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Biomedical subjects

D Heber

Publications and source records attributed to D Heber.

At least 37 records · Page 2Linked to original sources
PubMed2001

Insulin-leptin-visceral fat relation during weight loss.

INTRODUCTION: The relation between insulin-leptin-visceral fat axis during weight loss has not been studied previously. AIMS: To evaluate the insulin, leptin, and abdominal adiposity relation during weight loss in patients with upper body obesity. METHODOLOGY: Twenty volunteers (7 men, 13 women) with mean age 50.6+/-6.3 (SD) and upper body obesity (weight 105.4+/-12.3 kg, BMI 35.9+/-2.5 kg/m2) were recruited. Participants were enrolled in a one-arm clinical study using a calorie-deficient diet and an escalating dose regimen of sibutramine, starting with 5 mg daily and increasing in 5-mg increments to 20 mg per day. Body weight, insulin, leptin, glucose, lipids, abdominal computed tomography (CT), and total body electrical conductance (TOBEC) were measured serially at weeks 0, 4, 8, 12, and 24. RESULTS: Eighteen patients completed the 6-month study: one man and one woman discontinued because of adverse events. With diet and sibutramine, body weight was significantly and continuously reduced throughout the 6-month study. There was a 16.0% (p = 0.0001) reduction in body weight (p < 0.001) and 22.5% (p = 0.0001) decrease in total body fat mass. Abdominal CT scans showed a 28.3% (p = 0.0001) reduction in total abdominal fat, a 26.0% (p = 0.0001) reduction in subcutaneous fat (p < 0.001), and a 31.0% (p = 0.0003) reduction in visceral fat (p < 0.001). There was a 32.0% (p = 0.0008) reduction in leptin levels and 37.9% (p = 0.0001) reduction in insulin levels between baseline and week 4, but no further significant reduction in leptin and insulin levels was observed for the duration of the study. There was a significant correlation between insulin and leptin concentrations throughout the study (p = 0.0001). Leptin was presented as a function of insulin measured at the same time. Significant associations between visceral abdominal fat, subcutaneous fat, and leptin were also observed. CONCLUSION: In this study, we found that leptin and insulin were related in weight loss. The data suggest that insulin may act as a strong regulator of leptin secretion during weight loss and that circulating leptin levels can be predicted by insulin level. Using sibutramine in conjunction with hypocaloric diet reduced body weight and decreased fat mass significantly. Visceral and subcutaneous abdominal fat depots were shown to decrease. Whether sibutramine exerts any selective reduction of visceral abdominal fat as opposed to total body fat mass will require further clinical investigation.

Adipose Tissue↗
PubMed2001

Green tea and its catechins inhibit breast cancer xenografts.

Investigators have shown that green tea may decrease the risk of cancer. It is widely accepted that the main active component of green tea is epigallocatechin-3-gallate (EGCG). In this study, we examined the effect of green tea on breast cancer growth and endothelial cells in in vitro assays and in animal models. Furthermore, we compared the potency of the different catechin components of green tea extract (GTE), including EGCG. Our data showed that mixed GTE and its individual catechin components were effective in inhibiting breast cancer and endothelial cell proliferation. In mouse experiments, GTE suppressed xenograft size and decreased the tumor vessel density. Our results demonstrated the value of all catechins and argued for the use of a mixed GTE as a botanical dietary supplement, rather than purified EGCG, in future clinical trials.

Animals↗
PubMed2001

Inverse associations between plasma lycopene and other carotenoids and prostate cancer.

