Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
1.
Ocul Immunol Inflamm ; : 1-6, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38749068

RESUMEN

PURPOSE: This study aims to understand the practice patterns among ophthalmologists in North America who manage patients with acute, non-infectious anterior uveitis. METHODS: An eight-question survey was designed to elucidate the practice patterns of ophthalmologists across various geographic locations and practice settings regarding the management of anterior uveitis. This survey was distributed via the American Uveitis Society and Young Uveitis Specialists email listserv to ophthalmologists who self-identify as uveitis specialists and have a patient population that is at least 30% uveitis. RESULTS: A total of 102 responses were received and analyzed (37% response rate). Respondents practiced predominantly in North America, and 40% had received subspecialty training in uveitis. All respondents chose topical corticosteroid therapy as first-line treatment for acute, unilateral, or bilateral non-infectious idiopathic anterior uveitis. The most common initial frequency for prednisolone acetate administration was six times/day while the patient was awake (29.7%) and patients are typically seen in follow-up within a week (75% of respondents). If there is a lack of treatment response within 2-3 weeks with the initial topical treatment, 42 respondents (41.2%) chose to switch to difluprednate eye drops and 29 (28.4%) recommended switching to oral prednisone. CONCLUSION: Our results show that topical corticosteroid, most frequently prednisolone acetate 1%, is the treatment of choice for patients with acute noninfectious anterior uveitis. Reported initial medication dosing and follow-up care approaches are highly variable, which suggests heterogeneity in practice patterns. Further research on the optimal initial dosing is needed.

2.
J Law Biosci ; 10(1): lsad008, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37064046

RESUMEN

Innovative health technologies are not well regulated under current pathways, leading regulators to adopt contextual, life-cycle regulatory models, which authorize drugs based on earlier clinical evidence subject to the conduct of post-market trials that confirm clinical benefit and safety. In this paper, we evaluate all drugs authorized in Canada under the Notice of Compliance with conditions (NOC/c) policy from 1998 to 2021 to analyze its function, identify challenges and areas for improvement, and make recommendations to inform Health Canada's regulatory reforms. We analyzed a sample of 148 drugs authorized between 1998 and 2021, including characteristics about the pre- and post-market clinical trials, finding that most NOC/c authorizations are based on one, single-arm clinical trial using a surrogate endpoint. Post-market trials are more likely to be randomized, Phase III trials but mostly use surrogate endpoints. Based on our findings, we recommend increasing decision-making transparency throughout the regulatory process, developing comprehensive eligibility criteria for selecting appropriate health technologies, modernizing pre-market evidence requirements, adopting a more active role in designing post-market trials, and utilizing automatic expiry, stronger penalties, and ongoing disclosure of the status of post-market trials to promote compliance.

3.
ACG Case Rep J ; 8(1): e00528, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33490299

RESUMEN

Propofol is a widely used sedative for gastrointestinal endoscopic procedures. Drug-induced pancreatitis is a relatively rare disease possibly because of poor recognition. Propofol-induced pancreatitis is an extremely rare phenomenon. We present a 22-year-old healthy man who underwent esophagogastroduodenoscopy with propofol as a sedative. Soon after, he developed acute upper gastrointestinal symptoms and was diagnosed with pancreatitis. His prolonged hospital course was complicated with necrotizing pancreatitis, acute respiratory distress syndrome, septic shock, and other end-organ damages. We hope to increase awareness of a life-threatening adverse event of a commonly used anesthetic such as propofol.

4.
Curr Protoc Immunol ; 125(1): e71, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30615272

RESUMEN

Genome-wide association studies have found that polymorphisms in genes for IL-23 and its receptor are important in psoriasis, and blocking IL-23 is an effective therapy in the disease. The use of Aldara™ , a cream that contains the TLR7 and TLR8 agonist imiquimod (IMQ), was found to exacerbate psoriasis in some patients with pre-existing disease. Intradermal injections of IL-23 and topical application of Aldara/IMQ induce skin inflammation in mice with features similar to psoriasis-including epidermal hyperplasia and accumulation of inflammatory cells in epidermis and dermis-which is mediated by IL-17A, IL-22, and other factors implicated in the human disease. Consequently, these models can be used in preclinical studies to investigate the molecular and cellular pathogenesis of psoriasis, as well as in the evaluation of potential therapies. This article provides detailed methodologies for creating and evaluating the IL-23- and Aldara/IMQ-induced mouse models of psoriasis. The article also provides a protocol for analyzing skin leukocytes by flow cytometry. © 2019 by John Wiley & Sons, Inc.


