RESUMEN
BACKGROUND AND OBJECTIVES: Adverse reactions to platelet transfusions are a problem. Children with primary haematological and malignant diseases may experience allergic transfusion reactions (ATRs) to platelet concentrates (PCs), which can be prevented by giving washed PCs. A new platelet additive solution, using bicarbonated Ringer's solution and acid-citrate-dextrose formula A (BRS-A), may be better for platelet washing and storage, but clinical data are scarce. MATERIALS AND METHODS: A retrospective cohort study for consecutive cases was performed between 2013 and 2017. For 24 months, we transfused washed PCs containing BRS-A to children with primary haematological and malignant diseases and previous adverse reactions. Patients transfused with conventional PCs (containing residual plasma) were assigned as controls, and results were compared in terms of frequency of ATRs, corrected count increment (CCI) and occurrence of bleeding. We also studied children transfused with PCs washed by a different system as historical controls. RESULTS: Thirty-two patients received 377 conventional PC transfusions. ATRs occurred in 12 (37·5%) patients from transfused with 18 (4·8%) bags. Thirteen patients, who experienced reactions to regular PCs in plasma, then received 119 transfusion bags of washed PCs containing BRS-A, and none had ATRs to washed PCs containing BRS-A. Before study period, six patients transfused 137 classical washed PCs with different platelet additive solution, under same indication, ATRs occurred in one (16·7%) patient from transfused with one (0·7%) bags. CCIs (24 h) in were lower with classical washed PCs (1·26 ± 0·54) compared to regular PCs in plasma (2·07 ± 0·76) (P < 0·001), but there was no difference between washed PCs containing BRS-A (2·14 ± 0·77) and regular PCs (2·21 ± 0·79) (P = 0·769), and we saw no post-transfusion bleeding. CONCLUSION: Washed PCs containing BRS-A appear to prevent ATRs without loss of transfusion efficacy in children with primary haematological and malignant diseases. Their efficacy should be further evaluated through larger prospective clinical trials.
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Plaquetas/inmunología , Transfusión de Plaquetas/métodos , Reacción a la Transfusión/prevención & control , Plaquetas/efectos de los fármacos , Niño , Femenino , Humanos , Soluciones Isotónicas/farmacología , Masculino , Transfusión de Plaquetas/efectos adversos , Reacción a la Transfusión/inmunologíaRESUMEN
BACKGROUND AND OBJECTIVES: Allergic transfusion reactions (ATRs) and febrile non-haemolytic transfusion reactions (FNHTRs) are the two major types of transfusion-related adverse reactions (TRARs). Although prestorage leucocyte reduction and diversion of the first aliquot of blood (LR/D) could reduce FNHTRs and bacterial contamination in adult transfusion, ATRs are still problematic. In addition, there is little information about TRARs in paediatric population. MATERIALS AND METHODS: We conducted a single-centre retrospective analysis of all transfusions, except washing products, and TRARs for 153 months to evaluate related factors such as delivery of treatment and the characteristics of recipients. RESULTS: Most TRARs were FNHTRs and/or ATRs in children. In delivering blood products with LR/D, the frequencies of not only FNHTRs but also ATRs were significantly reduced with both platelet concentrates (PCs) and red cell concentrates (RCCs). TRARs of fresh-frozen plasma were infrequent in children. In addition, even after the introduction of LR/D, ATRs were significantly more frequent in patients with primary haematological and malignant diseases who received PCs and RCCs, older patients who received PCs and patients who received frequent RCCs. CONCLUSION: These results suggest that leucocytes or mediators from leucocytes are underlying cause of ATRs in addition to FNHTRs in children. Furthermore, particular characteristics of patients would be other risk factors for ATRs.
Asunto(s)
Hipersensibilidad/etiología , Reacción a la Transfusión/etiología , Niño , Preescolar , Transfusión de Eritrocitos/efectos adversos , Femenino , Humanos , Lactante , Leucocitos/citología , Masculino , Análisis Multivariante , Plasma/química , Transfusión de Plaquetas/efectos adversos , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de RiesgoRESUMEN
INTRODUCTION: Micafungin (MCFG) is used for the prophylaxis of invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (HSCT). However, the safety, efficacy, or optimal dosage/blood levels as prophylaxis is uncertain in pediatric HSCT-patients. METHODS: We prophylactically administered MCFG at 2 mg/kg once daily to 38 children and adolescents undergoing allogeneic HSCT. RESULTS: During MCFG prophylaxis, infusion reactions or adverse events (grades 2-5) related to MCFG use were not found in all the patients. Thus, MCFG prophylaxis was not discontinued and other antifungal agents were not added except for 2 patients in whom probable or possible IFDs developed (completion rate, 94.7 %). To elucidate the influence of HSCT-related complications/drugs on blood concentration of MCFG, we determined the plasma trough and peak levels in 13 and 10 among 38 patients, respectively. The mean trough and peak levels were 3.04 ± 1.21 µg/mL (569 samples) and 9.63 ± 3.62 µg/mL (44 samples), respectively. The peak levels were moderately correlated to the trough levels (R (2) = 0.466). In a patient, the trough level of MCFG transiently increased up to 10.21 µg/mL during hepatic dysfunction due to acute graft-versus-host disease. The MCFG trough levels strongly correlated with T-Bil value (R (2) = 0.894). There was no relationship between the trough levels of MCFG and the circulating concentrations of tacrolimus (R (2) = 0.040). Additionally, MCFG levels were not influenced by treatment with cyclophosphamide or corticosteroids. CONCLUSIONS: Prophylaxis with MCFG at 2 mg/kg once daily may be safe, tolerable, and feasible in pediatric HSCT-patients.
