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1.
J Nanosci Nanotechnol ; 14(8): 6386-9, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25936122

RESUMEN

In this study, titania photocatalyst was produced from the wastewater sludge of Ti-salt flocculation. The high photocatalytic activity of titania reported was evaluated based on a single organic substrate. However, the photocatalytic activity is a substrate-specific; one photocatalyst showed different photocatalytic degradation rates for different substrates. Thus, to investigate the substrate-specific photocatalytic activity of titania, various substrates of humic acid (HA), dichloroacetic acid (DCA), rhodamine B (RhB), metsulfuron methyl (M&M) and phenol were used under simulated solar light irradiation. Results showed titania had a high activity rate for RhB, moderate activity for HA and DCA and low activity for M&M and phenol indicating substrate-specific activities. When compared with Degussa-P25, titania showed higher activity for M&M, while the opposite was observed for HA and phenol. The specific-substrate behaviour of titania could depend on specific physicochemical and electronic interactions between titania, substrates, and their intermediates compounds formed.


Asunto(s)
Aguas del Alcantarillado , Luz Solar , Titanio/química , Catálisis , Floculación , Fotoquímica
2.
J Nanosci Nanotechnol ; 13(6): 4106-9, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23862456

RESUMEN

The main drawback of flocculation process with dye wastewater is the large amount of unrecyclable sludge which needs disposal. A novel process using Ti-salt flocculation to purify wastewater was developed to produced sludge that can be calcined to produce titania. In this study, iron-doped TiO2 nanomaterial was successfully produced from sludge obtained by the flocculation of dye wastewater with a composite floculant including TiCl4 and FeSO4. The titania was characterised using scanning electron microscopy (SEM/EDX), transmission electron microscopy (TEM), X-ray diffraction (XRD), and the photodecomposition of acetaldehyde. The XDR results showed that the anatase and rutile structures were found after sludge calcination at 550 degrees C and 640 degrees C respectively. The elemental analyses were carried out using EDX. The rutile titania sample consisted of Ti (35.7 wt.%), Fe (14.7 wt.%), O (42.3 wt.%), P (2.6 wt.%) and Ca (4.7 wt.%). The photocatalytic activity was monitored for the photodecomposition of gas acetaldehyde. Iron-doped titania seems to play an important role in increasing the photocatalytic activity under UV light irradiation.

3.
Ann Allergy Asthma Immunol ; 106(4): 292-300.e6, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21457877

RESUMEN

BACKGROUND: Signal-regulated palmitoylation of RGS7BP(regulator of G-protein-signaling 7-binding protein) initiates the activation of G-protein-coupled receptors (GPCRs), including muscarinic receptors, which contribute to the development of asthma and its subphenotypes. OBJECTIVE: To determine the association of RGS7BP gene polymorphisms with the development of aspirin-exacerbated respiratory disease (AERD). METHODS: We evaluated the association of RGS7BP gene polymorphisms with response to oral aspirin challenge and with responsiveness to methacholine challenge. RGS7BP messenger RNA splice variants in peripheral blood platelets from patients with different single-nucleotide polymorphisms were analyzed by reverse-transcription polymerase chain reaction. RESULTS: Logistic regression analysis of RGS7BP gene polymorphisms in patients with AERD (n = 102) and aspirin-tolerant asthma (n = 429) revealed that a haplotype of block 3 consisting of rare alleles +98092 C>G, +98853 C>T, and +104450 T>G of the RGS7BP gene was associated with AERD. Multiple linear regression analysis showed that asthmatic patients carrying ht2/ht2 in block 3 were more responsive to aspirin challenge than those not carrying ht2 (P = .008 in a codominant model). The log-transformed provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% for methacholine was significantly dependent on the BL3-ht2 haplotype. No significant differences in platelet expression of different RGS7BP messenger RNA splice variants were detected between those with and without the BL3-ht2 haplotype. CONCLUSION: BL3-ht2 of RGS7BP may be an important genetic variant associated with AERD. The haplotype of block 3 may play a protective role against aspirin hypersensitivity in asthma, perhaps by altering the responsiveness of muscarinic receptors.


