Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases.

INTRODUCTION: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. OBJECTIVE: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. METHODS: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. RESULTS: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38+ in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. CONCLUSIONS: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases.

Fenotipos de linfocitos periféricos en las enfermedades de Alzheimer y Parkinson / Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases

Introducción: La neuroinflamación está involucrada en la fisiopatología de diferentes trastornos neurológicos, en particular la enfermedad de Alzheimer (EA) y la enfermedad de Parkinson (EP). Las alteraciones en la barrera hematoencefálica pueden permitir la entrada al sistema nervioso central de linfocitos periféricos, los cuales pueden participar en la patología de las enfermedades. Objetivo: Evaluar el perfil de linfocitos periféricos en pacientes con EA y EP y su asociación con la enfermedad y su progresión. Métodos: Se incluyeron 20 pacientes con EA, 20 pacientes con EP y un grupo de individuos sanos. Diez de los pacientes con EA y 12 de los pacientes con EP fueron evaluados una segunda vez de 17 a 27 meses después del inicio del estudio. Las subpoblaciones de linfocitos y su estado de activación se determinaron mediante citometría de flujo. Todos los pacientes fueron evaluados neurológicamente utilizando escalas validadas internacionalmente. Resultados: Los pacientes con EA y EP mostraron un aumento significativo en los niveles de linfocitos activados, linfocitos susceptibles a la apoptosis, células T de memoria central y células T y B reguladoras con respecto a los sujetos sanos. A medida que las enfermedades progresaron se observó una disminución significativa de las células activadas (CD4+ CD38+ y CD8+ CD38+ en EP y EA; CD4+ CD69+ y CD8+ CD69+ en EP), de las células T susceptibles a la apoptosis y de algunas poblaciones reguladoras (CD19+ CD5+ IL10+ en EP y EA; CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ en EP). En pacientes con EA la progresión de la enfermedad se asoció con porcentajes más bajos de CD4 + CD38 + y mayores porcentajes de células CD4 efectoras al comienzo del estudio. Se observaron diferencias significativas entre ambas enfermedades. Conclusiones: Este estudio proporciona evidencia de cambios en los fenotipos de linfocitos periféricos asociados a EA y EP y a su gravedad. [...] (AU)

Introduction: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. Objective: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. Methods: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. Results: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38 + in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. Conclusions: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases. (AU)

Peripheral blood lymphocyte phenotypes in Alzheimer and Parkinson's diseases. / Fenotipos de linfocitos periféricos en las enfermedades de Alzheimer y Parkinson.

INTRODUCTION: Neuroinflammation is involved in the pathophysiology of various neurological disorders, in particular Alzheimer disease (AD) and Parkinson's disease (PD). Alterations in the blood-brain barrier may allow peripheral blood lymphocytes to enter the central nervous system; these may participate in disease pathogenesis. OBJECTIVE: To evaluate the peripheral blood lymphocyte profiles of patients with AD and PD and their association with the disease and its progression. METHODS: The study included 20 patients with AD, 20 with PD, and a group of healthy individuals. Ten of the patients with AD and 12 of those with PD were evaluated a second time 17 to 27 months after the start of the study. Lymphocyte subpopulations and their activation status were determined by flow cytometry. All patients underwent neurological examinations using internationally validated scales. RESULTS: Compared to healthy individuals, patients with AD and PD showed significantly higher levels of activated lymphocytes, lymphocytes susceptible to apoptosis, central memory T cells, and regulatory T and B cells. As the diseases progressed, there was a significant decrease in activated cells (CD4+ CD38+ and CD8+ CD38 + in PD and AD, CD4+ CD69+ and CD8+ CD69+ in PD), T cells susceptible to apoptosis, and some regulatory populations (CD19+ CD5+ IL10+ in PD and AD, CD19+ CD5+ IL10+ FoxP3+, CD4+ FoxP3+ CD25+ CD45RO+ in PD). In patients with AD, disease progression was associated with lower percentages of CD4+ CD38+ cells and higher percentages of effector CD4 cells at the beginning of the study. Significant differences were observed between both diseases. CONCLUSIONS: This study provides evidence of changes in peripheral blood lymphocyte phenotypes associated with AD and PD and their severity. Considering effective blood-brain communication, our results open new avenues of research into immunomodulation therapies to treat these diseases.

