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1.
Anticancer Res ; 39(10): 5755-5760, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570478

RESUMO

BACKGROUND/AIM: After primary resection of hepatocellular carcinoma (HCC), the impact of patient's characteristics at the initial hepatectomy, on long-term remnant liver function has not been reported. The aim of this study was to identify factors associated with the deterioration of remnant liver function among patients who developed recurrent HCC. PATIENTS AND METHODS: A total of 51 patients with intrahepatic recurrence after initial hepatic resection for HCC were included. We retrospectively investigated the relation between patient characteristics and the degree of deterioration of remnant liver function upon recurrence. RESULTS: In univariate analysis, significant predictors of deterioration of remnant liver function consisted of preoperative gastro-esophageal varices (p=0.0101), preoperative transcatheter arterial chemoembolization (p=0.0230) and hepatectomy beyond Makuuchi's criteria (p=0.0101). In multivariate analysis, the only significant independent predictor of deterioration of remnant liver function was hepatectomy beyond Makuuchi's criteria (p=0.0498). CONCLUSION: Hepatectomy beyond Makuuchi's criteria at the initial hepatectomy may predict deterioration of remnant liver function upon recurrence of HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/patologia , Fígado/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/cirurgia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Feminino , Hepatectomia/métodos , Humanos , Fígado/cirurgia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Fatores de Risco
2.
Medicine (Baltimore) ; 98(39): e17305, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574858

RESUMO

Until now, the recognition of sodium taurocholate cotransporting polypeptide (NTCP) deficiency has been mainly based on sporadic case reports. It was previously believed to be mildly symptomatic and resulting in mild liver dysfunction. However, to our knowledge, there have been no reports about the histopathologic and ultrastructural pathologic characteristics of the disease. The aim of the study was to analyze the clinical, histopathologic and ultrastructural pathologic characteristics of NTCP deficiency in 13 pediatric patients.From August 2012 to October 2018, this retrospective study conducted in the Department of Pediatrics of Tongji Hospital, China analyzed the data of 13 NTCP deficient patients with an SLC10A1 gene mutation. Except for NTCP deficiency, no other liver diseases were present in the patients, which was determined by both a genetic testing panel for jaundice and by reviewing medical records. The laboratory results, imaging, histopathologic, and ultrastructural pathologic information were recorded for analysis.The serum level of total bile acid was high in all 13 patients. All patients had adequate growth and development. Eight of the patients (8/13) presented with visible jaundice and 12 (12/13) were found to have hyperbilirubinemia. A needle liver biopsy was performed in 11 cases, which revealed slightly chronic inflammation in all 11 patients. One of the patients (1/13) was found to be suffering from gallstones.The data showed that although NTCP deficiency was often asymptomatic, some of the patients showed obvious clinical expressions, such as jaundice. Among the 13 pediatric patients with NTCP deficiency, both the biochemical and histopathologic features were similar to those of mild hepatocellular jaundice. In addition, it was determined that the clinical features in the patient with gallstones may have been caused by NTCP deficiency.


Assuntos
Ácidos e Sais Biliares/sangue , Icterícia , Hepatopatias , Fígado , Transportadores de Ânions Orgânicos Dependentes de Sódio , Simportadores , Desenvolvimento Infantil , Pré-Escolar , China/epidemiologia , Testes Genéticos/métodos , Humanos , Biópsia Guiada por Imagem/métodos , Lactente , Icterícia/diagnóstico , Icterícia/etiologia , Fígado/metabolismo , Fígado/patologia , Hepatopatias/diagnóstico , Hepatopatias/genética , Hepatopatias/fisiopatologia , Hepatopatias/terapia , Testes de Função Hepática/métodos , Glicoproteínas de Membrana/metabolismo , Mutação , Transportadores de Ânions Orgânicos Dependentes de Sódio/deficiência , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Pediatria/métodos , Estudos Retrospectivos , Simportadores/deficiência , Simportadores/genética
3.
Rev Soc Bras Med Trop ; 52: e20180526, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31508780

