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Biomedical subjects

S Reggio

Publications and source records attributed to S Reggio.

14 recordsLinked to original sources

Effects of nedocromil sodium on the oxidative burst of polymorphonuclear leukocytes: comparison with salbutamol.

The effects of nedocromil sodium and of salbutamol on the generation of oxygen-derived free radicals in human polymorphonuclear leukocytes (PMNs) were compared in vitro by the luminol-amplified-chemiluminescence (LACL) assay induced by both particulate (Candida albicans) and soluble formyl-methionyl-leucyl-phenylalanine (fMLP) stimulants. Inhibitory dose-effect linear regressions were observed from 10(-3) to 10(-8) M for nedocromil and salbutamol after a 3' period of incubation with either C. albicans or fMLP. There was a linear regression with nedocromil sodium after 30' incubation, but desensitization was observed with salbutamol after this longer period of incubation. The generation of oxygen-derived free radicals was significantly greater for asthmatic patients than for normal subjects; therefore antiasthmatic drugs with this inhibitory activity could be an extra pharmacological benefit in the treatment of asthmatic patients.

Albuterol

Penetration of brodimoprim into human neutrophils and intracellular activity.

The entry of an antibiotic into phagocytes is a prerequisite for its intracellular bioactivity against susceptible facultative or obligatory intracellular microorganisms. Brodimoprim is a dimethoxybenzylpyrimidine that has recently entered into clinical use, and its uptake into and elimination from human polymorphonuclear neutrophils (PMNs), together with its effects on normal phagocytic and antimicrobial mechanisms, have been investigated. Brodimoprim uptake by PMNs was determined by a velocity-gradient centrifugation technique under various experimental conditions and was expressed as the ratio of the intracellular to the extracellular drug concentration (C/E) in comparison with the C/E of trimethoprim, which was used as a control drug. After incubation with 7.5 micrograms of brodimoprim per ml, PMNs accumulated brodimoprim (C/E, 74.43 +/- 12.35 at 30 min) more avidly than trimethoprim (C/E, 20.97 +/- 6.61 at 30 min). The cellular uptake of brodimoprim was not affected by temperature, 2,4-dinitrophenol, or potassium fluoride and was increased with an increase in the pH of the medium. It was reduced in formaldehyde-killed PMNs. The efflux of brodimoprim was very rapid (46% after 5 min). The liposolubility of brodimoprim was about three times that of trimethoprim, as was the uptake. Therefore, a possible passive transmembrane diffusion mechanism might be proposed. Brodimoprim did not decrease either phagocytosis or phagocyte-mediated bactericidal activity, nor did it affect oxidative burst activity, as investigated by luminol-amplified chemiluminescence. On the basis of the pharmacokinetic data for brodimoprim, the concentration of 7.5 micrograms/ml was chosen as the highest concentration attainable in serum by oral therapy, and at this concentration of brodimoprim, the amount of drug that penetrated into PMNs was able to maintain its antimicrobial activity without interfering with the functions of the PMNs.

Anti-Infective Agents

Equivalence of pharmacokinetic characteristics and bronchodilating effect between two combined formulations of nedocromil sodium and salbutamol: MDI and nebulizer solution.

