[Role of the liver in the regulation of glucose metabolism in diabetes and chronic liver disease]. / Ruolo del fegato nella regolazione del metabolismo glucidico in corso di diabete e di epatopatia cronica.

The liver plays a major role in the regulation of glucose metabolism: plasma glucose concentration is the result of peripheral glucose utilization and liver production. Several hormones, including insulin, glucagon, growth hormone, cortisol, and catecholamines contribute to the regulation of glucose metabolism by the liver. In this review, we examine hepatic glucose metabolism, in particular the actions of insulin and contrainsular hormones on glucose hepatic uptake and production in patients with diabetes or chronic liver disease. The most frequent patterns of hepatic involvement that take place during diabetes, i.e. nuclear glycogenesis, steatosis, portal fibrosis, and diabetic steatonecrosis, are discussed. Also considered are anomalies of glucose homeostasis observed in chronic liver disease, including glucose intolerance, diabetes, and hypoglycemias. There is a strong correlation between diabetes mellitus and the liver: diabetic patients have typical histological lesions, while several glucose metabolism alterations are commonly found in subjects with chronic liver disease. The pathogenesis of impaired glucose metabolism during chronic liver disease has not yet been fully understood: further clinical and experimental studies should clarify this issue.

Conferring drug resistance by MDR1 gene transfection increases susceptibility to irradiation and lipid peroxidation in 3T3 cell line.

This study was performed to test the hypothesis that conferring multiple drug resistance reduces cell susceptibility to irradiation and iron-stimulated lipid peroxidation. Multidrug resistant (PN1A) and parental drug sensitive (PSI-2) cell lines were exposed to ADP-Fe or Ascorbate-Fe complexes at 37 degrees C and to irradiation. Lipid peroxidation was estimated by the TBA test, whereas x-ray effect was estimated by clonogenic assay. Cell glutathione-S-transferase (GST), total and Se-dependent glutathione peroxidase (GSH-Px) activities, and glutathione and vitamin E were measured. PN1A produced more peroxides than PSI-2 after exposure to iron complexes and formed fewer colonies after irradiation. Higher activities of GST and total and Se-GSH-Px were observed in PN1A. Vitamin E and total glutathione did not differ in the two cell subclones. These data show that the induction of the mdr1 phenotype by transfection of mdr1 gene in 3T3 cells increases susceptibility to irradiation and iron stimulated lipid peroxidation.

Thyroxine-binding globulin in elderly patients with hepatocellular carcinoma.

In order to evaluate the possible relevance of the increased serum levels of thyroxine binding globulin (TBG) in elderly patients with cirrhosis and hepatocellular carcinoma (HCC), TBG and alpha-fetoprotein (AFP) levels were measured in 3 groups: (i) 14 healthy subjects (mean age: 74 +/- 2 years); (ii) 15 patients with cirrhosis of the liver (mean age: 70 +/- 1 years); (iii) 17 patients with cirrhosis and HCC (mean age: 71 +/- 1 years). Both TBG and AFP levels were significantly higher (p < 0.01) in the patients with HCC, as compared to the healthy subjects or to the cirrhotic ones without HCC. The increased plasma TBG levels in cirrhotic patients with HCC is probably due to a derepression of the TBG gene in hepatocytes undergoing neoplastic transformation. The results suggest that TBG together with AFP may be of diagnostic value for the presence of HCC in aging patients with liver cirrhosis.

Susceptibility to lipid peroxidation of human hepatocellular carcinoma cell lines with different levels of multiple drug-resistant phenotype.

BACKGROUND: It has not been established whether the presence of intrinsic or acquired multiple drug-resistant (MDR) phenotype affects susceptibility to undergo iron-stimulated lipid peroxidation. EXPERIMENTAL DESIGN: To assess this point, human hepatocellular carcinoma cell lines with moderate, clinically relevant (P1) or elevated (P1(0.5)) MDR phenotype and their parental drug-sensitive (P5) cell line were exposed to ADP-Fe or ascorbate-Fe complexes and H2O2 in different experiments. Thiobarbituric acid-reactive substances (TBARS) were measured. Total cell glutathione, glutathione-S-transferase, total and selenium-dependent glutathione peroxidase activities, and cell alpha-tocopherol content were also determined. RESULTS: P5 and P1 cell lines showed similar and significant formation of TBAR after 1-hour incubation exposure to iron complexes, whereas P1(0.5) subclone did not. No accumulation of TBAR was observed during the exposure to H2O2 in the three cell lines. Among antioxidants, only alpha-tocopherol cell content was significantly higher in P1(0.5) in comparison with either P1 or P5. CONCLUSIONS: These data suggest that MDR phenotype development per se does not increase resistance to iron-related free radical attack in human hepatocellular carcinoma cell lines. Resistance to undergo lipid peroxidation is associated only to high degrees of drug resistance and appears more related to increased alpha-tocopherol cell content rather than an MDR phenotype.

