Impact of Myocardial Acceleration during Isovolumic Contraction in Evaluating Subclinical Right Ventricular Systolic Dysfunction in Type 2 Diabetes Mellitus Patients

Aim: In diabetes mellitus (DM) patients, left ventricular dysfunction is widely evaluated and established by conventional diagnostic methods, whereas right ventricular (RV) function is not as sufficiently evaluated. The aim of this study is to assess the preclinical effects of DM on RV function by using novel Tissue Doppler Imaging (TDI)‐derived indices. Methods: The study included 96 patients with type II DM [60 with DM only and 36 patients with coexisting DM and hypertension (DMHT)] and 40 healthy controls. Conventional parameters and TDI‐derived systolic velocities of tricuspid annulus [isovolumic myocardial acceleration (IVA), peak myocardial velocity during isovolumic contraction (IVV), peak systolic velocity during ejection period (Sa), RV Tei index] were measured. Results: TDI‐derived RV IVA was significantly lower in both DM and DMHT patients compared to controls indicating subclinical impairment in RV systolic function in the study patients (P = 0,0001). However RV IVA was similar in DM and DMHT subgroup supporting RV systolic impairment in DM was independent from HT. In correlation analysis, RV IVA was significantly correlated with the existence of diabetic nephropathy (r =?0,38; P = 0,003), retinopathy (r =?0,35; P = 0,006), insulin resistance (r =?0,52; P = 0,0001). Conclusions: Diabetes is associated with subclinical RV systolic dysfunction, regardless of coexisting hypertension. Tissue Doppler‐derived IVA; is a novel, non‐invasive parameter which may be used in early detection of RV systolic dysfunction in patients with DM. (Echocardiography 2010;27:1211‐1218)     

Comorbidities Do not Influence Primary Fistula Success in Incident Hemodialysis Patients: A Prospective Study

Background and objectives: Concern about primary fistula failure may contribute to the underuse of arteriovenous fistula. The objective of this study was to investigate the baseline clinical parameters associated with primary fistula success.Design, setting, participants, & measurements: Consecutive incident patients who commenced dialysis during a 28-mo period in a regional renal program were studied. Data on patient-related variables and on surgical approach (e.g., whether the surgeons routinely assess vessel size during the operation) were collected. Primary fistula success was defined as an arteriovenous fistula that was able to afford successful dialysis for 3 h with blood pump speed of ≥300 ml/min for three consecutive sessions.Results: A total of 205 (69%) patients had an AVF attempted as their first vascular access. The overall primary success rate was 64% and was similar for radiocephalic and brachiocephalic fistula. Logistic regression was done separately for patients with the two types of fistula because of the presence of statistical interaction. For radiocephalic fistula, male gender was the only parameter associated with primary fistula success (odds ratio 3.57; P = 0.01). The presence of comorbidity was not significantly associated with primary fistula failure.Conclusions: Despite significant patient comorbidity, there was a high primary fistula success rate among this incident hemodialysis cohort. Given that vessel size may be the ultimate determinant of fistula success, if surgeons assess vessel size perioperatively, then the presence of significant comorbidity might not preclude arteriovenous fistula from being attempted as the initial access.Given the well-documented advantages of arteriovenous fistula (AVF) over arteriovenous graft and central venous catheter (CVC), the current Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines suggest that AVF should be attempted as the initial vascular access in at least 50% of incident patients and that at least 40% of prevalent hemodialysis (HD) patients should undergo dialysis with an AVF (1–5). Despite these recommendations, it is clear that AVF are underused in many centers in North America, especially when compared with European centers (6,7). Recent data suggest that only 32% of prevalent US HD patients undergo dialysis with an AVF (8). In Canada, AVF are used by 53% of prevalent and only 26% of incident HD patients (7).One of the fears that may reduce the use of AVF is the high primary fistula failure rate (i.e., failure of AVF to mature) (9). Identifying risk factors that contribute to primary fistula failure may help clinicians and patients make an informed decision as to for whom to attempt an AVF. Only a few studies have prospectively examined the risk factors associated with primary fistula failure, which has been reported in 20 to 50% of patients (9–12).Most studies that have evaluated factors that are associated with primary fistula failure have typically used a retrospective design. For instance, Miller et al. (10) reported higher primary fistula failure rate in older and female patients with diabetes, although small numbers and a highly selected patient population limit the generalizability of these results. Feldman et al. (13) published data from a larger cohort (348 patients), reporting a primary success rate of 54%. Preexisting cerebrovascular disease, older age, and commencement of dialysis before access creation were noted to be associated with higher primary fistula failure in their study. Ravani et al. (11) noted that cardiovascular disease and late referral to nephrologists were associated with lower primary AVF success in patients from northern Italy.More recently, Lok et al. (14) studied a cohort of 422 HD patients who were undergoing their first AVF placement to identify preoperative clinical characteristics that are predictive of fistula failure to mature and to use this information to develop a prediction rule to estimate the risk for fistula failure to mature. This prediction rule was validated in an external data set from five North American centers. Age, peripheral vascular disease, coronary artery disease, and white race all were associated with fistula failure to mature in their study; however, in this and the previously mentioned studies, it is not clear whether there was any consistent surgical assessment performed perioperatively to guide fistula placement; as such, the results may not be applicable to programs that use pre- or intraoperative surgical assessment to guide fistula placement.Given these uncertainties, we sought to determine the association of various baseline clinical parameters with primary fistula success in a cohort that consisted of all incident dialysis patients between July 1, 1999, and November 1, 2001, in Calgary, Alberta, Canada, the majority of whom had an indirect assessment of vessel diameter intraoperatively to guide the location of fistula placement.     

