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Biomedical subjects

A Martelli

Publications and source records attributed to A Martelli.

At least 109 records · Page 6Linked to original sources

Comparative study of DNA damage and repair induced by ten N-nitroso compounds in primary cultures of human and rat hepatocytes.

Ten carcinogenic N-nitroso compounds were assayed for DNA-damaging activity in primary cultures of human and rat hepatocytes. DNA fragmentation was measured by the alkaline elution technique, and unscheduled DNA synthesis by quantitative autoradiography. Positive dose-related responses in the range of subtoxic concentrations indicated were obtained in cells of both species with N-nitrosodiethylamine (10-32 mM), N-nitrosodi-n-propylamine (1.8-10 mM), N-nitrosomorpholine (1-3.2 mM), N-nitrosopiperidine (1-3.2 mM), N-nitrosopyrrolidine (3.2-18 mM), N-nitroso-N-methylurea (0.32-1.8 mM), N-nitroso-N-ethylurea (0.32-1.8 mM), and N-nitroso-N-butylurea (0.1-0.32 mM). N-nitrosodi-n-butylamine was practically inactive at the maximal soluble concentration (1 mM). The responses of human hepatocytes were qualitatively similar to those of rat hepatocytes, but statistically significant differences between the two species in the amounts of DNA damage and/or unscheduled DNA synthesis were observed with N-nitrosodimethylamine, N-nitrosomorpholine, N-nitrosopiperidine, N-nitrosopyrrolidine, and N-nitroso-N-butylurea. On the other hand, quantitative differences in the genotoxic effects induced by 5 mM N-nitrosodimethylamine in cultures derived from 20 human donors and from 20 rats were greater than average interspecies differences displayed by this nitrosamine and by other N-nitroso compounds. These results indicate that the rat hepatocyte DNA repair assay is a valid model for predicting the genotoxic potential of N-nitroso compounds in human hepatocytes.

Adult↗

Induction and promotion of gamma-glutamyltranspeptidase-positive foci in the rat liver by methylglyoxal.

The effect of pre-(initiation) and post-(promotion) administration of methylglyoxal (MG) on the induction of gamma-glutamyltranspeptidase (GGT)-positive foci in the liver of F344 male rats was investigated. GGT-positive foci were produced in dose-related amounts by 0.05 and 0.2% MG in drinking water, either when administered to uninitiated rats or when given in the promotion phase.

2-Acetylaminofluorene↗

Cytotoxic, DNA-damaging and mutagenic properties of 2,6-dimethoxy-1,4-benzoquinone, formed by dimethophrine-nitrite interaction.

In conditions similar to those occurring in the stomach, the sympathomimetic drug dimethophrine was found to react with nitrite yielding 2,6-dimethoxy-1,4-benzoquinone (DMBQ). The in vitro and in vivo studies carried out to evaluate the capability of DMBQ to produce cytotoxic and genotoxic effects provided the following results. A dose-related reduction of V79 cells plating efficiency was observed for DMBQ concentrations ranging from 10 to 80 microM; a similar reduction in the fraction of viable cells excluding trypan blue occurred after exposure to 4-fold higher concentrations. A dose-dependent amount of DNA fragmentation was revealed by the alkaline elution technique either in V79 cells exposed to DMBQ concentrations ranging from 10 to 80 microM or in kidney, gastric mucosa and brain of rats treated with single p.o. doses ranging from 33 to 300 mg/kg. Both in vitro and in vivo DNA lesions were largely repaired within 24 hr, but their promutagenic character was demonstrated by the induction of 6-thioguanine-resistance in V79 cells. Primary cultures of rat hepatocytes displayed a greater resistance to the cytotoxic and DNA-damaging activities of DMBQ, and did not exhibit a clear evidence of DNA repair synthesis. Similarly, DNA fragmentation was practically undetectable in the rat liver. Therefore, DMBQ should be considered as a direct-acting genotoxic chemical which is metabolized to less, or nonreactive, species. These findings suggest that DMBQ could produce genotoxic effects in patients taking dimethophrine.

Animals↗

[Computerized tomography in surgically treated lumbar disk hernia. Multicenter study].

Results are reported of a multicenter analytic-statistical CT study on 128 postoperative lumbar herniated disk (HD) cases (50 at L4-L5, 64 at L5-S1, 2 at L3-L4, 12 multiple). CT was performed from 10 days to 204 months (47.7 months of mean) after surgery, in 51 patients without and in 77 with intravenous contrast medium (42 in bolus, 35 in perfusion). In 59 cases (38%) a recurrent hernia was found, and in 8% a new hernia. In 81% of patients epidural fibrous scars were demonstrated, in a rough 50% of cases associated with recurrent/new hernia: posterior fibrosis was found in 81% of cases, while unilaterally, bilaterally, or anteriorly extended fibroses were present in 20%, in 4.7%, and in 29% of cases respectively. In 72% of the patients injected with contrast medium, various kinds of fibrosis contrast enhancement were detected. In 8% neither fibrosis nor recurrent herniation was found. In 22% of cases lateral and/or central bony canal stenosis was present, in 26% vacuum disk, in 9% intracanalar calcifications, in 39% and in 19.5% dural sac stretching and compression respectively. In 5 cases a pseudomeningocele was found, and in 3 only a postoperative diskitis. Fibrosis is an almost inevitable postoperative consequence (4 out of 5 cases); it can be demonstrated by CT with high sensitivity and good specificity. A series of diagnostic criteria, such as the post-contrast media reaction, allow fibrosis to be discriminated from recurrent hernia. However, the possible association must be kept in mind of both diseases and/or of included roots in the scar. Myelography is hardly ever able to supply further resolutive diagnostic elements, while Myelo-CT is sometimes more useful. The importance of bone changes is questionable, with the exception of evident cases of canal stenosis, also because in most cases the radiologist cannot count on a preoperative CT study. Furthermore, the correlation between CT and clinical findings (possible asymptomatic fibrosis) is often difficult, which gives way to contrasting therapeutic attitudes.

