[Ischemic burden vs. coronary artery morphology : What is crucial for the indication of revascularization?]. / Ischämielast versus Koronarmorphologie : Was ist entscheidend für die Indikation zur Revaskularisation?

Ischemic heart disease still represents the leading cause of death in the western world despite a decrease of mortality in the last decade. For the diagnostics of coronary artery morphology, invasive coronary angiography represents the gold standard. Nevertheless, in recent years the importance of functional diagnostics of the coronary arteries has increased and various imaging procedures for the measurement of fractional flow reserve (FFR) during coronary angiography were established and recommended for ischemia testing in the actual guidelines on myocardial revascularization.Imaging modalities for diagnostics of the functional relevance of coronary artery disease include stress echocardiography, magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). These procedures enable advanced risk stratification and therapy guiding in patients with suspected or known coronary artery disease. In future algorithms, hybrid imaging may facilitate the determination of anatomical and functional aspects after only one investigation.In the present article, the role of ischemia testing is compared with morphological methods for the diagnosis of coronary artery disease, individual risk stratification, and therapy guiding.

A randomized, double-blind, placebo-controlled study of the effects of pomegranate extract on rising PSA levels in men following primary therapy for prostate cancer.

BACKGROUND: The primary objective of this study was to compare the effects of pomegranate juice on PSA doubling times (PSADT) in subjects with rising PSA levels after primary therapy for prostate cancer. METHODS: Double-blind, placebo-controlled multi-institutional study, evaluated the effects of pomegranate liquid extract on serum PSA levels. The primary end point of this study was change in serum PSADT. Additional secondary and exploratory objectives were to evaluate the safety of pomegranate juice and to determine the interaction of manganese superoxide dismutase (MnSOD) AA genotype and pomegranate treatment on PSADT. RESULTS: One-hundred eighty-three eligible subjects were randomly assigned to the active and placebo groups with a ratio of 2:1 (extract N=102; placebo N=64; juice N=17). The majority of adverse events were of moderate or mild grade. Median PSADT increased from 11.1 months at baseline to 15.6 months in the placebo group (P<0.001) compared with an increase from 12.9 months at baseline to 14.5 months in the extract group (P=0.13) and an increase from 12.7 at baseline to 20.3 in the juice group (P=0.004). However, none of these changes were statistically significant between the three groups (P>0.05). Placebo AA patients experienced a 1.8 month change in median PSADT from 10.9 months at baseline to 12.7 months (P=0.22), while extract patients experienced a 12 month change in median PSADT from 13.6 at baseline to 25.6 months (P=0.03). CONCLUSIONS: Compared with placebo, pomegranate extract did not significantly prolong PSADT in prostate cancer patients with rising PSA after primary therapy. A significant prolongation in PSADT was observed in both the treatment and placebo arms. Men with the MnSOD AA genotype may represent a group that is more sensitive to the antiproliferative effects of pomegranate on PSADT; however, this finding requires prospective hypothesis testing and validation.

Worker hazards associated with the use of grain vacuum systems.

Over the past two decades, there has been more widespread use of pneumatic handling of grain at commercial grain storage facilities and on farms as these operations have increased grain storage capacity and handle larger volumes of grain and feed In some cases, manufacturers have suggested that the use of these systems is a safer alternative to removing residual grain manually in conjunction with the use of sweep augers. The use of grain vacuum systems has also been increasingly documented as a strategy in responding to grain storage fires and human entrapment and engulfment in flowing grain. With greater utilization of these machines have come reports of entrapments and engulfments. This article summarizes 27 such documented incidents, including 21 fatalities, that resulted from the use of portable grain vacuum systems. It includes specific recommendations for engineering, educational, and regulatory strategies to reduce the risks associated with the use of these systems.