Exploring the QSAR's predictive truthfulness of the novel N-tuple discrete derivative indices on benchmark datasets.

Graph derivative indices (GDIs) have recently been defined over N-atoms (N = 2, 3 and 4) simultaneously, which are based on the concept of derivatives in discrete mathematics (finite difference), metaphorical to the derivative concept in classical mathematical analysis. These molecular descriptors (MDs) codify topo-chemical and topo-structural information based on the concept of the derivative of a molecular graph with respect to a given event (S) over duplex, triplex and quadruplex relations of atoms (vertices). These GDIs have been successfully applied in the description of physicochemical properties like reactivity, solubility and chemical shift, among others, and in several comparative quantitative structure activity/property relationship (QSAR/QSPR) studies. Although satisfactory results have been obtained in previous modelling studies with the aforementioned indices, it is necessary to develop new, more rigorous analysis to assess the true predictive performance of the novel structure codification. So, in the present paper, an assessment and statistical validation of the performance of these novel approaches in QSAR studies are executed, as well as a comparison with those of other QSAR procedures reported in the literature. To achieve the main aim of this research, QSARs were developed on eight chemical datasets widely used as benchmarks in the evaluation/validation of several QSAR methods and/or many different MDs (fundamentally 3D MDs). Three to seven variable QSAR models were built for each chemical dataset, according to the original dissection into training/test sets. The models were developed by using multiple linear regression (MLR) coupled with a genetic algorithm as the feature wrapper selection technique in the MobyDigs software. Each family of GDIs (for duplex, triplex and quadruplex) behaves similarly in all modelling, although there were some exceptions. However, when all families were used in combination, the results achieved were quantitatively higher than those reported by other authors in similar experiments. Comparisons with respect to external correlation coefficients (q2ext) revealed that the models based on GDIs possess superior predictive ability in seven of the eight datasets analysed, outperforming methodologies based on similar or more complex techniques and confirming the good predictive power of the obtained models. For the q2ext values, the non-parametric comparison revealed significantly different results to those reported so far, which demonstrated that the models based on DIVATI's indices presented the best global performance and yielded significantly better predictions than the 12 0-3D QSAR procedures used in the comparison. Therefore, GDIs are suitable for structure codification of the molecules and constitute a good alternative to build QSARs for the prediction of physicochemical, biological and environmental endpoints.

Event-based criteria in GT-STAF information indices: theory, exploratory diversity analysis and QSPR applications.

Versatile event-based approaches for the definition of novel information theory-based indices (IFIs) are presented. An event in this context is the criterion followed in the "discovery" of molecular substructures, which in turn serve as basis for the construction of the generalized incidence and relations frequency matrices, Q and F, respectively. From the resultant F, Shannon's, mutual, conditional and joint entropy-based IFIs are computed. In previous reports, an event named connected subgraphs was presented. The present study is an extension of this notion, in which we introduce other events, namely: terminal paths, vertex path incidence, quantum subgraphs, walks of length k, Sach's subgraphs, MACCs, E-state and substructure fingerprints and, finally, Ghose and Crippen atom-types for hydrophobicity and refractivity. Moreover, we define magnitude-based IFIs, introducing the use of the magnitude criterion in the definition of mutual, conditional and joint entropy-based IFIs. We also discuss the use of information-theoretic parameters as a measure of the dissimilarity of codified structural information of molecules. Finally, a comparison of the statistics for QSPR models obtained with the proposed IFIs and DRAGON's molecular descriptors for two physicochemical properties log P and log K of 34 derivatives of 2-furylethylenes demonstrates similar to better predictive ability than the latter.

