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1.
Zhonghua Zhong Liu Za Zhi ; 42(1): 50-54, 2020 Jan 23.
Artigo em Chinês | MEDLINE | ID: mdl-32023769

RESUMO

Objective: To explore the clinical features and risk factors of hepatic injury due to immune checkpoint inhibitors (CPI) therapy in malignant tumor. Methods: Data of 112 patients (64 men and 48 women) who received CPI between January 2016 and March 2019 in Chinese Academy of Medical Sciences and Peking Union Medical College Shenzhen Hospital, and Huazhong University of Science and Techology Union Shenzhen Hospital were retrospectively collected. The median age of these patients was 60 years. Results: Hepatic adverse events were observed in 30 patients out of 112 patients (26.8%). Among them, the incidence of grade 3-5 hepatic adverse events were 7.14% (8/112). The median time of hepatic adverse event occurrence was 3 weeks (2-30) after undergoing therapy. The results of univariate and multivariate analyses showed that liver cancer was attributed to the CPI induced hepatitis (P<0.05). Patients with severe hepatic injury got almost complete resolution after receiving methlprednisolone for 4 to 6 weeks. Conclusion: Live cancer is the risk factor of CPI-related hepatic adverse events.


Assuntos
Imunoterapia , Hepatopatias , Neoplasias , Feminino , Humanos , Imunoterapia/efeitos adversos , Fígado , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Estudos Retrospectivos , Fatores de Risco
2.
Medicine (Baltimore) ; 99(2): e18539, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914027

RESUMO

The purpose of this study was to determine the factors associated with parenteral nutrition-associated liver disease (PNALD) in infants who underwent surgery for necrotizing enterocolitis (NEC) and followed up the postoperative outcomes for long term parenteral nutrition (PN).This study included a retrospective review of 87 infants with NEC and managed surgically from July 2007 to May 2017 at the Children's Hospital, Chongqing Medical University. Clinical data and procedure information were collected and analyzed.Among the infants included, 16.1% of patients developed PNALD. Multivariable logistic regression analysis revealed progressive clinical deterioration (OR, 5.47; 95% CI, 1.10-26.96; P = .037) was independent risk factor for PNALD whereas congenital heart disease (OR, 0.068; 95% CI, 0.008-0.55; P = .012) presentation served as a protective factor.The current data suggested the distinct disease process for cardiac patients with NEC, which might help in the prevention and treatment of PNALD for patients with NEC.


Assuntos
Enterocolite Necrosante/complicações , Enterocolite Necrosante/cirurgia , Hepatopatias/etiologia , Nutrição Parenteral/efeitos adversos , Enterocolite Necrosante/dietoterapia , Enterocolite Necrosante/mortalidade , Feminino , Idade Gestacional , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/mortalidade , Humanos , Doença Iatrogênica/epidemiologia , Doença Iatrogênica/prevenção & controle , Incidência , Lactente , Recém-Nascido , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Masculino , Estudos Retrospectivos , Fatores de Risco
3.
J Agric Food Chem ; 67(50): 13948-13959, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31698901

RESUMO

The aim of this study was to investigate the protective effect of punicalagin (PU), which is a main component of pomegranate polyphenols, against liver injury induced by Type 2 diabetes mellitus (T2DM) and to explore the molecular mechanism based on autophagy in vivo and in vitro. In T2DM mice, we found that PU significantly improved liver histology, reversed serum biochemical abnormalities, and increased the autophagosome number in the liver. In HepG2 cells cultured in a high-glucose environment, PU upregulated the glucose uptake level. Both in vivo and in vitro, PU upregulated the expression of autophagy-related proteins, such as LC3b and p62, and reduced the phosphorylated Akt/total Akt and phosphorylated FoxO3a/total FoxO3a protein ratios, and these effects were enhanced by LY294002 (a PI3K/Akt inhibitor). In summary, our current findings suggest that PU protects against liver injury induced by T2DM by restoring autophagy through the Akt/FoxO3a signaling pathway.


Assuntos
Autofagia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Proteína Forkhead Box O3/metabolismo , Taninos Hidrolisáveis/administração & dosagem , Hepatopatias/prevenção & controle , Fígado/lesões , Substâncias Protetoras/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Proteína Forkhead Box O3/genética , Humanos , Fígado/metabolismo , Hepatopatias/etiologia , Hepatopatias/metabolismo , Hepatopatias/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos
4.
Mikrobiyol Bul ; 53(4): 464-471, 2019 Oct.
Artigo em Turco | MEDLINE | ID: mdl-31709944

