La solidez de la investigación homeopática fundamental / The strength of fundamental homeopathic research

La investigación fundamental en homeopatía ha avanzado considerablemente en los últimos 20 años: desde estudios exploratorios con animales y plantas hasta la caracterización de los efectos sistémicos de los medicamentos homeopáticos y estudios in vitro con sistemas celulares aislados para evaluar los cambios en los mecanismos de adaptación celular y señalización intracelular frente a tratamientos homeopáticos variables. El número de artículos publicados a lo largo del tiempo ha permitido realizar varias revisiones sistemáticas. Recientemente, la demostración de que los medicamentos homeopáticos podrían modificar las funciones celulares a través de mecanismos epigenéticos (metilación y desmetilación de ADN) preparó el camino para un campo de investigación completamente nuevo. En paralelo, el descubrimiento de las nanopartículas y propiedades físicas específicas de las diluciones homeopáticas ha arrojado luz hacia un campo antes poco conocido, dado que se consideraba que las diluciones homeopáticas no consistían más que de agua. Así las cosas, los retos para el futuro conciernen a la demostración, o no, de la interrelación entre ambos fenómenos.

Fundamental research in homeopathy has much advanced in the past 20 years. From exploratory studies with animals and plants to the characterization of the systemic effects of homeopathic medicines and in vitro studies with isolated cell systems to assess changes in the mechanisms of cell adaptation and intracellular signaling facing variable homeopathic treatments. The amount of articles published over time enabled several systematic reviews. Recently, demonstration that homeopathic medicines might modify cell functions through epigenetic mechanisms (DNA methylation and demethylation) paved the road for a fully new field of research. In parallel, the discovery of nanoparticles and specific physical properties of homeopathic dilutions brought light to a previously poorly known field, as it was believed that homeopathic dilutions consist in nothing but water. Thus being, challenges for the future concern the demonstration, or not, of the interrelationship between both phenomena.

Experimental cholesteatoma: a comparison between spontaneous and induced models

Abstract Objective: To compare the incidence and the histopathological aspect of spontaneous and two induced Mongolian gerbils' models of cholesteatoma: External Auditory Canal (EAC) obliteration model and the Auditory Tube (AT) cauterization model. Methods: Fifty-four ears of 27 animals were divided into EAC obliteration, AT cauterization, and control groups and histologically assessed for cholesteatoma incidence and classification at intervals of 2, 4, 8, and 16 weeks. Results: Cholesteatoma was diagnosed in 30 of the 53 ears evaluated with a significantly higher incidence in groups that received some type of intervention (p < 0.0001). It was not possible to histologically distinguish cholesteatomas of the same stage between the study groups. Conclusion: Although we observed a significant increase in cholesteatoma incidence with the two methods used when compared to the control group, all developed cholesteatomas were apparently identical from a histological point of view.

Mongolian Gerbils as a Model for the Study of Cholesteatoma: Otoendoscopic as a Diagnostic Tool

Abstract Introduction Cholesteatoma is a disease with significant clinical impact but is incompletely understood. The challenge of performing studies with long-term follow-up in humans is a factor that has restricted the advance of knowledge in this field. Thus, the use of animal models is highly pertinent, and the Mongolian gerbil model has emerged as one of the most useful. Objective The present study aims to evaluate, through serial otoendoscopies, the development and characteristics of pars flaccida retraction pocket and cholesteatoma in Mongolian gerbils after obliteration of the eustachian tube and compare it with the control group. Methods Forty Mongolian gerbils were divided into two groups of 20 animals each. In the intervention group, the animals were followed with serial otoendoscopies after eustachian tube obliteration. In the control group, the animals were only followed through serial otoendoscopies. Results At the end of the 16-week follow-up, cholesteatoma was present in 13 of 38 (34.2%) ears in the intervention group, and in 7 of 34 (20.6%) in the control group (p = 0.197). When we considered cholesteatoma and its potential precursor, pars flaccida retraction pocket, in a combined way, we verified it in 23 of 38 (60.8%) in the intervention group and in 11 of 34 (32.3%) in the control group (p = 0.016). Conclusions Over the 16 weeks of follow-up, serial otoendoscopies enabled us to evaluate the formation and development of pars flaccida retraction pockets and cholesteatomas in Mongolian gerbils and proved to be an excellent diagnostic tool.

