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Mira A.,Instituto Multidisciplinario Of Biologia Celular | Gili J.A.,CONICET | Lopez-Larraza D.M.,Instituto Multidisciplinario Of Biologia Celular | Lopez-Larraza D.M.,CONICET
Journal of Environmental Pathology, Toxicology and Oncology | Year: 2013

Nonprotein thiols are considered radioprotectors, preventing DNA damage by ionizing radiation. Because bleomycin (BLM) is a radiomimetic agent, it was proposed that thiols may prevent DNA damage produced by this antibiotic. However, results obtained with treatments combining thiols and BLM in living cells are contradictory. The goal of this study was to analyze the DNA damage induced by BLM and the influence of 3 nonprotein thiols of different electrical charges and chemical compositions at the level of single cells (comet assay). We also studied the morphological signs of apoptosis produced by BLM in these same conditions. We found that all thiols potentiated DNA damage induced by BLM, most probably by reactivating the BLM complex once it generated free radicals. Cysteamine (positive) potentiated BLM action the most, glutathione (negative) potentiated this antibiotic the least, whereas cysteine had an intermediate effect compared with the other two. © 2013 Begell House, Inc.


Glesmann L.A.,Instituto Multidisciplinario Of Biologia Celular | Martina P.F.,National University of Misiones | Catanesi C.I.,Instituto Multidisciplinario Of Biologia Celular
Human Biology | Year: 2013

The Wichí people from Chaco Province inhabit the region called Impenetrable Chaqueño, where the climatic conditions are extreme. Besides scarce communication with the main urban centers, the cultural patterns of the Wichí cause these communities to live in certain degree of isolation. The effect of this situation is an increased genetic differentiation from other populations, as it was observed through autosomal and Y chromosome markers. However, the genetic variation of X chromosome has not yet been fully analyzed. The patterns of allele distribution of different markers of X chromosome can be highly informative in comparative studies, because its special features make this chromosome a potential source to uncover ethnic differences. The aim of this study was to assess the variation of X chromosome present in the Wichí population living around Misión Nueva Pompeya, in Chaco Province, and to identify particular variation of X-repetitive markers (short tandem repeats, X-STRs) in Chaco Amerindians. We genotyped Wichí for 10 noncoding X-STRs and compared them with a Mocoví population and with published data on individuals coming from European immigration. We found high homozygote proportion and linkage disequilibrium values for the X chromosome in the Wichí population. The data showed the Wichí to be more distant from nonnative people than was the Mocoví population analyzed for comparison. We also found certain differences with Mocoví, possibly due to a higher genetic flow of the latter with nonnatives. A process of genetic drift seems to be enhanced by the social behavior of the Wichí, since they live apart from other native and nonnative groups. The geographic isolation and the extreme environmental conditions can also be considered as major factors contributing to the population differentiation. Although we found no new allele or undescribed variation, the whole pattern of variation for these markers gives the Wichí a particular population identity. © 2014 Wayne State University Press, Detroit, Michigan 48201-1309.


PubMed | Hospital Of Clinicas Of Porto Alegre, Programa Nacional da Hanseniase, Secretaria de Vigilancia em Saude, Instituto Multidisciplinario Of Biologia Celular and Federal University of Rio Grande do Sul
Type: | Journal: Reproductive toxicology (Elmsford, N.Y.) | Year: 2015

Thalidomide causes congenital defects in children, such as limb reduction defects. Currently, it is used for a few indications; in Brazil, where leprosy is endemic, thalidomide is used for the treatment of erythema nodosum leprosum, and recent cases of thalidomide embryopathy have been reported.We analyzed the frequency of births with phenotypes consistent with thalidomide embryopathy (TEP) and correlated this with the distribution of thalidomide and the prevalence of leprosy between 2005 and 2010 in Brazil.A total of 5,889,210 thalidomide tablets were distributed; the prevalence of limb reduction defects was 1.60 (CI95%: 1.54-1.66) and TEP was 0.11 (CI95%: 0.10-0.13) per 10,000 births. Poisson regression showed an increase in cases of TEP and limb reduction defects per 100,000 tablets dispensed. Clusters and geographical isolates were identified in several regions.There is a correlation between thalidomide and TEP showing that thalidomide embryopathy should be monitored in countries where this medication is available.


