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PURPOSE: Tryptophan metabolites have immunomodulatory functions, suggesting possible roles in cancer immunity. METHODS: Plasma tryptophan metabolites were measured using liquid chromatography/mass spectrometry before immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). RESULTS: The 19 patients with NSCLC had significantly lower levels of tryptophan (p = 0.002) and xanthurenic acid (p = 0.032), and a significantly higher level of 3-hydroxyanthranilic acid (3-HAA) (p = 0.028) compared with the 10 healthy volunteers. The patients achieving objective responses had significantly lower levels of 3-HAA than those who did not (p = 0.045). Receiver operating characteristic analyses determined that the cutoff value of 3-HAA for objective response was 35.4 pmol/mL (sensitivity: 87.5% and specificity: 83.3%). The patients with 3-HAA < 35.4 pmol/mL had significantly longer median progression-free survival (7.0 months) than those without (1.6 months, p = 0.022). CONCLUSIONS: Tryptophan metabolites may have a potential for predicting the efficacy of ICIs. REGISTRATION NUMBER: University Hospital Medical Information Network Clinical Trial Registry 000026140.
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Ácido 3-Hidroxiantranílico/análisis , Carcinoma de Pulmón de Células no Pequeñas/sangre , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/sangre , Triptófano/sangre , Xanturenatos/sangre , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/sangre , Antígeno B7-H1/metabolismo , Biomarcadores/sangre , Biomarcadores/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Prospectivos , Curva ROC , Análisis de Regresión , Sensibilidad y Especificidad , Resultado del Tratamiento , Triptófano/metabolismoRESUMEN
OBJECTIVES: To identify gaps in procedural approaches to knowledge translation and outline a more relational approach that addresses health inequities based on creating collaborative environments for reasonable action. METHODS: A literature review encompassing approaches to critical inquiry of the institutional conditions in which knowledge is created combined with a process for encouraging reflexive professional practice provide the conceptual foundation for our approach, called equity-focused knowledge translation (EqKT). RESULTS: The EqKT approach creates a matrix through which teams of knowledge stakeholders (researchers, practitioners, and policymakers) can set common ground for taking collaborative action on health inequities. CONCLUSIONS: Our approach can contribute to the call by the WHO Commission on the Social Determinants of Healths for more reasonable action on health inequities by being incorporated into numerous public health settings and processes. Further steps include empirical applications and evaluations of EqKT in real world applications.
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Conducta Cooperativa , Disparidades en el Estado de Salud , Difusión de la Información/métodos , Humanos , Salud Pública , Determinantes Sociales de la Salud , Justicia Social , Investigación Biomédica Traslacional , Organización Mundial de la SaludRESUMEN
Eph receptor tyrosine kinases and their ephrin ligands have been implicated in neuronal development and neovascularization. Overexpression of ephrin-A1 has been implicated in tumor progression and poor prognosis. However, the mechanisms are not clear. Here, we report a role of the Eph/ephrin system in a cell adhesion mechanism. Clustered erythropoietin-producing hepatocellular receptor A1 (EphA1)/ephrin-A1 complexes on the plasma membrane did not undergo endocytosis, and the cell remained adherent to one another. The cell-cell contacts were maintained in an Eph tyrosine kinase activity-independent manner even in the absence of E-cadherin. EphA1 and ephrin-A1 co-localized in pulmonary endothelial cells, and regulated vascular permeability and metastasis in the lungs. We identified ADAM12 (A disintegrin and metalloproteinase 12) as an EphA1-binding partner by yeast two-hybrid screening and found that ADAM12 enhanced ephrin-A1 cleavage in response to transforming growth factor-ß1 in primary tumors. Released soluble ephrin-A1 in the serum deteriorated the EphA1/ephrin-A1-mediated cell adhesion in the lungs in an endocrine manner, causing lung hyperpermeability that facilitated tumor cell entry into the lungs. Depletion of soluble ephrin-A1 by its neutralizing antibody significantly inhibited lung metastasis.
