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1.
Rev. cuba. cir ; 60(2): e989,
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1280220

RESUMO

Introducción: El cáncer de colon constituye un grave problema sanitario debido a su alta incidencia y mortalidad. Objetivo: Describir algunos aspectos epidemiológicos, etiopatogénicos, diagnósticos, terapéuticos y evolutivos del cáncer de colon con metástasis hepáticas. Métodos: Revisión documental en bases de datos bibliográficos biomédicas sobre el tema durante el período 2015-2020. Se seleccionaron 31 artículos relacionados con el objetivo propuesto. Desarrollo: Los pacientes con cáncer de colon con metástasis hepáticas sincrónicas son tratados mediante tres estrategias: la tradicional o clásica consiste en la resección quirúrgica del tumor primario y posteriormente, quimioterapia, radioterapia o ambas, para proceder a la resección de las lesiones hepáticas tres a seis meses después; la simultánea, consistente en la resección de la lesión tumoral primaria y de las metástasis hepáticas en un mismo acto quirúrgico, seguida de quimioterapia, radioterapia o ambas y la inversa, que administra de tres a seis ciclos de quimioterapia sistémica, seguidos por la resección de las metástasis hepáticas y en un segundo tiempo resecar el tumor primario, todo esto con quimioterapia durante el intervalo entre ambas cirugías. Conclusiones: El único tratamiento con potencial curativo en los pacientes con metástasis hepáticas debe ser la resección de todo el volumen tumoral hepático con márgenes adecuados y la suficiente preservación del parénquima sano (25 - 30 por ciento), según criterios oncológicos y anatómicos establecidos, lo que incide en la calidad de vida y la supervivencia de estos enfermos(AU)


Introduction: Colon cancer is a serious health concern due to its high incidence and mortality. Objective: To describe some epidemiological, etiopathogenic, diagnostic, therapeutic and evolutionary aspects of colon cancer with hepatic metastases. Methods: Documentary review about the subject carried out in biomedical bibliographic databases, during the period 2015-2020. Thirty-one articles related to the proposed objective were selected. Development: Colon cancer patients with synchronous hepatic metastases are treated using three strategies: the traditional, or classic, strategy consists in surgical resection of primary tumor and, subsequently, chemotherapy, radiotherapy or both, before proceeding then to resection of liver lesions three to three six months later; the simultaneous strategy consists in resection of primary tumor lesion and hepatic metastases in the same surgical procedure, followed by chemotherapy, radiotherapy or both; and the reverse strategy, in which three to six cycles of systemic chemotherapy are administered, followed by resection of hepatic metastases and, in a second stage, resection of primary tumor, all this with chemotherapy during the interval between both surgeries. Conclusions: The only treatment with curative potential in patients with hepatic metastases should be the resection of the entire hepatic tumor volume with adequate margins and sufficient preservation of the healthy parenchyma (25-30 percent), according to established oncological and anatomical criteria, which has an incidence on the quality of life and survival of these patients(AU)


Assuntos
Humanos , Qualidade de Vida , Bases de Dados Bibliográficas , Neoplasias do Colo/cirurgia , Neoplasias do Colo/epidemiologia , Metástase Neoplásica/terapia , Sobrevivência , Fígado/lesões
2.
Life Sci ; 278: 119583, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33957170

RESUMO

Despite unprecedented advances in modern medicine, no safe and effective drug is available to date for oral administration to combat drug-induced liver injury, which is a vital concern nowadays. The present study deals with the hepatoprotective effect of pure glabridin, a key phytoconstituent from Glycyrrhiza glabra with mechanistic investigations using an in-vivo methotrexate-induced liver injury model as there is no such precedent. The study was performed in the Swiss mice model where a single dose of methotrexate (40 mg/kg) was given on the 7th day through an intraperitoneal route to induce hepatotoxicity, and glabridin as a test compound was administered orally for eleven consecutive days at 10 to 40 mg/kg. Glabridin markedly improved serum biochemical parameters (SGPT, SGOT), proinflammatory cytokine (TNF-α) level, oxidative stress markers (MDA, GSH, SOD, CAT) as compared to methotrexate alone. Alterations in methotrexate-induced liver architecture were considerably prevented by glabridin treatment as suggested by liver histopathological examination and SEM investigation. Glabridin substantially prevented methotrexate-induced down-regulation of Nrf2, & activation of NF-κB, and caused up-regulation of BAX at different dose levels. Overall, glabridin is found to protect methotrexate-induced hepatotoxicity by improving important factors for oxidative stress, inflammation, and apoptosis.


