Attenuation of proteasome-induced proteolysis in skeletal muscle by {beta}-hydroxy-{beta}-methylbutyrate in cancer-induced muscle loss.

Loss of skeletal muscle is an important determinant of survival in patients with cancer-induced weight loss. The effect of the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) on the reduction of body weight loss and protein degradation in the MAC16 model of cancer-induced weight loss has been compared with that of eicosapentaenoic acid (EPA), a recognized inhibitor of protein degradation. HMB was found to attenuate the development of weight loss at a dose greater than 0.125 g/kg accompanied by a small reduction in tumor growth rate. When EPA was used at a suboptimal dose level (0.6 g/kg) the combination with HMB seemed to enhance the anticachectic effect. Both treatments caused an increase in the wet weight of soleus muscle and a reduction in protein degradation, although there did not seem to be a synergistic effect of the combination. Proteasome activity, determined by the "chymotrypsin-like" enzyme activity, was attenuated by both HMB and EPA. Protein expression of the 20S alpha or beta subunits was reduced by at least 50%, as were the ATPase subunits MSS1 and p42 of the 19S proteasome regulatory subunit. This was accompanied by a reduction in the expression of E2(14k) ubiquitin-conjugating enzyme. The combination of EPA and HMB was at least as effective or more effective than either treatment alone. Attenuation of proteasome expression was reflected as a reduction in protein degradation in gastrocnemius muscle of cachectic mice treated with HMB. In addition, HMB produced a significant stimulation of protein synthesis in skeletal muscle. These results suggest that HMB preserves lean body mass and attenuates protein degradation through down-regulation of the increased expression of key regulatory components of the ubiquitin-proteasome proteolytic pathway, together with stimulation of protein synthesis.

Biliopancreatic diversion with transitory gastric restriction and duodenal bulb preservation: 88 patients since 1992.

BACKGROUND: Over 10 years, 88 patients underwent biliopancreatic diversion with transitory gastric restriction (BPD-TGR) as a first choice operation or after gastric restrictive procedures. METHODS: From 1992 to 1999, BPD-TGR was performed on 71 patients as a first choice operation (Group 1 - BMI 41.9 +/- 6.5). The TGR was achieved by a polydioxanone (PDS) band. The duodenal bulb was maintained to 5 cm distal to the pylorus, constructing an end-to-side antecolic isoperistaltic duodeno-ileal anastomosis. Since 1993, a further 17 patients underwent BPD-TGR as a correction for restrictive procedures (Group 2 - BMI 37.4, range 27.2-61.0). RESULTS: Results in weight loss in Group 1 were similar to those in our previous classical BPD. Percent excess weight loss (%EWL) was 68.0 +/- 18.4, 75.9 +/- 12.3, and 75.4 +/- 12.0 at 1,5 and 10 years respectively. No patient had severe dysproteinemia (only 3% of patients had hypoalbuminemia of 3.0-3.4 g/dl). There was no case of diarrhea or halitosis. Anastomotic ulcers occurred in 2% of the patients. In Group 2, the patients had weight loss already present from the first operation, which continued after BPD-TGR with great variability from patient to patient. %EWL was 35.1 (range 0 to 72.5) and 35.2 (range 18.4 to 43.2) at 1 and 5 years. CONCLUSIONS: BPD-TGR appears to be an effective operation with few complications and also a satisfactory correction for failed gastric restrictive procedures, or even a sequential operation in the super-obese.

Dietary approaches for weight loss with increased fruit, vegetables and dairy.

