The presence of a-smooth muscle actin (smA)-positive cells has recently been reported in the fibrotic liver. Lipocytes have been considered to play important roles in hepatic fibrosis. However, the relation of the a-smA-positive cells and lipocytes has not been determined. The biological implication of a-smA expression remains unknown. To study these questions, we carried out double immunofluorescent staining of a-smA and desmin (a marker for lipocytes), or a-smA and collagen, and double immunohistochemical staining of a-smA and 5-bromo-2'-deoxyuridine (BrdUrd) in carbon tetrachloride-induced fibrotic rat livers. In normal and control livers, a-smA-positive cells were not seen in the lobules, whereas scattered desmin-positive cells were present. With the development of hepatic fibrosis, a-smA was expressed only in a portion of desmin-positive cells located predominantly around collagen bundles. A number of a-smA-positive cells in the lobules were labelled with BrdUrd. These results suggest phenotypic modulation in lipocytes and differentiation of lipocytes towards myofibroblast-like cells, since a-smA is expressed with desmin in myofibroblasts in scar tissue. The expression of a-smA may be related to events of the fibrotic process, such as tissue contraction or fibrogenesis per se.
Chronic alcohol administration to baboons results in perivenular lesions in the liver. To study possible mechanisms, the effect of ethanol on splanchnic oxygen consumption was measured. Acute ethanol administration increased splanchnic oxygen consumption in the control baboons, but the consequences of this effect on oxygenation of the perivenular zones were offset by a concomitant rise in blood flow, resulting in unchanged hepatic venous oxygen tensions. In alcohol-fed baboons, splanchnic oxygen consumption was not increased, either in the withdrawal state or after ethanol infusion. To study the magnitude of the shift in redox state induced by ethanol in the perivenular zones, we compared the effects of ethanol on the lactate/pyruvate ratio in hepatic venous blood (an approximation of that in perivenular hepatocytes) with the ratio in total liver. Prior to ethanol infusion, the lactate and pyruvate were the same in liver and in hepatic venous blood. By contrast, in all baboons, ethanol produced a much greater rise in the lactate/pyruvate ratio and decreased pyruvate more in hepatic venous blood than in total liver. Moreover, in isolated rat hepatocytes, the ethanol-induced redox shift was markedly exaggerated by oxygen tensions similar to those found in centrolobular zones. This suggests that the normally low oxygen tensions existing in perivenular zones exaggerate the ethanol-induced redox shift, a change which may contribute to the exacerbation of the damage in the perivenular area of the hepatic lobule.
The synergistic effects of tobacco smoking and alcohol consumption on the incidence of upper respiratory cancer may be linked to their common ability to produce acetaldehyde, an irritant and potential mutagen. Since alcohol consumption in most individuals results in very low concentrations of acetaldehyde in the blood, we determined whether bronchopulmonary cellular components are capable of oxidizing ethanol to acetaldehyde. We found that significant production of acetaldehyde occurred in vitro after incubation of human bronchopulmonary washings with 25 mM ethanol. Acetaldehyde production was increased in active smokers and related to microorganisms in the bronchopulmonary tract. It was abolished by preincubation of the washings with antibiotics and was reproduced in vitro with Streptococcus pneumoniae. Normal pulmonary cells in bronchopulmonary washings did not produce acetaldehyde from ethanol.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.