Martinez-Cortes G.,University of Guadalajara | Salazar-Flores J.,University of Guadalajara | Haro-Guerrero J.,University of Guadalajara | Rubi-Castellanos R.,University of Guadalajara | And 8 more authors.
American Journal of Physical Anthropology | Year: 2013

The maternal ancestry (mtDNA) has important applications in different research fields, such as evolution, epidemiology, identification, and human population history. This is particularly interesting in Mestizos, which constitute the main population in Mexico (∼93%) resulting from post-Columbian admixture between Spaniards, Amerindians, and African slaves, principally. Consequently, we conducted minisequencing analysis (SNaPshot) of 11 mitochondrial single-nucleotide polymorphisms in 742 Mestizos of 10 populations from different regions in Mexico. The predominant maternal ancestry was Native American (92.9%), including Haplogroups A, B, C, and D (47, 23.7, 15.9, and 6.2%, respectively). Conversely, European and African ancestries were less frequent (5.3 and 1.9%, respectively). The main characteristics of the maternal lineages observed in Mexican-Mestizos comprised the following: 1) contrasting geographic gradient of Haplogroups A and C; 2) increase of European lineages toward the Northwest; 3) low or absent, but homogeneous, African ancestry throughout the Mexican territory; 4) maternal lineages in Mestizos roughly represent the genetic makeup of the surrounding Amerindian groups, particularly toward the Southeast, but not in the North and West; 5) continuity over time of the geographic distribution of Amerindian lineages in Mayas; and 6) low but significant maternal population structure (FST = 2.8%; P = 0.0000). The average ancestry obtained from uniparental systems (mtDNA and Y-chromosome) in Mexican-Mestizos was correlated with previous ancestry estimates based on autosomal systems (genome-wide single-nucleotide polymorphisms and short tandem repeats). Finally, the comparison of paternal and maternal lineages provided additional information concerning the gender bias admixture, mating patterns, and population structure in Mestizos throughout the Mexican territory. © 2013 Wiley Periodicals, Inc.


Campana H.,Instituto Multidisciplinario Of Biologia Celular | Ermini M.,Hospital Italiano Of La Plata | Aiello H.A.,Hospital Italiano Of Buenos Aires | Krupitzki H.,Center for Medical Education and Clinical Research | And 4 more authors.
Journal of Ultrasound in Medicine | Year: 2010

Objective. The purpose of this study was to assess the accuracy of prenatal sonographic diagnosis of birth defects and the gestational age at detection according to the health insurance schemes of mothers in 450 malformed neonates from 18 South American hospitals on the basis of prenatal sonographic records. Methods. Between July 2000 and December 2003, 18 hospitals included in the Latin American Collaborative Study of Congenital Malformations (13 from Argentina [8 public and 5 nonpublic], 3 from Brazil [2 public and 1 nonpublic], 1 from Chile [nonpublic], and 1 from Venezuela [public]) voluntarily participated in this prospective observational study, recording fetuses with sonographically detected malformations. Prenatal sonographic descriptions of anomalies were compared with those recorded at birth. Results. Of 812 anomalies detected at birth, 457 had been prenatally detected (detection rate, 56.3%; 95% confidence interval, 52.8%-59.8%). Before 24 gestational weeks, anencephaly had the highest detection rate. Cleft lip and clubfoot were more easily detected when associated with other anomalies. The detection rates for central nervous system and renourinary malformations were greater than 80%. Detection rates between both health insurance schemes (public and nonpublic) did not show significant differences, but anencephaly, spina bifida, renourinary defects, and cleft lip with or without cleft palate were detected earlier in patients from nonpublic rather than in public hospitals. Conclusions. For specific anomalies, South America shows similar levels of prenatal sonographic detection as developed countries. Detection rates during pregnancy were similar for public and nonpublic hospitals, whereas cases were diagnosed earlier in patients from nonpublic hospitals. © 2010 by the American Institute of Ultrasound in Medicine.


