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1.
Ann Chir ; 130(9): 581-3, 2005 Oct.
Artigo em Francês | MEDLINE | ID: mdl-16199000

RESUMO

A 47-year old man complained about persistant pain and cholestasis 12-years after a cholescystectomy. In his family, all his brothers and sisters had cholecystectomy. Genetic explorations revealed a MDR3 gene mutation. All symptoms disappeared with a treatment by ursodesoxycholic acid. MDR3 gene mutation is to be researched in all cases of familial cholestasis.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/genética , Colestase Intra-Hepática/genética , Colagogos e Coleréticos/uso terapêutico , Colecistectomia , Colestase Intra-Hepática/patologia , Análise Mutacional de DNA , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Linhagem , Ácido Ursodesoxicólico/uso terapêutico
2.
Gut ; 53(12): 1844-9, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15542526

RESUMO

BACKGROUND/AIMS: Lipopolysaccharide (LPS) induces liver injury which is associated with upregulated endothelin (ET)-1 production. The aim of this study was to investigate the effects of tezosentan, a non-selective ETA and ETB receptor antagonist, in LPS challenged rats with cirrhosis. METHODS: Rats with cirrhosis received LPS and then tezosentan or placebo one hour later. Four hours after LPS administration, rats were killed to measure serum transaminase activity and plasma tumour necrosis factor alpha (TNF-alpha) levels. Hepatic inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), a marker of neutrophil infiltration, and cyclooxygenase (COX)-2 expression were also measured. RESULTS: LPS administration significantly decreased arterial pressure and significantly increased plasma endothelin levels. Following LPS and tezosentan administration, serum aspartate aminotransferase and alanine aminotransferase activities were similar to those in the control group while they were increased by more than 700% with LPS alone. Plasma TNF-alpha levels were significantly lower in rats receiving LPS and tezosentan (182 (38) pg/ml) compared with those receiving LPS alone (821 (212) pg/ml). Tezosentan significantly decreased hepatic MPO activity and hepatic neutrophils but had no effect on LPS induced iNOS or COX-2. Survival rate was significantly higher in rats receiving LPS plus tezosentan (80%) than in rats receiving LPS alone (50%). CONCLUSION: In LPS challenged cirrhotic rats, tezosentan administration prevents LPS induced liver injury by decreasing intrahepatic neutrophil infiltration. In addition, tezosentan increases survival in these rats.


Assuntos
Antagonistas dos Receptores de Endotelina , Endotoxemia/tratamento farmacológico , Cirrose Hepática/complicações , Piridinas/uso terapêutico , Tetrazóis/uso terapêutico , Vasodilatadores/uso terapêutico , Animais , Endotelinas/sangue , Endotoxemia/complicações , Endotoxemia/metabolismo , Lipopolissacarídeos , Fígado/enzimologia , Cirrose Hepática/metabolismo , Masculino , Infiltração de Neutrófilos/efeitos dos fármacos , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Transaminases/sangue , Fator de Necrose Tumoral alfa/metabolismo
3.
J Hepatol ; 35(3): 350-7, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11592596

RESUMO

BACKGROUND/AIMS: In vitro studies have shown that cirrhotic aortas are hyporeactive to the contractile effect of vasoconstrictors because upregulated endothelial nitric oxide-synthase (NOS) overproduces nitric oxide (NO). Although stimulation of endothelial small-conductance Ca2+-dependent K+ (SK(Ca)) channels may elicit vasorelaxation in normal arteries, the role of these channels in cirrhosis-induced hyporeactivity is unknown. Thus, the aim of the present study was to investigate the role of endothelial SK(Ca) channels in cirrhosis-induced, NO-mediated, in vitro aortic hyporeactivity to alpha1-adrenergic vasoconstrictors. METHODS: Isolated thoracic aortas from cirrhotic and normal rats were used. The effects of apamin, a selective SK(Ca) channel blocker, were measured on the vascular reactivity to phenylephrine. In addition, SK(Ca) channel protein expression was studied. The effects of iberiotoxin and charybdotoxin, blockers of other K(Ca) channels, were also studied in cirrhotic aortas. RESULTS: Apamin suppressed cirrhosis-induced aortic hyporeactivity to phenylephrine in an endothelium-dependent, NOS-inhibitor-sensitive manner. SK(Ca) channel protein was overexpressed in cirrhotic aortic walls. Iberiotoxin abolished cirrhosis-induced aortic hyporeactivity to phenylephrine in an endothelium-dependent but NOS-inhibitor-resistant manner. Charybdotoxin did not induce any significant increase in phenylephrine-elicited contraction. CONCLUSIONS: In cirrhotic aortas, the overexpression and overactivity of endothelial SK(Ca) channels contributes to in vitro NO-mediated hyporeactivity to the contractile action of alpha1-adrenergic agonists.


Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Aorta/efeitos dos fármacos , Cálcio/fisiologia , Cirrose Hepática Experimental/fisiopatologia , Óxido Nítrico/fisiologia , Canais de Potássio/fisiologia , Receptores Adrenérgicos alfa 1/fisiologia , Vasoconstrição/efeitos dos fármacos , Animais , Aorta/fisiologia , Apamina/farmacologia , Charibdotoxina/farmacologia , Técnicas In Vitro , Masculino , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo III , Ratos , Ratos Sprague-Dawley
5.
Eur J Gastroenterol Hepatol ; 13(3): 251-6, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11293444

RESUMO

OBJECTIVE: In patients with cirrhosis, the relationships between haemodynamic alterations and the development of ascites or the occurrence of refractory ascites are unknown. The aim of the present study was to compare haemodynamic measurements obtained in patients with non-refractory ascites to haemodynamic measurements obtained in patients without ascites and in patients with refractory ascites. METHODS: A cohort of 121 patients was prospectively studied, of whom 29 patients did not have ascites, 45 had non-refractory ascites and 47 had refractory ascites. Splanchnic, renal and systemic haemodynamics were measured in all patients. RESULTS: The hepatic venous pressure gradient was significantly higher in patients with non-refractory ascites than in patients without ascites (18.5 +/- 0.8 mmHg versus 15.8 +/- 0.7 mmHg). Renal and systemic haemodynamics did not significantly differ between patients with non-refractory ascites and patients without ascites. The glomerular filtration rate and renal blood flow were significantly lower in patients with refractory ascites than in patients with non-refractory ascites (77 +/- 4 versus 107 +/- 5 ml/min and 867 +/- 62 versus 1,008 +/- 68 ml/min, respectively). Splanchnic and systemic haemodynamics did not significantly differ between patients with refractory ascites and patients with non-refractory ascites. CONCLUSIONS: In patients with cirrhosis, an increase in portal hypertension was the sole haemodynamic alteration related to the development of ascites. Renal vasoconstriction (and subsequent renal hypoperfusion and hypofiltration) was the only haemodynamic alteration related to the occurrence of refractory ascites. The development of ascites or refractory ascites was not associated with any alteration in systemic haemodynamics.


Assuntos
Ascite/fisiopatologia , Hemodinâmica/fisiologia , Cirrose Hepática/fisiopatologia , Aldosterona/sangue , Feminino , Humanos , Rim/irrigação sanguínea , Fígado/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Renina/sangue
6.
J Hepatol ; 33(3): 376-81, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11019992

RESUMO

BACKGROUND/AIMS: Septic shock results in high mortality in patients with cirrhosis. Nitric oxide synthase 2 (NOS2) is induced by bacterial lipopolysaccharides (LPS) and plays a major role in the inflammatory response to bacterial infections. Little is known about the regulation of NOS2 in cirrhosis under septic conditions. Thus, the aim of this study was to determine tissue NOS2 activity, serum nitrate and tumor necrosis factor (TNF-alpha) levels and hepatic toxicity in cirrhotic rats after LPS administration. METHODS: Serum nitrates, TNF-alpha and transaminases were determined after LPS-administration in rats with secondary biliary cirrhosis and in sham-operated rats. Liver, lung, aortic and peritoneal macrophage NOS2 activities were determined by converting L[14C] arginine into L[14C] citrulline in a calcium free medium. Nitrate and TNF-alpha production were determined in a culture medium of peritoneal macrophages after in vivo LPS administration. RESULTS: LPS (1.5 mg/kg) induced 50% mortality in cirrhotic rats and no mortality in sham-operated rats. After LPS, TNF-alpha, nitrate and transaminase levels were significantly higher in cirrhotic rats compared to sham-operated rats. After LPS administration, there were no differences in NOS2 activity in the aorta, lungs, or peritoneal macrophages of the two groups, whereas NOS2 activity was significantly higher in the cirrhotic liver compared to the normal liver. CONCLUSIONS: In rats with cirrhosis, LPS administration induces higher mortality, hepatic toxicity, hepatic NOS2 activation and TNF-alpha release than in sham-operated rats. These results confirm the harmful role of septic shock in liver disease.