RESUMO

INTRODUCTION: Crotalus envenomations cause serious complications and can be fatal without appropriate treatment. Venom isoforms present and inter/intraspecific variations in the venom composition can result in different symptoms presented by bites by snakes from the same species but from different geographical regions. We comparatively evaluated the local and systemic effects caused by Crotalus durissus terrificus (Cdt), C.d. collilineatus (Cdcolli), and C.d. cascavella (Cdcasc) envenomation. METHODS: Venom chromatography was performed. Proteolytic, phospholipase, and LAAO activities were analyzed. Edema, myotoxicity, hepatotoxicity, nephrotoxicity, and coagulation alterations were evaluated. RESULTS: The venom SDS-PAGE analyses found the presence of convulxin, gyroxin, crotoxin, and crotamine in Cdt and Cdcolli venoms. Crotamine was not present in the Cdcasc venom. Cdt, Cdcollli, and Cdcasc venoms had no proteolytic activity. Only Cdcasc and Cdt venoms had phospholipase activity. LAAO activity was observed in Cdcolli and Cdcasc venoms. Cdcolli and Cdcasc venoms caused 36.7% and 13.3% edema increases, respectively. Cdt venom caused a 10% edema induction compared to those by other venoms. All venoms increased TOTAL-CK, MB-CK, and LDH levels (indicating muscle injury) and ALT, AST, GGT, and ALP levels (markers of liver damage) and were able to induce a neuromuscular blockade. Urea and creatinine levels were also altered in both plasma and urine, indicating kidney damage. Only Cdcolli and Cdcasc venoms increased TAPP and TAP. CONCLUSIONS: Together, these results allow us to draw a distinction between local and systemic effects caused by Crotalus subspecies, highlighting the clinical and biochemical effects produced by their respective venoms.


Assuntos
Venenos de Crotalídeos/toxicidade , Crotalus/classificação , Edema/induzido quimicamente , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fosfatase Alcalina/sangue , Fosfatase Alcalina/efeitos dos fármacos , Animais , Creatina Quinase/sangue , Creatina Quinase/efeitos dos fármacos , Creatinina/sangue , Edema/patologia , Eletroforese em Gel de Poliacrilamida , Rim/patologia , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/efeitos dos fármacos , Fígado/patologia , Camundongos , Modelos Animais , Transaminases/sangue , Transaminases/efeitos dos fármacos , Ureia/sangue
5.
Sud Med Ekspert ; 62(4): 58-60, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31407708

RESUMO

Eating mushrooms known to contain amatoxin is fraught with serious complications. The analysis of the relevant literature publications revealed no article with the description of the histological picture of the internal organs in the subjects intoxicated with amatoxin. It is known, however, that such poisoning is associated with the severe irreversible injuries to all intracellular protein structures the character of which depends on time. Specifically, acute amatoxin intoxication produces the well apparent clinical picture within 6 days after intake of the poison. It is characterized by acute renal and hepatic insufficiency in the combination with the injury to the conducting system of heart and the myocrardium itself. Thereafter, the disseminated intravascular coagulation (DIC) syndrome developed accompanied by the signs of progressive tissue hypoxia that ended in death on day 9. The histological study has demonstrated necrotic foci in the liver and oedematous hepatic stroma. Kidneys underwent multiple hemorrhages, necrosis of convoluted tubules and well apparent hydropic protein dystrophy of their epithelium. The adrenal glands showed up signs of necrosis and hemorrhage. It is concluded that poisoning with mushrooms (amatoxin) should be regarded as the most probable cause of the condition requiring differential diagnostics between acute gastroenteritis and renal insufficiency.


Assuntos
Amanita/química , Amanitinas/envenenamento , Rim/patologia , Fígado/patologia , Intoxicação Alimentar por Cogumelos/diagnóstico , Humanos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos
6.
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
7.
Presse Med ; 48(7-8 Pt 2): e245-e250, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31445698

RESUMO

Embolization and percutaneous ablations became well-established therapeutic options for hepatocellular carcinomas (HCC). All are performed under minimally invasive conditions using imaging guidance. Selection of a technique over another follows guidelines but also patient's status and availability of the techniques. The aim of this review is to present these techniques performed in routine to treat HCC and to report the outcomes.


Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Neoplasias Hepáticas/cirurgia , Cirurgia Assistida por Computador/métodos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/estatística & dados numéricos , Terapia Combinada , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Humanos , Fígado/irrigação sanguínea , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Radioterapia Guiada por Imagem/efeitos adversos , Radioterapia Guiada por Imagem/métodos , Cirurgia Assistida por Computador/efeitos adversos , Cirurgia Assistida por Computador/estatística & dados numéricos , Resultado do Tratamento
8.
Presse Med ; 48(7-8 Pt 2): e219-e231, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447333

RESUMO

Image-guided ablation is performed by percutaneously introducing ablation probes to deliver energy into a tumor to destroy it in a controlled and localized fashion. Ablation modalities can be broadly classified as thermal or non-thermal based on the mechanism of tumor destruction and are performed using different types of image guidance for planning, delivering and follow-up of the treatment. Ablation is performed in a minimally invasive fashion, providing greater residual organ preservation with minimal morbidity to the patient. Image-guided ablation is being used in the clinic for the treatment of primary and metastatic tumors, and this article reviews state of the art for the treatment of malignancies in the liver, lung, kidney and musculoskeletal tissue.


Assuntos
Ablação por Cateter/métodos , Neoplasias/cirurgia , Cirurgia Assistida por Computador/métodos , Ablação por Cateter/efeitos adversos , Tecido Conjuntivo/patologia , Tecido Conjuntivo/cirurgia , Humanos , Rim/patologia , Rim/cirurgia , Fígado/patologia , Fígado/cirurgia , Pulmão/patologia , Pulmão/cirurgia , Sistema Musculoesquelético/patologia , Sistema Musculoesquelético/cirurgia , Neoplasias/diagnóstico , Neoplasias/patologia , Especificidade de Órgãos , Complicações Pós-Operatórias/etiologia , Cirurgia Assistida por Computador/efeitos adversos , Resultado do Tratamento
9.
Exp Parasitol ; 205: 107733, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31408623

RESUMO

Toxoplasma gondii is a ubiquitous protozoan of major medical and veterinary importance. Its treatment is difficult since the available drugs have severe side effects and reactivation may occur anytime. Vaccination with irradiated parasites exhibits ideal characteristics for vaccine development. In our experimental mice model, the protection against challenge with the virulent RH strain was assessed, using 255Gy irradiated tachyzoites. Eighty mice were allocated into 3 groups: naive control group, challenged with virulent RH tachyzoites group and a third group which is challenged with 1 × 106 irradiated tachyzoites, administered as two biweekly doses intraperitoneally. Protection was tested by challenging vaccinated mice with the virulent type RH tachyzoites 30 days after the 2nd vaccination dose. The assessment was built on qualitative clinical, quantitative parasitological, histopathological parameters and measurement of serum Nitric Oxide (NO). The results showed prolonged survival rate, absence of tachyzoites in the peritoneal aspirate by counting, absence of tachyzoites in all examined organs by impression smears, amelioration of histopathological changes in the liver, spleen, brain and lung specimens and increase of the serum NO level in the vaccinated group. Therefore, we propose that irradiated Toxoplasma tachyzoites confer protection for challenged mice and could be an alternative immunization schedule for vaccine development especially for who are at risk of severe immunosuppression.


Assuntos
Toxoplasma/imunologia , Toxoplasma/efeitos da radiação , Toxoplasmose Animal/prevenção & controle , Toxoplasmose Animal/parasitologia , Vacinação/métodos , Animais , Líquido Ascítico/parasitologia , Encéfalo/parasitologia , Encéfalo/patologia , Colorimetria , Feminino , Raios gama , Fígado/parasitologia , Fígado/patologia , Pulmão/parasitologia , Pulmão/patologia , Camundongos , Óxido Nítrico/análise , Baço/parasitologia , Baço/patologia , Taxa de Sobrevida , Toxoplasmose Animal/imunologia , Toxoplasmose Animal/mortalidade
10.
Exp Parasitol ; 205: 107736, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31442455

