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1.
Nihon Shokakibyo Gakkai Zasshi ; 117(10): 907-913, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33041302

RESUMO

A 76-year-old woman suffered from repeated postprandial syncope of unknown cause. Computed tomography scanning revealed an enlarged hiatal hernia sac with food residues that compressed both the left atrium and inferior vena cava. As soon as the hernia cavity expanded during an upper gastrointestinal X-ray examination, she experienced a deterioration of her level of consciousness. Therefore, we diagnosed her of a swallow syncope due to left atrium compression by the huge hernia sac. The sac also compressed the inferior vena cava, and she experienced a transient elevation of her hepatobiliary enzyme level probably due to the influence of the congestive liver. Thus, clinicians should always keep this condition in mind when encountering patients with post-meal syncope.


Assuntos
Hérnia Hiatal , Idoso , Dilatação , Feminino , Hérnia Hiatal/complicações , Hérnia Hiatal/diagnóstico por imagem , Humanos , Fígado , Síncope/etiologia , Tomografia Computadorizada por Raios X
2.
Rev Col Bras Cir ; 47: e20202610, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33053064

RESUMO

Brazil, like most countries in the world, experiences the expansion of extended criteria donors, mainly due to the aging of the population and the obesity epidemic. Concerns regarding the quality of these organs along with the vast territorial areas of the country compromise the utilization rate of livers from donors and aggravate the discrepancy between the number of liver transplants performed and the needed. Ex situ liver machine perfusion offers superior preservation for livers from extended criteria donors, limiting cold ischaemia time and offering the possibility of evaluation of their function before transplantation as well as the reconditioning of marginal organs. Objections such as the financial cost, difficulty in transporting the device between hospitals, and demand of trained professionals in the handling of the device must be pondered with the possibility of increasing the number of transplants and the utilisation rate of donor organs. The optimal use of this resource, through the careful selection of donors and the appropriate technical and scientific knowledge, can ensure an effective and successful implementation of this technology.


Assuntos
Transplante de Fígado , Fígado Artificial , Preservação de Órgãos , Perfusão , Doadores de Tecidos , Brasil , Humanos , Fígado
3.
PLoS One ; 15(10): e0240400, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33031439

RESUMO

BACKGROUND & AIMS: Although metabolic risk factors are associated with more severe COVID-19, there is little evidence on outcomes in patients with non-alcoholic fatty liver disease (NAFLD). We here describe the clinical characteristics and outcomes of NAFLD patients in a cohort hospitalised for COVID-19. METHODS: This study included all consecutive patients admitted for COVID-19 between February and April 2020 at Imperial College Healthcare NHS Trust, with either imaging of the liver available dated within one year from the admission or a known diagnosis of NAFLD. Clinical data and early weaning score (EWS) were recorded. NAFLD diagnosis was based on imaging or past medical history and patients were stratified for Fibrosis-4 (FIB-4) index. Clinical endpoints were admission to intensive care unit (ICU)and in-hospital mortality. RESULTS: 561 patients were admitted. Overall, 193 patients were included in the study. Fifty nine patients (30%) died, 9 (5%) were still in hospital, and 125 (65%) were discharged. The NAFLD cohort (n = 61) was significantly younger (60 vs 70.5 years, p = 0.046) at presentation compared to the non-NAFLD (n = 132). NAFLD diagnosis was not associated with adverse outcomes. However, the NAFLD group had higher C reactive protein (CRP) (107 vs 91.2 mg/L, p = 0.05) compared to non-NAFLD(n = 132). Among NAFLD patients, male gender (p = 0.01), ferritin (p = 0.003) and EWS (p = 0.047) were associated with in-hospital mortality, while the presence of intermediate/high risk FIB-4 or liver cirrhosis was not. CONCLUSION: The presence of NAFLD per se was not associated with worse outcomes in patients hospitalised for COVID-19. Though NAFLD patients were younger on admission, disease stage was not associated with clinical outcomes. Yet, mortality was associated with gender and a pronounced inflammatory response in the NAFLD group.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Hepatopatia Gordurosa não Alcoólica/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Fatores Etários , Idoso , Betacoronavirus , Estudos de Coortes , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Feminino , Mortalidade Hospitalar , Humanos , Fígado/patologia , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/mortalidade , Hepatopatia Gordurosa não Alcoólica/patologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Fatores Sexuais
4.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1396-1399, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018250