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Proteínas ADAM/fisiología , Carcinoma Pulmonar de Lewis/enzimología , Efrina-A1/metabolismo , Neoplasias Pulmonares/enzimología , Proteína ADAM12 , Animales , Anticuerpos/farmacología , Antineoplásicos/farmacología , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Carcinoma Pulmonar de Lewis/secundario , Adhesión Celular , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Células HEK293 , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Ratones Endogámicos C57BL , Ratones Noqueados , Terapia Molecular Dirigida , Trasplante de Neoplasias , Proteolisis , Receptor EphA2/genética , Receptor EphA2/metabolismo , Factor de Crecimiento Transformador beta1/fisiología , Carga Tumoral/efectos de los fármacosRESUMEN
There is a growing awareness and concern in contemporary societies about potential health impacts of environmental contaminants on children. Mothers are traditionally more involved than other family members in managing family health and household decisions and thus targeted by public health campaigns to minimise risks. However little is known about how new mothers perceive and experience environmental health risks to their children. In 2010, we undertook a parallel case study using qualitative, in-depth interviews with new mothers and focus groups with public health key informants in two Public Health Units in Ontario Province, Canada. We found that the concern about environmental hazards among participants ranged from having no concerns to actively incorporating prevention into daily life. Overall, there was a common perception among participants that many risks, particularly in the indoor environment, were controllable and therefore of little concern. But environmental risks that originate outside the home were viewed as less controllable and more threatening. In response to such threats, mothers invoked coping strategies such as relying on the capacity of children's bodies to adapt. Regardless of the strategies adopted, actions (or inactions) were contingent upon active information seeking. We also found an optimistic bias in which new mothers reported that other children were at greater risk despite similar environmental circumstances. The findings suggest that risk communication experts must attend to the social and environmental contexts of risk and coping when designing strategies around risk reducing behaviours.
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INTRODUCTION: Asthma is a growing concern in First Nations and Inuit communities. As with many health indicators and outcomes, Aboriginal peoples living in remote areas experience greater disparities in respiratory health compared with non-Aboriginal Canadians. Therefore, it is critically important to take into account their unique needs when developing asthma educational materials and resources. The purpose of this study is to assess the cultural relevance of existing asthma education materials for First Nations and Inuit peoples. Five First Nations and Inuit communities from across Canada participated in the project. METHODS: A combination of quantitative evaluations (eg surveys) and qualitative approaches (eg open discussion, live chats) were used to assess printed and web-based asthma education materials. Participants represented First Nations and Inuit communities from across Canada and were selected on the basis of age and role: 6 to 12 years old (children), 12 and over (youth), parents and grandparents, community leaders and teachers, and community advisory group members. RESULTS: In general, the results showed that although participants of all age categories liked the selection of asthma educational materials and resources, they identified pictures and images related to First Nations and Inuit people living and coping with asthma as ways of improving cultural relevance. This reinforces findings that tailoring materials to include Aboriginal languages, ceremonies and traditions would enhance their uptake. Our findings also demonstrate that visually based content in both printed and virtual form were the preferred style of learning of all participants, except young children who preferred to learn through play and interactive activities. CONCLUSIONS: Asthma is a growing concern in First Nations and Inuit communities. Given this concern, it is essential to understand cultural needs and preferences when developing asthma education materials and resources. The findings from this research emphasize the need to adapt existing asthma educational materials to better suit First Nations and Inuit cultures and the importance of directly engaging community members in the process.
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Encuestas Epidemiológicas , Inuk/estadística & datos numéricos , Canadá , Estudios de Cohortes , Características Culturales , Estudios de Factibilidad , Guías como Asunto , Humanos , Estudios Longitudinales , Vigilancia de la Población/métodos , Proyectos de Investigación , Apoyo a la Investigación como Asunto , Sensibilidad y EspecificidadRESUMEN
Phage display technology has been utilized to select target molecules against circulating antibodies. The aims of this study were to isolate a peptide that binds with serum from Crohn's disease (CD) patients and to examine its diagnostic and pathogenic significance. A phage display library was constructed using cDNA from Caco-2 cells. Affinity selection using this cDNA library and serum samples from patients with CD was then performed. Phage clones that specifically reacted with the CD sera were then selected using a phage enzyme-linked immunosorbent assay (ELISA). After the DNA sequences of the selected phages were determined and converted to amino acid sequences, the synthesized peptides were examined using an ELISA. The effect of the synthesized peptides on cytokine release from cultured blood mononuclear cells was investigated. An ELISA analysis for TCP-353 demonstrated that while 61·7% of the samples from CD patients were seroreactive, seroreactivity was less common among patients with ulcerative colitis (7·3%), acute colitis (0%) or colon cancer (11·4%) and among normal subjects (2·8%). The induction of interleukin (IL)-1ß, IL-6 and tumour necrosis factor (TNF)-α release, but not IL-10 release, in response to TCP-353 peptide was enhanced in CD mononuclear cells only. We isolated a novel peptide that specifically binds to CD sera and stimulates the proinflammatory responses of CD mononuclear cells. TCP-353 may have diagnostic, pathogenic and therapeutic significance with regard to the treatment of CD.
