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Electron. j. biotechnol ; 51: 50-57, May. 2021. ilus, graf
Article in English | LILACS | ID: biblio-1343384


BACKGROUND: Molecular brain therapies require the development of molecular switches to control gene expression in a limited and regulated manner in time and space. Light-switchable gene systems allow precise control of gene expression with an enhanced spatio-temporal resolution compared to chemical inducers. In this work, we adapted the existing light-switchable Light-On system into a lentiviral platform, which consists of two modules: (i) one for the expression of the blue light-switchable transactivator GAVPO and (ii) a second module containing an inducible-UAS promoter (UAS) modulated by a light-activated GAVPO. RESULTS: In the HEK293-T cell line transfected with this lentiviral plasmids system, the expression of the reporter mCherry increased between 4 to 5 fold after light induction. A time expression analysis after light induction during 24 h revealed that mRNA levels continuously increased up to 9 h, while protein levels increased throughout the experiment. Finally, transduction of cultured rat hippocampal neurons with this dual Light-On lentiviral system showed that CDNF, a potential therapeutic trophic factor, was induced only in cells exposed to blue light. CONCLUSIONS: In conclusion, the optimized lentiviral platform of the Light-On system provides an efficient way to control gene expression in neurons, suggesting that this platform could potentially be used in biomedical and neuroscience research, and eventually in brain therapies for neurodegenerative diseases.

Gene Expression Regulation , Optogenetics/methods , Light , Neurons/metabolism , Immunoblotting , Gene Expression , Fluorescent Antibody Technique , Lentivirus
Article in Chinese | WPRIM | ID: wpr-879849


OBJECTIVE@#To study the role and mechanism of histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2) in mouse neuronal development.@*METHODS@#The mice with Synapsin1-Cre recombinase were bred with @*RESULTS@#The mice with @*CONCLUSIONS@#Deletion of

Animals , Blotting, Western , Histone Deacetylase 1/genetics , Histone Deacetylase 2 , Histone Deacetylases/genetics , Immunohistochemistry , Mice , Neurons/metabolism , Signal Transduction
Neuroscience Bulletin ; (6): 1325-1338, 2021.
Article in English | WPRIM | ID: wpr-922632


A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk. In humans, a large proportion of mental disorders are accompanied by impairments in risk avoidance. One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1 (DISC1), and animal models in which this gene has some level of dysfunction show emotion-related impairments. However, it is not known whether DISC1 mouse models have an impairment in avoiding potential risks. In the present study, we used DISC1-N terminal truncation (DISC1-N

Animals , Interneurons/metabolism , Mice , Mice, Transgenic , Nerve Tissue Proteins/metabolism , Neurons/metabolism , Nucleus Accumbens/metabolism , Parvalbumins/metabolism
Article in English | WPRIM | ID: wpr-878317


Objective@#In the present study, the ABCA1 was used as a label to capture specific exosomes, the level of ABCA1-labeled exosomal microRNA-135a (miR-135a) was evaluated for the diagnosis of Alzheimer's disease (AD), especially in patients with early stages of AD.@*Methods@#This is a preliminary research focused on the levels of ABCA1 in WBCs, RBCs, HT-22 cells, and neuron cells. The diagnostic value of ABCA1-labeled exosomal miR-135a was examined using the CSF and serum of APP/PS1 double transgenic mice, and 152 patients with SCD, 131 patients with MCI, 198 patients with DAT, and 30 control subjects.@*Results@#The level of ABCA1 exosomes harvested from HT-22 cells and neuron culture medium was significantly higher compared to that of RBCs and WBCs ( @*Conclusion@#This study outlines a method to capture specific exosomes and detect them using immunological methods, which is more efficient for early diagnosis of AD.

