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Biomedical subjects

M Bianchi

Publications and source records attributed to M Bianchi.

At least 307 records · Page 17Linked to original sources

[Postoperative high digestive-cutaneous fistula. Advantages of nutritional treatment].

Twenty-four patients (18 male and 6 female) with high post-surgery digestive fistulas (8 pancreatic-cutaneous, 7 duodenal-cutaneous, 4 jejunum-cutaneous, 4 ileal-cutaneous, 1 gastric cutaneous) were treated with T.P.N. and/or E.N. between 1980-1983. 17 patients (71%) recovered with spontaneous healing of fistulas in 9-92 (average 39) days. 3 patients underwent a second operation. 3 patients (12.5%) died: 2 for sepsis, 1 for cachexia. A.E. and T.P.N. were able to improve serious catabolic state and to get a better prognosis.

Adolescent↗

Enhanced xanthine oxidase activity in mice treated with interferon and interferon inducers.

Administration to mice of either interferon (IFN) or IFN inducers resulted in a marked increase of xanthine oxidase (XO) activity in different organs. Dose response studies revealed that serum XO was increased by administration of polyinosylic-polycyticylic acid (poly I-C) at doses as low as 0.1 mg/kg. In view of the well known ability of XO to generate superoxide radicals it is suggested that its induction might play a role in several biological effects of IFN.

Animals↗

An N-protected gamma-aminobutyric acid dipeptide with anticonvulsant action.

N-Pivaloyl-leucyl-gamma-aminobutyric acid (PLG) is a synthetic dipeptide with a partition coefficient of 1.67 in an ethyl acetate/water system that partially inhibits the synaptosomal uptake and activates the release of [U-14C]gamma-aminobutyric acid [( U-14C]GABA). The displacement of GABA from crude synaptic membranes by PLG occurs with an IC50 of 10(-5) M. The compound has the capacity to cross the blood-brain barrier and increase central GABA levels. Its ED50 on cardiazol -induced convulsions is 60-65 mg/kg. PLG is resistant to hydrolysis by chymotrypsin and partially inhibits the proteolytic activity of trypsin.

Animals↗

[Derivatives of N-hydroxyfenfluramine and their anorectic activity].

Some derivatives of N-hydroxyfenfluramine substituted at the oxygen atom with benzyl, N-methylcarbamoyl, aliphatic and aromatic acyl groups, were prepared and the anorectic activity was investigated in the rat in comparison with fenfluramine. The most interesting compound was N-(2,6-dimethoxybenzoyloxy)fenfluramine (XIV), which exhibited a LD50 about 5 times higher than that of fenfluramine and a remarkably delayed activity.

Animals↗

[Compounds with potential gastric antisecretory and anti-ulcer activity. IV. Synthesis of 3- and 4-phenyl-2-oxo-5-[2-(methylpiperazine-1-yl)-acetyl]- 1H-2,3,4,5-tetrahydropyrido[2,3-b] [1,4]diazepine].

Pyrenzepinelike compounds, namely 2-oxo-3-phenyl- and 2-oxo-4-phenyl-5-[2-(4-methylpiperazin-1-yl)-acetyl]- 1H-2,3,4,5-tetrahydropyrido[2,3-b] [1,4]diazepine [(VIII) and (XIV) resp.] were synthetized. Both compounds were found to be inactive in rats against carbachol stimulated gastric secretion and cold + restraint induced ulcers.

Animals↗

Bone marrow cell chromosomal aberrations and styrene biotransformation in mice given styrene on a repeated oral schedule.

Styrene's capacity to induce chromosomal aberrations was studied in bone marrow cells of CD1 male mice. No mutagenic effect could be detected after either a 4-day treatment course with daily oral doses of 500 mg/kg or a 70-day course with daily oral doses of 200 mg/kg. Urinary elimination of styrene metabolites related to styrene-7,8-oxide formation (i.e. phenylethylene glycol, mandelic acid, benzoic acid, phenylglyoxylic acid and total mercapturic acids) was quantitatively evaluated in the group of mice given the 200 mg/kg dose. In parallel, kinetic studies were made on styrene and styrene-7,8-oxide blood concentrations in the same group of animals. These determinations were carried out on days 1 and 70 of treatment by spectrophotometric, gas chromatographic and mass fragmentographic procedures. Not even nanograms of styrene-7,8-oxide were found in the blood of styrene-treated mice. This suggests that the metabolite does not migrate from the cellular compartment where it is formed being immediately metabolized or irreversibly bound to cellular structures. This observation could well explain the lack of mutagenic effects observed.

