Induction pegylated interferon Alfa-2a and high dose ribavirin do not increase SVR in heavy patients with HCV genotype 1 and high viral loads

Background & Aims Patients infected with hepatitis C virus (HCV) genotype 1, body weight <85 kg, and high baseline viral load respond poorly to standard doses of pegylated interferon (peginterferon) and ribavirin. We evaluated intensified therapy with peginterferon alfa-2a plus ribavirin. Methods This double-blind randomized trial included HCV genotype 1-infected outpatients from hepatology clinics with body weight <85 kg and HCV RNA titer <400,000 IU/mL. Patients were randomized to 180 μg/wk peginterferon alfa-2a for 48 weeks plus 1200 mg/day ribavirin (standard of care) (group A, n = 191) or 1400/1600 mg/day ribavirin (group B, n = 189). Additional groups included 360 μg/wk peginterferon alfa-2a for 12 weeks then 180 μg/wk peginterferon alfa-2a for 36 weeks plus 1200 mg/day ribavirin (group C, n = 382) or 1400/1600 mg/day ribavirin (group D, n = 383). Follow-up lasted 24 weeks after treatment. Results Sustained virologic response rates (HCV RNA level <15 IU/mL at end of follow-up) in groups A, B, C, and D were 38%, 43%, 44%, and 41%, respectively. There were no significant differences among the 4 groups or between pooled peginterferon alfa-2a regimens (A + B vs C + D: odds ratio [OR], 1.08; 95% confidence interval [CI], 0.831.39; P = .584) or pooled ribavirin regimens (A + C vs B + D: OR, 1.00; 95% CI, 0.791.28; P = .974). Conclusions In patients infected with HCV genotype 1 who are difficult to treat (high viral load, body weight <85 kg), a 12-week induction regimen of peginterferon alfa-2a and/or higher-dose ribavirin is not more effective than the standard regimen. © 2010 AGA Institute.

Analysis of HCV quasispecies dynamic under selective pressure of combined therapy

Background: The quasispecies composition of Hepatitis C virus (HCV) could have important implications with regard to viral persistence and response to interferon-based therapy. The complete NS5A was analyzed to evaluate whether the composition of NS5A quasispecies of HCV 1a/1b is related to responsiveness to combined interferon pegylated (PEG-IFN) and ribavirin therapy.Methods: Viral RNA was isolated from serum samples collected before, during and after treatment from virological sustained responder (SVR), non-responder (NR) and the end-of-treatment responder patients (ETR). NS5A region was amplified, cloned and sequenced. Six hundred and ninety full-length NS5A sequences were analyzed.Results: This study provides evidence that lower nucleotide diversity of the NS5A region pre-therapy is associated with viral clearance. Analysis of samples of NRs and the ETRs time points showed that genetic diversity of populations tend to decrease over time. Post-therapy population of ETRs presented higher genetic distance from baseline probably due to the bottleneck phenomenon observed for those patients in the end of treatment. The viral effective population of those patients also showed a strong decrease after therapy. Otherwise, NRs demonstrated a continuous variation or stability of effective populations and genetic diversity over time that did not seem to be related to therapy. Phylogenetic relationships concerning complete NS5A sequences obtained from patients did not demonstrate clustering associated with specific response patterns. However, distinctive clustering of pre/post-therapy sequences was observed. In addition, the evolution of quasispecies over time was subjected to purifying or relaxed purifying selection. Codons 157 (P03), 182 and 440 (P42), 62 and 404 (P44) were found to be under positive selective pressure but it failed to be related to the therapy.Conclusion: These results confirm the hypothesis that a relationship exists between NS5A heterogeneity and response to therapy in patients infected with chronic hepatitis C. © 2013 Jardim et al.; licensee BioMed Central Ltd.

