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Biomedical subjects

A Martelli

Publications and source records attributed to A Martelli.

At least 73 records · Page 4Linked to original sources
PubMed1994

Cinnamaldehyde-induced micronuclei in rodent liver.

Cinnamaldehyde, a widely used flavoring agent, has so far been subjected to a limited range of genotoxicity tests, mainly carried out in vitro, which produced contradictory results. Therefore we have examined cinnamaldehyde using additional in vivo genotoxicity end-points. In Sprague-Dawley rats, a single oral dose equal to 1/2 LD50 did not induce DNA fragmentation in liver and gastric mucosa as evaluated by the alkaline elution technique, increased the frequency of micronucleated hepatocytes but not of bone marrow micronucleated polychromatic erythrocytes, and gave rise to a significantly higher incidence of total nuclear anomalies but not of micronucleated cells in forestomach mucosa. In Swiss mice, the equitoxic dose of cinnamaldehyde caused the same clastogenic effect in the liver, whilst a negative response was observed in both bone marrow and forestomach mucosa. Finally, in rats initiated with N-nitrosodiethylamine the administration of 500 mg/kg/day cinnamaldehyde for 14 successive days produced a modest but statistically significant increase of the average diameter and area of gamma-glutamyltranspeptidase-positive foci that, together with changes observed in other parameters, might be considered indicative of a potential promoting activity. Taken as a whole, these findings confirm that high doses of cinnamaldehyde may induce genetic alterations at the chromosomal level, and suggest that the liver is the preferential target of its undesirable effects.

Acrolein↗
PubMed1994

Cytotoxic and genotoxic effects of five n-alkanals in primary cultures of rat and human hepatocytes.

Five n-alkanals were examined for cytotoxicity, as evaluated by the trypan blue exclusion test, and for genotoxicity, as evaluated by the induction of unscheduled DNA synthesis (UDS), in primary cultures of rat and human hepatocytes. After 20 h exposure, cytotoxicity was similar in cells of the two species, and increased with the length of the carbon chain. In rat hepatocytes, propanal (10-100 mM), butanal (10-100 mM), pentanal (3-30 mM) and hexanal (3-30 mM) induced a modest but significant and dose-dependent increase of net nuclear grain counts, while in human hepatocytes this effect was not detected. Nonanal (3-30 mM), which showed the highest cytotoxic effect, failed to induce UDS in both cell types. These results seem to suggest that at the concentrations which are presumably attained after ingestion with food or generated by lipid peroxidation processes the five n-alkanals tested are presumably unable to induce genotoxic effects in the human liver.

Aldehydes↗
PubMed1994

Cognitive and neuroradiological findings in congenital adrenal hyperplasia.

Nineteen patients with congenital adrenal hyperplasia (CAH) aged over 16 years were given a neuropsychological evaluation; no significant differences with individually matched normal controls were detected. CAH subjects, however, revealed slightly higher IQs with respect to the expected distribution. No significant learning disabilities could be detected. Fifteen patients underwent nuclear magnetic resonance (NMR); 4 subjects showed small areas of increased signal intensity in the white matter, without prevalence of side; this finding did not correlate with clinical and cognitive characteristics. The results are discussed in the light of possible hormonal influences.

Adolescent↗
PubMed1994

Low clastogenic activity in vivo of the N-nitroso derivatives of 5 beta-adrenergic-blocking drugs proved to be potent genotoxins in vitro.

The N-nitroso derivatives formed by the in vitro reaction of 5 beta-adrenergic-blocking drugs with sodium nitrite and previously found to induce DNA fragmentation and repair in primary cultures of both rat and human hepatocytes were tested for their ability to exert a clastogenic effect in vivo. In partially hepatectomized rats given by gavage a single dose of 1000 mg/kg, all 5 N-nitroso derivatives caused a statistically significant increase in the frequency of micronucleated hepatocytes, the clastogenic potencies of NO-propranolol, NO-metoprolol, and NO-nadolol being slightly greater than those of NO-atenolol and NO-sotalol. In contrast, none of them produced a significant increase in the frequency of micronucleated polychromatic erythrocytes in the bone marrow and the spleen. For all 5 N-nitroso derivatives the in vivo clastogenic potency, i.e. the ratio between the number of micronuclei observed in the liver and the dose administered, was markedly lower than the in vitro DNA-damaging potency calculated as the ratio between the amount of DNA fragmentation and the concentration tested. This suggests a preferential detoxification in vivo of the 5 N-nitroso derivatives.

Adrenergic beta-Antagonists↗
PubMed1993

Cytotoxic and genotoxic activity of 1,3-dichloropropene in cultured mammalian cells.

