Plant-derived antivirals against hepatitis c virus infection

Hepatitis C virus (HCV) infection is a worldwide public health burden and it is estimated that 185 million people are or have previously been infected worldwide. There is no effective vaccine for prevention of HCV infection; however, a number of drugs are available for the treatment of infection. The availability of direct-acting antivirals (DAAs) has dramatically improved therapeutic options for HCV genotype 1. However, the high costs and potential for development of resistance presented by existing treatment demonstrate the need for the development of more efficient new antivirals, or combination of therapies that target different stages of the viral lifecycle. Over the past decades, there has been substantial study of compounds extracted from plants that have activity against a range of microorganisms that cause human diseases. An extensive variety of natural compounds has demonstrated antiviral action worldwide, including anti-HCV activity. In this context, plant-derived compounds can provide an alternative approach to new antivirals. In this review, we aim to summarize the most promising plant-derived compounds described to have antiviral activity against HCV

Evaluation of canonical siRNA and Dicer substrate RNA for inhibition of hepatitis C virus genome replication - a comparative study

Hepatitis C virus (HCV) frequently establishes persistent infections in the liver, leading to the development of chronic hepatitis and, potentially, to liver cirrhosis and hepatocellular carcinoma at later stages. The objective of this study was to test the ability of five Dicer substrate siRNAs (DsiRNA) to inhibit HCV replication and to compare these molecules to canonical 21 nt siRNA. DsiRNA molecules were designed to target five distinct regions of the HCV genome - the 5′ UTR and the coding regions for NS3, NS4B, NS5A or NS5B. These molecules were transfected into Huh7.5 cells that stably harboured an HCV subgenomic replicon expressing a firefly luciferase/neoR reporter (SGR-Feo-JFH-1) and were also tested on HCVcc-infected cells. All of the DsiRNAs inhibited HCV replication in both the subgenomic system and HCVcc-infected cells. When DsiRNAs were transfected prior to infection with HCVcc, the inhibition levels reached 99.5%. When directly compared, canonical siRNA and DsiRNA exhibited similar potency of virus inhibition. Furthermore, both types of molecules exhibited similar dynamics of inhibition and frequencies of resistant mutants after 21 days of treatment. Thus, DsiRNA molecules are as potent as 21 nt siRNAs for the inhibition of HCV replication and may provide future approaches for HCV therapy if the emergence of resistant mutants can be addressed

CDH1 (cadherin 1, type 1, E-cadherin (epithelial))

Review on CDH1 (cadherin 1, type 1, E-cadherin (epithelial)), with data on DNA, on the protein encoded, and where the gene is implicated

ADAM23 (ADAM metallopeptidase domain 23)

Review on ADAM23 (ADAM metallopeptidase domain 23), with data on DNA, on the protein encoded, and where the gene is implicated

INTERFERÊNCIA DA NUTRIÇÃO NA RESISTÊNCIA MECÂNICA DO CÓLON E COMPARAÇÃO ENTRE DUAS TÉCNICAS DE SUTURA PARA A SÍNTESE DE COLOTOMIA EM RATOS

Trinta ratos, linhagem Wistar, fêmeas, com peso inicial médio de 150 gramas, foram divididos em seis grupos de cinco animais, sendo o grupo I - dieta controle (ração comercial), grupo II - dieta controle + colotomia e síntese com sutura contínua simples; grupo III - dieta controle + colotomia e síntese com sutura tipo Cushing, grupo IV - dieta não balanceada, grupo V - dieta não balanceada + colotomia e síntese com sutura contínua simples, grupo VI - dieta não balanceada + colotomia e síntese com sutura tipo Cushing. A colotomia foi executada no cólon descendente e no quinto dia do pós-operatório os animais foram sacrificados para estudo da tensão de ruptura, pelo método de explosão, nos cólons transverso e descendente. A média do ganho de peso com a dieta não balanceada foi aproximadamente a metade da controle. Não houve diferença estatística entre os tipos de sutura, nem entre o estado nutricional e técnicas de sutura. Em geral, os valores da tensão de ruptura no cólon transverso intacto e no cólon descendente dos animais operados (dieta controle e não balanceada), foram inferiores ao dos não operados com dieta controle. O epíplon dos ratos dos grupos V e VI apresentou-se menos volumoso e adelgaçado, o que promoveu aderências graves de outros órgãos sobre a região da colotomia. Essas adesões podem ter interferido na avaliação da tensão de ruptura do cólon descendente. Foi possível concluir que o método de força de explosão não permitiu estabelecer diferenças entre os padrões de sutura utilizados e o grau de nutrição. Nutrition interference on mechanic resistance of colon and comparison of two suture techniques for colotomy closure in rats Abstract Thirty female Wistar rats with initial average weight of 150 g, were divided in six experimental groups as follows: group 1 - control diet (commercial rat food); group II - control diet and colostomy with simple continuous suture; group III - control diet and colostomy with Cushings pattern suture; group IV - unbalanced diet; group V - unbalanced diet and colostomy with simple continuous suture; group VI - unbalanced diet and colostomy with Cushings pattern suture. Colostomy was carried out in descending colon. At the fifth day after surgery, the animals underwent euthanasia in order to measure the bursting strength of the transverse and descending colon. The gain of weight in the unbalanced diet was almost half of the control diet. here were no statistic differences between the sutures patterns, neither in regard to the nutritional conditions and suture techniques. Generally, the bursting strength values measured in both colons of the animals under either control and unbalanced diets, that underwent surgery, were lower than the ones found for rats under control diet that did not underwent surgery. The omentum of the rats from groups V and VI was less voluminous and thin causing serious adhesions to other organs at the colostomy area. These adherences might have interfered in the evaluation of the bursting strength in the descending colon. According to the results found, it was possible to conclude that evaluation of the bursting strength did not allow to establish differences between the suture patterns and the nutritional conditions of the experimental animals

