Compared to other Canadians, Aboriginal people suffer disproportionately from Type 2 diabetes and its complications. In an attempt to fill gaps in services for Aboriginal people to support better management of diabetes and to prevent further complications, the West Side Community Clinic launched a monthly outreach diabetes education program using an informal hands-on approach to learning about meal planning and other forms of diabetes management. The purpose of this qualitative study was to determine the impact that the program has had on the participants' health and well-being through the stories they shared in a group or individual interview. Out of the core group of 30 women, most of them Aboriginal, eleven participated in the group interview and five women participated in individual interviews.<p>Findings reveal that the program's impact on participants' health and well-being is embedded within the context of their lives. Diabetes is managed within multiple life realities in an individual, a familial and a community context. The women report learning management skills and sharing support among participants and staff of Diabetes Morning; and altered health status such as regulated blood glucose levels and weight loss. Opportunities for change include more programming like Diabetes Morning, more often, more information, access to low-cost diabetes-friendly foods, communication with health care practitioners, and integrating knowledge on a day-to-day basis. Domains for outcome indicators and contextual indicators are suggested for the program.

Damage to cardiac contractile proteins such as myosin light chain 1 (MLC1), during oxidative stress is mediated by reactive oxygen species such as peroxynitrite (ONOO-), resulting in impairment of cardiac systolic function. The purpose of this study is to investigate the effects of the increased level of ONOO- on MLC1 degradation by the proteolytic enzyme matrix metalloproteinase-2 (MMP-2) during oxidative stress which ultimately decreases cardiac function.<p> In the present study two distinct models were utilized to demonstrate the mechanism by which MLC1 is modified by ONOO- and how these post-translational modifications lead to its increased degradation by MMP-2. In a model of newborn hypoxia-reoxygenation in piglets we demonstrated that ONOO--induced nitration and nitrosylation of tyrosine and cysteine residues of MLC1 increase its degradation by MMP-2. Furthermore, we found nitration of a tyrosine residue located adjacent to the cleavage site for MMP-2. We verified these results by using a model of isolated rat heart myocytes to determine that the same mechanism responsible for cardiac dysfunction in newborn piglets occurs in isolated myocytes and that the MMP-2 involved in degradation of MLC1 is located within the myocytes. Moreover, we were able to determine that this mechanism occurs during ischemia itself before the onset of reperfusion. Furthermore, we have found that pharmacological intervention aimed at inhibition of MLC1 nitration/nitrosylation during ischemia by the ONOO- scavenger FeTPPS (5,10,15,20-tetrakis-[4-sulfonatophenyl]-porphyrinato-iron[III]), or inhition of MMP-2 activity with phenanthroline, provides an effective protection of cardiomyocyte contractility. The work presented here provides new evidence on the mechanisms of regulation of contractile proteins during the development of contractile dysfunction.

HSV-2 may have adverse consequences in HIV. I evaluated the impact of HSV-2 co-infection on (highly active antiretroviral therapy)-untreated HIV infection in a systematic review of observational studies (study 1) and a retrospective cohort (study 2). I further evaluated whether HSV reactivation rates in co-infected persons differ by use of suppressive cART (study 3). Study 1 found modest evidence that HSV-2 seropositivity may be associated with accelerated progression to opportunistic infection or clinical AIDS, but not with increased HIV viral load. Some evidence suggests that HSV-2 disease activity is associated with increased HIV viral load and decreased CD4 counts. Study 2 compared rates of CD4 count change by HSV-2 status (Focus HerpeSelect ELISA) among 218 patients with a past period of ART-untreated follow-up using mixed linear regression models. No significant difference in the rate of CD4 count change was observed in HSV-2 seropositives at +13.6 cells/mm3/year (p=0.12) in univariate analysis, and -4.5 cells/mm3/year (p=0.68) in analysis adjusted for sex, HSV-1, oral and genital HSV symptoms, immigrant status, and immigrant*time interaction. These findings support the need for carefully designed and executed studies of HSV-2 suppression as an adjunctive management strategy for HIV disease, but raise questions regarding the exact mechanism of negative synergy between these viruses and the relative importance of HSV-2 latency and replication in driving these effects. In Study 3, 44 cART-naïve and 41 treated (HIV RNA<50 copies/mL) HIV+ adults with HSV-1 and/or 2 co-infection collected oral, genital and anal swabs daily for 28 days. Negative binomial models were used to quantify the relationship between cART and HSV shedding (Roche LightCycler HSV1/2). Overall HSV shedding was low, at a median (IQR) of 3.6% (0, 14.3%) of days. No relationship was seen between cART and HSV-1 or 2 shedding in univariate (RR=1.55, 95%CI=0.83,2.87) or multivariate analysis adjusted for sex, baseline CD4, recent immigrant status, and time since HIV diagnosis (aRR=1.05, 95%CI=0.43,2.58). Null results were also observed for HSV-1 and HSV-2 considered separately. That HSV shedding persists despite cART suggests that trials of anti-HSV drugs for improving HIV outcomes may be warranted in such patients.

