Biomarcadores de estrés oxidativo en la enfermedad de Huntington y otros desórdenes neurológicos: estudio comparativo

Fundamento: los biomarcadores de estrés oxidativo en la enfermedad de Huntington pudieran predecir el curso de la enfermedad y evaluar nuevos tratamientos, pero su naturaleza inespecífica parece impedir la identificación de algún marcador útil. Esclarecer similitudes y diferencias de este fenómeno y su comportamiento con características clínicas puede ser esencial. Objetivo comparar biomarcadores de estrés oxidativo entre pacientes con enfermedad de Huntington y con otros desórdenes neurológicos. Métodos se realizó un estudio analítico, retrospectivo y caso-control (enfermedad de Huntington esclerosis lateral amiotrófica, ataxia espinocerebelosa tipo 2 e ictus isquémico: en etapa aguda y crónica). Se recogieron variables demográficas, clínicas y marcadores de daño oxidativo (malonildialdehído, productos avanzados de oxidación a proteínas) y antioxidantes (superóxido dismutasa: catalasa: glutatión peroxidasa, capacidad antioxidante del plasma). Resultados hubo diferencias significativas del malonildialdehído en la enfermedad de Huntington respecto al control (p=0,02), pero no con el resto de los grupos. La enzima superóxido dismutasa en enfermedad de Huntington fue menor estadísticamente en comparación con esclerosis lateral amiotrófica, aunque para la catalasa fue superior en relación con el resto de los pacientes. El FRAP en enfermedad de Huntington resultó menor significativamente versus esclerosis lateral amiotrófica e ictus isquémico agudo. Los productos avanzados de la oxidación de proteína se correlacionaron directamente con las edades biológicas y de inicio de la enfermedad de Huntington. La actividad motora en la esclerosis lateral amiotrófica y el déficit neurológico en el ictus isquémico agudo se correlacionaron con el malonildialdehído y glutatión peroxidasa respectivamente. Conclusiones la enfermedad de Huntington parece mostrar características específicas en su sistema antioxidante. La oxidación de proteínas pudiera estar relacionada con la acumulación de huntingtina mutada en el tiempo.

Foundation: biomarkers of oxidative stress in Huntington's disease could predict the course of the disease and evaluate new treatments, but their nonspecific nature seems to prevent the identification of any useful marker. Clarifying similarities and differences of this phenomenon and its behavior with clinical characteristics may be essential. Objective: compare biomarkers of oxidative stress between patients with Huntington's disease and other neurological disorders. Methods: an analytical, retrospective and case-control study was carried out (Huntington's disease, amyotrophic lateral sclerosis, spinocerebellar ataxia type 2 and ischemic stroke: acute and chronic stage). Demographic and clinical variables and markers of oxidative damage (malonildialdehyde, advanced protein oxidation products) and antioxidants (superoxide dismutase: catalase: glutathione peroxidase, plasma antioxidant capacity) were collected. Results: there were significant differences in malonyldialdehyde in Huntington's disease compared to the control (p=0.02), but not with the rest of the groups. The enzyme superoxide dismutase in Huntington's disease was statistically lower compared to amyotrophic lateral sclerosis, although for catalase it was higher in relation to the rest of the patients. FRAP in Huntington's disease was significantly lower versus amyotrophic lateral sclerosis and acute ischemic stroke. Advanced products of protein oxidation were directly correlated with the biological and onset ages of Huntington's disease. Motor activity in amyotrophic lateral sclerosis and neurological deficit in acute ischemic stroke were correlated with malonyldialdehyde and glutathione peroxidase, respectively. Conclusions: huntington's disease seems to show specific characteristics in its antioxidant system. Protein oxidation could be related to the accumulation of mutated huntingtin over time.

