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Biomedical subjects

R Utili

Publications and source records attributed to R Utili.

At least 55 records · Page 3Linked to original sources
PubMed1993

Clinical efficacy of dirithromycin versus miocamycin in tonsillopharyngitis.

A single-blind, randomized, parallel-group study was conducted to compare the efficacy and safety of dirithromycin with miocamycin in the treatment of streptococcal pharyngitis/tonsillitis caused by Group A streptococci. The study population consisted of 60 patients: 30 were randomized to receive 500 mg dirithromycin od and 30 to receive 600 mg miocamycin bd. All 30 dirithromycin-treated patients were eligible for efficacy analysis. A favourable clinical response was observed in 100% of these patients at the post-therapy visit. In the miocamycin-treated group, 28 of 30 (93.3%) patients were eligible for efficacy analysis; a favourable clinical response was observed in 100%. Bacteriological cure of evaluable dirithromycin- and miocamycin-treated patients was 96.7% and 92.9%, respectively. No statistically significant post-therapy differences in clinical or bacteriological response rates were noted between the two groups. Adverse event analysis showed no significant differences between treatment groups. There were no serious adverse events during the study. Two miocamycin-treated patients were prematurely withdrawn from the study due to adverse events (diarrhoea). Analysis of clinical laboratory data revealed no statistically significant differences between the treatment groups that were considered to be drug related. The results of this study suggest that dirithromycin has comparable safety and efficacy to miocamycin in the treatment of streptococcal pharyngitis/tonsillitis infections caused by Group A streptococci.

Adolescent↗
PubMed1992

Effects of bile salt infusion on chlorpromazine-induced cholestasis in the isolated perfused rat liver.

The present study has demonstrated that tauroursodeoxycholate (TUDC), but not taurocholate, can reverse chlorpromazine (CPZ)-induced cholestasis in the isolated perfused rat liver. At an infusion rate of 1.5 mumol/min, TUDC led to restoration of bile flow in the perfused rat liver made cholestatic by the addition of 250 microM CPZ. This reversal was accompanied by an increased excretion of CPZ and its metabolites. A higher infusion rate of 5.0 mumols TUDC/min, however, led to only a transient increase in bile flow and to no increase in CPZ excretion. In contrast to the effects of TUDC, infusion of taurocholate led to an exacerbation of CPZ-induced cholestasis. The differences in the efficacy of the two bile salts may be due to their relative detergent (hydrophobic) properties.

Animals↗
PubMed1992

Drug-induced cholestasis in the perfused rat liver and its reversal by tauroursodeoxycholate: an ultrastructural study.

Chlorpromazine at a concentration of 250 microM and estradiol-17 beta-D-glucuronide at 17.5 microM on infusion led to a sharp reduction in bile flow by the in vitro perfused rat liver. This was accompanied by fragmentation and a loss of canalicular microvilli, dilatation of canaliculi, and thickening of pericanalicular ectoplasm. Less prominent were the smooth endoplasmic reticulum dilatation, lysosomal lamination, and the appearance of amorphous bile in hepatocyte cytoplasm. The bile flow and electron microscopy appearance were restored to normal by infusion of tauroursodeoxycholate in a concentration of 5 mumols/min for the estradiol-17 beta-D-glucuronide-induced cholestasis and 1.5 mumol/min for the chlorpromazine-induced cholestasis. Changes in ultrastructure paralleled changes in bile flow. These observations demonstrate the feasibility of electron microscopy studies on the perfused liver, and the rapidity with which cholestatic changes appear.

Animals↗
PubMed1992

[Usefulness and limitations of vaccination against influenza].