Intensified peginterferon α-2a dosing increases sustained virologic response rates in heavy, high viral load hepatitis c genotype 1 patients with high low-density lipoprotein

BACKGROUND AND GOAL: Patients infected with hepatitis C virus (HCV) with elevated low-density lipoprotein (LDL) levels achieve higher sustained virologic response (SVR) rates after peginterferon (PegIFN)/ribavirin treatment versus patients with lower LDL. Our aim was to determine whether SVR rates in patients with low/elevated LDL can be improved by dose intensification. STUDY: In PROGRESS, genotype 1 patients with baseline HCV RNA≥400,000 IU/mL and body weight ≥85 kg were randomized to 48 weeks of 180 μg/wk PegIFN α-2a (40 kDa) plus ribavirin (A: 1200 mg/d; B: 1400/1600 mg/d) or 12 weeks of 360 μg/wk PegIFN α-2a followed by 36 weeks of 180 μg/wk, plus ribavirin (C: 1200 mg/d; D: 1400/1600 mg/d). This retrospective analysis assessed SVR rates among patients with low (<100 mg/dL) or elevated (≥100 mg/dL) LDL. Patients with high LDL (n=256) had higher baseline HCV RNA (5.86×10 IU/mL) versus patients with low LDL (n=262; 4.02×10 IU/mL; P=0.0003). RESULTS: Multiple logistic regression analysis identified a significant interaction between PegIFN α-2a dose and LDL levels on SVR (P=0.0193). The only treatment-related SVR predictor in the nested multiple logistic regression was PegIFN α-2a dose among patients with elevated LDL (P=0.0074); therefore, data from the standard (A+B) and induction (C+D) dose arms were pooled. Among patients with low LDL, SVR rates were 40% and 35% in the standard and induction-dose groups, respectively; SVR rates in patients with high LDL were 44% and 60% (P=0.014), respectively. CONCLUSIONS: Intensified dosing of PegIFN α-2a increases SVR rates in patients with elevated LDL even with the difficult-to-cure characteristics of genotype 1, high baseline viral load, and high body weight. Copyright © 2013 by Lippincott Williams & Wilkins.

Ticks' response to feeding on host immunized with glandular extracts of Rhipicephalus sanguineus females fed for 2, 4, and 6 days. I. Inactivity or early degeneration of salivary glands?

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

Secretory process of salivary glands of female Amblyomma cajennense (Acari: Ixodidae) ticks fed on resistant rabbits

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

Degenerative process and cell death in salivary glands of Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae) semi-engorged female exposed to the acaricide permethrin

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

Cell Death in Salivary Glands of Rhipicephalus (Boophilus) microplus (Canestrini, 1887) (Acari: Ixodidae) Females at Semi-engorged Feeding Stage

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

Impact of the in situ formed salivary pellicle on enamel and dentine erosion induced by different acids

Objective. To investigate and compare the protective impact of the in situ formed salivary pellicle on enamel and dentine erosion caused by different acids at pH 2.6. Methods. Bovine enamel and dentine samples were exposed for 120 min in the oral cavity of 10 healthy volunteers. Subsequently, enamel and dentine pellicle-covered specimens were extraorally immersed in 1 ml hydrochloric, citric or phosphoric acid (pH 2.6, 60 s, each acid n=30 samples). Pellicle-free samples (each acid n=10) served as controls. Calcium release into the acid was determined by atomic absorption spectroscopy. The data were analysed by two-way ANOVA and Tukey's test (alpha=0.05). Results. Pellicle-covered samples showed significantly less calcium loss compared to pellicle-free samples in all acid groups. The mean (SD) pellicle protection (% reduction of calcium loss) was significantly better for enamel samples [60.9 (5.3)] than for dentine samples [30.5 (5.0)], but revealed no differences among the acids. Conclusion. The efficacy of the in situ pellicle in reducing erosion was 2-fold better for enamel than for dentine. Protection of the pellicle was not influenced by the kind of acid when enamel and dentine erosion was performed at pH 2.6.

A novel neural model to electrical load forecasting in transformers

The paper describes a novel neural model to electrical load forecasting in transformers. The network acts as identifier of structural features to forecast process. So that output parameters can be estimated and generalized from an input parameter set. The model was trained and assessed through load data extracted from a Brazilian Electric Utility taking into account time, current, tension, active power in the three phases of the system. The results obtained in the simulations show that the developed technique can be used as an alternative tool to become more appropriate for planning of electric power systems.

