Acquired Senescent T-Cell Phenotype Correlates with Clinical Severity in GATA Binding Protein 2-Deficient Patients.

GATA binding protein 2 (GATA2) deficiency is a rare disorder of hematopoiesis, lymphatics, and immunity caused by spontaneous or autosomal dominant mutations in the GATA2 gene. Clinical manifestations range from neutropenia, lymphedema, deafness, to severe viral and mycobacterial infections, bone marrow failure, and acute myeloid leukemia. Patients also present with monocytopenia, dendritic cell, B- and natural killer (NK)-cell deficiency. We studied the T-cell and NK-cell compartments of four GATA2-deficient patients to assess if changes in these lymphocyte populations could be correlated with clinical phenotype. Patients with more severe clinical complications demonstrated a senescent T-cell phenotype whereas patients with lower clinical score had undetectable changes relative to controls. In contrast, patients' NK-cells demonstrated an immature/activated phenotype that did not correlate with clinical score, suggesting an intrinsic NK-cell defect. These studies will help us to determine the contribution of T- and NK-cell dysregulation to the clinical phenotype of GATA2 patients, and may help to establish the most accurate therapeutic options for these patients. Asymptomatic patients may be taken into consideration for hematopoietic stem cell transplantation when dysregulation of T-cell and NK-cell compartment is present.

Comparison of two analytical platforms for CSF biomarkers of Alzheimer's disease.

Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) are currently being assessed with two different assays. Our objective was to study if there is a correlation between values obtained by both techniques, to compare their validity and search for conversion factor between values obtained for every protein. We compared the performances of two commonly used platforms, an enzyme-linked immunosorbent assay (ELISA) and a multiplex (xMAP) technology for measurement of CSF Aß 1-42, total tau (T-tau), and phosphorylated tau 181 (P-tau 181p) proteins, in 30 AD patients and 28 control subjects. The relations between the variables of both techniques were evaluated using the Spearman p correlation coefficient (α = 0.05). Receiver operating characteristic and area under the curve (AUC) analyses were calculated for the variables of both techniques. The two assays platforms yielded different absolute values for the various analytes, always higher in ELISA. We found some correction factor between values: 2,1- to 3-fold for Aß 1-42; 4,1- to 4,6-fold for T-tau; and 1,4- to 1,6-fold for P-tau 181p. In addition, those values were highly correlated (Aß 1-42: r = 0.70, P < 0.01; T-tau: r = 0.90, P < 0.01; P-tau 181p: r = 0.85, P < 0.01) and the AUC for the variables showed very similar values. In conclusion, the results obtained with ELISA and xMAP platforms were highly correlated and its validity is very similar. Differences in absolute values point to the need for a clear description of the technique used. Moreover, we found some conversion factor between values of every protein that may be useful for transformation between both techniques.

Effect of incorporating prebiotics in coating materials for the microencapsulation of Saccharomyces boulardii.

The objective of this study was to microencapsulate Saccharomyces boulardii using the emulsion technique. To microencapsulate the yeast, alginate sodium blended with inulin and mucilage from Opuntiaficus-indica was used as a coating material. The textural properties of the gels formed by the encapsulating materials and the in vitro viability of the yeast strain in the simulated conditions were studied. Textural profile analyses of the gels revealed differences (p < 0.05) in hardness because alginate produced stronger gels, whereas the incorporation of other hydrocolloids with alginate decreased gel strength and resulted in a more uniform, cohesive gel matrix. When alginate was blended with mucilage and inulin, encapsulated yeast presented higher counts and more viable cells, as compared to free yeast following 30 days of storage at 4 °C. Encapsulated and free yeast had 76.1% and 63.3%, respectively, of cell viability after 35 days of storage.

