RESUMO
Volatile organic compounds (VOCs) in exhaled human breath serve as pivotal biomarkers for disease identification and medical diagnostics. In the context of diabetes mellitus, the noninvasive detection of acetone, a primary biomarker using electronic noses (e-noses), has gained significant attention. However, employing e-noses requires pre-trained algorithms for precise diabetes detection, often requiring a computer with a programming environment to classify newly acquired data. This study focuses on the development of an embedded system integrating Tiny Machine Learning (TinyML) and an e-nose equipped with Metal Oxide Semiconductor (MOS) sensors for real-time diabetes detection. The study encompassed 44 individuals, comprising 22 healthy individuals and 22 diagnosed with various types of diabetes mellitus. Test results highlight the XGBoost Machine Learning algorithm's achievement of 95% detection accuracy. Additionally, the integration of deep learning algorithms, particularly deep neural networks (DNNs) and one-dimensional convolutional neural network (1D-CNN), yielded a detection efficacy of 94.44%. These outcomes underscore the potency of combining e-noses with TinyML in embedded systems, offering a noninvasive approach for diabetes mellitus detection.
Assuntos
Diabetes Mellitus , Compostos Orgânicos Voláteis , Humanos , Nariz Eletrônico , Testes Respiratórios/métodos , Algoritmos , Diabetes Mellitus/diagnóstico , Aprendizado de Máquina , BiomarcadoresRESUMO
BACKGROUND: Several pieces of evidence have shown the neurotrophic effect of erythropoietin (EPO) and its introduction in the therapeutic practice of neurological diseases. However, its usefulness in the treatment of spinocerebellar ataxia type 2 (SCA2) has not been proven despite the fact that it is endogenously reduced in these patients. OBJECTIVE: The study aims to investigate the safety, tolerability, and clinical effects of a nasally administered recombinant EPO in SCA2 patients. METHODS: Thirty-four patients were enrolled in this double-blind, randomized, placebo-controlled, phase I-II clinical trial of the nasally administered human-recombinant EPO (NeuroEPO) for 6 months. The primary outcome was the change in the spinocerebellar ataxia functional index (SCAFI), while other motor, neuropsychological, and oculomotor measures were assessed. RESULTS: The 6-month changes in SCAFI score were slightly higher in the patients allocated to NeuroEPO treatment than placebo in spite of the important placebo effect observed for this parameter. However, saccade latency was significantly decreased in the NeuroEPO group but not in placebo. The frequency and severity of adverse events were similar between both groups, without evidences of hematopoietic activity of the drug. CONCLUSIONS: This study demonstrated the safety and tolerability of NeuroEPO in SCA2 patients after 6 months of treatments and suggested a small clinical effect of this drug on motor and cognitive abnormalities, but confirmatory studies are warranted. © 2022 International Parkinson and Movement Disorder Society.
Assuntos
Eritropoetina , Ataxias Espinocerebelares , Método Duplo-Cego , Epoetina alfa , Eritropoetina/uso terapêutico , Estudos de Viabilidade , Humanos , Proteínas Recombinantes/uso terapêutico , Ataxias Espinocerebelares/tratamento farmacológicoRESUMO
The objectives of this study were to gain further insight on Candida genotype distribution and percentage of clustered isolates between hospitals and to identify potential clusters involving different hospitals and cities. We aim to genotype Candida spp. isolates causing candidemia in patients admitted to 16 hospitals in Spain, Italy, Denmark, and Brazil. Eight hundred and eighty-four isolates (Candida albicans, n = 534; C. parapsilosis, n = 282; and C. tropicalis, n = 68) were genotyped using species-specific microsatellite markers. CDC3, EF3, HIS3, CAI, CAIII, and CAVI were used for C. albicans, Ctrm1, Ctrm10, Ctrm12, Ctrm21, Ctrm24, and Ctrm28 for C. tropicalis, and CP1, CP4a, CP6, and B for C. parapsilosis. Genotypes were classified as singletons (genotype only found once) or clusters (same genotype infecting two or more patients). Clusters were defined as intra-hospital (involving patients admitted to a single hospital), intra-ward (involving patients admitted to the same hospital ward) or widespread (involving patients admitted to different hospitals). The percentage of clusters and the proportion of patients involved in clusters among species, genotypic diversity and distribution of genetic diversity were assessed. Seven hundred and twenty-three genotypes were detected, 78 (11%) being clusters, most of which (57.7%; n = 45/78) were intra-hospital clusters including intra-ward ones (42.2%; n = 19/45). The proportion of clusters was not statistically different between species, but the percentage of patients in clusters varied among hospitals. A number of genotypes (7.2%; 52/723) were widespread (found at different hospitals), comprising 66.7% (52/78) of clusters, and involved patients at hospitals in the same city (n = 21) or in different cities (n = 31). Only one C. parapsilosis cluster was a widespread genotype found in all four countries. Around 11% of C. albicans and C. parapsilosis isolates causing candidemia are clusters that may result from patient-to-patient transmission, widespread genotypes commonly found in unrelated patients, or insufficient microsatellite typing genetic discrimination.
