Una aproximación actualizada hacia el tratamiento de la esclerosis múltiple / An updated approach to the treatment of multiple sclerosis

La presente es una revisión bibliográfica actualizada sobre el manejo de la Esclerosis Múltiple (EM), enfermedad neurológica progresiva de tipo desmielinizante más frecuente a nivel mundial. En Chile, su presentación remitente-recurrente (RRMS) es patología GES, por lo que se vuelve relevante para el médico general y estudiantes del área de la salud reconocer e identificar las terapias disponibles para el control de esta patología. Si bien la EM no es un cuadro frecuente, su sintomatología es alarmante e incapacitante, por lo que, con frecuencia, el primer acercamiento del paciente es a los servicios de urgencia, tornándose necesario contar con nociones básicas sobre el tratamiento y manejo. La presente revisión recopiló artículos publicados entre 2019 y 2023 de distintos motores de búsqueda con énfasis en el tratamiento farmacológico y no farmacológico de esta enfermedad. Además de describir el tratamiento convencional como la inmunomodulación, las terapias biológicas, el soporte con glucocorticoides y los fármacos remielinizantes, se abordan nuevas líneas de investigación prometedoras, como el rol inmunogénico de la microbiota intestinal, la capacidad epigenética de la dieta, estrategias de rehabilitación cognitiva y el potencial uso de cannabinoides para el manejo paliativo del dolor. Se concluye que un tratamiento oportuno con fármacos modificadores de la enfermedad, tanto de primera línea como de segunda, son imprescindibles para el manejo de la EM, sin embargo, la calidad de vida puede verse significativamente acrecentada por la incorporación de estrategias que se encuentran al alcance del médico general y que no requieren de derivación a nivel secundario.

This is an updated bibliographical review on the management of Multiple Sclerosis (MS), the most common progressive neurological disease of demyelinating disorders worldwide. In Chile, its relapsing-remitting presentation (RRMS) is a state-covered illness pathology, so it becomes relevant for the general practitioner and med students to recognize and identify therapies available for the control of this desease. Although MS is not a frequent condition, its symptoms are alarming and disabling, which is why, frequently, the first approach of the patient is to the emergency services, making it necessary to have basic knowledge about treatment and management. The present review compiled articles published between 2019 and 2023 from different search engines with an emphasis on the pharmacological and non-pharmacological treatment of the MS. In addition to describing conventional treatment such as immunomodulation, biological therapies, glucocorticoid support and remyelinating drugs, new promising lines of research are addressed, such as the immunogenic role of the intestinal microbiota, the epigenetic capacity of the diet, strategies on cognition rehabilitation and the potential use of cannabinoids for the palliative management of pain. It is concluded that the classic treatment with disease-modifying drugs, both first-line and second-line, are essential for the management of MS; however, quality of life can be significantly increased by incorporating strategies found at the reach of the general practitioner and do not require referral at a greater complexity center.

Experimental determination of Gd dose enhancement and Gd dose sparing by 192Ir brachytherapy source with Gafchromic EBT3 dosimeter.

This work evaluates experimentally the dose enhancement factor (DEF) and dose sparing factor (DSF) due to radiation self-shielding, produced by Gd infused in tumor phantom irradiated with brachytherapy HDR 192Ir source by Gafchromic EBT3 dosimeter. The phantom was made of a set of solid water slabs (30 × 30 × 1.0) cm3 and three acrylic slabs of (30 × 30 × 0.5) cm3 machined to contain in the central axis acrylics vials of (1 × 1 × 5) cm3. The first and second acrylic vials were filled with an identical Gd solution of 0, 10 and 20 mg/ml, simulating Gd-doped and undoped tumor, and the third vial was filled in all the measurement only with water, representing an organ at risk. Additional solid water slabs were used to complete a phantom of (30 × 30 × 16) cm3. In the phantom center an acrylic slab was machined to introduce the 2.5 mm flexible guide tube of GammaMed plus iX equipment and positioning the 192Ir source in the phantom central part. EBT3 fragments of (0.9 × 4) cm2 were placed on the inner edge of the second and third vials to measure dose enhancement and dose sparing simultaneously. Phantom CT images were acquired for planning and to prescribe a dose of 6.0 Gy at 2.0 cm of the source, achieving an isodose curve of 44.5% at 3.0 cm (positions of the EBT3 films). Additionally, Monte Carlo simulation of the identical experimental setup was implemented to compare measurement values. The results showed the feasibility of measuring a DEF of 1.15 ± 0.05 in 20 mg/ml of Gd concentration consistent with the Monte Carlo DEF of 1.112 ± 0.005 for the same concentration. DEF value for concentration of 10 mg/ml would not be detected (1.00 ± 0.04) by an expected under measurement of the EBT3 films associated with the non-detection of photoelectrons and Auger electrons of very low energy that cannot reach the radiosensitive substrate.

