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Biomedical subjects

A Martelli

Publications and source records attributed to A Martelli.

At least 19 recordsLinked to original sources
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↗
PubMed1992

In vitro and in vivo evaluation of the genotoxicity of N-nitrosooxprenolol.

N-nitrosooxprenolol (NO-oxprenolol) might be formed in the stomach of patients taking the beta-adrenergic blocking drug, oxprenolol. This nitroso derivative has previously been shown to induce DNA damage and repair in both rat and human cultured hepatocytes. The results of the present study show that in the presence of co-cultured rat hepatocytes, 0.03 mM NO-oxprenolol produced a significant increase in the frequency of 6-thioguanine-resistant but not of ouabain-resistant mutants. No mutagenic activity was detected in the absence of metabolic activation. In mice, NO-oxprenolol (1 g/kg) increased the incidence of micronucleated cells in the liver but not in the bone marrow and the spleen. These results suggest that NO-oxprenolol, consistent with its chemical nature of nitrosamine, is biotransformed into short-lived reactive species.

Animals↗
PubMed1992

Slowly progressive aphasia: report of a case.

We report on the case of a 66-year-old right-handed woman, who shows the clinical and behavioral features of "slowly progressive aphasia" described by MESULAM. At the age of 63 the patient began to develop progressive disturbances of word fluency and naming. The neuropsychological examination revealed amnestic aphasia and a mild impairment of verbal memory. Neuroradiological findings demonstrated left temporo-parietal atrophy. A neuropsychological evaluation performed two years later showed a worsening of language disorders and only a slight compromission in other cognitive areas, while the activities of daily living and the occupational functioning remained unimpaired.

Aged↗
PubMed1991

Formation of the N-nitroso derivatives of six beta-adrenergic-blocking agents and their genotoxic effects in rat and human hepatocytes.

Six beta-adrenergic-blocking drugs, atenolol, metoprolol, nadolol, oxprenolol, propranolol and sotalol, were found to react with sodium nitrite in HCl solution, yielding the corresponding N-nitrosamines. The genotoxic activity of the six nitrosamines was evaluated in primary cultures of both rat and human hepatocytes; DNA fragmentation was measured by the alkaline elution technique, and DNA repair synthesis by quantitative autoradiography. Positive dose-related responses were produced in cells of both species after 20 h of exposure to the following subtoxic concentrations: NO-propranolol, 0.01-0.1 mM; NO-oxprenolol, 0.03-1 mM; NO-atenolol and NO-metoprolol, 0.1-1 mM; and NO-nadolol and NO-sotalol, 0.3-3 mM. Modest but statistically significant differences between the DNA-damaging potencies for the two species were observed with NO-atenolol and NO-oxprenolol, which were both more active against rat hepatocytes, and with NO-propranolol, which was more active against human hepatocytes. At equal or higher concentrations, the six N-nitrosamines did not produce DNA fragmentation in Chinese hamster lung V79 cells; this indicates that they behave as indirectly acting compounds, which need to be transformed into reactive metabolites in order to exert a genotoxic effect.

Adrenergic beta-Antagonists↗
PubMed1991

Muscle basal lamina as a grafting material for elongation of axons from rat brain.

Autografts of peripheral nerve or allografts of muscle basal lamina were inserted into the putamen-caudate complex of rats, with the outer end of the implant being sutured to the temporalis muscle. Elongation of central axons within the grafts, as revealed by the horseradish peroxidase retrograde labelling technique, did occur in the presence of basal lamina implants. With both types of grafting materials stained neurones exhibited a comparable distribution, being mainly found in the proximity of the central tip of the grafts. However, labelled cells in the presence of basal lamina were limited in number, compared with peripheral nerve autografts. Therefore, the usefulness of implants of muscle basal lamina into the central nervous system, in order to direct regenerating central axons toward distant target regions, is limited. This material might be suitable, as an alternative grafting material, in experimental models where avoidance of neurological impairment or size and length of the graft are crucial factors.

Animals↗
PubMed1991

Genotoxicity testing of chloramphenicol in rodent and human cells.

The results of this work, carried out to extend the limited information at present available on the genotoxic potential of chloramphenicol (CAP), indicate that in millimolar concentrations this antibacterial agent produced a minimal amount of DNA fragmentation in both V79 cells and metabolically competent rat hepatocytes. Moreover, a level of DNA-repair synthesis indicative of a weak but positive response was detected in primary cultures of liver cells obtained from 2 of 3 human donors, and a borderline degree of repair was present in those prepared from rats. The promutagenic character of CAP-induced DNA lesions was confirmed by a low but significant increase in the frequency of 6-thioguanine-resistant clones of V79 cells, which, however, was absent when the exposure was done in the presence of co-cultured rat hepatocytes. Finally, oral administration to rats of 1/2 LD50 CAP did not increase the incidence of either micronucleated polychromatic erythrocytes or micronucleated hepatocytes. Taken as a whole these findings suggest that CAP should be considered a compound intrinsically capable of producing a very weak genotoxic effect, but only at concentrations about 25 times higher than those occurring in patients treated with maximal therapeutic dosages.

Animals↗
PubMed1991

[High resolution tridimensional study of the blood vessels of the neck and the intracranial circulation with magnetic resonance angiography].

