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1.
Health Qual Life Outcomes ; 19(1): 140, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962617

RESUMO

BACKGROUND: Health Related Quality of Life (HRQL) is a multi-dimensional construct that can comprehensively evaluate the patient's health status, including physical, emotional, mental and social well-being. In this study, we aimed to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on HRQL in a Chinese population. METHODS: In this national multicenter cross-sectional survey, patients with NAFLD were enrolled. Chronic Liver Disease Questionnaire (CLDQ)-NAFLD was used to qualify HRQL. Univariate and multivariate analysis were used to identify independent risk factors of HRQL. RESULTS: A total of 5181 patients with NAFLD from 90 centers were enrolled in this study (mean age, 43.8 ± 13.3 years; male, 65.8%). The overall CLDQ score was 5.66 ± 0.89. Multivariate logistic regression analysis showed that body mass index (BMI: HR, 1.642; 95% CI, 1.330-2.026), alanine transaminase (ALT: HR, 1.006; 95% CI, 1.001-1.011), triglyceride (HR, 1.184; 95% CI, 1.074-1.305), disease severity (HR, 3.203; 95% CI, 1.418-7.232) and cardiovascular disease (HR, 4.305; 95% CI, 2.074-8.939) were independent risk factors for overall CLDQ score. In the logistic analyses of individual domain, BMI and triglyceride were independent risk factors of all domains. ALT, disease severity, diabetes, depression and cardiovascular disease were influencing factors for the CLDQ score of several domains. CONCLUSIONS: This national multicenter cross-sectional survey in China indicated that the HRQL in patients with NAFLD was impaired. HRQL was found to be significantly associated with sociodemographic and clinical factors. Attention should be paid to the optimally managing care of patients with NAFLD to improve their HRQL.


Assuntos
Grupo com Ancestrais do Continente Asiático/psicologia , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Nível de Saúde , Hepatopatia Gordurosa não Alcoólica/psicologia , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Inquéritos e Questionários/normas , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
2.
Histol Histopathol ; 36(6): 653-662, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33870482

RESUMO

BACKGROUND: Inflammatory activation of hepatic macrophages plays a primary role in drug-induced liver injury (DILI). However, the exact mechanism underlying DILI remains unclear. METHODS: A total of 328 DILI patients and 80 healthy individuals were prospectively enrolled in this study. The DILI patients were categorized into subgroups based on either disease severity or histopathological patterns. Plasma soluble CD163 (sCD163) and hepatic CD163 were examined to determine hepatic macrophage activation, and CD8, CD20, and MUM-1 were assessed to determine cellular immunity using immunohistochemistry. The lipopolysaccharide (LPS) pathway proteins [e.g. LPS, soluble CD14 (sCD14), and LPS-binding protein (LBP)] were measured using enzyme-linked immunosorbent assay. RESULTS: Plasma sCD163 levels were nine-fold higher in DILI patients than in healthy controls at the baseline, but significantly decreased at the 4-week follow-up visit after treatment. The numbers of hepatic macrophages, B cells, and plasma cells were significantly higher in the liver tissues from DILI patients than those from healthy controls. Furthermore, the baseline levels of LPS pathway proteins in the DILI patients were significantly higher than those in the controls. Notably, these proteins significantly decreased at the 4-week follow-up visit but remained significantly higher than the levels for the controls. CONCLUSIONS: Hepatic inflammation in DILI involves the activation of hepatic macrophages and cellular immunity, in which the LPS pathway likely plays a role, at least in part. As such, this study has improved our understanding of the pathological mechanisms for DILI and may facilitate the development of better treatments for patients with DILI.