RESUMO

Cryptosporidium spp. is one of the leading causes of parasitic diarrhea. It is the most common parasite in humans all over the world with Giardia. Cryptosporidium is an important cause of chronic diarrhea in Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) patients. Patients with normal immune system may have an asymptomatic course or clinical presentation such as acute watery diarrhea without blood and persistent diarrhea. The severity and duration of the disease may be a reflection of the immune deficiency. Children under two years of age and children with malnutrition may have a risk of prolonged Cryptosporidium spp. infection, even if immunodeficiency work-up is normal, as they may have defects in the natural immune system and lymphocyte functions. Cryptosporidium spp. oocysts contaminate water sources, swimming pools, vegetables and fruits because oocysts are partially resistant to chlorination. So it may be problem for public health. Pets, livestock and humans can be carriers of Cryptosporidium spp. Factors such as developmental level of the countries, immune system, nutritional status, living in crowded environments, contact with contaminated water, close contact with animals, working at a hospital and hot and humid climate affect the incidence of Cryptosporidiosis. Cryptosporidium spp. may cause asymptomatic infection, mild diarrheal disease or severe diarrhea with high volume, which may be accompanied by nausea, vomiting, abdominal pain and fever, following a 1-7 day incubation period. Diarrhea may be acute or chronic, transient, intermittent, or continuous; loss of fluid can be up to 25 L/day in severe diarrhea. Cryptosporidium spp. are mainly located in intestines, but non-intestinal (bile ducts, pancreas, stomach, respiratory system, kidney) involvement may occur in immunocompromised patients. Hepatobiliary system involvement occurs in 10-30% of patients with AIDS; stone-free cholecystitis can lead to sclerosing cholangitis and pancreatitis. Hepatobiliary involvement is not expected in patients without immunodeficiency. In this article, we present a case of Cryptosporodiosis with hepatobiliary system involvement who were admitted to the pediatric emergency clinic with the complaints of severe diarrhea and Cryptosporidium spp. oocysts were detected in parasitological examination of the stool specimen. Immunodeficiency was not considered with her resume and laboratuary examinations. We would like to emphasize that Cryptosporodium spp. may be the cause of severe acute diarrhea in non-immunocompromised patients and may also involve hepatobiliary system involvement.


Assuntos
Doenças Biliares , Criptosporidiose , Cryptosporidium , Diarreia , Hepatopatias , Doenças Biliares/etiologia , Doenças Biliares/parasitologia , Criptosporidiose/complicações , Diarreia/etiologia , Feminino , Humanos , Imunocompetência , Hepatopatias/etiologia , Hepatopatias/parasitologia
5.
J Agric Food Chem ; 67(41): 11474-11480, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31537057

RESUMO

Patulin (PAT) is the most common food-borne mycotoxin found in fruits and fruit-derived products, while chlorpyrifos (CPF) is a widely used pesticide on fruit and other crops. On the basis of the residue data, certain types of fruits can be contaminated simultaneously by patulin and chlorpyrifos. However, there are no available data about the combined toxicity. Since liver is a possible toxic target of both patulin and chlorpyrifos, we tested whether the combination exposure can cause enhanced hepatotoxicity using both cell culture and animal models. Results showed that the combination resulted in synergistic cytotoxicity in vitro and significantly enhanced liver toxicity in vivo. Mechanistically, PAT inhibited catalase activity via PIG3 induction, while CPF decreased catalase expression. These two mechanisms were converged in response to the combination, leading to enhanced inactivating catalase and boosted reactive oxygen species generation. The finding implicated that it is necessary to consider the combined toxicity in safety assessment of these food-borne contaminants.


Assuntos
Inibidores de Caspase/toxicidade , Clorpirifos/toxicidade , Hepatopatias/etiologia , Patulina/toxicidade , Praguicidas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Animais , Caspases/metabolismo , Catalase/antagonistas & inibidores , Catalase/metabolismo , Sinergismo Farmacológico , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatias/genética , Hepatopatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos
6.
Expert Opin Investig Drugs ; 28(10): 891-902, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31550938

RESUMO

Introduction: Alpha-1 antitrypsin deficiency (AATD) is most often associated with chronic lung disease, early onset emphysema, and liver disease. The standard of care in lung disease due to AATD is alpha-1 antitrypsin augmentation but there are several new and emerging treatment options under investigation for both lung and liver manifestations. Areas covered: We review therapeutic approaches to lung and liver disease in alpha-1 antitrypsin deficiency (AATD) and the agents in clinical development according to their mode of action. The focus is on products in clinical trials, but data from pre-clinical studies are described where relevant, particularly where progression to trials appears likely. Expert opinion: Clinical trials directed at lung and liver disease separately are now taking place. Multimodality treatment may be the future, but this could be limited by treatment costs. The next 5-10 years may reveal new guidance on when to use therapeutics for slowing disease progression with personalized treatment regimes coming to the forefront.


