RESUMO
MR angiography (MRA) for pediatric moyamoya disease is important as a non-invasive examination to diagnose blood flow in the brain. Generally, the conventional 3D-TOF MRA is used for moyamoya disease. However, retrobulbar and subcutaneous fat of the head show high intensity signals. We found that using the conventional MRA to diagnose the details of brain blood flow is difficult and that it cannot differentiate moyamoya vessels and fat. It similarly obscures the ophthalmic artery and superficial temporal artery that overlap with fat in the direction of the maximum intensity projection (MIP). Therefore, we devised an MRA technique with fat suppression to diagnose blood flow in moyamoya disease patients: MR angiography with the principle of selective excitation technique (PROSET). The scan time does not need to be increased. We studied the TOF effect in constant and pulsatile flows and the water selective excitation method with the binominal pulse (PROSET) for the fat suppression effect for moyamoya disease. The results showed that PROSET-MRA achieved better image results than conventional MRA. The development of collaterals of the superficial temporal artery and occipital artery in pre- and post-operation moyamoya disease could be clearly visualized and evaluated. The PROSET-MRA method is useful for evaluating pre- and post-operation (encephalo-duro-arterio-synangiosis, encephalo-myo-synangiosis) blood flow reconstruction for patients who have moyamoya disease.
Assuntos
Circulação Cerebrovascular , Angiografia por Ressonância Magnética/métodos , Doença de Moyamoya/diagnóstico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Imagens de Fantasmas , Adulto JovemRESUMO
The spiral scan with a wide detector row such as the 64-detector row computed tomography (CT) system may increase radiation exposure for infants because the irradiation range is wider than the planned range. The adaptive dose shield (ADS) prevents radiation exposure greater than the planned range. We examined the usefulness of the protection effect of the ADS for the infant inner ear CT. To confirm the protection effect of the ADS, we scanned X-ray films by using the 64-detector row CT system and measured the difference of the planned range and the irradiation range. The result of that is that when the planned range was small, the protection effect for the scan ending side was inferior to the scan starting side. And also, when the gantry rotation speed and pitch factor (PF) were high values, the protection effect was inferior to a low gantry rotation speed and low PF. There was a combination of gantry rotation speed and PF at which the protection effect decreases. Due to changes of the scanning direction and PF for the infant inner ear, the crystalline lens radiation exposure dose decreased from 11.89 mGy to 4.37 mGy. In conclusion, the ADS can reduce the radiation exposure dose of an adjacent organ. Therefore, it was thought that the ADS was a useful radiation exposure reduction function for infants in the 64-detector row CT system.
Assuntos
Doses de Radiação , Proteção Radiológica/métodos , Tomografia Computadorizada Espiral , Orelha Interna/diagnóstico por imagem , Humanos , Lactente , Imagens de Fantasmas , CintilografiaRESUMO
BACKGROUND: Deficiency of ADAMTS13 (adisintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13) results in an increase in unusually large von Willebrand factor multimer (UL-VWFM) of the plasma and finally causes microcirculatory disturbance. Our previous study demonstrated that the imbalance of increased UL-VWFM over decreased ADAMTS13 activity may contribute to the development of multiorgan failure in patients with alcoholic hepatitis (AH). The aim of this study was to explore the potential mechanism to reduce the activity of plasma ADAMTS13. METHODS: Plasma cytokine levels including interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha), plasma endotoxin concentration, and the plasma inhibitor against ADAMTS13 were determined together with ADAMTS13 activity, VWF antigen (VWF:Ag), and UL-VWFM in 24 patients with AH and 5 patients with severe alcoholic hepatitis (SAH). RESULTS: The concentrations of IL-6, IL-8, and TNF-alpha on admission were significantly higher in patients with SAH than in those with AH and controls. The ADAMTS13 activity concomitantly decreased, and the VWF:Ag progressively elevated with increasing concentrations of these cytokines from normal range to over 100 pg/ml. Plasma endotoxin concentration was markedly higher in patients with SAH (mean 52.3 pg/ml) and AH (21.7 pg/ml) than in controls (7.9 pg/ml). The endotoxin concentration inversely correlated with ADAMTS13 activity and was higher in patients with UL-VWFM than those without. The inhibitor was detected in 4 patients with SAH (0.9 to 2.1 BU/ml) and 6 patients with AH (0.5 to 1.6 BU/ml). Patients with the inhibitor showed lower functional liver capacity, higher endotoxin concentration, and marked inflammatory signs than those without. At the recovery stage, the ADAMTS13 activity increased to normal range, the VWF:Ag decreased, and the UL-VWFM disappeared with the decrease in the concentrations of cytokines and endotoxin, and the disappearance of the inhibitor. CONCLUSION: Decreased ADAMTS13 activity and increased VWF:Ag could be induced not only by pro-inflammatory cytokinemia, but also by its inhibitor, both of which may be closely related to enhanced endotoxemia in patients with AH and SAH.
