The antihyperglycemic effect of curcumin in high fat diet fed rats. Role of TNF-α and free fatty acids

This study was conducted to investigate the effect of curcumin, obtained from Curcuma longa, in comparison with rosiglitazone on the progression of insulin resistance and type 2 diabetes mellitus (T2DM) and the mechanisms underlying this effect. Insulin resistance and T2DM was induced in male Sprague Dawley rats by high fat diet (HFD) feeding for 60 and for 75 days representing two regimens of the study, protection and treatment. Prophylactic oral administration of curcumin (80 mg/kg), rosiglitazone (1 mg/kg), their combination, or vehicle (in control groups) was started along with HFD feeding in different groups. Treatment is achieved by oral administration of the previously mentioned agents in the last 15 days of HFD feeding after induction of insulin resistance and T2DM in rats.Curcumin showed an anti-hyperglycemic effect and improved insulin sensitivity, and this action may be attributed at least in part to its anti-inflammatory properties as evident by attenuating TNF-α levels in HFD fed rats, and its anti-lipolytic effect as evident by attenuating plasma free fatty acids. The curcumin effects are comparable to those of rosiglitazone, which indicate that they may act similarly. Finally we can say that, curcumin could be a beneficial adjuvant therapy in patients with T2DM.     

The impact of nanoparticle ligand density on dendritic-cell targeted vaccines

Dendritic-cell (DC) targeted antigen delivery systems hold promise for enhancing vaccine efficacy and delivery of therapeutics. However, it is not known how the number and density of targeting ligands on such systems may affect DC function and subsequent T cell response. We modified the surface of biodegradable nanoparticles loaded with antigen with different densities of the mAb to the DC lectin DEC-205 receptor and assessed changes in the cytokine response of DCs and T cells. DEC-205 targeted nanoparticles unexpectedly induced a differential cytokine response that depended on the density of ligands on the surface. Strikingly, nanoparticle surface density of DEC-205 mAb increased the amount of anti-inflammatory, IL-10, produced by DCs and T cells. Boosting mice with DEC-205 targeted OVA-nanoparticles after immunization with an antigen in CFA induced a similar pattern of IL-10 response. The correlation between DC production of IL-10 as a function of the density of anti-DEC-205 is shown to be due to cross-linking of the DEC-205 receptor. Cross-linking also increased DC expression of the scavenger receptor CD36, and blockade of CD36 largely abrogated the IL-10 response. Our studies highlight the importance of target ligand density in the design of vaccine delivery systems.     

Intracardiac echo-guided image integration: optimizing strategies for registration

Introduction: Image integration is being used in ablation procedures. However, the success of this approach is dependent on the accuracy of the image integration process. This study aims to evaluate the in vivo accuracy and reliability of the integrated image.
Methods and Results: One hundred twenty-four patients undergoing radiofrequency (RF) ablation catheter ablation for atrial fibrillation (AF) were recruited for this study from three different centers. Cardiac computerized tomography (CT) was performed in all patients and a 3D image of the left atrium (LA) and pulmonary veins (PVs) was extracted for registration after segmentation using a software program (CartoMerge, Biosense Webster, Inc.). Different landmarks were selected for registration and compared. Surface registration was then done and the impact on integration and the landmarks was evaluated.
The best landmark registration was achieved when the posterior points on the pulmonary veins were selected (5.6 ± 3.2). Landmarks taken on the anterior wall, left atrial appendage (LAA) or the coronary sinus (CS) resulted in a larger registration error (9.1 ± 2.5). The mean error for surface registration was 2.17 ± 1.65. However, surface registration resulted in shifting of the initially registered landmark points leading to a larger error (from 5.6 ± 3.2 to 9.2 ± 2.1; 95% CI 4.2–3.05).
Conclusion: Posterior wall landmarks at the PV-LA junction are the most accurate landmarks for image integration in respect to the target ablation area. The concurrent use of the present surface registration algorithm may result in shifting of the initial landmarks with loss of their initial correlation with the area of interest.     

Real-time MR imaging of myocardial regional function using strain-encoding (SENC) with tissue through-plane motion tracking

PURPOSE: To implement real-time myocardial strain-encoding (SENC) imaging in combination with tracking the tissue displacement in the through-plane direction. MATERIALS AND METHODS: SENC imaging was combined with the slice-following technique by implementing three-dimensional (3D) selective excitation. Certain adjustments were implemented to reduce scan time to one heartbeat. A total of 10 volunteers and five pigs were scanned on a 3T MRI scanner. Spatial modulation of magnetization (SPAMM)-tagged images were acquired on planes orthogonal to the SENC planes for comparison. Myocardial infarction (MI) was induced in two pigs and the resulting SENC images were compared to standard delayed-enhancement (DE) images. RESULTS: The strain values computed from SENC imaging with slice-following showed significant difference from those acquired without slice-following, especially during systole (P < 0.01). The strain curves computed from the SENC images with and without slice-following were similar to those computed from the orthogonal SPAMM images, with and without, respectively, tracking the tag line displacement in the strain direction. The resulting SENC images showed good agreement with the DE images in identifying MI in infarcted pigs. CONCLUSION: Correction of through-plane motion in real-time cardiac functional imaging is feasible using slice-following. The strain measurements are more accurate than conventional SENC measurements in humans and animals, as validated with conventional MRI tagging.     

Disengagement from mental health services

This paper reviews the literature on disengagement from mental health services examining how the terms engagement and disengagement are defined, what proportion of patients disengage from services, and what sociodemographic variables predict disengagement. Both engagement and disengagement appear to be poorly conceptualised, with a lack of consensus on accepted and agreed definitions. Rates of disengagement from mental health services vary from 4 to 46%, depending on the study setting, service type and definition of engagement used. Sociodemographic and clinical predictors of disengagement also vary, with only a few consistent findings, suggesting that such associations are complex and multifaceted. Most commonly reported associations of disengagement appear to be with sociodemographic variables including young age, ethnicity and deprivation; clinical variables such as lack of insight, substance misuse and forensic history; and service level variables such as availability of assertive outreach provision. Given the importance of continuity of care in serious mental disorders, there is a need for a consensual, validated and reliable measure of engagement which can be used to explore associations between patient, illness and service related variables and can inform service provision for difficult to reach patients.