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1.
Medicine (Baltimore) ; 98(39): e17300, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574855

RESUMO

We investigated associations between inflammatory marker levels and hepatitis C virus (HCV)-related compensated liver cirrhosis risk in patients with chronic hepatitis C (CHC) infection in China. We used a case-control design and data from the records of 110 Chinese patients with CHC and cirrhosis for the study; 458 CHC patients who did not have a diagnosis of cirrhosis were matched to the case group by age and sex characteristics. We also investigated fatty liver disease risk factors. The group of patients with CHC infection and cirrhosis had lower platelet-to-lymphocyte ratio (PLR) values (60.63 [44.09, 89.31]) compared with the control group patients (80.24 [57.85, 111.08]). The results indicated that the group of patients with cirrhosis had higher 4-factor fibrosis index and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) values compared with the group of patients with CHC-only (1.66 [0.98, 2.60] vs 0.71 [0.45, 1.17], respectively; P < .001 and 2.12 [0.97, 4.25] vs 0.99 [0.51, 2.01], respectively; P < .001). Compared with the control group, the AST/alanine aminotransferase ratio (AAR) values in the group of patients with cirrhosis were significantly higher (P < .001). Logistic regression analysis that included model adjustment for demographic characteristics and other factors that could affect cirrhosis risk revealed that greater 1/PLR values were associated with an increased odds of having cirrhosis (adjusted odds ratio [AOR], 95% confidence interval [CI] 0.991 [0.985-0.996]); APRI and AAR values were also independent predictors of the presence of compensated cirrhosis. We found that compared with the patients with CHC-only, the triglyceride, cholesterol, and low-density lipoprotein cholesterol levels in the patients with both CHC and fatty liver disease were significantly higher. The multivariate analysis of the risk of fatty liver development in patients with CHC infection found that cholesterol level was a statistically significant risk factor (AOR [95% CI] 1.380 [1.089-1.750], P = .008). Increased 1/PLR, APRI, and AAR values were associated with increased risks for development of cirrhosis in this population of Chinese patients with CHC infection. Higher cholesterol levels increased the risk of development of fatty liver disease in patients with CHC.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Hepatite C Crônica , Cirrose Hepática , Biomarcadores/sangue , Estudos de Casos e Controles , China/epidemiologia , Fígado Gorduroso/sangue , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/epidemiologia , Feminino , Hepacivirus/isolamento & purificação , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Humanos , Lipoproteínas/sangue , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Contagem de Linfócitos/métodos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas/métodos , Fatores de Risco
2.
Zhonghua Gan Zang Bing Za Zhi ; 27(8): 615-620, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594079

RESUMO

Objective: To investigate the diagnostic value of endoscopic ultrasonography (EUS), Fibroscan, acoustic radiation force impulse (ARFI), and aspartate aminotransferase-to-platelet ratio (APRI) and their combination for early stage liver cirrhosis. Methods: Three hundred and twenty-two hospitalized patients who had been diagnosed with chronic viral liver disease from March 2016 to April 2018 were included. According to the clinical diagnosis, patients were divided into chronic hepatitis and the early stage liver cirrhosis group (Child-Pugh A grade). All patients were examined by Fibroscan to detect liver stiffness measurement (LSM), ARFI to detect liver virtual touch tissue quantification (VTQ) value, esophagogastroduodenoscopy and EUS to detect esophagogastric varices, laboratory and imaging examination. The index of EUS, Fibroscan, ARFI, and APRI was analyzed and the regression model was established by binary logistic regression, and the diagnostic efficacy of the above index and regression model for early stage of cirrhosis was evaluated by the area under a receiver operating characteristic curve (AUROCs). Results: An early stage cirrhosis group had significantly higher detection rate with EUS (esophagogastric varices), Fibroscan (LSM), ARFI (VTQ) and APRI than chronic hepatitis group [76.7% vs. 10.7%, 10.4 (7.8, 17.3) vs. 6.1 (5.2, 8.4) kPa, 1.71(1.48, 2.07) m/s vs. 1.25(1.14, 1.43) m/s and 0.65 (0.38, 1.15) vs. 0.38(0.26, 0.62), respectively]. The corresponding chi-square test were 140.86, Z = -9.069, Z = -9.948 and Z = -5.764, respectively and the differences were statistically significant (P < 0.01). The areas under the receiver operating characteristic curve and regression model were 0.830 (0.783 ~ 0.877), 0.793 (0.744 ~ 0.841), 0.821 (0.775 ~ 0.868), 0.686 (0.628 ~ 0.744) and 0.947 (0.925 ~ 0.969) for the diagnosis of early stage cirrhosis, respectively. Among them, the regression model of three indices (EUS, LSM and VTQ) had the largest AUROCs (0.947) and the corresponding sensitivity and specificity were 0.878 and 0.867, respectively. Conclusion: The combination of EUS, LSM and ARFI had a superior diagnostic value for early stage liver cirrhosis, and may improve the diagnosis rate and reduce the misdiagnosis rate.


