97 research outputs found
Endothelial function status in hypogonadal men
Background: Type 2 diabetes mellitus (T2DM) and hypogonadism are mutually aggravating diseases associated with the development and progression of cardiovascular pathology. The status of endothelial function in men with T2DM and hypogonadism hasn’t been studied.Aims: To assess the effect of hypogonadism on endothelial function in men with T2DM.Materials and methods: Patients underwent clinical studies, assessment of carbohydrate and lipid metabolism, the content of sex hormones (total testosterone (T), sex hormones binding globulin, free T, luteinizing hormone) and markers of endothelial function (nitric oxide (NO), endothelial nitric oxide synthase type 3 (eNOS3), endothelin, adhesion molecules ICAM-1, VCAM-1, p- and e-selectins, cadherin), ultrasound examinations of endothelium-dependent vasodilation (EDVD) of the brachial artery (BA) and carotid arteries with an assessment of the thickness of intima-media complex (TIM) were performed.Results: The study included 276 men with T2DM (age 54.0[49;60] years), who were divided into 2 groups: 1–124 patients with hypogonadism; 2–152 eugonadal patients. Reduction of the endothelial vasomotor function was detected in 32.4% of patients in the 2st group and in 55.3% of the 1nd group (χ2=6.1; p=0.01), which was associated with a decrease in EDVD by 29.8 % (p<0.001) and an increase in the time of development of maximal BA vasodilation by 30 seconds in patients with hypogonadism (p<0.001). The TIM of the carotid arteries was 10% more in group 1 compared with group 2 (p=0.03). The level of NO in the 1st group was reduced by 1.6 times (p=0.001), eNOS3–by 1.5 times (p=0.038) compared with the 2nd group. The concentrations of adhesion molecules were higher in group 1 compared to group 2: VCAM-1 by 32.5% (p<0.001), ICAM-1 by 43.5% (p<0.001), p-selectin–by 19.3% (p=0.004), cadherin–6 times (p<0.001).Conclusion: Hypogonadism in men with T2DM is associated with the development of endothelial dysfunction, which manifests in a weakening of the EDVD and a slowdown in its development, as well as disturbances of the secretory activity of endothelium–a decrease in NO synthesis and activation of the adhesion molecules expression, which can be regarded as an universal pathogenetic mechanism of the development of cardiovascular diseases in combination of T deficiency and T2DM
cis-Tetrachloridobis(1H-imidazole-κN 3)platinum(IV)
In the title complex, cis-[PtCl4(C3H4N2)2], the PtIV ion lies on a twofold rotation axis and is coordinated in a slightly distorted octahedral geometry. The dihedral angle between the imidazole rings is 69.9 (2)°. In the crystal, molecules are linked by N—H⋯Cl hydrogen bonds, forming a three-dimensional network
Testosterone deficiency and non-alcoholic fatty liver disease in men with type 2 diabetes mellitus
BACKGROUND: Current studies investigated diseases associated with testosterone (T) deficiency; however, data on the combination of non-alcoholic fatty liver disease (NAFLD) with hypogonadism and diabetes mellitus (DM) in men are extremely limited. AIMS: To evaluate the effects of hypogonadism on the formation and progression of NAFLD in men with type 2 DM. METHODS: The study included 90 men with type 2 DM [age 54 (49–57) years]. Patients underwent clinical examinations, biochemical analysis (alanine aminotransferase (ALT), aspartate aminotransferase, gamma-glutamyl transpeptidase (GGTP), fasting glucose, immunoreactive insulin, HOMA index, HbA1c, lipid profile), immune enzyme analysis (luteinising hormone, total T, sex hormone binding globulin, resistin, adiponectin, leptin) and magnetic resonance imaging with liver fat fraction determination were performed. Patients were divided into two groups: 1–32 eugonadal patients and 2–58 men with newly diagnosed hypogonadism. RESULTS: Increased insulin resistance, hyperinsulinemia, hypertriglyceridemia were observed in men with hypogonadism compared to eugonadal patients. Along with biochemical signs of impaired liver function, such as an increase in liver enzyme concentrations of ALT by 24.5% (p = 0.02), GGTP by 60.5% (p = 0.001), de Rytis coefficient by 60.4% (p = 0.047), of men in the 2nd group, the liver fat fraction also increased, which together indicates NAFLD progression. The proton density of the liver fat fraction according to MRI was 4.12 [2.25–5.30] % in the 1st group and 10.30 [7.78; 14.44] % in the 2nd group (p=0.001). This was accompanied by an increase in fat production of resistin by 2 times and leptin by 12 times (p <0.001) in patients of group 2 compared to 1. CONCLUSIONS: The combination of type 2 DM with hypogonadism in men leads not only to deterioration of carbohydrate and lipid metabolism but also to disturbance of liver function: increased ALT, GGTP concentrations and liver fat. Increased secretion of leptin and resistin in the adipose tissue is assumed to be a pathogenetically associated with the development of carbohydrate and lipid metabolism disorders, NAFLD and T deficiency
