Sirtinol Treatment Reduces Inflammation in Human Dermal Microvascular Endothelial Cells

Histone deacetylases (HDAC) are key enzymes in the epigenetic control of gene expression. Recently, inhibitors of class I and class II HDAC have been successfully employed for the treatment of different inflammatory diseases such as rheumatoid arthritis, colitis, airway inflammation and asthma. So far, little is known so far about a similar therapeutic effect of inhibitors specifically directed against sirtuins, the class III HDAC. In this study, we investigated the expression and localization of endogenous sirtuins in primary human dermal microvascular endothelial cells (HDMEC), a cell type playing a key role in the development and maintenance of skin inflammation. We then examined the biological activity of sirtinol, a specific sirtuin inhibitor, in HDMEC response to pro-inflammatory cytokines. We found that, even though sirtinol treatment alone affected only long-term cell proliferation, it diminishes HDMEC inflammatory responses to tumor necrosis factor (TNF)α and interleukin (IL)-1β. In fact, sirtinol significantly reduced membrane expression of adhesion molecules in TNFã- or IL-1β-stimulated cells, as well as the amount of CXCL10 and CCL2 released by HDMEC following TNFα treatment. Notably, sirtinol drastically decreased monocyte adhesion on activated HDMEC. Using selective inhibitors for Sirt1 and Sirt2, we showed a predominant involvement of Sirt1 inhibition in the modulation of adhesion molecule expression and monocyte adhesion on activated HDMEC. Finally, we demonstrated the in vivo expression of Sirt1 in the dermal vessels of normal and psoriatic skin. Altogether, these findings indicated that sirtuins may represent a promising therapeutic target for the treatment of inflammatory skin diseases characterized by a prominent microvessel involvement

How sowing date affects development and performance of safflower through climate variables

Safflower (Carthamus tinctorius L.) has unrealized potential as an alternative crop in many semiarid regions including central Argentina. Our objective was to relate how temperature and precipitation conditions with fall (5 June 2012 and 23 Apr. 2013) and winter sowing (13 Aug. 2012 and 20 Aug. 2013) affected phenology, yield, yield components, and oil percent in four winter and eight spring-type safflower accessions in the semiarid region of central Argentina. Fall sowing was associated with lower temperatures, higher precipitation, lower heat/moisture stress indices and precipitation deficits than winter sowing. Rosette period lasted 55 d longer, and stem elongation to anthesis period 30 d longer in fall than in winter sowing. However, anthesis was advanced only few days in fall sowing and duration of postanthesis development was comparable between sowing regimes and years. Fall sowing plants averaged 3,252 filled grains m–2 and a grain yield of 109.8 g m–2, whereas winter sowing plants averaged 1,443 filled grains m–2 and a grain yield of 49.3 g m–2. Grain yield was 35% higher in winter than in spring-type accessions, but winter types had lower oil percent (22.0%) than spring-types (33.3%). In the semiarid region of central Argentina, we recommend fall sowing as it extended the growing season in terms of days preanthesis and presented favorable climatic conditions for safflower development.Fil: Franchini, María Clara. Universidad Nacional del Sur. Departamento de Agronomía; ArgentinaFil: Flemmer, Andrea Cecilia. Universidad Nacional del Sur. Departamento de Agronomía; ArgentinaFil: Lindström, Lilia Ivone. Universidad Nacional del Sur. Departamento de Agronomía; ArgentinaFil: Carrin, Maria Elena. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Constenla, Diana Teresita. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Planta Piloto de Ingeniería Química. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina. Universidad Nacional del Sur; ArgentinaFil: Johnson, Richard Coburn. Washington State University; Estados Unido

Chronic pancreatitis: report from a multicenter Italian survey (PanCroInfAISP) on 893 patients

BACKGROUND: No data on chronic pancreatitis in Italy are available yet. AIM: To evaluate demographic, clinical, diagnostic and therapeutic aspects in patients suffering from chronic pancreatitis. PATIENTS AND METHODS: Eligible patients were prospectively enrolled from 2000 to 2005. Information concerning demographic data, lifestyle risk factors, family and clinical history, associated factors (alcohol, autoimmunity, cystic dystrophy of the duodenal wall, obstruction, genetic mutations) concomitant diseases, diagnostic findings, and pharmacological, endoscopic and surgical therapy were gathered. RESULTS: 893 patients (74% males, mean age 53.7+/-15.2 years) were evaluated. 519/859 patients (60%) were drinkers and 555/840 (66%) were smokers. A strong positive correlation between drinking and cigarette consumption (R=0.53; p80g of alcohol/day for more than 5 years) was considered the most important risk factor in 300 patients (34%), obstruction in 238 (27%), alcohol and obstruction in 82 (9%), autoimmunity in 34 (4%), cystic dystrophy of the duodenal wall/groove pancreatitis in 55 (6%), gene mutations in 36 (4%), and none (idiopathic) in 148 (17%). Bile stones were diagnosed in 287 patients (33%) and cholecystectomy was performed in 329 patients (38%). Pancreatic calcifications were diagnosed in 547/879 patients (62%). Pancreatic surgery was performed in 273 patients (31%). Endoscopic sphincterotomy was performed in 371 patients (42%). Exocrine and endocrine insufficiency were found, respectively, in 373/834 (45%) and 275/885 patients (31%