Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.623
Filtrar
1.
Klin Padiatr ; 232(3): 151-158, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32193885

RESUMO

BACKGROUND: Children with idiopathic acute liver failure (IALF) are at a high risk of developing life-threatening bone marrow failure (BMF). The aim of the study was to describe the development, therapy and prognosis of this hepatitis-associated aplastic anaemia (HAAA) in comparison to isolated acquired aplastic anaemia. RESULTS: We retrospectively found 18 patients (9 female) of HAAA between 1984 and 2017 with an age of 1.4-16.4 years. Fifteen of them fulfilled the SAA criteria, 3 had a bone marrow hypoplasia. Eleven of these children received liver transplantation (LTx) (these were 11 of 42 (26%) children receiving LTx for IALF), 6 patients recovered without LTx. The first signs of BMF, thrombocytopaenia and leucocytopaenia, occurred before LTx in all cases. During the follow-up period 8 patients reached haematological remission, 6 received haematopoietic stem cell transplantation (HSCT). Seven children died in a median of 304 days after the first symptoms mostly because of bleedings and infections. To date, extensive investigations failed to detect a genetically, viral or immunological aetiology. No AA was diagnosed in the 41 patients receiving liver transplants during the same period for ALF of known aetiology. As a comparison group, we collected the data of patients with isolated SAA. 73% achieved a remission after Immunosuppressive therapy (IST) without HSCT, and none of them died during the follow-up period. CONCLUSION: Blood counts should be examined early and regularly (0-22 days after onset) in patients with IALF. Aggressive treatment with LTx, IST and HSCT appears to improve the prognosis.


Assuntos
Anemia Aplástica/diagnóstico , Vírus de Hepatite/isolamento & purificação , Hepatite/diagnóstico , Falência Hepática Aguda/complicações , Adolescente , Anemia Aplástica/complicações , Anemia Aplástica/terapia , Anemia Aplástica/virologia , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Transplante de Medula Óssea , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas , Hepatite/complicações , Hepatite/tratamento farmacológico , Humanos , Lactente , Falência Hepática Aguda/terapia , Transplante de Fígado , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento
2.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4953-4961, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872606

RESUMO

To systemically analyze the efficacy and safety of Babaodan Capsules in treatment of viral hepatitis. Databases such as CNKI,Wan Fang Date,VIP,Sino Med,PubMed,and Cochrane Library were electronically searched for relevant randomized controlled trials about Babaodan Capsules in the treatment of viral hepatitis,from database establishment to November 11,2018. Two researchers independently screened the literature and extracted data according to the inclusion criteria. GRADE system was used to evaluate evidence quality,and we used the Cochrane Rev Man 5. 3 software for Meta-analysis. Six randomized controlled trials including 520 subjects were included. Babaodan Capsules combined with conventional treatment were used as intervention measures,and the conventional treatment was used as the control measures. The results showed Babaodan Capsules combined with conventional treatment had better efficacy on reducing the total bilirubin( MD =-16. 25,95% CI[-19. 86,-12. 63]),alanine aminotransferase( MD =-26. 62,95% CI[-41. 18,-12. 06]),total bile acid( MD=-46. 02,95%CI[-49. 18,-42. 85]) and improving clinical efficiency( RR = 1. 34,95%CI[1. 13,1. 59]) than conventional treatment alone. In addition,Babaodan Capsules combined with conventional treatment can delay the progression of liver fibrosis to some extent. Qualitative analysis showed that the combined treatment regimen was more effective in relieving clinical symptoms. There was no significant difference between the two regimens in increasing albumin and prothrombin activity. Babaodan Capsules combined with conventional treatment showed no adverse reactions. In summary,for patients with viral hepatitis,the combination of Babaodan Capsules and conventional treatment has more advantages in reducing total bilirubin,alanine aminotransferase and total bile acid and is more effective in improving clinical symptoms as compared with conventional Western medicine,with no serious adverse reactions. Its clinical application with syndrome differentiation method can be considered. However,due to the limited number and quality of the original researches,more multi-center,high-quality randomized controlled trials are needed for further verification.


