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Biomedical subjects

L Mariani

Publications and source records attributed to L Mariani.

At least 181 records · Page 10Linked to original sources

Liver DNA alkylation after a single carcinogenic dose of dimethylnitrosamine to newborn and adult CFW Swiss mice.

N-nitrosodimethylamine N-demethylase activity, DNA alkylation, capacity for O6-methylguanine repair and cell proliferation were measured in livers of newborn and adult CFW mice after a single carcinogenic dose of DMNA. DNA alkylation was found in newborn and adult mouse livers but it was significantly higher in the newborn. 6- and 7-methyl substitutions of guanine were identified by HPLC analysis in newborn and in adult mouse livers. Metabolic 14C incorporation into adenine and guanine was observed only in liver DNA of newborns. O6-methylguanine levels were higher in newborn than adult mice after a single i.p. dose of [14C]DNMA. Liver DNA repair capacity measured as O6-meG-DNA methyltransferase was higher in adults than in newborns. De novo liver DNA synthesis was more inhibited by DMNA pretreatment in newborn than in adult mice. The relationship between these parameters and the greater neonatal liver tumor susceptibility is discussed.

Alkylation↗

In vitro and in vivo methazolastone-induced DNA damage and repair in L-1210 leukemia sensitive and resistant to chloroethylnitrosoureas.

DNA damage caused by methazolastone [an analogue of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide which does not require metabolic activation] was investigated in L-1210 leukemia which is sensitive to this drug and in a L-1210 subline [L-1210/N,N-bis(2-chloroethyl)-N-nitrosourea (BCNU)] which is resistant to both chloroethylnitrosoureas and methyltriazenes. Both in vitro and in vivo metazolastone caused formation of DNA alkali-labile sites (assessed by alkaline elution techniques) which were present in similar amounts and repaired at a similar rate in L-1210 and L-1210/BCNU. This suggests that these lesions are not crucial to methyltriazenes activity. DNA alkali-labile sites may be due to the removal of 7-methylguanine by 7-methylguanine-DNA glycosylase which showed the same activity in L-1210 and L-1210/BCNU. Flow cytometry studies revealed that in L-1210 but not in L-1210/BCNU methazolastone induced an arrest of cells in SL-G2-M phases. This blockade was delayed, occurring after at least two cell divisions after drug treatment and therefore appeared temporally unrelated to the presence of DNA alkali-labile sites. There was three times more O6-methylguanine-DNA methyltransferase in L-1210/BCNU than in L-1210 suggesting that methylation of O6-guanine is an important lesion for methyltriazenes activity and resistance to this drug may be linked to its repair.

Animals↗

Results of clinical trials with ciprofloxacin in Italy.

The Authors report about the results of 23 clinical trials carried out in Italy with oral formulations of BAY o 9867 (ciprofloxacin) in the treatment of infections in various sites of the body. Altogether 644 patients were evaluated for therapeutic efficacy; positive clinical results were obtained in 95 to 100% of the treated patients, according to the site of the infection. The bacteriological examinations performed on 575 cases show eradication in 89.22%, eradication with relapse or reinfection in 2.26%, and persistence in 6.09%. Adverse reactions were observed in 38 out of 646 patients (5.89%); none of them, however, were severe or irreversible.

Adolescent↗

Cell cycle modelling.

Models able to describe the events of cellular growth and division and the dynamics of cell populations are useful for the understanding of functional control mechanisms and for the theoretical support for automated analysis of flow cytometric data and of cell volume distributions. This paper reports on models that we have developed with this aim for different kinds of cells. The models are composed by two subsystems: one describes the growth dynamics of RNA and protein, and the second accounts for DNA replication and cell division, and describe in a rather unitary frame the cell cycle of eukaryotic cells, like mammalian cells and yeast, and of prokaryotic cells. The model is also used to study the effects of various sources of variability on the statistical properties of cell populations, and we find that in microbial cells the main source of variability appears to be an inaccuracy of the molecular mechanism that monitors cell size. In normal mammalian cells another source of variability, that depends upon the interaction with growth factors which give competence, is apparent. An extended version of the model, which comprises also this additional variability, is presented and used to describe the properties of mammalian cell growth.

Amoeba↗

Oral route administration of medroxyprogesterone acetate (MAP) at high doses in the treatment of advanced breast cancer: clinical results.

Twenty-six patients with metastatic breast cancer were treated with high dose medroxyprogesterone acetate (MAP) p.o. according to currently available pharmacokinetic data (2000 mg/day b.i.d. for 30 days, 1000 mg/day for the following 60 days). Objective response (WHO criteria) was obtained in seven patients (CR + PR = 27%), with good results on visceral and soft tissue localizations; performance status improvement and/or pain relief was obtained in twenty-three (88%). Oral high dose MPA seems to be an effective and well tolerated palliative treatment in advanced breast cancer.

Administration, Oral↗

[Substances with central nervous system activity. Derivatives of octahydro-1,4-dihydroxypyrrolo(1,2-a)pyrazine-6-carboxylic acids].

Compounds with potential activity on the Central Nervous System were prepared starting either from 2,5-diethoxycarbonylpyrrolidine or from N-benzyloxycarbonyl-2,5-pyrrolidinedicarboxylic acid anhydride. By the Arndt-Eistert reaction it was possible to obtain chain lengthening at position 6. The carboxy group was also successfully reduced to a hydroxymethyl group. The synthetic work was completed with the synthesis of some derivatives having a phenyl ring condensed at position 7 and 8. Some pharmacological data on the Central Nervous System depressant activity of the prepared compounds are also reported.

Aggression↗

Lack of genotoxic properties of the hair-dye component N-methyl-amino-2-nitro-4-N',N'-bis-(2-hydroxyethyl)-aminobenzene, in mammalian cells in vitro, and in yeasts.

N-Methyl-amino-2-nitro-4-N',N'-bis-(2-hydroxyethyl)-aminobenzene is a hair-dye ingredient. Its potential ability to induce gene mutations, in the yeast S. pombe and in cultured mammalian CH-V79 cells, mitotic gene conversion in the yeast S. cerevisiae, and unscheduled DNA synthesis in cultured human HeLa cells was evaluated. The chemical proved unable to induce detectable genotoxic effects according to these tests. The present data, together with others that show that the chemical is not mutagenic in Salmonella typhimurium or Drosophila, and is not clastogenic in mammalian cytogenetic assays (in vitro or in vivo), strongly support the non-genotoxicity of the chemical.

Animals↗