Asunto(s)
Adyuvantes Inmunológicos , Modelos Animales de Enfermedad , Imiquimod , Interleucina-23 , Psoriasis/inducido químicamente , Administración Tópica , Animales , Citocinas/inmunología , Citometría de Flujo , Inyecciones Intradérmicas , Ratones , Psoriasis/inmunología , Piel/efectos de los fármacos , Piel/inmunología , Piel/patología
5.
Nat Commun ; 7: 13581, 2016 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-27982014

RESUMEN

Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1ß-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6Chi blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod. Moreover, we find that IL-23-induced inflammation requires expression of CCR6 by DCs or their precursors, and that CCR6 mediates monocyte trafficking into inflamed skin. Collectively, our results imply that monocyte-derived cells are critical contributors to psoriasis through production of inflammatory cytokines that augment the activation of skin T cells.


Asunto(s)
Células Dendríticas/fisiología , Inflamación/inducido químicamente , Células de Langerhans/fisiología , Monocitos/fisiología , Psoriasis/patología , Piel/citología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Aminoquinolinas/administración & dosificación , Aminoquinolinas/farmacología , Animales , Erupciones por Medicamentos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Imiquimod , Interleucina-23/administración & dosificación , Interleucina-23/farmacología , Células de Langerhans/clasificación , Complejo Mayor de Histocompatibilidad , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Noqueados
6.
Biomark Insights ; 10: 55-61, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26309391

RESUMEN

Molecular analysis of sputum can help diagnose lung cancer. We have demonstrated that Lung Flute can be used to collect sputum from individuals who cannot spontaneously expectorate sputum. The objective of this study is to further evaluate the performance of the Lung Flute by comparing the characteristics of parallel samples collected with and without the Lung Flute and the usefulness for diagnosis of lung cancer. Fifty-six early-stage lung cancer patients (40 current smokers and 16 former smokers) and 73 cancer-free individuals (52 current smokers and 21 former smokers) were instructed to spontaneously cough and use Lung Flute for sputum sampling. Sputum cytology and polymerase chain reaction analysis of three miRNAs (miRs-21, 31, and 210) were performed in the specimens. All 92 current smokers and 11 (28.7%) of 37 former smokers spontaneously expectorated sputum and also produced sputum when using the Lung Flute. Twenty-seven former smokers (70.3%) who could not spontaneously expectorate sputum, however, were able to produce sputum when using the Lung Flute. The specimens were of low respiratory origin without contamination from other sources, eg, saliva. There was no difference of sputum volume and cell populations, diagnostic efficiency of cytology, and analysis of the miRNAs in the specimens collected by the two approaches. Analysis of the sputum miRNAs produced 83.93% sensitivity and 87.67% specificity for identifying lung cancer. Therefore, sputum collected by the Lung Flute has comparable features as spontaneously expectorated sputum. Using the Lung Flute enables former smokers who cannot spontaneously expectorate to provide adequate sputum to improve sputum collection for lung cancer diagnosis.

7.
Clin Cancer Res ; 21(2): 484-9, 2015 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-25593345

RESUMEN

PURPOSE: The early detection of lung cancer in heavy smokers by low-dose CT (LDCT) can reduce the mortality. However, LDCT screening increases the number of indeterminate solitary pulmonary nodules (SPN) in asymptomatic individuals, leading to overdiagnosis. Making a definitive preoperative diagnosis of malignant SPNs has been a clinical challenge. We have demonstrated that sputum miRNAs could provide potential biomarkers for lung cancer. Here, we aimed to develop sputum miRNA biomarkers for diagnosis of malignant SPNs. EXPERIMENTAL DESIGN: Using quantitative RT-PCR, we evaluated expressions of 13 sputum miRNAs, previously identified sputum miRNA signatures of lung cancer, in a training set of 122 patients with either malignant (n = 60) or benign SPNs (n = 62) to define a panel of biomarkers. We then validated the biomarker panel in an internal testing set of 136 patients with either malignant (n = 67) or benign SPNs (n = 69), and an external testing cohort of 155 patients with either malignant (n = 76) or benign SPNs (n = 79). RESULTS: In the training set, a panel of three miRNA biomarkers (miRs21, 31, and 210) was developed, producing 82.93% sensitivity and 87.84% specificity for identifying malignant SPNs. The sensitivity and specificity of the biomarkers in the two independent testing cohorts were 82.09% and 88.41%, 80.52% and 86.08%, respectively, confirming the diagnostic value. CONCLUSIONS: Sputum miRNA biomarkers may improve LDCT screening for lung cancer in heavy smokers by preoperatively diagnosing malignant SPNs. Nevertheless, a prospective study in a large population to validate the biomarkers is needed.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/diagnóstico , MicroARNs/metabolismo , Nódulo Pulmonar Solitario/diagnóstico , Esputo/metabolismo , Anciano , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , MicroARNs/genética , Persona de Mediana Edad , Curva ROC , Nódulo Pulmonar Solitario/metabolismo
8.
BMC Cancer ; 11: 374, 2011 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-21864403

