Curcumin supplementation for relief of pain associated with osteoarthritis

NSAID Nonsteroidal Anti-inflammatory drug OA Osteoarthritis WOMAC Western Ontario and McMaster Universities Osteoarthritis Index VAS Visual analogue scale LPFI Lequesne Pain and Function Index KOA Knee osteoarthritis ROS Reactive oxygen species ADL Activity of daily living BMI Body mass index Objective: To determine if curcumin supplementation compared to nonsteroidal anti-inflammatory drugs (NSAIDs), placebo, and rescue medications is an effective treatment of arthritic symptoms in males and females between the ages of 50 and 80 with a diagnosis of osteoarthritis. Design: Systematic Literature Review Methods: Searches were done in PubMed, Google Scholar, and Scopus utilizing the terms “turmeric”, “curcumin”, “osteoarthritis”, “NSAIDs”, “ibuprofen”, and “placebo.” The following limits were applied: excluded if compared greater than two remedies for treatment of osteoarthritis or if turmeric was used as an “add-on” for treatment. Articles were included if they only dealt with human subjects, were published in 2014 or later, and were full-text. Results: A randomized control trial byKuptniratsaikul, V. et al concluded that curcumin was as efficacious as ibuprofen in reducing pain and improving function associated with Osteoarthritis (OA) with the benefit that curcumin resulted in less gastrointestinal complaints. Srivastave, S. et al concluded that curcumin can be used with diclofenac to provide relief in patients with knee OA. The results demonstrated that patients in the curcumin and diclofenac group had improvement in all three measures of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score when compared to patients in the placebo group. Panahi Y. et al study showed a statistical significant improvement in measures of the WOMAC score in the curcumin group while the placebo group showed no change in WOMAC parameters. The curcumin group also had significant reduction in Visual Analogue Scale (VAS) and Lequesne Pain and Function Index (LPFI) scores compared to placebo. Conclusion: Curcumin may provide relief of osteoarthritic symptoms as demonstrated by subjective measures of pain and objective measures of inflammation. Additionally, curcumin has a strong safety profile, a low potential for toxicity, and few adverse side effects those of which include gastrointestinal symptoms such as diarrhea and flatulence. Further research is needed to investigate the relationship between curcumin and the impact on osteoarthritic symptoms independent of NSAIDs. Additionally, population based studies are needed to see if the results of a small sample size can be applied to the general population

Physiological concentrations of bile acids down-regulate agonist induced secretion in colonic epithelial cells

In patients with bile acid malabsorption, high concentrations of bile acids enter the colon and stimulate Cl− and fluid secretion, thereby causing diarrhoea. However, deoxycholic acid (DCA), the predominant colonic bile acid, is normally present at lower concentrations where its role in regulating transport is unclear. Thus, the current study set out to investigate the effects of physiologically relevant DCA concentrations on colonic epithelial secretory function. Cl− secretion was measured as changes in short-circuit current across voltage-clamped T84 cell monolayers. At high concentrations (0.5–1 mM), DCA acutely stimulated Cl− secretion but this effect was associated with cell injury, as evidenced by decreased transepithelial resistance (TER) and increased lactate dehydrogenase (LDH) release. In contrast, chronic (24 hrs) exposure to lower DCA concentrations (10–200 μM) inhibited responses to Ca2+ and cAMP-dependent secretagogues without altering TER, LDH release, or secretagogue-induced increases in intracellular second messengers. Other bile acids – taurodeoxycholic acid, chenodeoxycholic acid and cholic acid – had similar antisecretory effects. DCA (50 μM) rapidly stimulated phosphorylation of the epidermal growth factor receptor (EGFr) and both ERK and p38 MAPKs (mitogen-activated protein kinases). The EGFr inhibitor, AG1478, and the protein synthesis inhibitor, cycloheximide, reversed the antisecretory effects of DCA, while the MAPK inhibitors, PD98059 and SB203580, did not. In summary, our studies suggest that, in contrast to its acute prosecretory effects at pathophysiological concentrations, lower, physiologically relevant, levels of DCA chronically down-regulate colonic epithelial secretory function. On the basis of these data, we propose a novel role for bile acids as physiological regulators of colonic secretory capacity

