Homocysteine augments BK channel activity and decreases exocytosis of secretory granules in rat GH3 cells

© 2016 Federation of European Biochemical SocietiesIn this study, we investigated the effects of L-homocysteine (Hcy) on maxi calcium-activated potassium (BK) channels and on exocytosis of secretory granules in GH3 rat pituitary-derived cells. A major finding of our study indicates that short-term application of Hcy increased the open probability of oxidized BK channels in inside-out recordings. Whole-cell recordings show that extracellular Hcy also augmented BK currents during long-term application. Furthermore, Hcy decreased the exocytosis of secretory granules. This decrease was partially prevented by the BK channel inhibitor paxilline and fully prevented by N-acetylcysteine, a reactive oxygen species scavenger. Taken together, our data show that elevation of cellular Hcy level induces oxidative stress, increases BK channel activity, and decreases exocytosis of secretory granules. These findings may provide insight into some of the developmental impairments and neurotoxicity associated with Hyperhomocysteinemia (HHcy), a disease arising due to abnormally elevated levels of Hcy in the plasma

Hydrogen sulfide induces hyperpolarization and decreases the exocytosis of secretory granules of rat GH3 pituitary tumor cells

© 2015 Elsevier Inc. All rights reserved. The aim of the present study was to evaluate the effects of hydrogen sulfide (H2S) on the membrane potential, action potential discharge and exocytosis of secretory granules in neurosecretory pituitary tumor cells (GH3). The H2S donor - sodium hydrosulfide (NaHS) induced membrane hyperpolarization, followed by truncation of spontaneous electrical activity and decrease of the membrane resistance. The NaHS effect was dose-dependent with an EC50 of 152 μM (equals effective H2S of 16-19 μM). NaHS effects were not altered after inhibition of maxi conductance calcium-activated potassium (BK) channels by tetraethylammonium or paxilline, but were significantly reduced after inhibition or activation of ATP-dependent potassium channels (KATP) by glibenclamide or by diazoxide, respectively. In whole-cell recordings NaHS increased the amplitude of KATP currents, induced by hyperpolarizing pulses and subsequent application of glibenclamide decreased currents to control levels. Using the fluorescent dye FM 1-43 exocytosis of secretory granules was analyzed in basal and stimulated conditions (high K+ external solution). Prior application of NaHS decreased the fluorescence of the cell membrane in both conditions which links with activation of KATP currents (basal secretion) and activation of KATP currents and BK-currents (stimulated exocytosis). We suggest that H2S induces hyperpolarization of GH3 cells by activation of KATP channels which results in a truncation of spontaneous action potentials and a decrease of hormone release

Improving the information system of university management

© 2015, Canadian Center of Science and Education. All rights reserved. University management is currently supported by information system providing storage and data structuring of information required. Managing the development and improvement of the educational process quality requires creation of a monitoring system covering all of its objects and various measurement tools, which monitors the set of all features. The paper presents the components of pedagogical management, considers indicators of pedagogical processes and methods of evaluation, which define the basis for monitoring the educational processes at the University. Also the structure of a software module is shown, that works on the principle of the expert system and identifies problem characteristics of the educational activity. The results of the experimental work show the effectiveness of the presented software, that supports management decision-making of university departments’ leadership and faculty