Assuntos
Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite/tratamento farmacológico , Cápsulas , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
3.
BMC Gastroenterol ; 19(1): 191, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31744461

RESUMO

BACKGROUND: Syphilis is a common disease that has been researched and focused on for many years, however, syphilitic hepatitis has not been well-recognized. We report this case of syphilitic hepatitis with intrahepatic cholestasis and liver granulomas to make a deeper impression. CASE PRESENTATION: A 47-year-old male was admitted with jaundice and rashes. The laboratory examination showed abnormal liver enzymes with significant increases in ALP and GGT but mild increases in ALT and AST. His HBV surface antigen was weakly positive, with negative HIV antibody, HCV antibody, and undetectable HBV DNA. The rapid plasma reagin test and the Treponema pallidum particle assay tests for Syphilis were both positive. Abdominal ultrasonography and magnetic resonance cholangiopancreatography revealed the normal biliary tract, liver, and spleen. The liver pathological examination showed cholangiocyte inflammation and micro-granulomas with coagulation necrosis. After 2 months of benzathine penicillin treatment, his liver enzyme decreased rapidly and remained normal after 1-year of follow-up. CONCLUSIONS: Increased liver enzymes, intrahepatic cholestasis and liver granulomas with well-response to antibiotics may provide clues for the diagnosis of syphilitic hepatitis.


Assuntos
Hepatite/microbiologia , Sífilis/diagnóstico , Antibacterianos/uso terapêutico , Colestase Intra-Hepática/patologia , Granuloma/patologia , Hepatite/diagnóstico , Hepatite/tratamento farmacológico , Hepatite/patologia , Humanos , Fígado/enzimologia , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Penicilina G Benzatina/uso terapêutico , Sífilis/tratamento farmacológico , Sífilis/patologia , Treponema pallidum/isolamento & purificação
4.
BMC Infect Dis ; 19(1): 874, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640598

RESUMO

BACKGROUND: Leishmaniasis is an emerging infectious disease. Due to human migration and tourism, visceral leishmaniasis may become more common in non-endemic areas. In the Mediterranean basin, visceral leishmaniasis typically occurs in rural regions. CASE PRESENTATION: We present an unusual urban case of acute liver failure due to visceral leishmaniasis, following a prolonged fever of unknown origin. After obtaining negative results from the bone marrow aspirate, we performed a liver biopsy that elucidated the diagnosis. The liver involvement in visceral leishmaniasis may appear as chronic granulomatous hepatitis. However diffuse hepatitis process, a necro-inflammatory pattern, without forming granulomas were observed in the liver biopsy specimens in this case. Intracytoplasmic Leishmania amastigotes were observed in the liver biopsy specimens and a polymerase chain reaction confirmed the diagnosis. Only five pathological confirmed cases of acute hepatitis due to visceral leishmaniasis have been described so far, just two in adults and both from Barcelona. A revision of the literature is performed. CONCLUSIONS: Acute hepatitis is an uncommon debut of visceral leishmaniasis in immunocompetent patients. Furthermore there are only few cases in the literature that describe the histopathological changes that we found in this patient. In conclusion, in case of acute hepatitis leading to liver failure, leishmaniasis should be considered a differential diagnosis (even in non-endemic countries and without clear epidemiological exposure) and liver biopsy can elucidate the diagnosis.


