3-Acetylpyridine-induced ataxic-like motor impairments are associated with plastic changes in the Purkinje cells of the rat cerebellum.

Ataxias are characterized by aberrant movement patterns closely related to cerebellar dysfunction. Purkinje cell axons are the sole outputs from the cerebellar cortex, and dysfunctional activity of Purkinje cells has been associated with ataxic movements. However, the synaptic characteristics of Purkinje cells in cases of ataxia are not yet well understood. The nicotinamide antagonist 3-acethylpyridine (3-AP) selectively destroys inferior olivary nucleus neurons so it is widely used to induce cerebellar ataxia. Five days after 3-AP treatment (65mg/kg) in adult male Sprague-Dawley rats, motor incoordination was revealed through BBB and Rotarod testing. In addition, in Purkinje cells from lobules V-VII of the cerebellar vermis studied by the Golgi method, the density of dendritic spines decreased, especially the thin and mushroom types. Western blot analysis showed a decrease in AMPA and PSD-95 content with an increase of the α-catenin protein, while GAD-67 and synaptophysin were unchanged. Findings suggest a limited capacity of Purkinje cells to acquire and consolidate afferent excitatory inputs and an aberrant, rigid profile in the movement-related output patterns of Purkinje neurons that likely contributes to the motor-related impairments characteristic of cerebellar ataxias.

Impact of plasmapheresis on severe COVID-19.

The clinical course of COVID-19 may show severe presentation, potentially involving dynamic cytokine storms and T cell lymphopenia, which are leading causes of death in patients with SARS-CoV-2 infection. Plasma exchange therapy (PLEX) effectively removes pro-inflammatory factors, modulating and restoring innate and adaptive immune responses. This clinical trial aimed to evaluate the impact of PLEX on the survival of patients with severe SARS-CoV-2 and the effect on the cytokine release syndrome. Hospitalized patients diagnosed with SARS-CoV-2 infection and cytokine storm syndrome were selected to receive 2 sessions of PLEX or standard therapy. Primary outcome was all-cause 60-days mortality; secondary outcome was requirement of mechanical ventilation, SOFA, NEWs-2 scores modification, reduction of pro-inflammatory biomarkers and hospitalization time. Twenty patients received PLEX were compared against 40 patients receiving standard therapy. PLEX reduced 60-days mortality (50% vs 20%; OR 0.25, 95%CI 0.071-0.880; p = 0.029), and this effect was independent from demographic variables and drug therapies used. PLEX significantly decreased SOFA, NEWs-2, pro-inflammatory mediators and increased lymphocyte count, accompanied with a trend to reduce affected lung volume, without effect on SatO2/FiO2 indicator or mechanical ventilation requirement. PLEX therapy provided significant benefits of pro-inflammatory clearance and reduction of 60-days mortality in selected patients with COVID-19, without significant adverse events.

Espinogénesis en motoneuronas de la médula espinal tras la lesión farmacológica de la corteza motora de ratas / Spinogenesis in spinal cord motor neurons following pharmacological lesions to the rat motor cortex

INTRODUCCIÓN: Diversas enfermedades neuropatologías asociadas a la degeneración del tracto corticoespinal muestran deterioro de las funciones motoras. Tales alteraciones neurológicas se asocian a diversos fenómenos plásticos subsecuentes, a nivel tanto presináptico como postsináptico. Sin embargo, no existe evidencia que indique la existencia de modificaciones en la transmisión de información del tracto corticoespinal a las motoneuronas espinales. MÉTODOS: Se indujo una lesión por vía estereotáxica en la corteza motora primaria de ratas hembra adultas con ácido kaínico y, 15 días después, se evaluó el desempeño motor mediante la escala BBB y en un dispositivo Rota-Rod. Paralelamente, se cuantificó la densidad numérica y proporcional de las espinas delgadas, en hongo y gordas, en motoneuronas de un segmento torácico-lumbar de la médula espinal. Así mismo, se registró la expresión de las proteínas espinofilina, sinaptofisina β III-tubulina. RESULTADOS: La lesión farmacológica provocó un desempeño motor deficiente. Así mismo, tanto la densidad de espinas como la proporción de espinas delgadas y gordas fue mayor, al igual que la expresión de las 3 proteínas estudiadas. CONCLUSIÓN: La aparición de los síntomas clínicos de daño neurológico provocado por la degeneración walleriana del tracto corticoespinal se acompaña de respuestas plásticas espontáneas de tipo compensador, a nivel sináptico. Lo anterior indica que durante la rehabilitación temprana de este tipo de pacientes, la plasticidad espontánea constituye un factor que se debe considerar para el diseño de estrategias de intervención más eficientes

