ABSTRACT
The ability of hepatitis C virus (HCV) to infect leukocytes could favour HCV pathogenesis. Although viral infection of these immunocompetent cells is poorly (or not) productive, the impact on their immunomodulatory functions could be important. Viral envelope glycoproteins E1 and E2, because of their crucial role in the recognition of viral receptors on permissive cells, could contribute to viral leukocytic tropism and, as a consequence, to the pathophysiology of HCV chronic infection.
Subject(s)
Genes, Viral , Hepacivirus/physiology , Leukocytes/virology , RNA, Viral/genetics , Viral Envelope Proteins/genetics , Viral Tropism/genetics , Hepacivirus/genetics , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/physiopathology , Hepatitis C, Chronic/virology , Humans , Sequence Analysis, RNA , Structure-Activity Relationship , Viral Envelope Proteins/chemistry , Viral Envelope Proteins/physiologyABSTRACT
The effects of corticosteroid have been studied in rats submitted to oral administration of prednisone (5 mg. per kg. per day) during 8, 15, 30, and 90 days. The results were compared to those obtained after parenteral administration of hydrocortisone acetate (50 mg. per kg. per day intramuscularly). The morphometric changes of the villus-crypt axis and the brush border enzymic content of the mucosa (sucrase, enterokinase, alkaline phosphatase, and aminopeptidase) were the parameters investigated at the duodenal, jejunal, and ileal levels. Oral administration of prednisone resulted in a significant increase of the duodenal villous height at the 15th (+ 13 per cent, p less than 0.01), 30th (+ 33 per cent, p less than 0.001), and 90th day (+ 56 per cent, p less than 0.001), whereas in the jejunum a constant decrease of the villous height was noted. Parenteral hydrocortisone administration did not affect intestinal morphology. Effects of oral corticosteroids on the microvillous enzymic activities were related to both intestinal level and duration of corticoids administration: (1) in the duodenum increase of sucrase, alkaline phosphatase, and aminopeptidase during 30 days followed by normalization at the 90th day, (2) an initial increase of sucrase, alkaline phosphatase, and aminopeptidase limited to the first 8 days in the jejunum, and (3) a significant rise of alkaline phosphatase (greater than 100 per cent, p less than 0.001) and enterokinase (greater than 100 per cent, p less than 0.001) in the ileum at the 15th day of treatment. Parenteral corticosteroid administration was associated with a significant increase of both sucrase and enterokinase activities. The present study suggests that: (1) Corticosteroids exert a direct effect on the intestinal morphology varying with the intestinal level and duration of treatment. (2) No correlation could be established between anatomic and functional changes. (3) Oral corticosteroids exert an enhancing effect of the brush border enzymic activities, even in the adult mucosa and particularly at the ileal level where they stimulate significantly the enterokinase mucosal activity. (4) Parenteral corticosteroids exert a more specific effect limited to sucrase and enterokinase enhancement.
Subject(s)
Adrenal Cortex Hormones/pharmacology , Intestines/drug effects , Administration, Oral , Animals , Duodenum/drug effects , Duodenum/ultrastructure , Hydrocortisone/administration & dosage , Hydrocortisone/pharmacology , Ileum/drug effects , Ileum/ultrastructure , Infusions, Parenteral , Intestines/ultrastructure , Jejunum/drug effects , Jejunum/ultrastructure , Male , Microvilli/drug effects , Microvilli/enzymology , Prednisone/administration & dosage , Prednisone/pharmacology , Rats , Rats, Inbred LewABSTRACT
The effect of graded (5, 10, 20, and 50%) chronic ethanol administration on the intestinal brush border enzymic activities has been investigated in the rat at three levels of the intestinal tract (duodenum, jejunum, ileum). Ethanol has been administered for 8, 15, 30, and 90 days. A 30% to 50% decrease of sucrase and alkaline phosphatase results, showing that the effect of alcohol appears in the first 8 days of intoxication is not reversible after 8 days of an alcohol-free diet. The effect of ethanol is not limited to disaccharidases. Impairment of alkaline phosphatase, peptidases and also enterokinases is observed. The decrease is more marked in the duodenum and jujunum than the ileum. The decrease of enzymic activity is generally maximal after 30 days of intoxication. There is then little further deterioration or even significant improvement. At the 30th day of ethanol administration, a clearcut dose-response relationship has been established. The results obtained suggest that ethanol exerts an effect on the intestinal mucosa which is not directly correlated to morphological villus changes.
Subject(s)
Cell Membrane/drug effects , Ethanol/adverse effects , Microvilli/drug effects , Alcoholism/enzymology , Alkaline Phosphatase/metabolism , Aminopeptidases/metabolism , Animals , Duodenum , Enteropeptidase/metabolism , Humans , Intestinal Mucosa/drug effects , Male , Microvilli/enzymology , Rats , Sucrase/metabolismABSTRACT
Rat small bowel was perfused in vivo and ex vivo in the absence of biliary and pancreatic secretion. Intraluminal release of sucrase, alkaline phosphatase, aminopeptidase and enterokinase was significantly increased after administration of PG E1 and E2 1 and 5 microgram/kg. This suggests a direct stimulation of the intestinal mucosa, which might be mediated through cyclic AMP; dibutyryl cAMP significantly stimulates intraluminal release of proteins, sucrase and enterokinase.