Endocrine regulations最新文献

Objective. Modified levels of pro- (caspase3, Bax) and anti-apoptotic (Bcl-2) regulatory proteins have been detected in certain brain areas of schizophrenic patients indicating a possible dysregulation of apoptosis. In the present study, effects of antipsychotics, haloperidol (HAL) and olanzapine (OLA), on the gene expression of caspase3 (casp3), Bax and Bcl-2 were studied in vitro in mouse hippocampal mHippoE-2 cell line and in vivo in the hippocampus of MK-801 animal schizophrenia model with the aim to provide evidence that antipsychotics may affect the activity of apoptosis-related markers. Methods. mHippoE-2 cells were incubated with MK-801 (20 µM), HAL (10 µM), and OLA (10 µM) alone or combined, MK-801+HAL/OLA, for 24, 48, and 72 h. Male Sprague Dawley rats were injected with saline or MK-801 (0.5 mg/kg) for 6 days and since the 7th day, they were treated with vehicle (VEH), HAL (1 mg/kg) or OLA (2 mg/kg) for the next 7 days. The casp3, Bax and Bcl-2 gene expression in mHippoE-2 cells and rat hippocampus was measured by RT-PCR. Results. In mHippoE-2 cells, casp3 gene expression was increased by MK-801 and OLA treatments alone for 48 h, HAL treatment alone for 24 and 72 h, and co-treatment with MK-801+OLA for 24 and 72 h compared to controls. HAL and OLA suppressed the stimulatory effect of MK-801 on casp3 mRNA levels in cells after 48 h of incubation. Bax mRNA levels in mHippoE-2 cells were decreased after HAL treatment for 24 and 48 h, and also after co-treatment with MK-801+HAL for 72 h. In vivo, MK-801 decreased mRNA levels of both pro-apoptotic markers, casp3 and Bax, in hippocampus of VEH-treated rats and Bax mRNA levels in hippocampus of HAL-treated animals. OLA reversed the inhibitory effect of MK-801 on casp3 expression in the VEH-treated animals. Neither MK-801 nor antipsychotics induced changes in the gene expression of anti-apoptotic marker Bcl-2 in mHippoE-2 cells as well as hippocampus of rats. Conclusions. The results of the present study demonstrate that antipsychotics, HAL and OLA, may affect mRNA levels of pro-apoptotic markers in hippocampal cells in vitro, but not in vivo. The obtained data do not clearly support the assumed potentiating role of MK-801 in inducing apoptosis in specific brain areas and a possible protective role of antipsychotics against induction of apoptosis. The obtained data may contribute to a deeper insight into the neurodevelopmental changes connected with schizophrenia.

Objective. The aim of the present study was to assess insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP3) as markers of insulin resistance in patients with prediabetes and type 2 diabetes mellitus (TDM2). Patients and Methods. This observational clinical study included 76 obese/overweight patients at the age of 45-75 years with T2DM on oral diabetic medication and ultrasonographically or by a computerized tomography (CT) diagnosed liver steatosis. Correlation analysis was performed between plasma levels of insulin, C-peptide, IGF-1, IGFBP3 and HOMA indexes on the one hand and between plasma levels of ALT, AST, triglyceride, cholesterol, and HDL cholesterol and body mass index (BMI) of patients on the other hand. In case of significant partial correlation coefficients, a multiple linear regression model with IGF-1 and IGFBP3 used as outcome variables adjusted for age and sex groups was calculated. According to these regression models, ROC curves were prepared with HOMA index=3 used as a classificator of insulin resistance. Results. Significant correlation was found between C-peptide and IGF-1 (r=0.24, p≤0.05), C-peptide and IGFBP3 (r=0.24, p≤0.05), IGFBP3 and cholesterol (r=0.22, p≤0.05) IGFBP3 and ALT (r=0.19, p≤0.05), HOMA index and triglycerides (r=0.22, p≤0.05), and HOMA index and ALT (r=0.23, p≤0.05). Significant correlation adjusted for age and gender was found between C-peptide and IGF-1 plasma levels (R2=0.20, p<0.05) with AUROC 0.685 (p≤0.01) and C-peptide and IGFBP3 plasma levels (R2=0.28, p<0.05) with AUROC 0.684 (p≤0.01). Significant correlation adjusted for age and gender was found between triglyceride and IGFBP3 plasma levels (R2=0.28, p<0.05) with AUROC 0.616 (p≤0.01). After the distribution of patients according to their IGFBP3 levels, we found a difference between the 1st and the 4th quartiles in terms of triglyceride levels. Conclusion. Our results demonstrate a fundamental role of IGF-1 and IGFBP3 in the patho-physiology of hepatic insulin resistance and suggest them as indirect indicators of the hepatic insulin resistance.