Assuntos
Técnicas de Imagem por Elasticidade , Endossonografia , Cirrose Hepática/diagnóstico por imagem , Aspartato Aminotransferases/sangue , Biópsia , Plaquetas , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Humanos , Fígado , Cirrose Hepática/sangue , Curva ROC
3.
Acta Cir Bras ; 34(8): e201900805, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618405

RESUMO

PURPOSE: To investigate the effect of sevoflurane preconditioning on ischemia/reperfusion (I/R)-induced pulmonary/hepatic injury. METHODS: Fifty-one Wistar rats were randomly grouped into sham, I/R, and sevoflurane groups. After reperfusion, the structural change of the lung was measured by Smith score, the wet and dry weights (W/D) were determined, malondialdehyde (MDA) myeloperoxidase (MPO) content was determined colorimetrically and by fluorescence, respectively, and matrix metalloprotein-9 (MMP-9) mRNA was quantified by RT-PCR. Biopsy and morphological analyses were performed on liver tissue, activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined, and tumor necrosis factor-alpha (TNF-α) level was determined. RESULTS: The sham group showed no changes in tissue structure. Structural lesions in the sevoflurane and I/R groups were mild and severe, respectively. Smith score, W/D, MDA, MPO, and MMP mRNA showed the same trend, and were increased in the I/R group and recovered in the sevoflurane group, compared with the sham group (both P<0.05). AST and ALT were significantly increased compared to the sham group (AST: 655±52.06 vs . 29±9.30 U/L; ALT: 693±75.56 vs . 37±6.71 U/L; P<0.05). In the sevoflurane group, AST and ALT levels were significantly decreased (464±47.71 and 516±78.84 U/L; P<0.001). TNF-α presented similar results. CONCLUSION: The protection of lung and liver by sevoflurane may be mediated by inhibited leukocyte recruitment and MMP-9 secretion.


Assuntos
Anestésicos Inalatórios/uso terapêutico , Precondicionamento Isquêmico/métodos , Fígado/irrigação sanguínea , Pulmão/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Sevoflurano/uso terapêutico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Modelos Animais de Doenças , Isquemia/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Malondialdeído/análise , Peroxidase/análise , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Fator de Necrose Tumoral alfa/sangue
4.
Acta Cir Bras ; 34(7): e201900710, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31531530

RESUMO

PURPOSE: To investigate the prognostic value of 17 platelet-based prognostic scores in patients with malignant hepatic tumors after TACE therapy. METHODS: In total, 92 patients were divided into death group and survival group according to long-term follow-up results. The AUC was calculated to determine the optimal cut-off values for predicting prognosis. To determine better prognostic models, platelet-based models were analyzed separately after being showed as binary according to cut-off values. Cumulative survival rates of malignant hepatic tumors were calculated using Kaplan-Meier curves and differences were analyzed by the log-rank test. Univariate and multivariate analyses were performed to identify platelet-based prognostic scores associated with overall survival. RESULTS: Univariate analysis showed that APGA, APRI, FIB-4, FibroQ, GUCI, King's score, Lok index, PAPAS, cirrhosis, number of tumors, vascular cancer embolus, AFP, ALP and APTT were significantly related to prognosis. A multivariate analysis showed that the APGA, number of tumors, ALP and APTT were independently associated with overall survival. CONCLUSION: This study showed that the APGA, a platelet-based prognostic score, was an independent marker of prognosis in patients with malignant hepatic tumors after TACE and was superior to the other platelet-based prognostic scores in terms of prognostic ability.


Assuntos
Aspartato Aminotransferases/sangue , Plaquetas/química , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Curva ROC , Estudos Retrospectivos
5.
Toxicol Lett ; 316: 85-93, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31513885

RESUMO

BACKGROUND: Apoptosis-stimulating protein 2 of p53 (ASPP2) has a variety of biological functions, and is involved in cellular apoptosis, autophagy and inflammatory reaction. However, the role of ASPP2 in acute hepatic injury remains unclear. METHODS: We established an animal model of acute hepatic injury by intraperitoneal injection of CCl4. The expression profile of ASPP2 was measured in wild type (ASPP2+/+) mice with acute hepatic injury induced by CCl4. Hepatic pathological changes and liver function, apoptosis, inflammation and autophagic levels were measured in ASPP2+/+and ASPP2 haploid deletion (ASPP2+/-) mice with acute hepatic injury, respectively. After 3-methyladenine (3-MA) treatment, indicators of hepatic injury were observed in ASPP2+/+and ASPP2+/- mice with CCl4 injection. RESULTS: During the development of acute hepatic injury, ASPP2 expression significantly upregulated at 24 h and 48 h after CCl4 injection. ASPP2 haplotype deletion protected against acute hepatic injury, and this was mainly reflected in decreased ALT and AST levels, less hepatic tissue hemorrhage and necrosis, and reduced cellular inflammation and apoptosis in ASPP2+/- mice compared with ASPP2+/+ mice with acute hepatic injury. ASPP2 haploid deletion activates autophagy in mice with acute hepatic injury, and protects mice from acute hepatic injury via the autophagic signal pathway. CONCLUSION: ASPP2 haplotype deletion protected mice against acute hepatic injury through autophagy activation, which inhibited inflammation and apoptosis in acute hepatic injury.