Advances in the establishment and application of experimental models of optic neuritis associated with neuromyelitis optica / 国际眼科杂志(Guoji Yanke Zazhi)

@#Neuromyelitis optica(NMO)is an inflammatory central nervous system(CNS)astrocytic disease with high incidence, neuro-ophthalmic intercross, and humoral immune-dominated in Asian population. It has attracted much attention due to its high pathogenicity, high risk of recurrence, and poor prognosis. It is difficult for patients with NMO-associated optic neuritis(NMO-ON)to benefit from routine treatment, and they are often left with different degrees of optic nerve atrophy. One limitation of the study of NMO-ON is the deficiency of the experimental model. Therefore, the progress and application of NMO and NMO-ON experimental model are reviewed in this paper, aiming to explore the pathological mechanism and possible treatment of NMO visual impairment.

¿Los protocolos experimentales son un símil real de la diabetes humana? / Are experimental protocols an authentic simile of human diabetes?

Resumen Para el estudio de la diabetes se dispone de diversas estrategias metodológicas en modelos animales, tales como, técnicas quirúrgicas, modificaciones dietéticas, incluso manipulación genética y la administración de fármacos específicos, por su toxicidad. En animales, la diabetes experimental se logra con el uso de fármacos, como la aloxana o la estreptozotocina, los cuales producen daño irreversible en las células β-pancreáticas, aunque causan una alta mortalidad, debido a la cetosis asociada al daño agudo de estas células pancreáticas. El objetivo de este trabajo fue analizar los protocolos farmacológicos y otras estrategias disponibles, para determinar si la diabetes experimental realmente emula la diabetes humana. La diabetes es un proceso progresivo y crónico, en el que la mayor parte de las alteraciones clínicas son consecuencia, en el largo plazo, de alteraciones micro y macrovasculares. Por ello, es conveniente diferenciar entre los efectos de una hiperglucemia aguda, con aquellos que se observan cuando la hiperglucemia se prolonga a lo largo del tiempo, a fin de establecer analogías, entre el modelo experimental animal, con el síndrome diabético humano, mediante datos de laboratorio y de tipo clínico, de uso habitual en el diagnóstico y manejo de la diabetes humana.

Abstract For the study of diabetes, several methodological strategies use animal models. Such methodologies involve surgical techniques, diet modifications, some genetic manipulations and specific toxic drugs. The experimental production of diabetes in animal models use the administration of alloxan or streptozotocin and these drugs produce irreversible damage to pancreatic β-cells. However, its use is associated to a ketosis high mortality rate due to the acute damage of pancreatic cells. The aim of this review consisted in the analysis of the pharmacological diabetes production protocols as well as other available strategies, in order to elucidate which is potentially the ideal protocol that emulates human diabetes. Diabetes is a progressive and chronic process, in which most of the clinical alterations are a long-term consequence of micro and macrovascular alterations. Therefore, it is convenient to establish a difference between the effects of acute hyperglycemia, with those effects observable when hyperglycemia is present over the long-term in order to reach enough analogies between the animal experimental model with the human diabetes syndrome, through the use of laboratory and clinical indicators commonly employed for the diagnoses and management of human diabetes.

Development of the urinary system in guinea pig females (Cavia porcellus) / Desenvolvimento do sistema urinário em fêmeas de porquinhos-da-índia (Cavia porcellus)

Guinea pigs are animal models widely used in research related to developmental biology. The objective of this work was to demonstrate the process of formation and differentiation of urinary organs in females of the species in the prenatal period. Four females were used at 25, 30, 45 and >65 DG (days of gestation). The animals were dissected, and then macroscopic and microscopic descriptions of the urinary organs were performed. At 25 DG metanephros were present in the urogenital crest into the abdominal cavity. Collecting ducts and glomerular precursor cells could be visualized. After this period, metanephros underwent microstructural modifications to form the kidneys at the end of the prenatal period. After 30 DG, the renal parenchyma already had a cortex, where the glomerulus and proximal convoluted tubules were present; and the medulla, where distal convoluted tubules, collecting ducts, and pelvis were present. The pelvis of each kidney was drained by the ureters. The ureters also underwent tissue differentiation to be differentiated (mucosa with transitional epithelium and lamina propria of connective tissue, muscular, and adventitia) at the end of the prenatal period. The urinary vesicle also underwent tissue changes to form the tunics similar to those found in the ureters, with emphasis on the greater volume of the muscular tunica and the lamina propria that constituted the submucosa in this organ. The pelvic urethra was evidenced by a mucosa lined by transitional epithelium, submucosa, muscular and adventitia. Finally, a partial clitoral urethra and a urethral meatus in the prepuce of the clitoris were also evidenced. The urethral channel began to form with the emergence of the urethral plate and the urethral groove at 30 DG and thereafter with the fusion of the urethral folds to form a partially channeled urethra in the clitoris. A urethral meatus was observed in the most distal portion of the clitoral tissue, formed by the fusion of the prepuce. It is concluded that the urinary organs of guinea pig have similar development to that described in domestic animals, except for the partial clitoral urethra and evident urethral meatus.(AU)