Assuntos
Apoptose , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Inflamação/terapia , Isoflavonas/farmacologia , Fígado/efeitos dos fármacos , Estresse Oxidativo , Fenóis/farmacologia , Animais , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Regulação para Baixo , Glycyrrhiza , Humanos , Fígado/lesões , Fígado/metabolismo , Metotrexato , Camundongos , NF-kappa B/metabolismo , Substâncias Protetoras/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
3.
Transplant Proc ; 53(5): 1611-1615, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33965241

RESUMO

AIM: This study aims to validate Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) and confirm the feasibility of performing transplantation. METHODS: We included 60 patients with acute liver injury. Demographic and clinical features were retrospectively collected, and the primary outcome was compared among 4 types: acute liver failure (ALF) with hepatic coma (n = 23), ALF without hepatic coma (n = 12), acute liver injury (n = 20), and ACLF (n = 5). Moreover, 80 transplanted patients were enrolled to compare the difficulty of transplantation between ALF (n = 8) vs non-ALF (n = 72) patients. RESULTS: Seven patients in the ALF with hepatic coma group and 1 patient in the ACLF with hepatic coma group were transplanted. Ten patients who could not be registered for transplantation died. In univariate analysis, liver failure type (P < .0001), total bilirubin level (P = .05), and prothrombin time internationalized ratio (P < .0001) were associated with patient survival. In multivariate analysis, liver failure type was associated with patient survival (P < .0001). The respective 1-, 3-, and 5-year patient survival rates were 45.9%, 45.9%, and 45.9% for ALF patients with hepatic coma; 100.0%, 100.0%, and 100.0% for ALF patients without hepatic coma and acute liver injury; and 80.0%, 80.0%, and 80.0% for ACLF patients (P < .0001). Chronic liver disease did not affect operation time (P = .46) and bleeding volume (P = .49). CONCLUSION: Patients diagnosed with ACLF via Japanese criteria presented significantly higher survival rates than ALF patients with hepatic coma.


Assuntos
Insuficiência Hepática Crônica Agudizada/mortalidade , Encefalopatia Hepática/mortalidade , Falência Hepática Aguda/mortalidade , Transplante de Fígado , Fígado/lesões , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/cirurgia , Humanos , Japão , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tempo de Protrombina , Estudos Retrospectivos , Taxa de Sobrevida
4.
Nat Commun ; 12(1): 2863, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001904

RESUMO

During injury, monocytes are recruited from the circulation to inflamed tissues and differentiate locally into mature macrophages, with prior reports showing that cavity macrophages of the peritoneum and pericardium invade deeply into the respective organs to promote repair. Here we report a dual recombinase-mediated genetic system designed to trace cavity macrophages in vivo by intersectional detection of two characteristic markers. Lineage tracing with this method shows accumulation of cavity macrophages during lung and liver injury on the surface of visceral organs without penetration into the parenchyma. Additional data suggest that these peritoneal or pleural cavity macrophages do not contribute to tissue repair and regeneration. Our in vivo genetic targeting approach thus provides a reliable method to identify and characterize cavity macrophages during their development and in tissue repair and regeneration, and distinguishes these cells from other lineages.


Assuntos
Fígado/fisiopatologia , Lesão Pulmonar/fisiopatologia , Macrófagos/fisiologia , Monócitos/fisiologia , Cavidade Peritoneal/fisiologia , Cavidade Pleural/fisiologia , Animais , Linhagem da Célula/genética , Células Cultivadas , Fígado/lesões , Ativação de Macrófagos/fisiologia , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Microscopia de Fluorescência/métodos , Monócitos/citologia , Monócitos/metabolismo , Cavidade Peritoneal/citologia , Fagocitose/fisiologia , Cavidade Pleural/citologia
5.
Pan Afr Med J ; 38: 89, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33889255

RESUMO

Introduction: although non-operative management of patients with blunt trauma to abdominal solid organs has become standard care, the role of peripheral hospitals remains poorly defined. This study reviews treatment and outcomes in patients with liver and spleen injuries at a regional hospital over a 10-year period. Methods: a retrospective review of prospectively collected data was performed and supplemented by case notes retrieval. All patients with solid visceral injuries managed between 2009 and 2019 at a rural surgical hospital in Zambia were included. On admission, the patients were offered either urgent laparotomy or non-operative management (NOM) depending on their haemodynamic status. Continuous variables were expressed as median and mean ± standard deviation; categorical data were expressed as percentages. Statistical evaluation of data was performed by two-sample t-test. Statistical significance was assigned at p<0.05. Results: fourty-three patients were included. The majority of victims sustained isolated spleen or liver injury. Twenty-three patients were urgently operated due to haemodynamic instability. Splenectomy performed in 17 patients, liver laceration sutured in 5 patients. One patient underwent concomitant splenectomy and liver repair. Conservative management was attempted in 20 (47%) patients and was successful in 18 (42%). In two patients NOM failed and splenectomy was performed urgently. Two patients died postoperatively. There were no deaths in NOM group. Conclusion: NOM of patients with injury to solid abdominal organs could be safely initiated in rural hospitals provided there is uninterrupted monitoring of patients' condition, well-trained staff and unrestricted access to the operating theatre (OT).


