Loss of dopamine D2 receptors induces atrophy in the temporal and parietal cortices and the caudal thalamus of ethanol-consuming mice

Background: The need of an animal model of alcoholism becomes apparent when we consider the genetic diversity of the human populations, an example being dopamine D2 receptor (DRD2) expression levels. Research suggests that low DRD2 availability is associated with alcohol abuse, while higher DRD2 levels may be protective against alcoholism. This study aims to establish whether (i) the ethanol‐consuming mouse is a suitable model of alcohol‐induced brain atrophy and (ii) DRD2 protect the brain against alcohol toxicity. Methods: Adult Drd2+/+ and Drd2?/? mice drank either water or 20% ethanol solution for 6 months. At the end of the treatment period, the mice underwent magnetic resonance (MR) imaging under anesthesia. MR images were registered to a common space, and regions of interest were manually segmented. Results: We found that chronic ethanol intake induced a decrease in the volume of the temporal and parietal cortices as well as the caudal thalamus in Drd2?/? mice. Conclusions: The result suggests that (i) normal DRD2 expression has a protective role against alcohol‐induced brain atrophy and (ii) in the absence of Drd2 expression, prolonged ethanol intake reproduces a distinct feature of human brain pathology in alcoholism, the atrophy of the temporal and parietal cortices.     

Cigarette Smoking and Tryptophan Hydroxylase 2 mRNA in the Dorsal Raphe Nucleus in Suicides

Cigarette smoking is associated with suicide and mood disorders and stimulates serotonin release. Tryptophan hydroxylase (TPH2) synthesizes serotonin and is over-expressed in suicides. We determined whether smoking is associated with TPH2 mRNA in suicides and controls. TPH2 mRNA was measured postmortem in the dorsal raphe nucleus (DRN) of controls (N = 26, 17 nonsmokers and nine smokers) and suicides (N = 23, 5 nonsmokers and 18 smokers). Psychiatric history was obtained by psychological autopsy. TPH2 mRNA was greater in suicide nonsmokers than suicide smokers, control smokers and control nonsmokers (p = 0.006). There was more TPH2 mRNA throughout the DRN. Smoking interferes with the TPH2 mRNA increase observed in suicide nonsmokers. The absence of altered TPH2 expression in non-suicide smokers suggests no pharmacological effect of smoking.     

Mirror neuron activity during contagious yawning—an fMRI study

Yawning is contagious. However, little research has been done to elucidate the neuronal representation of this phenomenon. Our study objective was to test the hypothesis that the human mirror neuron system (MNS) is activated by visually perceived yawning. We used functional magnetic resonance imaging to assess brain activity during contagious yawning (CY). Signal-dependent changes in blood oxygen levels were compared when subjects viewed videotapes of yawning faces as opposed to faces with a neutral expression. In response to yawning, subjects showed unilateral activation of their Brodmann’s area 9 (BA 9) portion of the right inferior frontal gyrus, a region of the MNS. In this way, two individuals could share physiological and associated emotional states based on perceived motor patterns. This is one component of empathy (motor empathy) that underlies the development of cognitive empathy. The BA 9 is reportedly active in tasks requiring mentalizing abilities. Our results emphasize the connection between the MNS and higher cognitive empathic functions, including mentalizing. We conclude that CY is based on a functional substrate of empathy.     

Severe deterioration of newly diagnosed Takayasu arteritis in a patient re-treated with interferon beta-1α for concomitant longstanding multiple sclerosis

A 52-year-old woman with Takayasu arteritis and a known history of multiple sclerosis had been treated with subcutaneous interferon (IFN) beta-1α. After the re-introduction of the IFN beta-1α, the patient had a gradual worsening of the arteritis, with claudication symptoms in the left arm and increased inflammation markers. An evaluation using Doppler ultrasound of the supra-aortic vessels revealed severe stenosis of the left axillary artery. The IFN beta-1α was withdrawn, with prompt clinical and laboratory improvement of the vasculitis.     

