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Biomedical subjects

R Leone

Publications and source records attributed to R Leone.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1984

Metabolic activation of 2-aminofluorene in the Salmonella mutagenicity assay by different S-9 preparations.

Before exerting a carcinogenic or mutagenic effect, many chemicals must undergo metabolic activation. The most widely used activation system is the 9,000 g supernatant fraction (S-9) of rat liver homogenate, prepared from male rats pretreated with Aroclor 1254 (AC). The present study compares the capabilities to induce metabolic activation of 2-aminofluorene (2-AF), using different sources of S-9 preparations as a test-promutagen, both in the Ames test and in the minimal saline liquid medium (MSLM). In particular, S-9 preparations of liver and kidney fractions from male rats and guinea pigs, with or without AC or phenobarbital (PB) pretreatment, were used. The 2-AF was tested in Salmonella typhimurium TA 1538 strain (frame-shift mutation) at different level of concentrations. In the Ames test the enzymatic activation of liver fractions, induced by PB, shows a large increase of mutagenicity of 2-AF in both animal species studied. The AC pretreatment in rats significantly reduced the mutagenic activity of 2-AF, when compared with controls. With rat renal microsomes no differences were observed in mutagenicity as compared with controls. A significant increase was seen in the microsomes of guinea pigs pretreated with AC. The experiments carried out with MSLM confirmed the results in full.

Animals↗
PubMed1980

The acute inflammatory process in copper-deprived rats.

Copper is clearly involved in experimental and human inflammation, as suggested by a large body of data, some of which obtained in our own laboratories. With the purpose to further investigate the role of copper in the inflammatory process, we have studied the development of carrageenan foot oedema and carrageenan pleurisy in rats treated with a copper-deficient diet according to the following schedule: (1) foot oedema in rats maintained on a 0.4 p.p.m. copper-deficient diet for 1 and 3 months; (2) foot oedema and pleurisy in rats maintained on a 0.2 p.p.m. copper-deficient diet for 1 month; (3) foot oedema and pleurisy in rats maintained on a 0.6-0.8 p.p.m. copper-deficient diet for 5 months. With these experiments we have shown an enhancement of the inflammatory reaction which, apparently, is both time and copper content dependent. The possibility that endogenous copper could play a key role in modulating the acute inflammatory process is discussed.

Acute Disease↗
PubMed1979

Concerning the role of endogenous copper in the acute inflammatory process.

The development of two models of acute inflammation (carrageenan-induced foot oedema and pleurisy) was studied in rats after 1 month of a 0.2 p.p.m. copper-deficient diet and after 5 months of a 0.6-0.8 p.p.m. copper-deficient diet. A 'pro-inflammatory' effect of copper deficiency was observed with the 0.2 p.p.m. diet, whilst no effect was evident following the 0.6-0.8 p.p.m. copper deficient diet. These results are briefly commented upon.

Acute Disease↗