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L Vega

Publications and source records attributed to L Vega.

At least 19 recordsLinked to original sources

Genetic polymorphisms and activity of PON1 in a Mexican population.

Human paraoxonase (PON1) plays a role in detoxification of organophosphorus (OP) compounds by hydrolyzing the bioactive oxons, and in reducing oxidative low-density lipoproteins, which may protect against atherosclerosis. Some PON1 polymorphisms have been found to be responsible for variations in catalytic activity and expression and have been associated with susceptibility to OP poisoning and vascular diseases. Both situations are of public health relevance in Mexico. Therefore, the aim of this study was to evaluate PON1 phenotype and the frequencies of polymorphisms PON1 -162, -108, 55, and 192 in a Mexican population. The studied population consisted of unrelated individuals (n = 214) of either gender, 18-52 years old. Serum PON1 activity was assayed using phenylacetate and paraoxon as substrates. PON1 variants, -162, 55, and 192, were determined by real-time PCR using the TaqMan System, and PON1 -108 genotype by PCR-RFLP. We found a wide interindividual variability of PON1 activity with a unimodal distribution; the range of enzymatic activity toward phenylacetate was 84.72 to 422.0 U/mL, and 88.37 to 1645.6 U/L toward paraoxon. All four PON1 polymorphisms showed strong linkage disequilibrium (D% >90). PON1 polymorphisms -108, 55, and 192 were independently associated with arylesterase activity; whereas the activity toward paraoxon was related only with PON1 192 polymorphism, suggesting that this polymorphism is determinant to infer PON1 activity. A better understanding of the phenotype and genotypes of PON1 in Mexican populations will facilitate further epidemiological studies involving PON1 variability in OP poisoning and in the development of atherosclerosis.

Adult↗

Differential effects of trivalent and pentavalent arsenicals on cell proliferation and cytokine secretion in normal human epidermal keratinocytes.

There is strong evidence from epidemiologic studies of an association between chronic exposure to inorganic arsenic (iAs) and hyperpigmentation, hyperkeratosis, and neoplasia in the skin. Although it is generally accepted that methylation is a mechanism of arsenic detoxification, recent studies have suggested that methylated arsenicals also have deleterious biological effects. In these studies we compare the effects of inorganic arsenicals (arsenite (iAs(III)) and arsenate (iAs(V))) and trivalent and pentavalent methylated arsenicals (methylarsine oxide (MAs(III)O), complex of dimethylarsinous acid with glutathione (DMAs(III)GS), methylarsonic acid (MAs(V)), and dimethylarsinic acid (DMAs(V))) in human keratinocyte cultures. Viability testing showed that the relative toxicities of the arsenicals were as follows: iAs(III) > MAs(III)O > DMAs(III)GS > DMAs(V) > MAs(V) > iAs(V). Trivalent arsenicals induced an increase in cell proliferation at concentrations in the 0.001 to 0.01 microM range, while at high concentrations (>0.5 microM) cell proliferation was inhibited. Pentavalent arsenicals did not stimulate cell proliferation. As seen in the viability studies, the methylated forms of As(V) were more cytotoxic than iAs(V). Exposure to low doses of trivalent arsenicals stimulated secretion of the growth-promoting cytokines, granulocyte macrophage colony stimulating factor and tumor necrosis factor-alpha. DMAs(V) reduced cytokine secretion at concentrations at which proliferation and viability were not affected. These data suggest that methylated arsenicals, products of the metabolic conversion of inorganic arsenic, can significantly affect viability and proliferation of human keratinocytes and modify their secretion of inflammatory and growth-promoting cytokines.

Adult↗

Automatic identification of metaphase spreads and nuclei using neural networks.

