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1.
Medicine (Baltimore) ; 98(45): e17851, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702644

RESUMO

To evaluate the safety and efficacy of the novel technique, transjugular portal vein embolization (TPVE).A single-center retrospective review of 18 patients (12 males and 6 females; mean age, 62 years) who underwent TPVE between January 2012 and January 2013 was conducted. The technical success rate, future liver remnant (FLR) volume, total liver volume (TLV) and FLR/TLV ratio after PVE were analyzed. Liver function, including total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and International Normalized Ratio (INR), was assessed before and after PVE. Any complications of TPVE and liver resection after TPVE were recorded.TPVE was performed on 18 patients before right hepatic resection for both primary and secondary hepatic malignancies (10 hepatocellular carcinomas, 4 cases of colorectal liver metastasis, and 4 cholangiocarcinomas). Technical success was achieved in 100% of patients (18 of 18). The mean FRL significantly increased to 580 ±â€Š155 mL (P < .001) after PVE. The mean FLR/TLV ratio (%) significantly increased to 34 ±â€Š4 (P < .001) after PVE. One patient suffered septicemia after TPVE. A small number patients experienced mild to moderate abdominal pain during TPVE. No other major complications occurred after TPVE in our study. The patient who developed septicemia died 3 days after the surgery as a result of this complication and subsequent multiple organ dysfunction syndrome (MODS).Transjugular portal vein embolization is a safe, efficacious, and promising novel technique to induce hypertrophy of the FLR.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Carcinoma Hepatocelular/terapia , Colangiocarcinoma/terapia , Embolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Idoso , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Neoplasias dos Ductos Biliares/metabolismo , Carcinoma Hepatocelular/metabolismo , Colangiocarcinoma/metabolismo , Embolização Terapêutica/efeitos adversos , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
2.
Pestic Biochem Physiol ; 159: 34-40, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31400782

RESUMO

The present study investigated the insecticidal activity of the different organic extracts from the entomopathogenic fungi, Cladosporium cladosporioides, Metarhizium anisopliae, Purpureocillium lilacinum, and Trichoderma longibrachiatum towards cotton aphid, Aphis gossypii. The methanol extracts from the mycelia and spores of C. cladosporioides and P. lilacinum exhibited the highest insecticidal activity against A. gossypii compared with other extracts, which LC50 values were recorded to be 57.60 and 94.18 ppm, respectively. The major constituents identified in both methanol extracts by GC-MS analysis were linoleic acid and palmitic acid. The methanol extracts of C. cladosporioides and P. lilacinum caused a voluminous increase in the total carbohydrates content of A. gossypii adults, while the total protein content was significantly decreased by both extracts. The activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly reduced by methanol extracts. The P. lilacinum extract caused a considerable reduction in the activity of glutathione-S-transferase (GST), α- and ß-esterase by 28.9, 27.9 and 23.4%, respectively. Both extracts induced a significant increase in phenoloxidase and chitinase activity of A. gossypii adults. These results suggest that C. cladosporioides and P. lilacinum methanol extracts could be used as a promising approach for the management of A. gossypii in many economically crops.


Assuntos
Afídeos/efeitos dos fármacos , Gossypium/parasitologia , Inseticidas/farmacologia , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Animais , Quitinases/genética , Quitinases/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Resistência a Inseticidas/genética , Dose Letal Mediana , Metanol/química , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/metabolismo
3.
An Acad Bras Cienc ; 91(3): e20180646, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31411259

RESUMO

The hepatoprotective effects of the ethanolic extracts of propolis (EEP) on alcohol-induced liver steatosis were investigated in Wistar rats. Chronic alcoholic fatty liver was induced by administration of 52% alcohol to male Wistar rats at the dose of 1% body weight for 7 weeks. Then animals were simultaneously treated with 50% ethanol solutions of EEP or normal saline at the dose of 0.1% body weight for 4 further weeks. Serological analyses and liver histopathology studies were performed to investigate the development of steatosis. Microarray analysis was conducted to investigate the alterations of hepatic gene expression profiling. Our results showed that 4-week treatment of EEP helped to restore the levels of various blood indices, liver function enzymes and the histopathology of liver tissue to normal levels. Results from the microarray analysis revealed that the hepatic expressions of genes involved in lipogenesis were significantly down-regulated by EEP treatment, while the transcriptional expressions of functional genes participating in fatty acids oxidation were markedly increased. The ability of EEP to reduce the negative effects of alcohol on liver makes propolis a potential natural product for the alternative treatment of alcoholic fatty liver.


