RESUMO
Hepatitis C is an inflammatory disease of the liver caused by a single-stranded RNA virus belonging to the Hepacivirus genus in the Flaviviridae family, called the hepatitis C virus. After initial infection, 70% to 85% of the patients develop chronic hepatitis C with hepatic fibrosis. In addition to specific liver changes, various extrahepatic manifestations have been associated with the hepatitis C virus infection or with medications used to treat the condition. We report the case of a patient with chronic hepatitis C who presented with the signs and symptoms of borderline tuberculoid leprosy and type 1 reaction four months after the start of treatment with a pegylated interferon/ribavirin combination.
Assuntos
Antivirais/efeitos adversos , Hepatite C/tratamento farmacológico , Interferons/efeitos adversos , Hanseníase Dimorfa/induzido quimicamente , Hanseníase Tuberculoide/induzido quimicamente , Ribavirina/efeitos adversos , Reação de Fase Aguda/induzido quimicamente , Quimioterapia Combinada/efeitos adversos , Hepatite C/complicações , Humanos , Hanseníase Dimorfa/patologia , Hanseníase Tuberculoide/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Hepatitis C is an inflammatory disease of the liver caused by a single-stranded RNA virus belonging to the Hepacivirus genus in the Flaviviridae family, called the hepatitis C virus. After initial infection, 70% to 85% of the patients develop chronic hepatitis C with hepatic fibrosis. In addition to specific liver changes, various extrahepatic manifestations have been associated with the hepatitis C virus infection or with medications used to treat the condition. We report the case of a patient with chronic hepatitis C who presented with the signs and symptoms of borderline tuberculoid leprosy and type 1 reaction four months after the start of treatment with a pegylated interferon/ribavirin combination.
A hepatite C é uma doença inflamatória fígado causada por um vírus RNA de fita simples, pertencente ao gênero Hepacivirus e à família Flaviviridae, denominado de vírus da hepatite C. Após infecção inicial 70 a 85% dos pacientes infectados evoluem para hepatite C crônica, com fibrose progressiva. Além das alterações hepáticas específicas, várias manifestações extra-hepáticas têm sido relacionadas à infecção pelo vírus da hepatite C ou às medicações utilizadas no seu tratamento. Nesse trabalho, apresenta-se caso de paciente portador de hepatite C crônica, que manifestou um quadro hanseníase boderline tuberculóide e reação hansênica do tipo I, quatro meses após início do tratamento com interferon peguilado associado à ribavirina.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Antivirais/efeitos adversos , Hepatite C/tratamento farmacológico , Interferons/efeitos adversos , Hanseníase Dimorfa/induzido quimicamente , Hanseníase Tuberculoide/induzido quimicamente , Ribavirina/efeitos adversos , Reação de Fase Aguda/induzido quimicamente , Quimioterapia Combinada/efeitos adversos , Hepatite C/complicações , Hanseníase Dimorfa/patologia , Hanseníase Tuberculoide/patologiaRESUMO
UNLABELLED: We have previously shown that tissue-type plasminogen activator (tPA) and rat plasma kallikrein (RPK) share a common, but not unique, pathway for liver clearance. AIM: To evaluate the hepatic clearance of both proteases in experimental liver fibrosis. METHODS: The hepatic clearance of these proteases was studied in porcine serum-induced liver fibrosis using the isolated and perfused rat liver model. To better interpret the results, we also studied four other experimental groups: the turpentine oil-induced acute-phase response (AP group), AP group followed by GdCl3 administration (AP/Gd group), CCl4-induced cirrhosis (CCl4 group) and normal group. RESULTS: The tPA clearance decreased significantly by both fibrotic and cirrhotic rat livers whereas the RPK clearance was not altered by the fibrotic rat liver. The hepatic clearance of tPA was reduced in the AP and AP/Gd groups; on the other hand, RPK clearance was increased in the AP group and, interestingly, this effect was neutralized by concomitant GdCl3 administration. CONCLUSIONS: We observed that tPA and RPK clearances were affected differently by fibrosis as well as by different stimuli of the acute-phase response, despite the fact that they share a common hepatic clearance mechanism in normal livers, and they were equally affected in cirrhosis.