The mitotic index (MI) is an important measure in cell proliferation studies. Determination of the MI is usually made by light-microscope analysis of slide preparations. The analyst identifies and counts thousands of cells and reports the percentage of mitotic shapes found among the interphase nuclei. Full automation of this process is an ambitious task, because there can exist very few mitotic shapes among hundreds of nuclei and thousands of artifacts, resulting in a high probability of false positives, i.e. objects erroneously identified as mitosis or nuclei. A semi-automated approach for MI calculation is reported, based on the development of a neural network (NN) for automatic identification of metaphase spreads and stimulated nuclei in digital images of microscope preparations at 10X magnification. After segmentation of the objects on each image, ten different morphometrical, photometrical and textural features are measured on each segmented object. An NN is used to classify the feature vectors into three classes: metaphases, nuclei and artifacts. The system has been able to classify correctly approximately 91% of the objects in each class, in a test set of 191 mitosis, 331 nuclei and 387 artifacts, obtained from 30 different microscope slides. Manual editing of false positives from the metaphase classification results allows the calculation of the MI with an error of 6.5%.

Humans↗

Comparative toxicity of trivalent and pentavalent inorganic and methylated arsenicals in rat and human cells.

Biomethylation is considered a major detoxification pathway for inorganic arsenicals (iAs). According to the postulated metabolic scheme, the methylation of iAs yields methylated metabolites in which arsenic is present in both pentavalent and trivalent forms. Pentavalent mono- and dimethylated arsenicals are less acutely toxic than iAs. However, little is known about the toxicity of trivalent methylated species. In the work reported here the toxicities of iAs and trivalent and pentavalent methylated arsenicals were examined in cultured human cells derived from tissues that are considered a major site for iAs methylation (liver) or targets for carcinogenic effects associated with exposure to iAs (skin, urinary bladder, and lung). To characterize the role of methylation in the protection against toxicity of arsenicals, the capacities of cells to produce methylated metabolites were also examined. In addition to human cells, primary rat hepatocytes were used as methylating controls. Among the arsenicals examined, trivalent monomethylated species were the most cytotoxic in all cell types. Trivalent dimethylated arsenicals were at least as cytotoxic as trivalent iAs (arsenite) for most cell types. Pentavalent arsenicals were significantly less cytotoxic than their trivalent analogs. Among the cell types examined, primary rat hepatocytes exhibited the greatest methylation capacity for iAs followed by primary human hepatocytes, epidermal keratinocytes, and bronchial epithelial cells. Cells derived from human bladder did not methylate iAs. There was no apparent correlation between susceptibility of cells to arsenic toxicity and their capacity to methylate iAs. These results suggest that (1) trivalent methylated arsenicals, intermediary products of arsenic methylation, may significantly contribute to the adverse effects associated with exposure to iAs, and (2) high methylation capacity does not protect cells from the acute toxicity of trivalent arsenicals.

Aged↗

Sodium arsenite reduces proliferation of human activated T-cells by inhibition of the secretion of interleukin-2.

Arsenic (As) is a common metalloid which contaminates drinking water in several regions of the world and chronic exposure is associated with skin, lung, bladder, and kidney cancer. Previous studies suggest that arsenic exposure leads to a diminution of phytohemaglutinin (PHA) stimulated T cell proliferation in humans. In order to understand the mechanism of this suppression, the effect of As was evaluated on the expression of CD25, and IL-2 secretion in human peripheral blood mononuclear cells (PBMC). Inhibition of proliferation was observed in all donors studied. Most of the donors did not show any change in the expression of CD25, but IL-2 secretion was inhibited in 6 of the 7 donors tested. Proliferative inhibition was due to a suboptimal levels of IL-2 secreted by lymphocytes, since the addition of recombinant IL-2 to the cultures reversed in a dose-dependent fashion the inhibitory effect of As. The determination of the mRNA of IL-2 and the intracellular IL-2 levels demonstrated that the inhibition is not at the transcriptional level. Electron microscopy studies revealed that cellular ultrastructure in Golgi apparatus, mitochondria, cytoskeleton, and perinuclear membrane were altered. These alterations suggest that due to sodium arsenite effects on cytoskeleton, the intracellular secretion of proteins is affected, including the one of IL-2, leading to an impaired proliferation of the T cells when stimulated with PHA.

Adult↗

Roughness feature of metaphase chromosome spreads and nuclei for automated cell proliferation analysis.

