Inhibition of Fenton reaction is a novel mechanism to explain the therapeutic effect of intra-articular injection of PRP in patients with chronic haemophilic synovitis

Introduction and Aim: Haemarthroses cause major morbidity in haemophilia resulting in chronic haemophilic synovitis (CHS) and arthropathy. Oxidation of haemoglobin-coupled iron released in synovium after haemolysis induces chondrocytes death and cartilage damage, allowing postulate using iron-chelating drugs as potential therapeutic tool for haemophilic joint damage. Considering that albumin, the most abundant plasma protein, is a physiologic iron chelator, we aim to demonstrate that impediment of haemoglobin oxidation is exerted by plasma as a mechanism involved in the therapeutic effect of intra-articular injection of platelet-rich plasma in CHS. Methods: Oxidation of haemoglobin (Hb) to methaemoglobin (MeHb) through Fenton reaction was induced in vitro by addition of potassium ferricyanide in the presence or absence of peripheral blood-derived platelets-rich or platelets-poor plasma (PRP/ PPP) or albumin. The relevance of in vitro findings was analysed in synovial fluid (SF) samples from one patient with CHS obtained before and after 6 months of PRP intraarticular injection. Results: MeHb formation was completely impaired either by of PPP, PRP or albumin indicating that PRP exerts an anti-oxidative effect, probably due by plasma albumin. Analysis of SF samples revealed the presence of MeHb levels and haemosiderinladen macrophages in SF obtained before PRP treatment. Reduction of synovial MeHb, normalization of cellular composition and improvement of health joint haemophilic score, pain and bleeding episodes were registered after 6 months of PRP intra-articular injection. Conclusion: Inhibition of Fenton reaction and the consequent normalization of joint cellular composition is a noncanonical mechanism underlying the therapeutic effect of PRP intra-articular injection in CHS.Fil: Caviglia, Horacio. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Daffunchio, Carla. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Galatro, Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Cambiaggi, Guillermo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Oneto, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Douglas Price, Ana Laura. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Landro, María Eulalia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Etulain, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

Prevalence of atopic dermatitis in Italian schoolchildren: Factors affecting its variation

The frequency of atopic dermatitis in Italian children and its relationship with selected variables were analysed in a large survey of skin health conducted in Italy. In 1997 we conducted a survey on schoolchildren aged 12-17 years from 13 areas of northern, central and southern Italy. For the present analyses, 3179 Caucasian children (1618 males, 1561 females) were considered. A diagnosis of atopic dermatitis was reported in 224 cases (7.0%). The frequency of reported atopic dermatitis was significantly higher in children with asthma (rate ratio (RR) 4.5; 95% confidence interval (CI) 3.1-6.5). The lifetime prevalence of a diagnosis of atopic dermatitis was higher among schoolchildren reporting a diagnosis of psoriasis (RR 5.5, 95% CI 3.0-10.1) and vitiligo, (RR 16.1, 95% CI 6.5-39.5). This study gives estimates of the lifetime prevalence of atopic dermatitis in adolescents in Italy and emphasizes the direct association between the condition and other immune-related skin diseases. \ufffd\ufffd 2009 The Authors. Journal Compilation \ufffd\ufffd 2009 Acta Dermato-Venereologica

Common variant in the <em>HMGA2</em> gene increases susceptibility to nephropathy in patients with type 2 diabetes

AIMS/HYPOTHESIS: Type 2 diabetes is a chronic metabolic disorder associated with devastating microvascular complications. Genome-wide association studies have identified more than 60 genetic variants associated with type 2 diabetes and/or glucose and insulin traits, but their role in the progression of diabetes is not established. The aim of this study was to explore whether these variants were also associated with the development of nephropathy in patients with type 2 diabetes. METHODS: We studied 28 genetic variants in 2,229 patients with type 2 diabetes from the local Malmö Scania Diabetes Registry (SDR) published during 2007-2010. Diabetic nephropathy (DN) was defined as micro- or macroalbuminuria and/or end-stage renal disease. Estimated glomerular filtration rate (eGFR) was assessed using the MDRD-4 formula. Replication genotyping of rs1531343 was performed in diabetic (Steno type 2 diabetes [n = 345], Genetics of Diabetes Audit and Research in Tayside Scotland [Go-DARTS] [n = 784]) and non-diabetic (Malmö Preventive Project [n = 2,523], Botnia study [n = 2,247]) cohorts. RESULTS: In the SDR, HMGA2 single-nucleotide polymorphism rs1531343 was associated with DN (OR 1.50, 95% CI 1.20, 1.87, p = 0.00035). In the combined analysis totalling 3,358 patients with type 2 diabetes (n = 1,233 cases, n = 2,125 controls), carriers of the C-allele had a 1.45-fold increased risk of developing nephropathy (95% CI 1.20, 1.75, p = 0.00010). Furthermore, the risk C-allele was associated with lower eGFR in patients with type 2 diabetes (n = 2,499, β ± SEM, -3.7 ± 1.2 ml/min, p = 0.002) and also in non-diabetic individuals (n = 17,602, β ± SEM, -0.008 ± 0.003 ml/min (log( e )), p = 0.006). CONCLUSIONS/INTERPRETATION: These data demonstrate that the HMGA2 variant seems to be associated with increased risk of developing nephropathy in patients with type 2 diabetes and lower eGFR in both diabetic and non-diabetic individuals and could thus be a common denominator in the pathogenesis of type 2 diabetes and kidney complications

Prevalence of atopic dermatitis in Italian schoolchildren: factors affecting its variation

The frequency of atopic dermatitis in Italian children and its relationship with selected variables were analysed in a large survey of skin health conducted in Italy. In 1997 we conducted a survey on schoolchildren aged 12-17 years from 13 areas of northern, central and southern Italy. For the present analyses, 3179 Caucasian children (1618 males, 1561 females) were considered. A diagnosis of atopic dermatitis was reported in 224 cases (7.0%). The frequency of reported atopic dermatitis was significantly higher in children with asthma (rate ratio (RR) 4.5; 95% confidence interval (CI) 3.1-6.5). The lifetime prevalence of a diagnosis of atopic dermatitis was higher among schoolchildren reporting a diagnosis of psoriasis (RR 5.5, 95% CI 3.0-10.1) and vitiligo (RR 16.1, 95% CI 6.5-39.5). This study gives estimates of the lifetime prevalence of atopic dermatitis in adolescents in Italy and emphasizes the direct association between the condition and other immune-related skin diseases