Assuntos
Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado/metabolismo , Proteínas Supressoras de Tumor/deficiência , Alanina Transaminase/sangue , Animais , Apoptose , Aspartato Aminotransferases/sangue , Autofagia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Predisposição Genética para Doença , Haplótipos , Fígado/patologia , Masculino , Camundongos Knockout , Necrose , Fenótipo , Transdução de Sinais , Fatores de Tempo , Proteínas Supressoras de Tumor/genética
6.
Medicine (Baltimore) ; 98(37): e17094, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517833

RESUMO

BACKGROUND: Liver disease in patients with HIV is common and typically has complex and multifactorial presentations that represent a major cause of morbidity and mortality. Autoimmune hepatitis (AIH) is rarely reported in patient with HIV and the disease course and clinical outcomes for treatment have not been well characterized. We are aiming to determine the patient characteristics, disease prevalence, and treatment outcomes from published articles of patients with HIV and AIH. METHOD: A systematic search of PubMed, Web of Science, and Google Scholar through February 20, 2019 identified 15 studies that reported the outcomes of AIH in patients with HIV. Because of the small sample sizes and skewed distributions, resampling tests of mean differences using permutation distributions (MAXn = 10,000 permutations) were utilized; analyses were performed using R (v. 3.5.1). Categorical differences were calculated using Fisher exact test for odds ratio = 1 (equal odds), and Cramer V was calculated for effect size; analyses were completed in SPSS (v. 25). RESULTS: By reviewing 15 studies reporting a total of 35 patients with AIH and HIV, male patients were found to have significantly higher aspartate transaminase and alanine transaminase levels at time of diagnosis. No other significant findings identified. The CD4 count and viral load did not show significant correlation with AIH diagnosis or its prognosis. All patients but one who presented with severe immune deficiency and responded to highly active anti-retroviral therapy received immunosuppressive treatment without side effects and achieved remission except 2 lost to follow-up and 3 expired. CONCLUSION: Although rare, but AIH can develop in patients with HIV and physicians should consider it in the differential diagnosis for HIV patients presented with abnormal liver function tests, especially after excluding hepatitis C virus and drug-induced liver injury.Patients with immune deficiency disorders who present with AIH can be treated safely with steroid either as monotherapy or in combination with another immune suppressant therapy.


Assuntos
Infecções por HIV/complicações , Hepatite Autoimune/complicações , Adulto , Alanina Transaminase/análise , Alanina Transaminase/sangue , Aspartato Aminotransferases/análise , Aspartato Aminotransferases/sangue , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Hepatite Autoimune/sangue , Hepatite Autoimune/epidemiologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
7.
Chem Biol Interact ; 312: 108819, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31499052

RESUMO

Cannabidiol (CBD), a compound obtained from Cannabis sativa, has wide range of therapeutic properties, including mitigation of diabetes and neurodegeneration. Cerebral ischemia and consequent learning disabilities are aggravated in elderly diabetic subjects. However, there are no studies showing the effect of CBD treatment in elderly diabetes patients suffering cerebral ischemia. The present work tested the hypothesis that CBD treatment improves metabolic dysfunctions in middle-aged diabetic rats submitted to chronic cerebral hypoperfusion. In this work, 350-day-old male Wistar streptozotocin-induced diabetic rats were used. To induce cerebral ischemia was used a chronic cerebral hypoperfusion (CCH), surgically, via the four-vessel occlusion/internal carotid artery (4-VO/ICA). Four diabetic groups were established: Non-CCH Treated Diabetic (DNT), CCH Treated Diabetic (DCT), Non-CCH Vehicle Diabetic (DNV), and CCH Vehicle Diabetic (DCV). Vehicle groups were not treated with CBD. The animals were treated during 30 days with 10 mg CBD/Kg bw/day. After treatment, the animals were euthanized, and blood levels of glucose, insulin, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, fructosamine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were evaluated. DCT group presented reduction of hyperglycemia and an increase of insulinemia. Also was observed lower fructosamine, LDL, HDL, triglycerides and total cholesterol levels. AST and ALT concentration were reduced in CBD treated groups. CBD may be used as therapeutic tool to protect metabolism against injuries from diabetes aggravated by cerebral ischemia.


Assuntos
Isquemia Encefálica/patologia , Canabidiol/uso terapêutico , Diabetes Mellitus Experimental/patologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Glicemia/análise , Isquemia Encefálica/complicações , Colesterol/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Insulina/sangue , Masculino , Ratos , Ratos Wistar
8.
Ann Hematol ; 98(10): 2257-2265, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31440871

RESUMO

Vascular complications of sickle cell anemia (SCA) are influenced by many factors. Elevated plasma homocysteine (Hcy) is supposed to be an independent risk factor and is either genetic or nutritional origin. The present study evaluated the plasma Hcy level, MTHFR C677T gene polymorphism, effect of folic acid (FA) supplementation' and hemato-biochemical parameters in SCA and their effect on the vaso-occlusive crisis (VOC) in SCA patients of an Asian-Indian haplotype population. One hundred twenty cases of SCA (HbSS) and 50 controls with normal hemoglobin(HbAA) were studied. It was found that the plasma Hcy level is significantly higher (p < 0.0001) in patients with SCA (22.41 ± 7.8 µmol/L) compared to controls (13.2 ± 4.4 µmol/L). Moreover, patients without FA supplementation had a significantly (p < 0.001) higher Hcy level (27 ± 7 µmol/L) compared to those with supplementation (17.75 ± 5.7 µmol/L). Turkey-Kramer multiple comparison tests show that there is a significant difference (p < 0.05) in HbF percent, hemoglobin (Hb), platelet count, serum bilirubin (direct:Bil-D and total:Bil-T), aspartate transaminase (AST), lactate dehydrogenase (LDH), and plasma Hcy levels between mild and severe VOC. Between moderate VOC and severe VOC, there was a significant difference (p < 0.05) in HbF%, Bil-D, AST, Hcy. Pearson correlation revealed that plasma Hcy had a significantly (p < 0.05) positive correlation with AST, serum bilirubin (indirect and total), LDH, jaundice, stroke, VOC per year, and hospitalization per year whereas it was inversely correlated with HbF percentage, Hb level, and FA treatment. In the study population, increased plasma Hcy level, hemolysis, and platelet activation were found to influence VOC in SCA.