Assuntos
Antiprotozoários/uso terapêutico , Leishmaniose Visceral/complicações , Leishmaniose Visceral/tratamento farmacológico , Falência Hepática Aguda/etiologia , Anfotericina B/uso terapêutico , Biópsia , Diagnóstico Diferencial , Febre/etiologia , Hepatite/tratamento farmacológico , Hepatite/etiologia , Hepatite/parasitologia , Humanos , Falência Hepática Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
5.
Chin Med J (Engl) ; 132(20): 2438-2445, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31651516

RESUMO

BACKGROUND: Adiponectin is the most abundant adipokines that plays critical roles in the maintenance of energy homeostasis as well as inflammation regulation. The half-life of adiponectin is very short and the small-molecule adiponectin receptor agonist has been synthesized recently. In the present study, the potential roles of AdipoRon, an adiponectin receptor agonist, in a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced acute hepatitis was explored. METHODS: BALB/c mice (n = 144, male) were divided into three sets. In set 1, 32 mice were randomized into four groups: the control group, the AdipoRon group, the LPS/D-Gal group, and the AdipoRon + LPS/D-Gal group. The mice in set 1 were sacrificed after LPS/D-Gal treatment, and the plasma samples were collected for detection of tumor necrosis factor-alpha (TNF-α). In set 2, the 32 mice were also divided into four groups similar to that of set 1. The mice were sacrificed 6 h after LPS/D-Gal injection and plasma samples and liver were collected. In set 3, 80 mice (divided into four groups, n = 20) were used for survival observation. The survival rate, plasma aminotransferases, histopathological damage were measured and compared between these four groups. RESULTS: AdipoRon suppressed the elevation of plasma aminotransferases (from 2106.3 ±â€Š781.9 to 286.8 ±â€Š133.1 U/L for alanine aminotransferase, P < 0.01; from 566.5 ±â€Š243.4 to 180.1 ±â€Š153.3 U/L for aspartate aminotransferase, P < 0.01), attenuated histopathological damage and improved the survival rate (from 10% to 60%) in mice with LPS/D-Gal-induced acute hepatitis. Additionally, AdipoRon down-regulated the production of TNF-α (from 328.6 ±â€Š121.2 to 213.4 ±â€Š52.2 pg/mL, P < 0.01), inhibited the activation of caspase-3 (from 2.04-fold to 1.34-fold of the control), caspase-8 (from 2.03-fold to 1.31-fold of the control), and caspase-9 (from 2.14-fold to 1.43-fold of the control), and decreased the level of cleaved caspase-3 (0.28-fold to that of the LPS/D-Gal group). The number of terminal deoxynucleotidyl transferase-mediated nucleotide nick-end labeling-positive apoptotic hepatocytes in LPS/D-Gal-exposed mice also reduced. CONCLUSIONS: These data indicated that LPS/D-Gal-induced acute hepatitis was effectively attenuated by the adiponectin receptor agonist AdipoRon, implying that AdipoRon might become a new reagent for treatment of acute hepatitis.


Assuntos
Hepatite/tratamento farmacológico , Piperidinas/uso terapêutico , Receptores de Adiponectina/agonistas , Doença Aguda , Animais , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Modelos Animais de Doenças , Galactosamina , Hepatite/metabolismo , Hepatite/patologia , Hepatócitos/patologia , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator de Crescimento Transformador alfa/sangue
6.
Psychiatry Res ; 281: 112597, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31629300

RESUMO

OBJECTIVE: Paliperidone, a second-generation antipsychotic, has been found to have minimal hepatotoxicity in patients with schizophrenia. However, long-term hepatic outcome in patients with schizophrenia and viral hepatitis remains unclear. METHODS: Data obtained from the Taiwan National Health Insurance Research Database was used to enroll newly diagnosed schizophrenic patients between January 2007 and December 2013. Patients with schizophrenia and viral hepatitis who were receiving paliperidone were allocated to the paliperidone group while those who were not receiving paliperidone were allocated to the control group. Using a 1:2 ratio, we matched the age, sex, and index year to select the control participants. Patients with severe hepatic outcomes (SHOs) before enrollment were excluded. The two groups were studied until December 31, 2013. The primary endpoint was the occurrence of SHOs including liver failure, liver decompensation, liver transplantation, or liver cancer. RESULTS: We identified 134 patients with schizophrenia and viral hepatitis who received paliperidone and 268 matched patients who did not receive paliperidone. Of the 402 patients, 22 (5.47%) developed SHOs during a mean follow-up period of 3.57 ±â€¯1.62 years, including 2 (1.49%) from the paliperidone cohort and 20 (7.46%) from the control group. Furthermore, the Cox multivariate proportional hazards analysis revealed that the risk decreased with paliperidone use (adjusted hazard ratio [HR]: 0.155, 95% confidence interval [CI]: 0.032-0.737, p = 0.019) after adjusted for confounding factors. CONCLUSION: Paliperidone treatment was associated with a reduced risk of SHOs in patients with schizophrenia and viral hepatitis.


