The potential for dietary factors to prevent or treat osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease for which there are no disease-modifying drugs. It is a leading cause of disability in the UK. Increasing age and obesity are both major risk factors for OA and the health and economic burden of this disease will increase in the future. Focusing on compounds from the habitual diet that may prevent the onset or slow the progression of OA is a strategy that has been under-investigated to date. An approach that relies on dietary modification is clearly attractive in terms of risk/benefit and more likely to be implementable at the population level. However, before undertaking a full clinical trial to examine potential efficacy, detailed molecular studies are required in order to optimise the design. This review focuses on potential dietary factors that may reduce the risk or progression of OA, including micronutrients, fatty acids, flavonoids and other phytochemicals. It therefore ignores data coming from classical inflammatory arthritides and nutraceuticals such as glucosamine and chondroitin. In conclusion, diet offers a route by which the health of the joint can be protected and OA incidence or progression decreased. In a chronic disease, with risk factors increasing in the population and with no pharmaceutical cure, an understanding of this will be crucial

Prevalence and phenotype of diabetes and prediabetes using fasting glucose vs HbA1c in a Caribbean population.

BACKGROUND: Both fasting plasma glucose (FPG) and HbA1c are recommended for the diagnosis of diabetes and prediabetes by the American Diabetes Association (ADA), and for diabetes by the World Health Organization. The ADA guidance is influential on clinical practice in many developing countries, including in the Caribbean and Latin America. We aimed to compare the prevalence and characteristics of individuals identified as having diabetes and prediabetes by FPG and HbA1c in a predominantly African ancestry Caribbean population. METHODS: A representative population-based sample of 1234 adults (≥25 years of age) resident in Barbados was recruited. Standard methods with appropriate quality control were used to collect data on height, weight, blood pressure, fasting lipids and history of diagnosed diabetes, and to measure fasting glucose and HbA1c. Those with previously diagnosed diabetes (n = 192) were excluded from the analyses. Diabetes was defined as: FPG ≥7.0 mmol/L or HbA1c ≥6.5%; prediabetes as: FPG ≥5.6 to <7mmol/L or HbA1c ≥5.7 to <6.5%. RESULTS: Complete data were available on 939 participants without previously diagnosed diabetes. The prevalence of undiagnosed diabetes was higher, but not significantly so, by HbA1c (4.9%, 95% CI 3.5, 6.8) vs FPG (3.5%, 2.4, 5.1). Overall 79 individuals had diabetes by either measure, but only 21 on both. The prevalence of prediabetes was higher by HbA1c compared to FPG: 41.7% (37.9, 45.6) vs 15.0% (12.8, 17.5). Overall 558 individuals had prediabetes by either measure, but only 107 on both. HbA1c, but not FPG, was significantly higher in women than men; and FPG, but not HbA1c, was significantly associated with raised triglycerides and low HDL cholesterol. CONCLUSION: The agreement between FPG and HbA1c defined hyperglycaemia is poor. In addition, there are some differences in the phenotype of those identified, and HbA1c gives a much higher prevalence of prediabetes. The routine use of HbA1c for screening and diagnosis in this population would have major implications for clinical and public health policies and resources. Given the lack of robust evidence, particularly for prediabetes, on whether intervention in the individuals identified would improve outcomes, this approach to screening and diagnosis cannot be currently recommended for this population

Heat Shock Protein-90 Inhibitors Enhance Antigen Expression on Melanomas and Increase T Cell Recognition of Tumor Cells