Assuntos
Cirrose Hepática Experimental/metabolismo , Fígado/metabolismo , Calicreína Plasmática/metabolismo , Ativador de Plasminogênio Tecidual/metabolismo , Reação de Fase Aguda/induzido quimicamente , Reação de Fase Aguda/metabolismo , Animais , Intoxicação por Tetracloreto de Carbono/metabolismo , Gadolínio , Células de Kupffer/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/patologia , Masculino , Ratos , Ratos Wistar , TerebintinaRESUMO
The effect of fat-rich diets on the acute inflammatory response was examined. Male Wistar rats aged 21 days were fed, for 6 weeks, with a control diet (4% fat content), or a control diet supplemented with coconut or soybean oils (15% fat content). Carrageenan-induced paw oedema and pleurisy were evaluated. Prostaglandin (PG) E2 and leukotriene (LT) C4/D4 concentrations were determined in the pleural exudate (ELISA). Pleural samples were tested for their effect on cutaneous vascular permeability of control rats and the effect of a LTD4 receptor antagonist (L660-711; 10 mg/kg; i.v.) examined. Relative to controls, rats fed both fat-rich diets presented a significant reduction in protein leakage and oedema formation without affecting the number of migrating leukocytes. Production of LTC4/D4 in pleural exudate was significantly increased from 1.8 +/- 0.2 ng/ml in controls to 2.8 +/- 0.2 and 3.0 +/- 0.3 ng/ml in animals fed coconut and soybean oil enriched diets, respectively, without changes in PGE2 production. The activity of these samples on cutaneous vascular permeability was 50% reduced, returning to control values after treatment of testing animals with a LTD4 receptor antagonist. Rats fed fat-rich diets presented a reduced inflammatory response due, at least in part, to the LTC4/D4 mediated vasoconstrictor effect.
Assuntos
Reação de Fase Aguda/dietoterapia , Gorduras na Dieta/administração & dosagem , Leucotrieno C4/metabolismo , Leucotrieno D4/metabolismo , Reação de Fase Aguda/induzido quimicamente , Reação de Fase Aguda/metabolismo , Animais , Permeabilidade Capilar/efeitos dos fármacos , Carragenina , Óleo de Coco , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/metabolismo , Ensaio de Imunoadsorção Enzimática , Exsudatos e Transudatos/metabolismo , Membro Posterior/efeitos dos fármacos , Antagonistas de Leucotrienos/farmacologia , Masculino , Óleos de Plantas/administração & dosagem , Derrame Pleural/metabolismo , Pleurisia/induzido quimicamente , Pleurisia/metabolismo , Propionatos/farmacologia , Quinolinas/farmacologia , Ratos , Ratos Wistar , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Óleo de Soja/administração & dosagemRESUMO
Chronic malnutrition is one of the most important causes of several metabolic, immune and neuroendocrine dysfunctions. The aim of the present study was to determine the influence of chronic food restriction on basal neuroendocrine, immune and adipocyte functions and during the acute-phase response to endotoxic shock in female rats. The effect of refeeding of undernourished rats on the above-mentioned functions was also investigated. For these purposes, plasma total protein, glucose, triglycerides, ACTH, corticosterone, tumor necrosis factor-alpha (TNF) and leptin (LEP) levels were determined in basal condition and 2 h after endotoxin (LPS; 180 microgram/kg body weight, i.p.) administration in 3 different groups: (1) well-nourished (WN) controls; (2) undernourished (UN) rats as a consequence of chronic food restriction, and (3) UN rats re-fed to restoration of their body weights in the WN rat range. The results indicate that UN rats, in comparison with WN controls, developed an arrest in body weight gain as well as in basal hypoglycemia, hypotriglyceridemia, hypoleptinemia, hypercorticosteronemia and enhanced adrenal glucocorticoid content; however, no changes in basal total protein, ACTH and TNF plasma levels and in anterior pituitary ACTH concentrations were found. When endotoxic shock was induced, the LPS-induced hypoglycemia developed in WN rats was abolished in UN animals, and both ACTH and TNF plasma concentrations after endotoxin, albeit significantly (p < 0.05) higher than the respective basal values, were significantly (p < 0.05) lower in UN than in WN control rats. Despite the high basal plasma corticosterone concentration in UN vs. WN rats, the LPS-induced glucocorticoid release was similar in WN and UN rats. Additionally, LPS treatment did not modify basal plasma LEP levels, regardless of the group. Interestingly, UN rats fed ad libitum for 15 days restored their body weight to WN rat range values, and the various metabolic dysfunctions seen in UN rats in both basal and post-LPS conditions were fully normalized. Our results clearly indicate that chronic undernutrition not only affects, as earlier described, reproductive function but also metabolic, neuroendocrine, immune and adipocyte functions, and that the effects induced by undernutrition can be fully reversed after recovery of normal body weight. The present study strongly supports the involvement of the metabolic status in the effectiveness of the defense mechanisms developed in patients in inflammatory stress conditions.
