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Biomedical subjects

M I Brenciaglia

Publications and source records attributed to M I Brenciaglia.

At least 19 recordsLinked to original sources

Synthesis and in vitro selective anti-Helicobacter pylori activity of pyrazoline derivatives.

In order to develop new anti-Helicobacter pylori agents, a series of N1-substituted 3,5-diphenyl pyrazolines P1-P13 was prepared and evaluated for their antibacterial activity. All synthesized compounds showed little or no activity against different species of Gram-positive and Gram-negative bacteria of clinical relevance and against various strains of pathogenic fungi. The same derivatives exhibited a significant degree of activity against a range of H. pylori strains, including those resistant to the reference compound metronidazole. Among the prepared compounds those with an N1-acetyl group and a 4-methoxy substituent in the 5-phenyl ring showed the best activity against H. pylori metronidazole resistant strains in the 1-4 microg/mL MIC range.

Anti-Bacterial Agents↗

Anti-Helicobacter pylori agents endowed with H2-antagonist properties.

New anti-Helicobacter pylori (H. pylori) agents endowed with H2-antagonists properties were obtained by combining the lamtidine derived pharmacophoric group with the antibiotic calvatic acid. All the compounds were tested for their irreversible H2-antagonist properties and for their ability to inhibit 20 H. pylori strains, two of them metronidazole resistant. The most active derivative (compound 4) displayed antimicrobial activity similar to metronidazole.

Animals↗

Helicobacter pylori: ureA, cagA and vacA expression during conversion to the coccoid form.

As viability of coccoid forms of Helicobacter pylori can only be verified by demonstrating the integrity of the DNA and active protein synthesis, we analysed the expression of ureA, cagA, vacA genes after prolonged incubation in a liquid medium. Exponentially growing and ageing phase cultures were used. Our results showed that, although the coccoid forms had decreased DNA and RNA levels after 31 days, they were not degraded and still expressed the urease, cytotoxic island and vacuolating toxin genes. Coccoid forms are therefore viable and may act as a transmissible agent that plays a crucial role in disease relapses after antibiotic therapy.

Antigens, Bacterial↗

Helicobacter pylori: cultivability and antibiotic susceptibility of coccoid forms.

Helicobacter pylori is an actively dividing helical bacterium that changes to coccoid morphology as the culture ages. It has been suggested that the coccoid forms may be involved in transmission of infection and in relapses following antimicrobial therapy. The aim of this investigation was to determine the survival and susceptibility of the coccoid forms to amoxycillin, erythromycin, gentamicin and metronidazole. Colony counts and microscopic examination were performed after 1-4 weeks of culture. At 2 and 4 weeks, identical cultures were treated with the antibiotics for 24 h. Our results showed that 4-week cultures of coccoid forms were cultivable after antibiotic treatment.

Amoxicillin↗

Activity of amoxicillin, metronidazole, bismuth salicylate and six aminoglycosides against Helicobacter pylori.

The in vitro activity of metronidazole, amoxicillin, bismuth salicylate and some aminoglycosides, such as ribostamycin, gentamicin, amikacin, tobramycin, streptomycin and netilmicin was evaluated against 60 clinical isolates of Helicobacter pylori using the agar dilution technique. All 60 strains were susceptible to amoxicillin, with minimum concentrations able to inhibit 50% (MIC 50) and 90% (MIC 90) of strains equal to 0.031 microgram/ml and 0.25 microgram/ml, respectively. Of the aminoglycosides, ribostamycin, streptomycin and amikacin had a little lower activity (MIC 50 of 2 micrograms/ml, MIC 90 of 4-8 micrograms/ml) than gentamicin, tobramycin and netilmicin, with MIC 50s of 0.125 microgram/ml and MIC 90s of 0.25 microgram/ml. Metronidazole was effective against the majority of the strains, but we found ten resistant strains. Finally, bismuth salicylate showed only slight antibacterial activity.

Aminoglycosides↗

Inhibitory and bactericidal activity of rokitamycin against Helicobacter pylori and morphological alterations.

Rokitamycin is a macrolide antibiotic, recently entered into clinical use. Its in vitro activity and kill kinetics against Helicobater pylori have been evaluated at 1 x the minimum inhibitory concentration (MIC), 2 x MIC and 4 x MIC at 2, 4, 8, 24 hours and compared with those of clarithromycin, erythromycin and amoxicillin. Morphological changes in H. pylori induced by rokitamycin incubation at these MICs and times were also investigated by scanning electron microscopy. All the antibiotics tested had good inhibitory activity against H. pylori, a slow growing microorganism. The order of MIC activity was clarithromycin > amoxicillin > rokitamycin > erythromycin. Rokitamycin killed more rapidly than the other antibiotics, in fact H. pylori strains were totally killed at 8 h (2 x MIC) and 4 h (4 x MIC) and after only 2 h incubation all concentrations greatly decreased the CFU/ml. These effects were also confirmed by the rapid appearance of surface and morphological alterations (focal blebs, constrictions, rounded forms) in the normal structure of H. pylori observed by scanning electron microscopy. Clinical studies should be conducted to investigate the in vivo activity of rokitamycin, as an agent to be used in the combination therapies against H. pylori.

Amoxicillin↗

Modification of Pseudomonas aeruginosa virulence factors by sub-inhibitory concentrations of antibiotics.