Assuntos
Anemia Falciforme , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Doenças Vasculares , Adolescente , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Anemia Falciforme/genética , Anemia Falciforme/fisiopatologia , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Plaquetas/metabolismo , Feminino , Hemoglobina Fetal/genética , Hemoglobina Fetal/metabolismo , Hemólise , Homocisteína/genética , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/sangue , Pessoa de Meia-Idade , Ativação Plaquetária , Contagem de Plaquetas , Doenças Vasculares/sangue , Doenças Vasculares/etiologia , Doenças Vasculares/genética , Doenças Vasculares/fisiopatologia
9.
Adv Exp Med Biol ; 1155: 463-470, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468423

RESUMO

We previously reported that taurine treatment inhibited arsenic (As)-induced apoptosis in the liver of mice. This study was designed to explore the effect of taurine on liver function and its underlying mechanism in As-exposed mice. Mice were randomly divided into 3 groups, ten mice in each group. Group 1, control group, only orally received drinking water alone. Group 2, As intoxication group, was exposed to 4 mg/L As2O3 via drinking water for 60 days. Group 3, taurine protection group, was treated with 4 mg/L As2O3 and 150 mg/kg both. Taurine administration significantly revered the increases of alanine transaminase (ALT) and aspartate transaminase (AST) activities in serum. The decrease of glutathione (GSH) was inhibited with taurine treatment in the liver of As-exposed mice. At the same time, taurine significantly inhihibited As-induced enhancement of malondialdehyde (MDA) in the liver. Here we show that taurine protective effect on liver function in As-exposed mice maybe involve lipid peroxidation.


Assuntos
Arsênico/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Estresse Oxidativo , Taurina/farmacologia , Alanina Transaminase/sangue , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/sangue , Suplementos Nutricionais , Glutationa/análise , Peroxidação de Lipídeos , Fígado/efeitos dos fármacos , Malondialdeído/análise , Camundongos , Distribuição Aleatória
10.
Chem Biol Interact ; 311: 108794, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31421115

RESUMO

Acanthoic acid (AA) is a pimaradiene diterpene isolated from Acanthopanax koreanum Nakai (Araliaceae), with anti-inflammatory and hepatic-protective effects. The present study intended to reveal the effect and mechanism of AA on nonalcoholic fatty liver disease (NAFLD) associated with lipid accumulation by activating Farnesoid X receptor (FXR) and liver X receptors (LXRs) signaling. C57BL/6 mice were received a modified Lieber-DeCarli diet with 71% high-fat (L-D) and treated with AA (20 and 40 mg/kg) or equal volume of saline for 12 weeks. The regulation of AA on lipid accumulation was also detected in pro-steatotic stimulated AML12 cells with palmitic acid (PA). When L-D diet-fed mice were treated with AA, loss in body weight, liver index, and liver lipid droplet were observed along with reduced triglyceride (TG) and serum transaminase. Furthermore, AA decreased sterol regulatory element binding protein 1 (SREBP-1) and target genes expression, regulated PPARα and PPARγ expressions, ameliorated hepatic fibrosis markers, enhanced hepatic FXR and LXR, and regulated AMPK-LKB1 and SIRT1 signaling pathway. Moreover, AA attenuated lipid accumulation via FXR and LXR activation in steatotic AML-12 cells, which was confirmed by guggulsterones (FXR antagonist) or GW3965 (LXR agonist). Activation of FXR and LXR signaling caused by AA might increase AMPK-SIRT1 signaling and then contribute to modulating lipid accumulation and fatty acid synthesis, which suggested that activated FXR-LXR axis by AA represented an effective strategy for relieving NAFLD.


Assuntos
Diterpenos/farmacologia , Lipogênese/efeitos dos fármacos , Receptores X do Fígado/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Peso Corporal/efeitos dos fármacos , Linhagem Celular , Dieta Hiperlipídica , Diterpenos/química , Regulação da Expressão Gênica/efeitos dos fármacos , Receptores X do Fígado/agonistas , Receptores X do Fígado/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , PPAR alfa/genética , PPAR alfa/metabolismo , Ácido Palmítico/farmacologia , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/genética , Transdução de Sinais/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/sangue
11.
Acta Cir Bras ; 34(6): e201900607, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31432998

RESUMO

PURPOSE: Coleus forskohlii Briq., a medicinal plant originally from India, has been indicated against heart disease, expiratory disorders, convulsions, and hepatic changes, among others. In view of the broad pharmacological potential of the plant and the scarce information about its effects, the objective of the present study was to investigate the effect of its use for pretreatment of partially hepatectomized rats. METHODS: The animals were divided into two experimental groups: Control (CG) receiving physiological saline for 10 days before partial hepatetctomy, and Treated (TG) receiving 40 mg Coleus forskohlii/kg/day for 10 days before partial hepatectomy. The treatments were performed by gastric gavage. After the surgical procedure, treatment was continued according to the following groups: CG 24 h, CG 48 h, TG 24 h, and TG 48 hs, and liver tissue and intracardiac blood samples were obtained for histological and biochemical analysis, respectively. RESULTS: No significant differences were observed in mitotic or apoptotic index or in the concentrations of the enzymes AST, ALT and alkaline phosphatase, and no areas of fibrosis were detected. CONCLUSION: Treatment with Coleus forskohlii did not interfere with the course of hepatic hyperplasia.