Assuntos
Proteínas ADAM/antagonistas & inibidores , Proteínas ADAM/sangue , Citocinas/sangue , Endotoxinas/sangue , Inibidores Enzimáticos/sangue , Hepatite Alcoólica/sangue , Proteína ADAMTS13 , Adulto , Idoso , Feminino , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue , Fator de von Willebrand/análiseRESUMO
Endoscopic retrieval of foreign bodies is sometimes a challenging task. We report a case of simultaneous removal of 5 coins from the stomach without causing mucosal injury using a specially-designed devices consisting of retrieval net, endoscopic attachment balloon and a disposable tip attachment. This technique has not been described before.
Assuntos
Corpos Estranhos/cirurgia , Gastroscopia/métodos , Corpos Estranhos/diagnóstico por imagem , Mucosa Gástrica/lesões , Gastroscópios , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , RadiografiaRESUMO
AIM: Cholestasis has been associated with the endocytic retrieval of multidrug resistance protein 2 (Mrp2), but its mechanism is still unclear. Recent studies have indicated that radixin, a cross-linker between the actin filaments and membrane proteins, may be activated by phosphorylation and may be required for the canalicular localization of Mrp2. METHODS: We investigated the role of radixin in the altered localization of Mrp2 in rat models of intrahepatic (ethinyl estradiol treatment) and extrahepatic (bile duct ligation) cholestasis using immunofluorescence microscopy. The changes in localization and expression were analyzed using Scion Image for Windows. RESULTS: In both models, Mrp2 was localized outside as well as inside the ZO-1 staining, indicating partial dislocation from the canalicular membrane. In contrast to the steep elevation of the immunostaining intensity curves for Mrp2 in the controls, the corresponding curves in both models were broadened and flattened, confirming endocytic retrieval into the hepatocytes. Mrp2 and radixin were colocalized at the canalicular domain in the controls, whereas in both cholestatic rats they were dissociated at some canaliculi, indicating the disturbed colocalization of Mrp2 and radixin in cholestasis. The fluorescence of phosphorylated radixin, an active form of radixin, markedly decreased in both cholestatic models, which was supported by the reduced peak fluorescence intensities. CONCLUSION: The disturbed colocalization of Mrp2 and radixin may contribute to the endocytic retrieval of Mrp2 in cholestasis due to the failure to anchor Mrp2 in the canalicular membrane, in which the phosphorylated radixin may play a major role.