Influenza viruses have caused major epidemics of respiratory disease and a high mortality in patients with advanced age and in those with underlying health conditions. It has been estimated in the USA that, during a moderate epidemic of influenza, there is an excess of 170,000 hospitalizations and approximately 20,000 to 40,000 influenza-associated deaths per years. Costs may exceed 1 billion dollars per year. Influenza viruses have been difficult to control because of a large animal reservoir and of the frequent change of the virus antigenic structure by major (shift) and minor (drift) variations. Current killed trivalent vaccines are made of two influenza A subtypes plus influenza B virus. Because of the antigenic variation, vaccine composition needs to be changed almost every year in order to contain the strains most likely to be effective. There are two types of vaccines--"whole" and "split". The latter has been treated to reduce pyrogenic components and is particularly indicated in children. Vaccine efficacy varies according to how closely the immunizing strains resemble the circulating wild strain. It also depends on the viral strains which had appeared in the preceding years (herd immunity), on the number of the doses administered and on the interval between the vaccination and the natural challenge. The antibody response to vaccine is short-lived. It is greatest in normal adults and lowest in aged and in immunosuppressed patients. Vaccination reduces clinical infections by 70-80% in children and adults, but only by 30% in elderly patients living in institutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Activity of aminoglycosides against phagocytosed bacteria.

The intracellular activity of streptomycin, gentamicin, and netilmicin on Escherichia coli phagocytosed by murine peritoneal macrophages was studied using a sensitive and standardized method. Intracellular activity of streptomycin and gentamicin at therapeutic concentrations was seen after 1 h of incubation of antibiotics with macrophages containing phagocytosed bacteria, whilst for netilmicin a significant intracellular activity was observed only after 3 h exposure. The activity of these antibiotics against intraphagocytic bacteria was significantly lower than that observed against extracellular bacteria. Sub-inhibitory concentrations of streptomycin were active against intracellular E. coli. Streptomycin was also active for a phagocytosed streptomycin-resistant strain of E. coli, but this activity was eliminated when the O2-dependent killing mechanisms of macrophages were inhibited by sodium fluoride. The data demonstrate that aminoglycosides may exert a dose-dependent intraphagocytic activity against E. coli that correlates with the time of incubation of the antibiotics with infected macrophages. Streptomycin appears to be the most effective agent followed by gentamicin and the least active was netilmicin. In the case of streptomycin, the intraphagocytic activity seems to be due, at least in part, to the stimulation of O2-dependent cellular microbactericidal mechanisms.

Animals↗
PubMed1991

Prolonged treatment of children with chronic hepatitis B with recombinant alpha 2a-interferon: a controlled, randomized study.

A prospective study was conducted to evaluate the efficacy and tolerance of alpha-interferon in 20 children with biopsy-proven HBsAg/HBeAg/HBV-DNA-positive, anti-delta-negative chronic hepatitis. Patients were randomized to receive alpha 2a-interferon (INF), 3 MU im three times weekly for 12 months, or no treatment (10 patients per group). Five patients receiving IFN showed a marked decrease or negativization of HBV-DNA during treatment. At the end of the study (after 18 month), three patients lost HBV-DNA permanently, and two of them seroconverted to HBeAb 10 and 11 months after disappearance of HBV-DNA with normalization of aminotransferase values. In the control group, one patient had spontaneous clearance of HBV-DNA with conversion to HBeAb and normalization of aminotransferase levels. All treated patients had a febrile reaction in the first month of treatment. The dose of IFN had to be decreased in two patients and was discontinued for persistent intolerance in one of them. Patients who showed a decreased viral replication had higher initial biochemical and histological activity than nonresponders. The data suggest that IFN treatment may favorably influence the progression of chronic B hepatitis in children with a history of acute hepatitis and active chronic disease.

Adolescent↗
PubMed1990

Estradiol-17 beta-D-glucuronide (E-17G) cholestasis in perfused rat liver: fate of E-17G and choleretic responses to bile salts.