The aim of this study was to determine the equivalence of single doses of two nedocromil sodium/salbutamol combined formulations, namely (a) metered dose inhaler (MDI) (nedocromil sodium 4 mg + salbutamol 0.2 mg) and (b) nebulizer solution (nedocromil sodium 10 mg + salbutamol 1.5 mg), in a group of healthy volunteers. The plasma pharmacokinetic profiles of nedocromil sodium and the pharmacodynamic effect (bronchodilation) of salbutamol were evaluated. Twelve healthy volunteers entered this randomized, cross-over study. All subjects completed the pharmacokinetic section of the study. Nine of them completed also the pharmacodynamic part of the study. After preliminary controls, treatments were administered on separate days and in random order. Blood samples were collected 5, 10, 20, 30, 45 min, 1, 1.5, 2, 3 and 4h after test medication. Specific airways resistance (sRaw) was measured 5, 10, 20, 30, 40, 50 and 60 min following test treatment administration. The pharmacokinetic profiles of nedocromil sodium were evaluated using the maximum plasma concentration (Cmax), the time to peak plasma concentration (tmax) and the area under the curve from 0 to infinity (AUCzero-->infinity), derived from the plasma concentration/time curves. The bronchodilating effect of the two test treatments were evaluated as sRaw percentage change at each time point, maximum sRaw percentage change (sRawMAX) and area under the curve (AUC) of sRaw percentage change plotted against the time of recording. The mean pharmacokinetic results for MDI and nebulizer solution were, respectively: Cmax = 7.59 ng.ml-1 +/- 4.99 and 9.64 ng.ml-1 +/- 5.22 (p = 0.36), tmax = 0.21 hour +/- 0.08 and 0.28 hour +/- 0.14 (p = 0.19), AUCzero-->infinity = 6.28 ng.ml-1.h +/- 2.91 and 12.91 ng.ml-1.h +/- 4.12 (p = 0.008), while the mean pharmacodynamic results were: sRawMAX = -37.91% +/- 13.77 and -39.69% +/- 9.69 (p = 0.69), AUC = -1465.5 delta %.h +/- 799.3 and -1683.4 delta %.h +/- 496.3 (p = 0.45). No statistically significant differences between treatments were found also for sRaw percentage change at each time point. The absorption of nedocromil sodium was proportional to the two administered nominal doses and similar to values obtained after administration of nedocromil sodium alone. The two combined formulations of nedocromil sodium and salbutamol produce an equivalent bronchodilating effect. These results confirm the pharmacological equivalence of the two products, whichever may be used according to specific therapeutic needs.

Administration, Intranasal

Correlation between reduction of surface hydrophobicity of S. aureus and the decrease in its adhesiveness induced by subinhibitory concentrations of brodimoprim.

Hydrophobic interactions are involved in the mechanism of adhesion of a variety of bacteria to host tissues. Bacterial attachment to human cells is modulated by a change in interfacial free energy and this is correlated with surface hydrophobicity of bacterial cells. In S. aureus (one ATCC25923+four clinical isolates) hydrophobicity before and after incubation with subinhibitory concentrations (sub-MICs) of brodimoprim (BMP), a dimethyoxypyrimidine recently entered clinical practice, was measured by sessile drop technique as the contact angle. BMP is a new molecule derived from trimethoprim by substitution of the OCH3 group in position 4 of the benzyl-ring with a bromine atom. Bacterial adhesiveness of the same S. aureus strains was measured under the same experimental conditions. BMP significantly decreased the surface hydrophobicity of S. aureus strains at one-half MIC and one-quarter MIC. At sub-MICs concentrations BMP also reduced the adhesiveness to human epithelial buccal cells but this effect was significant down to one-sixteenth MIC. The two phenomena are correlated and hydrophobicity is involved in bacterial adhesiveness but the molecular mechanisms for the two phenomena do not completely overlap, with adhesiveness the more complex and based on a system involving both the bacteria and the epithelial cells with their specific surface characteristics.

Bacterial Adhesion

Sub-inhibitory concentrations of brodimoprim inhibit adhesion of E. coli to human uroepithelial cells.

Bacterial adhesion to mucosal surfaces is a prerequisite for infection. Several antibiotics at sub-inhibitory concentrations (sub-MICs) have been shown to affect the adhesive ability of bacteria, usually decreasing adherence in vitro. The aim of the present study was to investigate the effect of brodimoprim, a broad-spectrum antibiotic, on E. Coli adhesiveness to uroepithelial cells. Sub-inhibitory concentrations of brodimoprim, up to 1/16 MIC, significantly reduced the percentage of adhesion of E. Coli to epithelial cells. At these concentrations, brodimoprim strongly diminished the adhesiveness of E. Coli, causing the growth of filamentous shapes lacking in pili and therefore unable to adhere to epithelial cells.

Bacterial Adhesion

Correlation between disc potency and zone size in temafloxacin activity in vitro.

A multi-test disc potency evaluation of a new fluoroquinolone, temafloxacin, has been prepared in order to evaluate the variation of the zone dimension with the disc antibiotic concentration. A direct correlation between these parameters has been demonstrated. All pathogens have been isolated in hospitalized patients.