ATP Binding Cassette Transporter 1/cerebrospinal fluid , Aged , Aged, 80 and over , Alzheimer Disease/cerebrospinal fluid , Animals , Biomarkers/cerebrospinal fluid , Cell Line , Cognitive Dysfunction/cerebrospinal fluid , Erythrocytes/metabolism , Exosomes , Female , Humans , Leukocytes/metabolism , Male , Mice, Transgenic , MicroRNAs/blood , Neurons/metabolism
Acta Physiologica Sinica ; (6): 295-305, 2021.
Article in Chinese | WPRIM | ID: wpr-878258


Cortical GABAergic inhibitory neurons are composed of three major classes, each expressing parvalbumin (PV), somatostatin (SOM) and 5-hydroxytryptamine receptor 3A (Htr3a), respectively. Htr3a

Animals , Interneurons/metabolism , Mice , Neurons/metabolism , Parvalbumins/metabolism , Receptors, Serotonin, 5-HT3/genetics , Serotonin , Somatostatin/metabolism
Acta Physiologica Sinica ; (6): 17-25, 2021.
Article in Chinese | WPRIM | ID: wpr-878231


This study was aimed to determine the effect of acute cerebral ischemia on the protein expression level of silent mating type information regulator 2 homolog 3 (Sirt3) in the neurons and clarify the pathological role of Sirt3 in acute cerebral ischemia. The mice with middle cerebral artery occlusion (MCAO) and primary cultured rat hippocampal neurons with oxygen glucose deprivation (OGD) were used as acute cerebral ischemia models in vivo and in vitro, respectively. Sirt3 overexpression was induced in rat hippocampal neurons by lentivirus transfection. Western blot was utilized to measure the changes in Sirt3 protein expression level. CCK8 assay was used to detect cell viability. Immunofluorescent staining was used to detect mitochondrial function. Transmission electron microscope was used to detect mitochondrial autophagy. The results showed that, compared with the normoxia group, hippocampal neurons from OGD1 h/reoxygenation 2 h (R2 h) and OGD1 h/R12 h groups exhibited down-regulated Sirt3 protein expression levels. Compared with contralateral normal brain tissue, the ipsilateral penumbra region from MCAO1 h/reperfusion 24 h (R24 h) and MCAO1 h/R72 h groups exhibited down-regulated Sirt3 protein expression levels, while there was no significant difference between the Sirt3 protein levels on both sides of sham group. OGD1 h/R12 h treatment damaged mitochondrial function, activated mitochondrial autophagy and reduced cell viability in hippocampal neurons, whereas Sirt3 over-expression attenuated the above damage effects of OGD1 h/R12 h treatment. These results suggest that acute cerebral ischemia results in a decrease in Sirt3 protein level. Sirt3 overexpression can alleviate acute cerebral ischemia-induced neural injuries by improving the mitochondrial function. The current study sheds light on a novel strategy against neural injuries caused by acute cerebral ischemia.

Animals , Brain Ischemia , Down-Regulation , Infarction, Middle Cerebral Artery , Mice , Mitochondria , Neurons/metabolism , Rats , Reperfusion Injury , Sirtuin 3/metabolism , Sirtuins
Revista Digital de Postgrado ; 9(2): 205, ago. 2020. tab
Article in Spanish | LILACS, LIVECS | ID: biblio-1102879


La Parálisis Cerebral (PC) es un conjunto de alteraciones motrices no progresivas en la población infantojuvenil, ocasionadas por lesión ­a nivel cerebral- de neuronas o fibras de esa vía, de sus aferencias o de las que la modulan; para su diagnóstico deben conocerse otras patologías también frecuentes y que pueden incidir simultánea o causalmente en la motricidad del paciente; la resultante sería disfunción motora tanto voluntaria como involuntaria, refleja o con propósito, de la postura y/o del tono muscular. Objetivo: detectar errores innatos metabólicos (EIM) que causan o se asocian con PC en una serie significativa. Métodos: Estudio descriptivo-interpretativo, se revisaron los expedientes clínicos del Centro de Parálisis Cerebral de Caracas, en cuyos diagnósticos se presentaron ambas alteraciones, entre los años 1988 y 2018. Resultados: De las 2.000 historias clínicas revisadas, el exámen clínico y las pruebas de laboratorio permitieron seleccionar 174 casos de EIM. Conclusiones: Se tipificaron los errores innatos metabólicos en diez formas clínicas distintas, se evidenciaron en pacientes con PC atendidos en un centro público de Caracas, es posible que la casuística sea varias veces mayor en Venezuela dado que ya no se aplica la pesquisa en los centros de atención pública(AU)