Assuntos
Hepatectomia/métodos , Fígado/patologia , Extratos Vegetais/administração & dosagem , Plectranthus/química , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Hepatócitos/efeitos dos fármacos , Hiperplasia/tratamento farmacológico , Fígado/efeitos dos fármacos , Fígado/cirurgia , Masculino , Ratos
12.
J Clin Pathol ; 72(10): 669-676, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31371396

RESUMO

AIMS: The role of liver biopsy in primary biliary cholangitis (PBC) is controversial, as is the optimal method of histological assessment. We compared the Ludwig and Ishak systems and three components of the Japanese (Nakanuma) staging system to evaluate their clinical and biochemical correlations and prognostic value. METHODS: We reviewed biopsies from 106 patients with PBC, derived from a previous trial of colchicine therapy with 24-34 years' follow-up, following which five clinical outcomes were evaluated: hepatic decompensation, cholestatic PBC death/liver transplant, portal hypertensive PBC death, all PBC deaths and overall survival. RESULTS: Ludwig and Ishak stages correlated well with prognostically significant parameters, including serum bilirubin, and both Mayo and Child Scores. Serum aspartate aminotransferase correlated with interface hepatitis (IFH), and alkaline phosphatase with orcein deposition, bile duct (BD) loss and cholestasis. Ludwig correlated with all five clinical outcomes, while Ishak stage was only significantly correlated with two. While sinusoidal fibrosis, orcein deposition, BD loss and cholestasis all predicted hepatic death/transplant, after correction for Mayo Score, the only histological parameters predictive of clinical outcomes were IFH (associated with two) and sinusoidal fibrosis (associated with all five). CONCLUSION: Liver biopsy is required in the diagnosis of around 20% of patients with PBC. The Ludwig system is of more prognostic value than both Ishak and any of the three individual components of the Nakanuma staging system, but the major histological parameter providing independent prognostic value beyond the Mayo Score is sinusoidal fibrosis.


Assuntos
Fibrose/diagnóstico , Cirrose Hepática Biliar/diagnóstico , Adulto , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Biópsia , Estudos de Coortes , Fibrose/patologia , Humanos , Fígado/patologia , Cirrose Hepática Biliar/patologia , Transplante de Fígado , Prognóstico , Adulto Jovem
13.
BMC Infect Dis ; 19(1): 680, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370795

RESUMO

BACKGROUND: A major challenge in dengue management in resource limited settings is the confirmation of diagnosis. Clinical features of dengue often overlap with other infections and molecular diagnostic tools are not readily accessible to clinicians at hospitals. In addition, the prediction of plasma leakage in dengue is also difficult. Hematocrit level and ultrasound scans (combined with clinical parameters) are helpful to detect plasma leakage once it has happened, not before. METHODS: Colombo Dengue Study (CDS) is a prospective cohort study of clinically suspected adult dengue patients recruited from the National hospital of Sri Lanka (within the first 3 days of fever) that aimed to a) identify clinical and basic laboratory test parameters to differentiate dengue from non-dengue fever, b) evaluate the comparative efficacy of loop-mediated isothermal amplification (LAMP) for dengue diagnosis (vs. NS1 antigen test and RT-qPCR) and c) identify early associations that are predictive of plasma leakage or severe dengue. The basic laboratory tests considered here included hematological parameters, serum biochemistry and inflammatory markers. RESULTS: Only 70% of clinically suspected patients were confirmed as having dengue by either the NS1 antigen test or RT-qPCR. On a Bayesian latent class model which assumes no "gold standard", LAMP performed equally or better than RT-qPCR and NS1 antigen test respectively. When confirmed dengue patients were compared with others, the earlier group had significantly lower lymphocyte counts and higher aspartate aminotransferase levels (AST) within the first 3 days of fever. Confirmed dengue patients with plasma leakage had a lower mean age and a higher median baseline AST level compared to those without plasma leakage (p < 0.05). CONCLUSION: Clinical suspicion overestimates the true number of dengue patients. RT-LAMP is a potentially useful low-cost diagnostic tool for dengue diagnosis. Confirmed dengue patients had significantly higher AST levels and lower lymphocyte counts in early disease compared to others. In confirmed dengue patients, younger age and a higher AST level in early infection were associated with subsequent plasma leakage.


