PGC1α Expression Defines a Subset of Human Melanoma Tumors with Increased Mitochondrial Capacity and Resistance to Oxidative Stress

1. Download : Download high-res image (72KB)
2. Download : Download full-size image

Highlights? PGC1α is elevated in a subset of human melanoma tumors and derived cell lines ? PGC1α-positive melanoma cells exhibit increased mitochondrial metabolism ? PGC1α-positive melanoma cells exhibit increased ROS detoxification capacity ? PGC1α-negative melanoma cells are more glycolytic and sensitive to ROS-inducing drugs     

Coronary Artery Disease in Women: A 2013 Update

Coronary artery disease (CAD) is a leading cause of death of women and men worldwide. CAD's impact on women traditionally has been underappreciated due to higher rates at younger ages in men. Microvascular coronary disease disproportionately affects women. Women have unique risk factors for CAD, including those related to pregnancy and autoimmune disease. Trial data indicate that CAD should be managed differently in women. In this review, we will examine risk assessment for CAD in women, CAD's impact on women, as well as CAD's female-specific presentation and management strategies.     

Quantitative evaluation of AgNORs in bone tumours

AIMS: Primary tumours of bone present a significant diagnostic and therapeutic challenge at times. Silver stained nucleolar organiser regions (AgNORs) have been widely used in a variety of tissues but with a limited study on bone tumours. Our study was aimed at the evaluation of AgNOR count in various neoplastic lesions of bone. METHODS: : One hundred biopsies of bone lesions were included in this study. Five samples of foetal lumbar vertebrae obtained from foetal autopsies were taken as control. The study included 58 males and 42 females with age ranging from 5 to 70 years. Fifty-two cases were malignant while 48 were benign in nature. Silver staining for nuclear organiser regions was performed according to one-step silver staining technique in these cases. NORs seen as black dots were counted in the nuclei of 100 cells. RESULTS: Our study revealed that the mean count was highest in malignant lesions (4.00+/-0.69) compared with benign lesions (2.16+/-0.43) and normal bone (1.32+/-0.14). Statistically, the AgNOR count showed a significant difference (P<0.001) in all these lesions. CONCLUSIONS: The results of the current study revealed that malignant lesions had a greater mean AgNOR count than benign tumours and the normal bone. Thus, quantification of AgNORs strongly correlates with the type as well as aggressiveness of the bone tumour and is diagnostically useful in tumour differentiation.     

Eudragit RL100 based microspheres for ocular administration of azelastine hydrochloride

In the present study, potential of polymeric microspheres for treatment of allergic conjunctivitis was investigated. Azelastine hydrochloride loaded Eudragit RL100 microspheres were prepared by solvent evaporation technique. The change in drug-polymer ratio on the particle size, zeta potential, entrapment efficiency and in?vitro drug release was investigated. As Eudragit concentration ranged from 40 to 80?mg/ml the size range obtained was 4.18-7.36?μm with positive zeta potential. With the increase in drug polymer ratio, the entrapment efficiency was increased with maximum 14.56%. In?vitro release studies demonstrated prolonged release of the drug over the period of 6?hr. Scanning electron micrographs showed that microspheres were spherical with distinct solid dense structure. Fourier transform infrared and differential scanning calorimetry studies concluded slight change in peak intensities of drug in microspheres. In?vivo studies in rat model indicated that reduction in eosinophil count number was more pronounced in azelastine hydrochloride microspheres than marketed formulation, Azelast?.     

Differential improvements in lipid profiles and Framingham recurrent risk score in patients with and without diabetes mellitus undergoing long-term cardiac rehabilitation

Carroll S, Tsakirides C, Hobkirk J, Moxon JWA, Moxon JWD, Dudfield M, Ingle L. Differential improvements in lipid profiles and Framingham recurrent risk score in patients with and without diabetes mellitus undergoing long-term cardiac rehabilitation.

Objective

To determine whether lipid profiles and recurrent coronary heart disease (CHD) risk could be modified in patients with and without diabetes mellitus undergoing long-term cardiac rehabilitation (CR).

Design

Retrospective analysis of patient case records.

Setting

Community-based phase 4 CR program.

Participants

Patients without diabetes (n=154; 89% men; mean ± SD age, 59.6±8.5y; body mass index [BMI], 27.0±3.5kg/m²) and patients with diabetes (n=20; 81% men; mean age, 63.0±8.7y; BMI, 28.7±3.3kg/m²) who completed 15 months of CR.

Interventions

Exercise testing and training, risk profiling, and risk-factor education.

Main Outcome Measures

Cardiometabolic risk factors and 2- to 4-year Framingham recurrent CHD risk scores were assessed.

Results

At follow up, a significant main effect for time was evident for decreased body mass and waist circumference and improved low-density lipoprotein cholesterol (LDL-C) level and submaximal cardiorespiratory fitness (all P<.05), showing the benefits of CR in both groups. However, a significant group-by-time interaction effect was evident for high-density lipoprotein cholesterol (HDL-C) level and total cholesterol (TC)/HDL-C ratio (both P<.05). TC/HDL-C ratio improved (5.0±1.5 to 4.4±1.3) in patients without diabetes, but showed no improvement in patients with diabetes (4.8±1.6 v 4.9±1.6).

Conclusions

We showed that numerous anthropometric, submaximal fitness, and cardiometabolic risk variables (especially LDL-C level) improved significantly after long-term CR. However, some aspects of cardiometabolic risk (measures incorporating TC and HDL-C) improved significantly in only the nondiabetic group.     

Primary cilia in the pathogenesis of dentigerous cyst: a new hypothesis based on role of primary cilia in autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD), an inherited disease, leads to cyst formation in the kidneys. In this condition, the kidneys are grossly enlarged with multiple cysts that result in kidney failure in a majority of individuals. This condition is also associated with cysts in other organs. Recent research has focused on defects in signaling mediated by the primary cilia as the causative factor in ADPKD. Primary cilia are also present in odontogenic epithelium. Dentigerous cyst also is a developmental cyst whose pathogenesis is controversial. Recent studies have shown that loss of Ptch and Shh signaling pathways are involved in the cystogenesis of dentigerous cyst. The Shh signaling pathway is active in the primary cilia. A scanning electron microscopic study of a dentigerous cyst wall in an ADPKD patient showed structures similar to primary cilia. Based on the presentation of a dentigerous cyst in an autosomal dominant polycystic kidney patient and the demonstration of primary cilia like structures on the cyst wall by using a scanning electron microscope, a new hypothesis for the pathogenesis of dentigerous cyst is proposed.     

Muscle-specific kinase-antibody-positive myasthenia gravis after autologous bone marrow transplantation

A 44-year-old man presented with oculobulbar weakness approximately 5 years after autologous bone marrow transplantation (BMT). His workup led to the diagnosis of muscle-specific kinase-antibody-related myasthenia gravis (MG). There has been only one case report of muscle-specific kinase-antibody-positive MG after BMT, which was allogeneic. We report the first case of autologous BMT-associated MG with muscle-specific kinase antibody. The pathogenic mechanisms of immune dysregulation leading to MG after BMT are discussed.