Assuntos
Desenvolvimento de Medicamentos/métodos , Drogas em Investigação/administração & dosagem , Deficiência de alfa 1-Antitripsina/tratamento farmacológico , Animais , Progressão da Doença , Drogas em Investigação/farmacologia , Humanos , Hepatopatias/tratamento farmacológico , Hepatopatias/etiologia , Pneumopatias/tratamento farmacológico , Pneumopatias/etiologia , Medicina de Precisão/métodos , Deficiência de alfa 1-Antitripsina/fisiopatologia
7.
J Agric Food Chem ; 67(42): 11627-11637, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31553177

RESUMO

Liver diseases alter the gut microbiota, but several lactic acid bacteria can reduce the degree of liver damage. The present study investigated whether Lactobacillus buchneri TCP016 reduces the degree of liver damage by modifying the gut microbiota via its exopolysaccharides (EPSs). First, it was illustrated that the main EPS (EPS016; molecular weight = 8.509 × 104 Da) comprised rhamnose, xylose, glucosamine, glucuronic acid, galactose, galacturonic acid, glucose, and mannose in molar ratios of 9.2:3.9:3.8:2.8:2.1:2.0:1.6:1.0. Our data showed that EPS016 alleviated the increase in plasma and hepatic enzyme and cytokine levels, increased superoxide dismutase and glutathione activity, and alleviated bacterial translocation to the liver and mesenteric lymph nodes in vivo. Furthermore, EPS016 ameliorated intestinal mucosal injury and gut flora dysbiosis, thereby decreasing the enrichment of Helicobacteraceae, Lachnospiraceae, and Enterobacteriaceae and increasing the abundance of Lactobacillus, Rikenellaceae, Bacteroidaceae, Bacteroidales_S24-7_group, and Prevotellaceae. These findings indicated that EPS016 inhibits lipopolysaccharides/d-galactosamine-induced liver injury and improves the modification of the gut microbiota.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Lactobacillus/química , Hepatopatias/tratamento farmacológico , Polissacarídeos Bacterianos/administração & dosagem , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Feminino , Galactosamina/efeitos adversos , Humanos , Lactobacillus/metabolismo , Lipopolissacarídeos/efeitos adversos , Hepatopatias/etiologia , Hepatopatias/microbiologia , Camundongos Endogâmicos BALB C , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/metabolismo
8.
Int J Mol Sci ; 20(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491992

RESUMO

Hepatocyte death is critical for the pathogenesis of liver disease progression, which is closely associated with endoplasmic reticulum (ER) stress responses. However, the molecular basis for ER stress-mediated hepatocyte injury remains largely unknown. This study investigated the effect of ER stress on dual-specificity phosphatase 5 (DUSP5) expression and its role in hepatocyte death. Analysis of Gene Expression Omnibus (GEO) database showed that hepatic DUSP5 levels increased in the patients with liver fibrosis, which was verified in mouse models of liver diseases with ER stress. DUSP5 expression was elevated in both fibrotic and acutely injured liver of mice treated with liver toxicants. Treatment of ER stress inducers enhanced DUSP5 expression in hepatocytes, which was validated in vivo condition. The induction of DUSP5 by ER stress was blocked by either treatment with a chemical inhibitor of the protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway, or knockdown of C/EBP homologous protein (CHOP), whereas it was not affected by the silencing of IRE1 or ATF6. In addition, DUSP5 overexpression decreased extracellular-signal-regulated kinase (ERK) phosphorylation, but increased cleaved caspase-3 levels. Moreover, the reduction of cell viability under ER stress condition was attenuated by DUSP5 knockdown. In conclusion, DUSP5 expression is elevated in hepatocytes by ER stress through the PERK-CHOP pathway, contributing to hepatocyte death possibly through ERK inhibition.


Assuntos
Fosfatases de Especificidade Dupla/genética , Estresse do Retículo Endoplasmático , Hepatócitos/metabolismo , Transdução de Sinais , Fator de Transcrição CHOP/metabolismo , eIF-2 Quinase/metabolismo , Animais , Apoptose/genética , Morte Celular/genética , Expressão Gênica , Hepatócitos/patologia , Humanos , Hepatopatias/etiologia , Hepatopatias/metabolismo , Camundongos
9.
Wien Klin Wochenschr ; 131(17-18): 395-403, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31493100

