RESUMO
The current study evaluated the effect of two beta adrenergic-blocking agents, propranolol (PRP) and atenolol (ATN), versus placebo on cerebral blood flow (CBF) of three homogeneous groups of cirrhotic patients with portal hypertension. CBF was measured by the noninvasive 133-Xenon inhalation method at rest and 1 hour after a single oral dose of PRP (40 mg), or ATN (100 mg), or placebo. Blood pressure and heart rate (HR) were measured at the beginning of each examination, and end-tidal pCO2(PeCO2) was monitored. The HR decreased significantly in both the PRP and ATN groups (P less than .01), whereas no changes were recorded for both PeCO2 and mean arterial blood pressure (MABP). The comparisons of the CBF differences among groups (ANOVA with the significance levels adjusted by the Bonferroni's correction) showed a significant increase in CBF after ATN as compared with both placebo (P less than .02) and PRP (P less than .01), whereas no significant differences were seen after PRP as compared with placebo. Our results confirm that PRP does not significantly affect CBF, whereas ATN induces an increase in CBF, although the underlying mechanism is difficult to explain.
Assuntos
Atenolol/farmacologia , Córtex Cerebral/irrigação sanguínea , Hipertensão Portal/complicações , Cirrose Hepática Alcoólica/complicações , Propranolol/farmacologia , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/farmacologia , Adulto , Idoso , Atenolol/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Propranolol/administração & dosagemRESUMO
A total of eight patients with chronic active HBsAg-positive hepatitis was treated with recombinant interferon-alpha 2b for 12 months and serum aspartate aminotransferase, alanine aminotransferase, gamma-globulin and prolyl hydroxylase concentrations were determined every 3 months. Liver biopsies after 12 months' treatment revealed a significant (P less than 0.05) reduction in the histological activity score. After 6 months, alanine aminotransferase (P less than 0.01) and aspartate aminotransferase (P less than 0.05) concentrations fell significantly compared with baseline concentrations. Serum prolyl hydroxylase concentrations declined significantly (P less than 0.05) after 15 months and remained depressed. It is concluded that interferon-alpha 2b therapy reduced fibrogenetic activity in chronic active hepatitis B.
Assuntos
Hepatite B/enzimologia , Interferon-alfa/uso terapêutico , Pró-Colágeno-Prolina Dioxigenase/sangue , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Feminino , Hepatite B/patologia , Hepatite B/terapia , Humanos , Interferon alfa-2 , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , gama-Globulinas/metabolismoRESUMO
To evaluate if a drug that affects splanchnic and portal flow reduces intestinal bile acid absorption, we studied the effect of propranolol (40 mg oral dose) both on the response of total bile acids (SBA) to oral chenodeoxycholic acid (CDCA 250 mg) and on the estimated hepatic flow by indocyanine green kinetics in 10 healthy and 14 cirrhotic subjects. In 18 subjects who showed a reduction in resting heart rate of almost -5%, propranolol significantly reduced the SBA area under the curve after CDCA in both healthy (mumol/l/h m +/- SD from 181.7 x 144.9 to 56.5 +/- 36.4 p less than 0.02) and cirrhotic (from 1412.1 +/- 1044.8 to 1129.2 +/- 978.8 p less than 0.01) subjects. Variable but not significant modifications were observed in estimated hepatic flow. These results suggest that the propranolol-induced changes in SBA response to CDCA could be a reflex reaction to changes in splanchnic/portal flow.
Assuntos
Ácidos e Sais Biliares/sangue , Ácido Quenodesoxicólico/farmacologia , Circulação Hepática/efeitos dos fármacos , Cirrose Hepática Alcoólica/fisiopatologia , Propranolol/farmacologia , Feminino , Humanos , Absorção Intestinal/efeitos dos fármacos , Cirrose Hepática Alcoólica/sangue , Masculino , Pessoa de Meia-Idade , Circulação Esplâncnica/efeitos dos fármacosRESUMO
The effects of ketanserin, atenolol and their association on portal vein pressure (PVP), portal and caval bile acid concentrations (PBA and CBA), and extraction ratio of bile acids (ER) after oral loading with chenodeoxycholic acid were investigated in anaesthetized cirrhotic rats. PVP was significantly reduced by ketanserin and by the association ketanserin plus atenolol; PBA was significantly decreased in all the treated groups, whereas the reduction of CBA was significant only in the rats treated with ketanserin and atenolol alone. ER was increased by atenolol and ketanserin, but it was not modified by their association. Moreover, a significant correlation was observed between PBA and CBA and between PVP and ER. These results suggest that, in anaesthetized cirrhotic rats, ketanserin reduces PVP probably through more complex mechanisms than the simple indirect reduction of portal flow, and that the association of ketanserin plus atenolol has no additive effect in reducing PVP.