The development and benefits of metformin in various diseases / 医学前沿

Metformin has been used for the treatment of type II diabetes mellitus for decades due to its safety, low cost, and outstanding hypoglycemic effect clinically. The mechanisms underlying these benefits are complex and still not fully understood. Inhibition of mitochondrial respiratory-chain complex I is the most described downstream mechanism of metformin, leading to reduced ATP production and activation of AMP-activated protein kinase (AMPK). Meanwhile, many novel targets of metformin have been gradually discovered. In recent years, multiple pre-clinical and clinical studies are committed to extend the indications of metformin in addition to diabetes. Herein, we summarized the benefits of metformin in four types of diseases, including metabolic associated diseases, cancer, aging and age-related diseases, neurological disorders. We comprehensively discussed the pharmacokinetic properties and the mechanisms of action, treatment strategies, the clinical application, the potential risk of metformin in various diseases. This review provides a brief summary of the benefits and concerns of metformin, aiming to interest scientists to consider and explore the common and specific mechanisms and guiding for the further research. Although there have been countless studies of metformin, longitudinal research in each field is still much warranted.

Importance of targeted next-generation sequencing in pediatric patients with developmental epileptic encephalopathy

SUMMARY OBJECTIVE: Childhood epilepsy is a common neurological disorder with a prevalence of 300-600 cases per 100,000 people. It is associated with refractory epilepsies, global developmental delay, and epileptic encephalopathies, causing epileptic syndromes characterized by cognitive and behavioral disorders. METHODS: In this retrospective cohort study, patients with refractory epilepsy and global developmental delay, defined as epileptic encephalopathy, who applied to the Aydın 7Maternity and Children's Hospital Genetic Diagnosis Center and were followed in the pediatric neurology clinic of our hospital, between July 2018 and July 2021, were included. RESULTS: Targeted next-generation sequencing molecular genetics results were reviewed, and 3 ALDH7A1, 1 AARS, 3 CACNA1A, 1 CTNNB1, 1 DCX, 2 DBH, 2 DOCK7, 1 FOLR1, 2 GABRB3, 2 GCH1, 1 VGRIN2B, 1 GUF1, 3 KCNQ2, 2 KCNT1, 1 NECAP1, 1 PCDH19, 1 PNPO, 1 SCN8A, 1 SCN9A, 4 SCN1A, 2 SLC25A22, 1 SLC2A1, 2 SPTAN1, 2 SZT2, 4 TBC1D24, 2 TH, and 1 PCDH19 (X chromosome) mutations were detected in three of the patients using the next-generation sequencing method. CONCLUSION: Although the development of gene panels aids in diagnosis, there are still unidentified disorders in this illness category, which is highly variable in genotype and phenotype. Understanding the genetic etiology is vital for genetic counseling and, maybe, the future development of remedies for the etiology.

Blood-cerebrospinal fluid (CSF) barrier dysfunction means reduced CSF flow not barrier leakage - conclusions from CSF protein data / Disfunção da barreira hemato-liquórica significa redução do fluxo de líquido cefalorraquidiano, e não quebra de barreira - conclusões a partir de estudos sobre as proteínas do LCR

ABSTRACT Background: Increased concentrations of serum proteins in cerebrospinal fluid (CSF) are interpreted as blood-CSF barrier dysfunction. Frequently used interpretations such as barrier leakage, disruption or breakdown contradict CSF protein data, which suggest a reduced CSF flow rate as the cause. Results: Even the severest barrier dysfunctions do not change the molecular size-dependent selectivity or the interindividual variation of the protein transfer across barriers. Serum protein concentrations in lumbar CSF increase with hyperbolic functions, but the levels of proteins that do not pass the barrier remain constant (brain proteins) or increase linearly (leptomeningal proteins). All CSF protein dynamics above and below a lumbar blockade can also be explained, independent of their barrier passage, by a reduced caudally directed flow. Local accumulation of gadolinium in multiple sclerosis (MS) is now understood as due to reduced bulk flow elimination by interstitial fluid (ISF). Nonlinear change of the steady state in barrier dysfunction and along normal rostro-caudal gradients supports the diffusion/flow model and contradicts obstructions of diffusion pathways. Regardless of the cause of the disease, pathophysiological flow blockages are found in bacterial meningitis, leukemia, meningeal carcinomatosis, Guillain-Barré syndrome, MS and experimental allergic encephalomyelitis. In humans, the fortyfold higher albumin concentrations in early fetal development decrease later with maturation of the arachnoid villi, i.e., with beginning CSF outflow, which contradicts a relevant outflow to the lymphatic system. Respiration- and heartbeat-dependent oscillations do not disturb net direction of CSF flow. Conclusion: Blood-CSF and blood-brain barrier dysfunctions are an expression of reduced CSF or ISF flow rate.

