Biomedical subjects

P Moroni

Publications and source records attributed to P Moroni.

At least 19 recordsLinked to original sources

PubMed1995

The flavin-containing monooxygenases in rat liver: evidence for the expression of a second form different from FMO1.

A second form of rat liver FMO, FMO-A, was separated and purified by chromatography on Blue Sepharose Fast flow 6. This FMO-A is different from FMO1 by antigenic properties (anti-FMO-A did not cross-react with FMO1, and reciprocally) and by catalytic properties (the Km for trimethylamine was 3.8 microM and 141.4 microM for FMO-A and FMO1, respectively; the Km for imipramine was 536 microM and 17.4 microM for FMO-A and FMO1, respectively). Furthermore, N-terminal amino sequencing revealed differences in the primary structure of these two FMOs although they both contained the highly conserved FAD-binding domain (Gly-X-Gly-X-X-Gly).

Amino Acid Sequence↗

PubMed1995

Chiral sulfoxidation of albendazole by the flavin adenine dinucleotide-containing and cytochrome P450-dependent monooxygenases from rat liver microsomes.

The enantioselectivity of the in vitro sulfoxidation of the prochiral drug albendazole was investigated in rat liver microsomes. When biological material obtained from control rats and phenobarbital-, 3-methylcholanthrene-, or dexamethazone-pretreated rats was subjected to specific immunological and chemical inhibitors, it was shown that two main enzymatic systems--cytochrome P450s and flavin-containing monooxygenase (FMO)--were responsible for the sulfoxidation. Purified FMO from rat liver was used to study the enantioselectivity of this enzyme in the sulfoxidation of albendazole. The enantiospecificity of FMO is the reverse of that of the P450s. Nevertheless, each P450 isoenzyme involved in this reaction presents its own individual stereoselectivity.

Age Factors↗

PubMed1993

Stereoselective S-oxygenation of an aryl-trifluoromethyl sulfoxide to the corresponding sulfone by rat liver cytochromes P450.

Toltrazuril sulfoxide (TZR.SO) is the metabolite of the antiparasitic drug toltrazuril (TZR; 1-methyl-3-[3-methyl-4-[4-[trifluoromethyl]thio]phenoxy]phenyl- 1,3,5-triazine-2,4,6(1H,3H,5H)-trione). The results of the present paper demonstrate that TZR.SO was metabolized by rat liver microsomes to the corresponding sulfone (TZR.SO2). The reaction was mediated almost exclusively by different cytochromes P450, the most active being cytochromes P450 3A. TZR.SO exists as a racemic mixture; when each enantiomer was incubated separately in the presence of untreated rat liver microsomes, a 7.3-fold difference in the rate of S-oxygenation was found, indicating a marked substrate enantioselectivity for the reaction.

Animals↗

PubMed1992

Fatty acid conjugates of 2'-deoxy-5-fluorouridine as prodrugs for the selective delivery of 5-fluorouracil to tumor cells.

We have prepared a novel class of prodrugs by coupling 2'-deoxy-5-fluorouridine (5dFU) to oleic (18:1) and docosahexaenoic (22:6) acids, respectively. The cytotoxic activity of the drug and its conjugates (5dFU-18:1 and 5dFU-22:6) has been assayed in vitro upon HT-29, a colon carcinoma cell line of human origin. After short term (2-hr) treatments with the drugs, both fatty acid conjugates of 5dFU showed cytotoxic activity in a dose-dependent way, while 5dFU alone was devoid of toxic effects within the whole range of concentrations (10-200 microM) tested. Following long term (24- or 48-hr) incubations only a fraction of the HT-29 cell population was sensitive to 5dFU, the rest of the population being resistant even at the highest concentration tested (200 microM). In contrast, 5dFU-oleic acid and, particularly, 5dFU-docosahexaenoic acids appeared toxic for the whole population of HT-29 cells under the same experimental conditions. The considerable gain in cell toxicity and, to a lesser extent, in selectivity resulted from the conjugation since the toxic effect of the drug alone was not modified when equimolar mixtures of 5dFU and fatty acids were assayed. These results confirm a previous study on the cytotoxicity of fatty acid derivatives of chlorambucil toward malignant lymphoblastoid cells and reinforce the potential use of fatty acid conjugates as efficient anti-tumor prodrugs.

Cell Survival↗

PubMed1986

Clinical pharmacology of tritoqualine: a comparative study against dexchlorpheniramine in allergic rhinitis.

The effect of tritoqualine on seasonal allergic rhinitis caused by grass pollen was compared to that of dexchlorpheniramine maleate (DCPM) in 21 patients randomly allocated into two parallel groups. There were rapid improvements of all symptoms considered after treatment with either tritoqualine or DCPM. A significant reduction of plasma histamine concentrations was observed during the treatment with tritoqualine whereas no modification occurred with DCPM. Finally, it was shown that tritoqualine did not modify reaction times to visual and auditive stimuli whereas DCPM induced a significant slowing-down of the reaction time to visual stimuli. From this pilot study tritoqualine appears to have the same efficacy for the treatment of seasonal allergic rhinitis as classic anti-H1 antihistamines, but without central nervous system side-effects.

Adolescent↗

PubMed1985

Skin pathology in industrial workers exposed to synthetic corticosteroids.

Systemic and cutaneous side effects observed in some workers of a company producing synthetic corticosteroids are described. The production process and the results of clinical and laboratory investigations are shown. A high incidence of skin and internal disorders (erythema, telangiectasia, acne, purpuric lesions and inhibition of the pituitary-adrenal axis) were found.

Acne Vulgaris↗

PubMed1983

[Effect of 13-cis-retinoic acid (Ro 4-3780) in the therapy of severe cystic acne].

Five subjects with serious cystic acne, two of which were also affected by hydrosadenitis, were examined during a treatment with 13-cis-retinoic acid. The drug was given at decreasing doses: 0.9 mg/kg body weight for a period of six weeks, followed by a second six weeks period at 0.6 mg/kg and lastly by another 9 months period at 0.3 mg/kg. The patients had a good response to the treatment with a rapid reduction of the number and of the severity of the acneic lesions, with the only exception of one subject who had a relapse at the 18th week. This study, limited to a small number of patients, suggest that 13-cis-retinoic acid may be used in severe cystic acne with a higher dosage in the presence of complicating hydrosadenitis.

Acne Vulgaris↗

PubMed1979