Assuntos
Fígado Gorduroso Alcoólico/metabolismo , Hepatopatias Alcoólicas/metabolismo , Extratos Vegetais/metabolismo , Própole/metabolismo , Substâncias Protetoras/metabolismo , Alanina Transaminase/metabolismo , Animais , Apiterapia/métodos , Aspartato Aminotransferases/metabolismo , Colesterol/metabolismo , Modelos Animais de Doenças , Etanol , Ácidos Graxos/biossíntese , Fígado Gorduroso Alcoólico/tratamento farmacológico , Fígado Gorduroso Alcoólico/genética , Fígado Gorduroso Alcoólico/patologia , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/patologia , Masculino , Oxirredução , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Própole/química , Própole/uso terapêutico , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Ratos Wistar , Análise Serial de Tecidos/métodos , Transcrição Genética/genética , Triglicerídeos/metabolismo
4.
J Assoc Physicians India ; 67(3): 67-70, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31304710

RESUMO

Background: Alanine aminotransferase (ALT) is commonly used to measure liver injury in resource limited settings. Elevations in ALT are predictive of increased mortality from liver disease and may be influenced by antiretroviral drugs and concomitant hepatitis B infection. Methods: A cross-sectional analysis of the prevalence and predictors of elevated ALT (defined as> 40 IU/L) on HIV patients on antiretroviral therapy (ART) was conducted. Baseline ALT levels and at two weeks, six weeks, twelve weeks, twenty four weeks and one year were recorded for 320 patients on ART. Hepatitis B surface antigen was also recorded at baseline. Results: Out of the total 320 patients, 249 were males and 71 females. A total of 252 patient records were used as controls who were not on ART. The mean ALT record before initiating ART was 30.6 IU/L. Peak rise in ALT was observed at twenty four weeks of therapy with mean ALT levels of 54.42 IU/L. Total toxicity was almost similar between the two regimes, nevirapine based being 17.62% and efavirenz based being 16.16%.Toxicty grades were lesser in Hepatitis B positive patients as compared with hepatitis B negative patients overall. Conclusions: This study concludes that elevated ALT levels are seen in patients on antiretroviral therapy and persist throughout the course of first year, though maximum levels are seen at around twenty four weeks of therapy. Total hepatotoxicity was found to be 16.89%. Longer follow up of patients is required to assess the effect of ALT elevations on morbidity and mortality of patients and a close monitoring of ALT is required in patients on ART and other hepatotoxic therapies.


Assuntos
Alanina Transaminase/metabolismo , Antirretrovirais/uso terapêutico , Infecções por HIV/metabolismo , Estudos Transversais , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Índia , Masculino
5.
Int J Clin Pharmacol Ther ; 57(8): 402-407, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31232278

RESUMO

OBJECTIVE: To investigate the population pharmacokinetics of delayed methotrexate (MTX) excretion in children with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A total of 1,659 plasma concentration samples of MTX from 190 patients with 1 - 4 courses (plasma concentrations > 0.1 µmol/L) were collected in this study. The data analysis was performed using Phoenix NLME 1.3 software. The covariates included age, body surface area (BSA), body weight, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminase (ALT), total bilirubin (TBIL), and serum creatinine (SCr). The final model was validated by bootstrap resampling procedures (1,000 runs) and visual predictive check (VPC) method. RESULTS: The data were best described by a two-compartment linear pharmacokinetic model. The mean values of clearance (CL) and distribution volume (Vd) of MTX were 6.53 L/h and 67.88 L, respectively. Analysis of covariates showed that BSA influenced the CL of MTX. CONCLUSION: The final model was demonstrated as appropriate and effective for assessing the pharmacokinetic parameters of delayed MTX excretion in children with ALL.


Assuntos
Antimetabólitos Antineoplásicos/farmacocinética , Metotrexato/farmacocinética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Aspartato Aminotransferases/metabolismo , Bilirrubina/sangue , Criança , Creatinina/sangue , Humanos
6.
Expert Opin Drug Saf ; 18(8): 753-758, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177863

RESUMO

Objectives: Z-Drugs (ZDs) have been developed to limit benzodiazepines (BZDs) abuse for sleep disorders. Data on the liver toxicity of zolpidem (ZLM) are lacking or anecdotal. The authors evaluated the presence of drug-induced liver injury (DILI) among a cohort of high-dose ZLM abusers. Methods: Retrospective study analyzing clinical records of 1112 consecutive patients admitted for BZDs detoxification from 2003 to 2018. Inclusion criteria: age >18 y.o.; ZLM abuse/dependence; high-dose ZDs abuse. Exclusion criteria: missing lab data; lack of informed consent. Main outcome was the presence of DILI measured as elevation of ALT/AST levels >250 U/l. Results: A total of 107 patients met the eligibility criteria. Liver enzymes alterations were present in 9.3% (95% CI 4.6-16.5%); one patient (0.9%, 95% CI 0.0-2.8%) showed DILI criteria. BMI significantly influenced transaminases levels. No correlations between duration nor doses of ZLM abuse and transaminases levels were found. Conclusion: The present study shows a very low prevalence of DILI among high-dose ZLM abusers. The prevalence of hypertransaminasemia was in line with general population. On one hand ZLM has a substantially safe liver profile but on the other hand ZLM abuse and dependence, especially at very high doses, represents an emerging problem.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Medicamentos Indutores do Sono/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/complicações , Zolpidem/administração & dosagem , Adulto , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Medicamentos Indutores do Sono/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Zolpidem/efeitos adversos
7.
Food Chem Toxicol ; 131: 110580, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202938

