Showing papers by "Paolo Pani published in 1995"

Transplantation of normal hepatocytes modulates the development of chronic liver lesions induced by a pyrrolizidine alkaloid, lasiocarpine.

Abstract: Lasiocarpine (LC), a pyrrolizidine alkaloid, is able to induce a series of chronic and progressive lesions in rat liver, including a long-lasting block in the cell cycle, the appearance of enlarged hepatocytes (megalocytosis), fibrosis, cirrhosis and malignant neoplasma. In this study the effect of transplantation of normal hepatocytes on the development of LC-induced chronic lesions in rat liver was examined. Two-month-old male Fischer 344 rats were given a single dose of LC (80 mumol/kg i.p.). Four weeks later all animals were subjected to 2/3 partial hepatectomy (PH). In addition, at the time of PH one group of rats were transplanted with normal hepatocytes isolated from a syngeneic donor (10(6) cells/rats via the portal vein), while the other group received only the culture medium. All rats were killed 14 weeks after the operation. Grossly, the liver of rats exposed to LC followed by PH with no transplantation of normal hepatocytes was small in size (% liver wt/body wt 1.66 +/- 0.08) and exhibited a few whitish nodules. Histologically, approximately 88% of the liver section was occupied by enlarged hepatocytes and hepatocyte nodules composed of smaller hepatocytes developed in every animal in this group. In addition, extensive bile ductular proliferation was present. However, the liver of rats that were similarly treated but received normal hepatocytes were significantly larger in size (% liver wt/body wt 2.16 +/- 0.07) and were almost completely free of megalocytosis, bile ductular proliferation and hepatocyte nodules. These findings indicate that transplantation of normal hepatocytes is able to modulate the development of chronic liver lesions induced by LC and may be relevant to the pathogenesis of progressive liver diseases such as neoplasia and cirrhosis.

Sexually differentiated response to choline in choline deficiency and ethionine intoxication.

Abstract: A sex difference exists in the response of rats to a choline deficient diet and to ethionine intoxication. Female rats are less susceptible than males to the acute effects of choline deficiency, such as fatty liver and impaired secretion of triglycerides into blood plasma, while they are more susceptible to inhibition of liver protein synthesis and triglyceride accumulation by ethionine. These differences have been ascribed to sex differences in the biosynthesis of phosphatidylcholine in the liver of rats. The available data indicate that females are more dependent than males on the stepwise methylation of phosphatidylethanolamine rather than the direct incorporation of preformed choline. Continuous prefeeding with choline for three weeks was able to shift the female pattern of response to choline deficiency and ethionine intoxication towards that observed in males; thus, choline caused accumulation of hepatic triglycerides and a decrease in plasma triglycerides after choline deficiency, while it protected against ethionine induced triglyceride accumulation and protein synthesis inhibition in the liver. These results suggest that choline prefeeding in females makes them more dependent on choline availability and, thus, more susceptible to a choline deficient diet and less sensitive to ethionine intoxication, as are males. No effect of choline was observed in either choline deficient or ethionine intoxicated male rats.

Clinical remission is associated with restoration of normal high-density lipoprotein cholesterol levels in children with malignancies.

Abstract: 1. Serum lipids and lipoprotein profiles were determined in children affected by different types of malignancies (leukaemias or lymphomas and solid tumours) both before any treatment and after remission of the disease following chemical or surgical therapy. 2. At the time of diagnosis, children bearing tumours showed hypertriglyceridaemia and reduced concentrations of plasma high-density lipoprotein cholesterol levels, the decrease being particularly prominent in patients with haematological tumours. Children bearing solid tumours displayed an increase of total cholesterol, while those with haematological cancer showed decreased phospholipid levels; low-density lipoprotein cholesterol in neoplastic patients was not significantly different from control values. High triacylglycerol and low high-density lipoprotein cholesterol levels were also evident in cancer patients divided according to age into three groups (0–5, 6–10 and 11–15 years) when compared with age-matched control subjects. Similarly, high triacylglycerol and low high-density lipoprotein cholesterol levels were also observed in both male and female children when patients were divided according to sex and compared with corresponding controls. 3. Clinical remission after therapy was accompanied by an increase of high-density lipoprotein cholesterol levels compared with values observed at diagnosis. In contrast, post-treatment levels of triacylglycerol were higher than those observed before therapy. These results support the hypothesis that alterations of high-density lipoprotein cholesterol levels may be related, at least in part, to the rate of tumour growth, while modifications of triacylglycerol levels may be mediated by different mechanisms.