RESUMO Introdução: Concentrações aumentadas de proteínas séricas no líquido cefalorraquidiano são interpretadas como disfunção da barreira (hemato-liquórica) sanguínea do LCR. Interpretações frequentemente usadas, como vazamento de barreira (quebra ou rompimento de barreira), rompimento ou quebra, contradiz os dados de proteína do LCR, que sugerem uma taxa de fluxo reduzida do LCR como a causa. Resultados: Mesmo as disfunções de barreira mais graves não alteram a seletividade dependente do tamanho molecular nem a variação interindividual da transferência de proteína através de barreiras. As concentrações de proteínas séricas no LCR lombar aumentam com as funções hiperbólicas, mas as proteínas que não passam a barreira permanecem constantes (proteínas do cérebro) ou aumentam linearmente (proteínas leptomeningeais). Toda a dinâmica das proteínas do LCR acima e abaixo de um bloqueio lombar também pode ser explicada, independente de sua passagem pela barreira, por um fluxo caudal reduzido. O acúmulo local de gadolínio na esclerose múltipla (EM) é agora entendido como decorrente da redução da eliminação do bulk flow pelo fluido intersticial (FIS). A mudança não linear do estado estacionário na disfunção da barreira e ao longo dos gradientes rostro-caudais normais apoia o modelo de difusão/fluxo e contradiz as obstruções das vias de difusão. Independentemente da causa da doença, os bloqueios fisiopatológicos do fluxo são encontrados na meningite bacteriana, leucemia, carcinomatose meníngea, síndrome de Guillain-Barré, EM e encefalomielite alérgica experimental. Em humanos, as concentrações de albumina quarenta vezes mais altas no desenvolvimento fetal inicial diminuem tarde com a maturação das vilosidades aracnoides, isto é, com o início do fluxo de LCR, o que contradiz um fluxo relevante para o sistema linfático. As oscilações dependentes da respiração e do batimento cardíaco não perturbam a direção do fluxo do LCR. Conclusão: As disfunções das barreiras hemato-liquórica e hemato-encefálica são uma expressão da redução da taxa de fluxo do LCR ou FIS.

Glucose metabolism: A link between traumatic brain injury and Alzheimer's disease / 中华创伤杂志(英文版)

Traumatic brain injury (TBI), a growing public health problem, is a leading cause of death and disability worldwide, although its prevention measures and clinical cares are substantially improved. Increasing evidence shows that TBI may increase the risk of mood disorders and neurodegenerative diseases, including Alzheimer's disease (AD). However, the complex relationship between TBI and AD remains elusive. Metabolic dysfunction has been the common pathology in both TBI and AD. On the one hand, TBI perturbs the glucose metabolism of the brain, and causes energy crisis and subsequent hyperglycolysis. On the other hand, glucose deprivation promotes amyloidogenesis via β-site APP cleaving enzyme-1 dependent mechanism, and triggers tau pathology and synaptic function. Recent findings suggest that TBI might facilitate Alzheimer's pathogenesis by altering metabolism, which provides clues to metabolic link between TBI and AD. In this review, we will explore how TBI-induced metabolic changes contribute to the development of AD.

