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Biomedical subjects

A Magni

Publications and source records attributed to A Magni.

At least 19 recordsLinked to original sources

Identification of respiratory isolates of Stenotrophomonas maltophilia by commercial biochemical systems and species-specific PCR.

One hundred strains of Stenotrophomonas maltophilia isolates from respiratory specimens were biochemically identified using the API 20NE strip and the VITEK2 ID-GNB card. The identification was confirmed by a species-specific PCR using two primers specific for the 23S rRNA gene. The API 20NE showed only 1 strain with "low discrimination" whereas the VITEK2 gave 12. In any case, the two biochemical systems showed good reliability compared to SS-PCR.

Bacteriological Techniques↗

Magnetization switching and microwave oscillations in nanomagnets driven by spin-polarized currents.

A novel theoretical approach to magnetization dynamics driven by spin-polarized currents is presented. Complete stability diagrams are obtained for the case where spin torques and external magnetic fields are simultaneously present. Quantitative predictions are made for the critical currents and fields inducing magnetization switching, for the amplitude and frequency of magnetization self-oscillations, and for the conditions leading to hysteretic transitions between self-oscillations and stationary states.

Journal Article↗

Correlation study of two routine bacteriology systems with previously characterised strains.

The objective of this study was to evaluate the performance of the VITEK 2 and Advanced Expert System (bioMérieux) for antimicrobial testing of previously characterised Gram-positive and Gram-negative bacterial strains. These strains obtained from bioMérieux, Mrcy Le Toille, France, were well characterized with regard to the existing resistance mechanisms and the Minimal Inhibitory Concentration (MIC) values were determined by agar dilution. VITEK 2 was also compared with the Sceptor system (Becton Dickinson) routinely used in our laboratory. The results obtained were equally good for VITEK 2 and Sceptor with a rate of agreement between the two systems of 91.4% and 88.2% respectively. When the results were evaluated in relation to the different antibiotic concentrations, the agreement was 94% for VITEK 2 and 62% for Sceptor. The resistance mechanisms associated with each resistance pattern were determined by the Advanced Expert System (AES) in 79.6% of strains. The VITEK 2 provided, in 3-4 hours, an acceptable level of accuracy in testing antimicrobial sensitivity in Gram-positive and Gram-negative strains with diverse mechanisms of resistance found in clinical situations.

Bacteriological Techniques↗

Substrate interaction with 5alpha-reductase enzyme: influence of the 17beta-chain chirality in the mechanism of action of 4-azasteroid inhibitors.

A series of steroidal compounds were synthesized in order to evaluate the possible influence of the configuration of a stereocenter in the 17beta-side chain on the inhibitory activity on the enzyme 5alpha-reductase (5AR). For this purpose diastereomerically pure 4-azasteroids epimers at C-22 were prepared (compounds 1-11) and tested as inhibitors of 5AR in "in vitro" tests. The obtained data showed that in most cases the couples of epimers possess a significant difference in their biological activity. We also considered, for the tested molecules, a series of chemico-physical parameters in order to find a possible correlation with their biological activity. The findings allowed us to propose a model of the binding site of 5AR which comprises also, for 4-azasteroid inhibitors, the configurational aspect of the 17beta-side chain.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

AP-PCR typing of Pseudomonas aeruginosa isolated from patients with cystic fibrosis.

Arbitrarily Primed Polymerase Chain Reaction has been used for an epidemiological evaluation of 42 strains of P. aeruginosa isolated from nine cystic fibrosis patients during a three-year investigation period. The resistance patterns of the same strains have also been evaluated. The AP-PCR type fingerprinting was perfomed with primers 10514 and 208. Resistance was evaluated by the Minimal Inhibitory Concentration method. With 10514 eleven different genotypes could be evidenced, while with 208 only five of them could be detected. During the investigation period patients were always colonised by the same genotype. A possible correlation between resistance pattern and genotype with both primers has shown, within the same patient, a correspondence of about 20% for 10514 and a correspondence of only 10% for 208. Patients are colonised by one or two strains of P. aeruginosa and there is no relation between genotype and resistance pattern.

Adult↗

Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer.