Assuntos
Traumatismos Abdominais/terapia , Fígado/lesões , Baço/lesões , Ferimentos não Penetrantes/terapia , Traumatismos Abdominais/fisiopatologia , Adolescente , Adulto , Idoso , Criança , Tratamento Conservador/métodos , Feminino , Hospitais Rurais , Humanos , Laparotomia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esplenectomia , Índices de Gravidade do Trauma , Ferimentos não Penetrantes/fisiopatologia , Adulto Jovem , Zâmbia
6.
Mol Med Rep ; 23(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33760198

RESUMO

Melatonin (MT) is an indoleamine hormone that can counteract ischemia­induced organ injury through its antioxidant effects. The aim of the present study was to investigate the protective effects of exogenous MT against hemorrhagic shock (HS)­induced hepatic ischemic injury in rats, and the role of the nuclear factor (NF)­κB signaling pathway in this process. A rat model of HS­induced hepatic ischemic injury was established. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), glutamate dehydrogenase (GDH), tumor necrosis factor (TNF)­α, interferon (IFN)­Î³, interleukin (IL)­6 and IL­1ß were measured every 6 h, and the 24­h survival rate of the rats was analyzed. All surviving rats were sacrificed after 24 h. Pathological changes in the liver and the hepatocyte apoptosis rate were observed by hematoxylin and eosin staining and TUNEL assay, respectively, and the expression levels of NF­κB p65 and NF­κB inhibitor α (IκBα) were analyzed by reverse transcription­quantitative PCR analysis and western blotting. The results demonstrated that the serum levels of ALT, AST, LDH, GDH, TNF­α, IFN­Î³, IL­6 and IL­1ß gradually increased after HS compared with those in rats subjected to a sham procedure, but this increase was attenuated by MT. Furthermore, the survival rate of the MT group was significantly higher compared with that of the HS group. The degree of pathological hepatic injury, the hepatocyte apoptosis rate, and the hepatic levels of TNF­α, IFN­Î³, IL­6 and IL­1ß were significantly decreased in the MT group compared with the HS group. In addition, the mRNA expression of NF­κB p65 was significantly decreased and the mRNA expression of IκBα was significantly increased in the MT group compared with the sham group. Furthermore, the NF­κB p65 protein levels in the MT group were significantly increased in the cytosol but decreased in the nucleus, and the IκBα protein levels were increased while those of phosphorylated IκBα were decreased compared with those in the HS group. Therefore, it may be inferred that exogenous MT alleviates HS­induced hepatic ischemic injury in rats via the inhibition of NF­κB activation and IκBα phosphorylation.


Assuntos
Fígado/efeitos dos fármacos , Melatonina/farmacologia , NF-kappa B/genética , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Modelos Animais de Doenças , Humanos , Fígado/lesões , Fígado/patologia , Masculino , Inibidor de NF-kappaB alfa/genética , Ratos , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Choque Hemorrágico/complicações , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/patologia , Transdução de Sinais/efeitos dos fármacos
7.
Afr J Paediatr Surg ; 18(2): 114-116, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33642413

RESUMO

Internal hernia through an iatrogenic defect in the hepatic falciform ligament and acquired jejunal atresia in a 8-day-old neonate was reported. The PubMed, MEDLINE, CNKI, Wanfang and Weipu databases were searched The literature about the hepatic falciform ligament iatrogenic defect causing internal hernia was analysed. Ten other cases were collected from the world literature. Herniated intestinal necrosis was found in four cases. All cases were recovered uneventfully after operation. Internal herniation through an iatrogenic defect in the hepatic falciform ligament is extremely rare. However, the case reports are increasing, especially in the era of laparoscopic surgery. Adequate closure or open the defect is essential to prevent internal hernia occurrence.


