Oxidative stress involvement in the molecular pathogenesis and progression of multiple sclerosis: a literature review.

Multiple sclerosis (MS) is an autoimmune debilitating disease of the central nervous system caused by a mosaic of interactions between genetic predisposition and environmental factors. The pathological hallmarks of MS are chronic inflammation, demyelination, and neurodegeneration. Oxidative stress, a state of imbalance between the production of reactive species and antioxidant defense mechanisms, is considered one of the key contributors in the pathophysiology of MS. This review is a comprehensive overview of the cellular and molecular mechanisms by which oxidant species contribute to the initiation and progression of MS including mitochondrial dysfunction, disruption of various signaling pathways, and autoimmune response activation. The detrimental effects of oxidative stress on neurons, oligodendrocytes, and astrocytes, as well as the role of oxidants in promoting and perpetuating inflammation, demyelination, and axonal damage, are discussed. Finally, this review also points out the therapeutic potential of various synthetic antioxidants that must be evaluated in clinical trials in patients with MS.

Difference in mortality rates in hospitalized COVID-19 patients identified by cytokine profile clustering using a machine learning approach: An outcome prediction alternative.

COVID-19 is a disease caused by the novel Coronavirus SARS-CoV-2 causing an acute respiratory disease that can eventually lead to severe acute respiratory syndrome (SARS). An exacerbated inflammatory response is characteristic of SARS-CoV-2 infection, which leads to a cytokine release syndrome also known as cytokine storm associated with the severity of the disease. Considering the importance of this event in the immunopathology of COVID-19, this study analyses cytokine levels of hospitalized patients to identify cytokine profiles associated with severity and mortality. Using a machine learning approach, 3 clusters of COVID-19 hospitalized patients were created based on their cytokine profile. Significant differences in the mortality rate were found among the clusters, associated to different CXCL10/IL-38 ratio. The balance of a CXCL10 induced inflammation with an appropriate immune regulation mediated by the anti-inflammatory cytokine IL-38 appears to generate the adequate immune context to overrule SARS-CoV-2 infection without creating a harmful inflammatory reaction. This study supports the concept that analyzing a single cytokine is insufficient to determine the outcome of a complex disease such as COVID-19, and different strategies incorporating bioinformatic analyses considering a broader immune profile represent a more robust alternative to predict the outcome of hospitalized patients with SARS-CoV-2 infection.

Neuromyelitis Optica Spectrum Disorder in Central America and the Caribbean: A Multinational Clinical Characterization Study.

Here, a study of NMOSD in Central America and the Caribbean with a multinational collaborative, multicentric and descriptive approach involving 25 institutions from 9 countries is presented. Demographics, clinical manifestations, expanded disability scale status (EDSS), brain and spinal cord MRI, serological anti-AQP4-IgG and anti-MOG-IgG antibodies, and cerebrospinal fluid (CSF) oligoclonal bands were included. A central serological repository utilized the cell-based assay. The specimens outside of this network employed diverse methodologies. Data were collected at the Gorgas Commemorative Institute of Health Studies (ICGES), Panama, and included 186 subjects, of which 84% were females (sex ratio of 5.6:1). Mestizos constituted 72% of the study group. The median age was 42.5 years (IQR: 32.0-52.0). Associated autoimmune diseases (8.1%) were myasthenia gravis, Sjögren's syndrome and systemic lupus erythematosus. The most common manifestation was optic neuritis-transverse myelitis (42.5%). A relapsing course was described in 72.3% of cases. EDSS scores of 0-3.5 were reported in 57.2% of cases and higher than 7.0 in 14.5%. Positive anti-AQP4-IgG antibody occurred in 59.8% and anti-MOG-IgG antibody in 11.5% of individuals. Antibody testing was lacking for 13.4% of patients. The estimated crude prevalence of NMOSD from Panama and the Dominican Republic was 1.62/100,000 (incidence of 0.08-0.41) and 0.73/100,000 (incidence 0.02-0.14), respectively. This multinational study contributes additional insights and data on the understanding of NMOSD in this Latin American region.

Intravenous tocilizumab in the management of rheumatoid arthritis: Clinical practice findings from a 6-month international, multicentre, observational study in Central America and the Caribbean / El tocilizumab intravenoso en el tratamiento de la artritis reumatoide: resultados de la práctica clínica de un estudio internacional, multicéntrico y observacional de 6 meses de duración en América Central y el Caribe

