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Biomedical subjects

F Ballet

Publications and source records attributed to F Ballet.

61 records · Page 4Linked to original sources
PubMedDate not supplied

Isolation, culture and characterization of adult human hepatocytes from surgical liver biopsies.

A technique is described for isolation and culture of adult human hepatocytes from surgical liver biopsies. The mean cell yield was 1.75 X 10(7) cells per gm liver and viability averaged 80%. Hepatocytes were maintained in primary culture for about 10 days. Cell morphology and histochemical characteristics were similar to hepatocytes in vivo. Bile canaliculi were observed by electron microscopy. Intracellular albumin was demonstrated up to the 7th day of culture; albumin secretion rate was maximal (0.6 +/- 0.33 micrograms per hr per 10(6) cells) 5 days after plating. These studies demonstrate that adult human hepatocytes can be isolated from surgical biopsies with high yield, and differentiated function can be maintained for several days.

Adult↗
PubMedDate not supplied

Effect of vasodilators on hepatic microcirculation: a study of the inhibition of norepinephrine-induced vasoconstriction in the isolated perfused rat liver.

We studied the effects of a series of 16 vasodilators on the intrahepatic vasoconstriction induced by norepinephrine in the isolated perfused rat liver. The vasodilators were nonselective alpha-adrenergic antagonists (phentolamine, ifenprofil, isoxsuprine and buflomedil), a nonselective beta-adrenergic antagonist (propranolol) and an agonist (isoproterenol), an alpha 2-adrenergic agonist (clonidine), calcium channel blockers (verapamil and diltiazem), nitrovasodilators (nitroglycerin, sodium nitroprusside), papaverine and other unclassified vasodilators, some of them with rheological properties (diazoxide, vincamine, cinepazide, naftidofuryl and pentoxifylline). The most potent drugs were ifenprofil, phentolamine, isoxsuprine, clonidine, sodium nitroprusside and buflomedil. Diazoxide, papaverine, pentoxifylline and trinitrine were less powerful. Verapamil, diltiazem, propranolol, isoproterenol, vincamine, cinepazide and naftidofuryl were ineffective. We conclude that different classes of pharmacological agents have significant vasodilatory properties on the hepatic microvasculature. This offers interesting perspectives in the treatment of cirrhosis and stressful states where high levels of circulating norepinephrine may contribute to the altered liver perfusion.

Animals↗
PubMedDate not supplied

Specificity of in vitro covalent binding of tienilic acid metabolites to human liver microsomes in relationship to the type of hepatotoxicity: comparison with two directly hepatotoxic drugs.

In order to better understand the first steps leading to drug-induced immunoallergic hepatitis, we studied the target of anti-LKM2 autoantibodies appearing in tienilic acid-induced hepatitis, and the target of tienilic acid-reactive metabolites. It was identified as cytochrome P450 2C9, (P450 2C9): indeed, anti-LKM2 specifically recognized P450 2C9, but none of the other P450s tested (including other 2C subfamily members, 2C8 and 2C18). Tienilic acid-reactive metabolite(s) specifically bound to P450 2C9, and experiments with yeast expressing active isolated P450s showed that P450 2C9 was responsible for tienilic acid-reactive metabolite(s) production. Results of qualitative and quantitative covalent binding of tienilic acid metabolite(s) to human liver microsomes were then compared to those obtained with two drugs leading to direct toxic hepatitis, namely, acetaminophen and chloroform. Kinetic constants (Km and Vmax) were measured, and the covalent binding profile of the metabolites to human liver microsomal proteins was studied. Tienilic acid had both the lowest Km and the highest covalent binding rate at pharmacological doses. For acetaminophen and chloroform, several microsomal proteins were covalently bound, while covalent binding was highly specific for tienilic acid and dihydralazine, another drug leading to immunoallergic hepatitis. Although low numbers of drugs were tested, these results led us to think that there may exist a relationship between the specificity of covalent binding and the type of hepatotoxicity.

Acetaminophen↗
PubMedDate not supplied

Effects of norepinephrine on hepatic amino acid metabolism in isolated perfused rat liver.

The effects of norepinephrine (NE) on hepatic amino acid exchanges were studied in the isolated perfused rat liver using a recirculating system with a medium containing amino acids at twice physiologic concentrations. Norepinephrine induced a significant decrease (25%) in portal blood flow at a concentration of 2 ng/ml (10(-8) M). The hormone also increased total hepatic amino acid uptake, essentially through a switch from glutamine release to net uptake. There was no modification in free intracellular amino acids, but glycogen was slightly decreased, and glucose production was increased. Taken as a whole, these results suggest that NE modulates hepatic protein balance.

Amino Acids↗