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Biomedical subjects

R Leone

Publications and source records attributed to R Leone.

At least 55 records · Page 3Linked to original sources

[The hadron therapy project].

The neologism "hadrontherapy" means radiotherapy with hadrons, which are the particles constituted by quarks, such as protons, neutrons and ions. The theoretical considerations about the clinical advantages this treatment modality can yield and the results obtained at the centers where it has already been used justify the proposal to project a center of this kind also in our Country. To this purpose, two of the authors of this paper (U. Amaldi, G. Tosi) founded the TERA Group formed by physicists, engineers and radiotherapists who work in close collaboration on a feasibility study for a hadrontherapy facility. The first aim of the Hadrontherapy Project is to design a center equipped with a synchrotron which, at the beginning, will accelerate negative hydrogen ions (H-) which will first produce 70-250 MeV proton beams and, then accelerate light ions (up to 16O) to 430 MeV/amu. This accelerator will serve four or five treatment rooms where patients can be irradiated simultaneously. Two rooms will be equipped with a fixed horizontal beam for the treatment of eye, head and neck tumors; the others will be equipped with rotating gantries to administer, in any clinical situation, really adequate treatment. Such a unit, when enough experience is fained, will allow at least 1000 patients to be treated yearly. The synchrotron injector will be designed so as to allow, parallel to the radiotherapy activities, other applications of medical and biological interest such as: the production of radioisotopes for diagnostic use (especially positron emitters), the analysis of trace elements through the PIXE technique and the production of thermal and epithermal neutrons for boron neutron capture therapy.

Biophysical Phenomena↗

Influence of glutathione administration on the disposition of free and total platinum in patients after administration of cisplatin.

The kinetics of platinum (Pt) was studied in 12 patients suffering from non-small-cell lung cancer or pleural mesothelioma. Each subject received an infusion of cisplatin (CDDP, 80 mg/m2), and six patients were pretreated with glutathione (GSH, 2.5 g given i.v.) at 15 min prior to the cisplatin infusion. After a 3- to 4-week interval, all patients were given a second course of treatment on the same schedule. A biexponential model was fitted to plasma concentrations of total and ultrafilterable Pt. The excretion of Pt in urine was evaluated during the first 48 h after the CDDP infusion. Following the administration of CDDP alone or with GSH pretreatment, the pharmacokinetic parameters of Pt did not significantly differ between the treatments. Also, the unbound fraction determined at each sampling time did not vary significantly between the treatments. However, it is noteworthy that the mean values obtained for the terminal half-life, the volume of distribution, the renal clearance, the percentage of the dose excreted in the urine, and the mean residence time of total Pt were higher in patients who had been pretreated with GSH, suggesting that GSH might increase both the rate of Pt elimination and the extent of Pt distribution and, as a consequence of the latter, might prolong the residence time of Pt in the body. In addition, the unbound fraction of Pt from the 4th to the 48th was higher following the first dose of CDDP+GSH than after treatment with CDDP alone. Because of the rather high variability in the values of the parameters obtained, further work is planned using a larger number of patients.

Antineoplastic Combined Chemotherapy Protocols↗

Mutagenic activity in wastewater concentrates from dye plants.

Wastewater concentrates from the wastewater treatment systems of three dye plants were tested for mutagenic activity in Salmonella typhimurium TA98 and Escherichia coli WP2uvrA using a fluctuation assay. Concentrates were prepared by passing samples of wastewater (5-6 or 30 litres) through two porous resins (XAD-2 and XAD-7) in series. S. typhimurium in the presence of microsomal activation proved to be the more sensitive marker of mutagenicity. Mutagenic responses were observed in concentrates from all three plants tested. The results show that mutagenic activity was particularly high in the incoming waters and increased after active, biological treatment. Physico-chemical treatment may be effective in decreasing mutagenic activity, but only if appropriately used.

Coloring Agents↗

Hepatic and intestinal effects of flurithromycin and erythromycin in the rat.

The effects of flurithromycin (30-100 mg/kg p.o.), a fluorinated macrolide, on rat hepatic enzymes and intestinal microflora have been compared with those of equal doses of erythromycin. This latter drug significantly decreases cytochrome b5, cytochrome P-450 and aminopyrine N-demethylase and moderately influences intestinal microbial flora. Flurithromycin showed almost opposite characteristics, with no hepatic interaction and marked effects on some bacterial species (e.g. Bacteroides) known to facilitate the colonization of pathogenetic bacteria.

Animals↗

Beta-adrenoceptor modulation in a case of pure autonomic failure.

In a patient with pure autonomic failure, exercise did not modify beta-adrenoceptor density, probably due to an insufficient increase in plasma catecholamines. Isoproterenol infusion increased the number of beta-adrenoceptor by only 17%. Since in control subjects an increased beta-adrenoceptor level was found, following both physical stress and isoproterenol infusion, we suggest that the lack of increased beta-adrenoceptor levels may contribute to the poor circulatory adjustments observed in autonomic dysfunction during activities involving the sympathetic nervous system.