Tetrachlorido(2,3-di-2-pyridylpyrazine-κ2 N 1,N 2)platinum(IV)
In the title complex, [PtCl4(C14H10N4)], the PtIV atom is six-coordinated in an octahedral configuration by two N atoms from one 2,3-di-2-pyridylpyrazine ligand and four terminal Cl atoms. Intermolecular C—H⋯Cl and C—H⋯N hydrogen bonds stabilize the crystal structure
New opportunities for the correction of non-alcoholic fatty liver disease in men with type 2 diabetes mellitus and hypogonadism
Background: The common pathogenetic relations of type 2 diabetes mellitus (T2DM), testosterone (T) deficiency and non-alcoholic fatty liver disease (NAFLD) have indicated a new direction in the study of their mutual influence. It was found that NAFLD is more pronounced in men with T2DM and hypogonadism than in eugonadal patients and associated with hyperinsulinemia, insulin resistance, impaired lipid metabolism and adipose tissue dysfunction. However, the effects of testosterone replacement therapy (TRT) on the severity of NAFLD in men with hypogonadism have not been studied.Aims: To study the effect of TRT on the severity of NAFLD in men with T2DM and hypogonadism.MATERIALS AND METHODS: Anthropometric data, biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltranspeptidase (GGTP), glucose, immunoreactive insulin, HOMA index, glycosylated hemoglobin, lipidogram), ELISA analysis (total T, LH, sex hormone binding globulin, resistin, adiponectin, leptin), as well as magnetic resonance imaging with determination of the liver fat fraction were examined.Results: The study included 60 men with T2DM and hypogonadism (mean age 54 [49; 57] years), who were randomized into 2 groups: 1 (n=30) - patients who received 1% transdermal T gel (50 mg/day) in addition to standard hypoglycemictherapy; 2 (n=30) - patients who received standard hypoglycemic therapy. The follow-up period was 6 months. T therapy was associated with a decrease in liver enzyme levels: AST by 31%, ALT by 21%, and GGTP by 15.9% (p<0.05) and the hepatic fat fraction by 1.7 times, which reflect the regress of liver inflammation, and, consequently, a decrease in the severity of NAFLD. Moreover, TRT has improved the function of adipose tissue - reduced the concentration of leptin by 1.4 times and resistin by 1.5 times, which was accompanied by an increase in adiponectin level by 1.3 times (p<0.01). The use of TRT was associated with decrease in the severity of visceral obesity, hyperinsulinemia by 1.5 times, an insulin resistance index HOMA by 2.2 times, fasting glycaemia and HbA1c levels, despite constant hypoglycemic therapy. Statistically significant decrease in the levels of total cholesterol and triglycerides was observed in men receiving TRT. Thus, a decrease in adipose tissue dysfunction and insulin resistance in men receiving TRT can be considered as a pathogenetic mechanism responsible for improving liver function and reducing the severity of NAFLD.Conclusions: TRT in men with T2DM and hypogonadism is accompanied by regress of inflammatory activity in liver and intensity of hepatocytes steatosis, reflected by decrease in liver enzymes levels and liver fat fraction
Heterobimetallic Catalysis: Platinum‐Gold‐Catalyzed Tandem Cyclization/C−X Coupling Reaction of (Hetero)Arylallenes with Nucleophiles
Heterobimetallic catalysis offers new opportunities for reactivity and selectivity but still presents challenges, and only a few metal combinations have been explored so far. Reported here is a Pt‐Au heterobimetallic catalyst system for the synthesis of a family of multi‐heteroaromatic structures through tandem cyclization/C−X coupling reaction. Au‐catalyzed 6‐endo‐cyclization takes place as the first fast step. Pt‐Au clusters are proposed to be responsible for the increased reactivity in the second step, that is, the intermolecular nucleophilic addition which occurs through an outer‐sphere mechanism by hybrid homogeneous‐heterogeneous catalysis