Although dietary intake of tomatoes and tomato products containing lycopene has been reported to reduce the risk of prostate cancer, few studies have been done on the relationship between plasma lycopene and other carotenoids and prostate cancer. This case-control study was conducted to investigate the effects of plasma lycopene, other carotenoids, and retinol, as well as alpha- and gamma-tocopherols on the risk of prostate cancer. The study included 65 patients with prostate cancer and 132 cancer-free controls; all of them were interviewed using a standard epidemiological questionnaire at the Memorial Sloan-Kettering Cancer Center from 1993 to 1997. Plasma levels of carotenoids, retinol, and tocopherols were measured by high performance liquid chromatography. An unconditional logistic regression model was used in bivariate and multivariate analyses using Statistical Analysis System (SAS). After adjusting for age, race, years of education, daily caloric intake, pack-years of smoking, alcohol consumption, and family history of prostate cancer, significantly inverse associations with prostate cancer were observed with plasma concentrations of the following carotenoids: lycopene [odds ratio (OR), 0.17; 95% confidence interval (CI), 0.04-0.78; P for trend, 0.0052] and zeaxanthin (OR, 0.22; 95% CI, 0.06-0.83; P for trend, 0.0028) when comparing highest with lowest quartiles. Borderline associations were found for lutein (OR, 0.30; 95% CI, 0.09-1.03; P for trend, 0.0064) and beta-cryptoxanthin (OR, 0.31; 95% CI, 0.08-1.24; P for trend, 0.0666). No obvious associations were found for alpha- and beta-carotenes, retinol, and alpha- and gamma-tocopherols. Our study confirmed the inverse associations between lycopene, other carotenoids such as zeaxanthin, lutein, and beta-cryptoxanthin, and prostate cancer. This study provides justification for further research on the associations between lycopene and other antioxidants and the risk of prostate cancer.

Adult↗
PubMed2001

Pharmacokinetics of morphine 3-esters after oral administration in rabbits.

Pharmacokinetics of three morphine 3-esters-3-(2,2-dimethylvaleroyl) morphine (A), 3-(2-phenylbenzoyl) morphine (B), and 3-(2,2-diphenylpropionyl) morphine (C) was characterized after single oral administration in rabbits. Blood was sampled up to 24 h and cerebro-spinal fluid (CSF) was collected with the last blood sample. The concentration of the morphine 3-esters, morphine, morphine 3-glucuronide and morphine 6-glucuronide were determined in plasma and CSF using HPLC UV-detection. The morphine 3-esters were suggested to be a subject to marked presystemic elimination, since, in comparison to the administration of the un-esterified morphine, relatively low concentrations of morphine and morphine glucuronides were detected in plasma. The rate of disposition of morphine was dependent on the hydrolytic stability of the esters. The mean (+/- S.E.) plasma half-life of morphine was 0.9 +/- 0.2 h, 2.5 +/- 0.6 h and 3.5 +/- 3.5 h after the administration of A, B and C, respectively, compared to 0.9 +/- 0.2 h as estimated after the administration of non-esterified morphine. An analgesic effect will be achieved, since morphine was detected in CSF even 24 h after the application of the ester pro-drugs. It is concluded that esterification at the 3-position may be adapted to obtain sustained plasma levels of morphine.

Administration, Oral↗
PubMed2001

Evidence of an inhibitory effect of diet and exercise on prostate cancer cell growth.

PURPOSE: A high fat diet and sedentary lifestyle may predispose men to prostate cancer through effects on serum factors such as hormones. We evaluated the effects of a low fat, high fiber diet and exercise intervention on serum stimulated growth of established prostate cancer cell lines. MATERIALS AND METHODS: Fasting serum was obtained from 13 overweight men before and after undergoing an 11-day low fat, high fiber diet and exercise intervention. Serum was also obtained from 8 men who had complied with the regimen for a mean of 14.2 years. Hormone dependent LNCaP and independent PC-3 prostate cancer cell lines were grown in culture medium containing 10% of subject pre-intervention or post-intervention serum and viable cells were counted after 48 hours. Anthropometry, serum free testosterone, lipids and glucose were measured in all subjects. RESULTS: Post-intervention serum from each of the 11-day intervention subjects reduced LNCaP cell growth by a mean of 30% compared with pre-intervention serum from each (p <0.01). LNCaP cell growth in serum from long-term subjects was 15% below that of post-intervention serum (p <0.01). There was no difference in the growth of PC-3 cells when cultured with serum from either intervention group. Serum free testosterone, body weight, glucose and lipids were significantly reduced in 11-day subjects. CONCLUSIONS: A low fat, high fiber diet and exercise intervention resulted in serum changes that significantly reduced the growth of androgen responsive LNCaP prostate cancer cells in vitro.

Adult↗
PubMed2001

Reduced length of stay by implementation of a clinical pathway for bariatric surgery in an academic health care center.