RESUMO

Goats are frequently described as an intermediate host for the protozoan Neospora caninum, manifesting the disease mainly by recurrent abortions with placentitis and encephalitis in fetuses. Several reports of natural and experimental infections in cattle and mice show differences in the immune response, and the outcome of the infection can be variable depending on the species affected and by the behavior of the infective strain. This study describes for the first time two Neospora caninum strains isolated from naturally infected goats from the state of Minas Gerais, Brazil. One placenta and one brain from different goats were processed for a first bioassay in gerbils (Meriones unguiculatus). Subsequently, a second bioassay was performed by inoculating the processed brain samples from gerbils into Interferon gamma (IFN-γ) knockout mice (KO mice). Tachyzoites collected from the peritoneal fluid of the KO mice were inoculated into VERO cell monolayers, where they presented a very slow growth rate. The tachyzoites were also inoculated into BALB/c mice with a dose of 106 tachyzoites per animal. After a 5-week follow up, the animals infected with both of the strains developed a strong polarized Th1 response with increased serum and spleen gene expression levels of pro-inflammatory cytokines (mainly IFN-γ and TNF-α) in the first week. Tissue lesions were mild in the animals infected with both strains. Despite the strong immune response preventing an infection in the visceral organs, the parasite was able to reach the brain, causing progressive brain lesions from the second to fifth week post infection. The NC-goat1-infected mice presented with severe meningoencephalitis, but the NC-goat2-infected animals had considerable histological brain lesions only at week 5. Immunohistochemical analysis of the mouse brains revealed a different pattern of inflammatory cells compared to the naturally infected goats. A severe inflammatory infiltrate of CD3+ T lymphocytes was found in the NC-goat1-infected mice. A more discrete infiltrate of CD3+ T cells was found in the NC-goat2-infected animals. Additionally, IBA1 IHC revealed an intense microglial reaction and monocyte perivascular cuffs in the NC-goat1-infected animals and lower microglia/monocyte infiltrates in the NC-goat2-infected mice. This work contributes knowledge on the pathogenicity of new Neospora caninum strains in mice, comparable with other well-established mouse models of the disease, and demonstrates the importance of studying goats as an intermediate host of this parasite.


Assuntos
Coccidiose/veterinária , Doenças das Cabras/parasitologia , Neospora/patogenicidade , Animais , Bioensaio/veterinária , Encéfalo/parasitologia , Encéfalo/patologia , Cercopithecus aethiops , Coccidiose/parasitologia , Coccidiose/patologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Gerbillinae , Doenças das Cabras/patologia , Cabras , Imuno-Histoquímica/veterinária , Interferon gama/genética , Interferon gama/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neospora/isolamento & purificação , Pâncreas/patologia , Placenta/patologia , Gravidez , Baço/metabolismo , Baço/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Células Vero
11.
Medicine (Baltimore) ; 98(35): e16909, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464924

RESUMO

RATIONALE: Congenital hepatic fibrosis (CHF) is an autosomal recessive disease characterized by periportal fibrosis, portal hypertension, and renal cystic disease. Essentially, CHF is a variant of fibrocystic disorder in which liver and kidney are commonly affected. Other frequently associated conditions include Caroli syndrome and polycystic kidney disease. CHF is also a known accompaniment in an array of inherited disorders with multiorgan involvement. PATIENT CONCERNS: The 20-year-old male patient with declining vision (14 years duration), intermittent gingival bleeding (7 years duration), and abdominal distension (5 years duration), presented with exacerbation of these symptoms during the prior 2 months. The patient had been previously diagnosed with retinal macular degeneration, idiopathic thrombocytopenic purpura, and hepatosplenomegaly. DIAGNOSES: Liver biopsy showed disordered hepatic acini and fibrous parenchymal banding, indicative of CHF. INTERVENTIONS: After the treatment of diuresis and liver protectants, the clinical symptoms of the patients were improved. We subsequently recommend chromosomal analysis, although the family refused. OUTCOMES: Three months after discharge, the patient was followed up by telephone. The patient had obvious abdominal distension and we advised that he should be admitted again. But the family refused. LESSONS: CHF is an AR disease resulting in portal hypertension and often associated with renal malformations. CHF is also linked to a number of other disorders, many of which are ciliopathies. Because the clinical manifestations of CHF are nonspecific or lacking, its diagnosis is problematic, relying largely on liver biopsy. Once CHF is identified, physicians are obligated to investigate other organ systems, particularly a search for neuromuscular, retina or renal involvement. This case underscores the value of radiologic imaging, pathologic examination, and genetic testing in successfully diagnosing a rare disease.