RESUMEN

BACKGROUND: Making a definitive preoperative diagnosis of solitary pulmonary nodules (SPNs) found by CT has been a clinical challenge. We previously demonstrated that microRNAs (miRNAs) could be used as biomarkers for lung cancer diagnosis. Here we investigate whether plasma microRNAs are useful in identifying lung cancer among individuals with CT-detected SPNs. METHODS: By using quantitative reverse transcriptase PCR analysis, we first determine plasma expressions of five miRNAs in a training set of 32 patients with malignant SPNs, 33 subjects with benign SPNs, and 29 healthy smokers to define a panel of miRNAs that has high diagnostic efficiency for lung cancer. We then validate the miRNA panel in a testing set of 76 patients with malignant SPNs and 80 patients with benign SPNs. RESULTS: In the training set, miR-21 and miR-210 display higher plasma expression levels, whereas miR-486-5p has lower expression level in patients with malignant SPNs, as compared to subjects with benign SPNs and healthy controls (all P ≤ 0.001). A logistic regression model with the best prediction was built on the basis of miR-21, miR-210, and miR-486-5p. The three miRNAs used in combination produced the area under receiver operating characteristic curve at 0.86 in distinguishing lung tumors from benign SPNs with 75.00% sensitivity and 84.95% specificity. Validation of the miRNA panel in the testing set confirms their diagnostic value that yields significant improvement over any single one. CONCLUSIONS: The plasma miRNAs provide potential circulating biomarkers for noninvasively diagnosing lung cancer among individuals with SPNs, and could be further evaluated in clinical trials.


Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , MicroARNs/sangre , Nódulo Pulmonar Solitario/diagnóstico , Nódulo Pulmonar Solitario/genética , Anciano , Área Bajo la Curva , Femenino , Humanos , Modelos Logísticos , Neoplasias Pulmonares/sangre , Masculino , MicroARNs/biosíntesis , Persona de Mediana Edad , Curva ROC , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Fumar/sangre , Fumar/genética , Nódulo Pulmonar Solitario/sangre , Estadísticas no Paramétricas
9.
Foodborne Pathog Dis ; 8(10): 1103-9, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21668373

RESUMEN

Pulsed electric field (PEF) treatments, a nonthermal process, have been reported to injure and inactivate bacteria in liquid foods. However, the effect of this treatment on bacterial cell surface charge and hydrophobicity has not been investigated. Apple juice (pH 3.8) purchased from a wholesale distributor was inoculated with cocktail of Escherichia coli O157:H7 at 7.4 log CFU/mL, processed with a PEF at a field strength of 18.4 kV/cm and 32.2 kV/cm at 25°C, 35°C, and 45°C with a treatment time of 160 µs and a flow rate of 120 mL/min. Bacterial cell surface charge and hydrophobicity of untreated and PEF-treated E. coli O157:H7 were determined immediately and after storage at 5°C and 23°C using hydrophobic and electrostatic interaction chromatography. Similarly, the populations surviving the PEF treatments including injured cells were determined by plating 0.1 mL of the sample on sorbitol MacConkey agar and tryptic soy agar (TSA) plates. The surviving populations of E. coli cells after PEF treatment varied depending on field strength and treatment temperature used. Percent injury in the surviving populations was high immediately after PEF treatment and varied among treatment temperatures. Cell surface charge of E. coli bacteria before PEF treatment averaged 32.10±8.12. PEF treatments at 25°C, 35°C, and 45°C reduced the above surface charge to 26.34±1.24, 14.24±3.30, and 6.72±2.82, respectively. Similarly, the surface hydrophobicity of untreated E. coli cells at 0.194±0.034 was increased to an average of 0.268±0.022, 0.320±0.124, and 0.586±0.123 after PEF treatments at 25°C, 35°C, and 45°C, respectively. The results of this study indicate that PEF treatment affects the outer cell envelope of E. coli bacteria as evidenced by the changes in surface hydrophobicity and cell surface charge leading to injury and subsequent inactivation of the cells.


