PubMed Health⌕ Search

Biomedical subjects

G Piatti

Publications and source records attributed to G Piatti.

At least 37 records · Page 2Linked to original sources

Bacterial adhesion to respiratory mucosa and its modulation by antibiotics at sub-inhibitory concentrations.

Respiratory infections develop after contact and successive adhesion of micro-organisms to airway mucosa. In fact, the bacterial adhesins are able to interact with a 'lock and key' mechanism with the analogous structures on epithelial surfaces when permissive conditions occur. It was observed that antibiotics at subinhibitory concentrations (sub-MICs) can modify bacterial ability of adhesion to host cells, in various ways. Bacterial adhesion is generally inhibited by antibiotics that, at these concentrations, do not kill bacteria but can change the surface architecture of the micro-organisms.

Anti-Bacterial Agents↗

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↗

The use of monoclonal antibodies for studying the biological properties of Staphylococcus aureus endo-beta-N-acetylglucosaminidase.

Staphylococcus aureus endo-beta-N-acetylglucosaminidase (SaG) has been suggested to function as a virulence determinant which interferes with the host cellular immune response. To further characterize the biological properties of SaG, monoclonal antibodies (mAbs) were raised against purified SaG. Four IgG1 subclass mAbs were obtained, none of which reacted with the reduced, sodium dodecyl sulphate pretreated or boiled enzyme. The ability of the mAbs to react with the enzymes present in supernatants obtained from 197 S. aureus strains indicated that they recognized epitopes which are highly conserved; bacteriolytic enzymes produced by staphylococci other than S. aureus did not show any cross-reactivity. After pretreatment of SaG with mAbs (mAb-SaG molar ratios varying from 1 to 20), it was shown that all selected mAbs caused, at a mAb:SaG molar ratio of 10, a 90% inhibition of SaG bacteriolytic activity and a statistically significant reduction of its ability to interfere with phagocytosis by human polymorphonuclear leukocytes. All selected mAbs reacted with several commercially available exo-beta-N-acetylglucosaminidases; mAb C1/10-11 also reacted with chicken and turkey egg muramidases and, at a mAb:SaG molar ratio of 10, inhibited their bacteriolytic activity by 97%. This suggests that one or more epitopes present in the above exo-glucosaminidases and muramidases share some degree of homology with others present in SaG.

Acetylglucosaminidase↗

Sub-lethal concentrations of clarithromycin interfere with the expression of Staphylococcus aureus adhesiveness to human cells.

It has been known for some time that some antibiotics, generally at sub-lethal concentrations, are able to alter the morphology and the shape of bacteria. However, more subtle molecular alterations can also be present, such as disorganization of bacterial surface architecture, which leads to changes in the surface electrical charge that can influence the forces of attraction or repulsion responsible for interaction of bacterial surfaces with environmental surfaces. Bacterial adhesion to epithelial cells is a phenomenon regulated by these mechanisms. Clarithromycin, a new macrolide, at sub-inhibitory concentrations from 1/2 to 1/16 of the MIC, that is to say, from 0.12 to 0.015 microgram/ml, significantly reduces adhesion of Staphylococcus aureus to human buccal epithelial cells. Clarithromycin, as other antibiotics that interfere with the bacterial protein synthesis, should also be able to disturb the synthesis of adhesins. These are ligand molecules located on the surface of bacteria, and thus reduce the ability of bacteria to bind specifically to complementary molecules on the surfaces of epithelial cells which is necessary for host colonization.

Bacterial Adhesion↗

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↗

Sub-minimum inhibitory concentrations of ceftibuten reduce adherence of Escherichia coli to human cells and induces formation of long filaments.

The minimal inhibitory concentrations (MICs) of an antibiotic are present for only a certain period of time, after which they become sub-inhibitory concentrations (sub-MICs). These sub-MICs are still active because they can interfere with the mechanism of bacterial adhesion, which is the first step in the sequence of events leading to infection. The purpose of the present study was to investigate the effects of sub-MICs of ceftibuten, a new third-generation cephalosporin, on the adhesion of Escherichia coli (E. coli) to human buccal cells. The degree of inhibition was maximal at 1/2 MIC and then gradually returned toward to the control values at 1/128 the MIC. The differences were statistically significant from 1/2 to 1/32 MIC. Since the MIC was 0.5 micrograms/ml, concentrations from 0.25 to 0.015 micrograms/ml significantly reduce bacterial adhesion. Ceftibuten also caused marked elongation of E. coli. These findings could help to explain the efficacy showed by ceftibuten in the treatment of respiratory and urinary tract infections when administered once daily.