3.
Hepatology ; 71(6): 1953-1966, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31600834

RESUMO

BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. Clinical trials use the NASH Clinical Research Network (CRN) system for semiquantitative histological assessment of disease severity. Interobserver variability may hamper histological assessment, and diagnostic consensus is not always achieved. We evaluate a second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) imaging-based tool to provide an automated quantitative assessment of histological features pertinent to NASH. APPROACH AND RESULTS: Images were acquired by SHG/TPEF from 219 nonalcoholic fatty liver disease (NAFLD)/NASH liver biopsy samples from seven centers in Asia and Europe. These were used to develop and validate qFIBS, a computational algorithm that quantifies key histological features of NASH. qFIBS was developed based on in silico analysis of selected signature parameters for four cardinal histopathological features, that is, fibrosis (qFibrosis), inflammation (qInflammation), hepatocyte ballooning (qBallooning), and steatosis (qSteatosis), treating each as a continuous rather than categorical variable. Automated qFIBS analysis outputs showed strong correlation with each respective component of the NASH CRN scoring (P < 0.001; qFibrosis [r = 0.776], qInflammation [r = 0.557], qBallooning [r = 0.533], and qSteatosis [r = 0.802]) and high area under the receiver operating characteristic curve values (qFibrosis [0.870-0.951; 95% confidence interval {CI}, 0.787-1.000; P < 0.001], qInflammation [0.820-0.838; 95% CI, 0.726-0.933; P < 0.001), qBallooning [0.813-0.844; 95% CI, 0.708-0.957; P < 0.001], and qSteatosis [0.939-0.986; 95% CI, 0.867-1.000; P < 0.001]) and was able to distinguish differing grades/stages of histological disease. Performance of qFIBS was best when assessing degree of steatosis and fibrosis, but performed less well when distinguishing severe inflammation and higher ballooning grades. CONCLUSIONS: qFIBS is an automated tool that accurately quantifies the critical components of NASH histological assessment. It offers a tool that could potentially aid reproducibility and standardization of liver biopsy assessments required for NASH therapeutic clinical trials.


Assuntos
Biópsia , Fígado Gorduroso , Hepatite , Interpretação de Imagem Assistida por Computador/métodos , Cirrose Hepática , Fígado , Hepatopatia Gordurosa não Alcoólica/patologia , Algoritmos , Grupo com Ancestrais do Continente Asiático , Biópsia/métodos , Biópsia/normas , Precisão da Medição Dimensional , Grupo com Ancestrais do Continente Europeu , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/etiologia , Feminino , Hepatite/diagnóstico por imagem , Hepatite/etiologia , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Padrões de Referência , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
4.
J Cell Mol Med ; 24(2): 1268-1275, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31851780

RESUMO

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small bile duct injury. Emperipolesis is one of cell-in-cell structures that is a potential histological hallmark associated with chronic hepatitis B. This study aimed to clarify the pathogenesis and characteristics of emperipolesis in PBC liver injury. Sixty-six PBC patients, diagnosed by liver biopsy combined with laboratory test, were divided into early-stage PBC (stages I and II, n = 39) and late-stage PBC (stages III and IV, n = 27). Emperipolesis was measured in liver sections stained with haematoxylin-eosin. The expressions of CK19, CD3, CD4, CD8, CD20, Ki67 and apoptosis of BECs were evaluated by immunohistochemistry or immunofluorescence double labelling. Emperipolesis was observed in 62.1% of patients with PBC, and BECs were predominantly host cells. The number of infiltrating CD3+ and CD8+ T cells correlated with the advancement of emperipolesis (R2  = 0.318, P < .001; R2  = 0.060, P < .05). The cell numbers of TUNEL-positive BECs and double staining for CK19 and Ki67 showed a significant positive correlation with emperipolesis degree (R2  = 0.236, P < .001; R2  = 0.267, P < .001). We conclude that emperipolesis mediated by CD8+ T cells appears to be relevant to apoptosis of BEC and thus may aggravate the further injury of interlobular bile ducts.


