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1.
Heliyon ; 6(3): e03534, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32181400

ABSTRACT

This paper presents a fuzzy-multiple objective optimization methodology to plan stand-alone electricity generation systems. The optimization process considers three main objectives, namely technology cost, environmental and societal impacts. For each feasible solution of the Pareto set, a system reliability index is evaluated along the lifetime of the project. As a key contribution, the decision making process is carried out by applying a fuzzy satisfaction method (FSM). The FSM accounts simultaneously four key performance indexes (KPI): technical, economic, environmental and social. The novelty of the proposal lies on the inclusion of societal impact (local wealth creation) in the FSM used here to select the more appropriate solution. Previous contributions on FSM only accounts two of four indexes considered in this paper. The methodology was applied in a Colombian case study. The results show the importance of the simultaneous consideration of technical, economic, environmental and social objectives in the evaluation of off-grid energization solutions.

2.
Int J Genomics ; 2017: 6489383, 2017.
Article in English | MEDLINE | ID: mdl-28791299

ABSTRACT

Increasing evidence that microRNAs (miRNAs) play important roles in the immune response against infectious agents suggests that miRNA might be exploitable as signatures of exposure to specific infectious agents. In order to identify potential early miRNA biomarkers of bacterial infections, human peripheral blood mononuclear cells (hPBMCs) were exposed to two select agents, Burkholderia pseudomallei K96243 and Francisella tularensis SHU S4, as well as to the nonpathogenic control Escherichia coli DH5α. RNA samples were harvested at three early time points, 30, 60, and 120 minutes postexposure, then sequenced. RNAseq analyses identified 87 miRNAs to be differentially expressed (DE) in a linear fashion. Of these, 31 miRNAs were tested using the miScript miRNA qPCR assay. Through RNAseq identification and qPCR validation, we identified differentially expressed miRNA species that may be involved in the early response to bacterial infections. Based upon its upregulation at early time points postexposure in two different individuals, hsa-mir-30c-5p is a miRNA species that could be studied further as a potential biomarker for exposure to these gram-negative intracellular pathogens. Gene ontology functional analyses demonstrated that programmed cell death is the first ranking biological process associated with miRNAs that are upregulated in F. tularensis-exposed hPBMCs.

3.
Arch Environ Contam Toxicol ; 71(3): 313-21, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27475645

ABSTRACT

The aim of this study was to determine the levels of different inorganic elements (lead [Pb], mercury [Hg], and arsenic [As]) and persistent chlorinated pollutants (including polychlorinated biphenyls [PCBs] and organochlorine pesticides [OCPs]) in blood and plasma of White stork (Ciconia ciconia) nestlings from northwest (NW) Spain. The concentrations of PCBs were lower than the limit of detection in all samples. The OCPs γ-HCH, 4,4'-DDE, HCB, and endosulfan were detected most frequently in plasma from White stork nestlings. These OCPs were detected in 98, 54, 39, and 37 % of all samples, respectively. However, the concentrations of organic pollutants were lower than the risk thresholds for birds. The mean levels of the inorganic elements Pb, Hg, and As were found to be 36.92 ± 33.48, 16.48 ± 12.87, and 9.813 ± 13.84 µg/L, respectively. These levels were also lower than the risk thresholds for birds. This study not only provides a snapshot of the levels of both inorganic and organic contaminants in wild White storks in NW Spain, it also provides a useful baseline for biomonitoring levels of the measured contaminants in this area.