4-Quinolones

Influence of subinhibitory concentrations of brodimoprim and trimethoprim on the adhesiveness, hydrophobicity, hemagglutination and motility of Escherichia coli.

In the present study the ability of subinhibitory concentrations (sub-MICs) of brodimoprim (a new 2,4-dimethoxybenzylpyrimidine) to interfere with some important aspects of bacterial cell function, such as surface hydrophobicity, fimbriation, motility and adhesiveness to mucosal cells, was investigated in comparison with those of trimethoprim. The inhibitory behavior of both diaminopyrimidines concerning hydrophobicity and hemagglutination (fimbriation) were essentially the same, while for adhesiveness and motility brodimoprim was more effective than trimethoprim. Diaminopyrimidines have high affinity for the bacterial enzyme dihydrofolate reductase, and this reduces the synthesis of essential purines and as a consequence of DNA and proteins. Our findings indicate that the synthesis and/or the expression of surface adhesins, which are proteins, was also affected by both brodimoprim and trimethoprim, the former being more active.

Animals

Influence of brodimoprim on polymorphonuclear leukocyte phagocytosis and oxidant radical production.

Antibiotics not only reach the site of infection, but also penetrate cyclically, during a treatment, into polymorphonuclear leukocytes (PMNs) and may influence their functions positively or negatively. With reference to these aspects, the influence of brodimoprim (BMP), a dimethoxybenzylpyrimidine recently entered into clinical use, on human PMN phagocytosis and oxidant radical production (chemiluminescence) was investigated. PMNs from healthy adult donors were incubated for 50 min in medium alone or in medium containing increasing concentrations (3.7, 7.5, 15, and 30 micrograms/ml) of BMP and trimethoprim (TMP). In unwashed PMNs, phagocytosis was not modified by BMP, but was significantly reduced by 30 micrograms/ml TMP; chemiluminescence was significantly reduced by 15 and 30 micrograms/ml BMP and by all concentrations of TMP. When PMNs were washed after incubation, phagocytosis was unaffected and chemiluminescence was significantly restored. BMP at therapeutic concentrations did not influence PMNs and was less toxic than TMP.

Anti-Bacterial Agents

[Acute effects of a new type of lipidic emulsion in critical patients].

A new type of 10% lipidic emulsion based on safflower oil and soya (Liposyn II, Abbott, Latina) characterised by a high linoleic/linolenic acid ratio was administered in random, double blind fashion with 10% Intralipid to 20 subjects submitted to major surgery of the digestive system. Dosage was 1.2 g/kg at an infusion rate of 2.6 ml/kg/h. In order to evidence possible in vivo inter-reactions between proteins of the acute post-aggressive phase and these emulsions, serial samples were used to measure haemogasanalytic parameters, plasma levels of triglycerides and serum levels of protein C-reactive and fourth complement factor. Both emulsions proved well tolerated and there was no evidence of general or administrative site reactions. The plasma levels of triglycerides underwent an increase during the test, with no significant differences between the two groups of patients. Notwithstanding the high serum levels of protein C-reactive of the subjects in question, there was no evidence of activation of the complement system nor alteration in haemogasanalytic parameters with the two lipidic emulsions adopted.

Aged

[Continuous intravenous infusion with patient-controlled anesthesia for postoperative analgesia in cesarean section: morphine versus buprenorphine].

A double blind comparison between morphine and buprenorphine was performed in 20 patients using a new demand and continuous infusion analgesic system to provide analgesia after cesarean section. The patients were randomized in two equal groups to receive either morphine 1 mg/h or buprenorphine 0.03 mg/h. The PCA system was set to deliver bolus of either morphine 1 mg or buprenorphine 0.03 mg, with a lockout interval of 10 and 15 min respectively. A loading dose of morphine 5 mg or buprenorphine 0.15 mg was given if necessary. The quality of analgesia, assessed by a visual analogue and a subjective scale was good with both drugs. No difference in side effects between the groups was observed. The mean potency ratio between buprenorphine and morphine was 32:1. Patients receiving buprenorphine showed a more prolonged analgesia and a significant improvement of sedation score.

Adult