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Antifúngicos/administración & dosificación , Quimioprevención/métodos , Equinocandinas/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Lipopéptidos/administración & dosificación , Micosis/prevención & control , Adolescente , Antifúngicos/efectos adversos , Antifúngicos/farmacocinética , Quimioprevención/efectos adversos , Niño , Preescolar , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Equinocandinas/efectos adversos , Equinocandinas/farmacocinética , Femenino , Humanos , Lactante , Lipopéptidos/efectos adversos , Lipopéptidos/farmacocinética , Masculino , Micafungina , Plasma/químicaRESUMEN
Nano-sized particles are diffusing in the environment with the development of nanotechnology. Polystyrene (PS) nanoparticles are modified industrial products and pharmaceutical agents, however, adverse effects of PS nanoparticles remain to be elucidated. In the present study, we investigated the effects of PS nanoparticles with different sizes on the atopic dermatitis (AD)-like skin lesions in NC/Nga mice assumed to show the skin barrier defect/dysfunction in the presence or absence of mite allergen. Male NC/Nga mice were injected intradermally with three different-sized PS nanoparticles (25, 50, or 100 nm) and/or mite allergen into their right ears. We evaluated clinical scores, ear thickening, histological findings and the local protein expression of inflammatory molecules in the ear and Ig production in serum. PS nanoparticles aggravated AD-like skin lesions related to mite allergen, which was paralleled by the local protein levels of interleukin-4, CCL2/monocyte chemotactic protein-1, CCL3/macrophage inflammatory protein-1 alpha, and CCL4/macrophage inflammatory protein-1 beta. In contrast, PS nanoparticles decreased interferon-gamma expression. Furthermore, exposure to PS nanoparticles induced ear swelling and CC-chemokine expression in the absence of allergen. These effects were greater with the smaller PS nanoparticles than with the larger ones regarding overall trend. These results suggest that exposure to PS nanoparticles under skin barrier defect/dysfunction can exacerbate AD-like skin lesions related to mite allergen in a size-dependent manner. The enhancing effects may be accounted for by T helper 2-biased immune responses. Furthermore, PS nanoparticles can evoke skin inflammation via the overexpression of CC-chemokines even in the absence of allergen in atopic subjects.
Asunto(s)
Dermatitis Atópica/inducido químicamente , Nanopartículas/toxicidad , Poliestirenos/toxicidad , Piel/efectos de los fármacos , Animales , Quimiocinas/biosíntesis , Dermatitis Atópica/inmunología , Dermatitis Atópica/patología , Inmunoglobulina E/sangre , Interleucina-4/sangre , Interleucina-5/sangre , Masculino , Ratones , Piel/patologíaRESUMEN
Fructooligosaccharides (FOS) are prebiotic supplements that can enhance immunological responses in the host to activate mucosal immunity, probably through regulation of gastrointestinal microflora. An area that has not been investigated, however, is the therapeutic potential of prebiotics on allergic airway diseases. The purpose of this study is to evaluate the effects of dietary supplementation with FOS on a murine model of allergic airway inflammation induced by the house dust mite allergen Dermatophagoides farinae (Der f). Male C3H/HeN mice were intratracheally administered with Der f and were fed a diet containing 0% or 2.5% FOS ad libitum. Supplementation with FOS alleviated mite allergen-related airway inflammation characterized by eosinophilic inflammation and goblet cell hyperplasia, which was evidenced by cytological and histological examinations. In addition, the FOS-supplemented diet reduced the serum allergen-specific IgG1 level as compared with a control diet in the presence of the mite allergen. Moreover, FOS tended to suppress the expression of IL-5 and eotaxin in the lungs, which is enhanced by mite allergen. These results suggest that dietary supplementation with FOS can prevent/improve allergic airway inflammation induced by the mite allergen. This effect can be at least partially associated with the inhibition of allergen-specific Ig production and probably with that of IL-5 and eotaxin expression.