Subject(s)
Birds/blood , Environmental Monitoring , Environmental Pollutants/metabolism , Hydrocarbons, Chlorinated/blood , Metalloids/blood , Metals/blood , Animals , Spain
4.
Gigascience ; 3: 20, 2014.
Article in English | MEDLINE | ID: mdl-25379175

ABSTRACT

BACKGROUND: Understanding the biological roles of microRNAs (miRNAs) is a an active area of research that has produced a surge of publications in PubMed, particularly in cancer research. Along with this increasing interest, many open-source bioinformatics tools to identify existing and/or discover novel miRNAs in next-generation sequencing (NGS) reads become available. While miRNA identification and discovery tools are significantly improved, the development of miRNA differential expression analysis tools, especially in temporal studies, remains substantially challenging. Further, the installation of currently available software is non-trivial and steps of testing with example datasets, trying with one's own dataset, and interpreting the results require notable expertise and time. Subsequently, there is a strong need for a tool that allows scientists to normalize raw data, perform statistical analyses, and provide intuitive results without having to invest significant efforts. FINDINGS: We have developed miRNA Temporal Analyzer (mirnaTA), a bioinformatics package to identify differentially expressed miRNAs in temporal studies. mirnaTA is written in Perl and R (Version 2.13.0 or later) and can be run across multiple platforms, such as Linux, Mac and Windows. In the current version, mirnaTA requires users to provide a simple, tab-delimited, matrix file containing miRNA name and count data from a minimum of two to a maximum of 20 time points and three replicates. To recalibrate data and remove technical variability, raw data is normalized using Normal Quantile Transformation (NQT), and linear regression model is used to locate any miRNAs which are differentially expressed in a linear pattern. Subsequently, remaining miRNAs which do not fit a linear model are further analyzed in two different non-linear methods 1) cumulative distribution function (CDF) or 2) analysis of variances (ANOVA). After both linear and non-linear analyses are completed, statistically significant miRNAs (P < 0.05) are plotted as heat maps using hierarchical cluster analysis and Euclidean distance matrix computation methods. CONCLUSIONS: mirnaTA is an open-source, bioinformatics tool to aid scientists in identifying differentially expressed miRNAs which could be further mined for biological significance. It is expected to provide researchers with a means of interpreting raw data to statistical summaries in a fast and intuitive manner.

5.
Blood ; 118(12): 3367-75, 2011 Sep 22.
Article in English | MEDLINE | ID: mdl-21791418

ABSTRACT

Genetic variation is thought to contribute to variability in platelet function; however, the specific variants and mechanisms that contribute to altered platelet function are poorly defined. With the use of a combination of fine mapping and sequencing of the platelet endothelial aggregation receptor 1 (PEAR1) gene we identified a common variant (rs12041331) in intron 1 that accounts for ≤ 15% of total phenotypic variation in platelet function. Association findings were robust in 1241 persons of European ancestry (P = 2.22 × 10⁻8) and were replicated down to the variant and nucleotide level in 835 persons of African ancestry (P = 2.31 × 10⁻²7) and in an independent sample of 2755 persons of European descent (P = 1.64 × 10⁻5). Sequencing confirmed that variation at rs12041331 accounted most strongly (P = 2.07 × 10⁻6) for the relation between the PEAR1 gene and platelet function phenotype. A dose-response relation between the number of G alleles at rs12041331 and expression of PEAR1 protein in human platelets was confirmed by Western blotting and ELISA. Similarly, the G allele was associated with greater protein expression in a luciferase reporter assay. These experiments identify the precise genetic variant in PEAR1 associated with altered platelet function and provide a plausible biologic mechanism to explain the association between variation in the PEAR1 gene and platelet function phenotype.


Subject(s)
Black People/genetics , Blood Platelets/metabolism , Coronary Artery Disease/genetics , Genetic Association Studies , Platelet Aggregation/genetics , Polymorphism, Single Nucleotide , Receptors, Cell Surface/genetics , White People/genetics , Alleles , Aspirin/administration & dosage , Blood Platelets/cytology , Cell Line , Coronary Artery Disease/drug therapy , Coronary Artery Disease/metabolism , Coronary Artery Disease/pathology , Gene Expression , Genes, Reporter , Genetic Variation , Genotype , Humans , Introns , Luciferases/analysis , Phenotype , Receptors, Cell Surface/chemistry , Receptors, Cell Surface/metabolism , Sequence Analysis, DNA , Transfection
6.
Rev. centroam. obstet. ginecol ; 16(2): 44-50, abr.-jun. 2011.
Article in Spanish | LILACS | ID: lil-733808