Bariatric surgery is being performed in increasing numbers in an era when reimbursements are being reduced. Academic health centers bear the responsibility for training surgeons to perform these operations yet must keep costs to a minimum and retain high quality. The UCLA Bariatric Surgery Program developed a clinical pathway for the pre- and postoperative management for gastric bypass patients to achieve these goals. Medical records for 182 consecutive gastric bypass patients were retrospectively reviewed before implementation of the pathway (Group I) during the fiscal year of 1998/1999. Data on average length of stay, average intensive care unit length of stay, average standard variable cost, percentage readmission rate, and percentage return to the operating room were collected. This information was compared with the data collected prospectively from 182 patients after implementation of the pathway in July of 1999 (Group II) during the fiscal year of 1999/2000. Hospital cost per admission was reduced by 40 per cent in Group II compared with Group I (P < 0.02). The average length of stay was reduced from 4.05 days in Group I to 3.17 days in Group II (P < 0.033). Overall readmission rate was decreased from 4.2 per cent in Group I to 3.2 per cent in Group II (P < 0.05). There were no differences in morbidities between both groups. The pathway reduced costs by reducing the hospital length of stay, intensive care unit utilization, and readmission rates. Quality was maintained as evidenced by a similar pattern of postoperative morbidities yet readmission rates were reduced. Our results indicate that implementation of a clinical pathway for bariatric surgery reduces cost and improves quality of care in an academic institution.

Academic Medical Centers↗
PubMed2000

Determination of morphine 3-esters in rabbit plasma by high-performance liquid chromatography with ultraviolet detection.

A sensitive high-performance liquid chromatographic (HPLC) method for the quantitation of the morphine 3-esters 1[3-(2, 2-dimethylvaleroyl)-morphine (A), 3-(2-phenylbenzoyl)-morphine (B) and 3-(2,2-diphenylpropionyl)-morphine (C)] in rabbit plasma is described. Sample preparation was based on reversed-phase solid-phase extraction. The compounds were separated on C(18) reversed-phase analytical columns and then determined by ultraviolet detection. The recovery from plasma was 78.7 +/- 7.4%, 69.1 +/- 6.9% and 75 +/- 7.2% (mean +/- SD) for A, B, and C, respectively. The present method enabled the detection limit of 0.2, 0.2 and 0.1 ng and quantification limit of 20, 10 and 10 ng/ml for A, B and C, respectively. The developed method was used for determination of the plasmakinetics of these morphine 3-esters in rabbits.

Animals↗
PubMed1999

Synthesis, pharmacological and biophysical characterization, and membrane-interaction QSAR analysis of cationic amphiphilic model compounds.

Cationic amphiphilic drugs have a propensity to interact with biological interphases. This study was designed to gain more insight into the molecular properties of catamphiphilic drugs which govern this type of interaction. A series of phenylpropylamine model compounds were synthesized in which modifications were incorporated at the aromatic part of the molecule. The replacement of (45)Ca(2+) from phosphatidylserine monolayers served to monitor drug binding to the phospholipid. The influence on the phase-transition temperature of liposomes of dipalmitoylphosphatidic acid was measured to assess the perturbing action of the drugs on the structural organization of phospholipid assemblies. The antiarrhythmic activity of the compounds was determined in Langendorff preparations of guinea pig hearts to assess the membrane-stabilizing action. Quantitative structure-activity relationship (QSAR) models for these endpoints were developed using both intra- and intermolecular QSAR descriptors. Intermolecular membrane-interaction descriptors were derived from molecular dynamics simulations of the compounds in a model phospholipid monolayer. QSAR models were derived for all endpoints using partial least-squares regression (PLS) and a genetic algorithm tool, the genetic function approximation (GFA). Membrane-interaction descriptors appear to be of a particular importance in explaining the influence of the compounds on the phase-transition temperature of DPPA liposomes, while the other endpoints can be adequately modeled by intramolecular descriptors. The calcium-displacing activity at phosphatidylserine monolayers is governed by the electrostatic properties of the compounds. Measures of lipophilicity and molecular size are of particular importance for antiarrhythmic activity. Possible improvements to both the molecular modeling and the applied computational protocol of membrane-solute systems are identified and discussed.

