The effect of fructose as a substitute for glucose in cell culture media was investigated in human skin fibroblast and liver cell cultures. Cells were grown for between 2 and 10 days in identical flasks in four different media, containing 5.5 mmol X 1-1 and 27.5 mmol X 1-1 glucose and fructose, respectively. In the presence of fructose, cell growth was stimulated, but less in liver cells than fibroblasts. At Day 6, increases were observed in [3H]thymidine incorporation, protein levels, and amino acid consumption, and a reduction was noted in ATP levels. In media containing 5.5 mmol X 1-1 glucose or fructose, consumption of fructose was four times lower than that of glucose at Day 3 and did not rise until Day 6. In fructose media, the lactate production was very low (four to five times less than that of glucose) and the pH values were always higher. Some findings were different for the fibroblasts and liver cells, owing to the specific characteristics of these two cell types in culture; this applied especially to the effects of glucose and fructose concentrations of 27.5 mmol X 1-1. Several possible explanations for the stimulation of cell growth in fructose medium were discussed.
Fourteen patients with cirrhosis and bleeding esophageal varices were treated with propranolol. The dose of propranolol was determined by decreasing the resting heart rate by 25% 12 hr after an oral dose of propranolol which was given twice a day. Significant decreases in the hepatic venous pressure gradient and cardiac output after 1 month of propranolol administration was observed. To assess beta-adrenergic blockade, the isoproterenol test and plasma propranolol levels were evaluated. Increasing doses of isoproterenol were injected to increase the resting heart rate 25 beats per minute (chronotropic dose 25 or CD25 ). Plasma propranolol concentrations were measured in blood samples drawn 4 hr after the last oral dose. The mean CD25 was 5 +/- 2 micrograms before and 146 +/- 84 micrograms after 1 month of propranolol administration. The plasma propranolol level after 1 month of drug administration was 0.69 +/- 0.47 microM per liter i.e. 2.33 +/- 1.59 micrograms per ml. A significant correlation was found between the CD25 measured after continuous propranolol administration and plasma propranolol level. In conclusion, the efficacy of beta-adrenergic blockade was estimated by the isoproterenol test which correlates with the plasma propranolol level in patients with cirrhosis. This study suggests that the isoproterenol test is useful in assessing beta-adrenergic blockade with propranolol in patients with cirrhosis.
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