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Biomedical subjects

G Brambilla

Publications and source records attributed to G Brambilla.

At least 181 records · Page 10Linked to original sources
PubMed1981

DNA-damaging activity in vivo and bacterial mutagenicity of sixteen hydrazine derivatives as related quantitatively to their carcinogenicity.

Sixteen hydrazine derivatives (hydrazine, 1,1-dimethylhydrazine, 1,2-dimethylhydrazine, phenylhydrazine, procarbazine, isoniazid, isocarboxazid, nialamide, 2,4-dinitrophenylhydrazine, phenelzine, hydralazine, dihydralazine, carbamylhydrazine, mebanazine, iproniazid, and 1-carbamyl-2-phenylhydrazine) were tested for DNA-damaging activity by the alkaline elution technique and for mutagenic activity in the Salmonella-microsome (Ames) test. The first nine compounds listed (56%) were found to induce a significant DNA fragmentation in the liver and/or in the lung of i.p.-treated male Swiss mice. The DNA-damaging potency varied over an approximately 30-fold range. Thirteen of the first 14 compounds listed (81% of the total), isocarboxazid being inactive, were positive in the Ames test, with a broad range of activity towards the five bacterial strains of Salmonella typhimurium used (TA1535, TA100, TA1537. TA1538, and TA98) and of metabolic behavior in the presence of S-9 mix containing rat liver, mouse liver, or mouse lung postmitochondrial preparations from Aroclor-treated animals. The mutagenic potency varied over an almost 7000-fold range. For 11 of the 16 hydrazine derivatives tested, homogeneous carcinogenicity data (induction of pulmonary tumors in mice chronically treated p.o.) were available from literature. Elaboration of these data showed that carcinogenic potency varied over an approximately 1900-fold range. The five most potent carcinogens were all positive in the DNA damage test. Their carcinogenic potency varied over a 130-fold rage and their DNA-damaging potency varied over a 22-fold range. DNA-damaging potency seemed to vary on a more compressed scale, but regression analysis indicated the existence of a strong positive correlation between in vivo DNA-damaging and carcinogenic potencies, while a lack of correlation was found between mutagenic and carcinogenic potencies. There was no correlation between DNA-damaging and mutagenic potencies.

Animals↗
PubMed1981

Myocardial infarction in a child aged ten with Duchenne muscular dystrophy.

The authors describe the clinical picture, ECG, vectorcardiographic, and serum enzyme assays in one case of acute myocardial infarction occurring after a severe physical exertion in a child aged 10 with progressive muscular dystrophy of the Duchenne type. The picture differs considerably from the electrical aspects of "pseudonecrosis" that interstitial fibrosis of some portions of the left ventricle may produce in this myopathy.

Child↗
PubMed1981

[Threatening arrhythmia by uncommon digitalic toxicosis (author's transl)].

The authors describe the case of a 38 year old woman who ate some buds of "Helleborus viridis" collected in the mountains mistaken for wild asparagus. The clinical patterns were like in the digitalic toxicosis: the woman presented both ventricular and supraventricular threatening arrhythmias, gastro-enteric troubles, systemic hypotension. The patient improved with the glucose, potassium chloride and magnesium sulphate infusion and intravenous xylocaine. The authors conclude that in case of patient with threatening arrhythmias of unknown genesis it is useful to pay attention to the wild vegetables ingestion.

Adult↗
PubMed1980

Detection by alkaline elution of rat liver DNA damage induced by simultaneous subacute administration of nitrite and aminopyrine.

DNA fragmentation induced in the livers of rats by oral treatment with NaNO2 and aminopyrine was evaluated by the alkaline elution technique. Whereas simultaneous administration of the two compounds in a single dose produced only a minimal increase of the DNA elution rate, their intake with drinking water for 20 successive days caused DNA fragmentation comparable to that observed after a single ip injection of 10-20 mg/kg N-nitrosodimethylamine. Either NaNO2 or aminopyrine alone induced borderline DNA damaging effects, if any, in both rats receiving a single dose and those treated for 20 successive days.

Aminopyrine↗
PubMed1980

Alkaline elution assay as a potentially useful method for assessing DNA damage induced in vivo by diazoalkanes.

