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Biomedical subjects

G Brambilla

Publications and source records attributed to G Brambilla.

At least 145 records · Page 8Linked to original sources
PubMed1985

DNA fragmentation by N-nitrosodimethylamine and methyl methanesulfonate in human hepatocyte primary cultures.

The ability of N-nitrosodimethylamine (DMN) and methyl methanesulfonate (MMS) to induce DNA damage in primary cultures of human hepatocytes was examined by the alkaline elution technique. Both the agents induced a dose-dependent increase in DNA elution rate, but appreciable differences in the degree of response to the procarcinogen DMN were observed among cultures obtained from the livers of four patients. A comparative analysis of DNA fragmentation indicated a substantial similarity between human and concurrently studied rat hepatocytes in their response to both DMN and MMS.

Aged↗
PubMed1985

Formation of DNA-damaging nitroso compounds by interaction of drugs with nitrite. A preliminary screening for detecting potentially hazardous drugs.

Fifty-seven theoretically nitrosatable widely used drugs that are commonly administered orally have been screened to determine the formation of nitroso compounds by drug-nitrite interaction and to evaluate the genotoxicity of their nitrosation products against Chinese hamster ovary (CHO) cells, measured as DNA-damaging potency by the alkaline elution technique. The drug (0.1 mmol) was reacted with NaNO2 (0.4 mmol) at pH 3-3.5 for 1 h. Nitroso compounds were present in varying yield in the nitrosation mixture of 47 drugs. Twenty-two drugs formed direct-acting nitroso compounds capable of producing DNA fragmentation, i.e., a statistically significant (p less than 0.01) increase in the elution rate of CHO cell DNA. On a molar basis, their DNA-damaging potency varied over a 570-fold range, with 12 exhibiting greater potency than that of N-nitroso-N-methylurea.

Animals↗
PubMed1985

Higher sensitivity for the detection of chemically-induced DNA damage: role of DNA unfolding in determining alkaline elution rate.

CHO-K1 cells exposed to log-spaced concentrations of methyl methanesulfonate (MMS) and liver cells from rats treated with log-spaced single i.p. doses of N-nitrosodimethylamine (DMN) were examined for changes in the rate of DNA alkaline elution induced by incubation in high ionic strength non-denaturing (pH 10) lysing solution. While the elution rate of DNA from control cells was marginally modified, that of treated cells increased proportionally to the length (from 0.5 to 48 h) of incubation, without any significant reduction of DNA average mol. wt. These experiments were suggested and then explained by a recently described physico-chemical model which has shown that the changes in DNA elution profiles are strongly determined also by related changes in DNA chain flexibility and packing. These chemical-induced changes in DNA superpacking and the subsequent differential kinetics of DNA unfolding in the lysing solution are compatible with previous results by independent physical methods. This allows significantly higher sensitivity in the detection of chemically-induced DNA damage, now possible even for a quite low chemical concentration. At the same time, it may be inferred that any material capable of altering DNA superpacking--by damaging either DNA itself or any other chromosomal constituents, such as protein--may well give rise to an increased elution of DNA from the filter.

Alkalies↗
PubMed1985

Methylglyoxal-induced DNA-protein cross-links and cytotoxicity in Chinese hamster ovary cells.

The technique of alkaline elution was applied to study the capacity of methylglyoxal to induce DNA damage and repair in Chinese hamster ovary cells. DNA cross-linking was observed after a 90-min exposure to a subtoxic dose (1.5 mM), and the cross-links were fully repaired by 24 h. The cross-linking appeared to be DNA-protein in nature, since proteinase treatment removed the effect. When the same cells were exposed to methylglyoxal in the presence of a rat liver metabolic system, both cytotoxicity and cross-linking frequency were significantly reduced.

Aldehydes↗
PubMed1985

Viscometric detection of liver DNA fragmentation in rats treated with ten aromatic amines. Discrepancies with results provided by the alkaline elution technique.

A new viscometric technique, capable of detecting DNA strand breaks and alkali-labile sites by monitoring time-dependent changes of DNA reduced viscosity, has been used to evaluate DNA fragmentation in liver of rats treated with single i.p. doses of ten aromatic amines. Persistent and dose-dependent changes of DNA viscometric parameters, which are considered indicative of DNA fragmentation, were produced by six hepatocarcinogenic aromatic amines: 2-naphthylamine, benzidine, 2,4-diaminotoluene, auramine O, 4-aminoazobenzene, and 4-dimethylaminoazobenzene. In contrast, changes of liver DNA viscometric parameters were minimal and transient or practically absent in rats treated with aniline, 1-naphthylamine, 4,4'-oxydianiline and 2,4-diaminoanisole, all of which are devoid of hepatocarcinogenic activity. The comparison with data previously obtained with the alkaline elution technique demonstrates that the two methods can give different results, and that viscometrically-detected DNA damage is better correlated with carcinogenic activity than DNA damage detected by alkaline elution.