Clinical efficacy of a medically supervised outpatient high-protein, low-calorie diet program is equivalent in prediabetic, diabetic and normoglycemic obese patients.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) affects approximately 10% of Americans, while 79 million Americans are estimated to have glucose intolerance or prediabetes (pre-DM). The present study was designed to determine whether obese patients with pre-DM or T2DM would lose weight as effectively as obese normoglycemic patients, in a medically supervised high-protein, low-calorie-weight management program. METHOD: Patients enrolled in a self-paid, university-based, outpatient weight loss program using prescribed very-low-calorie diet (VLCD) (500-800 cal per day) or LCD diet (800-1200 cal per day), recommended exercise and group behavioral counseling were studied retrospectively. Patients entering the program for the first time and attending weekly clinic visits for more than 4 weeks were included in the analysis. RESULTS: A total of 2093 obese patients, of whom 583 patients with pre-DM (fasting glucose 100 and <126 mg dl(-1)), 367 patients with T2DM and 1143 normoglycemic patients entered the program from 1991 to 2010, who met all the inclusion criteria were included in the analysis. The body weight at baseline was 104.0±20.0 kg for DM, 101.4±18.4 for pre-DM and 99.0±18.8 kg for non-DM. Weight loss and percent of weight loss within 12 months were analyzed using a linear mixed-effects model. There was no significant difference in weight loss between DM vs non-DM (P=0.4597) and pre-DM vs non-DM (P=0.6006) in 12 months. The length of enrollment in the program was positively correlated to weight loss rates in all patients (P<0.001). CONCLUSION: This study demonstrates that obese, pre-DM and DM patients all lost weight as effectively with VLCD or LCD over 12 months. Given the impact of weight loss on the progression of comorbid conditions, these data support the hypothesis that medically supervised diets, including VLCD and LCD, should be more widely used in the prevention and treatment of obese patients with pre-DM or T2DM.

Decrease of postprandial endothelial dysfunction by spice mix added to high-fat hamburger meat in men with Type 2 diabetes mellitus.

AIMS: Consumption of a high-fat diet has been demonstrated to promote endothelial dysfunction, possibly through an increase in lipid peroxidation and decrease in serum nitric oxide. The present study was designed to investigate whether consumption of a hamburger cooked with a polyphenol-rich spice mixture will reduce postprandial lipid oxidation and endothelial dysfunction in men with Type 2 diabetes. METHODS: Twenty-two subjects consumed burgers cooked with salt only (control burger) or with salt and spice mix (spice burger) in randomized order. The postprandial concentration of urinary malondialdehyde and nitrate/nitrite as well as the peripheral arterial tonometry score were determined. RESULTS: Eighteen subjects completed the study. Postprandial serum glucose, insulin and triglyceride concentrations were similar in all subjects after control burger or spice burger consumption. Urine malondialdehyde excretion in mmol/g creatinine was reduced by 31% (P < 0.001) after consuming the spice burger compared with the control burger. Two hours after consumption of the burgers, the peripheral arterial tonometry score was significantly different between control burger consumption (-9.7 ± 21.5%) and spice burger consumption (+18.0 ± 42.4%) (P = 0.025). Mean urinary nitrate/nitrite concentrations in urine collected during the 6 h after consumption of the control burger was 9.09 ± 5.7 mmol/g creatinine, but 12.37 ± 7.00 mmol/g creatinine after the spice burger (P = 0.053). CONCLUSION: Adding a spice mix to hamburger meat prior to cooking resulted in a reduction in urinary malondialdehyde, an increase in urinary nitrate/nitrite and improvement of postprandial endothelial dysfunction in men with Type 2 diabetes. Therefore, cooking a hamburger with a polyphenol-rich spice mixture may lead to potential cardiovascular benefits in patients with Type 2 diabetes mellitus.

Antimicrobial activity of doripenem against Gram-negative pathogens: results from INVITA-A-DORI Brazilian study

In vitro activity of doripenem and comparator antimicrobial agents was evaluated against Gram-negative bacilli recently isolated from Brazilian private hospitals that were enrolled in the INVITA-A-DORI Brazilian Study. A total of 805 unique Gram-negative bacilli were collected from patients hospitalized at 18 medical centers between May/08 and March/09. Each hospital was asked to submit 50 single Gram-negative bacilli isolated from blood, lower respiratory tract or intraabdominal secretions. Bacterial identification was confirmed and antimicrobial susceptibility testing was performed using Clinical Laboratory Standards Institute (CLSI) microdilution method at a central laboratory. CLSI M100-S21 (2011) or US-FDA package insert criteria (tigecycline) was used for interpretation of the antimicrobial susceptibility results. Doripenem was as active as meropenem and more active than imipenem against E. coli and K. pneumoniae isolates. A total of 50.0 percent of Enterobacter spp. isolates were resistant to ceftazidime but 85.7 percent of them were inhibited at doripenem MICs < 1 µg/mL. Polymyxin B was the only agent to show potent activity against Acinetobacter spp. (MIC50/90, < 0.5/1 µg/mL) and P. aeruginosa (MIC50/90, 1/2 µg/mL). Although high rates of imipenem (53.1 percent) and meropenem (44.5 percent) resistance were detected among P. aeruginosa, doripenem showed MIC50 of 16 µg/mL against imipenem-resistant P. aeruginosa and inhibited a greater number of imipenem-resistant P. aeruginosa (10.5 percent) at MIC values of < 4 µg/mL than did meropenem (0.0 percent). In this study, doripenem showed similar in vitro activity to that of meropenem and retained some activity against imipenem-resistant P. aeruginosa isolated from Brazilian medical centers.