ABSTRACT

Objetivos: describir la experiencia en el tratamiento de cáncer de cuello uterino con quimiorradioterapia concurrente. Métodos: estudio descriptivo de corte transversal sobre 60 pacientes con cáncer de cuello uterino estadíos no quirúrgicos según estadificación FIGO, atendidas entre junio 1999 y abril 2010 en el Servicio de Ginecología del Hospital Luis C. Lagomaggiore de la Provincia de Mendoza. A todas estas pacientes se les realizó quimiorradioterapia concurrente...


Subject(s)
Female , Cervix Uteri/pathology , Vaginal Smears/methods , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms
10.
BMC Med Genomics ; 3: 22, 2010 Jun 07.
Article in English | MEDLINE | ID: mdl-20529293

ABSTRACT

BACKGROUND: The inability of aspirin (ASA) to adequately suppress platelet aggregation is associated with future risk of coronary artery disease (CAD). Heritability studies of agonist-induced platelet function phenotypes suggest that genetic variation may be responsible for ASA responsiveness. In this study, we leverage independent information from genome-wide linkage and association data to determine loci controlling platelet phenotypes before and after treatment with ASA. METHODS: Clinical data on 37 agonist-induced platelet function phenotypes were evaluated before and after a 2-week trial of ASA (81 mg/day) in 1231 European American and 846 African American healthy subjects with a family history of premature CAD. Principal component analysis was performed to minimize the number of independent factors underlying the covariance of these various phenotypes. Multi-point sib-pair based linkage analysis was performed using a microsatellite marker set, and single-SNP association tests were performed using markers from the Illumina 1 M genotyping chip from deCODE Genetics, Inc. All analyses were performed separately within each ethnic group. RESULTS: Several genomic regions appear to be linked to ASA response factors: a 10 cM region in African Americans on chromosome 5q11.2 had several STRs with suggestive (p-value < 7 x 10-4) and significant (p-value < 2 x 10-5) linkage to post aspirin platelet response to ADP, and ten additional factors had suggestive evidence for linkage (p-value < 7 x 10-4) to thirteen genomic regions. All but one of these factors were aspirin response variables. While the strength of genome-wide SNP association signals for factors showing evidence for linkage is limited, especially at the strict thresholds of genome-wide criteria (N = 9 SNPs for 11 factors), more signals were considered significant when the association signal was weighted by evidence for linkage (N = 30 SNPs). CONCLUSIONS: Our study supports the hypothesis that platelet phenotypes in response to ASA likely have genetic control and the combined approach of linkage and association offers an alternative approach to prioritizing regions of interest for subsequent follow-up.


Subject(s)
Black or African American/genetics , Blood Platelets/physiology , Coronary Artery Disease/genetics , Genetic Predisposition to Disease , Platelet Activation , White People/genetics , Adult , Aspirin/pharmacology , Chromosomes, Human, Pair 5 , Coronary Artery Disease/ethnology , Coronary Artery Disease/etiology , Female , Genetic Linkage , Genome-Wide Association Study , Genotype , Humans , Male , Middle Aged , Phenotype , Polymorphism, Single Nucleotide , Principal Component Analysis
11.
Article in Spanish | LILACS, BDNPAR | ID: biblio-1342306

