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Biomedical subjects

G Corti

Publications and source records attributed to G Corti.

At least 19 recordsLinked to original sources

Measurement of the K0 charge radius and a CP-violating asymmetry and a search for CP-violating E1 direct photon emission in the rare decay KL--> pi+ pi- e+ e-.

Using the complete KTeV data set of 5,241 candidate K(L)--> pi(+) pi(-) e(+) e(-) decays (including an estimated background of 204 +/- 14 events), we have measured the coupling g(CR)= 0.163 +/- 0.0149(stat) +/- 0.023(syst) of the CP conserving charge radius process and from it determined a K(0) charge radius of = [-0.077 +/- 0.007(stat) +/- 0.011(syst)]fm(2). We have determined a first experimental upper limit of 0.04 (90% C.L.) /g(e1)/ / /g(M1)/ of the couplings for the E1 and M1 direct photon emission processes. We also report the measurement of /g(M1)/ including a vector form factor /g(M1)/(1 + (a(1)/a(2))/((M(2)(p)-(M(2)(k))= 2M(K)E(gamma*)), where vector /g(M1)/= 1.11+/- 0.12(stat) +/- 0.08(syst) and a(1)/a(2) = [-0.744 +/- 0.027(stat) +/- 0.032(syst)] GeV(2)/c(2). Finally, a CP-violating asymmetry of [13.6 +/- 1.4(stat) +/- 1.5(syst)]% in the CP and T odd angle phi between the decay planes of the e(+) e(-) and pi(+) pi(-) pairs in the K(L) center of mass is reported.

Journal Article↗

Simultaneous effect of cyclodextrin complexation, pH, and hydrophilic polymers on naproxen solubilization.

The effect of pH variation on complexation and solubilization of naproxen (pK(a) 4.2) with natural betaCyclodextrin (betaCyD) and various neutral, cationic and anionic betaCyD-derivatives has been investigated. The combined effect of pH variation and hydrophilic polymer addition on CyD solubilizing and complexing efficiency has also been determined. Phase-solubility analysis in buffered aqueous solutions (pH from 1.1 to 6.5) was used to study the interaction of the drug with each CyD, in the presence or not of the water-soluble polymer. A clear influence of the substituent type was observed, the methylderivative being the most efficient agent; on the contrary, unexpectedly, no influence of the CyD charge in the interaction with the ionizable drug was detected. As expected, total drug solubility increased with increasing pH; however, the solubility increment with respect to drug alone obtained by CyD complexation progressively decreased, with a parallel reduction of the complex stability, attributed to the reduced affinity of charged drug for the hydrophobic CyD cavity. The addition of the polymer in part counterbalanced the destabilizing effect obtained with increasing pH, by improving the CyD complexation power towards naproxen. In particular, the presence of PVP allowed an increase of the complex stability constant with hydroxypropyl betaCyD up to 60% with respect to the corresponding drug-CyD binary system. Therefore, the combined strategy of pH control and polymer addition to the CyD complexing medium can be successfully exploited to improve naproxen solubilization and reduce the amount of CyD needed. The construction of theoretical drug solubility curves as a function of pH for any given CyD and polymer concentration enables selection of the best experimental conditions for obtaining the desired drug solubility value.

Hydrogen-Ion Concentration↗

Influence of cyclodextrins and chitosan, separately or in combination, on glyburide solubility and permeability.

The effect of chitosan and of different concentrations of beta- or hydroxypropyl-beta-cyclodextrins, separately or in various (w/w) combinations, on the dissolution characteristics of glyburide (an oral hypoglycemic agent subject to incomplete and variable bioavailability) and on its permeability through Caco-2 cells has been investigated. Cyclodextrins (and particularly the hydroxypropyl-derivative, in virtue of its higher water solubility) were clearly more effective than chitosan in enhancing the drug dissolution properties: the aqueous glyburide solubility was improved 40-fold in the presence of 25 mM hydroxypropyl-beta-cyclodextrin, 25-fold in the presence of 13 mM beta-cyclodextrin (saturation solubility) and only 3-fold in the presence of chitosan at its saturation concentration (0.5% w/v). When chitosan and cyclodextrin were simultaneously present, a strong reduction of the cyclodextrin solubilizing efficiency towards the drug was observed, and it was attributed to a possible competition effect of polymer and glyburide for the interaction with the macrocycle. By contrast, permeation studies revealed that chitosan was more powerful than cyclodextrins in enhancing the glyburide permeability through Caco-2 cells. This was probably in virtue of the polymer's favourable effect on the tight junctions opening, as demonstrated by the significant decrease in the transepithelial electrical resistance recorded in its presence. Moreover, interestingly, when using the carriers together, conversely from solubility studies, a significant (P < 0.05) synergistic effect in enhancing glyburide apparent permeability was revealed in permeation experiments.