Asunto(s)
Aspirina/efectos adversos , Asma/inducido químicamente , Asma/genética , Proteínas Portadoras/genética , Hipersensibilidad a las Drogas/genética , Receptores Acoplados a Proteínas G/genética , Adolescente , Adulto , Anciano , Aspirina/inmunología , Asma/inmunología , Proteínas Portadoras/inmunología , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/inmunología , Femenino , Volumen Espiratorio Forzado , Genotipo , Humanos , Péptidos y Proteínas de Señalización Intracelular , Modelos Lineales , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Proteínas RGS , ARN/química , ARN/genética , Receptores Acoplados a Proteínas G/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto Joven
4.
J Am Chem Soc ; 132(35): 12200-2, 2010 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-20718409

RESUMEN

The organic molecular porous material 1 obtained by recrystallization of cucurbit[6]uril (CB[6]) from HCl shows a high CO(2) sorption capacity at 298 K, 1 bar. Most interestingly, 1 showed the highest selectivity of CO(2) over CO among the known porous materials so far. The remarkable selectivity of CO(2) may be attributed to the exceptionally high enthalpy of adsorption (33.0 kJ/mol). X-ray crystal structure analysis of CO(2) adsorbed 1 revealed three independent CO(2) sorption sites: two in the 1D channels (A and B) and one in the molecular cavities (C). The CO(2) molecules adsorbed at sorption site A near the wall of the 1D channels interact with 1 through hydrogen bonding and at the same time interact with those at site B mainly through quadrupole-quadrupole interaction in a T-shaped arrangement. Interestingly, two CO(2) molecules are included in the CB[6] cavity (site C), interacting not only with the carbonyl groups of CB[6] but also with each other in a slipped-parallel geometry. The exceptionally selective CO(2) sorption properties of 1 may find useful applications in the pressure swing adsorption (PSA) process for CO(2) separation not only in the steel industry but also in other industries such as natural gas mining.


Asunto(s)
Compuestos de Boro/química , Dióxido de Carbono/química , Adsorción , Cristalografía por Rayos X , Modelos Moleculares , Porosidad
5.
Pharmacogenet Genomics ; 20(12): 748-58, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20921925

RESUMEN

OBJECTIVE: Aspirin affects interleukin-4 (IL-4) synthesis; however, the genetic role of IL-4 has not been evaluated in asthmatics with aspirin hypersensitivity. The objective of the study was to examine the influence of single nucleotide polymorphisms (SNPs) in IL-4 gene on aspirin hypersensitivity in asthmatics at the genetic and molecular levels. METHODS: Aspirin-intolerant (AIA, n=103) and aspirin-tolerant asthmatics (n=270) were genotyped and functional promoter assays were performed. RESULTS: Of 15 SNPs tested, seven (-589T>C (rs2243250) in promoter, -33T>C (rs2070874) in the 5'-untranslated region, +4047A>G (rs2243266), +4144C>G (rs2243267), +4221C>A (rs2243268), +4367G>A (rs2243270), and +5090A>G (rs2243274) in introns) were significantly associated with AIA risk. The frequency of the rare allele (C) of -589T>C was higher in the AIA group than in the aspirin-tolerant asthmatic group (P=0.016), and a gene dose-dependent decline in forced expiratory volume in 1 s was noted after an aspirin challenge (P=0.0009). Aspirin unregulated IL-4 mRNA production in Jurkat T and K562 leukemia cells. A reporter plasmid assay revealed that aspirin augmented IL-4 promoter transactivation with the -589T>C C and -33T>C C alleles, compared with that bearing the -589T>C T and -33T>C T alleles. Further, electrophoretic mobility shift assay showed the formation of nuclear complexes with -33T>C and -589T>C allele-containing probes; this was augmented by aspirin. The complexes formed with the -33T>C and -589T>C probes were shifted by treatment with anti-CCAAT-enhancer-binding proteins ß and anti-nuclear factor of activated T-cells antibodies, respectively, indicating the inclusion of these transcription factors. CONCLUSION: Aspirin may regulate IL4 expression in an allele-specific manner by altering the availability of transcription factors to the key regulatory elements in the IL4 promoter, leading to aspirin hypersensitivity.