Cerebral Palsy (CP) is a set of non-progressive motor alterations in the child and youth population, caused by injury - at the brain level - of neurons or fibers of that pathway, their afferences or those that modulate it; for its diagnosis, other pathologies that are also frequent and that can simultaneously or causally affect the motor skills of the same patient must be known; The result would be both voluntary and involuntary motor dysfunction, reflected or with purpose, of posture and / or muscle tone. Objective: to detect inborn metabolic errors (EIM) that cause or are associated with CP in a significant series. Methods: Descriptive-interpretive study, we reviewed the clinical records of the Cerebral Palsy Center of Caracas, in whose diagnoses both alterations were presented, between the years 1988 and 2018. Results: Of the 2,000 clinical histories reviewed, the clinical examination and tests Laboratory tests allowed the selection of 174 cases of IMD. Conclusions: Inborn metabolic errors were typified in ten different clinical forms, they were evidenced in patients with CP treated in a public center in Caracas, it is possible that the casuistry is several times greater in Venezuela since the investigation is no longer applied in the centers of public attention(AU)

Humans , Male , Female , Child, Preschool , Child , Adolescent , Cerebral Palsy/pathology , Metabolism, Inborn Errors , Neurons/metabolism , Pediatrics , Nervous System Diseases
Braz. arch. biol. technol ; 63: e20190072, 2020. graf
Article in English | LILACS | ID: biblio-1132180


Abstract In live organisms, there is a balance between the production of reactive oxygen species (ROS) and their neutralization. The increased level of these species leads to a condition called redox imbalance. The aim of this study was to evaluate the protective action of isobenzofuranones in primary cultures of hippocampal neurons subjected to redox imbalance. To accomplish this, MTT and LIVE/DEAD assays were initially performed. In the cultures pretreated with isobenzofuranones 1 and 2, there was a higher number of live cells when compared to that in the untreated ones. Regarding redox imbalance, there was a significant increase in the intracellular levels of ROS. The cultures pretreated with isobenzofuranones showed a reduction in ROS levels. Lipid peroxidation caused by oxidative damage was significantly reduced in the cultures pretreated with isobenzofuranones 1 and 2. Taken together, these data show the ability of isobenzofuranones 1 and 2 to significantly minimize cytotoxicity, cell death, intracellular levels of ROS and lipid peroxidation induced by redox imbalance. These results suggest that isobenzofuranones 1 and 2 represent a possible alternative therapy for the neurodegenerative disturbances that are triggered by ROS production increases.

Animals , Male , Mice , Oxidation-Reduction/drug effects , Benzofurans/pharmacology , Reactive Oxygen Species , Neuroprotective Agents/pharmacology , Hydrogen Peroxide , Benzofurans/chemical synthesis , Cell Death , Primary Cell Culture , Hippocampus/cytology , Neurons/metabolism
Acta Physiologica Sinica ; (6): 559-565, 2020.
Article in Chinese | WPRIM | ID: wpr-878201


The pre-Bötzinger complex (pre-BötC) residing in the ventrolateral medulla oblongata, is thought to be the kernel of respiratory rhythmogenesis. Episodic hypoxia exerts respiratory long-term facilitation, being recognized as electrophysiological characteristic of respiratory motor neuroplasticity. Our previous study demonstrated up-regulated expression of phospho-protein kinase C θ (P-PKCθ) in the pre-BötC of rats receiving chronic intermittent hypoxic (CIH) challenge. The present study was aimed to examine subcellular distribution of P-PKC substrates (P-PKCsub) and explore PKC down-stream targeting proteins in the pre-BötC in normoxic and CIH rats. Using neurokinin-1 receptor (NK1R) as a marker of the pre-BötC, P-PKCsub immunoreactivity was revealed by immunofluorescence and immuno-electron microscopic double-labeling in the pre-BötC. Western blot was applied to analyze P-PKCsub proteins in ventrolateral medulla, containing the pre-BötC. The results showed that NK1R immunoreactivity (NK1R-ir) was expressed mainly along plasma membranes of somata and processes, outlining pre-BötC neurons under the light microscope. P-PKCsub immunoreactive (P-PKCsub-ir) fluorophores in dot-like appearance appeared in somata and processes. Some were in close apposition to plasma membranes. A majority of P-PKCsub-ir neurons was found with NK1R-ir. CIH challenge up-regulated the expression of P-PKCsub proteins in the ventrolateral medulla. Under the electron microscope, NK1R-ir product was found to distribute along the inner membrane surfaces of somata and dendrites. P-PKCsub-ir gold particles were located in somata and dendrites, and some were distributed along the inner membrane surfaces, as well as in the endoplasmic reticulum and postsynaptic dense body. These results suggest that CIH challenge up-regulates the expression of P-PKCsub proteins, probably including some receptor proteins in the postsynaptic membrane, which may contribute to respiratory neuroplasticity via activation of PKCθ in the pre-BötC.