Assuntos
Hérnia Abdominal/etiologia , Hérnia Interna/etiologia , Laparoscopia/efeitos adversos , Ligamentos/lesões , Fígado/lesões , Hérnia Abdominal/diagnóstico , Hérnia Abdominal/cirurgia , Humanos , Doença Iatrogênica , Recém-Nascido , Hérnia Interna/diagnóstico , Hérnia Interna/cirurgia , Enteropatias/cirurgia , Ligamentos/cirurgia , Masculino
8.
Biochem Biophys Res Commun ; 550: 15-21, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33677131

RESUMO

Liver ischemia-reperfusion (IR) injury is an unavoidable pathological process in transplantation, closely related to poor prognosis. To date, there has been no clear therapeutic measure. We previously reported that mild hypothermia (MH), a widely used therapy, can exert significant protective effect against liver IR injury. Among the multiple mechanisms underlying the therapeutic effect of MH, autophagy flux drew our special attention. In this study, we evaluated the role of autophagy flux in IR injury and thereby explored the relationship between MH and autophagy flux in IR injury. We developed in vivo and in vitro models for hepatic IR injury. By autophagy flux assay with Western blotting and immunofluorescence, we found that MH restricts heavy accumulation of autophagosomes (APs) during IR injury. Activation and blocking of the autophagy flux unraveled that accumulation of APs further aggravated IR injury. Further, MH reduces APs accumulation to restore autophagy flux by regulating the fusion of APs and lysosomes. Besides, MH upregulated the level of Rab7 protein expression that was seriously impaired during IR injury. Inhibition of Rab7 expression increased apoptosis of liver cells and reduced the degree of overlap between APs and lysosomes. The results were reversed upon activation of Rab7. In conclusion, MH can alleviate liver IR injury by regulating the Rab7-mediated APs-lysosomes fusion that reduces APs accumulation. This can provide a theoretical basis for the further application of MH in related clinical diseases.


Assuntos
Autofagossomos/metabolismo , Hipotermia Induzida , Fígado/citologia , Lisossomos/metabolismo , Fusão de Membrana , Traumatismo por Reperfusão/prevenção & controle , Proteínas rab de Ligação ao GTP/metabolismo , Animais , Autofagia , Fígado/lesões , Masculino , Camundongos
9.
Rev Col Bras Cir ; 48: e20202784, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33787764

RESUMO

OBJECTIVE: the aim of this study was to identify associated factors with the increased length of hospital stay for patients undergoing surgical treatment for liver trauma, and predictors of mortality as well as the epidemiology of this trauma. METHODS: retrospective study of 191 patients admitted to the Cajuru University Hospital, a reference in the treatment of multiple trauma patients, between 2010 and 2017, with epidemiological, clinicopathological and therapeutic variables analyzed using the STATA version 15.0 program. RESULTS: most of the included patients were men with a mean age of 29 years. Firearm injury represents the most common trauma mechanism. The right hepatic lobe was injured in 51.2% of the cases, and hepatorraphy was the most commonly used surgical correction. The length of hospital stay was an average of 11 (0-78) days and the length of stay in the intensive care unit was 5 (0-52) days. Predictors for longer hospital stay were the mechanisms of trauma, hemodynamic instability at admission, number of associated injuries, degree of liver damage and affected lobe, used surgical technique, presence of complications, need for reoperation and other surgical procedures. Mortality rate was 22.7%. CONCLUSIONS: the study corroborated the epidemiology reported by the literature. Greater severity of liver trauma and associated injuries characterize patients undergoing surgical treatment, who have increased hospital stay due to the penetrating trauma, hemodynamic instability, hepatic packaging, complications and reoperations.


Assuntos
Armas de Fogo , Ferimentos por Arma de Fogo , Adulto , Hospitalização , Humanos , Escala de Gravidade do Ferimento , Tempo de Internação , Fígado/lesões , Fígado/cirurgia , Masculino , Estudos Retrospectivos , Centros de Traumatologia
10.
Ann R Coll Surg Engl ; 103(3): e98-e100, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33645284

RESUMO

Pneumothorax resulting from traumatic thoracic injury is a potentially life-threatening emergency requiring prompt recognition and management with an intercostal drain. A 34-year-old woman was brought into the emergency department after sustaining a stab injury to the right upper outer quadrant of the right breast. She described noticing a jelly-like substance from her wound, on the background of a prior cosmetic breast augmentation. On examination, it was noted that the right breast was significantly swollen. Computed tomography demonstrated a large right sided pneumothorax with associated punctured right breast implant, a 'pneumocapsule' and extensive subcutaneous emphysema of the breast. This case highlights that the fibrous tissue capsule around a breast implant can function as an anatomical space in continuity with the thoracic cavity, masking the diagnosis of pneumothorax in penetrating trauma.


