Breast cancer biomarkers predict weight loss after gastric bypass surgery

<p>Abstract</p> <p>Background</p> <p>Obesity has long been associated with postmenopausal breast cancer risk and more recently with premenopausal breast cancer risk. We previously observed that nipple aspirate fluid (n) levels of prostate specific antigen (PSA) were associated with obesity. Serum (s) levels of adiponectin are lower in women with higher body mass index (BMI) and with breast cancer. We conducted a prospective study of obese women who underwent gastric bypass surgery to determine: 1) change in n- and s-adiponectin and nPSA after surgery and 2) if biomarker change is related to change in BMI. Samples (30-s, 28-n) and BMI were obtained from women 0, 3, 6 and 12 months after surgery.</p> <p>Findings</p> <p>There was a significant increase after surgery in pre- but not postmenopausal women at all time points in s-adiponectin and at 3 and 6 months in n-adiponectin. Low n-PSA and high s-adiponectin values were highly correlated with decrease in BMI from baseline.</p> <p>Conclusions</p> <p>Adiponectin increases locally in the breast and systemically in premenopausal women after gastric bypass. s-adiponectin in pre- and nPSA in postmenopausal women correlated with greater weight loss. This study provides preliminary evidence for biologic markers to predict weight loss after gastric bypass surgery.</p

The effectiveness and efficiency of diabetes screening in Ontario, Canada: a population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Little is known about the efficiency and effectiveness of the current level of diabetes screening activity in Ontario where there is universal access to health services. Our study aims were to: (i) determine how often Ontarians are screened for diabetes; (ii) estimate screening efficiency based on the number needed to screen (NNS) to diagnosis one diabetes case; (iii) examine the population effectiveness of screening as estimated by the number of undiagnosed diabetes cases.</p> <p>Methods</p> <p>Ontario respondents of the Canadian Community Health Survey who agreed to have their responses linked to health care data (n = 37,400) provided the cohort. The five-year probabilities of glucose testing and diabetes diagnoses were estimated using a Cox Proportional Hazards Model. We defined NNS as the ratio of diabetes tests to number of diabetes diagnoses over the study period. We estimated the number of undiagnosed diabetes by dividing the number not tested at the end of study period by the NNS.</p> <p>Results</p> <p>80% of women and 66% of men had a blood glucose test within 5 years. The efficiency of screening was estimated by a NNS of 14 among men and 22 among women. 127,100 cases of undiagnosed diabetes were estimated, representing 1.4% of the Ontario adult population. Increasing age, hypertension, immigrant and non-white ethnicity, and number of general practitioner visits were associated with an increased likelihood of having a glucose test (LR χ2 p < 0.001). Low income men were less likely to be tested.</p> <p>Conclusions</p> <p>Diabetes screening was high in this population-based cohort of Ontarians. Screening efficiency varied considerably in the population. Undiagnosed diabetes continues to be prevalent and remains concentrated in the highest risk groups for diabetes, especially among men.</p

Influence of low birth weight on C-reactive protein in asymptomatic younger adults: the bogalusa heart study

<p>Abstract</p> <p>Background</p> <p>Both low birth weight, an indicator of intrauterine growth restriction, and low grade systemic inflammation depicted by high sensitivity C-reactive protein (hs-CRP) have emerged as independent predictors of cardiovascular (CV) disease and type 2 diabetes. However, information linking low birth weight and hs-CRP in a biracial (black/white) population is scant. We assessed a cohort of 776 black and white subjects (28% black, 43% male) aged 24-43 years (mean 36.1 years) enrolled in the Bogalusa Heart Study with regard to birth weight and gestational age data were retrieved from Louisiana State Public Health Office.</p> <p>Findings</p> <p>Black subjects had significantly lower birth weight than white subjects (3.145 kg vs 3.441 kg, p < 0.0001) and higher hs-CRP level (3.29 mg/L vs 2.57 mg/L, p = 0.011). After adjusting for sex, age, body mass index (BMI), smoking status and race (for total sample), the hs-CRP level decreased across quartiles of increasing birth weight in white subjects (p = 0.001) and the combined sample (p = 0.002). Adjusting for sex, age, BMI, smoking status and race for the total sample in a multivariate regression model, low birth weight was retained as an independent predictor variable for higher hs-CRP levels in white subjects (p = 0.004) and the total sample (p = 0.007). Conversely, the area under the receiver operative curve (c statistic) analysis adjusted for race, sex, age, smoking status and BMI yielded a value of 0.777 with regard to the discriminating value of hs-CRP for predicting low birth weight.</p> <p>Conclusions</p> <p>The deleterious effect of low birth weight on systemic inflammation depicted by the hs-CRP levels in asymptomatic younger adults may potentially link fetal growth retardation, CV disease and diabetes, with important health implications.</p