A study of neurological disorders in pregnancy and puerperium

Background: Neurological diseases contribute to 20% of maternal deaths. The objective of this study was to find the prevalence of primary and secondary neurological disorders in pregnant and postpartum patients, to study their clinical features, feto-maternal outcome and diagnosis using radiological imaging.Methods: This is a prospective cross-sectional study done over a period of 1 year. Pregnant and postpartum women with neurological disorders except eclampsia were enrolled. A total of 100 cases were analysed out of which 92 underwent radiological imaging to confirm diagnosis. Primary outcome in the form of prevalence of neurological disorders and secondary outcome in the form of maternal and foetal outcome was assessed.Results: The prevalence of neurological disorders in pregnancy is 1150/100000 deliveries. 75 cases were classified as primary neurological disorders (prevalence of 862/100000) which included epilepsy, cerebrovascular accidents, CNS infections, neoplasm, neuropathies and miscellaneous. 25 cases were secondary neurological disorders (prevalence of 287/100000) which included hepatic and septic encephalopathy. Among primary disorders the prevalence of cerebrovascular accidents was found to be highest (33.3%) followed by epilepsy (32%) while that among secondary neurological disorder was of Hepatic encephalopathy (92%). Majority (68%) had recovery while 15%of women had residual deficit. There were 17 (17%) cases of maternal mortality.Conclusions: Neurological disorders were significantly associated with poor feto- maternal outcome. Radiological imaging in the form of MRI is an excellent diagnostic tool for confirming diagnosis of neurological disorders.

Hearing among children with neurological disorders

Background: Neurologic disorders are not rare in our environment but studies determining the hearing of these children are almost non- existent. This study therefore is to determine the prevalence of hearing loss in these children and also determine the care seeking attitude of the parents/guardians concerning the hearing.Methods: A hospital based descriptive study of all children attending the children neurologic clinic of university of Port Harcourt teaching hospital. A semi structured questionnaire was administered to parents / guardians who gave their consent for their children to be recruited into the study. Hearing loss in the children was taken as reported by the parents/guardians. Data collected were then entered into Microsoft Excel and then exported to the IBM Statistical Package for Social Sciences (SPSS) version 20 for statistical analysis.Results: The study comprised 49 children; 29 males and 20 females. Age range was from 8months to 18years.  Age group 1-5 years comprised the majority of the study population. Commonest neurological disorder seen was childhood epilepsy n=27, 55.1%. Prevalence of hearing loss was 26.5%. Children with childhood epilepsy had 15.4% having hearing loss while children with cerebral palsy, autistic spectrum disorder and microcephaly had 50% hearing loss recorded. Maternal illness during pregnancy was significantly related to the hearing loss with a p value = 0.045 and presence of neonatal illness with p value =0.009.  Only 7.7% was formally treated while 92.3% had no form of treatment whatsoever.Conclusions: Childhood epilepsy was the commonest type of neurologic disorder seen while highest point prevalence for hearing loss was in cerebral palsy. Majority of parents/caregivers did not seek medical care concerning the hearing loss neither were there any form of treatment given to the children.

Medical hypnotic management associated with drug dependence in patients with insomnia and neurological disorders

@#Objectives: We aimed to investigate the demographics and medical management factors associated with dependence on hypnotics among outpatients with neurological disorders and insomnia. Methods: We reviewed electronic medical records of patients who received an initial hypnotic prescription between January 2014 and January 2016 and had later visited a neurological outpatient clinic before January 2018. We assessed patient demographics, the effectiveness of hypnotics, prescription periods, and hypnotic intake methods during the follow-up period. Results: Of 242 patients diagnosed with insomnia, we enrolled 114 patients (more women than men, at 61.4 versus 38.6%) who visited outpatient clinics regularly during the follow-up period. The mean age at onset was 65.8 ± 14.4 years. The most frequent neurological disorder was cerebrovascular disease, followed by neurodegenerative disease. During the 2-year period, 35.9% of participants remained hypnotics-free. Patients on zolpidem showed significantly greater insomnia improvement with hypnotic discontinuation than those on benzodiazepines and combination therapy (p=0.004). However, the type of hypnotics and demographic factors were not found to be independent risk factors. Multivariable analysis showed that longer periods between regular visits and a lower ratio of receiving number of pills to the time interval (days) between regular visits were independent risk factors for dependence on hypnotics. Conclusions: We found that low-dose and/or intermittent intake of hypnotics as well as frequent doctor visits could prevent dependence on hypnotics. It is important to establish the best practical guidelines for medical hypnotics management in outpatient primary care settings, including neurological clinics.