Introduction: Mammalian cell recombinant bone morphogenetic protein (rBMP) synthesis is reported to be poor. The BMP pro-domain may be involved in folding, stability and secretion. Objectives: Investigate the effect of inhibition of pro-domain cleavage on rhBMP-2 production. Methods: CHO cells transfected with human BMP-2 (hBMP-2) were cultured in the presence of the proprotein convertase inhibitor 9DR in short (multi-well) and long-term (bioreactor) cultures. Mature and proBMP secretion was measured by ELISA and characterized by Western blot. BMP activity was determined by C2C12 bioassay. Results: 9DR significantly enhanced the yields of both pro- and mature hBMP-2 in short and long-term cultures, without any negative effects on cell growth or viability. The rhBMP-2 was biologically active. ProBMP-2 could be converted by exogenous furin treatment into mature BMP-2 as shown by Western blot. Conclusions: 9DR increases rhBMP-2 production and is a simple, but effective way to enhance the yield of active, mature BMP-2 in CHO cells.

Studies show that insulin induced activation and assembly of insulin receptor substrate-1 (IRS1) and phosphatidylinositol-3-kinase (PI3K), within remodelled actin structures is critical for GLUT4 translocation to the cell surface in muscle cells. This study identifies the F-actin binding protein, nexilin, as a novel IRS1 binding partner. Insulin stimulates nexilin to dissociate from IRS1 and interact with actin. Nexilin knockdown has no effect on insulin-stimulated IRS1 tyrosine phosphorylation, but does enhance insulin-stimulated IRS1-PI3K interaction, increasing PIP3 formation, PKB activation and glucose uptake. This study also shows that nexilin overexpression may have an inhibitory effect on PKB phosphorylation and glucose uptake in adipocytes. These findings suggest nexilin is a negative regulator of IRS1 action on PI3K and insulin-stimulated dissociation of IRS1-nexilin allows the formation of IRS1-PI3K complexes in cytoskeletal-membrane compartments. Nexilin also specifically associates with the PH domain of IRS1, and not IRS2, suggesting a mechanism for signaling specificity of these isoforms.

Glucagon-like peptide-2 (GLP-2) is an intestinotrophic and intestinal anti-inflammatory hormone. Hence, I hypothesized that treatment with degradation-resistant hGly2GLP-2 increases, while blocking endogenous GLP-2 decreases colorectal cancer (CRC) in rodents. In mice, treatment with dextran sodium sulphate (DSS) and azoxymethane (AOM) induced colitis-associated CRC, which was further increased by treatment with hGly2GLP-2 and reduced by blocking endogenous GLP-2 with the antagonist hGLP-23-33. Moreover, while colonic damage score (CDS) was not altered by hGly2GLP-2 or hGLP-23-33 treatment, hGly2GLP-2 increased small intestinal growth and hGLP-23-33 reduced jejunal crypt cell proliferation. In rats fed with of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and high fat (HF) diet for aberrant crypt foci (ACF) induction, treatment with hGly2GLP-2 increased small intestinal growth and ACF occurrence. Moreover, in rats fed with PhIP-HF diet for tumour induction, early treatment with hGly2GLP-2 appears to increase the occurrence of intestinal tumours. Collectively, these findings indicate a pro-carcinogenic role for both exogenous and endogenous GLP-2.

