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Biomedical subjects

M Trotta

Publications and source records attributed to M Trotta.

At least 19 recordsLinked to original sources

Observation of 54Ni: cross-conjugate symmetry in f7/2 mirror energy differences.

Gamma decays from excited states up to Jpi=6+ in the N=Z-2 nucleus 54Ni have been identified for the first time. Level energies are compared with those of the isobars 54Co and 54Fe and of the cross-conjugate nuclei of mass A=42. The good but puzzling f7/ cross-conjugate symmetry in mirror and triplet energy differences is analyzed. Shell model calculations reproduce the new data but the necessary nuclear charge-dependent phenomenology is not fully explained by modern nucleon-nucleon potentials.

Journal Article↗

Thermal response of contrast agent microbubbles: preliminary results from physico-chemical and US-imaging characterization.

Hyperthermia (HT) is a therapeutic strategy based on the selective damaging of tumoral cells when heated at temperatures in the range 41-45 degrees C. We are currently investigating the feasibility of Ultrasound (US) imaging to perform a non-invasive, efficient and cost effective temperature monitoring of heated tissues. Commercial US contrast agents (Sonovue, Bracco), consisting in microbubbles of SF(6) coated with a phospholipidic shell, greatly improve the US echo signal from tissues. Further investigations have been performed, consisting in physico-chemical and US-imaging characterization. In conclusion, we demonstrate that Sonovue microbubbles reach their maximal diameter at 40 degrees C, and then a sharp decrease is observed, possible due to the occurrence of gel-sol transition of the phospholipidic shell. At the same temperature the maximal backscattering intensity is predicted and actually experimentally observed. Sonovue, as well as other contrast agents based only on phospholipids, are, therefore, not suitable for use as non-invasive temperature monitoring medium since it is sensitive to temperatures below the hyperthermic range. Although microbubbles are in principle thermally effective, other coating materials should be investigated in order to increase their operative thermal range.

Contrast Media↗

Solid lipid micro-particles carrying insulin formed by solvent-in-water emulsion-diffusion technique.

The study aimed to produce solid lipid insulin-loaded micro-particles by the solvent-in-water emulsion-diffusion technique, using isobutyric acid as solvent phase, glyceryl monostearate or cetyl palmitate as lipid, soya lecithin and taurodeoxycholate as emulsifiers. Isobutyric acid, a partially water-miscible solvent with low toxicity, was used due to its high insulin-solubilization capacity. Solid lipid micro-particles of spherical shape were prepared by simple dilution of the emulsion with water. To increase the lipid load the process was conducted at 50 degrees C, and in order to reach sub-micron size, a high-shear homogeniser was used. Insulin encapsulation efficiency was about 80%. Analysis of microsphere content after processing showed that insulin did not undergo any chemical modification within the micro-particles. The in vitro release of insulin from the micro-particles was very low, and an initial burst effect of 20% of the dose was observed. After treatment of the solid lipid micro-particles with pepsin solution, an insulin loss of about 24% of the total englobed insulin was observed. The solid lipid micro-particles appear to have interesting possibilities as delivery systems for oral administration of insulin.

Animals↗

No enhancement of fusion probability by the neutron halo of 6He.

Quantum tunnelling through a potential barrier (such as occurs in nuclear fusion) is very sensitive to the detailed structure of the system and its intrinsic degrees of freedom. A strong increase of the fusion probability has been observed for heavy deformed nuclei. In light exotic nuclei such as 6He, 11Li and 11Be (termed 'halo' nuclei), the neutron matter extends much further than the usual nuclear interaction scale. However, understanding the effect of the neutron halo on fusion has been controversial--it could induce a large enhancement of fusion, but alternatively the weak binding energy of the nuclei could inhibit the process. Other reaction channels known as direct processes (usually negligible for ordinary nuclei) are also important: for example, a fragment of the halo nucleus could transfer to the target nucleus through a diminished potential barrier. Here we study the reactions of the halo nucleus 6He with a 238U target, at energies near the fusion barrier. Most of these reactions lead to fission of the system, which we use as an experimental signature to identify the contribution of the fusion and transfer channels to the total cross-section. At energies below the fusion barrier, we find no evidence for a substantial enhancement of fusion. Rather, the (large) fission yield is due to a two-neutron transfer reaction, with other direct processes possibly also involved.