RESUMO
BACKGROUND AND AIM: Endocytic retrieval of multidrug resistance protein 2 (MRP2) is closely associated with cholestasis and may be attributed to the disturbed linking of MRP2 and radixin, a cross-linker between actin filaments and membrane proteins. This study aimed to investigate the role of radixin in the altered localization of MRP2 in various human cholestatic liver diseases. METHODS: Using immunofluorescence microscopy, we investigated the localization and expression of MRP2 and radixin in various cholestatic liver diseases, such as drug-induced liver injury, obstructive jaundice, primary sclerosing cholangitis and autoimmune hepatitis. Changes in localization and expression were analyzed using Scion Image (software). RESULTS: In the icteric drug-induced liver injury, MRP2 was localized outside as well as inside of ZO-1 staining, indicating endocytic retrieval from the canalicular membrane into the pericanalicular compartments of the hepatocytes. The colocalization of MRP2 and radixin observed in the controls was disturbed, and MRP2 fluorescence disappeared in the canaliculi with disrupted radixin staining. Disturbed colocalization of MRP2 and radixin as well as endocytic retrieval of MRP2 was found in the poorly drained obstructive jaundice. When drainage was good, MRP2 was exclusively colocalized with radixin. Similar findings were observed in autoimmune hepatitis and primary sclerosing cholangitis. In the controls, the immunostaining intensity curves for MRP2 and radixin were steeply elevated in the canaliculi. The intensity curves for MRP2 and radixin were broadened in the icteric drug-induced liver injury and poorly drained obstructive jaundice, indicating endocytic retrieval into the hepatocytes. The peak fluorescence intensities for MRP2 and radixin decreased in the icteric liver. CONCLUSION: Disturbed colocalization of MRP2 and radixin was common in various cholestatic liver diseases, which may be associated with endocytic retrieval of MRP2 due to failure in anchoring MRP2 in the canalicular membrane.
Assuntos
Colestase/complicações , Proteínas do Citoesqueleto/análise , Hepatopatias/metabolismo , Fígado/química , Proteínas de Membrana/análise , Proteínas Associadas à Resistência a Múltiplos Medicamentos/análise , Adulto , Idoso , Canalículos Biliares/química , Estudos de Casos e Controles , Colestase/metabolismo , Endocitose , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Hepatopatias/etiologia , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Proteína 2 Associada à Farmacorresistência Múltipla , Fosfoproteínas/análise , Transporte Proteico , Proteína da Zônula de Oclusão-1RESUMO
Reactive oxygen species (ROS) is known to play an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH); however, as we previously reported, angiogenesis also plays a pivotal role in NASH progression - the development of liver fibrosis and hepatocellular carcinoma - in rats. The aim of the current study was to elucidate the role of angiogenesis in the development of fibrosis in NASH. Twenty-six patients with NASH and 11 with simple fatty liver (FL) disease were enrolled in the study and underwent clinicopathological examination. Immunohistochemical analysis of 4-hydroxy-2-noneal (4-HNE) and CD34 was employed for the detection of ROS and angiogenesis in the liver tissues, respectively. Both the NASH and FL samples displayed a marked staining of 4-HNE as compared to the healthy liver. Similar levels of 4-HNE were observed in NASH regardless of the grade of liver fibrosis. In sharp contrast, hepatic neovascularization developed significantly in NASH alone, whereas almost no neovascularization was observed in FL or the healthy liver. The degree of angiogenesis was almost parallel with the development of liver fibrosis. In conclusion, simple FL and NASH cases were both affected by ROS. However, only NASH was associated with marked neovascularization, proportional to the increase in the grade of liver fibrosis development. These results indicate that hepatic neovascularization may play an important role in the onset and progression of NASH.