An efficient neural approach to economic load dispatch in power systems

A neural approach to solve the problem defined by the economic load dispatch in power systems is presented in this paper, Systems based on artificial neural networks have high computational rates due to the use of a massive number of simple processing elements and the high degree of connectivity between these elements the ability of neural networks to realize some complex nonlinear function makes them attractive for system optimization the neural networks applyed in economic load dispatch reported in literature sometimes fail to converge towards feasible equilibrium points the internal parameters of the modified Hopfield network developed here are computed using the valid-subspace technique These parameters guarantee the network convergence to feasible quilibrium points, A solution for the economic load dispatch problem corresponds to an equilibrium point of the network. Simulation results and comparative analysis in relation to other neural approaches are presented to illustrate efficiency of the proposed approach.

Neural Network-Based Approach for Identification of the Harmonic Content of a Nonlinear Load in a Single-Phase System

In this paper an alternative method based on artificial neural networks is presented to determine harmonic components in the load current of a single-phase electric power system with nonlinear loads, whose parameters can vary so much in reason of the loads characteristic behaviors as because of the human intervention. The first six components in the load current are determined using the information contained in the time-varying waveforms. The effectiveness of this method is verified by using it in a single-phase active power filter with selective compensation of the current drained by an AC controller. The proposed method is compared with the fast Fourier transform.

Effect of abutment's height and framework alloy on the load distribution of mandibular cantilevered implant-supported prosthesis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

An investigation of pile diameter influence in the bearing capacity on Dynamic Load Test (DLT)

During the construction of five residential buildings in the city of Taubate, State of São Paulo, it was possible to carry out one comprehensive investigation of the behavior of precast concrete piles in clay shales. This paper describes the results of Dynamic Load Tests (DLT's) executed in three piles with different diameters and with the same embedded length. The tests were monitored using the PDA(R) (Pile Driving Analyzer) and the pile top displacement was measured by pencil and paper procedure. From the curves of RMX versus DMX resulted from CASE(R) method, CAPWAPC(R) analyses were made for signals where the maximum mobilized soil resistance was verified. The results were compared with the predicted bearing capacity using the semi-empirical method of Decourt & Quaresma (1978) and Decourt (1982) based on SPT values and the description of the soil profile. Some comments related to the values of quake and damping used for clay shales in the analyses are also presented.

Experience gained and difficulties in performing dynamic load test in composite piles made with steel rails

The results of dynamic instrumentation in two construction sites that used steel rails as pile foundation are presented in this paper. The first dynamic load tests were executed in piles made by single steel rails of the type TR32 and TR37. In the second group of dynamic tests, the piles were made by a composition of two and three steel rails of the same type TR37. The difficulties in placing the sensors, the effect of hammer blow eccentricity and the influence of the non-uniform welding along the pile length are presented in detail and discussed.

Influences of thermal and electric load fluctuations in the cogeneration attractiveness

The use of mean values of thermal and electric demand can be justifiable for synthesising the configuration and for estimating the economic results because it simplifies the analysis in a preliminary feasibility study of a cogeneration plant. For determining the cogeneration scheme that best fits the energetic needs of a process several cycles and combinations must be considered, and those technically feasible will be analysed according to economic models. Although interesting for a first approach, this procedure do not consider that the peaks and valleys present in the load patterns will impose additional constraints relatively to the equipment capacities. In this paper, the effects of thermal and electric load fluctuation to the cogeneration plant design were considered. An approach for modelling these load variability is proposed for comparing two competing thermal and electric parity competing schemes. A gas turbine associated to a heat recovery steam generator was then proposed and analysed for thermal- and electric-following operational strategies. Thermal-following option revealed to be more attractive for the technical and economic limits defined for this analysis. (c) 2006 Elsevier Ltd. All rights reserved.