Galactic Bulge Microlensing Optical Depth from EROS-2

We present a new EROS-2 measurement of the microlensing optical depth toward the Galactic Bulge. Light curves of $5.6\times 10^{6}$ clump-giant stars distributed over $66 \deg^2$ of the Bulge were monitored during seven Bulge seasons. 120 events were found with apparent amplifications greater than 1.6 and Einstein radius crossing times in the range 5 {\rm d}. This is the largest existing sample of clump-giant events and the first to include northern Galactic fields. In the Galactic latitude range 1.4\degr<|b|<7.0\degr, we find $\tau/10^{-6}=(1.62 \pm 0.23)\exp[-a(|b|-3 {\rm deg})]$ with $a=(0.43 \pm0.16)\deg^{-1}$. These results are in good agreement with our previous measurement, with recent measurements of the MACHO and OGLE-II groups, and with predictions of Bulge models.Comment: accepted A&A, minor revision

DISTÚRBIOS FÍSICOS E COMPORTAMENTAIS EM CÃES E GATOS IDOSOS

A senescência é um processo que se estende do nascimento até a morte e refere-se às disfunções que ocorrem com o avançar da idade. O trabalho teve por objetivo realizar um levantamento dasprincipais alterações físicas e comportamentais, bem como o estabelecimento de correlação entre peso corpóreo e o tipo de alimentação, em 63 cães e 27 gatos,com idade acima de oito anos. Os resultados permitiram concluir que o distúrbio físico de maiorocorrência foi a obesidade. Dentre as mudanças comportamentais, a ansiedade e a agressividade foram as mais prevalentes. A combinação de comida caseira com ração comercial constituiu na principal fonte de alimentação oferecida pelos proprietários, sendo a mais consumida pelos animais obesos.Senescence is a process that extends from birth until death, and refers to the dysfunction that occurs with aging. The aim of this study is to make a survey of the main physical and behavioral changes, aswell as to establish the correlation between the body weight and type of food in 63 dogs and 27 cats over 8 years old. It was possible to conclude that the obesity was the most frequent physical disturbance. Among the behavioral changes, anxiety and aggressiveness werethe most prevalent. The commercial pet food combined to home made diet was the principal type of food provided by the owners, and this food was the most ingested by the obese animals

Unraveling the Complex Solid-State Phase Transition Behavior of 1-Iodoadamantane, a Material for Which Ostensibly Identical Crystals Undergo Different Transformation Pathways

Phase transitions in crystalline molecular solids have important implications in the fundamental understanding of materials properties and in the development of materials applications. Herein, we report the solid-state phase transition behavior of 1-iodoadamantane (1-IA) investigated using a multi-technique strategy [synchrotron powder X-ray diffraction (XRD), single-crystal XRD, solid-state NMR, and differential scanning calorimetry (DSC)], which reveals complex phase transition behavior on cooling from ambient temperature to ca. 123 K and on subsequent heating to the melting temperature (348 K). Starting from the known phase of 1-IA at ambient temperature (phase A), three low-temperature phases are identified (phases B, C, and D); the crystal structures of phases B and C are reported, together with a re-determination of the structure of phase A. Remarkably, single-crystal XRD shows that some individual crystals of phase A transform to phase B, while other crystals of phase A transform instead to phase C. Results (from powder XRD and DSC) on cooling a powder sample of phase A are fully consistent with this behavior while also revealing an additional transformation pathway from phase A to phase D. Thus, on cooling, a powder sample of phase A transforms partially to phase C (at 229 K), partially to phase D (at 226 K) and partially to phase B (at 211 K). During the cooling process, each of the phases B, C, and D is formed directly from phase A, and no transformations are observed between phases B, C, and D. On heating the resulting triphasic powder sample of phases B, C, and D from 123 K, phase B transforms to phase D (at 211 K), followed by the transformation of phase D to phase C (at 255 K), and finally, phase C transforms to phase A (at 284 K). From these observations, it is apparent that different crystals of phase A, which are ostensibly identical at the level of information revealed by XRD, must actually differ in other aspects that significantly influence their low-temperature phase transition pathways. This unusual behavior will stimulate future studies to gain deeper insights into the specific properties that control the phase transition pathways in individual crystals of this material

