This review highlights a number of key questions that merit further investigation. These include (a) What mechanisms do cultural and experiential influences interact with androgenic hormone influences on human sexual motivation? (b) How would epigenetic effects in the human brain related to changes in motivation be investigated? (c) What are the effects of unpredictable traumatic and stressful human experiences on sexual motivation; (d) How such mechanisms are activated upon unpredictable traumatic and stressful insults? (e) What are the outstanding differences between sexual motivational drive and motivations driven by homeostatic systems such as hunger and thirst?

Uterine leiomyosarcoma (LMS) is rare but primary ovarian LMS is even rarer constituting less than 0.1% of all gynecologic disorders. Neither histologic features nor immunohistochemistry could be utilized to distinguish between uterine or ovarian origin. We illustrate a clinical case of metastatic LMS to the ovary in a woman with underlying uterine fibroid presenting with anemia with heavy menses.

Intramyometrial ectopic pregnancy (IMEP) is a rare form of ectopic pregnancy. It is defined as a conceptus implanted within the myometrium and is completely surrounded by myometrium with clear separation from both the uterine cavity and tubes. IMEP possesses not only diagnostic but also therapeutic challenge. The majority of reported cases were managed by hysterectomy. Early management of unruptured IMEP using methotrexate may help to preserve fertility. We, for the first time, report a case of ruptured IMEP managed successfully using suction and curettage followed by Bakri balloon tamponade and avoiding hysterectomy. Post-procedure, the patient received two doses of intramuscular methotrexate 50 mg/m 2 due to plateauing serial beta human chorionic gonadotropin (β-hCG) levels and subsequently achieved undetectable level 10 weeks post-methotrexate. She also had complete resolution of the ectopic intramyometrial mass.