RESUMO

Accurate detection of macro and microvesicles in rat models of fatty liver disease is crucial in evaluating the progression of liver disease and identifying potential hepatotoxic findings during drug development. In this paper, we present a deep-learning-based framework for the segmentation of vacuoles in liver images of Wistar rat and study the correlation of automated quantification with expert pathologist's manual evaluation. To address the issue of misclassification of lumina (vascular and bile duct) as large vacuoles, we propose a selective tiling technique to generate tiles that include complete lumina and large vacuoles. A binary encoder-decoder convolution neural network is trained to detect individual vacuoles. We report a sensitivity of 85% and specificity of 98%. Furthermore, the diameter and roundness of the segmented vacuoles are estimated with an error of less than 8%, which supports the high potential of our method in drug development process.


Assuntos
Fígado , Vacúolos , Animais , Fígado/diagnóstico por imagem , Redes Neurais de Computação , Ratos , Ratos Wistar , Sensibilidade e Especificidade
5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1608-1611, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018302

RESUMO

Computed tomography (CT) and magnetic resonance imaging (MRI) scanners measure three-dimensional (3D) images of patients. However, only low-dimensional local two-dimensional (2D) images may be obtained during surgery or radiotherapy. Although computer vision techniques have shown that 3D shapes can be estimated from multiple 2D images, shape reconstruction from a single 2D image such as an endoscopic image or an X-ray image remains a challenge. In this study, we propose X-ray2Shape, which permits a deep learning-based 3D organ mesh to be reconstructed from a single 2D projection image. The method learns the mesh deformation from a mean template and deep features computed from the individual projection images. Experiments with organ meshes and digitally reconstructed radiograph (DRR) images of abdominal regions were performed to confirm the estimation performance of the methods.


Assuntos
Imageamento Tridimensional , Tomografia Computadorizada por Raios X , Humanos , Fígado/diagnóstico por imagem , Imagem por Ressonância Magnética
6.
Nat Commun ; 11(1): 4964, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009394

RESUMO

Thrombosis leads to platelet activation and subsequent degradation; therefore, replenishment of platelets from hematopoietic stem/progenitor cells (HSPCs) is needed to maintain the physiological level of circulating platelets. Platelet-derived microparticles (PMPs) are protein- and RNA-containing vesicles released from activated platelets. We hypothesized that factors carried by PMPs might influence the production of platelets from HSPCs, in a positive feedback fashion. Here we show that, during mouse acute liver injury, the density of megakaryocyte in the bone marrow increases following an increase in circulating PMPs, but without thrombopoietin (TPO) upregulation. In vitro, PMPs are internalized by HSPCs and drive them toward a megakaryocytic fate. Mechanistically, miR-1915-3p, a miRNA highly enriched in PMPs, is transported to target cells and suppresses the expression levels of Rho GTPase family member B, thereby inducing megakaryopoiesis. In addition, direct injection of PMPs into irradiated mice increases the number of megakaryocytes and platelets without affecting TPO levels. In conclusion, our data reveal that PMPs have a role in promoting megakaryocytic differentiation and platelet production.


Assuntos
Plaquetas/metabolismo , Diferenciação Celular , Micropartículas Derivadas de Células/metabolismo , Megacariócitos/citologia , MicroRNAs/metabolismo , Animais , Sequência de Bases , Linhagem Celular , Endocitose , Perfilação da Expressão Gênica , Humanos , Fígado/lesões , Fígado/patologia , Masculino , Megacariócitos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/genética , Poliploidia , Proteína rhoB de Ligação ao GTP/metabolismo
7.
Mar Environ Res ; 160: 104992, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32907729