Animals , Hypoxia , Medulla Oblongata/metabolism , Neurons/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Neurokinin-1/metabolism
Mem. Inst. Oswaldo Cruz ; 115: e200007, 2020. graf
Article in English | SES-SP, LILACS, SES-SP | ID: biblio-1135242


BACKGROUND Behavioral and neurochemical alterations associated with toxoplasmosis may be influenced by the persistence of tissue cysts and activation of an immune response in the brain of Toxoplasma gondii-infected hosts. The cerebral extracellular matrix is organised as perineuronal nets (PNNs) that are both released and ensheath by some neurons and glial cells. There is evidences to suggest that PNNs impairment is a pathophysiological mechanism associated with neuropsychiatric conditions. However, there is a lack of information regarding the impact of parasitic infections on the PNNs integrity and how this could affect the host's behavior. OBJECTIVES In this context, we aimed to analyse the impact of T. gondii infection on cyst burden, PNNs integrity, and possible effects in the locomotor activity of chronically infected mice. METHODS We infected mice with T. gondii ME-49 strain. After thirty days, we assessed locomotor performance of animals using the open field test, followed by evaluation of cysts burden and PNNs integrity in four brain regions (primary and secondary motor cortices, prefrontal and somesthetic cortex) to assess the PNNs integrity using Wisteria floribunda agglutinin (WFA) labeling by immunohistochemical analyses. FINDINGS AND MAIN CONCLUSIONS Our findings revealed a random distribution of cysts in the brain, the disruption of PNNs surrounding neurons in four areas of the cerebral cortex and hyperlocomotor behavior in T. gondii-infected mice. These results can contribute to elucidate the link toxoplasmosis with the establishment of neuroinflammatory response in neuropsychiatric disorders and to raise a discussion about the mechanisms related to changes in brain connectivity, with possible behavioral repercussions during chronic T. gondii infection.

Animals , Mice , Cerebellum/metabolism , Toxoplasmosis/pathology , Toxoplasmosis, Animal , Extracellular Matrix/metabolism , Motor Neurons/cytology , Neurons/pathology , Toxoplasma , Cerebellum/cytology , Toxoplasmosis/metabolism , Disease Models, Animal , Motor Neurons/metabolism , Neurons/metabolism
Arq. neuropsiquiatr ; 76(9): 603-608, Sept. 2018. graf
Article in English | LILACS | ID: biblio-973951


ABSTRACT The neuropeptide orexin-A and its receptors are widely distributed in both hippocampal circuitry and pain transmission pathways. Objective: Involvement of the CA1 orexin 1 receptor (OX1R) on the modulation of orofacial pain and pain-induced changes in hippocampal expression of cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) was investigated. Methods: Orofacial pain was induced by an intra-lip injection of capsaicin (100 μg). Reverse transcription polymerase chain reaction and immunoblot analysis were used to indicate changes in hippocampal BDNF and COX-2 expression, respectively. Results: Capsaicin induces a significant pain response, which is not affected by either orexin-A or SB-334867-A, an OX1R antagonist. However, an increased expression of COX-2 and decreased expression of BDNF was observed in the hippocampus of animals that received capsaicin or SB-334867-A (80 nM) plus capsaicin. Meanwhile, orexin-A (40 pM) attenuated the effects of capsaicin on the expression of COX-2 and BDNF. Conclusions: CA1 OX1R activation moderates capsaicin-induced neuronal inflammation and neurotrophic deficiency.