Asunto(s)
Aspirina/farmacología , Asma/genética , Tolerancia a Medicamentos/genética , Interleucina-4/genética , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Adolescente , Adulto , Anciano , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Mapeo Cromosómico , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad , Heterocigoto , Humanos , Células Jurkat , Células K562 , Modelos Logísticos , Masculino , Persona de Mediana Edad , Unión Proteica/efectos de los fármacos , Factores de Riesgo , Factores de Transcripción/metabolismo , Transcripción Genética/efectos de los fármacos , Adulto Joven
6.
J Am Chem Soc ; 131(22): 7524-5, 2009 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-19438178

RESUMEN

The postsynthetic modification strategy is adopted to demonstrate for the first time the syntheses of catalytically active chiral MOPMs from a preassambled achiral framework, MIL-101, by attaching L-proline-derived chiral catalytic units to the open metal coordination sites of the host framework. Various characterization techniques (including PXRD, TGA, IR, and N(2) absorption measurements) indicated that the chiral units are successfully incorporated into MIL-101, keeping the parent framework intact. The new chiral MOPMs show remarkable catalytic activities in asymmetric aldol reactions (yield up to 90% and ee up to 80%). It is interesting to note that these heterogeneous catalysts show much higher enantioselectivity than the corresponding chiral catalytic units as homogeneous catalysts. This study demonstrates a simple and efficient route for the generation of catalytically active chiral MOPMs. A variety of chiral catalytic units can be, in principle, incorporated into chemically robust achiral MOPMs with large pores by postmodification and the resulting chiral MOPMs may find useful applications in catalytic asymmetric transformations.

7.
BMC Med Genet ; 10: 106, 2009 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-19840403

RESUMEN

BACKGROUND: We previously demonstrated that single nucleotide polymorphism (SNP) and haplotypes were associated with aspirin hypersensitivity in asthmatics. We investigated the genetic effects of the SNPs and haplotypes on the expression of the CysLTR2 gene. METHODS: We measured CysLTR2 protein and mRNA expression in EB virus-infected B cell lines from asthmatics having ht1+/+ and ht2+/+. A gel retardation assay was used to identify nuclear protein binding to the c.-819 promoter site. The function of promoter and 3'-UTR were assessed using pGL3 luciferase and pEGFP reporter system, respectively. RESULTS: We found that the expression of CysLTR2 protein was higher in B cell lines of asthmatics having ht2+/+ than in those having ht1+/+. PMA/ionomycin induced higher mRNA expression of CysLTR2 in B cell lines from ht2+/+ asthmatics than those from ht1+/+ asthmatics. A nuclear protein from the B cell lines showed stronger DNA binding affinity with a probe containing c.-819T than one containing c.-819G. The luciferase activity of the c.-819T type of CysLTR2 promoter was higher than that of the c.-819G type. EGFP expression was higher in the EGFP-c.2078T 3'-UTR fusion construct than in the c.2078C construct. CONCLUSION: The sequence variants of CysLTR2 may affect its transcription and the stability of its mRNA, resulting in altered expression of CysLTR2 protein, which in turn causes some asthmatics to be susceptible to aspirin hypersensitivity.