Journal Article↗

pH-sensitive fluorescent dye as probe for proton uptake in photosynthetic reaction centers.

Isolated and purified reaction centers (RC) from Rhodobacter sphaeroides R-26.1 were solubilised in detergent with excess quinone and external electron donors and illuminated in the presence of pyranine. The pH change accompanying the reaction center photocycle was monitored by recording the variation of the pyranine fluorescence intensity. Using Q(B)-depleted reaction centers or blocking the photocycle with terbutryne strongly reduced the pH change. The usefulness and limits of this technique in monitoring the pH changes during the RC photocycle are also discussed.

Arylsulfonates↗

Temperature monitoring using ultrasound contrast agents: in vitro investigation on thermal stability.

Invasiveness of temperature monitoring devices is presently one of the most serious limitations to the application of oncological hyperthermia (HT). A promising approach aims at detecting temperature variations by monitoring the mean grey level (MGL) of the ultrasonographic image of the tissue. Gaseous ultrasound contrast agents (UCA), enhancing Ultrasonic (US) imaging, are expected to be sensitive to temperature, and are therefore a good candidate as temperature monitoring medium. The present study evaluates the 'in vitro' temporal and thermal stability and the correlation between temperature and MGL using a gaseous UCA (SonoVue) as phantom. No statistical differences were detected between the MGL value of the phantom kept at 43.5 degrees C before (215.2+/-3.5) and after 1 h (214.8+/-2.5), showing good stability at HT temperatures. Data of MGL image vs. temperature were obtained during both heating and cooling experiments in the HT range (30-43 degrees C). A good linearity of MGL vs. temperature (R2=0.976) was found with a good accuracy (2.5%) and a sensitivity of about 6.6 MGL/degrees C.

Analysis of Variance↗

Elastic liposomes for skin delivery of dipotassium glycyrrhizinate.

The aim of this study was to evaluate the possibility of using liposomes for skin delivery of dipotassium glycyrrhizinate (KG), an anti-inflammatory agent employed in treating acute and chronic dermatitis, and of formulating such liposomes in an oil-in-water emulsion (O/W). KG had emulsifying properties and the possibility of producing elastic liposomes was verified. Liposomes containing soya lecithin (PC) or hydrogenated soya lecithin (HPC) mixed with KG in w/w ratios of 2:1, 4:1 or 8:1 were prepared by the solvent evaporation method and then passed through a high pressure homogeniser. Liposome size and entrapment efficiency were determined and the interaction between KG and HPC was investigated using differential scanning calorimetry (DSC). Transepidermal permeation through intact pig skin and skin deposition of KG from liposomes and O/W emulsion containing liposomes were assessed and compared with values for aqueous control solutions. No marked differences were observed between PC and HPC liposomes. Liposome sizes ranged from 90 to 120 nm. Entrapment efficiency depended on the lipid:KG ratio; the maximum efficiency was obtained at 4:1 w/w. KG interacted with liposomes disrupting and fluidising the lipid bilayer, forming elastic liposomes able to penetrate through membrane pores of diameter much smaller than their own diameter. The liposome structure was maintained when dispersed in an O/W emulsion. The skin fluxes were less than the HPLC detection limit for all systems, while skin deposition increased 4.5-fold compared with aqueous solutions when KG was formulated in liposomes.

Administration, Topical↗

Emulsions containing partially water-miscible solvents for the preparation of drug nanosuspensions.

The aim of this study was to investigate the feasibility of partially water-miscible solvents, such as benzyl alcohol, butyl lactate and triacetin, to prepare drug nanosuspensions by a solvent quenching technique. Mitotane, which possesses very poor water solubility and low bioavailability, was used as model drug. Preparation was by emulsifying an organic solution of the drug in an aqueous solution of a stabilising agent followed by rapid displacement of the solvent from the internal into the external phase, provoking solid particle formation. To verify the influence of emulsion droplet size on the drug particle size, 0.1 or 0.2% of different emulsifiers (Tween 80, caprylyl-capryl glucoside or lecithin) and different homogenisation conditions (Ultra Turrax or a high pressure homogenizer at 200 or 1000 bar for three cycles) were used. In general, emulsion droplet size decreased with high pressure homogenization and on increasing the number of cycles. The size of drug particles, obtained after adding water at a constant rate, was dependent on the droplet size in the emulsion. Drug particles of approximately 80 nm were obtained using butyl lactate, supporting the hypothesis that drug particle formation by the emulsification diffusion process involves generating regions of local supersaturation. Because of the increase in available surface area, the dissolution rate of diaultrafiltrated suspensions increased greatly compared to commercial product.