INTRODUCTION: Motor function is impaired in multiple neurological diseases associated with corticospinal tract degeneration. Motor impairment has been linked to plastic changes at both the presynaptic and postsynaptic levels. However, there is no evidence of changes in information transmission from the cortex to spinal motor neurons. METHODS: We used kainic acid to induce stereotactic lesions to the primary motor cortex of female adult rats. Fifteen days later, we evaluated motor function with the BBB scale and the rotarod and determined the density of thin, stubby, and mushroom spines of motor neurons from a thoracolumbar segment of the spinal cord. Spinophilin, synaptophysin, and β III-tubulin expression was also measured. RESULTS: Pharmacological lesions resulted in poor motor performance. Spine density and the proportion of thin and stubby spines were greater. We also observed increased expression of the 3 proteins analysed. CONCLUSION: The clinical symptoms of neurological damage secondary to Wallerian degeneration of the corticospinal tract are associated with spontaneous, compensatory plastic changes at the synaptic level. Based on these findings, spontaneous plasticity is a factor to consider when designing more efficient strategies in the early phase of rehabilitation

Spinogenesis in spinal cord motor neurons following pharmacological lesions to the rat motor cortex. / Espinogénesis en motoneuronas de la médula espinal tras la lesión farmacológica de la corteza motora de ratas.

INTRODUCTION: Motor function is impaired in multiple neurological diseases associated with corticospinal tract degeneration. Motor impairment has been linked to plastic changes at both the presynaptic and postsynaptic levels. However, there is no evidence of changes in information transmission from the cortex to spinal motor neurons. METHODS: We used kainic acid to induce stereotactic lesions to the primary motor cortex of female adult rats. Fifteen days later, we evaluated motor function with the BBB scale and the rotarod and determined the density of thin, stubby, and mushroom spines of motor neurons from a thoracolumbar segment of the spinal cord. Spinophilin, synaptophysin, and ß iii-tubulin expression was also measured. RESULTS: Pharmacological lesions resulted in poor motor performance. Spine density and the proportion of thin and stubby spines were greater. We also observed increased expression of the 3 proteins analysed. CONCLUSION: The clinical symptoms of neurological damage secondary to Wallerian degeneration of the corticospinal tract are associated with spontaneous, compensatory plastic changes at the synaptic level. Based on these findings, spontaneous plasticity is a factor to consider when designing more efficient strategies in the early phase of rehabilitation.

El aprendizaje motor induce cambios plásticos en las espinas dendríticas de las células de Purkinje del cerebelo de ratas / No disponible

INTRODUCCIÓN: El lóbulo paramediano del cerebelo está involucrado en el desempeño correcto de las habilidades motoras a través de la práctica. Las espinas dendríticas son estructuras dinámicas que regulan la estimulación sináptica excitadora. En este trabajo se estudiaron los posibles cambios plásticos en espinas de células de Purkinje del lóbulo paramediano cerebelar de ratas, durante el aprendizaje motor. MÉTODOS: Se entrenaron a ratas macho adultas durante un período de seis días, en un paradigma de aprendizaje motor acrobático y se cuantificó tanto la densidad como los tipos de espinas dendríticas en cada uno de los seis días de estudio, mediante una modificación al método de Golgi. RESULTADOS: La curva de aprendizaje reflejó una disminución consistente de los errores cometidos en el transcurso de los días de entrenamiento. Así mismo, se observaron más espinas dendríticas en los días 2 y 6 y, en particular, más espinas delgadas en los días 1, 3 y 6, menos espinas en hongo el día 3, menos espinas gordas el día 1 y más espinas anchas los días 4 y 6. CONCLUSIÓN: El período inicial de aprendizaje motor podría estar asociado con el procesamiento rápido de la información sináptica subyacente y con un aparente «silenciamiento» de los procesos de consolidación mnémica, en una base de regulación de la excitabilidad neuronal

