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R Utili

Publications and source records attributed to R Utili.

At least 73 records · Page 4Linked to original sources

Characterization of the effects of erythromycin estolate and erythromycin base on the excretory function of the isolated rat liver.

To investigate the mechanisms of erythromycin cholestasis, the effects of erythromycin estolate (EE) on the excretory function of the isolated perfused rat liver and on liver plasma membrane (LM) preparations were studied and compared to those of erythromycin base (EB) and lauryl sulfate (LS), added alone or in combination. EE (at 125 to 200 microM) caused dose-dependent reductions of bile and perfusate flows, bile acid (BA) excretion, and biliary BA concentration. The alterations of the excretory function were only in part due to the decreased perfusate flow. In contrast, both 200 and 300 microM concentrations of EB elicited similar choleretic responses, which were presumably related to the osmotic activity of the drug excreted in the bile. LS did not affect hepatic excretory functions. However, the simultaneous addition of EB and LS resulted in a rate of bile flow lower than that observed with EB alone. EE, but not EB, increased canalicular permeability to [14C]sucrose as measured by bile to plasma (B:P) ratio. Neither drugs altered [14C]erythritol B:P ratio. In LM preparations both Na+,K+- and Mg2+-ATPase activities were inhibited in a dose-dependent manner by EE, but not by EB. The data suggest that EE could affect bile flow by inhibiting cotransport of Na+ and BA and by altering LM permeability and support the view that the effect of erythromycins on the liver may be related to their surface activity.

Adenosine Triphosphatases↗

Effect of beta-lactam antibiotics at subinhibitory concentrations on the phagocytosis of Staphylococcus aureus by the perfused rat liver.

We evaluated whether the exposure of Staphylococcus aureus to a subinhibitory concentration of penicillin and cefamandole could modify its susceptibility to rat serum factors and to the phagocytic activity of the isolated and perfused rat liver. Control or sub-MIC treated bacteria were added to the circulating medium which contained homologous serum, and the disappearance of bacteria from the perfusate and their recovery in the liver was determined during the 10 min experimental time. Sub-MIC treated bacteria were more susceptible to the bactericidal activity of serum present in the perfusate. However, the clearance rate of bacteria by the liver was decreased for penicillin-treated organisms and unchanged for cefamandole-treated bacteria. The data suggest that beta-lactam antibiotics at sub-MIC levels may modify S. aureus susceptibility to host defense mechanisms.

Animals↗

[Cholestatic effect of amphotericin B on the isolated perfused rat liver. Preliminary observations].

We evaluated the effect of Amphotericin B, a polyen antimycotic agent, on the excretory functions of the isolated perfused rat liver. At 5 X 10(-6) and 10(-5) M, Amphotericin caused a rapid dose-dependent cholestasis. This effect was paralleled by an increase in canalicular permeability, as evaluated by sucrose C14 B/P ratio. The data indicate that Amphotericin B is a potent cholestatic agent in vitro and suggest that caution should be exercised in the use of this drug in hepatopatic patients.

Amphotericin B↗

[Bactericidal activity of the serum against Staphylococcus aureus grown in the presence of subinhibitory doses of cefamandole and gentamicin].

Growth of S. aureus in the presence of subinhibitory concentrations of cefamandole alone (at 1/5 the MIC) or with gentamicin (both at 1/5 the MIC) produced large, globular cells with reduced viability (50%) as compared to untreated bacteria. Gentamicin (1/5 the MIC) did not modify bacteria and also reduced viability of inoculum (57% vs. controls). Cefamandole treated bacteria were more susceptible to the rat serum bactericidal activity then control bacteria. The growth of S. aureus in the presence of cefamandole plus gentamicin did not modify further bacterial susceptibility to serum opsonins. The data suggest that even at subinhibitory concentrations cefamandole may exert an antibacterial effect by acting in cooperation with serum factors.

Animals↗

Increased phagocytosis and killing of Escherichia coli treated with subinhibitory concentrations of cefamandole and gentamicin in isolated rat livers.

Our purpose was to study whether treatment of Escherichia coli with subinhibitory concentrations of either cefamandole or gentamicin could change bacterial susceptibility to the serum bactericidal effect and to the phagocytic and killing activity of the rat liver reticuloendothelial system. Bacteria were grown overnight with 1/5 or 1/10 of the MIC of each antibiotic. At one-fifth of the MIC, cefamandole induced filamentous elongated bacteria whose viability was decreased by 75%. The susceptibility of control and antibiotic-treated bacteria to serum was tested by measuring the survival of organisms exposed to different concentrations of rat serum in vitro. Susceptibility of bacteria to hepatic macrophage activity was tested by following the hepatic clearance of bacteria after they were added to the perfusate of the isolated rat liver. E. coli treated with subinhibitory concentrations of cefamandole or gentamicin appeared somewhat more resistant to the lytic activity of serum at a concentration of 4%, but not at 20%. Bacteria treated with 1/5 or 1/10 of the MIC of cefamandole or with 1/5 of the MIC of gentamicin were significantly more susceptible to phagocytosis and to the bactericidal activity of liver macrophages. Cefamandole appeared more potent than gentamicin in inducing these effects. The results suggest that subinhibitory levels of antibiotics may alter bacterial cell surface (cefamandole) or may impair the expression of antiphagocytic material (gentamicin), thus favoring phagocytosis and killing by macrophages. Our study provides evidence that antibiotics at subinhibitory concentrations may cooperate with host defence mechanisms against bacterial infections.