Emulsions↗

Transfer of coenzyme Q0 from water to aqueous surfactant solutions: the case of Triton X-100.

The effect of UQ0 on the micellization equilibrium of Triton X-100 has been studied by the analysis of the UV absorption spectra of Triton X-100. In the range of the UQ0 concentration investigated, the critical micelle concentration (CMC) increases at increasing of the solute concentration. The dependence of the CMC on UQ0 concentration has been used to calculate the generalized Setchenov constant. Mixing and dilution enthalpies of aqueous solutions of UQ0 and Triton X-100 were measured and used to calculate the enthalpies of transfer of UQ0 from water to Triton X-100 aqueous solutions. From the dependence of the enthalpy of transfer on surfactant concentration, the distribution constant between aqueous and micellar phase and the standard enthalpy of transfer from water to Triton X-100 micelles were evaluated along with the standard transfer free energy and entropy. All measurements were carried out at 298 K.

Journal Article↗

Large enhancement of the sub-barrier fusion probability for a halo nucleus

The fusion-fission cross sections of the 4He+238U and 6He+238U systems have been measured, at Louvain-la-Neuve, for energies around and below the Coulomb barrier, using an array of Si detectors surrounding a UF4 target. The data taken with 4He are in good agreement with previous data and with the coupled channel fusion calculation performed with ECIS. The 6He data show a regular trend with a large enhancement below the barrier which is attributed to the halo structure of the 6He nucleus.

Journal Article↗

Investigation of the phase behaviour of systems containing lecithin and 2-acyl lysolecithin derivatives.

A series of modified phospholipids (m-PC) possessing different acyl chains in position 2, from butanoyl to hexadecanoyl, were prepared by partial synthesis from soybean lysolecithin. They were used with soybean lecithin to construct phase diagrams containing ethanol as cosolvent, water and medium chain triglycerides (MCT) or isopropyl myristate (IPM) as oils. The weight ratios lecithin:m-PC and surfactants:ethanol were kept constant at 1:1. The results indicate that the m-PCs have a strong effect on the microemulsion (L) and liquid crystalline (LC) domains in the water-rich/oil-poor part of the phase diagrams, although all diagrams correspond to a single lecithin:m-PC ratio. On decreasing the acyl chain length, and thus increasing the hydrophilicity of the surfactant, there was a corresponding increase in the L area, which moved towards the aqueous corner of the phase diagrams. The LC phase was detected only in the presence of the hexadecanoyl derivative for the systems containing MCT, and it was not detected only in the presence of the butanoyl derivative for the systems containing IPM. The use of a second hydrophilic surfactant to adjust the packing properties of the lecithin-alcohol systems, and/or to increase the fluidity of the surfactant film, increased the region of existence of the isotropic systems. This may be of importance in the formulation of drug delivery systems, especially those which are diluted by biological fluids upon administration.

Chemistry, Pharmaceutical↗

On the stability of ascorbic acid in emulsified systems for topical and cosmetic use.

Several O/W microemulsions, O/W and W/O emulsions and a W/O/W multiple emulsion were prepared using non-ionic, non-ethoxylated, skin compatible emulsifiers. Ascorbic acid (vitamin C) was added to the emulsified systems and its stability against oxidation was studied at 45.0 degrees C in aerobic conditions and compared with that in aqueous solutions at different pH values. All emulsified systems provided protection to ascorbic acid, as its degradation rate, which increased with increasing pH, was slower in emulsified systems than in aqueous solutions. The highest protection of ascorbic acid was when it was dissolved in the inner aqueous phase of the W/O/W multiple emulsion, both at 45 and at 20 degrees C for long storage. A pseudo first-order mechanism was hypothesised for ascorbic acid degradation in the experimental conditions for as long as abundant dissolved oxygen was present.

Administration, Topical↗

Influence of phase transformation on indomethacin release from microemulsions.