RESUMO

BACKGROUND: Liver disease impacts on hepatic synthesis of lipoproteins and lipogenesis but data on dyslipidemia during disease progression are limited. We assessed the patterns of dyslipidemia in (i) different liver disease etiologies and discriminated (ii) non-advanced (non-ACLD) from advanced chronic liver disease (ACLD) as it is unclear how progression to ACLD impacts on dyslipidemia-associated cardiovascular risk. METHODS: Patients with alcoholic liver disease (n = 121), hepatitis C (n = 1438), hepatitis B (n = 384), metabolic/fatty liver disease (n = 532), cholestatic liver disease (n = 119), and autoimmune hepatitis (n = 114) were included. Liver stiffness ≥15 kPa defined ACLD. Dyslipidemia was defined as total cholesterol >200 mg/dL, low-density lipoprotein (LDL)-cholesterol >130 mg/dL and triglycerides >200 mg/dL. RESULTS: Across all etiologies, total cholesterol levels were significantly lower in ACLD, when compared to non-ACLD. Accordingly, LDL-cholesterol levels were significantly lower in ACLD due to hepatitis C, hepatitis B, metabolic/fatty liver disease and autoimmune hepatitis. Triglyceride levels did not differ due to disease severity in any etiology. Despite lower total and LDL cholesterol levels in ACLD, etiology-specific dyslipidemia patterns remained similar to non-ACLD. Contrary to this "improved" lipid status in ACLD, cardiovascular comorbidities were more prevalent in ACLD: arterial hypertension was present in 26.6% of non-ACLD and in 55.4% of ACLD patients (p < 0.001), and diabetes was present in 8.1% of non-ACLD and 25.6% of ACLD patients (p < 0.001). CONCLUSION: Liver disease etiology is a major determinant of dyslipidemia patterns and prevalence. Progression to ACLD "improves" serum lipid levels while arterial hypertension and diabetes mellitus are more prevalent. Future studies should evaluate cardiovascular events after ACLD-induced "improvement" of dyslipidemia.


Assuntos
Dislipidemias , Hepatopatias , Adulto , LDL-Colesterol/sangue , Dislipidemias/epidemiologia , Feminino , Humanos , Hepatopatias/epidemiologia , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Triglicerídeos/sangue
10.
Transplant Proc ; 51(6): 1920-1922, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399176

RESUMO

INTRODUCTION: Following liver transplantation (LT), the majority of patients are treated with reduced-dose calcineurin inhibitors (CNIs) in combination with mycophenolate mofetil. The optimal timing for subsequent conversion to CNI monotherapy is not clearly defined. This study aims to evaluate the safety of conversion to CNI monotherapy after LT. METHODS: This was a single-center retrospective study of 100 consecutive patients who received CNI and mycophenolate mofetil combination regimen after LT at Singapore General Hospital from 2006 to 2018. Patient demographics, clinical parameters, and posttransplant complications (ie, rates of graft rejection, de novo malignancy, cytomegalovirus infection and renal impairment) were recorded. RESULTS: One hundred patients were recruited and mean follow-up time in months ± standard deviation was 60.36 ± 41.73. Patients were divided into 2 groups based on institution of CNI monotherapy within (group 1) or beyond (group 2) 6 months. Twenty-five (25%) patients were on CNI monotherapy within 6 months post-LT. Overall patient survival was 83.7% at 5-years posttransplant. There was no statistical difference in the rates of posttransplant complications including liver graft rejection (4.0% vs 18.7%, P = .11); de novo malignancy (0.0% vs 8.0%, P = .33); cytomegalovirus infection (4.0% vs 1.3%, P = .44); and renal impairment (20.0% vs 40.0%, P = .069) between the 2 groups. CONCLUSIONS: Successful institution of CNI monotherapy within 6 months is safe, and does not increase the risk of rejection.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Transplante de Fígado , Complicações Pós-Operatórias/epidemiologia , Tacrolimo/administração & dosagem , Fatores de Tempo , Adulto , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Humanos , Hepatopatias/epidemiologia , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Complicações Pós-Operatórias/etiologia , Insuficiência Renal/epidemiologia , Insuficiência Renal/etiologia , Estudos Retrospectivos
11.
Pediatr Neonatol ; 60(4): 396-404, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31409456