RESUMO

Livers from dab (Limanda limanda), plaice (Pleuronectes platessa) and flounder (Platichthys flesus) sampled from the Baltic Sea were used to determine the interaction of flatfish CYP1A enzymes with 2,4,6-trinitrotoluene (TNT) in vitro. Competitive inhibition of 7-ethoxyresorufin-O-deethylase (EROD) and 7-methoxyresorufin-O-deethylase (MROD) could be demonstrated for all three flatfish species. The highest inhibition of CYP1A activities was measured in liver samples of flounder resulting in a half maximal inhibitory concentration (IC50) of 28.1 µM TNT. Due to their lower inhibition (EROD IC50 65.2 µM TNT, MROD IC50 40.3 µM TNT), dab liver samples were used to conduct in vitro metabolization experiments with TNT. The metabolization of TNT in fish was investigated with post-mitochondrial fractions (PMF) of dab liver as a model system after adding different cofactors. Rapid and time-dependent enzymatic degradation of TNT was observed. The concentrations of 4-amino-2,6-dinitrotoluene and 2-amino-4,6-dinitrotoluene increased in the samples over time. Additionally, 2,2,6,6-tetranitro-4,4-azoxytoluene was detected in one sample. The results of this study indicate that in vitro experiments are useful to investigate the xenobiotic metabolism of fish under controlled conditions prior to field studies. The metabolites found can serve as target compounds for marine monitoring of TNT contamination in munition dumpsites.


Assuntos
Linguado , Trinitrotolueno , Poluentes Químicos da Água , Animais , Citocromo P-450 CYP1A1 , Fígado , Trinitrotolueno/farmacocinética , Trinitrotolueno/toxicidade , Poluentes Químicos da Água/farmacocinética , Poluentes Químicos da Água/toxicidade
8.
Am J Vet Res ; 81(10): 796-803, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32969732

RESUMO

OBJECTIVE: To determine the change in mean hepatic apparent diffusion coefficient (ADC) and hepatic fat fraction (HFF) during body weight gain in cats by use of MRI. ANIMALS: 12 purpose-bred adult neutered male cats. PROCEDURES: The cats underwent general health and MRI examination at time 0 (before dietary intervention) and time 1 (after 40 weeks of being fed high-energy food ad libitum). Sequences included multiple-echo gradient-recalled echo MRI and diffusion-weighted MRI with 3 b values (0, 400, and 800 s/mm2). Variables (body weight and the HFF and ADC in selected regions of interest in the liver parenchyma) were compared between time points by Wilcoxon paired-sample tests. Relationships among variables were assessed with generalized mixed-effects models. RESULTS: Median body weight was 4.5 and 6.5 kg, mean ± SD HFF was 3.39 ± 0.89% and 5.37 ± 1.92%, and mean ± SD hepatic ADC was 1.21 ± 0.08 × 10-3 mm2/s and 1.01 ± 0.2 × 10-3 mm2/s at times 0 and 1, respectively. Significant differences between time points were found for body weight, HFF, and ADC. The HFF was positively associated with body weight and ADC was negatively associated with HFF. CONCLUSIONS AND CLINICAL RELEVANCE: Similar to findings in people, cats had decreasing hepatic ADC as HFF increased. Protons associated with fat tissue in the liver may reduce diffusivity, resulting in a lower ADC than in liver with lower HFF. Longer studies and evaluation of cats with different nutritional states are necessary to further investigate these findings.


Assuntos
Doenças do Gato , Imagem de Difusão por Ressonância Magnética , Animais , Peso Corporal , Gatos , Fígado/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Ganho de Peso
9.
PLoS Pathog ; 16(8): e1008131, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32866196

