Neuroprotective effect of low-dose lidocaine in a rat model of transient focal cerebral ischemia.

BACKGROUND: A low concentration of lidocaine (10 microM) has been shown to reduce anoxic damage in vitro. The current study examined the effect of low-dose lidocaine on infarct size in rats when administered before transient focal cerebral isehemia. METHODS: Male Wistar rats (weight, 280-340 g) were anesthetized with isoflurane, intubated, and mechanically ventilated. After surgical preparation, animals were assigned to lidocaine 2-day (n = 10), vehicle 2-day (n 12), lidocaine 7-day (n = 13), and vehicle 7-day (n = 14) groups. A 1.5-mg/kg bolus dose of ildocaine was injected intravenously 30 mm before isehemia in the lidocaine 2-day and 7-day groups. Thereafter, an infusion was initiated at a rate of 2 mg x kg(-1) x h(-1) until 60 min of reperfusion after isehemia. Rats were subjected to 90 min of focal cerebral isehemia using the intraluminal suture method. Infarct size was determined by image analysis of 2,3,5-triphenyltetrazolium chloride-stained sections at 48 h or hematoxylin and eosin-stained sections 7 days after reperfusion. Neurologic outcome and body weight loss were also evaluated. RESULTS: The infarct size was significantly smaller in the lidocaine 2-day group (185.0+/-43.7 mm3) than in the vehicle 2-day group (261.3+/-45.8 mm3, P < 0.01). The reduction in the size of the infarct in the lidocaine 7-day group (130.4+/-62.9 mm3) was also significant compared with the vehicle 7-day group (216.6+/-73.6 mm3, P < 0.01). After 7 days of reperfusion, the rats in the lidocaine group demonstrated better neurologic outcomes and less weight loss. CONCLUSIONS: The current study demonstrated that a clinical anriarrhythmic dose of lidocaine, when given before and during transient focal cerebral isehemia, significantly reduced infaret size, improved neurologic outcome, and inhibited postisehemic weight loss.

Voluntary Weight Reduction in Older Men Increases Hip Bone Loss: The MrOS Study.

To test the hypothesis that weight loss in older men is associated with increased rates of hip bone loss irrespective of adiposity and intention to lose weight, we measured body weight, body composition, hip bone mineral density (BMD) and intention to lose weight in a cohort of 1,342 older men enrolled in the Osteoporotic Fractures in Men (MrOS) study and followed them prospectively for an average of 1.8 yr for changes in weight and BMD. The adjusted average rate of change in total hip BMD was 0.1% per year in men with weight gain, -0.3% per year in men with stable weight and -1.4% per year in men with weight loss (P for trend < 0.001). Higher rates of hip bone loss were observed in men with weight loss irrespective of category of body mass index, body composition, or intention to lose weight. Even among obese (body mass index >/= 30kg/m(2)) men trying to lose weight, those with documented voluntary weight reduction experienced an increase in hip bone loss (average rate of change in total hip BMD 0.5% per year in those with weight gain, -0.1% per year in those with stable weight and -1.7% per year in those with weight loss, P for trend < 0.001). Older men who experience weight loss have increased rates of hip bone loss, even among overweight and obese men undergoing voluntary weight reduction.

Effects of weight loss on PLTP activity and HDL particle size.

OBJECTIVE: Dyslipidaemia in obesity is characterized by hypertriglyceridaemia, low HDL-C levels, small, dense HDL particles and increased phospholipid transfer protein (PLTP) activity. METHODS: In the present study, we investigated PLTP activity and HDL particle size in 16 morbidly obese, middle-aged women, who underwent Swedish Adjustable Gastric Banding surgery. Study subjects were tested within 2 months before and 1 y after surgery. PLTP activity was determined by exogenous substrate assay and HDL particle size by gradient gel electrophoresis, respectively. RESULTS: Pronounced weight loss after gastric banding surgery resulted in a significant decrease of PLTP activity from 8.42+/-2.04 to 7.43+/-2.21 micromol/ml/h (P=0.02). The size of HDL(2) particles increased signficantly from 14.04+/-0.86 to 14.28+/-0.64 nm (P=0.02) after body weight reduction, while no change in HDL(3) particle size was apparent. DISCUSSION: Our results suggest that dyslipidaemia in obesity is--at least partially--reversible by weight loss. We hypothesize that reduction of PLTP activity and increase of HDL particle size are important component factors in converting the atherogenic lipoprotein profile of obese subjects into a less atherogenic profile with weight loss.

Pancreatin enhanced erosion of and macromolecule release from 2,2-bis(2-oxazoline)-linked poly(epsilon-caprolactone).