RESUMO
BACKGROUND: Severe alcoholic hepatitis (SAH) in addition to alcoholic hepatitis (AH) is a life-threatening complication of alcohol abuse, and its pathogenesis remains unclear. The deficiency of ADAMTS13 results in an increase of the plasma unusually large von Willebrand factor multimer (UL-VWFM) and finally causes microcirculatory disturbance and multiorgan failure. We investigated the relationship of ADAMTS13 and von Willebrand factor antigen (VWF:Ag) with the clinical features of AH and SAH. METHODS: The plasma levels of ADAMTS13 activity, VWF:Ag, and UL-VWFM were determined in 24 patients with AH, 5 with SAH, and 10 with alcoholic liver cirrhosis (LC). RESULTS: The ADAMTS13 activity was significantly lower in SAH (mean 24%), AH (62%), and LC (76%) than in the healthy subjects (102%, n=62). The VWF:Ag levels were higher in SAH (806%), AH (405%), and LC (514%) than in the healthy subjects (100%), resulting in a higher ratio of VWF:Ag to ADAMTS13 activity in SAH (102.2), AH (8.9), and LC (8.6) compared with the healthy subjects (1.0). In 3 nonsurvivors with SAH and multiorgan failure, the protease activity markedly decreased (from 4.5 to 16%), and VWF:Ag remarkably increased (from 560 to 1,202%), resulting in an extremely high ratio of VWF:Ag to the activity (from 35.0 to 240.4). At the recovery stage in the survivors with SAH and AH, the protease activity increased and the VWF:Ag decreased, whereas in a nonsurvivor with SAH, the activity remained extremely low and the VWF:Ag was still high. Unusually large von Willebrand factor multimer was detected in 80.0% of SAH and 55.6% of AH. Multivariate analysis showed that the serum albumin and platelet count independently correlated with VWF:Ag. CONCLUSION: The enhanced production of UL-VWFM over deficient activity of ADAMTS13 may, in part, contribute to not only the progression of liver injury but also the development of multiorgan failure through microcirculatory disturbance in SAH in addition to AH. The imbalance between the plasma ADAMTS13 activity and VWF:Ag could be a useful prognostic marker in AH.
Assuntos
Proteínas ADAM/sangue , Antígenos/sangue , Hepatite Alcoólica/sangue , Cirrose Hepática Alcoólica/sangue , Insuficiência de Múltiplos Órgãos/sangue , Proteína ADAMTS13 , Adulto , Idoso , Feminino , Hepatite Alcoólica/diagnóstico , Humanos , Cirrose Hepática Alcoólica/diagnóstico , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Fator de von Willebrand/imunologiaRESUMO
BACKGROUND: Oxidative stress plays a major role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Mitochondrial abnormality may be associated with the onset and progression of NASH via excessive formation of mitochondrial reactive oxygen species. This study aimed to investigate the role of mitochondrial abnormality in NASH in relation to oxidative stress. METHODS: Twenty-six patients with NASH, 11 with simple steatosis, and 10 healthy volunteers underwent clinico-pathological analysis. The liver/spleen ratio, an index of the hepatic fat content, was evaluated with computed tomography. Plasma glutathione levels were measured as an antioxidative marker, and the urinary 8-isoprostane levels and 3-nitrotyrosine staining in the liver as an oxidative stress marker. Mitochondrial abnormality was estimated by serum levels of mitochondria aspartate transaminase (mAST) and the mitochondrial staining in the liver. RESULTS: Urinary 8-isoprostane levels were higher in NASH than in the healthy volunteers, whereas plasma glutathione levels were similar in the 2 groups. In NASH, urinary 8-isoprostane levels positively correlated with alanine transaminase levels and negatively with the liver/spleen ratio. The 3-nitrotyrosine staining was more advanced in simple steatosis and NASH than in the normal liver, but was similar in simple steatosis and NASH. In contrast to the normal mAST levels in the healthy volunteers and simple steatosis, serum mAST levels were elevated in one-fourth of the NASH patients and positively correlated with urinary 8-isoprostane levels in NASH. Most cases of NASH showed diffuse or focal but intense mitochondrial staining in the liver in contrast to scattered staining in simple steatosis. CONCLUSIONS: Our present study demonstrated that in NASH, the enhanced oxidative stress may be associated with hepatic inflammation and the degree of fat infiltration in the liver. However, simple steatosis and NASH were both exposed to oxidative stress, while NASH alone was associated with mitochondrial abnormality. These findings indicate that mitochondrial abnormality may play a role in the onset and progression of NASH in correlation with oxidative stress.