Monte Carlo evaluation of the dose sparing and dose enhancement by combination of Gd-infused tumor and 241Am source for an endocavitary brachytherapy geometry.

In this work, the benefits in terms of dose enhancement and dose sparing via radiation shielding are evaluated, for a combined irradiation scheme with sources of 241Am and tumor-infused with Gd agents, regarding conventional 192Ir treatment. Monte Carlo simulations using PENELOPE code were implemented for endocavitary brachytherapy geometries, configuring a pelvis phantom of 15 cm radius and 30 cm length. Inside, it was defined cylindrical tumor phantoms of 2 cm radius and 4 cm-6 cm length (simulating initial stages) as well as tumors of extensive volume (2.5 and 3.0 cm radius) and difficult coverage. Tumor phantoms were doped with 68 mM and 138 mM of Gd in order to assess the effects of enhancement and protection based on the concentration and emission energy of the isotope. Obtained results for the first tumor group, shown the feasibility of achieving dose enhancements of 94.3%-117% and 160%-194% for 68 mM and 138 mM of Gd infused into the tumor and irradiation with 241Am, respectively. Similarly, reduced dose enhancements of 3.5-5.7% y 8.9%-11.2% for 68 mM and 138 mM of Gd are attained with 192Ir. In terms of dose sparing outer the tumor, the radiation shielding and dose enhancement allowed a higher reduction in the dose by 241Am of 17%-24% for 68 mM and 21%-32% for 138 mM of Gd, and non-negligible dose sparing are produced too by 192Ir of 2% and 5% for the same concentration of Gd. For the second tumors group, the combined use of 241Am and Gd agents simultaneously allowed to improve coverage and reduce the healthy tissue dose, showing the obtained results the possibility of achieving coverage of 95% of the prescribed dose in 100% of tumor volume together with dose sparing factor of 6-21% reduction in isodose of the studied point and dose enhancements of 75%-158% at the prescription point.

Experimental determination of the gadolinium dose enhancement in phantom irradiated with low energy X-ray sources by a spectrophotometer -Gafchromic-EBT3 dosimetry system.

This work reports the experimental determination of dose enhancement produced in phantoms containing target volumes doped with Gadolinium and irradiated with low-energy X-ray beams. EBT3 Gafchromic films were immersed into 5 ml target volumes to simulate tumor filling with 100% ultra-pure water (blank sample) and ultra-pure water infused with Gd solution (Omniscan®) in different concentration (9-24 mg/ml). The dose enhancement due to excitation of Gd K-edge (50.2 keV) was evaluated in terms of the increment in optical density, obtained by a Spectrophotometer-Gafchromic-EBT3 dosimetry system calibrated in terms of the dose-response for 1-8 Gy range. The dose enhancement was evaluated in two condition: a beam quality with spectrum above the absorption edge in a medium with and without Gd; and two beam qualities (above and below the absorption edge) in a medium with a fixed Gd concentration (18 mg/ml). The obtained results confirmed increments in relative dose enhancement according to Gd concentrations up to 18 mg/ml, with a dose enhancement of 1.1 Gy and an average percentage enhancement of 28.4%. For higher values of concentration, the attenuation interaction of the primary beam is more relevant instead of dose enhancement process. On the other hand, the dose enhancement obtained to comparison the spectra above and below the absorption edge, shown results up to 3.3 Gy of enhancement and average percentage enhancement of 88%.