Autonomic Nervous System Diseases↗

C-MYB activation and the pathogenesis of ovarian cancer.

We have detected the expression of the MYB proto-oncogene in ovarian cancer. This oncogene was thought to be expressed in a tissue-specific manner in cells of hematopoietic lineage. Total RNA from three established cell lines and four human primary ovary cancers was examined by Northern and Southern blot, RNAse protection, in situ hybridization and cytogenetic analysis. A 3.8 kb RNA transcript was present in one human primary cell culture which is the same size as that found in the immature myeloid HL60 cell line. No expression was detected in normal ovary tissue. Southern blot analysis of DNA from five ovarian tumors indicated that this gene is not rearranged. Chromosomal analysis of three samples show many abnormalities in two cases and a normal karyotype in another one. The presence of MYB transcript in ovarian cancer suggests that MYB may play a specific role in the pathogenesis of this disease.

Blotting, Northern↗

[The reduction of beta-adrenoceptor density and the suppression of ectopic ventricular activity with low doses of amiodarone].

In 5 patients with frequent premature ventricular ectopic beats, refractory to other antiarrhythmic treatments, amiodarone, given orally at the dose of 200 mg once a day for 4 weeks, reduced beta-adrenoceptor density from 202.9 +/- 62 to 101.1 +/- 33 fmol/mg protein (p < 0.01). Similarly, kd decreased from 21.0 +/- 6 to 3.9 +/- 1 (p < 0.05). Changes in beta-adrenoceptor population were accompanied by a marked reduction in mean premature ventricular complexes (PVC) frequency from the control value of 428.9 +/- 150.3 to 13.4 +/- 10.7 PVC/h (p < 0.05) and by a decrease in heart rate, from 83.8 +/- 4 to 73.9 +/- 4 b/min (p < 0.01). On the contrary, mean arterial pressure remained unchanged. Patients did not show side effects during treatment. Therefore, low dose oral amiodarone has important pharmacologic and therapeutic effects. It significantly reduces lymphocyte beta-adrenoceptor density and is effective in treatment of ventricular arrhythmias. Additional studies were performed in vitro exposing lymphocytes to increasing concentrations of amiodarone. The analysis of variance for repeated measures showed that amiodarone-induced reduction in lymphocyte beta-adrenoceptor density is a dose-depending phenomenon. Accordingly, treatment with doses of amiodarone higher than that used in the present study may induce a major reduction in lymphocyte beta-receptor density and exert a depressant cardiac effect.

Adult↗

Indomethacin induced hepatic alterations in mono-oxygenase system and faecal Clostridium perfringens enterotoxin in the rat.

The administration of indomethacin to rats, at the dose of 10 mg/kg once daily for three days, caused a loss of microsomal cytochrome P-450 and cytochrome b5 in the liver, and a fall in drug-metabolizing enzyme activities (i.e. aminopyrine N-demethylase, NADP cyt. c. reductase). Indomethacin also induced intestinal lesions and a significant increase in Clostridium perfringens enterotoxin levels in the feces at 24 hours after both the second and third day of treatment. The above findings suggest that the development of intestinal lesion and the accompanying release of Clostridium perfringens enterotoxin, as well as hepatic enzyme alterations in the rat, result from indomethacin administration. Some of the data in this paper were presented at the Meeting of British Pharmacological Society in Ireland, July 6th-8th, 1988.

Aminopyrine N-Demethylase↗

[Increase in the lymphocyte beta-adrenergic receptor population during physical exercise].

The risk of cardiac arrhythmias during exercise and the recovery period may be enhanced by sympathetic activity. Accordingly, lymphocyte beta-adrenoceptor density was measured in 5 healthy men, aged between 25 and 32 years, at rest, at peak exercise and during the recovery period. Exercise increased 3H-dihydroalprenolol binding from 125 +/- 58 to 234 +/- 70 fmol/mg protein (p less than 0.02). During recovery, beta-adrenoceptor density was still higher than at rest, being 192 +/- 36 fmol/mg protein (p less than 0.02). No significant difference was found between exercise and recovery values (Tab. I). Results did not change when binding data were standardized to lymphocyte number, thus demonstrating that increases in binding were independent of exercise-induced lymphocytosis. Kd did not change significantly during the study. Since lymphocytic beta-adrenoceptor density may parallel myocardial beta-adrenoceptor density, this study suggests the myocardium may be more sensitive to the arrhythmogenic properties of catecholamines during exercise.

Adult↗

Urinary mutagenicity tests in lead-exposed workers.

Urinary mutagenic activity detected by the bacterial fluctuation assay, using Salmonella typhimurium TA98 and Escherichia coli WP2 uvrA with and without metabolic activation (S9 mix), was studied in a group of 21 workers exposed to inorganic lead and a control group of 22 non-occupationally exposed subjects. Occupational exposure to inorganic lead had no effect on urinary mutagenicity in the strains considered, with or without metabolic activation. In smokers (exposed and non-exposed), urinary mutagenic activity appeared to increase compared to non-smokers (exposed and non-exposed), only with Salmonella typhimurium TA98 in the presence of S9 mix.

Adult↗