The hepatoprotective effect of aminoguanidine in acute liver injury caused by CCl4 in rats.

In this study, the hepatoprotective effect of aminoguanidine in acute liver damage caused by carbon tetrachloride-CCl4 at a dose of 1 mL/kg, i.p. was investigated in experimental rats. Ten days of preventive treatment with aminoguanidine before exposure to toxic CCl4, at a dose of 150 mg/kg, i.p., led to significant reduction in biochemical markers of acute liver injury-AST(p < 0.001), ALT (p < 0.01), SDH (p < 0.05) and reduction in pro-oxidative markers-H2O2 (p < 0.05), TOS (p < 0.01), TBARS, and LOOH (p < 0.001) in relation to rats treated only CCl4. Treatment with aminoguanidine resulted in a significant reduction in the consumption of antioxidant-GR (p < 0.01), GST, GPx, GSH (p < 0.001), and a decrease in pro-inflammatory-TNF-α (p < 0.01), IL-1ß, IL-6, NO and NGAL (p < 0.001) markers relative to animals exposed to CCl4 alone. Also, aminoguanidine pre-treatment leads to an increase in arginase activity (p < 0.001), and a decrease in citrulline concentration (p < 0.01), as well as polyamine catabolism enzyme activity-putrescin oxidase and spermine oxidase (p < 0.001) in comparison to the CCl4 group. Aminoguanidine led to a striking reduction of the necrotic field (p < 0.001), and a significant increase in the number of apoptotic hepatocytes (p < 0.001), as well as the proapoptotic markers-BAX and Caspase-3 (p < 0.05), compared to CCl4. The hepatoprotective mechanisms in CCl4 induce hepatotoxicity of aminoguanidine are based on the strong antioxidant effects, inhibition of pro-oxidative and pro-inflammatory mediators, as well as induction of damaged hepatocytes into apoptosis.

Unmet Needs in the Management of Type 2 Diabetes Mellitus Patients Starting Insulin Therapy with Basal or Premix Insulin in Routine Clinical Practice in Serbia.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a progressive disease with declining beta cell function, ultimately necessitating insulin therapy. Timely introduction of adequate insulin improves management of diabetes. The aim of this study was to evaluate the unmet needs in the management of T2DM patients recently initiated on insulin therapy in routine clinical practice in Serbia. METHODS: The NEED study was a cross-sectional, observational, multicenter, real-world study conducted in Serbia, involving 26 physicians, endocrinologists, treating individuals with T2DM from 17 secondary health care institutions. Study participants were newly initiated with insulin therapy, being treated with basal or premix insulin ± oral antidiabetics (OAD) for 6-12 months. RESULTS: Four hundred one individuals were included in the study between October 2016 and March 2017. The mean age of study patients was 61.8 ± 9.2 years with mean BMI 30.0 ± 5.0 kg/m2, and duration of diabetes, prior to initiation of insulin therapy, was 8.4 ± 5.9 years. A basal insulin regimen was used by 287 (71.6%) and premix insulin by 114 (28.4%) subjects. The average daily dose (39.8 ± 13.9 units premix vs. 26.3 ± 13.5 units basal), dose/kg (0.47 ± 0.15 units/kg premix vs. 0.31 ± 0.17 units/kg basal), and number of injections per day were higher in the premix compared with basal insulin regimen (p < 0.01). The percentage of T2DM participants with at least one unmet need was high (95.8%). The majority of participants had two or three unmet needs. The most common unmet needs were: HbA1c > 7.0% (79.3%), at least one documented symptomatic hypoglycemia (≤ 3.9 mmol/l) event in the previous 3 months (63.8%), and two or more doses of insulin per day (53.1%). The mean individual HbA1c target was 6.8% in the NEED study cohort, with only 16% of participants reaching it. Most participants [281 (70.1%)] experienced symptomatic hypoglycemia. CONCLUSIONS: The NEED study showed that new insulin users of either basal or premix HM insulin have many unmet needs in the first 6-12 months of treatment. This confirms that in real-life settings novel insulins should be considered in the management of T2DM to reduce the number of symptomatic hypoglycemic events and reach a better HbA1c level. FUNDING: Sanofi, Serbia.

Predicting the biological effects of mobile phone radiation absorbed energy linked to the MRI-obtained structure.

