RESUMO
SUMMARY: Hepatitis C virus (HCV) is a worldwide health problem. No vaccine is available against this pathogen and therapeutic treatments currently in use are of limited efficacy. In the present study, the immunogenicity of the therapeutic vaccine candidate CIGB-230, based on the mixture of pIDKE2, a plasmid expressing HCV structural antigens, with a recombinant HCV core protein, Co.120, was evaluated. CIGB-230 was administered by intramuscular injection on weeks 0, 4, 8, 12, 16 and 20 to 15 HCV-chronically infected individuals, non-responders to previous treatment with interferon (IFN) plus ribavirin. Interestingly, following the final immunization, neutralizing antibody responses against heterologous viral pseudoparticles were modified in eight individuals, including six de novo responders. In addition, 73% of vaccinees exhibited specific T cell proliferative response and T cell IFN-gamma secretory response 24 weeks after primary immunization with CIGB-230. Furthermore, 33.3% of individuals developed de novo cellular immune response against HCV core and the number of patients (46.7% at the end of treatment) with cellular immune response against more than one HCV structural antigen increased during vaccination (P = 0.046). In addition, despite persistent detection of HCV RNA, more than 40% percent of vaccinated individuals improved or stabilized liver histology, particularly reducing fibrosis, which correlated with cellular immune response against more than one HCV antigen (P = 0.0053). In conclusion, CIGB-230 is a promising candidate for effective therapeutic interventions based on its ability for enhancing the immune response in HCV chronically infected individuals.
Assuntos
Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/imunologia , Linfócitos T/imunologia , Vacinas de DNA/imunologia , Vacinas contra Hepatite Viral/imunologia , Adulto , Feminino , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Antígenos de Hepatite/genética , Antígenos de Hepatite/imunologia , Hepatite C Crônica/prevenção & controle , Hepatite C Crônica/virologia , Humanos , Imunização , Interferon gama/biossíntese , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , RNA Viral/sangue , Resultado do Tratamento , Vacinas de DNA/administração & dosagem , Vacinas de DNA/uso terapêutico , Proteínas do Core Viral/genética , Proteínas do Core Viral/imunologia , Vacinas contra Hepatite Viral/administração & dosagem , Vacinas contra Hepatite Viral/uso terapêutico , Carga ViralRESUMO
Interferon alfa (IFN-alpha) is the only approved treatment for chronic hepatitis B (HBV) infection. In a non-controlled study 33 pediatric patients infected with HBV and in chronic phase of the disease were included and treated with 3 to 5 x 10(6) IU/m2 body surface of Interferon alpha 2b, 3 times per week, during 4 months. The objective was to evaluate the efficacy of the treatment in terms of the histological, biochemical and viral markers evolution of the patients. The patients were evaluated carrying out determinations of alanine aminotransferase (ALAT), HBsAg and HBeAg before treatment, at the end of the treatment and every 4 months during one year of follow-up. Liver biopsy and Knodell index determination were carried out at the beginning and upon concluding the follow-up. 39.3% of the patients concluded the treatment with normal ALAT values; 7% became HBsAg negative and 14.3% became HBsAg negative. These values ascended after follow-up to 51.5%, 11% and 37.5% respectively. The histological analysis evidenced a decrease of the Knodell index in 69% of the patients, an increase in 14.2%, and 13.8% did not show variation. Correlating the biochemical and histological responses, a favorable outcome was obtained in 36.4% of the patients, evidencing a remarkable reduction of the hepatic cytolysis. The treatment was well tolerated, being the fever the most frequent adverse events. The results confirm that interferon alfa seems to be an effective treatment for children with chronic hepatitis B.
Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Alanina Transaminase/sangue , Criança , Feminino , Seguimentos , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/patologia , Humanos , Interferon alfa-2 , Masculino , Proteínas Recombinantes , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
Interferon alfa (IFN-alpha) is the only approved treatment for chronic hepatitis B (HBV) infection. In a non-controlled study 33 pediatric patients infected with HBV and in chronic phase of the disease were included and treated with 3 to 5 x 10(6) IU/m2 body surface of Interferon alpha 2b, 3 times per week, during 4 months. The objective was to evaluate the efficacy of the treatment in terms of the histological, biochemical and viral markers evolution of the patients. The patients were evaluated carrying out determinations of alanine aminotransferase (ALAT), HBsAg and HBeAg before treatment, at the end of the treatment and every 4 months during one year of follow-up. Liver biopsy and Knodell index determination were carried out at the beginning and upon concluding the follow-up. 39.3% of the patients concluded the treatment with normal ALAT values; 7% became HBsAg negative and 14.3% became HBsAg negative. These values ascended after follow-up to 51.5%, 11% and 37.5% respectively. The histological analysis evidenced a decrease of the Knodell index in 69% of the patients, an increase in 14.2%, and 13.8% did not show variation. Correlating the biochemical and histological responses, a favorable outcome was obtained in 36.4% of the patients, evidencing a remarkable reduction of the hepatic cytolysis. The treatment was well tolerated, being the fever the most frequent adverse events. The results confirm that interferon alfa seems to be an effective treatment for children with chronic hepatitis B
Assuntos
Humanos , Masculino , Feminino , Criança , Antivirais , Hepatite B Crônica , Interferon-alfa , Alanina Transaminase , Seguimentos , Antígenos E da Hepatite B , Antígenos de Superfície da Hepatite B , Fígado , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
Interferon alfa (IFN-alpha) is the only approved treatment for chronic hepatitis B (HBV) infection. In a non-controlled study 33 pediatric patients infected with HBV and in chronic phase of the disease were included and treated with 3 to 5 x 10(6) IU/m2 body surface of Interferon alpha 2b, 3 times per week, during 4 months. The objective was to evaluate the efficacy of the treatment in terms of the histological, biochemical and viral markers evolution of the patients. The patients were evaluated carrying out determinations of alanine aminotransferase (ALAT), HBsAg and HBeAg before treatment, at the end of the treatment and every 4 months during one year of follow-up. Liver biopsy and Knodell index determination were carried out at the beginning and upon concluding the follow-up. 39.3% of the patients concluded the treatment with normal ALAT values; 7% became HBsAg negative and 14.3% became HBsAg negative. These values ascended after follow-up to 51.5%, 11% and 37.5% respectively. The histological analysis evidenced a decrease of the Knodell index in 69% of the patients, an increase in 14.2%, and 13.8% did not show variation. Correlating the biochemical and histological responses, a favorable outcome was obtained in 36.4% of the patients, evidencing a remarkable reduction of the hepatic cytolysis. The treatment was well tolerated, being the fever the most frequent adverse events. The results confirm that interferon alfa seems to be an effective treatment for children with chronic hepatitis B (AU)
Assuntos
Humanos , Masculino , Feminino , Criança , Interferon-alfa/uso terapêutico , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Seguimentos , Estatísticas não Paramétricas , Alanina Transaminase/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Fígado/patologia , Resultado do TratamentoRESUMO
Interferon alfa (IFN-alpha) is the only approved treatment for chronic hepatitis B (HBV) infection. In a non-controlled study 33 pediatric patients infected with HBV and in chronic phase of the disease were included and treated with 3 to 5 x 10(6) IU/m2 body surface of Interferon alpha 2b, 3 times per week, during 4 months. The objective was to evaluate the efficacy of the treatment in terms of the histological, biochemical and viral markers evolution of the patients. The patients were evaluated carrying out determinations of alanine aminotransferase (ALAT), HBsAg and HBeAg before treatment, at the end of the treatment and every 4 months during one year of follow-up. Liver biopsy and Knodell index determination were carried out at the beginning and upon concluding the follow-up. 39.3
of the patients concluded the treatment with normal ALAT values; 7
became HBsAg negative and 14.3
became HBsAg negative. These values ascended after follow-up to 51.5
, 11
and 37.5
respectively. The histological analysis evidenced a decrease of the Knodell index in 69
of the patients, an increase in 14.2
, and 13.8
did not show variation. Correlating the biochemical and histological responses, a favorable outcome was obtained in 36.4
of the patients, evidencing a remarkable reduction of the hepatic cytolysis. The treatment was well tolerated, being the fever the most frequent adverse events. The results confirm that interferon alfa seems to be an effective treatment for children with chronic hepatitis B.
