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N Franceschini

Publications and source records attributed to N Franceschini.

At least 73 records · Page 4Linked to original sources

Inhibitors and inactivators of beta-lactamase from Mycobacterium fortuitum.

The inhibiting or inactivating effects of some beta-lactam antibiotics on beta-lactamase from Mycobacterium fortuitum were studied. Among all substrates tested, clavulanic acid and sulbactam were the strongest competitive inhibitors of the enzyme although the latter was slightly hydrolyzed. Imipenem and cefoxitin scarcely inhibited the beta-lactamase yet expressed good activity against the microorganism in vitro, suggesting that the effectiveness of these drugs on M. fortuitum might be due to high permeation through the cell wall. All the isoxazolylpenicillins tested and methicillin inactivated the enzyme of M. fortuitum by a first rapid phase of acylation followed by a steady-state process of enzyme reactivation (deacylation). Clavulanic acid and sulbactam showed Ki values for the enzyme inactivation closely corresponding to hematic concentrations achievable in vivo during antibiotic treatment.

Anti-Bacterial Agents↗

Do inert beta-lactamase inhibitors act as synergizers of beta-lactam antibiotics? Utility of boric and boronic acids.

Boric and boronic acids were used as inhibitors of beta-lactamases produced by two Citrobacter diversus strains and by one strain of Pseudomonas aeruginosa; all strains were clinical isolates. The beta-lactamases produced by the two Citrobacter diversus strains were inhibited by both borates and boronates, using cephazolin as substrate. The enzyme from Pseudomonas aeruginosa was inhibited only by boronates, using benzylpenicillin as substrate. These inhibitors were also used in combination with selected beta-lactams so as to determine if a synergism of antimicrobial activity occurred. All data reported in the present paper indicate that the minimum inhibitory concentration (MIC) values were lowered in the presence of these inhibitors for the two Citrobacter diversus strains. In the Pseudomonas aeruginosa strains the MIC values were not significantly altered, thus indicating the presence of a permeability barrier for 3-aminophenylboronic acid.

Anti-Bacterial Agents↗

The beta-lactamases of Citrobacter diversus and their hydrolysis kinetics for some structurally-related cephalosporins.

We measured the kinetics of hydrolysis of various cephalosporins by the chromosomally-encoded beta-lactamases of Citrobacter diversus ULA-27. Cefonicid, cefamandole, cefatrizine and cefoperazone were all hydrolyzed but these antibiotics showed a different feature in their kinetic parameters. Moreover, cefoperazone was a non-competitive inhibitor of this type of enzyme. Cefotetan was stable to hydrolysis and behaved like a progressive inactivator. The ability of these enzymes to inactivate the reported antibiotics contributes largely to the resistance of the studied strain. We conclude that hydrolysis is the main mechanism of resistance of this strain to the new cephalosporins.

Cell Cycle↗

Beta-lactamase production and biological characteristics in nitrosoguanidine induced Mycobacterium fortuitum mutants.

In order to elucidate the role of beta-lactamase in the resistance of M. fortuitum to beta-lactams, M. fortuitum ATCC 19542 and three mutants, strains D 316, D 319 and D 170 obtained from it by nitrosoguanidine treatment, were studied. Furthermore the kinetics of the beta-lactamase production during the bacterial growth and many biochemical and enzymatic characteristics of parent and mutant strains were investigated. Amoxicillin MICs well correlated with the beta-lactamase production in the high producer strains D 316 and D 319; on the contrary in strain D 170 a high MIC was joined with a moderate production of the enzyme showing that not only beta-lactamase but also other mechanisms can be effective in the resistance of M. fortuitum to beta-lactams. Clavulanic acid, an inhibitor of beta-lactamase, reduced MICs to amoxicillin in high and in low producer strains. The production of extracellular beta-lactamase occurred in a M. fortuitum mutant strain mainly during the stationary phase, indicating that a cell wall damage or initial autolysis could be responsible for the release of enzyme. Enzymatic and biochemical characteristics were not affected by nitrosoguanidine treatment except for nitrate test which showed only a weak positivity in high producer strains.

Anti-Bacterial Agents↗

'Photo-degeneration' of neurones after extracellular dye application.

Irradiation in the presence of a dye applied to the extracellular space was found to trigger neuronal degeneration in fly photoreceptor neurones. This phenomenon endowed the selected cells with a dark and fine-grained label such that they could be traced and scrutinized for synaptic specializations. It also initiated their phagocytotic removal from the neural network. Various states of degeneration fitting classical descriptions could be achieved by acting upon the light dose. The phenomenon seems to rely on photosensitization of the cell by the dye. The simplicity and precision with which this phenomenon can be induced makes 'photo-degeneration' an exciting prospective tool for combined anatomical and physiological studies on (natural) neural networks and may provide a new line of medical applications.

Animals↗

Citrobacter diversus ULA-27 beta-lactamases. Improved purification and general properties.