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Enfermedad de Crohn/sangre , Interleucina-1beta/biosíntesis , Interleucina-6/biosíntesis , Leucocitos Mononucleares/inmunología , Péptidos , Suero/química , Factor de Necrosis Tumoral alfa/biosíntesis , Adulto , Anticuerpos/sangre , Anticuerpos/inmunología , Células CACO-2 , Estudios de Casos y Controles , Colitis Ulcerosa/sangre , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/inmunología , Colitis Ulcerosa/patología , Neoplasias del Colon/sangre , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/inmunología , Neoplasias del Colon/patología , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/inmunología , Enfermedad de Crohn/patología , ADN Complementario/análisis , Ensayo de Inmunoadsorción Enzimática , Epítopos , Femenino , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Leucocitos Mononucleares/patología , Masculino , Biblioteca de Péptidos , Péptidos/química , Péptidos/inmunología , Péptidos/aislamiento & purificación , Péptidos/farmacología , Curva ROC , Análisis de Secuencia de ADN , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Bone loss is often observed in patients with ulcerative colitis, particularly if they require glucocorticoids. AIM: To determine whether the bisphosphonate, alendronate, is safe and effective in preserving bone mass compared to the active vitamin D3, alfacalcidol, in ulcerative colitis patients receiving glucocorticoids. METHODS: Thirty-nine patients with ulcerative colitis and treated with glucocorticoids were randomized to receive alendronate (5 mg/day) or alfacalcidol (1 microg/day) daily for 12 months. Loss of bone mass was evaluated by bone mineral density, bone resorption by urinary N-telopeptide for type I collagen, and bone formation by serum bone alkaline phosphatase. RESULTS: Alendronate, but not alfacalcidol, significantly increased bone mineral density in the lumbar spine. Alendronate decreased serum bone alkaline phosphatase levels, but alfacalcidol did not. Urinary N-telopeptide for type I collagen levels decreased in both groups, but were significantly lower in the alendronate group. There were no significant differences in the adverse events in the two groups. CONCLUSION: Our study indicates that alendronate is a safe, well-tolerated and more effective therapy than alfacalcidol for preventing glucocorticoid-associated bone loss in patients with ulcerative colitis.
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Alendronato/efectos adversos , Conservadores de la Densidad Ósea/efectos adversos , Colitis Ulcerosa/tratamiento farmacológico , Glucocorticoides/efectos adversos , Hidroxicolecalciferoles/efectos adversos , Osteoporosis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Alendronato/administración & dosificación , Biomarcadores/metabolismo , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/administración & dosificación , Femenino , Humanos , Hidroxicolecalciferoles/administración & dosificación , Masculino , Persona de Mediana Edad , Osteoporosis/inducido químicamente , Proyectos PilotoRESUMEN
OBJECTIVES: To study the involvement of cystatin C in the progression of ischemic white matter lesions (WMLs). MATERIALS AND METHODS: Cystatin C levels in the cerebrospinal fluid (CSF) of patients with cerebrovascular disease, and also in primary and established human neural cell cultures were investigated. For pathologic analysis, cystatin C immunoreactivity was investigated in the white matter of patients with severe WMLs, mild WMLs or controls. RESULTS: Cystatin C levels in the CSF of patients with Fazekas WML grade 3 [14 with hypertension; W/HT(+) and nine without hypertension; W/HT(-)] were lower than those in 38 patients with grade 0-1 (P = 0.0022 and P < 0.0001 respectively). Immunohistochemical study showed that the cystatin C immunoreactivity was found in astrocytes, and the number of astrocytes in the white matter in the severe WML group was decreased when compared with that in controls (P = 0.0027) and in the mild WML group (P = 0.0024). In human neural cell cultures, treatments with thrombin, matrix metalloproteinases and interleukin 1 beta increased the expression of cystatin C mRNA in human astrocytes and hybrid neurons, but an enzyme-linked immunosorbent assay revealed that only thrombin significantly increased the production and secretion of cystatin C in astrocytes. CONCLUSIONS: These results suggest that low levels of CSF cystatin C in ischemic WMLs might be due to the decreased number of astrocytes that secrete cystatin C in response to the stimuli of proteases and inflammatory cytokines.