In order to evaluate directly in vivo the extent of correlation existing between mutagenic-carcinogenic activity of diazoalkanes and their DNA damaging activity, alkaline elution was used to study the induction of single-strand breaks in and repair of DNA from mice treated with N-diazoacetylglycine amide (DGA). A dose-dependent DNA fragmentation was present, 4 hr after ip injection of single doses of DGA, in liver, lung, kidney, spleen, thymus, and bone marrow. The differences among these organs in the amount of DNA damage were small, even if sometimes statistically significant. Elution profiles indicated that a progressive conversion of alkali-labile sites to single-strand breaks took place in the first 50 min of elution. Twenty-four hr after treatment with 1000 mg/kg, DNA damage was only slightly reduced in liver, lung and bone marrow. A detailed statistical analysis of the variability of experimental results is reported in order to give information about the reliability of the method, and to allow the possibility of calculating the number of separate experiments required to reach statistical significance for a given increase of DNA elution rate.

Alkalies↗
PubMed1979

DNA damage and repair induced by diazoacetyl derivatives of amino acids with different mechanism of cytotoxicity. Correlations with mutagenicity and carcinogenicity.

Eight synthetic N-diazoacetyl amino acids, prepared by inserting a diazoacetyl group onto the alpha-nitrogen of a natural amino acid, and two natural diazoazetyl amino acids, azaserine (9-diazoacetyl-L-serine) and DON (6-diazo-5-oxo-L-norleucine), have been studied by autoradiography for their capacity to induce DNA repair synthesis in mouse cells cultivated "in vitro". Dose-dependent unscheduled DNA synthesis was present in cells treated with the eight N-diazoacetyl derivatives, and was absent in cells exposed to approximately equitoxic concentrations of azaserine and DON. Azaserine and DON, unlike N-diazoacetyl derivatives, did not alkylate gamma-(4-nitrobenzyl) pyridine at an appreciable extent. When DNA damage (single stranded breaks or weak points in alkali) was measured by the sensitive technique of alkaline elution, DGA was found about 4 times as potent as azaserine and about 12 times as DON on a molar basis, but about 800 and 17,000 times as potent as azaserine and DON respectively by extrapolating to equitoxic concentrations. Carcinogenicity and mutagenicity seem to follow mainly the capability of inducing DNA damage.

Alkylation↗
PubMed1979

Decreased high density lipoprotein-cholesterol levels in male patients with transient ischemic attacks.

Plasma lipid and lipoproteins levels were determined in a continuous series of 50 patients (36 males and 14 females), mean age around 50 years, with a clinical diagnosis of transient ischemic attacks (TIAs). TIA was defined as a sudden episode of focal cerebrovascular insufficiency, with complete resolution of the symptoms within 24 h. TIAs are considered an important prognostic symptom for ischemic cerebrovascular diseases, being manifest in approximately 45% of the patients later undergoing a complete stroke. Plasma total cholesterol levels did not differ in these patients, when compared with a similar series of patients of the same age and sex, free of cerebrovascular lesions. A slight elevation of mean triglyceride levels was detected in the patients of both sexes, as well as higher incidence of type IV hyperlipoproteinemia. The most significant finding, however, observed only in male TIA patients, was that of significantly reduced high density lipoprotein (HDL)-cholesterol levels. This reduction (-19.7% compared to the control group) is similar to that recently reported for patients with clear-cut ischemic cerebrovascular disease. The detection of decreased HDL-cholesterol levels in male TIA patients may be of considerable significance for a prognostic evaluation of this biochemical parameter.

Adult↗
PubMed1979

DNA fragmentation in some organs of rats and mice treated with cycasin.

Cycasin (methylazoxymethanol-beta-D-glucoside) is carcinogenic in several animal species. It produces a variety of malignant tumours, mainly in the liver of mice, and in the liver, kidney and large intestine in rats. It does not appear to be mutagenic in the Ames test, even in the presence of liver microsome fraction, and it is among those carcinogens (less than 10%) ranked as "false negatives" in this test. The ability of cycasin to damage in vivo liver, kidney, lung and colonic DNA of Wistar rats and C57BL/L mice was investigated by means of alkaline elution technique. Oral single-dose administration of cycasin, in the range of 50-400 mg/kg body weight, produced in the rat a clearly evident dose-dependent DNA fragmentation in the liver, and less marked damage to DNA from kidney and colon mucosa. In mice, the same treatment produced dose-dependent DNA damage only in the liver. DNA repair up to 18 h appeared to be incomplete both in mice and rats. Methylazoxymethanol acetate is considered to be an active form of cycasin. While in vivo methylazoxymethanol acetate caused DNA damage, in vitro it appeared inactive and required metabolic activation, possibly consisting in its hydrolysis by esterase activity, to be able to cause DNA fragmentation.

Animals↗
PubMed1978

DNA damage in liver, colon, stomach, lung and kidney of BALB/c mice treated with 1,2-dimethylhydrazine.