Two chromosome-encoded beta-lactamases have been purified from Citrobacter diversus ULA-27. They exhibited slightly different isoelectric points (6.8 and 6.2) and very similar Mr values (congruent to 29,000). Their specificity spectrum was rather wide, since they hydrolysed some cephalosporins with kcat: values similar to those observed with the best penicillin substrates. Cloxacillin, methicillin and imipenem were hydrolysed very slowly. Hydrolysis of azthreonam could not be detected.

Amino Acids↗

On the kinetic interaction between ceftriaxone and some beta-lactamases.

The activity of beta-lactamases from Citrobacter diversus ULA-27 on ceftriaxone, a widely recognized third-generation cephalosporin, has been examined and compared to the activity of various other beta-lactamases from different sources. Ceftriaxone (Roche S.p.A. Milan) was found to be resistant to hydrolysis by beta-lactamases from Enterobacter cloacae and Bacillus cereus, but susceptible to beta-lactamases from Mycobacterium fortuitum strain Cow 18 and, mostly, to beta-lactamases from various strains of Citrobacter diversus. Derivatives with substituents in the 3-position of ceftriaxone, namely cefotaxime (Roussel Maestretti S.p.A., Milan) and ceftizoxime (Farmitalia Carlo Erba, Milan), were much less susceptible to hydrolysis by C. diversus ULA-27 enzymes (22 and 6% of ceftriaxone hydrolysis, respectively), the hydrolysis rate being paralleled by differences in MIC values. Ceftriaxone inhibited the activity of E. cloacae beta-lactamases toward cefazolin as substrate, but the inhibition was totally abolished by preincubation of ceftriaxone with the enzyme before addition of the substrate. Overall, the data point to a relevance of C. diversus ULA-27 beta-lactamases in the mechanism of resistance of this strain to the various third-generation cephalosporins.

Bacillus↗

Stimulated drug uptake in a photoreceptor cell.

In many cells, organelle translocation requires structural integrity of microtubules [2,6,11,14, 5]. We have found that extracellular application of the antimicrotubular drug colchicine, which was expected to enter cells simply by diffusion, was ineffective at blocking pigment granule migration (PGM) inside fly photoreceptors. However, illumination of these receptors in the presence of colchicine resulted in complete PGM block. From a combined study using microphotometry, microfluorometry and intracellular recordings, we inferred that light permeabilized the cell to the drug. This hypothesis was supported by the observation that illumination caused the photoreceptor to take up an inert dye. The results show that target cells optically selected from a homogeneous population can be induced to take up an agent from the extracellular fluid. Remarkably, this process of light-induced drug uptake does not affect cell viability.

Animals↗

Illumination induces dye incorporation in photoreceptor cells.

Illumination of fly photoreceptors in the presence of the fluorescent dye Lucifer yellow initiates incorporation of the dye, which stains each cell down to its synaptic terminal. Unilluminated cells do not become stained. Experiments on animals in vivo show that selected cells can be stained without loss of viability. "Induced endocytosis" provides a plausible mechanism underlying this phenomenon.

Animals↗

Motion detection in flies: parametric control over ON-OFF pathways.

Microscopic illumination of two neighbouring photoreceptor cells within a single ommatidium induces a strong sequence-dependent response in a directionally selective, motion-sensitive neuron. The response is characterized by a strong facilitation in the preferred direction and a weaker inhibition in the reverse direction. The data suggest that for each direction of apparent movement the signal from an ON-OFF pathway is released into the neuron via a parametric control mechanism which is activated by an adjacent channel.

Animals↗

Fluorescence of photoreceptor cells observed in vivo.

Most rhabdomeres in the eye of the fly (Musca domestica) are fluorescent. One kind of fluorescent emission emanates from a photoproduct of the visual pigment, other kinds may be ascribed to photostable pigments. These phenomena provide not only a means of spectrally mapping the retina but also a new spectroscopic tool for analyzing the primary visual processes in vivo.

Animals↗

Evidence for a sensitising pigment in fly photoreceptors.

Many photoreceptor cells in invertebrates have a dual-peak spectral sensitivity. Evidence is presented that in fly photoreceptors the ultraviolet peak is due to a photostable pigment that absorbs light quanta and transfers the energy to the blue-absorbing visual pigment.

Animals↗

Photostable pigments within the membrane of photoreceptors and their possible role.

In the majority of ommatidia of the fly, the membrane of the central rhabdomere contains--besides the rhodopsin--a photostable pigment. Due to its selective absorption in the blue spectral range, this pigment (possibly a carotene) could modify the spectral senstivity of the central receptor cells. It furthermore may change the fluidity of the microvillus membrane and hence affect the alignment of rhodopsin molecules. Indirect evidence for a possible role of the photostable pigment as an "antenna" -pigment for rhodopsin is discussed.

Animals↗