984 resultados para Elimination


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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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A significant infection rate of bovine TB in the deer population of the northeastern lower peninsula poses a potential risk to several important values including public health, United States Department of Agriculture (U.S.D.A.) TB-free accreditation for Michigan cattle, wildlife health, wildlife-related recreation and tourism and economic stability in several sectors. A risk assessment study by the U.S. D.A. Centers for Epidemiology and Animal Health (Fort Collins, CO) predicted that if no changes were made in the management of the affected free-ranging deer population, the TB prevalence (compared to the current prevalence of 2.3%). Although the current annual risk of TB transfer to cattle in the affected area is .I%, the report estimated a 12% cumulative risk that at least one head of cattle would become infected over the next 25 years if no changes are made in deer and/or cattle management.

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A transparent (wide-area) wavelength-routed optical network may be constructed by using wavelength cross-connect switches connected together by fiber to form an arbitrary mesh structure. The network is accessed through electronic stations that are attached to some of these cross-connects. These wavelength cross-connect switches have the property that they may configure themselves into unspecified states. Each input port of a switch is always connected to some output port of the switch whether or not such a connection is required for the purpose of information transfer. Due to the presence of these unspecified states, there exists the possibility of setting up unintended alloptical cycles in the network (viz., a loop with no terminating electronics in it). If such a cycle contains amplifiers [e.g., Erbium- Doped Fiber Amplifiers (EDFA’s)], there exists the possibility that the net loop gain is greater than the net loop loss. The amplified spontaneous emission (ASE) noise from amplifiers can build up in such a feedback loop to saturate the amplifiers and result in oscillations of the ASE noise in the loop. Such all-optical cycles as defined above (and hereafter referred to as “white” cycles) must be eliminated from an optical network in order for the network to perform any useful operation. Furthermore, for the realistic case in which the wavelength cross-connects result in signal crosstalk, there is a possibility of having closed cycles with oscillating crosstalk signals. We examine algorithms that set up new transparent optical connections upon request while avoiding the creation of such cycles in the network. These algorithms attempt to find a route for a connection and then (in a post-processing fashion) configure switches such that white cycles that might get created would automatically get eliminated. In addition, our call-set-up algorithms can avoid the possibility of crosstalk cycles.

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Background: How damaged mitochondria are removed by mitophagy is not fully described. Results: Ischemia and reoxygenation (I/R)-induced injury triggers mitochondria association of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and mitophagy, and protein kinase Cδ (PKCδ) activation inhibits it. Conclusion: PKCδ-mediated phosphorylation of GAPDH inhibits mitophagy. Significance: GAPDH/PKCδ is a signaling switch, which is activated during ischemic injury to regulate the balance between cell survival by mitophagy and cell death by apoptosis.

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BACKGROUND: For almost 30 years, phosphatidylethanol (PEth) has been known as a direct marker of alcohol consumption. This marker stands for consumption in high amounts and for a longer time period, but it has been also detected after 1 high single intake of ethanol (EtOH). The aim of this study was to obtain further information about the formation and elimination of PEth 16:0/18:1 by simulating extensive drinking. METHODS: After 3 weeks of alcohol abstinence, 11 test persons drank an amount of EtOH leading to an estimated blood ethanol concentration of 1 g/kg on each of 5 successive days. After the drinking episode, they stayed abstinent for 16 days with regular blood sampling. PEth 16:0/18:1 analysis was performed using liquid chromatography-tandem mass spectrometry (high-performance liquid chromatography 1100 system and QTrap 2000 triple quadrupole linear ion trap mass spectrometer. Values of blood alcohol were obtained using a standardized method with headspace gas chromatography flame ionization detector. RESULTS: Maximum measured concentrations of EtOH were 0.99 to 1.83 g/kg (mean 1.32 g/kg). These values were reached 1 to 3 hours after the start of drinking (mean 1.9 hours). For comparison, 10 of 11 volunteers had detectable PEth 16:0/18:1 values 1 hour after the start of drinking, ranging from 45 to 138 ng/ml PEth 16:0/18:1. Over the following days, concentrations of PEth 16:0/18:1 increased continuously and reached the maximum concentrations of 74 to 237 ng/ml between days 3 and 6. CONCLUSIONS: This drinking experiment led to measurable PEth concentrations. However, PEth 16:0/18:1 concentrations stayed rather low compared with those of alcohol abusers from previous studies.