Assuntos
Apoptose , Ductos Biliares/patologia , Linfócitos T CD8-Positivos/imunologia , Emperipolese , Células Epiteliais/patologia , Cirrose Hepática Biliar/fisiopatologia , Ductos Biliares/imunologia , Ductos Biliares/lesões , Estudos de Casos e Controles , Proliferação de Células , Células Epiteliais/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
Am J Clin Pathol ; 148(6): 502-512, 2017 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-29165568

RESUMO

Objectives: Investigate subtle fibrosis similarities and differences in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using second harmonic generation (SHG). Methods: SHG/two-photon excitation fluorescence imaging quantified 100 collagen parameters and determined qFibrosis values by using the nonalcoholic steatohepatitis (NASH) Clinical Research Network (CRN) scoring system in 62 adult and 36 pediatric NAFLD liver specimens. Results: Six distinct parameters identified differences among the NASH CRN stages with high accuracy (area under the curve, 0835-0.982 vs 0.885-0.981, adult and pediatric). All portal region parameters showed similar changes across early stages 0, 1C, and 2, in both groups. Parameter values decreased in adults with progression from stage 1A/B to 2 in the central vein region. In children, aggregated collagen parameters decreased, but nearly all distributed collagen parameters increased from stage 1A/B to 2. Conclusions: SHG analysis accurately reproduces NASH CRN staging in NAFLD, as well as reveals differences and similarities between adult and pediatric collagen deposition not captured by currently available quantitative methods.


Assuntos
Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Adolescente , Adulto , Fatores Etários , Biópsia/métodos , Criança , Progressão da Doença , Feminino , Fibrose , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adulto Jovem
6.
Mil Med Res ; 2: 9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25914830

RESUMO

The ongoing Ebola outbreak poses an alarming risk to the countries of West Africa and beyond. On August 8, 2014, the World Health Organization (WHO) declared the cross-country Ebola outbreak a Public Emergency of International Concern. China has had no confirmed cases of Ebola. In this paper, virologic characteristics, pathogenesis, clinical manifestations, laboratory examination and prophylactic vaccines and therapeutic drugs of Ebola are summarized. Importantly, active responses and actions from China are introduced. Moreover, the key issues in the future prevention and control of Ebola were also addressed.

7.
Exp Ther Med ; 9(3): 999-1005, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25667667

RESUMO

Soluble cluster of differentiation 40 (sCD40) is proteolytically cleaved from membrane-bound CD40 and binds to CD154, thereby inhibiting CD40-CD154-mediated immune responses. The aim of the present study was to clarify the role of sCD40 in chronic hepatitis B (CHB). The sCD40 levels in sera from 132 patients with CHB and 33 healthy individuals were retrospectively measured. sCD40 concentrations in patients with CHB were higher than those in healthy controls, and sCD40 levels correlated positively with serum levels of the liver dysfunction biomarkers alanine transaminase (ALT) and aspartate transaminase (AST). sCD40 concentrations increased with a rise in the severity of liver necroinflammation and fibrosis. Patients with >75% liver tissue staining positive for hepatitis B virus (HBV) antigen expression showed significantly lower sCD40 levels than those who stained negative for the HBV antigen. The area under the receiver operating characteristic curve of sCD40 was greater than that of ALT and AST; thus, sCD40 levels have a high diagnostic accuracy for detecting severe liver inflammation in patients with CHB, and could serve as an immunological marker of hepatic tissue injury.

8.
Int J Infect Dis ; 30: 52-6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25461662

RESUMO

OBJECTIVES: MicroRNA-122 has been shown to be crucial for efficient HCV RNA replication in vitro. Pretreatment intrahepatic microRNA-122 levels in chronic hepatitis C (CHC) patients have been associated with the outcomes of interferon therapy. Here, we determined microRNA-122 serum levels in CHC patients and healthy donors using an absolute quantification approach and evaluated the correlation with liver inflammation grades and serum alanine aminotransferase (ALT) levels. METHODS: Serum samples were collected from 105 treatment-naive CHC patients, 11 acute hepatitis patients, and 33 healthy donors. Serum microRNA-122 was measured using the TaqMan RT-qPCR. The cycle threshold values were converted to copy numbers by drawing a standard curve using a chemical synthetic standard. For accurate quantification, copy numbers were further normalized according to the recovery ratios of spiked-in cel-miR-39. RESULTS: Serum levels of microRNA-122 were significantly higher in acute hepatitis and CHC patients than in healthy donors (p<0.001). However, there was no significant association between microRNA-122 and ALT serum levels or liver inflammation grades. CONCLUSIONS: The present study showed that serum microRNA-122 was elevated in acute and chronic hepatitis patients. However, this biomarker for acute liver injury did not reflect the liver inflammation activity in CHC patients.


