Radioresistance and radiosensitivity: a biophysical approach on bacterial cells robustness.

The study of radiosensitivity and radioresistance of organisms exposed to ionizing radiation has acquired additional relevance since a new bio-concept, coined as The primacy of Proteome over Genome, was proposed and demonstrated elsewhere a few years ago. According to that finding, genome integrity would require an actively functioning Proteome. However, when exposure to radiation takes place, Reactive Oxygen Species (ROS) from water radiolysis induce protein carbonylation (PC), an irreversible oxidative Proteome damage. The bio-models used in that study were the radiosensitive Escherichia coli and the extraordinarily robust Deinococcus radiodurans. The production of ROS induces protective reactions rendering them non-reactive forms. Protective entities present in the cytosol, moieties smaller than 3 kDa, shield the Proteome against ROS, yielding protection against carbonylation. Shown in the present study is the fact that the fate of proteins functionality is determined by the magnitude of the Protein Carbonylation Yield (YPC), a quantity here analytically defined using published YPC numerical results. Analytical YPC expressions for E. coli and D. radiodurans were the input for a phenomenological approach, where the radiobiological magnitudes PP and PN, the probabilities for production of protein damage and ROS neutralization, respectively, were also analytically deduced. These highly relevant magnitudes, associated with key radiosensitivity and radioresistance issues, are addressed and discussed in this study. Among the plethora of information and conclusions derived from the present study, those endowed with higher conceptual degree, vis-à-vis the "Primacy of Proteome over Genome" concept, are as follows: (1) the ROS neutralization process in D. radiodurans reaches a maximum at a dose interval corresponding to the repairing shoulder. Therefore, it is a signature of the higher efficiency of the PC neutralization process. (2) ROS neutralization in D. radiodurans is nearly one order of magnitude higher than in E. coli, thus accounting for its extraordinary radioresistance. (3) Both physical (ROS-induced carbonyl radicals) and biological (protein modifications) processes are imbedded in the Protein Carbonylation Yield. The amalgamation of these two processes was accomplished by means of a statistical formalism.

The number of optic neuritis attacks is a potential confounder when comparing patients with NMO vs. controls by voxel-based neuroimaging analysis.

BACKGROUND: Voxel-based morphometric (VBM) studies in neuromyelitis optica (NMO) have shown limited reproducibility. A previous study suggests that the number of optic neuritis (ON) attacks may be a confounding factor when comparing NMO patients with controls if it is not taken into account during VBM analysis. PURPOSE: To investigate the potential confounding effect of the number of ON attacks, for both tissue volumes and perfusion by voxel-based statistical analysis. MATERIAL AND METHODS: Volumetric magnetic resonance imaging (MRI) and perfusion SPECT were obtained from 15 controls and two patient subgroups: subgroup I was composed of nine patients with one or two ON attacks; and subgroup II of six patients with three or four ON attacks. We performed non-parametric voxel-based comparison of tissue volumes and perfusion between controls versus the two patient subgroups and for the whole patient group. RESULTS: Subgroup I presented no volume reductions, contrary to subgroup II that showed unequivocal reduction. We also found hypoperfusion in different brain regions in different subgroups. The results were quite different for the whole patient group. CONCLUSION: These findings highlight the confounding effect of the number of ON attacks, providing a new methodological insight that could explain the limited reproducibility of previous VBM studies in NMO.

The CreC Regulator of Escherichia coli, a New Target for Metabolic Manipulations.

The CreBC (carbon source-responsive) two-component regulation system of Escherichia coli affects a number of functions, including intermediary carbon catabolism. The impacts of different creC mutations (a ΔcreC mutant and a mutant carrying the constitutive creC510 allele) on bacterial physiology were analyzed in glucose cultures under three oxygen availability conditions. Differences in the amounts of extracellular metabolites produced were observed in the null mutant compared to the wild-type strain and the mutant carrying creC510 and shown to be affected by oxygen availability. The ΔcreC strain secreted more formate, succinate, and acetate but less lactate under low aeration. These metabolic changes were associated with differences in AckA and LdhA activities, both of which were affected by CreC. Measurement of the NAD(P)H/NAD(P)(+) ratios showed that the creC510 strain had a more reduced intracellular redox state, while the opposite was observed for the ΔcreC mutant, particularly under intermediate oxygen availability conditions, indicating that CreC affects redox balance. The null mutant formed more succinate than the wild-type strain under both low aeration and no aeration. Overexpression of the genes encoding phosphoenolpyruvate carboxylase from E. coli and a NADH-forming formate dehydrogenase from Candida boidinii in the ΔcreC mutant further increased the yield of succinate on glucose. Interestingly, the elimination of ackA and adhE did not significantly improve the production of succinate. The diverse metabolic effects of this regulator on the central biochemical network of E. coli make it a good candidate for metabolic-engineering manipulations to enhance the formation of bioproducts, such as succinate.