Objective. Nowadays, type 2 diabetes mellitus (T2D) is the most common chronic endocrine disorder affecting an estimated 5-10% of adults worldwide, and this disease also rapidly increased among the population in the Kurdistan region. This research aims to identify DNA methylation change in the TCF7L2 gene as a possible predictive T2D biomarker. Methods. One hundred and thirteen participants were divided into three groups: diabetic (47), prediabetic (36), and control (30). The study was carried out in patients who visited the private clinical sector between August and December 2021 in Koya city (Iraq Kurdistan region) to determine DNA methylation status using a methylation-specific PCR (MSP) with paired primers for each methylated and non-methylated region. In addition, the X2 Kruskal-Wallis statistical and Wilcoxon signed-rank tests were used, p<0.05 was considered significant. Results. The results showed hypermethylation of DNA in the promoter region in diabetic and prediabetic groups compared to the healthy controls. Different factors affected the DNA methylation level, including body max index, alcohol consumption, family history, and physical activity with the positive Coronavirus. Conclusion. The results obtained indicate that DNA methylation changes in the TCF7L2 promoter region may be used as a potential predictive biomarker of the T2D diagnosis. However, the findings obtained in this study should be supported by additional data.

Objective. Idiopathic hypogonadotropic hypogonadism in children is a disease leading to a puberty absence. Some hypothalamic and pituitary defects cause hypogonadotropic hypogonadism. Pituitary magnetic resonance imaging is routinely performed in these patients. In our study, we provide an information about pituitary pathologies associated with an idiopathic hypogonado-tropic hypogonadism in childhood. Methods. Twenty-two patients, who were admitted to the pediatric endocrine outpatient clinic of our hospital because of their undeveloped secondary sex characteristics during adolescence, were included in our study. Age, gender, history, physical examination findings, and laboratory tests were recorded in patients. Pituitary magnetic resonance imaging results were examined. The criteria for the diagnosis of hypogonadism were: absence of puberty or delayed puberty, clinical signs or symptoms of hypogonadism, and presence of low or normal gonadotropin levels. Results. In the present study, 22 patients were diagnosed with hypogonadotropic hypogonadism. The mean age of the patients was 15.90±1.09 years. Basal and stimulated luteinizing hormone and follicular stimulating hormone levels of the patients were found to be low. Prolactin, cortisol, adrenocorticotropic hormone, free thyroxine, and thyroid stimulating hormone levels were within normal limits in all patients. The pituitary magnetic resonance imaging revealed six patients with pituitary adenoma, one with empty sella turcica, and five with pituitary hypoplasia. Conclusions. The present data showed that in the presence of hypogonadotropic hypogonadism, the hypothalamic-pituitary abnormalities are more likely to be present in the children compared to the adult population. Thus, it can be strongly emphasized the importance of the pituitary imaging examination, especially in the idiopathic hypogonadotropic hypogonadism cases.

Objective. Hyperparathyroidism is a prevalent disease with parathyroid adenomas being the most common cause. Surgical excision remains the standard treatment for parathyroid adenoma. Successful preoperative localization of the parathyroid adenoma could facilitate the decision regarding the extent of surgical exploration. The aim of the current study was to assess the correlation between the preoperative values of parathyroid hormone and ionized calcium with the adenoma weight and volume in patient with primary hyperparathyroidism caused by single-gland adenoma. Patients and Methods. We did this retrospective review for all patients who were diagnosed with primary hyperparathyroidism due to a solitary parathyroid adenoma in our general surgery department over 4 years. SPSS software was used to get the correlation coefficient between the peak preoperative levels of calcium and parathyroid hormone with the parathyroid adenoma weight and volume. Results. Ninety-nine patients were included into the study. The average age at surgery was 62.65±12.00 years. The correlation coefficient between the adenoma volume and weight with the preoperative ionized calcium level was weakly positive (r=0.329, p<0.01) and (r=0.281, p=0.019), respectively, while the correlation with the preoperative parathyroid hormone level was stronger (r=0.708, p<0.01) and (r=0.650, p<0.01), respectively. Conclusions. The strong positive relationship between the preoperative parathyroid hormone and calcium levels with the parathyroid adenoma size and weight can help the surgeon to predict the volume of the involved gland and avoid an unnecessary dissection.