This study was designed to test the hypothesis that increasing the infusion rate of bile salts could overcome drug-induced cholestasis. Cholestasis was induced by administration of 17.5 mumol/L estradiol-17 beta-D-glucuronide during the infusion of taurocholate, tauroursodeoxycholate or dehydrocholate at 20 nmol/min/gm liver. After 30 min, a bolus of 10 mumol of the bile salts was added to the perfusate, and the infusion rate of each bile salt was increased. Taurocholate at a rate of 62 or 125 nmol/min/gm liver, caused a prompt dose-dependent increase of the depressed bile flow and bile salt excretion. A higher rate of taurocholate infusion (180 nmol/min/gm liver) was less effective than either the 62 or 125 rate in increasing bile flow. Infusion of tauroursodeoxycholate at 250 or 390 nmol/min/gm liver also led to a dose-dependent recovery. Further increase of tauroursodeoxycholate infusion rate of 580 nmol/min/gm liver did not provide any additional recovery in bile flow. Dehydrocholate, at rates of 62 or 125 nmol/min/gm liver, gave only a slight enhancement of bile flow. Both taurocholate and tauroursodeoxycholate caused a marked removal of the estradiol-17 beta-D-glucuronide, which had accumulated in the liver. At lower taurocholate infusion rates, the estradiol-17 beta-D-glucuronide was excreted mainly in the bile. At the highest rate, however, biliary excretion of estradiol-17 beta-D-glucuronide declined significantly, and a marked back-efflux of the estrogen into the perfusate was noted. In contrast, tauroursodeoxycholate led to enhanced biliary estradiol-17 beta-D-glucuronide excretion at all increased tauroursodeoxycholate infusion rates and to only a small increase in back-efflux of estradiol-17 beta-D-glucuronide at the two highest tauroursodeoxycholate infusion rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Influence of subinhibitory concentrations of loracarbef (LY 163892) and daptomycin (LY 146032) on bacterial phagocytosis, killing and serum sensitivity.

The aim of this study was to evaluate whether pre-exposure of bacteria to a subinhibitory concentration (sub-MIC) of loracarbef (LY 163892) or daptomycin (LY 146032) could modify bacterial susceptibility to serum bactericidal activity and to phagocytosis and killing by murine peritoneal macrophages and by human polymorphonuclear leucocytes. Escherichia coli, Haemophilus influenzae type b and Staphylococcus aureus grown in the presence of one quarter the MIC of loracarbef, and S. aureus exposed to one quarter the MIC of daptomycin were phagocytosed and killed in numbers significantly higher than non-exposed bacteria. Pre-exposure to loracarbef resulted in increased susceptibility of E. coli and H. influenzae type b to the bactericidal activity of antiserum, but exposure to loracarbef or daptomycin did not modify serum sensitivity of S. aureus. Loracarbef treatment and antiserum enhanced phagocytosis and killing of E. coli and H. influenzae type b to a greater extent than either antibiotic treatment or antiserum alone. These data indicate that loracarbef and daptomycin at sub-MIC enhance the susceptibility of bacterial pathogens to cellular and host defence mechanisms.

Bacteria↗
PubMed1989

Effects of amphotericin B on the excretory function and the colloid clearance capacity of the perfused rat liver.

The effects of amphotericin B (AmB) on the hepatic excretory function and the colloid clearance capacity were investigated in the perfused rat liver. AmB at 5 or 10 microM caused dose-dependent reductions in bile and perfusate flow rates and in biliary bile acid (BA) excretion. BA concentration in bile tended to increase, due to a prominent reduction in bile water induced by the drug. At 5 microM, AmB also caused an increase in [14C]sucrose clearance by the liver and a release of hepatocytic enzymes into the perfusate. These alterations were not related to the decrease in the perfusate flow induced by AmB. In addition, the drug, at 5 microM, caused a significant decrease in the colloidal carbon clearance by the liver. In this case also, the effect was independent of the reduction in the perfusate flow induced by the drug. The toxic effects of AmB on the rat liver could be interpreted as a derangement of the cell membrane functional integrity, which causes cholestasis, enzyme leakage and an impairment of the reticuloendothelial system function. This latter effect deserves careful evaluation of its clinical implications.

Amphotericin B↗
PubMed1989

Intracellular activity of cefamandole and aztreonam against phagocytosed Escherichia coli and Staphylococcus aureus.