Asunto(s)
Bebidas/microbiología , Cromatografía Liquida/métodos , Electricidad , Escherichia coli/fisiología , Malus/microbiología , Membrana Celular/fisiología , Recuento de Colonia Microbiana , Escherichia coli/crecimiento & desarrollo , Escherichia coli O157/crecimiento & desarrollo , Escherichia coli O157/fisiología , Manipulación de Alimentos , Microbiología de Alimentos , Conservación de Alimentos , Humanos , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Viabilidad Microbiana , Electricidad Estática , Temperatura , Factores de Tiempo
10.
Lab Invest ; 91(4): 579-87, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21116241

RESUMEN

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death. Developing minimally invasive techniques that can diagnose NSCLC, particularly at an early stage, may improve its outcome. Using microarray platforms, we previously identified 12 microRNAs (miRNAs) the aberrant expressions of which in primary lung tumors are associated with early-stage NSCLC. Here, we extend our previous research by investigating whether the miRNAs could be used as potential plasma biomarkers for NSCLC. We initially validated expressions of the miRNAs in paired lung tumor tissues and plasma specimens from 28 stage I NSCLC patients by real-time quantitative reverse transcription PCR, and then evaluated diagnostic value of the plasma miRNAs in a cohort of 58 NSCLC patients and 29 healthy individuals. The altered miRNA expressions were reproducibly confirmed in the tumor tissues. The miRNAs were stably present and reliably measurable in plasma. Of the 12 miRNAs, five displayed significant concordance of the expression levels in plasma and the corresponding tumor tissues (all r>0.850, all P<0.05). A logistic regression model with the best prediction was defined on the basis of the four genes (miRNA-21, -126, -210, and 486-5p), yielding 86.22% sensitivity and 96.55% specificity in distinguishing NSCLC patients from the healthy controls. Furthermore, the panel of miRNAs produced 73.33% sensitivity and 96.55% specificity in identifying stage I NSCLC patients. In addition, the genes have higher sensitivity (91.67%) in diagnosis of lung adenocarcinomas compared with squamous cell carcinomas (82.35%) (P<0.05). Altered expressions of the miRNAs in plasma would provide potential blood-based biomarkers for NSCLC.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , MicroARNs/sangre , Adenocarcinoma/diagnóstico , Adenocarcinoma del Pulmón , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/diagnóstico , Femenino , Humanos , Modelos Logísticos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad
11.
Cancer Prev Res (Phila) ; 3(12): 1571-8, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20864512

RESUMEN

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death. Early detection of NSCLC will improve its outcome. We previously identified genetic signatures whose genomic copy number aberrations were associated with early stage NSCLC. Here, we aimed to develop a panel of genes that could be detected in sputum for NSCLC early detection. We first optimized a panel of genes by using an in situ minichip for measuring changes of the signatures in sputum of a case-control cohort of 49 NSCLC patients, 49 patients with chronic obstructive pulmonary disease (COPD), and 49 healthy smokers. We then validated the genes in an independent cohort of 69 NSCLC patients and 65 noncancer subjects. The results were compared with those of sputum cytology. Fifteen genes showed significant differences of their copy number changes in sputum between NSCLC and both COPD and healthy subjects. A logistic regression model with the best prediction was built on the basis of 6 genes, ENO1, FHIT, HYAL2, SKP2, p16, and 14-3-3zeta. The composite of the 6 genes produced 86.7% sensitivity and 93.9% specificity in distinguishing stage I NSCLC patients from the noncancer individuals. Furthermore, the genes had higher sensitivity (86.9%) in identification of squamous cell carcinoma (SCC) than in adenocarcinoma of the lungs (80.8%; P < 0.05). Validation of the genes in the independent cohort confirmed their diagnostic power that also showed higher accuracy for lung SCCs than for sputum cytology. The gene panel could provide sputum-based markers that have the potential to improve early detection of lung SCCs.