Antimicrobial activity of doripenem against Gram-negative pathogens: results from INVITA-A-DORI Brazilian study.

In vitro activity of doripenem and comparator antimicrobial agents was evaluated against Gram-negative bacilli recently isolated from Brazilian private hospitals that were enrolled in the INVITA-A-DORI Brazilian Study. A total of 805 unique Gram-negative bacilli were collected from patients hospitalized at 18 medical centers between May/08 and March/09. Each hospital was asked to submit 50 single Gram-negative bacilli isolated from blood, lower respiratory tract or intraabdominal secretions. Bacterial identification was confirmed and antimicrobial susceptibility testing was performed using Clinical Laboratory Standards Institute (CLSI) microdilution method at a central laboratory. CLSI M100-S21 (2011) or US-FDA package insert criteria (tigecycline) was used for interpretation of the antimicrobial susceptibility results. Doripenem was as active as meropenem and more active than imipenem against E. coli and K. pneumoniae isolates. A total of 50.0% of Enterobacter spp. isolates were resistant to ceftazidime but 85.7% of them were inhibited at doripenem MICs < 1 µg/mL. Polymyxin B was the only agent to show potent activity against Acinetobacter spp. (MIC50/90, < 0.5/1 µg/mL) and P. aeruginosa (MIC50/90, 1/2 µg/mL). Although high rates of imipenem (53.1%) and meropenem (44.5%) resistance were detected among P. aeruginosa, doripenem showed MIC50 of 16 µg/mL against imipenem-resistant P. aeruginosa and inhibited a greater number of imipenem-resistant P. aeruginosa (10.5%) at MIC values of < 4 µg/mL than did meropenem (0.0%). In this study, doripenem showed similar in vitro activity to that of meropenem and retained some activity against imipenem-resistant P. aeruginosa isolated from Brazilian medical centers.

Fatty acid composition of California grown almonds.

Eight almond (Prunus dulcis L.) cultivars from 12 different California counties, collected during crop years 2004 to 2005 and 2005 to 2006, were extracted with petroleum ether. The extracts were subjected to GC-MS analyses to determine fatty acid composition of soluble lipids. Results indicated palmitic (C16:0), oleic (C18:1), linoleic (C18:2), and alpha-linolenic (C18:3) acid, respectively, accounted for 5.07% to 6.78%, 57.54% to 73.94%, 19.32% to 35.18%, and 0.04% to 0.10%; of the total lipids. Oleic and linoleic acid were inversely correlated (r=-0.99, P= 0.05) and together accounted for 91.16% to 94.29% of the total soluble lipids. Statistically, fatty acid composition was significantly affected by cultivar and county.

Feasibility of a low-fat/high-fiber diet intervention with soy supplementation in prostate cancer patients after prostatectomy.