Leptin Contributes to the Adaptive Responses of Mice to High-Fat Diet Intake through Suppressing the Lipogenic Pathway

Background: Leptin is an adipocyte-derived hormone that plays a critical role in energy homeostasis and lipid metabolism. Overnutrition-associated obesity is known to be accompanied by hyperleptinemia. However, the physiological actions of leptin in the metabolic responses to high-fat diet (HFD) intake remain to be completely elucidated. Here we characterized the metabolic features of mice fed high-fat diets and investigated the impact of leptin upon the lipogenic program which was found to be suppressed by HFD feeding through a proteomics approach. Results: When maintained on two types of high-fat diets for up to 16 weeks, mice with a higher fat intake exhibited increased body fat accumulation at a greater pace, developing more severely impaired glucose tolerance. Notably, HFD feeding at 4 weeks elicited the onset of marked hyperleptinemia, prior to the occurrence of apparent insulin resistance and hyperinsulinemia. Proteomic analysis revealed dramatically decreased expression of lipogenic enzymes in the white adipose tissue (WAT) from HFD-fed mice, including ATP-citrate lyase (ACL) and fatty acid synthase (FAS). The expression of ACL and FAS in the liver was similarly suppressed in response to HFD feeding. By contrast, HFD-induced downregulation of hepatic ACL and FAS was significantly attenuated in leptin receptor-deficient db/db mice. Furthermore, in the liver and WAT of wild type animals, intraperitoneal leptin administration was able to directly suppress the expression of these two lipogenic enzymes, accompanied by reduced triglyceride levels both in the liver and serum. Conclusions: These results suggest that leptin contributes to the metabolic responses in adaptation to overnutrition through suppressing the expression of lipogenic enzymes, and that the lipogenic pathway represents a key targeted peripheral component in exerting leptin's liporegulatory actions. © 2009 Jiang et al

Mirror-Mark Tests Performed on Jackdaws Reveal Potential Methodological Problems in the Use of Stickers in Avian Mark-Test Studies

Some animals are capable of recognizing themselves in a mirror, which is considered to be demonstrated by passing the mark test. Mirror self-recognition capacity has been found in just a few mammals having very large brains and only in one bird, the magpie (Pica pica). The results obtained in magpies have enormous biological and cognitive implications because the fact that magpies were able to pass the mark test meant that this species is at the same cognitive level with great apes, that mirror self-recognition has evolved independently in the magpie and great apes (which diverged 300 million years ago), and that the neocortex (which is not present in the bird's brains) is not a prerequisite for mirror self-recognition as previously believed. Here, we have replicated the experimental design used on magpies to determine whether jackdaws (Corvus monedula) are also capable of mirror self-recognition by passing the mark test. We found that our nine jackdaws showed a very high interest towards the mirror and exhibited self-contingent behavior as soon as mirrors were introduced. However, jackdaws were not able to pass the mark test: both sticker-directed actions and sticker removal were performed with a similar frequency in both the cardboard (control) and the mirror conditions. We conclude that our jackdaws' behaviour raises non-trivial questions about the methodology used in the avian mark test. Our study suggests that the use of self-adhesive stickers on sensitive throat feathers may open the way to artefactual results because birds might perceive the stickers tactilely.JMPS was funded by Ministerio de Educación and Consejería de Innovación, C 420 iencia y Empresa under International Excellence Campus Program (CEI Granada) and TPC was funded by Ministerio de Educación y Ciencia by a postdoctoral contract from the project CGL2011-25634