Análisis Multiplex de citoquinas intratecales en pacientes con deterioro cognitivo leve / Multiplex analysis of intrathecal cytokines in patients with mild cognitive impairment

Introducción. El estudio del papel de las citoquinas en los procesos neuroinmunológicos se ha intensificado en la última década, si bien los resultados han sido contradictorios debido al empleo de tecnologías poco sensibles. La implementación de la tecnología Multiplex en los inmunoensayos puede ser beneficiosa en la evaluación de pacientes con daño cognitivo leve (DCL) que evolucionan a enfermedad de Alzheimer (EA). Materiales y métodos. Treinta y siete pacientes con DCL y 24 sujetos control fueron estudiados mediante análisis Multiplex de citoquinas intratecales y en suero. Las variables del estudio fueron las citoquinas IL1β, IL2, IL5, IL6, IL7, IL8, IL10, IL12p70, IL13, factor necrosis tumoral alfa (TNFα), interferón gamma (IFNγ) y factor de crecimiento de granulocito-macrófago (GM-CSF) y los cocientes pro/antiinflamatorios IL6/IL10, IL6/IL5, IL8/IL10, IL8/IL5, TNFα/IL10 y TNFα/IL5. Se estudió la evolución a EA en los pacientes DCL y en los sujetos control en el período de un año. Resultados. Se encontraron diferencias significativas (p<0,05) para el cociente IL6/IL10 entre el grupo DCL y el grupo control (mediana [rango intercuartílico]): (1,39 [1,18-1,80] vs. 1,91 [2,68-1,18] pg/ml). De 37 pacientes con DCL, 14 evolucionaron a EA (DCL-EA) en el período de un año. De nuevo se encontraron diferencias significativas (p<0,05) en el cociente IL6/IL10 entre el grupo DCL-EA y DCL- S (o estable): (1,29 [0,84-1,56] vs. 1,42 [1,27-2,07] pg/ml). Ninguno de los sujetos control evolucionó a EA. Conclusiones. El descenso en el cociente IL6/IL10 en LCR puede ser un prometedor marcador diagnóstico de DCL y predictor/pronóstico de EA en DCL (AU)

Introduction. There has been an increase in the number of studies on the role of cytokines in neuro-immunological processes, over the last ten years, but some of these results have been contradictory due to a lack of sensitivity in the technology. The new Multiplex immunoassays can be beneficial for monitoring Mild Cognitive Impairment (MCI) patients who progress to Alzheimer Disease (AD). Methods. A study was conducted on 37 MCI patients and 24 control subjects by means of multiplex analysis of CSF cytokines. The variables measured were the following cytokines: IL1β, IL2, IL5, IL6, IL7, IL8, IL10, IL12p70, IL13, tumour necrosis factor alpha (TNFα), interferon gamma (IFNγ) and granulocyte – macrophage growth colony stimulating factor (GM-CSF), as well as the following pro/anti-inflammatory ratios: IL6/IL10, IL6/IL5, IL8/IL10, IL8/IL5, TNFα/IL10 and TNFα/IL5. Progress to AD in MCI patients was studied over a period of one year. Results. Significant differences were found (P<.05) for IL6/IL10 ratio between MCI patients and Control group (median [IR]): (1.39 [1.18-1.80] vs. 1.91 [2.68-1.18] pg/mL). Of the 37 MCI patients, 14 progressed to AD (DCL-EA group) within a year. Significant differences were also found (P<.05) for IL6/IL10 ratio between the DCL-EA group and the rest of MCI patients that did not progress (DCL-S or stable): (1.29 [0.84-1.56] vs. 1.42 [1.27-2.07] pg/mL). None of the control subjects progressed to AD. Conclusions. A decrease in CSF IL6/IL10 ratio could be a promising diagnostic biomarker in MCI and a prognostic biomarker of AD in MCI (AU)

[Biomarkers in the cerebrospinal fluid of patients with mild cognitive impairment: a meta-analysis of their predictive capacity for the diagnosis of Alzheimer's disease]. / Biomarcadores en el liquido cefalorraquideo de pacientes con deterioro cognitivo leve: metaanalisis de su capacidad predictiva para el diagnostico de la enfermedad de Alzheimer.