Utilización de escalas en el laboratorio de evaluación integral sicomotriz del Centro Internacional de Restauración Neurológica a pacientes que padecen de esclerosis múltiple / Utilization of scales laboratory psychomotor comprehensive assessment of the International Center for Neurological Restoration patients suffering from Multiple Sclerosis

La evaluación y diagnóstico de las funciones motrices se erige en un aspecto importante y vital para los especialistas y oacientes que acuden a nuestra nstitución a fin de valorar sus posibilidades neurorrestaurativas para cumplimentar un plan de rehabilitación, encaminado a recuperar parcial o totalmente estas funciones, teniendo en cuenta sus potencialidades; de ahí que la evaluación antes y después del tratamiento neurorrestaurativo cobre vital importancia en pacientes con patologías neurológicas como la Esclerosis Múltiple; por ello el objetivo de nuestro trabajo fue valorar la sensilibidad de los test que se aplican para dicha patología en el Laboratorio de Evaluación Integral Sicomotriz (LEIS), del Centro Internacional de Restauración Neurológica (CIREN), a través de la compacación de los resultados obtenidos en las evaluaciones (inicial y final al tratamiento neurorrestaurativo) para el conocimiento del estado real de los pacientes. La muestra estuvo conformada por 25 pacientes atendidos en la Clínica de Lesiones Raquimedulares y Enfermedades Neuromusculares, a los que se les aplicaron los test evaluativos antes y después del tratamiento neurorrestaurativo, comparándose ambos resultados, para ello también se utilizó la prueba de Significación Estadística: Wilcoxon matched pairs test, evidenciándose que los test aplicados en el LEIS permitieron definir los puntos de partida para el tratamiento de rehabilitación física y se cuantificaron de manera objetiva los cambios en la capacidad física ocurridos en los pacientes en el desarrollo de su rehabilitación.

Multiple sclerosis in Latin America: A different disease course severity? A collaborative study from the MSBase Registry.

Limited data suggest that multiple sclerosis (MS) in Latin America (LA) could be less severe than in the rest of the world. The objective was to compare the course of MS between LA and other regions. METHODS: Centers from 18 countries with >20 cases enrolled in the MSBase Registry participated. Patients with MS with a disease duration of >1 year and <30 years at time of EDSS measurement were evaluated. The MS Severity Score (MSSS) was used as a measure of disease progression. Comparisons among regions (North America, Europe, Australia and LA), hemispheres and countries were performed. RESULTS: A total of 9610 patients were included. Patients were from: Europe, 6290 (65.6%); North America, 1609 (16.7%); Australia, 1119 (11.6%); and LA, 592 (6.1%). The mean MSSS in patients from LA was 4.47 ± 2.8, 4.53 ± 2.8 in North America, 4.51 ± 2.8 in Europe and 4.49 ± 2.7 in Australia. Mean MSSS in the northern hemisphere was 4.51 ± 1.6 compared to 4.48 ± 1.9 in the southern hemisphere. No differences were found for MSSS among hemispheres (p = 0.68), regions (p = 0.96) or countries (p = 0.50). CONCLUSIONS: Our analyses did not discover any difference in mean MSSS among patients from different regions, hemispheres or countries.

Brain Tissue Volumes and Perfusion Change with the Number of Optic Neuritis Attacks in Relapsing Neuromyelitis Optica: A Voxel-Based Correlation Study.

Recent neuroimaging studies show that brain abnormalities in neuromyelitis optica (NMO) are more frequent than earlier described. Yet, more research considering multiple aspects of NMO is necessary to better understand these abnormalities. A clinical feature of relapsing NMO (RNMO) is that the incremental disability is attack-related. Therefore, association between the attack-related process and neuroimaging might be expected. On the other hand, the immunopathological analysis of NMO lesions has suggested that CNS microvasculature could be an early disease target, which could alter brain perfusion. Brain tissue volume changes accompanying perfusion alteration could also be expected throughout the attack-related process. The aim of this study was to investigate in RNMO patients, by voxel-based correlation analysis, the assumed associations between regional brain white (WMV) and grey matter volumes (GMV) and/or perfusion on one side, and the number of optic neuritis (ON) attacks, myelitis attacks and/or total attacks on the other side. For this purpose, high resolution T1-weighted MRI and perfusion SPECT imaging were obtained in 15 RNMO patients. The results showed negative regional correlations of WMV, GMV and perfusion with the number of ON attacks, involving important components of the visual system, which could be relevant for the comprehension of incremental visual disability in RNMO. We also found positive regional correlation of perfusion with the number of ON attacks, mostly overlapping the brain area where the WMV showed negative correlation. This provides evidence that brain microvasculature is an early disease target and suggests that perfusion alteration could be important in the development of brain structural abnormalities in RNMO.