Assuntos
Candidemia , Antifúngicos , Brasil/epidemiologia , Candida/genética , Candidemia/epidemiologia , Genótipo , Humanos , Itália/epidemiologia , EspanhaRESUMO
The capacity of Candida spp. to form biofilms allows them to attach either to living or inert surfaces, promoting their persistence in hospital environments. In a previous study, we reported strain-to-strain variations in Candida spp. biofilm development, suggesting that some genotypes may be greater biofilm formers than others. In this study, we hypothesize that isolates pertaining to clusters may be found more frequently in the environment due to their ability to form biofilms compared to singleton genotypes. Two hundred and thirty-nine Candida spp. isolates (78 clusters) from candidemia patients admitted to 16 hospitals located in different cities and countries-and the same number of singleton genotypes used as controls-were tested in terms of biofilm formation using the crystal violet and the XTT reduction assays. Candida albicans clusters showed higher biofilm formation in comparison to singleton genotypes (P < .01). The biofilms formed by intra-hospital C. albicans clusters showed higher metabolic activity (P < .05). Furthermore, marked variability was found among species and type of cluster. We observed that the higher the number of isolates, the higher the variability of biofilm production by isolates within the cluster, suggesting that the production of biofilm by isolates of the same genotype is quite diverse and does not depend on the type of cluster studied. In conclusion, candidemia Candida spp. clusters-particularly in the case of C. albicans-show significantly more biomass production and metabolic activity than singleton genotypes.
Assuntos
Biofilmes/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Candida albicans/genética , Candida parapsilosis/crescimento & desenvolvimento , Candida parapsilosis/genética , Candida tropicalis/crescimento & desenvolvimento , Candida tropicalis/genética , Brasil , Dinamarca , Variação Genética , Genótipo , Humanos , Itália , EspanhaRESUMO
Introducción: La enfermedad cerebrovascular constituye un importante problema de salud a nivel mundial. En la actualidad se desarrollan investigaciones científicas dedicadas al estudio de los efectos del campo magnético de frecuencia extremadamente baja para su tratamiento. No es suficientemente clara la información acerca de su inocuidad en las dosis estudiadas. Objetivo: Estudiar la seguridad de la aplicación del campo magnético de frecuencia extremadamente baja a nivel del sistema nervioso central a través de un estudio toxicológico a dosis aguda, repetida y ensayo de micronúcleos en médula ósea. Métodos: Se conformaron tres grupos experimentales con ratas Sprague Dawley Cenp:SPRD jóvenes y sanas para los experimentos de toxicidad y ratones CENP: NMRI para la evaluación mutagénica. Se utilizaron controles negativos no tratados. En el ensayo de micronúcleos se incorporó un grupo control positivo al que se administró Ciclofosfamida por vía intraperitoneal. Se aplicó un campo magnético no homogéneo con niveles de inducción magnética de 6,5 y 15 mT, tomando como referencia el valor máximo sobre la superficie de la bobina. Para la aplicación del campo magnético la bobina estimuladora se colocó sobre la cabeza asegurando la exposición completa del encéfalo. Resultados: En ninguno de los ensayos se detectaron signos de toxicidad. Se comprobó así mismo que no se indujeron efectos genotóxicos ni citotóxicos sobre las células somáticas. Conclusiones: El tratamiento con campo magnético de frecuencia extremadamente baja a nivel del sistema nervioso central en las condiciones experimentales y dosis estudiadas es seguro(AU)
Introduction: Stroke is a major health problem all over the world. Nowadays are developed scientific researches devoted to the study of extremely low frequency magnetic field effects over this illness. The information about it safety is unclear yet. Objective: To study the safety of extremely low frequency magnetic field applied at central nervous system level wasby means ofa toxicological assay (Acute, repeated doses and micronucleus in bone marrow assay) Methods: Three experimental groups were made with Sprague Dawley Cenp: SPRD young and healthy rats for toxicity experiments and CENP: NMRI mice for mutagen evaluation. Untreated negative controls were used. In the micronucleus assay, an additional positive control group was included. This group received Cyclophosphamide by intraperitoneal administration. Was applied a non-homogenousmagnetic fieldof 6,5 and 15 mT, taken as reference the maximum value over the coil surface. The coil was positioned over the head, ensuring full exposure of brain to magnetic field. Results : In none of trials were detected any sign of toxicity. It was also found no genotoxic or cytotoxic effects induced on somatic cells. Conclusions : These results indicated the safety of treatmentwith extremely low frequency magnetic field at central nervous system level for experimental conditions and doses studied(AU)