Assuntos
Implantes de Mama , Pneumotórax/diagnóstico por imagem , Traumatismos Torácicos/diagnóstico por imagem , Ferimentos Perfurantes/diagnóstico por imagem , Adulto , Mama/diagnóstico por imagem , Mama/lesões , Tubos Torácicos , Feminino , Humanos , Lacerações , Fígado/diagnóstico por imagem , Fígado/lesões , Pneumotórax/etiologia , Pneumotórax/terapia , Enfisema Subcutâneo , Traumatismos Torácicos/complicações , Toracostomia , Tomografia Computadorizada por Raios X , Ferimentos Perfurantes/complicações
11.
Curr Sports Med Rep ; 20(2): 69-75, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33560028

RESUMO

ABSTRACT: We describe 13 children who presented to the Penn State Health Milton S. Hershey Medical Center (HMC) with pediatric soccer-related abdominal organ injuries. A review of the Pennsylvania Trauma System Foundation's Trauma Registry was performed between 2001 and 2015 for children with soccer injuries hospitalized at trauma centers across Pennsylvania. Out of 52 children at Hershey Medical Center, 13 suffered abdominal organ injuries. Injuries included the spleen [5], kidney [4], liver [2], and combined organ involvement [2]. All patients presented with abdominal and/or flank pain. All patients with kidney injuries presented with hematuria. All patients presented after a player-to-player (P2P) contact. Nearly all patients (12/13) were treated nonsurgically. Our findings showed that abdominal organ injuries constitute a substantial portion of pediatric soccer injuries requiring hospitalization, with spleen being the organ injured most frequently. Soccer-related abdominal organ injuries should be suspected in players who suffer abdominal and/or flank pain, and/or hematuria after a P2P contact.


Assuntos
Traumatismos Abdominais/epidemiologia , Futebol/lesões , Traumatismos Abdominais/diagnóstico , Traumatismos Abdominais/etiologia , Traumatismos Abdominais/terapia , Adolescente , Criança , Feminino , Humanos , Incidência , Rim/lesões , Fígado/lesões , Masculino , Pennsylvania/epidemiologia , Prevalência , Estudos Retrospectivos , Baço/lesões
12.
Biochem Biophys Res Commun ; 546: 138-144, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33582556

RESUMO

Hepatic injury is common in patients who suffer from severe burns plus delayed resuscitation (B + DR). Stimulator of interferon genes (STING) is primarily expressed in Kupffer cells (KCs). We demonstrated that B + DR caused hepatic injury and oxidative stress. Reactive oxygen species (ROS) damage mitochondrial membranes in hepatocytes, leading to the release of mitochondrial DNA (mtDNA) into the hepatocyte cytosol and the circulation. The damaged hepatocytes then activate the mtDNA/STING pathway in KCs and trigger KCs polarization towards pro-inflammatory phenotype. SS-31 is a strong antioxidant that specifically concentrates in the inner mitochondrial membrane. SS-31 prevented hepatic injury by neutralizing ROS, inhibiting the release of mtDNA, protecting hepatocyte mitochondria, suppressing the activation of the mtDNA/STING pathway and inhibiting KCs polarization into pro-inflammatory phenotype.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Queimaduras/complicações , DNA Mitocondrial/efeitos dos fármacos , Macrófagos do Fígado/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/lesões , Proteínas de Membrana/metabolismo , Oligopeptídeos/farmacologia , Ressuscitação , Animais , DNA Mitocondrial/sangue , DNA Mitocondrial/metabolismo , Espaço Extracelular/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Macrófagos do Fígado/metabolismo , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo
13.
BMC Surg ; 21(1): 71, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33530973

RESUMO

BACKGROUND: Hemobilia due to rupture of hepatic artery pseudoaneurysm and recurrent hemorrhage caused by hepatic artery collateral circulation are both rare complications after liver trauma. There have been a number of separate reports of both complications, but no cases have been reported in which the two events occurred in the same patient. Here we report a recurrent hemorrhage in the bile duct due to hepatic artery pseudoaneurysm secondary to collateral circulation formation after hepatic artery ligation in a patient with liver trauma. CASE PRESENTATION: A 52-year-old male patient was admitted to our hospital for liver trauma (Grade IV according to the American Association for the Surgery of Trauma (AAST) grading system) with active bleeding after a traffic accident. Hepatic artery ligation was performed for hemostasis. Three months after the surgery, the patient was readmitted for melena and subsequent hematemesis. Selective angiography examination revealed the formation of collateral circulation between the superior mesenteric artery and right hepatic artery. Moreover, a ruptured hepatic artery pseudoaneurysm was observed and transcatheter arterial embolization (TAE) was performed for hemostasis at the same time. After the treatment, the patient recovered very well and had an uneventful prognosis until the last follow-up. CONCLUSION: For patients with hepatic trauma, the selection of the site of hepatic artery ligation and the diagnosis and treatment methods of postoperative biliary hemorrhage are crucial for the prognosis of the disease.


