Involvement of heparanase in the pathogenesis of acute kidney injury: Nephroprotective effect of PG545

Despite the high prevalence of acute kidney injury (AKI) and its association with increased morbidity and mortality, therapeutic approaches for AKI are disappointing. This is largely attributed to poor understanding of the pathogenesis of AKI. Heparanase, an endoglycosidase that cleaves heparan sulfate, is involved in extracellular matrix turnover, inflammation, kidney dysfunction, diabetes, fibrosis, angiogenesis and cancer progression. The current study examined the involvement of heparanase in the pathogenesis of ischemic reperfusion (I/R) AKI in a mouse model and the protective effect of PG545, a potent heparanase inhibitor. I/R induced tubular damage and elevation in serum creatinine and blood urea nitrogen to a higher extent in heparanase over-expressing transgenic mice vs. wild type mice. Moreover, TGF-\u3b2, vimentin, fibronectin and \u3b1-smooth muscle actin, biomarkers of fibrosis, and TNF\u3b1, IL6 and endothelin-1, biomarkers of inflammation, were upregulated in I/R induced AKI, primarily in heparanase transgenic mice, suggesting an adverse role of heparanase in the pathogenesis of AKI. Remarkably, pretreatment of mice with PG545 abolished kidney dysfunction and the up-regulation of heparanase, pro-inflammatory (i.e., IL-6) and pro-fibrotic (i.e., TGF-\u3b2) genes induced by I/R. The present study provides new insights into the involvement of heparanase in the pathogenesis of ischemic AKI.Our results demonstrate that heparanase plays a deleterious role in the development of renal injury and kidney dysfunction,attesting heparanase inhibition as a promising therapeutic approach for AKI

Cutaneous lymphoma in Japan: A nationwide study of 1733 patients

Types of cutaneous lymphoma (CL) and their incidences may vary among geographic areas or ethnic groups. The present study aimed to investigate the incidences of various CL in Japan, using epidemiological data from a nationwide registration system for CL. Between 2007 and 2011, 1733 new patients with CL were registered from over 600 dermatological institutes in Japan. The 1733 patients registered included 1485 (85.7%) patients with mature T- and natural killer (NK)-cell neoplasms, 224 (12.9%) with B-cell neoplasms and 24 (1.4%) with blastic plasmacytoid dendritic cell neoplasm. Mycosis fungoides (MF) is the most common CL subtype in the present study (750 patients, 43.3%). The proportion of MF patients with early-stage disease was 73%, similar to that of previous studies from other cohorts. The incidence rates of adult T-cell leukemia/lymphoma and extranodal NK/T-cell lymphoma, nasal type were 16.7% and 2.0%, respectively, which may account for the higher incidence of mature T- and NK-cell neoplasms in Japan, as compared with that in the USA and Europe. A male predominance was observed in most types of CL, except for several CL subtypes such as subcutaneous panniculitis-like T-cell lymphoma

Aggressive Epidermotropic Cutaneous CD8+ Lymphoma:A cutaneous lymphoma with distinct clinical and pathological features Report of an EORTC Cutaneous Lymphoma Task Force Workshop

Aims: Aggressive epidermotropic cutaneous CD8+ lymphoma is currently afforded provisional status in the WHO classification of lymphomas. An EORTC Workshop was convened to describe in detail the features of this putative neoplasm and evaluate its nosological status with respect to other cutaneous CD8+ lymphomas. Methods and results: Sixty-one CD8+ cases were analysed at the workshop; clinical details, often with photographs, histological sections, immunohistochemical results, treatment and patient outcome were discussed and recorded. Eighteen cases had distinct features and conformed to the diagnosis of aggressive epidermotropic cutaneous CD8+ lymphoma. The patients typically present with widespread plaques and tumours, often ulcerated and haemorrhagic, and histologically have striking pagetoid epidermotrophism. A CD8+/CD45RA+/CD45RO-/CD2-/CD5-/CD56- phenotype, with one or more cytotoxic markers, was found in seven of 18 patients, with a very similar phenotype in the remainder. The tumours seldom involve lymph nodes, but mucosal and central nervous system involvement are not uncommon. The prognosis is poor, with a median survival of 12 months. Examples of CD8+ mycosis fungoides, lymphomatoid papulosis and Woringer-Kolopp disease presented the typical features well documented in the CD4+ forms of those diseases. Conclusions: Aggressive epidermotropic cutaneous CD8+ lymphoma is a distinct lymphoma that warrants inclusion as a distinct entity in future revisions of lymphoma classifications

THE ROLE Of 5αR AND α1AR INHIBITORS IN MANAGEMENT OF BPH

BPH is a common progressive condition in the aging population. Several treatment modalities have been proposed aimed at inhibiting the sympathetic input to the prostate gland with a selective α1 adrenoreceptor inhibitor and interfering with the androgen metabolism in the gland with 5α Reductase inhibitor. This study will ask the question whether combination therapy with either dutasteride or finasteride in addition to an α1 blocker is superior over monotherapy and will review and compare the safety, efficacy and development of the agents involved in the treatment.egységes, osztatlanáltalános orvosango