Fate of goblet cells in experimental colitis

We sought to correlate the characteristic changes in goblet cell morphology in the chronically inflamed large intestine of IL10 ^–/– mice to specific changes in goblet cell gene expression. In healthy as well as IL10 ^–/– mice, marked differences were found among the large intestinal regions in goblet cell morphology and gene expression. The mucin Muc2, which is a major determinant of goblet cell morphology, was expressed in most goblet cells, yet only in cells staining positive for both Alcian blue and high iron diamine. TFF3 was expressed in only a small subset of goblet cells. Inflamed colon of IL10 ^–/– mice still contained high numbers of small, hypotrophic goblet cells with similar histochemical staining and Muc2 and TFF3 expression patterns, contradicting the often reported goblet cell depletion in colitis. Quantitatively, the Muc2 and TFF3 levels remained relatively stabile in IL10 ^–/– mice. Muc2 in distal IL10 ^–/– colon contained significantly less sulfate residues than in controls, which may compromise its protective properties.     

Maintenance of resting energy expenditure after weight loss in premenopausal women: potential benefits of a high-protein, reduced-calorie diet

The number of contemporary diet plans promoting high protein intakes for weight management has increased dramatically. Complementing this dietary approach with increased physical activity has proven to be beneficial. Recent studies have suggested that protein intakes in excess of the current Recommended Dietary Allowance (0.8 g/kg) may be of metabolic benefit during weight loss. This investigation assessed changes in resting energy expenditure and substrate oxidation in overweight and obese premenopausal women in response to a weight loss intervention that combined a high-protein, reduced-calorie diet with increased physical activity. Thirty-nine overweight and obese premenopausal women (age, 30.9 +/- 1.5 years; body mass index, 30.2 +/- 0.5 kg/m2) participated in a 10-week weight loss program in which they ate a reduced-calorie diet for which protein provided 30% of total energy and approximated 1.4 g/kg. Subjects incrementally increased physical activity (ie, steps walking) throughout the diet intervention period. Resting energy expenditure, substrate oxidation, and body composition were assessed before (PRE) and after (POST) the 10-week weight loss program. Subjects experienced a 5% decrease in body weight, with significant decreases in both fat mass (PRE, 35.5 +/- 1.2 kg; POST, 32.4 +/- 1.1 kg; P < .0001) and fat-free mass (PRE, 44.6 +/- 0.7 kg; POST, 43.6 +/- 0.7 kg; P < .0001). Changes in body weight or body composition did not alter resting energy expenditure. Protein oxidation increased (PRE, 18% +/- 1%; POST, 20% +/- 1%; P < .05) and fat oxidation decreased (PRE, 37% +/- 3%; POST, 30% +/- 3%; P < .05) after the 10-week intervention. These findings illustrate that a weight loss intervention combining consumption of a high-protein, reduced-calorie diet with increased physical activity promotes weight loss without negatively impacting resting energy expenditure in this population of women.     

Expression of six transmembrane protein of prostate 2 in human adipose tissue associates with adiposity and insulin resistance

CONTEXT: Six transmembrane protein of prostate 2 (STAMP2) is a counterregulator of adipose inflammation and insulin resistance in mice. Our hypothesis was that STAMP2 could be involved in human obesity and insulin resistance. OBJECTIVE: The objective of the study was to elucidate the role of adipose STAMP2 expression in human obesity and insulin resistance. DESIGN: The design was to quantify STAMP2 in human abdominal sc and omental white adipose tissue (WAT), isolated adipocytes, and stroma and in vitro differentiated preadipocytes and relate levels of STAMP2 in sc WAT to clinical and adipocyte phenotypes involved in insulin resistance. PARTICIPANTS: Nonobese and obese women and men (n = 236) recruited from an obesity clinic or through local advertisement. MAIN OUTCOME MEASUREMENT: Clinical measures included body mass index, body fat, total adiponectin, and homeostasis model assessment as measure of overall insulin resistance. In adipocytes we determined cell size, sensitivity of lipolysis and lipogenesis to insulin, adiponectin secretion, and inflammatory gene expression. RESULTS: STAMP2 levels in sc and visceral WAT and adipocytes were increased in obesity (P = 0.0008-0.05) but not influenced by weight loss. Increased WAT STAMP2 levels associated with a high amount of body fat (P = 0.04), high homeostasis model assessment (P = 0.01), and large adipocytes (P = 0.02). Subjects with high STAMP2 levels displayed reduced sensitivity of adipocyte lipogenesis (P = 0.04) and lipolysis (P = 0.03) to insulin but had normal adiponectin levels. WAT STAMP2 levels correlated with expression of the macrophage marker CD68 (P = 0.0006). CONCLUSION: Human WAT STAMP2 associates with obesity and insulin resistance independently of adiponectin, but the role of STAMP2 in obesity and its complications seems different from that in mice.     