Metabolic impact of an NADH-producing glucose-6-phosphate dehydrogenase in Escherichia coli.

In Escherichia coli, the oxidative branch of the pentose phosphate pathway (oxPPP) is one of the major sources of NADPH when glucose is the sole carbon nutrient. However, unbalanced NADPH production causes growth impairment as observed in a strain lacking phosphoglucoisomerase (Δpgi). In this work, we studied the metabolic response of this bacterium to the replacement of its glucose-6-phosphate dehydrogenase (G6PDH) by an NADH-producing variant. The homologous enzyme from Leuconostoc mesenteroides was studied by molecular dynamics and site-directed mutagenesis to obtain the NAD-preferring LmG6PDH(R46E,Q47E). Through homologous recombination, the zwf loci (encoding G6PDH) in the chromosomes of WT and Δpgi E. coli strains were replaced by DNA encoding LmG6PDH(R46E,Q47E). Contrary to some predictions performed with flux balance analysis, the replacements caused a substantial effect on the growth rates, increasing 59 % in the Δpgi strain, while falling 44 % in the WT. Quantitative PCR (qPCR) analysis of the zwf locus showed that the expression level of the mutant enzyme was similar to the native enzyme and the expression of genes encoding key enzymes of the central pathways also showed moderate changes among the studied strains. The phenotypic and qPCR data were integrated into in silico modelling, showing an operative G6PDH flux contributing to the NADH pool. Our results indicated that, in vivo, the generation of NADH by G6PDH is beneficial or disadvantageous for growth depending on the operation of the upper Embden-Meyerhof pathway. Interestingly, a genomic database search suggested that in bacteria lacking phosphofructokinase, the G6PDHs tend to have similar preferences for NAD and NADP. The importance of the generation of NADPH in a pathway such as the oxPPP is discussed.

(E)-3-Ferrocenyl-1-(2-hy-droxy-phen-yl)-prop-2-en-1-one.

The mol-ecular structure of the title compound, [Fe(C(5)H(5))(C(14)H(11)O(2))] consists of a ferrocenyl and 2-hy-droxy-phenyl group linked through the prop-2-en-1-one spacer and is stabilized by an intra-molecular O-H⋯O hydrogen bond between the hydroxyl and the carbonyl groups.

(Z)-3-(4-Bromo-anilino)-1-ferrocenylbut-2-en-1-one.

In the title compound, [Fe(C(5)H(5))(C(15)H(13)BrNO)], formed from the reaction of ferrocenoylacetone and 4-bromo-aniline, the mol-ecular structure is stabilized by an intra-molecular N-H⋯O hydrogen bond between the amine and carbonyl groups.

Evaluación y manejo integral de la disfagia orofaríngea / Oropharyngeal dysphagia: assesment and management

La disfagia corresponde a una “sensación de dificultad en el avance de la comida desde la boca al estómago” dada por una alteración en alguna de las cuatro etapas de la deglución. Su prevalencia en la población general es de un 6-9 por ciento y se asocia a complicaciones como neumonía aspirativa, desnutrición, deshidratación y obstrucción de la vía aérea. La disfagia orofaríngea es especialmente prevalente en mayores de 75 años, en portadores de cuadros neurológicos (p.ej. accidente vascular encefálico) y en pacientes que han requerido una instrumentación de su vía aérea (intubación orotraqueal y/otraqueostomía). El estudio de la disfagia orofaríngea puede realizarse mediante evaluación clínica, videofluoroscopía, estudio endoscópico con y sin evaluación sensitiva y en el laboratorio de señales de la deglución. El manejo de los pacientes con trastornos de la deglución orofaríngea es multidisciplinario: médico otorrinolaringólogo, fonoaudiólogo, nutricionista, médico fisiatra, radiólogo, KNT, terapeuta ocupacional y enfermera.