Assuntos
Animais , Transtornos Cerebrovasculares/terapia , Magnetoterapia/métodos , Sintomas Toxicológicos/toxicidade , Ratos Sprague-Dawley , Neuroproteção , Testes de Mutagenicidade/métodosRESUMO
BACKGROUND: Delivery of therapeutic agents as erythropoietin (EPO) into Central Nervous System through intranasal route could benefit patients with neurological disorders. A new nasal formulation containing a non-hematopoietic recombinant EPO (NeuroEPO) has shown neuroprotective actions in preclinical models. In the current study, the safety of NeuroEPO was evaluated for the first time in humans. METHODS: A phase I, randomized, parallel, open-label study was carried out in healthy volunteers. They received, intranasally, 1 mg of NeuroEPO every 8 h during 4 days (Group A) or 0.5 mg of NeuroEPO (Group B) with the same schedule. The working hypothesis was that intranasal NeuroEPO produce <10% of severe adverse reactions in the evaluated groups. Therefore, a rigorous assessment of possible adverse events was carried out, which included tolerance of the nasal mucosa and the effect on hematopoietic activity. Clinical safety evaluation was daily during treatment and laboratory tests were done before and on days 5 and 14 after starting treatment. RESULTS: Twenty-five volunteers, 56% women, with a mean age of 27 yrs. were included. Twelve of them received the highest NeuroEPO dose. Twenty types of adverse events occurred, with headache (20%) and increase of hepatic enzymes (20%) as the most reported ones. Nasopharyngeal itching was the most common local event but only observed in four patients (16%), all of them from the lowest dose group. About half of the events were very probably or probably caused by the studied product. Most of the events were mild (95.5%), did not require treatment (88.6%) and were completely resolved (81.8%). No severe adverse events were reported. During the study the hematopoietic variables were kept within reference values. CONCLUSIONS: NeuroEPO was a safe product, well tolerated at the nasal mucosa level and did not stimulate erythropoiesis in healthy volunteers. TRIAL REGISTRATION: Cuban Public Registry of Clinical Trials RPCEC00000157 , June 10, 2013.
Assuntos
Eritropoetina/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Administração Intranasal , Adulto , Eritropoetina/efeitos adversos , Feminino , Humanos , Masculino , Fármacos Neuroprotetores/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Adulto JovemRESUMO
Erythropoietin (EPO) is a cytokine known to have effective cytoprotective action in the brain, particularly in ischemic, traumatic, inflammatory, and neurodegenerative conditions. We previously reported the neuroprotective effect of a low sialic form of EPO, Neuro-EPO, applied intranasally in rodent models of stroke or cerebellar ataxia and in a non-transgenic mouse model of Alzheimer's disease (AD). Here we analyzed the protective effect of Neuro-EPO in APPSwe mice, a reference transgenic mouse model of AD. Mice were administered 3 times a day, 3 days in the week with Neuro-EPO (125, 250 µg/kg) intranasally, between 12 and 14 months of age. Motor responses, general activity, and memory responses were analyzed during and after treatment. The deficits in spontaneous alternation, place learning in the water-maze, and novel object recognition observed in APPSwe mice were alleviated by the low dose of Neuro-EPO. Oxidative stress, neuroinflammation, trophic factor levels, and a synaptic marker were analyzed in the hippocampus or cortex of the animals. The increases in lipid peroxidation or in GFAP and Iba-1 contents in APPSwe mice were significantly reduced after Neuro-EPO. Activation of intrinsic and extrinsic apoptotic pathways was analyzed. The increases in Bax/Bcl-2 ratio, TNFα, or Fas ligand levels observed in APPSwe mice were reduced by Neuro-EPO. Finally, immunohistochemical and ELISA analyses of Aß1-42 levels in the APPSwe mouse cortex and hippocampus showed a marked reduction in Aß deposits and in soluble and insoluble Aß1-42 forms. This study therefore confirmed the neuroprotective activity of EPO, particularly for an intranasally deliverable formulation, devoid of erythropoietic side effects, in a transgenic mouse model of AD. Neuro-EPO alleviated memory alterations, oxidative stress, neuroinflammation, apoptosis induction, and amyloid load in 14-month-old APPSwe mice.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Eritropoetina/administração & dosagem , Transtornos da Memória/prevenção & controle , Fármacos Neuroprotetores/administração & dosagem , Nootrópicos/administração & dosagem , Administração Intranasal , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Modelos Animais de Doenças , Eritropoetina/química , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Transtornos da Memória/metabolismo , Transtornos da Memória/patologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Atividade Motora/efeitos dos fármacos , Ácido N-Acetilneuramínico/química , Fármacos Neuroprotetores/química , Nootrópicos/químicaRESUMO
