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1.
Antiviral Res ; 226: 105889, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38631661

RESUMO

Hepatitis B virus (HBV) infections pose a major threat to human health. HBV can upregulate the expression of the transcription factor Yin Yang 1 (YY1) in in vitro cytological experiments, suggesting an association between YY1 and HBV infection. However, data on YY1 expression in chronic hepatitis B (CHB) patients are lacking. In this study, we aimed to assess the correlation between YY1 expression and HBV infection. We detected serum YY1 levels in 420 patients with chronic HBV infection, 30 patients with chronic hepatitis C virus infection, and 32 healthy controls using an enzyme-linked immunosorbent assay. The correlation between YY1 levels and clinical parameters was analyzed. Meanwhile, the changes of YY1 before and after interferon or entecavir treatment were analyzed. YY1 levels in the liver tissues were detected using immunofluorescence staining. The expression of YY1 in HBV-expressing cells was detected through western blotting. Meanwhile, we explored the effects of YY1 on HBV replication and gene expression. We found that YY1 was highly expressed in the serum and liver tissues of CHB patients. Serum YY1 levels positively correlated with HBV DNA and hepatitis B surface antigen (HBsAg). Additionally, HBV DNA levels increased but HBsAg levels decreased after HBV-expressing cells overexpress YY1. In conclusion, our study demonstrates that YY1 plays an important role in HBV replication and gene expression, providing a potential target for the treatment of CHB.


Assuntos
DNA Viral , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica , Fígado , Replicação Viral , Fator de Transcrição YY1 , Humanos , Fator de Transcrição YY1/metabolismo , Fator de Transcrição YY1/genética , Hepatite B Crônica/virologia , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/metabolismo , Vírus da Hepatite B/genética , Vírus da Hepatite B/fisiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , DNA Viral/genética , DNA Viral/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/metabolismo , Fígado/virologia , Fígado/metabolismo , Guanina/análogos & derivados , Antivirais/uso terapêutico , Antivirais/farmacologia , Interferons/metabolismo , Células Hep G2
2.
Histol Histopathol ; 36(9): 967-979, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34490599

RESUMO

BACKGROUND/AIMS: The Yiqi Huoxue (YQHX) recipe has been shown to attenuate liver fibrosis, but precise mechanisms have not yet been elucidated. Recently, Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling has been implicated in liver fibrogenesis. This study investigated whether the YAP/TAZ signaling is involved in the therapeutic effect of YQHX on hepatic fibrosis. MATERIALS AND METHODS: Wistar rats were used to generate a model of carbon tetrachloride (CCl4)-induced liver fibrosis. Chronic hepatitis B (CHB) patients with liver fibrosis were enrolled and assigned to receive either nucleoside/nucleotide analogues (NAs) or NAs plus YQHX. Histology, immunohistochemistry, qRT-PCR, and western blotting were conducted to mechanistically assess the therapeutic effects of YQHX on liver fibrosis. RESULTS: YQHX markedly alleviated morphological alterations in CCl4-induced liver fibrosis and decreased markers of hepatic fibrosis in rats. Furthermore, YQHX significantly suppressed CCl4-meidated activation of the transforming growth factor-beta (TGF-ß)/Smad signaling pathway. Notably, CCl4 induced up-regulation of YAP, TAZ, and connective tissue growth factor (CTGF), which were significantly abrogated by YQHX. Consistent with the above major findings in rats, CHB patients treated with NAs plus YQHX had greater improvement in liver fibrosis than those given NAs alone (71.4% vs. 28.6%; P = 0.057). In addition, hepatic and plasma levels of YAP were significantly decreased after YQHX treatment in CHB patients with liver fibrosis. CONCLUSION: YAP/TAZ signaling plays a role, at least in part, in the anti-fibrotic activity of YQHX. The findings may help to better understand the mechanisms of YQHX in the treatment of liver fibrosis.


Assuntos
Antifibróticos , Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Hepatite B Crônica , Cirrose Hepática , Fígado , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Proteínas de Sinalização YAP , Adulto , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antifibróticos/uso terapêutico , Antivirais/uso terapêutico , Tetracloreto de Carbono , Estudos de Casos e Controles , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/metabolismo , Hepatite B Crônica/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Ratos Wistar , Transdução de Sinais , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/metabolismo , Resultado do Tratamento , Proteínas de Sinalização YAP/metabolismo
3.
Sci Rep ; 11(1): 8402, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863948

RESUMO

The Chinese herbal formula TiaoGanYiPi (TGYP) showed effective against chronic hepatitis B (CHB) caused by hepatitis B virus (HBV) infection. Hence, we aimed to clarify the mechanisms and potential targets between TGYP and CHB. The active compounds and related putative targets of TGYP, and disease targets of CHB were obtained from the public databases. The key targets between TGYP and CHB were identified through the network construction and module analysis. The expression of the key targets was detected in Gene Expression Omnibus (GEO) dataset and normal hepatocyte cell line LO2. We first obtained 11 key targets which were predominantly enriched in the Cancer, Cell cycle and HBV-related pathways. And the expression of the key targets was related to HBV infection and liver inflammation verified in GSE83148 database. Furthermore, the results of real-time quantitative PCR and CCK-8 assay indicated that TGYP could regulate the expression of key targets including CCNA2, ABL1, CDK4, CDKN1A, IGFR and MAP2K1, and promote proliferation of LO2 cells. In coclusion, we identified the active compounds and key targets btween TGYP and CHB, and found that the TGYP might exhibite curative effect on CHB via promoting hepatocyte proliferation and inhibiting the liver inflammatory processes.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Hepatócitos/efeitos dos fármacos , Simulação de Acoplamento Molecular , Mapas de Interação de Proteínas/efeitos dos fármacos , Sobrevivência Celular , Hepatite B Crônica/metabolismo , Hepatite B Crônica/patologia , Humanos
4.
World J Gastroenterol ; 24(30): 3448-3461, 2018 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-30122883

RESUMO

AIM: To elucidate tongue coating microbiota and metabolic differences in chronic hepatitis B (CHB) patients with yellow or white tongue coatings. METHODS: Tongue coating samples were collected from 53 CHB patients (28 CHB yellow tongue coating patients and 25 CHB white tongue coating patients) and 22 healthy controls. Microbial DNA was extracted from the tongue samples, and the bacterial 16S ribosomal RNA gene V3 region was amplified from all samples and sequenced with the Ion Torrent PGM™ sequencing platform according to the standard protocols. The metabolites in the tongue coatings were evaluated using a liquid chromatography-mass spectrometry (LC-MS) platform. Statistical analyses were then performed. RESULTS: The relative compositions of the tongue coating microbiotas and metabolites in the CHB patients were significantly different from those of the healthy controls, but the tongue coating microbiota abundances and diversity levels were not significantly different. Compared with the CHB white tongue coating patients, the CHB yellow tongue coating patients had higher hepatitis B viral DNA (HBV-DNA) titers (median 21210 vs 500, respectively, P = 0.03) and a significantly lower level of Bacteroidetes (20.14% vs 27.93%, respectively, P = 0.013) and higher level of Proteobacteria (25.99% vs 18.17%, respectively, P = 0.045) in the microbial compositions at the phylum level. The inferred metagenomic pathways enriched in the CHB yellow tongue coating patients were mainly those involved in amino acid metabolism, which was consistent with the metabolic disorder. The abundances of bacteria from Bacteroidales at the order level were higher in the CHB white tongue coating patients (19.2% vs 27.22%, respectively, P = 0.011), whereas Neisseriales were enriched in the yellow tongue coating patients (21.85% vs 13.83%, respectively, P = 0.029). At the family level, the abundance of Neisseriaceae in the yellow tongue patients was positively correlated with the HBV-DNA level but negatively correlated with the S-adenosyl-L-methionine level. CONCLUSION: This research illustrates specific clinical features and bacterial structures in CHB patients with different tongue coatings, which facilitates understanding of the traditional tongue diagnosis.


Assuntos
Bactérias/isolamento & purificação , Microbioma Gastrointestinal/fisiologia , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/microbiologia , Língua/microbiologia , Adulto , Bactérias/genética , Bactérias/metabolismo , Estudos de Casos e Controles , DNA Viral/isolamento & purificação , Feminino , Voluntários Saudáveis , Vírus da Hepatite B/genética , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/metabolismo , Humanos , Masculino , Medicina Tradicional Chinesa/métodos , Metagenômica , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética
5.
J Ethnopharmacol ; 193: 133-139, 2016 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-27497639