Assuntos
Antipsicóticos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas , Hepatite/tratamento farmacológico , Palmitato de Paliperidona/uso terapêutico , Vigilância da População , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Estudos de Coortes , Feminino , Hepatite/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Palmitato de Paliperidona/efeitos adversos , Vigilância da População/métodos , Fatores de Risco , Esquizofrenia/epidemiologia , Índice de Gravidade de Doença , Taiwan/epidemiologia
7.
Gastroenterology ; 157(4): e8-e9, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31476298
9.
J Physiol Biochem ; 75(4): 463-473, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31396818

RESUMO

Hepatitis has become a major social, health, and economic problem worldwide. Herein, we tested the beneficial influence of baicalin, a flavonoid extracted from the roots of Scutellaria baicalensis, on human normal liver L-02 and THLE2 cell apoptosis and inflammatory reaction stimulated by lipopolysaccharide (LPS) and possible molecular mechanisms. L-02 and THLE2 cell viability and apoptosis after LPS and/or baicalin treatment were tested using CCK-8 assay and Annexin V-FITC/PI apoptosis kit, respectively. qRT-PCR was used to measure the MCP-1, IL-6, TNF-α, and lncRNA taurine upregulated gene 1 (TUG1) expressions in L-02 and THLE2 cells. sh-TUG1 was transfected to knockdown TUG1. SB203580 was used as inhibitor of p38MAPK pathway, while SP600125 was used as inhibitor of JNK pathway. We discovered that LPS stimulation caused L-02 and THLE2 cell apoptosis and inflammatory reaction. Baicalin relieved the L-02 and THLE2 cell apoptosis and inflammatory reaction stimulated by LPS. Moreover, LPS lowered the TUG1 expression in L-02 cells, while baicalin promoted the TUG1 expression in L-02 and L-02 and THLE2 cells, as well as inactivated p38MAPK and JNK pathways in LPS-stimulated L-02 cells. Besides, knockdown of TUG1 activated p38MAPK and JNK pathways and promoted inflammatory cytokine expression in L-02 cells. In conclusion, this study further affirmed the beneficial influences of baicalin on LPS-stimulated human normal liver cell apoptosis and inflammatory reaction. Baicalin relived liver cell inflammation stimulated by LPS might be via upregulating TUG1 and then inactivating p38MAPK and JNK pathways.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Flavonoides/farmacologia , Hepatite/tratamento farmacológico , Hepatócitos/efeitos dos fármacos , Inflamação/tratamento farmacológico , Fígado/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular , Hepatócitos/patologia , Humanos , Inflamação/induzido quimicamente , Lipopolissacarídeos , Fígado/patologia , MAP Quinase Quinase 4/metabolismo , RNA Longo não Codificante/metabolismo , Scutellaria baicalensis/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
J Sci Food Agric ; 99(15): 6822-6832, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31385307

