The pathogenesis of diabetic nephropathy (DN) remains incompletely understood. In previous studies, we observed the activation of Tyr kinase Src by high glucose (HG) and showed that Src is required for MAPK activation and synthesis of collagen IV in cultured rat mesangial cells (MCs). Reactive oxygen species (ROS) are also important mediators of DN, and our present study aimed to investigate the role of Src in HG-induced ROS generation. In MCs, we found that HG led to ROS accumulation that was blocked by Src inhibitors or Src-specific siRNA. Downstream of Src, Vav2 was phosphorylated/activated leading to Rac1-dependent NADPH oxidase activation. Long-term HG exposure resulted in Src-dependent Nox4 protein induction. Nox2-specific siRNA abrogated ROS production only in short-term HG, while Nox4-specific siRNA blocked ROS production only in long-term HG. Taken together, our data indicate Src to be important in mediating ROS generation from both Nox2- and Nox4-containing NADPH oxidases.

The pathogenesis of diabetic nephropathy (DN) remains incompletely understood. In previous studies, we observed the activation of Tyr kinase Src by high glucose (HG) and showed that Src is required for MAPK activation and synthesis of collagen IV in cultured rat mesangial cells (MCs). Reactive oxygen species (ROS) are also important mediators of DN, and our present study aimed to investigate the role of Src in HG-induced ROS generation. In MCs, we found that HG led to ROS accumulation that was blocked by Src inhibitors or Src-specific siRNA. Downstream of Src, Vav2 was phosphorylated/activated leading to Rac1-dependent NADPH oxidase activation. Long-term HG exposure resulted in Src-dependent Nox4 protein induction. Nox2-specific siRNA abrogated ROS production only in short-term HG, while Nox4-specific siRNA blocked ROS production only in long-term HG. Taken together, our data indicate Src to be important in mediating ROS generation from both Nox2- and Nox4-containing NADPH oxidases.

Thesis (M.A.)--Northern Kentucky University, 2007. / Made available through ProQuest. Publication number: AAT 1447083. ProQuest document ID: 1436380211. Includes bibliographical references (p. 25-26)

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 5 uppsatser.

Thesis (M.P.H.)--University of Adelaide, Dept. of Public Health, 1998. / Includes bibliographical references (leaves 274-289).

Thesis (Ph.D.)--University of Adelaide, Dept. of Public Health, 2003. / "January 2003." Bibliography: 10.1-10.11 leaves.

Thesis (Ph. D.)--University of Sydney, 2006. / Title from title screen (viewed Oct. 7, 2009) Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Discipline of Clinical Ophthalmology and Eye Health, Faculty of Medicine. Includes bibliography. Also available in print form.

Includes bibliographical references and index.

Background: The epidemic of type 2 diabetes poses an enormous and growing burden on health care globally. While the prevalence of diabetes is increasing worldwide, the developing countries will bear the greatest burden of this disease. Diabetes is one of the most common causes of kidney failure and nephropathy is a strong predictor of cardiovascular complications and death in these patients. Microalbuminuria represents a latent and early pre-symptomatic phase of nephropathy which can be stopped from progressing to an advanced stage if detected and treated early. The cost effectiveness of this screening and intervention has been researched and proven in the developed world, however similar studies in developing countries are non-existent. Microalbuminuria is not currently tested for in the public primary care sector. Aim and objectives: The aim was to assess the feasibility of introducing a screening test for microalbuminuria and the associated costs and consequences at Elsies River Community Health Centre (CHC) in the Metropolitan District of Cape Town. The objectives of the study are to assess the feasibility of implementing the test in our context, to assess any additional cost to the health services, to assess any measurable benefits in the quality of care for the patients, to extrapolate the likely long term consequences in terms of health outcomes, use of resources and costs and to make a policy recommendation to the Department of Health. Method: A cost and consequence study that describes the introduction of microalbuminuria testing in a cohort of type 2 diabetic patients at Elsies River Community Health Centre, Metro District Health Services, Cape Town, South Africa. Point of care status analyser microalbuminuria screening was introduced to the CHC after training of the chronic care team, and their fidelity to the protocol measured. All patients who met the inclusion criteria were screened. Patients whose first results were abnormal had a repeat test after 3-6 months, if both results were abnormal patient was diagnosed microalbuminuria positive, however a patient with a second normal result required a third test. Interventions included addition of an Angiotesin Converting Enzyme inhibitor to their treatment, more intensive glycaemic, blood pressure or lipid control via medication or lifestyle changes and treatment adherence health education. Field notes were taken by the researcher during visits and a recorded focus group interview conducted with the health workers to explore their views on the feasibility of the screening and intervention. Cost was assessed by the estimation of the additional resources required and the likely long term health outcomes extrapolated from available data and literature. Results: 15.2% of the sample population was noted to be microalbuminuria positive and they all received interventions. Additional cost required to screen a cohort of 100 patients was R1,109.40 per annum, out of which 15 patients at risk of developing nephropathy were identified and the cost of treating these patients was R1,393.20 for the first year. Qualitative data revealed that the test and interventions are feasible with an additional cost of staff time, medication and other materials which have been included in the cost above. Conclusion: This study represents the first attempt to successfully introduce screening for microalbuminuria in our public primary health care context. The chronic care team showed reasonable fidelity to the protocol and demonstrated the feasibility of screening and treating patients. The balance of costs and long term benefits suggests that this represents excellent value for money in a South African primary care setting.

BACKGROUND: Diabetic retinopathy (DR) is the leading cause of vision loss in the world. The Center for Disease Control and Prevention categorizes those with diabetes into three age groups, including a young adult group, ages 18-44. In the Boston metropolitan area, around 4.6% of this age population has diabetes. EYESPOT is a private eye care practice in Boston. Of the few diabetic patients seen, most do not fall within the young adult age range. Several studies have demonstrated the effectiveness of social media to promote awareness of healthy behaviors. OBJECTIVE: The goal of this study is to utilize social media in order to raise awareness of DR in the young adult population and encourage preventative behavior. METHODS: A Facebook page for EYESPOT Diabetes was created to engage the young adult patient population and was monitored over a four-month period. Four categories of Facebook posts, differentiated by type, were disseminated. Posts were targeted to different audiences during each month, creating three unique time blocks. Posts were analyzed for their Engagement (total number of people who interacted with the post via a “like”, click, or “share”) and their Reach (total number of people that saw the post). Preliminary Engagement measures of each post were standardized to account for measures of Reach, creating an additional measure of standardized engagement scores (SES). A 4x3 ANOVA was conducted using SPSS to evaluate the effects of post type and time block on SES. RESULTS: Main effects were found for both post type and time block. Posts of the “Advertising” type had a significantly lower SES than all other posts (p<.01). Posts in the “Promotional College Student” time block had a significantly higher SES (p<.01) than posts in other blocks. There was a significant type-by-block interaction for SES (p<.01). Post hoc analysis revealed that posts of the “Technological” type had higher SES when posted in the block aimed at College Students (p<.01). Of note, 96% of the Facebook users who saw our posts (n = 4050) fell in the young adult bracket. After the conclusion of the study, two new patients in the young adult range contacted EYESPOT with intent to make future appointments, citing our Facebook page as reference. CONCLUSION: Our study suggests that Facebook may be an effective tool to encourage the young adult population to be aware of and engage in beneficial health behaviors. Future studies will investigate how to utilize social media further to increase physical appointments and patient-clinician interactions.