[Obesity: a multifactorial disorder with difficult long-term treatment]. / Obesità: malattia multifattoriale di difficile trattamento a lungo termine.

Obesity is a social disease and amounts to a real medical problem. After considering its epidemiology, the authors discuss diagnostic methods, etiopathogenesis, clinical features, complications, and management of obesity. Special stress is laid upon particular problems concerning the causes of obesity which are often difficult to identify, and difficulties of long-term treatment. Thus it becomes obvious that the disorder must be prevented, and maximum attention must be placed on renewed weight increase.

[Osteoporosis. The recent findings on its etiopathogenesis, diagnosis and therapy. II. Therapy]. / Osteoporosi. Recenti acquisizioni in tema di etiopatogenesi, diagnosi e terapia. Parte II. - Terapia.

Management of osteoporosis has as yet a number of aspects that are not well understood and at times even contradictory, also in view of the fact that some physicians have their "personal therapeutic approach". While on the one hand, the US FDA recognizes calcium, estrogens and calcitonin as the sole remedies for osteoporosis, on the other a variety of drugs have been studied and are at present in use. Among the drugs considered are those apt to reduce bone resorption (calcium, vitamin D metabolites, estrogens, calcitonin, diphosphonates, and ipriflavone) and those favouring bone formation (fluorides, anabolic androgens, PTH and ipriflavone). In addition, future approaches to osteoporosis therapy are considered which may make use of anti-interleukin 1 and 6, as well as of growth factors with specific osteotropism. At present, the physician must know what types of treatment are available for the individual patient with osteoporosis and be able to evaluate the cost/benefit ratio of each drug together with its side effects.

[Osteoporosis. Current advances in etiopathogenesis, diagnosis and therapy. I.--Etiopathogenesis and diagnosis]. / Osteoporosi. Recenti acquisizioni in tema di etiopatogenesi, diagnosi e terapia. Parte I.--Etiopatogenesi e diagnosi.

Throughout life, bone is a tissue continuously remodelled with processes of bone formation followed by resorption. Osteoporosis, a social disease, is characterized by an unbalance of these processes with prevalence of resorption over neoformation. Numerous risk factors may cause or favour this disease. The classification of different types of osteoporosis is presented and the etiopathogenesis and clinical pattern of involutional and secondary osteoporosis are described. We have at our disposal a variety of diagnostic procedures which are also useful for prevention and management.

[Ursodeoxycholic hemisuccinate in the treatment of chronic active hepatitis. A controlled clinico-therapeutic study]. / L'emisuccinato dell'acido ursodesossicolico nel trattamento dell'epatite cronica attiva. Studio clinico-terapeutico controllato.

This controlled study was performed on 36 patients affected by HBV and/or HCV correlated chronic hepatitis (CAH). Eighteen of them received 300 mg of UDCA-hemisuccinate orally twice a day for six months; the other 18 received 200 mg of S-adenosyl-methionine (SAMe) twice a day for six months. The two groups were determined randomly. Treatment with UDCA-hemi-succinate produced a statistically significant reduction in ALT (from 167 +/- 17 to 119 +/- 15 U/l; p < 0.0001), AST (from 122 +/- 14 to 86 +/- 11 U/l; p < 0.0001) and y-GT (from 81 +/- 10 to 53 +/- 6 U/l, p < 0.0001). The results obtained suggest that UDCA-hemi-succinate may be useful in the long-term treatment of chronic liver diseases of viral aetiology because it improves the biochemical parameters of hepatocellular necrosis and/or increased liver cell permeability.

Estimate of prevalence of glucose intolerance in chronic liver disease. Degree of agreement among some diagnostic criteria.

In patients with chronic liver disease, the reliability of various criteria generally used to diagnose impaired glucose tolerance and diabetes was evaluated. Twenty-one patients with chronic persistent hepatitis, 68 patients with chronic active hepatitis and 57 patients with liver cirrhosis were studied. All subjects underwent an oral glucose tolerance test (75 g). Impaired glucose tolerance and diabetes were diagnosed according to the criteria established by: the National Diabetes Study Group; Fajans and Conn; the European Diabetes Study Group; Deutsche Diabetes Gesellschaft; Kobberling & Creutzfeld criteria 1 and 2; Wilkerson; and the University Group Diabetes Program. The results obtained are in partial agreement with other reported data, showing a high prevalence of both impaired glucose tolerance and diabetes in chronic liver disease, with a positive correlation to the severity of hepatic involvement. However, our results show that the agreement among the criteria most frequently used for diagnosing impaired glucose tolerance and diabetes is still far from satisfactory.