The intracellular activity of cefamandole and aztreonam against phagocytosed Escherichia coli and cefamandole against phagocytosed Staphylococcus aureus was studied using a sensitive and standardized method of murine peritoneal macrophages. Cefamandole and aztreonam exerted an intracellular antibacterial activity against E. coli which was greater than their extracellular one. With concentrations of both antibiotics up to 16 x MBC a dose-dependent decrease of the initial number of intracellular E. coli which ranged from 32% to 90% was observed. However, similar antibiotic concentrations above the MBC affected the viability of extracellular E. coli by only 20% to 30%. The intracellular antibacterial activity of both antibiotics against E. coli was further enhanced by immune serum. Cefamandole at 4 x the MBC did not affect the survival of intracellular S. aureus, but killed 41% of extracellular bacteria by 1 h and 99% after 3 h. The intracellular activity of both antibiotics against E. coli was also maintained in NaF-pulsed macrophages which have an impaired oxidative metabolism. The data suggest that both cefamandole and aztreonam possess an intracellular antibacterial activity against E. coli that seems at least in part due to a positive cooperation of antibiotics with the O2-independent microbicidal system of macrophages.

Animals↗
PubMed1988

Kinetics of phagocytosis and killing of E. coli by murine macrophages in presence of different serum preparations.

In this study we evaluated the kinetics of phagocytosis and killing of E. coli by thioglycollate-elicited murine peritoneal macrophages and the role of specific antibodies and complement present in different serum preparations in modulating these processes. In our system phagocytosis of E. coli by macrophage monolayer was exponential for 180 min. The killing activity was high in the first 30-60 min and then virtually ceased. The least phagocytosis and killing occurred in presence of heat-inactivated fetal calf serum (HFCS). These activities were 2-fold increased in presence of normal mouse serum (NMS) or heat-inactivated newborn calf serum (HNCS) and were highly stimulated in presence of immune mouse serum (IMS). IMS without complement was less efficient in enhancing phagocytosis and killing by macrophages. However when IMS or HNCS were deprived of specific antibodies their activity was remarkably reduced. When macrophages containing phagocytized bacteria were reincubated with different sera, multiplication of intracellular E. coli occurred with HFCS, NMS or antibody-deprived IMS or HNCS. In contrast, a significant decrease in the survival of intracellular bacteria was seen in presence of IMS, HNCS or complement-deprived IMS. The results indicated that specific bacterial antibodies play a major role in the phagocytic process and in the activation of killing mechanisms. However optimal macrophage activity resulted from the presence of both specific antibodies and complement.

Animals↗
PubMed1987

Presence of endotoxemia and its relationship to liver dysfunction in patients with typhoid fever.

Twenty-one patients with typhoid fever were studied to evaluate the presence of endotoxin in peripheral blood and its relationship to the incidence and features of hepatic dysfunction which may occur during this disease. The limulus test for endotoxin was positive in the plasma samples of all patients prior to treatment. Liver dysfunction, as assessed by fasting and postprandial serum bile acid levels and by standard biochemical tests, occurred in 90% of patients. In seven, the injury was purely cholestatic (elevation of postprandial serum bile acid levels, alone); in 12, it was of mixed cholestatic-hepatocellular type (elevation of both serum bile acids and aminotransferase levels). After recovering, the limulus test was negative and liver function tests returned to normal values in all patients. The results demonstrate that endotoxemia is present in patients with typhoid fever. In addition, since endotoxin can impair bile secretion, our results suggest that endotoxin may have a pathogenetic role in the development of liver injury during typhoid fever.

Adolescent↗
PubMed1987

Effect of endotoxin tolerance on drug hepatotoxicity: amelioration of taurolithocholate cholestasis in the perfused rat liver.

Induction of endotoxin tolerance may cause resistance not only to endotoxin itself but also to the hepatotoxic effects of other membrane-active agents. To further study this effect, we tested whether endotoxin tolerance could ameliorate the adverse effects of taurolithocholate (TLCA) which causes cholestasis by altering liver plasma membrane organization. Isolated perfused rat livers from endotoxin-tolerant rats had a lower basal bile flow than control livers. However, a bolus addition of TLCA at 3 X 10(-5) or 5 X 10(-5) M in the perfusate caused a marked and prolonged decrease of bile flow in controls, but only a transient and significantly less pronounced diminution of bile flow in endotoxin-tolerant livers. Likewise, TLCA caused a significantly lower alteration of hepatocyte membrane permeability, as measured by sucrose permeability studies, in endotoxin-tolerant livers than in controls. Analysis of bile acid composition of bile from endotoxin-tolerant livers demonstrated that they excreted greater amounts of total bile acids, in particular TLCA and taurocholate, than controls. These results demonstrated a protective effect of endotoxin-tolerance against TLCA toxicity which may result from an altered interaction of TLCA with liver membranes and an increased clearance of TLCA.

