Protective effect of bezafibrate on streptozotocin-induced oxidative stress and toxicity in rats

The present study was aimed to find out the protective effect of bezafibrate on lipid peroxidation (LPO), activities of both enzymatic and non-enzymatic antioxidants and histopathological examination of pancreas in streptozotocin (STZ)-induced diabetic rats. Experimental diabetes was induced by a single dose of STZ (60mg/kg, i.p.) injection. The oxidative stress was measured by tissue LPO level, reduced glutathione (GSH) content and by enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in liver and pancreas. Biochemical observations were further substantiated with histological examination of pancreas. The increase in blood glucose, LPO level with reduction in GSH content and decreased enzymatic activities were the salient features observed in diabetic control rats. Administration of bezafibrate (30mg/kg day, p.o.) for 15 days caused a significant reduction in blood glucose and LPO level in STZ treated rats (group III) when compared with diabetic control rats (group II). Furthermore, bezafibrate treated diabetic rats (group III) showed significant increase in the activities of both enzymatic and non-enzymatic antioxidants when compared to diabetic control rats (group II). Degenerative changes of pancreatic beta-cells in STZ treated rats were minimized to near normal morphology by administration of bezafibrate as evident by histopathological examination. The results obtained clearly indicate the role of oxidative stress in the induction of diabetes and suggest a protective effect of bezafibrate in this animal model.     

Nurses' attitudes, beliefs and confidence levels regarding care for those who abuse alcohol: impact of educational intervention

Alcohol abuse is a worldwide public health concern. Nurses, representing the largest body of health care providers, are a potential resource to provide screening and brief intervention for patients with alcohol problems. This study evaluates the effect of an educational intervention on the attitudes, beliefs, and confidence levels of nurses regarding screening and brief intervention for alcohol problems. One hundred eighty-one students at Vanderbilt University School of Nursing participated in a four-hour educational intervention to train providers in brief negotiated intervention (BNI) for screening, early detection and brief treatment of alcohol problems. Participants completed questionnaires before and after this training. Analysis of the data using paired t-test and one-way analysis of variance showed statistically significant positive change in the nurses’ attitudes, beliefs, and confidence levels regarding alcohol abuse and its treatment after the educational intervention. For example, the percentage of nurses who reported always having confidence in assessing patients’ readiness to change their behavior increased from 8.3% to 23.5% after training. In conclusion, the BNI educational intervention can be effective in promoting positive changes among nurses in attitudes, beliefs, and confidence levels regarding alcohol abuse and its treatment.     

Bone healing with electric current: a histological assessment

Skeletal relapse is a major concern after correction of retrognathism with surgical mandibular advancement. It was hypothesized that the stimulation from a direct electric current can accelerate the osseous repair through the enhancement of the maturation of fibrocartilage. Furthermore, this stimulation may enhance the mechanical properties of the facial osteotomy site and reduce the skeletal relapse. The purpose of the present study was to examine the osteotomy site histologically and determine the effect of post‐surgical electrical stimulation on the healing of a facial osteotomy site in a rat model. Three groups of adult male Sprague–Dawley rats, 15 in each group (direct electric current, electric sham, and control), were used to generate data. Electrodes were placed in both the direct electric current and the electric sham groups. A 20‐μA direct current was delivered to the osteotomy site only in the direct electric current group.
Histological slides of the osteotomy site for each animal were prepared and interpreted to characterize the healing process of the osteotomy site for each animal. The results showed no statistically significant difference among the three groups of animals (p>0.005). An examination with histology earlier in the healing process and the utilization of an experimental animal with a larger jaw are suggested for any further investigation that involves electrical stimulation and osseous healing in a facial osteotomy site.     

Real‐time single‐heartbeat fast strain‐encoded imaging of right ventricular regional function: Normal versus chronic pulmonary hypertension

Patients with pulmonary hypertension and suspected right ventricular (RV) dysfunction often have dyspnea at rest, making reliable assessment of RV function using traditional breath‐holding methods difficult to perform. Using single‐heartbeat fast strain encoding (Fast‐SENC) imaging, peak systolic RV circumferential and longitudinal strains were measured in 11 healthy volunteers and 11 pulmonary hypertension patients. Fast‐SENC RV longitudinal strain and circumferential strain measurements were compared to conventional SENC and MR tagging, respectively. Fast‐SENC circumferential and longitudinal RV shortening correlated closely with SENC measurements (r = 0.86, r = 0.90, P < 0.001 for all). Circumferential strain, by conventional tagging, showed moderate correlation with Fast‐SENC in pulmonary hypertension patients only (r = 0.5, P = 0.003). A nonuniform pattern of RV circumferential shortening was depicted in both groups. Peak systolic circumferential strain was significantly reduced at the basal RV in pulmonary hypertension patients (?18.06 ± 3.3 versus ?21.9 ± 1.9, P < 0.01) compared to normal individuals, while peak systolic longitudinal strain was significantly reduced at all levels (P < 0.01 for all). Fast‐SENC is a feasible and reliable technique for rapid quantification of RV regional function in a single‐heartbeat acquisition. Information derived from Fast‐SENC allows characterization of RV regional function in normal individuals and in pulmonary hypertension patients. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Recurrent acute pancreatitis as the first and sole presentation of undiagnosed primary hyperparathyroidism

IntroductionWe highlight the pitfalls in delaying the diagnosis of primary hyperparathyroidism (pHPT) in patients with acute pancreatitis as the sole clinical presentation. Primary hyperparathyroidism is a recognised, but rare, cause of acute pancreatitis. Hypercalcaemia caused by undiagnosed pHPT may be the only causative factor of recurrent acute pancreatitis.Patients and methodsThree patients with multiple admissions for acute pancreatitis were diagnosed having pHPT during the work-up to identify possible causative factors. None of the patients had any other common predisposing factor for acute pancreatitis as revealed by clinical examination, blood tests and imaging. In retrospect, all had abnormally elevated calcium during previous admissions which was not further assessed.ResultsAfter diagnosis of pPTH, patients underwent bilateral neck exploration and parathyroidectomy. Histology confirmed parathyroid adenomas. The blood calcium level returned to normal and the patients remain well and asymptomatic after operation.ConclusionsThe role of pHPT as a causative factor is underestimated when managing patients with acute pancreatitis, and frequently the underlying disease remains undiagnosed for a long time. Proper early diagnosis and management prevent unnecessary morbidity.     

