Zebrafish, a novel model system to study uremic toxins: The case for the sulfur amino acid lanthionine

The non-proteinogenic amino acid lanthionine is a byproduct of hydrogen sulfide biosynthesis: the third endogenous vasodilator gas, after nitric oxide and carbon monoxide. While hydrogen sulfide is decreased in uremic patients on hemodialysis, lanthionine is increased and has been proposed as a new uremic toxin, since it is able to impair hydrogen sulfide production in hepatoma cells. To characterize lanthionine as a uremic toxin, we explored its effects during the early development of the zebrafish (Danio rerio), a widely used model to study the organ and tissue alterations induced by xenobiotics. Lanthionine was employed at concentrations reproducing those previously detected in uremia. Light-induced visual motor response was also studied by means of the DanioVision system. Treatment of zebrafish embryos with lanthionine determined acute phenotypical alterations, on heart organogenesis (disproportion in cardiac chambers), increased heart beating, and arrhythmia. Lanthionine also induced locomotor alterations in zebrafish embryos. Some of these effects could be counteracted by glutathione. Lanthionine exerted acute effects on transsulfuration enzymes and the expression of genes involved in inflammation and metabolic regulation, and modified microRNA expression in a way comparable with some alterations detected in uremia. Lanthionine meets the criteria for classification as a uremic toxin. Zebrafish can be successfully used to explore uremic toxin effects

Prospects for detecting Gamma-Ray Bursts with the Cherenkov Telescope Array

The Large Area Telescope (LAT) on the Fermi gamma-ray satellite telescope observes Gamma-Ray Bursts (GRBs) at energies above 100 MeV. Thanks to a new detection algorithm and a new event reconstruction, it is expected to publish a catalogue with more than 100 GRBs. This work aims at revising the prospects for GRB alerts with the Cherenkov Telescope Array (CTA) based on the new LAT results. We start by considering the simulation of the observations with the full CTA of two extremely bright events, the long GRB 130427A and the short GRB 090510; then we investigate how these GRBs would be observed by different subsamples of the array pointing to different directions, adopting the \u201ccoupled divergent\u201d mode

Amifostine (wr-2721), A Cytoprotective Agent During High-dose Cyclophosphamide Treatment Of Non-hodgkin's Lymphomas: A Phase Ii Study.

Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY) (7 g/m2), used to mobilize peripheral blood progenitor cells (PBPC) and to reduce tumor burden. We enrolled 29 patients, 22 (75. 9%) affected by aggressive and 7 (24.1%) by indolent non-Hodgkin's lymphoma (NHL), who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients) affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0. 04). None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage) colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively). Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.33791-

Characteristics of structured physical training currently provided in cardiac patients: insights from the Exercise Training in Cardiac Rehabilitation (ETCR) Italian survey

Uncertainty exists about current delivery levels of exercise training (ET) during Cardiac Rehabilitation (CR) programmes. The aim of this study was to evaluate ET modalities in the real world of CR facilities in Italy. This was an observational survey of aggregate data, collected from CR facilities on a voluntary basis. Snapshots of a single working day at a local site were made, in terms of characteristics of patients and ET programmes delivered. Overall, 612 patients from 26 CR units were included, with an in-patient vs out-patient ratio of 3:1. Coronary artery disease (57.6%), heart failure (20.3%), and valve disease/surgery (22.1%) were the most represented target groups. The prevalence of endurance continuous training, interval training, and resistance/strength training was 66.7%, 11.1%, and 9.0%; other non-aerobic endurance and non-resistance training modalities such as respiratory muscle training and calisthenics were reported in 39.9% and 42.9% of cases respectively. Workloads for endurance exercise training were determined by cardiopulmonary test, conventional 12-leads ECG exercise testing, 6minwalking test, theoretical determination of heart rate, and rating of perceived exertion in 9%, 8%, 27%, 9%, and 40% of cases respectively. The average duration of the programmes (on an intention to treat basis) was 25 sessions of 42±11 min, with a frequency of >4 sessions/week in 67% of patients. Despite advances in CR interventions, there is a significant need for improvement of functional evaluation and exercise training prescription, and consideration of a wider range of training modalities in Ital

The Availability Of Full Match Sibling Donors And Feasibility Of Allogeneic Bone Marrow Transplantation In Brazil.

The feasibility of allogeneic bone marrow transplantation (alloBMT) in a developing country has not yet been demonstrated. Many adverse factors including social and economic limitations may reduce the overall results of this complex and expensive procedure. Our objective was to characterize the most important clinical, social and economic features of candidates for transplantation and their potential donors as well as the influence of these factors on overall survival in a retrospective and exploratory analysis at a university hospital. From July 1993 to July 2001, candidates for BMT were referred to the Bone Marrow Transplantation Unit by Hematology and Oncology Centers from several regions of Brazil. A total of 1138 patients were referred to us as candidates for alloBMT. Median age was 25 years (range: 2 months-60 years), 684 (60.1%) were males and 454 (39.9%) were females. The clinical indications were severe aplastic anemia and hematological malignancies. From the total of 1138 patients, 923 had HLA-typing; 497/923 (53.8%) candidates had full match donors; 352/1138 (30.8%) were eligible for alloBMT. Only 235 of 352 (66.7%) were transplanted. Schooling was 1st to 8th grade for 123/235 (52.3%); monthly family income ranged from US$60 (7$400 (36%). Overall survival for patients with chronic myeloid leukemia, severe aplastic anemia and acute myeloid leukemia was 58, 60 and 30%, respectively. Thus, overall survival rates for the most frequent hematological diseases were similar to those reported in the International Registry, except for acute myeloid leukemia. This descriptive and exploratory analysis suggests the feasibility of alloBMT in a developing country like Brazil.36315-2

Measurements and tests on FBK silicon sensors with an optimized electronic design for a CTA camera

In October 2013, the Italian Ministry approved the funding of a Research & Development (R&D) study, within the "Progetto Premiale TElescopi CHErenkov made in Italy (TECHE)", devoted to the development of a demonstrator for a camera for the Cherenkov Telescope Array (CTA) consortium. The demonstrator consists of a sensor plane based on the Silicon Photomultiplier (SiPM) technology and on an electronics designed for signal sampling. Preliminary tests on a matrix of sensors produced by the Fondazione Bruno Kessler (FBK-Trento, Italy) and on electronic prototypes produced by SITAEL S.p.A. will be presented. In particular, we used different designs of the electronics in order to optimize the output signals in terms of tail cancellation. This is crucial for applications where a high background is expected, as for the CTA experiment.Comment: 5 pages, 6 figures; Proceedings of the 10th Workshop on Science with the New Generation of High-Energy Gamma-ray experiments (SciNeGHE) - PoS(Scineghe2014)00