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora flavescens Aiton (Radix Sophorae Flavescentis, Kushen) is used in traditional Chinese medicine to treat chronic hepatitis B (CHB), and has the ability to clear heat and dampness from the body. Oxymatrine is one of the major bioactive compounds extracted from Sophora flavescens Aiton and constitutes more than 90% of the oxymatrine injection commonly used for CHB treatment in clinics in China. AIM OF THE STUDY: We aim to analyze the protein binding target of oxymatrine in treating CHB by screening a T7 phage display cDNA library of human CHB and examine the biochemistry of protein-ligand binding between oxymatrine and its ligands. MATERIALS AND METHODS: A T7 phage cDNA library of human CHB was biopanned by affinity selection using oxymatrine as bait. The interaction of oxymatrine with its candidate binding protein was investigated by affinity assay, molecular docking, Isothermal Titration Calorimetry (ITC) and Surface Plasmon Resonance (SPR). RESULTS: A library of potential oxymatrine binding peptides was generated. Ubiquinol-cytochrome c reductase binding protein (UQCRB) was one of the candidate binding proteins of oxymatrine. UQCRB-displaying T7 phage binding numbers in the oxymatrine group were significantly higher than that in the control group, biotin group, and matrine group (p<0.05 or p<0.01). Three-dimensional structure modeling of the UQCRB with oxymatrine showed that their binding interfaces matched and oxymatrine inserted into a deeper pocket of UQCRB, which mainly involved amino acid residues Tyr21, Arg33, Tyr83, Glu84, Asp86, Pro88, and Glu91. The binding affinity constant (Kb) from SPR was 4.2mM. The Kb from ITC experiment was 3.9mM and stoichiometry was fixed as 1, which fit very well with the result of SPR. The binding of oxymatrine to UQCRB was driven by strong enthalpy forces such as hydrogen bonds and polar interactions as the heat released was about 157kcal/mol and ΔG was less than zero. CONCLUSIONS: In this study, using the T7 phage display system, we have identified UQCRB as a direct binding protein of oxymatrine. Furthermore, the specificity and molecular interaction of oxymatrine with UQCRB were also determined. The binding of UQCRB to oxymatrine suggests that UQCRB is a potential target of oxymatrine in treating CHB. These results provide new understanding into the mechanism of oxymatrine and insights into the strategy on the treatment of CHB.


Assuntos
Alcaloides/farmacologia , Bacteriófago T7 , Hepatite B Crônica/tratamento farmacológico , Quinolizinas/farmacologia , Sophora , Alcaloides/metabolismo , Bacteriófago T7/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Hepatite B Crônica/metabolismo , Humanos , Ligação Proteica , Quinolizinas/metabolismo
6.
J Hepatol ; 62(3): 526-32, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25450709

RESUMO

BACKGROUND & AIMS: We aimed to compare the viral suppression, safety and rate of drug resistance between besifovir (a new acyclic nucleotide analogue) and entecavir. METHODS: Treatment-naïve chronic hepatitis B patients receiving besifovir 90 mg (n=31), 150 mg (n=28) and entecavir 0.5 mg (n=30) were monitored for liver biochemistry, viral serology, HBV DNA levels, development of drug resistance mutations, and adverse events throughout 96 weeks of treatment. RESULTS: The mean decline of HBV DNA levels from baseline to week 96 were 5.29, 5.15, and 5.67 logs IU/ml for patients receiving besifovir 90 mg, 150 mg and entecavir 0.5 mg, respectively (p>0.05). Undetectable HBV DNA (<20 IU/ml) were achieved in 80.7%, 78.6%, and 80%; ALT normalization in 90.3%, 78.6%, and 93.3%; and loss of HBeAg in 20%, 21.4%, and 22.2% of patients respectively (all p>0.05). One patient receiving besifovir 90 mg had a virological breakthrough due to drug non-compliance. No patient developed drug resistance mutations. Ten patients had serious adverse events, which were not related to the study medications. The most common side effect related to besifovir was carnitine depletion. Carnitine supplements were prescribed to 83.9% and 100% of patients, who had low carnitine level for any one time during follow-up, receiving besifovir 90 mg and 150 mg respectively. No patient had increased creatinine>0.5 mg/dl from baseline. CONCLUSIONS: Besifovir had the same antiviral property as compared to entecavir over 96 weeks of treatment for chronic hepatitis B patients. Besifovir was well tolerated and also had a good clinical safety profile.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adulto , Alanina Transaminase/sangue , Antivirais/efeitos adversos , Carnitina/deficiência , Carnitina/metabolismo , DNA Viral/sangue , DNA Viral/genética , Feminino , Guanina/efeitos adversos , Guanina/uso terapêutico , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/metabolismo , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/efeitos adversos , Soroconversão , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
7.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(11): 1324-8, 2014 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-25566623