Os porquinhos-da-índia são modelos animais amplamente utilizados em pesquisas relacionadas a biologia do desenvolvimento. O objetivo deste trabalho foi demonstrar o processo de formação e diferenciação dos órgãos urinários em fêmeas da espécie no período pré-natal. Foram utilizadas quatro fêmeas aos 25, 30, 45 e >65 DG (dias de gestação). Os animais foram dissecados e então, realizaram-se descrições macroscópicas e microscópicas dos órgãos urinários. Aos 25 DG os metanefros estavam presentes na crista urogenital da cavidade abdominal. Podiam ser visualizados ductos coletores e células precursoras glomerulares. Após este período, os metanefros sofreram modificações microestruturais para formar os rins ao final do período pré-natal. Após os 30 DG, o parênquima renal já apresentava um córtex, onde estavam presentes os glomérulos e túbulos convolutos proximais, e a medula onde estavam presentes túbulos convolutos distais, ductos coletores e a pelve. A pelve de cada rim era drenada pelos ureteres. Os ureteres também sofreram diferenciação tecidual para estarem com suas túnicas diferenciadas (mucosa com epitélio de transição e lâmina própria de tecido conjuntivo; muscular; e, adventícia) ao final do período pré-natal. A vesícula urinária também passou por modificações teciduais para formar as túnicas semelhantes as dos ureteres, com destaque para o maior volume da túnica muscular e a lâmina própria que constituiu a submucosa neste órgão. Uma uretra pélvica foi evidenciada por uma mucosa revestida por epitélio de transição, submucosa, muscular e adventícia. Por último, uma uretra parcialmente clitoriana e um meato uretral no prepúcio do clitóris também foi evidenciado. O canal uretral começou a se formar com o aparecimento da placa uretral e do sulco uretral aos 30 DG e posteriormente com a fusão das pregas uretrais para formar uma uretra parcialmente canalizada no clitóris. Observou-se um meato uretral na porção mais distal do tecido clitoriano, formado pela fusão do prepúcio. Conclui-se que os órgãos urinários do porquinho-da-índia possuem desenvolvimento semelhante ao descrito em animais domésticos, com exceção da uretra parcialmente clitoriana e do meato uretral evidente.(AU)

Aplicaciones de terapias de reemplazo celular al tratamiento de enfermedades poliglutamínicas / Applications of cell replacement therapies to the treatment of poly-glutamine diseases

Se realizó una revisión de la literatura especializada con el objetivo de evaluar el estado del arte en cuanto a la aplicación de terapias de reemplazo celular en enfermedades poliglutamínicas. Se consultaron las bases de datos HighWire y PubMed, con el uso de descriptores y operadores booleanos. Se recuperaron 84 artículos sobre la temática, publicados en revistas con un factor de impacto promedio de 5,42. Se discuten los estudios experimentales y pre-clínicos realizados con relación a terapias de reemplazo celular en enfermedades poliglutamínicas. Se demuestra la efectividad del uso de células madre de distintas fuentes en el mejoramiento de la función motora en modelos experimentales de enfermedades poliglutamínicas. Se revela la necesidad de realizar estudios multicéntricos a mediano y largo plazos, para la evaluación de los efectos terapéuticos de las terapias de reemplazo celular en enfermedades poliglutamínicas.