RESUMO
The epidermal growth factor has been shown to be mucoprotective and to accelerate healing of gastroduodenal ulcers in animals. A prospective, positively controlled clinical trial was conducted. Seventy five patients with duodenal ulcer were randomly distributed in three groups to receive oral human recombinant epidermal growth factor in 1% carboxymethyl cellulose at two different doses (450 mg or 600 mg/day), or cimetidine. Treatment was administered up to a maximum of 6 weeks. The most important assessment criteria was the proportion of patients healed after 2, 4 and 6 weeks of treatment determined by endoscopy. Treatment with both doses of epidermal growth factor showed a long-term healing effect in 76.5% at 6 weeks vs 92.5% with cimetidine (p = N.S.). The evolution of the clinical symptoms was similar in the three groups. Adverse reactions were not detected in any of the patients included in this study. To our knowledge, this is the first report on the oral use of epidermal growth factor in humans.
Assuntos
Úlcera Duodenal/tratamento farmacológico , Fator de Crescimento Epidérmico/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Fator de Crescimento Epidérmico/biossíntese , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/biossíntese , Fatores de TempoRESUMO
Liver tissue samples from four chimpanzees submitted to viral challenge in order to test a recombinant anti-hepatitis B virus vaccine, were studied by electron microscopy. The vaccinated monkeys showed no evidences of acute viral hepatitis (AVH), demonstrating the protection against an infective viral dose; on the contrary, the non-vaccinated chimps developed signs of AVH in hepatocytes such as: different size and shape, slight dilatation of the rough endoplasmic reticulum, disappearance of the mitochondrial crests, broadening of the normal space between the membranes of the nuclear coating and presence of laminar bodies and cytoplasmic vacuoles. Furthermore, the presence of the hepatitis B virus surface (HBV) antigen was confirmed in non-vaccinated monkeys using immunocytochemical techniques. Transmission electron microscopy and immunocytochemical analysis corroborated the protective effect of the recombinant vaccine against the HBV in the vaccinated animals.
Assuntos
Vacinas contra Hepatite B/uso terapêutico , Hepatite B/patologia , Fígado/patologia , Animais , Biópsia , Hepatite B/metabolismo , Hepatite B/prevenção & controle , Imuno-Histoquímica , Fígado/química , Fígado/ultraestrutura , Pan troglodytesRESUMO
Alagille's syndrome or arteriohepatic dysplasia has been described in Cuba in nine patients between nine months and 12 years of age (8 males and one female). Among the clinical features we found five major abnormalities: chronic cholestasis with neonatal jaundice (9/9), peculiar facies (9/9), peripheral pulmonary artery hypoplasia associated with cardiac murmur (6/9), butter-fly-like arch defects (4/9), and posterior embryotoxon (6/7). Two children had a severe xanthomatosis. Laparoscopy showed green hepatomegaly depending on the degree of cholestasis, and only one patient had incipient signs of micronodular cirrhosis. Liver histology showed a paucity of interlobular bile ducts. Survival was of 60%. One patient survived more than 30 years. Four patients died of liver carcinoma (unique report in infants), broncho-pneumonia, acute renal failure, and sudden death respectively. Among the minor features were mental retardation (5/9), a peculiar voice (3/9), growth retardation observed in some of our patients. This is the first report on Alagille's syndrome in Latin America, because so far reports have come only from Europe and North America.
Assuntos
Síndrome de Alagille/diagnóstico , Síndrome de Alagille/mortalidade , Síndrome de Alagille/patologia , Biópsia por Agulha , Criança , Pré-Escolar , Cuba/epidemiologia , Feminino , Humanos , Lactente , Laparoscopia , Fígado/patologia , MasculinoRESUMO
Se administró interferon leucocitario humano a 62 pacientes con hepatitis crónica activa tipo B, durante un período de seis meses a una dosis total de 400 millones U.I. Se siguieron mensualmente durante un periodo de un año, repitiéndose la biopsia hepática. Las cifras de alanino-amino-transferasa se normalizaron en el 67.7 por ciento de los pacientes y se logró la seroconversión antígeno-anticuerpo o en el 59 por ciento. El antígeno no fue detectable al final del tratamiento en solo cuatro pacientes. La histología hepática mostro una normalización en 17 pacientes y una mejoría en casi la mitad de los mismos. Solo 3 pacientes evolucionaron hacia una cirrosis hepática. Los mejores resultados se apreciaron en sujetos jóvenes y en aquellos que no habían recibido previamente terapia inmunosupresora
Assuntos
Humanos , Hepatite Crônica/tratamento farmacológico , Interferon-alfa/uso terapêuticoRESUMO
Seven patients with active chronic hepatitis who received Interferon Alfa showed a marked humoral and histological improvement one year after the treatment was concluded, in 3 patients the hepatic histology was almost normal, 2 evolved to a persistent chronic hepatitis and only one showed deterioration. These results differed from those obtained immediately after the treatment (p 0.05). Interferon Alfa proves to be of the most usefulness in this disease, studies should be continued up to one year after the treatment has ended.