OBJECTIVES: To evaluate the feasibility and long-term compliance with a low-fat diet supplemented with soy protein in men at increased risk for recurrence after radical prostatectomy. DESIGN: Randomized, control study. SETTING: Academic center in USA. SUBJECT: Forty men who had undergone radical prostatectomy and were at increased risk for recurrence. INTERVENTION: Low-fat (15% fat), high-fiber (18 g/1000 kcal) diet supplemented with 40 g soy protein isolate (n=26) was compared to USDA recommended diet (n=14). RESULTS: Over 4 years, subjects in the intervention group but not in the control group made and sustained significant changes in their diet as measured by the dietary assessment instruments and urinary isoflavone excretion. In the intervention group, dietary fat intake was reduced from 33.46+/-1.27% energy/day to 21.04+/-1.74% (P<0.05), fiber intake increased from 14.6+/-1.06 to 21.05+/-2.29 g/day. The insulin growth factor-1 (IGF-1) level was decreased from 260.4+/-8.6 ng/ml at baseline to 220.5+/-7.9 ng/ml at 6 months (P<0.05) in the intervention group with no significant change in the control group. An ex vivo assay demonstrated inhibition of LNCaP cell growth (-20.0+/-7.7%, P<0.05) by sera from patients in the intervention group after 6 months of dietary change compared to baseline. CONCLUSION: These data suggest that long-term low-fat dietary interventions as part of prospective randomized trials in prostate cancer survivors are feasible, and lead to reductions in circulating hormones or other growth factors stimulating prostate cancer growth ex vivo.

Weight cycling in a very low-calorie diet programme has no effect on weight loss velocity, blood pressure and serum lipid profile.

BACKGROUND: Many dieters lose and regain weight many times. It is unclear whether weight cycling is associated with adverse metabolic alterations or becomes more difficult with each attempt. METHODS: From 1988 to 2000, 2474 obese patients enrolled in our outpatient weight loss programme using a very low-calorie diet. Caloric intake consisted of meal replacement supplying 700-800 cal/day. RESULTS: Our search distinguished 480 patients who had restarted the weight reduction programme at least once and up to four times (restarts). All subjects remained on the programme for 2 weeks or more each time. Mean initial weight loss was 21.3 kg for women and 28.8 kg for men. Rate of weight loss on first restart was not different from initial weight loss for women [1.6 vs. 1.4 kg/week; not significant (NS)] or for men (2.2 vs. 2.1 kg/week; NS). Of the 480 patients, 85 women and 51 men entered the programme three times. Rate of weight loss was similar for all three entries (1.4, 1.6 and 2.1 kg/week for first, second and third entry in women, NS; 2.1, 2.1 and 2 kg/week for men, NS). Only 20 women and 18 men entered the programme four times. The rate of weight loss was again similar for both men (NS) and women (NS) during each re-entry. Cardiovascular risk factors including lipid profile and blood pressure were not adversely affected by weight cycling. In fact, lipid levels were lower at each restart. CONCLUSIONS: The present study refutes the hypothesis that repeated dieting makes further dieting efforts more difficult.

Phytoestrogens induce differential estrogen receptor alpha- or Beta-mediated responses in transfected breast cancer cells.

Increased intake of phytoestrogens may be associated with a lower risk of cancer in the breast and several other sites, although there is controversy surrounding this activity. One of the mechanisms proposed to explain the activity of phytoestrogens is their ability to bind and activate human estrogen receptor alpha (ERalpha) and human estrogen receptor beta (ERbeta). Nine phytoestrogens were tested for their ability to transactivate ERalpha or ERbeta at a range of doses. Mammary adenocarcinoma (MCF-7) cells were co-transfected with either ERalpha or ERbeta, and an estrogen-response element was linked to a luciferase reporter gene. Dose-dependent responses were compared with the endogenous ligand 17beta-estradiol. Purified genistein, daidzein, apigenin, and coumestrol showed differential and robust transactivation of ERalpha- and ERbeta-induced transcription, with an up to 100-fold stronger activation of ERbeta. Equol, naringenin, and kaempferol were weaker agonists. When activity was evaluated against a background of 0.5 nM 17beta-estradiol, the addition of genistein, daidzein, and resveratrol superstimulated the system, while kaempferol and quercetin were antagonists at the highest doses. This transfection assay provides an excellent model to evaluate the activation of ERalpha and ERbeta by different phytoestrogens in a breast cancer context and can be used as a screening bioassay tool to evaluate the estrogenic activity of extracts of herbs and foods.

Analysis of weight loss outcomes using VLCD in black and white overweight and obese women with and without metabolic syndrome.