In an effort to enhance antigen-specific T cell recognition of cancer cells, we have examined numerous modulators of antigen-expression. In this report we demonstrate that twelve different Hsp90 inhibitors (iHsp90) share the ability to increase the expression of differentiation antigens and MHC Class I antigens. These iHsp90 are active in several molecular and cellular assays on a series of tumor cell lines, including eleven human melanomas, a murine B16 melanoma, and two human glioma-derived cell lines. Intra-cytoplasmic antibody staining showed that all of the tested iHsp90 increased expression of the melanocyte differentiation antigens Melan-A/MART-1, gp100, and TRP-2, as well as MHC Class I. The gliomas showed enhanced gp100 and MHC staining. Quantitative analysis of mRNA levels showed a parallel increase in message transcription, and a reporter assay shows induction of promoter activity for Melan-A/MART-1 gene. In addition, iHsp90 increased recognition of tumor cells by T cells specific for Melan-A/MART-1. In contrast to direct Hsp90 client proteins, the increased levels of full-length differentiation antigens that result from iHsp90 treatment are most likely the result of transcriptional activation of their encoding genes. In combination, these results suggest that iHsp90 improve recognition of tumor cells by T cells specific for a melanoma-associated antigen as a result of increasing the expressed intracellular antigen pool available for processing and presentation by MHC Class I, along with increased levels of MHC Class I itself. As these Hsp90 inhibitors do not interfere with T cell function, they could have potential for use in immunotherapy of cancer

Are there gender differences in acute management and secondary prevention of acute coronary syndromes in Barbados? A cohort study.

OBJECTIVES: In Barbados, high case fatality rates have been reported after myocardial infarction (MI) with higher rates in women than men. To explore this inequality, we examined documented pharmacological interventions for ST-segment elevated myocardial infarction (STEMI), non-STEMI (NSTEMI) and unstable and chronic angina in women and men. DESIGN: Prospective cohort registry data for STEMI and NSTEMI and retrospective chart review for unstable and chronic angina. SETTING: Tertiary care (acute coronary syndromes) and primary care (chronic angina) centres in Barbados. PARTICIPANTS: For the years 2009-2016, a total of 1018 patients with STEMI or NSTEMI were identified via the prospective study. For unstable and chronic angina, 136 and 272 notes were reviewed respectively for the years 2010-2014. OUTCOME MEASURES: The proportions of patients prescribed recommended medication during the first 24 hours after an acute event, at discharge and for chronic care were calculated. Prescribed proportions were analysed by gender after adjustment for age. RESULTS: Between 2009 and 2016, for the acute management of patients with NSTEMI and STEMI, only two (aspirin and clopidogrel) of six drugs had documented prescription rates of 80% or more. Patients with STEMI (n=552) had higher prescription rates than NSTEMI (n=466), with gender differences being more pronounced in the former. Among patients with STEMI, after adjustment for age, diabetes, hypertension and smoking, men were more likely to receive fibrinolytics acutely, OR 2.28 (95% CI 1.24 to 4.21). Compared with men, a higher proportion of women were discharged on all recommended treatments; this was only statistically significant for beta-blockers: age-adjusted OR 1.87 (95% CI 1.16 to 3.00). There were no statistically significant differences in documented prescription of drugs for chronic angina. CONCLUSION: Following acute MI in Barbados, the proportion of patients with documented recommended treatment is relatively low. Although women were less likely to receive appropriate acute care than men, by discharge gender differences were reversed

Sodium and potassium excretion in an adult Caribbean population of African descent with a high burden of cardiovascular disease