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Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Cistatinas/metabolismo , Anciano , Anciano de 80 o más Años , Astrocitos/metabolismo , Isquemia Encefálica/etiología , Estudios de Casos y Controles , Técnicas de Cultivo de Célula , Cistatina C , Complicaciones de la Diabetes/complicaciones , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/patología , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/metabolismo , Hipertensión/patología , Masculino , Persona de Mediana Edad , Neuronas/metabolismoRESUMEN
Granulocytapheresis (GCAP) selectively removes large numbers of granulocytes and monocytes from peripheral blood by adsorptive apheresis, and in patients with ulcerative colitis GCAP has been associated with significant efficacy. However, the mechanism(s) of efficacy of this strategy is poorly understood. This rat model of dextran sodium sulfate (DSS)-induced colitis was to investigate the effect of GCAP on tumor necrosis factor (TNF)-alpha release by peripheral leukocytes. By using mini columns, an experimental GCAP setting was developed and applied to the DSS-induced colitis model. The production of TNF-alpha by lipopolysaccharide-activated leukocytes in whole blood was measured by enzyme-linked immunosorbent assay. In rats that received GCAP with columns containing leukocytapheresis carriers, TNF-alpha release by leukocytes was significantly (p < 0.05) suppressed, while no change in TNF-alpha production was seen in rats that received GCAP with sham columns. This first experimental setting in the rat colitis model suggests that GCAP is feasible in animals and should shed light on the mechanism(s) of GCAP in clinical settings. Given that TNF-alpha is a major inflammatory cytokine, down-modulation of TNF-alpha might represent one mechanism of antiinflammatory effects of GCAP.
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Colitis/terapia , Granulocitos/metabolismo , Leucaféresis/métodos , Monocitos/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Adsorción , Animales , Celulosa/análogos & derivados , Celulosa/química , Colitis/sangre , Colitis/inducido químicamente , Sulfato de Dextran , Modelos Animales de Enfermedad , Circulación Extracorporea , Estudios de Factibilidad , Femenino , Recuento de Leucocitos , Ratas , Ratas Sprague-Dawley , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
The c-Jun N-terminal kinase (JNK) participates in intracellular signalling cascades that mediate inflammatory responses. Therefore, the JNK signalling may be involved in gastric injury and inhibition of this pathway may form the basis of a new strategy for the treatment of gastric injury. The aim of this study was to determine whether JNK participates in the formation of gastric lesions in an experimental model. Acute gastric injury was induced in Sprague-Dawley rats by intragastric administration of 100% ethanol. The amount of phospho-JNK in the rat stomach was determined using immunohistochemistry and Western analysis. Animals received subcutaneous injections of a specific JNK inhibitor SP600125 or vehicle and the extent of mucosal damage in the stomach was determined. Western analysis revealed early phosphorylation of JNK and, to a lesser extent, p38 as well as late phosphorylation of the p42/44 extracellular signal-related kinases during the development of gastric lesions. JNK was phosphorylated in epithelial cells and in occasional mononuclear cells present at lesion sites. These cells were rarely found in samples from control specimens. Treatment with SP600125 significantly reduced the extent of gastric lesions. These findings indicate that experimental gastric injury is associated with activation of the JNK signalling pathway, and also suggest that JNK inhibitors may play a role in the treatment of gastric injury in humans.
