The effect of cortisone on hexosamine and mucopolysaccharide metabolism.

Radioautographic studies indicated that the synthesis of sulfated mucopolysaccharides (MPS) in cartilage, skin, aorta and liver was decreased in rats treated with relatively large doses of cortisone. Chemical analyses showed that the hexosamine and hexuronic acid content of aorta and skin was decreased as was also the glucosamine content of liver in the treated animals. The activity of fructose-6-p-D-glutamine amidotransferase was decreased in supernatants from the liver homogenates of rats treated with cortisone for three days or longer. Similarly, the amidotransferase activity was decreased on addition of the soluble hydrocortisone succinate to normal liver supernatants, although the two effects may have different mechanisms of action. Studies with glucosamine-14C indicated that cortisone treatment caused no additional block in the hexosamine pathway. Thus, one way by which cortisone exerts its influence on MPS metabolism is by inhibiting the first step of the hexosamine biosynthetic pathway

Phosphoglucoisomerase activity and connective tissue changes in the human aorta during atherosclerosis.

The work presented in this thesis represents, in part, an effort to ascertain some of the biochemical changes that occur in the aorta during the development of otherosclerosis. My interest was first stimulated during the course in pathology in the early part of medical training. [...

N-Butyrylated hyaluronic acid ameliorates gout and hyperuricemia in animal models

Context: Hyaluronic acid (HA) plays critical roles in the structural skeleton, joint lubrication, renal function and cell signaling. We previously showed that partially N-butyrylated, low molecular weight, hyaluronic acid (BHA) exhibited an anti-inflammatory effect in cultured human macrophage, where inflammation was induced either by a TL-4 agonist or the low molecular weight HA itself, in dose-dependent fashion. Objectives: To investigate the anti-inflammatory, antioxidative, and antihyperuricemic effects of BHA using animal models of acute gouty arthritis and hyperuricemia. Materials and methods: The anti-inflammatory effect of articular BHA (10 and 50 μg) injections was evaluated by measuring joint swelling and the serum levels of inflammatory cytokines in a model of acute gouty arthritis induced by intra-articular injection of monosodium urate crystals in Wistar rats (n = 10/group), in comparison to the control group with saline injection. Antioxidative and antihyperuricemic activities were investigated using intraperitoneal injections of oteracil potassium and yeast extract hyperuricemic Balb/C mice, which were treated with intraperitoneal injection of BHA at day 6–8 in the model. Results: In the gouty arthritis rat model, BHA at a higher dosage (50 μg) demonstrated a strong anti-inflammatory effect by reducing the degree of articular swelling and the serum levels of IL-1β, IL-8, IFN-γ, and MCP-1 by 5.56%, 6.55%, 15.58% and 33.18%. In the hyperuricemic mouse model, lower dosage BHA (10 μg) was sufficient to provide antioxidative activities by significantly decreasing the ROS levels in both serum and liver by 14.87% and 8.04%, while improving liver SOD by 12.77%. Intraperitoneal injection of BHA suppressed uric acid production through reducing liver XO activity by 19.78% and decreased the serum uric acid level in hyperuricemic mice by 30.41%. Conclusions: This study demonstrated for the first time that BHA exhibits anti-inflammatory, antioxidative and antihyperuricemic effects in vivo, suggesting a potential therapeutic application of BHA in gouty arthritis and hyperuricemia

A Low Molecular Weight Hyaluronic Acid Derivative Accelerates Excisional Wound Healing by Modulating Pro-Inflammation, Promoting Epithelialization and Neovascularization, and Remodeling Collagen

Recent knowledge of the cellular and molecular mechanisms underlying cutaneous wound healing has advanced the development of medical products. However, patients still suffer from the failure of current treatments, due to the complexity of healing process and thus novel therapeutic approaches are urgently needed. Previously, our laboratories produced a range of low molecular weight hyaluronic acid (LMW-HA) fragments, where a proportion of the glucosamine moieties were chemically N-acyl substituted. Specifically, N-butyrylation results in anti-inflammatory properties in a macrophage system, and we demonstrate the importance of N-acyl substituents in modulating the inflammatory response of LMW-HA. We have set up an inter-institutional collaborative program to examine the biomedical applications of the N-butyrylated LMW-HA (BHA). In this study, the potentials of BHA for dermal healing are assessed in vitro and in vivo. Consequently, BHA significantly promotes dermal healing relative to a commercial wound care product. By contrast, the “parent” partially de-acetylated LMW-HA (DHA) and the re-acetylated DHA (AHA) significantly delays wound closure, demonstrating the specificity of this N-acylation of LMW-HA in wound healing. Mechanistic studies reveal that the BHA-mediated therapeutic effect is achieved by targeting three phases of wound healing (i.e., inflammation, proliferation and maturation), demonstrating the significant potential of BHA for clinical translation in cutaneous wound healing