Assuntos
Falso Aneurisma , Aneurisma Roto , Hemobilia , Artéria Hepática , Ligadura/efeitos adversos , Fígado , Traumatismos Abdominais/complicações , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Falso Aneurisma/terapia , Aneurisma Roto/etiologia , Aneurisma Roto/terapia , Angiografia/métodos , Ductos Biliares/diagnóstico por imagem , Ductos Biliares/lesões , Circulação Colateral , Embolização Terapêutica , Hematemese/etiologia , Hematemese/terapia , Hemobilia/etiologia , Hemobilia/terapia , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/lesões , Artéria Hepática/cirurgia , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/lesões , Masculino , Melena/etiologia , Melena/terapia , Pessoa de Meia-Idade , Recidiva , Circulação Esplâncnica
14.
J Chromatogr A ; 1639: 461939, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33530009

RESUMO

Comprehensive analysis of fatty acids (FAs) has long been challenging due to their poor ionization efficiency, lack of characteristic fragment ions and difficulty of identifying C=C bond locations. In this study, a high coverage ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was established for the quantification and C=C bond location characterization of FAs using two structural analogues, 2-hydrazinyl-4,6-dimethylpyrimidine (DMP) and 2-hydrazinylpyrimidine (DP), as dual derivatization reagents. DP-labeled FA standards were used as internal standards to reduced matrix effects, which guaranteed the accurate quantification of FAs. The derivatization yields of FAs were larger than 99% and the sensitivities were increased by 400-fold compared with non-derivatized FAs. Pretreatment and instrumental analysis of FAs can be completed in 20 minutes. Only 5 µL rat plasma can satisfy the quantification of 36 FAs with good linearity (r>0.99). Both intra-day and inter-day accuracies were in the range of 85-105%, and the precisions were less than 15%. The extraction recoveries were investigated to be in the range of 88-112%. No obvious matrix effects were observed for the derivatized FAs. In addition, the locations of C=C bonds in DMP-derivatized FAs could be identified by diagnostic fragment ions generated from 1,4-hydrogen elimination and allylic cleavage under low energy collision induced dissociation (CID). The new method was finally employed for FA profiling in plasma from rats with moxifloxacin-induced liver injury. Significant downregulation of butyric acid was observed in moxifloxacin treated model rats, which was believed to be related to the liver injury.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ácidos Graxos/análise , Espectrometria de Massas em Tandem/métodos , Animais , Análise Discriminante , Ácidos Graxos/química , Análise dos Mínimos Quadrados , Fígado/lesões , Fígado/patologia , Masculino , Redes e Vias Metabólicas , Moxifloxacina/efeitos adversos , Ratos Wistar
15.
Nat Commun ; 12(1): 613, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504774

RESUMO

Induction of intrinsic liver regeneration is an unmet need that can be achieved by temporally activating key hepatocyte regenerative pathways. Here, we establish an efficient, safe, non-integrative method to transiently express hepatocyte-growth-factor (HGF) and epidermal-growth-factor (EGF) in hepatocytes via nucleoside-modified, lipid-nanoparticle-encapsulated mRNA (mRNA-LNP) delivery in mice. We confirm specific hepatotropism of mRNA-LNP via intravenous injection of firefly luciferase encoding mRNA-LNP, with protein expression lasting about 3 days. In the liver, virtually all hepatocytes are transfected along with a subpopulation of endothelial and Kupffer cells. In homeostasis, HGF mRNA-LNP efficiently induce hepatocyte proliferation. In a chronic liver injury mouse model recapitulating non-alcoholic fatty liver disease, injections of both HGF and EGF mRNA-LNP sharply reverse steatosis and accelerate restoration of liver function. Likewise, HGF and EGF mRNA-LNP accelerate liver regeneration after acetaminophen-induced acute liver injury with rapid return to baseline ALT levels. This study introduces mRNA-LNP as a potentially translatable safe therapeutic intervention to harness liver regeneration via controlled expression of endogenous mitogens in vivo.