Algorithms↗

Influence of formulation and process variables on in vitro release of theophylline from directly-compressed Eudragit matrix tablets.

Extended-release theophylline (TP) matrix tablets were prepared by direct compression of drug and different pH-dependent (Eudragit L100, S100 and L100-55) and pH-independent (Eudragit RLPO and RSPO) polymer combinations. The influence of varying the polymer/polymer (w/w) ratio and the drug incorporation method (simple blend or solid dispersion) was also evaluated. Drug release, monitored using the Through Flow Cell system, markedly depended on both the kind of Eudragit polymer combinations used and their relative content in the matrix. Maintaining a constant 1:1 (w/w) drug/polymers ratio, the selection of appropriate mixtures of pH-dependent and pH-independent polymers enabled achievement of a suitable control of TP release. In particular, matrices with a 0.7:0.3 w/w mixture of Eudragit L100-Eudragit RLPO showed highly reproducible drug release profiles, with an almost zero-order kinetic, and allowed 100% released drug after 360 min. As for the effect of the drug incorporation method, simple blending was better than the solid dispersion technique, which not only did not improve the release data reproducibility, but also caused, unexpectedly, a marked slowing down in drug release rate.

Acrylic Resins↗

Interaction of naproxen with ionic cyclodextrins in aqueous solution and in the solid state.

The possible role of the cyclodextrin charge in the interaction with an acidic drug such as naproxen (pKa 4.8) has been evaluated. Sulfobutylether-beta-cyclodextrin (SBE-betaCyd) and trimethylammonium-beta-cyclodextrin (TMA-betaCyd) were selected as, respectively, anionically and cationically charged carriers and their performance was compared with that of the parent beta-cyclodextrin (betaCyd) and of its methyl-derivative (Me betaCyd) previously found as the best partner for the drug. Interactions in solution were investigated by phase-solubility, fluorescence and circular dichroism analyses. Equimolar drug-carrier products prepared by different techniques (blending, cogrinding, sealed-heating, colyophilization) were characterized by differential scanning calorimetry and X-ray powder diffractometry and tested for drug dissolution properties. Anionic charges of SBE-betaCyd did not negatively influence interactions in unbuffered aqueous solutions (pH approximately 5) with the acidic drug. In fact, it was a very effective carrier, exhibiting solubilizing and complexing properties considerably better than the parent betaCyd and comparable to those of Me betaCyd. On the contrary, the positive charges of TMA-betaCyd did not favour interactions with the counter-ionic drug (despite the presence of about 60% ionised drug) and it was less efficacious also than native betaCyd. Therefore, the role of the Cyd charge on the complexing and solubilizing properties towards naproxen was not important whereas other factors, such as steric hindrance effects and favourable hydrophobic interactions were significant in determining the drug affinity for the Cyd inclusion. Solid state studies evidenced similar amorphizing properties of both charged Cyds towards naproxen. On the other hand, dissolution tests, in agreement with solution studies, showed that all products with SBE-betaCyd exhibited significantly better dissolution properties than the corresponding ones with TMA-betaCyd. A clear influence of the preparation method of drug-Cyd solid systems on the performance of the end product was also observed. Colyophilization was the most effective technique, followed by the cogrinding one. Colyophilized product with SBE-betaCyd allowed a 10-times increase in drug dissolution efficiency (D.E.) (with respect to the five-times increase obtained with the corresponding coground product) and a reduction of t(50%) from about 60 min (for the coground product) to less than 2 min.

Cyclodextrins↗

[The role of linezolid in the therapy of infections caused by multiresistant gram-positive cocci].

Gram-positive cocci are becoming more and more common agents of nasocomial infections, primarily enterococci and staphylococci in the field of surgical site and bloodstream infection. At the same time, the frequency of multiresistant enterococci and methicillin-resistant staphylococci has increased, whereas glycopeptide-resistant enterococcal strains and, recently, staphylococci with reduced susceptibility to glycopeptides have appeared, so making the use of glycopeptides as the "last-chance drugs" ineffective. Under those circumstances, the synthesis of new potent antibiotics, such as oxazolidinones, is both desirable and welcome. Linezolid possesses a high activity against all multiresistant gram-positive cocci, favourable pharmacokinetics, a good safety profile, a complete bioavailability after and administration permitting switch therapy, a low capacity of inducing resistance, and both clinical and microbiologic efficacy as demonstrated by a number of clinical trials conducted on thousands of patients. So, linezolid is an important therapeutic option in the treatment of infections caused by multiresistant enterococcal and staphylococcal strains.

