Biomedical subjects

M Dal Sasso

Publications and source records attributed to M Dal Sasso.

32 records · Page 2Linked to original sources

PubMed1995

Neltenexine: morphological investigation of protection against elastase-induced emphysema in rats.

The instillation of elastase into airways is a widely adopted experimental method to quickly produce emphysematous lesions that mimic human disease anatomically and physiologically. Experiments were undertaken to determine whether of not neltenexine, a new drug active on surfactant production, would diminish the severity of this disease. Anaesthetized rats were instilled tracheally with porcine pancreatic elastase (46 U/mg) dissolved in saline, in a single instillation of 0.33 mg/100 microliters. Neltenexine was administered in one experiment at the dose of 25 mg/kg i.p. daily for 30 days. In a second test, neltenexine was given at the same dose six days before the elastase instillation and then by the same schedule as in the first experiment; this was done in search of a possible preventive action. At the end of the treatment, lungs were removed and fixed, and slices were dehydrated, critically point dried, coated with gold and observed by scanning electron microscopy (SEM). Rats that were both pretreated and treated with neltenexine showed a significant reduction in the alveolar deformation induced by elastase. There were no differences between pretreated and treated animals. These experimental findings suggest that neltenexine might prove to be useful for preventing pulmonary emphysema. Biochemical studies in man are needed to confirm the clinical application of neltenexine.

Ambroxol↗

PubMed1995

Inhibition of Candida albicans adhesiveness to human buccal and vaginal cells by sub-inhibitory concentrations of rilopirox.

Candida albicans is an opportunistic dimorphic pathogenic yeast which is present on the human mucosal epithelial cell surface. Its adhesion is considered to be an important first step in colonization and in the subsequent symptomatic or asymptomatic infection of buccal or vaginal mucosa. Because the ability to adhere is an important element of the pathogenicity of Candida we investigated in this study the compared effects of sub-inhibitory concentrations (sub-MICs) of rilopirox (CAS 104153-37-9) with those of ciclopirox olamine (CAS 41621-49-2) in inhibiting Candida adhesion to human buccal (BEC) and vaginal cells (VEC). Rilopirox is a new hydroxypyridone antimycotic agent with strong activity, especially against Candida albicans. There was a significant reduction in the mean number of Candida adhering to both buccal and vaginal cells with up to 1/8 MIC rilopirox for buccal and 1/16 MIC for vaginal cells, while for ciclopirox olamine reduction was significant up to 1/16 MIC for buccal and 1/8 MIC for vaginal cells. There were no significant differences in the dose-effect curves for BEC and VEC with either rilopirox and ciclopirox olamine, but on a molar basis, rilopirox was more active than ciclopirox olamine. The present in-vitro results support the developmental concept of an oropharyngeal and vaginal preparation of rilopirox. It can be expected that even sub-inhibitory concentrations of rilopirox exert an important additional effect in the treatment of oral and vaginal candidosis by impairing the pathogenic adhesion process of the fungus.

Antifungal Agents↗

PubMed1994

Restoration of polymorphonuclear leukocyte function in elderly subjects by thymomodulin.

Senescence is a specific physiological evolution of human beings associated with a reduction in the functionality of several apparatuses, including the immune system. Thymomodulin (TMD) contains thymus polypeptides (< 10,000 D) and it has been used in a variety of disorders associated with defective immunological functions. The aim of this study was to investigate the effect on polymorphonuclear leukocyte (PMNs) phagocytosis and oxidative burst of a 6-week treatment with 160 mg/day TMD orally in elderly subjects (85.5 +/- 9.7 years). Elderly subjects have impaired PMN phagocytosis and the following release of oxidant radicals. Treatment with TMD for 6 weeks had a restoring effect; phagocytosis and the phagocytic index were significantly improved, with increases of 132.6% and 112.5%. These findings indicate that TMD might be given to enhance the immunodefenses of immunocompromised elderly subjects. Luminol-dependent chemiluminescence was increased by 15.6%, which was not significant, indicating a different response between phagocytosis and release of oxidant radicals.

Aged↗

PubMed1993

Antinociceptive activity of salmon calcitonin: electrophysiological correlates in a rat chronic pain model.