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Mucosa Gástrica/enzimología , Gastritis/enzimología , Proteínas Quinasas JNK Activadas por Mitógenos/análisis , Transducción de Señal , Animales , Antracenos/uso terapéutico , Western Blotting/métodos , Activación Enzimática , Inhibidores Enzimáticos/uso terapéutico , Etanol , Quinasas MAP Reguladas por Señal Extracelular/análisis , Femenino , Mucosa Gástrica/patología , Gastritis/patología , Gastritis/prevención & control , Inmunohistoquímica/métodos , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Proteínas Quinasas p38 Activadas por Mitógenos/análisisRESUMEN
The presence and the role of soluble gp130, the soluble form of a component of the interleukin (IL)-6 receptor complex, were investigated in inflammatory bowel disease. The serum concentrations of soluble gp130 were increased in ulcerative colitis (active disease, median, 93.5 ng/ml; interquartile range, 26-125 ng/ml; inactive disease, 81 ng/ml, 24.8-137.3 ng/ml) and to a lesser extent in Crohn's disease (active disease, 66 ng/ml, 44.4-87.6 ng/ml; inactive disease, 63 ng/ml, 43.5-82.5 ng/ml) compared to normal controls (43 ng/ml, 27-59 ng/ml). Paired analysis of serum samples showed a decrease of IL-6 and soluble IL-6 receptor concentrations in both diseases and an increase of soluble gp130 concentrations, especially in ulcerative colitis, just after the resolution of disease exacerbation. Size fractionation of the serum revealed that a part of the IL-6 co-eluted with soluble gp130 and soluble IL-6 receptor. The IL-6-induced proliferation of murine B9 hybridoma was enhanced by recombinant soluble IL-6 receptor, whereas the proliferation was inhibited by recombinant soluble gp130. These results indicate that soluble gp130 may function as a natural inhibitor of the IL-6 actions in inflammatory bowel disease.
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Receptor gp130 de Citocinas/sangre , Enfermedades Inflamatorias del Intestino/inmunología , Interleucina-6/sangre , Enfermedad Aguda , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Cromatografía en Gel , Colitis/inmunología , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Hibridomas , Interleucina-6/análisis , Masculino , Persona de Mediana Edad , Receptores de Interleucina-6/sangre , Estadísticas no ParamétricasRESUMEN
We have reported in the past that female rats fed a powdered diet showed better spatial learning and memory functions than female rats a fed pelleted diet. In the present study, we examined the effects of feeding with powdered diet on acetylcholine release in the hippocampus in both sexes of rats. After weaning (3 weeks of age), rats were fed either standard pelleted diet or powdered diet, and after maturation (9-12 weeks of age), they were used in an in vivo microdialysis study, in which no eserine (a cholinesterase inhibitor) was added to the perfusate. The dialysate was collected from the dorsal hippocampus at 20-min intervals under freely moving conditions for more than 24 h. Acetylcholine in the dialysate was measured by high performance liquid chromatography. As we reported previously, the acetylcholine release showed a clear daily rhythm in both sexes, and males showed significantly greater acetylcholine release in the hippocampus than females in rats fed pelleted diet. Conversely, in rats fed powdered diet, no sex difference in the acetylcholine release was observed, since feeding with powdered diet significantly increased the acetylcholine release only in females. To further examine the number of cholinergic neurons in the medial septum and horizontal limb of the diagonal band of Broca, immunocytochemistry for choline acetyltransferase was performed in both sexes of rats fed either standard pelleted diet or powdered diet. However, neither sex nor feeding conditions affect the number of choline acetyltransferase immunoreactive cells in the areas. These results suggest that powdered diet after weaning enhances spontaneous acetylcholine release in the hippocampus in female rats without changes in the number of cholinergic neurons in the areas. It is possible that this effect of feeding contributes to improve the performance in spatial learning and memory functions in female rats fed powdered diet.