Efectividad de un programa de rehabilitación respiratoria en pacientes con esclerosis múltiple / Effectiveness of a respiratory rehabilitation program on patients with multiple sclerosis

Las personas con esclerosis múltiple presentan alteraciones de la comunicación oral relacionadas con una insuficiencia respiratoria, lo que obliga a los especialistas en logopedia a trabajar en este problema desde la óptica de su especialidad. Objetivo Evaluar la efectividad de un programa intensivo de rehabilitación respiratoria en personas con esclerosis múltiple, para aumentar su capacidad respiratoria y mejorar la coordinación fonorrespiratoria. Métodos Estudio de intervención cuasi experimental en un grupo de 30 personas adultas de ambos sexos con esclerosis múltiple. Todos recibieron el programa durante cuatro semanas con una hora diaria de ejercitación. Para valorar la efectividad del programa, se realizó una evaluación inicial y otra final de la capacidad vital inspiratoria y espiratoria forzada y de la coordinación fonorrespiratoria, por personal externo. El deterioro neurológico se midió mediante la Escala Expandida de Discapacidad de Kurtzke. Resultados En la muestra hubo predominio de mujeres, una edad promedio de 40,43 ± 11,46 años y 13,40 ± 7,76 años de evolución de la enfermedad. Se encontró esclerosis múltiple progresiva en 22 pacientes y 8 tenían formas de brote-remisión. El deterioro neurológico fue de 5,8 (±1,51) como promedio, lo que habla a favor de una discapacidad moderada en la muestra. Se encontró un aumento de la capacidad vital inspiratoria y espiratoria forzada y un aumento en el tiempo máximo de fonación, en la emisión de series de palabras bisílabas y en la emisión de series de números. Conclusiones El programa intensivo de rehabilitación respiratoria, contribuye al aumento de la capacidad respiratoria de las personas con esclerosis múltiple, por lo que se recomienda su aplicación en el proceso de neurorrehabilitación(AU)

People with multiple sclerosis present with altered oral communication related to respiratory failure, which forces the speech therapists to work on this problem within their range of specialty. Objective To evaluate the effectiveness la efectividad) of an intensive respiratory rehabilitation program. Methods Quasi-experimental interventional study carried out in a group of 30 adults of both sexes suffering from multiple sclerosis. All these patients were included in the program for 4 weeks, having one-hour training every day. For assessing the effectiveness of the program, an initial and a final evaluation of the forced vital inspiratory and expiratory capacity and of the phonorespiratory coordination was made by outside experts. The neurological deterioration was measured according the Kurtzkeïs extended disability scale. Results Women predominated in the sample; the average age was 40.43 ± 11.46 years and progression of disease was 13.40 ± 7.76 years. Progressive multiple sclerosis was found in 22 patients and the onset-remission forms in 8 patients. The neurological deterioration amounted to 5.8 (±1.51) as an average, which speaks for the moderate disability rate present in the simple. There was observed increased vital forced inspiratory and expiratory capacities and increase in maximum phonation length and in pronouncing series of two-syllable words and series of numbers. Conclusions The intensive respiratory rehabilitation program helps to increase the respiratory capacity of the patients with multiple sclerosis, hence, its implementation in the neurorehabilitation process is recommended(AU)

Efectividad de un programa de rehabilitación respiratoria en pacientes con esclerosis múltiple / Effectiveness of a respiratory rehabilitation program on patients with multiple sclerosis

Las personas con esclerosis múltiple presentan alteraciones de la comunicación oral relacionadas con una insuficiencia respiratoria, lo que obliga a los especialistas en logopedia a trabajar en este problema desde la óptica de su especialidad. Objetivo Evaluar la efectividad de un programa intensivo de rehabilitación respiratoria en personas con esclerosis múltiple, para aumentar su capacidad respiratoria y mejorar la coordinación fonorrespiratoria. Métodos Estudio de intervención cuasi experimental en un grupo de 30 personas adultas de ambos sexos con esclerosis múltiple. Todos recibieron el programa durante cuatro semanas con una hora diaria de ejercitación. Para valorar la efectividad del programa, se realizó una evaluación inicial y otra final de la capacidad vital inspiratoria y espiratoria forzada y de la coordinación fonorrespiratoria, por personal externo. El deterioro neurológico se midió mediante la Escala Expandida de Discapacidad de Kurtzke. Resultados En la muestra hubo predominio de mujeres, una edad promedio de 40,43 ± 11,46 años y 13,40 ± 7,76 años de evolución de la enfermedad. Se encontró esclerosis múltiple progresiva en 22 pacientes y 8 tenían formas de brote-remisión. El deterioro neurológico fue de 5,8 (±1,51) como promedio, lo que habla a favor de una discapacidad moderada en la muestra. Se encontró un aumento de la capacidad vital inspiratoria y espiratoria forzada y un aumento en el tiempo máximo de fonación, en la emisión de series de palabras bisílabas y en la emisión de series de números. Conclusiones El programa intensivo de rehabilitación respiratoria, contribuye al aumento de la capacidad respiratoria de las personas con esclerosis múltiple, por lo que se recomienda su aplicación en el proceso de neurorrehabilitación

People with multiple sclerosis present with altered oral communication related to respiratory failure, which forces the speech therapists to work on this problem within their range of specialty. Objective To evaluate the effectiveness la efectividad) of an intensive respiratory rehabilitation program. Methods Quasi-experimental interventional study carried out in a group of 30 adults of both sexes suffering from multiple sclerosis. All these patients were included in the program for 4 weeks, having one-hour training every day. For assessing the effectiveness of the program, an initial and a final evaluation of the forced vital inspiratory and expiratory capacity and of the phonorespiratory coordination was made by outside experts. The neurological deterioration was measured according the Kurtzkeïs extended disability scale. Results Women predominated in the sample; the average age was 40.43 ± 11.46 years and progression of disease was 13.40 ± 7.76 years. Progressive multiple sclerosis was found in 22 patients and the onset-remission forms in 8 patients. The neurological deterioration amounted to 5.8 (±1.51) as an average, which speaks for the moderate disability rate present in the simple. There was observed increased vital forced inspiratory and expiratory capacities and increase in maximum phonation length and in pronouncing series of two-syllable words and series of numbers. Conclusions The intensive respiratory rehabilitation program helps to increase the respiratory capacity of the patients with multiple sclerosis, hence, its implementation in the neurorehabilitation process is recommended

Disruption of the 2-methylcitric acid cycle and evaluation of poly-3-hydroxybutyrate-co-3-hydroxyvalerate biosynthesis suggest alternate catabolic pathways of propionate in Burkholderia sacchari.

The objective of the present work was to evaluate the relevance of the 2-methylcitric acid cycle (2MCC) to the catabolism of propionate in Burkholderia sacchari. Two B. sacchari mutants unable to grow on propionate were obtained: one disrupted in acnM, and the other in acnM and prpC deleted. An operative 2MCC significantly reduces the bacterial ability to incorporate 3-hydroxyvalerate (3HV) into a biodegradable copolyester accumulated from carbohydrates plus propionate. The efficiency of the mutants in converting propionate to 3HV units (Y(3HV/prp)) increased from 0.09 g*g(-1) to 0.81-0.96 g*g(-1), indicating that acnM and prpC are both essential for growth on propionate. None of the mutations resulted in achievement of the maximum theoretical Y3HV/prp (1.35 g*g(-1)). When increasing concentrations of propionate were supplied, decreasing values of Y3HV/prp were observed. The results obtained corroborate the hypothesis of the presence of other propionate catabolic pathways in B. sacchari. The 2MCC would be the more operative pathway, but a second pathway, which remains to be elucidated, would assume more importance under propionate concentrations of 1 g*L(-1) or higher. The efficiency in converting propionate to 3HV units can be improved by decreasing the propionate concentrations, owing to the role of the 2MCC.