RESUMO

Invasion of hepatocytes by Plasmodium sporozoites initiates the pre-erythrocytic step of a malaria infection. Subsequent development of the parasite within hepatocytes and exit from them is essential for starting the disease-causing erythrocytic cycle. Identification of signaling pathways that operate in pre-erythrocytic stages provides insight into a critical step of infection and potential targets for chemoprotection from malaria. We demonstrate that P. berghei homologs of Calcium Dependent Protein Kinase 1 (CDPK1), CDPK4 and CDPK5 play overlapping but distinct roles in sporozoite invasion and parasite egress from hepatocytes. All three kinases are expressed in sporozoites. All three are required for optimal motility of sporozoites and consequently their invasion of hepatocytes. Increased cGMP can compensate for the functional loss of CDPK1 and CDPK5 during sporozoite invasion but cannot overcome loss of CDPK4. CDPK1 and CDPK5 expression is downregulated after sporozoite invasion. CDPK5 reappears in a subset of late stage liver stages and is present in all merosomes. Chemical inhibition of CDPK4 and depletion of CDPK5 in liver stages implicate these kinases in the formation and/or release of merosomes from mature liver stages. Furthermore, depletion of CDPK5 in merosomes significantly delays initiation of the erythrocytic cycle without affecting infectivity of hepatic merozoites. These data suggest that CDPK5 may be required for the rupture of merosomes. Our work provides evidence that sporozoite invasion requires CDPK1 and CDPK5, and suggests that CDPK5 participates in the release of hepatic merozoites.


Assuntos
Regulação para Baixo , Regulação Enzimológica da Expressão Gênica , Malária/epidemiologia , Merozoítos/enzimologia , Plasmodium berghei/enzimologia , Proteínas Quinases/biossíntese , Proteínas de Protozoários/biossíntese , Esporozoítos/enzimologia , Animais , Eritrócitos/enzimologia , Eritrócitos/parasitologia , Feminino , Células Hep G2 , Humanos , Fígado/enzimologia , Fígado/parasitologia , Malária/patologia , Camundongos
10.
Nat Commun ; 11(1): 4367, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868763

RESUMO

Invariant natural killer T (iNKT), mucosal-associated invariant T (MAIT), and γδ T cells are innate T cells that acquire memory phenotype in the thymus and share similar biological characteristics. However, how their effector differentiation is developmentally regulated is still unclear. Here, we identify analogous effector subsets of these three innate T cell types in the thymus that share transcriptional profiles. Using single-cell RNA sequencing, we show that iNKT, MAIT and γδ T cells mature via shared, branched differentiation rather than linear maturation or TCR-mediated instruction. Simultaneous TCR clonotyping analysis reveals that thymic maturation of all three types is accompanied by clonal selection and expansion. Analyses of mice deficient of TBET, GATA3 or RORγt and additional in vivo experiments corroborate the predicted differentiation paths, while human innate T cells from liver samples display similar features. Collectively, our data indicate that innate T cells share effector differentiation processes in the thymus.


Assuntos
Diferenciação Celular , Imunidade Inata , Linfócitos T/metabolismo , Timo/imunologia , Animais , Células Cultivadas , Seleção Clonal Mediada por Antígeno , Humanos , Fígado/citologia , Fígado/imunologia , Ativação Linfocitária , Camundongos , Células T Invariáveis Associadas à Mucosa/metabolismo , Células T Matadoras Naturais/metabolismo , Análise de Sequência de RNA , Análise de Célula Única , Células Th17/metabolismo , Timo/citologia
11.
Ann Hematol ; 99(11): 2507-2512, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32918595

RESUMO

Iron overload comprises one of the main complications of congenital dyserythropoietic anemia type I (CDA-I). When analyzing magnetic resonance imaging T2* (MRI T2*) results in CDA patients, two previous studies reported discordant results regarding iron load in these patients. To further understand iron loading pattern in this group of patients, we analyzed MRI T2* findings in 46 CDA-I patients. Mild to moderate hepatic iron overload was detected in 28/46 (60.8%) patients. A significant correlation was found between serum ferritin and liver iron concentration (LIC). A significant correlation (p value = 0.02) was also found between the patient's age and LIC, reflecting increased iron loading over time, even in the absence of transfusion therapy. Notably, no cardiac iron overload was detected in any patient. Transfusion-naive patients had better LIC and better cardiac T2* values. These results demonstrate that a high percentage of CDA-I patients have liver iron concentration above the normal values, risking them with significant morbidity and mortality, and emphasize the importance of periodic MRI T2* studies for direct assessment of tissue iron concentration in these patients, taking age and transfusional burden into consideration.