Adult↗

Axonal elongation into peripheral nerve grafts between thalamus and somatosensory cortex of the rat. An experimental model.

After destruction of the thalamocortical projections of one side in 12 adult rats, the ipsilateral thalamic ventrobasal nucleus was connected with the contralateral somatosensory cortex through an autologous peripheral nerve graft. Three months after the implanting procedure, horseradish peroxidase was applied to the transected nerve. Retrograde labeling of cells occurred in all examined animals. Evidence of newly formed thalamocortical connections provides the experimental basis to a model suitable for functional evaluations.

Animals↗

Induction of DNA fragmentation and DNA repair synthesis in human and rat hepatocytes by diethylstilbestrol.

The synthetic estrogen diethylstilbestrol (DES), a known human carcinogen, was examined for cytotoxicity, and the induction of DNA damage and repair in primary cultures of human and rat hepatocytes. In both species concentrations of DES ranging from 5.6 to 18 micrograms/ml constantly produced reduction of cell viability and DNA fragmentation in dose-related amounts. However, large individual quantitative differences in the sensitivity to the cytotoxic and DNA-damaging activities of DES were observed among cultures derived from the 5 human donors. DES capability of eliciting DNA-excision repair was weak but statistically significant in both human and rat hepatocytes. Taken as a whole these results contribute to support the hypothesis of a genotoxic mechanism in DES-induced carcinogenesis.

Animals↗

Action of famotidine and ranitidine on prostaglandin E2 (PGE2) content of fundic and duodenal mucosa in duodenal ulcer patients.

PGE2 plays an important role in gastric cytoprotection. Previous experience has shown that H2-blocker drugs may have a role in gastric cytoprotective mechanisms. The effects have been compared of ranitidine and famotidine on PGE2 content in duodenal ulcer patients. Twenty patients were treated for 4 weeks as follows: group A, ranitidine (150 mg twice daily); group B, famotidine (40 mg daily). The patients underwent EGDS before and after therapy. The results show that both famotidine and ranitidine significantly increase the PGE2 content of fundic mucosa (from 112.3 +/- 73 to 210.7 +/- 106 ng/g wet wt and from 109.6 +/- 52.4 to 230.2 +/- 104.6 ng/g wet wt, respectively) in duodenal ulcer patients (p less than 0.01). Similarly, the PGE2 content of duodenal mucosa significantly increases after famotidine treatment (from 51.9 +/- 27.5 to 105.3 +/- 55.6 ng/g wet wt) as well as ranitidine treatment (from 53.8 +/- 24 to 172.6 +/- 72.9 ng/g wet wt) (p less than 0.01). It is concluded that these drugs play an important role in gastric and duodenal cytoprotection.

Adult↗

[CT study of the carpal tunnel. Normal anatomy].

The standard technique for CT investigation of the carpal tunnel and its normal anatomy were studied. Ten healthy asymptomatic volunteers, age 25-45, underwent wrist CT. The hand is placed in prone position with the third metacarpus in line with the radius. Digital radiograph and four axial CT scans are performed respectively: at the distal end of the radius, at the scaphoid tubercle level, at the hamate hook level and at the carpal-metacarpal joint. Standard carpal tunnel diameters are thus available with good reliability and repeatability when correct technique is adopted. The results permit a morphological description of the osseous walls, transverse ligament, flexor tendons with synovial sheets and median nerve. Gujon's canal and its content can also be investigated.

Adult↗

[Neuroradiology of spontaneous cerebral hematomas].

Computed Tomography plays a fundamental role in the diagnosis of spontaneous intracerebral haemorrhage, providing important informations relevant to prognosis and therapy. Therefore angiography should be planned on the basis of the CT finding and of some clinical data such as age, presence of risk factors, etc. Also the neurosurgical approach, besides clinical status, will depend on the neuroradiological evaluation.

Adult↗

Critical nuclear DNA size and distribution associated with S phase initiation. Peripheral location of initiation and termination sites.

Using HeLa S-3 cells synchronized by selective detachment, in this paper we report a parallel study of nuclear morphology and autoradiography grain patterns between middle G1 and middle S phases. Our results show two distinct [3H]-thymidine labeling patterns. The first "peripheral" labeling pattern has a characteristic nuclear size distribution, in contrast to the heterogeneous and varying size distributions of Feulgen-stained nuclei, and apparently is characteristic of very early S phase. The sizes of the second labeling pattern--homogeneous or inhomogeneous grain distribution throughout the nucleus--are equal or larger than the first and vary with S phase progression. Together, the corresponding nuclear sizes of the labeled nuclei represent the larger extreme of nuclear areas, and the labeling index closely parallels the fraction of nuclei with areas larger than the minimum size of the labeled nuclei. These results suggest a characteristic nuclear size (reflecting unique intranuclear DNA distribution) as a necessary, if not sufficient, requirement for S phase initiation. Parallel experimentation with rat liver cells-synchronized in vivo by partial hepatectomy and analyzed by thin section autoradiography--confirms the existence of a peripheral labeling pattern in both the very early part and the very late part of S phase, which reconciles our data with previous results and points to the fact that both initiation and termination sites for DNA replication are near the nuclear periphery.

Animals↗