RESUMO O neuropeptídeo orexina-A e seus receptores estão amplamente distribuídos nos circuitos do hipocampo e nas vias de transmissão da dor. Objetivo: O envolvimento do receptor de orexina 1 CA1 (OX1R) na modulação da dor orofacial e alterações induzidas pela dor na expressão do hipocampo de ciclooxigenase-2 (COX-2) e fator neurotrófico derivado do cérebro (BDNF) foi investigado. Métodos: A dor orofacial foi induzida por injeção intra-labial de capsaicina (100 μg). A reação em cadeia da polimerase de transcrição reversa e a análise de imunotransferência foram utilizadas para indicar alterações na expressão de BDNF e COX-2 no hipocampo, respectivamente. Resultados: A capsaicina induz uma resposta significativa à dor, que não é afetada pela orexina-A ou pelo SB-334867-A, um antagonista do OX1R. No entanto, uma expressão aumentada de COX-2 e uma expressão diminuída de BDNF foi observada no hipocampo de animais que receberam capsaicina ou SB-334867-A (80 nM) mais capsaicina. Enquanto isso, a orexina A (40 pM) atenuou os efeitos da capsaicina na expressão de COX-2 e BDNF. Conclusões: A ativação de CA1 OX1R modera a inflamação neuronal induzida por capsaicina e a deficiência neurotrófica.

Animals , Male , Rats , Facial Pain/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Cyclooxygenase 2/metabolism , Orexin Receptors/metabolism , Orexins/pharmacology , Hippocampus/metabolism , Urea/analogs & derivatives , Urea/pharmacology , Benzoxazoles/pharmacology , Capsaicin , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Disease Models, Animal , Hippocampus/drug effects , Naphthyridines , Neurons/drug effects , Neurons/metabolism
Biol. Res ; 50: 26, 2017. graf
Article in English | LILACS | ID: biblio-950876


BACKGROUND: CCL2 was up-regulated in neurons and involved in microglia activation and neurological decline in mice suffering from hepatic encephalopathy (HE). However, no data exist concerning the effect of neuron-derived CCL2 on microglia activation in vitro. METHODS: The rats were pretreated with CCL2 receptor inhibitors (INCB or C021, 1 mg/kg/day i.p.) for 3 days prior to thioacetamide (TAA) administration (300 mg/kg/day i.p.) for inducing HE model. At 8 h following the last injection (and every 4 h after), the grade of encephalopathy was assessed. Blood and whole brains were collected at coma for measuring CCL2 and Iba1 expression. In vitro, primary neurons were stimulated with TNF-α, and then the medium were collected for addition to microglia cultures with or without INCB or C021 pretreatment. The effect of the medium on microglia proliferation and activation was evaluated after 24 h. RESULTS: CCL2 expression and microglia activation were elevated in the cerebral cortex of rats received TAA alone. CCL2 receptors inhibition improved neurological score and reduced cortical microglia activation. In vitro, TNF-α treatment induced CCL2 release by neurons. Medium from TNF-α stimulated neurons caused microglia proliferation and M1 markers expression, including iNOS, COX2, IL-6 and IL-1ß, which could be suppressed by INCB or C021 pretreatment. The medium could also facilitate p65 nuclear translocation and IκBα phosphorylation, and NF-κB inhibition reduced the increased IL-6 and IL-1ß expression induced by the medium. CONCLUSION: Neuron-derived CCL2 contributed to microglia activation and neurological decline in HE. Blocking CCL2 or inhibiting microglia excessive activation may be potential strategies for HE.

Animals , Rats , Hepatic Encephalopathy/metabolism , Microglia/metabolism , Chemokine CCL2/metabolism , Receptors, Chemokine/antagonists & inhibitors , Neurons/metabolism , Thioacetamide , Gene Expression , Hepatic Encephalopathy/chemically induced , Hepatic Encephalopathy/therapy , Interleukin-6/metabolism , Microglia/drug effects , Chemokine CCL2/antagonists & inhibitors , Culture Media/pharmacology , Disease Models, Animal , Nervous System Diseases
Yonsei Medical Journal ; : 748-753, 2016.
Article in English | WPRIM | ID: wpr-21837


