Polypharmacy for the elderly and associated factors were assessed. A cross-sectional study was conducted using data from the SABE Study (Health, Well-being and Aging), 2006. 1,115 individuals representing 422,377 elderly aged 65 or more, living in São Paulo City, were interviewed. Polypharmacy was defined as the use of five or more medications. A multivariate regression logistics was used. Polypharmacy prevalence was 36%. Female (OR = 1.7; IC 95%: 1.0; 2.9), age over 75 years (OR = 1.9; CI 95%: 1.3; 2.7), higher income (OR = 1.8; CI 95%: 1.2; 2.8), working (OR = 1.8; CI 95%: 1.1; 2.9), regular self assessed health (OR = 1.6; CI 95%: 1.1; 2.3) or poor (OR = 2.6; CI 95%: 1.4; 4.9), hypertension (OR = 2.0; CI 95%: 1.4; 2.9), diabetes (OR = 4.1; CI 95%: 2.2; 7.5), rheumatic diseases (OR = 2.3; CI 95%: 1.5; 3.6) and cardiac problems (OR = 2.9; CI 95%: 1.9; 4.5) were associated positively with polypharmacy. Using only the public health system (OR = 0.5, 95% CI: 0.3; 0.7) was inversely associated with polypharmacy. Medicines for the cardiovascular system and for the alimentary tract and metabolism were the most used. The knowledge of factors associated with polypharmacy, such as those identified in this study, may be useful to alert health professionals about the importance of identifying and monitoring the elderly groups most vulnerable to polypharmacy.

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Aim/hypothesis. By acting in the brain, insulin suppresses food intake. However, little is known with regard to insulin signalling in the hypothalamus in insulin-resistant states. Methods. Western blotting, immunohistochemistry and polymerase chain reaction assays were combined to compare in vivo hypothalamic insulin signalling through the PI3-kinase and MAP kinase pathways between lean and obese Zucker rats. Results. Intracerebroventricular insulin infusion reduced food intake in lean rats to a greater extent than that observed in obese rats, and pre-treatment with PI3-kinase inhibitors prevented insulin-induced anorexia. The relative abundance of IRS-2 was considerably higher than that of IRS-1 in hypothalamus of both lean and obese rats. Insulin-stimulated phosphorylation of IR, IRS-1/2, the associations of PI 3-kinase to IRS-1/2 and phosphorylation of Akt in hypothalamus were decreased in obese rats compared to lean rats. These effects seem to be mediated by increased phosphoserine content of IR, IRS-1/2 and decreased protein levels of IRS-1/2 in obese rats. In contrast, insulin stimulated the phosphorylation of MAP kinase equally in lean and obese rats. Conclusion/interpretation. This study provides direct measurements of insulin signalling in hypothalamus, and documents selective resistance to insulin signalling in hypothalamus of Zucker rats. These findings provide support for the hypothesis that insulin could have anti-obesity actions mediated by the PI3-kinase pathway, and that impaired insulin signalling in hypothalamus could play a role in the development of obesity in this animal model of insulin-resistance. [Diabetologia (2003[Diabetologia ( ) 46:1629[Diabetologia ( -1640 Keywords Obesity, insulin resistance, hypothalamus, anorexia, signal transduction, phosphatidylinositol 3-kinase/antagonists & inhibitors/*metabolism, mitogen-activated protein kinase. Abbreviations: ERK, extracellular signal-regulated kinase; Grb2, growth factor receptor binding protein 2; IR, insulin receptor; IRS, insulin receptor substrate; MAPK, mitogen-activated protein kinase; PI 3-kinase, phosphatidylinositol 3-kinase; PKC, Protein kinase C; Shc, Src-homology and collagen homology; SHP2, Src-homology phosphatase 2; TNF-α, Tumor-necrosis factor-α.

The ingestion of excessive amounts of saturated fatty acids (SFAs) and transfatty acids (TFAs) is considered to be a risk factor for cardiovascular diseases, insulin resistance, dyslipidemia, and obesity. The focus of this paper was to elucidate the influence of dietary SFA and TFA intake on the promotion of lipotoxicity to the liver and cardiovascular, endothelial, and gut microbiota systems, as well as on insulin resistance and endoplasmic reticulum stress. The saturated and transfatty acids favor a proinflammatory state leading to insulin resistance. These fatty acids can be involved in several inflammatory pathways, contributing to disease progression in chronic inflammation, autoimmunity, allergy, cancer, atherosclerosis, hypertension, and heart hypertrophy as well as other metabolic and degenerative diseases. As a consequence, lipotoxicity may occur in several target organs by direct effects, represented by inflammation pathways, and through indirect effects, including an important alteration in the gut microbiota associated with endotoxemia. Interactions between these pathways may perpetuate a feedback process that exacerbates an inflammatory state. The importance of lifestyle modification, including an improved diet, is recommended as a strategy for treatment of these diseases.

BackgroundIt is well known that high fat diets (HFDs) induce obesity and an increase in proinflammatory adipokines. Interleukin-6 (IL-6) is considered the major inflammatory mediator in obesity. Obesity is associated with a vitamin deficiency, especially of vitamins E and D3. We examined the effects of vitamin D3 and vitamin E supplementation on levels of IL-6 and IL-10 (as a marker of anti-inflammatory cytokines since, a balance between pro- and anti-inflammatory cytokines is maintained) protein expression in adipose tissue of mice provided with an HFD. Additionally, we measured the effects of vitamin E and vitamin D3 treatment on LPS-stimulated 3T3-L1 adipocytes IL-6 and IL-10 secretion.ResultsIL-6 protein levels and the IL-6/IL-10 ratio were decreased in epididymal white adipose tissue in groups receiving vitamins E and D3 supplementation compared to the HFD group. A 24-hour treatment of vitamin D3 and vitamin E significantly reduced the IL-6 levels in the adipocytes culture medium without affecting IL-10 levels.ConclusionsVitamin D3 and vitamin E supplementation in an HFD had an anti-inflammatory effect by decreasing IL-6 production in epididymal adipose tissue in mice and in 3T3-L1 adipocytes stimulated with LPS. Our results suggest that vitamin E and D3 supplementation can be used as an adjunctive therapy to reduce the proinflammatory cytokines present in obese patients.