RESUMO

BACKGROUND: Current knowledge on the clinical features and natural history of childhood primary sclerosing cholangitis - inflammatory bowel disease in Asia is limited. We described the presenting features and natural history of primary sclerosing cholangitis-inflammatory bowel disease seen in a cohort of Southeast Asian children. METHODS: We conducted a retrospective review of childhood primary sclerosing cholangitis-inflammatory bowel disease from three tertiary centers in Singapore and Malaysia. RESULTS: Of 24 patients (boys, 58%; median age at diagnosis: 6.3 years) with primary sclerosing cholangitis-inflammatory bowel disease (ulcerative colitis, n = 21; Crohn's disease, n = 1; undifferentiated, n = 2), 63% (n = 15) were diagnosed during follow-up for colitis, and 21% (n = 5) presented with acute or chronic hepatitis, 17% (n = 4) presented simultaneously. Disease phenotype of liver involvement showed 79% had sclerosing cholangitis-autoimmune hepatitis overlap, 54% large duct disease, and 46% small duct disease. All patients received immunosuppression therapy. At final review after a median [±S.D.] duration follow-up of 4.7 [±3.8] years, 12.5% patients had normal liver enzymes, 75% persistent disease, and 12.5% liver failure. The proportion of patients with liver cirrhosis increased from 13% at diagnosis to 29%; 21% had portal hypertension, and 17% had liver dysfunction. One patient required liver transplant. Transplant-free survival was 95%. For colitis, 95% had pancolitis, 27% rectal sparing, and 11% backwash ileitis at initial presentation. At final review, 67% patients had quiescent bowel disease with immunosuppression. One patient who had UC with pancolitis which was diagnosed at 3 years old developed colorectal cancer at 22 years of age. All patients survived. CONCLUSIONS: Liver disease in primary sclerosing cholangitis-inflammatory bowel disease in Asian children has variable severity. With immunosuppression, two-thirds of patients have quiescent bowel disease but the majority have persistent cholangitis and progressive liver disease.


Assuntos
Colagogos e Coleréticos/uso terapêutico , Colangite Esclerosante/tratamento farmacológico , Hepatite Autoimune/tratamento farmacológico , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Cirrose Hepática Biliar/etiologia , Adolescente , Grupo com Ancestrais do Continente Asiático , Criança , Pré-Escolar , Colangite Esclerosante/complicações , Colangite Esclerosante/fisiopatologia , Estudos de Coortes , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/fisiopatologia , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Doença de Crohn/fisiopatologia , Progressão da Doença , Feminino , Hepatite Autoimune/complicações , Hepatite Autoimune/fisiopatologia , Humanos , Hipertensão Portal/etiologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/fisiopatologia , Hepatopatias/etiologia , Transplante de Fígado , Malásia , Masculino , Estudos Retrospectivos , Singapura , Adulto Jovem
12.
J Therm Biol ; 83: 8-21, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31331528

RESUMO

Heat stress (HS) is a major international problem which has attracted a considerable attention due to its oxidative tissue effects and high morbidity and mortality rates, especially among elderly people. Discovering an effective antioxidant is pivotal for overcoming HS-induced injury. Therefore, the aim of this study was to estimate the hepatic protective effects of orally supplemented resveratrol (RES) against HS-mediated liver injury in young and old male Wistar albino rats. Compared to control rats, RES administered orally at a dose of 20 mg/kg BW for 21 successive days efficiently ameliorated HS-induced oxidative damage by significantly increasing (P ≤ 0.05) the level of reduced glutathione and glutathione peroxidase, and decreasing the levels of malondialdehyde and TNF-α in hepatic tissue of both young and aged rats. However, level of NF-κB was downregulated significantly in aged rats rather than young rats. Moreover, RES significantly decreased (P ≤ 0.05) the serum levels of aspartate transaminase and alkaline phosphatase in both ages of rats compared to their corresponding HS-stressed rats. Furthermore, RES upregulated the immunohistochemical expression of caspase 3 and heat shock protein 70 in young and aged rats, however it was more pronounced in young one. In addition, RES administration moderately normalized (P ≤ 0.0001) the harmful effects of HS on the hepatic architecture of both young and aged rats. In conclusion, this study reveals for the first time that RES exerts promising hepato-ameliorative effects against HS-induced oxidative stress in the young and aged rats via its antioxidant, anti-inflammatory, and anti-apoptotic effect, as well as via its inhibitory effect against the NF-κB signalling in a cellular system.


Assuntos
Antioxidantes/uso terapêutico , Proteínas de Choque Térmico HSP70/metabolismo , Transtornos de Estresse por Calor/complicações , Hepatopatias/tratamento farmacológico , NF-kappa B/metabolismo , Resveratrol/uso terapêutico , Fosfatase Alcalina/sangue , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Apoptose , Aspartato Aminotransferases/sangue , Fígado/efeitos dos fármacos , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Hepatopatias/etiologia , Hepatopatias/metabolismo , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Resveratrol/administração & dosagem , Resveratrol/farmacologia , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
13.
Food Funct ; 10(8): 4861-4867, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31334539