Animals↗
PubMed1987

Effects of lipid A content, hydrocortisone and polymyxin B on endotoxin-induced decreases in in vivo drug metabolism.

Using hexobarbital sleeping and zoxazolamine paralysis time as indices of in vivo hepatic drug metabolism, the effects of endotoxin on drug action appear to be time- and dose-dependent and the lipid A moiety of endotoxin appears to be responsible for its inhibitory effects. These studies have also demonstrated that polymyxin B can ameliorate the adverse effects of endotoxin on drug metabolism. Since hydrocortisone protects mice from endotoxin lethality, but does not alter the prolongation of hexobarbital sleeping time caused by endotoxin, it is possible to separate the lethal effects of endotoxin from its effects on drug metabolism.

Animals↗
PubMed1986

Influence of tauroursodeoxycholic and taurodeoxycholic acids on hepatic metabolism and biliary secretion of phosphatidylcholine in the isolated rat liver.

Studies were carried out using an isolated rat liver system to define: the contribution of exogenous phosphatidylcholine (PC) to biliary phospholipid secretion; and its hepatic metabolism during perfusion of the livers with conjugated bile salts with different hydrophilic/hydrophobic properties. A tracer dose of sn-1-palmitoyl-sn-2-[14C]linoleoylPC was injected as a bolus into the recirculating liver perfusate, under constant infusion of 0.75 mumol/min of tauroursodeoxycholate or taurodeoxycholate. The effects on bile flow, biliary lipid secretion, 14C disappearance from the perfusate and its appearance in bile, as well as hepatic and biliary biotransformation were determined. With both the bile salts, about 40% of the [14C]PC was taken up by the liver from the perfusate over 100 min. During the same period less than 2% of the given radioactivity was secreted into bile. More than 95% of the 14C recovered in bile was located within the identical injected PC molecular species. The biliary secretion of labeled as well as unlabeled PC, however, was significantly higher in livers perfused with taurodeoxycholate than tauroursodeoxycholate, while the reverse was observed with respect to bile flow and total bile salt secretion. The exogenous PC underwent extensive hepatic metabolization which appeared to be influenced by the type of bile salt perfusing the liver. After 2 h perfusion, the liver radioactivity was found, in decreasing order, in PC, triacylglycerol, phosphatidylethanolamine and diacylglycerol. In addition, the specific activity of triacylglycerol was significantly higher in tauroursodeoxycholate than in taurodeoxycholate-perfused livers (P less than 0.025), while the reverse was true for the specific activity of hepatic PC (P less than 0.01). Because taurodeoxycholate and tauroursodeoxycholate showed opposite effects on both biliary lipid secretion and hepatic PC biotransformations, we conclude that the hepatic metabolism of glycerolipids is influenced by the physiochemical properties of bile salts.

Animals↗
PubMed1986

Prevention of the toxicity of erythromycin estolate in the perfused rat liver by endotoxin.

The possibility that endotoxin pretreatment could prevent the hepatotoxic effects of erythromycin estolate (EE) was investigated using the isolated perfused rat liver. The addition of E. coli endotoxin (25 micrograms/ml) to the perfusate, 30 min prior to EE administration at 150 or 200 microM, significantly ameliorated the decreases in bile and perfusate flow caused by either concentrations of the drug in control liver preparations. This phenomenon was also studied using liver isolated from rats pretreated in vivo with endotoxin for three days. In these preparations, EE at both concentrations did not alter bile flow and caused reductions of perfusate flow which were far less than those observed in untreated control livers. Furthermore, in livers from endotoxin-treated rats EE induced less reduction of bile acid excretion and, at 150 microM, it did not increase the bile to perfusate ratio of sucrose seen in control preparations after the drug, which may be an expression of altered hepatocytic membrane permeability. Since it is known that both endotoxin and EE interact with membranes, it is suggested that the "protective" effects of endotoxin may occur at the membrane level.

Animals↗