Objective - To assess the consumption of fruit, vegetables and non-fat dairy products of subjects in a weight loss study where strategies were used to increase intakes. Design - Subjects were randomised to one of two diet and exercise weight loss programs for 12 weeks (n=40). The WELL diet (a Dietary Approaches to Stop Hypertension (DASH) type diet with a weight loss focus) included daily targets of four serves of fruits, four serves of vegetables and three serves of no fat dairy. The National Heart Foundation's (NHF) 'Healthy Weight Guide' diet included general advice to increase fruit and vegetable consumption but no specific targets. Subjects were visited or phoned fortnightly. They received group weight loss feedback as well as a personalized program that included lifestyle advice, feedback and goal setting. A food group counter recorded servings of fruit, vegetables and dairy products on three consecutive days of each week. Results of the first eight weeks are reported. Results - At week 8, number of serves/day of targeted foods were greater for the WELL diet than the NHF diet (mean difference+/-SEM): Fruit: 1.5+/-0.3, vegetables: 1.5+/-0.2, dairy: 1.3+/-0.1 serves/day (all P<0.01). Vegetables serves/day (mean+/-SEM) on the WELL diet increased from week two to week eight (week two: 3.3+/-0.2, week eight: 4.1+/-0.4 serves/day (P<0.05)). Daily fruit intake remained above target (week two: 4.7+/-0.2, week eight: 4.8+/-0.1 serves/day). Daily dairy intake remained below target (week two: 2.7+/-0.2, week eight: 2.8 +/-0.2serves/day). Conclusions - Changing dietary patterns may require different adjustment periods depending on the food type. Increasing fruit intake can be implemented quickly, whereas it takes a longer time to increase vegetable intake. Providing specific dietary targets appears to promote greater adherence to guidelines than general advice to increase intakes alone.

Liver volume and visceral obesity in women with hepatic steatosis undergoing gastric banding.

OBJECTIVE: To investigate the relationships between visceral obesity and hepatic steatosis in obese patients undergoing adjustable silicone gastric banding with the LAP-BAND. RESEARCH METHODS AND PROCEDURES: Six premenopausal, morbidly obese women with an ultrasonographic diagnosis of liver steatosis were evaluated before surgery and 8 and 24 weeks after surgery. Liver volume and body fat distribution were simultaneously analyzed by total-body multislices magnetic resonance imaging. RESULTS: Before surgery, the only variable found to be correlated with liver volume was visceral adipose tissue volume (r = 0.91; p < 0.01). weight loss was 9.9 +/- 3.8 kg in the period from 0 to 8 weeks (p < 0.01) and 7.1 +/- 4.9 kg in the the period from 8 to 24 weeks (p < 0.05). Total fat showed a statistically significant reduction of 6.2 +/- 4.0 liters in the 0- to 8-week period and a further significant reduction of 7.7 +/- 3.9 liters in the 8- to 24-week period. Visceral adipose tissue showed a statistically significant reduction of 1.0 +/- 0.9 liters in the 0- to 8-week period (p < 0.05) but only a further, not significant reduction of 0.6 +/- 0.7 liters in the 8- to 24-week period. The relative reduction of visceral fat in the 0-to 8-week period was higher than the relative reduction of total fat. Liver volume also showed a statistically significant reduction of 0.24 +/- 0.26 liters in the first phase of weight loss (p < 0.05), corresponding to a relative reduction of 12.3 +/- 10.6%. During the 8- to 24-week period, liver volume was substantially stable. DISCUSSION: Hepatomegaly was associated with visceral obesity in morbidly obese women with liver steatosis. In the phase of rapid weight loss after gastric surgery, a preferential mobilization of visceral fat, compared with total adipose tissue, occurred. This preferential visceral fat loss was associated with a significant reduction in liver volume.

Substance use and weight loss tactics among middle school youth.

OBJECTIVE: diet pills (DP) and vomiting or laxative (VL) use as weight loss tactics are associated with substance use in older adolescent populations. This study examined the association of weight loss tactics and substance use among middle school students. METHODS: A Youth Risk Behavior Survey was administered to 6,957 middle school students in eastern North Carolina. Multiple logistic regression examined substance use as predictors of DP and VL use. RESULTS: DP and VL use was reported by 6.0% and 7.1% of students, respectively, with each reported more frequently by females and White students. Regression analysis demonstrated alcohol, cigarette, or marijuana use as predictors for individual race/gender groups whereas steroid use was a predictor for all race/gender groups. We found a clustering effect of alcohol and cigarette use with both DP and VL use. DISCUSSION: Substance use is associated with weight loss tactics as early as middle school. More research in the areas of clustering of behaviors and age at onset is needed. Copyright 2002 by Wiley Periodicals, Inc.