Usefulness of Acarbose and Dietary Modifications to Limit Glycemic Variability Following Roux-en-Y Gastric Bypass as Assessed by Continuous Glucose Monitoring

Abstract Background: About 70% of the patients operated on for a gastric bypass (Roux-en-Y gastric bypass [RYGB]) suffer from dumping syndrome. In these patients, previous studies have demonstrated a high glycemic variability with hypoglycemia and with altered continuous glucose monitoring (CGM) profiles. The aim of this study was to evaluate the effect of treatment with dietary counseling plus acarbose administration on the symptoms and on the characteristics of the CGM profile. Subjects and Methods: Eight consecutive patients with dumping syndrome were given dietary counseling for 6 weeks and also treated with acarbose (50-100?mg three times a day). Their symptoms and the features of the CGM were compared before and after treatment. Results: The symptoms disappeared in seven patients. There was a significant increase in the time to the interstitial glucose (IG) peak and a reduction in the rate of the IG increase after a meal and in the rate of the IG decrease following the peak. The time below 60?mg/dL was significantly decreased, and the minimal IG value was significantly increased. The maximum and mean IG levels and the time above 140?mg/dL were decreased, but not significantly. Six patients spent more than 1% of the time with IG values below 60?mg/dL before treatment, but after treatment this was reduced to one patient. Before treatment only one patient had an IG level neither below 60 or above 140?mg/dL, and after treatment four patients were in this category. Conclusions: Dietary counseling and acarbose treatment eliminated the symptoms and improved the CGM profile of patients suffering from dumping syndrome after RYGB.     

Eating Behavior and Glucagon-Like Peptide-1-Producing Cells in Interposed Ileum and Pancreatic Islets in Rats Subjected to Ileal Interposition Associated with Sleeve Gastrectomy

Background

Ileal interposition–sleeve gastrectomy (II–SG) has been developed as a metabolic surgery based on the hindgut hypothesis. The aim of the present study was to test this hypothesis by studying the eating behavior, metabolic changes, and glucagon-like peptide-1 (GLP-1)-producing cells in rat models.

Methods

Male Sprague–Dawley rats were subjected to laparotomy, II, SG, or II–SG. Eating behavior and metabolic parameters were monitored by an open-circuit indirect calorimeter designed for a comprehensive laboratory animal monitoring system. GLP-1-producing cells were examined by quantitative immunohistochemistry.

Results

After II alone, satiety ratio, i.e., intermeal interval/meal size, was reduced, while calorie intake was increased at 2 and 6 weeks postoperatively. Respiratory exchange ratio, VCO₂/VO₂, was increased to above 1.0 (i.e., carbohydrate metabolism) during both daytime and nighttime at 2 weeks postoperatively. After SG alone, GLP-1-producing cells were increased in the pancreatic islets (in terms of volume density), but not in the ileum (number/mm). After II–SG, the rate of eating was reduced, while meal duration (min) was increased during both daytime and nighttime at 2 weeks postoperatively. GLP-1-producing cells were increased by about 2.5-fold in the interposed ileum and also increased to the same extent in the pancreatic islets as seen after SG alone. The increased GLP-1-producing cells in the pancreatic islets after SG or II–SG were located around the insulin-producing β cells.

Conclusions

The present study provides evidence supporting the hindgut hypothesis. II–SG increased GLP-1 production both in the interposed ileum and in the pancreatic islets, leading to metabolic beneficial effects and altered eating behavior.     

Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells

Purpose

Aspirating bone marrow from the iliac crest using small volumes of 1–4 ml with a 10-ml syringe has been historically proposed for harvesting adult mesenchymal stem cells and described as a standard technique to avoid blood dilution. The disadvantage of repeated small aspirations is that there is a significantly increased time to harvest the bone marrow. However, it is not known if a large volume syringe can improve the rate of bone marrow aspiration without increasing blood dilution, thus reducing the quality of the aspirate. We compared the concentrations of mesenchymal stem cells obtained under normal conditions with two different size syringes.

Methods

Thirty adults (16 men and 14 women with a mean age of 49?±?14 years) underwent surgery with aspiration of bone marrow from their iliac crest. Bilateral aspirates were obtained from the iliac crest of the same patients with a 10-ml syringe and a 50-ml syringe. Cell analysis determined the frequencies of mesenchymal stem cells (as determined by the number of colonies) from each size of syringe. The cell count, progenitor cell concentration (colonies/ml marrow) and progenitor cell frequency (per million nucleated cells) were calculated. All bone marrow aspirates were harvested by the same surgeon.

Results

Aspirates of bone marrow demonstrated greater concentrations of mesenchymal stem cells with a 10-ml syringe compared with matched controls using a 50-ml syringe. Progenitor cell concentrations were on average 300 % higher using a 10-ml syringe than matched controls using a 50-ml syringe (p?<?0.01).

Conclusions

In normal human donors, bone marrow aspiration from 30 patients demonstrated a reduced mesenchymal stem cell number in aspirates obtained using a larger volume syringe (50 ml) as compared with a smaller volume syringe (10 ml).