1,3-Dichloropropene (DCP), a widely used soil fumigant previously found to be carcinogenic in both mice and rats, was evaluated for its cytotoxic and genotoxic effects in cultured rodent and human cells. A reduction of cell viability that was dependent on the dose and the length of treatment was observed with the trypan blue and the neutral red assay in both V79 cells and rat hepatocytes exposed to DCP concentrations ranging from 0.18 to 5.6 mM. In the absence of a metabolic activation system, a dose-dependent frequency of DNA single-strand breaks, that were only partially repaired within 24 hr, was revealed by the alkaline elution technique in V79 cells exposed to subtoxic DCP concentrations. The genotoxicity of DCP was confirmed by the results obtained in metabolically competent primary cultures of both rat and human hepatocytes which displayed similar dose-related amounts of DNA fragmentation and DNA repair synthesis, and showed, in comparison to metabolically deficient V79 cells, a somewhat greater sensitivity to the cytotoxic and DNA-damaging effects of DCP. The increase in the frequency of DNA breaks observed in rat hepatocytes after GSH depletion confirms the role of this tripeptide in DCP detoxification; its reduction in hepatocytes simultaneously exposed to metyrapone is consistent with a cytochrome P450-dependent biotransformation of DCP to more toxic metabolites.

Allyl Compounds↗
PubMed1993

Genotoxic activity of 1,3-dichloropropene in a battery of in vivo short-term tests.

The genotoxic activity of 1,3-dichloropropene, which has been classified as possibly carcinogenic to humans, was investigated in rats given high single doses of this chloroolefin. A dose-related amount of DNA fragmentation was observed at doses ranging from 62.5 to 250 mg/kg in liver and gastric mucosa, both of which are targets of DCP carcinogenic activity, as well as in the kidney. The frequency of DNA breaks, that were to a large extent repaired within 24 hr, was higher after po than after ip administration in the liver, while the converse occurred in the kidney. Any evidence of DNA fragmentation was, in contrast, absent in lung, bone marrow, and brain which are not sites of DCP-induced tumor development. A role of cytochrome P450 in the activation of DCP is suggested by the lower degree of liver DNA fragmentation observed in rats pretreated with methoxsalen. DCP produced a dose-dependent reduction of the liver GSH level, an effect that presumably hinders its detoxification and thus favors its DNA-damaging activity. In contrast with the satisfactory prediction of DCP carcinogenic activity provided by the results of the in vivo DNA damage/alkaline elution assay, neither the in vivo rat hepatocyte DNA repair assay nor the micronucleus assay, carried out on bone marrow, spleen, and liver cells of partially hepatectomized rats, supplied any evidence of DCP genotoxicity.

Allyl Compounds↗
PubMed1993

Diffuse leptomeningeal melanomatosis of the spinal cord: a case report.

A rare case of diffuse leptomeningeal melanosis presenting with symptoms of spinal cord compression due to the presence of anterolateral arachnoid cyst and treated with Spetzler's drainage system is reported. The diagnosis of diffuse melanosis of the leptomeninges is rarely possible during life. In the present case MRI was of great help in the definition of the limits of the pathological process and the presence of the anterior compressing cyst. After laminectomy and a biopsy of the pathological tissue which achieved the histological diagnosis, an external drainage was inserted to reduce the cyst extension and to exclude the presence of melanocytes in the cystic fluid before a peritoneal shunt was placed. At 8th month of follow-up the patient is doing well with a dramatic reduction of symptoms and a significant reduction of spinal cord compression. The diagnostic role of MRI and the relationship between leptomeningeal melanosis and arachnoid cyst are discussed.

Adult↗
PubMed1993

Comparison of micronucleus formation in mouse bone marrow and spleen.

The frequencies of micronucleated erythrocytes were compared in bone marrow and spleen of mice killed 24 and 48 h after a single i.p. dose of one directly acting carcinogen, N-nitroso-N-ethylurea (NEU, 100 mg/kg), and two indirectly acting ones, N-nitrosodimethylamine (NDMA, 50 mg/kg) and 7,12-dimethylbenz[a]anthracene (7,12-DMBA, 50 mg/kg). The treated/control ratio of the incidence of micronucleated polychromatic erythrocytes (MnPCEs) was similar in the two tissues for NDMA at 24 h (sampling at 48 h was precluded by toxicity) and for 7,12-DMBA at 48 h, while it was higher in the bone marrow than in the spleen for NEU at both 24 and 48 h and for 7,12-DMBA at 24 h. Concerning micronucleated normochromatic erythrocytes (MnNCEs), their frequency in both tissues was always lower than that of MnPCEs; however, while in bone marrow a marked increase in their incidence was induced by NEU and 7,12-DMBA, any response was absent in spleen, thus suggesting that this organ does not sequester micronucleated erythrocytes. These results already indicate that the spleen is not a useful alternative to the bone marrow in the micronucleus assay. Moreover, counting of MnPCEs in the spleen is made more difficult and prone to error by the low frequency of PCEs, and by their greater toxicity-induced reduction. This last effect was found to be enhanced by the use of old mice.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Lack of evidence of omeprazole genotoxicity in Sprague-Dawley rats.