Induction of apoptosis and inhibition of growth of human hepatoma HepG2 cells by heparin

BACKGROUND/AIMS: Apoptotic and anti-proliferative effects of heparin on a number of cancers have been described. There have been no studies analyzing the effect of heparin on human hepatoma cells. The aim of this study was to investigate the effect of heparin on human hepatoma cell line, HepG2. METHODOLOGY: HepG2 cell line was cultured with different concentrations of heparin. Colony count, viability assay, percentage of the apoptosis and proliferative index were assessed at the end of the 7th day. Trypan blue was used to assess viability. Apoptosis and proliferative indexes were assessed by flow-cytometry. RESULTS: Hepatoma cells were arrested at the G0/G1 phase with heparin incubation and proliferative indexes decreased significantly in 20, 40 and 80 U/mL of heparin concentrations in comparison with the control (36 +/- 1%, 30 +/- 5% and 29 +/- 8% vs. 44 +/- 1%, p < 0.01). Flow cytometry revealed a statistically significant increase in apoptosis in groups incubated with 40 and 80 U/mL of heparin in comparison with the control (39 +/- 26% and 58 +/- 18% vs. 0.83 +/- 1.3%, p < 0.01). Colony counts per well and viable cells per microL decreased significantly in 80 U/mL of heparin. CONCLUSIONS: Heparin leads to a significant anti-proliferative and an apoptotic effect on human hepatoma cells in vitro.     

Protective role of melatonin given either before ischemia or prior to reperfusion on intestinal ischemia-reperfusion damage

Tissue injury resulting from ischemia-reperfusion is of fundamental importance. Experimental evidence suggests that the generation of reactive oxygen species is significantly responsible for this type of injury. In the present study, besides investigating the protective role of melatonin on tissue damage caused by intestinal ischemia-reperfusion, the protective activity of this compound was also analyzed in both pre- and post ischemia melatonin-treated rats. The activities of the main antioxidative enzymes, catalase, superoxide dismutase and glutathione peroxidase in the intestine showed significant (P < 0.05) increases in melatonin-treated animals that were subjected to ischemia/reperfusion compared with those subjected only to ischemia/reperfusion. Also, results clearly indicate that the level of malondialdeyhde, an index of lipid peroxidation, decreased significantly (P < 0.05) when rats subjected to intestinal/reperfusion were given melatonin either before ischemia or before reperfusion.     