RESUMO

This study investigates the acute anti-inflammatory activity of Mangifera indica L. leaf extract and mangiferin in the liver of rats fed a cafeteria diet. This study was a randomized longitudinal experimental study. The animals were divided into three groups - Control: cafeteria diet (CD); Extract: CD + leaf extract (250 mg kg-1); and Mangiferin: CD + mangiferin (40 mg kg-1). Body weight and food intake were measured every week. On day eight, mRNA and protein expression of inflammatory markers were evaluated in the liver. Also, liver weight, SOD activity and malondialdehyde concentration were measured. Treatment for only eight days with mango leaf extract and mangiferin increased SOD activity. Mangiferin intake increased the mRNA expression of PPAR-α and HSP72. The leaf extract treatment enhanced PPAR-α mRNA expression. Mangiferin and leaf extract consumption caused a lower concentration of NFκB (p65) in nuclear extracts, and greater IL-10 mRNA and protein levels. This study highlights the potential of acute treatment with mango leaf extract and mangiferin to prevent liver inflammation caused by fat-rich diets. These results indicate a new use for a product that has low cost, is found in great amounts, and is not routinely used.


Assuntos
Anti-Inflamatórios/administração & dosagem , Hepatopatias/tratamento farmacológico , Mangifera/química , Extratos Vegetais/administração & dosagem , Animais , Dieta Hiperlipídica/efeitos adversos , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Hepatopatias/etiologia , Hepatopatias/genética , Hepatopatias/imunologia , Masculino , Malondialdeído/imunologia , PPAR alfa/genética , PPAR alfa/imunologia , Fitoterapia , Folhas de Planta/química , Ratos
14.
J Med Food ; 22(8): 833-840, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31268397

RESUMO

Piceatannol (PIC) is a natural hydroxylated analog of resveratrol (RSV) and considered as a potential metabolic regulator. The purpose of this study was to compare the effects of PIC and RSV on parameters affecting inflammation, oxidative stress, and sirtuins (Sirt). Male C57BL/6J mice, 20 weeks old, were assigned to the following groups; (1) lean control, (2) high-fat diet control (HF), (3) HF_PIC, and (4) HF_RSV. Oral administration of PIC and RSV (10 mg/kg/day) for 4 weeks improved glucose control as shown by decreasing levels of area under the curve (AUC) during the oral glucose tolerance test compared with HF group. PIC improved glycemic control by increasing hepatic levels of insulin receptor and AMP-activated protein kinase. PIC increased the levels of Sirt1, Sirt3, and Sirt6 and also increased two downstream targets of Sirt, peroxisome proliferator-activated receptor gamma coactivator 1-alpha and forkhead box O1, in the liver. The inflammatory markers, interleukin (IL)-1 and IL-6, in the liver were downregulated by RSV treatment. Exposure to PIC and RSV significantly lowered hepatic levels of tumor necrosis factor-alpha. However, PIC and RSV treatments showed minimal effects on hepatic markers of oxidative stress. The levels of antioxidant enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), were only increased in livers of RSV-treated mice compared with HF control mice. In conclusion, PIC was superior to an equal concentration of RSV in the regulation of Sirt and its downstream targets as well as insulin signaling-related parameters, while RSV potentially suppressed levels of proinflammatory markers and increased NQO1 protein levels.


Assuntos
Hepatopatias/tratamento farmacológico , Fígado/imunologia , Resveratrol/administração & dosagem , Sirtuínas/genética , Estilbenos/administração & dosagem , Animais , Dieta Hiperlipídica/efeitos adversos , Humanos , Fígado/efeitos dos fármacos , Hepatopatias/etiologia , Hepatopatias/genética , Hepatopatias/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/imunologia , Estresse Oxidativo/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/imunologia , Sirtuínas/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
15.
Rev Gastroenterol Peru ; 39(2): 127-131, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31333228

RESUMO

INTRODUCTION: Alfa 1-antitrypsin deficiency is one of the most prevalent genetic diseases in the human being, sadly it is not a commonly suspected clinical entity. With more than 100 known mutations, those associated with hepatic disease are the Z homocygote allele mutations in the gene a1AT which occur in every 2000-3500 births. Opposing to the pulmonary disease, in which de sequelae are caused by the deficit of this protein which in turn fastens the enzymatic destruction of the airway microstructure, the hepatic compromise is secondary to the intracellular accumulation of the aberrant misfolded protein. This accumulation causes cellular damage, hepatitis, fibrosis, cirrhosis and hepatocellular carcinoma through activation of a series of mechanisms which culminate in hepatocitary apoptosis, regeneration and chronic cellular injury. MATERIALS AND METHODS: 9 cases of confirmed a1AT deficiency are presented, from different ages ranging from adolescence through elderly patients. RESULTS: Each of one of them with different clinical presentation going from asymptomatic liver enzyme elevations to transplanted cirrhosis in which the diagnosis was post procedural. CONCLUSION: We comment about the management of the chronic liver disease and the evolution of these patients through time in the liver clinic.