INTRODUCTION: Several studies have reported alterations in the cerebrospinal fluid biomarkers (Abeta-42, T-tau and P-tau proteins), both in Alzheimer's disease (AD) and in mild cognitive impairment (MCI). AIM: To perform a meta-analysis of the diagnostic yield of this technique for the prediction of patients with MCI who are going to progress to AD. MATERIALS AND METHODS: A search was conducted in PubMed and Embase of papers published between 1999 and September 2008, and as a result only prospective studies were included for the systematic review. The sensitivity and specificity for each biomarker were studied separately and also jointly. RESULTS: Of the 12 studies that were included, 6 quantified the Abeta-42 protein, 11 the T-tau protein and seven the P-tau protein. In three of the studies data was obtained from the three biomarkers in combination. The sensitivity of the quantification of the T-tau and P-tau proteins is 82%, with a diagnostic odds ratio of 12.09 (confidence interval 95%, CI 95% = 7.71-18.99; p = 0.1) and 16.29 (CI 95% = 9.69-27.4; p = 0.9), respectively. Alteration of any of the three biomarkers has a specificity of 87%, with a diagnostic odds ratio of 35.97 (CI 95% = 7.8-164.6; p = 0.04). CONCLUSIONS: The isolated alteration of T-tau or P-tau levels in cerebrospinal fluid is very sensitive for differentiating between patients with MCI who are going to develop AD and those who are going to remain stable. Normality of the three biomarkers is a very reliable way of ruling out the progression of AD in patients with MCI.

Efecto bactericida de la cal hidratada en solución acuosa / Bactericidal effect of hydrated lime in aqueous solution

Se determinó el efecto bactericida de los sebrenadantes de las soluciones saturadas de cal común y de hidróxido de calcio (Ca(OH)2) micronizado (1500 mg/L), que se usó a manera de testigo, comparándolo con el de los desinfectantes constituídos por soluciones de plata coloidal al 0,33 por ciento (0,0016mg/L), sulfacloramina de tolueno (41 mg/L) con bicarbonato de sodio (9 mg/L) e hipoclorito de sodio (5 mg/L). Para ello se emplearon cuatro cepas de Vibrio cholerae No. 01, V. parahaemolyticus, Escherichia coli, salmonella typhimurium, shigella flexneri, Sh. sonnei y Sa. enteritidis. Estas bacterias se usaron para inocular las sustancias bactericidas ya citadas y, después de distintos tiempos de incubación, las bacterias sobrevivientes se cuantificaron in vitro por medio de la técnica de vaciado en placa. El resultado se expresó en unidades formadoras de colonias (UFC). Se estimó in situ la carga de V. cholerae soltada por 35 fresas y 35 rábanos (con un peso aproximado de 10 g por unidad) al lavarlos bajo un chorro de agua potable, sumergirlos en el sobrenadantes de una solución saturada de cal (1,5 g/L), y ambas cosas. El mayor efecto bactericida se obtuvo con V. cholerae O1 y se observó a los 3 minutos. Otras enterobacterias resistieron el efecto bactericida hasta 30 minutos (AU)

Efecto bactericida de la cal hidratada en solución acuosa / Bactericidal effect of hydrated lime in aqueous solution

Se determinó el efecto bactericida de los sebrenadantes de las soluciones saturadas de cal común y de hidróxido de calcio (Ca(OH)2) micronizado (1500 mg/L), que se usó a manera de testigo, comparándolo con el de los desinfectantes constituídos por soluciones de plata coloidal al 0,33 por ciento (0,0016mg/L), sulfacloramina de tolueno (41 mg/L) con bicarbonato de sodio (9 mg/L) e hipoclorito de sodio (5 mg/L). Para ello se emplearon cuatro cepas de Vibrio cholerae No. 01, V. parahaemolyticus, Escherichia coli, salmonella typhimurium, shigella flexneri, Sh. sonnei y Sa. enteritidis. Estas bacterias se usaron para inocular las sustancias bactericidas ya citadas y, después de distintos tiempos de incubación, las bacterias sobrevivientes se cuantificaron in vitro por medio de la técnica de vaciado en placa. El resultado se expresó en unidades formadoras de colonias (UFC). Se estimó in situ la carga de V. cholerae soltada por 35 fresas y 35 rábanos (con un peso aproximado de 10 g por unidad) al lavarlos bajo un chorro de agua potable, sumergirlos en el sobrenadantes de una solución saturada de cal (1,5 g/L), y ambas cosas. El mayor efecto bactericida se obtuvo con V. cholerae O1 y se observó a los 3 minutos. Otras enterobacterias resistieron el efecto bactericida hasta 30 minutos (AU)