OBJECTIVE: To evaluate the efficacy of very low calorie diet (VLCD) in black and white obese women. Changes in weight, metabolic profile, and body composition are assessed. METHOD: Patients are enrolled in a self-paid, university-based, outpatient weight loss program. All are prescribed VLCD (500-800 Cal/day), an exercise regimen, and group behavioral counseling. Black and white patients are matched for age, weight, body mass index, and by metabolic syndrome (MS) status. RESULTS: A total of 304 black and white women (152 in each group) were included the analysis. Approximately 40% of patients had MS (white women: 39.5%; black women: 41.2%). Mean baseline weights were similar. After 12 weeks, weight reduction of 9.97% was seen in white women and 9.02% drop was seen in black women (both P<0.0001). However, the degree of weight change was not different between the groups (P = 0.244). Marked improvements in fasting glucose, total cholesterol, LDL, triglyceride, and blood pressures (BP) were observed (all P<0.01); however, no difference between cohorts were seen. Patients with MS had higher baseline weight, BP, glucose and triglyceride levels when compared to patients without MS (all P<0.01). Significant reductions in % body fat were seen in white and black patients, independent of MS status. CONCLUSION: Obese patients, independent of race, were able to achieve significant weight loss when enrolled in a structured outpatient program. Weight loss significantly correlated with all aspects of MS. Our results suggest that differences seen in past studies may be influenced by socioeconomic and behavioral factors rather than differences in physiological response to dieting.

Long-term efficacy of soy-based meal replacements vs an individualized diet plan in obese type II DM patients: relative effects on weight loss, metabolic parameters, and C-reactive protein.

BACKGROUND: Achieving significant weight loss and glycemic control in diabetic patients remains a challenging task. OBJECTIVE: This study compared the effects of a soy-based meal replacement (MR) plan vs an individualized diet plan (IDP; as recommended by the American Diabetes Association) on weight loss and metabolic profile. DESIGN/SUBJECTS: A total of 104 subjects were randomized prospectively to the two treatments for a total of 12 months. RESULTS: In all, 77 of the 104 subjects completed the study. Percentage weight loss in MR group (4.57+/-0.81%) was significantly greater (P<0.05) than in IDP group (2.25+/-0.72%). Fasting plasma glucose was significantly reduced in MR group (126.4+/-4.9 mg/dl) compared with IDP group (152.5+/-6.6 mg/dl, P<0.0001) at 6 months but not at 12 months. Controlling for baseline levels, hemoglobin Alc level improved by 0.49+/-0.22% for those receiving MR when compared to IDP group (P<0.05). A greater number of subjects in MR group reduced their use of sulfonylureas (P<0.0001) and metformin (P<0.05) as compared to IDP group. High-sensitivity C-reactive protein (hs-CRP) decreased -26.3% (P = 0.019) in MR group compared to -7.06% (P = 0.338) in IDP group at 6 months. Similar changes were observed at 12 months with MR groups, with hs-CRP decreasing by -25.0% (P = 0.019) compared to -18.7% (P = 0.179) in IDP group. CONCLUSION: This study demonstrates that MR is a viable strategy for weight reduction in diabetic patients, resulting in beneficial changes in measures of glycemic control and reduction of medications.

Feasibility of a partial meal replacement plan for weight loss in low-income patients.

BACKGROUND: Low-income patients are disproportionately affected by obesity. Routine care is available to this population at the Venice Family Clinic (VFC) in Los Angeles. The current study examined the effectiveness of nutrition clinic utilizing meal replacements (Slim-Fast, Slim-Fast Foods Co., FL, USA) in low-income patients over a 6-month period compared with the routine care by their primary care physician (PMD) prior to enrolling in the nutrition clinic at similar time intervals. METHODS: In total, 63 patients (51 F; 49+/-0.8 yo) who had been followed at the VFC by their PMD for at least 6 months were enrolled in this study. Patients had a body mass index (BMI) of 40+/-1.1 kg/m2, were 72% Hispanic, 25% Caucasian, and 3% African American. They had the following co-morbidities: hypertension (HTN) 45%, diabetes mellitus II (DM II) 50%, gastroesophageal reflux disease (GERD) 34%, osteoarthritis 51%, and hypercholesterolemia 48%. All patients were provided with meal replacements to be taken twice a day and were instructed to consume one complete low calorie meal per day. Weights at the first visit to the nutrition clinic, 1, 3, and 6 months after enrollment in nutrition clinic were compared to their weights at the same time intervals during routine visits to their PMD prior to enrollment in the nutrition clinic. RESULTS: There was no significant weight change during the 6 months prior to enrollment in the nutrition program despite receiving care by a PMD. At 6 months after participating in the nutrition program, there was a mean decrease of 7% body weight with a reduction in BMI from 40-37 kg/m2 (P< or =0.05). CONCLUSION: Implementation of nutrition clinic utilizing meal replacements in this low-income patient population was effective in achieving a significant reduction in weight over 6 months of treatment..