Age-Related Changes in the Epithelial and Stromal Compartments of the Mammary Gland in Normocalcemic Mice Lacking the Vitamin D3 Receptor

The vitamin D3 receptor (VDR) serves as a negative growth regulator during mammary gland development via suppression of branching morphogenesis during puberty and modulation of differentiation and apoptosis during pregnancy, lactation and involution. To assess the role of the VDR in the aging mammary gland, we utilized 12, 14, and 16 month old VDR knockout (KO) and wild type (WT) mice for assessment of integrity of the epithelial and stromal compartments, steroid hormone levels and signaling pathways. Our data indicate that VDR ablation is associated with ductal ectasia of the primary mammary ducts, loss of secondary and tertiary ductal branches and atrophy of the mammary fat pad. In association with loss of the white adipose tissue compartment, smooth muscle actin staining is increased in glands from VDR KO mice, suggesting a change in the stromal microenviroment. Activation of caspase-3 and increased Bax expression in mammary tissue of VDR KO mice suggests that enhanced apoptosis may contribute to loss of ductal branching. These morphological changes in the glands of VDR KO mice are associated with ovarian failure and reduced serum 17β-estradiol. VDR KO mice also exhibit progressive loss of adipose tissue stores, hypoleptinemia and increased metabolic rate with age. These developmental studies indicate that, under normocalcemic conditions, loss of VDR signaling is associated with age-related estrogen deficiency, disruption of epithelial ductal branching, abnormal energy expenditure and atrophy of the mammary adipose compartment

Absence of an adipogenic effect of rosiglitazone on mature 3T3-L1 adipocytes: increase of lipid catabolism and reduction of adipokine expression

Aims/hypothesis: The thiazolidinedione (TZD) rosiglitazone is a peroxisome proliferator-activated receptor-¿ agonist that induces adipocyte differentiation and, hence, lipid accumulation. This is in apparent contrast to the long-term glucose-lowering, insulin-sensitising effect of rosiglitazone. We tested whether the action of rosiglitazone involves specific effects on mature adipocytes, which are different from those on preadipocytes. Materials and methods: Differentiated mature 3T3-L1 adipocytes were used as an in vitro model. Transcriptomics, proteomics and assays of metabolism were applied to assess the effect of rosiglitazone in different insulin and glucose conditions. Results: Rosiglitazone does not induce an increase, but rather a decrease in the lipid content of mature adipocytes. Analysis of transcriptome data, confirmed by quantitative RT-PCR and measurements of lipolysis, indicates that an altered energy metabolism may underlie this change. The pathway analysis shows a consistent picture dominated by lipid catabolism. In addition, we confirmed at both mRNA level and protein level that rosiglitazone represses adipokine expression and production, except for genes encoding adiponectin and apolipoprotein E. Moreover, transcriptome changes indicate that a general repression of genes encoding secreted proteins occurs. Conclusions/ interpretation: Our findings suggest that the change of adiposity as seen in vivo reflects a shift in balance between the different effects of TZDs on preadipocytes and on mature adipocytes, while the changes in circulating adipokine levels primarily result from an effect on mature adipocyte

Curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes

<p>Abstract</p> <p>Background</p> <p>Adipocytes express inflammatory mediators that contribute to the low-level, chronic inflammation found in obese subjects and have been linked to the onset of cardiovascular disorders and insulin resistance associated with type 2 diabetes mellitus. A reduction in inflammatory gene expression in adipocytes would be expected to reverse this low-level, inflammatory state and improve cardiovascular function and insulin sensitivity. The natural products, curcumin and resveratrol, are established anti-inflammatory compounds that mediate their effects by inhibiting activation of NF-κB signaling. In the present study, we examined if these natural products can inhibit NF-κB activation in adipocytes and in doing so reduce cytokine expression.</p> <p>Methods</p> <p>Cytokine (TNF-α, IL-1β, IL-6) and COX-2 gene expression in 3T3-L1-derived adipocytes was measured by quantitative real-time PCR (qRT-PCR) with or without TNFα-stimulation. Cytokine protein and prostaglandin E₂(PGE₂) expression were measured by ELISA. Effects of curcumin and resveratrol were evaluated by treating TNFα-stimulated adipocytes with each compound and 1) assessing the activation state of the NF-κB signaling pathway and 2) measuring inflammatory gene expression by qRT-PCR and ELISA.</p> <p>Results</p> <p>Both preadipocytes and differentiated adipocytes express the genes for TNF-α, IL-6, and COX-2, key mediators of the inflammatory response. Preadipocytes were also found to express IL-1β; however, IL-1β expression was absent in differentiated adipocytes. TNF-α treatment activated NF-κB signaling in differentiated adipocytes by inducing IκB degradation and NF-κB translocation to the nucleus, and as a result increased IL-6 (6-fold) and COX-2 (2.5-fold) mRNA levels. TNF-α also activated IL-1β gene expression in differentiated adipocytes, but had no effect on endogenous TNF-α mRNA levels. No detectable TNFα or IL-1β was secreted by adipocytes. Curcumin and resveratrol treatment inhibited NF-κB activation and resulted in a reduction of TNF-α, IL-1β, IL-6, and COX-2 gene expression (IC₅₀= 2 μM) and a reduction of secreted IL-6 and PGE₂(IC₅₀~ 20 μM).</p> <p>Conclusion</p> <p>Curcumin and resveratrol are able to inhibit TNFα-activated NF-κB signaling in adipocytes and as a result significantly reduce cytokine expression. These data suggest that curcumin and resveratrol may provide a novel and safe approach to reduce or inhibit the chronic inflammatory properties of adipose tissue.</p

Avoidable costs of physical treatments for chronic back, neck and shoulder pain within the Spanish National Health Service: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Back, neck and shoulder pain are the most common causes of occupational disability. They reduce health-related quality of life and have a significant economic impact. Many different forms of physical treatment are routinely used. The objective of this study was to estimate the cost of physical treatments which, despite the absence of evidence supporting their effectiveness, were used between 2004 and 2007 for chronic and non-specific neck pain (NP), back pain (BP) and shoulder pain (SP), within the Spanish National Health Service in the Canary Islands (SNHSCI).</p> <p>Methods</p> <p>Chronic patients referred from the SNHSCI to private physical therapy centres for NP, BP or SP, between 2004 and 2007, were identified. The cost of providing physical therapies to these patients was estimated. Systematic reviews (SRs) and clinical practice guidelines (CPGs) for NP, BP and SP available in the same period were searched for and rated according to the Oxman and AGREE criteria, respectively. Those rated positively for ≥70% of the criteria, were used to categorise physical therapies as Effective; Ineffective; Inconclusive; and Insufficiently Assessed. The main outcome was the cost of physical therapies included in each of these categories.</p> <p>Results</p> <p>8,308 chronic cases of NP, 4,693 of BP and 5,035 of SP, were included in this study. Among prescribed treatments, 39.88% were considered Effective (physical exercise and manual therapy with mobilization); 23.06% Ineffective; 13.38% Inconclusive, and 23.66% Insufficiently Assessed. The total cost of treatments was € 5,107,720. Effective therapies accounted for € 2,069,932.</p> <p>Conclusions</p> <p>Sixty percent of the resources allocated by the SNHSCI to fund physical treatment for NP, BP and SP in private practices are spent on forms of treatment proven to be ineffective, or for which there is no evidence of effectiveness.</p