RESUMO

OBJECTIVE: To explore different microRNA expression profiles between chronic hepatitis B (CHB) patients of Pi-Wei dampness-heat syndrome (PWDHS) and Gan depression Pi deficiency syndrome (GDPDS). METHODS: By applying gene chip technology, blood samples from CHB patients of PWDHS (3 cases), GDPDS (3 cases), and healthy volunteers (3 cases) were withdrawn and microRNA detected. The microRNA was screened and functional analyses performed by using SAS system. RESULTS: Totally 77 microRNAs with differential expression were screened from CHB patients of PWDHS and healthy volunteers, including 60 up-regulated microRNAs and 17 down-regulated microRNAs. Functions of target genes were mainly associated with transcription factors, gas exchange, adverse stimulating, regulation of enzyme activities, developing of the immune system, and the process of actin filaments. Totally 41 microRNAs with differential expression were screened from CHB patients of GDPDS and healthy volunteers, including 32 up-regulated microRNAs and 9 down-regulated microRNAs. Functions of target genes were mainly associated with binding to nucleotide or chromatin, inhibition and activation of transcription, biosynthesis, regulation of metabolic process, regulation of enzyme activities, developing of the immune system, the process of actin filaments, and IL-12. Totally 6 microRNAs with differential expression were screened from CHB patients of PWDHS and CHB patients of GDPDS, including 1 up-regulated microRNA and 5 down-regulated microRNAs. Functions of target genes were mainly associated with transmembrane transport, regulation of transcription factors, metabolism of hormones, developing of the immune system, the process of actin filaments, regulation of metabolic process, response to exterior stimulation, and so on. CONCLUSION: There existed differentially expressed microRNAs (spectrum) between CHB patients of PWDHS and CHB patients of GDPDS.


Assuntos
Hepatite B Crônica/metabolismo , Medicina Tradicional Chinesa , MicroRNAs/metabolismo , Depressão , Hepatite B Crônica/genética , Temperatura Alta , Humanos , Interleucina-12/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Pesquisa , Síndrome
8.
PLoS One ; 7(11): e49460, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23185336

RESUMO

BACKGROUND: High serum levels of lipopolysaccharide (LPS) with LPS-MD-2/TLR4 complex activated NF-kb and cytokine cause hepatic necrosis in animal models. We investigated the dynamic changes of LPS levels in patients with acute on chronic hepatitis B liver failure (ACHBLF). METHODS: We enrolled ACHBLF patients for a 12-week study. Patients' LPS levels were measured along with 10 healthy controls. Patients on supportive care and recovered without intervention(s) were analyzed. Patients' LPS levels during the disease progression phase, peak phase, and remission phase were compared with healthy controls. RESULTS: Among 30 patients enrolled, 25 who received interventions or expired during the study period were excluded from the analysis, five patients on supportive care who completed the study were analyzed. Significant abnormal distributions of LPS levels were observed in patients in different phases (0.0168±0.0101 in progression phase; 0.0960±0.0680 in peak phase; 0.0249±0.0365 in remission phase; and 0.0201±0.0146 in controls; respectively, p<0.05). The highest level of LPS was in the peak phase and significantly elevated when compared to controls (0.0201±0.0146 vs. 0.0960±0.0680, p = 0.007). There were no statistically significant differences in LPS levels between healthy controls and subjects in the progression phase or remission phase. Dynamic changes of LPS were correlated with MELD-Na in the progression phase (p = 0.01, R = 0.876) and in the peak phase (p = 0.000, R = -1.00). CONCLUSIONS: Significant abnormal distributions of LPS levels were observed in ACHBLF with the highest level in the peak phase. The dynamic changes of LPS were correlated with disease severity and suggested LPS causing secondary hepatic injury.


Assuntos
Hepatite B Crônica/metabolismo , Lipopolissacarídeos/metabolismo , Falência Hepática Aguda/virologia , Tálamo/metabolismo , Animais , Mapeamento Encefálico/métodos , Modelos Animais de Doenças , Eletrodos , Retroalimentação , Fígado/patologia , Falência Hepática Aguda/metabolismo , Masculino , Neurônios/metabolismo , Oscilometria/métodos , Córtex Pré-Frontal/fisiologia , Ratos , Ratos Long-Evans , Reprodutibilidade dos Testes
9.
World J Gastroenterol ; 18(31): 4156-61, 2012 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-22919248