Assuntos
Alanina Transaminase/sangue , Hepatite C Crônica/diagnóstico , MicroRNAs/sangue , Doença Aguda , Adulto , Idoso , Biomarcadores/sangue , Feminino , Hepatite/sangue , Hepatite C Crônica/sangue , Hepatite C Crônica/patologia , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Biomed Res Int ; 2014: 836025, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25243186

RESUMO

Caveolin-1 and flotillin-1 are considered as markers of lipid rafts which can be regarded as sorting platforms for targeted transport of transmembrane proteins and are involved in fundamental cellular events such as signal transduction, cell adhesion, lipid/protein sorting, and human cancer. We addressed caveolin-1 and flotillin-1 expression in 90 human hepatocellular carcinoma (HCC) and adjacent noncancerous tissues (ANT) samples by SDS-PAGE and immunoblotting with specific antibodies. Significant caveolin-1 and flotillin-1 overexpression was found in HCC tissues compared to ANT and was confirmed by immunohistochemistry. Raft-associated Akt signaling pathway components involved in the regulation of cell survival were altered by western blotting in HCC microdomain-enriched subcellular fractions purified from paired HCC and ANT samples. Our results demonstrated that the activity of raft-associated but not total membrane Akt determines its cellular functions. Lipid rafts differ in different types of tissues, which allows for the possibility of tissue-type-specific targeting for cell survival.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Microdomínios da Membrana/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Caveolina 1/análise , Caveolina 1/metabolismo , Sobrevivência Celular/fisiologia , Feminino , Humanos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Masculino , Proteínas de Membrana/análise , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade
10.
J Gastroenterol Hepatol ; 29(3): 554-60, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24117714

RESUMO

BACKGROUND AND AIM: Liver transplantation (LT) for hepatitis B virus (HBV)-related disease can be complicated by HBV recurrence. The aim of this study was to evaluate the risk factors, prophylaxis treatment, and histological characteristics of HBV recurrence after LT when using long-term, low-dose hepatitis B immunoglobulin (HBIG) plus nucleoside analog (lamivudine [LAM] or entecavir [ETV]). METHODS: Retrospective data from 253 adult LT patients using long-term, low-dose HBIG plus nucleoside analog after LT, for a mean treatment duration of 1-72 months, were collected from a single center in Beijing, China. Univariate analyses were conducted to determine the association among gender, age, hepatocellular carcinoma, hepatitis B e antigen-positive status, HBV-DNA level and tyrosine-methionine-aspartate-aspartate (YMDD) mutations on HBV recurrence in these patients. RESULTS: Overall, the HBV recurrence rate was 6.32% (16/253). There was no significant difference in the survival rate between the HBV recurrence and non-recurrence groups. Risk factors for HBV recurrence were: hepatitis B e antigen positivity, HBV-DNA > 10(5) copies/mL, hepatocellular carcinoma, and YMDD mutation. Sixteen patients receiving LAM had HBV recurrence (16/169; mean treatment duration: 61.8 ± 18.3 months). No HBV recurrence occurred in patients receiving ETV after LT (0/84; mean treatment duration: 57.1 ± 15.9 months). Differences in rate of mortality and HBV recurrence were not significant between the two groups. CONCLUSIONS: LT is an effective treatment for HBV-related end-stage liver disease. The combination of ETV and intramuscular HBIG for HBV recurrence prophylaxis after LT was more effective than LAM, especially in Chinese patients with HBV recurrence risk factors.