Assuntos
Hepatite Crônica/terapia , Interferon Tipo I/uso terapêutico , Seguimentos , Antígenos de Superfície da Hepatite B/análise , Hepatite Crônica/imunologia , Hepatite Crônica/patologia , Humanos , Replicação Viral/efeitos dos fármacosRESUMO
Seven patients with active chronic hepatitis who received Interferon Alfa showed a marked humoral and histological improvement one year after the treatment was concluded, in 3 patients the hepatic histology was almost normal, 2 evolved to a persistent chronic hepatitis and only one showed deterioration. These results differed from those obtained immediately after the treatment (p 0.05). Interferon Alfa proves to be of the most usefulness in this disease, studies should be continued up to one year after the treatment has ended.
RESUMO
Fine structure and function are closely related in the cells of the different tissues. For this reason a comparative study combining histochemical techniques and scanning electron microscopy can result a potentially useful tool in the search for cell markers of preneoplastic stages of the colon mucosa. With this purpose, samples of normal colon mucosa, adenomatous polyps and adenocarcinomas obtained by colonoscopy were studied by histochemical techniques for the detection of epithelial mucosubstances and by scanning electron microscopy. Differences were shown in the architectural arrangement of the colon epithelium between the normal mucosa, the adenocarcinoma and the polyps studied, while between tubular an tubulovillous adenomas no marked differential ultrastructural features were found. Acid mucosubstances distribution pattern showed that sialomucin predominated in the colon mucosa harboring a carcinoma and in the tubulo-villous polyps as well as in the mucosa remote from adenocarcinoma and from the two cases of familial polyposis coli histologically considered as tubulo-villous adenomas. On the other hand tubular adenomas and normal mucosa showed a predominance of sulfomucin.
Assuntos
Neoplasias do Colo/metabolismo , Lesões Pré-Cancerosas/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/ultraestrutura , Adenoma/metabolismo , Adenoma/ultraestrutura , Biópsia , Carcinoma/metabolismo , Carcinoma/ultraestrutura , Colo/metabolismo , Colo/ultraestrutura , Neoplasias do Colo/ultraestrutura , Histocitoquímica , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/ultraestrutura , Microscopia Eletrônica de Varredura , Lesões Pré-Cancerosas/ultraestruturaRESUMO
A previous report of members of our group demonstrated, in most adenocarcinomas and some adenomatous polyps with areas of malignant transformation, the presence of glycogen in cells that failed to show the synthesis of ordinary mucosubstances. The presence of glycogen in non-differentiated epithelium of the digestive tract of embryos, where it precedes ordinary mucus secretion, has lead some authors to suggest that the changes to glycogen secretion that occurs in malignant colonic cells, reflects the general regression to a less differentiated level of structure and function. It is well established that patients with carcinomas of the colon classified as less differentiated or higher grade tumors have significantly less chance of cure and consequently a worse prognosis than patients with lower grade tumors. The present ultrastructural study of the morphological differentiation characteristics of the glycogen containing cells previously encountered, revealed a strong association of glycogen to undifferentiated cells of the colonic adenocarcinomas and precancerous polypoid lesions studied. This undoubtedly seems to encourage the testing for the presence of glycogen in routine procedures as a possible marker of diagnostic and prognostic significance.
