Pioglitazone increases non-esterified fatty acid clearance in upper body obesity

Aims/hypothesis Plasma NEFA concentrations are largely determined by adipose tissue lipolysis. Insulin suppression of lipolysis is commonly impaired with insulin resistance and improves with thiazolidinedione treatment of type 2 diabetes. The present studies were designed to assess the effects of thiazolidinedione on NEFA (oleate) metabolism that are independent of improved glycaemic control. Materials and methods We measured plasma oleate concentration and flux ([³H]oleate), glucose kinetics ([6-²H₂]glucose) and substrate oxidation (indirect calorimetry) before and after pioglitazone (30 mg/day for ∼20 weeks) in 20 non-diabetic adults with upper body obesity. To assess the effects of improved insulin sensitivity per se we performed the same measurements in a matched group of volunteers treated with diet/exercise. Half of the two groups underwent these measurements during a hyperinsulinaemic–euglycaemic clamp, and the other half had their measurements taken during a (control) saline infusion before and after the intervention. Results Both interventions increased insulin-stimulated glucose disposal and reduced plasma oleate concentrations during the insulin clamp. After diet/exercise, oleate flux decreased (p=0.03) during the insulin clamp and oleate clearance remained unchanged (p=0.55), whereas in the pioglitazone group, oleate flux during the clamp was unchanged (p=0.97) and oleate clearance increased (p=0.003). Oleate clearance in the saline control condition was increased in the pioglitazone group compared with the diet/exercise group (p=0.02). Conclusions/interpretation In insulin-resistant, non-diabetic adults, pioglitazone increases NEFA clearance during physiological hyperinsulinaemia, whereas improved insulin sensitivity achieved by diet/exercise does not alter NEFA clearance but enhances insulin suppression of NEFA release. This action of pioglitazone may contribute to improved glucose metabolism in type 2 diabetes.     

Human lung epithelial cells express a functional cold-sensing TRPM8 variant

Several transient receptor potential (TRP) ion channels sense and respond to changes in ambient temperature. Chemical agonists of TRP channels, including menthol and capsaicin, also elicit sensations of temperature change. TRPM8 is a cold- and menthol-sensing ion channel that converts thermal and chemical stimuli into neuronal signals and sensations of cooling/cold. However, the expression and function of TRPM8 receptors in non-neuronal cells and tissues is a relatively unexplored area. Results presented here document the expression and function of a truncated TRPM8 variant in human bronchial epithelial cells. Expression of the TRPM8 variant was demonstrated by RT-PCR, cloning, and immunohistology. Receptor function was characterized using the prototypical TRPM8 agonist, menthol, and exposure of cells to reduced temperature (18 degrees C). The TRPM8 variant was expressed primarily within endoplasmic reticulum membranes of lung epithelial cells and its activation was attenuated by thapsigargin, the cell-permeable TRPM8 antagonist N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide, and shRNA-induced suppression of TRPM8 expression. Activation of the TRPM8 variant in lung cells was coupled with enhanced expression of the inflammatory cytokines IL-6 and IL-8. Collectively, our results suggest that this novel TRPM8 variant receptor may function as a modulator of respiratory physiology caused by cold air, and may partially explain asthmatic respiratory hypersensitivity to cold air.     

A comparison of curved canal transportation with balanced force versus lightspeed

The Flex-R file was compared with the Lightspeed nickel-titanium file in respect to canal center movement and final canal area after instrumentation. Thirty-eight root canals in extracted human molars were divided into two equal groups of 19, in all of which the angle of curvature ranged from 20 to 35 degrees. After mounting in a mold, each root was sectioned at two locations, providing an apical and coronal section. Pre- and postinstrumentation 35 mm photographic slides of each section were projected, traced, and then scanned into a computer. From these computerized pre- and postinstrumentation images, the movement of the canal center and the area of each canal were computed at both the apical and coronal sections. Results showed significant difference in the apical canal center movement and postinstrumentation area with the Lightspeed yielding smaller values in both cases. Coronally, the Flex-R Lightspeed instruments demonstrated no significant difference in canal movement or postinstrumentation area. No significant correlation was found between the angle of root curvature and canal movement or the angle of root curvature and postinstrumentation canal area.     

A survey of family physicians and psychiatrists: Psychotropic prescribing practices and educational needs

The purpose of this study was to compare the psychotropic prescribing practices of family physicians and psychiatric physicians, and to assess their satisfaction with education about psychotropic prescribing. A survey was mailed to 461 active members of the Minnesota Psychiatric Society and to a randomized sample of 461 active members of the Minnesota Academy of Family Physicians. Major depression, panic disorder, and dementia with behavioral disturbance were selected for study. For each disorder, we asked for the estimated number of patients seen and treated as well as a list in order of preference of the three medications they most commonly use. Those surveyed were also asked about their level of satisfaction with the training they received in medical school, residency, and continuing medical education (CME) courses on the topic of psychotropic prescribing. The two physician groups reported similar prescribing practices for the single-drug treatment of depression. Family physicians more frequently prescribed minor tranquilizers and older generation psychotropics than did psychiatrists when treating panic disorder and dementia with behavioral disturbance. Patients with depression were the least likely to be referred to other health professionals. Neither physician group was satisfied with medical school education in this area; family physicians were less satisfied with residency training and in related CME courses than were psychiatric physicians. Additional study is needed to better understand interspecialty practice variation for commonly encountered psychiatric disorders. Medical education programs at all levels could better meet the reported needs of their graduates by providing more attention to prescribing psychotropic agents.     

Effect of deferoxamine on post-hypoxic-ischemic reperfusion injury of the newborn lamb heart

Post-hypoxic-ischemic (HI) reperfusion induces excess production of non-protein-bound iron (NPBI), leading to formation of the highly reactive hydroxyl radical. We investigated whether the iron-chelator deferoxamine (DFO) could reduce reperfusion injury and improve left ventricular (LV) function. We produced severe HI in 14 newborn lambs and measured pre-HI, upon reperfusion, 60 and 120 min after HI the following parameters: mean aortic blood pressure, total peripheral resistance, stroke volume (SV), ejection fraction (EF) and LV contractility (pre-HI, 60 and 120 min post-HI). These parameters were assessed by measuring LV pressure (tip manometer) and volume (conductance catheter), using inflow occlusion to obtain slope (Ees) and volume intercept of the end-systolic P-V relationship (V10). We determined the antioxidative capacity, i.e. the ratio of ascorbic acid and dehydroascorbic acid (AA/DHAA) and malondialdehyde from coronary sinus blood at pre-HI and at 15, 60 and 120 min post-HI. Seven lambs received DFO (10 mg/kg i.v.) immediately after HI, 6 control lambs received a placebo. While neither Ees nor EF changed significantly in either group, the volume intercept V10 in the DFO-treated group was significantly smaller (0.25 +/- 0.03 vs. 0.70 +/- 0.09, p < 0.05), whereas SV was larger (3.6 +/- 0.6 vs. 2.2 +/- 0.2 ml, p < 0.05) and the AA/DHAA ratio was significantly lower at 15 min post-HI (p < 0.05) providing evidence for HI damage and for the protective effect of DFO. In conclusion: post-HI treatment of the newborn lamb with DFO has a modifying effect on free radical-induced damage to the myocardium and protects myocardial performance.