Assuntos
Fígado Gorduroso/fisiopatologia , Mitocôndrias Hepáticas/fisiologia , Estresse Oxidativo/fisiologia , Adulto , Aspartato Aminotransferases/metabolismo , Biópsia , Dinoprosta/análogos & derivados , Dinoprosta/metabolismo , Fígado Gorduroso/diagnóstico por imagem , Feminino , Glutationa/metabolismo , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Mitocôndrias Hepáticas/patologia , Valores de Referência , Baço/diagnóstico por imagem , Estatística como Assunto , Tomografia Computadorizada por Raios X , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
AIM: To evaluate the effect of combination treatment with the interferon (IFN) and angiotensin-converting enzyme inhibitor (ACE-I) on several fibrotic indices in patients with refractory chronic hepatitis C (CHC). METHODS: Perindopril (an ACE-I; 4 mg/d) and/or natural IFN (3 MU/L; 3 times a week) were administered for 12 mo to refractory CHC patients, and several indices of serum fibrosis markers were analyzed. RESULTS: ACE-I decreased the serum fibrosis markers, whereas single treatment with IFN did not exert these inhibitory effects. However, IFN significantly augmented the effects of ACE-I, and the combination treatment exerted the most potent inhibitory effects. The serum levels of alanine transaminase and HCV-RNA were not significantly different between the groups, whereas the plasma level of transforming growth factor-beta was significantly attenuated almost in parallel with suppression of the serum fibrosis markers. CONCLUSION: The combination therapy of an ACE-I and IFN may have a diverse effect on disease progression in patients with CHC refractory to IFN therapy through its anti-fibrotic effect.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Perindopril/uso terapêutico , Idoso , Progressão da Doença , Resistência a Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta/sangueRESUMO
Nonalcoholic steatohepatitis (NASH) may cause fibrosis, cirrhosis, and hepatocellular carcinoma (HCC); however, the exact mechanism of disease progression is not fully understood. Angiogenesis has been shown to play an important role in the progression of chronic liver disease. The aim of this study was to elucidate the role of angiogenesis in the development of liver fibrosis and hepatocarcinogenesis in NASH. Zucker rats, which naturally develop leptin receptor mutations, and their lean littermate rats were fed a choline-deficient, amino acid-defined diet. Both Zucker and littermate rats showed marked steatohepatitis and elevation of oxidative stress markers (e.g., thiobarbital acid reactive substances and 8-hydroxydeoxyguanosine). In sharp contrast, liver fibrosis, glutathione-S-transferase placental form (GST-P)-positive preneoplastic lesions, and HCC developed in littermate rats but not in Zucker rats. Hepatic neovascularization and the expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, only increased in littermate rats, almost in parallel with fibrogenesis and carcinogenesis. The CD31-immunopositive neovessels were mainly localized either along the fibrotic septa or in the GST-P-positive lesions. Our in vitro study revealed that leptin exerted a proangiogenic activity in the presence of VEGF. In conclusion, these results suggest that leptin-mediated neovascularization coordinated with VEGF plays an important role in the development of liver fibrosis and hepatocarcinogenesis in NASH.
Assuntos
Carcinoma Hepatocelular/etiologia , Fígado Gorduroso/fisiopatologia , Fibrose/etiologia , Glutationa S-Transferase pi/metabolismo , Leptina/fisiologia , Neovascularização Patológica/fisiopatologia , Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Colina/administração & dosagem , Modelos Animais de Doenças , Progressão da Doença , Fígado Gorduroso/patologia , Masculino , Estresse Oxidativo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Ratos , Ratos ZuckerRESUMO
A 22-year-old woman was admitted into our hospital because of generalized purpura and abnormalities in her chest X-ray. Isolated thrombocytopenia and elevated platelet-associated IgG levels were detected, while the bone marrow examination was normal. Mycobacterium tuberculosis was detected in the bronchoalveolar lavage fluid, and consequently she was diagnosed as having active tuberculosis. High-dose immunoglobulin therapy combined with anti-tuberculosis drugs not only rapidly and continuously corrected thrombocytopenia but also cured pulmonary tuberculosis. This case suggests a causal association between immune thrombocytopenia and tuberculosis as well as the safety and efficacy of the anti-tuberculosis drugs combined with high-dose immunoglobulin therapy.