Alzamendi A.,Instituto Multidisciplinario Of Biologia Celular | Castrogiovanni D.,Instituto Multidisciplinario Of Biologia Celular | Gaillard R.C.,University of Lausanne | Spinedi E.,Instituto Multidisciplinario Of Biologia Celular | Giovambattista A.,Instituto Multidisciplinario Of Biologia Celular
Endocrinology | Year: 2010

An adverse endogenous environment during early life predisposes the organism to develop metabolic disorders. We evaluated the impact of intake of an iso-caloric fructose rich diet (FRD) by lactating mothers (LM) on several metabolic functions of their male offspring. On postnatal d 1, ad libitum eating, lactating Sprague-Dawley rats received either 10% F (wt/vol; FRD-LM) or tap water (controls, CTR-LM) to drink throughout lactation. Weaned male offspring were fed ad libitum a normal diet, and body weight (BW) and food intake were registered until experimentation (60 d of age). Basal circulating levels of metabolic markers were evaluated. Both iv glucose tolerance and hypothalamic leptin sensitivity tests were performed. The hypothalamus was dissected for isolation of total RNA and Western blot analysis. Retroperitoneal (RP) adipose tissue was dissected and either kept frozen for gene analysis or digested to isolate adipocytes or for histological studies. FRD rats showed increased BW and decreased hypothalamic sensitivity to exogenous leptin, enhanced food intake (between 49-60 d), and decreased hypothalamic expression of several anorexigenic signals. FRD rats developed increased insulin and leptin peripheral levels and decreased adiponectinemia; although FRD rats normally tolerated glucose excess, it was associated with enhanced insulin secretion. FRD RP adipocytes were enlarged and spontaneously released high leptin, although they were less sensitive to insulin-induced leptin release. Accordingly, RP fat leptin gene expression was high in FRD rats. Excessive fructose consumption by lactating mothers resulted in deep neuroendocrine-metabolic disorders of their male offspring, probably enhancing the susceptibility to develop overweight/obesity during adult life. Copyright © 2010 by The Endocrine Society.


PubMed | Instituto Multidisciplinario Of Biologia Celular
Type: Journal Article | Journal: Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine | Year: 2010

The purpose of this study was to assess the accuracy of prenatal sonographic diagnosis of birth defects and the gestational age at detection according to the health insurance schemes of mothers in 450 malformed neonates from 18 South American hospitals on the basis of prenatal sonographic records.Between July 2000 and December 2003, 18 hospitals included in the Latin American Collaborative Study of Congenital Malformations (13 from Argentina [8 public and 5 nonpublic], 3 from Brazil [2 public and 1 nonpublic], 1 from Chile [nonpublic], and 1 from Venezuela [public]) voluntarily participated in this prospective observational study, recording fetuses with sonographically detected malformations. Prenatal sonographic descriptions of anomalies were compared with those recorded at birth.Of 812 anomalies detected at birth, 457 had been prenatally detected (detection rate, 56.3%; 95% confidence interval, 52.8%-59.8%). Before 24 gestational weeks, anencephaly had the highest detection rate. Cleft lip and clubfoot were more easily detected when associated with other anomalies. The detection rates for central nervous system and renourinary malformations were greater than 80%. Detection rates between both health insurance schemes (public and nonpublic) did not show significant differences, but anencephaly, spina bifida, renourinary defects, and cleft lip with or without cleft palate were detected earlier in patients from nonpublic rather than in public hospitals.For specific anomalies, South America shows similar levels of prenatal sonographic detection as developed countries. Detection rates during pregnancy were similar for public and nonpublic hospitals, whereas cases were diagnosed earlier in patients from nonpublic hospitals.