The release rates of indomethacin from microemulsions containing water, isopropyl myristate, lecithin, lysolecithin and alcohol are reported. Depending on the composition, the microemulsions transformed on contact with the release medium into emulsions, liquid crystals, or remained as microemulsions. The release rates, measured by monitoring the change in pH of an acceptor phase as the release system was diluted into it, were consistent with an interfacial barrier being the rate-limiting step for solute release. The release rates were found to be dependent on the size of the disperse phase after dilution with the release medium, and on the alcohol used in the formulation. Microemulsions that remained transparent after dilution produced rate constants lower than those that transformed into emulsions. The rate constant for the microemulsion that transforms into liquid crystals was not calculated because of the broad dispersion, but the percentage of drug released was much lower than those from the others systems. The release rates were too rapid to allow sustained drug release, while the release observed for the microemulsion that transformed into liquid crystals was consistent with the slow release required for drug delivery applications.

Anti-Inflammatory Agents, Non-Steroidal↗

Investigation on the detergent role in the function of secondary quinone in bacterial reaction centers.

In this paper are reported studies on the detergent role in isolated reaction centers (RC) from Rhodobacter sphaeroides, over a large range of lauryldimethylamino-N-oxide (LDAO) concentrations, in influencing the thermodynamics of the quinone exchange reaction as well as the protein aggregation. The occurrence of the quinone exchange reaction between the QB-binding site (where QB is the second quinone molecule of two in the RC) and the ubiquinone 0 dissolved in the different environments (water, LDAO micelles and detergent phase of the protein-detergent complex) has also been analyzed. Measurements carried out in QB-depleted RC to which exogenous quinone has been added show that the relative amplitudes of the slow and fast phase of the recombination reaction depend on this parameter. The overall amount of the restored QB-functionality is affected by the concentration of the LDAO in solution. Interpolation of the titration curves with a quadratic function obtained by simple considerations allowed the binding constant of UQ0 to the QB-binding site to be calculated. From the fitting procedure, the distribution of the quinone in the different environments present in solution was evaluated, indicating that the exchange reaction can take place only between the QB-site and the detergent phase. The dependence of the quinone pool size upon the volume of the phase in which the interacting quinone is solubilized is also discussed. The increasing difficulty in saturating the QB-pocket above the LDAO critical micellar concentration is finally related to the association of protein-detergent complexes to form large protein clusters.

Detergents↗

Primary tuberculosis of the penis.

We present a case of primary tuberculosis of the inner lining of the prepuce in a 63-year-old man. The condition resembled carcinoma. The diagnosis was based on histopathology and on M. tuberculosis culture. Successful treatment was by a combined medical and surgical approach. The rarity of the case is emphasized.

Antitubercular Agents↗

Chronic cryptosporidiosis in patients with AIDS: stable remission and possible eradication after long-term, low dose azithromycin.

AIMS: To investigate the effectiveness of long term, low dose azithromycin treatment for chronic cryptosporidiosis in patients with AIDS. METHODS: Azithromycin was administered as initial daily treatment to 13 patients with AIDS: 6 patients received 500 mg for 30 to 40 days (mean 35); 3 patients received 1000 mg for 21 to 50 days (mean 37); and 4 patients received 1500 mg for 20 days. Nine of the 13 patients were also given low dose maintenance treatment with different schedules of azithromycin for 30 to 360 days (mean 129). Patients were monitored, during and after treatment, for parasite shedding in stool and for daily stool frequency and body weight. All but one patient had severe immunodeficiency. RESULTS: Long term, low dose maintenance treatment was associated with major clinical and parasitological benefits: there was probable eradication of infection in 2 patients, and 7 patients showed a complete response with persistent high decrease (5 patients) or clearance (2 patients) of parasite in stool. The drug was well tolerated, and there was no relapse either during treatment or during follow up (up to 21 months). These results were more impressive than those observed after the short term initial course of azithromycin, which was unable at any tested dose to achieve parasite clearance in stool (except in the patient with less advanced immunodeficiency) or to prevent relapse in 3 patients who discontinued treatment. Reversible side effects occurred with the 1500 mg daily dose. CONCLUSIONS: Long term, low dose azithromycin is well tolerated and may induce stable remission of chronic cryptosporidiosis in patients with AIDS. It may lead to probable eradication of the infection in some patients, even those with severe immunodeficiency.

AIDS-Related Opportunistic Infections↗