RESUMO
Hepatitis B virus (HBV) genotypes and subgenotypes show distinct geographical prevalence. A genotyping analysis of 28 samples from asymptomatic HBV carriers from the Philippines gave a distribution of HBV genotypes as expected from a previous study: 54% B (15/28), C5 18% (5/28), 14% D (4/28), 7% A1 (2/28). In addition, 7% (2/28) of the samples showed a double infection with genotypes B and D. One of the isolates sequenced completely, ph105, did not group into one of the known subgenotypes after phylogenetic analysis. Ph105 formed a separate clade in genotype C. With a genome length of 3,215 nt. and a serological subtype adr, ph105 exhibited the main features of most genotype C strains. However, ph105 differed by 4.1-7.2% from HBV subgenotypes C1 to C5 when comparing the nucleotide sequence of whole genomes. With only 4.1% difference ph105 was most closely related to subgenotype C2. SimPlot analysis gave no indication for recombination with known HBV genotypes. Ph105 fulfils all criteria for a new subgenotype C6.
Assuntos
Portador Sadio/virologia , DNA Viral/genética , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Hepatite B/virologia , Análise por Conglomerados , Genoma Viral , Genótipo , Vírus da Hepatite B/isolamento & purificação , Humanos , Dados de Sequência Molecular , Filipinas , Filogenia , Análise de Sequência de DNA , SorotipagemRESUMO
Schistosomiasis is caused by infection with Schistosoma haematobium, S. mansoni, S. japonicum, or S. mekongi. S. japonicum infection results in liver cirrhosis at the final stage. A "network" (NW) echogenic pattern on hepatic ultrasonography appears to be specific to S. japonicum infection. The principal aim of the present study was to determine the exact year(s) or even month(s) required for the establishment of the liver NW echogenic pattern from the initial infection in young patients with schistosomiasis japonica since there are few data on this important point. We conducted yearly ultrasonographic, serologic, coprologic, and physical examinations of schistosomiasis patients in the Philippines from 1996 up to the present. During that period, the total number of patients examined was approximately 2,000, among whom we selected 2 patients for determination of the duration required for NW establishment, when they were 10 years old. Although the exact time of initial exposure to schistosomes cannot be determined, the duration for the establishment of NW was definitively confirmed in patient no. 1 to be between 19-24 months based on the results of serologic and coprologic examinations. For patient no. 2, the circumstantial evidence suggested that the establishment of a NW might require 5 to 6 years at maximum. To the best of our knowledge, this is the first evidence-based report on the determination of the period required for the establishment of a liver NW echogenic pattern in S. japonicum infection in the Philippines.
Assuntos
Hepatopatias Parasitárias/diagnóstico por imagem , Fígado/diagnóstico por imagem , Esquistossomose Japônica/diagnóstico por imagem , Animais , Anti-Helmínticos/administração & dosagem , Criança , Ensaio de Imunoadsorção Enzimática/métodos , Fezes/parasitologia , Feminino , Humanos , Fígado/parasitologia , Hepatopatias Parasitárias/tratamento farmacológico , Testes de Função Hepática , Praziquantel/administração & dosagem , Schistosoma japonicum/isolamento & purificação , Esquistossomose Japônica/tratamento farmacológico , Fatores de Tempo , UltrassonografiaRESUMO
Adults 40 years of age and older have been shown to be hypo-responsive immunologically to the currently available hepatitis B virus (HBV) vaccines. Three intramuscular doses of a Toll-like receptor 9 agonist, 1018 immunostimulatory sequence (1018 ISS) adjuvant, combined with recombinant hepatitis B surface antigen (HBsAg) demonstrated faster, superior, and more durable seroprotection than three doses of a licensed comparator HBV vaccine (Engerix-B(®)). This investigational vaccine, HBsAg-1018 ISS, was well tolerated with a safety profile similar to the comparator vaccine. These results suggest that HBsAg-1018 may be more effective in this hypo-responsive population.
Assuntos
Vacinas contra Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B/prevenção & controle , Adjuvantes Imunológicos , Adulto , Idoso , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Hepatite B/imunologia , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/genética , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/efeitos adversos , Vacinas contra Hepatite B/genética , Humanos , Imunidade Humoral , Masculino , Pessoa de Meia-Idade , Oligodesoxirribonucleotídeos/genética , Oligodesoxirribonucleotídeos/imunologia , Placebos , Receptor Toll-Like 9/agonistas , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/imunologiaRESUMO
In human immunodeficiency virus type 1 (HIV-1) latently infected cells, NF-kappaB plays a major role in the transcriptional induction of HIV-1 replication. Hence, downregulation of NF-kappaB activation has long been sought for effective anti-HIV therapy. Tumor necrosis factor alpha (TNF-alpha) stimulates IkappaB kinase (IKK) complex, a critical regulator in the NF-kappaB signaling pathway. A novel IKK inhibitor, ACHP {2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl-nicotinonitrile}, was developed and evaluated as a potent and specific inhibitor for IKK-alpha and IKK-beta. In this study, we examined the ability of this compound to inhibit HIV-1 replication in OM10.1 cells latently infected with HIV. When these cells were pretreated with ACHP, TNF-alpha-induced HIV-1 replication was dramatically inhibited, as measured by the HIV p24 antigen levels in the culture supernatants. Its 50% effective concentration was approximately 0.56 microM, whereas its 50% cytotoxic concentration was about 15 microM. Western blot analysis revealed inhibition of IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 nuclear translocation, and p65 phosphorylation. ACHP was also found to suppress HIV-1 long terminal repeat (LTR)-driven gene expression through the inhibition of NF-kappaB activation. Furthermore, ACHP inhibited TNF-alpha-induced NF-kappaB (p65) recruitment to the HIV-1 LTR, as assessed by chromatin immunoprecipitation assay. These findings suggest that ACHP acts as a potent suppressor of TNF-alpha-induced HIV replication in latently infected cells and that this inhibition is mediated through suppression of IKK activity.
Assuntos
Fármacos Anti-HIV/farmacologia , HIV-1/efeitos dos fármacos , Quinase I-kappa B/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Replicação Viral/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Linhagem Celular , Repetição Terminal Longa de HIV/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Quinase I-kappa B/metabolismo , Quinase I-kappa B/fisiologia , Fosforilação , Fator de Transcrição RelA/antagonistas & inibidores , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Latência ViralRESUMO
The progress in the use of HAART for the treatment of HIV-infected individuals has been limited by the development of viral resistance and the maintenance of viral latency. New therapeutic strategies geared toward improvement in the host's immune response are now being considered. We found that IFN-gamma induces CIITA through the JAK-STAT pathway and inhibits HIV-1 replication in latently infected cells. Its effect appears to be mediated through the reciprocal action of Tat and CIITA. With this beneficial effect, IFN-gamma and its inducers can be considered as an adjunct to the currently available therapy. We also addressed the safety of using simvastatin, an HMG-CoA reductase inhibitor, to treat dyslipidemia often associated with the use of protease inhibitors. Simvastatin did not show any unfavorable effects on HIV replication, thus could be used safely unless there are any drug interactions when administered.