Increased C-reactive protein in acute ischemic stroke patients is age dependent / El incremento de la proteína C reactiva en pacientes con ictus isquémico agudo varía con la edad

Introduction: Several studies investigating blood biomarkers such as C-reactive protein (CRP) in the prognosis and mortality of stroke have not been conclusive. This may be related to the fact that age has not been taken into account for these analyses. Objective: In the present study, we evaluated the possible relationship of blood markers with the age and clinical characteristics of ischemic stroke patients. Methods: Two groups of acute ischemic stroke patients (≤ 55 years and > 55 years of age) who were paired with a control group were included. CRP, alpha 1 antitrypsin (AAT), complements C3 and C4, microalbuminura, ceruloplasmin, glucose, cholesterol, triglycerides, glutamic-piruvic transaminase (GPT), glutamic-oxalacetic transaminase (GOT), gamma glutamiltranspeptidase (GGT), creatinine, and uric acid were determined. Other clinical information, including NIH stroke scale was collected. Results: AAT, ceruloplasmin, microalbuminuria, GPT, GOT and GGT were significantly increased with respect to control subjects in both age groups. Nevertheless, CRP was increased only in patients older than 55 years. CRP and age were directly correlated in stroke patients, but not in the control group joint analysis of age and NIHSS revealed a tendency towards even higher CRP values in older patients with more severe neurological impairment. Levels of CRP increased significantly with age according to NIH score. Conclusions: Age should be considered when evaluating the usefulness of CRP and other blood biomarkers as clinical tools for predicting long or short-term neurological outcome or stroke recurrence events in ischemic stroke patients(AU)

Introducción: Los estudios sobre marcadores sanguíneos incluido la proteína C reactiva (PCR) en el pronóstico y mortalidad del ictus no han sido concluyentes, quizás porque en sus análisis no se ha tenido en cuenta la edad los pacientes. Objetivo: Evaluar la relación de los marcadores sanguíneos con la edad y características clínicas de pacientes con ictus isquémico. Métodos: Se incluyeron en el estudio 2 grupos de pacientes con ictus isquémico (( y > 55 años) quienes fueron pareados con grupos controles. Fueron determinados: PCR, alfa 1 antitripsina (AAT), complementos C3 y C4, microalbuminuria, ceruloplasmina, glucosa, colesterol, triglicéridos, transaminasa glutámico-pirúvico (TGP), transaminasa glutámico-oxalacético (TGO), gamma glutamiltranspeptidasa (GGT), creatinina, y ácido úrico. También, se recogió información clínica (escala neurológica, etiología y localización del ictus). Resultados: La AAT, ceruloplasmina, microalbuminuria, TGP, TGO y GGT aumentaron significativamente respecto al grupo control de ambos grupos de estudio. Sin embargo, la PCR se incrementó solamente en pacientes mayores de 55 años. La PCR se correlacionó directamente con la edad de los pacientes, pero no en el grupo control. A su vez, se observó una tendencia hacia el aumento de la PCR en pacientes mayores de 55 años con mayor la severidad neurológica. Los valores de PCR se incrementaron estadísticamente con la edad de acuerdo al déficit neurológico. Conclusiones: La edad debiera ser considerada en la evaluación de la utilidad de la PCR y de otros marcadores como herramientas clínicas para predecir un desenlace neurológico fatal o recurrencia de nuevos eventos en pacientes con ictus isquémico(AU)

CSF oligoclonal band frequency in a Cuban cohort of patients with multiple sclerosis. comparison with Latin American countries and association with latitude.