Asunto(s)
Asma/genética , Estabilidad del ARN/genética , ARN Mensajero/biosíntesis , Receptores de Leucotrienos/genética , Aspirina/efectos adversos , Asma/inducido químicamente , Línea Celular , Hipersensibilidad a las Drogas/genética , Ensayo de Cambio de Movilidad Electroforética , Citometría de Flujo , Expresión Génica , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Luciferasas , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas
8.
J Allergy Clin Immunol ; 120(5): 1110-7, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17983872

RESUMEN

BACKGROUND: Eosinophilic infiltration and peripheral blood eosinophilia in asthma require the cooperation of eosinophil-specific cytokines and chemokines and their receptors. OBJECTIVE: We investigated the association of polymorphisms in CCR3 and IL5RA with asthma susceptibility or peripheral blood eosinophilia and the effects of the polymorphisms on receptor expression. METHODS: Polymorphisms in CCR3 and IL5RA were identified and genotyped in 576 asthmatic patients and 180 healthy control subjects. CCR3 and IL-5 receptor alpha (IL-5R alpha) protein expression on eosinophils was measured by means of flow cytometry. RESULTS: Although polymorphisms in CCR3 were not associated with asthma susceptibility, the CCR3 haplotype ht2 showed a negative gene dose effect on the eosinophil count (P = .003-.009). IL5RA c.-5091G>A was weakly associated with eosinophil count. The effects of ht2 were greater when paired with IL5RA c.-5091A (P = .001-.002). CCR3 protein expression was higher on eosinophils of asthmatic patients without ht2 than in those with ht2. Asthmatic patients with the IL5RA c.-5091A allele showed higher IL-5R alpha expression than those who were homozygous for the G allele. CONCLUSION: The genetic association between CCR3 polymorphisms and the number of circulating eosinophils was revealed as a novel finding. These associations were more pronounced when the CCR3 polymorphisms were paired with polymorphisms in IL5RA. The protein expression levels of CCR3 and IL-5R alpha on peripheral blood eosinophils are associated with the polymorphisms on their own genes. CLINICAL IMPLICATIONS: The identification of single nucleotide polymorphisms and haplotypes of CCR3 and IL5RA might be useful in developing markers for intermediate phenotypes of eosinophil number and in designing strategies to control diseases related to hypereosinophilia.


Asunto(s)
Asma/inmunología , Eosinofilia/genética , Eosinófilos/inmunología , Subunidad alfa del Receptor de Interleucina-5/genética , Polimorfismo de Nucleótido Simple , Receptores CCR3/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Asma/genética , Niño , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad
9.
Chem Commun (Camb) ; (40): 4113-5, 2007 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-17925946

RESUMEN

Sulfonic acid-incorporated-MCM-41 mesoporous materials prepared using a silane containing tetrasulfide linkages showed exceptional yields of the acetylated product in the acetylation of anisole due to their high content of strong acid sites.

10.
J Nanosci Nanotechnol ; 16(5): 4505-11, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27483782

RESUMEN

In this study, the synthesis of porous titania-silica (TiO2-SiO2) composite aerogel at ambient pressure by using non-hazardous chemicals as a source of silica was investigated. TiO2-SiO2 composite aerogels were characterised and their photocatalytic performances were investigated for the removal efficiency of acetaldehyde and NO(x) under UV light. Results showed that porous composite aerogel with aggregated morphology, high surface area and an increased mesoporosity were formed. TiO2-SiO2(1.8) composite, with high Ti/Si ratio, showed the best results in terms of photocatalytic removal of acetaldehyde and nitrogen oxide.