Experimental and clinical evidence testifies to an antinociceptive action of salmon calcitonin (sCT), administered in different ways, on the central nervous system. These studies were performed almost exclusively in acute pain models. The purpose of the present study was to investigate the effects of sCT, injected directly into the lateral cerebral ventriculi, on the firing of single nociceptive thalamic neurons, detected by electrophysiological techniques in an experimental model of prolonged or chronic pain, such as rats rendered arthritic by injection of Freund's adjuvant into the left hindfoot. The noxious test stimuli used were either extension or flexion of the ankle or mild lateral pressure on the heel. With increasing doses of sCT (5, 10, 20, 40 micrograms, 5 microliters/i.c.v.) it was possible to observe correspondingly increasing inhibitory and long-lasting effects on the evoked firing, with a significant dose-effect relationship. In agreement with electrophysiological findings, preliminary data, obtained with a patch clamp technique, on depression of calcium fluxes through neuronal membrane, induced by sCT, oriented the attention to a direct action of sCT on CNS.

Analgesics↗

PubMed1993

Thymomodulin stimulates phagocytosis in vitro by rat macrophages and human polymorphonuclear cells.

Activation of non-specific host defenses can increase resistance to infection in patients and especially those with reduced immune response. Thymomodulin is a calf thymic derivative containing low molecular weight peptides, which exerts immunomodulating activity probably through an enhancement of lymphocyte functions. To explore this possibility, rat macrophages (MP) and human polymorphonuclear (HPMN) cells were incubated in vitro with 100, 200, 400 micrograms/ml of thymomodulin at 37 degrees C for 60 min and their phagocytic activity was investigated. The number of phagocytosing cells was significantly increased following increasing concentrations of thymomodulin and the percentage of phagocytosis was increased more for human PMNs in comparison with rat MP, while the values of the phagocytic index were not modified after challenge with thymomodulin both for MPs and HPMNs.

Animals↗

PubMed1993

Antitussive effect of oxatomide on citric acid-induced cough in conscious guinea pig. Preliminary communication.

Oxatomide (CAS 60607-34-3), a diphenylmethyl-piperazine benzimidazole derivative is a new oral antiallergic drug useful in asthma in preventing allergic attacks. Using the model of citric acid-induced coughing in the unanesthetized, unrestrained guinea pig the antitussive effect of oxatomide was investigated. The animals were treated with logarithmically increasing doses of oxatomide (0.5, 1, 2 mg/kg, suspended in 0.5 ml of polyethylene glycol 200 + 0.5 ml of saline) and with the vehicle alone administered intraperitoneally (1 ml) 45 min before the challenge. Oxatomide reduced the number of coughs during the 3 min of challenge, lengthened the time of onset and reduced the number of coughs after cessation of the challenge significantly and a linear dose-effect regression was observed.

Animals↗

PubMed1992

The effects of calcitonin nasal preparations and their excipients on mucociliary clearance in an ex-vivo frog palate test.

The topical tolerability of the commercial preparation of 1-7 Asu-eel and salmon calcitonin with 2% ammonium glycyrrhyzinate and 0.01% benzalkonium chloride, respectively, and of their excipients mixture in solution with increasing concentrations of ammonium glycyrrhyzinate and benzalkonium chloride, respectively, were assessed by investigating their effects on the mucociliary transport velocity in the ex-vivo frog palate preparation. This preparation provides an integrated biological model readily usable in the laboratory which closely resembles human nasal mucociliary clearance mechanism and can be used for rapid testing and toxicity of agents proposed for topical administration in the upper and lower airways. Frog-Ringer control, 1-7 Asu-eel and salmon calcitonin commercial spray preparations and the excipients plus 2% ammonium glycyrrhyzinate and plus 0.01% benzalkonium chloride did not modify significantly the mucociliary transport velocity, confirming their very good tolerability on ciliated epithelium. Higher concentrations of ammonium glycyrrhyzinate (10 and 20%) caused significant slowing, on average -32 and -55%, respectively. Higher concentrations of benzalkonium chloride (0.05 and 0.1%) also caused significant slowing, on average, -43.5 and -87%, respectively.

Administration, Intranasal↗

PubMedDate not supplied

Influence of sub-minimum inhibitory concentrations of cefodizime on the phagocytosis, intracellular killing and oxidative bursts of human polymorphonuclear leukocytes.

It is generally recognized that sub-minimum inhibitory concentrations (sub-MICs) of antibiotics are still capable of interfering with some bacterial virulence parameters, thus facilitating host neutrophilic defenses such as phagocytosis, killing and oxidative bursts. This study investigated the interaction of Escherichia coli with these neutrophilic functions after pretreatment with various sub-MICs of cefodizime. E. coli exposed to 1/2 to 1/8 MICs of cefodizime showed the extensive production of long and very long filaments that interfere with the precise measurement of phagocytic and killing parameters. Our analysis was consequently extended to the activity of 1/16 to 1/64 MICs. The interesting finding was that, although phagocytosis was unaffected, killing was significantly increased in one strain at 1/16 MIC and in another at 1/32 MIC while in the last strain it was unaffected. Oxidative bursts were not modified by any of the sub-MICs. The knowledge that these sub-MICs are still effective in increasing bacteria killing, correlated with the pharmacokinetic curve of a common single dose of cefodizime 1 g i.m., showed that the killing effects of sub-MICs may last for as long as 12 h after the activity of the MIC value. This integrated information extends our knowledge of the ultimate efficacy of an antibiotic and provides further information for optimizing scheduling.