A review of the specialized literature was carried out with the aim of evaluating the state of the art regarding the application of cell replacement therapies in polyglutamine diseases. The HighWire and PubMed databases were consulted, with the use of Boolean descriptors and operators. 84 articles were retrieved on the subject, published in journals with an average impact factor of 5.42. The experimental and pre-clinical studies carried out in relation to cell replacement therapies in polyglutamine diseases are discussed. The effectiveness of the use of stem cells from different sources in the improvement of motor function in experimental models of polyglutamine diseases is demonstrated. The need to perform multicenter studies in the medium and long term is revealed, for the evaluation of the therapeutic effects of cell replacement therapies in polyglutamine diseases.

Applied genomic in cerebrovascular disease / Genómica funcional en la enfermedad vascular cerebral

Abstract Cerebrovascular disease involve the alterations caused by pathology process of the sanguineous vessels, affecting one or many brain areas. Cerebrovascular disease is also known like stroke or ictus; it is the third cause of death around the world and is the neurologic pathology with the most prevalence rate. Cerebrovascular disease induces several changes in genetic expression inside the neurovascular unit (glia cells, neurons and ependymal cells); principally, changes in the oxidative stress and calcium inflow into the cells, this could start cellular death and tissue destruction, causing an irreversible injury in brain, losing several functions. The injury causes the activation of signaling pathways to respond to the stress, where many molecules such as proteins and mRNA are involved to act as intermediaries to activate or deactivate stress mechanisms; these molecules are able to transmit extracellular signals into the nucleus activating early gene expression like proto-oncogenes and several transcription factors to repair the cerebral injury. It is important to know the relation of the changes in genetic expression and proteins to avoid the development of injury and to activate the brain recovery. This knowledge let us diagnose the injury rate and propose therapeutic mechanisms to reduce or avoid the adverse effects on time, before the cellular death start.

Resumen Las enfermedades cerebrovasculars implican las alteraciones causadas por el proceso patológico de los vasos sanguíneos, que afectan a una o varias áreas del cerebro. La enfermedad cerebro-vascular también se conoce como ictus o ictus; Es la tercera causa de muerte en todo el mundo y es la patología neurológica con mayor tasa de prevalencia. La enfermedad cerebrovascular induce varios cambios en la expresión genética dentro de la unidad neurovascular (células gliales, neuronas y células ependimales); Principalmente, los cambios en el estrés oxidativo y la entrada de calcio en las células, podrían iniciar la muerte celular y la destrucción del tejido, causando una lesión irreversible en el cerebro, perdiendo varias funciones. La lesión hace que la activación de las vías de señalización responda al estrés, donde muchas moléculas, como las proteínas y el ARNm, actúan como intermediarios para activar o desactivar los mecanismos de estrés; estas moléculas son capaces de transmitir señales extracelulares en el núcleo activando la expresión génica temprana como protooncogenes y varios factores de transcripción para reparar la lesión cerebral. Es importante conocer la relación de los cambios en la expresión genética y las proteínas para evitar el desarrollo de lesiones y activar la recuperación del cerebro. Este conocimiento nos permite diagnosticar la tasa de lesiones y proponer mecanismos terapéuticos para reducir o evitar los efectos adversos a tiempo, antes de que comience la muerte celular.

Systematic review of the synergist muscle ablation model for compensatory hypertrophy / Revisão sistemática do modelo de ablação dos músculos sinérgicos na hipertrofia compensatória

Summary Objective: The aim was to evaluate the effectiveness of the experimental synergists muscle ablation model to promote muscle hypertrophy, determine the period of greatest hypertrophy and its influence on muscle fiber types and determine differences in bilateral and unilateral removal to reduce the number of animals used in this model. Method: Following the application of the eligibility criteria for the mechanical overload of the plantar muscle in rats, nineteen papers were included in the review. Results: The results reveal a greatest hypertrophy occurring between days 12 and 15, and based on the findings, synergist muscle ablation is an efficient model for achieving rapid hypertrophy and the contralateral limb can be used as there was no difference between unilateral and bilateral surgery, which reduces the number of animals used in this model. Conclusion: This model differs from other overload models (exercise and training) regarding the characteristics involved in the hypertrophy process (acute) and result in a chronic muscle adaptation with selective regulation and modification of fast-twitch fibers in skeletal muscle. This is an efficient and rapid model for compensatory hypertrophy.