Supplementation with epigallocatechin-3-gallate has been determined to aid in the prevention of obesity. Decaffeinated green tea extract appears to restore a normal hepatic metabolic profile and attenuate high-fat diet (HFD)-induced effects, thereby preventing non-alcoholic fatty liver disease in mice. Mice were maintained on either a control diet (CD) or HFD for 16 weeks and supplemented with either water or green tea extract (50 mg/kg/day). The body mass increase, serum adiponectin level, and lipid profile were measured over the course of the treatment. Furthermore, the AMPK pathway protein expression in the liver was measured. From the fourth week, the weight gain in the CD + green tea extract (CE) group was lower than that in the CD + water (CW) group. From the eighth week, the weight gain in the HFD + water (HFW) group was found to be higher than that in the CW group. Moreover, the weight gain in the HFD + green tea extract (HFE) group was found to be lower than that in the HFW group. Carcass lipid content was found to be higher in the HFW group than that in the CW and HFE groups. Serum analysis showed reduced non-esterified fatty acid level in the CE and HFE groups as compared with their corresponding placebo groups. Increased adiponectin level was observed in the same groups. Increased VLDL-TG secretion was observed in the HFW group as compared with the CW and HFE groups. Increased protein expression of AdipoR2, SIRT1, pLKB1, and pAMPK was observed in the HFE group, which explained the reduced expression of ACC, FAS, SREBP-1, and ChREBP in this group. These results indicate that the effects of decaffeinated green tea extract may be related to the activation of AMPK via LKB1 in the liver of HFD-fed mice.

Obesity is positively correlated to dietary lipid intake, and the type of lipid may play a causal role in the development of obesity-related pathologies. A major protein secreted by adipose tissue is adiponectin, which has antiatherogenic and antidiabetic properties. The aim of this study was to evaluate the effects of four different high-fat diets (enriched with soybean oil, fish oil, coconut oil, or lard) on adiponectin gene expression and secretion by the white adipose tissue (WAT) of mice fed on a selected diet for either 2 (acute treatment) or 60 days (chronic treatment). Additionally, 3T3-L1 adipocytes were treated for 48 h with six different fatty acids: palmitic, linoleic, eicosapentaenoic (EPA), docosahexaenoic (DHA), lauric, or oleic acid. Serum adiponectin concentration was reduced in the soybean-, coconut-, and lard-enriched diets in both groups. Adiponectin gene expression was lower in retroperitoneal WAT after acute treatment with all diets. The same reduction in levels of adiponectin gene expression was observed in epididymal adipose tissue of animals chronically fed soybean and coconut diets and in 3T3-L1 cells treated with palmitic, linoleic, EPA, and DHA acids. These results indicate that the intake of certain fatty acids may affect serum adiponectin levels in mice and adiponectin gene expression in mouse WAT and 3T3-L1 adipocytes. The effects appear to be time dependent and depot specific. It is postulated that the downregulation of adiponectin expression by dietary enrichment with soybean oil or coconut oil may contribute to the development of insulin resistance and atherosclerosis.

for the Chronic Diseases and Informed Decisions (CHRONIDE) Group IMPORTANCE As the rate of publication of new and sometimes conflicting medical research increases, clinicians rely heavily on clinical practice guidelines (CPGs) to inform practice. However, CPGs are of widely variable quality, and there are no existing objective measures to rate the quality of CPGs.OBJECTIVE To systematically assess 421 CPGs for the management of common noncommunicable diseases in primary care using the validated Appraisal of Guidelines for Research and Evaluation Instrument, version II (AGREE-II) tool and elucidate the factors associated with quality of CPGs.EVIDENCE REVIEW MEDLINE, Embase, the Cochrane Library, and 12 websites for CPGs were searched for CPGs for the management of common noncommunicable diseases in primary care published between January 1, 2011, and August 30, 2017. The assessment of the quality of CPGs was performed by 3 appraisers using the 6 domains of the AGREE-II instrument. A multiple logistic regression was performed to identify factors associated with quality of CPGs.FINDINGS Of the 421 CPGs reviewed, 23.5% (99) were classified as high quality. Among included guidelines, clarity of presentation (70%) and scope and purpose (61%) had the highest median AGREE-II scores. The domains with the lowest median scores were applicability (22%) and rigor of development (33%). Factors associated with high-quality CPGs included having more than 20 authors (odds ratio, 9.08; 95% CI, 3.35-24.62), development at governmental institutions (odds ratio, 10.38; 95% CI, 2.72-39.60), and reporting funding (odds ratio, 10.34; 95% CI,. Year of publication, region, guideline version, and scope were not associated with quality among included CPGs.CONCLUSIONS AND RELEVANCE Primary care professionals and policymakers should be aware that CPGs in primary care are of widely variable quality, with less than 25% of included CPGs rated as high quality. High-quality CPGs were associated with a higher number of authors, governmental institutions, and the report of funding. Region of origin was not associated with quality of CPGs, which suggests that the improvement of the quality of CPGs should be an international concern.