INTRODUCTION: The paramedian lobule of the cerebellum is involved in learning to correctly perform motor skills through practice. Dendritic spines are dynamic structures that regulate excitatory synaptic stimulation. We studied plastic changes occurring in the dendritic spines of Purkinje cells from the paramedian lobule of rats during motor learning. METHODS: Adult male rats were trained over a 6-day period using an acrobatic motor learning paradigm; the density and type of dendritic spines were determined every day during the study period using a modified version of the Golgi method. RESULTS: The learning curve reflected a considerable decrease in the number of errors made by rats as the training period progressed. We observed more dendritic spines on days 2 and 6, particularly more thin spines on days 1, 3, and 6, fewer mushroom spines on day 3, fewer stubby spines on day 1, and more thick spines on days 4 and 6. CONCLUSION: The initial stage of motor learning may be associated with fast processing of the underlying synaptic information combined with an apparent "silencing" of memory consolidation processes, based on the regulation of the neuronal excitability

Motor learning induces plastic changes in Purkinje cell dendritic spines in the rat cerebellum. / El aprendizaje motor induce cambios plásticos en las espinas dendríticas de las células de Purkinje del cerebelo de ratas.

INTRODUCTION: The paramedian lobule of the cerebellum is involved in learning to correctly perform motor skills through practice. Dendritic spines are dynamic structures that regulate excitatory synaptic stimulation. We studied plastic changes occurring in the dendritic spines of Purkinje cells from the paramedian lobule of rats during motor learning. METHODS: Adult male rats were trained over a 6-day period using an acrobatic motor learning paradigm; the density and type of dendritic spines were determined every day during the study period using a modified version of the Golgi method. RESULTS: The learning curve reflected a considerable decrease in the number of errors made by rats as the training period progressed. We observed more dendritic spines on days 2 and 6, particularly more thin spines on days 1, 3, and 6, fewer mushroom spines on day 3, fewer stubby spines on day 1, and more thick spines on days 4 and 6. CONCLUSION: The initial stage of motor learning may be associated with fast processing of the underlying synaptic information combined with an apparent "silencing" of memory consolidation processes, based on the regulation of the neuronal excitability.

Functional comparison of corticostriatal and thalamostriatal postsynaptic responses in striatal neurons of the mouse.

Synaptic inputs from cortex and thalamus were compared in electrophysiologically defined striatal cell classes: direct and indirect pathways' striatal projection neurons (dSPNs and iSPNs), fast-spiking interneurons (FS), cholinergic interneurons (ChINs), and low-threshold spiking-like (LTS-like) interneurons. Our purpose was to observe whether stimulus from cortex or thalamus had equivalent synaptic strength to evoke prolonged suprathreshold synaptic responses in these neuron classes. Subthreshold responses showed that inputs from either source functionally mix up in their dendrites at similar electrotonic distances from their somata. Passive and active properties of striatal neuron classes were consistent with the previous studies. Cre-dependent adeno-associated viruses containing Td-Tomato or eYFP fluorescent proteins were used to identify target cells. Transfections with ChR2-eYFP driven by the promoters CamKII or EF1.DIO in intralaminar thalamic nuclei using Vglut-2-Cre mice, or CAMKII in the motor cortex were used to stimulate cortical or thalamic afferents optogenetically. Both field stimuli in the cortex or photostimulation of ChR2-YFP cortical fibers evoked similar prolonged suprathreshold responses in SPNs. Photostimulation of ChR2-YFP thalamic afferents also evoked suprathreshold responses. Differences previously described between responses of dSPNs and iSPNs were observed in both cases. Prolonged suprathreshold responses could also be evoked from both sources onto all other neuron classes studied. However, to evoke thalamostriatal suprathreshold responses, afferents from more than one thalamic nucleus had to be stimulated. In conclusion, both thalamus and cortex are capable to generate suprathreshold responses converging on diverse striatal cell classes. Postsynaptic properties appear to shape these responses.

Pharmacological evaluation of a selective bradykinin B1 antagonist in a canine model of arthritis.

The effects of a selective bradykinin 1 receptor antagonist, compound A, were evaluated in a canine model of acute inflammatory model of arthritis. Despite detection of the B1 receptor in canine type B synoviocytes using a fluorescent ligand, oral administration of compound A (9 and 27 mg/kg) did not improve weight bearing of dogs injected intra-articularly with IL-1ß in a force plate analysis. Analysis of the synovial fluid of IL-1ß-treated dogs indicated high levels of bradykinin postchallenge. Excellent exposure, coupled with evidence of the presence of the B1 receptor during an acute inflammatory model of pain, indicates an inability of the receptor to mediate inflammatory pain in canines.