The slow scientific development in Latin America in recent decades has delayed the incorporation of laboratory animal experimentation; however, this situation has started to change. Today, extraordinary scientific progress is evident, which has promoted the introduction and increased use of laboratory animals as an important tool for the advancement of biomedical sciences. In the aftermath of this boom, the need to provide the scientific community with training and guidance in all aspects related to animal experimentation has arisen. It is the responsibility of each country to regulate this practice, for both bioethical and legal reasons, to ensure consideration of the animals' rights and welfare. The following manuscript is the result of papers presented at the International Workshop on Laboratory Animal Testing held at the Technical University of Ambato, Ecuador; it contains information regarding the current state of affairs in laboratory animal testing and emphasizes critical aspects such as main species used, ethical and legal principles, and experimental and alternative designs for animal use. These works aim to ensure good practices that should define scientific work. This document will be relevant to both researchers who aim to newly incorporate animal testing into their research and those who seek to update their knowledge.
Assuntos
Experimentação Animal , Bem-Estar do Animal , Animais , Animais de Laboratório , Equador , Projetos de PesquisaRESUMO
RESUMEN El lento desarrollo científico experimentado en América Latina en las últimas décadas ha retrasado la incorporación de la experimentación con animales de laboratorio, sin embargo, esta realidad ha comenzado a cambiar. En la actualidad, se evidencia un extraordinario progreso científico que ha promovido la introducción e incremento del uso de animales de laboratorio como una importante herramienta para el avance de las ciencias biomédicas. A raíz de este auge, surge la necesidad de proporcionar a la comunidad científica la formación y directrices en todos los aspectos relacionados con la experimentación animal. Es responsabilidad de cada país legislar esta práctica para que no solo por razones bioéticas, sino también legales, se considere el derecho de los animales y con ello su bienestar. El siguiente manuscrito es el resultado de las comunicaciones presentadas en el Taller Internacional en Ciencias de Animales de Laboratorio celebrado en la Universidad Técnica de Ambato, Ecuador; contiene la actualidad en la ciencia de animales de laboratorio, haciendo énfasis en aspectos fundamentales, tales como: principales especies utilizadas y su biología, principios éticos y legales, diseño experimental y alternativas al uso de animales, todas ellas encaminadas a garantizar las buenas prácticas que deben caracterizar el quehacer científico. Sin duda, este documento será relevante tanto para aquellos investigadores que pretenden incorporar la experimentación animal a sus investigaciones, como para aquellos que, aun teniendo experiencia, pretendan actualizar sus conocimientos.
ABSTRACT The slow scientific development in Latin America in recent decades has delayed the incorporation of laboratory animal experimentation; however, this situation has started to change. Today, extraordinary scientific progress is evident, which has promoted the introduction and increased use of laboratory animals as an important tool for the advancement of biomedical sciences. In the aftermath of this boom, the need to provide the scientific community with training and guidance in all aspects related to animal experimentation has arisen. It is the responsibility of each country to regulate this practice, for both bioethical and legal reasons, to ensure consideration of the animals' rights and welfare. The following manuscript is the result of papers presented at the International Workshop on Laboratory Animal Testing held at the Technical University of Ambato, Ecuador; it contains information regarding the current state of affairs in laboratory animal testing and emphasizes critical aspects such as main species used, ethical and legal principles, and experimental and alternative designs for animal use. These works aim to ensure good practices that should define scientific work. This document will be relevant to both researchers who aim to newly incorporate animal testing into their research and those who seek to update their knowledge.
