Inflammation and oxidative stress are involved in brain damage following stroke, and tryptophan oxidation along the kynurenine pathway contributes to the modulation of oxidative stress partly via the glutamate receptor agonist quinolinic acid and antagonist kynurenic acid, and via redox-active compounds such as 3-hydroxyanthranilic acid. We have confirmed that following a stroke, patients show early elevations of plasma neopterin, S100B and peroxidation markers, the latter two correlating with infarct volume assessed from computed tomography (CT) scans, and being consistent with a rapid inflammatory response. We now report that the kynurenine pathway of tryptophan metabolism was also activated, with an increased kynurenine : tryptophan ratio, but with a highly significant decrease in the ratio of 3-hydroxyanthranilic acid : anthranilic acid, which was strongly correlated with infarct volume. Levels of kynurenic acid were significantly raised in patients who died within 21 days compared with those who survived. The results suggest that increased tryptophan catabolism is initiated before or immediately after a stroke, and is related to the inflammatory response and oxidative stress, with a major change in 3-hydroxyanthranilic acid levels. Together with previous evidence that inhibiting the kynurenine pathway reduces brain damage in animal models of stroke and cerebral inflammation, and that increased kynurenine metabolism directly promotes oxidative stress, it is proposed that oxidative tryptophan metabolism may contribute to the oxidative stress and brain damage following stroke. Some form of anti-inflammatory intervention between the rise of S100B and the activation of microglia, including inhibition of the kynurenine pathway, may be valuable in modifying patient morbidity and mortality.

SUMMARY The urothelium is an epithelia barrier lined by a luminal layer of binucleated, octoploid, superficial cells. Superficial cells are critical for production and transport of uroplakins, a family of proteins that assemble into a waterproof crystalline plaque that helps protect against infection and toxic substances. Adult urothelium is nearly quiescent, but rapidly regenerates in response to injury. Yet the mechanism by which binucleated, polyploid, superficial cells are produced remains unclear. Here, we show that superficial cells are likely to be derived from a population of binucleated intermediate cells, which are produced from mononucleated intermediate cells via incomplete cytokinesis. We show that binucleated intermediate and superficial cells increase DNA content via endoreplication, passing through S phase without entering mitosis. The urothelium can be permanently damaged by repetitive or chronic injury or disease. Identification of the mechanism by which superficial cells are produced may be important for developing strategies for urothelial repair.

A substantial number of persons anticipated a barrier to diabetes education. Interventions at multiple levels that address the demographic and socioeconomic obstacles to diabetes education are needed to ensure successful self-management training.

Limited access to health care is associated with adverse outcomes, but few studies have examined its effect on glycemic control in minority populations. Our observational cross-sectional study examined whether differences in health care access affected hemoglobin A1c (HbA1c) levels in 605 patients with diabetes (56% women; 89% African American; average age, 50 years; 95% with type 2 diabetes) initially treated at a municipal diabetes clinic. Patients who had difficulty obtaining care had higher A1c levels (9.4% vs. 8.7%; p=0.001), as did patients who used acute care facilities (9.5%; p<0.001) or who had no usual source of care (10.3%; p<0.001) compared with those who sought care at doctors' offices or clinics (8.6%). In adjusted analyses, HbA1c was higher in persons who gave a history of trouble obtaining medical care (0.57%; p=0.04), among persons who primarily used an acute care facility to receive their health care (0.49%; p=0.047), and in patients who reported not having a usual source of care (1.08%; p=0.009). Policy decisions for improving diabetes outcomes should target barriers to health care access and focus on developing programs to help high-risk populations maintain a regular place of health care.

Recognition of patient exercise preferences and barriers should help in developing exercise strategies for improving glycemic control.