ABSTRACT

El consumo y dependencia de sustancias, es un serio problema social con alta morbilidad materno-fetal. El aumento de la oferta y el contexto social favorecedor, permitió que la difusión del consumo sustancias tóxicas ilícitas, conlleve una incidencia creciente en gestantes consumidoras de sustancias y aumento de recién nacidos afectados por las prácticas tóxicas de sus madres. La evaluación del riesgo cuando la gestación es expuesta a las drogas es difícil, los resultados pueden estar sesgados por el consumo concomitante de otros tóxicos o por factores sicológicos y socio-sanitarios desfavorables. Aunque tampoco se definió un patrón específico de anomalías congénitas, se considera que el abuso de drogas, en general, comporta mayor riego de desenlace anómalo del embarazo, por un incremento del riesgo de malformaciones congénitas, debido a la probable teratogenicidad de algunas sustancias o de la morbilidad perinatal afectando el crecimiento fetal o el normal desarrollo del embarazo. También existen posibles repercusiones a largo plazo en la capacidad de aprendizaje y comportamiento de los niños expuestos intraútero, aunque no demostró efectivamente. Por lo tanto, todo embarazo en el que se detecto un hábito tóxico se debe considerar de mayor riesgo, tomando las medidas oportunas para lograr que las pacientes se alejen de éstas prácticas, apoyadas por un equipo multidisciplinario, idealmente antes del inicio del embarazo, lo que implica la adopción de medidas profilácticas de información y concienciación de las mujeres en edad fértil y de apoyo durante el embarazo y la lactancia para el abandono de la dependencia


Illicit drug use and dependence is a serious social problem with high maternal and fetal morbidity. Supply increase and propitious social context allowed that the diffusion of the use of illicit toxic substances entails a growing incidence in pregnant women who use illicit drugs and an increase of newborns affected by the practices of their mothers. Risk evaluation is difficult when gestation is exposed to illicit drugs because the results could be biased by the concomitant consumption of others toxic substances or by psychological and socio-sanitary unfavorable factors. Though a specific pattern of congenital anomalies has not been defined, in general it is considered that drug abuse has an increased risk of anomalous outcomes in pregnancies. This risk is caused by an increase in the risk of congenital malformations due to the probable teratogenicity of some substances or the perinatal morbility affecting the fetal growth or normal pregnancy development. Although it has not been demonstrated effectively, there are also possible long-term repercussions in the learning capacity and behavior of the children exposed intra uterus. In conclusion, all pregnancies exposed to illicit drugs must be considered high risk pregnancies and measures should be taken so that the patients avoid these practices supported by a multidisciplinary team. Ideally, this team should start working before pregnancy implying the adoption of preventive measures such as information and public awareness of women in fertile age and support during pregnancy and maternal lactation


Subject(s)
Marijuana Abuse , Cocaine-Related Disorders , Marijuana Use , Lactation , Pregnancy , Cocaine , Heroin , Amphetamines , Lysergic Acid Diethylamide
12.
Thromb Res ; 124(3): 311-7, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19185906

ABSTRACT

BACKGROUND: Markers of systemic inflammation, including blood leukocyte count, are associated with increased cardiovascular risk, but the mechanisms underlying this association are unclear. Leukocytes may promote platelet reactivity and thrombus formation, providing a basis for increased risk, but a relation between leukocyte count and platelet function has not been studied. METHODS: We evaluated the relation of blood leukocyte count, C-reactive protein (CRP), and interleukin-6 (IL-6) to platelet aggregation to collagen, ADP and arachidonic acid, and to urinary excretion of 11-dehydro thromboxane B2. Studies were conducted in 1600 individuals (45.0+/-12.9 years, 42.7% male) at risk for coronary artery disease (CAD) before and after low dose aspirin. RESULTS: At baseline, platelet reactivity increased with increasing quartile of leukocyte count (median counts for each quartile were normal) for all measures of platelet function (P<0.0001). These relations were unchanged by aspirin. The relation between leukocyte count and each measure of platelet reactivity remained significant (P<0.05) after multivariable adjustment for CRP, IL-6, cardiac risk factors, hematologic variables, and platelet thromboxane production. CRP and IL-6 were independently associated with few measures of platelet reactivity. CONCLUSIONS: Increasing quartile of leukocyte count, even within the normal range, is associated with increasing platelet reactivity in individuals at risk for CAD. This relationship is not altered by aspirin and is independent of inflammatory markers and platelet thromboxane production. Additional studies are needed to determine the mechanism(s) for this association and therapies to reduce cardiovascular risk in patients with elevated leukocyte counts.