Assuntos
Animais , Bem-Estar do Animal , Experimentação Animal , Projetos de Pesquisa , Equador , Animais de LaboratórioRESUMO
Spinocerebellar ataxia type 2 (SCA2) is a redox-sensitive neurodegenerative disease affecting the cerebellum, fibre connections in the cerebellum, the peripheral nervous system, and extracerebellar central pathways. Currently, Cuba has the highest reported global rate for this disease. The aim of this review article is to summarize and discuss the current knowledge about evidence of oxidative stress during SCA2. Recent reports have suggested that ataxin 2 and other related factors contribute to the redox imbalance in this disease. It is important to recognize and clarify the molecular mechanisms associated with the redox imbalance to consider ataxias innovative approaches to counteract oxidative stress-induced tissue damage, through alternative therapeutic or nutritional intervention in SCA2 and related diseases.
Assuntos
Estresse Oxidativo , Ataxias Espinocerebelares/metabolismo , Adulto , Ataxinas , Cuba/epidemiologia , Humanos , Proteínas do Tecido Nervoso/metabolismo , Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/genéticaRESUMO
Cuban patients with Spinocerebellar Ataxia type 2 (SCA2) have reduced concentrations of zinc in serum and cerebrospinal fluid (CSF). To assess the effect and safety of zinc supplementation, 36 Cuban SCA2 patients were randomly assigned to receive daily either 50 mg ZnSO(4) or placebo, together with neurorehabilitation therapy in a randomized, double-blind, placebo-controlled clinical trial during 6 months. Outcome measures included the changes of zinc levels in CSF and serum, ataxia score, oxidative stress and saccadic eye movements. At the end of the study, the Zinc-treated group showed: (i) a significant increase of the Zn levels in the CSF, (ii) mild decrease in the ataxia scale subscores for gait, posture, stance and dysdiadochocinesia (iii) reduction of lipid's oxidative damage, and (iv) reduction of saccadic latency when compared with the placebo group. The treatment was safe and well tolerated by all subjects. This study demonstrated the efficacy and safety of Zn supplementation, combined with neurorehabilitation for SCA2 patients and therefore it may encourage further studies on the clinical effect of zinc supplementation in SCA2 based in the conduction of future clinical trials with higher number of subjects.
Assuntos
Suplementos Nutricionais , Placebos , Ataxias Espinocerebelares/tratamento farmacológico , Sulfato de Zinco/administração & dosagem , Sulfato de Zinco/uso terapêutico , Adolescente , Adulto , Catalase/sangue , Cuba , Método Duplo-Cego , Humanos , Malondialdeído/sangue , Pessoa de Meia-Idade , Movimentos Sacádicos/fisiologia , Ataxias Espinocerebelares/fisiopatologia , Ataxias Espinocerebelares/reabilitação , Superóxido Dismutase/sangue , Resultado do Tratamento , Adulto Jovem , Zinco/sangueRESUMO
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant cerebellar ataxia characterized by a progressive cerebellar syndrome associated to saccadic slowing, peripheral neuropathy, cognitive disorders, and other multisystem features. SCA2 is caused by the abnormal expansion of cytosine-adenine-guanine triplet repeats in the encoding region of the ATXN2 gene and therefore the expression of toxic polyglutamine expansions in the ataxin 2 protein, which cause progressive neuronal death of Purkinje cells in the cerebellum and several pontine, mesencephalic, and thalamic neurons among other cells. Worldwide, SCA2 is the second most frequent type of spinocerebellar ataxia, only surpassed by SCA3. Nevertheless, in Holguin, Cuba, the disease reaches the highest prevalence, resulting from a putative foundational effect. This review discusses the most important advances in the genotypical and phenotypical studies of SCA2, highlighting the comprehensive characterization reached in Cuba through clinical, neuroepidemiological, neurochemical, and neurophysiological evaluation of SCA2 patients and pre-symptomatic subjects, which has allowed the identification of new disease biomarkers and therapeutical opportunities. These findings provide guidelines, from a Cuban viewpoint, for the clinical management of the disease, its diagnosis, genetic counseling, and therapeutical options through rehabilitative therapy and/or pharmacological options.