Assuntos
Adenocarcinoma/ultraestrutura , Neoplasias do Colo/ultraestrutura , Pólipos do Colo/ultraestrutura , Glicogênio/metabolismo , Lesões Pré-Cancerosas/ultraestrutura , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adenoma/diagnóstico , Adenoma/metabolismo , Adenoma/ultraestrutura , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/metabolismo , Pólipos do Colo/diagnóstico , Pólipos do Colo/metabolismo , Histocitoquímica , Humanos , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/metabolismo , PrognósticoRESUMO
En 25 pacientes portadores de Giardiasis comprobada por sondaje duodenal se realizaron pruebas de funcionalismo hepático y biopsia hepática con trócar de Menghini. El 60% de los pacientes presentaron alteraciones en la histología hepática: el 36% esteatosis y el 24% lesiones inflamatorias, de ellos 3 Hepatitis Crónica Persistente y 2 Hepatitis Crónica Activa. Estas lesiones regresaron sólo con el tratamiento antiparasitario y la reaparición de las mismas estuvo en dependencia con reinfectaciones del parásito en algunos casos. Se concluye que la Giardia Lamblia puede ocasionar lesiones hepáticas importantes y conducir a una enfermedad crónica activa del hígado. Se recomienda en todo paciente con diagnóstico de Hepatitis Crónica no viral descartar una Giardiasis, y tratarla, antes de decidir otro tipo de conducta terapéutica (AU)
Assuntos
Adulto , Humanos , Masculino , Feminino , Fígado/fisiopatologia , Giardíase/fisiopatologia , Fígado/patologia , Giardíase/complicações , Hepatopatias/etiologia , Testes de Função HepáticaRESUMO
En 25 pacientes portadores de Giardiasis comprobada por sondaje duodenal se realizaron pruebas de funcionalismo hepático y biopsia hepática con trócar de Menghini. El 60% de los pacientes presentaron alteraciones en la histología hepática: el 36% esteatosis y el 24% lesiones inflamatorias, de ellos 3 Hepatitis Crónica Persistente y 2 Hepatitis Crónica Activa. Estas lesiones regresaron sólo con el tratamiento antiparasitario y la reaparición de las mismas estuvo en dependencia con reinfectaciones del parásito en algunos casos. Se concluye que la Giardia Lamblia puede ocasionar lesiones hepáticas importantes y conducir a una enfermedad crónica activa del hígado. Se recomienda en todo paciente con diagnóstico de Hepatitis Crónica no viral descartar una Giardiasis, y tratarla, antes de decidir otro tipo de conducta terapéutica
Assuntos
Adulto , Humanos , Masculino , Feminino , Fígado/fisiopatologia , Giardíase/fisiopatologia , Fígado/patologia , Giardíase/complicações , Hepatopatias/etiologia , Testes de Função HepáticaRESUMO
In 25 patients with diagnostic of Giardiasis by duodenal intubation we studied the hepatic functional tests and hepatic biopsy. 60% of patients presented alterations of hepatic histology; 36% steatosis and 24% inflammatory lesions, chronic persistent hepatitis 3 cases and chronic active hepatitis two of them. Hepatic lesions regression was reached only with antiparasitic treatment and in some cases reappearance of lesions depended on parasitic's reinfections. For every patient with histologic diagnosis of chronic hepatitis without viral markers we suggested to dismiss Giardiasis and to treat it before to undergo other therapeutical behavior.
Assuntos
Giardíase/fisiopatologia , Hepatopatias Parasitárias/fisiopatologia , Fígado/fisiopatologia , Adulto , Feminino , Giardíase/patologia , Hepatite/etiologia , Hepatite/patologia , Hepatite/fisiopatologia , Humanos , Fígado/patologia , Hepatopatias Parasitárias/patologia , Testes de Função Hepática , MasculinoRESUMO
In 25 patients with diagnostic of Giardiasis by duodenal intubation we studied the hepatic functional tests and hepatic biopsy. 60
of patients presented alterations of hepatic histology; 36
steatosis and 24
inflammatory lesions, chronic persistent hepatitis 3 cases and chronic active hepatitis two of them. Hepatic lesions regression was reached only with antiparasitic treatment and in some cases reappearance of lesions depended on parasitics reinfections. For every patient with histologic diagnosis of chronic hepatitis without viral markers we suggested to dismiss Giardiasis and to treat it before to undergo other therapeutical behavior.
RESUMO
Coeliac disease is generally considered to be a disease of Europe, North America, and Australasia. A series of well-authenticated cases from Cuba is presented. One of the factors responsible for the presence of this disease in Cuba may be the increase in wheat consumption in the last few years. It is likely that coeliac disease exists in other tropical countries.