RESUMO

In present study, the acute, genetic, and sub-chronic toxicities of flaxseed derived Maillard reaction products (MRPs) were investigated. Acute toxicity results showed that the 50% lethal dose (LD50) of MRPs in rats was >15.0 g/kg body weight (BW); whereas, the 50% effective dose (ED50) of MRPs was 12.3 g/kg BW. Ames test demonstrated that the back-mutation colonies for MRPs addition of 5,000 µg/dish was positive, which displayed certain mutagenicity. There were no significant differences in micronucleus rate and sperm deformity rate among different dose groups. The sub-chronic toxicity confirmed that less than 0.75 gMRPs/kg BW intake did not affect weight, food intake, mortality, gross pathology, histology, hematology, and serum biochemistry. The obtained results can provide an imperative reference on the safety of a meat flavoring agents.


Assuntos
Linho/química , Produtos Finais de Glicação Avançada/toxicidade , Sementes/química , Alanina Transaminase/metabolismo , Animais , Medula Óssea/patologia , Feminino , Rim/patologia , Fígado/patologia , Masculino , Camundongos , Testes de Mutagenicidade , Mutagênicos/toxicidade , Ratos Sprague-Dawley , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica
8.
Molecules ; 24(11)2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31167480

RESUMO

Lauridia tetragona (L.f) R.H. Archer is routinely used in traditional medicine; however, its hepatoprotective property is yet to be scientifically proven. To this effect, the hepatoprotective activity of the polyphenolic-rich fractions (PPRFs) was investigated against acetaminophen (APAP) injured HepG2 cells. The ability of the PPRF to scavenge free radicals was tested against 2,2-diphenyl-1-picrylhydrazyl (DPPH), and [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonicacid)] (ABTS). The ferric ion reducing power (FRAP) was also evaluated as a cell-free antioxidant assay. The hepatoprotective activity was then investigated by observing the effect of PPRFs against APAP-induced reduction in cell viability of HepG2 cells. The concentrations of alanine aminotransferase (AST), aspartate aminotransferase (ALT) and lactate dehydrogenase (LDH) released into the medium were evaluated while the underlying mechanism was further explored through western blot analysis. Thereafter, the isolated PPRFs were identified using UHPLC-QToF-MS. All six fractions of the PPRFs isolated showed significant antioxidant properties that were evident by the effective scavenging of DPPH, ABTS, and higher FRAP. The results indicated that PPRF pretreatments ameliorated APAP-induced hepatocellular injury by significantly inhibiting the leakage of AST, ALT, and LDH into the medium. The most active fractions for hepatoprotection were PPRF4 and PPRF6 with IC50 of 50.243 ± 8.03 and 154.59 ± 1.9 µg/mL, respectively. PPRFs markedly increased activities of liver superoxide dismutase, total antioxidant capacity, and liver glutathione concentration. Both PPRF4 and PPRF6 significantly increased the expression of Nrf2 and translocation. The LC-MS analysis revealed the presence of a wide variety of polyphenolics such as coumarin, ferulic acid, and caffeine among the dominant constituents. In conclusion, this study demonstrates that the isolated PPRFs have potential hepatoprotective activity that may be due to the increased expression of antioxidative genes dependent on Nrf2.


Assuntos
Acetaminofen/efeitos adversos , Celastraceae/química , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Substâncias Protetoras/farmacologia , Alanina Transaminase/metabolismo , Antioxidantes/química , Antioxidantes/farmacologia , Aspartato Aminotransferases/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas , Relação Dose-Resposta a Droga , Antagonismo de Drogas , Ativação Enzimática/efeitos dos fármacos , Glutationa/metabolismo , Células Hep G2 , Humanos , Concentração Inibidora 50 , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Polifenóis/química , Substâncias Protetoras/química
9.
Wei Sheng Yan Jiu ; 48(2): 295-302, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-31133111

RESUMO

OBJECTIVE: To verify the health effect and the point of departure(POD) of chromium in drinking water by animal experiment, and acquire the short-term health advisory(HA). METHODS: A total of 120 SPF SD rats were randomly divided into 6 groups. Deionized water was used as a negative control and the concentration of chromium was 0, 7. 2, 8. 3, 14. 4, 24. 0, 28. 8 mg/(kg·d) and the potassium chromate(K_2CrO_4) was used as a positive control. Blood analysis, blood biochemical parameters and histopathology were determined after exposure 14 and 28 days. The results were analyzed by one-way ANOVA, P<0. 05 showed that the difference was significant. RESULTS: After 28 days of chromium exposure, the liver weights of the female rats in each dose group were lower than the control group. There were significant differences between the 24. 0, 28. 8 mg/(kg·d) dose groups with the control group. The liver weight of female rats in the 24. 0, 28. 8 mg/(kg·d) groups were(6. 68±0. 90)g and(7. 08±0. 36)g, respectively, which were significantly higher than those in the control group(P<0. 05). After 28 days exposure, alanine transaminase(ALT) in male rats at 24. 0 and 28. 8 mg/(kg·d) levels were(59. 04±10. 98)U/L and(63. 78±5. 89)U/L, respectively, which were significantly higher than those in the control group(P<0. 05). Alkaline phosphatase(ALP) levels in blood of the two groups were lower than those in the control group, that were(130. 52±23. 22)U/L and(126. 34±28. 25)U/L(P<0. 05). CONCLUSION: With index of rat liver damage(liver weight, ALT, ALP) as indicators of health effect, LOAEL is 24 mg/(kg·d), and NOAEL is 14. 4 mg/(kg·d). Referring to the calculation method of HA value formulated by the United States Environmental Protection Agency(USEPA), the HA is 1. 44 mg/L, which is consistent with the result obtained by USEPA.


