The des-gamma-carboxyprothrombin for the diagnosis of hepatocellular carcinoma.

Des-gamma-carboxyprothrombin level was measured by enzyme immunoassay in the plasma of 39 patients suffering from hepatocellular carcinoma and 26 controls. Two of these were anticoagulated by warfarin and revealed very high positive values; the remaining 24, 8 healthy subjects and 16 patients with cirrhosis or chronic hepatitis, were negative. Values indicating pathology were found in 56.40% of patients suffering from hepatocellular carcinoma. All malignancies presenting diameter < or = 3 cm were negative, while high positive levels were found in patients with more advanced neoplasia. The alpha-fetoprotein was increased in 43.58% of the patients with hepatocellular carcinoma and in 6.25% of controls with chronic liver diseases. Positive values for both des-gamma-carboxyprothrombin and alpha- fetoprotein were detected in 12/39 patients. An increase of sensitivity (from 43.58 to 69.23%) in detecting hepatocellular carcinoma was found by the complementary use of the two markers relative to sole use of alpha-fetoprotein.

Endotoxin tolerance and polymyxin B modify liver damage and cholestasis induced by a single dose of alpha-naphthylisothiocyanate in the rat.

A single oral dose of alpha-naphthylisothiocyanate (ANIT) induces intrahepatic cholestasis and endotoxemia in the rat. To assess if a pathogenic relationship between endotoxin and ANIT-induced liver injury could be postulated, rats were pretreated by either induction of endotoxin tolerance, or with the anti-endotoxin agent polymyxin B. A single oral dose (10 or 20 mg/100 g body wt) of ANIT was then given to ascertain whether these methods of modifying endotoxicity would protect the animals against ANIT damage. Both pretreatments significantly reduced the incidence of endotoxemia after ANIT administration, as detected by either lead acetate enhancement method or the Limulus gelation test (LGT). The lethality of a single 20 mg/100 g body wt dose of ANIT was reduced from 55% to 15% by polymyxin B administration, and to 10% by an endotoxin-tolerant state. Moreover, when 10 mg/100 g body wt ANIT was given none of the animals died in 10 days, and the serum levels of bilirubin, alkaline phosphatase (AlPh), gamma-glutamyl transferase (gamma-GT), and transaminases (evaluated 1, 2, and 5 days after treatments) were significantly lower in the endotoxin-tolerant or polymyxin B administered rats; this biochemical protection was mirrored in the lack of histological alteration. The results demonstrate that the modification of endotoxicity offers significant protection against acute liver damage induced by ANIT. Thus the development of endotoxemia may play a pathogenic role in ANIT-induced liver injury. This conclusion is supportive of the hypothesis that endotoxins are necessary for the hepatotoxic agent to exert its full effects.

[Nutrition and andrological problems]. / Alimentazione e problemi andrologici.

Andrologic problems were considered as nutrition is concerned: vitamin and oligo-element deficiencies, metabolic alterations, and toxic intake. Ethanol role was examined and discussed for its relevance in psychological and organic impairment due to both chronic abuse and acute intake, mainly for its role on hypothalamic-pituitary-gonadal axis. Rational nutrition is a clue in sexual disturbance prevention, correction and integrated care.

Sodium taurocholate affects prostacyclin constitutive production by cultured human vascular endothelial cells.

The prostaglandin system is impaired in cholestasis; bile salts, which are a specific biochemical feature of this condition, have been shown to affect functional properties of cells and tissues, and, in some cases, their action is mediated through an alteration of prostaglandin pathway. Endothelium is a privileged site for the production and the action of arachidonate metabolites-prostacyclin in particular. To determine the effects of bile salts on the properties of vascular endothelium, cultured human endothelial cells were studied. Cholic acid sodium salt was seen to induce a direct injury on endothelial cells, as was demonstrated by a massive dismission of the intracellular radiolabel chromium 51. In the absence of detectable toxic effect, sodium taurocholate caused a significant depression of prostacyclin constitutive production from human endothelial cells. The action of sodium taurocholate was related to its concentration and to the time of exposure, and the alteration of prostacyclin production was found to be reversible. Conversely, the generation of thromboxane A2 was not influenced by this bile salt, which may suggest a specific action of sodium taurocholate on arachidonic acid metabolism. These findings indicate that bile salts may directly alter some functional properties of cultured human endothelial cells and may provide a basis for explaining some generalized manifestations that are observed in pathologic conditions characterized by cholemia.

[Bile salts and spontaneous release of PGI2, TxA2 and fVIII from cultured human endothelial cells]. / Sali biliari e rilascio spontaneo di PGI2, TxA2 e fVIII dalle cellule endoteliali umane in coltura.

