ABSTRACT
Great effort has been paid to identify novel targets for pharmaceutical intervention to control inflammation associated with different diseases. We have studied the effect of signalling inhibitors in the secretion of the proinflammatory and profibrogenic cytokine interleukin (IL)-1ß in monocyte-derived macrophages (M-DM) obtained from the ascites of cirrhotic patients and compared with those obtained from the blood of healthy donors. Peritoneal M-DM were isolated from non-infected ascites of cirrhotic patients and stimulated in vitro with lipopolysaccharide (LPS) and heat-killed Candida albicans in the presence or absence of inhibitors for c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase kinase 1 (MEK1), p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). The IL1B and CASP1 gene expression were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of IL-1ß and caspase-1 were determined by Western blot. IL-1ß was also assayed by enzyme-linked immunosorbent assay (ELISA) in cell culture supernatants. Results revealed that MEK1 and JNK inhibition significantly reduced the basal and stimulated IL-1ß secretion, while the p38 MAPK inhibitor had no effect on IL-1ß levels. On the contrary, inhibition of PI3K increased the secretion of IL-1ß from stimulated M-DM. The activating effect of PI3K inhibitor on IL-1ß release was mediated mainly by the enhancement of the intracellular IL-1ß and caspase-1 content release to the extracellular medium and not by increasing the corresponding mRNA and protein expression levels. These data point towards the role of MEK1 and JNK inhibitors, in contrast to the PI3K-protein kinase B inhibitors, as potential therapeutic tools for pharmaceutical intervention to diminish hepatic damage by reducing the inflammatory response mediated by IL-1ß associated with liver failure.
Subject(s)
Ascites/immunology , Interleukin-1beta/metabolism , Liver Cirrhosis/immunology , Macrophages, Peritoneal/immunology , Phosphatidylinositol 3-Kinases/physiology , Proto-Oncogene Proteins c-akt/physiology , Adult , Aged , Caspase 1/physiology , Chromones/pharmacology , Female , Humans , Interleukin-1beta/genetics , MAP Kinase Signaling System/physiology , Macrophages, Peritoneal/metabolism , Male , Middle Aged , Morpholines/pharmacology , Phosphoinositide-3 Kinase InhibitorsSubject(s)
Antineoplastic Agents/adverse effects , Chemical and Drug Induced Liver Injury/etiology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Liver Failure/surgery , Liver Transplantation , Piperazines/adverse effects , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Adult , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/therapeutic use , Benzamides , Contraceptives, Oral, Hormonal/adverse effects , Contraceptives, Oral, Hormonal/pharmacokinetics , Cytochrome P-450 CYP3A/metabolism , Drug Interactions , Female , Humans , Imatinib Mesylate , Liver Failure/chemically induced , Piperazines/pharmacokinetics , Piperazines/therapeutic use , Protein Kinase Inhibitors/pharmacokinetics , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/pharmacokinetics , Pyrimidines/therapeutic useABSTRACT
Budd-Chiari syndrome can be defined as an interruption or diminution of the normal blood flow out of the liver. Patients with Budd-Chiari syndrome present with varying degrees of symptomatology that can be divided into the following categories: fulminant, acute, subacute and chronic. The subacute form is the most common presentation. A majority of patients with Budd-Chiari syndrome have an underlying hypercoagulability state. We present the case of a young woman with Crohn s disease on oral contraceptives who developed bilateral pulmonary thromboembolism and Budd-Chiari syndrome.