Регионарная анестезия при каротидной эндартерэктомии у пациентов в остром периоде ишемического инсульта (пилотное исследование)
Objective. The aim of this study is to assess the safety of the use of regional anesthesia for performing carotid endarterectomy (CEA) in patients in the acute phase of ischemic stroke.Material and methods. The study included 66 patients in the acute phase of ischemic stroke (atherothrom botic subtype according to the TOAST classification) who underwent carotid endarterectomy. The inclusion criteria for the study were as follows: acute phase of atherothrombotic ischemic stroke (first 28 days), ipsilateral symptomatic “ 50% stenosis of the internal carotid artery, 1–4 points neurological deficit according to the mod ified Rankin Scale (mRS), 1–13 points neurological deficit according to the National Institutes of Health Stroke Scale (NIHSS), size of the cerebral ischemic lesion ™ 4 cm. This singlecenter prospective cohort study compared two anesthetic approaches, regional anesthesia (RA, 46 patients) and general anesthesia (GA, 20 patients). The RA techniques included ultrasoundguided superficial and deep cervical plexus blocks on the side of the surgery.Results. The study found no significant differences in the baseline patient characteristics, surgery techniques and clinical outcomes between the groups. There were no neurological or cardiovascular toxic reactions to the local anesthetics. Conversions from RA to GA were not performed. In the RA group, recurrent ipsilateral ischemic strokes, myocardial infarctions, wound hemorrhagic complications and lethal outcomes did not occur.Conclusion. This pilot study has demonstrated the safety of RA for performing CEA in patients in the acute phase of ischemic stroke. RA provides adequate neuromonitoring and timely intraoperative recognition of «new» ischemic complications. To compare the efficacy of RA and GA for performing CEA in patients with acute ischemic stroke, large randomized controlled trials are needed.Цель исследования. Оценка безопасности регионарной анестезии при выполнении каротидной эндартерэктомии (КЭЭ) у пациентов в остром периоде ишемического инсульта.Материалы и методы. В одноцентровое проспективное когортное исследование включили 66 паци ентов в остром периоде ишемического инсульта, соответствующего атеротромботическому подтипу по классификации TOAST, которым была выполнена КЭЭ. Критериями включения являлись: ишемический инсульт атеротромботического подтипа (первые 28 дней), ипсилатеральный ишемическому инсульту стеноз ВСА 50% и более, неврологический дефицит 1–4 балла по модифицированной шкале Rankin, нев рологический дефицит 1–13 баллов по шкале инсульта NIHSS, размер ишемического очага в головном мозге не более 4 см. Сравнили два анестезиологических подхода — регионарную анестезию (РА) и общую анестезию (ОА). У 46 пациентов применяли РА, у 20 больных — ОА. РА выполняли под ультразвуковой навигацией в объеме блокады поверхностного и глубокого шейных сплетений на стороне операции.Результаты. Статистически значимых различий в исходных характеристиках пациентов, особен ностях хирургических операций и клинических исходах между группами не выявили. Токсических реакций на местный анестетик в виде неврологических или сердечнососудистых реакций не отме тили. Конверсии с РА на ОА не выполняли. На госпитальном этапе повторного ишемического ипси латерального инсульта, инфаркта миокарда, раневых геморрагических осложнений, а также леталь ных исходов в группе РА не произошло.Заключение. В пилотном исследовании продемонстрировали безопасность РА при выполнении КЭЭ у пациентов в остром периоде ишемического инсульта. РА позволяет осуществлять адекватный нейромониторинг и своевременную интраоперационную диагностику «новых» ишемических ослож нений. Для сравнения эффективности РА и ОА при КЭЭ у пациентов в остром периоде ишемического инсульта необходимо проведение крупных рандомизированных исследований
Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry
Background and purpose: Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). Methods: In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3 years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Results: The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0 years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19). Conclusions: Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013
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