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Biomedical subjects

A Andreoni

Publications and source records attributed to A Andreoni.

At least 37 records · Page 2Linked to original sources

Time-resolved luminescence spectroscopy of photosensitizers of biomedical interest.

Studying the fluorescence decay of chromophores, either used as fluorescent labels to stain specific biomolecules or as photosensitizers to produce irreversible chemical or physico-chemical modifications on biological substrates, is being demonstrated to be a valuable method of investigating the interactions underlying a variety of phenomena. In fact, all possible primary steps in a photosensitized biological system are phenomena that may occur during the chromophore S1 lifetime and act as quenching mechanisms of the S1 state. Thus they can be identified, and the relative importance of the corresponding transient species quantitatively determined, with suitable techniques of time-resolved fluorescence spectroscopy. The examples discussed in this paper concern both tumor photosensitizing drugs, such as anthracyclines and porphyrins, and skin sensitizers (e.g. furocoumarins).

Luminescence↗

Effects of cholinergic muscarinic antagonist pirenzepine on GH response to GHRH 1-40 in patients with anorexia nervosa.

The effects of cholinergic muscarinic receptor antagonist pirenzepine on the GHRH-induced GH release were studied in 10 adolescent females with anorexia nervosa at different stages of the disease, in 5 adolescent females with eating disorders and in 5 normal adolescents. The patients were characterized according to psychological (DSM III-R), endocrinological (GnRH test), nutritional (Somatomedin-C, T3), and clinical (% IBW, duration of the amenorrhoea) criteria. On two separate occasions, each subject received an i.v. bolus injection of GHRH 1-40 (1 microgram/kg) alone or preceded by pirenzepine (0.6 mg/kg i.v. 5 min before GHRH 1-40). GHRH 1-40 injection induced a significantly (P less than 0.05) higher GH increase in the patients with anorexia nervosa at the acute stage as compared with the controls. Pirenzepine did not abolish opportunely the exaggerated GH response to GHRH 1-40 in anorectic patients at the acute stage unlike the control, who showed the blockade of GHRH-induced GH release by the cholinergic muscarinic antagonist (P less than 0.05). The anorectic adolescents at the non acute stage and the adolescents with eating disorders showed varying reductions of GH response; however, pirenzepine produced a blunted suppression of GHRH-induced GH increase as compared to the controls, which was not statistically significant. Somatomedin-C values were significantly (P less than 0.05) lower in anorectic patients at the acute stage as compared with controls. The abnormal activity of cholinergic system in anorectic patients, as our data show, could induce the GH hypersecretion through an inhibitory influence on the somatostatinergic function. The reduced somatomedin-C levels, a specific malnutrition index in anorectic patients, produce a modified feed-back on the hypothalamic site (somatostatin) and/or directly on the pituitary, following the GH hypersecretion.

Adolescent↗

Recent developments in imaging diagnosis in fractures of the acetabulum: the role of CAT and tridimensional reconstruction.

The authors report their experience in a radiographic study of the treatment of 22 cases of fractures of the acetabulum. All the patients were studied using both traditional radiography and CAT, and the results were then compared. In 17 cases (77%) the CAT images were integrated with a tridimensional reconstruction (3D). The diagnostic aid provided by CAT was of crucial importance in planning treatment and selecting the most suitable surgical approach. Furthermore, 3D reconstruction may provide a valuable link between traditional radiography and CAT in evaluating complex fractures. The authors conclude that a comprehensive radio-diagnostic study should be a routine preoperative procedure in complex fractures of the acetabulum, and in all cases where traditional radiography yields doubtful results.

Acetabulum↗

Cell photosensitization by 5-iminodaunomycin activated with red light.