Magnetic Resonance-Guided Focused Ultrasound in Neurosurgery: Taking Lessons from the Past to Inform the Future

Magnetic resonance-guided focused ultrasound (MRgFUS) is a new emerging neurosurgical procedure applied in a wide range of clinical fields. It can generate high-intensity energy at the focal zone in deep body areas without requiring incision of soft tissues. Although the effectiveness of the focused ultrasound technique had not been recognized because of the skull being a main barrier in the transmission of acoustic energy, the development of hemispheric distribution of ultrasound transducer phased arrays has solved this issue and enabled the performance of true transcranial procedures. Advanced imaging technologies such as magnetic resonance thermometry could enhance the safety of MRgFUS. The current clinical applications of MRgFUS in neurosurgery involve stereotactic ablative treatments for patients with essential tremor, Parkinson's disease, obsessive-compulsive disorder, major depressive disorder, or neuropathic pain. Other potential treatment candidates being examined in ongoing clinical trials include brain tumors, Alzheimer's disease, and epilepsy, based on MRgFUS abilities of thermal ablation and opening the blood-brain barrier. With the development of ultrasound technology to overcome the limitations, MRgFUS is gradually expanding the therapeutic field for intractable neurological disorders and serving as a trail for a promising future in noninvasive and safe neurosurgical care.

Anesthetic management of a pediatric patient with Rett syndrome: A case report

Rett syndrome is a neurodevelopmental disease that almost always affects female patients. It is caused by mutations in MeCP2 in the majority of cases. Patients diagnosed with Rett syndrome may experience serious adverse events even with smaller amounts of medication for sedation and anesthesia. The major anesthetic concerns associated with Rett syndrome are lack of cooperation, abnormal continuous limb movements, abnormal respiratory control, difficult positioning secondary to scoliosis, and altered sensitivity to painful stimuli. Because of the risks caused by these problems, anesthesiologists should be aware of the specific anesthetic concerns of patients with Rett syndrome in order to safely administer anesthesia. Here, we describe the management of a pediatric patient diagnosed with Rett syndrome.

Ischemic myelopathy caused by fibrocartilaginous embolism in a horse / Mielopatia isquêmica associada a embolismo fibrocartilaginoso em um equino

ABSTRACT: This report described clinical, epidemiological, and pathological aspects of ischemic myelopathy caused by fibrocartilaginous embolism (FCE) in a 10-year-old, mixed breed gelding. Clinically, the horse presented acute hind limbs paralysis, with a clinical course of approximately 24 hours. At necropsy, no gross lesions were observed. Cross-sections of the spinal cord revealed focally extensive areas of malacia from the T10 to L4 segments. Focally extensive areas of liquefactive necrosis involving the gray matter and adjacent white matter were observed on histologic sections. The lumen of multiple blood vessels in the periphery of the necrotic areas was occluded by fibrocartilaginous emboli that strongly stained with alcian blue. Clinical signs, gross necropsy, and histological findings observed in this case were identical to those described in the literature for ischemic myelopathy caused by FCE in the horse and other species.

RESUMO: Este relato descreve os aspectos epidemiológicos, clínicos e anatomopatológicos de um caso de mielopatia isquêmica por embolismo fibrocartilaginoso (FCE) em um equino, macho castrado, sem raça definida, com 10 anos de idade. Clinicamente, o equino apresentou paralisia aguda dos membros pélvicos com evolução de aproximadamente 24 horas. Na necropsia não foram observadas alterações. Após serem realizados vários cortes transversais na medula espinhal, observou-se área focalmente extensa de malacia entre o segmento T10 até L4. Histologicamente haviam áreas focalmente extensas de necrose de liquefação envolvendo a substância cinzenta e a substância branca adjacente. Múltiplos vasos sanguíneos da periferia das áreas de necrose estavam ocluídos por êmbolos fibrocartilaginosos, que reagiram fortemente pela técnica de azul alciano. Os sinais clínicos, as lesões macroscópicas e os achados histológicos observados neste caso, são idênticos aos descritos na literatura para FCE em equinos e nas demais espécies.