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Acetilcolina/metabolismo , Dieta , Hipocampo/metabolismo , Animales , Colina O-Acetiltransferasa/metabolismo , Cromatografía Líquida de Alta Presión , Banda Diagonal de Broca/metabolismo , Femenino , Hipocampo/química , Inmunohistoquímica , Masculino , Microdiálisis , Neuronas/metabolismo , Embarazo , Ratas , Tabique del Cerebro/metabolismo , Caracteres Sexuales , DesteteRESUMEN
Infiltration by circulating inflammatory cells is a prominent local inflammatory feature of ulcerative colitis (UC). Several trials have suggested that leukocytapheresis by filtration can benefit patients with active UC. We investigated how this therapy might modulate the inflammatory response. Patients with active UC who were beginning repeated filtration leukocytapheresis were studied. Mononuclear cell preparations were obtained from blood before and after the first treatment, and expression of cytokine signalling components and the cell-proliferative response were analysed in vitro. Leukocytapheresis reduced lipopolysaccharide-induced production of proinflammatory cytokines (interleukin-1, -6, -8 and tumour necrosis factor-alpha, P < 0.05 for all) and activation of intracellular signalling components (nuclear factor-kappaB, mitogen-activated protein kinases, and signal transducer and activator of transcription-3), as well as surface expression of toll-like receptor-4 (P < 0.05) in mononuclear cells. The therapy also reduced the cell-proliferative response by mononuclear cells stimulated with sonicated bacterial preparations from autologous intestine (P < 0.05). These results indicate that activated mononuclear cells in the peripheral blood of patients with active UC are removed by leukocytapheresis and replaced by cells with a lower activation status. This replacement may partly explain the therapeutic benefit.
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Bacterias/inmunología , Colitis Ulcerosa/terapia , Citocinas/biosíntesis , Leucaféresis , Leucocitos Mononucleares/inmunología , Adulto , Recuento de Células Sanguíneas , Western Blotting , Proliferación Celular , Colitis Ulcerosa/inmunología , Citocinas/genética , Femenino , Expresión Génica , Humanos , Intestinos/microbiología , Lipopolisacáridos/inmunología , Subgrupos Linfocitarios/inmunología , Masculino , Glicoproteínas de Membrana/sangre , ARN Mensajero/genética , Receptores de Superficie Celular/sangre , Transducción de Señal/inmunología , Receptor Toll-Like 4 , Receptores Toll-LikeRESUMEN
To examine the sex difference in the 24-h profile of the acetylcholine (ACh) release in the hippocampus, in addition to the effects of housing conditions on this profile, we performed an in vivo microdialysis study in intact male and cycling female rats that had been living in large (diameter=35 cm) or small (diameter=19 cm) cylindrical cages. Each rat was individually housed in a cage for 4 days. On the day of the experiment, the dialysate was collected from the dorsal hippocampus at 20-min intervals and sequential blood samples were simultaneously obtained at 2-h intervals, under the freely moving condition for more than 24 h. ACh in the dialysates was measured by the high performance liquid chromatography system, while the corticosterone concentration in the serum was measured by radiostereoassay. Although the ACh release showed a clear daily rhythm in both sexes of rats, the amount of ACh released in female rats was significantly lower than that in males. Furthermore, the housing in the small cage significantly attenuated the ACh release during the dark phase in male rats, but not in female rats. Conversely, the serum corticosterone concentration showed a clear daily rhythm and the mean concentration of serum corticosterone in female rats was significantly higher than that in male rats. Housing in the small cage did not affect the corticosterone rhythm in either sex. These results reveal a sex difference in the 24-h profile of the ACh release, which suggests vulnerability of the cholinergic system in male rats depending on its housing conditions.