ЖЕЛЕЗИСТАЯ ГИПЕРПЛАЗИЯ ЭНДОМЕТРИЯ. ДИАГНОСТИКА, КЛИНИКА, ЛЕЧЕНИЕ

The results of examination and treatment of 105 patients with glandular hyperplasia of the endometrium, have done.  The age of women ranged from  24 to 55 years, the average was equal to 42.3 +3.1 years ; reproductive age was 61 patients, 44 menopausal period. The diagnosis of glandular endometrial hyperplasia (ZHE) is set on the basis of ultrasound TVUZI, hysteroscopy, morphological study scraping the uterine mucosa. All patients carried hormone therapy for 6 months: estrogenprogestin, antiestrogen , progestin, progestogens. Efficacy in patients of reproductive age was observed in 43 (70.5  %)  patients, in patients with perimenopausal in 30 ( 68.2 %) coses.In 34,8% patients relapse  glandular hyperplasia of the  endometrium (for  the  period from  1 to 3 years).  Transcervical electrosurgical resection ( ablation) of the  endometrium were  performed. The results  showed the  effectiveness of  endometrial ablation surgery in 90.6% of  patients. Thus,  in the  absence of  therapeutic effect of  hormone therapy, recurrent  uterine  bleeding   and   endometrial  hyperplasia, glandular,  has  hysteroscopic resection surgery (ablation) of the endometrium the high efficacy.Представлены результаты обследования и лечения  105 пациенток с железистой гиперплазией эндометрия. Возраст женщин колебался от 24 до 55 лет, в среднем был равен  42,3+3,1 года;  в репродуктивном возрасте находилась 61 больная, в периоде перименопаузы-44. Диагноз  железистой гиперплазии эндометрия (ЖГЭ) установлен на основании данных  УЗИ, ТВУЗИ, гистероскопии, морфологического исследования соскоба  слизистой оболочки матки.  Всем пациенткам проводилась гормонотерапия в течение  6 месяцев: эстроген-гестагенами, антиэстрогенами, гестагенами, прогестагенами.  Эффективность у больных  репродуктивного возраста отмечена у 43(70,5%) пациенток, у больных  в перименопаузе – у 30(68,2%).У 34,8% пациенток выявлен рецидив ЖГЭ (за период от 1 до 3 лет). Им была выполнена трансцервикальная электрохирургическая резекция (аблация)  эндометрия. Результаты  аблации эндометрия показали эффективность операции у 90,6% больных. Таким образом, при отсутствии лечебного эффекта гормонотерапии, рецидивах маточных  кровотечений и железистой гиперплазии эндометрия высокой  эффективностью обладает гистероскопическая операция-резекция (аблация) эндометрия.

Impact of COVID-19 Lockdown in Eating Disorders: A Multicentre Collaborative International Study

Background. The COVID-19 lockdown has had a significant impact on mental health. Patients with eating disorders (ED) have been particularly vulnerable. Aims. (1) To explore changes in eating-related symptoms and general psychopathology during lockdown in patients with an ED from various European and Asian countries; and (2) to assess differences related to diagnostic ED subtypes, age, and geography. Methods. The sample comprised 829 participants, diagnosed with an ED according to DSM-5 criteria from specialized ED units in Europe and Asia. Participants were assessed using the COVID-19 Isolation Scale (CIES). Results. Patients with binge eating disorder (BED) experienced the highest impact on weight and ED symptoms in comparison with other ED subtypes during lockdown, whereas individuals with other specified feeding and eating disorders (OFSED) had greater deterioration in general psychological functioning than subjects with other ED subtypes. Finally, Asian and younger individuals appeared to be more resilient. Conclusions. The psychopathological changes in ED patients during the COVID-19 lockdown varied by cultural context and individual variation in age and ED diagnosis. Clinical services may need to target preventive measures and adapt therapeutic approaches for the most vulnerable patients

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

High performance magneto-fluorescent nanoparticles assembled from terbium and gadolinium 1,3-diketones

Polyelectrolyte-coated nanoparticles consisting of terbium and gadolinium complexes with calix[4]arene tetra-diketone ligand were first synthesized. The antenna effect of the ligand on Tb(III) green luminescence and the presence of water molecules in the coordination sphere of Gd(III) bring strong luminescent and magnetic performance to the core-shell nanoparticles. The size and the core-shell morphology of the colloids were studied using transmission electron microscopy and dynamic light scattering. The correlation between photophysical and magnetic properties of the nanoparticles and their core composition was highlighted. The core composition was optimized for the longitudinal relaxivity to be greater than that of the commercial magnetic resonance imaging (MRI) contrast agents together with high level of Tb(III)-centered luminescence. The tuning of both magnetic and luminescent output of nanoparticles is obtained via the simple variation of lanthanide chelates concentrations in the initial synthetic solution. The exposure of the pheochromocytoma 12 (PC 12) tumor cells and periphery human blood lymphocytes to nanoparticles results in negligible effect on cell viability, decreased platelet aggregation and bright coloring, indicating the nanoparticles as promising candidates for dual magneto-fluorescent bioimaging

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Of target programmes on women's health and child evaluation welfare

We studied performance indicators target program of the Republic of Bashkortostan “Mother and child” for 2007-2011. Established a reduction of infant and maternal mortality, neonatal morbidity. Social efficiency was expressed in the reduction in the number of child deaths (462 cases in 5 years), a decrease of abortions (60 222 cases for 5 years). Defined the probability of production gross domestic product by reducing infant mortality in the amount of 12 286 313 thousand roubles