This study's objectives were to evaluate the effects of subminimum inhibitory concentrations (MICs) of tobramycin, gentamicin, netilmicin, streptomycin, ciprofloxacin, cefotaxime and piperacillin on proteinase production, alginate and siderophore synthesis by two strains of Pseudomonas aeruginosa. One of these strains, of recent clinical isolation, was mucoid. In fact it is well known that mucoid strains are more resistant than non-mucoid; there is, moreover, evidence that in cystic fibrotic lungs the non-mucoid P. aeruginosa are invariably replaced by mucoid variants. Our results show that subinhibitory concentrations of beta-lactams and quinolones significantly reduced the amount of alginate. Protease production was affected by all antibiotics tested.

Alginates↗

Adherence of Pseudomonas aeruginosa elastase deficient mutant.

Pseudomonas aeruginosa produces several extracellular substances such as enzymes and toxins which seem to contribute to its pathogenicity. In particular, alkaline protease and elastase production seems to affect bacterial adherence. Aim of this study was to isolate an elastase deficient mutant of P. aeruginosa and to demonstrate a possible correlation between enzyme production and adherence to WEHI cells. Mutant strain showed a significant reduction of elastase and protease alkaline activity, as the decrease of absorbance values demonstrate. Furthermore the adherence to WEHI cells of mutant strain was strongly reduced with respect to the wild strain. Our results prove that proteolytic enzymes play an important role in adherence, probably modifying the cell surfaces and so enhancing adherence.

Bacterial Adhesion↗

Role of alkaline protease and elastase in the adherence of Pseudomonas aeruginosa to WEHI cells.

Recent clinical isolates were tested for production of some extracellular factors such as alkaline protease and elastase. They were also assayed for adhesiveness to WEHI cells. It is well known that extracellular production of substances other than toxins is related to virulence and may increase adherence. The present investigation aimed to evaluate the role of extracellular proteins in adherence. Alkaline protease production was assayed using a test performed with casein as substrate while elastase activity was investigated with the elastin-congored method. Our results demonstrated that P. aeruginosa strains which are good alkaline protease and elastase producers adher better than those showing no or low protease and elastase activity.

Bacterial Adhesion↗

The influence of antifungal drugs on adherence of Candida albicans to buccal epithelial cells.

The adherence of two strains of Candida albicans serotype A to human epithelial cells was measured after exposure to different concentrations of amphotericin B, 5-fluorocytosine, nystatin, miconazole and ketoconazole. Germ-tube formation after different exposure times to the antifungal drugs as a preliminary test was carried out. Pretreatment of blastospores with minimum inhibitory concentrations (MIC) and sub-MIC (1/2 and 1/4 of MIC values) for 3 and 72 h did not affect adherence for all drugs tested except amphotericin B. This antimycotic agent reduces significantly the adherence either after 3 or 72 h exposure time. The other antifungal drugs interfere with adherence only after 72 h and at the highest concentrations tested, above MIC values. The decrease in adherence by antifungal drugs suggests that some of these drugs would be useful in the prophylaxis of patients at high risk for candidosis.

Adhesiveness↗

Comparison between adherence of C. albicans and Candida spp. to human epithelial cells.

A comparison was made of the adherence of different Candida species to human epithelial cells. Three strains each of C. albicans serotype A, serotype B, C. stellatoidea, C. tropicalis, C. krusei and C. glabrata recently clinical isolated were studied. The adherence assay, run in triplicate, was carried out using pooled buccal epithelial cells from healthy donors. The results indicate that both serotypes of C. albicans adhere to buccal epithelial cells in a significantly greater degree than the other species tested and there is no differences between C. albicans serotypes A and B. The rate of adherence of C. stellatoidea and C. tropicalis was similar to that of C. albicans serotypes A and B respectively. Among different strains of C. stellatoidea, C. tropicalis and C. glabrata, the adherence varied significantly and it is possible that there exist a relationship with different degree of pathogenicity of these particular strains.

Candida↗

Susceptibility of Candida species strains to five antifungal agents: comparison between agar dilution and disk diffusion tests.

The in vitro activity of five antifungal agents were compared against 180 Candida strains. The drugs were: two imidazoles (miconazole and ketoconazole), nystatin, 5-fluorocytosine and amphotericin B. Agar dilution and disk diffusion methods were used. Nystatin, miconazole and amphotericin B were the most active agents. 5-fluorocytosine had high activity except against C. albicans serotype B, of which a high percentage were resistant. Finally, a good correlation between the two methods was observed.

Agar↗

Effect of cyclosporin A on natural killer cells' response during viral infections.

In the this study the modification of lymphocyte subsets (T3, T4, T8) and Natural Killer (NK) cells in organ transplanted patients treated with Cyclosporin A (CyA) in the course of viral infection, have been analyzed. Different subsets have been studied with the monoclonal antibody method and infective processes have been verified by serological data of seroconversion. Our study has shown that CyA at the adopted doses does not alter NK response to viral infection; in fact, in patients with seroconversion, higher NK values and lower OKT4/OKT8 ratio values have been found with respect to patients who did not show any viral infection serologic data. Furthermore an increased incidence of reject crisis has been observed in patients with seroconversion.

Antibodies, Monoclonal↗