RESUMO

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitory peptides were found to alleviate acute hepatitis significantly. In this study, we purified and identified ACE inhibitory peptide from cashew to evaluate its protective role on alcohol-induced acute hepatitis in mice. RESULTS: The ACE inhibitory peptides were purified by using consecutive chromatographic techniques. One of these peptides (FETISFK) exhibited the highest ACE inhibition rate (91.04 ± 0.31%). In vivo, the results showed that ACE inhibitory peptide decreased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) caused by alcohol exposure. Moreover, it could increase the activities of superoxide dismutase (SOD) and glutathione (GSH), and decrease the level of malondialdehyde (MDA). It was also found to down-regulate markedly the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). It could also decrease the expression of ACE, angiotensin II (AngII) and angiotensin II type 1 receptor (AT1 R). CONCLUSION: These findings support the view that the ACE inhibitory peptide alleviated acute hepatitis by down-regulating the ACE-AngII-AT1 R axis, broadening the research approach to prevent acute hepatitis, and providing experimental data for the development and utilization of cashews. © 2019 Society of Chemical Industry.


Assuntos
Anacardium/química , Inibidores da Enzima Conversora de Angiotensina/química , Hepatite/tratamento farmacológico , Peptídeos/química , Extratos Vegetais/química , Doença Aguda/terapia , Álcoois/efeitos adversos , Angiotensina II/genética , Angiotensina II/metabolismo , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Animais , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Hepatite/enzimologia , Hepatite/etiologia , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Nozes/química , Peptídeos/administração & dosagem , Peptídeos/isolamento & purificação , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
11.
Eur J Med Chem ; 179: 182-195, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31254920

RESUMO

A series of (1,2,4)triazole[4,3-a]pyridine (TZP) derivatives have been designed and synthesized. Compound 8d was identified as having the most potent inhibitory activity on NO release in response to lipopolysaccharide (LPS) stimulation and inhibition of the migration induced by MCP-1 protein on RAW264.7 macrophages. Based on the screening data, an immunofluorescence assay and a real-time qPCR assay were conducted, indicating that compound 8d suppressed NF-κB p65 translocation and expression of inflammatory genes by concanavalin A (Con A)-induced RAW264.7 macrophages. More importantly, 8d also exhibited potent efficacy, alleviating Con A-induced hepatitis by downregulating the levels of plasma alanine transaminase (ALT), aspartate transaminase (AST) and inflammatory infiltration in a mouse autoimmune hepatitis (AIH) model. In addition, the flow cytometry (FCM) data showed that compound 8d inhibited the accumulation of MDSCs in the liver of Con A-induced mice. These findings raise the possibility that compound 8d might serve as a potential agent for the treatment of AIH.


Assuntos
Concanavalina A/antagonistas & inibidores , Hepatite/tratamento farmacológico , Piridinas/farmacologia , Triazóis/farmacologia , Animais , Sobrevivência Celular , Células Cultivadas , Concanavalina A/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Desenho de Fármacos , Feminino , Hepatite/metabolismo , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Óxido Nítrico/análise , Óxido Nítrico/biossíntese , Piridinas/síntese química , Piridinas/química , Células RAW 264.7 , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química
12.
Biol Pharm Bull ; 42(8): 1415-1418, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31167986

RESUMO

The protective effects of G protein-coupled receptor 39 (GPR39) on concanavalin A (Con A)-induced hepatitis in mice was examined. In a dose dependent manner and at 24 h after the elicitation by Con A, oral administration of TC-G 1008, a GPR39 agonist, reduced both, the glutamic-pyruvic transaminase levels (a marker for liver injury) and the necrosis area, as revealed by the histological analysis of tissues from mice with Con A-induced hepatitis. TC-G 1008 also suppressed serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α significantly at 6 h after the elicitation, suggesting that the cells producing IL-6 and/or TNF-α are the targets of TC-G 1008. One potential target cell appears to be a monocyte-derived macrophages because TC-G 1008 treatment suppressed lipopolysaccharide-induced IL-6 production from U937 macrophages in vitro. Taken together, GPR39 agonist TC-G 1008 ameliorates liver injury in the Con A model by blocking pro-inflammatory cytokine production. Use of GPR39 agonists for monotherapy or in combination with immunosuppressants might prove to be beneficial in the treatment of autoimmune hepatitis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Hepatite/tratamento farmacológico , Pirimidinas/farmacologia , Receptores Acoplados a Proteínas-G/agonistas , Receptores Acoplados a Proteínas-G/metabolismo , Sulfonamidas/farmacologia , Animais , Técnicas de Cultura de Células , Doença Hepática Induzida por Substâncias e Drogas/patologia , Concanavalina A/farmacologia , Humanos , Imidazóis/farmacologia , Interleucina-10/sangue , Interleucina-10/metabolismo , Interleucina-6/sangue , Interleucina-6/metabolismo , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Pirazóis/farmacologia , Piridazinas/farmacologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo , Células U937
14.
Food Funct ; 10(6): 3514-3534, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31144698