Objective. Homeobox genes play a fundamental role in the embryogenesis, but some of them have been linked to oncogenesis. The present study is aimed to investigate the impact of glucose and glutamine deprivations on the expression of homeobox genes such as PAX6 (paired box 6), PBX3 (PBX homeobox 3), PBXIP1 (PBX homeobox interacting protein 1), MEIS1 (MEIS homeobox 1), and MEIS2 in ERN1 knockdown U87 glioma cells with the intent to reveal the role of ERN1 (endoplasmic reticulum to nucleus signaling 1) signaling pathway on the endoplasmic reticulum stress dependent regulation of homeobox genes. Methods. The control (transfected by empty vector) and ERN1 knockdown (transfected by dominant-negative ERN1) U87 glioma cells were exposed to glucose and glutamine deprivations for 24 h. The cells RNA was extracted and reverse transcribed. The expression level of PAX6, PBX3, PBXIP1, MEIS1, and MEIS2 genes was evaluated by a real-time quantitative polymerase chain reaction analysis and normalized to ACTB. Results. It was found that glucose deprivation down-regulated the expression level of PAX6, MEIS1, and MEIS2 genes in control glioma cells, but did not significantly alter PBX3 and PBXIP1 genes expression. At the same time, ERN1 knockdown significantly modified the sensitivity of all studied genes to glucose deprivation. Other changes in gene expression were detected in control glioma cells under the glutamine deprivation. The expression of PBX3 and MEIS2 genes was down- while PAX6 and PBXIP1 genes up-regulated. Furthermore, ERN1 knockdown significantly modified the effect of glutamine deprivation on the majority of studied genes expression in U87 glioma cells. Conclusion. The results of the present study demonstrate that the exposure of U87 glioma cells under glucose and glutamine deprivations affected the expression of the majority of the studied homeobox genes and that the sensitivity of PAX6, PBX3, PBXIP1, MEIS1, and MEIS2 genes expression under these experimental conditions is mediated by ERN1, the major pathway of the endoplasmic reticulum stress signaling.

Objective. Ovarian torsion is a gynecological emergency that occurs mostly during the female reproductive years due to ovarian masses or surgical manipulation. This work aims to explore the probable protective effect of leptin on rat ovaries due to ischemia-reperfusion (IR) injury. Methods. Wistar albino rats were divided into four groups: 1) control group; 2) ovarian IR group (OVIR); 3) leptin group I [OVIR + leptin (10 µg/kg body weight, b.w.)]; and 4) leptin group II (OVIR + leptin (100 µg/kg b.w.)]. Serum levels of estradiol and anti-Mullerian hormone (AMH) were measured. Levels of oxidative stress and inflammatory markers in ovarian tissue were determined along with the expression of sirtuin 1 (Sirt1), nuclear erythroid factor-2 (Nrf2), cyclooxygenase-2 (COX-2), nuclear factor kappa (NF-κB), toll like receptor-4 (TLR4), and caspase-3. Results. Serum estradiol and AMH levels were decreased with increased expression of COX-2, TLR4, caspase-3, and NF-κB and decreased expression of Sirt1and Nrf2 in ovary of the OVIR group, which were improved by exogenous administration of both leptin doses. Conclusion. Leptin administration dose-dependently reduced the severity of OVIR injury via modulation of Sirt-1/Nrf2 and TLR4/NF-kB/caspase-3 signaling pathways. Thus, leptin may be used as an adjuvant measure to prevent ovarian damage and improve the outcomes. However, clinical studies are needed to evaluate these results in humans.