Asunto(s)
Alérgenos/toxicidad , Antígenos Dermatofagoides/inmunología , Dieta , Suplementos Dietéticos , Oligosacáridos/uso terapéutico , Pyroglyphidae/inmunología , Hipersensibilidad Respiratoria/tratamiento farmacológico , Administración por Inhalación , Alérgenos/administración & dosificación , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Quimiocinas/biosíntesis , Citocinas/biosíntesis , ADN/biosíntesis , ADN/genética , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulinas/biosíntesis , Inflamación/tratamiento farmacológico , Inflamación/patología , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C3H , Hipersensibilidad Respiratoria/patología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Compared to the significant immunomodulation of cell wall component(s) of bacterium such as lipopolysaccharide (E. Coli), that of pathogenic fungi has not been well elucidated, especially in vivo. Furthermore, although it has been implied that beta-(1, 3)-glucan of fungi possesses various biological activities, the impacts of the component have not been properly clarified, possibly due to its insolubility in water and alkali solutions. Previously, we isolated a soluble type of beta-(1, 3) -glucan from Aspergillus (referred to as ASBG). The present study investigated the effects of a single pulmonary exposure to ASBG on the immune (proinflammatory) responses in naïve mice. ASBG (12.5-100micorg/animal) exposure Induced neutrophilic lung inflammation with an enhanced local expression of proinflammatory cytokines such as interleukin (IL)-1beta and chemokines such as macrophage inflammatory protein -1a, and keratinocyte-derived chemoattractant in a dose-dependent fashion with overall trends. On the other hand, ASBG at relatively lower doses significantly amplified the lung expression of IL-2, IL-6, and IL-12 as compared with vehicle. ASBG significantly induced pulmonary edema. Furthermore, ASBG augmented the nuclear translocation of nuclear factor (NF)-kB and its binding capacity to the promoter site of DNA in the lung homogenate. These results suggest that pulmonary exposure to ASBG confers lung inflammation, at least partly, via the enhanced local expression of proinflammatory cytokines, likely through NF-kB-dependent pathway.
Asunto(s)
Aspergillus niger/química , Pared Celular/química , Pulmón/efectos de los fármacos , Neumonía/inducido químicamente , beta-Glucanos/toxicidad , Transporte Activo de Núcleo Celular , Animales , Sitios de Unión , Líquido del Lavado Bronquioalveolar/inmunología , Permeabilidad Capilar/efectos de los fármacos , Quimiocinas/metabolismo , Citocinas/metabolismo , ADN/metabolismo , Relación Dosis-Respuesta a Droga , Mediadores de Inflamación/metabolismo , Pulmón/irrigación sanguínea , Pulmón/inmunología , Masculino , Ratones , Ratones Endogámicos ICR , FN-kappa B/metabolismo , Infiltración Neutrófila/efectos de los fármacos , Neumonía/inmunología , Edema Pulmonar/inducido químicamente , beta-Glucanos/administración & dosificación , beta-Glucanos/aislamiento & purificaciónRESUMEN
Particulate matters can enhance antigen-related airway inflammation and immunoglobulin production. The present study was designed to determine the effects of different sizes of nanoparticles on the antigen-presenting cells (APC) in the lung. ICR mice were exposed to vehicle, carbon black (CB) nanoparticles (14 nm or 56 nm), ovalbumin (OVA), or OVA + nanoparticles intratracheally. The expression of major histocompatibility complex (MHC) class II, costimulatory molecules (CD80, CD86, CD11c), and DEC205 (dendritic cell marker), F4/80 (macrophage marker), and CD19 (B-cell marker) in the lung cells was measured by flow cytometry. 14 nm nanoparticles, but not 56 nm nanoparticles, increased the number of the total lung cells. Combination of OVA and 14 nm or 56 nm nanoparticles increased the total lung cells. The expression of MHC class II and/or costimulatory molecules and the number of APC in the lung were increased by 14 nm nanoparticles in the presence or absence of OVA. The increases were more prominent with combination of OVA and 14 nm nanoparticles. 56 nm nanoparticles did not show any significant effects. 14 nm CB nanoparticles can increase the expression of MHC class II and costimulatory molecules and the number of APC in the lung, especially in the presence of antigen, which can result in subsequent antigen-related airway inflammation and immunoglobulin production.