Asunto(s)
Adenocarcinoma/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Marcadores Genéticos/genética , Neoplasias Pulmonares/diagnóstico , Esputo/metabolismo , Adenocarcinoma/genética , Anciano , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/genética , Estudios de Casos y Controles , Estudios de Cohortes , Diagnóstico Precoz , Femenino , Humanos , Hibridación Fluorescente in Situ , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Curva ROC , Sensibilidad y Especificidad
12.
J Food Prot ; 73(5): 812-8, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20501030

RESUMEN

Antimicrobial films of polylactic acid polymer incorporated with nisin, EDTA, sodium benzoate (SB), potassium sorbate (PS), and their combinations were developed, and their antimicrobial effects on the inactivation of Escherichia coli O157:H7 and natural background microflora (total aerobic bacteria, molds, and yeasts) in strawberry puree at 10 and 22 degrees C were determined. Direct addition of SB+PS to strawberry puree was also used as a comparison with SB+PS film treatment. The combination treatment reduced the cell populations of E. coli O157:H7 from 3.5 log CFU/ml to undetectable levels (<1 CFU/ml) after 14 days and 1 day at 10 and 22 degrees C, respectively, while the cells of E. coli O157:H7 in control samples survived up to 48 days at 10 degrees C and more than 14 days at 22 degrees C. The SB+PS film treatment produced a greater reduction of population of E. coli O157:H7 cells than did the SB+PS direct addition treatment. Similar results were observed for inactivation of natural microflora. In general, the antimicrobial effect was in the following order: film combination > SB+PS film > SB+PS direct addition > EDTA film > nisin film. The data obtained in this study suggest two approaches toward the development of control interventions against E. coli O157:H7 and extension of the microbiological shelf life of strawberry puree: (i) using antimicrobial packaging and (ii) using combinations of preservatives. The film formulas developed here can be used to make bottles or as coatings on the surface of bottles for use in liquid food packaging.


Asunto(s)
Antibacterianos/farmacología , Biopolímeros/farmacología , Escherichia coli O157/efectos de los fármacos , Conservación de Alimentos/métodos , Conservantes de Alimentos/farmacología , Fragaria/microbiología , Biopelículas , Recuento de Colonia Microbiana , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Sinergismo Farmacológico , Escherichia coli O157/crecimiento & desarrollo , Microbiología de Alimentos , Embalaje de Alimentos/métodos , Humanos , Nisina/farmacología , Temperatura , Factores de Tiempo
13.
Int J Food Microbiol ; 139(1-2): 1-8, 2010 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-20223544

RESUMEN

Pulsed electric field (PEF) technology has been used for the inactivation of microorganisms and to prevent flavor loss in liquid foods and beverages in place of thermal pasteurization. When used to pasteurize orange juice, PEF may prevent loss of volatile sensory attributes. Enterohemorrhagic E. coli O157:H7 (EHEC), two strains of Salmonella Typhimurium, and twenty strains of non-pathogenic bacteria were screened for inactivation in orange juice by PEF at 22 and 20kV/cm at 45 and 55 degrees C, respectively. Higher populations of both salmonellae were inactivated (2.81 and 3.54 log CFU/ml) at 55 degrees C, in comparison with the reduction of EHEC (2.22 log). When tested under the same conditions, inactivation of EHEC was slightly greater than that of a non-pathogenic E. coli (NPEC) ATCC 35218 (2.02 log). NPEC was further tested as a surrogate for EHEC by comparing inactivation kinetics at 45, 50 and 55 degrees C at field strengths of between 7.86 and 32.55kV/cm. Statistical comparison of revealed that EHEC and NPEC inactivation curves were homogeneous at outlet temperatures of 45 and 50 degrees C; however, EHEC was slightly more sensitive to PEF than the surrogate NPEC at 55 degrees C. The higher PEF resistance of non-pathogenic E. coli 35218 at 55 degrees C may provide a desirable margin of safety when used in pilot plant challenge studies in place of E. coli O157:H7.


Asunto(s)
Bebidas/microbiología , Citrus sinensis , Electricidad , Microbiología de Alimentos , Conservación de Alimentos/métodos , Viabilidad Microbiana , Escherichia coli , Escherichia coli O157 , Frutas , Lactobacillus , Salmonella , Salmonella typhimurium
14.
J Immunol ; 184(7): 3450-60, 2010 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-20194716

RESUMEN

Donor Ag-reactive CD4 and CD8 T cell production of IFN-gamma is a principal effector mechanism promoting tissue injury during allograft rejection. The CXCR3-binding chemokines CXCL9 and CXCL10 recruit donor-reactive T cells to the allograft, but their role during the priming of donor-reactive T cells to effector function is unknown. Using a murine model of MHC-mismatched cardiac transplantation, we investigated the influence of CXCL9 and CXCL10 during donor-reactive T cell priming. In allograft recipient spleens, CXCL9 and CXCL10 were expressed as early as 24 h posttransplant and increased with similar kinetics, concurrently with CXCR3 expression on T cells. CXCL9, but not CXCL10, expression required NK cell production of IFN-gamma. The absence of CXCL9 in donor allografts, recipients, or both significantly decreased the frequency of donor-reactive CD8 T cells producing IFN-gamma and increased the frequency of donor-reactive CD8 T cells producing IL-17A. In contrast, the absence of CXCL10 increased the frequency of IFN-gamma-producing CD8 T cells in a CXCL9-dependent manner. These data provide novel evidence that donor-reactive CD8 T cells use the CXCR3 chemokine axis as a costimulation pathway during priming to allografts where CXCL9 promotes the development of IFN-gamma-producing CD8 T cells, and CXCL10 antagonizes this skewing.