Subject(s)
Aspirin/administration & dosage , Coronary Artery Disease/blood , Coronary Artery Disease/prevention & control , Cytokines/blood , Leukocyte Count , Platelet Activation/drug effects , Adult , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Coronary Artery Disease/genetics , Drug Tolerance , Female , Humans , Male
13.
Vitae (Medellín) ; 15(1): 141-149, jan.-jun. 2008. tab, graf
Article in Spanish | LILACS | ID: lil-502230

ABSTRACT

En las últimas décadas, la búsqueda de sustancias antineoplásicas en organismos marinos y especialmente en algas marinas, muestra resultados promisorios en el desarrollo de fármacos antitumorales. Entre estas algas se encuentra Digenia simplex, la cual contiene una fracción química en su extracto etanólico con potente efecto antimitótico y citotóxico. Para dilucidar la estructura molecular de los compuestos constituyentes de ésta fracción bioactiva, se realiza un análisis por resonancia magnética nuclear (RMN), y cromatografía de gases acoplada a espectrometría de masas (CG-EM) de los derivados trimetilsililéteres (derivados TMS). El análisis permite inferir la presencia de una mezcla de compuestos, tales como: azúcares libres, ácidos grasos, nitrilos alifáticos, aminas secundarias alifáticas y monoacilgliceroles


Subject(s)
Seaweed
14.
Arterioscler Thromb Vasc Biol ; 28(8): 1484-90, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18511696

ABSTRACT

OBJECTIVE: Platelet endothelial aggregation receptor-1 (PEAR1) is a recently identified platelet transmembrane protein that becomes activated by platelet contact. We looked for novel genetic variants in PEAR1 and studied their association with agonist-induced native platelet aggregation and with the inhibitory effect of aspirin on platelets. METHODS AND RESULTS: We genotyped PEAR1 for 10 single nucleotide polymorphisms (SNPs), selected for optimal gene coverage at a density of 4 kb, in 1486 apparently healthy individuals from two generations of families with premature CAD. Subjects had a mean age of 45 years; 62% were white and 38% black. Platelet aggregation to collagen, epinephrine, and ADP was measured in platelet rich plasma, at baseline and after 2 weeks of aspirin (ASA, 81 mg/d), and genotype-phenotype associations were examined separately by ethnicity using multivariable generalized linear models adjusted for covariates. The C allele of SNP rs2768759 [A/C], located in the promoter region of the gene, was common in whites and uncommon in blacks (allele frequency 70.2% versus 17.7%). The C allele was generally associated in both ethnic groups with increased aggregation of native platelets to each agonist. After ASA, the associations were stronger and more consistent and remained significant when post-ASA aggregation was adjusted for baseline aggregation, consistent with a relationship between the C allele and reduced platelet responsiveness to ASA. The PEAR1 SNP explained up to 6.9% of the locus specific genetic variance in blacks and up to 2.5% of the genetic variance in whites after ASA. CONCLUSIONS: PEAR1 appears to play an important role in agonist-induced platelet aggregation and in the response to ASA in both whites and blacks.


Subject(s)
Genetic Predisposition to Disease/genetics , Platelet Aggregation/genetics , Polymorphism, Single Nucleotide/genetics , Receptors, Cell Surface/genetics , Adult , Black or African American , Aged , Aspirin/pharmacology , Coronary Artery Disease/genetics , Female , Genotype , Humans , Male , Middle Aged , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacology , White People
15.
Article in Spanish | LILACS, BDNPAR | ID: lil-574623

