Endocrine regulations最新文献

Objective. The aim of the current study was to investigate the expression of genes encoded homeobox proteins such as MEIS3 (Meis homeobox 3), SPAG4 (sperm associated antigen 4), LHX1 (LIM homeobox 1), LHX2, and LHX6 in U87 glioma cells in response to glutamine deprivation in control glioma cells and cells with knockdown of ERN1 (endoplasmic reticulum to nucleus signaling 1), the major pathway of the endoplasmic reticulum stress signaling, for evaluation of a possible dependence on the expression of these important regulatory genes from glutamine supply and ERN1 signaling. Methods. The expression level of MEIS3, SPAG4, LHX, LHX2, and LHX6 genes was studied by real-time quantitative polymerase chain reaction in control U87 glioma cells (transfected by vector) and cells with ERN1 knockdown after exposure to glutamine deprivation. Results. It was shown that the expression level of MEIS3 and LHX1 genes was up-regulated in control glioma cells treated by glutamine deprivation. At the same time, the expression level of three other genes (LHX2, LHX6, and SPAG4) was down-regulated. Furthermore, ERN1 knockdown significantly modified the effect of glutamine deprivation on LHX1 gene expression in glioma cells, but did not change significantly the sensitivity of all other genes expression to this experimental condition. Conclusion. The results of this investigation demonstrate that the exposure of U87 glioma cells under glutamine deprivation significantly affected the expression of all genes studied encoding the homeobox proteins and that this effect of glutamine deprivation was independent of the endoplasmic reticulum stress signaling mediated by ERN1, except LHX1 gene.

Objective. The present study sought to verify the effects of an exercise training on the memory along with the morphological assessment of the adrenal gland tissue in the rats with experimental autoimmune encephalomyelitis (EAE). Methods. Female Lewis rats were randomly divided into three groups: EAE group, EAE group with exercise (EAE+Ex), and control group (CO). Each group contained 10 rats. To evaluate the memory, all rats were subjected to the Morris water maze learning test for four consecutive days and one day for a prop test. EAE was induced by guinea pig spinal cord homogenate emulsified in incomplete Freund's adjuvant and heat-mycobacterium. The exercise training on a motorized treadmill was initiated 3 weeks before EAE induction and disconnected 2 weeks post-induction. Results. We found that exercise training for five weeks produced an improved swimming velocity related to memory improvement in EAE+Ex group in comparison with EAE group, but not an incurable adrenal gland tissue after EAE induction. Conclusions. The experimental design selected for this study appears to be an effective treatment for memory in rats with experimental autoimmune encephalomyelitis.

Objectives. Given the high prevalence of subclinical hypothyroidism (SCH), defined as high thyroid stimulating hormone (TSH) and normal free thyroxine (FT4), and uncertainty on treatment, one of the major challenges in clinical practice is whether to initiate the treatment for SCH or to keep the patients under surveillance. There is no published study that has identified predictors of short-term changes in thyroid status amongst patients with mild elevation of TSH (4.5-10 mIU/L). Subjects and Results. A cohort study was conducted on patients with SCH detected through a general population screening program, who were followed for six months. This project identified factors predicting progression to hypothyroid status, persistent SCH and transient cases. A total of 656 participants joined the study (431 controls and 225 were patients with SCH). A part of participants (12.2%) developed biochemical hypothyroidism during the follow-up, while 73.8% of the subjects became euthyroid and the remained ones (13.4%) stayed in the SCH status. The incidence of overt hypothyroidism for participants with TSH above 6.9 mIU/L was 36.7%, with incidence of 42.3% for females. Anti-thyroid peroxidase antibodies (TPO) positivity is an important predictor of development of hypothyroidism; however, it could be also positive due to transient thyroiditis. Conclusions. It can be concluded that females with TSH above 6.9 mIU/L, particularly those with free triiodothyronine (FT3) and FT4 in the lower half of the reference range, are more likely to develop biochemical hypothyroidism. Therefore, it is recommended to give them a trial of levothyroxine replacement. It is also recommended to repeat TSH after six months for male subjects and participants with baseline TSH equal or less than 6.9 mIU/L.