Animals↗
PubMed1999

Novel 20-epi-vitamin D3 analog combined with 9-cis-retinoic acid markedly inhibits colony growth of prostate cancer cells.

BACKGROUND: 1,25 dihydroxyvitamin D3 (1,25D) and retinoids may play an important role in preventing progression of prostate cancer. METHODS: We examined the ability of four novel 20-epi-vitamin D3 analogs (CB1093, KH1060, KH1266, and CB1267), either alone or in combination with 9-cis retinoic acid (RA) to inhibit colony growth of a human prostate cancer cell line, LNCaP, using soft agar as well as bone marrow stroma. Also, the effect of these analogs on the cell cycle and expression of Ki-67, p21(waf-1), and p27(kip1) in LNCaP cells was examined. RESULTS: The analog CB1267 was the most potent, with 8 x 10(-10) M of the analog inhibiting 50% colony growth (ED50) of LNCaP. 9-cis-RA also inhibited colony growth of LNCaP (ED50, 5 x 10(-7) M). Combined, CB1267 and 9-cis-RA synergistically inhibited colony growth and significantly increased the number of LNCaP cells in G0/G1 phase. Cell cycle arrest was associated with increased levels of p21(waf-1) and p27(kip1) and decreased expression of Ki-67 protein. Pulse-exposure to this combination (5 x 10(-8) M) irreversibly inhibited colony growth, both in soft agar and on normal human bone marrow stroma. CONCLUSIONS: Combination of a new vitamin D3 analog (CB1267) and a retinoid (9-cis-RA) potently inhibited colony formation of LNCaP prostate cancer cells in vitro, suggesting further studies in animal models. This combination may afford an interesting therapeutic approach to low-burden prostate cancer.

Alitretinoin↗
PubMed1999

Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial.

CONTEXT: Orlistat, a gastrointestinal lipase inhibitor that reduces dietary fat absorption by approximately 30%, may promote weight loss and reduce cardiovascular risk factors. OBJECTIVE: To test the hypothesis that orlistat combined with dietary intervention is more effective than placebo plus diet for weight loss and maintenance over 2 years. DESIGN: Randomized, double-blind, placebo-controlled study conducted from October 1992 to October 1995. SETTING AND PARTICIPANTS: Obese adults (body mass index [weight in kilograms divided by the square of height in meters], 30-43 kg/m2) evaluated at 18 US research centers. INTERVENTION: Subjects received placebo plus a controlled-energy diet during a 4-week lead-in. On study day 1, the diet was continued and subjects were randomized to receive placebo 3 times a day or orlistat, 120 mg 3 times a day, for 52 weeks. After 52 weeks, subjects began a weight-maintenance diet, and the placebo group (n = 133) continued to receive placebo and orlistat-treated subjects were rerandomized to receive placebo 3 times a day (n = 138), orlistat, 60 mg (n = 152) or 120 mg (n = 153) 3 times a day, for an additional 52 weeks. MAIN OUTCOME MEASURES: Body weight change and changes in blood pressure and serum lipid, glucose, and insulin levels. RESULTS: A total of 1187 subjects entered the protocol, and 892 were randomly assigned on day 1 to double-blind treatment. For intent-to-treat analysis, 223 placebo-treated subjects and 657 orlistat-treated subjects were evaluated. During the first year orlistat-treated subjects lost more weight (mean +/- SEM, 8.76+/-0.37 kg) than placebo-treated subjects (5.81+/-0.67 kg) (P<.001). Subjects treated with orlistat, 120 mg 3 times a day, during year 1 and year 2 regained less weight during year 2 (3.2+/-0.45 kg; 35.2% regain) than those who received orlistat, 60 mg (4.26+/-0.57 kg; 51.3% regain), or placebo (5.63+/-0.42 kg; 63.4% regain) in year 2 (P<.001). Treatment with orlistat, 120 mg 3 times a day, was associated with improvements in fasting low-density lipoprotein cholesterol and insulin levels. CONCLUSIONS: Two-year treatment with orlistat plus diet significantly promotes weight loss, lessens weight regain, and improves some obesity-related disease risk factors.

Adult↗
PubMed1999

Nutrition and prostate cancer.