Assuntos
Doenças Genéticas Inatas/diagnóstico , Cirrose Hepática/diagnóstico , Fígado/patologia , Biópsia , Doenças Genéticas Inatas/complicações , Doenças Genéticas Inatas/patologia , Hemorragia Gengival/etiologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Degeneração Macular , Masculino , Recusa do Paciente ao Tratamento , Adulto Jovem
13.
Acta Gastroenterol Belg ; 82(2): 267-272, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314187

RESUMO

PURPOSE: In this study we aimed to compare and evaluate the efficacies of the low and high b value diffusion weighted imaging (DWI) sequences with three different T2-weighted (T2W) sequences. MATERIALS AND METHODS: 255 liver lesions of 147 patients who had undergone MR examinations of the upper abdomen were evaluated. A maximum number of 4 lesions was taken for consideration in patients with multiple lesions. Low and high b valued DWI and 3 different T2W sequences (SSFSE, FIESTA, and PROPELLER FSE) were utilized. The evaluations were done by 3 different radiologists, by utilizing the double blind principle. RESULTS: The lesion detection performances of the b 0 DWI, b 600 DWI, FIESTA T2W, SSFSE T2W, and PROPELLER FSE T2W sequences, were 95.7 %, 66.3 %, 94.4 %, 92.8 %, and 93.8 %, in sequence order. The high b value DWI sequence was able to detect malignant lesions with a higher accuracy rate than the T2W sequences. There was a moderate to high rate of agreement among the interpreters, and the lesion-detection rates of the interpreters were in line with their levels of expertise. CONCLUSION: Even though the higher lesion detection rates of the DWI sequences were not found to be statistically significant, it was concluded that making the evaluations with the addition of DWI to the imaging protocol would certainly decrease the lesion-missing rate, and it would be wise to utilize the DWI technique in routine liver MR imaging.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias Hepáticas/diagnóstico , Fígado/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Método Duplo-Cego , Humanos , Fígado/patologia
14.
Cell Physiol Biochem ; 53(2): 301-322, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31343125

RESUMO

BACKGROUND/AIMS: Propolis is one of the most promising natural products, exhibiting not only therapeutic but also prophylactic actions. Propolis has several biological and pharmacological properties, including hepatoprotective activities. The present study aimed to investigate the underlying molecular mechanisms of propolis against CCl4-mediated liver fibrosis. METHODS: Three groups of male BALB/c mice (n=15/ group) were used: group 1 comprised control mice; groups 2 and 3 were injected with CCl4 for the induction of liver fibrosis. Group 3 was then orally supplemented with propolis (100 mg/kg body weight) for four weeks. Different techniques were used to monitor the antifibrotic effects of propolis, including histopathological investigations using H&E, Masson's trichrome and Sirius red staining; Western blotting; flow cytometry; and ELISA. RESULTS: We found that the induction of liver fibrosis by CCl4 was associated with a significant increase in hepatic collagen and α-smooth muscle actin (α-SMA) expression. Moreover, CCl4-treated mice also exhibited histopathological alterations in the liver architecture. Additionally, the liver of CCl4-treated mice exhibited a marked increase in proinflammatory signals, such as increased expression of HSP70 and increased levels of proinflammatory cytokines and ROS. Mechanistically, the liver of CCl4-treated mice exhibited a significant increase in the phosphorylation of AKT and mTOR; upregulation of the expression of BAX and cytochrome C; downregulation of the expression of Bcl2; a significant elevation in the levels of TGF-ß followed by increased phosphorylation of SMAD2; and a marked increase in the expression of P53 and iNOS. Interestingly, oral supplementation of CCl4-treated mice with propolis significantly abolished hepatic collagen deposition, abrogated inflammatory signals and oxidative stress, restored CCl4-mediated alterations in the signaling cascades, and hence repaired the hepatic architecture nearly to the normal architecture observed in the control mice. CONCLUSION: Our findings revealed the therapeutic potential and the underlying mechanisms of propolis against liver fibrosis.