Animals↗

[Sensitivity of bacteria exposed to subinhibitory concentrations of antibiotics to the action of serum and liver phagocytes].

Incubation of E.coli and S. aureus with subinhibitory concentration (1/5 MIC) of cefamandole modified bacterial morphology and resistance to host defence mechanisms. In fact, cefamandole induced filamentous forms of E. coli, when added to the perfusing medium of the isolated rat liver system, were phagocytized at a much fortes rate then control bacteria, but appeared less sensitive to serum bactericidal activity. In contrast, S.aureus, after exposure to the antibiotic, was more sensitive to the bactericidal activity of serum then controls, while treated and untreated cells were phagocytized at the some rate. The data suggest that even at low doses some antibiotics may alter bacterial structure and increase their susceptibility to host factors.

Animals↗

Hyperendemicity of viral hepatitis in the Neapolitan area: an epidemiological study.

An epidemiological study was performed in order to evaluate the diffusion pattern and risk factors in an area of hyperendemicity of viral hepatitis in the Neapolitan hinterland. Eight hundred-fifty seven asymptomatic subjects, aged 10 to 65 years, who consecutively went to the public health office of the city of Afragola to ask for a health certificate, were studied. They were interviewed with an epidemiological questionnaire and tested for a basic liver profile and serological markers of both hepatitis A and B viruses. Ninety-five percent of the studied population, had anti-HAV with a prevalence of 73% in the class 10-14 years, and of 98% in the class 45-65 years; 78% had either HBsAg or antibodies anti-HBV (60% in the class 10-14 years and 96% in the class 45-65 years). Healthy carriers state was found in 11.4% of the population and acute asymptomatic type B hepatitis in 3%. For HBV infection the interhuman contact in the family setting appeared to play a major role in viral diffusion. Other favouring factors appeared to be the ingestion of raw shellfish and parenteral therapies with glass syringes not properly sterilized. The data suggest that strategies of prevention of hepatitis diffusion in the Neapolitan area should be based on both reinforcing hygienic measures and the educational level of population and active prophylaxis addressed to people in the very young age.

Adolescent↗

Effects of acute and chronic endotoxin treatment on glucagon and insulin receptors on rat liver plasma membranes.

The effects of acute and chronic endotoxin treatment on the plasma levels of insulin and glucagon and their binding to rat liver plasma membranes were examined. Both acute and chronic endotoxin administration increased plasma glucagon levels and decreased the glucagon to insulin molar ratio. Acute, but not chronic, endotoxin decreased blood glucose and insulin levels. Glucagon binding was increased in membranes prepared from the acutely treated rats. However, in membranes obtained from rats treated chronically with endotoxin, only insulin binding was increased. The increases in the binding of both insulin and glucagon were the result of increases in receptor sites.

Animals↗

Endotoxemia in a series of 104 patients with chronic liver diseases: prevalence and significance.

Endotoxemia, measured by Limulus amebocyte lysate (LAL) assay, was found to be present in 34 (46%) out of 72 patients with liver cirrhosis and in 7 (22%) out of 32 patients with chronic active hepatitis (CAH). In cirrhotics, no difference in the alteration of liver function tests and renal function was found between the two groups. However, 18 months mortality was higher in the group with endotoxemia in respect to the group without endotoxemia (p less than 0.05). In CAH patients, the Limulus-positive group showed a higher level of serum gamma-globulins, compared to the Limulus-negative group (p less than 0.005). Moreover, CAH patients with a positive LAL test showed marked histological activity and bridging necrosis more frequently than those with a negative test. This suggests that in these patients the appearance of endotoxemia may indicate a more advanced stage of the disease.

Adult↗

Decreased phagocytic and bactericidal activity of the hepatic reticuloendothelial system during chronic ethanol treatment and its restoration by levamisole.

The effect of chronic ethanol feeding (3 weeks) on the phagocytic and the bactericidal activity of hepatic RES versus viable Escherichia coli was studied using the isolated rat liver perfused with a serum-containing medium. Controls or ethanol-fed animals were used as liver or serum donors. The bactericidal activity of serum from ethanol-fed rats was similar to controls and accounted for the disappearance of nearly one-tenth of the bacterial inoculum from the system. When control livers were perfused with a medium containing serum from ethanol-fed animals, phagocytosis was comparable to controls while intracellular killing was greatly reduced. When livers were isolated from ethanol-fed rats, phagocytosis was significantly depressed and no killing occurred, irrespective of the source of serum. Levamisole was able to restore the macrophage activity depressed by ethanol. Our data indicate that the direct effect of ethanol on hepatic macrophages plays a major role in reducing the bactericidal activity of hepatic RES, although alterations of serum factors may contribute to an ineffective preparation of bacteria for intracellular killing.