Assuntos
Hepatopatias/etiologia , Deficiência de alfa 1-Antitripsina/complicações , Adolescente , Adulto , Idoso , Doença Crônica , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
J Med Case Rep ; 13(1): 171, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31159864

RESUMO

BACKGROUND: Vascular complications of acute pancreatitis are common. Splanchnic thrombosis accounts for 11% of these complications, whereas extrasplanchnic thrombosis remains a rare entity. These complications are associated with high morbidity and mortality. Diagnosis is established on the basis of clinical and radiological evaluation, especially computed tomography. Renal vein thrombosis has been reported previously, but only in association with thrombosis of the inferior vena cava. To our knowledge, renal vein thrombosis without inferior vena cava thrombosis has never been reported in the literature. We report a case of a woman who developed acute pancreatitis complicated with splanchnic thrombosis and renal vein thrombosis with a patent inferior vena cava. CASE PRESENTATION: A 48-year-old Moroccan woman with no significant past medical history presented to our emergency department with worsening epigastric pain and vomiting. Her physical examination was notable only for moderate epigastric tenderness. She was apyrexic and had no jaundice or any features of liver failure. An initial computed tomographic scan showed Balthazar grade C pancreatitis with multiple splanchnic thromboses involving the portal vein, superior mesenteric vein, and left renal vein and enteromesenteric venous infarct with no signs of bowel perforation. The inferior vena cava was patent. Therapeutic anticoagulation and analgesia were started with resumption of enteral feeding 72 h later. The result of a thrombophilia screen was negative. Two months later, the patient was admitted to the intensive care unit with acute liver failure. Computed tomography of the abdomen showed worsening ischemic liver lesions and no signs of bowel perforation. Biochemical analysis showed acute hepatitis with hepatocellular insufficiency. The clinical evolution was unfavorable, and the patient died 48 h later. CONCLUSIONS: Association of splanchnic and renal vein thrombosis without inferior vena cava thrombosis as a complication of acute pancreatitis has never been reported before. There are no specific aspects of management of this complication; therapeutic anticoagulation and symptomatic treatment are the main measures used owing to the lack of available organs for liver transplant. The prognosis depends on the consequences of splanchnic thrombosis and their complications.


Assuntos
Isquemia Mesentérica/etiologia , Pancreatite/complicações , Trombose Venosa/etiologia , Anticoagulantes/uso terapêutico , Evolução Fatal , Feminino , Insuficiência Hepática/etiologia , Humanos , Isquemia/diagnóstico por imagem , Isquemia/etiologia , Hepatopatias/diagnóstico por imagem , Hepatopatias/etiologia , Isquemia Mesentérica/diagnóstico por imagem , Isquemia Mesentérica/tratamento farmacológico , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Veia Porta/diagnóstico por imagem , Veias Renais/diagnóstico por imagem , Circulação Esplâncnica , Tomografia Computadorizada por Raios X , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/tratamento farmacológico
17.
Oxid Med Cell Longev ; 2019: 9549506, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205591

RESUMO

It has been demonstrated that vagus nerve stimulation (VNS) plays a protective role in ischemia/reperfusion (I/R) injury of various organs. The present study investigates the protective effect of VNS on hepatic I/R injury and the potential mechanisms. Male Sprague-Dawley rats were randomly allocated into three groups: the sham operation group (Sham; n = 6, sham surgery with sham VNS); the I/R group (n = 6, hepatic I/R surgery with sham VNS); and the VNS group (n = 6, hepatic I/R surgery plus VNS). The I/R model was established by 1 hour of 70% hepatic ischemia. Tissue samples and blood samples were collected after 6 hours of reperfusion. The left cervical vagus nerve was separated and stimulated throughout the whole I/R process. The stimulus intensity was standardized to the voltage level that slowed the sinus rate by 10%. VNS significantly reduced the necrotic area and cell death in I/R tissues. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were also decreased by VNS. In addition, VNS suppressed inflammation, oxidative stress, and apoptosis in I/R tissues. VNS significantly increased the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) in the liver. These data indicated that VNS may attenuate hepatic I/R injury by inhibiting inflammation, oxidative stress, and apoptosis possibly via the Nrf2/HO-1 pathway.