Assuntos
Doença Hepática Terminal/terapia , Hepatite B/complicações , Hepatite B/prevenção & controle , Transplante de Fígado , Adulto , Fatores Etários , Antivirais , Ácido Aspártico/genética , Carcinoma Hepatocelular , China/epidemiologia , DNA Viral , Quimioterapia Combinada , Doença Hepática Terminal/etiologia , Guanina/administração & dosagem , Guanina/análogos & derivados , Hepatite B/epidemiologia , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Humanos , Imunoglobulinas/administração & dosagem , Lamivudina/administração & dosagem , Neoplasias Hepáticas , Masculino , Metionina/genética , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Fatores de Risco , Prevenção Secundária , Fatores Sexuais , Tirosina/genética
11.
Artigo em Chinês | MEDLINE | ID: mdl-23189846

RESUMO

OBJECTIVE: To explore whether the cellular apoptosis susceptibility (CAS) protein could serve as a pathologic marker for HCC diagnosis and the roles of CAS expression in HBV infection associated HCC. METHODS: The expression of CAS protein in HCC and its paracarcinoma tissues, non-tumor liver cirrhosis and hepatitis tissues were detected by immunohistochemistry. Meanwhile, HBsAg, HBcAg and HBV DNA in HCC tissues with HBV infection were examined by immunohistochemistry and in situ hybridization respectively. RESULTS: The expression of CAS protein was significantly higher in HCC than in its paracarcinomas tissues (P < 0.01), and higher in paracarcinomas tissues than in non-tumor liver cirrhosis and hepatitis tissues (P < 0.01). Poorly differentiated tumors immunochemically stained stronger than moderately or well differentiated (P < 0.01). CAS protein expression was significantly higher in HBV-infected HCC tissues than that of in non-HBV infection (P < 0.01). Meanwhile, in HBV-infected HCC tissues, the staining intensity score of CAS protein in HBV DNA positive HCC tissues was significantly higher than HBV DNA negative tissues (P < 0.05). CONCLUSIONS: Higher expression of CAS protein is found in HCC tissues,and the intensity of CAS protein expression is related closely to tumor differentiation. We suggested that CAS protein might serve as a marker for HCC diagnosis and differentiation estimation, and deduced that CAS might play an important role in the initiation of HBV infection associated HCC through upregulating expression of CAS.


Assuntos
Carcinoma Hepatocelular/genética , Proteína de Suscetibilidade a Apoptose Celular/genética , Vírus da Hepatite B/fisiologia , Neoplasias Hepáticas/genética , Adulto , Idoso , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Proteína de Suscetibilidade a Apoptose Celular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Antígenos do Núcleo do Vírus da Hepatite B/genética , Antígenos do Núcleo do Vírus da Hepatite B/metabolismo , Antígenos de Superfície da Hepatite B/genética , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade
12.
Zhonghua Gan Zang Bing Za Zhi ; 20(4): 300-3, 2012 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-22964153

RESUMO

OBJECTIVE: To investigate the etiology, pathology, and clinical characteristics of cryptogenic liver diseases in order to develop a pathogenic profile for clinical diagnosis and therapeutic design. METHODS: The data of the 566 patients diagnosed with abnormal liver function and who had undergone liver biopsy at our institute between January 2006 to March 2010 were retrospectively analyzed. The Chi-squared (x²) test was used to assess disease correlation with sex and the rank sum test was used to assess disease correlation with continuous data since all data had asymmetric distribution. RESULTS: Among the 566 patients, abnormal liver function was attributed to alcoholic liver disease (n=175; 30.92%), drug-induced or environmentally-induced liver disease (n=101; 17.84%), hereditary and metabolic disease (n=93; 16.43%), infectious hepatitis disease (n=84; 14.84%), fatty liver disease (n=53; 9.36%), and autoimmune liver disease (n=30; 53.00%). Thirty patients had unknown etiology, despite liver biopsy analysis. Among these disease subgroups, there were distinct correlations with sex, age, and levels of alanine transaminase (ALT) and gamma-glutamyltransferase (GGT). The autoimmune liver disease group was correlated with sex (q=9.14, 7.435, 5.071, 9.529, and 12.5, respectively; P less than or equal to 0.01). The alcoholic liver disease group and autoimmune liver disease group were correlated with age (vs. genetic metabolic disease group: q=17.254 and 10.302; infectious hepatitis group: q=17.523 and 10.697); drug/environmentally-induced liver damage group: q=9.170 and 5.266); fatty liver group: q=7.118 and 4.661) (P less than or equal to 0.01). In addition, the alcoholic and autoimmune liver disease groups were correlated with GGT levels (vs. genetic metabolic disease group: q=8.003; infectious hepatitis group: q=4.793; drug/environmentally-induced liver damage group: q=4.404) (P less than or equal to 0.01). CONCLUSION: Liver pathology is important for the diagnosis of cryptogenic liver diseases. Patient age, sex, and biochemistry index may facilitate diagnosis and treatment in the absence of pathology.