Assuntos
Anemia Diseritropoética Congênita , Sobrecarga de Ferro , Ferro/sangue , Fígado , Imagem por Ressonância Magnética , Miocárdio/metabolismo , Adolescente , Adulto , Anemia Diseritropoética Congênita/sangue , Anemia Diseritropoética Congênita/diagnóstico por imagem , Criança , Pré-Escolar , Ferritinas/sangue , Seguimentos , Humanos , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/diagnóstico por imagem , Fígado/diagnóstico por imagem , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
PLoS Pathog ; 16(9): e1008891, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32956401

RESUMO

The transitions between developmental stages are critical points in the Plasmodium life cycle. The development of Plasmodium in the livers of their mammalian hosts bridges malaria transmission and the onset of clinical symptoms elicited by red blood cell infection. The egress of Plasmodium parasites from the liver must be a carefully orchestrated process to ensure a successful switch to the blood stage of infection. Cysteine protease activity is known to be required for liver-stage Plasmodium egress, but the crucial cysteine protease(s) remained unidentified. Here, we characterize a member of the papain-like cysteine protease family, Plasmodium berghei serine repeat antigen 4 (PbSERA4), that is required for efficient initiation of blood-stage infection. Through the generation PbSERA4-specific antisera and the creation of transgenic parasites expressing fluorescently tagged protein, we show that PbSERA4 is expressed and proteolytically processed in the liver and blood stages of infection. Targeted disruption of PbSERA4 results in viable and virulent blood-stage parasites. However, upon transmission from mosquitoes to mice, Pbsera4(-) parasites displayed a reduced capacity to initiate a new round of asexual blood-stage replication. Our results from cultured cells indicate that this defect results from an inability of the PbSERA4-deficient parasites to egress efficiently from infected cells at the culmination of liver-stage development. Protection against infection with wildtype P. berghei could be generated in animals in which Pbsera4(-) parasites failed to establish infection. Our findings confirm that liver-stage merozoite release is an active process and demonstrate that this parasite-encoded cysteine protease contributes to parasite escape from the liver.


Assuntos
Cisteína Proteases/metabolismo , Fígado/parasitologia , Malária/enzimologia , Plasmodium berghei/enzimologia , Proteínas de Protozoários/metabolismo , Animais , Cisteína Proteases/genética , Fígado/metabolismo , Malária/genética , Camundongos , Plasmodium berghei/genética , Proteínas de Protozoários/genética , Ratos , Ratos Sprague-Dawley
13.
Nat Commun ; 11(1): 4810, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968061

RESUMO

Chimeric antigen receptor (CAR) therapy is a promising immunotherapeutic strategy for treating multiple refractory blood cancers, but further advances are required for solid tumor CAR therapy. One challenge is identifying a safe and effective tumor antigen. Here, we devise a strategy for targeting hepatocellular carcinoma (HCC, one of the deadliest malignancies). We report that T and NK cells transduced with a CAR that recognizes the surface marker, CD147, also known as Basigin, can effectively kill various malignant HCC cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models. To minimize any on-target/off-tumor toxicity, we use logic-gated (log) GPC3-synNotch-inducible CD147-CAR to target HCC. LogCD147-CAR selectively kills dual antigen (GPC3+CD147+), but not single antigen (GPC3-CD147+) positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic mouse model. In conclusion, these findings support the therapeutic potential of CD147-CAR-modified immune cells for HCC patients.


Assuntos
Basigina/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Imunoterapia Adotiva/métodos , Neoplasias Hepáticas/tratamento farmacológico , Receptores de Antígenos Quiméricos/efeitos dos fármacos , Animais , Basigina/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Células Hep G2 , Humanos , Células Matadoras Naturais , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Chem Biol Interact ; 330: 109245, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32866465