The degradation and erosion of solvent cast films and injection molded bars prepared from poly(epsilon-caprolactone) (PCL) and 2,2'-bis(2-oxazoline) linked poly(epsilon-caprolactone) (PCL-O) were evaluated in simulated gastric fluid (SGF) (pH 1.2, pepsin present) and in simulated intestinal fluid (SIF) (pH 7.5, pancreatin present). After incubation of the polymer films (10 mg) and bars (70 mg) in the medium, the resulting decrease in molecular weight (degradation) was determined by size exclusion chromatography and the weight loss of the preparations was measured. In addition, the effect of pancreatin on FITC-dextran (MW 4400) release from PCL and PCL-O microparticles, prepared by w/o/w double emulsion technique, was studied. No degradation or weight loss was observed for either PCL or PCL-O films in SGF (12 h incubation, 37 degrees C). When compared to PBS pH 7.4, pancreatin hardly enhanced the weight loss of PCL films and bars. In contrast, pancreatin enhanced substantially erosion of PCL-O films and bars. Unlike PCL preparations, the PCL-O preparations showed surface erosion in SIF. Pancreatin increased considerably FITC-dextran release from both PCL and PCL-O microparticles. In conclusion, the present results demonstrate the enzyme sensitivity of the novel PCL-O polymer. In addition, the results show that pancreatin present in intestinal fluid may substantially affect drug release from PCL based preparations.

Glycemic control in diabetic patients after bariatric surgery.

BACKGROUND: Morbid obesity is associated with a high prevalence of diabetes mellitus, and weight loss is fundamental to improve glycemic control. The aim of the present study was to evaluate the impact of weight reduction during the late postoperative period (> or = 12 months) after gastric bypass on the glycemic control of diabetic patients. METHODS: Fasting glycemia (glucose oxidase) and glycohemoglobin A1c (enzymatic fluorescence, reference value: 4-6%) were determined before and after surgery. Results were compared by the Student t-test for paired samples (P <0.05). RESULTS: 23 women and 8 men with diabetes, with a mean follow-up of 27.2 months and a mean age of 42.5 years (30-68), were studied. Before surgery, mean +/- SD weight, BMI, excess weight, glycemia and glycohemoglobin were 135.9+/-11.6 kg, 51.8+/-6.4 kg/m2, 68.3+/-14.5 kg, 173+/-71.2 mg/dl, and 7.4+/-1.9%, respectively. After surgery, mean weight, BMI, excess weight, percent weight loss, percent excess weight loss, glycemia and glycohemoglobin were 89.7+/-8.8 kg, 35+/-4.5 kg/m2, 24.6+/-11.6 kg, 32.6%+/-1.8 (12.6-46.5%), 64.7+/-18.3%, 98+/-17.3 mg/dl (P <0.01), and 5.4+/-1.0% (P <0.05), respectively. Oral anti-diabetic drug and/or insulin treatment was discontinued in 89.2% of the patients. After surgery, 90.3% of the patients maintained glycohemoglobin A1c levels <7.0%. CONCLUSION: weight loss led to a significant and sustained improvement of glycemic control in these patients submitted to bariatric surgery.

Determination of insulin, leptin and neuropeptide y by radioimmunoanalysis in patients with morbid obesity and anorexia nervosa after therapeutic interventionThe present study was conducted in order to analyze the relationship existing between leptin, insulin and neuropeptide Y (NPY) levels in massive weight loss and weight recovery. Twenty-three patients with severe obesity, 23 patients with anorexia nervosa and 28 healthy control subjects were studied. Patients with severe obesity underwent a vertical banded gastroplasty followed by an 800 kcal/day diet during 16 weeks, with evaluation taking place before (Body mass index, BMI, 52,1 8 Kg/m2) and after the drastic weight loss (BMI 39,2 6,2 Kg/m2). Patients with anorexia nervosa were treated with nutritional therapy exclusively during 16 weeks, and they were evaluated in the low weight situation (BMI 15,3 1,7 Kg/m2) and after weight recovery (BMI 18,9 2,8 Kg/m2). Normal subjects had a normal BMI from 20 to 27 (average 21,8 2 Kg/m2). BMI, percentage of body fat, and serum levels of leptin, insulin, and NPY, were determined in each patient and normal subjects. In severe obese patients serum leptin and insulin decreased significantly after drastic weight reduction (leptin: from 48,8 19,2 to 24,3 9,8 ng/ml; insulin: from 26,2 10,8 to 18 6 U/ml). In patients with anorexia nervosa serum leptin mean levels were significantly higher after weight recovery (3,7 1,9 vs 9,2 5,1 ng/ml). In subjects with morbid obesity NPY levels decreased after weight loss below those of control group (43,5 16,1 vs 57,3 12,8 pmol/l). On the other hand, patients with anorexia nervosa had NPY levels superior to those of control group. In subjects with anorexia, NPY levels decreased after weight recovery (69,1 16,7 a 59,1 20,3 pmol/l). In the whole population, Leptin and NPY plasma levels were correlated with body fat percentage. Leptin was positively correlated with BMI and body fat percentage in obese and anorectic subjects after weight loss or recovery, respectively. NPY was inversely correlated with body fat percentage in controls and obese subjects before treatment. These data reveal that the concentration of serum leptin and NPY correlates significantly with the total adiposity in subjects with a wide weight range and caloric intake. Leptin plasma levels are proportional to fat stores in patients with severe obesity and anorexia nervosa after drastic weight loss or recovery, respectively. NPY serum levels are negatively correlated with de total body fat in normal weight subjects and obese patients in their initial weight.

Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin, peptide YY, and insulin.

To help understand the mechanisms by which weight loss is maintained after Roux-en-Y gastric bypass (RYGBP), we measured circulating concentrations of total and bioactive octanoylated ghrelin, peptide YY (PYY), glucose, and insulin in the fasted state and in response to a liquid test meal in three groups of adult women: lean (n = 8); weight-stable 35 +/- 5 months after RYGBP (n = 12; mean body mass index, 33 kg/m(2)); and matched to the surgical group for body mass index and age (n = 12). Fasting plasma total ghrelin levels were nearly identical between RYGBP (425 +/- 54 pg/ml) and the matched controls (424 +/- 28 pg/ml) and highest in lean controls (564 +/- 103 pg/ml). The response to the test meal was comparable between lean and RYGBP groups, with 27% and 20% maximal suppression, respectively, whereas the magnitude of suppression was significantly diminished in the matched controls (17%) compared with the lean group. Fasting levels of octanoylated ghrelin were highest in the lean controls, 220 +/- 36 pg/ml vs. 143 +/- 27 in the RYGBP group (P = 0.05) and 127 +/- 12 pg/ml in the matched controls (P < 0.05). The magnitude of maximal postmeal suppression of octanoylated ghrelin was more marked than with total ghrelin, but similar among groups, ranging from 44-47%. In response to the test meal, there was an early exaggerated rise in PYY in the RYGBP group, such that the peak PYY concentration was 163 +/- 24 pg/ml compared with 58 +/- 17 (P < 0.01) and 77 +/- 23 (P < 0.05) in the matched and lean controls, respectively; area under the curve at 90 min was significantly greater compared with both control groups. Leptin and fasting insulin concentrations and homeostasis model of assessment insulin resistance indices were nearly identical between lean and RYGBP subjects and significantly higher in the body mass index-matched controls. In summary, the absence of a compensatory increase in ghrelin concentrations that usually occurs with diet-induced weight loss, and the exaggerated postprandial PYY response after RYGBP, may contribute to weight loss and to the ability of an individual to maintain weight loss after this surgical procedure.

Effect of weight loss on QT dispersion in obesity.

BACKGROUND: Sudden cardiac death in patients on a liquid protein diet has been suggested to be related to repolarization abnormalities. Although increased QT dispersion is also associated with sudden cardiac death, it has not been examined in the setting of weight loss using liquid protein diet. METHODS AND RESULTS: Sixty-three patients (mean age 42 years, 18 men) with a mean initial weight of 116 kg were randomly chosen from patients who had completed 26 weeks of liquid protein diet therapy. QT, corrected QT interval, QT dispersion and corrected QT dispersion were measured blindly along with serum albumin and electrolytes at the beginning and end of 26 weeks of liquid protein diet therapy. In 57 patients (89.5%) (group 1), QT dispersion shortened after weight loss while it was prolonged in 6 patients (10.5%) (group 2). The mean weight loss (group 1: 115+/-21 to 91+/-16 kg; group 2: 122+/-21 to 98+/-13 kg), and serum albumin and electrolyte levels before weight loss were the same in both groups. The decrease in QT dispersion in group 1 was due to increase in the minimum QT interval (350+/-22 v. 375+/-21 mis, p<0.01) after weight loss. However, the QT dispersion increase in group 2 was due to prolongation of the maximum QT interval (402+/-27 v. 441+/-19 ms, p<0.05) after weight loss. This suggests that shortening of the minimum QT interval causes the increased QT dispersion in obesity. Half the patients in group 2 showed a drop in the serum albumin level and 2 patients had an abnormally high phosphorous level at the end of the treatment. CONCLUSIONS: QT dispersion shortens in most patients (89.5%) using liquid protein diet for weight loss. However, increase of QT dispersion is seen in 10.5% of patients. The cause of increased QT dispersion in obesity (before weight loss) differs from that in patients after weight-loss using liquid protein diet. QT dispersion changes observed in this study may explain the risk of sudden cardiac death in these patients.