PURPOSE: The pathophysiology of discogenic low back pain is not fully understood. Tetrodotoxin-sensitive voltage-gated sodium (NaV) channels are associated with primary sensory nerve transmission, and the NaV1.7 channel has emerged as an analgesic target. Previously, we found increased NaV1.7 expression in dorsal root ganglion (DRG) neurons innervating injured discs. This study aimed to examine the effect of blocking NaV1.7 on sensory nerves after disc injury. MATERIALS AND METHODS: Rat DRG neurons innervating the L5/6 disc were labeled with Fluoro-Gold (FG) neurotracer. Twenty-four rats underwent intervertebral disc puncture (puncture group) and 12 rats underwent sham surgery (non-puncture group). The injury group was divided into a saline infusion group (puncture+saline group) and a NaV1.7 inhibition group, injected with anti-NaV1.7 antibody (puncture+anti-NaV1.7 group); n=12 per group. Seven and 14 days post-surgery, L1 to L6 DRGs were harvested and immunostained for calcitonin gene-related peptide (CGRP) (an inflammatory pain marker), and the proportion of CGRP-immunoreactive (IR) DRG neurons of all FG-positive neurons was evaluated. RESULTS: The ratio of CGRP-IR DRG neurons to total FG-labeled neurons in the puncture+saline group significantly increased at 7 and 14 days, compared with the non-puncture group, respectively (p<0.05). Application of anti-NaV1.7 into the disc significantly decreased the ratio of CGRP-IR DRG neurons to total FG-labeled neurons after disc puncture at 7 and 14 days (40% and 37%, respectively; p<0.05). CONCLUSION: NaV1.7 antibody suppressed CGRP expression in disc DRG neurons. Anti-NaV1.7 antibody is a potential therapeutic target for pain control in patients with lumbar disc degeneration.

Animals , Antibodies , Calcitonin Gene-Related Peptide/metabolism , Disease Models, Animal , Ganglia, Spinal/metabolism , Intervertebral Disc/drug effects , Intervertebral Disc Degeneration/metabolism , Low Back Pain/physiopathology , Lumbar Vertebrae/injuries , Male , /metabolism , Neurons/metabolism , Pain/metabolism , Rats , Rats, Sprague-Dawley , Stilbamidines
Dental press j. orthod. (Impr.) ; 20(3): 109-117, May-Jun/2015. graf
Article in English | LILACS | ID: lil-751407


INTRODUCTION: The indirect bonding technique optimizes fixed appliance installation at the orthodontic office, ensuring precise bracket positioning, among other advantages. In this laboratory clinical phase, material and methods employed in creating the transfer tray are decisive to accuracy. OBJECTIVE: This article describes a simple, efficient and reproducible indirect bonding technique that allows the procedure to be carried out successfully. Variables influencing the orthodontic bonding are analyzed and discussed in order to aid professionals wishing to adopt the indirect bonding technique routinely in their clinical practice. .

INTRODUÇÃO: a técnica de colagem indireta prioriza a otimização do procedimento de montagem do aparelho fixo na clínica ortodôntica, assegurando, entre outras, vantagens relacionadas à precisão no posicionamento dos braquetes. Nesse procedimento clínico laboratorial, o material e o método de confecção da moldeira de transferência são determinantes no quesito precisão. OBJETIVO: este artigo descreve uma técnica de colagem indireta simples, eficiente e reprodutível, para que o procedimento possa ser realizado com sucesso. Variáveis que exercem influência sobre o procedimento são analisadas e discutidas, a fim de auxiliar o profissional a adotar, de forma rotineira, a técnica de colagem indireta em sua prática clínica. .

Humans , Ion Channels/metabolism , Patch-Clamp Techniques/methods , Cerebral Cortex/cytology , Cerebral Cortex/metabolism , Ion Channel Gating , Ion Channels/chemistry , Neurons/metabolism , Receptors, N-Methyl-D-Aspartate/chemistry , Receptors, N-Methyl-D-Aspartate/metabolism
Rev. panam. salud pública ; 37(3): 133-139, Mar. 2015. ilus, tab
Article in Spanish | LILACS | ID: lil-746672