RESUMO

The calcineurin inhibitor, cyclosporin A (CsA) is one of the most common immunosuppressive agents used in organ transplantation. However, its clinical use is often limited by several unwanted effects including nephrotoxicity and hepatotoxicity. By using immunohistochemical and ELISA techniques, it was found that CsA administration causes a rapid activation of a disintegrin and metalloproteases-17 (ADAM-17), epidermal growth factor receptor (EGFR) and subsequent ERK1/2 phosphorylation in the liver and kidney of albino mice. Furthermore, this study presents mechanistic relevance of this signaling cascade involving reactive oxygen species (ROS)-mediated ADAM-17/EGFR/ERK1/2 activation as indicated by a clear reduction in ADAM-17 and EGFR activities as well as ERK1/2 phosphorylation when the animals pretreated with Polyethylene glycol-superoxide dismutase (PEG-SOD) before CsA administration. Collectively, our findings demonstrate that CsA has the ability to activate ADAM-17-mediated EGFR/ERK1/2 phosphorylation in the liver and kidney of albino mice in ROS-dependent manner. Finally, these data may support the concept of using antioxidant therapy as a valuable approach for the prevention of CsA-induced nephrotoxicity and hepatotoxicity.


Assuntos
Ciclosporina/toxicidade , Rim/metabolismo , Fígado/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Polietilenoglicóis/farmacologia , Superóxido Dismutase/farmacologia , Proteína ADAM17/metabolismo , Animais , Ciclosporina/farmacologia , Interações Medicamentosas , Receptores ErbB/metabolismo , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Camundongos , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
15.
Am J Vet Res ; 81(10): 810-820, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32969725

RESUMO

OBJECTIVE: To characterize the biochemical, functional, and histopathologic changes associated with lomustine-induced liver injury in dogs. ANIMALS: I0 healthy purpose-bred sexually intact female hounds. PROCEDURES: Dogs were randomly assigned to receive lomustine (approx 75 mg/m2, PO, q 21 d for 5 doses) alone (n = 5) or with prednisone (approx 1.5 mg/kg, PO, q 24 h for 12 weeks; 5). For each dog, a CBC, serum biochemical analysis, liver function testing, urinalysis, and ultrasonographic examination of the liver with acquisition of liver biopsy specimens were performed before and at predetermined times during and after lomustine administration. Results were compared between dogs that did and did not receive prednisone. RESULTS: 7 of the I0 dogs developed clinical signs of liver failure. For all dogs, serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, bile acid concentrations, and liver histologic score increased and hepatic reduced glutathione content decreased over time. Peak serum ALT (r = 0.79) and ALP (r = 0.90) activities and bile acid concentration (r = 0.68) were positively correlated with the final histologic score. Prednisone did not appear to have a protective effect on histologic score. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, liver enzyme activities, particularly ALT and ALP activities, should be closely monitored during lomustine treatment and acute increases in those activities may warrant discontinuation of lomustine to mitigate liver injury. Nonspecific ultrasonographic findings and abnormal increases in liver function tests were not detected until the onset of clinical liver failure. Glutathione depletion may have a role in lomustine-induced hepatopathy and warrants further investigation.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas/veterinária , Doenças do Cão/induzido quimicamente , Doenças do Cão/tratamento farmacológico , Lomustina , Alanina Transaminase , Fosfatase Alcalina , Animais , Cães , Feminino , Fígado , Lomustina/efeitos adversos
16.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(4): 504-512, 2020 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895103

RESUMO

Objective To explore the clinicopathological and immunohistochemical characteristics of follicular dendritic cell sarcoma(FDCS)and the expressions of IgG and IgG4. Methods We retrospectively analyzed the clinicopathological and immunohistochemical data of 9 pathologically confirmed FDCS cases in Peking Union Medical College Hospital from January 2005 to December 2018.Immunohistochemical staining of IgG and IgG4 were performed,and Epstein-Barr virus(EBV)-encoded RNA(EBER)in situ hybridization were carried out. Results Nine cases of FDCS included 4 men and 5 women aged 16-53 years [mean(38.2±9.7)years].The clinical manifestations included masses,lymph node enlargement,rash,and fever.The tumors were located in lymph node,retroperitoneal region,adrenal gland,neck,axillary region,and liver,respectively.Ultrasound showed clear boundary cystic or solid mass with maximum diameters of 1.5-15.0 cm.Microscopically,the spindle tumor cells were arranged in solid and storiform patterns with abundant and slightly stained cytoplasm,vacuolated nuclei,and small nucleoli.The mitosis was 1-3/10 high power fields,and necrosis was found in 5 cases.Immunohistochemically,the tumor cells were positive for CD21(6/9),CD35(6/9),and CD23(7/9). Conclusions FDCS is a rare malignant tumor,which is easy to be missed.The combination of CD21,CD35,and CD23 is helpful for diagnosis.Hyaline-vascular type Castleman's disease may be the precursor of FDCS,and there may be only a small number of IgG4-positive plasma cells in FDCS.Surgical resection remains the main treatment for FDCS.