Magnetic Resonance Angiography (MRA) is a modern vascular imaging technique which allows the noninvasive and direct imaging of vessels. The authors aimed at evaluating the diagnostic accuracy of MRA in the study of pathologic conditions in the neck and intracranial vessels; spatial resolution of the technique was also investigated. Twenty-four healthy volunteers and 82 patients suffering from various diseases of the head and neck vessels were included in the study. First of all, MRA capabilities were investigated in visualizing normal vessels of both neck and intracranial circle. The diagnostic accuracy of the method was then evaluated in the study of vascular diseases, and the results compared with conventional/digital angiographic findings. The comparison demonstrated how stenoses and atherosclerotic plaques tend to be overestimated by MRA because of technical artifacts inherent to the technique itself, whereas vascular ulcerations and aneurysms are frequently underestimated. However, this data was steady and therefore evaluable--the exact knowledge of the artifacts making diagnosis reliable. The diagnostic and technical problems relative to the various vascular diseases are discussed. Finally, several hypotheses of diagnostic iter are suggested.

Angiography, Digital Subtraction↗
PubMed1990

Endourologic procedures for ureteropelvic junction stenosis: techniques and results.

Twenty-two cases of stenosis of the ureteropelvic junction were treated by endourologic procedures; 13 were associated with renal stones. Three techniques were used, depending on the type and degree of obstruction: (1) anterograde or retrograde dilation with a double-lumen balloon dilator catheter; (2) incision of the stricture with a cold knife after a percutaneous approach to the kidney; and (3) incision of the stenosis with a new flexible knife through a nephrostomy tract. Balloon dilation was always performed after the incision. No immediate complications were observed following the procedure. The average follow-up was eight months. A routine excretory urogram was done three months after treatment. There were four reobstructions, and in 1 patient the ureteropelvic junction could not be identified. Success rate was 77.3 percent.

Catheterization↗
PubMed1990

Mutation induction in Chinese hamster lung V79 cells by five alk-2-enals produced by lipid peroxidation.

Five alk-2-enals--pent-2-enal, hex-2-enal, hept-2-enal, oct-2-enal and non-2-enal--produced by lipid peroxidation were tested for mutagenic activity in V79 Chinese hamster cells. At concentrations ranging from 0.003 to 0.3 mM all 5 alk-2-enals induced a dose-dependent increase in the frequency of 6-thioguanine-resistant mutants, and their mutagenic potency was found to increase with the length of the carbon chain. In contrast, only hept-2-enal produced a statistically significant increase in the number of mutations to ouabain resistance.

Aldehydes↗
PubMed1990

Comparison of the sensitivity of human and rat hepatocytes to the genotoxic effects of metronidazole.

Metronidazole (MNZ), an antiprotozoan and antibacterial agent, has been shown to yield DNA-damaging reactive species after nitroreductive biotransformation. The genotoxic effect of MNZ was studied in primary cultures of both rat and human hepatocytes. In millimolar concentrations MNZ produced DNA fragmentation, as measured by the alkaline elution technique, and unscheduled DNA synthesis, as evaluated by quantitative autoradiography, in rat hepatocytes. The amount of DNA damage was directly related to the dose and the length of exposure, was increased by hypoxia and GSH depletion, and was markedly reduced by inhibition of cytochrome P-450 activity. In the same experimental conditions human hepatocytes resulted constantly more resistant than rat hepatocytes to the genotoxic activity of MNZ. These findings suggest that the rat hepatocyte model might be an inappropriate predictor of nitroimidazoles genotoxicity.

Adult↗
PubMed1990

[CT study of the carpal tunnel. The carpal tunnel syndrome].

The authors describe the CT aspects of carpal tunnel syndrome. Seventy-seven patients with signs and symptoms of carpal tunnel syndrome were studied, together with 28 postoperative controls (8 with and 20 without recurrence of symptoms) and 10 normal subjects. CT studies were carried out according to the conventional technique employing 3 high-definition axial slices respectively at the proximal end, in the middle and at the distal end of carpal tunnel. The patients affected with carpal tunnel syndrome presented changes in median nerve volume, in synovial sheet thickness, and in shape and density of the flexor tendons. Postoperative CT patterns of asymptomatic patients were similar to those of normal subjects. In the group of patients presenting postoperative recurrence of symptoms, 3 main findings were observed: incomplete surgery, newly formed cysts on the volar surface of the tunnel, and abnormal soft tissue interposed between the tendons. All the above findings were histologically confirmed during a second surgery. The authors believe CT to be a very useful tool in the evaluation of carpal tunnel syndrome, for both the first diagnosis and the demonstration of the causes of postoperative recurrences.

Adolescent↗
PubMed1989

Genotoxicity of N-nitrosochlordiazepoxide in cultured mammalian cells.

Chlordiazepoxide, a benzodiazepine derivative commonly used for the treatment of anxiety, was found to react with sodium nitrite in HCl aqueous solution yielding, at pH ranging from 0.5 to 5,N-nitrosochlordiazepoxide (NO-CDE). In the absence of a metabolic activation system, a dose-dependent frequency of DNA single-strand breaks was revealed by the alkaline elution technique in V79 cells exposed to subtoxic NO-CDE concentrations ranging from 33 to 330 microM. DNA lesions were only partially repaired within 48 hr, and their promutagenic character was demonstrated by the induction of 6-thioguanine resistance in the same cells. The genotoxicity of NO-CDE was confirmed by results obtained in metabolically competent primary cultures of both rat and human hepatocytes, which displayed similar dose-related amounts of DNA fragmentation and of DNA repair synthesis after treatment with concentrations ranging from 33 to 1000 microM. In conclusions similar to those which might occur in the stomach of a patient taking chlordiazepoxide the concentration of NO-CDE in the reaction mixture (50 microM) was of the same order as the concentrations found to induce a genotoxic effect in cultured mammalian cells.

Animals↗