Assuntos
Aspartato Aminotransferases/sangue , Técnicas de Amplificação de Ácido Nucleico/métodos , Dengue Grave/diagnóstico , Dengue Grave/etiologia , Adulto , Teorema de Bayes , Biomarcadores/sangue , Estudos de Coortes , Dengue/diagnóstico , Vírus da Dengue/genética , Feminino , Febre/virologia , Humanos , Testes Imunológicos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Medição de Risco , Sensibilidade e Especificidade , Dengue Grave/sangue , Sri Lanka
14.
Int J Nanomedicine ; 14: 5817-5829, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440049

RESUMO

Purpose: Acetylcholinesterase (AChE) plays a critical role in the transmission of nerve impulse at the cholinergic synapses. Design and synthesis of AChE inhibitors that increase the cholinergic transmission by blocking the degradation of acetylcholine can serve as a strategy for the treatment of AChE-associated disease. Herein, an operational targeted drug delivery platform based on AChE-responsive system has been presented by combining the unique properties of enzyme-controlled mesoporous silica nanoparticles (MSN) with clinical-used AChE inhibitor. Methods: Functionalized MSNs were synthesized by liquid phase method and characterized by using different analytical methods. The biocompatibility and cytotoxicity of MSNs were determined by hemolysis experiment and MTT assay, respectively. Comparison of AChE activity between drug-loading system and inhibitor was developed with kits and by ELISA method. The efficacy of drug-loaded nanocarriers was investigated in a mouse model. Results: Compared with AChE inhibitor itself, the inhibition efficiency of this drug delivery system was strongly dependent on the concentration of AChE. Only AChE with high concentration could cause the opening of pores in the MSN, leading to the controlled release of AChE inhibitor in disease condition. Critically, the drug delivery system can not only exhibit long duration of drug action on AChE inhibition but also reduce the hepatotoxicity in vivo. Conclusion: In summary, AChE-responsive drug release systems have been far less explored. Our results would shed lights on the design of enzyme controlled-release multifunctional system for enzyme-associated disease treatment.


Assuntos
Acetilcolinesterase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Inibidores da Colinesterase/farmacologia , Portadores de Fármacos/química , Fígado/patologia , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Calixarenos/química , Sobrevivência Celular , Doença Hepática Induzida por Substâncias e Drogas/patologia , Liberação Controlada de Fármacos , Fluoresceína/química , Hemólise , Fígado/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Nanopartículas/química , Nanopartículas/ultraestrutura , Fenóis/química , Porosidade , Ratos , Dióxido de Silício/química , Temperatura Ambiente , Fatores de Tempo
15.
Zhongguo Zhong Yao Za Zhi ; 44(12): 2566-2571, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359725

RESUMO

This study was to investigate the mechanism of safflower yellow injection for regulating inflammatory response against myocardial ischemia-reperfusion injury( MIRI) in rats. Male Wistar rats were randomly divided into sham operation group,model group,Hebeishuang group,safflower yellow injection high,medium and low dose groups. MIRI model was established by ligating left anterior descending coronary artery. Myocardial histopathological changes were observed by HE staining; myocardial infarct size was detected by TTC staining; content and changes of tumor necrosis factor-α( TNF-α) and interleukin-6( IL-6),serum creatine kinase( CK),aspartate aminotransferase( AST),and lactate dehydrogenase( LDH) were detected by biochemical method or enzyme-linked immunosorbent assay( ELISA). Western blot assay was used to detect the protein expression of Toll-like receptor 4( TLR4) and nuclear factor-κB( NF-κB p65) in myocardial tissues. The results showed that as compared with the sham operation group,the myocardial arrangement of the model group was disordered,with severe edemain the interstitial,significantly increased area of myocardial infarction,increased activities of AST,CK and LDH in serum,and significantly increased contents of TNF-α and IL-6; the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were also increased. As compared with the model group,the myocardial tissues were arranged neatlyin the Hebeishuang group and safflower yellow injection high,medium and low dose groups; the edema was significantly reduced; the myocardial infarct size was significantly reduced; the serum AST,CK,LDH activity and TNF-α,IL-6 levels were significantly decreased,and the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were decreased. As compared with the Hebeishuang group,the myocardial infarct size was larger in the safflower yellow injection high,medium and low dose groups; the activities of AST,CK and LDH in serum and the contents of TNF-α and IL-6 in serum were higher,but there was no statistically significant difference in the expression levels of TLR4 and NF-κB( p65) protein in tissues. It is suggested that safflower yellow injection has a significant anti-MIRI effect,and its mechanism may be related to the regulation of TLR-NF-κB pathway to inhibit inflammatory response.


Assuntos
Anti-Inflamatórios/farmacologia , Chalcona/análogos & derivados , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição RelA/metabolismo , Animais , Aspartato Aminotransferases/sangue , Chalcona/farmacologia , Creatina Quinase/sangue , Interleucina-6/metabolismo , L-Lactato Desidrogenase/sangue , Masculino , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
16.
Zhongguo Zhong Yao Za Zhi ; 44(12): 2594-2599, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359729