Abstract Background High sodium diets with inadequate potassium and high sodium-to-potassium ratios are a known determinant of hypertension and cardiovascular disease (CVD). The Caribbean island of Barbados has a high prevalence of hypertension and mortality from CVD. Our objectives were to estimate sodium and potassium excretion, to compare estimated levels with recommended intakes and to identify the main food sources of sodium in Barbadian adults. Methods A sub-sample (n = 364; 25–64 years) was randomly selected from the representative population-based Health of the Nation cross-sectional study (n = 1234), in 2012–13. A single 24-h urine sample was collected from each participant, following a strictly applied protocol designed to reject incomplete samples, for the measurement of sodium and potassium excretion (in mg), which were used as proxy estimates of dietary intake. In addition, sensitivity analyses based on estimated completeness of urine collection from urine creatinine values were undertaken. Multiple linear regression was used to examine differences in sodium and potassium excretion, and the sodium-to-potassium ratio, by age, sex and educational level. Two 24-h recalls were used to identify the main dietary sources of sodium. All analyses were weighted for the survey design. Results Mean sodium excretion was 2656 (2488–2824) mg/day, with 67% (62–73%) exceeding the World Health Organization (WHO) recommended limit of 2000 mg/d. Mean potassium excretion was 1469 (1395–1542) mg/d; < 0.5% met recommended minimum intake levels. Mean sodium-to-potassium ratio was 2.0 (1.9–2.1); not one participant had a ratio that met WHO recommendations. Higher potassium intake and lower sodium-to-potassium ratio were independently associated with age and tertiary education. Sensitivity analyses based on urine creatinine values did not notably alter these findings. Conclusions In this first nationally representative study with objective assessment of sodium and potassium excretion in a Caribbean population in over 20 years, levels of sodium intake were high, and potassium intake was low. Younger age and lower educational level were associated with the highest sodium-to-potassium ratios. These findings provide baseline values for planning future policy interventions for non-communicable disease prevention

A comparison of postrelease survival parameters between single and mass stranded delphinids from Cape Cod, Massachusetts, U.S.A.

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Marine Mammal Science 32 (2016): 161–180, doi:10.1111/mms.12255.The viability of healthy single stranded dolphins as immediate release candidates has received little attention. Responders have been reluctant to release lone delphinids due to their social needs, even when they pass the same health evaluations as mass stranded animals. This study tracked postrelease success of 34 relocated and released satellite tagged delphinids from single and mass strandings. Three postrelease survival parameters (transmission duration, swim speed, and daily distance) were examined to evaluate whether they differed among single stranded/single released (SS/SR), mass stranded/single released (MS/SR), or mass stranded/mass released (MS/MR) dolphin groups. Comparisons were also made between healthy and borderline release candidates. Satellite tags transmitted for a mean of 21.2 d (SD = 19.2, range = 1–79), daily distance traveled was 42.0 km/d (11.25, 20.96–70.72), and swim speed was 4.3 km/h (1.1, 2.15–8.54). Postrelease parameters did not differ between health status groups, however, SS/SR dolphins transmitted for a shorter mean duration than MS/MR and MS/SR groups. Postrelease vessel-based surveys confirmed conspecific group location for two healthy, MS/SR dolphins. Overall, these results support the potential to release healthy stranded single delphinids; however, further refinement of health assessment protocols for these challenging cases is needed.National Oceanic and Atmospheric Administration's National Marine Fisheries Service (NOAA NMFS); John H. Prescott Marine Mammal Rescue Assistance Program Grant Numbers: NA11NMF4390078, NA11NMF4390079, NA11NMF439009

Hematological, biochemical, and morphological parameters as prognostic indicators for stranded common dolphins (Delphinus delphis) from Cape Cod, Massachusetts, U.S.A.

© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Marine Mammal Science 30 (2014): 864–887, doi:10.1111/mms.12093.The current paucity of published blood values and other clinically relevant data for short-beaked common dolphins, Delphinus delphis, hinders the ability of veterinarians and responders to make well-informed diagnoses and disposition decisions regarding live strandings of this species. This study examined hematologic, clinical chemistry, and physical parameters from 26 stranded common dolphins on Cape Cod, Massachusetts, in light of their postrelease survival data to evaluate each parameter's efficacy as a prognostic indicator. Statistically and clinically significant differences were found between failed and survived dolphins, including lower hematocrit, hemoglobin, TCO2, and bicarbonate and higher blood urea nitrogen, uric acid, and length-to-girth ratios in animals that failed. In general when compared to survivors, failed dolphins exhibited acidosis, dehydration, lower PCVs, and decreased body condition. Additionally, failed dolphins had the highest ALT, AST, CK, LDH, GGT, and lactate values. These blood values combined with necropsy findings indicate that there are likely a variety of factors affecting postrelease survival, including both preexisting illness and stranding-induced conditions such as capture myopathy. Closer evaluation of these parameters for stranded common dolphins on point of care analyzers in the field may allow stranding personnel to make better disposition decisions in the future.The John H. Prescott Marine Mammal Rescue Assistance Program provided support for stranding response efforts during this study period (Grants: NA11NMF4390078, NA11NMF4390079, NA11NMF4390093). We would like to thank the Pegasus Foundation and Barbara Birdsey for their support and funding for the IFAW Satellite Tag Program. This project would not have been possible without a summer research grant from the US Army Medical Research and Material Command through Tufts Cummings School of Veterinary Medicine (TCSVM)