Assuntos
Sarcoma de Células Dendríticas Foliculares , Adolescente , Adulto , Feminino , Humanos , Hibridização In Situ , Fígado , Linfonodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
17.
Ann Agric Environ Med ; 27(3): 368-373, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32955216

RESUMO

INTRODUCTION: Chlorpyrifos (CPF) is a organophosphate insecticide widely used in agriculture with attendant adverse health outcomes. Chronic exposure to CPF induces oxidative stress and elicits harmful effects, including hepatic dysfunction. Molecular hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. OBJECTIVE: The aim of this study was to determine whether the intake of hydrogen-rich water (HRW) could protect rats from hepatotoxicity caused by sub-chronic exposure to CPF. MATERIAL AND METHODS: Rats were treated with hydrogen-rich water by oral intake for 8 weeks. Biochemical indicators of liver function, SOD and CAT activity, GSH and MDA levels were determined by the spectrophotometric method. Liver cell damage induced by CPF was evaluated by histopathological and electron microscopy analysis. PCR array analysis was performed to investigated the effects of molecular hydrogen on the regulation of oxidative stress related genes. RESULTS: Both the hepatic function tests and histopathological analysis showed that the liver damage induced by CPF could be ameliorated by HRW intake. HRW intake also attenuated CPF induced oxidative stress, as evidenced by restored SOD activities and MDA levels. The results of PCR Array identified 12 oxidative stress-related genes differentially expressed after CPF exposure, 8 of chich, including the mitochondrial Sod2 gene, were significantly attenuated by HRW intake. The electron microscopy results indicated that the mitochondrial damage caused by CPF was alleviated after HRW treatment. CONCLUSIONS: The results obtained suggest that HRW intake can protect rats from CPF induced hepatotoxicity, and the oxidative stress signaling and the mitochondrial pathway may be involved in the protection of molecular hydrogen.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Clorpirifos/toxicidade , Hidrogênio/farmacologia , Inseticidas/toxicidade , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Relação Dose-Resposta a Droga , Masculino , Estresse Oxidativo/genética , Ratos , Ratos Wistar
18.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(5): 555-559, 2020 May 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879106

RESUMO

OBJECTIVES: To analyze the clinical characteristics in patients of coronavirus disease 2019 (COVID-19) complicated with liver injury, to explore the relationship between COVID-19 clinical classification and liver injury, and to elucidate whether COVID-19 complicated with hepatitis B virus can aggravate liver injury. METHODS: The abnormal liver function in 110 patients in the First Hospital of Changsha, who were confirmed COVID-19 and admitted to the designated hospital from January 17, 2020 to February 20, 2020, wereretrospectively analyzed. The detection indexes included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBIL). RESULTS: A total of 49.1% of the COVID-19 patients had liver injury. There were significant difference in the ALT, AST, ALB (all P<0.05), but there was no significant difference in the TBIL (P>0.05) between the severe (critical) patients and the general (light) patients. There was also no significant difference in the liver function injury between the HBsAg-positive COVID-19 patients and HBsAg-negative COVID-19 patients (P>0.05). Acute liver injury was not found to be a direct cause of death in the patients. CONCLUSIONS: In the COVID-19 patients, the incidence of liver injury is high with the increase of ALT and AST and the decrease of ALB. Severe and critical patients have obvious liver injury, and those patients complicated with hepatitis B virus infection don't show aggravated liver injury.


