The creatine kinase system and pleiotropic effects of creatine

The pleiotropic effects of creatine (Cr) are based mostly on the functions of the enzyme creatine kinase (CK) and its high-energy product phosphocreatine (PCr). Multidisciplinary studies have established molecular, cellular, organ and somatic functions of the CK/PCr system, in particular for cells and tissues with high and intermittent energy fluctuations. These studies include tissue-specific expression and subcellular localization of CK isoforms, high-resolution molecular structures and structure–function relationships, transgenic CK abrogation and reverse genetic approaches. Three energy-related physiological principles emerge, namely that the CK/PCr systems functions as (a) an immediately available temporal energy buffer, (b) a spatial energy buffer or intracellular energy transport system (the CK/PCr energy shuttle or circuit) and (c) a metabolic regulator. The CK/PCr energy shuttle connects sites of ATP production (glycolysis and mitochondrial oxidative phosphorylation) with subcellular sites of ATP utilization (ATPases). Thus, diffusion limitations of ADP and ATP are overcome by PCr/Cr shuttling, as most clearly seen in polar cells such as spermatozoa, retina photoreceptor cells and sensory hair bundles of the inner ear. The CK/PCr system relies on the close exchange of substrates and products between CK isoforms and ATP-generating or -consuming processes. Mitochondrial CK in the mitochondrial outer compartment, for example, is tightly coupled to ATP export via adenine nucleotide transporter or carrier (ANT) and thus ATP-synthesis and respiratory chain activity, releasing PCr into the cytosol. This coupling also reduces formation of reactive oxygen species (ROS) and inhibits mitochondrial permeability transition, an early event in apoptosis. Cr itself may also act as a direct and/or indirect anti-oxidant, while PCr can interact with and protect cellular membranes. Collectively, these factors may well explain the beneficial effects of Cr supplementation. The stimulating effects of Cr for muscle and bone growth and maintenance, and especially in neuroprotection, are now recognized and the first clinical studies are underway. Novel socio-economically relevant applications of Cr supplementation are emerging, e.g. for senior people, intensive care units and dialysis patients, who are notoriously Cr-depleted. Also, Cr will likely be beneficial for the healthy development of premature infants, who after separation from the placenta depend on external Cr. Cr supplementation of pregnant and lactating women, as well as of babies and infants are likely to be of benefit for child development. Last but not least, Cr harbours a global ecological potential as an additive for animal feed, replacing meat- and fish meal for animal (poultry and swine) and fish aqua farming. This may help to alleviate human starvation and at the same time prevent over-fishing of oceans

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Rotavirus detection and isolation from chickens with or without symptoms

Rotaviruses have been identified as one of the main etiological agents of diarrhea and enteritis in mammals, including humans, and in avian species. Few studies have been published about enteric viruses in Brazilian poultry, including those related to rotavirus infection. Such studies demonstrate significant occurrence and the importance of enteric viruses in poultry presenting intestinal problems. Enteric viruses are the primary cause of injuries to the gut, allowing other agents, especially bacteria, to attach, to penetrate, and to replicate in the enteric tissue, leading to further damage. The aim of the present study was to detect rotavirus in the intestinal contents of layers and broilers by polyacrylamide gel electrophoresis (PAGE) and virus isolation in MA-104 cell culture. A total of 45.3% of all samples were positive to rotavirus; rotavirus frequencies were 48.7% in samples from flocks with diarrhea, 46.4% in flocks with delayed growth, and 30% in asymptomatic flocks. It was possible to isolate rotavirus in MA-104 cells from the nine rotavirus-positive randomly chosen samples. These results indicate that rotavirus may have an important role in pathogenesis of enteric disease

The Global Flood Partnership

Every year riverine flooding affects millions of people in developing countries, due to the large population exposure in the floodplains and the lack of adequate flood protection. Preparedness and monitoring are effective ways to reduce flood risk. State-of-the-art technologies relying on satellite remote sensing as well as numerical hydrological and meteorological predictions can detect and monitor severe flood events at the global scale. This chapter describes the emerging role of the Global Flood Partnership (GFP), a global network of scientists, users, and private and public organizations active in global flood risk management. Currently, a number of GFP partner institutes regularly share results from their experimental products, developed to predict and monitor where and when flooding is taking place in near real time. Products of the GFP have already been used on several occasions by national environmental agencies and humanitarian organizations to support emergency operations and to reduce the overall socioeconomic impacts of disasters. The chapter includes a discussion on existing challenges and ways forward to improve rapid access to flood information and increase resilience to flooding

Investigation of Enteric Viruses in the Feces of Neotropical Migratory Birds Captured on the Coast of the State of Pará, Brazil

Made available in DSpace on 2018-12-11T16:53:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-01. Added 1 bitstream(s) on 2019-10-09T18:29:42Z : No. of bitstreams: 1 S1516-635X2018000100161.pdf: 376041 bytes, checksum: 32723ae502ce34e68b81829514936c67 (MD5)Migratory birds can become long-distance vectors for a wide range of microorganisms and can cause human disease, being the Brazilian coast a gateway for northern migratory birds. These animals are considered natural reservoirs of different viruses that cause important diseases, being relevant research of viral pathogens in migratory birds to epidemiology surveillance. The objective of the study was to investigate the presence of avian rotavirus (AvRV), avian reovirus (ARV) and picobirnavirus (PBV) in Neotropical migratory birds captured on the coast of Brazil. A total of 23 individual fecal samples of the migratory birds species Calidris pusilla (20 birds), Numenius phaeopus (1 bird) and Charadrius semipalmatus (2 birds) were collected. Fecal suspensions were prepared from the collected samples for subsequent extraction of double-stranded RNA (dsRNA), which was subjected to polyacrylamide gel electrophoresis (PAGE) and reverse transcription polymerase chain reaction (RT-PCR). The electrophoretic profiles were not detected by PAGE, and the amplification for the studied viruses PBV, ARV and AvRV (specie D, gene VP6 and NSP4) were negative. Positivity for AvRVD, VP7 gene was of 4.35% (1/23) for the migratory bird Calidris pusilla. After sequencing and building the tree of phylogenetic relationships avian Rotavirus Group D identified in this study was phylogenetically related and grouped into one branch, together to previously reported AvRVD from Brazil in chicken flocks with 99.8% nucleotide and 100% amino acid similarities.Laboratório de Zoonoses Faculdade de Medicina Veterinária Universidade Federal do Pará, Campus Castanhal, Rodovia BR-316 Km 62 s/n, SaudadeInstituto Evandro Chagas (IEC), BR-316 Km 7 s/n, Distrito de LevilândiaLaboratório Nacional de Agricultura (Lana-gro/PA) Ministério da Agricultura Pecuária e Abastecimento (MAPA), Av. Almirante Barroso1234, Distrito de MarcoUniversidade Federal Rural da Amazônia (UFRA), Av. Presidente Tancredo Neves 2501Universidade Estadual Paulista (UNESP), Distrito de Rubião Jr. S/NUniversidade Estadual Paulista (UNESP), Distrito de Rubião Jr. S/

Multi-institutional pooled analysis on adjuvant chemoradiation in pancreatic cancer

To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma