ANA LOURDES GARRIDO SALAZAR - Academia.edu (original) (raw)
Papers by ANA LOURDES GARRIDO SALAZAR
Propiedad Intelectual, 2021
Las sociedades del mundo han evolucionado de manera tal que cada día son más las personas que tom... more Las sociedades del mundo han evolucionado de manera tal que cada día son más las personas que toman la iniciativa de emprender individualmente, en lugar de trabajar para una organización o empresa ajena. Esto ha generado la necesidad de diferenciar los bienes y servicios a través de marcas, requiriendo para ello de un proceso para su creación, dentro del cual resulta prioritario distinguir una figura fundamental conocida como el naming o técnica de creación léxica, que se traduce en el proceso creativo mediante el cual se concibe o asigna el nombre de una marca, siendo una tarea compleja y determinante para el éxito o fracaso de la misma.
Sept populations de nématodes à kyste de la pomme de terre (#Globodera rostochiensis$ et #G. pall... more Sept populations de nématodes à kyste de la pomme de terre (#Globodera rostochiensis$ et #G. pallida$) ont été analysées au moyen de marqueurs provenant de fragments d'ADN amplifiés au hasard (RAPD), d'amorces de microsatellites amplifiés en chaîne par réaction de polymérase (PCR) et d'électrophorèse de protéines totales en deux dimensions sur gel. Un degré élevé de polymorphisme a été détecté chez tous les types de marqueurs. De plus, des réactions de virulence des populations et de l'hôte, de même qu'une interaction hautement significative entre ces deux variables, ont été observés. Les distances génétiques entre populations de nématodes, fondées sur les données moléculaires et les réactions de virulence ont été estimées. Des analyses en grappes ont été réalisées et les matrices de distance en résultant comparées. Une bonne consistance entre les différents dendrogrammes, de même que des coefficients de corrélation hautement significatifs ont été observés lorsqu...
Ciencias de la Salud, 2014
Cell Biology International, 2008
The aim of this work was to study the effect of the drug idebenone on the growth of a strain of S... more The aim of this work was to study the effect of the drug idebenone on the growth of a strain of Saccharomyces cerevisiae yeast and its respiratory-deficient mutant (rho 0). We took this yeast as a model system of the interaction of the drug with mammalian cells. The effect of idebenone was evaluated in rich and minimal media. In the S288c strain, idebenone exerted a growth inhibitory effect in concentrations higher than 50 mM in media containing a carbon source consumed at mitochondrial level. In conditions of low oxygen supply, idebenone allows yeast to keep a cellular yielding comparable with conditions of normal oxygen supply. Also, the presence of idebenone in the growth media increased by 50% the fluorescence signal of rhodamine 123, indicating a higher mitochondrial membrane potential. The results could explain the effect of idebenone in the treatment of diseases in which oxygen deficiency alters the energetic metabolism of the cell.
Cancer research, 1983
In early studies using high dosages of Escherichia coli asparaginase (10 doses of 1000 ID/kg each... more In early studies using high dosages of Escherichia coli asparaginase (10 doses of 1000 ID/kg each) for the treatment of acute lymphoblastic leukemia, hepatotoxicity was a major com plication of therapy. Biochemical evidence of hepatic dysfunction occurred in 75% of patients during the first 2 weeks of treatment. Currently, the use of lower dosages of E. coli asparaginase (three doses of 6000 ID/sq m each) has reduced the incidence of hepatic complication. Hepatic dysfunction in the form of severe life-threatening thromboembolic coagulopathy, however, contin ues to be associated with the use of this enzyme. Our previous work has established that the fatty degenerative changes and hepatocellular dysfunction associated with short-term (1 week) £.coli asparaginase treatment does not occur in mice treated with a glutaminase-free asparaginase from Vibrio succinogenes. In this report, we examined the hepatotoxic effects of prolonged treatment with E. coli and Erwinia carotovora asparaginases and compared the observed toxicities to those observed with the glutaminase-free asparaginase from V. succinogenes. Using a murine model, our data indicate that the hepatotoxicity of £. coli asparaginase parallels the toxicity observed in humans with a rapid increase in liver lipid levels and decreased plasma levels of albumin, antithrombin III, cholesterol, and triglycéridesoccurring in the first and second weeks followed by a resumption to normal hepatic function during Weeks 3 and 4. In contrast, prolonged treatment of mice with V. succinogenes asparaginase is not associated with significant hepatotoxicity. Er. carotovora aspa raginase treatment is associated with an intermediate level of toxicity as indicated by increased hepatic lipid concentration occurring during the second and fourth weeks of treatment. Hepatic function as determined by plasma lipids and proteins was normal in Er. carotovora asparaginase-treated mice. Our data suggest that the combined physiological depletion of asparagine and glutamine following administration of E. coli or Er. carotovora asparaginases may result in pronounced hepato toxicity. In contrast, a glutaminase-free asparaginase with potent antilymphoma activity isolated from V. succinogenes is not hep atotoxic even after prolonged treatment. Therefore, it may prove to be a more efficacious antitumor agent in humans.
BMJ Open, 2013
receptor polymorphisms are an associated risk factor for mild cognitive impairment and Alzheimer ... more receptor polymorphisms are an associated risk factor for mild cognitive impairment and Alzheimer disease in women APOE ɛ4 carriers: a casecontrol study. BMJ Open 2013;3:e003200.
Journal of Vegetation Science, 2014
Questions What are the temporal and spatial variations of groundwater depth along topographic gra... more Questions What are the temporal and spatial variations of groundwater depth along topographic gradients in Neotropical savannas? Are patterns of tree density and species diversity along topographic gradients in Neotropical savannas controlled by water table depth? Do soil and groundwater nutrient concentrations differ along topographic gradients in Neotropical savannas? Location Fire-protected savannas of central Brazil. Methods Over 16 mo, we monitored temporal and spatial variations in groundwater levels using automated submersible pressure transducers installed in ten wells located along two topographic gradients (five wells per gradient) of 950 m and 1703 m in length, representing elevations of 47 and 37 m a.s.l., respectively. We located the wells according to changes in vegetation physiognomies from woody savannas at high elevations, to open shrubby grasslands at low elevations. Along each topographic gradient we determined soil and groundwater nutrient concentrations as well as richness, density, basal diameter and height of trees within two plots of 14 × 14 m (392 m2) adjacent to each well. Results Along the two gradients, groundwater levels exhibited larger fluctuations at lower than at higher elevations where the water table was deeper. Richness, density and diversity of trees decreased significantly at lower elevations where soils were waterlogged during the wet season. Soil pH and soil concentrations of carbon, nitrogen and manganese decreased significantly as elevation increased along the topographic gradients, but soil nutrient concentrations of phosphorus, aluminium and iron did not change with elevation. Groundwater samples contained only trace amounts of nutrients and were poorly correlated with elevation along the topographic gradients. Conclusions In Neotropical savannas, the minimum distance between the soil surface and water table depth (reached during the wet season) and the relatively large fluctuations in groundwater limit tree density and diversity at low elevations as savanna trees cannot cope with extended waterlogging during the wet season and with low soil water availability during the dry season. Thus, variations of tree density and diversity along topographic gradients are more related to spatial and temporal variations in water table depth than to soil and groundwater nutrient variations in Neotropical savannas.
Archives of Medical Research, 2014
Calpain activity has been implicated in several cellular processes such as cell signaling, apopto... more Calpain activity has been implicated in several cellular processes such as cell signaling, apoptosis, exocytosis, mitochondrial metabolism and cytoskeletal remodeling. Evidence has indicated that the impairment of calpain expression and the activity of different calpain family members are involved in diverse pathologies. Calpain-10 has been implicated in the development of type 2 diabetes, and polymorphisms in the CAPN10 gene have been associated with an increased risk of developing this disease. The present work focused on the molecular biology of calpain-10, supporting its key participation in glucose metabolism. Current knowledge regarding the role of calpain-10 in the development of type 2 diabetes mellitus and diabetes-related diseases is additionally reviewed.
Current Pharmaceutical Design, 2014
Preterm birth is the leading cause of perinatal morbidity and mortality. Pathological processes t... more Preterm birth is the leading cause of perinatal morbidity and mortality. Pathological processes that have been linked with preterm birth infection and / or intrauterine inflammation are most frequently found associated with their induction. Studies in animal models and human research showed prior infections to the induction of labor, the anteriority of infection over labor induction, and the existence of a subclinical latency phase between these two phenomena. The ascending route from the vagina and the cervix is preponderant but also microorganisms may access the amniotic cavity and the fetus by other pathways. During inflammation associated to infection, Prostaglandins are released simultaneously with Nitric oxide and their overproduction could be detrimental. Prostaglandins promote uterine contractions contributing to embryonic and fetal expulsion. Therefore aberrant activation of the inflammatory response may cause premature labor and this does not seem to depend on how the microoorganisms accessed the uterus.
Transplantation, 1993
Rapamycin prolongs allograft survival and induces donor-specific tolerance in some small animal t... more Rapamycin prolongs allograft survival and induces donor-specific tolerance in some small animal transplant models. Large animal studies, however, are limited. We studied rapamycin in a porcine renal allograft model. Donor-recipient combinations were chosen based on high response in pretransplant MLCs. Allografts were anastomosed to the aorta and vena cava and the native kidneys removed. There were 5 treatment groups: (a) no immunosuppression; (b) triple therapy (CsA, 1 mg/kg/day; AZA, 2–3 mg/kg/day; and PRED, 3–4 mg/kg/day); (c) rapamycin (0.75 mg/kg/day i.m.) in carboxymethylcellulose (CMC); (d) rapamycin (0.25 mg/kg/day i.m. in CMC); and (e) a vehicle (CMC) control. Serum creatinine levels were determined every other day. Most allografts were biopsied once a week. Immunosuppression was stopped after 30 days. Mean graft survival in nonimmunosuppressed recipients was 6.8±3.6 days. Mean graft survival in triple therapy recipients (n=10) was 45.7±36 days vs. 59.6±11.4 days in rapamycin (0.25 mg/kg/day) recipients (n=7) (P=0.51). Both triple therapy and rapamycin improved renal allograft survival versus nonimmunosuppressed controls (P=0.0025 and 0.001, respectively). Serum creatinine levels were significantly lower (P<0.05) in rapamycin versus triple therapy recipients. We conclude that rapamycin is a potent immunosuppressant in a porcine renal allograft model and may avoid the elevated serum creatinine levels associated with CsA.
Toxicology and Applied Pharmacology, 2008
An increase in the prevalence of type 2 diabetes has been consistently observed among residents o... more An increase in the prevalence of type 2 diabetes has been consistently observed among residents of high arsenic exposure areas. We have previously shown that in rat pancreatic beta-cells, low arsenite doses impair the secretion of insulin without altering its synthesis. To further study the mechanism by which arsenite reduces insulin secretion, we evaluated the effects of arsenite on the calcium-calpain pathway that triggers insulin exocytosis in RINm5F cells. Cell cycle and proliferation analysis were also performed to complement the characterization. Free [Ca2+]i oscillations needed for glucose-stimulated insulin secretion were abated in the presence of subchronic low arsenite doses (0.5-2 microM). The global activity of calpains increased with 2 microM arsenite. However, during the secretion of insulin stimulated with glucose (15.6 mM), 1 microM arsenite decreased the activity of calpain-10, measured as SNAP-25 proteolysis. Both proteins are needed to fuse insulin granules with the membrane to produce insulin exocytosis. Arsenite also induced a slowdown in the beta cell line proliferation in a dose-dependent manner, reflected by a reduction of dividing cells and in their arrest in G2/M. Data obtained showed that one of the mechanisms by which arsenite impairs insulin secretion is by decreasing the oscillations of free [Ca(2+)]i, thus reducing calcium-dependent calpain-10 partial proteolysis of SNAP-25. The effects in cell division and proliferation observed with arsenite exposure can be an indirect consequence of the decrease in insulin secretion.
Seed Science Research, 2011
A large fraction of tree species forming persistent soil seed-banks and with dormant seeds are ex... more A large fraction of tree species forming persistent soil seed-banks and with dormant seeds are expected to be found in strongly seasonal ecosystems such as Neotropical savannas, where seedling recruitment could be highly variable. In the savannas of Central Brazil, we studied seed characteristics (type of dormancy, longevity and moisture content) of 14 representative woody species differing in seed dispersal season. We also studied the dynamics of soil seed-banks and similarity patterns in woody species composition among seed rain, soil seed-bank, seedling bank and standing vegetation along shallow topographic gradients that differ in canopy cover. Woody species composition of the soil seed-bank largely differed from the standing vegetation, the seed rain and the seedling bank species composition, suggesting low recruitment of woody species from the soil seed-bank. Seeds of the 14 woody species remained viable for less than 16 months in laboratory dry-storage conditions. Of those, m...
PLoS ONE, 2012
Prostaglandins (PG) are effective abortifacients and are important mediators of lipopolisaccharid... more Prostaglandins (PG) are effective abortifacients and are important mediators of lipopolisaccharide (LPS)-induced embryonic resorption (ER). Besides, anandamide (AEA) has been described as one of the major endocannabinoids present in the uterus suggesting that it might play a role in reproduction. It has been reported that high levels of AEA are associated with pregnancy failure and that LPS increases AEA production. Also, it has been observed that AEA modulates PG production in different tissues. In this sense, we studied whether LPS-induced PG production is modulated by AEA and we also assessed the effect of this endocannabinoid on PG metabolism in an in vitro model. Uterine explants from BALB/c implantation sites were cultured in the presence of LPS plus cannabinoid receptor (CB) specific antagonists and PG production was assessed. Then, we studied the effect of exogenous AEA on different steps of PG metabolic pathway. We showed that AEA is involved in LPS-induced PG biosynthesis. Also, we observed that AEA exerts opposite effects on PGE 2 and PGF 2a biosynthesis, by inhibiting PGE 2 production and increasing PGF 2a levels. We suggest that AEA could be involved in the mechanisms implicated in LPS-induced ER. A better understanding of how AEA could be affecting ER could help developing specific interventions to prevent this pathology.
Plant Ecology, 2011
The failure of seeds to arrive at all suitable sites (seed limitation) greatly affects plant dist... more The failure of seeds to arrive at all suitable sites (seed limitation) greatly affects plant distribution and abundance. In contrast to tropical forests, the degree of seed limitation in Neotropical savannas is unclear because empirical studies at the community level are scarce. We estimated seed limitation of 23 woody species from annual seed rain measurements along a tree density gradient in the savannas of Central Brazil. These savannas differ in tree density and canopy cover, from closed to open savannas, and are located along shallow topographic gradients. We also studied post-dispersal seed predation and removal of 17 representative woody species, and seed viability loss over time of 12 common woody species under dry-storage conditions. Annual seed rain was lower in open (410 seeds/m 2) than in closed savannas (773 seeds/m 2). Average seed limitation across woody species was higher than 80% along the tree density gradient. More than 60% of seeds of the studied woody species were predated or removed within 30-45 days in all savannah types. Seeds of most common woody species (66%) lost their viability in less than 12 months of dry storage. This study shows that Neotropical savannah woody plants are strongly seedlimited because of low and poor distribution of seeds among sites, post-dispersal seed removal, and short seed longevity. The high seed limitation of tree species in Neotropical savannas, particularly in open savannas, also may contribute to maintain their relatively low tree densities and help to explain the spatial variation of tree abundance along topographic gradients.
Neuroimmunomodulation, 2010
Even though the understanding of the cause of early pregnancy loss due to chromosomal abnormaliti... more Even though the understanding of the cause of early pregnancy loss due to chromosomal abnormalities has improved, there is a dearth of knowledge of the causes of loss in euploid conceptuses. Maternal infections are a cause of abort in humans, but the mechanisms are not clear, so we have developed a murine model to study the mechanism of septic abortion by inducing embryonic resorption (ER) with lipopolysaccharide (LPS). We demonstrated that augmented production of nitric oxide (NO) and prostaglandins (PG) is involved in ER, and that inhibitors of their synthesis could prevent ER. Also, we observed an increase in the oxidative damage, evidenced by nitration of tyrosine proteins, due to the peroxynitrite anion. Since an association between chronic marijuana smoking and early miscarriage has been shown in women, we studied the participation of anandamide (AEA), the principal endocannabinoid, on the mechanism of action of LPS. We showed that LPS-induced NO synthesis and tissue damage we...
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2009
Human exposure to multiple chemicals compromises the integrity of genetic material. Hence, it is ... more Human exposure to multiple chemicals compromises the integrity of genetic material. Hence, it is essential to determine the extent of DNA damage induced by xenobiotics. In cell lines, the induction of p53 expression in response to treatments with DNA-damaging agents has been proposed as a tool for the detection of genotoxic damage, although a direct correlation between a marker of chromosomal damage and p53 expression has not previously been studied. The micronucleus assay is a widely used genotoxicity test that has been shown to detect structural and numerical chromosomal damage. The present study was designed to characterize the relationship between micronuclei and p53 induction. RKO cells were cultured and treated with non-cytotoxic concentrations of colchicine, vinblastine, bleomycin or arsenic. Mannitol and clofibrate, which are non-genotoxic chemicals, were also included. The frequency of micronuclei was evaluated using the cytokinesis-block assay, and p53 induction was measured by Western blot assay. Our data showed that a significant induction of micronuclei and of p53 protein occurred only with the genotoxic chemicals. No differences in p53 induction were associated with the clastogenic or aneuplodogenic potential of the chemical exposure. The linear regression analysis revealed a direct relationship between p53 levels and the induction of micronuclei (p=0.0001, r(2)=0.9372), indicating that the level of p53 is associated with chromosomal damage.
Molecular and Cellular Endocrinology, 2013
Increased anandamide concentrations are associated with pregnancy failure. Anandamide levels are ... more Increased anandamide concentrations are associated with pregnancy failure. Anandamide levels are regulated by the fatty acid amide hydrolase (FAAH). The aim of the study was to investigate the role of progesterone (P) on FAAH modulation in murine peripheral blood mononuclear cells (PBMC) under septic conditions. We observed that in vivo administration of LPS to non-pregnant (NP) mice decreased FAAH activity of PBMC while in pregnant mice no changes in FAAH activity were observed. NP animals administered with P had a similar response to LPS as the pregnant animals. Also, NP mice injected with P antagonist and P showed that the effect of P on LPS-reduced FAAH activity was impaired. Furthermore, LPS produced a decrease in the ratio of PR-B/PR-A in NP animals. Our results showed that, in our model the endotoxin decreased PBMC's FAAH activity and this condition was reverted by P in a receptor-mediated fashion.
Journal of Pineal Research, 2014
Preterm delivery is the leading cause of neonatal mortality and contributes to delayed physical a... more Preterm delivery is the leading cause of neonatal mortality and contributes to delayed physical and cognitive development in children. At present, there is no efficient therapy to prevent preterm labor. A large body of evidence suggests that intra-amniotic infections may be a significant and potentially preventable cause of preterm birth. This work assessed the effect of melatonin in a murine model of inflammation-associated preterm delivery which mimics central features of preterm infection in humans. For this purpose, preterm labor was induced in BALB/c mice by intraperitoneal injections of bacterial lipopolysaccharide (LPS) at 10.00 hr (10 lg LPS) and 13.00 hr (20 lg LPS) on day 15 of pregnancy. On day 14 of pregnancy, a pellet of melatonin (25 mg) had been subcutaneously implanted into a group of animals. In the absence of melatonin, a 100% incidence of preterm birth was observed in LPS-treated animals, and the fetuses showed widespread damage. By comparison, treatment with melatonin prevented preterm birth in 50% of the cases, and all pups from melatonin-treated females were born alive and their body weight did not differ from control animals. Melatonin significantly prevented the LPS-induced rises in uterine prostaglandin (PG) E 2 , PGF 2a , and cyclooxygenase-2 protein levels. In addition, melatonin prevented the LPS-induced increase in uterine nitric oxide (NO) production, inducible NO synthase protein, and tumor necrosis factor-alpha (TNFa) levels. Collectively, our results suggest that melatonin could be a new therapeutic tool to prevent preterm labor and to increase offspring survival.
Journal of Ecology, 2012
1. Seedling dynamics are crucial for understanding spatial plant distribution patterns, yet littl... more 1. Seedling dynamics are crucial for understanding spatial plant distribution patterns, yet little is known about seedling establishment in Neotropical savannas because empirical studies at the community level are scarce. 2. Over 2 years, we studied the recruitment and survival of an initial seedling assemblage and three cohorts of recruits of woody plants within 216 plots of 1 m 2 located along a tree density gradient in the savannas of central Brazil. These savannas differ in tree density and canopy cover, from closed (high canopy cover) to open savannas (low canopy cover), and are located along shallow topographic gradients. 3. We measured community-wide seedling limitation (i.e. proportion of 1-m 2 plots without seedlings of any woody species), photosynthetic photon flux density, litter cover, soil moisture and soil nutrients in each savanna type. Because closed savannas had lower PPFD and higher leaf litter cover than open savannas, we evaluated the effects of light level and litter cover on seedling emergence of nine dominant savanna woody species under controlled conditions in a glasshouse. 4. Density, recruitment and survival of seedlings decreased over time because of mortality in all savanna types, but they were consistently higher in closed than in open savannas. Community-wide seedling limitation was significantly lower in closed (0.16 ± 0.03) than in open (0.30 ± 0.05) savannas. 5. In the glasshouse, high litter cover and very low light levels reduced seedling emergence of most species, suggesting an adaptation to delay seed germination until the wet season when soil water availability is high and leaf litter rapidly decomposes. 6. Synthesis: In Neotropical savannas, tree canopy cover facilitates seedling establishment of woody species by reducing stressful environmental conditions. In particular, low irradiance and high litter cover in closed savannas enhance the recruitment and survival of woody seedlings relative to open savannas by reducing soil water deficits and increasing nutrient availability in the upper soil layers. The higher seedling limitation of tree species in open than in closed savannas contributes to maintain relatively different balances between trees and herbaceous plants along topographic gradients in Neotropical savannas and helps to explain spatial distribution patterns of woody species in these ecosystems.
International Journal of Cancer, 1982
Successful treatment of neoplastic disease has been impeded by the lack of therapeutic agents whi... more Successful treatment of neoplastic disease has been impeded by the lack of therapeutic agents which specifically destroy tumor cells. Enzymes which selectively deplete substrates required by tumor cells, but not by normal tissue, could improve therapeutic indices dramatically. Presently, microbial asparaginases are used clinically for treating acute lymphocytic leukemia. While these enzymes should destroy neoplastic cells and spare normal tissues, their use is accompanied by many toxic effects and immunosuppression. The administration of Escherichia colior Erwinia carotovora asparaginase depletes circulating glutamine as well as asparagine. It has been suggested
Propiedad Intelectual, 2021
Las sociedades del mundo han evolucionado de manera tal que cada día son más las personas que tom... more Las sociedades del mundo han evolucionado de manera tal que cada día son más las personas que toman la iniciativa de emprender individualmente, en lugar de trabajar para una organización o empresa ajena. Esto ha generado la necesidad de diferenciar los bienes y servicios a través de marcas, requiriendo para ello de un proceso para su creación, dentro del cual resulta prioritario distinguir una figura fundamental conocida como el naming o técnica de creación léxica, que se traduce en el proceso creativo mediante el cual se concibe o asigna el nombre de una marca, siendo una tarea compleja y determinante para el éxito o fracaso de la misma.
Sept populations de nématodes à kyste de la pomme de terre (#Globodera rostochiensis$ et #G. pall... more Sept populations de nématodes à kyste de la pomme de terre (#Globodera rostochiensis$ et #G. pallida$) ont été analysées au moyen de marqueurs provenant de fragments d'ADN amplifiés au hasard (RAPD), d'amorces de microsatellites amplifiés en chaîne par réaction de polymérase (PCR) et d'électrophorèse de protéines totales en deux dimensions sur gel. Un degré élevé de polymorphisme a été détecté chez tous les types de marqueurs. De plus, des réactions de virulence des populations et de l'hôte, de même qu'une interaction hautement significative entre ces deux variables, ont été observés. Les distances génétiques entre populations de nématodes, fondées sur les données moléculaires et les réactions de virulence ont été estimées. Des analyses en grappes ont été réalisées et les matrices de distance en résultant comparées. Une bonne consistance entre les différents dendrogrammes, de même que des coefficients de corrélation hautement significatifs ont été observés lorsqu...
Ciencias de la Salud, 2014
Cell Biology International, 2008
The aim of this work was to study the effect of the drug idebenone on the growth of a strain of S... more The aim of this work was to study the effect of the drug idebenone on the growth of a strain of Saccharomyces cerevisiae yeast and its respiratory-deficient mutant (rho 0). We took this yeast as a model system of the interaction of the drug with mammalian cells. The effect of idebenone was evaluated in rich and minimal media. In the S288c strain, idebenone exerted a growth inhibitory effect in concentrations higher than 50 mM in media containing a carbon source consumed at mitochondrial level. In conditions of low oxygen supply, idebenone allows yeast to keep a cellular yielding comparable with conditions of normal oxygen supply. Also, the presence of idebenone in the growth media increased by 50% the fluorescence signal of rhodamine 123, indicating a higher mitochondrial membrane potential. The results could explain the effect of idebenone in the treatment of diseases in which oxygen deficiency alters the energetic metabolism of the cell.
Cancer research, 1983
In early studies using high dosages of Escherichia coli asparaginase (10 doses of 1000 ID/kg each... more In early studies using high dosages of Escherichia coli asparaginase (10 doses of 1000 ID/kg each) for the treatment of acute lymphoblastic leukemia, hepatotoxicity was a major com plication of therapy. Biochemical evidence of hepatic dysfunction occurred in 75% of patients during the first 2 weeks of treatment. Currently, the use of lower dosages of E. coli asparaginase (three doses of 6000 ID/sq m each) has reduced the incidence of hepatic complication. Hepatic dysfunction in the form of severe life-threatening thromboembolic coagulopathy, however, contin ues to be associated with the use of this enzyme. Our previous work has established that the fatty degenerative changes and hepatocellular dysfunction associated with short-term (1 week) £.coli asparaginase treatment does not occur in mice treated with a glutaminase-free asparaginase from Vibrio succinogenes. In this report, we examined the hepatotoxic effects of prolonged treatment with E. coli and Erwinia carotovora asparaginases and compared the observed toxicities to those observed with the glutaminase-free asparaginase from V. succinogenes. Using a murine model, our data indicate that the hepatotoxicity of £. coli asparaginase parallels the toxicity observed in humans with a rapid increase in liver lipid levels and decreased plasma levels of albumin, antithrombin III, cholesterol, and triglycéridesoccurring in the first and second weeks followed by a resumption to normal hepatic function during Weeks 3 and 4. In contrast, prolonged treatment of mice with V. succinogenes asparaginase is not associated with significant hepatotoxicity. Er. carotovora aspa raginase treatment is associated with an intermediate level of toxicity as indicated by increased hepatic lipid concentration occurring during the second and fourth weeks of treatment. Hepatic function as determined by plasma lipids and proteins was normal in Er. carotovora asparaginase-treated mice. Our data suggest that the combined physiological depletion of asparagine and glutamine following administration of E. coli or Er. carotovora asparaginases may result in pronounced hepato toxicity. In contrast, a glutaminase-free asparaginase with potent antilymphoma activity isolated from V. succinogenes is not hep atotoxic even after prolonged treatment. Therefore, it may prove to be a more efficacious antitumor agent in humans.
BMJ Open, 2013
receptor polymorphisms are an associated risk factor for mild cognitive impairment and Alzheimer ... more receptor polymorphisms are an associated risk factor for mild cognitive impairment and Alzheimer disease in women APOE ɛ4 carriers: a casecontrol study. BMJ Open 2013;3:e003200.
Journal of Vegetation Science, 2014
Questions What are the temporal and spatial variations of groundwater depth along topographic gra... more Questions What are the temporal and spatial variations of groundwater depth along topographic gradients in Neotropical savannas? Are patterns of tree density and species diversity along topographic gradients in Neotropical savannas controlled by water table depth? Do soil and groundwater nutrient concentrations differ along topographic gradients in Neotropical savannas? Location Fire-protected savannas of central Brazil. Methods Over 16 mo, we monitored temporal and spatial variations in groundwater levels using automated submersible pressure transducers installed in ten wells located along two topographic gradients (five wells per gradient) of 950 m and 1703 m in length, representing elevations of 47 and 37 m a.s.l., respectively. We located the wells according to changes in vegetation physiognomies from woody savannas at high elevations, to open shrubby grasslands at low elevations. Along each topographic gradient we determined soil and groundwater nutrient concentrations as well as richness, density, basal diameter and height of trees within two plots of 14 × 14 m (392 m2) adjacent to each well. Results Along the two gradients, groundwater levels exhibited larger fluctuations at lower than at higher elevations where the water table was deeper. Richness, density and diversity of trees decreased significantly at lower elevations where soils were waterlogged during the wet season. Soil pH and soil concentrations of carbon, nitrogen and manganese decreased significantly as elevation increased along the topographic gradients, but soil nutrient concentrations of phosphorus, aluminium and iron did not change with elevation. Groundwater samples contained only trace amounts of nutrients and were poorly correlated with elevation along the topographic gradients. Conclusions In Neotropical savannas, the minimum distance between the soil surface and water table depth (reached during the wet season) and the relatively large fluctuations in groundwater limit tree density and diversity at low elevations as savanna trees cannot cope with extended waterlogging during the wet season and with low soil water availability during the dry season. Thus, variations of tree density and diversity along topographic gradients are more related to spatial and temporal variations in water table depth than to soil and groundwater nutrient variations in Neotropical savannas.
Archives of Medical Research, 2014
Calpain activity has been implicated in several cellular processes such as cell signaling, apopto... more Calpain activity has been implicated in several cellular processes such as cell signaling, apoptosis, exocytosis, mitochondrial metabolism and cytoskeletal remodeling. Evidence has indicated that the impairment of calpain expression and the activity of different calpain family members are involved in diverse pathologies. Calpain-10 has been implicated in the development of type 2 diabetes, and polymorphisms in the CAPN10 gene have been associated with an increased risk of developing this disease. The present work focused on the molecular biology of calpain-10, supporting its key participation in glucose metabolism. Current knowledge regarding the role of calpain-10 in the development of type 2 diabetes mellitus and diabetes-related diseases is additionally reviewed.
Current Pharmaceutical Design, 2014
Preterm birth is the leading cause of perinatal morbidity and mortality. Pathological processes t... more Preterm birth is the leading cause of perinatal morbidity and mortality. Pathological processes that have been linked with preterm birth infection and / or intrauterine inflammation are most frequently found associated with their induction. Studies in animal models and human research showed prior infections to the induction of labor, the anteriority of infection over labor induction, and the existence of a subclinical latency phase between these two phenomena. The ascending route from the vagina and the cervix is preponderant but also microorganisms may access the amniotic cavity and the fetus by other pathways. During inflammation associated to infection, Prostaglandins are released simultaneously with Nitric oxide and their overproduction could be detrimental. Prostaglandins promote uterine contractions contributing to embryonic and fetal expulsion. Therefore aberrant activation of the inflammatory response may cause premature labor and this does not seem to depend on how the microoorganisms accessed the uterus.
Transplantation, 1993
Rapamycin prolongs allograft survival and induces donor-specific tolerance in some small animal t... more Rapamycin prolongs allograft survival and induces donor-specific tolerance in some small animal transplant models. Large animal studies, however, are limited. We studied rapamycin in a porcine renal allograft model. Donor-recipient combinations were chosen based on high response in pretransplant MLCs. Allografts were anastomosed to the aorta and vena cava and the native kidneys removed. There were 5 treatment groups: (a) no immunosuppression; (b) triple therapy (CsA, 1 mg/kg/day; AZA, 2–3 mg/kg/day; and PRED, 3–4 mg/kg/day); (c) rapamycin (0.75 mg/kg/day i.m.) in carboxymethylcellulose (CMC); (d) rapamycin (0.25 mg/kg/day i.m. in CMC); and (e) a vehicle (CMC) control. Serum creatinine levels were determined every other day. Most allografts were biopsied once a week. Immunosuppression was stopped after 30 days. Mean graft survival in nonimmunosuppressed recipients was 6.8±3.6 days. Mean graft survival in triple therapy recipients (n=10) was 45.7±36 days vs. 59.6±11.4 days in rapamycin (0.25 mg/kg/day) recipients (n=7) (P=0.51). Both triple therapy and rapamycin improved renal allograft survival versus nonimmunosuppressed controls (P=0.0025 and 0.001, respectively). Serum creatinine levels were significantly lower (P<0.05) in rapamycin versus triple therapy recipients. We conclude that rapamycin is a potent immunosuppressant in a porcine renal allograft model and may avoid the elevated serum creatinine levels associated with CsA.
Toxicology and Applied Pharmacology, 2008
An increase in the prevalence of type 2 diabetes has been consistently observed among residents o... more An increase in the prevalence of type 2 diabetes has been consistently observed among residents of high arsenic exposure areas. We have previously shown that in rat pancreatic beta-cells, low arsenite doses impair the secretion of insulin without altering its synthesis. To further study the mechanism by which arsenite reduces insulin secretion, we evaluated the effects of arsenite on the calcium-calpain pathway that triggers insulin exocytosis in RINm5F cells. Cell cycle and proliferation analysis were also performed to complement the characterization. Free [Ca2+]i oscillations needed for glucose-stimulated insulin secretion were abated in the presence of subchronic low arsenite doses (0.5-2 microM). The global activity of calpains increased with 2 microM arsenite. However, during the secretion of insulin stimulated with glucose (15.6 mM), 1 microM arsenite decreased the activity of calpain-10, measured as SNAP-25 proteolysis. Both proteins are needed to fuse insulin granules with the membrane to produce insulin exocytosis. Arsenite also induced a slowdown in the beta cell line proliferation in a dose-dependent manner, reflected by a reduction of dividing cells and in their arrest in G2/M. Data obtained showed that one of the mechanisms by which arsenite impairs insulin secretion is by decreasing the oscillations of free [Ca(2+)]i, thus reducing calcium-dependent calpain-10 partial proteolysis of SNAP-25. The effects in cell division and proliferation observed with arsenite exposure can be an indirect consequence of the decrease in insulin secretion.
Seed Science Research, 2011
A large fraction of tree species forming persistent soil seed-banks and with dormant seeds are ex... more A large fraction of tree species forming persistent soil seed-banks and with dormant seeds are expected to be found in strongly seasonal ecosystems such as Neotropical savannas, where seedling recruitment could be highly variable. In the savannas of Central Brazil, we studied seed characteristics (type of dormancy, longevity and moisture content) of 14 representative woody species differing in seed dispersal season. We also studied the dynamics of soil seed-banks and similarity patterns in woody species composition among seed rain, soil seed-bank, seedling bank and standing vegetation along shallow topographic gradients that differ in canopy cover. Woody species composition of the soil seed-bank largely differed from the standing vegetation, the seed rain and the seedling bank species composition, suggesting low recruitment of woody species from the soil seed-bank. Seeds of the 14 woody species remained viable for less than 16 months in laboratory dry-storage conditions. Of those, m...
PLoS ONE, 2012
Prostaglandins (PG) are effective abortifacients and are important mediators of lipopolisaccharid... more Prostaglandins (PG) are effective abortifacients and are important mediators of lipopolisaccharide (LPS)-induced embryonic resorption (ER). Besides, anandamide (AEA) has been described as one of the major endocannabinoids present in the uterus suggesting that it might play a role in reproduction. It has been reported that high levels of AEA are associated with pregnancy failure and that LPS increases AEA production. Also, it has been observed that AEA modulates PG production in different tissues. In this sense, we studied whether LPS-induced PG production is modulated by AEA and we also assessed the effect of this endocannabinoid on PG metabolism in an in vitro model. Uterine explants from BALB/c implantation sites were cultured in the presence of LPS plus cannabinoid receptor (CB) specific antagonists and PG production was assessed. Then, we studied the effect of exogenous AEA on different steps of PG metabolic pathway. We showed that AEA is involved in LPS-induced PG biosynthesis. Also, we observed that AEA exerts opposite effects on PGE 2 and PGF 2a biosynthesis, by inhibiting PGE 2 production and increasing PGF 2a levels. We suggest that AEA could be involved in the mechanisms implicated in LPS-induced ER. A better understanding of how AEA could be affecting ER could help developing specific interventions to prevent this pathology.
Plant Ecology, 2011
The failure of seeds to arrive at all suitable sites (seed limitation) greatly affects plant dist... more The failure of seeds to arrive at all suitable sites (seed limitation) greatly affects plant distribution and abundance. In contrast to tropical forests, the degree of seed limitation in Neotropical savannas is unclear because empirical studies at the community level are scarce. We estimated seed limitation of 23 woody species from annual seed rain measurements along a tree density gradient in the savannas of Central Brazil. These savannas differ in tree density and canopy cover, from closed to open savannas, and are located along shallow topographic gradients. We also studied post-dispersal seed predation and removal of 17 representative woody species, and seed viability loss over time of 12 common woody species under dry-storage conditions. Annual seed rain was lower in open (410 seeds/m 2) than in closed savannas (773 seeds/m 2). Average seed limitation across woody species was higher than 80% along the tree density gradient. More than 60% of seeds of the studied woody species were predated or removed within 30-45 days in all savannah types. Seeds of most common woody species (66%) lost their viability in less than 12 months of dry storage. This study shows that Neotropical savannah woody plants are strongly seedlimited because of low and poor distribution of seeds among sites, post-dispersal seed removal, and short seed longevity. The high seed limitation of tree species in Neotropical savannas, particularly in open savannas, also may contribute to maintain their relatively low tree densities and help to explain the spatial variation of tree abundance along topographic gradients.
Neuroimmunomodulation, 2010
Even though the understanding of the cause of early pregnancy loss due to chromosomal abnormaliti... more Even though the understanding of the cause of early pregnancy loss due to chromosomal abnormalities has improved, there is a dearth of knowledge of the causes of loss in euploid conceptuses. Maternal infections are a cause of abort in humans, but the mechanisms are not clear, so we have developed a murine model to study the mechanism of septic abortion by inducing embryonic resorption (ER) with lipopolysaccharide (LPS). We demonstrated that augmented production of nitric oxide (NO) and prostaglandins (PG) is involved in ER, and that inhibitors of their synthesis could prevent ER. Also, we observed an increase in the oxidative damage, evidenced by nitration of tyrosine proteins, due to the peroxynitrite anion. Since an association between chronic marijuana smoking and early miscarriage has been shown in women, we studied the participation of anandamide (AEA), the principal endocannabinoid, on the mechanism of action of LPS. We showed that LPS-induced NO synthesis and tissue damage we...
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2009
Human exposure to multiple chemicals compromises the integrity of genetic material. Hence, it is ... more Human exposure to multiple chemicals compromises the integrity of genetic material. Hence, it is essential to determine the extent of DNA damage induced by xenobiotics. In cell lines, the induction of p53 expression in response to treatments with DNA-damaging agents has been proposed as a tool for the detection of genotoxic damage, although a direct correlation between a marker of chromosomal damage and p53 expression has not previously been studied. The micronucleus assay is a widely used genotoxicity test that has been shown to detect structural and numerical chromosomal damage. The present study was designed to characterize the relationship between micronuclei and p53 induction. RKO cells were cultured and treated with non-cytotoxic concentrations of colchicine, vinblastine, bleomycin or arsenic. Mannitol and clofibrate, which are non-genotoxic chemicals, were also included. The frequency of micronuclei was evaluated using the cytokinesis-block assay, and p53 induction was measured by Western blot assay. Our data showed that a significant induction of micronuclei and of p53 protein occurred only with the genotoxic chemicals. No differences in p53 induction were associated with the clastogenic or aneuplodogenic potential of the chemical exposure. The linear regression analysis revealed a direct relationship between p53 levels and the induction of micronuclei (p=0.0001, r(2)=0.9372), indicating that the level of p53 is associated with chromosomal damage.
Molecular and Cellular Endocrinology, 2013
Increased anandamide concentrations are associated with pregnancy failure. Anandamide levels are ... more Increased anandamide concentrations are associated with pregnancy failure. Anandamide levels are regulated by the fatty acid amide hydrolase (FAAH). The aim of the study was to investigate the role of progesterone (P) on FAAH modulation in murine peripheral blood mononuclear cells (PBMC) under septic conditions. We observed that in vivo administration of LPS to non-pregnant (NP) mice decreased FAAH activity of PBMC while in pregnant mice no changes in FAAH activity were observed. NP animals administered with P had a similar response to LPS as the pregnant animals. Also, NP mice injected with P antagonist and P showed that the effect of P on LPS-reduced FAAH activity was impaired. Furthermore, LPS produced a decrease in the ratio of PR-B/PR-A in NP animals. Our results showed that, in our model the endotoxin decreased PBMC's FAAH activity and this condition was reverted by P in a receptor-mediated fashion.
Journal of Pineal Research, 2014
Preterm delivery is the leading cause of neonatal mortality and contributes to delayed physical a... more Preterm delivery is the leading cause of neonatal mortality and contributes to delayed physical and cognitive development in children. At present, there is no efficient therapy to prevent preterm labor. A large body of evidence suggests that intra-amniotic infections may be a significant and potentially preventable cause of preterm birth. This work assessed the effect of melatonin in a murine model of inflammation-associated preterm delivery which mimics central features of preterm infection in humans. For this purpose, preterm labor was induced in BALB/c mice by intraperitoneal injections of bacterial lipopolysaccharide (LPS) at 10.00 hr (10 lg LPS) and 13.00 hr (20 lg LPS) on day 15 of pregnancy. On day 14 of pregnancy, a pellet of melatonin (25 mg) had been subcutaneously implanted into a group of animals. In the absence of melatonin, a 100% incidence of preterm birth was observed in LPS-treated animals, and the fetuses showed widespread damage. By comparison, treatment with melatonin prevented preterm birth in 50% of the cases, and all pups from melatonin-treated females were born alive and their body weight did not differ from control animals. Melatonin significantly prevented the LPS-induced rises in uterine prostaglandin (PG) E 2 , PGF 2a , and cyclooxygenase-2 protein levels. In addition, melatonin prevented the LPS-induced increase in uterine nitric oxide (NO) production, inducible NO synthase protein, and tumor necrosis factor-alpha (TNFa) levels. Collectively, our results suggest that melatonin could be a new therapeutic tool to prevent preterm labor and to increase offspring survival.
Journal of Ecology, 2012
1. Seedling dynamics are crucial for understanding spatial plant distribution patterns, yet littl... more 1. Seedling dynamics are crucial for understanding spatial plant distribution patterns, yet little is known about seedling establishment in Neotropical savannas because empirical studies at the community level are scarce. 2. Over 2 years, we studied the recruitment and survival of an initial seedling assemblage and three cohorts of recruits of woody plants within 216 plots of 1 m 2 located along a tree density gradient in the savannas of central Brazil. These savannas differ in tree density and canopy cover, from closed (high canopy cover) to open savannas (low canopy cover), and are located along shallow topographic gradients. 3. We measured community-wide seedling limitation (i.e. proportion of 1-m 2 plots without seedlings of any woody species), photosynthetic photon flux density, litter cover, soil moisture and soil nutrients in each savanna type. Because closed savannas had lower PPFD and higher leaf litter cover than open savannas, we evaluated the effects of light level and litter cover on seedling emergence of nine dominant savanna woody species under controlled conditions in a glasshouse. 4. Density, recruitment and survival of seedlings decreased over time because of mortality in all savanna types, but they were consistently higher in closed than in open savannas. Community-wide seedling limitation was significantly lower in closed (0.16 ± 0.03) than in open (0.30 ± 0.05) savannas. 5. In the glasshouse, high litter cover and very low light levels reduced seedling emergence of most species, suggesting an adaptation to delay seed germination until the wet season when soil water availability is high and leaf litter rapidly decomposes. 6. Synthesis: In Neotropical savannas, tree canopy cover facilitates seedling establishment of woody species by reducing stressful environmental conditions. In particular, low irradiance and high litter cover in closed savannas enhance the recruitment and survival of woody seedlings relative to open savannas by reducing soil water deficits and increasing nutrient availability in the upper soil layers. The higher seedling limitation of tree species in open than in closed savannas contributes to maintain relatively different balances between trees and herbaceous plants along topographic gradients in Neotropical savannas and helps to explain spatial distribution patterns of woody species in these ecosystems.
International Journal of Cancer, 1982
Successful treatment of neoplastic disease has been impeded by the lack of therapeutic agents whi... more Successful treatment of neoplastic disease has been impeded by the lack of therapeutic agents which specifically destroy tumor cells. Enzymes which selectively deplete substrates required by tumor cells, but not by normal tissue, could improve therapeutic indices dramatically. Presently, microbial asparaginases are used clinically for treating acute lymphocytic leukemia. While these enzymes should destroy neoplastic cells and spare normal tissues, their use is accompanied by many toxic effects and immunosuppression. The administration of Escherichia colior Erwinia carotovora asparaginase depletes circulating glutamine as well as asparagine. It has been suggested