Scientific evidence suggests that differences in the diet may, in large part, account for the variability of prostate cancer rates around the world. Epidemiologic studies and animal experiments have yielded compelling results to warrant clinical intervention studies on nutrition from scientists who work on the prevention and treatment of prostate cancer. This article reviews the most recent evidence as to possible mechanisms of action of various dietary constituents, and explores evidence of various nutritional strategies for the prevention of prostate cancer progression.

Animals↗
PubMed1999

Reduced epinephrine-stimulated lipolytic activity in male golden-mantled ground squirrel during hibernation: an in situ microdialysis study.

We studied lipolytic activities in vivo in golden mantle ground squirrels during pre-hibernation and hibernation using microdialysis technique. Microdialysis probes were inserted into the abdominal subcutaneous adipose tissues. Baseline lipolysis were assessed by measuring glycerol concentration. Epinephrine-stimulated lipolysis was also examined. Eight squirrels (four male, four female) were studied in each of the two stages. Basal glycerol concentrations were lower in the hibernating state than in the pre-hibernation state in male squirrels (P < 0.05). Epinephrine application induced glycerol release in male and female squirrels (P < 0.001) in both stages. Male squirrels demonstrated a reduced epinephrine-stimulated glycerol release in the hibernating state, which was not observed in female squirrels.

Adipose Tissue↗
PubMed1999

Pharmacotherapy in the treatment of obesity.

The incorporation of pharmacotherapy into the comprehensive office-based management of obesity can improve outcomes significantly for patients meeting specific clinical guidelines in whom diet and lifestyle change alone is not successful. With an improved understanding of the mechanisms of action of various pharmacotherapies, it becomes possible for the primary care physician to help obese patients select successful therapeutic approaches and strategies. Some agents work primarily on central nervous system mechanisms related to satiety, while other agents affect metabolism and absorption of nutrients. It is of critical importance not to use pharmacotherapy alone, but rather combined with an aggressive program of diet and lifestyle change. The temptation of patients to find a magic pill that will close the refrigerator door is not likely to lead to a successful result. By gearing patients' expectations to realistic and achievable weight-loss goals, practitioners can reduce the risks of comorbid diseases, enhance ongoing treatment of existing comorbidities, and improve the overall quality of life for the obese patient.

Anti-Obesity Agents↗
PubMed1999

Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement.

BACKGROUND: We examined the cholesterol-lowering effects of a proprietary Chinese red-yeast-rice supplement in an American population consuming a diet similar to the American Heart Association Step I diet using a double-blind, placebo-controlled, prospectively randomized 12-wk controlled trial at a university research center. OBJECTIVE: We evaluated the lipid-lowering effects of this red-yeast-rice dietary supplement in US adults separate from effects of diet alone. DESIGN: Eighty-three healthy subjects (46 men and 37 women aged 34-78 y) with hyperlipidemia [total cholesterol, 5.28-8.74 mmol/L (204-338 mg/dL); LDL cholesterol, 3.31-7.16 mmol/L (128-277 mg/dL); triacylglycerol, 0.62-2.78 mmol/L (55-246 mg/dL); and HDL cholesterol 0.78-2.46 mmol/L (30-95 mg/dL)] who were not being treated with lipid-lowering drugs participated. Subjects were treated with red yeast rice (2.4 g/d) or placebo and instructed to consume a diet providing 30% of energy from fat, <10% from saturated fat, and <300 mg cholesterol daily. Main outcome measures were total cholesterol, total triacylglycerol, and HDL and LDL cholesterol measured at weeks 8, 9, 11, and 12. RESULTS: Total cholesterol concentrations decreased significantly between baseline and 8 wk in the red-yeast-rice-treated group compared with the placebo-treated group [(x+/-SD) 6.57+/-0.93 mmol/L (254+/-36 mg/dL) to 5.38+/-0.80 mmol/L (208+/-31 mg/dL); P < 0.001]. LDL cholesterol and total triacylglycerol were also reduced with the supplement. HDL cholesterol did not change significantly. CONCLUSIONS: Red yeast rice significantly reduces total cholesterol, LDL cholesterol, and total triacylglycerol concentrations compared with placebo and provides a new, novel, food-based approach to lowering cholesterol in the general population.

Adult↗