RESUMO

This study was conducted to investigate the beneficial effects and possible mechanism of action of mangiferin (MF) in alcohol hepatitis (AH) rats. Building on our previous study, the damage-associated molecular patterns (DAMPs), lipid metabolic disorder and mitochondrial dysfunction were investigated. MF effectively regulated the abnormal liver function, the levels of alcohol, FFAs and metal elements in serum. More importantly, MF improved the expression levels of mRNA and protein of PPAR-γ, OPA-1, Cav-1, EB1, NF-κB p65, NLRP3, Cas-1 and IL-1ß, and decreased the positive protein expression rates of HSP90, HMGB1, SYK, CCL20, C-CAS-3, C-PARP and STARD1. Additionally, MF decreased the levels of fumarate, cAMP, xanthurenic acid and d-glucurone-6,3-lactone, and increased the levels of hippuric acid and phenylacetylglycine, and then adjusted the changes of phenylalanine metabolism, TCA cycle and ascorbate and aldarate metabolic pathways. The above results suggested that MF can effectively prevent AH by modulating specific AH-associated genes, potential biomarkers and metabolic pathways in AH rats, etc.


Assuntos
Álcoois/efeitos adversos , Hepatite/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Xantonas/administração & dosagem , Animais , Glicina/análogos & derivados , Glicina/metabolismo , Hepatite/etiologia , Hepatite/genética , Hepatite/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Mitocôndrias/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Xanturenatos/metabolismo
15.
Nature ; 569(7756): 428-432, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31043740

RESUMO

Combined PD-1 and CTLA-4-targeted immunotherapy with nivolumab and ipilimumab is effective against melanoma, renal cell carcinoma and non-small-cell lung cancer1-3. However, this comes at the cost of frequent, serious immune-related adverse events, necessitating a reduction in the recommended dose of ipilimumab that is given to patients4. In mice, co-treatment with surrogate anti-PD-1 and anti-CTLA-4 monoclonal antibodies is effective in transplantable cancer models, but also exacerbates autoimmune colitis. Here we show that treating mice with clinically available TNF inhibitors concomitantly with combined CTLA-4 and PD-1 immunotherapy ameliorates colitis and, in addition, improves anti-tumour efficacy. Notably, TNF is upregulated in the intestine of patients suffering from colitis after dual ipilimumab and nivolumab treatment. We created a model in which Rag2-/-Il2rg-/- mice were adoptively transferred with human peripheral blood mononuclear cells, causing graft-versus-host disease that was further exacerbated by ipilimumab and nivolumab treatment. When human colon cancer cells were xenografted into these mice, prophylactic blockade of human TNF improved colitis and hepatitis in xenografted mice, and moreover, immunotherapeutic control of xenografted tumours was retained. Our results provide clinically feasible strategies to dissociate efficacy and toxicity in the use of combined immune checkpoint blockade for cancer immunotherapy.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígeno CTLA-4/antagonistas & inibidores , Imunoterapia/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores do Fator de Necrose Tumoral/farmacologia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Antígeno CTLA-4/imunologia , Colite/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/imunologia , Sulfato de Dextrana/farmacologia , Feminino , Doença Enxerto-Hospedeiro , Hepatite/tratamento farmacológico , Humanos , Ipilimumab/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nivolumabe/efeitos adversos , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Phytomedicine ; 62: 152948, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31129431