Assuntos
Hepatopatias/patologia , Fígado/patologia , Adolescente , Adulto , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Hepatopatias/classificação , Hepatopatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 3): o745, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22412624

RESUMO

In the title compound, C(21)H(25)NO(4), the dihydropyridine ring adopts a flattened boat conformation. The N atom and the sp(3) C atom deviate in the same direction from the mean plane of the other four C atoms, by 0.269 (6) and 0.111 (6) Å, respectively. This mean plane is inclined to the 4-methoxy-phenyl ring by 87.3 (5)°. The cyclohexenone ring has a sofa conformation with the C atom bearing the methyl groups deviating from the mean plane through the other five C atoms by 0.628 (6) Å. There is a short C-H⋯O hydrogen bond in the molecule. In the crystal, molecules are linked by an N-H⋯O hydrogen bond to form chains propagating along the c-axis direction.

14.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 9): o2362-3, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22064645

RESUMO

The title mol-ecule, C(17)H(19)NO(5), was prepared by a Hantzsch dihydro-pyridine synthesis from 4-hy-droxy-benzaldehyde, methyl acetoacetate and NH(4)HCO(3). In the mol-ecular structure of the title compound, the dihydro-pyridine ring adopts a flattened boat conformation and the plane of the base of the boat forms a dihedral angle of 80.8 (2)° with the aromatic six-membered ring. The packing is stabilized by strong inter-molecular N-H⋯O(carbon-yl), O(hydrox-y)-H⋯O(carbon-yl) and weak intra-molecular C-H⋯O hydrogen bonds.

15.
Zhonghua Gan Zang Bing Za Zhi ; 19(11): 815-7, 2011 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-22433301

RESUMO

OBJECTIVE: To quantitatively detect intrahepatic HBV covalently closed circular DNA (cccDNA) and serum HBsAg; and to analyze the relationship between the two parameters and with serum HBV DNA level. METHODS: Intrahepatic cccDNA (copies/cell) was quantitated by plasmid-safe ATP-dependent Danes (PSAD) digestion in combination with rolling circle amplification and gap-spanning selective real-time PCR assay using formalin fixed paraffin-embedded liver biopsy samples. HBsAg was measured by chemiluminescence's reagent manufactured by Abbott Company using sera sampled at time-point of liver biopsy. RESULTS: Intrahepatic cccDNA level was positively correlated with serum HBsAg level (r = 0.459, P < 0.001), but not correlated with serum HBV DNA level. Serum HBsAg level was positively correlated with serum HBV DNA level (r = 0.328, P = 0.015), and reversely correlated with HBV replicative efficiency defined as the ratio of serum HBV DNA to cccDNA (r = -0.373, P = 0.005). CONCLUSION: In patients with chronic hepatitis B, intrahepatic cccDNA level is correlated with serum HBsAg level. The two parameters combined with serum HBV DNA may comprehensively reflect HBV replication activity and help evaluation of antiviral therapeutic efficacy.


Assuntos
DNA Circular/análise , DNA Viral/análise , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Feminino , Vírus da Hepatite B/genética , Humanos , Fígado/virologia , Masculino , Carga Viral
16.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 1): o150, 2010 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-21522658

RESUMO

In the title compound, C(12)H(12)O(3), the meth-oxy and prop-2-yn-yloxy groups are nearly coplanar with the attached benzene ring [C-O-C-C torsion angles = 1.2 (3) and 2.2 (3)°, respectively]. In the crystal, inversion dimers linked by pairs of C-H⋯O inter-actions occur.