BACKGROUND: Fenretinide, a vitamin A analogue, has been shown to inhibit breast carcinogenesis in preclinical studies. We determined the efficacy of fenretinide in preventing a second breast malignancy in women with breast cancer. METHODS: We randomly assigned 2972 women, aged 30-70 years, with surgically removed stage I breast cancer or ductal carcinoma in situ to receive for 5 years either fenretinide orally (200 mg/day) or no treatment. The primary end point was the incidence of contralateral breast cancer or ipsilateral breast cancer 7 years after randomization. Other end points considered post hoc were the same outcomes stratified by menopausal status, incidence of distant metastases, overall mortality, and tumors in other organs. The hazards of breast cancer occurrence were determined by Cox proportional hazards regression analysis. Statistical tests were two-sided. RESULTS: At a median observation time of 97 months, there were no statistically significant differences in the occurrence of contralateral breast cancer (P =.642) or ipsilateral breast cancer (P =.177) between the two arms. However, an interaction was detected between fenretinide treatment and menopausal status in both outcomes (P for interaction in both outcomes =.045), with a possible beneficial effect in premenopausal women (contralateral breast cancer: adjusted hazard ratio [HR] = 0.66, and 95% confidence interval [CI] = 0.41-1.07; ipsilateral breast cancer: adjusted HR = 0.65, and 95% CI = 0.46-0. 92) and an opposite effect in postmenopausal women (contralateral breast cancer: adjusted HR = 1.32, and 95% CI = 0.82-2.15; ipsilateral breast cancer: adjusted HR = 1.19, and 95% CI = 0.75-1. 89). There were no statistically significant differences between the two arms in tumors in other organs, incidence of distant metastasis, and all-cause mortality. CONCLUSIONS: Fenretinide treatment of women with breast cancer for 5 years appears to have no statistically significant effect on the incidence of second breast malignancies overall, although a possible benefit was detected in premenopausal women. These studies, particularly the post hoc analyses, are considered exploratory and need to be confirmed.

Adult↗

Functional integration approach to hysteresis.

A general formulation of scalar hysteresis is proposed. This formulation is based on two steps. First, a generating function g(x) is associated with an individual system, and a hysteresis evolution operator is defined by an appropriate envelope construction applied to g(x), inspired by the overdamped dynamics of systems evolving in multistable free-energy landscapes. Second, the average hysteresis response of an ensemble of such systems is expressed as a functional integral over the space G of all admissible generating functions, under the assumption that an appropriate measure mu has been introduced in G. The consequences of the formulation are analyzed in detail in the case where the measure mu is generated by a continuous, Markovian stochastic process. The calculation of the hysteresis properties of the ensemble is reduced to the solution of the level-crossing problem for the stochastic process. In particular, it is shown that, when the process is translationally invariant (homogeneous), the ensuing hysteresis properties can be exactly described by the Preisach model of hysteresis, and the associated Preisach distribution is expressed in closed analytic form in terms of the drift and diffusion parameters of the Markovian process. Possible applications of the formulation are suggested, concerning the interpretation of magnetic hysteresis due to domain wall motion in quenched-in disorder and the interpretation of critical state models of superconducting hysteresis.

Journal Article↗

Antibody response to P. aeruginosa in patients with cystic fibrosis: evaluation of two methods.

The immunological response to Ps. aeruginosa antigens may be a sensitive and early indicator of the colonisation of the lungs with these organisms in patients with cystic fibrosis. This study used an immunoenzymatic system and immunoblotting to evaluate the antibody response of 20 patients without apparent Ps. aeruginosa lung infection. These was an agreement in the results obtained with the two methods in 87.5% of cases.

Antibodies, Bacterial↗

Study of IgG antibodies to Pseudomonas aeruginosa in early cystic fibrosis infection.

Intermittent colonization, which then becomes chronic, characterises pseudomonas lung infection in cystic fibrosis (C.F.) patients. Bacteriologic studies do not always detect this evolution, which, however, may be identified by serological examinations. The aim of this study was to apply the immunoblotting method in order to monitor the antibody response toward a Ps. aeruginosa standard antigen (St-Ag). The results were analyzed and focussed on the bacterial and clinical data. Patients with intermittent colonization were studied between 1995 and 1997. Ninety per cent of the patients were positive to total IgG and subclass IgG1 in correspondence with the bacteriological finding. Further investigation is called for regarding the presence of IgG4 in order to establish whether it could be considered an index of chronic status.

Antibodies, Bacterial↗

A practical route for the synthesis of 17 substituted steroidal 3-thioxamides.

A facile method for the synthesis of a series of new steroidal 3-thioxamides from the 3-oxo compound, variously substituted at the 17 position, is described. The "one pot" reaction, using Lawesson's reagent (4-methoxyphenylthionophosphine sulphide dimer) in dichloromethane solution, gives the desired compounds with a high degree of chemoselectivity, in good yields (> 80%).