ABSTRACT

El consumo y dependencia de sustancias, es un serio problema social con alta morbilidad materno-fetal. El aumento de la oferta y el contexto social favorecedor, permitió que la difusión del consumo sustancias tóxicas ilícitas, conlleve una incidencia creciente en gestantes consumidoras de sustancias y aumento de recién nacidos afectados por las prácticas tóxicas de sus madres. La evaluación del riesgo cuando la gestación es expuesta a las drogas es difícil, los resultados pueden estar sesgados por el consumo concomitante de otros tóxicos o por factores sociológicos y socio-sanitarios desfavorables. Aunque tampoco se definió un patrón específico de anomalías congénitas, se considera que el abuso de drogas, en general, comporta mayor riego de desenlace anómalo del embarazo, por un incremento del riesgo de malformaciones congénitas, debido a la probable teratogenicidad de algunas sustancias o de la morbilidad perinatal afectando el crecimiento fetal o el normal desarrollo del embarazo. También existen posibles repercusiones a largo plazo en la capacidad de aprendizaje y comportamiento delos niños expuestos intraútero, aunque no demostró efectivamente. Por lo tanto, todo embarazo en el que se detecto un hábito tóxico se debe considerar de mayor riesgo, tomando las medidas oportunas para lograr que las pacientes se alejen de éstas prácticas, apoyadas por un equipo multidisciplinario, idealmente antes del inicio del embarazo, lo que implica la adopción de medidas profilácticas de información y concienciación de las mujeres en edad fértil y de apoyo durante el embarazo y la lactancia para el abandono de la dependencia.


Illicit drug use and dependence is a serious social problem with high maternal and fetal morbidity. Supply increase and propitious social context allowed that the diffusion of theuse of illicit toxic substances entails a growing incidence in pregnant women who use illicit drugs and an increase of newborns affected by the practices of their mothers. Risk evaluation is difficult when gestation is exposed to illicit drugs because the results could be biased by the concomitant consumption of others toxic substances or by psychological and socio-sanitary unfavorable factors. Though a specific pattern of congenital anomalies has not been defined, in general it is considered that drug abuse has an increased risk ofanomalous outcomes in pregnancies. This risk is caused by an increase in the risk of congenital malformations due to the probable teratogenicity of some substances or the perinatal morbility affecting the fetal growth or normal pregnancy development. Although it has not been demonstrated effectively, there are also possible long-term repercussions in the learning capacity and behavior of the children exposed intra uterus. In conclusion, all pregnancies exposed to illicit drugs must be considered high risk pregnancies and measures should be taken so that the patients avoid these practices supported by a multidisciplinary team. Ideally, this team should start working before pregnancy implying the adoption of preventive measures such as information and public awareness of women in fertile age and support during pregnancy and maternal lactation.


Subject(s)
Marijuana Abuse , Lysergic Acid Diethylamide/adverse effects , Heroin , Amphetamines/adverse effects , Cocaine/adverse effects , Pregnancy , Lactation
16.
J Thromb Haemost ; 5(8): 1617-23, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17663734

ABSTRACT

BACKGROUND: Variations in platelet function among individuals may be related to differences in platelet-related genes. The major goal of our study was to estimate the contribution of inheritance to the variability in platelet function in unaffected individuals from white and African American families with premature coronary artery disease. METHODS: Platelet reactivity, in the absence of antiplatelet agents, was assessed by in vitro aggregation and the platelet function analyzer closure time. Heritability was estimated using a variance components model. RESULTS: Both white (n = 687) and African American (n = 321) subjects exhibited moderate to strong heritability (h(2)) for epinephrine- and adenosine diphosphate-induced aggregation (0.36-0.42 for white and >0.71 for African American subjects), but heritability for collagen-induced platelet aggregation in platelet-rich plasma was prominent only in African American subjects. Platelet lag phase after collagen stimulation was heritable in both groups (0.47-0.50). A limited genotype analysis demonstrated that the C825T polymorphism of GNB3 was associated with the platelet aggregation response to 2 muM epinephrine, but the effect differed by race. CONCLUSIONS: Considering the few and modest genetic effects reported to affect platelet function, our findings suggest the likely existence of undiscovered important genes that modify platelet reactivity, some of which affect multiple aspects of platelet biology.


