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.

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.

[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.

[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.

[Type B viral hepatitis. Recent findings]. / Epatite virale di tipo B. Recenti acquisizioni.

The discovery of hepatitis B surface antigen by Blumberg in 1965 offered a specific marker that could readily be employed in the clinical, epidemiological and experimental investigation of type B viral hepatitis. It has since been followed by the continuous gathering of further knowledge concerning this disease. The morphology and immunological and biochemical features of virus B, the epidemiology and prevention of hepatitis B, and marker determination techniques are examined in an overview of the present situation.

[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)

[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.

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.

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.

Recovery of renal lactate dehydrogenase (LDH) isoenzyme pattern after obstruction relief in experimental hydronephrosis.

The release of ureteral occlusion leads to a progressive recovery in LDH isoenzyme pattern with gradual increase of anodic fractions and decrease of middle and cathodic ones. Our findings demonstrate that the recovery is accomplished on the 10-14th day, in agreement with morphological and metabolic observation.

Renal lactate dehydrogenase (LDH) isoenzyme pattern in short-term experimental obstructive nephropathy.

The lactate dehydrogenase isoenzyme pattern of different zones of rat kidney has been investigated at different stages after unilateral ureteral obstruction. In the obstructed kidney, the cortical tissue showed an early (3 days) progressive shift toward a cathodic zymogram; at 7 days LDH-5 isoenzyme was the predominant fraction (44.7 +/- 2.5). In the outer medullary tissue a similar change was observed even though middle fractions were always quite evident. No significant changes were found in the inner medullary tissue. The observed enzymatic abnormalities are related to renal hypoxia and to the occurrence of a less differentiated nephronic cell population. They represent a metabolic marker of the morphologic and functional alterations which occur in obstructive nephropathy.

[Isolated hepatosplenic tuberculosis: 1 case]. / La tuberculose hépato-splénique isolée: a propos d'une observation.

A 27-year-old woman presented with high spiking fevers, progressive malaise, weight loss, and marked hepatosplenomegaly. The clinical picture and laboratory findings (including hepatic scintiscan, coeliac arteriography and abdominal lymphangiography) prompted surgical exploration of hypochondriac organs. On laparotomy, both liver and spleen surface exhibited extensive inflammatory lesions. Histopathologic investigations on hepatic tissue showed microscopic caseating granulomata. Specific stains and cultures for mycobacterium, fungi etc. were negative in tissue preparations. Antituberculous and steroid therapy elicited a rapid response. Follow-up observations indicated the resolution of specific hepatic lesions.

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.

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.