As a step towards automation of mitotic index estimation for cell proliferation studies, a roughness feature of surface-intensity images is introduced: the mean depth-width ratio of extrema (MDWRE). This feature allows identification of variable-shaped metaphases and interphase nuclei in the presence of many artefacts (one metaphase per hundreds of nuclei and thousands of artefacts). The texture of the cytological objects (seen as rough surfaces) is quantified by scanning, in one dimension, the lines contained in a closed contour. MDWRE proves to be suitable for image magnifications by a factor of as low as ten, making faster scanning of slides possible. The use of this feature gives +14%, +65%, +133% and +133% better performance figures than classical textural features derived from co-occurrence matrices, such as contrast, energy, entropy and angular second moment, respectively, and +51% better than the relative extrema density (RED). The MDWRE per object and the shape of the histogram of the depth-width ratio of grey-level roughs have been shown to be very useful as textural features for the classification of metaphase images.

Cell Culture Techniques↗

Low levels of urinary iodine excretion in schoolchildren of rural areas in Cuba.

OBJECTIVE: We set up a baseline data on urinary iodine excretion from a nationwide representative sample of rural schoolchildren before instituting iodine supplementation. DESIGN: Stratified multistage cluster sampling in three different strata: lowlands, foothills and mountainous areas. Early morning urine samples were collected for evaluation of iodine status. SETTING: Field study in 25 municipalities in 11 out of 14 provinces. The study was carried out from October to December 1995. SUBJECTS: Three thousand and twenty-seven schoolchildren of either sex, 6 to < 12 y from 87 primary schools. RESULTS: The median urinary iodine excretion was 95 microg/L for the whole sample. The situation in a few foothills and all mountainous areas showed a moderate to severe deficiency. In the mountainous stratum, the median urinary iodine excretion values was less than 20 microg/L. CONCLUSIONS: Cuba has a mild iodine deficiency public health problem with respect to WHO criteria, which in the mountainous areas is severe. The Government of Cuba has started a national Plan of Action and funds are being mobilized to introduce nationwide iodized salt.

Altitude↗

Cytogenetic effects in human exposure to arsenic.

The cytogenetic effects of arsenic exposure were studied among rural populations that live in the same geographical area and have similar socioeconomic status, but different degree of exposure to inorganic arsenic (As) via drinking water. A group of inhabitants of Santa Ana (408.17 micrograms/l of As in drinking water) were considered the exposed individuals and a group of inhabitants of Nazareno (29.88 micrograms/l) were considered as controls. Blood and urine samples were obtained from volunteers. Past and current exposure, health, and nutritional status as well as the presence of arsenic skin lesions were ascertained in study participants through questionnaires and physical examination. The frequencies and types of chromosomal aberrations in first-division metaphases were studied in whole blood lymphocyte cultures while the presence of micronuclei (MN) was studied in exfoliated epithelial cells obtained from the oral mucosa and from urine samples. Total arsenic (TAs) content, and the relative proportions of inorganic arsenic (IAs), and the metabolites monomethylarsonic (MMA) and dimethylarsinic (DMA) acid were determined in urine samples. Exposed individuals showed a significant increase in the frequency of chromatid and isochromatid deletions in lymphocytes and of MN in oral and urinary epithelial cells. Males were more affected than females, and a higher number of micronucleated oral cells were found among those individuals with skin lesions. The type of cytogenetic damage observed gives evidence of arsenic as a clastogenic/aneugenic carcinogen.

Adult↗

What happened to street kids? An analysis of the Mexican experience.

This paper documents some possible reasons of failure of programs for street children in Mexico, and provides background information on demographic and socioeconomic trends that underlay self-employment as well as a historical perspective of the social context of street children. It also describes the strategies used to survive in the streets, trends in drug use/misuse, the felt needs of children and the social responses to this problem. It documents how underlying failure there are unrealistic goals, a fragmented perception of the problem and consequently, a fragmented response to it. It also refers to the great pressure on institutions for results, lack of continuity of the programs and disregard of the perception and felt needs of working children who should benefit from these programs.

Adolescent↗

Genotoxic effects of bistratene A on human lymphocytes.