Objective. Adjuvant therapy with sodium-glucose cotransport 2 inhibitors (SGLT2i) in type 1 diabetes (T1D) is associated with an improvement in glycemic control, but increases the risk of diabetic ketoacidosis (DKA). However, real-life studies in individuals with T1D under continuous subcutaneous insulin infusion (CSII) are still scarce. We present the first real-life study performed in patients with T1D exclusively treated with CSII. The aim of the present study was to assess the metabolic impact and safety of SGLT2i in T1D individuals under CSII. Methods. Retrospective study includes 34 T1D adult individuals under CSII, who started SGLT2i until 30th June 2021. Data regarding the glycemic control and acute diabetes complications at the moment of introduction of SGLT2i and after 3, 6, and 12 months of use were collected. Results. Twenty-three individuals were included. Comparing with the moment of SGLT2i introduction after 3, 6, and 12 months of use, there was a statistically significant increase of time in range (TIR) (∆_T3M=12.8%; ∆_T6M=11.5%; ∆_T12M=11.1%), and a decrease in time above range (∆_T3M=13.6%; ∆T6M=11.9%; ∆_T12M=10.5%). There were no significant differences in time below the range. Mean glucose and mean glucose management indicator significantly reduced in the 3 evaluated moments. A significant reduction in median weight was also observed (∆_T6M=2 kg; ∆_T12M=4.5 kg). Two patients (8.7%) developed mild euglycemic DKA during SGLT2i treatment, both were women and had body mass index (BMI) <27 kg/m². One of them had a total daily insulin dose (TDDI) reduction of 26.9% after 3 months of use. Conclusions. The use of SGLT2i, as an adjuvant treatment in T1D individuals under CSII, was associated with a significant increase of TIR without increasing time in hypoglycemia. It also had a weight benefit. Careful use in selected participants is necessary to reduce the occurrence of DKA.

Alkaptonuria (AKU, OMIM, No. 203500) is a rare, slow-progressing, irreversible, multisystemic disease resulting from a deficiency of the homogentisate 1,2-dioxygenase enzyme, which leads to the accumulation of homogentisic acid (HGA) and subsequent deposition as pigment in connective tissues called ochronosis. As a result, severe arthropathy of large joints and spondyloarthropathy with frequent fractures, ligament ruptures, and osteoporosis develops in AKU patients. Since 2020, the first-time treatment with nitisinone has become available in the European Union. Nitisinone significantly reduces HGA production and arrests ochronosis in AKU patients. However, blocking of the tyrosine metabolic pathway by the drug leads to tyrosine plasma and tissue concentrations increase. The nitisinone-induced hypertyrosinemia can lead to the development of corneal keratopathy, and once it develops, the treatment needs to be interrupted. A decrease in overall protein intake reduces the risk of the keratopathy during nitisinone-induced hypertyrosinemia in AKU patients. The low-protein diet is not only poorly tolerated by patients, but over longer periods, leads to a severe muscle loss and weight gain due to increased energy intake from carbohydrates and fats. Therefore, the development of novel nutritional approaches is required to prevent the adverse events due to nitisinone-induced hypertyrosinemia and the negative impact on skeletal muscle metabolism in AKU patients.

Objective. Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases characterized by the presence of ectopic fat in the liver and steatosis, which cannot be explained by alcohol consumption. The association between NAFLD and type 2 diabetes mellitus (T2DM) is well established. As liver fibrosis progresses in a patient with NAFLD, insulin resistance (IR) increases and may worsen diabetes control. The aspartate aminotransferase platelet ratio index (APRI) score is a simple and inexpensive bedside marker that can detect liver fibrosis and cirrhosis. Several studies have shown an association between APRI and NAFLD. However, there is a gap in correlation with IR in patients with diabetes. In this study, we sought to correlate IR and NAFLD in diabetes using the APRI score. Methods. This observational hospital-based cross-sectional study was conducted in the Department of General Medicine, one of the tertiary care hospitals in North India, from February 2019 to July 2020. A total of 70 patients were taken for the study. Patients with T2DM, aged >30 years, who had no history of alcohol use and who had or were newly diagnosed with NAFLD were enrolled in the study. Results. Significant differences in mean HbAc1, AST, serum insulin, APRI score and homeo-static model assessment-2 (HOMA2) IR between NAFLD grade 1, grade 2, and grade 3 groups were found. Pearson correlation between APRI score and HOMA2 IR total values revealed a significant positive correlation between them. Conclusions. The data of the present study indicate that the APRI score can be used to assess the IR degree and provide important information for improving glycemic control in T2DM patients with NAFLD.