Effects of Resveratrol on Inflammatory Biomarkers in Glaucomatous Human Trabecular Meshwork Cells.

PURPOSE: Resveratrol (RSV), an antioxidant polyphenol, has demonstrated beneficial effects in various ocular diseases including glaucoma. Our study was designed to evaluate the effects of RSV on nitric oxide synthase (NOS) enzymes, nitric oxide (NO) and interleukin-1 alpha (IL-1 α), in human glaucomatous trabecular meshwork (TM) cells. METHODS: Western blot was utilized to determine endothelial and inducible NOS (eNOS, iNOS) expression. The concentration-related effects of RSV on IL-1 α and NO levels were assessed using the respective ELISA kits. RESULTS: Densitometry data showed concentration-related increases in eNOS, and reduction in iNOS expression at high RSV concentrations. RSV treatment (0.1, 1, 10 and 100 µM) resulted in increased NO levels (6 ± 0.7, 7 ± 0.8, 7.3 ± 0.7 and 9.5 ± 1 nM/mg protein, respectively). The average value obtained for control was 4.8 ± 0.6 nM/mg protein. Significant increases in IL-1α levels were observed with lower concentrations of RSV. However, at higher RSV concentrations (10-100 µM), IL-1 levels decreased. CONCLUSIONS: Resveratrol increased NO in glaucomatous TM cells, possibly by increasing eNOS expression. Thus, RSV-induced NO production supports the beneficial effects of this antioxidant in glaucoma. Furthermore, our results showing a reduction in iNOS, a contributor to oxidative stress expression, further support RSV's antioxidant capabilities in vision.

Perspectives on optimizing care of patients in multidisciplinary chronic kidney disease clinics.

PURPOSE OF REVIEW: To summarize a jointly held symposium by the Canadian Society of Nephrology (CSN), the Canadian Association of Nephrology Administrators (CANA), and the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) entitled "Perspectives on Optimizing Care of Patients in Multidisciplinary Chronic Kidney Disease (CKD) Clinics" that was held on April 24, 2015, in Montreal, Quebec. SOURCES OF INFORMATION: The panel consisted of a variety of members from across Canada including a multidisciplinary CKD clinic patient (Randall Russell), nephrology fellow (Dr. David Collister), geriatrician (Dr. Josee Verdon), and nephrologists (Dr. Monica Beaulieu, Dr. Adeera Levin). FINDINGS: The objectives of the symposium were (1) to gain an understanding of the goals of care for CKD patients, (2) to gain an appreciation of different perspectives regarding optimal care for patients with CKD, (3) to examine the components required for optimal care including education strategies, structures, and tools, and (4) to describe a framework and metrics for CKD care which respect patient and system needs. This article summarizes the key concepts discussed at the symposium from a patient and physician perspectives. Key messages include (1) understanding patient values and preferences is important as it provides a framework as to what to prioritize in multidisciplinary CKD clinic and provincial renal program models, (2) barriers to effective communication and education are common in the elderly, and adaptive strategies to limit their influence are critical to improve adherence and facilitate shared decision-making, (3) the use of standardized operating procedures (SOPs) improves efficiency and minimizes practice variability among health care practitioners, and (4) CKD scorecards with standardized system processes are useful in approaching variability as well as measuring and improving patient outcomes. LIMITATIONS: The perspectives provided may not be applicable across centers given the differences in patient populations including age, ethnicity, culture, language, socioeconomic status, education, and multidisciplinary CKD clinic structure and function. IMPLICATIONS: Knowledge transmission by collaborative interprovincial and interprofessional networks may play a role in facilitating optimal CKD care. Validation of system and clinic models that improve outcomes is needed prior to disseminating these best practices.