Omeprazole is a proton pump inhibitor of increasingly wide use in the treatment of peptic ulcers. Although omeprazole has been subjected to an extensive range of genotoxicity tests, which have all been concluded as negative, the ability of this compound to interact with DNA and elicit unscheduled DNA synthesis in the rat gastric mucosa has been the subject of debate. Therefore, we have examined omeprazole using other genotoxicity end-points. In female Sprague-Dawley rats, the administration by the oral route of 100 mg/kg, either as neutral (pH 7.0) suspension or as suspension acidified to pH 1.5, which favours its transformation into the active form of sulphenamide, did not induce DNA fragmentation in gastric mucosa and liver, as detected by the alkaline elution technique. In the same experimental conditions, a frequency of total nuclear anomalies (micronuclei, pyknosis and karyorrhexis) that was significantly higher than in controls was detected with both types of suspension in forestomach and descending colon mucosa. However, in both tissues this higher frequency of nuclear anomalies was mostly due to pyknosis and karyorrhexis, which may be the outcome of a non-genotoxic effect, whereas there was no significant increase in the number of micronucleated cells, and this suggests the absence of clastogenic activity. Finally, in rats initiated with N-nitrosodiethylamine, the oral administration of 100 mg/kg omeprazole for 14 successive days produced a modest but statistically significant increase of liver gamma-glutamyltranspeptidase positive foci, which is consistent with a potential promoting activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of alfuzosin on quality of life in benign prostatic hyperplasia patients: preliminary results. Italian Alfuzosin Co-Operative Group.

Recently urologists have focused their attention not only on classical evaluation parameters for patients suffering from benign prostatic hyperplasia (BPH), such as symptoms and uroflowmetry, but also on the impact of therapy on the patients' quality of life. An observational, open-label, uncontrolled trial was designed to evaluate the impact of a 3-month therapy with alfuzosin (2.5 mg t.i.d.) on the quality of life of patients complaining of BPH-related symptoms for at least 6 months. Nine hundred and ninety patients were enrolled in 86 Italian centers of urology. At baseline and after 84 days of treatment the following assessments were performed: the Maine Medical Assessment Program Symptom Score, a quality of life questionnaire, and at selected centers, uroflowmetry and residual volume measurement. Preliminary results on 498 evaluable patients (who completed the study by March 1992), showed the ability of alfuzosin to improve BPH symptoms significantly (total mean score from 12.02 +/- 0.17 to 7.27 +/- 0.12, -39.5%), mostly in patients with severe symptoms at baseline (-46.8%). All the three indices describing patients' quality of life improved significantly: mental health +2.3% (p < 0.01); general health +4.3% (p < 0.01), and especially, activity +12.9% (p < 0.01). A marked improvement was observed in patients with severe symptoms (activity index +23.8%). Uroflowmetric data obtained from 255 patients showed a significant increase in peak (+4.14 ml/s) and mean (+2.58 ml/s) flows, associated with a marked decrease in residual volume (-34.1 ml, -52.6%). Thirty-three patients experienced one or more adverse medical events, mainly within the first 4 weeks of treatment (20 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1993

Human hepatocyte primary cultures in toxicity assessment.

Forty-two compounds of various chemical families were tested for their cytotoxicity and for their ability to induce DNA fragmentation and DNA repair synthesis in primary cultures of hepatocytes obtained from 74 human donors, and a comparison was carried out with data provided in the same experimental conditions by rat hepatocytes. The results indicate that for the majority of chemicals the intraspecies variability was greater than the average interspecies difference. Some chemicals, however, produced quite different effects in the hepatocytes of the two species, and this suggests that rat hepatocytes might be sometimes inappropriate predictor of the human response.

Animals↗
PubMed1993

[Our experience in urologic surgery with a new polyglycolic acid (Darvin)].

Catgut chromic has long been used as an absorbable suture and recently polyglycolic acid has been used widely as a suturing material causing minor tissue reaction. The aim of this study is to consider the bioavailability of a new absorbable suture which is a modified polyglycolic acid: Darvin. We considered 10 consecutive patients surgically treated for a bladder disease. They were cystoscopically followed 30 and 90 days after surgery. We noted a complete integration of the suture material in the bladder wall and no side reactions of the bladder.