RESUMO

To study the mechanism and action of Cinnamomi Ramulus in ameliorating intrahepatic cholestasis induced by α-isothiocyanate( ANIT) in rats by regulating FXR pathway. Forty SD rats were randomly divided into normal group,model group,positive control( ursodeoxycholic acid) group( 60 mg·kg~(-1)),Cinnamomi Ramulus treatment( 60 mg·kg~(-1)·d~(-1)) group,and Cinnamomi Ramulus treatment( 20 mg·kg~(-1)·d~(-1)) group,with 8 rats in each group. Except for the normal control group,the other groups were intragastrically administered with the corresponding concentrations of continuous aqueous solution( 0. 005 m L·g~(-1)),once a day,for 7 days.Except for the normal group,the other groups were treated with ANIT( 100 mg·kg~(-1)),once a day,for 3 days. Blood was taken from the abdominal aorta 24 hours after the last administration,and serum alanine aminotransferase( ALT),aspartate aminotransferase( AST),total bilirubin( TBi L),and total bile acid( TBA) were measured. 1. 5-2 cm of rat liver tissue was taken. After fixation with10% formaldehyde,paraffin-embedded sections were taken,HE staining was performed,and immunohistochemistry( IHC) was used to analyze the expression of FXR. RNA and protein were extracted from rat liver tissue to detect FXR mRNA expression,as well as bile acid synthesis and detoxification,transport related SHP,UGT2 B4,BSEP protein expressions at downstream of FXR. Compared with the normal group,serum ALT,AST,TBi L,and TBA levels were elevated in the model group( P<0. 01),liver damage was severe,FXR protein's optical density decreased,FXR mRNA expression decreased,and SHP,UGT2 B4,BSEP protein expressions were decreased( P<0. 05,P<0. 01). Compared with the model group,the drug group could reduce serum ALT,AST,TB,TBA levels to different degrees( P<0. 05,P<0. 01),alleviate liver tissue damage,increase the optical density of FXR protein,and promote the expressions of FXR mRNA and FXR,SHP,BSEP and UGT2 B4 proteins( P<0. 05,P<0. 01). Cinnamomi Ramulus can alleviate ANIT-induced intrahepatic cholestasis,and reduce hepatocyte injury and serum ALT,AST,TBi L and TBA levels. The mechanism may be through FXR-SHP,FXR-UGT2 B4,FXR-BSEP signaling pathways. Therefore,in the pathogenesis of intrahepatic cholestasis,we can try to further explore in alleviating intrahepatic cholestasis with Cinnamomi Ramulus,so as to provide effective drugs for clinical treatment of intrahepatic cholestasis.


Assuntos
Colestase Intra-Hepática/tratamento farmacológico , Cinnamomum/química , Extratos Vegetais/farmacologia , Proteínas de Ligação a RNA/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Ácidos e Sais Biliares/sangue , Bilirrubina/sangue , Colestase Intra-Hepática/induzido quimicamente , Isotiocianatos , Fígado , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
17.
Zhonghua Gan Zang Bing Za Zhi ; 27(6): 430-435, 2019 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-31357758

RESUMO

Objective: To evaluate the using value of FibroTouch and six serological models in detecting the degree of liver fibrosis in patients with chronic hepatitis B, in an attempt to provide reference for accurate diagnosis. Methods: Two hundred and fifty-eight cases with chronic hepatitis B admitted to Xixi Hospital of Hangzhou from September 1, 2015 to September 1, 2017 were selected. All patients underwent liver histopathological examination and FibroTouch measurement to determine liver stiffness (LSM). Serum biochemical parameters were detected and the scoring values of six serological models were calculated. SAS 9.4 statistical software was used for statistical analysis, and the correlation between FibroTouch and the six serological models was analyzed by Spearman correlation. The diagnostic value of FibroTouch and six serological models was analyzed by receiver operating characteristic curve (ROC) based on liver histopathological findings. Results: The median LSM of 258 cases with chronic hepatitis B was 9.4 (6.5-13.8) kPa. In the six serological models, the median value of aspartate transaminase to platelet ratio index (APRI), FIB-4 index, S-index, Forn's index, PRPindex, and FIB-5 were 0.42 (0.28-0.62), 1.27 (0.78-2.03), 0.11 (0.07-0.20), 6.95 (5.89-8.51), 0.000 8 (0.000 6-0.000 9),and 38.59 (36.28-40.97). FibroTouch had positive correlation with APRI, FIB-4, S-index, Forn's index, PRP, fibrosis stage (r= 0.73,P< 0.001) and inflammation grade, and had negative correlation with FIB-5, and both had statistical significance. The area under curve (AUC) of FT-LSM at S≥2, S≥3, S = 4 were 0.89, 0.90 and 0.85, respectively, which was significantly higher than serological models (P< 0.001). The AUC of S-index model at S≥2, S≥3, S = 4 were higher than other five serological models. Conclusion: The diagnostic performance of FibroTouch is significantly better than serological model. S-index model has the best diagnostic performance in the six serological models, and the combination of S-index and FT-LSM may better diagnose the grading of liver fibrosis, and thus can be applied and promoted in clinic.


Assuntos
Biomarcadores , Hepatite B Crônica , Cirrose Hepática , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/patologia , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Curva ROC
18.
J Zoo Wildl Med ; 50(2): 330-336, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260197

RESUMO

Analysis of serum parameters provides information about body condition, nutritional state, and health status of individuals/species, and has broad application in ecological research and veterinary diagnosis. This study establishes baseline values for serum chemistries of the Olrog's gull (Larus atlanticus). Glucose, urea, uric acid, total protein, globulin, albumin, cholesterol, triglyceride, calcium, and phosphorus concentrations were determined, as was the activity of the following enzymes: alkaline phosphatase, creatine phosphokinase, aspartate aminotransferase, and alanine aminotransferase. Thirty nonbreeding gulls (juvenile and subadult individuals) were captured and studied in Mar Chiquita Reserve (Buenos Aires, Argentina) during the wintering periods 2016 (n = 17) and 2017 (n = 13). In general terms, most values for the parameters reported were in line with those previously described for other seabirds. The year had a significant effect on several of the biochemical parameters evaluated, and the sex had a significant effect on the alkaline phosphatase and calcium. This study has defined the serum biochemical reference signatures for free-ranging Olrog's gulls during the nonbreeding period, and contributes to the knowledge of the overall health status of this threatened and endemic species.