Resumo Objetivo: Avaliar a eficácia do modelo experimental de ablação dos sinergistas para promover a hipertrofia muscular, determinar o período de maior hipertrofia, sua influência sobre os tipos de fibras musculares e determinar diferenças na remoção unilateral ou bilateral para reduzir o número de animais utilizados nesse modelo. Método: Após a aplicação dos critérios de elegibilidade para sobrecarga mecânica do músculo plantar em ratos, 19 artigos foram incluídos na revisão. Resultados: Ocorre maior hipertrofia entre os dias 12 e 15, o que torna o modelo eficiente para alcançar a hipertrofia rapidamente. O membro contralateral também pode ser usado, pois não houve diferença entre a cirurgia unilateral e bilateral, o que reduz o número de animais usados no experimento. Conclusão: O modelo difere de outros modelos de sobrecarga (exercício e treinamento) em razão das características envolvidas no processo de sobrecarga imposta (aguda), resultando em uma adaptação crônica muscular com modificação de fibras de contração rápida do músculo esquelético. É um modelo rápido e eficiente para se estudar hipertrofia compensatória.

Zika virus congenital syndrome: experimental models and clinical aspects

Viral infections have long been the cause of severe diseases to humans, increasing morbidity and mortality rates worldwide, either in rich or poor countries. Yellow fever virus, H1N1 virus, HIV, dengue virus, hepatitis B and C are well known threats to human health, being responsible for many million deaths annually, associated to a huge economic and social cost. In this context, a recently introduced flavivirus in South America, called Zika virus (ZIKV), led the WHO to declare in February 1st 2016 a warning on Public Health Emergency of International Concern (PHEIC). ZIKV is an arbovirus of the Flaviviridae family firstly isolated from sentinels Rhesus sp. monkeys at the Ziika forest in Uganda, Africa, in 1947. Lately, the virus has well adapted to the worldwide spread Aedes aegypti mosquito, the vector for DENV, CHIKV, YFV and many others. At first, it was not considered a threat to human health, but everything changed when a skyrocketing number of babies born with microcephaly and adults with Guillain-Barré syndrome were reported, mainly in northeastern Brazil. It is now well established that the virus is responsible for the so called congenital Zika syndrome (CZS), whose most dramatic features are microcephaly, arthrogryposis and ocular damage. Thus, in this review, we provide a brief discussion of these main clinical aspects of the CZS, correlating them with the experimental animal models described so far.(AU)

Zika virus congenital syndrome: experimental models and clinical aspects

Abstract Viral infections have long been the cause of severe diseases to humans, increasing morbidity and mortality rates worldwide, either in rich or poor countries. Yellow fever virus, H1N1 virus, HIV, dengue virus, hepatitis B and C are well known threats to human health, being responsible for many million deaths annually, associated to a huge economic and social cost. In this context, a recently introduced flavivirus in South America, called Zika virus (ZIKV), led the WHO to declare in February 1st 2016 a warning on Public Health Emergency of International Concern (PHEIC). ZIKV is an arbovirus of the Flaviviridae family firstly isolated from sentinels Rhesus sp. monkeys at the Ziika forest in Uganda, Africa, in 1947. Lately, the virus has well adapted to the worldwide spread Aedes aegypti mosquito, the vector for DENV, CHIKV, YFV and many others. At first, it was not considered a threat to human health, but everything changed when a skyrocketing number of babies born with microcephaly and adults with Guillain-Barré syndrome were reported, mainly in northeastern Brazil. It is now well established that the virus is responsible for the so called congenital Zika syndrome (CZS), whose most dramatic features are microcephaly, arthrogryposis and ocular damage. Thus, in this review, we provide a brief discussion of these main clinical aspects of the CZS, correlating them with the experimental animal models described so far.

The soundness of homeopathic fundamental research

Fundamental research in homeopathy has much advanced in the past 20 years. From exploratory studies with animals and plants to the characterization of the systemic effects of homeopathic medicines and in vitro studies with isolated cell systems to assess changes in the mechanisms of cell adaptation and intracellular signaling facing variable homeopathic treatments. The amount of articles published over time enabled several systematic reviews. Recently, demonstration that homeopathic medicines might modify cell functions through epigenetic mechanisms (DNA methylation and demethylation) paved the road for a fully new field of research. In parallel, the discovery of nanoparticles and specific physical properties of homeopathic dilutions brought light to a previously poorly known field, as it was believed that homeopathic dilutions consist in nothing but water. Thus being, challenges for the future concern the demonstration, or not, of the interrelationship between both phenomena.