RESUMO

AIM: To screen for genes related to metabotropic receptors that might be involved in the development of chronic hepatitis. METHODS: Assessment of 20 genes associated with metabotropic receptors was performed in liver specimens obtained by punch biopsy from 12 patients with autoimmune and chronic hepatitis type B and C. For this purpose, a microarray with low integrity grade and with oligonucleotide DNA probes complementary to target transcripts was used. Evaluation of gene expression was performed in relation to transcript level, correlation between samples and grouping of clinical parameters used in chronic hepatitis assessment. Clinical markers of chronic hepatitis included alanine and aspartate aminotransferase, γ-glutamyltranspeptidase, alkaline phosphatase and cholinesterase activity, levels of iron ions, total cholesterol, triglycerides, albumin, glucose, hemoglobin, platelets, histological analysis of inflammatory and necrotic status, fibrosis according to METAVIR score, steatosis, as well as anthropometric body mass index, waist/hip index, percentage of adipose tissue and liver size in ultrasound examination. Gender, age, concomitant diseases and drugs were also taken into account. Validation of oligonucleotide microarray gene expression results was done with the use of quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The highest (0.002 < P < 0.046) expression among genes encoding main components of metabotropic receptor pathways, such as the α subunit of G-coupled protein, phosphoinositol-dependent protein kinase or arrestin was comparable to that of angiotensinogen synthesized in the liver. Carcinogenesis suppressor genes, such as chemokine ligand 4, transcription factor early growth response protein 1 and lysophosphatidic acid receptor, were characterized by the lowest expression (0.002 < P < 0.046), while the factor potentially triggering hepatic cancer, transcription factor JUN-B, had a 20-fold higher expression. The correlation between expression of genes of protein kinases PDPK1, phosphoinositide 3-kinase and protein kinase A (Spearman's coefficient range: 0.762-0.769) confirmed a functional link between these enzymes. Gender (P = 0.0046) and inflammation severity, measured by alanine aminotransferase activity (P = 0.035), were characterized by diverse metabotropic receptor gene expression patterns. The Pearson's coefficient ranging from -0.35 to 0.99 from the results of qRT-PCR and microarray indicated that qRT-PCR had certain limitations as a validation tool for oligonucleotide microarray studies. CONCLUSION: A microarray-based analysis of hepatocyte metabotropic G-protein-related gene expression can reveal the molecular basis of chronic hepatitis.


Assuntos
Hepatite B Crônica/metabolismo , Hepatite C Crônica/metabolismo , Fígado/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transcriptoma , Proteínas Quinases Dependentes de 3-Fosfoinositídeo , Adulto , Arrestinas/genética , Arrestinas/metabolismo , Biópsia , Cromograninas , Feminino , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Hepatite B Crônica/genética , Hepatite B Crônica/patologia , Hepatite C Crônica/genética , Hepatite C Crônica/patologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Estudos Retrospectivos , beta-Arrestinas
11.
Klin Med (Mosk) ; 87(1): 49-52, 2009.
Artigo em Russo | MEDLINE | ID: mdl-19256261

RESUMO

The aim of the study was to measure plasma levels of stable metabolites of nitric oxide, nitrates, and nitrites (NOx) in patients with chronic viral hepatitis and evaluate the possibility of their correction by low-power laser irradiation. NO metabolites (total nitrites and nitrates) were measured colorimetrically from the development of colour in the reaction of nitrite with sulfanilamide diazotization in Griess reagent. Colour intensity was determined with Victor2 enzyme immunoanalyzer, Perkin Elmaer (Finland). The patients were divided into three groups. In group 1 (control, n = 30) they received combined medicamentous therapy, in group 2 (n = 45) medicamentous therapy and a course of intravenous laser therapy, in goup 3 (n = 45) medicamentous therapy and skin laserotherapy. The results indicate that medicamentous treatment of patients with chronic hepatitis does not bring any beneficial changes in plasma NOx whose levels are significantly improved in case of simultaneous laser therapy. It is concluded that different laserotherapeutic modalities have beneficial effect on NO-producing function of endothelium and thereby improve its functional state. Compensation of NO deficit by laser therapy ensures overall protection of the organism against free radicals and decreases severity of oxidative stress.


Assuntos
Endotélio Vascular/fisiopatologia , Hepatite B Crônica/radioterapia , Hepatite C Crônica/radioterapia , Terapia com Luz de Baixa Intensidade/métodos , Estresse Oxidativo/efeitos da radiação , Vasodilatação/efeitos da radiação , Adulto , Endotélio Vascular/metabolismo , Endotélio Vascular/efeitos da radiação , Feminino , Seguimentos , Hepatite B Crônica/metabolismo , Hepatite B Crônica/fisiopatologia , Hepatite C Crônica/metabolismo , Hepatite C Crônica/fisiopatologia , Humanos , Masculino , Óxido Nítrico/metabolismo , Resultado do Tratamento , Vasodilatação/fisiologia
12.
Adv Ther ; 26(2): 155-69, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19225726