Subject(s)
Budd-Chiari Syndrome/complications , Contraceptives, Oral/adverse effects , Crohn Disease/complications , Ethinyl Estradiol/adverse effects , Pulmonary Embolism/chemically induced , Adult , Budd-Chiari Syndrome/diagnostic imaging , Colonoscopy , Crohn Disease/diagnosis , Crohn Disease/diagnostic imaging , Female , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/drug therapy , Radiography, Abdominal , Radiography, Thoracic , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
El síndrome de Budd-Chiari consiste en la interrupción o disminuciónde flujo de las venas suprahepáticas. Tiene una gran variabilidadclínica en cuanto a su forma de presentación siendo la másfrecuente la forma subaguda. La gran mayoría de los pacientesresponden a estados de hipercoagulabilidad. Presentamos el casode una paciente joven con enfermedad de Crohn que estaba entratamiento con anticonceptivos orales y desarrolló un cuadro clínicode tromboembolismo de pulmón bilateral y síndrome deBudd-Chiari(AU)
Budd-Chiari syndrome can be defined as an interruption or diminutionof the normal blood flow out of the liver. Patients withBudd-Chiari syndrome present with varying degrees of symptomatologythat can be divided into the following categories: fulminant,acute, subacute and chronic. The subacute form is the mostcommon presentation. A majority of patients with Budd-Chiarisyndrome have an underlying hypercoagulability state. We presentthe case of a young woman with Crohns disease on oralcontraceptives who developed bilateral pulmonary thromboembolismand Budd-Chiari syndrome(AU)
Subject(s)
Humans , Female , Adult , Budd-Chiari Syndrome/complications , Contraceptives, Oral/adverse effects , Crohn Disease/complications , Colonoscopy/methods , Ethinyl Estradiol/adverse effects , Pulmonary Embolism/chemically induced , Budd-Chiari Syndrome , Crohn Disease/diagnosis , Crohn Disease , Heparin, Low-Molecular-Weight/therapeutic use , Pulmonary Embolism/drug therapy , Pulmonary Embolism , Radiography, Abdominal/methods , Radiography, Thoracic/methods , Tomography, X-Ray Computed/methods , Treatment OutcomeABSTRACT
Hepatic hemangioma is the most frequent liver's tumor. The majority are small, asymptomatic and have an excellent prognosis. Those larger than 5 cm can be associated to a consumptive coagulopathy called Kasabach-Merrit syndrome. We present a patient with a giant hepatic hemangioma with multiple hemangimatosis associated to Kasabach-Merrit syndrome.
Subject(s)
Disseminated Intravascular Coagulation/complications , Hemangioma/complications , Liver Neoplasms/complications , Adult , Hemangioma/pathology , Humans , Liver Neoplasms/pathology , MaleABSTRACT
El hemangioma hepático es el tumor benigno más frecuentedel hígado. La gran mayoría de ellos son de pequeño tamaño,asintomáticos y con un pronóstico excelente. En raras ocasionesson de mayor tamaño y pueden estar asociados a una coagulopatíade consumo denominada síndrome de Kasabach-Merrit. Presentamosel caso de un paciente varón joven con un hemangiomahepático gigante y hemangiomatosis múltiple asociado al síndromede Kasabach-Merrit
Hepatic hemangioma is the most frequent livers tumor. Themajority are small, asymptomatic and have an excellent prognosis.Those larger than 5 cm can be associated to a consumptivecoagulopathy called Kasabach-Merrit syndrome. We present a patientwith a giant hepatic hemangioma with multiple hemangimatosis associated to Kasabach-Merrit syndrome (AU)
Subject(s)
Humans , Male , Adult , Disseminated Intravascular Coagulation/complications , Hemangioma/complications , Liver Neoplasms/complications , Hemangioma/pathology , Liver Neoplasms/pathologyABSTRACT
We have evaluated the clinical and epidemiological features of hepatic cirrhosis in a retrospective study of 200 patients admitted to our Area Hospital from 1984 to 1987. 77% of patients were 40-69 years old and 74% were males, with a M/F ratio of 2.84. 56% were caused by high alcohol intake, 25% were cryptogenic and 13% post-hepatitis. 29.2% were diagnosed in a compensated stage of the disease. 52.2% presented with ascites, and 30.5% with upper gastrointestinal hemorrhage. We found superimposed hepatocellular carcinoma in 4.5% of patients, all of them males, with a mean age of 63.5 years. 18% died during their hospital admission, 50% from hepatic coma, 19.4% from hypovolemic shock and 16.6% from hepatorenal syndrome. Survival from the time of diagnosis in the patients who died was shorter than one year in 41.5%.
Subject(s)
Liver Cirrhosis/epidemiology , Adult , Aged , Female , Humans , Liver Cirrhosis/etiology , Liver Cirrhosis/mortality , Male , Middle Aged , Spain/epidemiologyABSTRACT
A case is presented of chronic intestinal ischemia due to arteriosclerotic obstruction of the celiac trunk and superior mesenteric artery. The diagnosis was reached by right transfemoral aortography. Surgical treatment was direct reimplantation of the superior mesenteric artery on the anterior aspect of the healthy aorta and installation of a retrograde Dacron graft between the aorta and common hepatic artery. The patient's postoperative course was satisfactory, with total remission of the symptomatology; revascularization was confirmed by a new aortography at six months. The diagnostic and therapeutic problems posed by this pathology are commented.