Exercise training on cardiovascular diseases: Role of animal models in the elucidation of the mechanisms

Abstract Cardiovascular diseases, which include hypertension, coronary artery disease/myocardial infarction and heart failure, are one of the major causes of disability and death worldwide. On the other hand, physical exercise acts in the preventionand treatment of these conditions. In fact, several experiments performed in human beings have demonstrated the efficiency of physical exercise to alter clinical signals observed in these diseases, such as high blood pressure and exercise intolerance. However, even if human studies demonstrated the clinical efficiency of physical exercise, most extensive mechanisms responsible for this phenomenon still have to be elucidated. In this sense, studies using animal models seem to be a good option to demonstrate such mechanisms. Therefore, the aims of the present study are describing the main pathophysiological characteristics of the animal models used in the study of cardiovascular diseases, as well as the main mechanismsassociated with the benefits of physical exercise.(AU)

Experimental models for the study of neuropathic pain / Modelos experimentais para o estudo da dor neuropática

ABSTRACT BACKGROUND AND OBJECTIVES: Ideal models should reproduce just sensory deficits, such as alodynia, hyperalgesia and spontaneous pain for short periods. There are different types of animal models to evaluate different neuropathic pain etiologies and manifestations. Some models study neuropathic pain peripheral mechanisms and other study its central mechanisms. This review focuses on animal models most commonly used for neuropathic pain research. CONTENTS: Animal models based on peripheral nerves ligation which are more commonly used are described. From all models described in this review, spared nerve injury is that producing more reproducible behavioral abnormalities for a longer period, while chronic sciatic nerve compression produces behavioral signs of less predictable painful neuropathies. Spinal hemisection and cytokines-induced spinal injury are the models of choice for the study of central pain mechanisms. Other specific models are used for the study of the specific etiology of pain. CONCLUSION: Since neuropathic pain is multifactorial, different neuropathic pain animal models were developed throughout the years, which have been critical for the study of neuropathic pain, since much of current knowledge comes from studies with rats and mice. Current animal models need to be further refined and more efforts should be made to determine which animal models may be more predictive, with less biases and more complex and objective analysis parameters.

RESUMO JUSTIFICATIVA E OBJETIVOS: Os modelos ideais deveriam reproduzir apenas déficits sensitivos, como alodínea, hiperalgesia e dor espontânea por curtos períodos de tempo. Existem diversos tipos de modelos animais, que avaliam as diversas etiologias e manifestações da dor neuropática. Alguns modelos estudam os mecanismos periféricos e outros estudam mecanismos centrais da dor neuropática. Esta revisão enfoca os modelos animais mais comumente utilizados para pesquisa em dor neuropática. CONTEÚDO: São descritos modelos animais baseados em ligadura de nervos periféricos que são mais comumente empregados. De todos os modelos descritos nesta revisão, a lesão poupadora de nervo é aquela que produz anormalidades comportamentais mais reprodutíveis, por um período mais longo, ao passo que a constrição crônica do ciático produz sinais comportamentais de neuropatia dolorosas menos previsíveis. Hemisecção espinhal e lesão espinhal induzida por citocinas são os modelos de escolha para estudar mecanismos de dor central. Outros modelos específicos são utilizados para estudo da etiologia específica da condição dolorosa. CONCLUSÃO: Como a dor neuropática é multifatorial, diferentes modelos animais de dor neuropática foram desenvolvidos ao longo dos anos que têm sido fundamentais para o estudo da dor neuropática, uma vez que muito do conhecimento atual provém de estudos em ratos e camundongos. São necessários maiores refinamentos nos modelos animais atualmente empregados e mais esforços para determinar quais modelos animais podem ser mais preditivos, com menos vieses e com parâmetros de análises mais complexos e objetivos.

Progeria: A rare genetic premature ageing disorder.