Assuntos
Ataxias Espinocerebelares , Animais , Cuba/epidemiologia , Predisposição Genética para Doença , Humanos , Incidência , Fenótipo , Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/fisiopatologia , Ataxias Espinocerebelares/terapiaRESUMO
Vascular illness of the brain constitutes the third cause of death and the first cause of disability in Cuba and many other countries. Presently, no medication has been registered as a neuroprotector. Neuroprotection with intranasal Neuro-EPO (EPO, erythropoietin) has emerged as a multifunctional therapy that plays a significant role in neural survival and functional recovery in an animal model of stroke. On the other hand, there is limited access to the brain through the blood brain barrier (BBB) for intravenously applied EPO, and the high EPO dosages needed to obtain a protective effect increase the danger of elevated hematocrit levels and practically exclude chronic or subchronic treatment with EPO. A promising approach has been recently developed with a nonerythropoietic variant of EPO, Neuro-EPO, with low sialic acid content, a very short plasma half-life, and without erythropoietic activity, probably similar to endogenous brain EPO. The objective of this work was to determine the neuroprotective effect of intranasal Neuro-EPO in comparison with the human recombinant EPO injected intraperitoneally in the acute phase of cerebral ischemia, employing the common carotid artery occlusion model in gerbils. Neuro-EPO has demonstrated a better neuroprotective effect, evidenced through increased viability, improvements of the neurological state and cognitive functions, as well as protection of the CA3 region of the hippocampus, temporal cortex, and the thalamus. In conclusion, the intranasal application of Neuro-EPO has a better neuroprotective effect than intraperitoneal EPO, evidenced by the significant improvement of neurological, cognitive, and histological status in the animal model of stroke employed.
Assuntos
Isquemia Encefálica/prevenção & controle , Cognição/efeitos dos fármacos , Eritropoetina/farmacologia , Fármacos Neuroprotetores/farmacologia , Administração Intranasal , Animais , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Eritropoetina/administração & dosagem , Gerbillinae , Humanos , Masculino , Fármacos Neuroprotetores/administração & dosagem , Distribuição Aleatória , Proteínas Recombinantes , Resultado do TratamentoRESUMO
Intranasal delivery provides a practical, noninvasive method of bypassing the blood-brain barrier (BBB) in order to deliver therapeutic agents to the brain. This method allows drugs that do not cross the BBB to be delivered to the central nervous system in a few minutes. With this technology, it will be possible to eliminate systemic administration and its potential side effects. Using the intranasal delivery system, researchers have demonstrated neuroprotective effects in different animal models of stroke using erythropoietin (EPO) as a neuroprotector or other different types of EPO without erythropoiesis-stimulating activity. These new molecules retain their ability to protect neural tissue against injury and they include Asialoerythropoietin (asialoEPO) carbamylated EPO (CEPO), and rHu-EPO with low sialic acid content (Neuro-EPO). Contrary to the other EPO variants, Neuro-EPO is not chemically modified, making it biologically similar to endogenous EPO, with the advantage of less adverse reactions when this molecule is applied chronically. This constitutes a potential benefit of Neuro-EPO over other variants of EPO for the chronic treatment of neurodegenerative illnesses. Nasal administration of EPO is a potential, novel, neurotherapeutic approach. However, it will be necessary to initiate clinical trials in stroke patients using intranasal delivery in order to obtain the clinical evidence of its neuroprotectant capacity in the treatment of patients with acute stroke and other neurodegenerative disorders. This new therapeutic approach could revolutionize the treatment of neurodegenerative disorders in the 21st century.
Assuntos
Administração Intranasal , Eritropoetina/administração & dosagem , Eritropoetina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Assialoglicoproteínas/administração & dosagem , Barreira Hematoencefálica , Isquemia Encefálica/tratamento farmacológico , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Eritropoetina/análogos & derivados , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Receptores da Eritropoetina/metabolismo , Proteínas RecombinantesRESUMO
Desde finales del siglo XX se han obtenido notables progresos en el campo de la ciencia y la tecnología, que han dejado un impacto positivo en la Neurobiología. Muchos de estos estudios van dirigidos a identificar los mecanismos neuronales de los procesos cognitivos normales, así como la comprensión de cómo estos se ven alterados en los trastornos mentales. En este trabajo presentaremos en forma resumida las fundamentales bases neuroquímicas de uno de los fundamentales trastornos mentales: la esquizofrenia, dando aquellos elementos que nos lleva a formular los primeros elementos para una nueva teoría que pudiera explicar los orígenes de la misma, donde los factores neurotróficos, específicamente las neurotrofinas desempeñan un papel protagónico