BACKGROUND: The diagnostic sensitivity of CSF specific oligoclonal bands (OCBs) in multiple sclerosis (MS), using state of the art methods, has been clearly established to be over 95% in patients with a predominantly Caucasian background. This is not the case for other geographical regions, where reports of OCB prevalence can be much lower, and a relationship between OCB frequency and latitude has been suggested. OBJECTIVE: The aim of the present study was to assess the frequency of OCBs in a cohort of MS patients evaluated at the Institute of Neurology and Neurosurgery (Havana, Cuba), and to review the scientific literature in order to investigate the possible relationship between OCB status and latitude in the region of Latin America. METHODS: Fifty-three patients (47 with definite MS and 6 with clinically isolated syndrome - CIS) were included. Isoelectric focusing (IEF) with IgG immunoblotting for OCB analyses, was performed placing paired CSF and serum samples in the same analytical run. PubMed, Scielo and Google Scholar were searched for papers containing information concerning CSF OCB status (employing isoelectric focusing with IgG immunoblotting) in patients with definite MS in Latin America and the Caribbean. RESULTS: In Cuban patients with definite MS, an OCB prevalence of 87% was observed, while the frequency in CIS patients was lower (67%). The prevailing pattern was that of OCBs restricted to the CSF (type 2), which was observed in 71% of definite MS patients and in all CIS patients with intrathecal IgG synthesis. OCB prevalence was slightly lower, but very close to that reported in Caucasian populations. Comparison with other Latin American countries revealed a significant correlation between OCB prevalence and latitude. CONCLUSIONS: A prevalence of CSF restricted OCBs of 87% was observed in definite MS patients, a frequency which was slightly lower, but similar to that reported in Caucasian populations. The analysis of OCB frequency in Latin American countries revealed a possible relationship between OCB prevalence and latitude, but this must be further investigated in more countries and larger samples of patients.

Serum neuron specific enolase could predict subclinical brain damage and the subsequent occurrence of brain related vascular events during follow up in essential hypertension.

The object of this work was to explore if blood based biomarkers of brain damage could predict subclinical brain lesions and clinical outcome during follow-up in asymptomatic hypertensive patients. This was a cross-sectional study including 101 patients with essential hypertension and no clinical evidence of neurological disease and 53 healthy controls, followed by a longitudinal study of 62 hypertensive patients for an average of 33 months. Serum concentrations of two brain specific proteins (S100B and neuron specific enolase - NSE) were determined at inclusion. Fundoscopic exploration, brain MRI and echocardiographic studies were also performed. Clinical outcome at follow-up was registered: transient ischemic attack (TIA), stroke, vascular headache or migraine, cardiovascular events and death. Higher serum NSE and S100B concentrations were observed in hypertensive patients; and multiple regression analysis revealed independent associations of clinical variables and more severe white matter lesions only with NSE concentration. A panel combining two clinical variables (blood pressure>140/90 and years of hypertension>10) and serum NSE>13 µg/L predicted more severe white matter lesions with 80% sensitivity and 94.4% specificity. Higher NSE levels at inclusion were associated not only with the occurrence of vascular events related with the CNS (stroke, TIA and vascular headache), but also with an earlier presentation of these events during the follow-up period. Serum NSE concentration could be a useful biomarker to predict subclinical brain damage and future vascular events related with the CNS in hypertension. Blood based biomarkers could aid in filtering hypertensive patients with a higher risk of cerebrovascular disease for brain MRI scanning.

Association of status redox with demographic, clinical and imaging parameters in patients with Huntington's disease.

UNLABELLED: Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder, caused by an expanded trinucleotide CAG sequence of the huntingtin (Htt) gene, which encodes a stretch of glutamines in the Htt protein. The mechanisms of neurodegeneration associated with the accumulation of Htt aggregates still remains unclear. OBJECTIVES: To determine oxidative stress biomarkers in HD patients and their relationship with clinical, demographic and neuroimaging parameters. DESIGN AND METHODS: Fourteen patients and 39 controls paired by age and sex participated in this study. Oxidative damage was assayed in blood by measuring malondialdehyde (MDA) and advanced oxidative protein products (AOPPs). Antioxidant status was determined by activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH), protein thiols and total antioxidant capacity (FRAP). The Unified Huntington Disease Rating Scale (UHDRS) and neuroimaging studies were also employed. RESULTS: MDA, AOPP and GPx were significantly increased in HD patients with respect to the control group, while GR activity was decreased. FRAP correlated with age of disease onset, AOPP with motor severity (UHDRS score), age of patients and age of disease onset. Caudate atrophy was associated with lower plasma concentrations of GSH. CONCLUSIONS: These findings point to a redox imbalance in HD patients. GR activity could be a potential biomarker for symptom onset in asymptomatic gene carriers, while plasmatic GSH could be useful in monitoring the progression of neurodegeneration - as an expression of caudate atrophy - during the course of the disease.