Asunto(s)
Células Presentadoras de Antígenos/inmunología , Pulmón/inmunología , Nanopartículas/toxicidad , Hollín/toxicidad , Animales , Linfocitos B/inmunología , Antígeno B7-1/análisis , Células Dendríticas/inmunología , Citometría de Flujo , Antígenos de Histocompatibilidad Clase II/análisis , Pulmón/patología , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos ICR , Ovalbúmina/inmunología , Estrés OxidativoRESUMEN
Effects of nano-sized materials (nanomaterials) on subjects with predisposing inflammatory disorders have not been well elucidated. This study examined the effects of pulmonary exposure to TiO2 nanomaterials on lung inflammation induced by lipopolysaccharide (LPS) and consequent systemic inflammation with coagulatory disturbance in mice, in particular regarding their size-dependency. Also, gene expression pattern in the lung was compared among the experimental groups using cDNA microarray analysis. ICR male mice were divided into 8 experimental groups that intratracheally received vehicle, three sizes (15, 50, 100 nm) of TiO2 nanomaterials (8 mg/kg), LPS (2.5 mg/kg), or LPS plus nanomaterials. Twenty four h after the treatment, these nanomaterials exacerbated the lung inflammation and vascular permeability elicited by LPS, with an overall trend of amplified lung expressions of cytokines such as interleukin (IL)-1beta, macrophage chemoattractant protein (MCP)-1, and keratinocyte chemoattractant (KC). LPS plus nanomaterials, especially of a size less than 50 nm, elevated circulatory levels of fibrinogen, IL-1beta, MCP-1, and KC, and von Willebrand factor as compared with LPS alone. The enhancement tended overall to be greater with the smaller nanomaterials than with the larger ones. cDNA microarray analyses revealed that there was no difference in gene expression pattern between the LPS group and the LPS + nanomaterial. These results suggest that nanomaterials exacerbate lung inflammation related to LPS with systemic inflammation and coagulatory disturbance, and that the exacerbation is more prominent with smaller nanomaterials than with larger ones.
Asunto(s)
Trastornos de la Coagulación Sanguínea/inducido químicamente , Nanoestructuras/toxicidad , Neumonía/inducido químicamente , Titanio/toxicidad , Animales , Permeabilidad Capilar/efectos de los fármacos , Quimiocinas/biosíntesis , Citocinas/biosíntesis , Perfilación de la Expresión Génica , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos ICR , Estrés OxidativoRESUMEN
We have previously demonstrated the protective role of interleukin (IL)-6 against septic lung injury induced by lipopolysaccharide (LPS) using IL-6 knock-out (-/-) mice. This protection is mediated, at least partly, through the inhibition of the enhanced local expression of proinflammatory cytokines. In the present study, we addressed whether IL-6 regulates oxidative stress in the lung generated by LPS exposure using IL-6 (-/-) and corresponding wild type (WT) mice. Intraperitoneal LPS (1 mg/kg) challenge induced transcriptional expressions of inducible nitric oxide synthase and heme oxygenase -1 in the lung of mice with both genotypes. In the presence of LPS, these expressions were significantly greater in IL-6 (-/-) than in WT mice. Immunohistochemistry also showed that LPS induced a significant increase in 8-hydroxy-2'-deoxyguanosine formation in the lung as compared to vehicle. Furthermore, the formation was more intense in IL-6 (-/-) than in WT mice in the presence of LPS challenge. In the presence of LPS, lipid peroxidation in the lung was significantly greater in IL-6 (-/-) than in WT mice. These data suggest that the possible mechanisms in which endogenous IL-6 protects against septic lung injury induced by LPS involve, at least in part, its antioxidative properties.
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Antioxidantes/fisiología , Interleucina-6/fisiología , Pulmón/metabolismo , Sepsis/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Daño del ADN , Desoxiguanosina/análogos & derivados , Desoxiguanosina/biosíntesis , Hemo-Oxigenasa 1/genética , Peroxidación de Lípido , Lipopolisacáridos/toxicidad , Masculino , Ratones , Óxido Nítrico Sintasa de Tipo II/genéticaRESUMEN
Epidemiological and experimental studies have suggested that diesel exhaust particles (DEPs), which generate reactive oxygen species, may be involved in the recent increase in the prevalence of lung diseases. Cacao liquor proanthocyanidins (CPs) are naturally occurring polyphenols with antioxidative activities. We carried out a study in mice to investigate the effects of dietary supplementation of CPs on lung injury induced by intratracheal administration of DEPs (500 microg/body). Dietary supplementation with 1.0 percent CPs inhibited DEP-induced lung injury, characterized by neutrophil sequestration and edema. Immunohistochemical analyses showed that CPs prevented enhanced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 caused by DEPs in the lung injury. Numerous adducts of nitrotyrosine, N-(hexanonyl) lysine, 4-hydroxy-2-nonenal, and 8-OHdG were also observed immunohistochemically in the lungs of mice treated with DEPs. However, these indicators of oxidative stress were barely visible in mice pretreated with CP supplementation. In addition, the level of thiobarbituric acid reactive substances in the lung was decreased by CP supplementation in the presence of DEPs. These results suggest that CPs inhibit DEP-induced lung injury by reducing oxidative stress, in association with a reduction in the expression of adhesion molecules.