Assuntos
Infecções por Coronavirus/diagnóstico , Hepatopatias/virologia , Fígado/fisiopatologia , Pneumonia Viral/diagnóstico , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Betacoronavirus , Bilirrubina/sangue , Humanos , Fígado/virologia , Pandemias , Albumina Sérica Humana/análise
19.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(7): 766-773, 2020 Jul 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879079

RESUMO

OBJECTIVES: To investigate the role of transient receptor potential cation channel subfamily M member 2 (TRPM2) in hepatic ischemia-reperfusion injury of mouse (HIRI) and the possible mechanisms. METHODS: Sixty adult male C57BL/6 mice were randomly divided into 4 groups: a sham group (S group), a HIRI model group (M group), a TRPM2 adenovirus interference vector group (T group), and a TRPM2 adenovirus control vector group (C group) (n=15 in each group). The liver tissues of mice before perfusion were obtained. The efficiency of adenovirus infection was detected by fluorescence microscopy, and the silencing efficiency of adenovirus against TRPM2 was detected by real-time PCR.The abdominal aorta blood and liver tissues were collected from mice at 2, 4 and 8 h after reperfusion. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of mice were detected. Hepatic pathological changes were examined by hematoxylin-eosin (HE) staining. The protein expression of TRPM2 and Rac family small GTPase 1 (RAC1) in liver tissues was detected by Western blotting. Changes of malondialdehyde (MDA), superoxide dismutase (SOD) and myeloperoxidase (MPO) activities in liver tissues were detected by enzyme-linked immunosorbent assay. RESULTS: A strong signal of green fluorescence was observed in the liver tissues of mice in the T and C groups compared to the S or M group. Compared with the S, M or C group, the expression of TRPM2 mRNA in liver tissue in the T group was significantly down-regulated (all P<0.05). The morphology of hepatocytes was normal in the S group under light microscope.Hepatic sinus dilatation, congestion, hepatocyte degeneration, central necrosis of lobule, and massive inflammatory granulocyte infiltration were observed in the M and C group, respectively. The degree of hepatocyte damage in the T group was significantly reduced compared with that in the M and C group, respectively. Compared with the S group, the serum ALT and AST activities in the M, T and C groups were significantly increased at 2, 4 and 8 h after reperfusion (all P<0.05). Compared with the M or C group, the serum ALT and AST activities in the T group were significantly lower in serum of mice at 2, 4, and 8 h after reperfusion (all P<0.05). Compared with the M or C group, the serum SOD activity in the T group was significantly increased at 2, 4, and 8 h after reperfusion (all P<0.05), while the serum MDA and MPO activities were significantly decreased (all P<0.05). The protein expression of TRPM2 and RAC1 in liver tissues in the T group were significantly lower than those in the M and C groups at 2, 4 and 8 h after reperfusion (all P<0.05). CONCLUSIONS: Pretreatment with TRPM2 adenovirus interference vector can effectively silence TRPM2 gene expression in liver tissues of mice and attenuate HIRI, which may be related to inhibiting oxidative stress and reducing the expression of RAC1 protein.


Assuntos
Traumatismo por Reperfusão , Canais de Cátion TRPM/genética , Canais de Receptores Transientes de Potencial , Alanina Transaminase , Animais , Aspartato Aminotransferases , Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuropeptídeos , Ratos Sprague-Dawley , Proteínas rac1 de Ligação ao GTP
20.
Georgian Med News ; (304-305): 148-152, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32965266

RESUMO

In case of mechanical cholestasis, along with stagnation in the veins and bile ducts, lymph production increases, which contributes to the accumulation of ascitic fluid. In the peribiliaryareas, where the extramural biliary glands are located, an accumulation of lymphatic vessels has been observed in all the preparations.In these same areas, a contrast-enhanced microtomography showed transition of the ink-gelatin contrast agents (using gelatin and India ink) from the extramural part of the mucous glands to the lumen of the lymphatic capillaries and blood vessels.Lymphobiliary connections were visualized during the preparation of the sections of the portal triad of the lobar and sectoral portal tracts under a binocular microscope. More reliable evidence of the existence of lymphobiliary connections in the portal triad region was revealed on histological preparations stained with traditional methods.; Thus, anatomically, the area of the portal triad appears to be one of the alternative areas of lymphobiliary communications, which further confirms its high adaptive capacity in case of stagnation of bile.


Assuntos
Ductos Biliares/diagnóstico por imagem , Colestase/diagnóstico , Humanos , Fígado/diagnóstico por imagem , Sistema Porta
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