TNF-alpha and IL-10 downregulation and marked oxidative stress in Neuromyelitis Optica

ABSTRACT: BACKGROUND: Neuromyelitis optica is a central nervous system demyelinating and inflammatory syndrome. The objective of this study is to identify cytokines related to the cellular immune response as well as blood brain barrier integrity and oxidative stress. METHODS: We performed a molecular characterization of cellular immune response and oxidative stress in serum from relapsing-NMO (R-NMO) patients and established the correlations between the clinical measurements and molecular parameters using the Bayesian approach.Serum samples from 11 patients with R-NMO diagnosed according to Wingerchuk criteria and matched in terms of age, gender and ethnicity with the healthy controls were analyzed. The levels of TNF-alpha, IFN-gamma, IL-10, MMP-9, TIMP-1 and oxidative stress markers: malondialdehyde, advanced oxidation protein products, peroxidation potential, superoxide dismutase, catalase, and total hydroperoxides were measured. RESULTS: We found almost undetectable levels of TNF-alpha, a decreased production of IL-10 and a significant up-regulation of every oxidative stress biomarker studied. The insufficient production of TNF-alpha and IL-10 in R-NMO patients, which are two important players of T cell mediated immunoregulation, suggest an effector - regulator imbalance. The overproduction of oxygen reactive species as a consequence of the chronic inflammatory milieu is reflected on the excess of oxidative damage mediators detected. Furthermore, Multidimensional Scaling and a Bayesian linear regression model revealed a significant linear dependence between Expanded Disability Status Scale Kurtzke and TIMP-1; pointing to a possible predictive or prognostic value of this clinical-molecular relationship. CONCLUSION: These results suggest that there is a breakdown in immunoregulatory mechanisms and noteworthy pro-oxidant environment contributing to NMO pathogenesis(AU)

TNF-alpha and IL-10 downregulation and marked oxidative stress in Neuromyelitis Optica.

BACKGROUND: Neuromyelitis optica is a central nervous system demyelinating and inflammatory syndrome. The objective of this study is to identify cytokines related to the cellular immune response as well as blood brain barrier integrity and oxidative stress. METHODS: We performed a molecular characterization of cellular immune response and oxidative stress in serum from relapsing-NMO (R-NMO) patients and established the correlations between the clinical measurements and molecular parameters using the Bayesian approach.Serum samples from 11 patients with R-NMO diagnosed according to Wingerchuk criteria and matched in terms of age, gender and ethnicity with the healthy controls were analyzed. The levels of TNF-alpha, IFN-gamma, IL-10, MMP-9, TIMP-1 and oxidative stress markers: malondialdehyde, advanced oxidation protein products, peroxidation potential, superoxide dismutase, catalase, and total hydroperoxides were measured. RESULTS: We found almost undetectable levels of TNF-alpha, a decreased production of IL-10 and a significant up-regulation of every oxidative stress biomarker studied. The insufficient production of TNF-alpha and IL-10 in R-NMO patients, which are two important players of T cell mediated immunoregulation, suggest an effector - regulator imbalance. The overproduction of oxygen reactive species as a consequence of the chronic inflammatory milieu is reflected on the excess of oxidative damage mediators detected. Furthermore, Multidimensional Scaling and a Bayesian linear regression model revealed a significant linear dependence between Expanded Disability Status Scale Kurtzke and TIMP-1; pointing to a possible predictive or prognostic value of this clinical-molecular relationship. CONCLUSION: These results suggest that there is a breakdown in immunoregulatory mechanisms and noteworthy pro-oxidant environment contributing to NMO pathogenesis.

An epidemiological study of neuromyelitis optica in Cuba.

INTRODUCTION: Two population-based studies of neuromyelitis optica (NMO) in non-white populations provided prevalence rates of 0.32 and 3.1 per 100,000 population. OBJECTIVE: To estimate NMO prevalence in the multiethnic Cuban population by nation-wide case ascertainment. METHODS: The study was conducted from October 1, 2003 to November 30, 2004. Ninety percent of general practitioners and all neurologists responded positively to the request for information on cases suspected of optic neuritis (ON), transverse myelitis (TM), multiple sclerosis, or NMO. Among the population of 11,177,743 there were 798 suspected cases, including 89 with possible NMO, relapsing ON (RON) and TM. Of the 89, 87 were examined by two of us (Cabrera JA, Lara R) who selected the NMO cases according to the 1999 Mayo Clinic criteria as well as those with relapsing TM and RON. RESULTS: 58 cases provided a prevalence rate of 0.52 per 100,000 (95% CI 0.39-0.67). The 7 males and 51 females gave rates of 0.13 (CI 0.05-0.26) and 0.91 (CI 0.68-1.20). The estimated average annual incidence rate was 0.053 per 100,000 (CI 0.040-0.068). Prevalence rates did not differ significantly among the three ethnic groups. Black NMO cases were significantly older, with more relapses and motor deficit, as well as more abnormalities in brainstem evoked potentials and in brain MRI (not meeting MS criteria). The predominant clinical form was relapsing over monophasic. CONCLUSIONS: This Cuban multiethnic population had a prevalence of NMO of 0.52 per 100,000 and an estimated average annual incidence rate of 0.053 per 100,000 with no differences by ethnicity. Black patients were older, with more relapses and motor impairment.