Biocompatible Materials↗
PubMed1992

Evaluation in a battery of in vivo assays of four in vitro genotoxins proved to be noncarcinogens in rodents.

2-Chlorethanol, 8-hydroxyquinoline, 2,6-toluenediamine, and eugenol, previously found to behave as genotoxins in in vitro systems and as noncarcinogens in rodents, were evaluated for their ability to induce genotoxic effects in vivo. Rats were given by gavage a single or two successive doses equal to one-half the corresponding LD50, killed at different times after treatment, and examined for the following end points: the frequency of both micronucleated polychromatic erythrocytes in the bone marrow and micronucleated hepatocytes (after partial hepatectomy); the in vivo-in vitro induction of DNA fragmentation, as measured by the alkaline elution technique, and of unscheduled DNA synthesis, as measured by autoradiography, in hepatocyte primary cultures. The two latter end points were also evaluated after in vitro exposure of hepatocytes to log-spaced subtoxic concentrations. 2-Chloroethanol, 8-hydroxyquinoline, and eugenol never produced effects indicative of genotoxic activity. The same happened with 2,6-toluenediamine, with the exception of a significant increase over controls in the amounts of DNA damage and repair displayed by hepatocyte cultures obtained from rats given two 1/2 LD50 separated by a 24 h interval. Our results, which, apart the above mentioned exception, are in concordance with the rodent carcinogenicity results, contribute to underline the role of in vivo short-term tests for the detection of potential genotoxic carcinogens.

Animals↗
PubMed1992

Ipriflavone inhibits osteoclast differentiation in parathyroid transplanted parietal bone of rats.

Ipriflavone, a synthetic isoflavone-derived flavonoid, was shown to have inhibitory effect on bone resorption. In order to study its mechanism of action directly on bone, 46 female Wistar rats were divided into six groups and medicated orally for 25 days as follows: groups 1 and 2 were given 1% carboxymethylcellulose solution (vehicle), groups 3, 4, 5, and 6 were administered ipriflavone at doses of 0.178, 0.356, 0.712, and 1.424 mmol/kg/day (suspended in vehicle), respectively. On the 22nd day, parathyroid glands, taken from donor rats, were transplanted in contact with the outer surface of the periosteum of both the right and the left parietal bones of rats from groups 2, 3, 4, 5, and 6. The group 1 rats underwent sham operation. Bone histomorphometry, performed on the ectocranial periosteum of parietal bones, showed that absolute erosion boundary, absolute eroded area, absolute erosion depth, number of tartrate-resistant acid phosphatase (TRAP)-positive polynucleated osteoclasts, and number of TRAP-positive mononucleated cells decreased in ipriflavone-treated rats compared with group 2 rats. The reduction was roughly proportional to the increase of drug dosage and reached statistical significance in rats of groups 5 and 6. The same parameters were extremely low in group 1 rats. Mineral apposition rate did not differ in any of the groups. Significant increase of serum calcium and significant decrease of serum phosphate were found in group 2 rats compared with group 1 rats, whereas no differences from controls were detected in ipriflavone-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Grain counting in the in vitro hepatocyte DNA-repair assay.

The in vitro hepatocyte DNA-repair assay is a widely used useful method in assessing the genotoxic activity of both directly and indirectly acting chemical agents. This article discusses the criteria presently employed in the autoradiographic evaluation of unscheduled DNA synthesis, and suggests that the subtraction of either the average or the highest cytoplasmic grain count, usually carried out to obtain the net nuclear grain count, may represent a potential source of errors when the test compound is a weakly genotoxic or a non-genotoxic agent. As a matter of fact, a response can be classified as positive or negative depending on the procedure used to quantitate the cytoplasmic background, and the subtraction of this background from the nuclear count is not founded on a sound theoretical basis because of the following reasons: the different nature of the processes responsible for the generation of nuclear and cytoplasmic grains; and the quantitatively different effect that the test compounds may have on the nuclear and the cytosolic labelling.

Animals↗
PubMed1992

Neuropsychological assessment in MS: clinical, neurophysiological and neuroradiological relationships.

We assessed cognitive performance and its relationship with clinical and anatomic disease severity in MS with mild to moderate handicap; 34 definite MS and 18 healthy subjects matched for age and education were submitted to a neuropsychological test battery. Both groups were examined for anxiety. MS patients underwent magnetic resonance imaging examination. MS performed worse than controls on all WAIS-P subtests and had learning, short- and long-term verbal memory impairment. Cognitive deficits were not related to abnormal emotional states, but were found to be associated with attentional process and information-processing speed impairment. Cognitive impairment did not correlate with severity of physical disability. The most severe memory deficits were found in patients with extensive periventricular damage.

Adult↗