OBJETIVO: Determinar la sobrevida de pacientes con diagnóstico de cáncer gástrico en 2009-2010 en el Perú. MÉTODOS: Se realizó un estudio de tipo cohorte retrospectivo de pacientes con diagnóstico de cáncer gástrico registrados en el Sistema Nacional de Vigilancia Epidemiológica (SNVE) de la Dirección General de Epidemiología (DGE) y del Registro de Hechos Vitales (RHV) de la Oficina General de Estadística e Informática (OGEI) para los años 2009-2010. RESULTADOS: Se incluyeron 3 568 pacientes del SNVE, 51,5% eran hombres y 48,5% eran mujeres; la media de edad fue 63,9 años, 60,07% tenían 60 años o más. Se halló que 33,6% tenía adenocarcinoma de tipo intestinal, 18,7% tenía carcinoma de tipo difuso y 4,1% tenía linfoma gástrico primario. La sobrevida global fue de 29,7 ± 0,8 meses y fue mejor para los menores de 60 años (P = 0,034), para las mujeres (P = 0,014) y para el adenocarcinoma de tipo intestinal (P < 0,001). No hubo diferencias (P = 0,713) entre la sobrevida de los pacientes con linfoma gástrico y aquellos con adenocarcinoma. Para evaluar la tasa de mortalidad se incluyeron 6 069 registros de pacientes del RHV, la tasa de mortalidad nacional fue de 10,3 por cada 100 000 habitantes y las regiones con mayor mortalidad fueron Huánuco, Huancavelica y Junín. CONCLUSIONES: La sobrevida general fue de 29,7 ± 0,8 meses, las mujeres, los menores de 60 años y los pacientes con adenocarcinoma de tipo intestinal tienen mejor sobrevida. La mayor mortalidad por cáncer gástrico se concentra en las regiones más pobres del Perú, donde es probable que las condiciones de vida faciliten la alta transmisibilidad de Helicobacter pylori.

OBJECTIVE: Determine the survival rate of patients diagnosed with stomach cancer in 2009-2010 in Peru. METHODS: A retrospective cohort study was conducted of patients diagnosed with stomach cancer registered in the National Epidemiological Surveillance System (SNVE) of the Directorate General of Epidemiology (DGE) and the Register of Vital Statistics (RHV) of the General Office of Statistics and Information (OGEI) for the years 2009-2010. RESULTS: 3 568 patients of the SNVE were included; 51.5% were men and 48.5% were women; the average age was 63.9 years; 60.07% were 60 years old or older. It was found that 33.6% had intestinal type adenocarcinoma, 18.7% had diffuse type carcinoma, and 4.1% had primary gastric lymphoma. The overall survival rate was 29.7 ± 0.8 months and was better for those under 60 years (P = 0.034), for women (P = 0.014) and for intestinal type adenocarcinoma (P< 0.001). There was no difference (P = 0.713) between the survival rate of gastric lymphomas and adenocarcinomas. In order to evaluate mortality, 6 069 patient records from the RHV were included; national mortality was 10.3 per 100 000 population; the regions with the highest mortality were Huánuco, Huancavelica, and Junín. CONCLUSIONS: The general survival rate was 29.7 ± 0.8 months; women, those under 60 years, and patients with intestinal type adenocarcinoma had better survival rates. The highest mortality from stomach cancer is concentrated in the poorest regions of Peru, where it is probable that living conditions facilitate the high communicability of Helicobacter pylori.

Animals , Rats , Amyloid beta-Peptides/physiology , Astrocytes/cytology , Biopolymers/physiology , Neurons/cytology , Astrocytes/enzymology , Astrocytes/metabolism , Calcium/metabolism , /metabolism , Enzyme Activation , Neurons/enzymology , Neurons/metabolism , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism
Salud colect ; 11(1): 99-114, ene.-mar. 2015. ilus, tab
Article in Spanish | LILACS | ID: lil-746687


El Consejo Federal de Medicina de Brasil (CFM) -órgano normativo y fiscalizador del ejercicio ético de la medicina- prohibió, en 2008, la participación de médicos brasileños en investigaciones que utilizaran placebo para enfermedades con tratamiento eficaz y efectivo, en contraposición a la Declaración de Helsinki, que permite su uso en condiciones metodológicamente justificadas. Con el objetivo de verificar si la normativa ética del CFM modificó el uso de placebo en ensayos clínicos de fase III en Brasil, se analizaron varias características de sus registros en el, en los períodos de 2003 a 2007 y de 2009 a 2013. Se concluye que: a) la normativa promulgada por el CFM en 2008 fue ineficaz y prevaleció la posición adoptada por la Declaración de Helsinki; b) el patrocinio de ensayos con placebo por parte de la industria farmacéutica multinacional fue significativo; c) predominaron las investigaciones de fármacos para enfermedades crónicas, y fueron poco significativas para las enfermedades postergadas, de importancia para Brasil.