Brain magnetic resonance imaging findings in relapsing neuromyelitis optica.

BACKGROUND: Some studies showed abnormalities in brain magnetic resonance imaging (MRI) of relapsing neuromyelitis optica (R-NMO) from 12 to 46%. These abnormalities are described as compatible/non-compatible with multiple sclerosis (MS). OBJECTIVE: To describe the abnormal brain MRI lesions in R-NMO with imaging studies conducted with more sensitive white matter change techniques. METHODS: Thirty patients with R-NMO were selected. All MRI brain studies were performed with a 1.5-T Siemens MRI system according to the Standardized MR Imaging Protocol for Multiple Sclerosis from the Consortium of MS Centers Consensus Guidelines. RESULTS: Brain MRI images were evaluated in 29 R-NMO cases because in one case the MRI images were not appropriate for the study. Of these 29 brain MRI studies, 19 cases (65.5%) had at least one or more lesions (1-57) and 10 were negative (34.4%). Brain MRI findings in 19 cases were characterized in T2/fluid-attenuated inversion-recovery (FLAIR) by the presence of subcortical/deep white matter lesions in 16 (84.2%) cases (1-50), most of them <3 mm and without juxtacortical localization. Periventricular lesions were observed in 13 (68.4%) cases, but morphologically they were not oval, ovoid or perpendicularly orientated. Infratentorial lesions, all >3 mm, were observed in 4 (21.05%) cases without cerebellar involvement. T1 studies demonstrated absence of hypointense regions. Optic nerve enhancement was observed in 6/19 patients (31.5%). None of the brain MRI abnormalities observed were compatible with Barkhof et al. criteria of MS. CONCLUSIONS: This study, based on a Cuban patient population, with long duration of disease, good sample size and detailed characterization by MRI, demonstrated the brain MRI pattern of R-NMO patients, which is different from MS.

Metaloproteinasas de matríz en pacientes con esclerosis múltiple / Matrix metalloproteinases in patients with multiple sclerosis

Fundamento: La ruptura proteolítica de la matriz extracelular por las metaloproteinasas 2 y 9 es uno de los aspectos que puede influir en la alteración de la permeabilidad de la barrera hematoencefálica en la esclerosis múltiple. Objetivo: Determinar la actividad de las metaloproteinasas con actividad gelatinasa en pacientes con esclerosis múltiple. Métodos: Las muestras de líquido cefalorraquídeo se obtuvieron de 31 pacientes con esclerosis múltiple y un grupo control conformado por 21 pacientes sin enfermedad neurológica. Las actividades de las metaloproteinasas 2 y 9 en el líquido cefalorraquídeo se determinaron mediante técnica zimográfica por electroforesis en gel de poliacrilamida, después las bandas fueron identificadas por sus pesos moleculares y se calculó la actividad relativa de la metaloproteinasa 9. Se evaluaron las concentraciones de proteínas totales, albúmina e IgG, el índice IgG y el índice Q para evaluar síntesis intratecal de IgG y estado funcional de la barrera hematoencefálica. Resultados: Se detectó actividad de metaloproteinasa 2 en el líquido cefalorraquídeo de todos los pacientes y controles, mientras que la 9 solo se detectó en los pacientes (61, 3 por ciento). La presencia de actividad relativa de metaloproteinasa 9 no se asoció con las variables clínicas, ni con las variables de laboratorio. Se encontró asociación entre su presencia y las bandas oligoclonales en los pacientes con esclerosis múltiple, en aquellos sometidos a tratamiento inmunomodulador esta se presentó con menor frecuencia. Conclusiones: Existe una posible participación de la metaloproteinasa 9 en los mecanismos inmunopatológicos de la esclerosis múltiple(AU)

Fundament: The proteolitic rupture of the extracellular matrix due to metalloproteinase 2 and 9 is one of the aspects that can influence in the alteration of the permeability of the blood-brain barrier (BBB) in multiple sclerosis. Objective: To determine metalloproteinase activity with gelatinous activity in patients suffering from multiple sclerosis. Methods: the cerebrospinal fluid (CSF) samples taken from 31 patients suffering from multiple sclerosis and a control group formed by 21 patients without neurological disease. The metalloproteinase 2 and 9 activities in the cerebrospinal fluid were determined by zimográfica technique through polyacrylamide gel electrophoresis. The bands were later analysed by their molecular weight and the relative metalloproteinase 9 activity was calculated. Total protein concentrations, albumin and immunoglobulin G (IgG), the IgG rate and the Q rate were assessed to evaluate the IgG intrathecal and the functional state of the blood-brain barrier. Results: metalloproteinase 2 activity was detected in the cerebrospinal fluid of all patients and control group. Metalloproteinase 9 activity was only found in the 61.3 percent of the patients. The presence of relative metalloproteinase 9 activity was neither associated with the clinical variables nor the laboratory ones. An association was found between its presence and the oligoclonal bands in patients with multiple sclerosis. In those patients under immunomodular treatment it was presented with less frequency. Conclusions: There is a possible participation of Metalloproteinase 9 in the immunopathological mechanisms of the multiple sclerosis(AU)