Metodología geométrica para la evaluación de la saturación arterial de oxígeno en pacientes de la Unidad de Cuidados Intensivos / Geometric methodology for the saturation evaluation arterial oxygen in patients of the Care Unit Intensive

Introducción: En cardiología, la aplicación de teorías, como la de los sistemas dinámicos y la geometría fractal, han generado nuevos diagnósticos matemáticos que diferencian, de manera geométrica y cuantitativa, el comportamiento normal del enfermo a partir de la ocupación del atractor caótico cardíaco. El objetivo de este estudio fue desarrollar, en el contexto de la teoría de los sistemas dinámicos, una metodología de evaluación de la saturación arterial de oxígeno para pacientes en la Unidad de Cuidados Intensivos. Materiales y Métodos: Se seleccionaron 10 pacientes con diferentes enfermedades, provenientes de la Unidad de Cuidados Intensivos, a los cuales se les registró la saturación arterial de oxígeno durante su estancia en la Unidad, y se construyeron atractores caóticos en el mapa de retardo. Posteriormente, se establecieron cuantificaciones de los valores mínimos y máximos del atractor. Resultados: Los valores máximos y mínimos de los atractores de la saturación de oxígeno variaron entre el 100% y el 70%, para los pacientes que fallecieron, mientras que para aquellos que vivieron, se mantuvo entre el 99% y el 85%. Conclusiones: Se observó un comportamiento caótico asociado a la saturación arterial de oxígeno, cuantificable a partir de los valores máximos y mínimos hallados de la totalidad del atractor, estableciendo una nueva medida matemática y física del paciente crítico en la Unidad de Cuidados Intensivo (AU)

Introduction: In cardiology, the application of theories, such as dynamical systems and fractal geometry, has generated new mathematical diagnoses that differentiate geometrically and quantitatively the normal from the diseased behavior through the occupation of the cardiac chaotic attractor. The objective of this study was to develop, in the context of the dynamical systems theory, a methodology for the evaluation of arterial oxygen saturation in patients of the Intensive Care Unit. Materials and Methods: Ten patients with different pathologies from the Intensive Care Unit were selected. The arterial oxygen saturation was recorded during their stay in the Intensive Care Unit and chaotic attractors were built in the delay map. Subsequently, quantifications of the minimum and maximum values of the attractor were established. Results: The maximum and minimum values of the oxygen saturation attractors varied between 100% and 70% for patients who died, whereas for those who lived, saturation values between 99% and 85% were maintained. Conclusions: A chaotic behavior associated with arterial oxygen saturation, quantifiable through the maximum and minimum values found in the entire attractor, was observed, establishing a new mathematical and physical measurement of the critical patient in the Intensive Care Unit.(AU)

Detection and phylogenetic analysis of infectious pancreatic necrosis virus in Chile.

Infectious pancreatic necrosis virus (IPNV) is the etiological agent of a highly contagious disease that is endemic to salmon farming in Chile and causes great economic losses to the industry. Here we compared different diagnostic methods to detect IPNV in field samples, including 3 real-time reverse transcription PCR (qRT-PCR) assays, cell culture isolation, and indirect fluorescent antibody test (IFAT). Additionally, we performed a phylogenetic analysis to investigate the genogroups prevailing in Chile, as well as their geographic distribution and virulence. The 3 qRT-PCR assays used primers that targeted regions of the VP2 and VP1 genes of the virus and were tested in 46 samples, presenting a fair agreement within their results. All samples were positive for at least 2 of the qRT-PCR assays, 29 were positive for cell culture, and 23 for IFAT, showing less sensitivity for these latter 2 methods. For the phylogenetic analysis, portions of 1180 and 523 bp of the VP2 region of segment A were amplified by RT-PCR, sequenced and compared with sequences from reference strains and from isolates reported by previous studies carried out in Chile. Most of the sequenced isolates belonged to genogroup 5 (European origin), and 5 were classified within genogroup 1 (American origin). Chilean isolates formed clusters within each of the genogroups found, evidencing a clear differentiation from the reference strains. To our knowledge, this is the most extensive study completed for IPNV in Chile, covering isolates from sea- and freshwater salmon farms and showing a high prevalence of this virus in the country.

A Golgi study of the plasticity of dendritic spines in the hypothalamic ventromedial nucleus during the estrous cycle of female rats.