Hipertensión inducida por el embarzo en adolescents: un studio multicéntrico / Pregnancy-induced hipertensión in young women: a multicenter study

Se evaluó la situación psicosocial percibida durante el proceso gestacional por dos grupos de adolescentes, un grupo se formó por 114 mujeres en quienes se estableció el diagnóstico de hipertensión inducida por el embarazo (HIE) y el otro por mujeres que fueron cualificadas como "sanas" (n=223). Fueron entrevistadas 337 mujeres adolescentes de las ciudades de Durango, Zacatecas, Fresnillo, Morelia y ciudad de México, que acudieron a instituciones hospitalarias de la Secretaría de Salud (SSA), y del Instituto Mexicano del Seguro Social (IMSS), de septiembre de 1998 a enero del 2000. Se aplicó a todas las participantes un cuestionario, para la identificación de estresores psicosociales y apoyo psicosocial. Se emplearon estadísticos descriptivos; X2 y estimación logarítmica media de razón de momios con IC. a 95%. Se observó una percepción más favorable de la situación psicosocial en las integrantes del grupo control. La situación psicosocial desfavorable identificada en el grupo de casos, sugiere su vinculación con los mecanismos biológicos responsables de la expresión de la HIE

To evaluate the psychosocial condition during pregnancy, as seen by two groups of young pregnant women from five cities in Mexico, women suffering from pregnancy-induced hypertension (PIH) were gathered into a group (n=l14). While women with a normal pregnancy formed another group (n=223). 337 young women from Durango, Zacatecas, Fresnillo, Morelia and Mexico City, were interviewed. They were submitted for obstetric care into hospitals belonging to the Mexican Ministry of Health (SSA) and the Mexican Social Security Institute (IMSS), between September 1998, and January 2000. All of the participating women answered a questionnaire, in order to identify psychosocial stressors and psychosocial support. Descriptive statistics, X2 and estimated mean log-odds ratio with 95% confidence intervals were used. A more favorable perception of psychosocial condition with figures statistically significative in the members of the control group were observed. The unfavorable psychosocial condition of the cases group, suggests its vinculation with the biologic process of the PIH

Diferencias en ansiedad estado-rasgo entre adolescentes con hipertension inducida por el embarazo y adolescentes embarazadas sanas / Differences in state-trait anxiety between adolescents with pregnancy induced hypertension and healthy pregnant adolescents

Se establecen y comparan los niveles de ansiedad percibidos por dos grupos de adolescentes, uno de ellos con el diagnóstico de hipertensión inducida por el embarazo (HIE), y el otro grupo conformado por adolescentes cualificadas como sanas. Es un estudio colaborativo de casos y controles, en el cual fueron escogidas 128 adolescentes embarazadas, que acudieron al servicio de gineco-obstetricia en hospitales de la Secretaría de Salud en las ciudades de Durango y México. El grupo de casos se integró por 46 adolescentes en quienes se estableció el diagnóstico de HIE por personal médico hospitalario, el grupo control se conformó por 82 adolescentes, que fueron cualificadas como sanas de acuerdo con criterios explícitos del estudio; tanto el grupo de casos como el de controles se integraron por adolescentes de ambas ciudades. Las participantes accedieron a responder el Inventario de Ansiedad EstadoRasgo (IDARE). Percepciones de ansiedad estado y rasgo difieren significativamente entre adolescentes con HIE y el grupo control. Los resultados muestran que el grupo de adolescentes con hipertensión inducida por el embarazo, presentan niveles de ansiedad significativamente más altos que el grupo control. (AU)

[Psychosocial status of adolescents and pregnancy toxemia]. / Situación psicosocial de las adolescentes y toxemias del embarazo.

OBJECTIVE: To compare the perception of psychosocial conditions (during pregnancy) between two groups of adolescents; one group was integrated by young women diagnosed with pregnancy induced-hypertension and the other group by clinically healthy women. MATERIAL AND METHODS: A case-control study design where 39 cases and 88 controls were chosen from pregnant adolescents seeking care at the General Hospital of Durango City, México, from July 1996 to February 1997, and from September 1998 to January 1999. Participants agreed to answer a semi-structured questionnaire to collect data on psychosocial support; psychosocial source of stress; coping responses; intention, desire and acceptance of pregnancy; and attitude and quality of socialization during pregnancy. Data analysis consisted of descriptive statistics, chi 2 and odds ratios with 95% confidence intervals. RESULTS: The two groups' sociodemographic and gyneco-obstetric characteristics were similar. Perception of stressors was higher among cases; sources of support were greater among controls. Positive attitudes and satisfactory socialization during pregnancy were more frequently reported by controls, with statistically significant differences between groups. CONCLUSIONS: We found qualitative differences in the perception of psychosocial conditions among study participants, with statistically significant favorable perceptions among controls.