Subject(s)
Blood Platelets/physiology , Coronary Artery Disease/blood , Adult , Coronary Artery Disease/complications , Coronary Artery Disease/ethnology , Family Health , Female , Fibrinogen/metabolism , Genotype , Humans , Male , Middle Aged , Platelet Aggregation , Polymorphism, Genetic , Thrombosis/complications , Thrombosis/diagnosis , Thromboxane B2/blood , von Willebrand Factor/metabolism
17.
Circulation ; 115(19): 2490-6, 2007 May 15.
Article in English | MEDLINE | ID: mdl-17470694

ABSTRACT

BACKGROUND: The inability of aspirin (acetylsalicylic acid [ASA]) to adequately suppress platelet function is associated with future risk of myocardial infarction, stroke, and cardiovascular death. Genetic variation is a proposed but unproved mechanism for insufficient ASA responsiveness. METHODS AND RESULTS: We examined platelet ASA responsiveness in 1880 asymptomatic subjects (mean age, 44+/-13 years; 58% women) recruited from 309 white and 208 black families with premature coronary heart disease. Ex vivo platelet function was determined before and after ingestion of ASA (81 mg/d for 2 weeks) with the use of a panel of measures that assessed platelet activation in pathways directly and indirectly related to cyclooxygenase-1, the enzyme inhibited by ASA. The proportion of phenotypic variance related to CHD risk factor covariates was determined by multivariable regression. Heritability of phenotypes was determined with the use of variance components models unadjusted and adjusted for covariates. ASA inhibited arachidonic acid-induced aggregation and thromboxane B2 production by > or = 99% (P<0.0001). Inhibition of urinary thromboxane excretion and platelet activation in pathways indirectly related to cyclooxygenase-1 was less pronounced and more variable (inhibition of 0% to 100%). Measured covariates contributed modestly to variability in ASA response phenotypes (r2=0.001 to 0.133). Phenotypes indirectly related to cyclooxygenase-1 were strongly and consistently heritable across races (h2=0.266 to 0.762; P<0.01), but direct cyclooxygenase-1 phenotypes were not. CONCLUSIONS: Heritable factors contribute prominently to variability in residual platelet function after ASA exposure. These data suggest a genetic basis for the adequacy of platelet suppression by ASA and potentially for differences in the clinical efficacy of ASA.


Subject(s)
Aspirin/pharmacology , Black or African American/genetics , Blood Platelets/physiology , Coronary Disease/blood , Cyclooxygenase Inhibitors/pharmacology , Genetic Variation , Platelet Activation/genetics , Platelet Aggregation Inhibitors/pharmacology , Thrombophilia/genetics , White People/genetics , Adult , Arachidonic Acid/antagonists & inhibitors , Arachidonic Acid/pharmacology , Aspirin/therapeutic use , Blood Platelets/drug effects , Blood Platelets/enzymology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Cyclooxygenase 1/blood , Cyclooxygenase 1/physiology , Cyclooxygenase Inhibitors/therapeutic use , Drug Resistance/genetics , Dyslipidemias/epidemiology , Female , Genetic Heterogeneity , Genetic Predisposition to Disease , Humans , Hyperglycemia/epidemiology , Hypertension/epidemiology , Male , Membrane Proteins/blood , Membrane Proteins/physiology , Middle Aged , Phenotype , Platelet Activation/drug effects , Platelet Aggregation/drug effects , Platelet Aggregation/genetics , Platelet Aggregation Inhibitors/therapeutic use , Prospective Studies , Risk Factors , Sex Characteristics , Smoking/epidemiology , Thrombophilia/drug therapy , Thrombosis/prevention & control , Thromboxane B2/analogs & derivatives , Thromboxane B2/metabolism , Thromboxane B2/urine , beta-Thromboglobulin/metabolism
18.
Vitae (Medellín) ; 13(2): 83-87, mar.-dic. 2006. graf
Article in Spanish | LILACS | ID: lil-441000