Bacterial Adhesion↗

Rapid methods for identification of Staphylococcus aureus when both human and animal staphylococci are tested: comparison with a new immunoenzymatic assay.

A new immunoenzymatic assay (IEA) for the identification of Staphylococcus aureus strains of both human and animal origin was compared with rapid commercial kits. The sensitivities and specificities of the commercial kits varied from 90.2 to 96% and 90.8 to 93.7%, respectively. The IEA did not give any false-negative or false-positive results, while commercial kits gave high percentages of false-positive results among clumping factor-positive non-S. aureus strains. The IEA is particularly useful for isolates for which identification is doubtful, for large-scale epidemiological studies, and for identifying isolates from animals as S. aureus.

Animals↗

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↗

Delaying effects of dietary eicosapentaenoic-docosahexaenoic acids on development of "fatty streaks" in hypercholesterolaemic rabbits. A morphological study by scanning electron microscopy.

Besides causing functional and clinical damage, hypercholesterolaemia also causes morphological alterations of vascular endothelium. Rabbits fed a diet with 1% cholesterol for 4, 6, or 8 weeks are experimental models for hypercholesterolaemia, with pathological structural changes in vascular luminal surface. Morphological investigation by scanning electron microscopy was performed to reveal the tridimensional growth of these lesions and the differences in this growth induced by concomitant dietary assimilation of fish-oil (2 g/day). Macroscopic reduction in fatty-streak production was clearly seen in rabbits fed fish-oil. Scanning electron microscopy confirmed that the area of intimal lesions was only 21 +/- 6% in this group, while in the group fed cholesterol without fish oil, the lesioned area attained 76 +/- 5%. Endothelial swelling was less marked, probably due to reduced intracellular lipid accumulation into the foam cells. Adherent macrophages were also fewer. The differences might be correlated with protection against the lipoproteins' atherogenic effects and to hemorheological benefits produced by the Omega-3 fatty acid (85%) present in fish-oil.

Animals↗

Inhibition of bacterial adhesion by sub-inhibitory concentrations: brodimoprim vs trimethoprim.

There is accumulating evidence that sub-inhibitory concentrations (sub-MICs) of many antibiotics are not without effect on bacteria and even though they do not kill bacteria, they are still able to interfere with some important aspects of bacterial cell function. The aim of the present study was to investigate the effect of sub-MICs of brodimoprim and trimethoprim on Escherichia coli and Staphylococcus aureus adhesiveness to human mucosal cells. Sub-MICs of brodimoprim down to 1/32 MIC (0.03 microgram/ml) significantly reduced the E. coli adhesion to human buccal epithelial cells and this inhibition was significantly higher than the corresponding pattern for trimethoprim. Adhesion of S. aureus was significantly reduced down to 1/16 MIC for both brodimoprim and trimethoprim but no significant differences resulted between the two patterns. 2,4 Diaminopyrimidines and related structures have a high affinity for the enzyme dihydrofolate reductase and this causes a reduction in the synthesis of essential purines, thus reducing also DNA and the synthesis or expression of surface adhesins.

Bacterial Adhesion↗

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↗

Influence of enoxacin sub-MICs on the adherence of Staphylococcus aureus and Escherichia coli to human buccal and urinary epithelial cells.

Bacterial adhesion is the first step in the sequence of events leading to infection. It has been observed that subinhibitory concentrations of antibiotics can interfere with the mechanism of bacterial adhesion. The purpose of the present study was to investigate the capacity of sub-MICs of enoxacin, a new 4-quinolone with 6-fluoro and 7-piperazino substituents, to interfere with the adhesiveness of Staphylococcus aureus and Escherichia coli to human buccal cells and of E. coli to urinary epithelial cells. A significant decrease was observed with 1/2-1/64 the MIC for the adhesion of S. aureus to buccal cells. Inhibition of adhesion was also observed for E. coli strains, but in this case a marked decrease was observed across the range from 1/2 to 1/128 the MIC for urinary cells, and from 1/2 to 1/256 the MIC for buccal cells. Enoxacin also caused elongation of E. coli.