A randomised controlled trial of integrated electrical stimulation and physiotherapy to improve mobility for people less than 6 months post stroke

Purpose: To investigate the feasibility of combining physiotherapy and functional electrical stimulation to improve gait post stroke. Methods: A parallel group partially single-blinded randomised clinical trial. Adults living at home, less than 6 months post stroke, were randomised to Group A (physiotherapy, n?=?10) or Group B (physiotherapy and common peroneal nerve stimulation, n?=?10). Assessments were conducted before randomisation (Week 1), after intervention (Week 8) and after 12 weeks follow-up (Week 20). Results: No between group differences were observed. There were statistically significant within group differences after the intervention period in both groups for walking speed and distance walked (without stimulation), Rivermead Mobility Index and Canadian Occupational Performance Measure, maintained at Week 20. There was statistically significant improvement in 10-m walking speed (Group B) when the stimulator was used at Week 8 (p?=?0.03, median 0.04?m/s (8%)). Only Group B had statistically significant within group change in Rivermead Visual Gait Analysis (Week 8), maintained at Week 20. Conclusions: Integrating electrical stimulation and physiotherapy was feasible and improved walking speed. There was no evidence of a training effect compared with physiotherapy alone. One-hundred forty-four participants per group would produce an adequately powered study based on this protocol.

• Implications for Rehabilitation

• At the end of the intervention period participants using electrical stimulation to correct dropped foot walked faster.

• It was feasible for electrical stimulation to be combined with physiotherapy for people less than 6 months post stroke.

• A larger adequately powered study is required to establish whether there are training effects associated with use of stimulation in this population.

     

Does Acetaldehyde Mediate Ethanol Action in the Central Nervous System?

BACKGROUND: Some of the effects of ethanol in the central nervous system are due to changes in function of ligand-gated ion channels. Production of detectable amounts of acetaldehyde, a primary metabolite of ethanol, has been demonstrated in brain homogenates. The aim of this study was to determine whether central actions that are often attributed to ethanol may actually be mediated by acetaldehyde. METHODS: The effects of acetaldehyde (1-1000 microM) were tested by two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes expressing 10 different ligand-gated ion channel receptors [alpha1 glycine; alpha1beta2gamma2Sgamma-aminobutyric acid (GABA)A; rho1 GABAc; 5-hydroxytryptamine-3A; NR1a/NR2A NMDA; GluR1/GluR2 AMPA; GluR6/KA2 kainate; and alpha4beta2, alpha4beta4, and alpha2beta4 nicotinic-acetylcholine] and the G-protein-coupled inward rectifying potassium channel GIRK2. We also investigated the effect of acetaldehyde on the dopamine transporter (DAT), performing dopamine uptake assays in oocytes expressing DAT. RESULTS: Acetaldehyde (1 and 10 microM) significantly enhanced alpha1 glycine receptor-mediated currents. Acetaldehyde did not affect the function of any of the other receptors tested or the potassium currents measured in GIRK2 channels. Moreover, acetaldehyde did not alter the DAT-mediated dopamine uptake. CONCLUSIONS: Our results suggest a potential minor role for acetaldehyde in the glycine receptor-mediated effects of ethanol. Otherwise, acetaldehyde does not modulate function of the neuronal receptors tested in this study, in GIRK channels or DAT, when expressed recombinantly in Xenopus laevis oocytes.