Assuntos
Apoptose/efeitos dos fármacos , Cirrose Hepática Experimental/patologia , Própole/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Tetracloreto de Carbono/toxicidade , Citocinas/metabolismo , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase Tipo II/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína Smad2/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo
15.
Cancer Immunol Immunother ; 68(8): 1369-1378, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31338558

RESUMO

Intrahepatic cholangiocarcinoma (ICC) is a rare malignancy with poor prognosis. The evaluation of recurrence risk after liver resection is of great importance for ICCs. We aimed to assess the prognostic value of intra- and peritumoral immune infiltrations and to establish a novel histopathology-related immunoscore (HRI) associated with ICC recurrence. A total of 280 ICC patients who received curative resection between February 2005 and July 2011 were enrolled in our study. Patients were randomly assigned to the derivation cohort (n = 176) or the validation cohort (n = 104). Sixteen immune biomarkers in both intra- and peritumoral tissues were examined by immunohistochemistry. The least absolute shrinkage and selection operator (LASSO) Cox model was used to establish the HRI score. Cox regression analysis was used for multivariate analysis. Nine recurrence-related immune features were identified and integrated into the HRI score. The HRI score was used to categorize patients into low-risk and high-risk groups using the X-tile software. Kaplan-Meier analysis presented that the HRI score showed good stratification between low-risk and high-risk groups in both the derivation cohort (P < 0.001) and the validation cohort (P = 0.014), respectively. Multivariate analysis demonstrated that serum γ-glutamyl transpeptidase, carbohydrate antigen 19-9, lymphoid metastasis, tumor numbers, and the HRI score were independent risk factors associated with recurrence-free survival (RFS). The combination of Shen's model and HRI score provided better performance in recurrence prediction compared with traditional staging systems. The HRI score might serve as a promising RFS predictor for ICC with prognostic values.


Assuntos
Antígenos Glicosídicos Associados a Tumores/metabolismo , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/diagnóstico , Neoplasias Hepáticas/diagnóstico , Fígado/metabolismo , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Estudos de Coortes , Feminino , Hepatectomia , Humanos , Fígado/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Prognóstico , Projetos de Pesquisa , Análise de Sobrevida , Carga Tumoral , gama-Glutamiltransferase/metabolismo
16.
Medicine (Baltimore) ; 98(28): e16429, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305465

RESUMO

Significant liver histological changes (SLHC) were defined as moderate to severe liver inflammation (A2 or higher) and/or fibrosis (F2 or higher) using the METAVIR scoring system. This study aimed to develop an algorithm for the non-invasive detection of SLHC in patients with chronic hepatitis B (CHB) and normal or mildly elevated alanine transaminase (ALT) levels.Using liver histology as gold standard, we developed a simple algorithm for the diagnosis of SLHC in a training set (504 patients), and then validated the diagnostic accuracy in a validation set (166 patients).A new algorithm (AAG) attributed to age, ALT, and gamma-glutamyl transpeptidase (GGT) was developed. In the training set, the area under ROC curve (AUROC) of AAG was significantly higher than that of ALT, aspartate transaminase (AST), GPR, and APRI for the diagnosis of SLHC (0.74, 0.68, 0.65, 0.56, and 0.53, respectively; all P < .05). In the validation set, the AUROC of AAG was also higher than that of ALT, AST, GPR, and APRI (0.73, 0.65, 0.62, 0.62, and 0.61, respectively; all P < .05). Using AAG ≥ 2, the sensitivity and negative predictive value was 84% to 98% and 75% to 94%, respectively, for the diagnosis of SLHC. Using AAG ≥ 6, the specificity and positive predictive value was 93% to 97% and 67% to 79%, respectively, for the diagnosis of SLHC.The AAG algorithm represents a novel noninvasive method for the diagnosis of SLHC in CHB patients with normal or mildly elevated ALT levels.