Asunto(s)
Cacao/química , Enfermedades Pulmonares/prevención & control , Proantocianidinas/farmacología , Emisiones de Vehículos/toxicidad , Animales , Líquido del Lavado Bronquioalveolar/citología , Catequina/química , Catequina/farmacología , Moléculas de Adhesión Celular , Quimiocinas/biosíntesis , Citocinas/biosíntesis , Inmunohistoquímica , Indicadores y Reactivos , Intubación Intratraqueal , Peroxidación de Lípido/efectos de los fármacos , Enfermedades Pulmonares/inducido químicamente , Masculino , Ratones , Ratones Endogámicos ICR , Estrés Oxidativo/efectos de los fármacos , Proantocianidinas/química , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Asian sand dust (ASD) containing microbiological materials, sulfate (SO(4)(2)), and nitrate (NO(3)(-) ) derived from air pollutants in East China, reportedly cause adverse respiratory health effects. ASD aggravates ovalbumin (OVA)-associated experimental lung eosinophilia. In this study, the toxic materials adsorbed onto ASD were excluded by heat treatment at 360 degrees C for 30 min. The effects of nonheated ASD or heated ASD (H-ASD) toward the allergic lung inflammation were compared in murine lungs. ICR mice were administered intratracheally with normal saline (control), H-ASD, ASD, OVA, OVA + H-ASD, and OVA + ASD, four times at 2-week intervals. ASD only increased neutrophils in bronchoalveolar lavage fluids (BALFs) along with pro-inflammatory mediators, such as keratinocyte chemoattractant (KC). H-ASD and ASD enhanced eosinophil recruitment induced by OVA in the alveoli and in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. The two ASDs synergistically increased interleukin-5 (IL-5), monocyte chemotactic protein-3 (MCP-3), and eotaxin, which were associated with OVA, in BALF. The enhancing effects were much greater in ASD than in H-ASD. The two ASDs induced the adjuvant effects to specific IgE and IgG1 production by OVA. In the in vitro study using RAW264.7 cells, ASD increased the expression of Toll-like receptor 2 (TLR 2) mRNA but not TLR4 mRNA. H-ASD caused no expression of either TLR mRNA. These results suggest that the aggravated lung eosinophilia by ASD may be due to activation of Th2-associated immune response via the activation of TLR2 by microbial components adhered to ASD.
Asunto(s)
Microbiología del Aire/normas , Contaminantes Atmosféricos/toxicidad , Polvo/análisis , Neumonía/etiología , Hipersensibilidad Respiratoria/etiología , Dióxido de Silicio/análisis , Animales , Lavado Broncoalveolar , Líquido del Lavado Bronquioalveolar , Desastres , Modelos Animales de Enfermedad , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos ICR , Tamaño de la Partícula , Neumonía/inmunología , Neumonía/metabolismo , Neumonía/patología , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Respiratoria/metabolismo , Hipersensibilidad Respiratoria/patologíaRESUMEN
Bioactivity of cell wall component(s) of fungi has not been fully elucidated, especially in vivo. We isolated Candida soluble beta-D-glucan (CSBG) from Candida albicans (C. albicans). We investigated the effects of airway exposure to CSBG on the immune systems in the airways in mice. CSBG exposure induced neutrophilic and eosinophilic inflammation in the lung, which was concomitant with the increased local expression of proinflammatory cytokines including tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, macrophage inflammatory protein -1alpha, macrophage chemoattractant protein -1, RANTES (regulated on activation and normal T cells expressed and secreted), and eotaxin. The lung inflammation with enhanced expression of proinflammatory proteins caused by CSBG was directly related to its structure, since structurally degraded products of CSBG by formic acid induced negligible responses in the lung. CSBG enhanced nuclear localization of phosphorylated signal transducer and activator of transcription (STAT)-6 in the lung. These results suggest that airway exposure to CSBG induces lung inflammation, at least partly, via the enhanced expression of proinflammatory cytokines and the activation of STAT-6 pathway, and can be a proper murine model for fungal lung inflammation.