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Acetilcolina/metabolismo , Hipocampo/metabolismo , Vivienda para Animales , Caracteres Sexuales , Corteza Suprarrenal/metabolismo , Análisis de Varianza , Animales , Ritmo Circadiano/fisiología , Corticosterona/sangre , Femenino , Masculino , Microdiálisis/métodos , Ratas , Ratas WistarRESUMEN
The sensory testing method applied under Japanese law to measure odor concentration has a lower detection limit of 10 in the specified Odor Index. To measure odor below the limit, a condensing procedure using solid sorbents (Tenax-TA, Unicarbon B and Carbosieve SIII) has been developed and used in Japan. This procedure however cannot condense all odorous substances, and is specifically unsuited to hydrogen sulfide, methyl mercaptan, dimethyl sulfide, ammonia, and other typical odorous substances. In the present study, cryogenic trapping was tested to improve recovery rate. As water in sample air causes choking of the trap tube, vacant pre-columns to condense the water were connected to the Tenax-TA-packed column. The columns were chilled with liquid oxygen before passage of 100 L of sample air. The columns were then heated to 200 degrees C under passage of 50 mL/min of nitrogen carrier gas to desorb odors. The desorbed gases were captured in sampling bags made of polyethylene terephthalate film. The total volume of desorbed gases was approximately 1 L. The method showed good recovery rates for hydrogen sulfide, methyl mercaptan, dimethyl sulfide and ammonia, and was useful for determining low-level odor concentrations during measurement of odor in ambient air at various sites in Osaka City.
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Contaminantes Atmosféricos/análisis , Odorantes/análisis , Absorción , Filtración , Japón , Política Pública , Sensibilidad y Especificidad , Eliminación de Residuos LíquidosRESUMEN
In 2000, 2001, and 2002, interlaboratory comparison of olfactometry was carried out in order to collect basic data for the establishment of a quality control procedure and the determination of quality criteria for the triangular odour bag method. In 2000, interlaboratory comparison was conducted by using a measurement method for samples taken at smoke stacks. On the other hand, the measurement method for samples taken at boundary lines was used for interlaboratory comparison in 2001. A total of seven olfactometry laboratories in Japan participated in each test, and mean values, repeatability standard deviations, reproducibility standard deviations, and standard deviations under intermediate conditions of detection threshold of ethyl acetate were calculated from the results. These values can be used in a quality control process of olfactometry. In 2002, interlaboratory comparison was carried out by using a measurement method for samples taken at smoke stacks. A total of 137 olfactometry laboratories in Japan participated in the test, and 69% of them lay within the permissible range of the odour index.
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Contaminantes Atmosféricos/análisis , Odorantes/análisis , Olfato , Humanos , Japón , Laboratorios/normas , Control de Calidad , Reproducibilidad de los ResultadosRESUMEN
In the course of structural studies of diol dehydratase-cobalamin complexes, it was found that the electron density corresponding to the cyano group of the enzyme-bound cyanocobalamin is almost not observable at room temperature and very low even at cryogenic temperatures, suggesting its dissociation from the Co atom upon X-ray irradiation. On the contrary, the adenine moiety of the enzyme-bound adeninylpentylcobalamin was clearly located in the electron density map. When the enzyme-adeninylpentylcobalamin complex was illuminated with visible light, the electron density between the C5' and Co atoms disappeared, and the temperature factors of the atoms comprising the pentamethylene group became much larger than those in the dark. This indicates a Co-C bond cleavage and that the adenine moiety remains held by hydrogen bonds with some residues in the enzyme. Thus, the formation of an adenine-anchored radical upon illumination was demonstrated crystallographically with this complex. These observations clearly indicate that homolysis of the Co-C bond of alkylcobalamin takes place upon illumination with visible light but is not readily cleaved during X-ray irradiation.