Dietary patterns in Canadian men and women ages 25 and older: relationship to demographics, body mass index, and bone mineral density

Background: Previous research has shown that underlying dietary patterns are related to the risk of many different adverse health outcomes, but the relationship of these underlying patterns to skeletal fragility is not well understood. The objective of the study was to determine whether dietary patterns in men (ages 25-49, 50+) and women (pre-menopause, post-menopause) are related to femoral neck bone mineral density (BMD) independently of other lifestyle variables, and whether this relationship is mediated by body mass index. Methods: We performed an analysis of 1928 men and 4611 women participants in the Canadian Multicentre Osteoporosis Study, a randomly selected population-based longitudinal cohort. We determined dietary patterns based on the self-administered food frequency questionnaires in year 2 of the study (1997-99). Our primary outcome was BMD as measured by dual x-ray absorptiometry in year 5 of the study (2000-02). Results: We identified two underlying dietary patterns using factor analysis and then derived factor scores. The first factor (nutrient dense) was most strongly associated with intake of fruits, vegetables, and whole grains. The second factor (energy dense) was most strongly associated with intake of soft drinks, potato chips and French fries, certain meats (hamburger, hot dog, lunch meat, bacon, and sausage), and certain desserts (doughnuts, chocolate, ice cream). The energy dense factor was associated with higher body mass index independent of other demographic and lifestyle factors, and body mass index was a strong independent predictor of BMD. Surprisingly, we did not find a similar positive association between diet and BMD. In fact, when adjusted for body mass index, each standard deviation increase in the energy dense score was associated with a BMD decrease of 0.009 (95% CI: 0.002, 0.016) g/cm2 for men 50+ years old and 0.004 (95% CI: 0.000, 0.008) g/cm2 for postmenopausal women. In contrast, for men 25-49 years old, each standard deviation increase in the nutrient dense score, adjusted for body mass index, was associated with a BMD increase of 0.012 (95% CI: 0.002, 0.022) g/cm2. Conclusions: In summary, we found no consistent relationship between diet and BMD despite finding a positive association between a diet high in energy dense foods and higher body mass index and a strong correlation between body mass index and BMD. Our data suggest that some factor related to the energy dense dietary pattern may partially offset the advantages of higher body mass index with regard to bone health.Land and Food Systems, Faculty ofMedicine, Department ofMedicine, Faculty ofNon UBCReviewedFacult

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ABSTRACT. Objective. To assess driving problems experienced by patients with rheumatoid arthritis (RA) and to examine the relationship between functional status and driving difficulty. Methods. Using the South Eastern Ontario Medical Organization (SEAMO) database, we identified 721 patients with RA from both urban and rural backgrounds. They completed a cross-sectional, selfadministered mail survey that included the Health Assessment Questionnaire (HAQ-DI) and a comorbidity questionnaire. We assessed the proportion of drivers versus non-drivers and patients who reported difficulty driving and who used vehicle adaptations. Results. Survey response rate was 74% and 92.2% of the subjects were current drivers. Fifty percent of the current drivers reported a little difficulty, 6.8% reported quite a bit of difficulty, and 1.5% a great deal of difficulty driving. Major reasons given for why RA limited their driving were stiffness and pain. Frequent use of mobility aids (adjusted odds ratio, OR: 5.85), HAQ-DI ≥ 1 (adjusted OR: 3.40), and older age (adjusted OR: 1.04) were significant predictors of an individual with RA discontinuing driving. Higher levels of disability (HAQ-DI) were associated with a greater number of problems reported with driving and with curtailment of driving. A multivariate logistic regression determined that having a HAQ-DI ≥ 1 (adjusted OR: 4.3) and difficulties sitting in the vehicle (adjusted OR: 2.9) were associated with RA limiting driving. Conclusion. Over 50% of respondents reported some degree of difficulty driving due to their RA. Scores on HAQ-DI ≥ 1 were associated with difficulty driving. Further validation of our findings needs to be performed. (J Rheumatol 2005;32:2337-42