Administration, Oral↗

4-aminobutyric acid methyl ester hydrochloride, a precursor of 4-aminobutyric acid.

4-Aminobutyric methyl ester hydrochloride (GME) is able to cross the blood-brain barrier after intracardiac administration to the rat. GME has an LD50 of 1300 mg/kg in mice and 950 mg/kg in rats, exhibits an antiaggressive effect and is able to decrease isoniazid-induced convulsions in the rat. GME is hydrolyzed to 4-aminobutyric acid (GABA) by brain homogenates, acts as an inhibitor of GABA binding to crude synaptic plasma membranes, activates the release and inhibits the uptake of GABA by rat synaptosomes and acts as a competitive inhibitor of the so-called GABAse system in vitro.

Animals↗

Distribution, metabolism, and irreversible binding of hexamethylmelamine in mice bearing ovarian carcinoma.

The covalent binding of hexamethylmelamine (HMM) and its metabolites was studied in liver, tumor, blood, kidney, spleen, lung, brain, heart, and small intestine after a single IP injection of 2,4,6-14C-hexamethylmelamine (50 mg/kg) to C57Bl/6J female mice bearing 20-day-old M5076/73A ovarian cancer. Covalent binding to tissue macromolecules was measured 2, 10, and 40 h after injection of the drug. At 2 h liver and small intestine showed the highest levels of irreversibly bound metabolites, the lowest being found in brain and heart. Except in the small intestine, where a decrease was observed between 2 and 10 h, the level of covalent binding was constant up to 40 h. HMM metabolism was also studied. Tissue distribution of pentamethylmelamine (PMM), 2,2,4,6-tetramethylmelamine (TMM), and 2,4,6-trimethylmelamine (TriMM) was determined at the three times considered. At 2 h the drug was already extensively metabolized, TriMM being the major metabolite among those determined.

Altretamine↗

Synapsis and the formation of paranemic joints by E. coli RecA protein.

E. coli RecA protein promotes the homologous pairing of a single strand with duplex DNA even when certain features of the substrates, such as circularity, prohibit the true intertwining of the newly paired strands. The formation of such nonintertwined or paranemic joints does not require superhelicity, and indeed can occur with relaxed closed circular DNA. E. coli topoisomerase I can intertwine the incoming single strand in the paranemic joint with its complement, thereby topologically linking single-stranded DNA to all of the duplex molecules in the reaction mixture. The efficiency of formation of paranemic joints, the time course, and estimates of their length, all suggest that they represent true synaptic intermediates in the pairing reaction promoted by RecA protein.

DNA↗

Unwinding associated with synapsis of DNA molecules by recA protein.

In the presence of adenosine 5'-[gamma-thio]triphosphate, a nonhydrolyzable analog of ATP, Escherichia coli recA protein extensively unwinds duplex DNA in a reaction that is strongly stimulated by either homologous or heterologous single-stranded DNA [Cunningham, R.P., Shibata, T., DasGupta, C. & Radding, C.M. (1979) Nature (London) 281, 191-195]. In the presence of ATP and homologous circular single-stranded DNA, recA protein also unwinds circular duplex DNA that is nicked at a heterologous site. When DNA ligase seals this nick, the product is a highly negatively superhelical molecule that can be relaxed by E. coli topoisomerase I. This unwinding requires a high degree of homology since phi X174 single-stranded DNA does not serve as a cofactor in the unwinding of G4 DNA, even though these molecules are 70% homologous. Like synapsis itself, and unlike strand exchange which follows synapsis, unwinding is sensitive to inhibition by ADP. Because recA protein unwinds duplex DNA when neither the single-stranded DNA nor the duplex DNA has a free end in the region of homology, unwinding can be initiated or mediated by a synaptic structure that differs from that of a simple D loop. The paired circular single strand in the synaptic structure behaves like one strand of an under-wound helix because E. coli topoisomerase I can interwind it with its complement.