Paraneoplastic Neurological Disorder in Nasopharyngeal Carcinoma

Paraneoplastic neurological disorder (PND) is a condition due to immune cross-reactivity between the tumour cells and the normal tissue, whereby the “onconeural” antibodies attack the normal host nervous system. It can present within weeks to months before or after the diagnosis of malignancies. Nasopharyngeal carcinoma is associated with paraneoplastic syndrome, for example, dermatomyositis, and rarely with a neurological disorder. We report on a case of nasopharyngeal carcinoma with probable PND. Otolaryngologists, oncologists and neurologists need to be aware of this condition in order to make an accurate diagnosis and to provide prompt treatment.

Relación entre el funcionamiento familiar y la capacidad de afrontamiento y adaptación de la familia con un niño con problema neurológico crónico del Servicio de Neuropediatr¡a del Instituto Nacional de Salud del Niño. Lima - Perú / Relationship between family functioning and capacity coping and adaptation of the family with a child with chronic problem neurological of Neuropediatrics the National Institute of Child Health. Lima - Perú

Objetivos: determinar la relación del funcionamiento familiar y la capacidad de afrontamiento y adaptación de la familia con un niño con problema neurológico crónico. Material y Métodos: estudio descriptivo correlacional de corte transversal. La recolección de datos se realizó en los meses de marzo a mayo del 2015, en 29 familiares, a quienes se les entrevistó y aplicó el cuestionario, previa firma del consentimiento informado, en un servicio de hospitalización de neuropediatría. Se realizó la validación del instrumento a través de juicio de expertos y prueba piloto obteniendo una confiabilidad de 0,771 de alfa de Crombach. Los datos obtenidos fueron calificados en una base diseñada en el programa Excel, luego se realizó el análisis para ver la relación entre las variables mediante Rho de Spearman en el programa SPSS versión 22. Los resultados se presentan en tablas estadísticas. Resultados: el tipo familiar con mayor porcentaje fue el extremo y de rango medio, con un 48,3%. La capacidad de afrontamiento y adaptación en mayor porcentaje fue la de mediano rango 55,2%; y alta, 20,7%. Conclusiones: el funcionamiento familiar tiene tendencia a la disfuncionalidad en la familia con un niño con enfermedad neurológica crónica y presenta mediana capacidad de afrontamiento y adaptación con propensión a la baja, no se encontró relación estadística significativa.

Objectives: to determine the relationship between family functioning and coping skills and adaptation of the family with a child with chronic neurological problem. Material and Methods: descriptive correlational cross-sectional study. Data collection was conducted in the months of March to May 2015, 29 fathers, mothers or aunts, who were interviewed and applied the questionnaire after signing the informed consent, in an inpatient pediatric neurology service. Validation of the instrument was performed using expert judgment and a pilot test obtaining a reliability Crombach’s alpha 0.771. The data obtained was graded with an excel data base sheet, then the analysis was performed to see the relationship between variables using Spearman Rho SPSS version 22. The results are presented in statistical tables. Results: the family type with the highest percentage was the end and midrange, 48.3%. The ability to cope and adapt to a greater percentage was 55.2% medium range; high, 20.7%. Conclusions: family functioning has the tendency towards families with a child with chronic neurological disease and has medium capacity for coping and adapting prone to diminish; no statistically significant relationship was found.

Neurological Disorders Associated with Pregnancy: A Hospital Based Imaging Study of 57 Cases in North-East India.