Minimal change glomerulonephritis following a wasp sting.

We report the case of a young white male who developed the nephrotic syndrome after being stung by a wasp. A percutaneous renal biopsy was done revealing minimal change glomerulonephritis. The patient was treated with oral prednisone with resolution of proteinuria. Corticosteroids were gradually tapered, the patient did not experience a relapse, and remains in good health with normal renal function. Herein, we also include a review of the literature on wasp bite associated nephrotic syndrome in patients who underwent a renal biopsy.     

Scanning electron microscopy of Blastocystis hominis cysts

Scanning electron microscopy of Blastocystishominis cysts reveals that some cysts have an outer coat, whereas others are naked. If intact, the outer coat forms a fan-like structure around the cyst and its surface is granular. The fragmented outer coat adheres to other cysts and bacteria, forming irregular clumps. Received: 15 September 1997 / Accepted: 2 December 1997     

Effects of subunit types of the recombinant GABAA receptor on the response to a neurosteroid.

When vertebrate brain poly(A)+ RNA is expressed in Xenopus oocytes the response of the GABA receptors formed is found to be inhibited allosterically by a neurosteroid, pregnenolone sulphate (PS). This negative modulation was reproduced after expressing RNAs encoding bovine GABAA receptor subunits in the combinations alpha i + beta 1, or alpha i + beta 1 + gamma 2 (where i = 1, 2 or 3). The characteristics of this inhibition vary significantly with the type of the alpha subunit (alpha 1, alpha 2, or alpha 3) used. When the bovine gamma 2L alternate form of the gamma 2 subunit was replaced by the human gamma 2S subunit, the behaviour was unchanged: the human gamma 2S subunit used is a newly-cloned form, which encodes a polypeptide with two amino acid differences from the human gamma 2 subunit previously described. The results of co-application of PS and 3 alpha-hydroxy-5 alpha-pregnan-ol-20-one, a neurosteroid which is a positive modulator of the GABAA receptor, indicate that these act at different sites on the receptor. PS also increases the desensitisation of the receptor by GABA. This effect, also, is alpha-subunit-type dependent and occurs by an acceleration of the fast phase of desensitisation.     

Statin therapy alone and in combination with an acyl-CoA:cholesterol O-acyltransferase inhibitor on experimental atherosclerosis

The ability to modify the enzymatic processes involved in promoting atherosclerotic plaque disruption and to serially monitor atherosclerotic evolution could provide novel information in the management of patients with atherosclerosis. We studied the effects of a statin (atorvastatin) and its combination with an acyl-CoA:cholesterol O-acyltransferase (ACAT) inhibitor (avasimibe) on atherosclerotic regression and plaque stability as measured by matrix metalloproteinase 1 and 3 (MMP-1 and MMP-3) levels. Watanabe Heritable Hyperlipidemic (WHHL) rabbits treated with atorvastatin alone experienced an attenuated increase in atherosclerotic burden versus controls as determined by MR imaging. The mean vessel wall area (VWA) prior to drug therapy was 5.57 +/- 0.01 mm2. The VWA increased to 6.71 +/- 0.03 and 7.16 +/- 0.03 mm2, respectively, in atorvastatin-treated and control groups (p < 0.0001 for both). The combination of atorvastatin and avasimibe induced a significant regression of the previously established atherosclerotic lesions, with the VWA decreasing to 4.54 +/- 0.04 mm2 (p = 0.009). Atorvastatin alone induced a nonsignificant reduction in the percent staining of MMP-1 in atherosclerotic lesions, but the combination treatment with avasimibe led to a significant reduction versus controls (p = 0.005). However, a reduction in MMP-3 staining was significant for rabbits treated with both atorvastatin alone (p = 0.007) and in combination with avasimibe (p = 0.04) versus controls. In this animal model, the addition of avasimibe to atorvastatin has beneficial effects on both atherosclerotic plaque regression and stabilization.     

Cell-mediated immune responses in humans after immunization with one or two doses of oral live attenuated typhoid vaccine CVD 909

CVD 909 is a novel live attenuated S. Typhi oral vaccine candidate derived from strain CVD 908-htrA which constitutively expresses Vi. Herein we investigated whether the genetic manipulations involved in modifying CVD 908-htrA altered its ability to induce potent T-cell immune responses (CMI) after a single dose (five subjects) and, in a separate trial, whether a second dose (eight subjects) further enhanced its immunogenicity. In these clinical trials we observed that CVD 909 immunization elicits a wide array of CMI, including cytotoxic T cells (CTL), IFN-gamma, TNF-alpha and IL-10 (but not IL-2, IL-4 or IL-5) production, and proliferation to S. Typhi antigens. However, the administration of a second dose did not result in increases in CMI. These results suggest that the genetic manipulations to constitutively express Vi did not adversely affect the ability of CVD 909 to elicit a wide array of CMI responses. These observations add impetus for the continuing evaluation of CVD 909 as a typhoid vaccine candidate.