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BACKGROUND: Kinetic assessment of urea, the main end product of protein metabolism, could serve to assess protein catabolism in dogs with chronic kidney disease (CKD). Protein malnutrition and catabolism are poorly documented in CKD and they often are neglected clinically because of a lack of appropriate evaluation tools. HYPOTHESIS: Generation and excretion of urea are altered in dogs with CKD. ANIMALS: Nine dogs with spontaneous CKD (IRIS stages 2-4) and 5 healthy research dogs. METHODS: Endogenous renal clearance (Clrenal) of urea and creatinine was measured first. Exogenous plasma clearance (Clplasma, total body clearance) of the 2 markers then was determined by an IV infusion of urea (250-1,000 mg/kg over 20 minutes) and an IV bolus of creatinine (40 mg/kg). Extrarenal clearance (Clextra) was defined as the difference between Clplasma)and Clrenal. Endogenous urea generation was computed assuming steady-state conditions. RESULTS: Median Clrenal and Clextra of urea were 2.17 and 0.21 mL/min/kg in healthy dogs and 0.37 and 0.28 mL/min/kg in CKD dogs. The proportion of urea cleared by extrarenal route was markedly higher in dogs with glomerular filtration rate<1 mL/kg/min than in normal dogs, reaching up to 85% of the total clearance. A comparable pattern was observed for creatinine excretion, except in 1 dog, Clextra remained<20% of Clplasma. CONCLUSION: Extrarenal pathways of urea excretion are predominant in dogs with advanced CKD and justify exploring adjunctive therapies based on enteric nitrogen excretion in dogs. A trend toward increased urea generation may indicate increased catabolism in advanced CKD.

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This study was initiated to assess the quantitative impact of patient anthropometrics and dihydropyrimidine dehydrogenase (DPYD) mutations on the pharmacokinetics (PK) of 5-fluorouracil (5FU) and to explore limited sampling strategies of 5FU.

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Catheter ablation of ventricular tachycardia (VT) is effective and particularly useful in patients with frequent defibrillator interventions. Various substrate modification techniques have been described for unmappable or hemodynamically intolerable VT. Noninducibility is the most frequently used end point but is associated with significant limitations, so the optimal end point remains unclear. We hypothesized that elimination of local abnormal ventricular activities (LAVAs) during sinus rhythm or ventricular pacing would be a useful and effective end point for substrate-based VT ablation. As an adjunct to this strategy, we used a new high-density mapping catheter and frequently used epicardial mapping.

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Neutralizing antibody (nAb) responses to lymphocytic choriomeningitis virus (LCMV) in mice and immunodeficiency virus and hepatitis C virus in humans are usually weak and slow to develop. This may be the result of structural properties of the surface glycoprotein, a low frequency of B cells with neutralizing specificity, and the necessity of prolonged affinity maturation of specific nAbs. In this study, we show that during LCMV infection, CD27 signaling on CD4+ T cells enhances the secretion of interferon-gamma and tumor necrosis factor-alpha. These inflammatory cytokines lead to the destruction of splenic architecture and immunodeficiency with reduced and delayed virus-specific nAb responses. Consequently, infection with the otherwise persistent LCMV strain Docile was eliminated after CD27 signaling was blocked. Our data provide a novel mechanism by which LCMV avoids nAb responses and suggest that blocking the CD27-CD70 interaction may be an attractive strategy to prevent chronic viral infection.

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We evaluated whether a probiotic supplementation in dogs with food responsive diarrhoea (FRD) has beneficial effects on intestinal cytokine patterns and on microbiota. Twenty-one client-owned dogs with FRD were presented for clinically needed duodeno- and colonoscopy and were enrolled in a prospective placebo (PL)-controlled probiotic trial. Intestinal tissue samples and faeces were collected during endoscopy. Intestinal mRNA abundance of interleukin (IL)-5, -10, -12p40 and -13, tumour necrosis factor-alpha, transforming growth factor-beta1 and interferon (IFN)-gamma were analysed and numbers of Lactobacillus spp., Bifidobacterium spp., Enterococcus spp. and Enterobacteriaceae and supplemented probiotic bacteria were determined in faeces. The Canine Inflammatory Bowel Disease Activity Index, a scoring system comprising general attitude, appetite, faecal consistency, defecation frequency, and vomitus, decreased in all dogs (p < 0.0001). Duodenal IL-10 mRNA levels decreased (p = 0.1) and colonic IFN-gamma mRNA levels increased (p = 0.08) after probiotic treatment. Numbers of Enterobacteriaceae decreased in FRD dogs receiving probiotic cocktail (FRD(PC)) and FRD dogs fed PL (FRD(PL)) during treatment (p < 0.05), numbers of Lactobacillus spp. increased in FRD(PC after) when compared with FRD(PC before) (p < 0.1). One strain of PC was detected in five of eight FRD(PC) dogs after probiotic supplementation. In conclusion, all dogs clinically improved after treatment, but cytokine patterns were not associated with the clinical features irrespective of the dietary supplementation.