Asora Fux

Adiponectin and vascular properties in obese patients: is it a novel biomarker of early atherosclerosis?

Objectives:Adiponectin is an adipocyte-derived collagen-like protein, highly specific to adipose tissue and may represent an important link between obesity and atherosclerosis. The present study was designed to investigate a possible association between serum adiponectin levels and early vascular changes in obese patients as determined by intima media thickness (IMT) and arterial pulse-wave contour analysis.Design:Obese subjects (n=47) were evaluated for arterial structure and function, metabolic parameters and serum adiponectin levels.Measurements:IMT was measured by ultrasound. Arterial elasticity was evaluated using pulse-wave contour analysis. Insulin resistance was assessed by homeostasis model assessment (HOMA-IR).Results:Adiponectin was significantly, inversely associated with mean IMT (r=−0.369, P=0.011) and significantly positively associated with large artery elasticity index (LAEI) (r=0.467, P=0.001) as well as small artery elasticity index (SAEI) (r=0.462, P=0.001). In separate multivariate models, adiponectin remained significantly associated with mean IMT, LAEI and SAEI even after adjustment for cardiovascular confounders. Among metabolic parameters, adiponectin was significantly positively associated with HDL cholesterol and inversely associated with triglycerides. Adiponectin was significantly inversely associated with fasting insulin and HOMA-IR. In addition, a marginally inverse association between adiponectin and ALT was observed.Conclusions:In this study, serum adiponectin levels were significantly associated with indices of subclinical atherosclerosis, such as IMT and arterial compliance in obese patients. This association was independent of traditional cardiovascular risk factors.

Serum leptin level in women with idiopathic intracranial hypertension

Leptin is a protein secreted by adipose cells which influences regulation of energy balance and body weight. Idiopathic intracranial hypertension (IIH) is recognised as a neurological disorder mainly affecting obese females. The aim of this study was to evaluate the association between IIH and serum leptin level in 15 obese patients and compare the results with those for 16 obese and 15 non-obese women. A significantly higher serum leptin level was found in patients with IIH than in controls (p<0.0001), and this did not correlate with body mass index (BMI). Serum leptin levels were significantly associated with BMI in both control groups (p<0.0006). Additional factors must therefore be involved in the phenomenon of serum leptin increase beyond weight gain. The cause can only be hypothesised, but it seems that the origin is central, probably hypothalamic.

Different degrees of fetal oxidative stress in elective and emergent cesarean section.

Background: Several studies have addressed the influence of labor and mode of delivery on oxidative stress. Still it is unclear whether oxidative stress is related to delivery itself or whether it reflects a pre-existing fetal oxidative status. Objective: To investigate whether the degree of fetal oxidative stress is different between distressed fetuses that were delivered by emergent cesarean section and non-distressed fetuses that were delivered by elective cesarean section. Methods: The protocol of this prospective study was approved by the Institutional Review Board Committee. Amniotic fluid and umbilical artery blood were prospectively collected from 21 parturients who were delivered by an emergent cesarean section for non-reassuring fetal heart rate pattern and from 21 parturients who were delivered by an elective cesarean section in a tertiary care center. Oxidative stress was evaluated in amniotic fluid, umbilical cord plasma and erythrocytes by determining malondialdehyde concentration and glutathione peroxidase (GPX) activity. Results: Malondialdehyde concentration was higher in amniotic fluid (mean ± SEM) (2.2 ± 0.7 nmol/l vs. 0.6 ± 0.02 nmol/l, p < 0.05), in umbilical cord plasma (1.2 ± 0.2 nmol/l vs. 0.7 ± 0.3 nmol/l, p < 0.05) and in umbilical cord erythrocytes (159.6 ± 48.6 nmol/g Hb vs. 85.8 ± 5.2 nmol/g Hb, p < 0.05) in women delivering by emergent cesarean compared to those delivering by elective cesarean. GPX activity was enhanced in amniotic fluid (12.4 ± 2.2 U/l vs. 5.1 ± 0.6 U/l, p < 0.05) and GPX activity/hemoglobin ratio was higher in cord blood (22.0 ± 0.8 U/g Hb vs. 18.7 ± 0.9 U/g Hb, p < 0.05) in women delivering by emergent cesarean compared to those delivering by elective cesarean. Conclusion: Distressed fetuses delivered by emergency cesarean exhibited increased malondialdehyde concentrations, an indicative parameter for oxidative damage, and enhanced GPX activity an antioxidant enzyme, in amniotic fluid and umbilical cord blood compared to non-distressed fetuses delivered by elective cesarean section. This is probably an indication of higher fetal oxidative stress.