17.
Hepatol Res ; 39(12): 1198-207, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19788691

RESUMO

AIMS: This study attempts to characterize the feature of immunologically competent cells (ICCs) and evaluate its clinical implication in patients with acute-on-chronic liver failure (ACLF) in relation to chronic hepatitis B virus (HBV) infection. METHODS: Circulating ICCs were examined in ACLF patients (n = 75), as well as in patients with hepatitis B (CHB, n = 31), CHB-related liver cirrhosis (LC, n = 36), and normal controls (NC, n = 30). Intrahepatic ICCs in some patients were further analyzed via immunohistochemical and flow cytometric assays. RESULTS: Total lymphocytes, CD4(+) T cells, CD8(+) T cells, and NK cells in circulation were numerically lower in the ACLF and LC groups compared to the CHB and NC groups. Importantly, the number of these cells was significantly lower in non-surviving ACLF patients compared with surviving ACLF patients. In comparison to NC, ACLF patients displayed a significantly higher ratio of liver-infiltrating CD4(+) T-cell frequency than its circulating counterpart, suggesting that the possiblility of the ICCs compartmentalization from the peripheral blood into the liver in ACLF. Immunohistochemical analysis showed that intrahepatic CD4(+) cells, CD8(+) cells, and CD56(+) cells were significantly higher in the ACLF group compared with the other three groups, suggesting a stronger cellular immune response-mediated inflammation in ACLF group than other patient groups. CONCLUSIONS: The abnormal prevalence of circulating and intrahepatic ICCs possibly acts as an important factor that may drive the progression of HBV-related ACLF.

18.
Scand J Gastroenterol ; 44(9): 1121-31, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19606393

RESUMO

OBJECTIVE: Hepatic oxidative stress plays a key role in the development of non-alcoholic steatohepatitis (NASH). However, the protective effects of antioxidants on NASH are largely unknown. The aim of this study was to elucidate the effect and mechanism of antioxidants on NASH in mice. MATERIAL AND METHODS: C57BL6/J mice were fed a methionine-choline-deficient (MCD) diet for 10 days or 3 weeks to induce steatohepatitis. Antioxidants (vitamin E, ABT, or vitamin E plus ABT) were supplemented in mice fed a MCD diet, respectively. The effect of antioxidants on oxidative stress and apoptosis was assessed, and activation of adiponectin and expressions of inflammatory factors, apoptosis-related genes, and fibrosis-related genes were assayed. RESULTS: MCD feeding in mice showed increasing serum alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) levels, and progressive hepatic injury including hepatic steatosis and inflammatory infiltration. Administration of antioxidants vitamin E and/or ABT significantly lowered serum ALAT and ASAT levels (p<0.001) and ameliorated hepatic steatosis and necroinflammation. These effects were associated with repressed hepatic lipid peroxides through reducing hepatic MDA content and enhancing hepatic superoxide dismutase (SOD) activity; down-regulated inflammatory factor COX-2, lowered activity of NF-kappaB, up-regulated anti-apoptotic gene Bcl-2, and down-regulated pro-apoptotic gene Bax suppressed expression of the fibrotic genes TGF-beta1 and MMP2. Moreover, expression of the anti-inflammatory factor adiponectin was also induced by vitamin E or ABT. A combination of vitamin E and ABT showed an additive effect on preventing liver injury. CONCLUSIONS: The present study provides morphological and molecular biological evidence for the protective role of the antioxidant vitamins E and ABT in ameliorating oxidative stress, hepatic apoptosis, and necroinflammation in experimental nutritional steatohepatitis.