Acetamides↗

Search for the KL-->pi 0 pi 0 e+e- decay in the KTeV experiment.

The recent discovery of a large CP violating asymmetry in KL-->pi+pi-e+e- mode has prompted us to seach for the associated KL-->pi 0 pi 0 e+e- decay mode in the KTeV-E799 experiment at Fermilab. In 2.7 x 10(11) K(L) decays, one candidate event has been observed with an expected background of 0.3 event, resulting in an upper limit for the KL-->pi 0 pi 0 e+e- branching ratio of 6.6 x 10(-9) at the 90% C.L.

Journal Article↗

Radiative decay width measurements of neutral kaon excitations using the primakoff effect.

We use K(L)'s in the 100-200 GeV energy range to produce 147 candidate events of the axial vector pair K1(1270)-K1(1400) in the nuclear Coulomb field of a Pb target and determine the radiative widths Gamma(K1(1400)-->K0+gamma)=280.8+/-23.2(stat)+/-40.4(syst) keV and Gamma(K1(1270)-->K0+gamma)=73.2+/-6.1(stat)+/-28.3(syst) keV. These first measurements appear to be lower than the quark-model predictions. We also place upper limits on the radiative widths for K(*)(1410) and K(*)(2)(1430) and find that the latter is vanishingly small in accord with SU(3) invariance in the naive quark model.

Journal Article↗

Measurement of the K(L) charge asymmetry.

We present a measurement of the charge asymmetry delta(L) in the mode K(L)-->pi(+/-)e(-/+)nu based on 298 x 10(6) analyzed decays. We measure a value of delta(L) = [3322+/-58(stat)+/-47(syst)]x10(-6), in good agreement with previous measurements and 2.4 times more precise than the current best published result. The result is used to place more stringent limits on CPT and DeltaS = DeltaQ violation in the neutral kaon system.

Journal Article↗

First measurement of form factors of the decay Xi(0) --> Sigma(+)e(-)nu macro(e).

We present the first measurement of the form factor ratios g(1)/f(1) (direct axial vector to vector), g(2)/f(1) (second class current), and f(2)/f(1) (weak magnetism) for the decay Xi(0)-->Sigma(+)e(-)nu macro(e) using the KTeV (E799) beam line and detector at Fermilab. From the Sigma(+) polarization measured with the decay Sigma(+)-->p pi(0) and the e(-)-nu; correlation, we measure g(1)/f(1) to be 1.32+/-(0.21)(0.17)(stat)+/-0.05(syst), assuming the SU(3)(f) (flavor) values for g(2)/f(1) and f(2)/f(1). Our results are all consistent with exact SU(3)(f) symmetry.

Journal Article↗

Branching ratio measurement of the decay K(L) --> e(+)e(-)mu(+)mu(-).

We have collected a 43 event sample of the decay K(L)-->e(+)e(-)mu(+)mu(-) with negligible backgrounds and measured its branching ratio to be (2.62+/-0.40+/-0.17)x10(-9). We see no evidence for CP violation in this decay. In addition, we set the 90% confidence upper limit on the combined branching ratios for the lepton flavor violating decays K(L)-->e(+/-)e(+/-)mu(-/+)mu(-/+) at B(K(L)-->e(+/-)e(+/-)mu(-/+)mu(-/+))< or =1.23x10(-10), assuming a uniform phase space distribution.

Journal Article↗

Measurement of the branching ratio and form factor of K(L)-->mu(+)mu(-)gamma.

We report on the analysis of the rare decay K(L)-->mu(+)mu(-)gamma the 1997 data from the KTeV experiment at Fermilab. A total of 9327 candidate events are observed with 2.4% background, representing a factor of 40 increase in statistics over the current world sample. We find that B(K(L)-->mu(+)mu(-)gamma) = (3.62 +/- 0.04(stat) +/- 0.08(syst)) x 10(-7). The form factor parameter alpha(K*) is measured to be alpha(K*) = -0.160(+0.026)(-0.028). In addition, we make the first measurement of the parameter alpha from the D'Ambrosio-Isidori-Portolés form factor, finding alpha = -1.54 +/- 0.10. In that model, this alpha measurement limits the Cabibbo-Kobayashi-Maskawa parameter rho>-0.2.

Journal Article↗

Measurements of the rare decay K(L) --> e(+)e(-)e(+)e(-).