Bistratene A, a toxin isolated from the colonial ascidian Lissoclinum bistratum causes a decrease in mitotic index and retardation of lymphocyte proliferation kinetics when it is added at 48 h to 72-h human lymphocyte cultures. In the same cultures, the incidence of sister chromatid exchanges was not altered by this compound. We also observed an increase in the number of polyploid cells in the cultures, and alterations of the beta-tubulin organization by immunocytochemistry with an antibody against beta-tubulin. Bistratene A induces DNA damage in a dose-dependent fashion in leukocytes, as measured by the alkaline single cell gel electrophoresis assay. These results show that bistratene A interferes with microtubule assembly, is cytotoxic and cytostatic, and that it causes DNA damage.

Acetamides↗

Aneugenic effect of sodium arsenite on human lymphocytes in vitro: an individual susceptibility effect detected.

Arsenic is a well known carcinogenic environmental pollutant although its mechanism of action remains unknown. Since alterations in chromosome segregation have been observed in individuals exposed to high concentrations of arsenic in the drinking water, the aneuploidogenic potential of arsenic was evaluated in vitro. Whole blood cultures were incubated for 72 h and treated with various concentrations of sodium arsenite for the last 24 h. Cells were harvested and samples were processed specially for aneuploidy evaluation. The number of chromosomes in 200 metaphases of first and second division cells was scored. A dose-related effect was observed: the highest concentration (10(-2) microM) induces 28.33% and 22.4% hyperploid cells in first and second division respectively and 29% tetraploid cells. The colchicine-like effect of arsenic was also evaluated. Mitotic arrest was evaluated in cultures treated for the last 2 h. Sodium arsenite can produce 40.24% and 12.93% of the colcemid effect (mitotic arrestant effect at 10(-2) microM and 10(-10) microM respectively). A different individual susceptibility effect was observed in both parameters and confirmed with the chromosome aberrations levels induced by arsenic in the same donors. Data indicate that sodium arsenite has an aneuploidogenic and a mitotic arrestant effect.

Aneuploidy↗

Lipoprotein (a) and other risk factors in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND: Studies have established a relationship between lipoprotein (a) [Lp(a)] levels and cardiovascular disease, but few have studied Lp(a) in patients with non-insulin-dependent diabetes mellitus (NIDDM). METHODS: We determined Lp(a) concentrations, levels of glycated hemoglobin, and the personal and family history of atherosclerosis in 88 patients with NIDDM (53 men and 35 women; age, 33-70 years) and 90 age- and sex-matched controls. Twenty-three patients with NIDDM had cardiovascular disease (CVD group) and 65 did not (non-CVD group). RESULTS: Lp(a) levels were higher in CVD than non-CVD patients (P < 0.01). Triglyceride levels negatively correlated with Lp(a) (r = -0.51, P < 0.05), independently of the metabolic control of diabetes. Patients with poor metabolic control (glycated hemoglobin > 7.5%) had higher Lp(a) levels than the control group (P < 0.05). Lp(a) levels were higher than 0.30 milligram in 11% of patients without CVD and 55% of those with CVD (P < 0.05). Cluster analysis showed that Lp(a), as well as total cholesterol, triglycerides, apolipoprotein B100, and age were independently related to CVD in patients with NIDDM (P < 0.001 for triglycerides and P < 0.05 for the other variables). CONCLUSIONS: Lp(a) levels can be considered an independent risk factor for the development of atherosclerosis in NIDDM.

Adult↗

Inorganic arsenic effects on human lymphocyte stimulation and proliferation.

Lymphocyte cultures from individuals exposed to high levels of hydroarsenicism showed a slower cell cycle kinetics than cultures from low-exposed individuals. Since this difference in proliferation could be due to chronic arsenic exposure, the in vitro effects of inorganic arsenic in human whole blood lymphocyte cultures were investigated. When lymphocytes were exposed to concentrations of arsenite and arsenate similar to those found in the blood of exposed subjects (10(-7), 10(-8) and 10(-9) M) during the last 24 h before harvesting, a dose-related inhibition of proliferation was observed. Cultures were also treated with 10(-9) M of arsenite and arsenate for 2, 6 and 24 h at the beginning of the cultures in the presence or absence of phytohemagglutinin (PHA). Inhibition of stimulation and proliferation was directly related to the length of treatment. The results show that, at the concentrations tested, arsenite and arsenate impair lymphocyte stimulation and proliferation and confirm the fact that chronic arsenic exposure can affect the proliferation of whole blood lymphocytes.

Adult↗