5-Iminodaunomycin, an anthracycline antitumor drug exhibiting an absorption peak at 595 nm, is shown to photosensitize in vitro cell kill. The photoactivation is performed irradiating the culture dishes during the incubation with the drug for 2 h with 34 mW/cm2 intensity, that is with light doses of up to 245 J/cm2. Long-term effects of administering 50 ng/ml and light for 2 h are studied in terms of growth curves. We show that photoactivation enhances the dark toxicity by a factor of about 10. Immediate cell death is produced by irradiating the cells in the presence of higher drug concentrations (e.g., 1000 ng/ml) which, however, are not toxic in the short term if administered in the dark. The viable cell percentage decreases at increasing light doses, being about 0.6% at the maximum dosage. Administering lower light doses, such as 30 J/cm2, which corresponds to an exposure duration of 15 min, has a short-term effect on the cell survival that strongly depends on the timing of the exposures within the incubation period.

Animals↗

Triplet state characteristics and singlet oxygen generation properties of anthracyclines.

The triplet states of adriamycin (Ad), daunomycin (D) and two daunomycin analogues, daunomycinone (Dc) and daunomycin N-trifluoroacetamide (DAc), have been studied using laser flash photolysis and pulse radiolysis techniques. Triplet lifetimes, molar absorption coefficients, energy levels and quantum yields have been obtained for Dc and DAc, and estimated for D and Ad. Time-resolved near-infrared singlet oxygen luminescence measurements have been carried out on D, Ad and 5-iminodaunomycin (5-ID) in 2H2O solution and Dc in benzene solution at room temperature. Singlet oxygen quenching by the water-soluble anthracyclines was observed and a second-order rate constant of approx. 10(8) M-1.s-1 obtained. Electron spin resonance experiments have demonstrated that D photoexcited at lambda less than or 365 nm gives rise to singlet oxygen as shown by its reaction with 2,2,6,6-tetramethyl-4-piperidone to give the corresponding nitroxyl radical. Although all the anthracyclines studied have the ability to photosensitize the formation of singlet oxygen, the quantum yields are very low (phi delta approximately 0.02-0.03), suggesting that these anthracyclines would be poor photodynamic sensitisers.

Acetamides↗

Laser time-resolved fluorescence study of the interaction between anthracyclines and cardiolipin.

The molecular interaction between cardiolipin vesicles and two representative anthracyclines, daunomycin and 5-iminodaunomycin, has been studied at pH 7.1 by laser time-resolved fluorescence, for a cardiolipin-to-anthracycline ratio r ranging from 0.02 to 5. The fluorescence lifetime of daunomycin is 1.03 ns. For r = 0.3 - 5 a longer-lived transient (1.91 - 1.49 ns) is present and originates from the excitation of daunomycin bound on a single phosphate group of cardiolipin. At r = 0.3 two lifetimes are observed, the second one being due, partially, to free daunomycin and bound drug molecules embedded in the lipid bilayer. The fastest-decaying species is present for r = 0.5 - 2.0 and identified as two adjacent, stacked-up daunomycin molecules bound onto the two phosphate groups of the cardiolipin. In the case of 5-iminodaunomycin, a less cardiotoxic analogue, three-exponential decay is never observed and a fast-decaying component, pi approximately 0.2 ns, is already present at low r and vanishes for r greater than 0.5. The constancy of the lifetimes of the longer-lived species may originate from the reorientation of the bound drug from the hydrophilic to the lipid domain.

Antibiotics, Antineoplastic↗

A double-blind comparative study of ketanserin with atenolol in essential hypertension.

Sixty patients, with mild to moderate essential hypertension, were considered for a double-blind trial comparing the effects of ketanserin and atenolol. After 2 weeks of placebo, a group of 30 patients was given ketanserin 20 mg twice daily for 15 days and 40 mg twice daily for the subsequent 45 days, while the second group (30 patients) was given atenolol for 60 days at the dose of 100 mg once daily. Blood pressure and pulse rate in the supine and standing positions were evaluated every 15 days. After the beginning of treatment with ketanserin, there was a gradual but highly significant decrease of the diastolic and systolic blood pressure values. No important side-effects or significant alterations in the biochemical parameters considered were observed during treatment with ketanserin.

