Urinary excretion of free and acetylated polyamines in hepatocellular carcinoma.

Polyamines (putrescine, spermidine and spermine) are essential for the proliferation of normal and neoplastic cells, and have been repeatedly recommended as tumor markers, with contrasting and elusive results. In the present study the urinary excretion of free and acetylated polyamines was measured in patients with hepatocellular carcinoma (HCC), cirrhotics and control subjects. Separation and quantification of dansyl-derivatives of free, acetylated and total polyamines was performed by reverse-phase high-performance liquid chromatography. The results show that the urinary excretion of total, free, and acetylated polyamines is significantly higher in HCC patients than in cirrhotics and controls (p < 0.001). The N1/N8 acetyl-spermidine molar ratio was found to be higher in HCC patients than in cirrhotics and controls (p < 0.001). No correlation was found between urinary excretion of polyamines and serum alpha-fetoprotein, tumor size and severity of liver cirrhosis. The results show that increased urinary excretion of free and acetylated polyamines, as well as an altered N1/N8-acetyl-spermidine molar ratio, is a sensible but not specific feature of HCC patients; polyamines may play a role in human carcinogenesis, but their determination does not seem reliable for the early detection of liver cancer.

Serum neopterin levels in patients with hepatocellular carcinoma.

Increased concentrations of neopterin have been found in conditions causing a stimulation of cellular immunity, including various malignancies. In liver diseases, serum or urinary neopterin levels have been studied in acute viral hepatitis, chronic hepatitis, fatty liver and liver cirrhosis. In the present study neopterin serum levels have been measured in 16 patients with hepatocellular carcinoma (HCC), in 32 patients with liver cirrhosis, and in 28 healthy subjects as controls. Mean values of serum neopterin were significantly increased (p < 0.01) in patients with HCC (15.89 +/- 6.34 nmol/l) when compared with those of normal subjects (4.74 +/- 2.13 nmol/l), but no difference was observed between patients with HCC (associated or not with liver cirrhosis) and patients with liver cirrhosis. Neopterin concentrations are not affected by liver cirrhosis aetiology, nor by its clinical severity, and are not correlated to the values of serum alpha-fetoprotein, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl-transferase, and gamma-globulin. The results show that there is a consistent overlap of values in patients with HCC and liver cirrhosis; macrophage activation seems to be a feature of chronic liver diseases, irrespective of HCC development.

Serum neopterin levels in liver cirrhosis.

Neopterin is a pyrazino-pyrimidine compound which is biosynthesized by macrophages. Increased concentrations of neopterin have been reported in conditions causing a stimulation of cellular immunity, such as viral and other infections, graft versus host disease, autoimmune disease and different malignancies. Recently, urinary neopterin levels have been found increased in patients with acute viral hepatitis and NANB chronic hepatitis. In the present study, neopterin serum levels have been measured in 23 cirrhotic patients (6 HBV related, and 17 cryptogenetic cirrhosis, 7 of them occurring in alcoholic subjects) and in 24 normal subjects. Mean values of serum neopterin were significantly increased in cirrhotics (3.92 +/- 3.28 ng/ml versus 1.24 +/- 0.51 ng/ml in controls, p less than 0.01). Serum neopterin values were not found to be significantly different in cirrhotics assessed in three different clinical classes according to Child's classification and in cirrhotics with and without serological findings of active disease. In fact, in cirrhotic patients, serum neopterin levels did not correlate with the values of serum AST, ALT, ALP, GGT and gamma-globulin. These data show that increased levels of serum neopterin occur in cirrhotic patients, but there is no relation between serum neopterin values and the activity or the clinical severity of the disease. The results are consistent with the hypothesis that activated macrophages are involved in all stages of liver cirrhosis irrespective of its aetiology.

Insulin and glucagon degradation in liver are not affected by hepatic cirrhosis.

Hyperinsulinemia and impaired glucose tolerance are associated with liver cirrhosis. To investigate whether insulin-degrading activity in liver tissue plays a role in hyperinsulinemia, we assayed this activity in biopsy tissue from healthy and cirrhotic subjects. There was no difference in insulin degradation between these two groups. Also glucagon-degrading activity in liver tissue, which is catalyzed by the same enzyme as insulin-degrading activity, did not differ between the two groups studied. Therefore, insulin-degrading activity does not appear to be involved in the hyperinsulinemia that occurs in liver cirrhosis. The study provides indirect evidence that hyperinsulinemia and impaired glucose metabolism in liver cirrhosis are due to different mechanisms (receptorial and post-receptorial defects, and altered feedback inhibition of insulin secretion).

[Blood levels of neopterin in patients with liver cirrhosis]. / Studio dei livelli sierici di neopterina in pazienti con cirrosi epatica.

Neopterin is a pyrazino-pyrimidine compound which is biosynthesized by macrophages. Increased concentrations of neopterin have been reported in conditions causing stimulation of cellular immunity, such as viral and other infections, graft versus host disease, autoimmune diseases and different malignancies. Recently, increased urinary neopterin levels have been found in patients with acute viral hepatitis and NANB chronic hepatitis. In the present study, neopterin serum levels were measured in 23 cirrhotic patients (6 HBV related, 7 alcoholic and 10 cryptogenetic cirrhosis) and in 24 normal subjects. Mean values of serum neopterin were statistically increased in cirrhotics (3.92 +/- 3.28 ng/mL versus 1.24 +/- 0.51 ng/mL in controls, p less than 0.01). Serum neopterin values were not statistically different either in cirrhotics assessed in three different classes according to Child's classification or in cirrhotics with or without serological findings of active disease. In fact, in cirrhotic patients, serum neopterin levels did not correlate with serum aspartate and alanine aminotransferases, alkaline phosphatase, gamma-glutamyltransferase and gammaglobulins values. These data show that increased levels of serum neopterin occur in cirrhotic patients, but there is no relation between serum neopterin values and the histological activity or the clinical severity of the disease. The results are consistent with the hypothesis that activated macrophages are involved in all forms and in all stages of liver cirrhosis.

[Membranoproliferative glomerulonephritis as an unusual initial manifestation in a case of plasmacytoma]. / Glomerulonefrite membranoproliferativa quale insolita manifestazione d'esordio in un caso di plasmocitoma.

The Authors describe a case of membranoproliferative glomerulonephritis associated with nephrotic syndrome in a 50-year-old man with plasmocytoma. The bone marrow and the immunoelectrophoresis of the serum and urine showed a Bence-Jones positive multiple myeloma with plasma cells secreting only k light chain. The patient responded immediately to monthly courses of cyclophosphamide, melphalan, vincristine and prednisone. He showed still, 27 months after the diagnosis, complete remission of the disease.