Estradiol-induced plasticity involves changes in dendritic spine density and in the relative proportions of the different dendritic spine types that influence neurons and neural circuits. Such events affect brain structures that control the timing of neuroendocrine and behavioral processes, influencing both reproductive and cognitive functions during the estrous cycle. Accordingly, to investigate the dendritic spine-related plastic changes that may affect the neural processes involved in mating, estradiol-mediated dendritic spine plasticity was studied in type II cells situated in the ventrolateral portion of the ventromedial hypothalamic nucleus (VMN) of female, adult rats. The rats were assigned to four different groups (n=6) in function of their stage in the estrous cycle: proestrus, estrus, metaestrus, and diestrus. Dendritic spine density and the proportions of the different spine types on type II neurons were analyzed in the ventrolateral region of the VMN of these animals. Dendritic spine density on primary dendrites of VMN type II neurons was significantly lower in metaestrus than in diestrus, proestrus and estrus (with no differences between these latter stages). However, a significant variation in the proportional density of the different spine types was found, with a higher proportion of thin spines in diestrus, proestrus and estrus than in metaestrus. Likewise, a higher proportion of mushroom spines was seen in diestrus and proestrus than in metaestrus, and a higher proportion of stubby spines in estrus than in diestrus and metaestrus. Very few branched spines were found during proestrus and they were not detected during estrus or metaestrus. The different types of dendritic spines in non-projection neurons of the VMN could serve to maintain greater synaptic excitatory activity when receptivity and estradiol levels are maximal. However, they may also fulfill an additional functional role when receptivity and estradiol decline. To date specific roles of the different types of spines in neural hypothalamic activity during the estrous cycle remain unknown and they clearly deserve further study.

Importancia del tamaño de las tuberosidades en las complicaciones del complejo esclerosis tuberosa / Significance of tuber size for complications of tuberous sclerosis complex

Introducción: El complejo esclerosis tuberosa (CET) es uno de los trastornos neurocutáneos más frecuentes. Las tuberosidades corticales son las alteraciones patológicas más frecuentes y están relacionadas directamente con las principales expresiones clínicas, crisis epilépticas, retraso mental y comportamiento autista. El motivo de este trabajo es mostrar la importancia de los diferentes tipos de tuberosidades en la expresión clínica de los pacientes. Objetivo: La finalidad de este trabajo es relacionar el tamaño de las tuberosidades con la severidad de las alteraciones clínicas. Material y métodos: Se estudiaron retrospectivamente los hallazgos clínicos y neurorradiológicos de 45 pacientes infantiles (22 mujeres y 23 varones) con CET y comparamos los hallazgos clínicos con la localización, el tamaño y el número de las tuberosidades corticales en cada paciente. Resultados: Cuatro pacientes tenían tuberosidades muy voluminosas en los hemisferios cerebrales. Todas mostraban crisis epilépticas muy rebeldes y retraso mental profundo con comportamiento autista en 3 de ellos, pese a que se extirparon las tuberosidades en los 4 casos. Trece pacientes tenían tuberosidades de tamaño promedio-grande. Todos tenían crisis epilépticas muy rebeldes y retraso mental. Nueve pacientes habían tenido espasmos infantiles durante el primer año de vida y presentaban comportamiento autista. Veintiocho pacientes mostraban muchas tuberosidades de tamaño promedio-pequeño. La mayoría de ellos tenían crisis con buena respuesta al tratamiento farmacológico y poca prevalencia del autismo. Tres pacientes mostraban tuberosidad córtico-subcortical única en un polo frontal u occipital, todos ellos con crisis controladas con medicación y cociente intelectual normal. Trece pacientes de los 45 tenían tuberosidades cerebelosas, siempre asociadas a algún tipo de tuberosidad hemisférica y generalmente presentes en casos con mayor expresividad clínica. Conclusiones: Las tuberosidades de gran tamaño, aunque sean poco numerosas, tienen mucha mayor relación con la presencia de sintomatología clínica severa —crisis epilépticas, retraso mental y comportamiento autista— que las tuberosidades de pequeño-mediano tamaño, aunque sean muy numerosas (AU)

Introduction: Tuberous sclerosis complex (TSC) is one of the most frequent neurocutaneous disorders. Cortical tubers are the most common pathological changes in TSC and they are directly related to the disease's main clinical manifestations: seizures, mental retardation, and autistic behaviour. Objective: The aim of this study is to establish a correlation between tuber size and the severity of clinical features in TSC. Material and methods: We performed a retrospective study of the clinical and imaging findings from 45 TSC patients (22 females and 23 males) and compared the clinical features with the location, size, and number of the cortical tubers in each patient. Results: Four patients had voluminous tubers located in 1 or both cerebral hemispheres. All of these patients had intractable seizures and severe mental retardation; 3 of these cases also presented with autistic behaviour, despite tubers having been resected in all 4 patients. Thirteen patients had tubers of large-to-average size, and all patients in this group showed intractable seizures and mental retardation. Nine patients who had experienced infantile spasms during the first year of life presented autistic behaviour. Multiple tubers of small to average size were found in 28 patients. In general, this group had seizures that responded well to antiepileptic drugs and a low prevalence of autism. In 3 patients who all presented good seizure control and normal intelligence, single cortical/subcortical tubers were located in the frontal or occipital lobes. Of the total of 45 patients, 13 had cerebellar as well as cerebral tubers; these were generally present in cases with more severe clinical features. Conclusions: Although large tubers are less common than small to medium-sized ones, they are much more likely to be accompanied by severe clinical symptoms (seizures, mental retardation and autistic behaviour), even when the smaller tubers are quite numerous (AU)