Glucagon-like peptide-2 (GLP-2) is an intestinotrophic and intestinal anti-inflammatory hormone. Hence, I hypothesized that treatment with degradation-resistant hGly2GLP-2 increases, while blocking endogenous GLP-2 decreases colorectal cancer (CRC) in rodents. In mice, treatment with dextran sodium sulphate (DSS) and azoxymethane (AOM) induced colitis-associated CRC, which was further increased by treatment with hGly2GLP-2 and reduced by blocking endogenous GLP-2 with the antagonist hGLP-23-33. Moreover, while colonic damage score (CDS) was not altered by hGly2GLP-2 or hGLP-23-33 treatment, hGly2GLP-2 increased small intestinal growth and hGLP-23-33 reduced jejunal crypt cell proliferation. In rats fed with of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and high fat (HF) diet for aberrant crypt foci (ACF) induction, treatment with hGly2GLP-2 increased small intestinal growth and ACF occurrence. Moreover, in rats fed with PhIP-HF diet for tumour induction, early treatment with hGly2GLP-2 appears to increase the occurrence of intestinal tumours. Collectively, these findings indicate a pro-carcinogenic role for both exogenous and endogenous GLP-2.

Anthocyanins are the most important class of water-soluble pigments responsible for red to blue colors in various plants. Anthocyanins naturally occur in a broad range of plants and studies have shown associations between fruit consumption and reduction of certain diseases thought to be related to the presence of these and other polyphenolics. However, anthocyanin absorption is fairly poor which hinders their potential to be utilized in the human body. Absorption of anthocyanins extracted from açaí puree and port wine was assessed. Various combinations of terpenes and phospholipids were added to anthocyanins to modulate and increase their transport within a model system. Açaí and port wine anthocyanins were poorly transported in the absence of phospholipids and terpenes. The addition of terpenes and phospholipids significantly increased the transport of anthocyanins. Additionally, the presence of phospholipids and terpenes did not influence the way anthocyanins degraded over a 40 day period of time at three different temperatures. Transport of anthocyanins was not dependent on dosage since absorption results were similar at both concentrations of anthocyanins tested. Two methods to mix anthocyanins, phospholipids, and terpenes were also assessed (Sonication and French Press). Comparisons illustrated that both technologies created matrices that maintained the properties of phospholipids and terpenes as transport enhancers. Finally, a study to determine the efficacy of phospholipids and terpenes on a different type of polyphenolic compound was assessed. Transport of gallic acid was enhanced by the use of these agents that cemented the idea that phospholipids and terpenes can enhance the transport of various types of polyphenolics. The aiding effect of phospholipids and terpenes was well established and could play an important role in future investigation in this field. Further research needs to be conducted to reveal more information about the nature of these vesicles or associations that phospholipids and terpenes may have with anthocyanins. In vivo studies need to be considered to confirm these effects in rat models and, ideally, in humans. Nevertheless, these findings open a new line of investigation that could harvest promising results for the future of ingredient development for food products.

Introduction: Mammalian cell recombinant bone morphogenetic protein (rBMP) synthesis is reported to be poor. The BMP pro-domain may be involved in folding, stability and secretion. Objectives: Investigate the effect of inhibition of pro-domain cleavage on rhBMP-2 production. Methods: CHO cells transfected with human BMP-2 (hBMP-2) were cultured in the presence of the proprotein convertase inhibitor 9DR in short (multi-well) and long-term (bioreactor) cultures. Mature and proBMP secretion was measured by ELISA and characterized by Western blot. BMP activity was determined by C2C12 bioassay. Results: 9DR significantly enhanced the yields of both pro- and mature hBMP-2 in short and long-term cultures, without any negative effects on cell growth or viability. The rhBMP-2 was biologically active. ProBMP-2 could be converted by exogenous furin treatment into mature BMP-2 as shown by Western blot. Conclusions: 9DR increases rhBMP-2 production and is a simple, but effective way to enhance the yield of active, mature BMP-2 in CHO cells.

Studies show that insulin induced activation and assembly of insulin receptor substrate-1 (IRS1) and phosphatidylinositol-3-kinase (PI3K), within remodelled actin structures is critical for GLUT4 translocation to the cell surface in muscle cells. This study identifies the F-actin binding protein, nexilin, as a novel IRS1 binding partner. Insulin stimulates nexilin to dissociate from IRS1 and interact with actin. Nexilin knockdown has no effect on insulin-stimulated IRS1 tyrosine phosphorylation, but does enhance insulin-stimulated IRS1-PI3K interaction, increasing PIP3 formation, PKB activation and glucose uptake. This study also shows that nexilin overexpression may have an inhibitory effect on PKB phosphorylation and glucose uptake in adipocytes. These findings suggest nexilin is a negative regulator of IRS1 action on PI3K and insulin-stimulated dissociation of IRS1-nexilin allows the formation of IRS1-PI3K complexes in cytoskeletal-membrane compartments. Nexilin also specifically associates with the PH domain of IRS1, and not IRS2, suggesting a mechanism for signaling specificity of these isoforms.