Sulforaphane represses matrix-degrading proteases and protects cartilage from destruction in vitro and in vivo:Sulforaphane is protective in the articular Joint

Sulforaphane (SFN) has been reported to regulate signaling pathways relevant to chronic diseases. The aim of this study was to investigate the impact of SFN treatment on signaling pathways in chondrocytes and to determine whether sulforaphane could block cartilage destruction in osteoarthritis

A Complete Expression Profile of Matrix-Degrading Metalloproteinases in Dupuytren’s Disease

Dupuytren’s disease (DD) is a common fibrotic condition of the palmar fascia, leading to deposition of collagen-rich cords and finger contractions. The metzincin superfamily contains key enzymes in the turnover of collagen and other extracellular matrix macromolecules. A number of broad-spectrum matrix metalloproteinase inhibitors, used in cancer clinical trials, caused side effects of DD-like contractures. We tested the hypothesis that changes in the expression of specific metalloproteinases underlie or contribute to the fibrosis and contracture seen in DD. We collected tissue from patients with DD and used normal palmar fascia as a control. We profiled the expression of the entire matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMP), and a disintegrin and metalloproteinase domain with thrombospondin motif (ADAMTS) gene families in these tissues using real-time reverse-transcription polymerase chain reaction. A number of metalloproteinases and inhibitors are regulated in DD. The expression of 3 key collagenases, MMP1, MMP13, and MMP14 is increased significantly in the DD nodule, as is the expression of the collagen biosynthetic enzyme ADAMTS14. The expression of MMP7, an enzyme with broad substrate specificity, is increased in the DD nodule and remains equally expressed in the DD cord. TIMP1 expression is increased significantly in DD nodule compared with normal palmar fascia. This study measured the expression of all MMP, ADAMTS, and TIMP genes in DD. Contraction and fibrosis may result from: (1) increased collagen biosynthesis mediated by increased ADAMTS-14; (2) an increased level of TIMP-1 blocking MMP-1– and MMP-13–mediated collagenolysis; and (3) contraction enabled by MMP-14–mediated pericellular collagenolysis (and potentially MMP-7), which may escape inhibition by TIMP-1. The complete expression profile will provide a knowledge-based approach to novel therapeutics targeting these genes

Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action

Background Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro. Methods Cross-sectional study conducted in a large population-based volunteer cohort of twins. Food intake was evaluated using the Food Frequency Questionnaire; OA was determined using plain radiographs. Analyses were adjusted for age, BMI and physical activity. Subsequent in vitro studies examined the effects of allium-derived compounds on the expression of matrix-degrading proteases in SW1353 chondrosarcoma cells. Results Data were available, depending on phenotype, for 654-1082 of 1086 female twins (median age 58.9 years; range 46-77). Trends in dietary analysis revealed a specific pattern of dietary intake, that high in fruit and vegetables, showed an inverse association with hip OA (p = 0.022). Consumption of 'non-citrus fruit' (p = 0.015) and 'alliums' (p = 0.029) had the strongest protective effect. Alliums contain diallyl disulphide which was shown to abrogate cytokine-induced matrix metalloproteinase expression. Conclusions Studies of diet are notorious for their confounding by lifestyle effects. While taking account of BMI, the data show an independent effect of a diet high in fruit and vegetables, suggesting it to be protective against radiographic hip OA. Furthermore, diallyl disulphide, a compound found in garlic and other alliums, represses the expression of matrix-degrading proteases in chondrocyte-like cells, providing a potential mechanism of action