The effects of hypothyroidism in rats on serum leptin concentrations and leptin mRNA levels in adipose tissue and relationship with body fat composition

Both thyroid hormones and leptin affect sympathetic nervous system activity, basal metabolic rate, body fat mass, food intake, and thermogenesis, and each one also affects the actions of the other. We examined the alterations in serum leptin concentrations and leptin mRNA expression in hypothyroid rats and investigated the relation between serum leptin and leptin mRNA levels with the total adipose tissue mass and total body weight. Twenty male Wistar rats were divided into 2 groups, euthyroid and hypothyroid. Their body compositions were examined by Dual Energy X-ray Absorptiometry at the beginning and end of the study. Serum leptin concentrations and levels of leptin mRNA in the retroperitoneal white adipose tissue were measured at the end of the study. Serum leptin concentrations did not show any difference between the two groups (1.9 +/- 0.2 ng/ml in the hypo and euthyroid group, P > 0.05), but the fat mass of the hypothyroid rats were lower than the euthyroid rats (21.1 +/- 2.5 g in the euthyroid group and 14.2 +/- 1.9 g in the hypothyroid group, P > 0.05 between groups at the end of the study) although the difference between the groups was statistically not significant. Leptin mRNA level was significantly higher in the hypothyroid group than in the euthyroid group (21.6 +/- 1.6 vs. 15.1 +/- 1.2 ng respectively, P = 0.002) although the dissected retroperitoneal fat weight was significantly lower in the hypothyroid group versus the euthyroid group (1.0 +/- 0.2 vs. 1.8 +/- 0.2 g respectively, P = 0.013). In conclusion, the change of leptin mRNA expression in white adipocytes was thought to be the direct result of hypothyroidism or a compensatory response to metabolic changes caused by hypothyroidism.     

Serum copper and zinc concentrations in patients with chronic hepatitis C

The aim of this study was to measure the alterations in serum trace elements, including zinc and copper in patients with chronic hepatitis C and to compare them with the results of healthy individuals. Seventeen patients with chronic hepatitis C and 17 healthy individuals were included in this study. Serum zinc and cooper concentrations were measured by using atomic absorption spectrophotometer of patients with chronic hepatitis C and the results were statistically compared with those of healthy individuals. Serum zinc concentrations were 105.6+/-22.8 microg/dl in patients with chronic hepatitis C and 94.41+/-19 microg/dl in healthy controls, respectively. Serum copper concentrations were 103.17+/-20.8 microg/dl in patients with chronic hepatitis C and 90.8+/-14.3 microg/dl in healthy subjects, respectively. Serum zinc and copper concentrations were not found statistically different in patients with chronic hepatitis C compared with those of healthy individuals (p>0.05). In conclusion, serum trace element concentrations did not show statistical alterations in patients with chronic hepatitis C compared to healthy subjects.     

Poor coronary collateral circulation is associated with higher concentrations of soluble adhesion molecules in patients with single-vessel disease

OBJECTIVE: As the endothelium and inflammatory cells play a crucial role in the development of collaterals after a sudden or slowly progressing stenosis of coronary arteries, the levels of soluble endothelial adhesion molecules (CAMs) including vascular cell adhesion molecule (VCAM-1) intercellular adhesion molecule-1 (ICAM-1) and E-selectin were compared between patients with poor coronary collaterals and patients with well-developed collaterals. METHODS: In the study, 97 non-diabetic subjects with single-vessel disease were included. Collateral supply to the stenotic coronary artery was determined by angiographic grading system of 0-3 (Rentrop et al. J Am Coll Cardiol 1985; 5:587-592). Serum levels of adhesion molecules were measured by enzyme-linked immunosorbent assay. RESULTS: Patients were divided into two groups according to the collateral degree (group A: 50 patients with grade 0 and 1; group B: 47 patients with grade 2 and 3 collaterals). The groups were well matched with respect to baseline clinical and angiographic characteristics. Levels of soluble VCAM-1 (mean+/-SEM; 875+/-26.6 versus 742.7+/-35.1 ng/ml; P=0.004), ICAM-1 (322.4+/-12.4 versus 269.4+/-13.3 ng/ml; P=0.005), and E-selectin (43.6+/-2.6 versus 33+/-2.4 ng/ml; P=0.004) were found to be significantly higher in group A in comparison with group B. In addition, when patients were divided into four groups according to the collateral degree, patients with grade 0 collaterals had the highest values and those with grade 3 collaterals had the lowest values for all these molecules. CONCLUSIONS: We concluded that poor collateral circulation is associated with increased levels of soluble CAMs in patients with obstructive coronary artery disease. However, further studies are needed to elucidate the exact role of these inflammatory markers in the setting of poor collateral circulation.