OBJECTIF DE LA REVUE: Cette revue se veut une récapitulation des thèmes abordés lors du colloque intitulé « Perspectives on Optimizing Care of Patients in Multidisciplinary Chronic Kidney Disease Clinics ¼. Ce colloque organisé conjointement par la Société Canadienne de Néphrologie, la Canadian Association of Nephrology Administrators (CANA) et la Canadian Kidney Knowledge Translation and Generation Network (CANN-NET), s'est tenu le 24 avril 2015 à Montréal, au Canada. SOURCES: Cette table ronde réunissait des membres provenant de partout au Canada. Les intervenants invités à discuter lors de ce colloque comptaient un patient fréquentant une clinique multidisciplinaire en suivi des maladies rénales chroniques (Randall Russell) un chercheur boursier en néphrologie (Dr David Collister), une gériatre (Dre Josée Verdon) et deux néphrologues (Dre Monica Beaulieu et Dre Adeera Levin). OBSERVATIONS: Ce colloque visait plusieurs objectifs. D'abord on voulait se faire une meilleure idée des objectifs fixés en matière de soins offerts aux patients souffrant d'IRC. On a ensuite tenté de faire le portrait des différents points de vue en matière de soins optimaux à prodiguer aux patients atteints d'IRC et se pencher sur les éléments requis pour y arriver, notamment les structures et outils nécessaires, et les méthodes pédagogiques à favoriser. Finalement, ce colloque visait à définir un cadre et des paramètres de soins en IRC qui respectent les besoins des patients et du système de santé. Le présent article résume les concepts-clés discutés lors de ce colloque du point de vue du médecin traitant, mais également de celui d'un patient atteint d'IRC. Les messages-clés abordés incluent les observations suivantes: 1) Il est important de tenir compte des valeurs et des préférences du patient dans l'établissement des priorités des cliniques multidisciplinaires et des modèles de programmes provinciaux en IRC. 2) On constate que les obstacles à une communication et à un enseignement efficaces sont fréquents chez les patients âgés. Ainsi les stratégies adaptatives limitant leur influence sont cruciales pour améliorer l'adhésion du patient au traitement et faciliter la prise de décision conjointe. 3) On observe que l'usage de procédures opérationnelles normalisées améliore l'efficacité et minimise la variabilité dans la pratique chez les professionnels de la santé. 4) Les fiches d'évaluation en IRC doublées d'une uniformisation des systèmes et des procédés, sont utiles pour aborder le traitement de la variabilité tout autant que pour mesurer et améliorer les résultats pour les patients. LIMITES DE L'ÉTUDE: Les points de vue exprimés peuvent ne pas s'appliquer dans tous les centres de soins compte tenu des différences appréciables parmi les patients souffrant d'IRC. Ces différences incluent notamment l'âge l'origine ethnique, les différences culturelles, la langue parlée, le statut socio-économique, le niveau de scolarité, de même que la structure et les fonctions de la clinique multidisciplinaire de suivi en IRC fréquentée par le patient. CONCLUSION: La transmission des connaissances par l'entremise d'un réseau interprovincial et interprofessionnel de collaboration pourrait contribuer à faciliter l'administration de soins optimaux en IRC. Une validation du système et des modèles cliniques permettant l'amélioration des résultats pour les patients est requise préalablement à la diffusion de ces pratiques exemplaires.

Kappa opioid receptor localization and coupling to nitric oxide production in cells of the anterior chamber.

PURPOSE: The present study was designed to determine whether kappa opioid receptors (KORs) are localized to cells of the inflow and outflow pathways of the eye and if activation of these receptors has an effect on nitric oxide (NO) production, because these effects could play a role in KOR agonist-mediated reduction of IOP. METHODS: Human nonpigmented ciliary epithelial (NPCE) and trabecular meshwork (HTM-3) cells were treated with spiradoline (SPR), a selective KOR agonist, or estradiol, for 24 hours. Some cells were pretreated with the selective KOR antagonist norbinaltorphimine (norBNI) or the nonselective NO synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) for 30 minutes, followed by the addition of SPR. Immunofluorescent localization of KORs was determined in isolated rabbit iris-ciliary bodies (ICBs) and NPCE and HTM-3 cells. RESULTS: Immunohistochemical data show the localization of KORs to the rabbit ICB and more specifically to the ciliary epithelial layer. KORs were also found on cell membranes of NPCE and HTM-3 cells. Treatment of both these cell types with spiradoline caused concentration-dependent increases in the release of NO. Spiradoline-induced release of NO from both cell types was inhibited by pretreatment with norBNI and L-NAME. CONCLUSIONS: Results from this study show the presence of KORs on rabbit ICBs and also on NPCE and HTM cells. Activation of these KORs on both cell types resulted in KOR-mediated increases in NO production. These findings provide evidence that previously demonstrated KOR-mediated reduction in IOP could be caused, in part, by NO production in both the ciliary body and the trabecular meshwork.