PubMed | Instituto Multidisciplinario Of Biologia Celular
Type: Journal Article | Journal: Mutation research | Year: 2012

We analyzed the behavior of interstitial telomeric sequences (ITSs) in the progeny of Chinese Hamster Ovary (CHO) cells exposed to the radiomimetic compound bleomycin (BLM) in order to determine if ITSs play some role in the long-term clastogenic effect of this antibiotic. To this end, CHO cells were treated with a single concentration of BLM (2.5g/ml), and the frequency of unstable chromosomal aberrations was determined at several times after treatment (18h, and 6, 15 and 34/36 days) by using PNA-FISH with a pan-telomeric probe [(TTAGGG)n repeats]. Cytogenetic analysis revealed a higher frequency of aberrations at 18h and 6 days after treatment in BLM-exposed cultures vs. untreated cultures, although the yield of BLM-induced aberrations decreased on average five times 6 days after treatment compared with the one induced 18h after treatment. Moreover, no significant differences in the frequency of aberrations were observed between untreated and BLM-exposed cells at 15 or 34/36 days after treatment. These data indicate that, in terms of unstable aberrations, the in vitro clastogenic effect of BLM on CHO cells persists for at least 6 days but less than 15 days after exposure. In addition, we found that BLM induces ITSs instability, cytogenetically detectable as acentric fragments (18h after treatment) or additional (new) FISH signals (6 days after treatment). We propose that the delayed effect of BLM on ITSs mainly results from breakage of heterochromatic ITSs blocks and further insertion of these sequences at the sites of monochromatid breaks occurring at G2 phase of the cell cycle, since most of the additional FISH signals were present as single dots and located at interstitial sites of the involved chromosomes.


PubMed | Instituto Multidisciplinario Of Biologia Celular
Type: Journal Article | Journal: Mutation research | Year: 2012

We analyzed the induction of chromosomal aberrations in Chinese hamster ovary (CHO) cells exposed to the radiomimetic compound streptonigrin (SN), in order to determine whether interstitial telomeric sequences (ITSs) are involved in the long-term clastogenic effect of this antibiotic. CHO cells were treated with a single concentration of SN (100ng/ml), and the frequency of unstable chromosomal aberrations was determined at three times after treatment (18h, and 6 and 15 days) by using PNA-FISH with a pan-telomeric probe. Cytogenetic analysis revealed a higher frequency of aberrations at 18h and 6 days after treatment in SN-exposed cultures vs. untreated cultures. The percentage of damaged cells and the yield of SN-induced aberrations at 6 days after treatment increased on average twofold compared with the ones at 18h after treatment. Moreover, a significant decrease in the frequency of aberrations was observed in SN-exposed cells at 15 days after treatment, resulting in a frequency of aberrations significantly lower than the frequency of aberrations observed in the corresponding control cultures. These data indicate that SN induces delayed chromosomal instability in CHO cells, and that the in vitro clastogenic effect of this compound persists for at least 6 days but less than 15 days after treatment. In addition, we found that SN induces delayed ITSs instability, cytogenetically detectable as additional FISH signals and centromeric breaks involving dissociation of the telomeric signal 6 days after treatment. We propose that the delayed effect of SN on ITSs results from breakage of heterochromatic centromeric ITSs blocks and further insertion of these sequences at the sites of mono- or isochromatid breaks occurring at G2 or G1-S phases of the cell cycle, respectively, since most of the additional FISH signals were present as single or double dots, and located at interstitial sites of the involved chromosomes.


PubMed | Instituto Multidisciplinario Of Biologia Celular
Type: Journal Article | Journal: Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer | Year: 2013

Nonprotein thiols are considered radioprotectors, preventing DNA damage by ionizing radiation. Because bleomycin (BLM) is a radiomimetic agent, it was proposed that thiols may prevent DNA damage produced by this antibiotic. However, results obtained with treatments combining thiols and BLM in living cells are contradictory. The goal of this study was to analyze the DNA damage induced by BLM and the influence of 3 nonprotein thiols of different electrical charges and chemical compositions at the level of single cells (comet assay). We also studied the morphological signs of apoptosis produced by BLM in these same conditions. We found that all thiols potentiated DNA damage induced by BLM, most probably by reactivating the BLM complex once it generated free radicals. Cysteamine (positive) potentiated BLM action the most, glutathione (negative) potentiated this antibiotic the least, whereas cysteine had an intermediate effect compared with the other two.

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