Assuntos
Hepatócitos/patologia , Lipídeos/química , Regeneração Hepática/fisiologia , Fígado/patologia , Nanopartículas/química , Nucleosídeos/metabolismo , RNA Mensageiro/metabolismo , Acetaminofen , Animais , Proliferação de Células/efeitos dos fármacos , Doença Crônica , Modelos Animais de Doenças , Fator de Crescimento Epidérmico/farmacologia , Feminino , Proteínas de Fluorescência Verde/metabolismo , Fator de Crescimento de Hepatócito/farmacologia , Hepatócitos/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Injeções , Fígado/efeitos dos fármacos , Fígado/lesões , Fígado/fisiopatologia , Testes de Função Hepática , Regeneração Hepática/efeitos dos fármacos , Camundongos Endogâmicos C57BL
16.
Mol Biol Rep ; 48(1): 637-644, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33439409

RESUMO

CP is one of the most widely used antineoplastic agents. However, its clinical application is very limited due to its severe toxic effects. The present study aimed to reveal the effects of NAC, which exhibits broad biological activities in reducing CP-induced liver damage, in consideration of biochemical, genetic, and histopathological findings. Twenty-eight wistar rats were randomly divided into four groups of seven animals. A dose of saline was administered (i.p.) to the control group for 5 days. One dose of NAC (200 mg/kg) was administered to the NAC group for 5 days (i.p.). To the NAC + CP group, a dose of CP (7.5 mg/kg) was administered on days 2 and 5 of the experiment, a dose of NAC (200 mg/ kg) (i.p.) was administered for 5 day of the experiment. CP (7.5 mg/kg) was administered to the CP group on days 2 and 5 of the experiment. At the end of the experiment, the biochemical, histological, and mRNA expression analyses of the liver tissues isolated from all the rats were performed. A statistically significant decrease was observed in the AST and ALT enzyme activities in Group NAC + CP compared to Control and CP groups. In addition, it was determined that the NAC administration reduced CP-induced inflammation by increasing the level of NF-κB and decreased CP-caused oxidative stress by decreasing the GPx level. Moreover, the histopathological analyses showed that NAC improved liver morphology. It was revealed by Western blotting analysis that NAC promoted Bcl-2 signaling and decreased p53 signaling. The findings herein showed that NAC could help alleviate hepatotoxicity, a serious therapeutic complication, by reducing CP-induced oxidative stress and playing an effective part in the regulation of apoptotic markers.


Assuntos
Acetilcisteína/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Cisplatino/efeitos adversos , Inflamação/tratamento farmacológico , Neoplasias/complicações , Animais , Antineoplásicos/efeitos adversos , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Cisplatino/farmacologia , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Fígado/efeitos dos fármacos , Fígado/lesões , Neoplasias/tratamento farmacológico , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
17.
Nat Commun ; 12(1): 16, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397898

RESUMO

Autophagy contributes to the selective degradation of liquid droplets, including the P-Granule, Ape1-complex and p62/SQSTM1-body, although the molecular mechanisms and physiological relevance of selective degradation remain unclear. In this report, we describe the properties of endogenous p62-bodies, the effect of autophagosome biogenesis on these bodies, and the in vivo significance of their turnover. p62-bodies are low-liquidity gels containing ubiquitin and core autophagy-related proteins. Multiple autophagosomes form on the p62-gels, and the interaction of autophagosome-localizing Atg8-proteins with p62 directs autophagosome formation toward the p62-gel. Keap1 also reversibly translocates to the p62-gels in a p62-binding dependent fashion to activate the transcription factor Nrf2. Mice deficient for Atg8-interaction-dependent selective autophagy show that impaired turnover of p62-gels leads to Nrf2 hyperactivation in vivo. These results indicate that p62-gels are not simple substrates for autophagy but serve as platforms for both autophagosome formation and anti-oxidative stress.


Assuntos
Autofagossomos/metabolismo , Estresse Oxidativo , Proteína Sequestossoma-1/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Autofagossomos/ultraestrutura , Autofagia , Linhagem Celular , Géis , Hepatócitos/metabolismo , Hepatócitos/ultraestrutura , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fígado/lesões , Fígado/patologia , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ligação Proteica , Lipossomas Unilamelares
18.
BMC Surg ; 21(1): 16, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407367

RESUMO

BACKGROUND: The treatment of hepatic injury can be complex. Medical clinical centers are often the first line hospitals for the diagnosis and treatment of hepatic trauma in China. The aim of the study is to summarize the experience in the diagnosis and treatment of hepatic trauma in one medical clinical center in China. METHODS: This retrospective study included patients with hepatic trauma admitted between January 2002 and December 2019 at the Xishan People's Hospital of Wuxi. The outcomes were cure rate and death within 14 days post-discharge. RESULTS: Among the 318 patients with hepatic trauma, 146 patients underwent surgical treatment, and 172 received conservative treatment; three patients were transferred to other hospitals for further treatment; 283 patients were cured, and 35 died. Severe hepatic trauma occurred in 74 patients, with a mortality rate of 31.1% and accounting for 65.7% of total mortality. American Association for the Surgery of Trauma (AAST) grading ≥ III (OR = 3.51, 95%CI: 1.32-9.37, P = 0.012) and multiple organ injury (OR = 7.51, 95%CI: 2.51-22.46, P < 0.001) were independently associated with death. Among patients with AAST grading ≥ III, surgery was an independent protective factor for death (OR = 0.08, 95%CI: 0.01-0.45, P = 0.004). Among patients with ASST ≥ III and who underwent surgery, age (OR = 5.29, 95%CI: 1.37-20.33, P = 0.015) and peri-hepatic packing (PHP) (OR = 5.54, 95%CI: 1.43-21.487, P = 0.013) were independently associated with death. CONCLUSIONS: AAST grading ≥ III and multiple organ injury were independently associated with death. Among patients with AAST grading ≥ III, surgery was an independent protective factor for death. Among patients with ASST ≥ III and who underwent surgery, age and PHP were independently associated with death.