Assuntos
Alanina Transaminase/sangue , Algoritmos , Hepatite B Crônica/diagnóstico , Inflamação/diagnóstico , Cirrose Hepática/diagnóstico , Adulto , Biomarcadores/sangue , Biópsia , Feminino , Hepatite B Crônica/enzimologia , Humanos , Inflamação/enzimologia , Fígado/patologia , Cirrose Hepática/enzimologia , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
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
18.
Exp Parasitol ; 204: 107728, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31348915

RESUMO

BACKGROUND: Co-infection with Leishmania major and Schistosoma mansoni may have significant consequences for disease progression, severity and subsequent transmission dynamics. Pentavalent antimonials and Praziquantel (PZQ) are used as first line of treatment for Leishmania and Schistosoma infections respectively. However, there is limited insight on how combined therapy with the standard drugs impacts the host in comorbidity. The study aimed to determine the efficacy of combined chemotherapy using Pentostam (P) and PZQ in murine model co-infected with L. major and S. mansoni. METHODS: A 3 × 4 factorial design with three parasite infection groups (Lm, Sm, Lm + Sm to represent L. major, S. mansoni and L. major + S. mansoni respectively) and four treatment regimens [P, PZQ, P + PZQ, and PBS designating Pentostam (GlaxoSmithKline UK), Praziquantel (Biltricide®, Bayer Ag. Leverkusen, Germany), Pentostam + Praziquantel and Phosphate buffered saline] as factors was applied. RESULTS: Significant changes were observed in the serum Interferon gamma (IFN-γ), and Macrophage inflammatory protein-one alpha (MIP-1α) levels among various treatment groups between week 8 and week 10 (p < 0.05). There was increased IFN-γ in the L. major infected mice subjected to PZQ and PBS, and in L. major + S. mansoni infected BALB/c mice treated with P + PZQ. Subsequently, MIP-1α levels increased significantly in both the L. major infected mice under PZQ and PBS and in L. major + S. mansoni infected BALB/c mice undergoing concurrent chemotherapy with P + PZQ between 8 and 10 weeks (p < 0.05). In the comorbidity, simultaneous chemotherapy resulted in less severe histopathological effects in the liver. CONCLUSION: It was evident, combined first line of treatment is a more effective strategy in managing co-infection of L. major and S. mansoni. The findings denote simultaneous chemotherapy compliments immunomodulation in the helminth-protozoa comorbidity hence, less severe pathological effects following the parasites infection. Recent cases of increased incidences of polyparasitism in vertebrates call for better ways to manage co-infections. The findings presented necessitate intrinsic biological interest on examining optimal combined chemotherapeutic agents strategies in helminth-protozoa concomitance and the related infections abatement trends vis-a-vis host-parasite relationships.


Assuntos
Anti-Helmínticos/uso terapêutico , Antiprotozoários/uso terapêutico , Comorbidade , Leishmania major/patogenicidade , Leishmaniose Cutânea/complicações , Esquistossomose mansoni/complicações , Análise de Variância , Animais , Anti-Helmínticos/administração & dosagem , Gluconato de Antimônio e Sódio/administração & dosagem , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/administração & dosagem , Quimiocina CCL3/sangue , Modelos Animais de Doenças , Quimioterapia Combinada , Interferon gama/sangue , Leishmania major/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/patologia , Fígado/parasitologia , Fígado/patologia , Camundongos , Camundongos Endogâmicos BALB C , Praziquantel/administração & dosagem , Praziquantel/uso terapêutico , Schistosoma mansoni/efeitos dos fármacos , Schistosoma mansoni/patogenicidade , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/patologia
19.
Zhonghua Gan Zang Bing Za Zhi ; 27(7): 481-482, 2019 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-31357770

RESUMO

Liver cancer (HCC) holds third position for cause of cancer-related death worldwide. Therefore, it is urgent to explore new strategies for the diagnosis and treatment of liver cancer. Illustrating the successful experience of other tumors on precancerous lesions, this paper puts forward the idea of advance strategy for the diagnosis and treatment through dysplastic nodules, especially high-grade dysplastic nodules, which can reduce or delay the carcinogenesis of some patients with cirrhosis. It is hoped that this measure might improve the present situation of diagnosis and treatment of liver cancer in coming days in China.


Assuntos
Carcinoma Hepatocelular , Cirrose Hepática , Neoplasias Hepáticas , Fígado/patologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/terapia , China , Humanos
20.
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
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