Assuntos
Animais Selvagens , Charadriiformes/sangue , Testes Hematológicos/veterinária , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Argentina , Aspartato Aminotransferases/sangue , Glicemia , Proteínas Sanguíneas , Cálcio/sangue , Charadriiformes/fisiologia , Colesterol/sangue , Creatina Quinase/sangue , Feminino , Masculino , Fósforo/sangue , Estações do Ano , Albumina Sérica , Soroglobulinas , Triglicerídeos/sangue , Ureia/sangue , Ácido Úrico/sangue
19.
Int J Nanomedicine ; 14: 4723-4739, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308655

RESUMO

Background: Much consideration has been paid to the toxicological assessment of nanoparticles prior to clinical and biological applications. While in vitro studies have been expanding continually, in vivo investigations of nanoparticles have not developed a cohesive structure. This study aimed to assess the acute toxicity of different concentrations of chitosan-coated silver nanoparticles (Ch-AgNPs) in main organs, including liver, kidneys, and spleen. Materials and methods: Twenty-eight male albino rats were used and divided into 4 groups (n=7). Group 1 was kept as a negative control group. Groups 2, 3, and 4 were treated intraperitoneally with Ch-AgNPs each day for 14 days at doses of 50, 25, and 10 mg/kg body weight (bwt) respectively. Histopathological, morphometric and immunohistochemical studies were performed as well as oxidative stress evaluations, and specific functional examinations for each organ were elucidated. Results: It was revealed that Ch-AgNPs induced dose-dependent toxicity, and the repeated dosing of rats with 50 mg/kg Ch-AgNPs induced severe toxicities. Histopathological examination showed congestion, hemorrhage, cellular degeneration, apoptosis and necrosis in hepatic and renal tissue as well as lymphocytic depletion with increasing tangible macrophages in the spleen. The highest levels of malondialdehyde, alanine aminotransferase, aspartate aminotransferase (MDA, ALT, AST) and the lowest levels of reduced glutathione, immunoglobulin G, M and total protein (GSH, IgG, IgM, TP) were observed in this group. On the other hand, repeated dosing with 25 mg/kg induced mild to moderate disturbance in the previous parameters, while there was no significant difference in results of pathological examination and biochemical tests between the control group and those treated with 10 mg/kg bwt Ch-AgNPs. Conclusion: Chitosan-coated silver nanoparticles induce dose-dependent adverse effects on rats.


Assuntos
Quitosana/química , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Nitrogênio da Ureia Sanguínea , Caspase 3/metabolismo , Creatinina/sangue , Glutationa/metabolismo , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Nanopartículas Metálicas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos Wistar , Baço/efeitos dos fármacos , Baço/patologia
20.
Toxicol Lett ; 313: 188-195, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31284022

RESUMO

Brucine is one of the main bioactive and toxic constituents of the herb drug Semen Strychni. Here we aimed to determine dosing time-dependent hepatotoxicity of brucine, and to investigate the role of metabolism in generation of brucine chronotoxicity. Brucine was administered to wild-type or Npas2-/- (a clock disrupted model) mice at different circadian time points for toxicity and pharmacokinetic characterization. The hepatotoxicity was evaluated by plasma alanine aminotransferase and aspartate aminotransferase measurements and histopathological analysis. The role of Cyp3a11 in brucine metabolism was determined by chemical inhibition assays and Cyp3a11-overexpressing HEK293 cells. Hepatic circadian Cyp3a11 mRNA and protein levels were determined by qPCR and Western blotting, respectively. The toxicity of brucine was more severe in the light phase [Zeitgeber time (ZT) 2 and ZT8] than in the dark phase (ZT14 and ZT20). Chemical inhibition and substrate metabolism assays suggested Cyp3a11 as a significant contributor to brucine metabolism. The Cyp3a11 mRNA, protein and activity in the livers of wild-type mice displayed significant circadian fluctuations. Npas2 ablation markedly down-regulated Cyp3a11 mRNA, protein and activity, and abrogated their circadian rhythms. The circadian time differences in brucine pharmacokinetics and liver distribution were lost in Npas2-/- mice, so were the time differences in brucine hepatotoxicity. In conclusion, chronotoxicity of brucine was determined by circadian variations in Cyp3a11 metabolism. The findings have implications in improving brucine (and possibly Semen Strychni) efficacy via dosing time optimization.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Ritmo Circadiano , Citocromo P-450 CYP3A/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Proteínas de Membrana/metabolismo , Fotoperíodo , Estricnina/análogos & derivados , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Ritmo Circadiano/genética , Cronoterapia Farmacológica , Células HEK293 , Humanos , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Estricnina/administração & dosagem , Estricnina/metabolismo , Estricnina/farmacocinética , Estricnina/toxicidade
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