DNA single-strand breaks induced in various organs of BALB/c mice by treatment with a single dose of 1,2-dimethylhydrazine (DMH) were studied by means of the alkaline elution method modified in order to allow the evaluation of DNA damage in vivo with no need of radioactive prelabelling. DNA damage was detected in liver, lung, kidney, stomach and colon mucosa, with the liver showing the greatest amount of damage. Its degree was dependent on the dose and route of administration. A differential effect was evident in colon mucosa from Swiss and C57BL/6 mice which are respectively susceptible and resistant to the induction of bowel tumors by DMH. The higher degree of DNA damage found in liver in comparison with colon mucosa is consistent with the previously reported higher degree of DNA methylation, but does not correlate with the specificity of this carcinogen in inducing tumors of the large intestine in mice given repeated subcutaneous injections.

Animals↗
PubMed1978

A practical procedure for testing DNA damage in vivo, proposed for a pre-screening of chemical carcinogens.

The alkaline elution method was adapted to the evaluation of DNA damage induced in vivo through a practical and reliable microfluorometric procedure, without any need for tissue pre-labeling. The DNA damage induced in vivo by treatment with a single dose of N-nitrosodimethylamine (DMNA), N-methyl-N-nitroso-urea (MNU), 1,2-dimethylhydrazine (DMH) or cycasin has been detected in different organs of mice or rats. The results obtained are rather consistent with the organotropism of these carcinogens, and show a satisfactory dose dependent of DNA damage. DMH and cycasin, both negative in the Ames' Salmonella/microsome mutagenicity test, are clearly positive with in vivo DNA damage/alkaline elution assay. This latter method, complemented with other short-term tests, may play a useful role in the pre-screening of chemical carcinogens.

Animals↗
PubMed1978

DNA repair synthesis in primary cultures of kidneys from BALB/c and C3H mice treated with dimethylnitrosamine.

A combined 'in vivo--in vitro' autoradiographic method was employed to examine the DNA repair induced in the kidney by a single dose of dimethylnitrosamine (DMNA). Unscheduled DNA synthesis was found to be dose-dependent in primary kidney cultures of DMNA-treated mice, and practically not detectable in controls. Its amount was positively correlated with the different susceptibility of C3H and BALB/c mice to kidney tumor induction by DMNA. This experimental model appears sensitive and able to provide repeatable results. It may be useful to detect the organotropic activity of a carcinogen toward the kidney.

Animals↗
PubMed1978

[Long-term cardiac pacing: survival above 10 years (author's transl)].

The authors reports data of pacemaker patients surviving above 10 years. They have considered 241 patients undergone pace-maker first insertion from January 1961 to June 1967 (168 treated with epicardial and 73 with transvenous electrodes). At the last control on July 1977, 52 (27 males and 25 females) were surviving, equivalent to 21% of all patients treated in that period. The age of these patients ranged from 5 to 83 (mean 60 years) at first implantation. At present 51 patients are treated with transvenous systems, only 1 patient is stimulated with epicardial pace-maker. 382 pace-makers were used in these 52 patients: the average life of every pacer was 20 months. Complications relative to epicardial and endocardial pacing are reported: with the transvenous system the percent of complications was lower (15,6% to 50,4%). Finally present clinical states of the 52 patients are reported, basing on the reccomendations of Criteria Committee of the New Heart Association.

Adolescent↗
PubMed1978

[Upper urinary tract filling defects (author's transl)].

The distinctive features of true and false filling defects in the radio-opaque image of the upper urinary tract are discussed. The differential diagnosis of intrinsic intraluminal and parietal lacune is examined and several cases are presented by way of illustration.

Humans↗
PubMed1977

Relationships between mutation and transformation frequencies in mammalian cells treated "in vitro" with chemical carcinogens.

An analytical quantitative comparison of data from the literature about frequencies of mutations and transformations induced by mutagenic-carcinogenic compounds in mammalian cells was carried out without any selection of unfitting data. The analysis was performed for equitoxic doses and background level. Data on transformation frequency came from 105 experiments performed with 34 carcinogenic compounds: those on mutation frequency came from 66 experiments performed with 26 mutagenic compounds; 7 compounds were assayed for both these activities. The difference in frequency between structural mutations and transformations was about 10(2)-10(3) and it appears statistically extremely significant. These results seem to indicate an absolute difference between structural mutations and transformations. In the framework of other observations it is suggested that structural alterations in a single gene are perhaps only a component of the steps present in the oncogenetic process. We may regard as "epigenetic" type phenomena the other steps involved in this process.

Animals↗