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Compuestos Organometálicos/química , Compuestos Organometálicos/efectos de la radiación , Propanodiol Deshidratasa/química , Propanodiol Deshidratasa/efectos de la radiación , Cristalografía por Rayos X , Radicales Libres/química , Radicales Libres/efectos de la radiación , Técnicas In Vitro , Sustancias Macromoleculares , Modelos Moleculares , Fotoquímica , Conformación Proteica , Electricidad EstáticaRESUMEN
Despite rapid progress in methods for analyzing radiation effects, much remains to be learned about the mechanisms and processes of radiation-induced immunological dysfunction. Among 17,899 sera obtained from atomic bomb survivors in Nagasaki, Japan, sera from 484 participants who complied with a reexamination for alkaline phosphatase (ALP) were tested for antimitochondrial antibody (AMA) by indirect immunofluorescence, and autoantibodies against 2-oxo-acid dehydrogenase complex (2-OADC) by immunoblotting to investigate the prevalence of primary biliary cirrhosis (PBC). Of these 484 sera, 28 (5.8%) were seropositive for AMA. The 484 participants were divided into three groups according to distance from the hypocenter: 72 who were exposed within 1999 m (closest group), 368 from 2000 to 5999 m (intermediate distant group), and 44 outside 6000 m (distant group). The positivity rates for AMA in these three groups were 6/72 (8.3%), 22/368 (6.0%), and 0/44 (0%), respectively (P =.08). Furthermore, high titers ( > 1:320) of AMA were observed in 3/6 (50%) AMA-positive sera from the closest group, in contrast to 4/22 (18%) from the intermediate distant group, although there was no significant correlation between AMA titer and distance from the hypocenter (P =.07). Of these 28 AMA-positive sera, 11 (39%) were from participants who had already been diagnosed with PBC, and 25 (89%) contained antibodies against at least one component of 2-OADC enzymes by immunoblotting. Therefore, the prevalence of PBC was estimated to be at least 615 cases per million (792 per million women). Our results suggest that the prevalence of PBC in atomic bomb survivors in Nagasaki is higher than that reported for the general population in Japan, and a further survey of the environmental factors, including radiation exposure, that predispose to PBC would be needed for understanding this disease of unknown etiology.
Asunto(s)
Cirrosis Hepática Biliar/epidemiología , Guerra Nuclear , Sobrevivientes , Anciano , Anciano de 80 o más Años , Fosfatasa Alcalina/sangre , Relación Dosis-Respuesta en la Radiación , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Japón/epidemiología , Cirrosis Hepática Biliar/etiología , Masculino , PrevalenciaRESUMEN
The present study evaluated a new technique that has the potential to improve the border detection of in-stent neointima using an echogenic contrast agent during intravascular ultrasound (IVUS). To confirm the reproducibility of IVUS imaging for measuring the cross-sectional in-stent neointima area, inter- and intra-observer variability and correlation were determined. Conventional IVUS (plain IVUS) and IVUS using a contrast agent (contrast IVUS) were performed in 24 subjects 6.5+/-1.5 months after undergoing a Palmaz-Schatz coronary stent implant. Conventional IVUS delineated completely the in-stent neointima in 6 subjects (25%). In the remaining 18 subjects (75%), delineation of the neointima was incomplete despite the use of various combinations of imaging conditions (eg, transmission, compress, post-process). With contrast IVUS, the boundary of the neointima, and therefore the neointima area, was clearly distinguishable, and this resulted in complete delineation of the neointima in all 24 subjects. With a contrast agent, inter- and intra-observer variability significantly decreased (0.94+/-0.69mm2 conventional IVUS vs 0.37+/-0.40mm2 contrast IVUS, p<0.001; 0.69+/-0.56mm2 conventional IVUS vs 0.07+/-0.10mm2 contrast IVUS, p<0.0001; respectively). Thus, contrast IVUS provides a reproducible method for the quantitative analysis of in-stent neointima with excellent inter- and intra-observer correlation.
Asunto(s)
Enfermedad Coronaria/terapia , Stents , Túnica Íntima/diagnóstico por imagen , Ultrasonografía Intervencional/normas , Anciano , Medios de Contraste/farmacología , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Implantación de Prótesis , Reproducibilidad de los Resultados , Túnica Íntima/patologíaRESUMEN
Adsorption using activated carbon is one of the most reliable techniques for preventing odor by substances such as H2S. Concurrent substances in effluent gas often reduce the removal capacity of activated carbon for H2S. As a means of restoring capacity under such conditions, ozone injection into an activated carbon column was examined. When activated carbon was saturated with substances such as toluene, ethanol, n-butanol, or iso-butanol, its capacity to remove H2S decreased in proportion to the amount of the saturating substance. Under such conditions, ozone injection greatly increased capacity. Toluene, which is not easily decomposed by ozone, was displaced by ozone and by oxidized products of H2S. Ethanol, which is adsorbed in small amounts by activated carbon and easily decomposed by ozone, was removed by ozone injection. Butanols, which are also decomposed by ozone and adsorbed in large quantities by activated carbon, showed intermediate behavior between that of toluene and ethanol.