Assuntos
Acidentes , Fígado , Ferimentos e Lesões , China , Estudos Transversais , Feminino , Hospitais , Humanos , Fígado/lesões , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Traumatologia , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/etiologia , Ferimentos e Lesões/terapia
19.
Life Sci ; 269: 119094, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33482193

RESUMO

AIM: Environmental heat stress alters physiological and biochemical functions which leads to multiorgan dysfunction including severe hepatic injury in animals. We hypothesize that heat preconditioning can be potential intervention in combating heat illnesses. MAIN METHODS: Sprague Dawley rats were exposed to moderate heat stress, severe heat stress and heat preconditioning in heat simulation chamber. Mean arterial pressure, heart rate, skin and core temperature were monitored in pre and post heat exposed animals. After stress exposure, blood for hemodynamic and liver tissue for liver function tests, oxidative stress, inflammatory variables and structural studies were collected from rats. Hepatic mitochondria were isolated to study the key structural alterations and functional changes by transmission electron microscopy. KEY FINDINGS: The effect of heat precondition shows improvement in time to attain the core temperature, weight loss, blood pressure and heart rate in rats. Results exhibited decreased levels of liver function tests, elevated levels of free radicals and inflammatory cytokines in heat exposed liver as compared with heat preconditioned animals. Expression levels of mitochondrial heat shock protein 60, superoxide dismutase 1 and uncoupling protein 1 along with activity of electron transport chain complexes I-V were examined and found to be increased in heat preconditioned as compared to heat stressed animals. Morphological studies of liver parenchyma demonstrated reduction in structural deterioration of hepatic lobules and restoration of mitochondrial structural integrity in heat preconditioned rats. SIGNIFICANCE: Present study suggests that heat preconditioning intervention plays a crucial role in protection against heat induced hepatic injury in animals.


Assuntos
Metabolismo Energético , Transtornos de Estresse por Calor/terapia , Resposta ao Choque Térmico , Temperatura Alta , Fígado/metabolismo , Estresse Oxidativo , Animais , Transtornos de Estresse por Calor/etiologia , Transtornos de Estresse por Calor/metabolismo , Transtornos de Estresse por Calor/patologia , Proteínas de Choque Térmico/metabolismo , Fígado/lesões , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Oxirredução , Ratos , Ratos Sprague-Dawley
20.
Nutrients ; 13(1)2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33401667

RESUMO

Liver fibrosis represents the consequences of chronic liver injury. Individuals with alcoholic or nonalcoholic liver diseases are at high risk of magnesium deficiency. This study aimed to evaluate the association between magnesium and calcium intakes and significant liver fibrosis, and whether the associations differ by alcohol drinking status. Based on the National Health and Nutrition Examination Survey (NHANES) 2017-2018, the study included 4166 participants aged >18 years who completed the transient elastography examination and had data available on magnesium intake. The median liver stiffness of 8.2 kPa was used to identify subjects with significant fibrosis (≥F2). The age-adjusted prevalence of significant fibrosis was 12.81%. Overall total magnesium intake was marginally associated with reduced odds of significant fibrosis (p trend = 0.14). The inverse association of total magnesium intake with significant fibrosis was primarily presented among those who had daily calcium intake <1200 mg. There were no clear associations for significant fibrosis with calcium intake. Findings suggest that high total magnesium alone may reduce risk of significant fibrosis. Further studies are needed to confirm these findings.


Assuntos
Ingestão de Alimentos , Cirrose Hepática/epidemiologia , Magnésio/administração & dosagem , Adulto , Consumo de Bebidas Alcoólicas , Cálcio/administração & dosagem , Feminino , Humanos , Fígado/lesões , Deficiência de Magnésio/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Estado Nutricional , Prevalência , Estados Unidos/epidemiologia
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