Assuntos
Cromo/toxicidade , Água Potável/química , Fígado/efeitos dos fármacos , Alanina Transaminase/metabolismo , Animais , Feminino , Fígado/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Abastecimento de Água
10.
J Oleo Sci ; 68(6): 581-589, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31092797

RESUMO

Non-alcoholic fatty liver disease (NAFLD), a common chronic liver disease characterized by hepatic steatosis, affects 30-40% of the population in the world. The seed of Euryale ferox salisb. possesses several pharmacological actions, including metabolic syndrome. However, the seed coat of E. ferox was usually discarded as waste, which contains comparatively abundant polyphenols, and its biological activity has been rarely investigated. In this work, we evaluate the hepatoprotective effect of E. ferox seed coat extract (EFSCE), in NAFLD mice induced by high-fat diet (HFD). The HPLC-MS analysis indicated that the main components of EFSCE were polyphenols. And then, mice were treated with HFD for 4 weeks to induce NAFLD. The result showed that the body weight, weight of adipose tissue, the ratio of liver to body weight in NAFLD mice increased compared with control group. In addition, blood lipids parameters including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL) also increased in NAFLD mouse model. It was showed that, after treated with EFSCE (15 and 30 mg/kg/day) for 4 weeks, the body weight, lipids deposition in the liver and blood lipids in HFD-induced NAFLD mice markedly reduced. Compared with NAFLD mice, EFSCE administration could also prevent malondialdehyde (MDA) overproduction and strengthen Superoxide Dismutase (SOD) activity to counteract oxidative stress. Moreover, EFSCE was also found effective in reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in HFD-induced NAFLD model, which indicated liver injury in NAFLD. Therefore, EFSCE (rich in polyphenols) is indicated as bioactive nature product for HFD-induced NAFLD treatment, by eliminating lipid accumulation and oxidative stress via regulation of IRs-1 and CYP2E1.


Assuntos
Citocromo P-450 CYP2E1/metabolismo , Dieta Hiperlipídica/efeitos adversos , Proteínas Substratos do Receptor de Insulina/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Nymphaeaceae/química , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sementes/química , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Modelos Animais de Doenças , Inibidores Enzimáticos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos ICR , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Polifenóis/análise , Estimulação Química , Superóxido Dismutase/metabolismo
11.
Mol Med Rep ; 19(6): 5177-5184, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059036

RESUMO

Gap junctions (GJs) and tight junctions (TJs) are essential to maintain the function of hepatocytes. Changes in biliary tract pressure and the effect of lipopolysaccharide (LPS) may lead to acute obstructive cholangitis (AOC) and cause liver injury via GJ and TJ dysfunction. Hydrogen has been confirmed to have a protective role in various organs during pathological conditions and inflammation. The present study investigated the function of junction proteins and the potential application of H2 in AOC­induced liver injury. An AOC rat model was established by LPS injection through a bile duct catheter, while the distal bile duct was closed. The catheter sealing caps were removed and bile was allowed to flow out from the catheters at 12 h after LPS infusion. The potential application of H2 was studied in the AOC rat model with biliary drainage. It was observed that AOC induced the disruption of junction proteins of both GJs and TJs. H2 administration reversed AOC­induced disruption of GJs and TJs after biliary drainage. The mechanism of this phenomenon suggests that H2 may have effectively attenuated AOC­induced inflammatory and oxidative damage, and decreased matrix metalloproteinase activity. H2 may accelerate the reversal of AOC­induced liver dysfunction, and this phenomenon may depend on reversing the inhibition of GJs and TJs.


Assuntos
Colangite/patologia , Junções Comunicantes/metabolismo , Hidrogênio/farmacologia , Hepatopatias/etiologia , Junções Íntimas/metabolismo , Doença Aguda , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Colangite/complicações , Colangite/tratamento farmacológico , Conexinas/metabolismo , Modelos Animais de Doenças , Hidrogênio/química , Hidrogênio/uso terapêutico , Lipopolissacarídeos/toxicidade , Fígado/metabolismo , Masculino , Metaloproteinases da Matriz/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Solução Salina/química , Proteína da Zônula de Oclusão-1/metabolismo
12.
J Korean Med Sci ; 34(19): e143, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31099193