Assuntos
Púrpura Trombocitopênica/etiologia , Tuberculose Pulmonar/complicações , Adulto , Antituberculosos/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Imunização Passiva , Púrpura Trombocitopênica/tratamento farmacológico , Púrpura Trombocitopênica/imunologia , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
A 54-year-old man with a past history of multi-operation for solitary fibrous tumor was hospitalized for hypoglycemia. Computed tomography demonstrated multiple tumors in the liver but not in the pancreas. His serum insulin-like growth factor (IGF)-II level was normal, but immunoblot analysis and immunohistochemistry revealed a high molecular weight form of IGF-II in the serum and tumor. Surgical resection was impossible, because of tumor dissemination. Hypoglycemia was repeated despite infusion of glucose and glucagon. Glucocorticoid dramatically and continuously abolished hypoglycemia. In cases of inoperable IGF-II-producing tumor, glucocorticoid therapy may be promising for hypoglycemia.
Assuntos
Fibroma/metabolismo , Glucocorticoides/uso terapêutico , Hipoglicemia/tratamento farmacológico , Fator de Crescimento Insulin-Like II/metabolismo , Neoplasias Hepáticas/metabolismo , Prednisolona/uso terapêutico , Fibroma/complicações , Humanos , Hipoglicemia/sangue , Hipoglicemia/etiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-IdadeRESUMO
Although it has been shown that a simultaneous administration of the vascular endothelial growth factor (VEGF); a potent angiogenic factor, could improve the overall survival of chemically induced acute hepatic failure (AHF) in rats, it has not been elucidated yet whether this salvage effect can be observed in the on-going AHF or not. For future clinical application, we examined the effect of VEGF on the on-going AHF. A combination of d-galactosamine (Gal-N) and lipopolysaccharide (LPS) was administered to induce AHF in rats. The survival rate and several indices were compared with or without VEGF treatment at 12 and 24h after the intoxication. Even after the establishment of severe liver injury, the overall survival and the serum ALT elevation were significantly improved by treatment with VEGF. The proliferation of the hepatocytes and sinusoidal endothelial cells (SEC) was also stimulated by VEGF. Furthermore, VEGF prevented the destruction of the architecture of the hepatic sinusoids. Since VEGF significantly improved the survival of the on-going AHF, the exogenous VEGF administration may represent a feasible new therapeutic strategy for AHF in the future.
RESUMO
AIM: Recent studies have demonstrated that obesity is the common feature of cryptogenic cirrhosis (CC) and non-alcoholic steatohepatitis. However, there is little information on CC in the region where obesity is not prevalent. METHODS: The clinical features, and the liver-related morbidity and mortality of CC were analyzed in Japan where the prevalence of obesity is low. Among 652 cirrhotic patients, we identified 29 patients (4.4%) with CC. Of these, 24 CC patients who were followed up for more than 6 months were compared in a case-control study with age-, sex-, and Child-Pugh score-matched controls having cirrhosis of viral etiology. RESULTS: Obesity (BMI>or=25 kg/m(2)), diabetes mellitus, and hypertriglyceridemia were more frequent, and the visceral fat area was larger in the CC patients than in the controls. The indices of insulin resistance were higher and the serum aminotransferase levels were lower in the CC patients than in the controls. Logistic regression analysis identified the elevated hemoglobin A1c, BMI>or=25 kg/m(2), and normal aminotransferase levels as independent predictors of CC. Kaplan-Meier analysis demonstrated lower occurrence of hepatocellular carcinoma and higher survival rate in the CC than in the controls in contrast to the similar cumulative probability of liver-related morbidity between those groups. CONCLUSION: CC more frequently presents with the clinical features suggestive of non-alcoholic steatohepatitis compared with controls even in the region where obesity is not prevalent. The lower occurrence of hepatocellular carcinoma and higher survival rate may indicate an indolent clinical course in CC as compared with viral cirrhosis.