Asunto(s)
Quimiocina CXCL10/inmunología , Quimiocina CXCL9/inmunología , Rechazo de Injerto/inmunología , Activación de Linfocitos/inmunología , Linfocitos T/inmunología , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Separación Celular , Quimiocina CXCL10/metabolismo , Quimiocina CXCL9/metabolismo , Citometría de Flujo , Supervivencia de Injerto/inmunología , Trasplante de Corazón/inmunología , Interferón gamma/biosíntesis , Interferón gamma/inmunología , Ratones , Ratones Transgénicos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Trasplante Homólogo
15.
Int J Food Microbiol ; 138(1-2): 91-9, 2010 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-20045211

RESUMEN

This study evaluated the efficacy of a supercritical carbon dioxide (SCCO(2)) system with a gas-liquid porous metal contactor for eliminating Escherichia coli K12 in apple cider. Pasteurized, preservative-free apple cider was inoculated with E. coli K12 and processed using the SCCO(2) system at CO(2) concentrations of 0-10% (wt.%, g CO(2)/100g product), outlet temperatures of 34, 38, and 42 degrees C, a system pressure of 7.6 MPa, and a flow rate of 1L/min. Increased CO(2) concentrations and temperatures significantly (P<0.05) enhanced the bactericidal effect, resulting in a maximum reduction of 7.31 log CFU/mL at 8% CO(2) and 42 degrees C. A response surface model indicated that minimum CO(2) concentrations of 9.9% at 34 degrees C, 7.4% at 38 degrees C, and 5.4% at 42 degrees C are needed to achieve a 5-log reduction of E. coli K12 in apple cider. SEM observations showed morphological changes in the cell envelope after SCCO(2) processing. At a processing condition of 8% and 38 degrees C, the reduction of E. coli was 6.03 log and the sublethal injury of the survivors was 84%. The regrowth or survival of E. coli in SCCO(2) processed apple cider was not observed during storage for 28 days at 4, 8, and 20 degrees C. Thus this study showed the potential of SCCO(2) processing with a gas-liquid porous metal contactor for the nonthermal pasteurization of apple cider.


Asunto(s)
Bebidas/microbiología , Dióxido de Carbono/farmacología , Escherichia coli K12/efectos de los fármacos , Conservación de Alimentos/métodos , Malus/microbiología , Recuento de Colonia Microbiana , Seguridad de Productos para el Consumidor , Relación Dosis-Respuesta a Droga , Escherichia coli K12/crecimiento & desarrollo , Contaminación de Alimentos/análisis , Contaminación de Alimentos/prevención & control , Microbiología de Alimentos , Humanos , Presión Hidrostática , Temperatura
16.
Int J Cancer ; 127(12): 2870-8, 2010 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-21351266

RESUMEN

Adenocarcinoma is the most common type of lung cancer, the leading cause of cancer deaths in the world. Early detection is the key to improve the survival of lung adenocarcinoma patients. We have previously shown that microRNAs (miRNAs) were stably present in sputum and could be applied to diagnosis of lung cancer. The aim of our study was to develop a panel of miRNAs that can be used as highly sensitive and specific sputum markers for early detection of lung adenocarcinoma. Our study contained 3 phases: (i) marker discovery using miRNA profiling on paired normal and tumor lung tissues from 20 patients with lung adenocarcinoma; (ii) marker optimization by real-time reverse transcription-quantitative polymerase chain reaction on sputum of a case-control cohort consisting of 36 cancer patients and 36 health individuals and (iii) validation on an independent set of 64 lung cancer patients and 58 cancer-free subjects. From the surgical tissues, 7 miRNAs with significantly altered expression were identified, of which "4" were overexpressed and "3" were underexpressed in all 20 tumors. On the sputum samples of the case-control cohort, 4 (miR-21, miR-486, miR-375 and miR-200b) of the 7 miRNAs were selected, which in combination produced the best prediction in distinguishing lung adenocarcinoma patients from normal subjects with 80.6% sensitivity and 91.7% specificity. Validation of the marker panel in the independent populations confirmed the sensitivity and specificity that provided a significant improvement over any single one alone. The sputum markers demonstrated the potential of translation to laboratory settings for improving the early detection of lung adenocarcinoma.