RESUMO

BACKGROUND: Acute necrotizing encephalopathy (ANE) is a rare, but potentially life threatening neurological condition in children. This study aimed to investigate its clinical spectrum, diagnostic and therapeutic dilemma, and prognosis. METHODS: Twelve children with ANE were included in the study. The diagnosis was made by clinical and radiological characteristics from January 1999 to December 2017 and their clinical data were retrospectively analyzed. RESULTS: A total of 12 children aged 6 to 93 months at onset (5 male: 7 female) were evaluated. The etiology was found in 4 of them (influenza A, H1N1; coxsackie A 16; herpes simplex virus; and RANBP2 gene/mycoplasma). The most common initial presentations were seizures (67%) and altered mental status (58%). The majority of the subjects showed elevation of aspartate aminotransferase/alanine aminotransferase with normal ammonia and increased cerebrospinal fluid protein without pleocytosis. Magnetic resonance imaging revealed increased T2 signal density in bilateral thalami in all patients, but the majority of the subjects (67%) also had lesions in other areas including tegmentum and white matter. Despite the aggressive immunomodulatory treatments, the long-term outcome was variable. One child and two sisters with genetic predisposition passed away. CONCLUSION: ANE is a distinctive type of acute encephalopathy with diverse clinical spectrum. Even though the diagnostic criteria are available, they might not be watertight. In addition, treatment options are still limited. Further studies for better outcome are needed.


Assuntos
Doença de Leigh/diagnóstico , Doença Aguda , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Criança , Pré-Escolar , Infecções por Coxsackievirus/complicações , Infecções por Coxsackievirus/diagnóstico , Feminino , Humanos , Lactente , Influenza Humana/complicações , Influenza Humana/diagnóstico , Doença de Leigh/etiologia , Imagem por Ressonância Magnética , Masculino , Chaperonas Moleculares/genética , Infecções por Mycoplasma/complicações , Infecções por Mycoplasma/diagnóstico , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Estudos Retrospectivos
13.
Life Sci ; 230: 68-75, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31129140

RESUMO

AIMS: The aim of the present study was to investigate the protective effects of AGK2 as a selective SIRT2 inhibitor on thioacetamide (TAA)-induced acute liver failure (ALF) in mice and its potential mechanism. MAIN METHODS: All male C57BL/6 mice were separated into control, TAA, AGK2 + TAA, and AGK2 groups. The histological changes were observed by hematoxylin and eosin (HE) staining. The apoptosis cells of liver tissues were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were used to evaluate the damage of liver function. The inflammatory cytokines of iNOS, TNF-α, IL-1ß was detected by Western blotting and RT-PCR assay. The expression of mitogen-activated protein kinase (MAPK), NF-κB, and apoptosis pathways was determined by Western blotting. KEY FINDINGS: AGK2 improved the damage of TAA-induced liver pathology and function. AGK2 pretreatment also reduced the levels of pro-inflammatory cytokines in ALF liver tissues. AGK2 improved the TAA-induced survival rate. Moreover, AGK2 administration suppressed the increase of phosphorylation NF-κB-p65 and the activation of MAPK pathway. In addition, pretreatment alleviated TAA-induced the liver cells apoptosis. SIGNIFICANCE: AGK2 improve TAA-induced survival rate in mice with ALF, suppress the inflammatory responses by inhibition of MAPK and NF-κB signaling pathways, and decrease the hepatocyte necrosis by inhibition of apoptosis. Pharmacologic inhibition of SIRT2 may be a promising approach for the treatment of ALF.


Assuntos
Furanos/farmacologia , Falência Hepática Aguda/tratamento farmacológico , Fígado/patologia , Quinolinas/farmacologia , Alanina Transaminase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/metabolismo , Citocinas/metabolismo , Furanos/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Falência Hepática Aguda/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Quinolinas/metabolismo , Transdução de Sinais , Sirtuína 2/antagonistas & inibidores , Tioacetamida/farmacologia , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
14.
Phytomedicine ; 59: 152782, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31005808

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease. Swertia bimaculata (Sieb. et Zucc.) Hook. Thoms.ex Clarke, a glabrous or procumbent perennial herb, is a traditional herb medicine. Swertiamarin, a secoiridoid glycoside, is a representative ingredient in this medical plant crude extract and shows antidiabetic and antihyperlipidaemic activities and protective effect against hepatic injury. PURPOSE: The present study aimed to determine whether swertiamarin can attenuate NAFLD in fructose-fed mice. METHODS: Healthy male mice freely drank water containing 10% fructose for 12 consecutive weeks, whereas animals in those swertiamarin tested groups received different doses of swertiamarin (25, 50 and 100 mg/kg) by intragastric administration once a day from the ninth week to the twelfth week. RESULTS: At the end of the experiment, fructose-fed mice administrated with swertiamarin showed low levels of serum glucose, triglycerides, uric acid, alanine aminotransferase and aspartate transaminase. Histological examinations suggested the alleviation of hepatic ballooning degeneration and steatosis by swertiamarin treatment. Moreover, swertiamarin administration mitigated hepatic oxidative stress along with decreases of hepatic pro-inflammation cytokines, which was associated with decrease of hepatic xanthine oxidase (XO) activity and enhancements of anti-oxidant defense system enzymes, as well as activation of nuclear factor E2-related factor 2 (Nrf2) in fructose-fed mice. In addition, swertiamarin down-regulated expression of sterol-regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1) in liver of fructose-fed mice. CONCLUSION: The present study demonstrates that swertiamarin alleviates NAFLD and metabolic alterations in fructose-fed mice.