A normally functioning vascular endothelium is required for vascular tone modulation and blood fluidity. Systemic and local circulatory and coagulation alterations, even to the point of renal failure, may be observed in obstructive jaundice; bile salts are included among the potential pathogenetic factors. To assess the effects of taurocholic acid, glycocholic acid, and cholic acid on the integrity and properties of the endothelium, cultured human endothelial cells (HUVEC) were studied. Taurocholic and glycocholic acids (up to 2000 mumoles/L) did not exhibit any significant effect on 51Cr release from HUVEC after 6 h incubation. Following HUVEC exposure to 2000 mumoles/L of the unconjugated compound, cholic acid, a significant discharge of the radiolabel and LDH leakage in the supernatant were observed, to some extent prevented by the presence of human plasma or albumin (physiologic carrier). Prostacyclin spontaneous release from HUVEC was significantly depressed by both taurocholic and glycocholic acid; the action was related to bile salt concentration (200-1000 mumoles/L) and to the time of exposure (1 to 24 h); the reduced production of PGI2 was demonstrated to be reversible. Conversely, spontaneous TxA2 generation and fVIII release were not affected by the presence of bile salts in culture medium. Previous investigations showed that experimental obstructive jaundice could impair prostacyclin release from rat aortic tissue. The same effect was also demonstrated after in vitro exposure of the vessel wall to jaundiced serum and bile salts alone; furthermore, bile salts exert toxic effects on the integrity of several cells and impair the prostaglandin system of different tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of propranolol on platelet aggregation and thromboxane B2 production from platelet-rich plasma and whole blood.

The beta-adrenoceptor antagonist propranolol is used in the therapy of hypertension and ischemic heart disease. The aim of our study was to evaluate the effects of this drug on platelet aggregation and on synthesis of thromboxane B2 (the stable metabolite of Thromboxane A2) from platelet rich plasma (PRP), whole blood samples and during spontaneous clotting. The results indicate that propranolol at concentrations near the therapeutic range, significantly inhibit collagen and thrombin-induced platelet aggregation and TxB2 synthesis from PRP. Furthermore the drug demonstrates inhibitory activity on B-TG release and TxB2 production from whole blood samples and on spontaneous clotting. The results suggest that some benefits of propranolol in the treatment of patients with coronary artery disease or cardiovascular conditions associated with platelet hyperaggregability may also be related to interference with platelet activation "in vivo" and with TxA2 generation.

Influence of urapidil on in vitro platelet response to adrenaline and other aggregating agents.

The effects of hypotensive drug urapidil on human platelet functions were investigated. Urapidil failed to evidence direct aggregating properties or potentiating effects. Furthermore, drug high concentrations inhibited the platelet response to ADP, PAF, collagen, adrenaline and bovine thrombin, and influenced the platelet release reaction induced by ADP and PAF. Data indicate that urapidil possesses negligible agonistic effects on human platelet alpha 2-adrenoceptors and interferes at high concentrations with the platelet activation, as evidenced for other anti-aggregating compounds.

Urinary enzyme release following aminoglycoside administration in single low dose.

Urinary enzyme excretion was investigated in healthy volunteers before and after infusion of single low doses of aminoglycoside (gentamicin, tobramycin and amikacin) in the same subjects. Significant increases were detected in urinary leucine aminopeptidase, lactate dehydrogenase and alkaline phosphatase following gentamicin infusion; after amikacin administration only urinary release of leucine aminopeptidase was found to be increased. No difference was detected compared to basal values in enzyme excretion after tobramycin infusion. Urinary enzyme release in our conditions suggests low tubular damage after single doses of gentamicin and amikacin.

Increased incidence of cancer in chronic pancreatitis.

Patients affected by chronic pancreatitis were followed between 1970 and 1984 in a study set up to evaluate the natural history of the disease. The study population included 172 consecutive patients diagnosed as having chronic pancreatitis in the Gastroenterology Unit of the S. Giovanni Battista Hospital in Torino, Italy. Of them, 23 were found to be affected by cancer during the 14-year follow-up period. The incidence calculated using the person-year method was compared with data from the General Population Cancer Registry of Piemonte Region. The age-specific relative risks of cancer were increased manifold. Sex- and age-specific relative risks were markedly increased for liver, tongue, lip, and rectum tumors in males, and for liver, bone, and breast tumors in females. Selection bias did not seem to be an adequate explanation of this association. Survival curves were plotted by the estimation methods of Cutler-Ederer with year intervals for the complete study population and for the different type of cancer. Known risk factors and indicators for the expected tumors were evaluated by the Cox Proportional Hazard Regression Model. The incidence of cancer increases significantly with age but not with smoking, alcohol use, and diabetes. Our epidemiological study suggests an increased risk of pancreatic as well as extrapancreatic cancer in patients with chronic pancreatitis compared with the general population. Cancer seems to be a main determinant in the natural history of the disease.

Influence of age on polymorphonuclear leukocytes in vitro: phagocytic activity in healthy human subjects.

Polymorphonuclear leukocytes (PMNs) represent an important defensive mechanism against infectious agents. Some of their functions are impaired in old people, with a decreased effectiveness of nonspecific immunity. In vitro PMN phagocytic activity was studied with different techniques on 74 healthy subjects (20-82.5 years; 40 males, 34 females). Serum-mediated ingestion resulted to be impaired with age with a lower ratio of active PMNs and a lower activity of phagocytosing cells. The behavior of these parameters was age-related, without significant difference between males and females; the decline was found to be a continuous phenomenon with no threshold age. Serum-independent ingestion had very low values and was not impaired with aging. The present data can represent a further explanation for the finding of a higher incidence and mortality of bacterial diseases in elderly population.