Assuntos
Reação de Fase Aguda , Adipócitos/metabolismo , Sistema Imunitário/fisiopatologia , Sistemas Neurossecretores/fisiopatologia , Distúrbios Nutricionais , Choque Séptico , Reação de Fase Aguda/sangue , Reação de Fase Aguda/induzido quimicamente , Reação de Fase Aguda/imunologia , Reação de Fase Aguda/metabolismo , Adipócitos/efeitos dos fármacos , Hormônio Adrenocorticotrópico/sangue , Envelhecimento/fisiologia , Animais , Glicemia/análise , Corticosterona/sangue , Feminino , Privação de Alimentos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/imunologia , Leptina/sangue , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/farmacologia , Análise por Pareamento , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/metabolismo , Distúrbios Nutricionais/sangue , Distúrbios Nutricionais/imunologia , Distúrbios Nutricionais/metabolismo , Ratos , Ratos Sprague-Dawley , Choque Séptico/sangue , Choque Séptico/induzido quimicamente , Choque Séptico/imunologia , Choque Séptico/metabolismo , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/análise , Aumento de PesoRESUMO
1. The liver is the main organ clearing both plasma and tissue kallikreins from the circulation. Hepatocytes are responsible for the internalization of rat plasma kallikrein (RPK) and the clearance of plasma kallikrein by the liver is Ca(2+)-independent. The binding site of RPK to the liver cell is located on its heavy chain which is not exposed on prokallikrein. An S-type lectin accounts for the receptor-mediated endocytosis of RPK. 2. These properties of the liver are affected by pathological situations, particularly the acute-phase response to inflammation, in which the kallikrein-kinin system plays a major role. The hepatic clearance of the alpha 2-macroglobulin-plasma kallikrein complex is less efficient than the clearance of the free enzyme.
Assuntos
Calicreínas/metabolismo , Fígado/metabolismo , Reação de Fase Aguda/induzido quimicamente , Reação de Fase Aguda/metabolismo , Animais , Endocitose , Pirogênios , Ratos , Terebintina , alfa-Macroglobulinas/metabolismoRESUMO
1. The liver is the main organ clearing both plasma and tissue kallikereins from the circulation. Hepatocytes are responsible for the internalization of rat plasma kallikrein (RPK) and liver cell is located on its heavy chain which is not exposed on prokallikrein. An S-type lectin accounts for the receptor-mediated endocytosis of TPK. 2. These properties of the liver are affected by pathological situations, particularly the acute-phase response to inflammation, in which the kallikrein-kinin system plays a major role. The hepatic clearance of the alfa2-macroglobulin-plasma kallikrein complex is less efficient than the clearance of the free enzyme
Assuntos
Ratos , Animais , Calicreínas/metabolismo , Fígado/metabolismo , alfa-Macroglobulinas/metabolismo , Endocitose , Pirogênios , Reação de Fase Aguda/induzido quimicamente , Reação de Fase Aguda/metabolismo , TerebintinaRESUMO
The effect of the acute-phase response on the clearance rate of plasma kallikrein by the exsanguinated liver was studied in three groups of rats: a control group and two other groups that received either turpentine or an endogenous pyrogen preparation. The plasma kallikrein clearance rates were significantly higher in both inflamed groups.
Assuntos
Reação de Fase Aguda/metabolismo , Calicreínas/metabolismo , Fígado/metabolismo , Reação de Fase Aguda/induzido quimicamente , Animais , Camundongos , Pirogênios , Coelhos , Ratos , Ratos Wistar , TerebintinaRESUMO
This study analyzes the effects of treatment with a hyperosmotic NaCl solution on carrageenan-induced inflammatory edema and vascular permeability in rats. Given 15 min before carrageenan, this treatment reduced paw edema measured for up to 6 h by 27 to 44%. Similarly, when the rats were treated 30 min after injection of the irritant, paw volume was significantly reduced (35 to 53%) between 1 and 6 h when compared to that of untreated animals. Increases in vascular permeability were significantly reduced at 30 min (73%) and 1 h (54%) in rats treated 15 min before, and at 1 h (49%) in animals treated 30 min after carrageenan. Treatment with hyperosmotic mannitol or isotonic NaCl solutions did not show any changes in inflammatory response to carrageenan. These data suggest that chemical mediator(s) of inflammation may be involved in the mechanism(s) of action of a hyperosmotic NaCl solution on the acute inflammatory response.