RESUMO

BACKGROUND: Huangqi decoction (HQD), a classic traditional herbal medicine, has been used for liver fibrosis, but its effect on intrahepatic chronic cholestatic liver injury remains unknown. PURPOSE: In the present study, we investigated the hepatoprotective effect of HQD and the underlying molecular mechanisms in 3, 5-diethoxycarbonyl-1, 4-dihydroxychollidine (DDC)-induced chronic cholestatic mice. METHODS: The DDC-induced cholestatic mice were administrated HQD for 4 or 8 weeks. Serum biochemistry and morphology were investigated. The serum and liver bile acid (BA) levels were detected by ultra performance liquid chromatography-tandem mass spectrometry. The liver expression of BA metabolizing enzymes and transporters, and inflammatory and fibrotic markers was measured by real-time polymerase chain reaction, western blotting, and immunohistochemistry. RESULTS: HQD treatment for 4 or 8 weeks ameliorated DDC-induced liver injury by improving impaired hepatic function and tissue damage. HQD treatment for 8 weeks further decreased the liver expression of cytokeratin 19, tumor growth factor (TGF)-ß, collagen I, and α-smooth muscle actin, and ameliorated ductular reaction and liver fibrosis. HQD markedly decreased the accumulation of serum and liver BA. The expression of BA-metabolizing enzymes, cytochrome P450 2b10 and UDP glucuronosyltransferase 1 A1, and multidrug resistance-associated protein 2, Mrp3, and Mrp4 involved in BA homeostasis was increased by 4 weeks of HQD treatment. The expression of BA uptake transporter Na+-taurocholate cotransporting polypeptide was decreased and that of Mrp4 was increased after 8 weeks of HQD treatment. Nuclear factor-E2-related factor-2 (Nrf2) was remarkably induced by HQD treatment. Additionally, HQD treatment for 8 weeks decreased the liver expression of inflammatory factors, interleukin (IL)-6, IL-1ß, tumor necrosis factor-α, monocyte chemoattractant protein-1, and intracellular adhesion molecule-1. HQD suppressed the nuclear factor (NF)-κB pathway. CONCLUSION: HQD protected mice against chronic cholestatic liver injury and biliary fibrosis, which may be associated with the induction of the Nrf2 pathway and inhibition of the NF-κB pathway, ameliorating BA-stimulated inflammation.


Assuntos
Ácidos e Sais Biliares/metabolismo , Colestase Intra-Hepática/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Animais , Colestase Intra-Hepática/induzido quimicamente , Colestase Intra-Hepática/metabolismo , Colestase Intra-Hepática/patologia , Dicarbetoxi-Di-Hidrocolidina , Medicamentos de Ervas Chinesas/química , Enzimas/metabolismo , Hepatite/tratamento farmacológico , Hepatite/etiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Masculino , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Substâncias Protetoras/farmacologia
17.
Int J Mol Sci ; 20(4)2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30781399

RESUMO

Radiotherapy for treatment of hepatocellular carcinoma causes severe side effects, including acute hepatitis and chronic fibrosis. Complementary and alternative medicine (CAM) has emerged as an important part of integrative medicine in the management of diseases. Antrodia cinnamomea (AC), a valuable medicinal fungus originally found only in Taiwan, has been shown to possess anti-oxidation, vaso-relaxtation, anti-inflammation, anti-hepatitis, and anti-cancer effects. In this paper we evaluate the protective effects of ethanol extract of Antrodia cinnamomea (ACE) against radiotoxicity both in normal liver cell line CL48 and in tumor-bearing mice. In CL48, ACE protects cells by eliminating irradiation-induced reactive oxygen species (ROS) through the induction of Nrf2 and the downstream redox system enzymes. The protective effect of ACE was also demonstrated in tumor-bearing mice by alleviating irradiation-induced acute hepatitis. ACE could also protect mice from CCl4-induced hepatitis. Since both radiation and CCl4 cause free radicals, these results indicate that ACE likely contains active components that protect normal liver cells from free radical attack and can potentially benefit hepatocellular carcinoma (HCC) patients during radiotherapy.


