Insulin sensitivity: modulation by nutrients and inflammation

Insulin resistance is a major metabolic feature of obesity and is a key factor in the etiology of a number of diseases, including type 2 diabetes. In this review, we discuss potential mechanisms by which brief nutrient excess and obesity lead to insulin resistance and propose that these mechanisms of action are different but interrelated. We discuss how pathways that "sense" nutrients within skeletal muscle are readily able to regulate insulin action. We then discuss how obesity leads to insulin resistance via a complex interplay among systemic fatty acid excess, microhypoxia in adipose tissue, ER stress, and inflammation. In particular, we focus on the hypothesis that the macrophage is an important cell type in the propagation of inflammation and induction of insulin resistance in obesity. Overall, we provide our integrative perspective regarding how nutrients and obesity interact to regulate insulin sensitivity.     

Canal transportation caused by one single-file and two multiple-file rotary systems: A comparative study using cone-beam computed tomography

Aim

This ex-vivo study aimed to compare canal transportation in mesio-buccal canal of mandibular first molars prepared with Mtwo and Revo-S multi-file and Neoniti single-file nickel–titanium (Ni–Ti) rotary systems using cone-beam computed tomography (CBCT).

Soluble HLA class I molecules in malignant pleural and peritoneal effusions and its possible role on NK and LAK cytotoxicity

PURPOSE: To examine the amount of sHLA-I in malignant pleural and peritoneal effusions and its possible role in natural immune defense. METHODS: Three groups of patients (75 patients with malignancy, 21 with infection, and 27 with other diseases) were studied for sHLA-I value using an ELISA method. Cytolytic activity of freshly isolated pleural and peritoneal effusion-associated lymphoid (EAL) cells from 14 of cases with malignancy were examined and compared to that of ten non-cancerous patients. EAL cells were co-cultured with the autologous cell-free effusions immediately after collection and 3 days after incubation with IL-2. RESULTS: The mean value of sHLA-I in effusions was 1.01+/-1.36 micro g/ml, 0.97+/-1.20 micro g/ml, and 0.49+/-0.45 micro g/ml, respectively. Despite higher mean sHLA-I levels in malignant and infected patients, no significant difference between these groups was observed ( P >0.05). Generally, the amount of sHLA-I in peritoneal effusions was higher than that for pleural effusions, but the difference was not significant. There were also no statistical differences in the sHLA-I levels between sub-groups of patients with malignancy. EAL cells' killing activity in malignant and infected effusions was 68.15+/-11.73 and 78.28+/-14.41, respectively ( P=0.08). No correlation between sHLA-I level and NK activity of EAL cells from the patients was found. Almost all malignant cases after exposure to cell-free effusions displayed an increase in NK activity (from 68.66+/-11.13 to 74.2+/-12.39, P=0.042) and a decrease in LAK activity (74.5+/-18.30 vs 67.72+/-16.46, P=0.040). Whereas, the same experiment performed for non-malignant effusions showed a decrease in both NK activity and LAK activity. Changes in NK and LAK activity were not correlated with the amount of sHLA-I in the effusions. CONCLUSION: The presence of sHLA-I, particularly in malignant effusions, suggests a role for these molecules in tumor immunity in the peritoneal or plural environment; however, at least with these group of patients, sHLA-I appears not to be a unique determining factor on EAL cells' killing activity.     

PPARγ activation in adipocytes is sufficient for systemic insulin sensitization

Although peroxisome proliferator-activated receptor gamma (PPARγ) agonists such as thiazolidinediones (TZDs) are widely used to treat type 2 diabetes, how its activation in individual tissues contributes to TZD''s therapeutic action remains controversial. As TZDs are known to have receptor-independent effects, we sought to establish gain-of-function animal models to delineate the receptor''s insulin-sensitizing actions. Unexpectedly, we find that selective activation of PPARγ in adipocytes, but not in macrophages, is sufficient for whole-body insulin sensitization equivalent to systemic TZD treatment. In addition to improved adipokine, inflammatory, and lipid profiles, PPARγ activation in mature adipocytes normalizes serum insulin without increased adipogenesis. Co-culture studies indicated that PPARγ-activated adipocytes broadly suppress induction of inflammatory cytokines and C-X-C family chemokines in macrophages. Collectively, these data describe an “adipocentric” model in which adipose activation of PPARγ is sufficient for complete insulin sensitization and suggest a specific application for fat selective PPARγ modulators in diabetic therapy.     