We observe 441 K(L)-->e(+)e(-)e(+)e(-) candidate events with a background of 4.2 events and measure B(K(L)-->e(+)e(-)e(+)e(-)) = [3.72+/-0.18(stat)+/-0.23(syst)]x10(-8) in the KTeV/E799II experiment at Fermilab. Using the distribution of the angle between the planes of the e(+)e(-) pairs, we measure the CP parameters beta(CP) = -0.23+/-0.09(stat)+/-0.02(syst) and gamma(CP) = -0.09+/-0.09(stat)+/-0.02(syst). We also present the first detailed study of the e(+)e(-) invariant mass spectrum in this decay mode.

Journal Article↗

Measurement of the branching ratio and asymmetry of the decay Xi degrees -->Sigma degrees gamma.

We have studied the rare weak radiative hyperon decay Xi degrees -->Sigma degrees gamma in the KTeV experiment at Fermilab. We have identified 4045 signal events over a background of 804 events. The dominant Xi degrees -->Lambdapi degrees decay, which was used for normalization, is the only important background source. An analysis of the acceptance of both modes yields a branching ratio of B(Xi degrees -->Sigma degrees gamma)/B(Xi degrees -->Lambdapi degrees ) = (3.34+/-0.05+/-0.09)x10(-3). By analyzing the final state decay distributions, we have also determined that the Sigma degrees emission asymmetry parameter for this decay is alpha(XiSigma) = -0.63+/-0.09.

Journal Article↗

Study of the K(0)(L) --> pi(+)pi(-)gamma Direct Emission Vertex.

We have performed studies of the K(0)(L)-->pi(+)pi(-)gamma direct emission ( DE) and inner Bremsstrahlung ( IB) vertices, based on data collected by KTeV during the 1996 Fermilab fixed target run. We find a(1)/a(2) = -0.737+/-0.034 GeV2 for the DE form-factor parameter in the rho-propagator parametrization, and report on fits of the form factor to linear and quadratic functions as well. We concurrently measure gamma(K(0)(L)-->pi(+)pi(-)gamma,E(*)(gamma)>20 MeV)/gamma(K(0)(L)-->pi(+)pi(-)) = (20.8+/-0.3)x10(-3), and a K(0)(L)-->pi(+)pi(-)gamma DE/(DE+IB) branching ratio of 0.683+/-0.011.

Journal Article↗

Search for the decay KL --> pi(0)e+e-.

We report on a search for the decay KL-->pi(0)e+e- carried out by the KTeV/E799 experiment at Fermilab. This decay is expected to have a significant CP violating contribution and the measurement of its branching ratio could support the Cabibbo-Kobayashi-Maskawa mechanism for CP violation or could point to new physics. Two events were observed in the 1997 data with an expected background of 1.06+/-0.41 events, and we set an upper limit B(KL-->pi(0)e+e-)<5.1 x 10(-10) at the 90% confidence level.

Journal Article↗

Antistaphylococcal (MSSA, MRSA, MSSE, MRSE) antibiotics.

S. aureus and coagulase-negative staphylococci such as S. epidermidis are important causes of infection of the bloodstream, cardiac valves, implanted devices, and skin, with repercussions on mortality and increased economic costs. Treatment of staphylococcal infections is made difficult by the increasing emergence of resistance to beta-lactams and other antimicrobials, including reduced susceptibility to glycopeptides. Penicillin must be used for infrequent penicillin-susceptible isolates, oxacillin and nafcillin are to be considered the major option for penicillin-resistant staphylococci, and glycopeptides are the drugs of choice for infections caused by methicillin-resistant strains. Co-trimoxazole, lincosamides, macrolides, tetracyclines, and fluoroquinolones are alternative agents, primarily in subjects allergic to beta-lactams. Newly introduced or experimental drugs, such as streptogramins (quinupristin-dalfopristin), oxazolidinones (linezolid), carbapenems (LY 333328), everninomicins (SCH 27899), and derivatives of tetracyclines (glycylcyclines), could be useful for therapy of infections caused by multiresistant staphylococci.

Anti-Bacterial Agents↗

Infections in multiple myeloma.

Multiple myeloma is a relatively rare but severe hematologic malignancy. Marked depression in production of normal immunoglobulins, mild neutropenia, and alkylant/steroid therapy or BMT/SCT all produce major suppression of the immune system in the totality of patients. Recurrent bacterial, fungal, and viral infections are an important cause of morbidity and the most common cause of death in these subjects. Prompt diagnosis and appropriate anti-infective chemotherapy are essential in order to reduce the risk of mortality.

Bacterial Infections↗