Amines↗
PubMed1985

Spontaneous pregnancies in hyperprolactinemic women.

29 pregnancies occurred spontaneously in 28 women with mild to moderate hyperprolactinemia (prolactin levels up to 100 ng/ml). Only 4 of them showed tomographic evidence of microprolactinoma; 1 of the prolactinoma patients experienced a visual field defect at week 30, which was quickly controlled by bromocriptine treatment. Pregnancy was uneventful in the rest of the patients. Subjects who wished to lactate successfully breast-fed their babies. Of 22 women in whom prolactin levels were reevaluated at least 1 month after delivery and/or lactation, normal values were found in 9.

Adult↗
PubMed1985

Effect of fenfluramine oral administration on serum prolactin levels in healthy and hyperprolactinemic women.

The effects of two different doses (40 and 80 mg orally) of fenfluramine on serum prolactin (PRL) levels have been evaluated in healthy and hyperprolactinemic women and compared with those of the potent dopamine antagonist sulpiride (100 mg i.m.). The lower fenfluramine dose resulted in a significant PRL rise in healthy women (n = 16) but not in hyperprolactinemics (n = 14). A dose-response effect was shown between 40 and 80 mg in control subjects (n = 7); in 4 hyperprolactinemics the higher dose also failed to increase PRL levels. Sulpiride resulted in a much greater PRL response. Since fenfluramine at the low doses used does not seem to exert antidopaminergic action, it is suggested that the mild PRL stimulation observed be mediated by the known brain serotoninergic activation induced by the drug.

Administration, Oral↗
PubMed1985

Absence of DNA damage in mice and rats given high doses of five beta-adrenergic blocking agents.

Five beta-blockers (propranolol, metoprolol, oxprenolol, pindolol, and sotalol) were tested for their in vivo DNA-damaging activity by two different techniques: alkaline denaturation of DNA followed by hydroxylapatite chromatography, and a new viscometric method markedly more sensitive in detecting DNA fragmentation. DNA damage, as checked by the first technique, was absent either in liver and kidney of mice or in liver and gastric mucosa of rats given a single p.o. administration of 1/2 LD50 of the drugs. The subsequent viscometric analysis of liver DNA from rats treated with the same doses confirmed the above negative results.

Adrenergic beta-Antagonists↗
PubMed1984

DNA-damaging activity of biotic and xenobiotic aldehydes in Chinese hamster ovary cells.

Alkaline elution was employed to study DNA damage in CHO-Kl cells treated with a series of biotic and xenobiotic aldehydes. DNA cross-linking was measured in terms of the reduction in the effect of methyl methanesulphonate on the kinetics of DNA elution and was observed in cells treated with formaldehyde, acetaldehyde, methylglyoxal and malonaldehyde. Propionaldehyde, valeraldehyde, hexanal and 4-hydroxynonenal produced DNA single-strand breaks, or lesions which were converted to breaks in alkali. Both types of DNA damage occurred in cells exposed to malealdehyde. These findings support the hypothesis of a carcinogenic effect of the aldehydic products (malonaldehyde, methylglyoxal, propionaldehyde, hexanal, 4-hydroxynonenal) released in biomembranes during lipid peroxidation.

Aldehydes↗
PubMed1984

Phase transitions in nuclei and chromatin. Is nuclear volume controlled by the chromatin or by the nuclear matrix?

Changes in the volume of rat liver nuclei have been monitored as a function of modifications in ionic environment (from 0 to 20 mM), temperature (from 4 to 37 degrees C), and pH (from 1 to 8). An abrupt reduction of nuclear volume occurred with increasing ion concentration, this contraction being more pronounced with bivalent (either Ca2+ or Mg2+) than with monovalent (either Na+ or K+) cations. The lowering of pH produced a similar effect. Parallel changes in chromatin structure took place at the same time as phase-like transitions. Atomic absorption spectroscopy allowed determination of free and nuclei-bound ions, pointing to the presence of a sizeable number of free binding sites for chromatin-DNA even within intact nuclei. DNA-phosphate sites appear to be neutralized by ions strictly according to the size of the electric charge and polyelectrolyte theory. Partial digestion (by micrococcal nuclease) or simple breaks (by chemical carcinogens) of the chromatin-DNA fiber caused respectively elimination or reduction of the abrupt volume changes in the intact nuclei. The apparent role of chromatin structure versus nuclear matrix in determining the shape and volume of intact nuclei is briefly discussed.