RESUMO

INTRODUCTION: The treatment of chronic hepatitis B virus (HBV) infection has been revolutionized in the past decade by the increased availability of effective antiviral agents. Telbivudine is an L-nucleoside that is structurally related to lamivudine and has recently been approved for use in patients with chronic HBV infection. Telbivudine is highly selective for HBV DNA and inhibits viral DNA synthesis with no effect on human DNA or other viruses. This article reviews the pharmacology, pharmacokinetics, therapeutic efficacy and safety of telbivudine, and discusses its place in the current armamentarium against HBV. METHODS: Relevant publications were identified from searches of Medline and PubMed between 2000 and 2008, using the search terms "hepatitis B/HBV," "telbivudine/LdT," "beta-L-thymidine," "pharmacokinetics," "safety," "adverse events," and "resistance." The reference lists of retrieved articles were searched for relevant studies. RESULTS: Phase 3 clinical studies demonstrate that telbivudine is superior to lamivudine over a 2-year period in hepatitis B e-antigen (HBeAg)-positive and HBeAg-negative patients. Telbivudine was associated with a statistically significantly greater reduction in HBV DNA, greater proportion of alanine aminotransferase normalization, and greater histological response than lamivudine. Furthermore, telbivudine use resulted in fewer cases of treatment failure and less virological resistance than lamivudine. However, after 2 years of therapy, telbivudine resistance was appreciable (25%) and considerably higher than that seen with other new antivirals such as tenofovir and entecavir. Overall, telbivudine was found to be safe, although grade 3 or 4 adverse events, including elevations in creatine kinase, were more commonly found in patients receiving telbivudine than lamivudine. Telbivudine is not active against lamivudine-resistant HBV. CONCLUSIONS: Telbivudine is a new antiviral agent joining the armamentarium against HBV. It is superior to lamivudine in terms of therapeutic response and resistance profile. However, concerns about resistance with long-term use, along with inferior cost-effective analyses, have relegated telbivudine to a second-line agent in the management of chronic HBV infection.


Assuntos
Hepatite B Crônica/tratamento farmacológico , Nucleosídeos/uso terapêutico , Pirimidinonas/uso terapêutico , Alanina Transaminase/sangue , Alanina Transaminase/efeitos dos fármacos , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , DNA Viral/biossíntese , DNA Viral/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Interações Medicamentosas , Farmacorresistência Viral/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/metabolismo , Hepatite B Crônica/virologia , Humanos , Nucleosídeos/química , Nucleosídeos/farmacologia , Pirimidinonas/química , Pirimidinonas/farmacologia , Segurança , Telbivudina , Timidina/análogos & derivados , Resultado do Tratamento , Replicação Viral/efeitos dos fármacos
13.
Gastroenterology ; 135(3): 969-79, 979.e1, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18602920

RESUMO

BACKGROUND & AIMS: Numerous studies have linked the proliferation of liver progenitor cells (LPCs) during chronic liver disease to the risk for development of hepatocellular carcinoma. Thus, selective inhibition of LPC growth during preneoplastic injury may prevent or delay the onset of liver cancer. Rats carrying a germ-line mutation in c-kit have an impaired LPC response to liver injury. Therefore, we hypothesized that the c-kit inhibitor imatinib mesylate (IM) would suppress LPC growth and, therefore, may exert antitumorigenic effects in the liver. METHODS: Expression of IM target proteins was examined in chronically injured rodent and human livers. The effect of IM was examined in vitro using LPC lines and in vivo in mice fed a choline-deficient, ethionine-supplemented (CDE) diet. Livers were examined following short-term (up to 1 month) or long-term (up to 14 months) feeding of CDE diet and drug treatments. RESULTS: C-kit was significantly up-regulated in chronic injury and expressed by LPCs. IM was antiproliferative to LPC lines, and knockdown of c-kit reduced this response. IM treatment inhibited the LPCs response and early fibrogenesis induced by a short-term CDE diet. On the longer term, IM treatment reduced the extent of fibrosis and significantly inhibited tumor formation. CONCLUSIONS: Tyrosine kinase inhibitors, such as IM, may be suited for the prevention of hepatocellular carcinoma in the setting of chronic liver injury via antiproliferative effects on c-kit-expressing LPCs.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Neoplasias Hepáticas Experimentais/patologia , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Pirimidinas/farmacologia , Células-Tronco/efeitos dos fármacos , Animais , Benzamidas , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Colina/administração & dosagem , Dieta , Relação Dose-Resposta a Droga , Etionina/administração & dosagem , Hepatite B Crônica/metabolismo , Hepatite B Crônica/patologia , Hepatócitos/patologia , Humanos , Mesilato de Imatinib , Técnicas In Vitro , Fígado/efeitos dos fármacos , Fígado/metabolismo , Neoplasias Hepáticas Experimentais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Proto-Oncogênicas c-abl/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Células-Tronco/patologia
14.
J Altern Complement Med ; 14(3): 299-301, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18370584

