Pharmacological dose of {alpha}-tocopherol induces cardiotoxicity in Wistar rats determined by echocardiography and histology

The effect of pharmacological dose of α-tocopherol on heart health was determined in Wistar rats. Animals were randomly assigned to either C (control, n = 11) or E (α-tocopherol, n = 11) group. Animals received corn oil (C) or α-tocopherol dissolved in corn oil (250 mg α-tocopherol/[kg body wt/day]) (E) by gavage for a 7-week period. Rats underwent echocardiogram and were analyzed for cardiomyocyte histology and cardiac α-tocopherol absorption at the end of the study period. As compared to the C group, α-tocopherol-supplemented group showed significantly (p < 0.05) lower body weight (E, 412.8 g vs C, 480.3 g) and total cardiac weight (E, 0.94 g vs C, 1.08 g); cardiomyocyte histological impairment; smaller left ventricle (LV) (LV end-diastolic diameter (E, 7.22 mm vs C, 7.37 mm), lower LV systolic [left ventricle fractional shortening (E, 47.6% vs C, 53.6%) and ejection fraction ratio (E, 85.4 vs C, 89.9)] and diastolic [early peak velocities of diastolic transmitral flow (E, 64.6 cm/sec vs C, 75.1 cm/sec)] function. The α-tocopherol uptake in target tissue was confirmed by determination of α-tocopherol concentration medians in cardiac tissue (E, 109.91 nmol/kg vs C, 52.09 nmol/kg). The current study indicates that pharmacological dose of α-tocopherol supplementation can induce cardiotoxicity in healthy rats.     

Positron Emission Tomography Detection of Distant Metastatic or Synchronous Disease in Patients with Locally Advanced Rectal Cancer Receiving Preoperative Chemoradiation

Background Patients with locally advanced rectal cancer may present with synchronous distant metastases. Choice of optimal treatment—neoadjuvant chemoradiation versus systemic chemotherapy alone—depends on accurate assessment of distant disease. We prospectively evaluated the ability of [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET) to detect distant disease in patients with locally advanced rectal cancer who were otherwise eligible for combined modality therapy (CMT). Methods Ninety-three patients with locally advanced rectal cancer underwent whole-body [¹⁸F]FDG PET scanning 2–3 weeks before starting CMT. Sites other than the rectum, mesorectum, or the area along the inferior mesenteric artery were considered distant and were divided into nine groups: neck, lung, mediastinal lymph node (LN), abdomen, liver, colon, pelvis, peripheral LN, and soft tissue. Two nuclear medicine physicians blinded to clinical information used PET images and a five-point scale (0–4) to determine certainty of disease. A score greater than 3 was considered malignant. Confirmation was based on tissue diagnosis, surgical exploration, and subsequent imaging. Results At a median follow-up of 34 months, the overall accuracy, sensitivity, and specificity of PET in detecting distant disease were 93.7%, 77.8%, and 98.7% respectively. Greatest accuracy was demonstrated in detection of liver (accuracy = 99.9%, sensitivity = 100%, specificity = 98.8%) and lung (accuracy = 99.9%, sensitivity = 80%, specificity = 100%) disease; PET detected 11/12 confirmed malignant sites in liver and lung. A total of 10 patients were confirmed to have M1 stage disease. All 10 were correctly staged by pre-CMT PET; abdominopelvic computed tomography (CT) scans accurately detected nine of them. Conclusion Baseline PET in patients with locally advanced rectal cancer reliably detects metastatic disease in liver and lung. PET may play a significant role in defining extent of distant disease in selected cases, thus impacting the choice of neoadjuvant therapy. An erratum to this article can be found at     

New anti-angiogenic compound based on chemically modified heparin

Graefe's Archive for Clinical and Experimental Ophthalmology - The purpose of this study was to measure the anti-angiogenic effect of N-desulfated Re–N-acetylated, a chemically modified...     

Effects of the treatment with glibenclamide, an ATP-sensitive potassium channel blocker, on intestinal ischemia and reperfusion injury

Intestinal ischemia and reperfusion injury is dependent on the recruitment and activation of neutrophils. Glibenclamide, an ATP-sensitive potassium channel (K(ATP)) blocker, has been shown to suppress neutrophil migration and chemotaxis during acute inflammatory responses by a mechanism dependent on its K(ATP) channel blocking activity. In the present study, we evaluated whether the treatment with glibenclamide prevented local, remote and systemic injury following reperfusion of the ischemic superior mesenteric artery in rats. The artery was made ischemic for a period of 30 or 120 min followed by 30 (mild I/R) or 120 (severe I/R) min of reperfusion, respectively. Glibenclamide (0.8 to 20 mg/kg) or vehicle was administered subcutaneously 40 min prior to the reperfusion. Glibenclamide dose-dependently inhibited the reperfusion-associated increase in vascular permeability and neutrophil accumulation in mild I/R. In the severe injury model, glibenclamide inhibited inflammatory parameters, as assessed by Evans blue extravasation, neutrophil influx and haemoglobin content, and the increase in TNF-alpha (tumor necrose factor-alpha) and IL (interleukin)-6 levels in the intestine and lung. The drug did not affect the increase in IL-1beta and IL-10 levels. TEA, a nonselective potassium channel blocker, also inhibited reperfusion injury in both intestine and lungs of animals submitted to mild and severe I/R. Our experiments suggest a role for K(ATP) channels in mediating neutrophil influx and consequent reperfusion-associated injury in rats. The lack of effect of these drugs on the reperfusion-associated hypotension and lethality may limit their usefulness after severe reperfusion injury.     

Single-session endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography for evaluation of pancreaticobiliary disorders

Background  

Endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) often are required in the evaluation and treatment of patients with pancreaticobiliary disorders. Few reports of single-session EUS-ERCP have raised questions regarding its safety and accuracy or about which procedure should be performed first.     

Mutagenicity and Genotoxicity in Gill Erythrocyte Cells of Poecilia reticulata Exposed to a Glyphosate Formulation

Poecilia reticulata were exposed to herbicide Roundup Transorb^® for micronucleus test, nuclear abnormalities and comet assay. The exposure-concentrations were based on CL_50–96 h following 0, 1.41, 2.83, 4.24 and 5.65 μL L^?1 for 24 h. Micronucleus and comets were significantly increased in the gill erythrocyte cells after herbicide exposure compared with the non-exposed group. Results showed a gradual increase in the number of damaged cells, indicating a concentration-dependent effect and that this herbicide was mutagenic and genotoxic to P. reticulata and this effect could be attributed to a combination of compounds contained in the formulation with the active ingredient glyphosate.