Animals↗
PubMed1984

The usefulness of viscometric analysis for detecting minimal levels DNA fragmentation.

Basic requirements for a method used to study the genotoxic potential of xenobiotic agents in the intact animal are sensitivity and capability of detecting the effect of the compound under test in various tissues. A new viscometric technique, which has been found capable of measuring DNA damage in liver, kidney, and lung of rats treated with small single doses of 10 chemical carcinogens, seems to possess such requirements. Single-strand breaks and probably other types of lesions indeed cause changes in DNA supercoiling which can be sensitively measured by monitoring time-dependent changes of DNA viscosity. The main advantage of this technique is that clear-cut modifications of viscometric parameters can be obtained with doses of various carcinogens markedly lower than those found to be the minimal effective ones in other commonly employed short-term in vivo tests. The importance of studying the genotoxic effects of pharmacologically meaningful doses is discussed.

Animals↗
PubMed1984

[Comparative evaluation of mexiletine and propafenone by dynamic electrocardiography].

We have compared the efficacy of Propafenon and Mexiletine in 12 subjects (7 males and 5 females, age range of 22-61 year) affected by chronic ventricular extrasystolic beats. Propafenon and Mexiletine were orally administered in doses of 900 mg/day and 600 mg/day respectively in a single blind, cross-over fashion. Our results show that: Propafenon is better tolerated; Propafenon has caused a statistically significant reduction of the total number of ventricular ectopic beats/24 hours; the efficacy of Propafenon has been greater than that of Mexiletine (66% and 25% respectively); with both drugs, in 2 cases, there was an increase of the total number of ventricular ectopic beats/24 hours; Propafenon has induced clear-cut electrocardiogram changes (statistically significant lengthening of P-Q and Q-T intervals).

Adult↗
PubMed1984

[Aneurysms of the splenic artery. Considerations on 33 cases].

After a short historical, pathogenetic and clinical review, the value of the radiological examinations in the diagnosis of splenic artery aneurysms is analyzed. A personal series of 33 cases is reported, 25 of which in patients with portal hypertension; incidence, number, site, size and other features are discussed. The strict relationships with portal hypertension and the choice of the best surgical treatment for each case are studied.

Adult↗
PubMed1983

Physico-chemical model for DNA alkaline elution: new experimental evidence and differential role of DNA length, chain flexibility and superpacking.

For a better understanding of data provided by DNA alkaline elution technique, a new analytical model has been developed which takes into consideration both the physicochemical properties of in situ DNA strand (length and flexibility/superpacking) and the geometric and hydrodynamic configuration of the elution apparatus (flow and filter conditions). Simulation by this model of experimental data previously obtained before and after carcinogens administration, has shown that for constant flow and filter conditions elution profiles are dependent, not only from DNA molecular weight, but also from a parameter critically related to modifications in chain flexibility/superpacking. This has been confirmed by several independent observations, including the time-dependent changes in non-denaturing lysing solution monitored by hydroxylapatite and alkaline elution techniques.

Animals↗
PubMed1983

Quaternary and quinternary structures of native chromatin DNA in liver nuclei: differential scanning calorimetry.

Differential scanning calorimetry of chromatin isolated from rat liver cells revealed three discrete thermal transitions whose temperatures and melting enthalpies depend on ionic strength in the range 0 to 600 millimolar NaCl. Intact nuclei showed a fourth thermal transition at a lower temperature and different melting enthalpies for the other three transitions still present at temperatures similar to those obtained in isolated chromatin. The data are discussed in terms of the tertiary, quaternary, and quinternary structures of chromatin DNA.

Animals↗
PubMed1983

Genotoxicity of cimetidine in primary cultures of rat hepatocytes.

The genotoxicity of cimetidine was examined in the hepatocyte primary culture/DNA-repair test and by the DNA-damage/alkaline-elution assay. A dose-dependent amount of unscheduled DNA synthesis was elicited by cimetidine, whereas DNA fragmentation occurred only in hepatocytes exposed to the highest (3 mM) concentration of the drug. These findings are in contrast with the negative results previously obtained in long-term and short-term carcinogenesis assays.

Animals↗