Assuntos
Cirrose Hepática/etiologia , Adulto , Idoso , Biópsia , Índice de Massa Corporal , Carcinoma Hepatocelular/etiologia , Fígado Gorduroso/complicações , Humanos , Japão , Fígado/patologia , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Pessoa de Meia-Idade , ObesidadeRESUMO
AIM: To investigate whether adrenomedullin, a potent vasodilator peptide, plays a role in the circulatory disturbance in cirrhosis. METHODS: Cirrhosis was induced in rats by weekly gavage of carbon tetrachloride. Hemodynamic studies were performed in vivo using radioactive microspheres and in vitro using isolated aortic rings. The adrenomedullin concentrations were measured by radioimmunoassay. RESULTS: Acute administration of adrenomedullin to the control rats reduced the systemic arterial pressure along with an increase of serum levels of the stable metabolite of nitric oxide (NOx), in a dose-dependent manner. Chronic infusion of adrenomedullin reduced the vascular resistance and increased the blood flow in the systemic and splanchnic circulation. Intravenous administration of anti-adrenomedullin antibody did not affect any hemodynamic parameters in the cirrhotic rats, whereas this antibody ameliorated the blunted contractile response to phenylephrine, alpha-adrenergic receptor agonist, in the aortic rings of the cirrhotic rats. The adrenomedullin concentrations in the aorta were higher in the cirrhotic rats than in the controls, and correlated with the mean arterial pressure in the cirrhotic rats. Moreover, adrenomedullin blunted the contractile response to phenylephrine in both of the control aorta and cirrhotic aorta, but not in the presence of NG-nitro-L-arginine methyl ester, an NO synthase inhibitor. CONCLUSION: Adrenomedullin overproduced in the vascular wall may contribute to the circulatory disturbance in cirrhosis as a local regulator of the vascular tonus rather than a circulating hormone.
Assuntos
Débito Cardíaco Elevado/etiologia , Hipotensão/etiologia , Cirrose Hepática Experimental/fisiopatologia , Peptídeos/farmacologia , Resistência Vascular , Adrenomedulina , Animais , Pressão Sanguínea/efeitos dos fármacos , Cirrose Hepática Experimental/complicações , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/fisiologia , Peptídeos/sangue , Fenilefrina/farmacologia , Ratos , Ratos Sprague-Dawley , Resistência Vascular/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacosRESUMO
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection are major causes of gastric mucosal lesions. In Japan, histamine-2 receptor antagonists are frequently prescribed, but the literature regarding their efficacy is limited. In this study, we compare the effects of famotidine and rebamipide on NSAID-associated gastric mucosal lesions using upper gastrointestinal endoscopy. METHODS: This study examined 112 patients taking NSAIDs for either gastric hemorrhage or erosion. Before treatment, the patients were assessed by endoscopy. Using blind randomization, patients were divided into two groups: group F (famotidine, 20 mg/day) and group R (rebamipide, 300 mg/day). Efficacy was examined 4 weeks later using endoscopy. RESULTS: After treatment, the Lanza score decreased significantly in group F (P < 0.001) but not in group R (P = 0.478). The change in the Lanza score in group F was significantly greater (P = 0.002) than that in group R. CONCLUSIONS: Famotidine was superior to rebamipide in treating NSAID-associated mucosal lesions.