11.
Chest ; 128(5): 3127-32, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16304252

RESUMEN

STUDY OBJECTIVE: Eosinophilic infiltration of airway tissue is a central feature of aspirin-induced asthma (AIA). Eotaxins belong to the family of CC chemokines, which coordinate the recruitment of inflammatory cells bearing chemokine (C-C motif) receptor-3 to sites of allergic inflammation. In the present study, the levels of eotaxin-1, eotaxin-2, and eotaxin-3 following an oral aspirin provocation test (APT) were measured, and the relationship between the eotaxin level and clinical parameters in patients with asthma was evaluated. PATIENTS AND DESIGN: An APT was performed in patients with asthma. Twenty AIA patients and 23 aspirin-tolerant asthma (ATA) patients were identified. Plasma levels of eotaxin-1, eotaxin-2, and eotaxin-3 levels were measured by enzyme-linked immunosorbent assay in the 43 patients with asthma and in 39 control subjects. RESULTS: The proportion of blood eosinophils was significantly higher in asthmatic patients than in control subjects. Nasal polyps were more common in AIA patients than in ATA patients (p < 0.05). In addition, the eotaxin-1 level was higher in AIA and ATA patients than in control subjects (p < 0.01 for each). The eotaxin-2 level was higher in ATA patients than in either the AIA patients (p < 0.05) or control subjects (p < 0.01). Similarly, the eotaxin-3 level was higher in ATA patients than in control subjects. A trend toward higher plasma levels of eotaxin-1 and eotaxin-3 at baseline and at 4 h after APT administration in the ATA group was noted but was not significant. Eotaxin-2 was also higher in ATA patients than in AIA patients at baseline and at 4 h after the APT. CONCLUSION: This study shows that eotaxin-2 is differentially secreted in patients with asthma according to aspirin intolerance, and that secretion is not time-dependent in response to the APT in AIA and ATA patients. It therefore appears that eotaxin-2 may be up-regulated and may act differentially in patients with ATA.


Asunto(s)
Asma/sangre , Quimiocinas CC/sangre , Eosinófilos/inmunología , Adulto , Aspirina/efectos adversos , Asma/inducido químicamente , Quimiocina CCL11 , Quimiocina CCL24 , Quimiocina CCL26 , Quimiocinas CC/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/sangre , Regulación hacia Arriba/fisiología
12.
J Nanosci Nanotechnol ; 15(7): 5326-9, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26373134

RESUMEN

In the past few years, silica-modified titania has drawn increasing attention due to their special properties making them ideal candidates for a wide range of applications. In this study, we report a novel method for the synthesis of silica-modified titania by a sol-gel method using sodium silicate solution (1 M). The hydrolysis and condensation reactions of titanium dioxide (TiO2, Degussa Aeroxide® P25) in sodium silicate solution proceeded with citric acid (3 M) as a catalyst. The orbital shaking method was followed for the removal of sodium salt formed during the sol-gel process. Solvent exchange was carried out using methanol and hexane. Finally, chemical modification of the gel was conducted using trimethylchlorosilane followed by ambient pressure drying. The obtained silica-modified titania was characterised for nanostructural analysis using scanning electron microscopy and transmission electron microscopy. The nitrogen adsorption-desorption measurements were employed to investigate the BET surface area, pore structure and pore volume of specimens. Thermal gravimetric analysis showed exothermic peaks at temperature range of 90-190 °C representing the oxidation of organic groups from--Si-R network. The silica-modified titania showed high photocatalytic activity and an easy recovery using crystal violet as model water pollutant.

13.
Allergy Asthma Immunol Res ; 5(5): 258-76, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24003382

RESUMEN

Although aspirin-exacerbated respiratory disease (AERD) has attracted a great deal of attention because of its association with severe asthma, it remains widely under-diagnosed in the asthmatic population. Oral aspirin challenge is the best method of diagnosing AERD, but this is a time-consuming procedure with serious complications in some cases. Thus, development of non-invasive methods for easy diagnosis is necessary to prevent unexpected complications of aspirin use in susceptible patients. For the past decade, many studies have attempted to elucidate the genetic variants responsible for risk of AERD. Several approaches have been applied in these genetic studies. To date, a limited number of biologically plausible candidate genes in the arachidonate and immune and inflammatory pathways have been studied. Recently, a genome-wide association study was performed. In this review, the results of these studies are summarized, and their limitations discussed. In addition to the genetic variants, changes in methylation patterns on CpG sites have recently been identified in a target tissue of aspirin hypersensitivity. Finally, perspectives on application of new genomic technologies are introduced; these will aid our understanding of the genetic pathogenesis of aspirin hypersensitivity in asthma.