Caracterización y factores pronósticos de la enfermedad cerebrovascular en la provincia de Cienfuegos

Las enfermedades cerebrovasculares constituyen la tercera causa de muerte y la primera de discapacidad grave del adulto en los países con sistemas de salud desarrollados similares al nuestro. Caracterizar a los pacientes con enfermedades cerebrovasculares y determinar las variables que influyen en su pronóstico una vez establecidas. Estudio de tipo prospectivo, descriptivo, longitudinal, de serie de casos realizado en el Hopital Universitario Dr Gustavo Aldereguía Lima. Se aplicaron formularios al total de pacientes que cumplieron los criterios de inclusión (n- 1318). Se constató una edad media de 66,08 años, predominó el color de la piel blanca (75,26 porciento ), y el sexo masculino(56,67 porciento).El marcador de riesgo más reportado fue la hipertensión arterial(43,24 porciento). La evolución para vivos sin discapacidad fue de 14,71 porciento, vivos con discapacidad 57,96 porciento y fallecidos 27,31 porciento. Predominó la enfermedad cerebrovascular isquémica con 46,13 porciento de infartos aterotrombóticos y 14,94 porciento cardioembólicos; en las hemorrágicas el 13,42 porciento fueron hemorragias intracerebrales y 4,55 porciento hemorragias subaracnoideas. Se comprobó correlación pronóstica para las variables clínicas: conciencia, mirada, sensibilidad, lenguaje, tono, reflejo de Babinski, reflejos osteotendinosos, y fuerzas musculares(AU)

Creación y validación de un instrumento para el seguimiento de pacientes con enfermedad cerebrovascular / Creation and validation of an instrument for the follow-up of stoke patients

Se realizó un estudio para crear y validar un instrumento para el seguimiento de pacientes con enfermedad cerebrovascular, y determinar las variables necesarias para evaluarlos y establecer procedimientos para obtener un puntaje y estratificación por grupos que permitan una clasificación pronóstica y evolutiva de nuevos casos. Se analizó una muestra multicéntrica, de 1 218 enfermos, por métodos estadísticos: V de Cramer. Detector Automático de Interacciones, Chi cuadrado, regresión logística, método de Spearman, escalamiento óptimo, análisis factorial, etc., sobre bases de datos EXCEL transferida al paquete estadístico para Ciencias Sociales. Se obtuvo un instrumento manual y 2 implementados en sistema computadorizado: clínico y general, con porcentajes correctos de clasificación superiores a 90 y válidos en resultado global con 90,09; 92,98 y 94,14 por ciento, respectivamente. Los puntajes y clasificación se realizaron sobre la base de los coeficientes obtenidos en un intervalo de 0-1. Resultaron 3 grupos de riesgo: bajo (vivo sin discapacidad: 0 ú puntaje ú 0,33), medio (vivo con discapacidad 0,33 < puntaje < 0,67) y alto (fallecido 0,67 ú puntaje ú 1), algunos clasifican directamente por interacciones. Se obtuvo un instrumento de rigor científico cuanticualitativo, único en el país, de fácil aplicación, para atender pacientes con enfermedad cerebrovascular y, sobre esta base tomar decisiones para ejecutar una práctica médica de mayor calidad(AU)

Creación y validación de un instrumento para el seguimiento de pacientes con enfermedad cerebrovascular / Creation and validation of an instrument for the follow-up of stoke patients