Animals↗

[Effect of pretreatment with bacterial endotoxin on erythromycin estolate-induced cholestasis].

The effect of acute and chronic endotoxin (LPS) treatment on the erythromycin estolate (EE) induced cholestasis, was studied using the isolated perfused rat liver. Addition of EE markedly reduced bile and perfusate flows in livers from control rats but did not alter these parameters in livers from endotoxin pretreated rats or in vitro treated with LPS. We suggest that changes in membrane organization induced by LPS may alter the diplay of EE toxicity.

Animals↗

Treatment of chronic active hepatitis (CAH): a retrospective review of 130 patients.

The authors review the course of disease in 130 patients (87 HBsAg-positive and 43 HBsAg-negative) with chronic active hepatitis (CAH) observed in the last six years. Patients were treated with prednisone (36 HBsAg-positive an 8 HBsAg-negative), azathioprine (7 HBsAg-positive and 12 HBsAg-negative) or a combination of prednisone and azathioprine (23 HBsAg-positive and 14 HBsAg-negative), or remained untreated (21 HBsAg-positive and 9 HBsAg-negative). Among HBsAg-positive patients improvement was observed in 54% of the 66 patients treated, and in none of the 21 untreated patients (P less than 0.001). Treatment did not modify the course of the disease in HBsAg-negative patients with CAH; this is probably related either to the small number of patients in each treatment group, or to geographical differences. Furthermore treatment was not effective in patients older than 40 years, whether HBsAg-positive or HBsAg-negative. Three out of 87 HBsAg-positive patients, and two out of the 43 HBsAg-negative patients had died by the end of the observation period irrespective of treatment. Full remission with clearance of HBsAg was observed only in one patient after 4 years of treatment with steroids.

Adolescent↗

Endotoxin protects against chlorpromazine-induced cholestasis in the isolated perfused rat liver.

Induction of endotoxin tolerance or acute chlorpromazine treatment caused a decrease in bile and perfusate flow in the isolated perfused rat liver. The primary effects of each appeared to be on the bile acid-independent fraction of bile. Both the induction of endotoxin tolerance and the in vitro treatment of the perfused rat liver with endotoxin partially blocked the adverse effects of chlorpromazine on bile formation and perfusate flow. Although the "protective" effects of the in vitro endotoxin treatment were dose-dependent, the protection afforded by endotoxin tolerance was greater. Preincubation of isolated hepatocytes with endotoxin, before the addition of chlorpromazine, caused dose-dependent reductions in the chlorpromazine-induced release of aspartate transaminase. However, neither the incubation of endotoxin with chlorpromazine, before addition of membranes isolated from control rats, nor isolation of membranes from endotoxin-tolerant rats affected the inhibitory effects of chlorpromazine on sodium, potassium-, or magnesium-activated adenosine triphosphatase. If endotoxin exerts its protective effects at the membrane level, these data suggest that endotoxin is able to protect the intact, but not the isolated, hepatocyte membrane or that inhibition of adenosine triphosphatases by chlorpromazine is not important in the adverse effects of chlorpromazine on the perfused rat liver and isolated rat hepatocytes.

Animals↗

Effect of bacterial endotoxin on lysosomal enzyme activities of normal and mucolipidosis III fibroblasts.

The effect of bacterial endotoxin (LPS) on lysosomal enzyme activities of fibroblasts from normals and mucolipidosis III patients was investigated. Exposure of normal fibroblasts to LPS for 24 hours resulted in enhanced intracellular activities of beta-glucuronidase, beta-galactosidase, alpha-L-iduronidase and beta-N-acetylglucosaminidase. Endotoxin also led to an increased extracellular activity of beta-N-acetylglucosaminidase. In contrast, mucolipidosis III fibroblasts did not show either intracellular or extracellular increase of lysosomal hydrolases after LPS treatment. Difference in cellular responsiveness to LPS may be related to the mechanism of LPS-cell interaction.

Endotoxins↗

[Alterations in liver function produced by erythromycin estolate in isolated and perfused rat liver].

Erythromycin estolate (EE) added to perfusing medium of isolated rat liver caused a dose-dependent decrease of both perfusate and bile flows. Biliary bile acid analysis showed that EE decreased both bile acid excretion rate and concentration. This suggests that EE interferes with the formation of bile acid dependent fraction of bile. EE is known to cause, in some individuals a reversible cholestatic hepatic injury. Our data if applicable to clinical setting indicate that an intrinsic toxicity of EE may contribute to the development of hepatic damage.

Animals↗