5-alpha Reductase Inhibitors↗

Different serological examinations in cystic fibrosis patients: response to Pseudomonas aeruginosa St-Ag.

Crossed immunoelectrophoresis (CIE), enzyme linked immunosorbent assay (ELISA) and immunoblotting (IMB) were used to look for the presence of anti-bodies to Pseudomonas aeruginosa standard antigen in the sera of cystic fibrosis patients with intermittent (CF +/- P) and chronic (CF + P) colonization. Our results show that CIE is too complex a method to use when monitoring the infection over time, that with ELISA a correlation with the patient's clinical status may be made and that IMB can evidence an early, albeit low, reaction in the CF +/- P patient.

Adult↗

Outer membrane alterations in Pseudomonas aeruginosa after five-day exposure to quinolones and carbapenems.

A Pseudomonas aeruginosa strain (P.aeruginosa), recently isolated in clinical practice, was tested to evaluate the changes induced in the minimal inhibitory concentration (MIC) values and in the outer membrane (OM) components by a five-day exposure to sub-MIC concentrations of the quinolones ciprofloxacin and PD-131.628 and the carbapenems imipenem and meropenem. The treated strain showed a thirty two-fold increase in MIC values for quinolones and a sixteen-fold increase for carbapenems. The electrophoretic profile of the OM proteins of the strain treated with quinolones showed that ciprofloxacin induces loss of the 47 Kd protein band, whereas PD-131.628 modifies the protein pattern of the strain only after five days of exposure. The carbapenems engendered disappearance of the same protein band. Qualitative lipopolysaccaride (LPS) analysis did not reveal any change after antibiotic treatment of the strain, whereas the 2-keto-3-deoxyoctonic acid (KDO) assay showed considerable reduction in the strain treated with sub-MIC doses of meropenem. It can therefore be safely stated that the D2 protein plays an important though not exclusive role in enhancing strain resistance against the two classes of antibiotics tested in our study.

Anti-Infective Agents↗

Synthesis and preliminary pharmacological evaluation of pidotimod, its enantiomer, diastereomers and carboxamido derivatives.

A new compound with a peptide-like structure, (R)-3-[(S)-(5-oxo-2-pyrrolidinyl)carbonyl]-thiazolidine-4-carboxylic acid, its enantiomer, diastereomers and carboxamido derivatives were synthesized and tested for immunostimulant activity. Synthesis, preliminary, pharmacological data and structure-activity relationships are reported. (R)-3-[(S)-(5-Oxo-2-pyrrolidinyl)carbonyl]-thiazolidine-4-carboxylic acid (Ib, Pidotimod, PGT/1A, CAS 121808-62-6) was selected for further research.

Adjuvants, Immunologic↗

Effects of continuous exposure to ciprofloxacin on the outer membrane of P. aeruginosa.

The present work evaluated the effect of ciprofloxacin on the outer membrane proteins (OMPs), lipopolysaccharide (LPS) and the variation of minimal inhibitory concentrations (M.I.C.) of three P. aeruginosa strains after using 1/2 and 1/16 sub-M.I.C. drug doses for five days. Ciprofloxacin significantly modified the M.I.C. values. After contact with sub-M.I.C. drug doses two strains showed a decreased expression of a band migrating at 46 Kd, i.e. in the region of protein D that some authors claim is involved in quinolone diffusion. No major alteration of LPS structure was observed.

Bacterial Outer Membrane Proteins↗

Retinoids, breast cancer and NK cells.

N-(4-hydroxyphenyl) retinamide (4-HPR) is a synthetic retinoid which reduces the incidence of experimental tumours in animals and has been chosen for its weak toxicity to be tested as a chemopreventive agent in humans. The mechanism of antineoplastic action is still unknown but a possible immunoenhancing effect may be postulated. We investigated the NK activity of PBMC from a group of women treated with 4-HPR as a part of a large scale randomised phase III trial on chemoprevention of contralateral disease in mastectomised women. After 180 days of treatment the NK activity was augmented 1.73 times as compared to that of patients given a placebo. The NK activity of PBMC from 4-HPR treated women is maximised, being higher than the basal and even the rIL-2 or alfa-rIFN stimulated activity of controls. For this reason in the majority of cases it cannot be further augmented by incubation with either rIL-2 or alfa-rIFN in vitro. The increased NK activity of 4-HPR treated women is not due to an enhanced production of endogenous IL-2, because PBMC cultures from patients treated with 4-HPR or placebo, incubated in vitro with a panel of different stimulators (recall antigens, PHA, allogeneic and xenogeneic cells) produce similar amounts of IL-2. The functional activity, but not the number of NK cells is increased in 4-HPR treated women. The mechanism by which 4-HPR stimulates NK activity is not a function of direct action on NK cells. Indeed incubation of PBMC from blood donors with 4-HPR or its major metabolite N-(4-methoxyphenyl) retinamide (4-MPR) does not modify their natural cytotoxicity.