Aims: To evaluate and characterize the Computed Tomography and Magnetic Resonance Imaging findings of the various neurological conditions of the central nervous system and pituitary gland that can occur during pregnancy and post partum period. Place and Duration of Study: The study was carried out in the Department of Radiology, Gauhati Medical College and Hospital, Guwahati, from August 2012 to July 2013. Methodology: A total of 57 patients of neurological disorders of the central nervous system and pituitary gland associated with pregnancy, who were referred to the Department for radiological evaluation and who had positive imaging findings were taken up for the study. CT scan was performed in those cases referred for imaging. For further evaluation, cases were referred to MRI or wherever possible, cases were directly referred for MRI. Contrast CT was avoided in most of the cases. Results: Out of 57 patients, 54.39% patients were in age between 20 to 30 years. Headache was the most common presenting complaint (71.93%) in all the neurological disorders. Hypertensive encephalopathy (40.35%) was the most common neurological disorder followed by Cerebral Venous Thrombosis (17.54%). Infarct was the commoner complication of hypertensive encephalopathy accounting for 21.74% of cases. Magnetic resonance was able to detect infarct in 21.74% of cases compared to CT which could detect infarct in 13.04% of cases. P value 0.3534 and sensitivity 72%, 95% Confidence Interval 0.46 to 0.90 with negative predictive value 50% with 95% Confidence Interval 0.18 to 0.81. Conclusion: Both CT and MRI can depict the characteristic imaging features of these neurological disorders in pregnancy as well as development of complications, hence leading to early and prompt diagnosis of these disorders and better management of these patients. ABBREVIATIONS: CI: Confidence Interval, TOF MRA: Time of Flight Magnetic Resonance Agiography, MRV: Magnetic Resonance Venography, TR: repetation time, TE: echo time, FLAIR: Fluid Attenuated Inversion Recovery, DWI: diffusion weighted image, SWI: Susceptibility Weighted Imaging, NECT: non enhanced computed tomography, ESR: erythrocyte sedimentation rate, ADC: Apparent diffusion coefficient.

Advances of the traditional Chinese medicines modulating endoplasmic reticulum stress / 中国药科大学学报

@#The endoplasmic reticulum is an important organelle for eukaryotic cell protein synthesis, folding and secretion. Perturbation of endoplasmic reticulum homeostasis causes endoplasmic reticulum stress. It has been considered as one of important ways and new strategies to regulate endoplasmic reticulum stress in the treatment of multiple diseases. This paper mainly reviews the advances in the research on traditional Chinese medicines for modulating endoplasmic reticulum stress related to cancer, cardiovascular diseases, neurological diseases, diabetes and other complex diseases in recent years, aiming to provide some clues and references for exploring the characteristics and possible mechanism of traditional Chinese medicines treating related diseases.

Griscelli syndrome type 2: a novel mutation in RAB27A gene with different clinical features in 2 siblings: a diagnostic conundrum / 소아과

Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disease caused by mutations in the RAB27A gene. It is characterized by cutaneous hypopigmentation, immunodeficiency, and hemophagocytic lymphohistiocytosis. We describe 2 brothers who had GS2 with clinically diverse manifestations. The elder brother presented with a purely neurological picture, whereas the younger one presented with fever, pancytopenia, hepatosplenomegaly, and erythema nodosum. Considering that cutaneous hypopigmentation was a common feature between the brothers, genetic analysis for Griscelli syndrome was performed. As the elder sibling had died, mutation analysis was only performed on the younger sibling, which revealed a novel homozygous mutation in the RAB27A gene on chromosome 15 showing a single-base substitution (c.136T>A p.F46I). Both parents were heterozygous for the same mutation. This confirmed the diagnosis of GS2 in the accelerated phase in both siblings. The atypical features of GS2 in these cases are a novel mutation, isolated neurological involvement in one sibling, association with erythema nodosum, and 2 distinct clinical presentations in siblings with the same genetic mutation.