Asunto(s)
Candida albicans/metabolismo , Pared Celular/metabolismo , Pulmón , Neumonía , beta-Glucanos/toxicidad , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Permeabilidad Capilar/efectos de los fármacos , Citocinas/inmunología , Eosinófilos/citología , Eosinófilos/inmunología , Recuento de Leucocitos , Pulmón/irrigación sanguínea , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos ICR , Infiltración Neutrófila/efectos de los fármacos , Infiltración Neutrófila/inmunología , Proteínas Nucleares/metabolismo , Neumonía/inducido químicamente , Neumonía/inmunología , Solubilidad , beta-Glucanos/aislamiento & purificaciónRESUMEN
This study examines the effects of DEP components on circulatory CC and CXC chemokines, potent activators and chemoattractants for macrophage and leukocyte subpopulations, in a murine model of lung inflammation. ICR mice were divided into six experimental groups which received intratracheal inoculation of vehicle, LPS alone (2.5 mg/kg), organic chemicals in DEP (DEP-OC: 4 mg/kg) extracted with dichloromethane, residual carbonaceous nuclei after the extraction (washed DEP: 4 mg/kg), DEP-OC + LPS, or washed DEP + LPS. Intratracheal instillation of each DEP component alone did not significantly change the circulatory level of macrophage inflammatory protein (MIP)-1alpha, MIP-2, and macrophage chemoattractant protein-1 (MCP-1) 24 h after the exposure as compared with vehicle instilled alone. In the LPS group, MCP-1, but not MIP-1alpha or MIP-2, was significantly greater than in the vehicle group. The combined administration of LPS and washed DEP caused a further three to five-fold increase in MIP-1alpha, MIP-2, and MCP-1 proteins in the serum as compared with LPS administered alone. No significant difference between the LPS + DEP-OC group and the LPS group was observed. These results indicate that pulmonary exposure to washed DEP enhances circulatory level of chemokines during lung inflammation. The enhancement may be important in the aggravations of systemic inflammatory responses and ischemic cardiovascular conditions associated with air pollution.
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Quimiocinas/sangre , Neumonía/inducido químicamente , Neumonía/metabolismo , Emisiones de Vehículos/toxicidad , Animales , Quimiocina CCL2/sangre , Quimiocina CCL3 , Quimiocina CCL4 , Quimiocina CXCL2 , Quimiocinas CXC/sangre , Exposición por Inhalación , Lipopolisacáridos/farmacología , Proteínas Inflamatorias de Macrófagos/sangre , Masculino , Ratones , Ratones Endogámicos ICR , Monocinas/sangreRESUMEN
Ambient particulate matter (PM) exacerbates allergic airway diseases. Our previous study showed that diesel exhaust particles, the main constituents in urban PM, enhance airway hyperresponsivness in mice. In addition, health effects of PM with a diameter of less than 100 nm, called nanoparticles, have been reported, and we have also demonstrated that carbon nanoparticles exacerbate antigen-related airway inflammation. The present study investigates the effects of pulmonary exposure to two sizes of carbon nanoparticles on lung physiology and lung expression of Muc5ac in the presence or absence of antigen in mice. Nanoparticles alone or ovalbumin (OVA) alone moderately enhanced cholinergic airway reactivity, as assessed by total respiratory system resistance (R) and Newtonian resistance (Rn). In the nanoparticle + OVA groups, all the parameters for lung responsiveness, such as R, compliance, elastance, Rn, tissue damping, and tissue elastance, were worse than those in the vehicle group, the corresponding nanoparticle groups or the OVA group. The lung mRNA level for Muc5ac was significantly higher in the OVA group than in the vehicle group, and further increased in the nanoparticle + OVA groups than in the OVA or the nanoparticle groups. These data suggest that carbon nanoparticles can enhance lung hyperresponsiveness, especially in the presence of antigen. The effects may be mediated, at least partly, through the enhanced lung expression of Muc5ac.
Asunto(s)
Antígenos/farmacología , Pulmón/fisiología , Nanopartículas/toxicidad , Material Particulado/toxicidad , Animales , Relación Dosis-Respuesta a Droga , Intubación Intratraqueal , Pulmón/inervación , Masculino , Cloruro de Metacolina , Ratones , Ratones Endogámicos ICR , Mucina 5AC , Mucinas/biosíntesis , Mucinas/genética , Agonistas Muscarínicos , Ovalbúmina/inmunología , Ovalbúmina/farmacología , Sistema Nervioso Parasimpático/efectos de los fármacos , Sistema Nervioso Parasimpático/fisiología , Tamaño de la Partícula , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Among 11 JMML children, two had an abnormal karyotype, and nine had a normal karyotype at onset. In one patient with trisomy 8 and four patients with a normal karyotype, a new clone with an aberrant karyotype emerged 1-14 months after 6-mercaptopurine (6-MP) therapy as shown by G-banding analyses. Fluorescence in situ hybridization disclosed that an abnormal clone existed in approximately 3-6% of bone marrow cells at onset or before 6-MP therapy in all the four cases examined, and increased to approximately 12-90% during the treatment. In culture with granulocyte-macrophage colony-stimulating factor, cytogenetically abnormal clones that proliferated during 6-MP therapy possessed significantly less sensitivity to the antimetabolite, compared with cells that decreased in numbers after the therapy. A PTPN11 mutation was detected in all of granulocyte-macrophage colonies irrespective of karyotypic aberration in one patient, whereas approximately 80% of erythroid colonies and 20% of mixed colonies possessed neither a PTPN11 mutation nor chromosomal abnormalities. The appearance of chromosomal aberrations shown by G-banding during 6-MP therapy in some JMML cases may result, in part, from the growth of a 6-MP-refractory clone that already exists at onset. It is possible that treatment with 6-MP promotes progression of the disease.