Low HDL levels and the risk of death, sepsis and malignancy

AbstractBackgroundHigh density lipoprotein (HDL) plays an important role as an anti-atherogenic molecule, but also possesses anti-inflammatory and anti-angiogenic properties. The effect of extremely low levels of HDL on the risk of sepsis and malignancy were therefore examined.MethodsA retrospective analysis of patients hospitalized at the Edith Wolfson Medical center was conducted. Patients were divided into Group 1: 108 patients with serum HDL levels ≤20 mg/dl. Group 2: 96 patients with serum HDL levels ≥65 mg/dl. Medical history and laboratory data was recorded. ResultsThe mean HDL levels in Group 1 were 16.1 ± 33 mg/dl compared to 74.9 ± 12.6 mg/dl in Group 2. Using a multivariate logistic regression analysis, low HDL was inversely associated with death (OR 0.96, 95% 0.93–0.99, P = 0.02), 3.98 fold increase in odds of fever (OR 3.98, 95% CI 1.3–11.8, P = 0.01), and 6.7-fold increase in the risk of cancer (OR 6.68, 95% CI 1.8–24.5, P = 0.004). HDL serum levels were inversely associated with sepsis. For each 1 mg/dl increase in HDL, a relative 11% decrease in odds of sepsis was observed (OR 0.886, 95% CI 0.8–0.976, P = 0.01).ConclusionsExtremely low serum HDL levels (≤20 mg/dl) are associated with an increased risk of death, sepsis and malignancy.

Serum homocysteine, folate, vitamin B12 levels and arterial stiffness in diabetic patients: which of them is really important in atherogenesis?

Hyperhomocystinaemia is associated with macro‐ and microangiopathic diabetic complications. However, the role of homocysteine (Hcy), serum folate, and vitamin B12 level in the development of premature vascular damage in type 2 diabetic patients is not clear. The present study was designed to assess the relationship between total Hcy, folate, and vitamin B12 levels and arterial stiffness, an early marker of generalized atherosclerosis.

Effect of homocysteine-lowering therapy on arterial elasticity and metabolic parameters in metformin-treated diabetic patients.

Metformin may affect the risk of atherothrombotic disease. However, metformin increases levels of homocysteine (Hcy), considered an independent risk factor for atherosclerosis. We evaluate whether homocysteine-lowering has a beneficial effect on arterial elasticity and metabolic parameters in metformin-treated diabetic patients. In double-blind, placebo-controlled study, 60 diabetic patients treated with high dose of metformin were randomly assigned to receive daily oral supplementation with folate (1000 mcg), vitamins B12 (400 mcg) and B6 (10mg) (group 1) or placebo (group 2). Lipid profile, HbA1C, insulin, C-peptide, hs-CRP, vitamin B12, folic acid, homocysteine, endothelin, homeostasis model assessment-insulin resistance (HOMA-IR) were measured. Arterial elasticity was evaluated using pulse wave contour analysis (HDI CR 2000, Eagan, MN). The two groups were similar at baseline in terms of hemodynamic and arterial elasticity parameters. After a 4-month small artery elasticity index (SAEI) was significantly greater in patients who received Hcy-lowering agents than in the placebo group: 4.3+/-2.04 ml/mm Hg x 100 versus 3.2+/-1.1 ml/mm Hg x 100, p=0.01. Post-treatment vitamin B12 and folic acid levels were greater in group 1 versus group 2: 738.1+/-279.9 pg/ml versus 566.1+/-167.4 pg/ml, p=0.007 and 14.9+/-4.8 ng/ml versus 8.3+/-2.9 ng/ml, p<0.0001, respectively. Hcy level decreased significantly in the treatment group from 10.0+/-4.4 to 7.6+/-2.5 micromol/l, p=0.002 and did not change in placebo group (p=0.9). Hcy-lowering therapy improved small arterial elasticity in diabetic patients treated with high dose of metformin. The improvement was associated with a decrease in Hcy as well as an increase in folic acid and vitamin B12. These findings suggest that Hcy-lowering may have beneficial vascular effect in metformin-treated diabetic patients.

The association between the renin–angiotensin–aldosterone system and arterial stiffness in young healthy subjects

Aldosterone might affect arterial stiffening, in both the short‐ and long‐term. We investigated a possible association between excess aldosterone, reflected by an increased aldosterone : renin ratio (ARR) and pulse wave velocity (PWV) in young healthy adults. In a single‐centre study, 60 subjects were evaluated for lipid profile, glucose, hs‐CRP, renin and aldosterone. PWV was performed as a simple non‐invasive recording and computer analysis of the two artery sites pressure waveform using SphygmoCor (version 7·1, AtCor Medical, Sydney, Australia). The ARR was significantly, positively associated with PWV: r = 0·298, P = 0·02. ARR was not associated with anthropometric variables, blood pressure (BP), metabolic and inflammatory parameters. In conclusion, the ARR was significantly associated with PWV and may exhibit direct effects of aldosterone on the vascular wall, which are not related to changes in conventional cardiovascular risk factors.