A novel substitution in NS5A enhances the resistance of hepatitis C virus genotype 3 to daclatasvir

Hepatitis C virus (HCV) genotype 3 presents a high level of both baseline and acquired resistance to direct-acting antivirals (DAAs), particularly those targeting the NS5A protein. To understand this resistance we studied a cohort of Brazilian patients treated with the NS5A DAA, daclatasvir and the nucleoside analogue, sofosbuvir. We observed a novel substitution at NS5A amino acid residue 98 [serine to glycine (S98G)] in patients who relapsed post-treatment. The effect of this substitution on both replication fitness and resistance to DAAs was evaluated using two genotype 3 subgenomic replicons. S98G had a modest effect on replication, but in combination with the previously characterized resistance-associated substitution (RAS), Y93H, resulted in a significant increase in daclatasvir resistance. This result suggests that combinations of substitutions may drive a high level of DAA resistance and provide some clues to the mechanism of action of the NS5A-targeting DAAs

Human respiratory syncytial virus in children hospitalized for acute lower respiratory infection

OBJETIVO: Avaliar a prevalência e a sazonalidade do vírus respiratório sincicial humano (VRSH) em crianças de 0 a 6 anos hospitalizadas por infecção aguda das vias aéreas inferiores (IVAI) em São José do Rio Preto (SP) e a associação entre faixa etária, diagnóstico e VRSH. MÉTODOS: Entre maio de 2004 e setembro de 2005, foram estudados 290 episódios consecutivos de IVAI adquiridos na comunidade em crianças de 0 a 6 anos internadas no Hospital de Base de São José do Rio Preto. Para identificação do VRSH, foram coletadas amostras de secreção de nasofaringe e realizou-se análise molecular por meio da técnica de RT-PCR. RESULTADOS: A prevalência de VRSH foi de 29,3% nos episódios de IVAI hospitalizados. A IVAI foi frequente em lactentes (mediana de idade = 13,5 meses). O VRSH foi mais frequente nos casos de bronquiolite (64%) e no primeiro ano de vida (35%). Os episódios de infecção por VRSH ocorreram entre o outono e a primavera, com frequência maior em 2004 do que em 2005. Os critérios clínicos e radiológicos não foram suficientes para o diagnóstico de infecção pelo VRSH. Em 78,8% dos episódios de VRSH, houve tratamento com antibiótico. CONCLUSÕES: A prevalência do VRSH em crianças de 0 a 6 anos hospitalizadas por IVAI foi elevada, com predomínio nas mais jovens ou com bronquiolite. A circulação do vírus variou nos dois anos estudados. Os resultados sugerem necessidade de diagnóstico laboratorial do VRSR na prática clínica.OBJECTIVE: To evaluate the prevalence and seasonality of human respiratory syncytial virus (HRSV) in children aged 0 to 6 years, hospitalized with acute lower respiratory infection (ALRI) in São José do Rio Preto, SP, Brazil, and the association between age, diagnosis, and HRSV. METHODS: Between May 2004 and September 2005, we studied 290 consecutive episodes of community-acquired ALRI in children aged 0 to 6 years admitted to the Hospital de Base of São José do Rio Preto. In order to detect HRSV, nasopharyngeal secretion samples were collected and RT-PCR molecular analysis was performed. RESULTS: The HRSV prevalence was 29.3% for the cases of hospitalized patients with ALRI. ALRI was common in infants (median age = 13.5 months). HRSV was more frequent in cases of bronchiolitis (64%) and during the first year of life (35%). Episodes of HRSV infection occurred between fall and spring, showing higher frequency in 2004 than in 2005. Clinical and radiological criteria were not sufficient to establish the diagnosis of infection with HRSV. Antibiotic therapy was used in 78.8% of episodes of HRSV. CONCLUSIONS: There was a high prevalence of HRSV in children aged 0 to 6 years who were hospitalized for ALRI, predominantly in younger patients or those with bronchiolitis. The circulation of the virus varied in the two years studied. Our results suggest the need for laboratory diagnosis of HRSV in the clinical practice