Bacterial Adhesion↗

The influence of seaprose on erythromycin penetration into bronchial mucus in bronchopulmonary infections.

In bronchopulmonary infections antibiotics can be combined with other drugs, called mucoactive drugs, that act to reduce the abnormal viscoelasticity of the mucus enabling a deeper penetration of more antibiotic into the mucus. Seaprose is a protease that interacts with the polymeric fibrillar structure of the bronchial mucus to shorten the long chains of mucoproteins, DNA and other macromolecules, thus reducing the viscosity of the mucus. In order to assess whether the combination of seaprose (60 mg/8 h) plus erythromycin (500 mg/8 h) allows higher antibiotic levels in sputum than erythromycin (500 mg/8 h) plus placebo, the pharmacokinetic behaviour in sputum and in blood of these two treatments was investigated in a double-blind study in two groups of twenty patients each with bronchopulmonary infections. Serum and sputum levels were determined for each patient at the first and seventh day of the two drug regimens. Statistically significant differences for peak, AUC and MRT, were observed for erythromycin between the first and last dose in the group of patients treated with seaprose plus erythromycin; moreover significant differences for these parameters were observed between the two groups. These findings indicate the presence of a pharmacokinetic synergism between seaprose and erythromycin which allows erythromycin to penetrate bronchial secretion more easily and in higher amounts, performing a sterilizing action with therapeutic advantages.

Bronchial Diseases↗

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↗

Effects of subinhibitory concentrations of ciclopirox on the adherence of Candida albicans to human buccal and vaginal epithelial cells.

At present, only a limited number of studies of the effects of sub-inhibitory antifungal agents on the adherence of Candida to epithelial (buccal and vaginal) host cells are available. The adherence of Candida albicans to the epithelial cell surface is accepted as an important first step in persistent colonization and in the following symptomatic or asymptomatic infection of mucosal surface. Ciclopirox (ciclopiroxolamine, CAS 29342-05-0) is a substituted pyridone antimycotic drug, unrelated to the imidazole derivatives and its topical application ensures maximum local bioavailability. The present study was done to investigate the effects of sub-inhibitory concentrations of ciclopirox on the adherence of Candida albicans to human buccal and vaginal epithelial cells. The findings on the adherence of different strains of Candida indicate that the drug caused a significant reduction in the mean number of Candida adhering to both buccal and vaginal cells. This reduction was maximal at concentration of 1/2 MIC and still significant at 1/4, 1/8, 1/16 MIC, but with progressive return to mean control values at 1/32 MIC. Ciclopirox acts on fungi by inhibiting the intracellular uptake of essential substrates and ions and this probably acts on the Candida ability to express its adherence mechanisms.

Antifungal Agents↗

Clinical use of GM-CSF in autologous bone marrow transplantation.

Over the last decade, the key role of specific glycoproteins (hematopoietic growth factors) in the proliferation and maturation of hematopoietic cells (in conjunction with some of their particular functional activities) has been demonstrated through in vitro and in vivo studies. These glycoproteins have been evaluated for their potential application in reducing the duration of myelosuppression following conventional chemotherapy and autologous bone marrow transplantation. Preliminary results using granulocyte-macrophage colony-stimulating factor to restore neutrophil competence seem to be encouraging.

Agranulocytosis↗

Idarubicin in combination with intermediate-dose cytarabine in the treatment of refractory or relapsed acute leukemias.

13 patients with refractory or relapsed acute lymphoblastic leukemia (ALL) and 7 patients with acute myeloid leukemia (AML) were treated with a regimen that included idarubicin 12 mg/m2 intravenously daily for 3 d plus cytarabine 2 g/m2 by infusion over 3 hours daily for 3 d. There were 10 remissions (ALL:7; AML:3) in the 15 relapsed patients and 4 (ALL:3) in the 5 patients with primary refractory disease. Severe myelosuppression was observed in all patients. Toxicity of this regimen caused nausea and vomiting, stomatitis, infections and/or liver enzymes increase. Cardiac toxicity was not observed. 2 patients died in aplasia of Gram-negative septicemia and brain hemorrhage. In conclusion, the combination of idarubicin and intermediate-dose cytarabine (IDARA-C) seems to be highly effective and sufficiently well-tolerated for the treatment of refractory and relapsed acute leukemias.

Adolescent↗