Gene transfer of active Akt1 by an infectivity-enhanced adenovirus impacts β-cell survival and proliferation differentially in vitro and in vivo

Type 1 Diabetes is characterized by an absolute insulin deficiency due to the autoimmune destruction of insulin producing β-cells in the pancreatic islets. Akt1/Protein Kinase B is the direct downstream target of PI3 Kinase activation, and has shown potent anti-apoptotic and proliferation-inducing activities. This study was designed to explore whether gene transfer of constitutively active Akt1 (CA-Akt1) would promote β-cell survival and proliferation, thus be protective against experimental diabetes. In the study, a fiber-modified infectivity-enhanced adenoviral vector, Ad5RGDpK7, was used to deliver rat insulin promoter (RIP)-driven CA-Akt1 into β-cells. Our data showed this vector efficiently delivered CA-Akt1 into freshly isolated pancreatic islets, and promoted islet cell survival and β-cell proliferation in vitro. The therapeutic effect of the vector in vivo was assessed using streptozotocin (STZ)-induced diabetes mice. Two means of vector administration were explored: intravenous and intra-bile ductal injections. While direct vector administration into pancreas via bile-ductal injection resulted in local adverse effect, intravenous injection of the vectors offered therapeutic benefits. Further analysis suggests systemic vector administration caused endogenous Akt expression and activation in islets, which may be responsible, at least in part, for the protective effect of the infectivity-enhanced CA-Akt1 gene delivery vector. Taken together, our data suggest CA-Akt1 is effective in promoting β-cell survival and proliferation in vitro, but direct in vivo use is compromised by the efficacy of transgene delivery into β-cells. Nonetheless, the vector evoked the expression and activation of endogenous Akt in the islets, thus offering beneficial bystander effect against STZ-induced diabetes.     

Correlation of Quantitative Assay of HBsAg and HBV DNA Levels During Chronic HBV Treatment

Background and aim Viral load is used for the diagnosis and monitoring the treatment of chronic hepatitis B (CHB). These methods are molecular-based and are expensive. Previous studies suggest that quantitative hepatitis B surface antigen (HBsAg) studied by automated chemiluminescent microparticle immunoassay can be a surrogate marker. In this study, we aimed to investigate whether quantitative HBsAg correlates hepatitis B virus (HBV) DNA levels during CHB treatment. Methods The study included 18 patients (13 male, 5 female, mean age: 33 ± 9 years) with CHB. They were given pegylated interferon ± lamivudine for 52 months and serum samples were obtained in weeks 0, 4, 8, 24, 48, 52, and 76. HBV DNA was measured by TaqMan polymerase chain reaction (PCR; Erasmus MC, University Medical Center, Rotterdam, The Netherlands). Quantitative HBsAg was studied by automated chemiluminescent microparticle immunoassay (Architect HBsAg, Abbott, IL). Results HBV DNA levels were measured as follows: 9.66, 7.69, 7.06, 5.93, 5.89, 5.88, and 7.27 logarithmic genome equivalent/ml, respectively. The corresponding HBsAg quantitation results were 42,888, 31,176, 37,882, 27,277, 28,279, 29,471, and 31,535 IU/ml, respectively. They showed a significant correlation (canonical correlation = 0.85). Conclusions HBsAg studied by automated chemiluminescent microparticle immunoassay correlates with HBV DNA and can be a surrogate marker during the monitoring of the efficacy of HBV treatment.     

Ultrasonographic Evaluation of Lower Extremity Entheseal Sites in Diabetic Patients Using Glasgow Ultrasound Enthesitis Scoring System Score

Objective

The prevalence of musculoskeletal complications in diabetes mellitus (DM) increases with the duration of disease and with poor glycemic control. Our aim was to evaluate lower extremity musculoskeletal complications in patients with DM using the Glasgow Ultrasound Enthesitis Scoring System, and to reveal the relationship between clinical and sonographic findings.

Evaluation of the chemopreventive effects of Ankaferd Bloodstopper in 7,12-dimethylbenz[a]anthracene-induced oral epithelial dysplasia

Clinical Oral Investigations - Ankaferd BloodStopper® (ABS) is an herbal extract which has been used historically as a hemostatic agent in traditional Turkish medicine. ABS comprises of...     

Evaluation of 3 Different Retreatment Techniques in Maxillary Molar Teeth by Using Micro–computed Tomography

Introduction

Nonsurgical retreatment procedure involves the complete removal of the previous filling material to allow thorough instrumentation, disinfection, and refilling of root canal system. We aimed to determine the residuals of the root-filling material by using 3 different retreatment techniques with the aid of micro–computed tomography.

Carotid CT-angiography: low versus standard volume contrast media and low kV protocol for 128-slice MDCT

Availability and utilization of computed tomography angiography has been increasing recently. We aimed to assess the effectiveness of low amount of contrast media and low kV value in order to reduce possible side effects of contrast media and to provide optimization of kV value in the evaluation of the carotid artery with multi-detector computed tomography angiography. Forty one patients were randomized into two groups. Contrast media was administered at a dose of 1 ml/kg in group A patients and of 0.5 ml/kg in group B patients. kV value of 120 in group A and 100 in group B were chosen. Bolus tracking technique was used. Attenuation values of certain arterial segments were measured, and values over 200 HU were considered as significant. North American Symptomatic Carotid Endartherectomy Trial criteria were utilized in the evaluation of stenosis. Image quality in arterial segments of all cases was found to be sufficient for diagnosis. Arterial attenuation values were found to be higher in group B than group A. When compared separately in all arterial segments, there was no statistically significant difference between the groups. For stenosis, 615 arterial segments were evaluated. Moderate stenosis in eight segments and severe stenosis in three segments were identified in group A. Occlusion in three segments, severe stenosis in three segments, and moderate stenosis in 25 segments were detected in group B. Better image quality can be obtained, and the amount of contrast media can be reduced using low kV technique in carotid artery multi-detector computed tomography angiography examination.