Entometabolomics: applications of modern analytical techniques to insect studies

Metabolomic analyses can reveal associations between an organism's metabolome and further aspects of its phenotypic state, an attractive prospect for many life-sciences researchers. The metabolomic approach has been employed in some, but not many, insect study systems, starting in 1990 with the evaluation of the metabolic effects of parasitism on moth larvae. Metabolomics has now been applied to a variety of aspects of insect biology, including behaviour, infection, temperature stress responses, CO2 sedation, and bacteria–insect symbiosis. From a technical and reporting standpoint, these studies have adopted a range of approaches utilising established experimental methodologies. Here, we review current literature and evaluate the metabolomic approaches typically utilised by entomologists. We suggest that improvements can be made in several areas, including sampling procedures, the reduction in sampling and equipment variation, the use of sample extracts, statistical analyses, confirmation, and metabolite identification. Overall, it is clear that metabolomics can identify correlations between phenotypic states and underlying cellular metabolism that previous, more targeted, approaches are incapable of measuring. The unique combination of untargeted global analyses with high-resolution quantitative analyses results in a tool with great potential for future entomological investigations

Body Image Dissatisfaction Among Third, Fourth, and Fifth Grade Children

Body image dissatisfaction has become increasingly more prevalent among the preadolescent population over recent years. This study examines the level of body image dissatisfaction among 261 third, fourth, and fifth grade girls and boys. A pictorial scale was used to assess how the participants viewed their current body shape, their ideal body shape, and what they believed to be the ideal body shape of the opposite gender. Overall results indicated that 50.6% of the children surveyed were dissatisfied with their current body shape, 41.8% wanted to be thinner, while 8.8% wanted to be larger. Fifty percent of the girls were dissatisfied with their current body shape, with 45.1% wishing to be thinner. Boys showed similar trends, with 48.9% dissatisfied and 38.9% wishing to be thinner. A greater percentage of boys wanted to be larger than their current body shape (12.3%) compared to girls (4.9%). A significant difference was found between genders regarding the difference between scores of their current self and ideal self, where girls selected a smaller ideal body shape than the boys. An encouraging finding was that the level of body dissatisfaction decreased from third grade to fifth grade among both genders. Girls, however, still wished to be thinner over time. Boys, on the other hand, indicated a preference for a somewhat larger body shape over time. These results indicate that body image dissatisfaction exists prior to adolescence among this sample of children. Prevention strategies and education are encouraged among this age group

R-Ras regulates β1-integrin trafficking via effects on membrane ruffling and endocytosis

<p>Abstract</p> <p>Background</p> <p>Integrin-mediated cell adhesion and spreading is dramatically enhanced by activation of the small GTPase, R-Ras. Moreover, R-Ras localizes to the leading edge of migrating cells, and regulates membrane protrusion. The exact mechanisms by which R-Ras regulates integrin function are not fully known. Nor is much known about the spatiotemporal relationship between these two molecules, an understanding of which may provide insight into R-Ras regulation of integrins.</p> <p>Results</p> <p>GFP-R-Ras localized to the plasma membrane, most specifically in membrane ruffles, in Cos-7 cells. GFP-R-Ras was endocytosed from these ruffles, and trafficked via multiple pathways, one of which involved large, acidic vesicles that were positive for Rab11. Cells transfected with a dominant negative form of GFP-R-Ras did not form ruffles, had decreased cell spreading, and contained numerous, non-trafficking small vesicles. Conversely, cells transfected with the constitutively active form of GFP-R-Ras contained a greater number of ruffles and large vesicles compared to wild-type transfected cells. Ruffle formation was inhibited by knock-down of endogenous R-Ras with siRNA, suggesting that activated R-Ras is not just a component of, but also an architect of ruffle formation. Importantly, β₁-integrin co-localized with endogenous R-Ras in ruffles and endocytosed vesicles. Expression of dominant negative R-Ras or knock down of R-Ras by siRNA prevented integrin accumulation into ruffles, impaired endocytosis of β₁-integrin, and decreased β₁-integrin-mediated adhesion. Knock-down of R-Ras also perturbed the dynamics of another membrane-localized protein, GFP-VSVG, suggesting a more global role for R-Ras on membrane dynamics. However, while R-Ras co-internalized with integrins, it did not traffic with VSVG, which instead moved laterally out of ruffles within the plane of the membrane, suggesting multiple levels of regulation of and by R-Ras.</p> <p>Conclusions</p> <p>Our results suggest that integrin function involves integrin trafficking via a cycle of membrane protrusion, ruffling, and endocytosis regulated by R-Ras, providing a novel mechanism by which integrins are linked to R-Ras through control of membrane dynamics.</p

Cohort effects explain the increase in autism diagnosis among children born from 1992 to 2003 in California

The incidence and prevalence of autism have dramatically increased over the last 20 years. Decomposition of autism incidence rates into age, period and cohort effects disentangle underlying domains of causal factors linked to time trends. We estimate an age-period-cohort effect model for autism diagnostic incidence overall and by level of functioning