ABSTRACT

Las esponjas marinas del género Topsentia son conocidas como fuente de sustancias biológicamente activas. En este trabajo se reporta la preparación y caracterización del triacetato de halistanol, un derivado acetilado del halistanol, obtenido a partir de la fracción biológicamente activa del extracto metanólico de la esponja colombiana Topsentia ophiraphidites, colectada en la Bahía de Santa Marta (Mar Caribe Colombiano). El derivado acetilado se caracteriza a partir de sus datos cromatográficos, espectrales y químicos. La fracción bioactiva de T. ophiraphidites presenta actividad contra el microorganismo Gram-positvo Staphylococcus aureus


Subject(s)
Porifera
19.
JAMA ; 295(12): 1420-7, 2006 Mar 22.
Article in English | MEDLINE | ID: mdl-16551714

ABSTRACT

CONTEXT: Recent randomized trials suggest that women may not accrue the same cardioprotective benefits as men do from low-dose aspirin therapy used in primary prevention. Failure of aspirin to suppress platelet aggregation in women is one hypothesized mechanism. OBJECTIVE: To examine differential platelet reactivity to low-dose aspirin therapy by sex. DESIGN, SETTING, AND PARTICIPANTS: A clinical trial of aspirin at 81 mg/d for 14 days was conducted in 571 men and 711 women. Baseline and post-aspirin therapy measures included platelet aggregation to arachidonic acid, adenosine diphosphate, epinephrine, and platelet function analyzer closure time. MAIN OUTCOME MEASURE: Sex differences in cyclooxygenase 1 (COX-1) direct and indirect platelet activation pathways before and after administration of aspirin. RESULTS: In 10 of the 12 platelet agonist exposures, women's platelets were significantly more reactive at baseline. However, after aspirin therapy, the percent aggregation to arachidonic acid (the direct COX-1 pathway) decreased more in women than in men (P<.001) and demonstrated near total suppression of residual platelet reactivity in both men and women. In COX-1 indirect pathways, women experienced the same or more platelet inhibition than men in 8 of the 9 assays yet retained modestly greater platelet reactivity after aspirin therapy. In multivariable analysis, female sex significantly predicted aggregation to 2 muM and 10 muM of adenosine diphosphate (P = .02 and <.001, respectively) and collagen at 5 mug/mL (P<.001) independent of risk factors, age, race, menopausal status, and hormone therapy. CONCLUSIONS: Women experienced the same or greater decreases in platelet reactivity after aspirin therapy, retaining modestly more platelet reactivity compared with men. However, most women achieved total suppression of aggregation in the direct COX-1 pathway, the putative mechanism for aspirin's cardioprotection.


Subject(s)
Aspirin/therapeutic use , Cyclooxygenase Inhibitors/therapeutic use , Platelet Activation/drug effects , Platelet Aggregation Inhibitors/therapeutic use , Adenosine Diphosphate/pharmacology , Arachidonic Acid/pharmacology , Aspirin/pharmacology , Cardiovascular Diseases/prevention & control , Collagen/pharmacology , Cyclooxygenase 1/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Epinephrine/pharmacology , Female , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/pharmacology , Platelet Function Tests , Regression Analysis , Sex Factors
20.
Vitae (Medellín) ; 11(1/2): 35-41, sept. 2003-mar. 2004. tab
Article in Spanish | LILACS | ID: lil-383638

ABSTRACT

Este artículo es la segunda parte de una revisión que comprende una selección de artículos consultados en diferentes bases de datos, en los cuales se reportan los estudios de actividad antibacteriana, antimicótica y antiviral de compuestos derivados de organismos marinos y otras fuentes naturales, en el período comprendido entre 1988 y 2003.


Subject(s)
Marine Flora , Biological Factors , Biomarkers, Tumor
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