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Biomedical subjects

M Sordo

Publications and source records attributed to M Sordo.

9 recordsLinked to original sources

DNA breakage due to metronidazole treatment.

The mutagenicity of metronidazole [1-(hidroxyethyl)-2-methyl-5-nitroimidazole] (MTZ) has been shown in different prokaryotic systems. However, data on human cells are still contradictory. In this study DNA damage was determined by the single cell gel electrophoresis (SCGE) assay, in lymphocytes from 10 healthy subjects treated with therapeutic doses of this drug. Samples were obtained before treatment, as well as 1 and 15 days after ending treatment. Results showed a significant increase of DNA strand breaks 1 day after ending treatment, although, an inverse correlation between the amount of DNA damage and plasma concentrations of MTZ was obtained. Thus, the observed damage may be induced by some MTZ metabolite rather than by the parent drug. Interestingly, the amount of DNA damage returned to basal levels 15 days after ending treatment, except in two individuals. This persistent damage should be further investigated.

Adolescent↗

Cytotoxic and genotoxic effects of As, MMA, and DMA on leukocytes and stimulated human lymphocytes.

Inorganic arsenic is a human carcinogen associated with different types of cancer. Arsenic metabolism produces two methylated species: monomethylarsonic and dimethylarsinic acids. Although this metabolic route has been involved in arsenic detoxification, it is still not clear whether these methylated metabolites participate in the carcinogenic process. In this work, we studied the cytotoxic and genotoxic effects of arsenic and its metabolites. Cytotoxicity was evaluated in cultured lymphocytes from three donors. Mitotic and replication indices were the parameters analyzed. The results indicate a clear cytotoxic effect by sodium arsenite but not by its metabolites. Genotoxicity was assessed by the single cell gel electrophoresis assay. Sodium arsenite increased DNA migration in stimulated lymphocytes only at doses greater than 5 x 10(-6) M; meanwhile in leukocytes a weak response was observed. Monomethylarsonic acid produced in leukocytes a weak induction of DNA damage, while in stimulated lymphocytes, a dose-increase in DNA migration was observed. The injury caused by dimethylarsinic acid was more evident than that observed in cultures treated with sodium arsenite and monomethylarsonic acid in stimulated lymphocytes, although in leukocytes no effect on DNA migration was found. In conclusion, only sodium arsenite had the capacity to alter mitotic and replication indices, while sodium arsenite and its metabolites were capable of inducing single strand DNA breaks on stimulated human lymphocytes treated in vitro for 24 h; however, the differences observed were between individual responses, one donor being more susceptible even at the lower doses. This individual susceptibility to arsenic compounds has been repeatedly observed for different end-points and should be studied further.

Arsenic↗

Combining decision support and image processing: a PROforma model.

This paper addresses two important problems in medical image interpretation:(1) integration of numeric and symbolic information, (2) access to external sources of medical knowledge. We have developed a prototype in which image processing algorithms are combined with symbolic representations for reasoning, decision making and task management in an integrated, platform-independent system for the differential diagnosis of abnormalities in mammograms. The prototype is based on PROforma, a generic technology for building decision support systems based on clinical guidelines. The PROforma language defines a set of tasks, one of which, the enquiry, is used as means of interaction with the outside world. However, the current enquiry model has proved to be too limited for our purposes. In this paper we outline a more general model, which can be used as an interface between symbolic functions and image or other signal data.

Algorithms↗

CADMIUM II: acquisition and representation of radiological knowledge for computerized decision support in mammography.

CADMIUM II is a system for the interpretation of mammograms. A novel aspect of the system is that it combines symbolic reasoning with image processing, in contrast with most other approaches, which use only image processing and rely on artificial neural networks (ANNs) to classify mammograms. A problem of ANNs is that the advice they give cannot be traced back to communicable diagnostic inferences. Our approach is to provide advice based on explicit knowledge about the diagnostic process. To this end, we have conducted a knowledge elicitation study which looked at the descriptors used by expert radiologists when making diagnostic decisions about mammograms. The analysis of the radiologists' reports yielded a set of salient diagnostic features. These were used to inform the advice provided by the symbolic decision making component of CADMIUM II.