ABSTRACT Tocilizumab (TCZ), an 1interieukin-6 receptor-α Inhibitor, is Indicated in patients with moderate to severe rheumatoid arthritis with inadequate response to disease modifying drugs. ACT UP is a multinational project co11ecting information from severa1 post-marketing TCZ studies. Aim: To determine the proportion of patients in the routine clinical care setting receiving intravenous TCZ after 6 months treatment. Identification of TCZ treatment patterns, efficacy, and safety were also recorded. Method: This prospective non-interventional 6-month study, collected real-world information from 169 Central American and Caribbean patients. No interventional procedures or additional visits outside routine clinical care practice were performed. Statistical analysis was essentially descriptive. Results: Adherence rate was 74.0%, with 97% of patients receiving TCZ as first biological therapy line and there were no deviations from the local label. Almost 85% of patients started with combination therapy, and the majority remained under this scheme throughout the study. A significant decrease in disease activity assessments and acute phase reactants values were detected during TCZ treatment. The percentage of patients that achieved improvement according to the different levels of the American College of Rheumatology (ACR) increased during the study, and relevant enhancements in quality of life were also accomplished. Adverse events (AEs) occurred in 35 patients, with metabolic and nutritional disorders being the most common. Serious AEs were reported in 3% of patients, and special interest AEs occurred in 6 patients. Conclusion: Treatment adherence was mainly determined by follow-up and compliance with the administration schedule. Efficacy analysis showed better results than those reported in international literature. The incidence of AEs was also lower than in previously published data.

RESUMEN El tocilizumab (TCZ) está indicado en la artritis reumatoide moderada a severa, principalmente en respuestas inadecuadas a fármacos convencionales. ACT UP es un proyecto multinacional que recopila información relacionada con varios estudios de poscomercialización. Objetivo: Determinar la proporción de pacientes en la atención clínica de rutina que continúan en tratamiento con TCZ intravenoso después de 6 meses. Se llevó a cabo la identificación de patrones de administración, eficacia y seguridad. Método: Este estudio observacional prospectivo recopiló información de la vida real de 169 pacientes de América Central y el Caribe. No se hicieron intervenciones ni visitas adicionales fuera de la práctica clínica habitual. El análisis estadístico fue esencialmente descriptivo. Resultados: La tasa de adherencia al tratamiento fue del 74,0%, el 97% de los pacientes reci bieron TCZ como primera línea biológica y no existieron desviaciones en las indicaciones de administración según el inserto local. Aproximadamente el 85% de los pacientes inició TCZ como terapia combinada, y la mayoría permaneció bajo este esquema. Se evidenció una dis minución en la actividad de la enfermedad y un aumento en el porcentaje de pacientes que lograron respuesta según los diferentes grados del Colegio Americano de Reumatología. En 35 pacientes se presentaron eventos adversos (EA), siendo los relacionados con metabolismo y nutrición los más comunes. Se informaron EA graves en el 3% de los pacientes y de interés especial en 6 casos. Conclusión: El seguimiento de los pacientes y el cumplimiento del programa fueron los prin cipales determinantes en la adherencia. El análisis de eficacia mostró mejores resultados que los reportados previamente y la incidencia de EA fue menor que en otros estudios.

Contact dermatitis: Clinical practice findings from a single tertiary referral hospital, a 4-Year retrospective study.

BACKGROUND: It is estimated that 20% of the general population is sensitized to some kind of contact allergen. Contact dermatitis is one of the major occupational diseases worldwide. This disease has a higher prevalence in the female gender and is more frequently observed in the third or fourth decade of life. The main objective of this study was to describe the main sociodemographic and clinical characteristics of patients with contact dermatitis treated in the Allergy Unit of the San Juan De Dios Hospital - Caja Costarricense de Seguro Social. METHODS: Clinical records of contact dermatitis outpatients from a single hospital were analyzed, in a 4-year retrospective observational study. RESULTS: At the time of the patch testing, patients showed a mean age of 42.2 years. Disease frequency was higher in the female population (female/male ratio of 4.2:1) and in patients mostly dedicated to household workchores. Most patients presented several years of disease history, and the hands were the highest affected body part. Patch testing revealed that nickel sulfate, Cl+Me-Isothiazolinone (Kathon CG), and thimerosal were allergens regularly associated with contact dermatitis in the analyzed population. CONCLUSIONS: To a great extent, sociodemographic and clinical characteristics identified in these patients resemble what is reported in other regions, including the Americas and worldwide. It is worth highlighting a high female proportion rate probably related to cultural aspects, a smaller percentage of irritant contact dermatitis that may be associated to institutional patient management, and a slight difference in the most common allergens when compared to other published studies.

Biological models in multiple sclerosis.

Considering the etiology of multiple sclerosis (MS) is still unknown, experimental models resembling specific aspects of this immune-mediated demyelinating human disease have been developed to increase the understanding of processes related to pathogenesis, disease evolution, evaluation of therapeutic interventions, and demyelination and remyelination mechanisms. Based on the nature of the investigation, biological models may include in vitro, in vivo, and ex vivo assessments. Even though these approaches have disclosed valuable information, every disease animal model has limitations and can only replicate specific features of MS. In vitro and ex vivo models generally do not reflect what occurs in the organism, and in vivo animal models are more likely used; nevertheless, they are able to reproduce only certain stages of the disease. In vivo MS disease animal models in mammals include: experimental autoimmune encephalomyelitis, viral encephalomyelitis, and induced demyelination. This review examines and describes the most common biological disease animal models for the study of MS, their specific characteristics and limitations.