Spinal cord compression in cattle after the use of an oily vaccine / Compressão medular em bovinos após o uso de vacina oleosa

An outbreak of compressive myelopathy in cattle associated with the improper use of an oil vaccine is described. Neurological signs were observed in 25 out of 3,000 cattle after 60 days of being vaccinated against foot and mouth disease. The clinical picture was characterized by progressive paralysis of the hind limbs, difficulty in standing up, and sternal recumbency during the course of 2-5 months. A filling defect between the L1 and L3 vertebrae was seen through myelography performed in one of the affected animals. A yellow-gray, granular and irregular mass was observed in four necropsied animals involving the spinal nerve roots and epidural space of the lumbar (L1-L4) spinal cord; the mass was associated with a whitish oily fluid. This fluid was also found in association with necrosis of the longissimus dorsi muscle. Microscopic changes in the epidural space, nerve roots, and spinal musculature were similar and consisted of granulomas or pyogranulomas around circular unstained spaces (vacuoles). These spaces were located between areas of severe diffuse hyaline necrosis of muscle fibers and resembled the drops of oil present in the vaccine.

Relatamos um surto de mielopatia sas medulares e espaço epidural da região lombar (L1-L4); compressiva lombar em bovinos associada à aplicação de esse material era associado com líquido brancacento e vacina oleosa de forma inadequada. De um total de 3000 oleoso. Havia também áreas de necrose no músculo Lonbovinos, 25 apresentaram distúrbios neurológicos apro-gissimus dorsi com material similar ao do espaço epidural. ximadamente 60 dias após terem sido vacinados contra a Microscopicamente, as alterações observadas no espaço febre aftosa. O quadro clínico foi caracterizado por parali-epidural, raízes nervosas medulares e na musculatura fosia progressiva de membros posteriores, dificuldade para ram similares sendo caracterizadas pela formação de múlpermanecer em estação e decúbito esternal com evolução tiplos granulomas ou piogranulomas envolvendo espaços de 2-5 meses. A mielografia realizada em um animal reve-(vacúolos) circulares não corados (aparentemente, o local lou defeito de enchimento na altura das vértebras L1 e L3. antes ocupado por gotículas de óleo presente na vacina), Quatro animais foram necropsiados e foi visualizado massa além de necrose hialina severa difusa de fibras musculares.

Estado y salud buco-dental del paciente pediátrico con daño neurológico / Status and health oral-dental pediatric patient with neurological damage

Este documento describe a groso modo las características bucales que presentan los pacientes con daño neurológico, además de las consideraciones y el manejo en la atención estomatológica de este grupo de población infantil que puede variar de daño neurológico leve hasta severo, incluyendo a los de atención intrahospitalaria. Este tipo de pacientes sufre de severos problemas bucales especialmente la alta incidencia de caries dental y enfermedades que afectan el periodonto debido a las características propias de su diagnóstico que contribuye y dificulta el cuidado bucal por parte de sus cuidadores y por déficit en la atención estomatológica de los profesionales de la salud bucal, quienes desconocen en su mayoría las consideraciones a tomar en la atención de este grupo de pacientes

This document describes the characteristics of oral that presenting patients with neurological damage, in addition to the considerations and the handling in the stomatological care of this group of children which can vary from mild to severe neurological damage, including those for inpatient care. This type of patients suffering from severe oral problems especially the high incidence of dental caries and diseases which affect the periodont because of the specificity characteristics of her diagnosis that helps and hinders the oral care by their caregivers and deficits in attention stomatological of oral health professionals those who are unaware of the considerations to take care of this patient group

Neural Stem Cells for Neurological Disorders

Recent progress shows that neurons suitable for transplantation can be generated from neural stem cells (NSCs) in culture, and that the adult brain produces new neurons from its own stem cells in response to injury. In this article, we discuss how the subventricular zone of the forebrain is the most active neurogenetic area and the richest source of NSCs. This review also focuses on the nature and functional properties of NSCs of the adult mammalian brain, and we propose our views on the strategy from bench to the clinic with particular concerns and considerations.