Assuntos
Ketanserina/farmacologia , Cirrose Hepática Experimental/fisiopatologia , Circulação Esplâncnica/efeitos dos fármacos , Animais , Atenolol/farmacologia , Ácidos e Sais Biliares/metabolismo , Pressão Sanguínea , Tetracloreto de Carbono , Ácido Quenodesoxicólico/administração & dosagem , Hemodinâmica/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
The effect of triglycylvasopressin (TGVP) on the absorption of chenodeoxycholic acid (CDCA) was investigated in three groups of six rats (controls, CDCA, CDCA + TGVP) through the evaluation of portal and caval serum bile acids (SBA) concentrations after an oral load with CDCA to investigate whether changes in this parameter reflect variations in splanchnic blood flow induced by a vasoconstrictor. The results indicate that CDCA was absorbed and led to a significant increase in SBA. This increase was reduced by TGVP administration: portal blood 380.0 +/- 61.2 vs 279.7 +/- 45.3; caval blood 151.8 +/- 45.7 vs 41.7 +/- 12.5 (mumol/l; mean +/- s.d.). This suggests that variations in SBA concentrations could reflect changes in splanchnic circulation.
Assuntos
Ácidos e Sais Biliares/sangue , Ácido Quenodesoxicólico , Lipressina/análogos & derivados , Circulação Esplâncnica/efeitos dos fármacos , Animais , Depressão Química , Lipressina/farmacologia , Masculino , Sistema Porta/metabolismo , Ratos , Ratos Endogâmicos , TerlipressinaRESUMO
The effects of triglycylvasopressin on portal vein pressure and portal bile acid concentration after oral loading with chenodeoxycholic acid were evaluated in normal and cirrhotic rats. Triglycylvasopressin significantly reduced the portal vein pressure and portal bile acid concentration in both populations (normal: portal vein pressure 21.2%, p less than 0.05; portal bile acid concentration 43.2%, p less than 0.005; cirrhotic: portal vein pressure 19.8%, p less than 0.025; portal bile acid concentration 20.3%, p less than 0.05). Both in normal and cirrhotic rats, portal vein pressure and portal bile acid concentration resulted correlated. These results support that the combined determination of portal vein pressure and portal bile acid concentration could represent an interesting approach to the study of drugs which are potentially active on portal circulation and could indirectly provide information as to portal flow.
Assuntos
Ácidos e Sais Biliares/sangue , Pressão Sanguínea/efeitos dos fármacos , Cirrose Hepática Experimental/sangue , Lipressina/análogos & derivados , Animais , Ácido Quenodesoxicólico/farmacologia , Injeções Intraperitoneais , Lipressina/farmacologia , Masculino , Veia Porta/fisiologia , Ratos , Ratos Endogâmicos , Fluxo Sanguíneo Regional/efeitos dos fármacos , TerlipressinaRESUMO
Glycogen storage disease type II (GSD II) is an autosomal recessive inherited disorder due to the deficiency of the enzyme acid alpha-glucosidase, which causes an accumulation of glycogen in lysosomes. The deletion of exon 18 (delta 18) is a frequent mutation associated with a severe phenotype. We analyzed 25 Italian patients, 5 of whom were found to be delta 18 carriers. All these 5 patients came from Catania, a town in Sicily. We report on the analysis of 5 intragenic single-point polymorphic markers in the delta 18 patients and on the subsequent characterization of a delta 18-associated haplotype. The frequency of this haplotype in GSD II patients and normal individuals was 1 and 0.196, respectively (chi(2) = 20.9; p < 0.001). The high frequency of the delta 18 allele in this Italian subpopulation is likely to be due to a founder effect.