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

FEATURES OF CORONARY HEART DISEASE IN PATIENTS WITH 5-YEAR HISTORY OF MYOCARDIAL INFARCTION DEPENDING OF ADHERENCE

Purpose: To study the peculiarities of the course of coronary heart disease (CHD) patients with a 5-year history of myocardial infarction (AMI) depending on the adherence to therapy.Materials and methods: the study involved 168 patients with 5-year history of AMI. 4 (2.4%) patients dropped out of the study by 2010-2011. Depending on adherence to therapy all the patients were divided into 2 groups: group 1 - patients regularly take antiaggregants, beta-blockers, statins and blockers RAAS, within 5 years, group 2 - patients, who have not taken regularly therapy. Conducted analysis of the course of ischemic heart disease after suffering AMI.Results: it was noted that among the patients not devoted to therapy were 15% more deaths, on a 32% increase in the frequency of detection of stable angina, and 20% - AG, the more pronounced the progression of heart failure (CHF).Findings: identified low adherence of patients to treatment (46,3%). In the group of patients, not devoted to therapy, there was a significantly more high percentage of mortality, including in connection with the repeated AMI as well as the increase in the number of patients with hypertension, stable angina pectoris and progression of CHF

A NEW MARKER OF METABOLIC DISORDERS IN MEN WITH TYPE 2 DIABETES

Purpose: to evaluate the effect of the degree of severity of obesity on metabolic profile, the LAP index, leptin levels and C-reactive protein (CRP) in men with type 2 diabetes c.Materials and methods: 120 male patients aged 40-65 years with obesity and Type 2 diabetes (mean age 54.3 ± 5.3 years). To assess the influence of the degree of severity of obesity on metabolic parameters was undertaken a comparative analysis of the data, depending on the body mass index (BMI). The metabolic profile was evaluated in terms of lipid profile, fasting glucose, of HbA1c, insulin resistance index HOMA. The study of leptin and CRP concentrations produced using laboratory kits for ELISA eBioscience (Austria). We used a new indicator for the integrated assessment of metabolic and cardio-vascular risks — LAP index.Results: analysis revealed no significant differences in fasting glucose, HbA1c and total cholesterol (TC) between the groups. In all groups, the study revealed an increase HOMA index from the first to the fourth group, which indicates an increase in the severity of insulin resistance.Summary: the increase in body mass index is a factor that by enhancing insulin resistance and adipokines production, leading to aggravation of metabolic disorders and the rise of cardiovascular risk in men with obesity and type 2 diabetes. LAP index is a more accurate marker of metabolic disorders than conventional carbohydrate and lipid metabolism

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

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

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

Androgen receptor gene CAG-trinucleotide repeat length affects function of endothelium in men with hypogonadism and type 2 diabetes mellitus

Introduction. The influence of the length of the number of CAG repeats in the androgen receptor gene (nCAG AR) on endothelial dysfunction (EnD) is currently understudied.Objective. The study aimed to evaluate the relationship between the nCAG AR and the dynamics of biochemical and ultrasound markers of EnD in men with functional hypogonadism and type 2 diabetes mellitus (T2DM) receiving testosterone replacement therapy (TRT).Materials & methods. This study included 45 hypogonadal men with T2DM, receiving TRT for 1 year. Patients were assessed for carbohydrate and lipid metabolism parameters; total and free T; sex hormone-binding globulin; biochemical markers of EnD (NO, eNOS3, endothelin) and the nCAG AR; brachial artery (BA) vasoreactivity. Patients were divided into 3 groups: group I — 9 men with nCAG AR < 19; group II — 27 men with nCAG AR > 19 – 24; and group III — 9 men with nCAG AR >24.Results. Patients with nCAG AR < 19 exhibited a 2-fold greater and faster increase in BA vasoreactivity on TRT compared to patients with nCAG AR 19-24 and 3-fold greater than men with nCAG AR >24 (p < 0.05). Patients with nCAG AR < 19 also demonstrated the most pronounced rise in NO and eNOS3 on TRT compared to men with nCAG AR > 24. Patients with nCAG AR < 19 experienced the most pronounced decreases in weight, waist circumference, and HbA1c on TRT compared to other patients (p < 0.05).Conclusion. The nCAG AR length significantly affects the response to TRT in men with hypogonadism and T2DM. The most significant improvements are seen in patients with short nCAG AR

TESTOSTERONE AS A TOOL OF METABOLIC CONTROL OF MEN’S HEALTH (REVIEW)

Nowadays late-onset hypogonadism in men is considered as one of the risk factors of cardiovascular diseases as well as obesity and type 2 diabetes. The pathogenetic mechanisms of testosterone metabolic effects on carbohydrate and lipid metabolism, the current data about the role of the imbalance of proinflammatory cytokines - interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), C-reactive protein (CRP) in the pathogenesis of metabolic disorders and late-onset hypogonadism in men considered in this review

BOTULINUM TOXIN TREATMENT OF POSTSTROKE SPASTICITY: POSITION IN THE CONCEPT OF SUCCESSFUL REHABILITATION

The literature review analyzed the modern concept of successful rehabilitation of functional motor impairments after stroke, in particular the need for correction of spasticity as a significant component of the disability of patients. Submitted the epidemiology, occurrence, phenomenology and diagnostics of poststroke spasticity. Reflected the general principles of treatment and selection of individual treatment strategies based on modern methods of evidence-based medicine. Discussed the possibility of using botulinum toxin A in acute stroke in the development of spasticity. There is the reasonable necessity of a system approach to the implementation of Botulinum toxin therapy in routine clinical practice of primary vascular branches the implementation of educational programs

Regional Anesthesia for Carotid Endarterectomy in Patients with Acute Ischemic Stroke (Pilot Study)

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 modified 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 single-center prospective cohort study compared two anesthetic approaches, regional anesthesia (RA, 46 patients) and general anesthesia (GA, 20 patients). The RA techniques included ultrasound-guided 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