Asunto(s)
Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , MicroARNs/genética , Esputo/química , Adenocarcinoma/genética , Anciano , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/genética , Estudios de Casos y Controles , Detección Precoz del Cáncer , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , Curva ROC
17.
Foodborne Pathog Dis ; 6(4): 487-94, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19415973

RESUMEN

The effect of nisin (0 or 300 IU/mL), ethylenediamine tetraacetic acid (EDTA, 20 mM), and nisin (300 IU)-EDTA (20 mM) on growth parameters, including lag period (LP) and generation time, of Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella spp. in the presence or absence of aerobic mesophilic bacteria of apple cider during storage at 5 degrees C for up to 16 days or 23 degrees C for 16 h was investigated. The growth data were analyzed and fitted to the modified Gompertz model. The LP values for aerobic mesophilic bacteria of apple cider (control) and those amended with EDTA and nisin during storage at 5 degrees C were 1.61, 1.76, and 5.45 days, respectively. In apple cider stored at 23 degrees C for 16 h, the LP values for the same bacteria and treatment were 3.24, 3.56, and 5.85 h, respectively. The LP values for E. coli O157:H7 determined in the presence of aerobic mesophilic bacteria of apple cider stored at 23 degrees C for 16 h was 1.48 h, while populations for L. monocytogenes and Salmonella in the same cider declined. In sterile apple cider left at 23 degrees C for 16 h, the LP values for E. coli O157:H7, Salmonella, and L. monocytogenes averaged 2.74, 2.37, and 3.16 h, respectively. The generation time for these pathogens were 0.402, 0.260, and 0.187 log (CFU/mL)/h, respectively. Addition of nisin and EDTA combination caused a decline in lag phase duration and the populations for all pathogens tested, suggesting possible addition of this additive to freshly prepared apple cider to enhance its microbial safety and prevent costly recalls.


Asunto(s)
Bacterias Aerobias/crecimiento & desarrollo , Bebidas/microbiología , Escherichia coli O157/crecimiento & desarrollo , Conservación de Alimentos/métodos , Conservantes de Alimentos/farmacología , Listeria monocytogenes/crecimiento & desarrollo , Salmonella/crecimiento & desarrollo , Bacterias Aerobias/efectos de los fármacos , Recuento de Colonia Microbiana , Seguridad de Productos para el Consumidor , Sinergismo Farmacológico , Ácido Edético/farmacología , Escherichia coli O157/efectos de los fármacos , Cinética , Listeria monocytogenes/efectos de los fármacos , Malus/microbiología , Modelos Biológicos , Nisina/farmacología , Salmonella/efectos de los fármacos , Temperatura , Factores de Tiempo
18.
J Food Prot ; 72(3): 644-9, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19343957

RESUMEN

In this study, the ability of pectin-nisin films in combination with ionizing radiation to eliminate Listeria monocytogenes and inhibit its postirradiation proliferation was evaluated. Pectin films containing 0.025% nisin were made by extrusion. The surface of a ready-to-eat turkey meat sample was inoculated with L. monocytogenes at 10(6) CFU/cm2 and covered with a piece of pectin-nisin film. The samples were vacuum packaged and irradiated at 0, 1, and 2 kGy. The treated samples were stored at 10 degrees C and withdrawn at 0, 1, 2, 4, and 8 weeks for microbial analysis. Reductions in L. monocytogenes viability of 1.42, 1.56, 2.85, 3.78, and 5.36 log CFU/cm2 were achieved for the treatments of 1 kGy, pectin-nisin film, 2 kGy, 1 kGy plus pectin-nisin film, and 2 kGy plus pectin-nisin film, respectively. The greatest reduction (5.5 log CFU/cm2) was observed at 1 week for the 2 kGy plus pectin-nisin film treatment, suggesting that nisin was further released from the film to the surface of meat samples. Pectin-nisin films used in this study did not prevent but did significantly slow (P < 0.05) the proliferation of the L. monocytogenes cells that survived irradiation during 8 weeks of storage at 10 degrees C. These data indicate the potential use of pectin-nisin films alone or in combination with ionizing radiation for preventing listeriosis due to postprocessing contamination of ready-to-eat meat products.


Asunto(s)
Irradiación de Alimentos , Conservación de Alimentos/métodos , Conservantes de Alimentos/farmacología , Listeria monocytogenes/efectos de la radiación , Productos de la Carne/microbiología , Animales , Recuento de Colonia Microbiana , Seguridad de Productos para el Consumidor , Relación Dosis-Respuesta en la Radiación , Embalaje de Alimentos/métodos , Rayos gamma , Humanos , Listeria monocytogenes/efectos de los fármacos , Listeria monocytogenes/crecimiento & desarrollo , Nisina/farmacología , Pectinas/farmacología , Factores de Tiempo , Pavos , Vacio
19.
J Food Prot ; 72(3): 656-61, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19343959

RESUMEN

Radio frequency electric fields (RFEF) nonthermal processing effectively inactivates gram-negative bacteria in juices, but has yet to be shown effective at reducing gram-positive bacteria. Apple cider containing Lactobacillus plantarum ATCC 49445, a gram-positive bacterium, was RFEF processed under the following conditions: field strength of 0.15 to 15 kV/cm, temperature of 45 to 55 degrees C, frequency of 5 to 65 kHz, treatment time of 170 micros, and holding time of 5 to 50 s. The effect of refrigerating the inoculated cider prior to processing, the extent of sublethal injury, and the effect of storing the treated cider for 35 days were investigated. The population of L. plantarum was reduced by 1.0 log at 15 kV/cm, 20 kHz, and 50 degrees C, with a 5-s hold time. There is a synergistic effect between RFEF and heat above 50 degrees C. Inactivation significantly (P < 0.05) increased as frequency was decreased from 65 to 5 kHz. Inactivation increased linearly with field above 8 kV/cm. Holding cider at 55 degrees C after RFEF treatment for 5 and 50 s resulted in 2.5- and 3.1-log reductions, respectively. The surviving population was composed of 1.4-log sublethally injured cells. Storing processed cider at 4 degrees C for 35 days steadily and significantly (P < 0.05) reduced L. plantarum from 4.5 to 0.9 log CFU/ml. The electrical energy density was 51 J/ml. This provides the first evidence that nonthermal RFEF processing inactivates gram-positive bacteria, and that surviving cells may die off during refrigerated storage.


Asunto(s)
Manipulación de Alimentos/métodos , Irradiación de Alimentos , Lactobacillus plantarum/crecimiento & desarrollo , Malus/microbiología , Ondas de Radio , Bebidas/microbiología , Recuento de Colonia Microbiana , Seguridad de Productos para el Consumidor , Microbiología de Alimentos , Conservación de Alimentos/métodos , Calor , Humanos , Lactobacillus plantarum/efectos de la radiación , Malus/efectos de la radiación , Refrigeración , Factores de Tiempo
20.
J Agric Food Chem ; 57(3): 924-9, 2009 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-19154152

RESUMEN

Aroma composition and microbial quality of identical lots of apple cider treated by pulsed electric field (PEF), ultraviolet irradiation (UV), or thermal pasteurization stored at 4 degrees C were compared at 0 and 4 weeks. Conditions were optimized to achieve identical 5 log reductions in Escherichia coli K12 for each treatment. PEF and thermal pasteurization maintained acceptable microbial quality for 4 weeks, but UV samples fermented after 2 weeks. Twenty-eight volatiles were quantified using gas chromatography-mass spectrometry (GC-MS) and odor activity values (OAV) determined. OAVs of 69:hexyl acetate, 41:hexanal, 25:2-methylbutyl acetate, 23:2-methyl ethyl butyrate, and 14:2-(E)-hexenal were observed for the control cider. Significant differences (p < 0.05) in the levels of these odorants were observed between treated apple ciders only after 4 weeks of storage. Thermal samples lost 30% of the major ester and aldehyde volatiles during storage with significant decreases (p < 0.05) in butyl acetate, 2-methylbutyl acetate, hexanal, and 2-(E)-hexenal. In UV cider, hexanal and 2-(E)-hexenal were completely lost after 4 weeks of storage. Microbial spoilage in UV cider after 4 weeks of storage was chemically confirmed by the detection of the microbial metabolite 1,3-pentadiene. PEF cider lost <2% of its total ester and aldehydes after 4 weeks of storage and was preferred by 91% of the sensory panel over thermally treated cider.


Asunto(s)
Bebidas/análisis , Manipulación de Alimentos/métodos , Frutas/química , Calor , Malus/química , Odorantes/análisis , Bebidas/microbiología , Electricidad , Fermentación , Cromatografía de Gases y Espectrometría de Masas , Humanos , Olfato , Factores de Tiempo , Rayos Ultravioleta , Volatilización
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...