Induction of monocyte chemoattractant protein-1 expression by angiotensin II in the pancreatic islets and beta-cells

Angiotensin II (AngII), the principal hormone of the renin-angiotensin system, is actively generated in the pancreas and has been suggested as a key mediator of inflammation. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays an important role in the recruitment of mononuclear cells into the pancreatic islets. In this study, we investigated the potential molecular basis for the role of AngII in islet inflammation through studying its effect on MCP-1. AngII significantly increased the expression of MCP-1 mRNA and protein in the RINm5F beta-cell line and activated MCP-1 promoter. AngII-MCP-1 mRNA induction was inhibited by an AngII type 1 receptor antagonist but was unchanged by an AngII type 2 receptor antagonist. AngII-MCP-1 induction was inhibited by the tyrosine kinase inhibitor genistein, suggesting a MAPK signaling mechanism. AngII activated the phosphorylation of ERK1/2 but not p38 or c-Jun NH(2)-terminal MAPKs. Inhibition of ERK1/2 activation reduced the AngII-induced MCP-1 synthesis. In nonobese diabetic mice pancreata, the temporal pattern of angiotensin-converting enzyme expression correlated well with progression of insulitis and beta-cell destruction. Immunostaining of pancreatic serial sections show colocalization of angiotensin-converting enzyme with MCP-1 in beta-cells in the islets. In freshly isolated islets from normoglycemic mice, AngII alone and in combination with IL-1beta elicited an inflammatory response by stimulation of MCP-1. Our data suggest a positive autocrine/paracrine action for the local pancreatic AngII-generating system during insulitis and provide the first insight into an AngII-initiated signal transduction pathway that regulates MCP-1 as a possible inflammatory mechanism in the islets.     

Neuroanatomical correlates of executive functioning in depressed adults with type 2 diabetes

Depression is often comorbid with type 2 diabetes. Depression may increase vulnerability to and/or exacerbate existing cognitive deficits. Little is known about the brain pathophysiology underlying depression and cognitive abnormalities in diabetes. The aim of this study was to examine the relationship of orbitofrontal and anterior cingulate volumes with executive functioning and attention/processing speed in type 2 diabetic participants with and without major depression. A total of 21 diabetic participants with major depression, 23 diabetic participants with no depression, and 22 healthy controls were compared. Using brain magnetic resonance imaging, volumetric measures of the prefrontal cortex were examined in relation to executive functioning and attention/processing speed. Partial correlations suggested a significant positive relationship between right orbitofrontal regions and executive functioning in the group with diabetes and depression only, indicating that neurobiological changes in the orbitofrontal region may contribute to observed cognitive dysfunction.     

Polyflex self-expanding,removable plastic stents: assessment of treatment efficacy and safety in a variety of benign and malignant conditions of the esophagus

Background Historically, esophageal fistulas, perforations, and benign and malignant strictures have been managed surgically or with the placement of permanent endoprostheses or metallic stents. Recently, a removable, self-expanding, plastic stent has become available. The authors investigated the use of this new stent at their institution. Methods The study reviewed all the patients who received a Polyflex stent for an esophageal indication at the authors’ institution between January 2004 and October 2006. Duration of placement, complications, and treatment efficacy were recorded. Results A total of 37 stents were placed in 30 patients (14 women and 16 men) with a mean age of 68 years (range, 28–92 years). Stent placement included 7 for fistulas, 3 for perforations, 1 for an anastomotic leak, 7 for malignant strictures, and 19 for benign strictures (8 anastomotic, 1 caustic, 5 reflux, 2 radiation, and 2 autoimmune esophagitis strictures, and 1 post-Nissen gas bloat stricture). The mean follow-up period was 6 months. Stent deployment was successful for all the patients, and no complications resulted from stent placement or removal. Nine stents migrated spontaneously. Three of three perforations and three of five fistulas sealed. Only one stent was removed because of patient discomfort. One patient with a radiation stricture experienced tracheoesophageal fistulas secondary to pressure necrosis. Of 20 patients with stricture, 18 experienced improvement in their dysphagia. Conclusion Self-expanding, removable plastic stents are easily and safely placed and removed from the esophagus. This has facilitated their use in the authors’ institution for an increasing number of esophageal conditions. Further studies to help define their ultimate role in benign and malignant esophageal pathology are warranted.     

A geometric method for nipple localization

BACKGROUND:

An important part of preoperative assessment in breast reduction surgery is to locate the site of the nipple-areola complex for the newly structured breast. Inappropriate location is difficult to correct secondarily. Traditional methods of nipple localization taught and practiced suggest the nipple to be located anterior to the inframammary fold. Trying to project this point on the anterior surface of the breast requires either large calipers or feeling the posteriorly placed finger on the anterior surface of a large breast. This certainly introduces some subjectivity to the calculation.

OBJECTIVES:

To introduce an easy and accurate method of nipple localization to reduce the learning curve for trainee surgeons.

METHODS:

Aesthetic placement of the nipples is at the lower angles of an equilateral or a short isosceles triangle on the chest with its apex at the sternal angle. This triangle can be thought of as two right-angled triangles with their Y-axis on the median plane. The base and vertical limb are measured, and the hypotenuse is calculated. The location of the lower angle is marked on the anterior surface of the breast and represents the new position of the nipple.

RESULTS:

Forty patients had nipple localization performed in the above-described manner, with satisfactory placement of the nipple-areola complex.

CONCLUSIONS:

The above technique introduces some objective measurements to the localization of the nipple in breast reduction surgery. It is easy to practice, and infuses confidence in trainees marking their initial breast reductions.     

The 5-HT2A receptor binding pattern in the human brain is strongly genetically determined

With the appropriate radiolabeled tracers, positron emission tomography (PET) enables in vivo human brain imaging of markers for neurotransmission, including neurotransmitter synthesis, receptors, and transporters. Whereas structural imaging studies have provided compelling evidence that the human brain anatomy is largely genetically determined, it is currently unknown to what degree neuromodulatory markers are subjected to genetic and environmental influence. Changes in serotonin 2A (5-HT(2A)) receptors have been reported to occur in various neuropsychiatric disorders and an association between 5-HT(2A) receptor gene variants and neuropsychiatric illness susceptibility also exists. In a classical twin design involving 24 healthy male subjects (6 monozygotic twin pairs and 6 dizygotic twin pairs), we examined the relative contribution of genetic and environmental factors to interindividual variability in cortical 5-HT(2A) receptor binding as measured with [(18)F]altanserin PET imaging. The intraclass correlation coefficients were 0.67 for dizygotic and 0.87 for monozygotic twin pairs. For comparison, the intraclass correlation coefficient was 0.93 in a group of six male healthy subjects examined twice within two weeks with an identical experimental setup. Multivariate analysis was used to separate the phenotypic variance of individuals into additive genetic (heritability) effect (A), shared (family) environment (C), and non-shared (individual-specific) environment (E). Irrespective of whether a full ACE model or a reduced AE model was used to fit the data, the variance due to non-shared environment was below 10% indicating that the contribution of individual specific environmental factors to 5-HT(2A) receptor binding is limited.