Progeria is characterized by clinical features that mimic premature ageing. Although the mutation responsible for this syndrome has been deciphered, the mechanism of its action remains elusive. Progeria research has gained momentum particularly in the last two decades because of the possibility of revealing evidences about the ageing process in normal and other pathophysiological conditions. Various experimental models, both in vivo and in vitro, have been developed in an effort to understand the cellular and molecular basis of a number of clinically heterogeneous rare genetic disorders that come under the umbrella of progeroid syndromes (PSs). As per the latest clinical trial reports, Lonafarnib, a farnesyltranferase inhibitor, is a potent ‘drug of hope’ for Hutchinson-Gilford progeria syndrome (HGPS) and has been successful in facilitating weight gain and improving cardiovascular and skeletal pathologies in progeroid children. This can be considered as the dawn of a new era in progeria research and thus, an apt time to review the research developments in this area highlighting the molecular aspects, experimental models, promising drugs in trial and their implications to gain a better understanding of PSs.

Establecimiento de las condiciones para el trasplante de células de médula ósea en un modelo de enfermedad de Huntington y su efecto funcional a través de la conducta motora / Establishment of the conditions for the bone marrow cells transplants in a model of Huntington´s disease and functional effect on the motor behavior

La enfermedad de Huntington (EH) es un trastorno degenerativo hereditario que afecta a personas con predisposición genética. No existe hasta hoy un tratamiento efectivo; la enfermedad avanza lentamente y el paciente termina en incapacidad o muerte después de 15 o 20 años. Los estudios relacionados con el tratamiento de las manifestaciones clínicas que aparecen en la enfermedad, incluyen tratamientos medicamentosos y el uso de trasplante de células. En la actualidad se conoce que es posible reproducir algunas características de la enfermedad en modelos experimentales para ensayar posibles terapéuticas (ej. el modelo de lesión estriatal por inyección de ácido quinolínico; [AQ]). No se conoce el efecto restaurativo de las células de médula ósea (CMO) en este modelo. Objetivos: 1) Caracterizar morfológicamente la lesión por inyección intraestriatal de AQ. 2) Caracterizar inmunocitoquímicamente las CMO. 3) Evaluar la concentración óptima de CMO para el trasplante en el modelo y 4) Evaluar el estado funcional del trasplante de CMO, a través de la conducta motora.

Huntington Disease (HD) is a heritable neurodegenerative disease that affects people with genetic history. Until today, an effective treatment doesn't exist; the illness advances slowly and the patient finishes in inability or death after 15 or 20 years. The studies related with the treatment of the clinical manifestations, include treatments with medications and the use of cells transplant. At the present time it is known that it is possible to reproduce, some characteristics of the disease in experimental models for to use possible therapies [example: estriatal lesion of quinolínico acid; (QA)]. the restorative effect of the bone marrow cells (BMC) is not known in this model. Objectives. 1) characterizationmorphofological of the estriatal lesion whith QA. 2) to characterization immunochemical of BMC. 3) to evaluate the BMC concentration for the transplant and 4) to evaluate the functional state of BMC transplant, through the motor behavior.

Animal models for the study of arterial hypertension.

Hypertension is one of the leading causes of disability or death due to stroke, heart attack and kidney failure. Because the etiology of essential hypertension is not known and may be multifactorial, the use of experimental animal models has provided valuable information regarding many aspects of the disease, which include etiology, pathophysiology, complications and treatment. The models of hypertension are various, and in this review, we provide a brief overview of the most widely used animal models, their features and their importance.

Modelling of Cerebral Tuberculosis: Hope for Continuous Research in Solving the Enigma of the Bottom Billion’s Disease

Cerebral tuberculosis is a severe type of extrapulmonary disease that is highly predominant in children. It is thought that meningeal tuberculosis, the most common form of cerebral tuberculosis, begins with respiratory infection followed by early haematogenous dissemination to extrapulmonary sites involving the brain. Host genetic susceptibility factors and specific mycobacteria substrains could be involved in the development of this serious form of tuberculosis. In this editorial the different animal models of cerebral tuberculosis are commented, highlighting a recently described murine model in which BALB/c mice were infected by the intratracheal route with clinical isolates, which exhibited rapid dissemination and brain infection. These strains were isolated from the cerebrospinal fluid of patients with meningeal tuberculosis; they showed specific genotype and induced a peculiar immune response in the infected brain. This model could be a useful tool to study host and bacilli factors involved in the pathogenesis of the most severe form of tuberculosis.