Breast Diseases↗

DNA damage in exfoliated buccal cells of smokers assessed by the single cell gel electrophoresis assay.

The alkaline single-cell gel electrophoresis assay or comet assay is a sensitive and rapid method for DNA strand breaks and detection of alkali labile sites at the single cell level, it further provides information on the presence of damage among individual cells. In this paper we explore the use of this technique utilizing exfoliated buccal mucosa cells from non-smokers (9 donors) and smokers (11 donors). The extent of DNA image length was found to be significantly increased in the smoker group (89.30 +/- 16.18 microns) than in the non-smoker group (52.01 +/- 10.43 microns). Our results indicate that the single-cell gel electrophoresis assay could be applied to human monitoring using exfoliated buccal epithelial cells.

Adult↗

Genotoxic effects of Karwinskia humboldtiana toxin T-514 in peripheral blood lymphocytes.

Toxicity by Karwinskia humboldtiana, a Rhamnaceae plant, has been assessed in a number of studies. Four dimmeric anthracenones, named T-496, T-514, T-516 and T-544 for their molecular weight, have been isolated from this plant. T-514, in particular, has been shown to be toxic to liver and lung as well as to tumoral cell lines, preferentially to those from liver tumors. For this reason it has been suggested that the toxin could be used as an antineoplastic agent. The present study was performed to characterize the biological activity of T-514 as a potential cytostatic and genotoxic agent. Peripheral blood lymphocytes in culture were used as a test system, where chromosomal aberrations and sister chromatid exchanges were scored in order to evaluate genotoxicity, and mitotic index and cell proliferation kinetics were used as parameters for cytostatic and cytotoxic ability. Genotoxicity to lymphocytes was negative. However, proliferation was affected by the toxin, demonstrating a cytostatic activity independent of genotoxic damage.

Adult↗

Mitotic index and cell proliferation kinetics for identification of antineoplastic activity.

The mitotic index (MI) and cell proliferation kinetics (CPK) of human blood lymphocyte cultures were determined to evaluate the effects of six antineoplastic drugs with well known cytostatic activity: cisplatin, melphalan, bleomycin, methotrexate, 5-fluorouracil and 6-mercaptopurine. All six drugs showed a clear effect on the inhibition of MI. The first three drugs interact directly with DNA showing a dose-related retardation of CPK. Methotrexate, 5-fluorouracil and 6-mercaptopurine, which act on ribonucleotide biosynthesis, showed no significant effects on CPK. The results suggest that CPK and MI measurements are useful for the prescreening of drugs with potential cytostatic activity.

Adult↗

Are mitotic index and lymphocyte proliferation kinetics reproducible endpoints in genetic toxicology testing?

Lymphocyte proliferation kinetics is an endpoint used in genetic toxicology which has recently been proposed as an alternative for the screening of new cytostatic drugs. Although great variability for this parameter has been reported, there are few reports about the intra- and inter-individual variation of the effects of chemicals on this endpoint. For this reason, experiments were conducted to evaluate the reproducibility of the effects of a well-known cytostatic, mitomycin C (MMC), on the proliferation of PHA-stimulated human lymphocytes, both over time and among samples from several donors. Although inter-individual variability was shown in both parameters in untreated and treated cultures, this variation was not significant. Intra-individual variation was significantly detected only in cultures treated with 0.1 microM MMC.

Adult↗

[Isolation of Plesiomonas shigelloides from a pediatric patient].

We report the isolation of P. shigelloides in the stools of a child with acute diarrhea living in the surroundings of Buenos Aires who usually drank untreated water. P. shigelloides has been implicated as an etiological agent in many sporadic cases of diarrhea, probably associated with drinking untreated water, eating uncooked seafood or foreign travel.

Argentina↗