Genetic diversity of Echinacea species based upon amplified fragment length polymorphism markers.

The taxonomy of Echinacea is based on morphological characters and has varied depending on the monographer. The genus consists of either nine species and four varieties or four species and eight varieties. We have used amplified fragment length polymorphisms (AFLP) to assess genetic diversity and phenetic relationships among nine species and three varieties of Echinacea (sensu McGregor). A total of 1086 fragments, of which approximately 90% were polymorphic among Echinacea taxa, were generated from six primer combinations. Nei and Li's genetic distance coefficient and the neighbor-joining algorithm were employed to construct a phenetic tree. Genetic distance results indicate that all Echinacea species are closely related, and the average pairwise distance between populations was approximately three times the intrapopulation distances. The topology of the neighbor-joining tree strongly supports two major clades, one containing Echinacea purpurea, Echinacea sanguinea, and Echinacea simulata and the other containing the remainder of the Echinacea taxa (sensu McGregor). The species composition within the clades differs between our AFLP data and the morphometric treatment offered by Binns and colleagues. We also discuss the suitability of AFLP in determining phylogenetic relationships.

The prototypic antidepressant drug, imipramine, but not Hypericum perforatum (St. John's Wort), reduces HPA-axis function in the rat.

Dysregulation in corticotropin-releasing hormone (CRH) secretion in the hypothalamus-pituitary-adrenal (HPA) axis may be involved in the etiology of major depressive disorder (MDD). Chronic therapy with standard antidepressant drugs, such as imipramine, can downregulate HPA axis function, indicating that the HPA axis may be an important target for antidepressant action. We tested several doses of a standardized commercial preparation of Hypericum perforatum plant extract (popularly known as St. John's Wort), a medicinal herb used for treating mild depressive symptoms, to determine whether it also modulated HPA axis function. Chronic imipramine treatment (daily injections for 8 weeks) of male Sprague-Dawley rats significantly downregulated circulating plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone compared to animals treated with saline. However, chronic St. John's Wort treatment (daily gavage for 8 weeks) had no effect on plasma ACTH or corticosterone, even at the highest doses tested. Our results confirm previous findings that imipramine may have significant peripheral HPA axis-mediated effects. However, our data does not support any role for H. perforatum in modulation of HPA axis function, suggesting that alternative pathways may be involved in mediating its antidepressant effects.

Psychometric characteristics of the General Well-Being Schedule (GWB) with African-American women.

The General Well-Being Schedule (GWB) is a brief, reliable, and valid instrument used in population studies to assess psychological well-being, although its validity with African-Americans has yet to be established. This study evaluated the reliability, validity, and factor structure of the GWB in a sample of 599 overweight African-American women who participated in multicenter weight loss trial. The results of the factor analysis indicate that the GWB is primarily unidimensional and that the existence of the six hypothesized subscales was not supported. The GWB demonstrated evidence of concurrent and construct validity when examined in association with measures of self-concept, depression, and several health behaviors. The results of this study suggest that the GWB is a reliable and valid measure of psychological well-being in African-American women.

Novel therapeutic approach: ligands for PPARgamma and retinoid receptors induce apoptosis in bcl-2-positive human breast cancer cells.

Effective treatment of tumors is often associated with activation of the endogenous apoptosis pathways. We have studied eight breast cancer cell lines (MCF-7, BT20, BT474, MDA-MB-231, MDA-MB-436, SKBR3, T-47D, ZR-75-1) possessing a variety of genetic defects. The clonogenic growth of breast cancer cell lines was inhibited by a ligand for PPARgamma (troglitazone, TGZ) combined with a ligand for either retinoid X receptor (RXR) (LG10069) (4/8 cell lines), RAR (ATRA) (5/8 cell lines) or RAR/RXR and RXR/RXR (9-cis-RA) (5/8 cell lines) independent of their expression of bcl-2, bag-1, ERalpha, and p53. The cell lines (MCF-7, T-47D, ZR-75-1), which expressed both BRCA1 and p27, were extremely sensitive to the inhibitory effect of the combination of TGZ and either ATRA or 9-cis-RA (ED90, 2-5 x 10(-11) M). However, only MCF-7, MDA-MB-231, and ZR-75-1 cells, which expressed a high level of bcl-2 protein, underwent apoptosis when exposed to the combination of TGZ and either ATRA or 9-cis-RA. Importantly, this effect was independent of expression levels of p53, ERalpha, HER-2/neu, bag-1, and BRCA1. Therefore, the combination of ligands for PPARgamma and retinoid receptors may have a therapeutic role for breast cancer.

