Aberrant glycosylation in IgA nephropathy (IgAN)

Aberrant glycosylation in IgA nephropathy (IgAN). Immunoglobulin A nephropathy (IgAN) patients exhibit circulating IgA1 with reduced galactose (Gal) and/or sialic acid (Neu5Ac) and increased exposure of N-acetylgalactosamine (GalNAc). These IgA glycoforms fix complement and in mesangial cells regulate integrin expression, enhance nitric oxide synthase (NOS) activity, decrease endothelial growth factor synthesis, meanwhile depressing proliferation and increasing apoptotis. Drugs can be targeted to the effects enhanced by aberrantly glycosylated IgA1 on mesangial cells. Recent data suggest that aberrant IgA1 glycosylation may modulate clinical expression and progression of IgAN

Healthy lifestyle empowerment: A manual for healthcare professionals

This manual provides guidance to healthcare professionals and managers working in clinical settings on how to empower patients and their relatives, hospital visitors and healthcare professionals towards healthier choices. Chapter 1 provides recommendations based on the highest level of evidence, resulting from overviews of high quality systematic reviews (AMSTAR score higher than 8) including randomised controlled trials testing interventions aimed at modifying behaviours known to be associated with non communicable chronic diseases. Chapter 2 offers guidance to translate evidence into practice and to organise empowering activities. This chapter includes essential activities such as policy management, individual risk profling, designing and managing empowering initiatives and preparing a sustainability plan. Chapter 3 describes how to integrate empowerment activities and initiatives offered at the hospital and those available in the hospital jurisdiction. This chapter also suggests how to involve stakeholders and to manage their contributions according to the WHO ‘Health in all’ principles

GLI INTERVENTI PER LA PROMOZIONE DI UN\u2019ALIMENTAZIONE CORRETTA IN ITALIA

OBJECTIVES: to describe the prevention interventions conducted by the Regional health services to promote a healthy diet. MATERIAL AND METHODS: the database ProSA, which contains prevention interventions conducted by some Italian regions, has been analysed. Programmes identified as \uabDiet \u2013 physical activity\ubb were selected, and the ones that had the promotion of healthy diet in unselected populations as objective were included. Then, the programmes were analysed and described. RESULTS: a total of 87 programmes were included, 23 of which are certainly conducted during 2013-14. 91%are school-based, particularly targeted tomiddle schools, and 37%are based on classroomlessons.No programmemade any reference to specific evidence, while 11%of themcited scientific generic but relevant papers. 15% of the programmes described some evaluation process, but only 1% has proposed a study design with controls. Limiting the analysis to the region that contributed with the largest amount of recorded programmes, it can be estimated that programmes does not reached more than 0.03% of the general population, and 4% of the school population. CONCLUSIONS: in Italy, there is not a survey system to collect preventive interventions conducted by regional health authorities. The analysis of ProSA, an experimental system, allows us to highlight that the promotion of a healthy diet is based on interventions targeting only the school population and referring to scientific evidence in a very limited way. Moreover, they seem to cover very small part of the target population

Association of Autoimmunity to Autonomic Nervous Structures With Nerve Function in Patients With Type 1 Diabetes: A 16-Year Prospective Study

OBJECTIVE We prospectively evaluate the association between autoimmunity to autonomic nervous structures and autonomic neuropathy in type 1 diabetes in relation to clinical variables. RESEARCH DESIGN AND METHODS A cohort of 112 patients with type 1 diabetes was prospectively followed from adolescence (T0) to approximately 4 (T4) and 16 (T16) years later. Standard cardiovascular (CV) tests and neurological examination were performed and related to the presence of circulating antibodies (Ab) to autonomic nervous structures detected at T0 and T4. Quality of life was assessed by a diabetes-specific questionnaire. RESULTS Sixty-six patients (59% of the cohort) were re-examined at T16 (age 31.4 ± 2 years; disease duration 23.4 ± 3.7 years). Nineteen had circulating Ab to autonomic structures. Prevalence of abnormal tests and autonomic symptoms were higher in Ab-positive (68 and 26%, respectively) than Ab-negative (32 and 4%) patients ( P 1c increase). Presence of Ab carried over a 68% probability of developing an altered CV test; absence of Ab carried a 91% probability of not having an altered DB test and an 89% probability of not having an altered Valsalva ratio. Autonomic neuropathy was independently associated with worse quality of life. CONCLUSIONS Circulating Ab to autonomic structures are associated with the development of autonomic dysfunction in young diabetic patients independent of glycemic control

A possible role for nitric oxide in modulating the functional cyclosporine toxicity by arginine

A possible role for nitric oxide in modulating the functional cyclosporine toxicity by arginine. The renal damage consequent to cyclosporine A (CsA) administration ranges from hemodynamic alterations to irreversible chronic lesions. The initial vasoconstriction depends upon the imbalance between the various modulators of the renal vascular tone, among which the most powerful are endothelins and nitric oxide (NO). CsA could play a crucial role by inhibiting the Ca++/calmodulin-mediated activation of the constitutive NO synthase (NOS) isoform, which converts L-arginine (L-Arg) into NO and citrulline, with a 1:1 stoichiometry. To investigate the possibility of modulating CsA nephrotoxicity with L-Arg we studied six groups (G) of Lewis rats treated with daily gavage up to eight weeks: G1, CsA 40 mg/kg; G2, G1 plus L-Arg 300 mg/kg; G3, G2 plus the competitive inhibitor of NOS, NG-nitro-L-Arg (L-NNA); G4, L-Arg alone; G5, L-NNA alone; and G6, controls receiving vehicle alone. After eight weeks L-Arg treated rats were protected against the toxic effects of CsA [creatinine (Cr) values, G2, 0.62 ± 0.05 mg/dl vs. G1, 0.99 ± 0.16 mg/dl, P < 0.001; proteinuria (P), G2, 7.2 ± 1.02 mg/day vs. G1, 15.1 ± 1.9 mg/day, P < 0.01]. The administration of L-NNA abolished the protective effect of L-Arg (G3, Cr 1.23 ± 0.16 mg/dl; P 16.9 = 2.3; P < 0.02 and P < 0.005, respectively vs. G2). The levels of Cr in G2 rats were superimposable to control groups. The NOS activity, evaluated by measuring [3H]citrulline formation from [3H]L-Arg in kidney homogenates, was blocked by L-NNA in G5 (0.019 ± 0.009 pmol/min/mg proteins vs. G6 0.047 ± 0.002, P < 0.01). NOS activity was significantly increased versus controls in G1 (0.110 ± 0.032, P < 0.01) and G2 (0.088 ± 0.009, P < 0.02), while L-NNA reversed this phenomenon (G3, 0.052 ± 0.03). The expression of mRNA encoding for cNOS and iNOS was only slightly increased in CsA-treated rats. We suggest that CsA treatment increases NOS activity in the kidney by a mechanism which does not require a de novo synthesis of the enzyme. Such an increase, that may be devoted to counterbalance the vasoconstrictive effects of the drug, is unable to reduce the toxic effect of CsA in the absence of exogenous L-Arg. Administration of L-Arg is likely to reduce CsA nephrotoxicity by accomplishing the higher request of activated NOS for its substrate, thus potentiating NO synthesis in the kidney.