Asunto(s)
Antineoplásicos/uso terapéutico , Aberraciones Cromosómicas , Leucemia Mielomonocítica Aguda/tratamiento farmacológico , Leucemia Mielomonocítica Aguda/genética , Mercaptopurina/uso terapéutico , Bandeo Cromosómico , Genes ras , Humanos , Hibridación Fluorescente in Situ , Péptidos y Proteínas de Señalización Intracelular/genética , Leucemia Mielomonocítica Aguda/patología , Mutación , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Proteínas Tirosina Fosfatasas/genéticaRESUMEN
In search of efficient thermoelectric nanostructures, many theoretical works predicted that nanopillars, placed on the surface of silicon membranes, nanobeams, or nanowires, can reduce the thermal conductivity of these nanostructures. To verify these predictions, we experimentally investigate heat conduction in suspended silicon nanobeams with periodic arrays of aluminium nanopillars. Our room temperature time-domain thermoreflectance experiments show that the nanobeams with nanopillars have 20% lower thermal conductivity as compared to pristine nanobeams. We discuss possible explanations of these data, including coherent effects, and conclude that the thermal conductivity is reduced mainly by phonon scattering at the pillar/beam interface due to the intermixing of aluminium and silicon atoms, as supported by the transmission electron microscopy. As this intermixing does not only reduce thermal conductivity but may also increase electrical conductivity, these nanostructures are exceptionally promising for thermoelectric applications.
RESUMEN
Difference of 8-hydroxy-deoxyguanosine (8-OH-dG) formation in liver DNA in C3H/HeN and in C57BL/6 mice--fed oxidized lard and dietary oils (soybean and sardine)--was investigated. The blank levels of 8-OH-dG were higher in C3H/HeN mice (highly sensitive to liver tumorigenesis) than in C57BL/6 mice (resistant strain). The level of 8-OH-dG increased much more in C3H/HeN mice than in the C57BL/6 mice fed by oxidized lard and dietary oil treatment. Feeding oxidized lard and dietary oils increased 8-oxo-guanine DNA glycosylase I (OGG1) and mRNA 8-oxo-dGTPase in C57BL/6 mice. On the other hand, no appreciable change of mRNA in the C3H/HeN mice was observed. The formation differences of 8-OH-dG from the two murine strains fed with oxidized lard and dietary oils may be associated with the different mRNA levels in the DNA repair enzymes because the mRNA levels in the DNA repair enzymes were much lower in C3H/HeN mice than in C57BL/6 mice.
Asunto(s)
ADN/metabolismo , Grasas de la Dieta/toxicidad , Guanina/análogos & derivados , Hígado/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina/análogos & derivados , Animales , Peso Corporal/efectos de los fármacos , Daño del ADN , ADN Glicosilasas/biosíntesis , ADN Glicosilasas/genética , ADN Glicosilasas/metabolismo , Enzimas Reparadoras del ADN/biosíntesis , Enzimas Reparadoras del ADN/genética , Enzimas Reparadoras del ADN/metabolismo , Dieta , Grasas de la Dieta/administración & dosificación , Aceites de Pescado/administración & dosificación , Aceites de Pescado/toxicidad , Guanina/biosíntesis , Guanina/metabolismo , Hígado/enzimología , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/etiología , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Monoéster Fosfórico Hidrolasas/biosíntesis , Monoéster Fosfórico Hidrolasas/genética , Monoéster Fosfórico Hidrolasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Aceite de Soja/administración & dosificación , Aceite de Soja/toxicidadRESUMEN
The present study was undertaken to study the effect of varying types of anti-arthritic drugs on Th1 and Th2 immune responses in mice. To immunize mice, ovalbumin (OVA) emulsified with complete Freund's adjuvant was injected s.c. at the base of the tail (day 0). Indomethacin (IND) as a non-steroidal antiinflammatory drug (NSAID), dexamethasone (DEX) as a steroidal antiinflammatory drug, methotrexate (MTX), auranofin (AUR), and D-penicillamine (D-PA) as an anti-rheumatic drugs were orally administrated daily from days 0 to 20. On day 21, anti-OVA IgG2a and interferon (IFN)-gamma as indicators of Th1 responses and anti-OVA IgG1 and interleukin (IL)-10 as those of Th2 responses were measured. Treatments with IND, DEX, MTX and AUR were followed by decreases in OVA-specific IgG and proliferation of spleen cells to the antigen. Treatments with IND, DEX, MTX and AUR inhibited both Th1 and Th2 immune responses, although the inhibitory effects of these drugs on the antigen-specific IgG2a and IFN-gamma production appeared to be greater than those on IgG1 and IL-10 production. D-PA failed to influence anti-OVA IgG, IgG2a and IgG1 production as well as IFN-gamma and IL-10 secretion. Administrations of all the drugs used resulted in suppression of antigen (OVA)-induced arthritis in mice which was associated with inhibition of anti-OVA IgG2a but not IgG1 production. These results suggest that anti-arthritic drugs including IND, DEX, MTX and AUR appear to suppress Th1 and, to a lesser extent, Th2 immune responses, and their anti-inflammatory effects on human rheumatoid arthritis might be at least in part explained by downregulation by these drugs of Th1 responses involved in the disease.
