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Biomedical subjects

R Leone

Publications and source records attributed to R Leone.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1990

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↗
PubMed1990

[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↗
PubMed1989

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↗
PubMed1988

Pharmacokinetics and human tissue penetration of flurithromycin.

The relationship between concentrations in serum and levels in tissue of flurithromycin, a new fluorinated macrolide, was determined in patients undergoing maxillofacial surgery and thoracotomy. All patients received 500 mg of flurithromycin orally every 8 h. Drug levels in serum, bone, soft tissue, lung, and pericardial fluid were determined microbiologically. The total amount of antibiotic per gram of tissue was calculated on the basis of the concentration in the supernatant of the homogenate. From the parallel course between free concentrations in serum and calculated contents in interstitial fluid tissue, it was concluded that the tissues examined were easily accessible by flurithromycin; penetration values measured by the ratio of areas under the curve were 8.3 for lung, 3.6 for bone, and 0.8 for soft tissue. The results of the pharmacokinetic study suggest that accumulation of the drug during repetitive multiple doses is predictable. Mean residence times were 10.2 and 8.3 h in groups 1 and 2, respectively. For bacteriostatic drugs such as macrolides, not only very high but also prolonged concentrations in tissue lead to favorable therapeutic result.

Adult↗
PubMed1988

Incidence and prognostic significance of autoantibodies against erythrocytes and platelets in chronic lymphocytic leukemia (CLL).

Antiglobulin Test (AT), and Dixon Tests (DT) have been studied in 100 patients with CLL. Thirty-five patients were Rai stage 0 and I, 19 patients stage 2, 13 patients stage 3 and 33 patients stage 4. Twelve patients showed a Red Blood Cells Autoantibodies (RBCAb) positivity; a positivity (direct, indirect, or both) of DT was present in 74% of patients. The presence of autoantibodies against erythrocytes and platelets did not influence survival curves, but anemia and thrombocytopenia are risk factors for survival, independently of the presence of an autoimmune disorder. Nine patients RBCAb positive and DT positive showed the worst survival curve, five out of these were anemic and one thrombocytopenic and anemic.

Aged↗
PubMed1987

Multisystem toxicity of indomethacin: effects on kidney, liver and intestine in the rat.

Some studies on the relationships among toxic effects in rat liver, kidney and intestine have been carried out. Indomethacin caused a marked reduction in microsomal enzymes, such as cytochrome P450, cytochrome b5 and aminopyrine N-demethylase in the kidney and the liver, greater in the former and for a shorter time than in the latter. Indomethacin induced intestinal lesions and marked overgrowth of intestinal bacteria, mainly of aerobic bacteria in the first 24 hours after its administration and anaerobic bacteria such as Clostridii in the second day. These findings enable us to suggest that the drug induces multisystem lesions through different mechanisms involving either a direct effect on the tissue or other microbiological or pharmacological factors.

Aminopyrine N-Demethylase↗
PubMed1987

Two-cycle cisplatin kinetics in patients with ovarian and mammary cancer.

The kinetics of platinum (Pt) in patients treated for two-cycle therapy with cis-DDP for ovarian or mammary carcinoma were investigated. Cis-DDP, at a dose of 65 mg/m2, was administered i.v. over 60 min to 6 patients every 3 weeks. Plasma was collected before and 1, 2, 4, 8, 24, and 48 h after the start of the first and second infusions. The levels of Pt in the patients' plasma were determined by flameless atomic absorption spectroscopy. Plasma levels were analyzed by a two-compartment open pharmacokinetic model. Plasma decline was biphasic, both after the first and the second cycle. In all patients, the calculated t1/2 of the rapid phase increased after the second cycle (from a mean value of 0.39 h to 2.45 h), whereas the t1/2 of the slow phase increased about threefold in 3 subjects. In the latter, we observed an increase of AUC and a decrease of total body clearance.

Adult↗
PubMed1987

Kinetics of platinum in cancer patients treated with cisplatin at different doses.

In previous work the authors observed that platinum (free and bound) does not seem to accumulate in the peripheral compartment following the administration of two courses of cisplatin (cis-DDP) therapy (65 mg/m2) in patients with mammary and ovarian cancer. The aim of the present work was to study the disposition of platinum (Pt) after a higher dose of cis-DDP, to verify the rate of free drug penetration into the tissue and to observe changes in protein binding relative to the dose. cis-DDP, at the dose of 100 mg/m2, was administered i.v. over 60 min to patients with lung cancer. Serum and urine were collected before infusion and at various intervals afterwards. The plasma and urine levels of Pt were determined by flameless atomic absorption spectrophotometry, using a Varian model AAS 1475-GTA 95. Serum levels were analysed by a two-compartment open pharmacokinetic model. After the higher dose there was a substantial increase in central volume Pt and slight increase in peripheral volume Pt as compared with levels observed previously at the lower dose. In some subjects receiving high doses elimination half-life decreased and total body clearance increased, while in others these kinetic parameters were unchanged in comparison with those observed after a low dose. Protein binding seems to influence the persistence of platinum in the vascular space, modifying to a minor degree tissue penetration of the drug.

Adult↗