Invaginación intestinal ileoileal causada por divertículo de Meckel / Ileoileal intussusception due to Meckel's diverticulum

Introducción: La invaginación intestinal constituye la principal causa de obstrucción intestinal en lactantes. En este rango etáreo, la mayoría de los casos son idiopáticos y de localización ileocecal, siendo infrecuentes las invaginaciones ileoileales originadas por una alteración anatómica del tracto gastrointestinal como el Divertículo de Meckel. Objetivo: Presentar 2 casos de invaginación intestinal ileoileal en lactantes causadas por Divertículo de Meckel. Casos clínicos: El primer caso corresponde a una lactante de sexo femenino de 6 meses que presentó cuadro de dolor abdominal cólico asociado a vómitos y deposiciones sanguinolentas. El segundo, a un lactante de sexo masculino de 1 año y 11 meses con antecedentes de Tetralogía de Fallot operada y Síndrome de Di George que consultó por compromiso del estado general, vómitos y deshidratación severa, asociándose en los días siguientes deposiciones semilíquidas no sanguinolentas. Conclusiones: La invaginación intestinal ileoileal es infrecuente, en especial las causadas por alteraciones anatómicas como el Divertículo de Meckel en lactantes. Esta asociación no tiene signos patognomónicos y su estudio no difiere del habitual de intususcepción intestinal, pero es importante considerarla para el manejo, pues posee indicación quirúrgica y está contraindicada la reducción neumática.

Introduction: Intussusception is the most common cause of intestinal obstruction in infants. At this age, most cases are idiopathic and involve ileocecal locations; meanwhile ileoileal invaginations caused by an anatomic abnormality of the gastrointestinal tract, such as Meckel's diverticulum, are rare. Objective: To report two cases of infant ileoileal intussusception due to Meckel's diverticulum. Case reports: The first patient was a 6 month-old female infant who presented colicky abdominal pain associated with vomiting and bloody stools. The second patient, a 23 month-old male infant with a history of Tetralogy of Fallot and corrective surgery, and DiGeorge syndrome, who consulted the specialists for health worsened due to vomits and severe dehydration, presenting the following days, semi-liquid and non-bloody stools. Conclusions: Ileoileal intussusception is rare in infants, especially those caused by anatomical changes such as Meckel's diverticulum. This association has no pathognomonic signs and its study does not differ from the usual study of intestinal intussusception, but it is important to consider it for management purposes as it involves surgical intervention and considering that the pneumatic reduction is contraindicated.

Significance of tuber size for complications of tuberous sclerosis complex.

INTRODUCTION: Tuberous sclerosis complex (TSC) is one of the most frequent neurocutaneous disorders. Cortical tubers are the most common pathological changes in TSC and they are directly related to the disease's main clinical manifestations: seizures, mental retardation, and autistic behaviour. OBJECTIVE: The aim of this study is to establish a correlation between tuber size and the severity of clinical features in TSC. MATERIAL AND METHODS: We performed a retrospective study of the clinical and imaging findings from 45 TSC patients (22 females and 23 males) and compared the clinical features with the location, size, and number of the cortical tubers in each patient. RESULTS: Four patients had voluminous tubers located in 1 or both cerebral hemispheres. All of these patients had intractable seizures and severe mental retardation; 3 of these cases also presented with autistic behaviour, despite tubers having been resected in all 4 patients. Thirteen patients had tubers of large-to-average size, and all patients in this group showed intractable seizures and mental retardation. Nine patients who had experienced infantile spasms during the first year of life presented autistic behaviour. Multiple tubers of small to average size were found in 28 patients. In general, this group had seizures that responded well to antiepileptic drugs and a low prevalence of autism. In 3 patients who all presented good seizure control and normal intelligence, single cortical/subcortical tubers were located in the frontal or occipital lobes. Of the total of 45 patients, 13 had cerebellar as well as cerebral tubers; these were generally present in cases with more severe clinical features. CONCLUSIONS: Although large tubers are less common than small to medium-sized ones, they are much more likely to be accompanied by severe clinical symptoms (seizures, mental retardation and autistic behaviour), even when the smaller tubers are quite numerous.