Assuntos
Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/intoxicação , Cirrose Hepática/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Óxido Nítrico Sintase/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Animais , Lipopolissacarídeos/toxicidade , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Masculino , Nitratos/metabolismo , Óxido Nítrico Sintase Tipo II , Ratos , Ratos Sprague-Dawley , Transaminases/sangue , Fator de Necrose Tumoral alfa/análise
7.
Hepatology ; 32(5): 935-41, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11050042

RESUMO

In cirrhosis, in splanchnic arteries, endothelium-dependent relaxation may persist even if overactive nitric oxide synthase (NOS) and cyclooxygenase (COX) are inhibited. In normal arteries, a significant endothelium-dependent relaxation to acetylcholine persists after NOS/COX inhibition. This relaxation is caused by smooth muscle cell (SMC) membrane hyperpolarization, which is sensitive to a combination of the potassium channel blockers apamin and charybdotoxin, and is mediated by an endothelium-derived hyperpolarizing factor (EDHF). The aim of this study was to detect EDHF and evaluate its pathophysiologic role in isolated superior mesenteric arteries from cirrhotic rats. Arterial rings were obtained and exposed to N(w)-nitro-L-arginine (L-NNA, a NOS inhibitor) and indomethacin (a COX inhibitor). Acetylcholine-induced membrane potential responses and concentration-response curves to the relaxant of acetylcholine were obtained with and without apamin plus charybdotoxin. Acetylcholine-induced responses were measured in certain rings from endothelium-denuded arteries. Contractions caused by the alpha(1)-adrenoceptor agonist phenylephrine were obtained in cirrhotic and normal rings with and without apamin and charybdotoxin. Significant acetylcholine-induced, endothelium-dependent, apamin- and charybdotoxin-sensitive, SMC membrane hyperpolarization and relaxation were found. An apamin- and charybdotoxin-sensitive hyporesponsiveness to the contractile action of phenylephrine was found in cirrhotic rings. In conclusion, in cirrhotic rats, in the superior mesenteric artery exposed to NOS/COX-inhibitors, an EDHF exists that may replace NOS/COX products to induce endothelium-dependent arterial relaxation.


Assuntos
Fatores Biológicos/metabolismo , Cirrose Hepática/metabolismo , Artérias Mesentéricas/metabolismo , Acetilcolina/farmacologia , Animais , Apamina/farmacologia , Bário/farmacologia , Charibdotoxina/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Combinação de Medicamentos , Inibidores Enzimáticos/farmacologia , Técnicas In Vitro , Indometacina/farmacologia , Cirrose Hepática/fisiopatologia , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiopatologia , Nitroarginina/farmacologia , Ouabaína/farmacologia , Ratos , Ratos Sprague-Dawley , Valores de Referência , Vasodilatação , Vasodilatadores/farmacologia
8.
Ann Med Interne (Paris) ; 151(8): 667-8, 2000 Dec.
Artigo em Francês | MEDLINE | ID: mdl-11173712

RESUMO

We report the case of a 40-year-old-man who developed febrile cytolysis as the presenting sign of hemorragic fever with renal syndrome (HFRS). On admission, he had fever (40 degrees C) and epigastric pain. The AST level was at 2N, the ALT at 3N. There was a thrombocytopenia (61 000/mm(3)) without anemia or hyperleukocytosis. Three days after admission, the platelet count decreased to 40 000/mm(3), serum urea and creatinine increased from normal rate to 10.8mmol/l, 204.0 micromol/l, respectively. The HIV, HBV, HCV, leptospirosis antibodies were negative. The Hantavirus serology was positive (Ig G: 1/512). This case suggests that HFRS should be entertained as a possible cause of cytolysis with thrombocytopenia in patients with fever and no initial sign of renal involvement in North-Eastern France.


Assuntos
Febre Hemorrágica com Síndrome Renal/diagnóstico , Adulto , Humanos , Masculino
10.
Ann Biol Clin (Paris) ; 55(4): 275-87, 1997.
Artigo em Francês | MEDLINE | ID: mdl-9309226

RESUMO

Numerous viruses found in the gut are not associated with primary infection or disease of the gastrointestinal tract. Other groups or viruses are not classically associated with infection of the gut but can infect the gastrointestinal tract in immunocompromised individuals (herpes simplex virus, cytomegalovirus, papillomavirus ....). The viruses associated with gastroenteritis represent a large number of taxonomic group. Because these viruses have in general been difficult to cultivate, most members of this group were firstly detected by electron microscopic examination (adenovirus, astrovirus, calicivirus, coronavirus, rotavirus ....). The most widely used diagnostic techniques for adenovirus (40/41), rotavirus and astrovirus detection in faecal samples include immunoassays such as Elisa and latex agglutination. Nucleic acid hybridization techniques have generally not proven to be substantially sensitive and the more sensitive techniques recently developed use the polymerase chain reaction (adenovirus) or the reverse transcription/polymerase chain reaction (astrovirus, calicivirus, coronavirus, rotavirus). Special efforts have been made in the search for efficient procedures to extract viral nucleic acids, and to establish the optimal conditions for the amplification and identification of PCR products but the candidate viruses were very different, consensus procedures were not determined, and amplification kits were not actually commercialized.


Assuntos
Gastroenterite/virologia , Viroses/virologia , Técnicas de Laboratório Clínico/métodos , Gastroenterite/diagnóstico , Gastroenterite/epidemiologia , Humanos , Viroses/diagnóstico , Viroses/epidemiologia , Vírus/classificação , Vírus/isolamento & purificação
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