The nature of an electromagnetic field is not the same outside and inside a biological subject. Numerical bioelectromagnetic simulation methods for penetrating electromagnetic fields facilitate the calculation of field components in biological entities. Calculating energy absorbed from known sources, such as mobile phones when placed near the head, is a prerequisite for studying the biological influence of an electromagnetic field. Such research requires approximate anatomical models which are used to calculate the field components and absorbed energy. In order to explore the biological effects in organs and tissues, it is necessary to establish a relationship between an analogous anatomical model and the real structure. We propose a new approach in exploring biological effects through combining two different techniques: 1) numerical electromagnetic simulation, which is used to calculate the field components in a similar anatomical model and 2) Magnetic Resonance Imaging (MRI), which is used to accurately locate sites with increased absorption. By overlapping images obtained by both methods, we can precisely locate the spots with maximum absorption effects. This way, we can detect the site where the most pronounced biological effects are to be expected. This novel approach successfully overcomes the standard limitations of working with analogous anatomical models.

[Serum concentration of soluble adhesive molecules in patients with different forms of coronary artery disease].

BACKGROUND/AIM: Vascular cell adhesion molecules-1 (VCAM-1) and intercellular cell adhesive molecules-1 (ICAM-1) play an important role in developing and progression of coronary atherosderosis. The aim of the paper was to compare concentrations of soluble forms of VCAM-1 and ICAM-1 in patients with different clinical presentations of coronary artery disease (CAD) and patients without CAD. METHODS: Blood samples were taken from 25 patients with acute myocardial infarction (AMI), 25 patients with unstable angina pectoris (UAP), 25 with stable angina pectoris (SAP) and from 15 control patients without CAD, and concentrations of solubile adhesive molecules (VCAM-1, ICAM-1) were determined. RESULTS: Obesity was more prominent in the NAP than in the SAP and the control patients (p < 0.05). There were no significant differences in gender distribution, age, duration of the CAD and body mass index between the groups. Hypertension and diabetes mellitus type 2 were more frequent in the CAD patients than in the controls (p < 0.01). Family history of the CAD was more frequent in the AMI and the UAP group than in the controls (p < 0.05). Serum concentrations of VCAM-1 was similar in the patients with AMI (955.9 +/- 117.8 ng/mL), UAP (952.4 +/- 139.1 ng/mL) and SAP (931 +/- 169.8 ng/mL), and significantly higher in these groups compared with the controls (823.4 +/- 97.6; p < 0.05, p < 0.05 and p < 0.1 respectively). Serum concentration of ICAM-1 was similar in the patients with AMI (699.2 +/- 125.6 ng/mL), UAP (727.6 +/- 171.8 ng/mL) and SAP (697.5 +/- 165.6 ng/mL), and significantly higher in these groups compared with the controls (583.4 +/- 86.6; p < 0.1, p < 0.05 and p < 0.1 respectively). CONCLUSION: Increased concentrations of VCAM-1 and ICAM-1, as markers of inflammation, showed the importance of inflammatory processes in development of atherosclerosis and clinical expresion of CAD. Measurement of soluble ICAM-1 and VCAM-1 concentrations is a usefull indicator of atherosclerosis presence but not severity of CAD clinical presentation.

Effects of physical exercise on inflammatory parameters and risk for repeated acute coronary syndrome in patients with ischemic heart disease.

BACKGROUND/AIM: Inflammation is an important factor in the pathogenesis of atherosclerosis, and several markers of inflammation have been associated with an increased risk of cardiovascular events. Physical activity may lower the risk for coronary heart disease (CHD) by mitigating inflammation. The aim of this study was to investigate the effects of aerobic physical exercise on systemic inflammatory response in patients with stable coronary disease participating in a cardiovascular rehabilitation exercise program. METHODS: Male (n=29) and female (n=23) patients with stable coronary heart disease were enrolled in this study. All the patients were divided into two groups: the group with regular aerobic physical training during cardiovascular rehabilitation program phase II for 3 weeks in our rehabilitation center and 3 weeks after that in their home setting, and sedentary lifestyle group. There were no significant differences in gender distribution among the analysed groups. Student's t-test showed no significant differences in average age, waist circumference (OS) and waist/hip ratio (WHR). RESULTS: The degree of obesity was measured by BMI and there was a significant improvement in BMI in the patients who undertook 6-week physical training compared to the controls (p<0.05). Physical training during 6-week appeared not to have any effects on leukocite count and ICAM-1 levels compared to controls. Exercise induced reduction in plasma CRP levels by 23.72% (p<0.001) and reduction in plasma VCAM-1 levels by 10.23%, (p<0.05). CONCLUSION: Moderate aerobic exercise resulted in a significant reduction of inflammatory state by decreasing CRP and VCAM-1 levels with significant obesity reduction but without visceral obesity reduction. The obtained results indicate that regular physical activity is clinically desirable in primary and secondary prevention of coronary heart disases.