Se realizó un estudio para crear y validar un instrumento para el seguimiento de pacientes con enfermedad cerebrovascular, y determinar las variables necesarias para evaluarlos y establecer procedimientos para obtener un puntaje y estratificación por grupos que permitan una clasificación pronóstica y evolutiva de nuevos casos. Se analizó una muestra multicéntrica, de 1 218 enfermos, por métodos estadísticos: V de Cramer. Detector Automático de Interacciones, Chi cuadrado, regresión logística, método de Spearman, escalamiento óptimo, análisis factorial, etc., sobre bases de datos EXCEL transferida al paquete estadístico para Ciencias Sociales. Se obtuvo un instrumento manual y 2 implementados en sistema computadorizado: clínico y general, con porcentajes correctos de clasificación superiores a 90 y válidos en resultado global con 90,09; 92,98 y 94,14 por ciento, respectivamente. Los puntajes y clasificación se realizaron sobre la base de los coeficientes obtenidos en un intervalo de 0-1. Resultaron 3 grupos de riesgo: bajo (vivo sin discapacidad: 0 ú puntaje ú 0,33), medio (vivo con discapacidad 0,33 < puntaje < 0,67) y alto (fallecido 0,67 ú puntaje ú 1), algunos clasifican directamente por interacciones. Se obtuvo un instrumento de rigor científico cuanticualitativo, único en el país, de fácil aplicación, para atender pacientes con enfermedad cerebrovascular y, sobre esta base tomar decisiones para ejecutar una práctica médica de mayor calidad

Creación y validación de un instrumento para el seguimiento de pacientes con enfermedad cerebrovascular / Creation and validation of an instrument for the follow-up of stoke patients

Se realizó un estudio para crear y validar un instrumento para el seguimiento de pacientes con enfermedad cerebrovascular, y determinar las variables necesarias para evaluarlos y establecer procedimientos para obtener un puntaje y estratificación por grupos que permitan una clasificación pronóstica y evolutiva de nuevos casos. Se analizó una muestra multicéntrica, de 1 218 enfermos, por métodos estadísticos: V de Cramer. Detector Automático de Interacciones, Chi cuadrado, regresión logística, método de Spearman, escalamiento óptimo, análisis factorial, etc., sobre bases de datos EXCEL transferida al paquete estadístico para Ciencias Sociales. Se obtuvo un instrumento manual y 2 implementados en sistema computadorizado: clínico y general, con porcentajes correctos de clasificación superiores a 90 y válidos en resultado global con 90,09; 92,98 y 94,14 por ciento, respectivamente. Los puntajes y clasificación se realizaron sobre la base de los coeficientes obtenidos en un intervalo de 0-1. Resultaron 3 grupos de riesgo: bajo (vivo sin discapacidad: 0 menor o igual puntaje mayor o igual 0,33), medio (vivo con discapacidad 0,33 menor puntaje mayor 0,67) y alto (fallecido 0,67 menor o igual puntaje mayor o igual 1), algunos clasifican directamente por interacciones. Se obtuvo un instrumento de rigor científico cuanticualitativo, único en el país, de fácil aplicación, para atender pacientes con enfermedad cerebrovascular y, sobre esta base tomar decisiones para ejecutar una práctica médica de mayor calidad(AU)

Interferón alfa y enfermedad de Alzheimer / Alfha interferon and Alzheimer disease

La enfermedad de Alzheimer (EA) es la causa más frecuente de demencia, su etiología es desconocida y carece de tratamiento específico para detener el curso de la enfermedad. Los interferones (IFN) son proteínas que tienen efecto antiviral, antiproliferativo e inmunomodulador en el SNC ejercen sus acciones a través de los receptores opiáceos y el sistema dopaminérgico. Existen evidencias de que la EA pudiera estar relacionada con las enfermedades priónicas y con determinados virus, y que el sistema de IFN se encuentra deteriorado en la EA. Se presenta una revisión de los pacientes con EA tratados con IFN alfa. El primer caso conocido en la literatura fue un hombre de 69 años con EA definida (NINCDS-ADRDA) a quien se le administró IFN alfa leucocitario por vía intratecal y cuya sospecha clínica inicial había sido el de una enfermedad de Creutzfeldt-Jakob, luego de concluido el tratamiento con IFN alfa se observó estabilización de los signos neurológicos. Posteriormente, se analizan los resultados de un ensayo clínico, aleatorizado, controlado en 16 pacientes con EA probable (NINCDS-ADRDA) en los que se utilizó IFN alfa 2b recombinante por vía intramuscular, en los que no se observaron cambios, luego de un año de tratamiento, en las evaluaciones clínicas y neuropsicológicas. Sin embargo, se observó mejoría significativa, en uno de los parámetros que midieron calidad de vida, y una tendencia a una menor mortalidad en los pacientes tratados con IFN alfa. Estos resultados deben ser investigados en futuros estudios a la luz de los hallazgos actuales en las alteraciones neuropatológicas en la EA, las citoquinas pro-inflamatorias, muchas de sus acciones son contrarrestadas por el IFN alfa, pueden producir un efecto deletéreo en la evolución de la EA.