Baicalin is a major component of PC-SPES which inhibits the proliferation of human cancer cells via apoptosis and cell cycle arrest.

BACKGROUND: PC-SPES is an eight-herb mixture that was shown to have activity against prostate cancer. Recently, we isolated a major component (6% of the total ethanolic extract) known as baicalin from PC-SPES by high performance liquid chromatography (HPLC). METHODS: Baicalin was evaluated for its ability to inhibit clonal growth, and to induce cell cycle arrest of various cancer types (PC-3, DU145, LNCaP prostate cancer cell lines, MCF-7 breast cancer cell line, HL-60 myeloblastic leukemia cell line, and NB4 promyelocytic leukemia cell line). The ability of baicalin to induce apoptosis of cancer cells was examined by both staining with Annexin V and detection of cleavage of Poly (ADP-ribose) polymerase (PARP)(3). Western blot analysis examined the effect of baicalin on levels of p21(waf1) and p27(kip1) in those cells. Futhermore, induction of differentiation in HL-60 cells was measured by expression of CD11b. RESULTS: Baicalin inhibited the clonal proliferation of LNCaP and PC3 prostate cancer cell lines, and the HL-60 and NB4 myeloblastic/promyelocytic leukemia cell lines with a 50% inhibition (ED(50)) that ranged between 6.4 x 10(-6) to 12 x 10(-6) mol/L. Cell cycle analysis showed that baicalin (2 x 10(-5) mol/L, 4 days) caused a G(0)/G(1) and G(2)/M accumulation of LNCaP and HL-60 cells, respectively. Concomitantly, differentiation and apoptosis were induced in HL-60 cells, as measured by expression of CD11b antigen, staining with annexin V, and detection of cleavage of PARP. Moreover, baicalin enhanced the expression of the cyclin-dependent kinase inhibitor, p27(kip1) in LNCaP and HL-60 cells. CONCLUSIONS: Baicalin inhibited the proliferation of cancer cells via apoptosis and cell cycle arrest, in which p27(kip1) may play a role. Baicalin may be a novel, adjunctive therapy for selected malignancies including prostate cancer.

Biexponential model for predicting weight loss after gastric surgery for obesity.

BACKGROUND: Following gastric restrictive surgery, morbidly obese patients rarely achieve their ideal body weight defined by Metropolitan Life tables. The final body weight will depend on the initial body composition because there will be greater weight loss from fat than lean body mass. The purpose of this study was to develop a mathematical model that accurately estimates the rate and extent of weight loss following gastric bypass surgery. METHODS: Patients underwent gastric bypass followed by intensive medical therapy and serial bioelectrical impedance analysis (BIA) body composition measurements. Differential equations were derived to model weight loss. RESULTS: Weight loss in the fat and lean body compartments followed monoexponential decay kinetics with differing rate constants. Total body weight loss (W(T)) at time t was W(T) = k(f)(k(f) - k(l)) (W(f(o))e(-k(f)t) + W(l(o))e(-k(l)t)), where W(fo) and W(lo) are the initial fat and lean body masses determined by BIA and k(f) and k(l) are the rate constants for the fat and lean compartments, respectively. Following surgically induced weight loss, k(f) = 7.61 +/- 1.27 x 10(-2), and k(l) = -0.93 +/- 0.13 x 10(-2), with the ratio of residual sum of the squares to the total sum of the squares of 98.8%. CONCLUSION: Accurate prediction of weight loss depends on the initial fat and lean compartment mass since each of these loses weight at a different rate and to a different extent. When these effects are accounted for, the total body weight loss can be accurately predicted for any given time following surgery.