Objectives. The balance between DNA methylation and demethylation is crucial for the brain development. Therefore, alterations in the expression of enzymes controlling DNA methylation patterns may contribute to the etiology of neurodevelopmental disorders, including autism. SH3 and multiple ankyrin repeat domains 3 (Shank3)-deficient mice are commonly used as a well-characterized transgenic model to investigate the molecular mechanisms of autistic symptoms. DNA methyltransferases (DNMTs), which modulate several cellular processes in neurodevelopment, are implicated in the pathophysiology of autism. In this study, we aimed to describe the gene expression changes of major Dnmts in the brain of Shank3-deficient mice during early development. Methods and Results. The Dnmts gene expression was analyzed by qPCR in 5-day-old homo-zygous Shank3-deficient mice. We found significantly lower Dnmt1 and Dnmt3b gene expression levels in the frontal cortex. However, no such changes were observed in the hippocampus. However, significant increase was observed in the expression of Dnmt3a and Dnmt3b genes in the hypothalamus of Shank3-deficient mice. Conclusions. The present data indicate that abnormalities in the Shank3 gene are accompanied by an altered expression of DNA methylation enzymes in the early brain development stages, therefore, specific epigenetic control mechanisms in autism-relevant models should be more extensively investigated.

Objectives. We aim to report the clinical repercussions of a nutritional approach in a patient diagnosed with Niemann Pick disease type C (NPC) using miglustat as pharmacological therapy. Case report. A 33-year-old woman diagnosed with NPC using miglustat was instructed to look for a dietary management at our nutrition service. Patient's symptoms were weight loss and important gastrointestinal alterations. Our nutritional prescription was a high-calorie and high-protein, lactose- and sucrose-free diet, as well as a daily supplementation of L-glutamine, probiotics, omega 3, and coenzyme Q10. After two months, the patient had weight gain and improvement in the intestinal health. Conclusions. We found that nutritional prescription aided in the treatment of NPC and revealed that nutritional care represents an important strategy in the management of rare genetic diseases.

Objective. Brain-derived neurotrophic factor (BDNF) is identified as an important growth factor involved in learning and memory. Patients with Hashimoto's thyroiditis can suffer from cognitive dysfunction, whereas BDNF is directly regulated by thyroid hormones. It seems reasonable to propose that changes in BDNF expression underlie some of the persistent neurological impairments associated with hypothyroidism. Methods. The study involved a total of 153 patients with various forms of thyroid pathology. BDNF levels in the sera of the patients and healthy individuals were quantified using enzyme-linked immunosorbent assay with highly sensitive Human BDNF ELISA Kit. Genotyping of the BDNF (rs6265) gene polymorphism using TaqMan probes and TaqMan Genotyping Master Mix (4371355) on CFX96™Real-Time PCR Detection System. Polymerase chain reaction (PCR) for TaqMan genotyping was carried out according to the kit instructions. Results. Distribution rs6265 variants in the patients depending on the different types of thyroid pathology showed no significant difference in the relative frequency of BDNF polymorphic variants. Presence of hypothyroidism, regardless of its cause (autoimmune or postoperative), there was a decrease in the serum BDNF levels in all genotypes carriers compared with the control group. The analysis of the correlation between BDNF levels and the levels of thyroid-stimulating hormone (TSH), thyroxine (T4), anti-thyroglobulin (anti-Tg), and anti-thyroid peroxidase (anti-TPO) antibodies showed a significant inverse relationship between BDNF and TSH levels (p<0.001), a direct correlation between BDNF and T4 levels in the blood (p<0.001), and a weak direct relationship between anti-Tg and BDNF levels (p=0.0157). Conclusion. The C allele presence is protective and associates with the lowest chances for reduced serum BDNF levels in thyroid pathology patients in the West-Ukrainian population. However, the T-allele increases the risk of low BDNF levels almost 10 times in observed subjects.

Objective. Significantly underdiagnosed, diabetes-associated cardiac autonomic neuropathy (CAN) causes a wide range of cardiac disorders that may cause life-threatening outcomes. This study investigated the effects of alpha-lipoic acid (ALA) on arterial stiffness and insulin resistance (IR) parameters in type 2 diabetes mellitus (T2D) patients and definite CAN. Methods. A total of 36 patients with T2D and a definite stage of CAN were recruited. This investigation was carried out on two separate arms: traditional hypoglycemic therapy (n=18, control) and ALA (n=18) 600 mg in film-coated tablets/q.d. in addition to traditional hypoglycemic therapy. The duration of the study was three months. Results. In subjects with T2D and definite stage of СAN, treatment with ALA resulted in a significant decrease of glucose, immunoreactive insulin concentration, and Homeostasis Model Assessment (HOMA)-IR (HOMA-IR) parameters; pulse wave velocity (PWV), aorta augmentation index (AIxao) during the active period of the day and decrease of PWV, AIxao, and brachial augmentation index during the passive period of the day compared with the results, obtained in the control group. Therefore, the administration of ALA to patients with T2D for three months promotes the improvement of glucose metabolism and arterial stiffness parameters. Conclusions. In patients with T2D and definite stage of СAN treatment with ALA improved HOMA-IR and arterial stiffness parameters. These findings can be of clinical significance for the complex treatment of diabetes-associated CAN.