Adenosine Diphosphate↗

Micronucleus induction in Vicia faba roots. Part 1. Absence of dose-rate, fractionation, and oxygen effect at low doses of low LET radiations.

Micronucleus indication in Vicia faba roots has been evaluated after irradiation with 60Co gamma-rays. The dependence of the damage on dose, dose rate, fractionation, and oxygen has been studied. The best fit to the experimental data in the dose region between 7 and 190 cGy is represented, for single-dose exposures, by a linear + quadratic relationship. In the low-dose region, between 7 and 20 cGy, where the linear dose dependence is dominant, no dose-rate, fractionation, or oxygen effect could be observed. These effects were, however, present in the high-dose region, where the quadratic dependence is dominant.

Cell Nucleus↗

Micronucleus induction in Vicia faba roots. Part 2. Biological effects of neutrons below 1 cGy.

A dose-effect relationship has been established for high-energy neutrons (maximum energy 600 MeV) within a dose range of 0.2 to 80 cGy and for low-energy neutrons produced by a 252Cf source (mean energy 2.35 MeV) for doses between 0.2 and 5 cGy. The frequency of micronuclei was found to increase linearly with dose. The relative biological effectiveness (r.b.e) values calculated using 60Co radiation as a reference were, in the high-dose region, 4.7 +/- 0.4 and 11.8 +/- 1.3 for the high- and low-energy neutrons, respectively. At doses below 1 cGy constant values of 25.4 +/- 4.4 and 63.7 +/- 12 were reached for the respective neutron energies.

Cell Nucleus↗

Pharmacokinetics and in vitro effects of a 4-aminobutyric acid derivative with anticonvulsant action.

N-trimethyl-acetyl-4-aminobutyric acid, called PG2, is a new anticonvulsant acting as a 4-aminobutyric acid (GABA) pro-drug. The stimulatory effect of PG2 on synaptosomal 14C-GABA release and its inhibitory effect of synaptosomal 14C-GABA uptake were studied together with its pharmacokinetics after intracardiac and oral administration to rat. PG2 is a weak inhibitor of the GABAse system in vitro with an apparent Ki value of 0.83 mmol/l.

Animals↗

The RBE of the leakage radiation from the Hiletron neutron therapy unit.

The RBE of the leakage radiation from the Hiletron 14.7 MeV neutron therapy unit has been measured using three sensitive biological systems in mice, which differ markedly in their radiobiological characteristics. These systems comprise type A spermatogonia and bone marrow stem cells, which are affected insignificantly by dose rate, and pigment abnormalities in hair follicles which are affected markedly by dose rate. For mice irradiated at 10 cm depth in a water phantom, the leakage radiation up to 40 cm from the beam axis was virtually as effective as the primary beam for the latter two biological systems, and for spermatogonia in mice when irradiated in air. At this distance, the total dose rate was about 0.2 cGy (rad) per minute (3% of that in the primary beam), and the gamma-ray component was about 70%. This equal effectiveness of the total dose for all three systems was considered fortuitous, and it implied high RBE values for equal effect with the small neutron component at far distances. Considering published data on RBE versus neutron energy, the evidence suggested either a positive interaction of neutron and gamma-ray components in killing bone marrow stem cells when the neutron component was less than 40% of the total dose, or an increased efficiency of neutrons when delivered at very low dose rates. However the components were additive in killing spermatogonia.

Air↗

PB:PRM ratio in patients with epilepsy treated with primidone.

Phenobarbitone (PB) and primidone (PRM) plasma concentrations were measured in 88 patients of both sexes with different types of epilepsy and treated with PRM, alone or in association with carbamazepine (CBZ), phenytoin (PHT), ethosuximide (ESM) or valproic acid (VPA). A correlation was observed between the dose and the levels of both PRM and PB. Plasma PB:PRM ratio was high variable, especially interindividually. These changes seemed to be linked to age and particularly to pharmacological associations. In fact, PB:PRM ratio was increased with CBZ, ESM, VPA and PHT respectively. Moreover, a correlation was observed between the PB:PRM ratio and PHT plasma levels. The possibility of monitoring PB and PRM plasma levels during long-term treatment with PRM is discussed.

Adolescent↗