Psychosis and delirium following metabolife use.

Weight gain is a well-known complication of antipsychotic therapy, especially when using newer atypical antipsychotic agents. In addition to the risk of medical comorbidities associated with weight gain, such as diabetes mellitus and cardiovascular disease, a further risk of antipsychotic-induced weight gain is that patients may resort to over-the-counter preparations to aid in weight loss. We report on a case in which a patient with schizophrenia began using Metabolife, an herbal preparation containing ephedra, for weight reduction and subsequently developed an exacerbation of his psychosis with superimposed delirium. We mention several relatively safe alternatives to herbal supplements for weight loss, as well as emphasize the need for clinicians to educate their patients regarding the potential risks of over-the-counter weight loss agents.

Factors of importance for weight loss in elderly patients with Parkinson's disease.

OBJECTIVE: weight loss is reported frequently in patients with Parkinson's disease (PD). The objective of this study was to find the underlying factors of this phenomenon. PARTICIPANTS AND METHODS: Twenty-six L-dopa-treated patients with PD and 26 age- and sex-matched healthy controls were assessed twice within a 1-year interval. Body weight, body fat mass, resting energy expenditure, physical activity, energy intake, thyroid hormones and cognitive function were investigated. RESULTS: Nineteen (73%) of the PD patients lost body weight, although energy intake and the time for rest increased. weight loss was most marked in patients with more severe PD symptoms and in whom cognitive function had decreased. Multiple regression analyses showed that determinants for weight loss were female gender, age and low physical activity. CONCLUSION: weight loss was common in PD patients, in spite of the increased energy intake and was most obvious in patients with increased PD symptoms and decreased cognitive function.

Surface modification of poly(ether urethane urea) with modified dehydroepiandrosterone for improved in vivo biostability.

In this study, a fatty acid urethane derivative of dehydroepiandrosterone (DHEA) was synthesized and evaluated as a polyurethane additive to increase long-term biostability. The modification was hypothesized to reduce the water solubility of the DHEA and physically anchor the additive in the polyurethane during implantation. Polyurethane film weight loss in water as a function of time was studied to determine the polymer retention of the modified DHEA. The polyurethane film with unmodified DHEA had significant weight loss in the first day (10%) that was previously correlated to rapid leaching of the additive. The polyurethane film with modified DHEA had significantly less weight loss at all time points indicating improved polymer retention. The effect of the modified DHEA additive on the biostability of a poly(ether urethane urea) was examined after 5 weeks of subcutaneous implantation in Sprague-Dawley rats. Optical micrographs and infrared analysis of the specimens indicated that the modified DHEA bloomed to the surface of the film forming a crystalline surface layer approximately 10-15 microns thick. After explantation, this surface layer was intact without measurable differences in surface chemistry as monitored by attenuated total reflectance-Fourier transform infrared spectroscopy. There was no evidence of degradation of the polyurethane underneath the modified DHEA surface layer as compared with the polyurethane control. We have concluded that the modified DHEA self-assembled into a protective surface coating that inhibited degradation of the polyurethane. The roughness of the modified DHEA surface layer prevented adherent cell analysis to determine if the additive retained the ability to down-regulate macrophage activity. Subsequent studies will investigate the ability of surface-modifying additives to modulate cellular respiratory bursts in addition to the formation of an impermeable barrier. This bimodal approach to improving biostability holds great promise in the field of polyurethane biomaterials. (c) 2005 Wiley Periodicals, Inc. J Biomed Mater Res 73A: 108-115, 2005.