14.
J Colloid Interface Sci ; 361(2): 612-7, 2011 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-21700293

RESUMEN

The adsorption of pyridine onto the metal organic framework MIL-101 was investigated by experimental and theoretical methods. The amount of pyridine adsorbed on MIL-101 was extraordinarily large at 20 °C, corresponding to about 950 mg/g of dried MIL-101 and approximately half of the voids being filled. Most of the pyridine that had filled the voids was rapidly removed by evacuation at room temperature, but some of the pyridine was so strongly adsorbed that it was retained even under evacuation at 150 °C. Although IR spectra of the adsorbed pyridine indicated the adsorption of pyridine as pyridinium ions and coordinated pyridine at low temperatures, increasing the adsorption temperature induced partial cleavage of the pyridine rings. The high stabilization energy of pyridine on the coordinative unsaturated sites (CUS) of MIL-101, obtained by theoretical calculation, -103 kJ/mol, supported the strong adsorption of pyridine on the CUS.

15.
Allergy Asthma Immunol Res ; 3(4): 265-72, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21966607

RESUMEN

PURPOSE: We sought to identify asthma-related genes and to examine the potential of these genes to predict asthma, based on expression levels. METHODS: The subjects were 42 asthmatics and 10 normal healthy controls. PBMC RNA was subjected to microarray analysis using a 35K array; t-tests were used to identify genes that were expressed differentially between the two groups. A multiple logistic regression analysis was applied to the differentially expressed genes, and area under the curve (AUC) values from receiver operating characteristic (ROC) curves were obtained. RESULTS: In total, 170 genes were selected using the following criteria: P≤0.001 and ≥2-fold change. Among these genes, 57 were up-regulated and 113 were down-regulated in asthmatics versus normal controls. A multiple logistic regression analysis was done using more stringent criteria (P≤0.001 and ≥5-fold change), and eight genes were selected as candidate asthma biomarkers. Using these genes, 255 models (2(8)-1) were generated. Among them, only 85 showed P≤0.05 by multiple logistic regression analysis. Based on the AUCs from ROC curves for the 85 models, we found that the best model consisted of the genes MEPE, MLSTD1, and TRIM37. The model showed 0.9928 of the AUC with 98% sensitivity and 80% specificity. CONCLUSIONS: MEPE, MLSTD1, and TRIM37 may be useful biomarkers for asthma.

16.
Pharmacogenomics ; 12(3): 351-63, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21449675

RESUMEN

AIM: Thromboxane A synthase (TBXAS1) converts prostaglandin H to thromboxane A, a potent constrictor of smooth respiratory muscle. Thus, functional alterations of the TBXAS1 gene may contribute to aspirin-intolerant asthma (AIA). MATERIALS & METHODS: We investigated the relationship between SNPs in the TBXAS1 gene and AIA. Asthmatics (n = 470) were categorized into AIA (20% or greater decreases in forced expiratory volume in 1 s [FEV(1)], or 15% to 19% decreases in FEV(1) with naso-ocular or cutaneous reactions) and aspirin-tolerant asthma (ATA). A total of 101 SNPs were genotyped. mRNA expression of the TBXAS1 gene by peripheral blood mononuclear cells and plasma thromboxane B2 (TXB2) concentrations were measured by reverse transcriptase (RT)-PCR and ELISA. RESULTS: Logistic regression analysis showed that the rare allele frequency of rs6962291 in intron 9 was significantly lower in the AIA group (n = 115) than in the ATA group (n = 270) (p(corr) = 0.04). The linear regression analysis revealed a strong association of rs6962291 with the aspirin challenge-induced FEV(1) fall (p = 0.003). RT-PCR revealed an exon-12-deleted splice variant. We measured TBXAS1 mRNA levels in peripheral blood mononuclear cells. The mRNA levels of the full-length wild-type and splice variant were significantly higher in the TT homozygotes than in the AA homozygotes of rs6962291 (1.00 ± 0.18 vs 0.57 ± 0.03 and 1.00 ± 0.18 vs 0.21 ± 0.05, p = 0.047 and 0.001, respectively). The plasma TXB2 level was significantly lower in rs6962291 AA carriers than in rs6962291 TT (p = 0.016) carriers. CONCLUSION: The rare allele of rs6962291 may play a protective role against aspirin hypersensitivity via a lower catalytic activity of the TBXAS1 gene, attributed to the increase of a nonfunctioning isoform of TBXAS1.


Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Asma Inducida por Aspirina/genética , Tromboxano-A Sintasa/genética , Adolescente , Adulto , Anciano , Alelos , Antiinflamatorios no Esteroideos/administración & dosificación , Aspirina/administración & dosificación , Femenino , Volumen Espiratorio Forzado/genética , Frecuencia de los Genes , Enfermedades Genéticas Congénitas/genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Polimorfismo de Nucleótido Simple , Tromboxano B2/sangre , Tromboxano-A Sintasa/sangre , Adulto Joven
17.
Allergy Asthma Immunol Res ; 2(1): 48-54, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20224678

RESUMEN

PURPOSE: Leukotriene receptor antagonists (LTRAs) are used to treat aspirin-intolerant asthma (AIA); however, the protective effects of long-term LTRA administration against aspirin-induced bronchospasm have not been evaluated. OBJECTIVES: We investigated the efficacy of a 12-week treatment with a LTRA in protecting against aspirin-induced asthma in AIA patients. METHODS: Fifty-two adult patients with AIA underwent an aspirin challenge test just before administration of montelukast (10 mg/day) and just after 12 weeks of treatment. The protective effect was assessed as the disappearance of aspirin-induced bronchospasm after 12 weeks of treatment. The results were compared according to the patients' clinical and physiological parameters. RESULTS: The decline in FEV1 following aspirin challenge was significantly reduced from 28.6+/-1.9% to 10.2+/-1.7% (P=0.0001) after 12 weeks of montelukast treatment. However, 14 subjects (30%) still showed a positive response (>15% decline in FEV1) to aspirin challenge. Grouping the subjects into good and poor responders according to post-treatment responses revealed that the pretreatment aspirin-induced FEV1 decline was significantly greater in the poor responders and that the triggering dose of aspirin and the induction time for a positive response were lower and shorter, respectively, in the poor responders. Histories of aspirin hypersensitivity and sinusitis were more prevalent among the poor responders than among the good responders. CONCLUSIONS: Twelve weeks of treatment with montelukast protected against aspirin-induced bronchospasm in 70% of the AIA cases. A poor response was associated with more severe aspirin-induced bronchospasms before treatment and a history of aspirin hypersensitivity or sinusitis. CLINICAL IMPLICATIONS: A severe response to aspirin challenge may be a predictor of poor responsiveness to leukotriene antagonist treatment.

18.
Hum Immunol ; 71(11): 1147-53, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20674643

RESUMEN

Nuclear factor-κB (NF-κB) orchestrates the expression of genes responsible for airway inflammation and remodeling in asthma. The activity of NF-κB is tightly regulated by IKBA, which may be modulated by genetic polymorphisms of the IKBA gene. We investigated the association between asthma susceptibility and IKBA gene polymorphisms in a Korean population. Genotyping was performed in BA (bronchial asthma) and NC (normal control). We measured reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay, and luciferase reporter assays, respectively. A -673A>T (rs2233407) was associated with asthma development in subjects with atopic asthma (odds ratio = 0.56, p = 0.004). The IKBA mRNA level was higher in B-cell lines with the rs2233407 TT genotype compared with those with the AA genotype (p = 0.024). The luciferase activity of the rs2233407 T genotype was higher than that of the A (p = 0.002). The cytoplasmic levels of total IKBA and IKBA [p-S32] were higher in B cell lines of the rs2233407 TT genotype than those of the AA (p = 0.016 and p = 0.036, respectively), whereas nuclear NF-κB activity in cells with the IKBA rs2233407 AA genotype was higher than in cells with the AA (p = 0.038). The IKBA rs2233407 A>T polymorphism may predispose individuals to the development of atopic asthma via regulation of IKBA gene expression at the transcriptional level.