Adult↗

Two-step photoactivation of hematoporphyrin by excimer-pumped dye-laser pulses.

The selective excitation of high lying singlet or triplet states of hematoporphyrin has been achieved using high peak-power nanosecond pulses generated by excimer-pumped dye lasers. The interaction involves two steps: a pulse at 630 nm raises the molecules to the S1 state and a second one, at 481 nm, further excites them either to a higher singlet state if shed simultaneously or to a triplet state higher in energy than T1 if it arrives delayed with respect to the pulse at 630 nm by a time interval longer than the S1 lifetime. Photodegradation of L-tryptophan (100 microM in 30vol.%methanol-70vol.% buffer, pH 7.4) sensitized by 21 microM hematoporphyrin is reported. While a pure type-II mechanism, which obeys the time-intensity reciprocity law up to peak-intensity values of about 20 MW cm-2, is photosensitized by pulses at 630 nm, strong non-linearities are found for pulsed irradiation at both 630 nm and 481 nm, i.e. when the sensitizer is pumped to high lying singlet states and when it is pumped to high lying triplet states. The dependence of the subsequent reactions on the presence of oxygen and their competition with the photodynamic action has been investigated; in particular, a pathway was observed in which an electron was photoejected from a hematoporphyrin high energy triplet, showing maximum efficiency when the pulses were delayed by 16.4 ns.

Hematoporphyrins↗

Photodynamic therapy in vitro and in vivo with hematoporphyrin derivative and laser light.

Photodynamic therapy is currently under investigation as a new form of treatment for solid malignant tumors in animals and in humans. The method involves photosensitization of drugs and fluorescent dyes, such as hematoporphyrin derivative (Hpd), after preferential incorporation by neoplastic cells. In in vitro experiments laser light activation completely destroys Hpd-pretreated EL4 cells. Mice bearing MS-2 fibrosarcoma treated with Hpd and laser light survived indefinitely, in comparison with control animals that were untreated or treated only with Hpd or laser light. In mice bearing the highly metastatic tumors B16 melanoma and Lewis lung carcinoma (LLC) treated with Hpd and laser light delivered through a quartz fiber optic significantly prolonged the median survival time. This therapy was compared with surgical excision of primary tumors and, for superficial nonmetastatic neoplasma MS-2, the photodynamic therapy was more effective than surgery, while for metastatic tumors B16 and LLC, there was no significant difference between the two methodologies. However, phototherapy is much less traumatic to the animals.

Animals↗

Linearity and noise sources in flow cytometry.

A model of pulse formation in flow cytometers is presented that demonstrates the proportionality between the area (or the peak height) of the fluorescence signal produced by the photomultiplier and the number of fluorochrome molecules present in the cell that cause the signal. The model clarifies the possible instrumental origins of inaccuracy in this linearity that results in a broadening of the histograms obtained. A comprehensive formula for the coefficient of variation of the unimodular histograms of an homogeneous population is presented that clearly discriminates among the different contributions of staining, possible inhomogeneity of the examined population, photon statistics, and instrumental instabilities. Finally, some experimental data are presented that show the agreement with the proposed formula.

Animals↗

Acebutolol-induced decrease of mononuclear leukocyte beta-adrenoceptors in hypertension.

The regulatory action exerted on receptors by acebutolol, a cardioselective beta-blocker containing intrinsic sympathomimetic activity, has been investigated. beta-Adrenoceptor affinity and density of human mononuclear leukocytes were assayed in hypertensive patients before and after treatment with 400 mg/day acebutolol. While receptor affinity showed no changes between pre- and post-treatment values, a statistically significant decrease has been demonstrated in receptor density following treatment. Blood pressure and heart rate were also measured in order to test the efficacy of the administered drug. All these parameters showed a fall in the post-treatment values. It is concluded that the partial agonist acebutolol, in spite of the fact that it acts clinically as a beta-blocker, has the regulatory mechanism characteristic of agonists.

Acebutolol↗