Molecular Pathogenesis of Alzheimer's Disease: An Update.

Dementia is a chronic or progressive syndrome, characterized by impaired cognitive capacity beyond what could be considered a consequence of normal aging. It affects the memory, thinking process, orientation, comprehension, calculation, learning ability, language, and judgment; although awareness is usually unaffected. Alzheimer's disease (AD) is the most common form of dementia; symptoms include memory loss, difficulty solving problems, disorientation in time and space, among others. The disease was first described in 1906 at a conference in Tubingen, Germany by Alois Alzheimer. One hundred and ten years since its first documentation, many aspects of the pathophysiology of AD have been discovered and understood, however gaps of knowledge continue to exist. This literature review summarizes the main underlying neurobiological mechanisms in AD, including the theory with emphasis on amyloid peptide, cholinergic hypothesis, glutamatergic neurotransmission, the role of tau protein, and the involvement of oxidative stress and calcium.

Caracterización de los pacientes con epilepsia refractaria de un hospital de tercer nivel en Costa Rica / Characteristics of patients with refractory epilepsy attended in a tertiary referral center in Costa Rica

Introducción. El 30% de los pacientes con epilepsia presenta convulsiones recurrentes, porcentaje que representa aproximadamente a 15 millones de personas en el mundo y constituye una población escasamente descrita. Objetivo. Caracterizar sociodemográfica y clínicamente la población de pacientes diagnosticados con epilepsia refractaria en un hospital terciario de Costa Rica. Pacientes y métodos. Se analizan los registros médicos de los pacientes con epilepsia refractaria valorados en la unidad de epilepsia del Hospital San Juan de Dios de la Caja Costarricense del Seguro Social desde agosto de 2012 a octubre de 2014. Resultados. Se incluyen los expedientes clínicos de 91 pacientes. La edad media de inicio fue de 13,1 ± 11,1 años. Las crisis secundariamente generalizadas constituyen el tipo predominante (81,3%), la etiología más frecuente es la esclerosis mesial temporal (48,3%) y la mayoría de los pacientes presentaba exámenes neurológicos normales y valoraciones neuropsicológicas normales o bajas. Alrededor de la mitad (48,8%) de los pacientes había sido medicada con un rango de 4-6 fármacos antiepilépticos, y los más prescritos fueron lamotrigina, carbamacepina, ácido valproico y fenitoína. Las principales recomendaciones en estos pacientes fueron: optimización de tratamiento, neurocirugía y reingreso. Se observan diferencias entre la edad de inicio y el sexo, la frecuencia de las crisis y el sexo, el tiempo de evolución de la patología y la cantidad de tratamientos fallidos, y el tiempo de evolución de la enfermedad y la ocupación. Conclusiones. Las características sociodemográficas, el manejo de los pacientes, los fármacos antiepilépticos utilizados y las diferencias encontradas son similares a las descritas en otras latitudes (AU)

Introduction. Thirty percent of patients with epilepsy have recurrent seizures, representing fifteen million people in the world. This population has been scarcely described. Aim. To characterize sociodemographic and clinically the patients diagnosed with refractory epilepsy in a tertiary referral hospital of the Costa Rican social security. Patients and methods. This study presents an analysis of all cases of refractory epilepsy evaluated at the epilepsy unit of San Juan de Dios Hospital from August, 2012 to October, 2014. Results. Clinical records of 91 patients were studied; patients with psychogenic seizures were analyzed separately. The mean age of onset was 13.1 ± 11.1 years, secondary generalized seizures were the predominant type (81.3%), the most frequent etiology was mesial temporal sclerosis (48.3%) and the majority had normal neurological exams and normal or low neuropsychological assessments. Around half (48.8%) of the patients had been medicated with a range of 4-6 antiepileptic drugs, being lamotrigine, carbamazepine, valproic acid and phenytoin the most prescribed. Treatment optimization, neurosurgery, and further analysis were standard recommendations. Sociodemographic characteristics, patient management, and antiepileptic drugs used are similar to the described in other latitudes. Differences between the age of onset and gender; seizure frequency and gender; age of onset and failed treatments and time of evolution of the disease and employment were observed. The percentage and characteristics of recurrent seizures of psychogenic nature found are comparable to other refractory epilepsy studies. Conclusion. Sociodemographic characteristics, management of patients, antiepileptic drugs used and the differences observed are similar to those previously described (AU)