Assuntos
Antrodia/química , Hepatite/tratamento farmacológico , Protetores contra Radiação/uso terapêutico , Doença Aguda , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Citoproteção/efeitos dos fármacos , Feminino , Depuradores de Radicais Livres/farmacologia , Hepatite/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/efeitos da radiação , Humanos , Inflamação/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução , Transporte Proteico/efeitos dos fármacos , Protetores contra Radiação/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Soluções , Raios X
19.
Intern Med ; 58(10): 1429-1432, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30626835

RESUMO

A 74-year-old man developed hepatic injury after intravesical Bacillus Calmette-Guérin (BCG) therapy for bladder carcinoma. Although hepatitis-associated disseminated BCG was suspected, granulomatous formations were undetectable. The hepatic injury was considered to have resulted from an allergic reaction to BCG therapy because a histopathological assessment revealed enlarged portal areas with eosinophils and neutrophils. The hepatic injury was resolved by prednisolone. This case suggested that hepatic injury associated with BCG therapy might be due to an allergic mechanism unrelated to disseminated BCG disease. A liver biopsy is needed to confirm the histopathological findings of hepatic injury after BCG therapy in order to differentiate allergic hepatic injury from infectious hepatic injury.


Assuntos
Vacina BCG/uso terapêutico , Hepatite/tratamento farmacológico , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/etiologia , Fígado/fisiopatologia , Prednisolona/uso terapêutico , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Idoso , Hepatite/etiologia , Humanos , Masculino , Resultado do Tratamento
20.
Complement Ther Med ; 42: 248-254, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30670249

RESUMO

OBJECTIVES: Little information is available about the impact of Chinese herbal medicine (CHM) treatment on acute exacerbation of hepatitis. This study aimed to assess the risk of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma in HBV patients with and without CHM use. DESIGN AND SETTING: This population-based case-control study used data from the Taiwan Longitudinal Health Insurance Database from 2000 to 2013. Newly diagnosed HBV patients had acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma as the case group, while another patients had no acute exacerbation of hepatitis and cirrhosis and hepatoma as the control group. To correct the differences in sociodemographic factors and Western medication use between the two groups, propensity score matching was used at a 1:1 ratio, and resulted in a comparison of 1306 and 805 patients per group, respectively. MAIN OUTCOME MEASURES: Occurrence of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma. RESULTS: Overall rate of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma was 7.9% and 4.8%, respectively. Patients receiving CHM had a significantly lower risk of acute exacerbation of hepatitis (adjusted odds ratio [aOR] =0.20, 95% confidence interval [95%CI]: 0.13-0.31) and subsequent cirrhosis and hepatoma (aOR = 0.29, 95%CI: 0.18-0.49) than those not receiving CHM after adjusting for relevant covariates. However, no dose-dependent relationship was exhibited for either incidence of acute exacerbation of hepatitis and cirrhosis and hepatoma. CONCLUSION: These findings highlight that the use of CHM was associated with a significantly reduced risk of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma in patients with HBV. Future research could further explore the benefit of CHM therapies for treatment of acute hepatitis exacerbation.


Assuntos
Doença Aguda/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Hepatite/tratamento farmacológico , Hepatite/virologia , Adulto , Idoso , Estudos de Casos e Controles , Bases de Dados Factuais , Feminino , Hepatite/prevenção & controle , Hepatite B/virologia , Humanos , Incidência , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Masculino , Medicina Tradicional Chinesa/métodos , Pessoa de Meia-Idade , Taiwan , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA