Angiotensin receptor blockade increases pancreatic insulin secretion and decreases glucose intolerance during glucose supplementation in a model of metabolic syndrome

Renin-angiotensin system blockade improves glucose intolerance and insulin resistance, which contribute to the development of metabolic syndrome. However, the contribution of impaired insulin secretion to the pathogenesis of metabolic syndrome is not well defined. To assess the contributions of angiotensin receptor type 1 (AT?) activation and high glucose intake on pancreatic function and their effects on insulin signaling in skeletal muscle and adipose tissue, an oral glucose tolerance test (oGTT) was performed in five groups (n = 10/group) of rats: 1) lean strain-control 2) obese Otsuka Long-Evans Tokushima Fatty (OLETF), 3) OLETF + angiotensin receptor blocker (ARB; 10 mg/kg · d olmesartan for 6 wk; OLETF ARB), 4) OLETF + 5% glucose water (HG) for 6 wk (OLETF HG), and 5) OLETF + HG + ARB (OLETF HG/ARB). The glucose response to the oGTT increased 58% in OLETF compared with lean-strain control, whereas glucose supplementation increased it an additional 26%. Blockade of angiotensin receptor reduced the oGTT response 19% in the ARB-treated groups and increased pancreatic insulin secretion 64 and 113% in OLETF ARB and OLETF HG/ARB, respectively. ARB treatment in OLETF ARB and OLETF HG/ARB did not have an effect on insulin signaling proteins in skeletal muscle; however, it reduced pancreatic AT? protein expression 20 and 27%, increased pancreatic glucagon-like peptide-1 (GLP-1) receptor protein expression 41 and 88%, respectively, and increased fasting plasma GLP-1 approximately 2.5-fold in OLETF ARB. The results suggest that improvement of glucose intolerance is independent of an improvement in muscle insulin signaling, but rather by improved glucose-stimulated insulin secretion associated with decreased pancreatic AT? activation and increased GLP-1 signaling.     

Eosinophilic ulcer of oral mucosa: a case report

Eosinophilic Ulcer (EU) is a rare self-limiting chronic benign lesion of the oral mucosa with pathogenesis still unclear, however it may resemble malignancies, traumatic ulcerations and some infections such as deep fungal infections, tuberculosis and primary syphilis. This is a case report of a patient with EU in the lateral border of the tongue with no history of associated trauma and refractory to treatment with drugs. The ulcer rapidly healed after an incisional biopsy and the definite diagnosis was achieved only combining histologic findings and the clinical follow-up.     

Errors and near misses in digestive endoscopy units

Background

Not much is known about errors and near misses in digestive endoscopy.

Aims

To verify whether an incident report, with certain facilitating features, gives useful information about unintended events, only excluding errors in medical diagnosis.

Method

Nine endoscopy units took part in this cross sectional, prospective, multicentre study which lasted for two weeks. Members of the staff were required to report any unintended, potentially dangerous event observed during the daily work. A form was provided with a list of “reminders” and facilitators were appointed to help.The main outcome measurements were type of event, causes, corrective interventions, stage of occurrence in the workflow and qualification of the reporters.

Results

A total of 232 errors were reported (two were not related to endoscopy). The remaining 230 amount to 10.3% of 2239 procedures; 66 (29%) were considered errors with consequences, 164 (71%) “near misses”. There were 150 pre-operative errors (65%), 22 operative (10%) and 58 post-operative (25%). Corrective interventions were provided for 60 cases of errors and 119 near misses. Most of the events were reported by the nurses (106 out of 232, 46%).

Conclusions

Short-term incident reporting focusing on near misses, using forms with lists of “reminders”, and the help of a facilitator, can give useful information on errors and near misses in digestive endoscopy.     

Amyloid-beta in Alzheimer disease: the null versus the alternate hypotheses

For nearly 20 years, the primary focus for researchers studying Alzheimer disease has been centered on amyloid-beta, such that the amyloid cascade hypothesis has become the "null hypothesis." Indeed, amyloid-beta is, by the current definition of the disease, an obligate player in pathophysiology, is toxic to neurons in vitro, and, perhaps most compelling, is increased by all of the human genetic influences on the disease. Therefore, targeting amyloid-beta is the focus of considerable basic and therapeutic interest. However, an increasingly vocal group of investigators are arriving at an "alternate hypothesis" stating that amyloid-beta, while certainly involved in the disease, is not an initiating event but rather is secondary to other pathogenic events. Furthermore and perhaps most contrary to current thinking, the alternate hypothesis proposes that the role of amyloid-beta is not as a harbinger of death but rather a protective response to neuronal insult. To determine which hypothesis relates best to Alzheimer disease requires a broader view of disease pathogenesis and is discussed herein.     

Mls-1-like superantigen in the MA/MyJ mouse is encoded by a new mammary tumor provirus that is distinct from Mtv-7

Mls-1 is an endogenous superantigen that leads to in vivo deletion and in vitro stimulation of T cell receptor (TCR) V beta 6-, 7-, 8.1-, and 9-expressing cells. The MA/MyJ mouse deletes the identical set of TCR from its mature T cell repertoire; however, it does not contain Mtv-7, the murine mammary tumor provirus (MMTV), whose sag gene encodes Mls-1. Interestingly, the superantigen activity of this mouse strain segregates with a new mammary tumor provirus, Mtv-43, not seen in other inbred strains. The predicted amino acid sequence of the sag gene of Mtv-43 was compared with that of Mtv-7. Strikingly, the COOH terminus of the two molecules is very similar, while all other MMTV-encoded superantigens differ 100% in this segment.     

Application of Innovative Methods of Predictive Control in Projects Involving Intelligent Steel Processing Production Systems

This paper describes the enhancement of the existing predictive system of quality management in the processes of metallurgic manufacturing. Specifically, it addresses steel-strip manufacturing. The main quality management innovation is the transition from the current methodological process of a single-step defect evaluation to a two-step evaluation. A two-step defect check of the strip’s surface involves checking for defects during the hot-rolling process first, and double-checking it during the process of pickling. These defects are detected in a well-established process of camera imaging in the production process. The recorded image is then processed mathematically to find the degree of defect correlation in those processes. The two-step evaluation enables a more detailed focus on a particular defect and its position on the strip. Decisions concerning further processing are based on defect evaluation, for instance, whether a rework is necessary to maximize the product utilization and minimize the eventual negative impact of the defect on production equipment. A crucial aspect is also the reduced probability of failures in the manufacturing process.     

Funnel-web spider venom and a toxin fraction block calcium current expressed from rat brain mRNA in Xenopus oocytes.

Injection of rat brain mRNA into Xenopus oocytes has been shown to induce a calcium current (ICa) that is insensitive to dihydropyridine and omega-conotoxin. We examined the effect of funnel-web spider venom on two aspects of this expressed ICa: (i) the calcium-activated chloride current [ICl(Ca)] and (ii) the currents carried by barium ions through calcium channels (IBa). In the presence of 1.8 mM extracellular calcium, ICl(Ca) tail current became detectable between -30 and -40 mV from a holding potential of -80 mV and reached a maximal amplitude between 0 and +10 mV. Total spider venom partially (83%) and reversibly blocked the calcium-activated chloride current without changing its voltage sensitivity. A chromatographic toxin fraction from the venom also blocked this current (64%). The venom had a minimal effect on INa and IK. Direct investigation of inward current mediated by calcium channels was carried out in high-barium solution. IBa had a higher threshold of activation (-30 to -20 mV) and reached its maximal amplitude at about +20 mV. Total venom or a partly purified chromatographic toxic fraction blocked IBa partially and reversibly without changing its current-voltage characteristics. Furthermore, the extent of the total venom block depended on the concentration of extracellular barium. Only 35% of the IBa was blocked in 60 mM Ba2+, whereas the block increased to 65% and 71%, respectively, for 40 and 20 mM Ba2+. On the basis of these results, we propose that the calcium channels expressed from rat brain mRNA in Xenopus oocytes is similar to the recently discovered P-type channels.