Objectives. The effectiveness of exogenously triggered serotonin (e.g., dietary supplements, drugs) increase is varied. However, since urinary serotonin concentrations were found to correlate with those in the cerebrospinal fluid, the olfactory system might be an efficient and testable pathway to quickly elevate serotonin levels due to its fast-acting central neurophysiological and peripheral pathways. However, little research has been devoted to investigate this assumption. This paper extends previous findings of parasympathetic activation of a specially designed essential oil inhaler (AromaStick® Balance) by experimentally testing its impact on urine serotonin and saliva cortisol excretion. Method. Two experiments involving healthy individuals were conducted to test the efficacy of essential oil application to the nose by employing different inhalation protocols and control conditions. Results. In the pilot study (n=8), serotonin urine excretion was increased after six inhalations (effect size Cohen's d=0.7). In the second experiment (n=80), inhalations proved superior to both the natural control condition and the pseudo placebo condition after three and six inhalation cycles (0.6Conclusion. Short and deep inhalations of essential oil scents directly delivered to the olfac-tory system appear to result in an enhanced serotonin and a reduced cortisol release in healthy individuals of both sexes.

Objective. Changes in the brain derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR) expression in the prefrontal cortex (PFC) and hippocampus (HIP) are associated with psychiatric diseases and stress response. Chronic mild stress (CMS) may alter BDNF as well as GR levels in both the PFC and the HIP. The aim of the present study was to find out whether chronic treatment with a typical antipsychotic haloperidol (HAL) and an atypical antipsychotic aripiprazole (ARI) may modify the CMS effect on the BDNF and GR expression in the above-mentioned structures. Methods. The rats were exposed to CMS for 3 weeks and from the 7^th day of CMS injected with vehicle (VEH), HAL (1 mg/kg) or ARI (10 mg/kg) for 4 weeks. BDNF and GR mRNA levels were established in the PFC and the HIP by Real Time PCR, whereas, PFC and HIP samples were obtained by punching them from 500 µm thick frozen sections. C-Fos immunoreactivity was analyzed in the PFC and the HIP on 30 µm thick paraformaldehyde fixed sections. Weight gain and corticosterone (CORT) levels were also measured. Results. The CMS and HAL suppressed the BDNF and GR mRNA levels in the PFC. In the HIP, CMS elevated BDNF mRNA levels that were suppressed by HAL and ARI treatments. The CMS decreased the c-Fos immunoreactivity in the PFC in both HAL- and ARI-treated animals. In the HIP, HAL increased the c-Fos immunoreactivity that was again diminished in animals exposed to CMS. Stressed animals gained markedly less weight until the 7^th day of CMS, however, later their weight gain did not differ from the unstressed ones or was even higher in CMS+HAL group. Un-stressed HAL and ARI animals gained less weight than the VEH ones. Neither CMS nor HAL/ARI affected the plasma CORT levels. Conclusion. The present data indicate that HAL and ARI in the doses 1 mg/kg or 10 mg/kg, respectively, does not modify the effect of the CMS preconditioning on the BDNF and GR mRNA levels in the PFC or the HIP. However, HAL seems to modify the CMS effect on the HIP activation.

Objective. Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by chronic hypophosphatemia and osteomalacia. We present case of a patient with a protracted clinical course of TIO. TIO profoundly affected every aspect of his life with subsequent profound physical and psychosocial disabilities. Method. The review of a complex clinical presentation, serial laboratory investigations, and imaging modalities of a patient with TIO caused by a mesenchymal tumor. Results. The patient presented with chronic lower back pain, severe bilateral leg weakness, and multiple pathological fractures due to severe osteoporosis. His investigations revealed hypophosphatemia, low 1,25 dihydroxyvitamin D, phosphaturia and normal serum calcium, and parathyroid hormone. Elevated fibroblast growth factor 23 (FGF23) confirmed the diagnosis of TIO and ⁶⁸Ga-DOTATATE-positron emission tomography/computed tomography (PET/CT) imaging correctly identified a tumor in the left femoral head. His clinical features and biochemical abnormalities promptly recovered after successful surgical resection of the mesenchymal tumor. Conclusion. The present case demonstrated the need to extensively investigate causes of generalized bone pain in patients with hypophosphatemia, as TIO is highly curable. Importantly, ⁶⁸Ga-DOTATATE PET/CT imaging successfully identified the FGF23 producing tumor, which was undetectable by conventional imaging, favoring its early use in suspected TIO presentation. The present report highlights the importance of timely diagnosis of this complex medical condition, aiming to improve general awareness and enable better clinical outcomes for this rare disorder.