An acute reversible experimental model of pneumonia in pigs: time-related histological and clinical signs changes.

The objective of this study was to evaluate the long-term survival rates, clinical response, and lung gross and microscopic changes in pigs treated intratracheally with lipopolysaccharide of Escherichia coli 0111:B4 (LPS-Ec). Healthy pigs were randomly allocated to three groups: (i) no-LPS-Ec (n=1), (ii) LPS-Ec-T1 (1 mg/mL, 10 mL/pig) (n=7), and (iii) LPS-Ec-T2 (0.5 mg/mL, 10 mL/pig) (n=6). Two pigs from each dose group were euthanized at 24 (n=3 for T1), 48 and 144 h post-LPS-Ec challenge. LPS-Ec-treated animals showed macroscopic lesions in middle lobes of the lung. A reversible recruitment of macrophages and neutrophils was observed at 24, 48, and 144 h post-LPS-Ec challenge. The highest cellular infiltration level was observed at 24 h after challenge. The highest clinical scores were evident in both experimental dose levels within 3 and 5 h after LPS-Ec administration. Administration of LPS-Ec, under the conditions evaluated, can be used to induce a reproducible model of acute pulmonary inflammation in pigs.

Pulmonary pharmacokinetics of tulathromycin in swine. Part 2: Intra-airways compartments.

The objective of this study was to assess the pharmacokinetics of tulathromycin in pulmonary and bronchial epithelial lining fluid (PELF and BELF) from pigs. Clinically healthy pigs were allocated to two groups of 36 animals each. All animals were treated with tulathromycin (2.5 mg/kg/i.m). Animals in group 2 were also challenged intratracheally with lipopolysaccharide from Escherichia coli 3 h prior to tulathromycin administration. Both PELF and BELF samples were harvested using bronchoalveolar lavage fluid and bronchial micro-sampling probes, respectively. Samples were taken for 17 days post-tulathromycin administration. No statistical differences in the concentration of tulathromycin were observed in PELF between groups. The concentration vs. time profile in BELF was evaluated only in Group 1. Tulathromycin distributed rapidly and extensively into the airway compartments. The time to maximal (Tmax ) concentration was 6 h postdrug administration in PELF but 72 h post-tulathromycin administration for BELF. In group 2, the Tmax was seen at 24 h post-tulathromycin administration. The area under the concentration time curve (h*ng/mL) was 522 000, 348 000 and 1 290 000 for PELFGroup-1 , PELFGroup-2 , and BELFGroup-1 , respectively. Tulathromycin not only distributed rapidly into intra-airway compartments at relatively high concentrations but also resided in the airway lining fluid for a long time (>4 days).

Pulmonary pharmacokinetics of tulathromycin in swine. Part I: Lung homogenate in healthy pigs and pigs challenged intratracheally with lipopolysaccharide of Escherichia coli.

The objective of the study was to assess the pharmacokinetics of tulathromycin in lung tissue homogenate (LT) and plasma from healthy and lipopolysaccharide (LPS)-challenged pigs. Clinically healthy pigs were allocated to two dosing groups of 36 animals each (group 1 and 2). All animals were treated with tulathromycin (2.5 mg/kg). Animals in group 2 were also challenged intratracheally with LPS from Escherichia coli (LPS-Ec) 3 h prior to tulathromycin administration. Blood and LT samples were collected from all animals during 17-day post-tulathromycin administration. For LT, one sample from the middle (ML) and caudal lobes (CL) was taken. The concentration of tulathromycin was significantly lower in the ML after the intratracheal administration of LPS-E. coli (P < 0.02). In healthy pigs and LPS-challenged animals, the distribution of the drug into the lungs was rapid and persisted at high levels for 17-day postadministration. The distribution of the drug within the lung seems to be homogenous, at least between the middle and caudal lobes within dosing groups. The concentration versus time profile of the drug and pharmacokinetic parameters in two different lung areas (middle and caudal lobe) were consistent within the groups. The clinical significance of these findings is unknown.