Assuntos
Frutose/efeitos adversos , Glucosídeos Iridoides/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Pironas/farmacologia , Acetil-CoA Carboxilase/metabolismo , Alanina Transaminase/metabolismo , Animais , Citocinas/metabolismo , Ácido Graxo Sintases/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Xantina Oxidase/metabolismo
15.
Int J Med Mushrooms ; 21(4): 367-380, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002632

RESUMO

This study investigates the hepatoprotective effect of a water-alcohol extract of the medicinal mushroom Phellinus caryophylli (Racib.) G. Cunn. (PCE) against acetaminophen (APAP)-induced hepatotoxicity in Swiss albino mice. The mice orally received APAP (150 mg/kg body weight), followed by PCE extract (250 or 500 mg/kg body weight). The liver damage induced by APAP was analyzed on the basis of blood serum parameters (glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, and alkaline phosphatase), antioxidant assays (reduced glutathione and glutathione peroxidase), and tissue peroxidation based on malondialdehyde level. The molecular mechanism underlying the prevention of APAP-induced damage by PCE was also analyzed. Liver damage was confirmed on the basis of increased serum parameter values, decreased antioxidant levels, and cellular and molecular alterations, which PCE restored in a dose-dependent manner. At a transcriptional level, PCE downregulated expression of the preapoptototic gene Bax and the inflammatory gene Cox2 but upregulated the antiapoptotic gene Bcl2 in the mice that received APAP. PCE exerted a hepatoprotective effect by preventing apoptotic and inflammatory events caused by APAP. Thus, this study demonstrates a hepatoprotective effect of PCE, which could be explored further for managing hepatopathy.


Assuntos
Antioxidantes/farmacologia , Artocarpus/microbiologia , Basidiomycota/química , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Acetaminofen/efeitos adversos , Alanina Transaminase/metabolismo , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Aspartato Aminotransferases/metabolismo , Biomarcadores/sangue , Modelos Animais de Doenças , Etanol , Depuradores de Radicais Livres/metabolismo , Glutationa Peroxidase/metabolismo , Índia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Camundongos , Óxido Nítrico/metabolismo , Água
16.
Methods Mol Biol ; 1981: 25-53, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016646

RESUMO

Cholestasis, the impairment of bile flux out of the liver, is a common complication of many pathological liver disorders, such as cholangiopathies, primary biliary sclerosis, and primary biliary cirrhosis. Besides accumulation of bile acids in the liver and blood, it leads to a proliferative response of the biliary tree termed as a ductular reaction. The ductular reaction is characterized by enhanced proliferation of cholangiocytes, which form the epithelial lining of bile ducts. This strong reaction of the biliary tree has been reported to generate a source of progenitor cells that can differentiate to hepatocytes or cholangiocytes during regeneration. On the other hand, it can cause periportal fibrosis eventually progressing to cirrhosis and death. In 2D histology, this leads to the appearance of an increased number of duct lumina per area of tissue. Yet, the biliary tree is a 3D vstructure and the appearance of lumina in thin slices may be explained by the appearance of novel ducts or by ramification or convolution of existing ducts in 3D. In many such aspects, traditional 2D histology on thin slices limits our understanding of the response of the biliary tree. A comprehensive understanding of architecture remodeling of the biliary network in cholestasis depends on robust 3D sample preparation and analysis methods. To that end, we describe pipe-3D, a processing and analysis pipeline visualization based on immunofluorescence, confocal imaging, surface reconstructions, and automated morphometry of the biliary network in 3D at subcellular resolution. This pipeline has been used to discover extensive remodeling of interlobular bile ducts in cholestasis, wherein elongation, branching, and looping create a dense ductular mesh around the portal vein branch. Surface reconstructions generated by Pipe-3D from confocal data also show an approximately fivefold enhancement of the luminal duct surface through corrugation of the epithelial lamina, which may increase bile reabsorption and alleviate cholestasis. The response of interlobular ducts in cholestasis was shown to be in sharp contrast to that of large bile ducts, de novo duct formation during embryogenesis. It is also distinct from ductular response in other models of hepatic injury such as choline-deficient, ethionine-supplemented diet, where parenchymal tissue invasion by ducts and their branches is observed. Pipe-3D is applicable to any model of liver injury, and optionally integrates tissue clearing techniques for 3D analysis of thick (>500 µm) tissue sections.