RESUMO

BACKGROUND: Hepatitis B is a global health problem. Use of complementary and alternative medicine has been popular among patients with hepatitis B. This 1-year open-label pilot study aims to observe whether Agaricus blazei Murill extract improves liver function in patients with hepatitis B. METHODS: This study involved 12 months of clinical observation. Four (4) patients with hepatitis B who met the criteria (1) aged between 20 and 65 years; (2) being Chinese; (3) having been a hepatic B carrier (HBAg(+)) for more than 3 years; (4) alanine aminotransferase > 100 IU/L; and (5) not taking lamivudine, alpha-interferon, or other drugs for hepatitis participated in the study with informed consent. The enrolled patients were given Agaricus blazei Murill (ABM) extract of 1500 mg daily for 12 months. The level of alanine aminotransferase was taken as the major outcome measurement. RESULTS: At the end of the study, the mean level of aspartate aminotransferase and alanine aminotransferase decreased from 246.0 (+/- standard deviation [SD] 138.9) to 61.3 (+/- SD 32.6) IU/L and 151.0 (+/- SD 86.9) to 46.1 (+/- SD 22.5) IU/L, respectively. CONCLUSIONS: Our initial observation seems to indicate the potential benefit of ABM extract in normalizing liver function of patients with hepatitis B. Controlled studies with larger samples should be conducted in the future.


Assuntos
Agaricus , Antivirais/administração & dosagem , Misturas Complexas/administração & dosagem , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/metabolismo , Fígado/efeitos dos fármacos , Fitoterapia/métodos , Administração Oral , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento
15.
J Tradit Chin Med ; 27(2): 108-10, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17710804

RESUMO

OBJECTIVE: To probe into the methods and therapeutic effects of electroacupuncture (EA) on hepatitis B. METHODS: 60 hospitalized cases of mild or moderate hepatitis B were randomly divided into a treatment group (30 cases) and a control group (30 cases). EA was applied at the points selected according to the differentiation of symptoms and signs. The treatment was given once daily for 30 minutes, and 2 weeks of treatments constituted a therapeutic course, with 2-3 courses on average in the treatment group. Conventional treatment for liver protection was given in the control group. RESULTS: As compared with the control group, the duration of the treatment for recovery of the hepatic functions was significantly shorter, and the IL-8 level significantly lower in the treatment group. CONCLUSION: In treating hepatitis B, EA is effective in improving symptoms, recovering hepatic functions, and regulating immune functions to certain extent.


Assuntos
Eletroacupuntura , Hepatite B Crônica/terapia , Feminino , Hepatite B Crônica/metabolismo , Humanos , Interleucina-8/metabolismo , Masculino
16.
Turk J Gastroenterol ; 17(4): 260-6, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17205403

RESUMO

BACKGROUND/AIMS: The aim of the study was to assess bone metabolism and impact of disease on bone mineral density in patients with non-cirrhotic chronic hepatitis B or C. METHODS: 105 patients with chronic hepatitis B or C receiving antiviral agents and 60 healthy controls were included. Subgroups (n=15) were defined on the basis of age (males) or menopausal status (females). Bone mineral density; serum parathyroid hormone (PTH), calcium (Ca), phosphorus (P), total alkaline phosphatase, and 25-hydroxy vitamin D levels; 24-hour urinary levels of Ca and P; and urinary telopeptide (NTX) were measured. Statistical comparisons were made between patient groups and the matched controls. RESULTS: Compared to controls, the average serum levels of PTH were lower and 24-hour urinary mean Ca levels and T scores were higher in chronic hepatitis B patients between 20 and 40 years of age. Men with chronic hepatitis B and aged 40 - 65 years had lower mean serum P concentrations. Postmenopausal women with chronic hepatitis B had significantly higher NTX levels. Men with chronic hepatitis C had significantly elevated levels of 24-hour mean urinary P levels. The serum 25 OH vitamin D levels were significantly higher in premenopausal women with chronic hepatitis C. Postmenopausal women with chronic hepatitis C had significantly lower serum P concentrations. Other parameters and T scores did not differ significantly between patient groups and matched controls. CONCLUSION: Our results suggest that chronic hepatitis B and C infections do not pose a risk for osteoporosis and low bone mineral density.