Malnutrition and experimental epilepsy / Desnutrição e epilepsia experimental

INTRODUCTION: Disturbances in intrauterine environment can have harmful effects on the fetus and pathological consequences persisting throughout adolescence and adulthood. Protein restriction during the prenatal period has a significant impact on growth and development of the central nervous system. Food restriction increases the risk of neurological disorders such as epilepsy. OBJECTIVE: To relate the programming model by malnutrition and its implications in experimental epilepsy. Material and methods: There has been research papers published in the databases Medline, PubMed, CAPES journals, ScienceDirect and Scielo. The keywords selected for the study included epilepsy, Status Epilepticus, pilocarpine, malnutrition, programming. RESULTS AND DISCUSSION: Several studies in animal models or humans highlights the possible adverse effects of malnutrition at the onset of epileptic seizures. The vulnerability immunological, biochemical and electrolyte abnormalities and hypoglycemia may be the factors responsible for the intensification of the epileptogenic process in malnourished individuals. CONCLUSION: Malnutrition negatively changes the epileptogenic circuitry.

INTRODUÇÃO: Perturbações ao ambiente intrauterino podem ter efeitos prejudiciais sobre o feto e consequências patológicas persistentes ao longo da adolescência e da idade adulta. Restrição protéica durante o período pré-natal tem repercussões significativas sobre a ontogenia e o desenvolvimento do sistema nervoso central. Restrição alimentar nessa fase da vida aumenta o risco de distúrbios neurológicos como a epilepsia. OBJETIVO: Relacionar o modelo de programação pela desnutrição e suas implicações na epilepsia experimental. MATERIAL E MÉTODOS: Procedeu-se a pesquisa em artigos científicos publicados nos Bancos de Dados Medline, PubMed, Periódicos CAPES, ScienceDirect e Scielo. As palavras-chave selecionadas para a pesquisa incluíram epilepsia, status epilepticus, pilocarpina, desnutrição, programming. RESULTADOS E DISCUSSÃO: Diversos estudos realizados em modelos animais ou humanos destacam os possíveis efeitos adversos da desnutrição no início das crises epilépticas. A vulnerabilidade imunológica, alterações bioquímicas como anormalidades eletrolíticas e hipoglicemia podem ser os fatores responsáveis pela intensificação dos processos epileptogênicos em indivíduos desnutridos. Conclusão: A desnutrição altera negativamente a circuitaria epileptogênica.

The role of magnesium sulfate in prevention of seizures induced by pentylenetetrazole in rats / O papel do sulfato de magnésio na prevenção de crises induzidas por pentilenotetrazol em ratos

Magnesium sulfate (MgSO4) has been used to prevent seizures in eclampsia. This study examined the central effects of MgSO4 on different types of pentylenetetrazole (PTZ)-induced seizures. Male Wistar rats were submitted to intracerebroventricular (ICV) administration of MgSO4 at different doses followed by intraperitoneal administration of PTZ. The latency to the onset of the first seizure induced by PTZ was significantly increased by ICV administration of MgSO4 at a dose of 100 µg compared to the control treatment. In addition, the total period during which animals presented with seizures was significantly reduced at this dose of MgSO4. Furthermore, the latency to the onset of the first partial complex seizure was significantly increased by the lowest dose of MgSO4. However, a high dose of MgSO4 had no effect or even potentiated the effect of PTZ. These results suggest that, depending on the dose, MgSO4 may be important in prevention of epileptic seizures.

Sulfato de magnésio (MgSO4) é utilizado para prevenir crises epilépticas na eclampsia. Este estudo examina os efeitos do MgSO4 em diferentes tipos de crise induzidas por pentilenotetrazol (PTZ). Ratos Wistar foram submetidos à administração intracerebroventricular (ICV) de diferentes doses de MgSO4 seguida de administração intraperitoneal de PTZ. A latência para o início da primeira crise induzida por PTZ foi aumentada pela administração ICV de MgSO4 na dose de 100 µg quando comparada ao tratamento controle. Além disso, o período durante o qual os animais apresentaram crises foi reduzido com a mesma dose de MgSO4. A latência para o início da primeira crise parcial complexa também foi aumentada com a dose menor de MgSO4 (32 µg). No entanto, a maior dose (320 µg) de MgSO4 não foi efetiva ou até potencializou os efeitos do PTZ. Esses resultados sugerem que, dependendo da dose, o MgSO4 pode ser útil na prevenção de crises epilépticas.