Asunto(s)
Asma/genética , Asma/inmunología , Linfocitos B/metabolismo , Proteínas I-kappa B/genética , FN-kappa B/metabolismo , Adulto , Asma/epidemiología , Linfocitos B/inmunología , Linfocitos B/patología , Línea Celular Tumoral , Análisis Mutacional de ADN , Activación Enzimática/genética , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Corea (Geográfico) , Masculino , Inhibidor NF-kappaB alfa , FN-kappa B/genética , Polimorfismo Genético , Pruebas de Función Respiratoria
19.
BMB Rep ; 43(6): 445-9, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20587336

RESUMEN

Aspirin-intolerant asthma (AIA) is characterized by severe asthmatic attack after ingestion of aspirin and/or non-steroidal anti-inflammatory drugs. In this study, we investigated the relationship between Prostaglandin E2 receptor (PTGER) gene family polymorphisms and AIA in 243 AIA patients and 919 aspirin-tolerant asthma (ATA) controls of Korean ethnicity in two separate study cohorts. After genotyping 120 SNPs of the PTGER gene family for the 1(st) cohort study, four SNPs in PTGER1, ten in PTGER3, six in PTGER3, and a haplotype of PTGER2 showed association signals with decreased or increased risk of AIA. Among the positively associated SNPs, one in PTGER1 and four in PTGER3 were analyzed in the 2(nd) cohort study. The results show that rs7543182 and rs959 in PTGER3 retained their effect, although no statistical significance was retained in the 2(nd) cohort study. Our findings provide further evidence that polymorphisms in PTGER3 might play a significant role in aspirin hypersensitivity among Korean asthmatics.


Asunto(s)
Aspirina/efectos adversos , Asma/genética , Polimorfismo Genético , Receptores de Prostaglandina E/genética , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Adulto Joven
20.
Pharmacogenomics ; 11(7): 951-8, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20602614

RESUMEN

AIMS: Cysteinyl leukotrienes are inactivated by acetyl coenzyme A-dependent N-acetyltransferase (NAT). Thus, functional alterations of the NAT gene may contribute to the risk of aspirin-intolerant asthma. MATERIALS & METHODS: Asthmatics (n = 438) were categorized into aspirin-intolerant asthma (15% or greater decrease in the forced expiratory volume in 1 s or cutaneous reactions, n = 170) or aspirin-tolerant asthma (n = 268) groups. In total, 14 polymorphisms of the NAT2 gene were genotyped by a single-base extension method. RESULTS: The distributions of all loci of the 14 SNPs were in Hardy-Weinberg equilibrium (p > 0.05). Among the 14 SNPs, six common SNPs (minor allele frequency >5%) in a Korean population were used for haplotype construction and further statistical analysis. The logistic regression analysis demonstrated that NAT2 -9246G>C and haplotype 2 (TCACGG) were significantly associated with the risk of aspirin-intolerant asthma. The rare allele frequencies of the SNP and Ht2 were significantly higher in the aspirin-intolerant asthma group than in the aspirin-tolerant asthma group (p(corr) = 0.03 and p(corr) = 0.02 in codominant model). CONCLUSION: In a large genetic epidemiology study of aspirin-intolerant asthma in a Korean population, genetic polymorphisms of NAT2 were found to be related to a risk of aspirin hypersensitivity among asthmatics.


Asunto(s)
Arilamina N-Acetiltransferasa/genética , Aspirina/efectos adversos , Asma/genética , Hipersensibilidad a las Drogas/genética , Polimorfismo Genético , Adulto , Alelos , Pueblo Asiatico/genética , Aspirina/inmunología , Asma/fisiopatología , Estudios de Casos y Controles , Cisteína/inmunología , Tolerancia a Medicamentos/genética , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Corea (Geográfico) , Leucotrienos/inmunología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple
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