Assuntos
Ductos Biliares/metabolismo , Colestase/metabolismo , Imunofluorescência/métodos , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Microscopia Confocal
17.
Methods Mol Biol ; 1981: 133-147, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016652

RESUMO

Cholestasis can be induced by obstruction of bile ducts or intrahepatic toxicity of drugs and chemicals. However, the mode of cell death during cholestasis, i.e., apoptosis or necrosis, has been controversial. There are fundamental reasons for the controversies, both of which are discussed here, namely the design of experiments and the use of parameters with limited specificity for a certain mode of cell death. Based on the assumption that cholestatic liver injury is caused by accumulation of bile acids, rodent (mainly rat) hepatocytes have been exposed to hydrophobic, glycine-conjugated bile acids, which resulted in apoptotic cell death. The problems with this experimental design are that in rodents bile acids are predominantly taurine conjugated and rodent hepatocytes are never exposed to these levels of glycine-conjugated bile acids. In contrast, taurine-conjugated bile acids trigger inflammatory gene activation in rodent hepatocytes and a necro-inflammatory injury in vivo. On the other hand, human hepatocytes are more resistant to glycine-conjugated bile acids and die by necrosis when exposed to high biliary levels of these bile acids. In this chapter, we describe multiple assays including the caspase activity assay, which is specific for apoptosis, and the general cell death assays alanine aminotransferase or lactate dehydrogenase activities in cell culture medium or plasma. An increase in these enzyme activities without caspase activity indicates necrotic cell death. Thus, both the experimental design and the selection of cell death parameters are critical for the relevance of the experiments for the human pathophysiology.


Assuntos
Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Alanina Transaminase/metabolismo , Animais , Apoptose/efeitos dos fármacos , Ácidos e Sais Biliares/química , Ácidos e Sais Biliares/farmacologia , Caspases/metabolismo , Glicina/química , Humanos , L-Lactato Desidrogenase/metabolismo , Camundongos , Ratos , Taurina/química
18.
Cochrane Database Syst Rev ; 4: CD008205, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30985922

RESUMO

BACKGROUND: Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately, the improved prognosis has been accompanied by the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood cancer. However, among long-term childhood cancer survivors, the risk of hepatic late adverse effects is largely unknown. To make informed decisions about future cancer treatment and follow-up policies, it is important to know the risk of, and associated risk factors for, hepatic late adverse effects. This review is an update of a previously published Cochrane review. OBJECTIVES: To evaluate all the existing evidence on the association between antineoplastic treatment (that is, chemotherapy, radiotherapy involving the liver, surgery involving the liver and BMT) for childhood cancer and hepatic late adverse effects. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2018, Issue 1), MEDLINE (1966 to January 2018) and Embase (1980 to January 2018). In addition, we searched reference lists of relevant articles and scanned the conference proceedings of the International Society of Paediatric Oncology (SIOP) (from 2005 to 2017) and American Society of Pediatric Hematology/Oncology (ASPHO) (from 2013 to 2018) electronically. SELECTION CRITERIA: All studies, except case reports, case series, and studies including fewer than 10 patients that examined the association between antineoplastic treatment for childhood cancer (aged 18 years or less at diagnosis) and hepatic late adverse effects (one year or more after the end of treatment). DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection and 'risk of bias' assessment. The 'risk of bias' assessment was based on earlier checklists for observational studies. For the original version of the review, two review authors independently performed data extraction. For the update of the review, the data extraction was performed by one reviewer and checked by another reviewer. MAIN RESULTS: Thirteen new studies were identified for the update of this review. In total, we included 33 cohort studies including 7876 participants investigating hepatic late adverse effects after antineoplastic treatment (especially chemotherapy and radiotherapy) for different types of childhood cancer, both haematological and solid malignancies. All studies had methodological limitations. The prevalence of hepatic late adverse effects, all defined in a biochemical way, varied widely, between 0% and 84.2%. Selecting studies where the outcome of hepatic late adverse effects was well-defined as alanine aminotransferase (ALT) above the upper limit of normal, indicating cellular liver injury, resulted in eight studies. In this subgroup, the prevalence of hepatic late adverse effects ranged from 5.8% to 52.8%, with median follow-up durations varying from three to 23 years since cancer diagnosis in studies that reported the median follow-up duration. A more stringent selection process using the outcome definition of ALT as above twice the upper limit of normal, resulted in five studies, with a prevalence ranging from 0.9% to 44.8%. One study investigated biliary tract injury, defined as gamma-glutamyltransferase (γGT) above the upper limit of normal and above twice the upper limit of normal and reported a prevalence of 5.3% and 0.9%, respectively. Three studies investigated disturbance in biliary function, defined as bilirubin above the upper limit of normal and reported prevalences ranging from 0% to 8.7%. Two studies showed that treatment with radiotherapy involving the liver (especially after a high percentage of the liver irradiated), higher BMI, and longer follow-up time or older age at evaluation increased the risk of cellular liver injury in multivariable analyses. In addition, there was some suggestion that busulfan, thioguanine, hepatic surgery, chronic viral hepatitis C, metabolic syndrome, use of statins, non-Hispanic white ethnicity, and higher alcohol intake (> 14 units per week) increase the risk of cellular liver injury in multivariable analyses. Chronic viral hepatitis was shown to increase the risk of cellular liver injury in six univariable analyses as well. Moreover, one study showed that treatment with radiotherapy involving the liver, higher BMI, higher alcohol intake (> 14 units per week), longer follow-up time, and older age at cancer diagnosis increased the risk of biliary tract injury in a multivariable analysis. AUTHORS' CONCLUSIONS: The prevalence of hepatic late adverse effects among studies with an adequate outcome definition varied considerably from 1% to 53%. Evidence suggests that radiotherapy involving the liver, higher BMI, chronic viral hepatitis and longer follow-up time or older age at follow-up increase the risk of hepatic late adverse effects. In addition, there may be a suggestion that busulfan, thioguanine, hepatic surgery, higher alcohol intake (>14 units per week), metabolic syndrome, use of statins, non-Hispanic white ethnicity, and older age at cancer diagnosis increase the risk of hepatic late adverse effects. High-quality studies are needed to evaluate the effects of different therapy doses, time trends, and associated risk factors after antineoplastic treatment for childhood cancer.