Assuntos
Densidade Óssea , Remodelação Óssea/fisiologia , Hepatite B Crônica/metabolismo , Hepatite C Crônica/metabolismo , Adulto , Fatores Etários , Idoso , Fosfatase Alcalina/sangue , Calcifediol/sangue , Cálcio/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fósforo/metabolismo , Fatores Sexuais
18.
Vopr Pitan ; 71(4): 27-31, 2002.
Artigo em Russo | MEDLINE | ID: mdl-12462952

RESUMO

We have studied the effect of dietary supplement "ExPress" on clinical and biochemical parameters and on the activity of detoxification enzymes of liver in patients with chronic viral hepatitis B and C. 24 patients (19 females and 5 males aged 16-39 years) were enrolled in the study. Patients in case group received dietary supplement "ExPress" in addition to basic treatment. Average indices of total bilirubin in cases after treatment were 26.98 +/- 2.85 mmol/l, while in controls--34.31 +/- 5.72 mmol/l (p > 0.05). Average indices of alanin-aminotransferase and aspartate-aminotransferase were 78.75 +/- 11.25 and 160.75 +/- 23.67 units while in controls--208.5 +/- 56.4 and 330.25 +/- 65.14 units respectively (p < 0.05). In case group we observed full normalization of thymol test--from 9.99 +/- 1.51 to 4.03 +/- 0.73 units (p = 0.001), while in controls--from 7.9 +/- 1.56 only to 5.2 +/- 1.15 units (p = 0.194). Contents of non-metabolized antipyrine in cases decreased from 9.76 +/- 1.2% (p = 0.0002) whilst in controls--from 9.38 +/- 1.28% only to 3.93 +/- 1.18% (p = 0.01). Results of the study show that dietary supplement "ExPress" induces the activity of detoxification enzymes of liver and increases the efficiency of basic treatment.


Assuntos
Antipirina/análogos & derivados , Hepatite B Crônica/dietoterapia , Hepatite C Crônica/dietoterapia , Indóis/uso terapêutico , Isotiocianatos/uso terapêutico , Adolescente , Adulto , Alanina Transaminase/metabolismo , Antipirina/metabolismo , Antipirina/farmacocinética , Antipirina/urina , Aspartato Aminotransferases/metabolismo , Bilirrubina/metabolismo , Estudos de Casos e Controles , Suplementos Nutricionais , Edaravone , Feminino , Hepatite B Crônica/metabolismo , Hepatite C Crônica/metabolismo , Humanos , Inativação Metabólica , Fígado/metabolismo , Masculino
19.
Zhong Yao Cai ; 25(6): 451-3, 2002 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-12583341

RESUMO

OBJECTIVE: To explore the correlation of clinical effect and TCRV beta 7 expression of He Jie Decoction (HJD) on chronic hepatitis B patients. METHODS: 45 patients of chronic hepatitis B were divided randomly into two groups. 30 patients in the treated group were treated by HJD, and 15 patients in the control group were treated by usual western medicine. The TCRV beta 7 level were detected before and after being treated. RESULTS: After six months treatment, the ALT level of two groups were obviously decreased (P < 0.01), TCRV beta 7 expression were detected out in 6 patients of the treated group, and HBV-DNA and HBeAg of the 6 patients were negative conversion. The TCRV beta 7 expression couldn't be detected out in the control group, and HBV-DNA and HBeAg of the control group weren't negative conversion. There was no significant difference between the clinical total effective rate of the two groups (P > 0.05), but the apparent rate of the treated group was significantly higher than that of the control group (P < 0.01). CONCLUSION: HJD might have the effect on improving the TCRV beta 7 expression of chronic hepatitis B patients, which might be the ways of HJD inhibiting and killing hepatitis B virus.


Assuntos
Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Plantas Medicinais , Receptores de Antígenos de Linfócitos T alfa-beta/biossíntese , Adolescente , Adulto , Idoso , Bupleurum/química , DNA Viral/sangue , Medicamentos de Ervas Chinesas/isolamento & purificação , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/metabolismo , Humanos , Pessoa de Meia-Idade , Pinellia/química , Plantas Medicinais/química , Scutellaria baicalensis/química
20.
Klin Med (Mosk) ; 78(6): 56-9, 2000.
Artigo em Russo | MEDLINE | ID: mdl-10900874

RESUMO

A trial of a novel hepatoprotective plant drug lochein (Salsola extract) developed in Russia was performed in 110 patients with a verified chronic hepatitis of viral (73 patients) or alcohol (36 patients) etiology versus well-known hepatoprotector corsil given to 40 patients. Lochein demonstrated more potent effect than corsil.


Assuntos
Antioxidantes/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite Alcoólica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Adulto , Feminino , Hepatite B Crônica/metabolismo , Hepatite Alcoólica/metabolismo , Humanos , Testes de Função Hepática , Masculino , Indução de Remissão/métodos , Silimarina/uso terapêutico , Resultado do Tratamento
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