Assuntos
Antioxidantes/farmacologia , Fígado Gorduroso/prevenção & controle , Triazóis/farmacologia , Vitamina E/farmacologia , Alanina Transaminase/sangue , Análise de Variância , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/sangue , Western Blotting , Ciclo-Oxigenase 2/sangue , Fígado Gorduroso/sangue , Genes bcl-2/efeitos dos fármacos , Inflamação/prevenção & controle , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Subunidade p50 de NF-kappa B/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta1/efeitos dos fármacos , Proteína X Associada a bcl-2/efeitos dos fármacos
19.
Zhonghua Gan Zang Bing Za Zhi ; 17(1): 12-5, 2009 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-19203444

RESUMO

OBJECTIVES: To establish a new grading system to evaluate liver inflammation and necrosis in patients with chronic hepatitis B through clinical biochemical assays. METHODS: Clinical and pathological data were collected from 255 cases with chronic hepatitis B. 19 biochemical items were analyzed and 5 items were selected for our grading system. Each of the five items was scored 0 to 4 based on the different values. The extent of liver inflammation and necrosis was evaluated according to the total score. RESULTS: ALT, AST, ChE, GGT and TBA were selected for our grading system. The grade of liver inflammation and necrosis was considered less than 2.0 if total score lower than 6, and higher grade was considered with higher total score. The estimated results shared an identity of 82.8% with the real grades of liver inflammation and necrosis. When this grading system was applied to patients with liver inflammation and necrosis equal to or higher than grade 2.0, it exhibited a sensitivity of 83.8%, a specificity of 81.2%, a positive prediction value of 88.6%, a negative prediction value of 74.2% in all cases, and 88.0%, 84.7%, 90.6%, 82.4% respectively in patients older than 12 years. CONCLUSION: Our data suggest that the grading system can be used to evaluate the extent of liver inflammation and necrosis in patients with chronic hepatitis B.


Assuntos
Biomarcadores/sangue , Hepatite B Crônica/sangue , Hepatopatias/patologia , Adolescente , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Ácidos e Sais Biliares/sangue , Biópsia por Agulha/métodos , Colinesterases/sangue , Feminino , Hepatite B Crônica/patologia , Humanos , Testes de Função Hepática , Masculino , Necrose , Índice de Gravidade de Doença , Adulto Jovem , gama-Glutamiltransferase/sangue
20.
J Clin Gastroenterol ; 43(2): 182-90, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18633332

RESUMO

GOALS: This study attempts to determine expressions of intrahepatic proinflammatory and anti-inflammatory cytokines and their secreting immunocytes to evaluate their roles in the pathogenesis of acute-on-chronic liver failure (ACLF) in chronically hepatitis B virus (HBV)-infected patients. BACKGROUND: ACLF generally affects patients with established, compensated chronic liver diseases who develop an acute deterioration in liver function. In China, HBV-associated ACLF patients account for more than 80% of ACLF patients owing to a high prevalence of chronic HBV infection. Clinical observation showed that the deterioration of this disease may correlate with host immune responses, but related underlying mechanism remains largely unknown. STUDY: In situ expressions of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), and their secreting CD4, CD8 T cells, and Kupffer cells (KCs) were analyzed in the livers of patients with ACLF, chronic hepatitis B (CHB), and normal controls (NC) using immunohistochemistry. RESULTS: Intrahepatic proinflammatory IFN-gamma and TNF-alpha expressions were markedly up-regulated in ACLF compared with CHB and NC. However, similar anti-inflammatory IL-10 expressions were observed in ACLF and CHB. IFN-gamma overexpression correlated significantly with increased CD4 and CD8 T-cell accumulation. TNF-alpha up-regulation also correlated significantly with increased KCs. CONCLUSIONS: The imbalanced expression of proinflammatory and anti-inflammatory cytokines and increased accumulation of CD4, CD8 T cells, and KCs may contribute to immunopathogenesis in HBV-infected ACLF.


Assuntos
Citocinas/metabolismo , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/fisiopatologia , Cirrose Hepática/fisiopatologia , Falência Hepática Aguda/fisiopatologia , Adulto , Idoso , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Humanos , Imuno-Histoquímica , Interferon gama/metabolismo , Interleucina-10/metabolismo , Macrófagos do Fígado/imunologia , Fígado/citologia , Fígado/imunologia , Cirrose Hepática/imunologia , Cirrose Hepática/virologia , Falência Hepática Aguda/imunologia , Falência Hepática Aguda/virologia , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
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