The term dysphagia refers to a “feeling of difficulty in the advance of food from the mouth to the stomach” caused by an alteration in any of the four stages of swallowing. The prevalence of dysphagia rises to 6-9 percent of the general population and is associated to complications like aspirative pneumonia, malnutrition, dehydration, and airway obstruction. Oropharyngeal dysphagia is specially frequent in patients older than 75 years, individuals with neurologic diseases (i.e. stroke), and patients who have required intervention of their airways (endotracheal tubes or tracheostomy). Oropharyngeal dysphagia can be examined through clinical evaluation, modified barium swallow, functional endoscopic evaluation of swallowing with or without sensory testing, and in the laboratory of swallowing signals. The management of patients with oropharyngeal swallowing disorders is multidisciplinary: otolaryngologist, speech-language pathologist, nutritionist, physiatrist, radiologist, physical therapist, occupational therapist, and nurse.

Evaluación fibroscópica de la deglución / Fibroscopic evaluation of swallowing

Introducción: La disfagia orofaríngea es una condición patológica frecuente, especialmente en pacientes añosos. Se asocia a una serie de enfermedades (principalmente neuroiógicas y traumáticas), y conlleva un riesgo considerable de aspiración y neumonía. La evaluación fibroscópica de la deglución es una técnica que permite estudiar la fisiología de la deglución, estimar el riesgo de aspiración y orientar sobre la forma más segura de alimentar al paciente. Objetivo: Revisar la experiencia de nuestra institución en la evaluación fibroscópica de la deglución. Material y método: Entre abril de 2006 y julio de 2007 se evaluaron prospectivamente 75 pacientes, realizándose 96 exámenes en total. Hubo un franco predominio masculino (2/3 del grupo), y la edad promedio de los pacientes evaluados fue de 65,6 + 23,3 años (rango: 12-99 años). El examen se realizó utilizando un nasofaríngolaríngoscopio flexible y administrando alimento (papilla y líquido espeso) teñido con colorante azul natural. En ficha especialmente diseñada se registraron los hallazgos del examen, en especial la presencia de penetración laríngea y de aspiración traqueal del alimento. Resultados: Los diagnósticos neurológicos fueron los más habituales (54,7%), predominando la patología cerebrovascular, el traumatismo encéfalo-craneano y la patología neurológica degenerativa. Sólo el 17,8% de los pacientes presentaron una evaluación completamente normal. La alteración más frecuente fue la presencia de residuos alimentarios posdeglución (79,3%); la penetración laríngea y aspiración traqueal se demostraron en el 46,1% y el 27,3% de las evaluaciones, respectivamente. Tanto la presencia de traqueostomía como la retención de secreciones hipofaríngeas se asociaron, en forma significativa, al hallazgo de aspiración alimentaria. No se logró demostrar una asociación entre el diagnóstico de base del paciente y la severidad de la aspiración. No hubo complicaciones...

Introduction. Oropharyngeal dysphagia is a frequent pathological condition, specially in the elderly It is associated to several diseases (mainly neurological and traumatic) and it carries a risk of pneumonia and aspiration. Fibroscopic evaluation of swallowing allows the study of the physiology of swallowing, the assessment of aspiration risk, and enables counseling as to the safest way to feed the patient. Aim. To review the experience in fibrocopic evaluation of swallowing in our institution Material and method: Seventy five patients were prospectively evaluated between April 2006 and July 2007, for a total of 96 fibroscopies. Two-thirds of the evaluated patients were males, with an average age of 65.6 +/- 23.3 years (ranging from 12 to 99 years). Examination was made by means of a flexible nasopharyngoscope while administering food (purée and thick liquid) stained with a natural blue dye. Findings were registered in a custom-designed data sheet, emphasizing the presence of laryngeal penetration and tracheal aspiration offood. Results. The more frequent diagnoses were neurological (54.7%), with a predominance of cerebrovascular pathology cranial trauma and degenerative neurological pathology Only 17.8% of evaluations were considered completely normal. The most frequent alteration was the presence of post-swallowing food residues (79.3%); laryngeal penetration and tracheal aspiration were demonstrated in 46.1% and 27.3% of evaluations, respectively Both the presence of tracheostomy and of hypopharyngeal secretion retention were significantly associated to food residues presence. An association between the patient s diagnosis and the aspiration severity failed to be demonstrated. No complications were reponed during examination. Conclusion. Swallowing evaluation by fibroscopy is a validated, safe and sensitive examination technique for the evaluation of oropharyngeal dysphagia. It has the advantage of easy-to-carry...