Assuntos
Alanina/análogos & derivados , Antiulcerosos/uso terapêutico , Famotidina/uso terapêutico , Mucosa Gástrica/patologia , Quinolonas/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Adulto , Idoso , Alanina/administração & dosagem , Alanina/uso terapêutico , Antiulcerosos/administração & dosagem , Endoscopia Gastrointestinal , Famotidina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica Hemorrágica/tratamento farmacológico , Quinolonas/administração & dosagemRESUMO
BACKGROUND/AIMS: The role of the vascular endothelial growth factor (VEGF), a potent angiogenic factor, in liver regeneration following acute severe liver injury (ALI) has not been elucidated. The aims of the current study were to investigate the role of VEGF, and to find out whether VEGF can improve the outcome of ALI in rats. METHODS: ALI was induced in male rats by combination of D-galactosamine (Gal-N) and lipopolysaccharide (LPS). The survival rate and several indices were chronologically compared with or without VEGF treatment. RESULTS: The overall survival rate of the VEGF-treated group significantly improved as compared with the untreated group (100 vs. 27%, respectively). The serum ALT elevation, with a peak at 24 h after Gal-N+LPS intoxication, was markedly attenuated with VEGF treatment. The proliferation of hepatocytes and sinusoidal endothelial cells (SEC) was stimulated by VEGF with a peak at 36 and 96 h, respectively. The immunohistochemical analysis revealed that VEGF drastically prevented destruction of the SEC architecture in ALI. Our in vitro study showed that VEGF significantly prevented the Gal-N+LPS-induced cytotoxicity and apoptosis of SEC. CONCLUSIONS: VEGF treatment significantly reduced the mortality rate of ALI in the rat, and it may provide a new therapeutic strategy for ALI.
Assuntos
Falência Hepática Aguda/tratamento farmacológico , Terapia de Salvação/métodos , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Seguimentos , Galactosamina/toxicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Imuno-Histoquímica , Lipopolissacarídeos/toxicidade , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/mortalidade , Regeneração Hepática/efeitos dos fármacos , Masculino , Ratos , Taxa de Sobrevida , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/farmacocinéticaRESUMO
BACKGROUND: The pathogenesis of alcoholic hepatitis (AH) remains unclear and the prognosis of severe alcoholic hepatitis (SAH) is very poor. Deficiency of von Willebrand factor (VWF)-cleaving protease (VWF-CP/ADAMTS13) results in an increase of the plasma unusually large VWF multimer and leads to platelet clumping, which causes microcirculatory disturbance and finally multiorgan failure. The aim of this study was to explore the potential role of ADAMTS13 on the development of liver disturbance and multiorgan failure in AH. METHODS: The activity of plasma ADAMTS13 and its clinical correlation were determined in 14 patients with AH, 4 with SAH (Maddrey score, mean 62), and 10 with alcoholic liver cirrhosis (LC). RESULTS: The activity of the plasma ADAMTS13 significantly decreased in patients with AH (mean 59%, p < 0.001), SAH (17%, p < 0.001) and LC (76%, p < 0.02) as compared with the healthy subjects (102%, n = 60). The activity was markedly lower in SAH than in AH (p < 0.02) and LC (p < 0.02). In three nonsurvivors with SAH who had multiorgan failure, it was extremely low (4.5%, 5.0%, and 16.0%, respectively), but in a survivor with SAH it remained mild decrease (44%). In AH, the protease activity increased at the recovery stage (42% --> 75%, p < 0.05). In the univariate analysis, the activity correlated with 10 clinical variables including functional liver capacity, inflammation signs, renal function, and platelet count in patients with AH and SAH. Among these, multivariate analysis showed that serum total bilirubin and C-reactive protein independently correlated with the protease activity. CONCLUSION: The activity of plasma ADAMTS13 markedly decreased in SAH in addition to AH. The activity was closely related to hyperbilirubinemia and inflammation signs, and was extremely low in nonsurvivors with SAH and multiorgan failure. The marked decrease of plasma ADAMTS13 may, in part, contribute to not only the progression of liver disturbance in AH, but also the development of multiorgan failure in SAH through microcirculatory disturbance.