Frecuencia de administración de psicoestimulantes en escolares de primero a sexto básico en Talca / Stimulant drugs intake among first to sixth grade schoolchildren in Talca

Introducción: Los psicoestimulantes son medicamentos de primera línea en el tratamiento del síndrome por déficit atencional (TDA). Su indicación en menores varía según edad y sexo. Existen pocos datos a nivel nacional de frecuencia de uso de psicoestimulantes en niños y no hay datos en nuestra región. Objetivo: Estudiar la frecuencia de uso de psicoestimulantes en escolares de primero a sexto básico en Talca y los factores asociados a su uso. Material y Método: Estudio de corte de alumnos entre primero y sexto básico provenientes de establecimientos educacionales del radio urbano de Talca, estratificados según nivel socioeconómico. Se obtuvo lista con sexo y edad de los alumnos desde la dirección de cada establecimiento. La información acerca de la prescripción de psicoestimulantes fue proporcionada por el profesor jefe o encargado de educación diferencial. Resultados: De una muestra de 2.905 niños, el 1,76 por ciento utilizaba psicoestimulantes, 0,96 por ciento, metilfenidato y 0,76 por ciento, anfetaminas. La probabilidad de consumo de psicoestimulantes fue mayor en varones (OR = 5,8; 95 por ciento, IC: 2,6-13,2), alumnos de cuarto básico (OR = 2,3; 95 por ciento, IC: 1,26-4,15) y de 11 años de edad (OR = 2,4; 95 por ciento, IC: 1,35-4,43). En el nivel socioeconómico alto se registró el mayor consumo de metilfenidato (p = 0,0495) y en el medio bajo la mayor utilización de anfetaminas (p = 0,0014). Discusión: La frecuencia de uso de psicoestimulantes en Talca es baja en relación a la encontrada en otras regiones del país. La frecuencia y tipo de fármaco utilizado en el tratamiento del TDA, se asocia con la edad, el sexo y el nivel socioeconómico de los alumnos.

Background: Stimulant drugs are frequently prescribed in the treatment of Attention-Deficit/ Hyperactivity Disorder (ADHD) in children. Drug prescription is associated with children's age and gender. Chile has few reports of Stimulant drugs prescription and there are no records in our region. Objective: To evaluate the prevalence of Stimulant drugs intake in schoolchildren from first to sixth grade in Talca. Material and Methods: A cross-sectional study in schoolchildren attending first to sixth grade at urban schools in Talca was performed. The schools were stratified according to socioeconomic status. A list with sex and age of the children was obtained from the headmaster of each school. The information about stimulant drugs prescription was provided by the class teacher or the person in charge of special education. Results: We studied 2,905 children, 1.76 percent of them were under stimulant drugs, 0.96 percent took methylphenidate and 0.76 percent took dexamphetamine. Administration of ADHD drugs was higher in boys than in girls (OR = 5.8; 95 percent IC: 1.35-4.43), in fourth grade students (OR = 2.3; 95 percent, IC: 1.26-4.15) and in 11-year-old children (OR = 2,4; 95 percent, IC: 1,35-4,43). Intake of methylphenidate was higher in the highest socioeconomic status (p = 0.0496), while the highest intake of dexamphetamine was found in the lowest socioeconomic status (p = 0.0014). Discussion: The use of stimulant drugs medication is low in Talca compared to national records. The prescription of these drugs is related to the age, sex of the students while the kind of drug prescribed was related to the socioeconomic status of the child.

[Neuromyelitis optica: a clinical update]. / Neuromielitis optica: actualizacion clinica.

INTRODUCTION: Neuromyelitis optica (NMO) or Devic's disease is an autoimmune, inflammatory and demyelinating central nervous system disorder that affects mainly to optic nerve and spinal cord. Recent advances have substantially permitted to expand the knowledge about this entity. AIM: To present a clinical update on the current understanding of the nature, progression, diagnosis and treatment of NMO. DEVELOPMENT: Due to its demyelinating nature and its recurrent behavior in most cases, NMO was first considered a form of multiple sclerosis (MS). However, recent findings have led to the conclusion that NMO is a distinct disorder, presenting important immunopathological, clinical, prognostic and therapeutic differences from MS. Fundamental in the under-standing of the disease was the recent discovery of antibodies directed against aquaporin-4 (anti-AQP4, also known as NMO-IgG), which are present in the majority of NMO cases clinically defined, and in a minority of patients with MS. Despite the knowledge on its immunopathogenesis and advances in diagnosis, the treatment of NMO is still challenging. CONCLUSION: NMO is a demyelinating disease different from MS. Current diagnostic criteria have been enriched with the recent description of the humoral disorder underlying NMO. However, current treatment options for NMO are far from being ideal.