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)

Efectos adversos por el uso de la biomodulina T y la corticotropina en pacientes con esclerosis múltiple / Adverse effects due to the usage of T biomodulina and corticotropin in patients suffering from Multiple Sclerosis

Fundamento: La biomodulina T es unproducto natural tímico con acción antinflamatoria y acción inmunomoduladora. La corticotropina es un esteroide utilizado también en el tratamiento de la esclerosis múltiple. Objetivo: Comparar el comportamiento de efectos adversos de la biomodulina y la corticotropina en el tratamiento de la esclerosis múltiple. Métodos: Ensayo clínico fase II, abierto, aleatorizado y controlado, sobre 17 pacientes con esclerosis múltiple a los que se les aplicó el siguiente tratamiento: a un grupo se le suministró 100 miligramos por vía endovenosa de biomodulina por 10 días, 20 miligramos los siguientes 20 días; al otro grupo 1 miligramo de corticotropina por 10 días, seguido de 0, 5 mg por los restantes 20 días. Se evaluaron los eventos adversos a los 10 y 30 días, clasificando su intensidad como ausentes, ligeros, moderados, severos, muy severos, así como duración y tipo de evento. Resultados: Se evaluó la seguridad en 8 pacientes con biomodulina y 7 con corticotropina. Ocurrieron 40 eventos adversos: 24 con corticotropina y 16 con biomodulina (80 y 53,3 por ciento respectivamente). Fueron más frecuentes los eventos ligeros con biomodulina que con corticotropina (56 y 18 por ciento respectivamente), mientras fueron más frecuentes los moderados con corticotropina. Fue más corto el tiempo de duración de los eventos producidos por biomodulina. Conclusiones: La biomodulina fue segura en el tratamiento de la esclerosis múltiples pues sus efectos adversos fueron menos intensos y de menor duración(AU)

Background: T biomodulina is a thymic natural product with anti-inflammatory and immunomodulator action. Corticotropin is a steroid which is also used in the treatment of multiple sclerosis. Objetives: To compare the adverse effects of the biomodulina and corticotroprin in the treatment of multiple sclerosis. Methods: Phase II clinical trial, open, randomized and controlled on 17 patients suffering from multiple sclerosis to whom the following treatment was applied: group one, 100mg IV biomodulina during 10 days, 20 mg the following 20 days; group two: 1 mg of corticotroprin during 10 days followed by 0,5 mg the very next 20 days. The adverse events were evaluated from the 10th day up to the 30th day classifying its intensity as absent, mild, moderate, severe, very severe. The duration and the type of event were also classified. Results: Safeness on 8 patients treated with biomodulina and 7 patients treated with cortcotropin were assessed. 40 adverse events took place: 24 patients in whose corticotropin was used, 16 in the treatment with biomodulina (80 and 53, 3 percent respectively), while the moderate adverse reactions in the usage of corticotropin were more frequent. The shorter period of time of the events was produced by biomodulina. Conclusions: The usage of biomodulina was safer in the treatment of multiple sclerosis because the adverse events as well as the period of time were less intense(AU)

[Gene expression of Interleukin 1 in vitamin A and proteins deficiency]. / Expresión génica de interleucina 1 en la deficiencia de proteínas y vitamina A.

The influence of low levels of protein and vitamin A on indicators of the immune response was assayed in rats. The levels of protein and vitamin A intake of the Cuban population affected by epidemic neuropathy in 1993 was reproduced in 4 diets: control, protein deficiency (DP), vitamin A deficiency (DA), protein and vitamin A deficiency (DAP). The Peyer's patches evaluated the Interleukin 1 expression gene and was related with corporal weight, food intake, serum protein, vitamin A, immunology indicators and histology evaluation (spleen, thymus and liver). Protein deficiency generated a significant decrease of the expression gene of Interleukin 1. Atrophy signs in lymphoid tissues and morphologic changes in the liver were associated with the dietary protein utilization. Protein and vitamin A deficiency generated significant stimulation of the Interleukin 1 expression gene with increase of the level of the inflammatory state indicators as serum alpha protein, total complement and neutrophils. This stimulation could be generated by a deficient retinol mobilization to tissues. These results support the hypothesis of the function of cytokines as mediators of subclinical symptoms of the immune system during the nutritional affectations.