Inhaled corticosteroid use in HIV‐positive individuals taking protease inhibitors: a review of pharmacokinetics,case reports and clinical management

As a consequence of inhibition of the hepatic cytochrome P450 3A4 isozyme, treatment with HIV protease inhibitors can result in significant drug?drug interactions. One noteworthy interaction is between protease inhibitors and inhaled or intranasal corticosteroids. This interaction can result in adrenal insufficiency and iatrogenic Cushing's syndrome (with symptoms such as rapid weight gain, obesity, facial hirsutism and swelling), as well as hypertension, osteoporosis and decreased CD4 cell count. In this paper, we review and unite pharmacokinetic data, case reports and current research regarding this drug?drug interaction in order to suggest options for the clinical management of HIV‐positive patients requiring treatment with protease inhibitors and inhaled or intranasal corticosteroids.     

The value of radius bone in prediction of sex and height in the Iranian population

ObjectiveMeasurement of anthropometric parameters of long bones can be applied in sex determination and height prediction. The aim of this study was to investigate the value of length of the radius in forensic identification.Materials and methodsCross-sectional analysis of anthropometric parameters of the radius was done by Legal Medicine Organization of Tehran, Iran studying fresh cadavers of Iranian population during 2009 and 2010.ResultsThis study surveyed length of radius of 106 fresh Iranian cadavers, 61 men and 45 women, in the age range of 10–85 years old. The study showed that genders can be distinguished using the length of radius with a sensitivity of 83% and specificity of 96%. Using the regression test, there was significant relation between the height of persons and the length of radius bone. The equations were obtained to estimate the height of the individuals on the basis of radius bone length in different age groups, with an exception in females of 40–64 Years old.ConclusionIn the cases of fresh cadavers, by using the length of radius, we could be able to determine the length of height and gender with high confidence.     

Prenatal Diagnosis for β-Thalassemia Major in the Iranian Province of Hormozgan

β-Thalassemias are a group of heterogenous recessive disorders common in many parts of the world. Despite the great advances in the treatment of thalassemia, there is so far no cure, but perhaps bone marrow transplantation (BMT) is a possibility. Prevention, using prenatal diagnosis and selective abortion in the cases where the fetus is found to be affected, should be considered as a sensible alternative. During the past 5 years, 112 couples have been referred to our Center for detection of their β-thalassemia (β-thal) carrier status. In this group, common and rare mutations were detected. Of these, 106 couples (94.6%) came for counseling during pregancy and six (5.4%) came before becoming pregnant. Prenatal diagnosis was performed for the 106 couples at risk. Fetal DNA was obtained from both chorionic villus sampling (CVS) (99) and amniotic fluid (). Using reverse hybridization, 64 (60.4%) were found to be heterozygous for a β-thal mutation and 24 (22.6%) were normal. Eighteen (17.0%) were found to carry an affected fetus and these pregnancies were terminated.     

Increased frequency of steroid non-responsive nephrotic syndrome in Iranian children

During an eight year period, 66 Iranian children with nephrotic syndrome without renal failure were studied for their response to prednisone therapy. Twentysix (39·3%) of these were early steroid non-responsive. Of 40 responders, 70 per cent responded within the first 2 wk, 22·5 per cent within the second 2 wk, and 3 children during the next 4 wk of therapy. Two patients (3·03%) were steroid late non-responders.