Adult↗

PubMedDate not supplied

Bacterial adhesiveness: effects of the SH metabolite of erdosteine (mucoactive drug) plus clarithromycin versus clarithromycin alone.

After metabolization, erdosteine (a mucoactive drug) produces an active metabolite (Met I) with an SH group that is capable of opening disulphide bonds, including those of pilin, a protein of bacterial fimbriae. This induces stereochemical conformational changes that interfere with the binding of bacterial adhesins (fimbriae) to receptors on eukaryotic cells. At subinhibitory concentrations, the macrolide clarithromycin inhibits the expression of adhesins on bacterial cell surfaces. The addition of 5 and 10 microg/ml of Met I to 1/8, 1/16 and 1/32 MIC of clarithromycin potentiated the inhibition of Staphylococcus aureus adhesiveness to human mucosal cells in comparison with the antibiotic alone. This finding opens up a new possibility of interfering with bacterial adhesiveness and its resulting pathogenicity not only by using antibiotics but also by means of their combination with agents devoid of antibacterial activity.

Anti-Bacterial Agents↗

PubMedDate not supplied

The in vitro effects of ceftibuten on the host defense mechanism.

The in vitro effects of ceftibuten on human polymorphonuclear leukocyte (PMN) chemotaxis, phagocytosis and chemiluminescence were investigated. PMN from healthy adult donors were incubated for 1 h in medium alone or in medium containing increasing concentrations of ceftibuten (4, 8 and 40 times the MIC for Escherichia coli). Up to 40 MIC ceftibuten did not significantly interfere with the function of PMN.

Adult↗

PubMedDate not supplied

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↗

PubMedDate not supplied

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↗

PubMedDate not supplied

Experimental evidences for a role of subinhibitory concentrations of rilopirox, nystatin and fluconazole on adherence of Candida spp. to vaginal epithelial cells.

Candidiasis is frequently localized in the mucosal epithelium which covers the vaginal and oral cavity. The pathogenicity of Candida is correlated with its ability to adhere to epithelial cells and this is the resultant of both fungal and host cell properties and their physicochemical interactions. This study was performed to investigate the ability of subinhibitory concentrations (sub-MICs) of rilopirox, a new antimycotic drug, to interfere with the adhesion of Candida albicans, Candida tropicalis and Candida glabrata to human vaginal cells, in comparison with sub-MICs of nystatin and fluconazole. The three drugs are more active on C. albicans, followed by C. tropicalis and, last, C. glabrata, on which fluconazole was inactive (MIC > 24 micrograms/ml). Rilopirox, nystatin and fluconazole have different mechanisms of action, and different molecular weights, so a comparative analysis of data was performed by means of their sub-MICs. On this basis the order of activity was nystatin [symbol: see text] rilopirox > fluconazole. These findings can be of use for optimizing also the posologic design by regarding sub-MICs which are still active in reducing the adhesiveness of Candida to cells of the vaginal mucosa.

Anti-Bacterial Agents↗

PubMedDate not supplied

Effects of rokitamycin on phagocytosis and release of oxidant radicals of human polymorphonuclear leukocytes.

A rational choice of an antimicrobial agent must take into account not only the activity against the specific pathogen but also any possible negative or positive effects on the host defense system. Rokitamycin (RKM) is an orally active 16-membered-ring macrolide; there are no reports of specific investigations of these activities in the literature. Polymorphonuclear neutrophils (PMNs) from healthy adult donors were incubated in medium alone or in medium containing increasing concentrations (1, 10, 50, 100 micrograms/ml) of RKM. In unwashed PMNs phagocytosis was unaffected by RKM, while luminol-amplified chemiluminescence (LACL) was significantly reduced by 50 and 100 micrograms/ml. When PMNs were washed after incubation phagocytosis was not modified but LACL was significantly restored. These characteristics of RKM were similar to those of roxithromycin and can be put in correlation with the cellular/extracellular ratio (30.5 for PMNs and 120 for macrophages) that was similar to that of roxithromycin but higher than of other macrolides. The molecular mechanisms by which high concentrations of these two macrolides produce such an impairment of LACL are still unclear. RKM has no unwanted effects on PMNs because the serum concentrations that can be obtained with the highest doses administered to man are lower than the concentrations which did not affect PMN functions in our study.

Adult↗