Reduced Pseudocholinesterase Activity in Patients With HELLP Syndrome

The authors previously reported a case of decreased pseudocholinesterase activity in a patient with HELLP syndrome. It was assumed that the reduced pseudocholinesterase activity in HELLP syndrome is associated with impaired liver function. The present study assesses the prevalence of low pseudocholinesterase in patients with HELLP syndrome. Serum pseudocholinesterase activity was determined with spectrophotometer in 15 patients with HELLP syndrome. Two control groups matched for gestational age were recruited: 15 healthy women with uncomplicated pregnancy and 15 women with severe preeclampsia without HELLP. The prevalence of reduced pseudocholinesterase activity lower than normal limit was 60.0% (9/15) in patients with HELLP syndrome, 33.3% (5/15) in patients with severe preeclampsia, and 6.6% (1/15) in women with normal pregnancy, respectively (P =.009). The pseudocholinesterase activity was found to correlate with serum alanine aminotransferase levels (r = 0.417, P = .006) and with serum aspartate aminotransferase levels (r = 0.462, P = .002). Considering the increased prevalence of reduced pseudocholinesterase activity in patients with HELLP syndrome, the authors suggest that whenever general anesthesia is applied in these patients, the anesthesiologist should be aware that the patient may show slow metabolic degradation of choline-ester drugs.

Effect of atorvastatin on IgA nephropathy in the rat.

BACKGROUND IgA nephropathy (IgAN) is the most common chronic glomerulonephritis in humans and is a major cause of end-stage kidney disease worldwide. There is no agreement on the exact underlying mechanism or therapeutic intervention for this disorder. Mesangial proliferation typifies the renal histopathology in IgAN. Statin drugs, as prenylationinhibitors, have been shown to have an antiproliferative effect on renal mesangial cells and to reduce IgAN-associated glomerulusclerosis and proteinuria. The aim of this study is to examine the effect of atorvastatin on kidney function, proteinuria and kidney histology changes in IgANinduced rats. METHODS IgAN was induced in Wistar-Kyoto rats by bovine γ-globulin (BGG). Four groups of rats were treated in metabolic cages: 1) control; 2) atorvastatin (2 mg/kg body weight/day through nasogastric tube) - treated rats; 3) IgAN-rats; 4) IgAN-rats treated with atorvastatin. Urine volume, urine protein excretion, blood urea and creatinine concentrations in addition to creatinine clearance were examined every 14 days, throughout the duration of the study (56 days). All kidneys from sacrificed rats were examined for histology including glomerular cell nuclei count and immunofluorescence. RESULTS There were no differences in blood creatinine concentrations between the groups. Creatinine clearance was lower on the 42nd day and proteinuria was higher on Days 14, 42 and 56, in rats in Group 3 compared to all others; additionally, histology examination revealed a higher glomerular cell nuclei count in this group. Immunofluorescence was equally positive for IgA in mesangial cells in the kidneys from rats of Groups 2, 3 and 4. CONCLUSIONS Atorvastatin attenuates kidney-function impairment, proteinuria and mesangial cell proliferation in BGG model of IgANinduced rats.

The effect of poly (ADP-ribose) polymerase inhibition on aminoglycoside-induced acute tubular necrosis in rats.

INTRODUCTION Aminoglycosides (AG) cause nephrotoxicity in 10 - 20% of patients. One of the mechanisms is by generating reactive oxygen species (ROS), leading to DNA destruction and activation of poly(ADPribose) polymerase (PARP) causing necrotic tubular cell death. PARP inhibition on gentamicin-induced nephrotoxicity was studied. METHODS 19 female Wistar-Kyoto rats divided into 3 groups: control (3 rats receiving no treatment); gentamicin-treated group (8 rats); and 8 rats treated with gentamicin combined with 3-aminobenzamide (3 AB). Kidney functions, protein, and gentamicin levels as well as urinary trypsin inhibitory activity (TIA) were measured. Tissue microscopic examination and immunohistochemical study for proliferative cell nuclear antigen (PCNA) were determined. The effect of PARP inhibitor on the bactericidal activity of gentamicin was also assessed. RESULTS The following results were statistically significant: urea (mg/dL) 39.9 ± 5.86, 88.3 ± 50.3, and 48.5 ± 12.7 (p = 0.048); serum creatinine (mg/dL): 0.6 ± 0.26, 1.05 ± 0.7, 0.6 ± 0.06 (p = 0.043); proteinuria (mg/24-hours): 7.27 ± 3.65, 41.2 ± 18.1, and 17.6 ± 13.9 (p = 0.050); the number of tubular macronuclei (per 10 mm2): 18.33 ± 16.07, 218 ± 101.8, 41.7 ± 36.2 (p = 0.012); the number of dilated tubes (per 10 mm2): 61.67 ± 12.58, 276.3 ± 112.7, 140.0 ± 90.9 (p = 0.04); and the number of PCNA positive nuclei (per 10 mm2): 223.3 ± 95.69, 3,585 ± 2,215.3, 626.7 ± 236.9 (p = 0.034) in the control, gentamicin, and gentamicin+3AB-treated groups, respectively. The following biochemical and histologic parameters were also examined, however, they showed no statistically significant difference: TIA (p = 0.055), mitoses (p = 0.14), mononuclear infiltrate (p = 0.188), and intratubular cast formation (p = 0.084). No effect on bactericidal activity was observed. CONCLUSION This study illustrates that PARP inhibitor significantly attenuates gentamicin-induced nephrotoxicity in rats with no effect on the bactericidal activity.