The natural organosulfur compound dipropyltetrasulfide prevents HOCL-induced systemic sclerosis in the mouse

PublishedArticleIntroduction: The aim of this study was to test the naturally occurring organosulfur compound dipropyltetrasulfide (DPTTS) found in plants, which has antibiotic and anti-cancer properties, as a treatment of HOCl-induced systemic sclerosis in the mouse. Methods: The pro-oxidative, anti-proliferative and cytotoxic effects of DPTTS were evaluated ex vivo on fibroblasts from normal and HOCl-mice. In vivo, the anti-fibrotic and immunomodulating properties of DPTTS were evaluated in the skin and lungs of HOCl-mice. Results: H2O2 production was higher in fibroblasts derived from HOCl-mice than in normal fibroblasts (P<0.05). DPTTS did not increase H2O2 production in normal fibroblasts, but DPTTS dose-dependently increased H2O2 production in HOCl-fibroblasts (P<0.001 with 40μM DPTTS). Because H2O2 reached a lethal threshold in cells from HOCl-mice, the anti-proliferative, cytotoxic and pro-apoptotic effects of DPTTS were significantly higher in HOCl-fibroblasts than for normal fibroblasts. In vivo, DPTTS decreased dermal thickness (P<0.001), collagen content in skin (P<0.01) and lungs (P<0.05), SMA (P<0.01) and pSMAD2/3 (P<0.01) expression in skin, formation of advanced oxidation protein products and anti-DNA topoisomerase-1 antibodies in serum (P<0.05) versus untreated HOCl- mice. Moreover, in HOCl-mice, DPTTS reduced splenic B cell counts (P<0.01), the proliferative rates of B-splenocytes stimulated by lipopolysaccharide (P<0.05) and T-splenocytes stimulated by anti-CD3/CD28 mAb (P<0.001). Ex vivo, it also reduced the production of IL-4 and IL-13 by activated T cells (P<0.05 in both cases). Conclusions: The natural organosulfur compound DPTTS prevents skin and lung fibrosis in the mouse through the selective killing of diseased fibroblasts and its immunomodulating properties. DPTTS may be a potential treatment of Systemic sclerosis.This work was supported by European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement 215009 RedCat for financial support. The authors are grateful to Ms Agnes for her excellent typing of the manuscript

Mangafodipir Protects against Hepatic Ischemia-Reperfusion Injury in Mice

Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP) was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse.Mice were subjected to 70% hepatic ischemia (continuous ischemia) for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg) or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT) activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity). The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia.<0.01), and by higher rates of survival in treated than in untreated animals (P<0.001). The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning.Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury

Epidemiology, Species Distribution, Antifungal Susceptibility and Outcome of Nosocomial Candidemia in a Tertiary Care Hospital in Italy

Candida is an important cause of bloodstream infections (BSI), causing significant mortality and morbidity in health care settings. From January 2008 to December 2010 all consecutive patients who developed candidemia at San Martino University Hospital, Italy were enrolled in the study. A total of 348 episodes of candidaemia were identified during the study period (January 2008–December 2010), with an incidence of 1,73 episodes/1000 admissions. Globally, albicans and non-albicans species caused around 50% of the cases each. Non-albicans included Candida parapsilosis (28.4%), Candida glabrata (9.5%), Candida tropicalis (6.6%), and Candida krusei (2.6%). Out of 324 evaluable patients, 141 (43.5%) died within 30 days from the onset of candidemia. C. parapsilosis candidemia was associated with the lowest mortality rate (36.2%). In contrast, patients with C. krusei BSI had the highest mortality rate (55.5%) in this cohort. Regarding the crude mortality in the different units, patients in Internal Medicine wards had the highest mortality rate (54.1%), followed by patients in ICU and Hemato-Oncology wards (47.6%)

EFfects on yield, net photosynthesis, and leaf duration, of a well-defined water stress applied on sunflower from beginning flowering to maturity

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The Effects of Allicin, a Reactive Sulfur Species from Garlic, on a Selection of Mammalian Cell Lines

Garlic (Allium sativum L.) has been used as a spice and medicinal plant since ancient times. Garlic produces the thiol-reactive defence substance, allicin, upon wounding. The effects of allicin on human lung epithelium carcinoma (A549), mouse fibroblast (3T3), human umbilical vein endothelial cell (HUVEC), human colon carcinoma (HT29) and human breast cancer (MCF7) cell lines were tested. To estimate toxic effects of allicin, we used a standard MTT-test (methylthiazoltetrazolium) for cell viability and 3H-thymidine incorporation for cell proliferation. The glutathione pool was measured using monobromobimane and the formation of reactive species was identified using 2′,7′-dichlorofluoresceine-diacetate. The YO-PRO-1 iodide staining procedure was used to estimate apoptosis. Allicin reduced cell viability and cell proliferation in a concentration dependent manner. In the bimane test, it was observed that cells treated with allicin showed reduced fluorescence, suggesting glutathione oxidation. The cell lines tested differed in sensitivity to allicin in regard to viability, cell proliferation and glutathione oxidation. The 3T3 and MCF-7 cells showed a higher proportion of apoptosis compared to the other cell types. These data show that mammalian cell lines differ in their sensitivity and responses to allicin

ABA content and some key enzyme activities in response to water stress

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Medical Decision-Making Processes and Online Behaviors Among Cannabis Dispensary Staff

Background: Most cannabis patients engage with dispensary staff, like budtenders, for medical advice on cannabis. Yet, little is known about these interactions and how the characteristics of budtenders affect these interactions. This study investigated demographics, workplace characteristics, medical decision-making, and online behaviors among a sample of budtenders. Methods: Between June and September 2016, a cross-sectional Internet survey was administered to budtenders in the San Francisco Bay Area and Greater Los Angeles. A total of 158 budtenders fully responded to the survey. A series of comparisons were conducted to determine differences between trained and untrained budtenders. Results: Among the 158 budtenders, 56% had received formal training to become a budtender. Several demographic differences were found between trained and untrained budtenders. For workplace characteristics, trained budtenders were more likely to report budtender as their primary job (74% vs 53%), practice more than 5 years (34% vs 11%), and receive sales commission (57% vs 16%). Trained budtenders were significantly less likely to perceive medical decision-making as very important (47% vs 68%) and have a patient-centered philosophy (77% vs 89%). Although trained budtenders had significantly lower Internet usage, they were significantly more likely to exchange information with patients through e-mail (58% vs 39%), text message (46% vs 30%), mobile app (33% vs 11%), video call (26% vs 3%), and social media (51% vs 23%). Conclusions: Budtenders who are formally trained exhibit significantly different patterns of interaction with medical cannabis patients. Future studies will use multivariate methods to better determine which factors independently influence interactions and how budtenders operate after the introduction of regulations under the newly passed Proposition 64 that permits recreational cannabis use in California