Asunto(s)
Antirreumáticos/farmacología , Células TH1/inmunología , Células Th2/inmunología , Animales , Artritis/inmunología , Artritis/patología , Proliferación Celular/efectos de los fármacos , Citocinas/biosíntesis , Regulación hacia Abajo/efectos de los fármacos , Femenino , Inmunoglobulina G/biosíntesis , Inmunosupresores/farmacología , Interferón gamma/metabolismo , Ratones , Ratones Endogámicos DBA , Ovalbúmina/inmunología , Bazo/citología , Bazo/efectos de los fármacos , Células TH1/efectos de los fármacos , Células Th2/efectos de los fármacosRESUMEN
We investigated the effects of aminoguanidine, a relatively selective inhibitor of inducible nitric oxide (NO) synthase, on the systemic inflammatory response syndrome induced by platelet activating factor (PAF) and by lipopolysaccharide in rats, with emphasis on NO production in vivo. Aminoguanidine treatment improved survival rates after lipopolysaccharide challenge, whereas it aggravated the lethality caused by PAF. Lipopolysaccharide induced a marked increase in the concentrations of nitrate and nitrite in plasma compared with vehicle administration, and the increase was prevented by aminoguanidine. In contrast, PAF challenge with or without aminoguanidine did not affect the concentrations of nitrate and nitrite in plasma compared with vehicle administration. These results suggest that NO derived from inducible NO synthase is not a major participant in the systemic inflammatory response syndrome induced by PAF. Aminoguanidine is not likely to provide beneficial effects in conditions where PAF is produced and the concentrations of nitrate and nitrite in plasma are not significantly increased.
Asunto(s)
Inhibidores Enzimáticos/uso terapéutico , Guanidinas/uso terapéutico , Lipopolisacáridos/toxicidad , Óxido Nítrico Sintasa/biosíntesis , Nitroarginina/uso terapéutico , Factor de Activación Plaquetaria/toxicidad , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Inducción Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/farmacología , Guanidinas/administración & dosificación , Guanidinas/farmacología , Inyecciones Intravenosas , Lipopolisacáridos/administración & dosificación , Masculino , Nitratos/sangre , Nitritos/sangre , Nitroarginina/administración & dosificación , Nitroarginina/farmacología , Factor de Activación Plaquetaria/administración & dosificación , Ratas , Síndrome de Respuesta Inflamatoria Sistémica/inducido químicamente , Síndrome de Respuesta Inflamatoria Sistémica/enzimologíaRESUMEN
To clarify the relationship between the manifestations of allergic airway inflammation modulated by diesel exhaust particles (DEP) and immunoglobulin production in response to an antigen, airway inflammation characterized by the infiltration of eosinophils, goblet cell proliferation, and antigen-specific immunoglobulin (Ig) production was investigated in five strains of mice after immunization with ovalbumin (OA). Mice were injected intratracheally with OA (1 microg) or OA (1 microg) + DEP (50 microg) four times at 3-week intervals. The order of antigen-specific IgG1 production in plasma of mouse strains treated with OA alone was CBA/2N Asunto(s)
Inmunoglobulinas/biosíntesis
, Ovalbúmina/inmunología
, Hipersensibilidad Respiratoria/inmunología
, Inhibidores de Serina Proteinasa/inmunología
, Emisiones de Vehículos/efectos adversos
, Animales
, Antígenos/inmunología
, Bronquios/efectos de los fármacos
, Bronquios/inmunología
, Bronquios/patología
, División Celular/efectos de los fármacos
, División Celular/inmunología
, Eosinófilos/inmunología
, Epitelio/efectos de los fármacos
, Epitelio/inmunología
, Epitelio/patología
, Inmunoglobulina E/análisis
, Inmunoglobulina G/análisis
, Ratones
, Ratones Endogámicos
, Hipersensibilidad Respiratoria/inducido químicamente
, Hipersensibilidad Respiratoria/patología
, Especificidad de la Especie