Assuntos
Antineoplásicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Radioterapia/efeitos adversos , Adolescente , Alanina Transaminase/metabolismo , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Humanos , Lactente , Hepatopatias , gama-Glutamiltransferase/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-30987355

RESUMO

An association between exposure to air pollution and liver enzymes in certain areas or older people has been reported in the literature; however, it cannot be generalized to the general population. We investigated the association between air pollution, liver enzyme levels, and alcohol consumption using nationwide data of South Korean adults. Air pollutants included particulate matter with an aerodynamic diameter ≤10 µm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO). Liver enzymes included alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Exposure to air pollutants were significantly associated with elevation of log ALT and log AST, especially increases from 0.0073 IU/L (95% confidence interval (CI) = 0.0042, 0.0104) to 0.0251 IU/L (95% CI = 0.0132, 0.0371) per interquartile range (IQR) increase of each pollutant (all pollutants: p < 0.001). Association of the liver enzymes with PM10 (ß (95% CI) = 0.0285 IU/L (0.0201, 0.0368) for log ALT; ß (95% CI) = 0.0139 IU/L (0.0079, 0.0198) for log AST) and CO (ß (95% CI) = 0.0247 IU/L (0.0182, 0.0311) for log ALT; ß (95% CI) = 0.0164 IU/L (0.0118, 0.0210) for log AST) were only significant among drinkers. Our findings suggest that chronic exposure to PM10 and CO is a risk factor for liver enzymes increases among the general adult population who admitted to drinking alcohol.


Assuntos
Poluição do Ar/efeitos adversos , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Exposição Ambiental/efeitos adversos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Adulto , Idoso , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Consumo de Bebidas Alcoólicas/epidemiologia , Exposição Ambiental/análise , Feminino , Humanos , Coreia (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Material Particulado/análise , Fatores de Risco
20.
Environ Sci Pollut Res Int ; 26(17): 17535-17547, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31025280

RESUMO

Epoxiconazole (EPX) is a triazole fungicide commonly used in agriculture and for domestic purposes around the world. The excessive application of this pesticide may result in a variety of adverse effects on non-target organisms, including humans. Since, the liver and kidneys are the target organs of this fungicide, potential hepatotoxic and nephrotoxic effects are of high relevance. Thus, our study aimed to investigate the toxic effects of EPX on the liver and kidney of Wistar rats. The exposure of rats to EPX at these concentrations (8, 24, 40, 56 mg/kg bw representing, respectively, NOEL (no observed effect level), NOEL × 3, NOEL × 5, and NOEL × 7) for 28 days significantly enhances hepatic and renal lipid peroxidation which is accompanied by an increase in the level of protein oxidation. Furthermore, the results of the present study clearly indicated that EPX administration induces an increase in the levels of DNA damage in a dose-dependent manner. In addition, the activities of liver and kidney antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) are increased significantly in EPX-treated rats at concentrations of 8, 24, and 40 mg/kg bw. However, with the dose NOEL × 7 (56 mg/kg bw of EPX), the activities of CAT, GPx, and GST are decreased. Indeed, EPX-intoxicated rats revealed a significant reduction in acetylcholinesterase (AChE) activity in both liver and kidney compared with the control group. Also, our results demonstrated that the EPX administration leads to a disruption of the hepatic (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH)) and renal (uric acid and creatinine) functions. The biochemical perturbations obtained in the present study are corroborated with the histopathological modifications. Since EPX treatment caused severe damage in the overall histo-architecture of liver and kidney tissues, these results suggest that administration of EPX induced a marked deregulation of liver and kidney functions. Graphical abstract.


Assuntos
Alanina Transaminase/metabolismo , Antioxidantes/metabolismo , Aspartato Aminotransferases/metabolismo , Catalase/metabolismo , Dano ao DNA/efeitos dos fármacos , Compostos de Epóxi/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Rim/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Triazóis/metabolismo , Alanina Transaminase/química , Animais , Aspartato Aminotransferases/química , Catalase/química , Compostos de Epóxi/química , Glutationa Peroxidase/química , Glutationa Transferase/química , L-Lactato Desidrogenase/química , Masculino , Oxirredução , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Triazóis/química
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