Adult↗

Five-year administration of fenretinide: pharmacokinetics and effects on plasma retinol concentrations.

PURPOSE: Monitoring of fenretinide (4HPR) levels, kinetics, and effects on retinal was performed in patients who participated in a phase I trial and who continued to be treated for 5 years as phase III trial patients. Accumulation of 4HPR in the breast was also assessed. PATIENTS AND METHODS: Plasma concentrations of 4HPR, of its main metabolite N-(4-methoxyphenyl)retinamide (4MPR), and of retinol were assayed by high-performance liquid chromatography (HPLC) in breast cancer patients treated orally with 4HPR 200 mg/d for 5 years with a 3-day drug interruption at the end of each month. RESULTS: 4HPR, at 200 mg/d, resulted in average 4HPR plasma levels of approximately 1 mumol/L, which remained steady and caused steady retinol level reduction; 4MPR levels, similar to those of 4HPR, slightly but significantly increased during the first 35 months, but at 5 years they were similar to those at 5 months. During daily treatment, baseline retinol concentrations were reduced by 71%; after a 3-day drug interruption, all patients recovered and the mean reduction was 38%. After discontinuation of 5-year treatment, 4HPR and 4MPR half-lives (t1/2 beta) were 27 and 54 hours, respectively, similar to those reported after 28 daily treatments. After 6 and 12 months, the concentrations of 4HPR were at the limit of detectability (0.01 mumol/L), whereas those of 4MPR were five times higher. Baseline retinol concentrations were already recovered after 1 month. Accumulation of this retinoid in the breast was evidenced by concentrations of 4HPR and 4MPR in nipple discharge and in breast biopsies that were 10 and 20 times higher, respectively, than those found in plasma. CONCLUSION: 4HPR, at 200 mg/d for 5 years, resulted in constant drug plasma levels and constant retinol level reduction. After treatment interruption, 4HPR plasma concentrations decreased at the limit of detectability at 6 months and baseline retinol plasma concentrations were recovered after 1 month.

Adult↗

Subinhibitory concentrations of antibacterial drugs and Pseudomonas aeruginosa virulence factors.

Pseudomonas aeruginosa is an important, opportunistic pathogen responsible for nosocomial infections in the immunocompromised host and resistant to antibacterial drugs. Its pathogenicity is related to many virulence factors such as proteases, alginate, exotoxin A and exoenzyme S. Our previous study showed a down-regulation of some P. aeruginosa virulence factors by subinhibitory concentrations of antibacterial drugs. This study aimed to compare the effects of subinhibitory concentrations of a new difluoroquinolone, PD 131,628, a betalactam, aztreonam and an aminoglycoside, netilmicin.

Alginates↗

Outer membrane proteins and lipopolysaccharide changes after exposure of Pseudomonas aeruginosa to antibacterial drugs.

Many studies show the low sensitivity of P. aeruginosa to antimicrobial agents, due to the permeability degree of the outer membrane (OM). Since the alterations of porins and lipopolysaccharides (LPS) are responsible for permeability to antibacterial drugs, the aim of this study was to evaluate the sub-M.I.C. effects of different antibiotics on the OM components. The M.I.C.s of five P. aeruginosa strains were determined and sub-M.I.C.s. versus PD-131,628, a new difluoroquinolone, aztreonam and netilmicin were calculated. The OM components were extracted before and after contact with the antibacterial drugs. We noted a decrease in M.I.C. values in two strains, and simultaneously an increase in the 19 and 38 Kd bands after using aztreonam. The M.I.C.s tended to increase in three strains after using netilmicin. The electrophoresis profile showed a decrease in the 38, 41 and 45 Kd bands and in one strain also in the 19 Kd band. The use of the quinolone did not significantly modify the M.I.C. values, although an evident increase in 38 and 41 Kd bands occurred in three strains. LPS alterations were observed with aztreonam and netilmicin, but not when PD 131,628 was used.

Anti-Bacterial Agents↗