Urinary enzyme excretion in acute and subacute experimental lithium administration.

Blood lithium (Li) levels, renal functional parameters and urine excretion of enzymatic activities having different intracellular sites were investigated on rats submitted to acute and subacute Li chloride administration. In acute experiments increased levels of all detected enzymes were assayed following Li single doses of 5 and 10 mEq/kg b.w. In subacute poisoning, urine output of lactate dehydrogenase, aspartate transaminase and alanine transaminase was significantly over the basal ranges following 15 days in concomitance with marked elevation of plasma Li levels and exhibited progressive increase until 30 days; on the 10th day following Li withdrawal, elevated excretion of enzymatic activities was still assayed. The results are in agreement with data about the localization of the histologic lesions involving different sites of the nephron in acute Li poisoning and the distal tubular tract in subacute toxicity. In subacute administration the output of cytoplasmic and mitochondrial activities can be assumed as an index of damage of the nephron cells which can persist following Li withdrawal. Our findings indicate that the urine enzyme assay is a valuable tool to detect renal damage in experimental Li nephropathy.

Duodenal lactoferrin in patients with chronic pancreatitis and gastrointestinal diseases.

Lactoferrin (LF), chymotrypsin and lipase activity were measured in duodenal juice during pancreatic stimulation. Secretin (0.5 CU/kg/h) plus cerulein (75 ng/kg/h) were infused intravenously in 98 subjects: 33 patients without organic diseases (C), 40 patients affected by chronic pancreatitis (CP), and 25 patients with different gastrointestinal diseases (GID). LF was determined by means of a new noncompetitive immunoenzymatic assay with a sensitivity in the duodenal juice of 5 ng/ml. Duodenal LF concentrations were significantly higher in CP than in C or GID (p less than 0.001). LF was in a normal range in acute relapsing pancreatitis due to biliary stones or pancreas divisum. In the diagnosis of the chronic pancreatitis, LF/lipase ratios showed a specificity of 93% and a sensitivity of 95%. Our results show that LF immunoassay in duodenal juice is a sensitive and accurate assay to apply in pancreatic function tests involving duodenal content analysis.

[Hepatic granulomatosis]. / Granulomatosi epatiche.

Granulomatous hepatitis is not a uniform disease entity but a generic histopathologic diagnosis. The present review of aetiology and epidemiology of granulomas in the liver, shows that in the past tuberculosis and sarcoidosis were the most frequent but there remained a large percentage of "undiagnosis" cases; at the present drug-induced granulomatous hepatitis are frequently reported and "undiagnosed cases" are rare. Analysis of the hystological features of the most common granulomas is presented.

Ultrasonographic findings in portal hypertension: correlation with the presence and size of oesophageal varices.

This study assesses the usefulness of ultrasonography in the diagnosis of portal hypertension. Several ultrasonographic signs were correlated with the presence and size of oesophageal varices detected by endoscopy in 32 patients suffering from alcoholic liver cirrhosis. Ultrasonography is proposed as a simpler and earlier method for screening of portal hypertension than endoscopy.

Urinary enzyme excretion and renal lactate dehydrogenase isoenzyme pattern in acute HgCl2 nephropathy of rat.

The activity of several enzymes with different intracellular sites was determined in urine at various times following nonfatal acute tubular necrosis induced by mercuric chloride administration. The excretion rate of all tested enzymes rose on the 1st and 2nd day; in the next observations (days 7-15) enzymatic values approached the basal values. The lactate dehydrogenase isoenzyme pattern of the renal cortical zone showed an early shift towards cathodic fractions and later (7 days) an increase of middle ones; the normal anodic zymogram recovered after a suitable time interval (30 days). The isoenzymatic changes are related both to the renal hypoxia and to the appearance of less differentiated cells. The behaviour of functional parameters (urine flow, osmolality, urea clearance, creatinine clearance) were well in agreement with the observed enzyme and renal isoenzyme changes.

[Immunological aspects of diabetes]. / Aspetti immunologici della malattia diabetica.

The incidence of immunological disorders seems to play a primary, significative role in the genesis of insulin-dependent diabetes mellitus (IDDM). Auto-immunological anti-pancreas alterations, both cell-mediated and humoral, have been detected in course of IDDM; moreover, the presence of antipancreatic antibodies seems to correlate with progressive destruction of islet cells and increased insulin deficiency. Animal models and human studies, revealing the pathologic entity of "insulitis", are consistent with an autoimmune component playing a part in the pathogenesis of diabetes mellitus. Furthermore, genotypic factors may be considered: recent studies prove the association between HLA system and IDDM; specifically, HLA antigens B8 and BW15 are found in significantly higher frequencies in juvenile onset insulin-dependent diabetics. Therefore, it can be hypothesized, in the pathogenesis of the disease, an altered immune response to an additional environmental diabetogenic factor; it has been postulated, on the ground of epidemiologic and experimental studies, the interference of a viral infection, that may act as a triggering event to pancreatic cell damage with a latent period of variable duration.