Assuntos
Modelos Animais de Doenças , Heme Oxigenase (Desciclizante)/metabolismo , Hepatopatias/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Traumatismo por Reperfusão/prevenção & controle , Estimulação do Nervo Vago/métodos , Animais , Apoptose , Heme Oxigenase (Desciclizante)/genética , Hepatopatias/etiologia , Hepatopatias/patologia , Masculino , Fator 2 Relacionado a NF-E2/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia
18.
Molecules ; 24(11)2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151312

RESUMO

Curcuma zedoaria (dry stenophora of Curcuma phaeocaulis Val., Curcuma kwangsiensis S. G. Lee et C. F. Liang, or Curcuma wenyujin Y. H. Chen et C.Ling) is a representative herb with clinical effects on liver diseases after being vinegar-processed. The crude Curcuma zedoaria and the processed Curcuma zedoaria (vinegar-boil) have been widely used as mixtures, but their equivalence has not been fully investigated. In this manuscript, quality markers of processed (vinegar-boil) Curcuma zedoaria were investigated by comparison of the compounds and hepatoprotective activities with the crude (three spices) ones. First, GC-MS-based untargeted metabolomics were applied to reveal the discriminatory components and discover potential markers. As a result, a total of six components were identified as potential markers. Then, the hepatoprotective activities were evaluated by dual cell damage models induced by a certain concentration of H2O2 or tertbutyl hydfroperoxide (t-BHP) (55 µM H2O2 or 40 µM t-BHP), which highlighted the potential of the processed Curcuma zedoaria on oxidative stress. Finally, epicurzerenone was identified as its quality marker on oxidative liver injury based on the above results and the cell-based biological assay. Overall, vinegar-processed Curcuma zedoaria was more suitable for the treatment of oxidative liver diseases, and epicurzerenone could be considered as its quality marker.


Assuntos
Ácido Acético , Curcuma/química , Hepatopatias/etiologia , Hepatopatias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores , Hepatopatias/tratamento farmacológico , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Solventes
19.
Arab J Gastroenterol ; 20(2): 109-113, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31175077

RESUMO

Liver diseases are among the most challenging health care problems worldwide. In Egypt, we established different care programs to combat liver diseases including schistosomiasis and viral hepatitides. A lot of research work addressing liver diseases in Egypt have been published with special focus on these two major fields. Other liver disease seems to be neglected although present and contributing to the liver disease burden in Egypt. In this report we reviewed the available evidence published from Egypt and elucidate areas of weakness and future research needs. Our search for Egyptian liver disease evidence retrieved 4683 articles, 67% of them were relevant to the topic. Out of the relevant articles; 1646/3265 (50.4%) were discussing clinical science, 1131 (34.7%) were discussing basic science and 488 (14.9%) were discussing both basic and clinical sciences. Cairo university (16.8%, n = 513) and Mansoura university (9.3%, n = 285) had the largest number of publications related to liver disease in Egypt respectively. The most commonly reported diseases were hepatitis C in 719/3361 articles (21.4%), parasitic liver infestations in 663 articles (19.7%), hepatocellular carcinoma in 544 articles (16.2%), liver fibrosis or cirrhosis in 537 articles (16%), and drug induced liver injury in 516 articles (15.4%). Most of the reviewed articles (36%) were discussing treatment of chronic liver diseases (n = 1201) followed by diagnostics (28%, n = 940), pathogenesis and pathophysiology (21%, n = 706). This review will direct attention to areas with less research like hepatitis B related liver disease, HIV/HCV co-infections, and non-alcoholic fatty liver disease (NAFLD) to encourage future research in these topics. In conclusion; our results ring a bell inviting the development of a roadmap for liver research in Egypt targeting to put future policies to cover areas of weakness in liver research with an ultimate goal of tackling liver disease and its overwhelming socioeconomic burden in our developing country.


Assuntos
Bibliometria , Pesquisa Biomédica , Hepatopatias/diagnóstico , Hepatopatias/terapia , Egito , Humanos , Hepatopatias/etiologia
20.
BMJ Case Rep ; 12(6)2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31239319

RESUMO

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) is a rare pulmonary disorder characterised by classic radiological findings and symptoms of obstructive lung disease. DIPNECH is considered a precursor to carcinoid tumours in the lungs. In this case, we describe a patient with years of unexplained dry cough presenting with 2 weeks of progressive nausea and vomiting, and found to have massive hepatomegaly on examination. By CT-PE, she was diagnosed with DIPNECH, and abdominal MRI revealed metastatic carcinoid tumours. Despite its non-specific presentation, DIPNECH has characteristic radiological findings of mosaic attenuation with numerous pulmonary nodules. DIPNECH requires early identification and close surveillance to prevent progression to carcinoid tumours. Thus, it is critical for frontline providers to consider this diagnosis as part of their differential when other common causes of obstructive lung disease have been ruled out.


Assuntos
Hepatopatias/patologia , Pneumopatias/patologia , Células Neuroendócrinas/patologia , Lesões Pré-Cancerosas/patologia , Humanos , Hiperplasia , Hepatopatias/diagnóstico , Hepatopatias/etiologia , Pneumopatias/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos
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