Expresión génica de interleucina 1 en la deficiencia de proteínas y vitamina A / Gene expression of interleukin 1 in vitamina A and protein deficiency

Tomando como referencia los niveles de ingestion de proteínas y vitamina A informados en los estudios de la población cubana durante la epidemia de neuropatía de 1993, se ejecutó un biomodelo en ratas, con el objetivo de evaluar la incidencia de estos niveles sobre algunos indicadores de estado nutricional y de la respuesta inmune. Para ello se ensayaron 4 dietas: control, deficiente en proteínas, deficiente en vitamina A y deficiente en proteínas y vitamina A. La Interleucina 1 (IL-1) se evaluó a partir de su expresión en las placas de Peyer y los resultados obtenidos se relacionaron con indicadores del estado nutricional como peso, ingesta, recambio proteico, proteínas plasmáticas y vitamina A, con indicadores inmunológicos (conteo celular y complemento hemolítico total) y con el estudio histológico realizado en timo, bazo e hígado. La deficiencia de proteínas disminuyó la expresión génica de IL-1, la cual se asoció con lesiones degenerativas y de atrofia en los órganos estudiados. La deficiencia de proteínas y vitamina A provocó una estimulación de la expresión génica de IL-1, asociada además con indicadores sensibles del estado inflamatorio, que pudiera ser el resultado de una movilización deficiente de retinol hacia los tejidos. Los resultados obtenidos en el biomodelo abren la posibilidad de utilización de las citocinas en la detección de afectaciones subclínicas del sistema inmune provocadas por deficiencias nutricionales

Isoenzimas de la deshidrogenasa láctica en la distrofia muscular progresiva tipo Duchenne / Izoenzye of lactic dehydrogenase in Duchenne's type progressive muscular dystrophy

Se determinaron las isoenzimas de la deshidrogenasa láctica (LD) en un grupo de sujetos sanos, en pacientes con distrofia muscular progresiva tipo Duchenne (DMD) y en posibles portadoras de esta enfermedad. La separación se realizó por electroforesis en gel de poliacrilamida al 6,2

, con tinción específica de las isoenzimas mediante reacción enzimática en presencia de lactato, dinucleótido de adenina nicotinamida (NAD+), metosulfato de fenacina y nitro blue tetrazolium (NBT). Se observó un incremento de la isoenzima LD2, con disminución de LD1 en el grupo de pacientes con DMD; las mayores alteraciones se vieron en aquellos apcientes con más tiempo de evolución de la enfermedad. En el grupo de posibles portadoras se demostró aumento de la isoenzima LD2. Se concluyó que le empleo del isoenzimograma de la LD sérica pude resultar tan útil como la determinación de creatinoquinasa (CK) para la detección de portadoras

Isoenzimas de la deshidrogenasa láctica en la distrofia muscular progresiva tipo Duchenne / Izoenzyme of lactic dehydrogenase in Duchenne's type progressive muscular dystrophy

Se determinaron las isoenzimas de la deshidrogenasa láctica (LD) en un grupo de sujetos sanos, en pacientes con distrofia muscular progresiva tipo Duchenne (DMD) y en posibles portadoras de esta enfermedad. La separación se realizó por electroforesis en gel de poliacrilamida al 6,2 %, con tinción específica de las isoenzimas mediante reacción enzimática en presencia de lactato, dinucleótido de adenina nicotinamida (NAD+), metosulfato de fenacina y nitro blue tetrazolium (NBT). Se observó un incremento de la isoenzima LD2, con disminución de LD1 en el grupo de pacientes con DMD; las mayores alteraciones se vieron en aquellos apcientes con más tiempo de evolución de la enfermedad. En el grupo de posibles portadoras se demostró aumento de la isoenzima LD2. Se concluyó que le empleo del isoenzimograma de la LD sérica pude resultar tan útil como la determinación de creatinoquinasa (CK) para la detección de portadoras