In 2008, Brazil's Federal Council of Medicine [Conselho Federal de Medicina] (CFM) - regulatory and supervisory agency on the ethical practice of medicine - banned the participation of Brazilian doctors in studies using placebos for diseases with efficient and effective treatment. This position differs with the Helsinki Declaration, which allows the use of placebos in methodologically justified conditions. To ascertain whether the CMF's ethical regulation modified the use of placebos in phase III clinical trials in Brazil, characteristics of the records in were researched in the periods from 2003 to 2007 and from 2009 to 2013. The conclusions reached were: a) the regulations issued by the CFM in 2008 were ineffective and the position adopted by the Helsinki Declaration prevails; b) there was significant sponsorship by the multinational pharmaceutical industry of trials with placebos; c) the research was predominantly on new drugs for chronic diseases, with little study done of the neglected diseases which are of great importance to Brazil.

Animals , Rats , Apoptosis/genetics , Gene Expression Regulation, Enzymologic/genetics , Heme/deficiency , Nerve Degeneration/genetics , Neurons/metabolism , Porphyrias/complications , Apoptosis/drug effects , Caspases/drug effects , Caspases/metabolism , Cell Survival/drug effects , Cell Survival/genetics , Collagen Type XI/drug effects , Collagen Type XI/metabolism , Cyclic AMP Response Element-Binding Protein/drug effects , Cyclic AMP Response Element-Binding Protein/genetics , Cyclic AMP Response Element-Binding Protein/metabolism , Down-Regulation/drug effects , Down-Regulation/physiology , Enzyme Inhibitors , Gene Expression Regulation, Enzymologic/drug effects , Heptanoates , Heme/biosynthesis , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/physiology , Membrane Proteins/drug effects , Membrane Proteins/genetics , Membrane Proteins/metabolism , Nerve Degeneration/metabolism , Nerve Degeneration/physiopathology , Nerve Tissue Proteins/drug effects , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neural Cell Adhesion Molecules/drug effects , Neural Cell Adhesion Molecules/genetics , Neural Cell Adhesion Molecules/metabolism , Neurons/drug effects , Neurons/pathology , Poly(ADP-ribose) Polymerases , Porphyrias/metabolism , Porphyrias/physiopathology , RNA, Messenger/drug effects , RNA, Messenger/metabolism , RNA-Binding Proteins/drug effects , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , SMN Complex Proteins , Up-Regulation/drug effects , Up-Regulation/physiology , Vesicular Transport Proteins/drug effects , Vesicular Transport Proteins/genetics , Vesicular Transport Proteins/metabolism
Colomb. med ; 46(1): 19-25, Jan.-Mar. 2015. ilus
Article in English | LILACS | ID: lil-753531


Background: Prefrontal cortex (PFC) represents the highest level of integration and control of psychic and behavioral states. Several dysfunctions such as autism, hyperactivity disorders, depression, and schizophrenia have been related with alterations in the prefrontal cortex (PFC). Among the cortical layers of the PFC, layer II shows a particular vertical pattern of organization, the highest cell density and the biggest non-pyramidal/pyramidal neuronal ratio. We currently characterized the layer II cytoarchitecture in human areas 10, 24, and 46. Objective: We focused particularly on the inhibitory neurons taking into account that these cells are involved in sustained firing (SF) after stimuli disappearance. Methods: Postmortem samples from five subjects who died by causes different to central nervous system diseases were studied. Immunohistochemistry for the neuronal markers, NeuN, parvalbumin (PV), calbindin (CB), and calretinin (CR) were used. NeuN targeted the total neuronal population while the rest of the markers specifically the interneurons. Results: Cell density and soma size were statically different between areas 10, 46, 24 when using NeuN. Layer II of area 46 showed the highest cell density. Regarding interneurons, PV+-cells of area 46 showed the highest density and size, in accordance to the proposal of a dual origin of the cerebral cortex. Interhemispheric asymmetries were not identified between homologue areas. Conclusion: First, our findings suggest that layer II of area 46 exhibits the most powerful inhibitory system compared to the other prefrontal areas analyzed. This feature is not only characteristic of the PFC but also supports a particular role of layer II of area 46 in SF. Additionally, known functional asymmetries between hemispheres might not be supported by morphological asymmetries.

Antecedentes: La corteza prefrontal (CPF) representa el nivel más alto de integración y control de funciones psíquicas y comportamentales. Varias patologías como autismo, desórdenes de hiperactividad, depresión y esquizofrenia se han relacionado con alteraciones de la CPF. La lámina II de las áreas que constituyen la CPF posee un patrón de organización vertical, una alta densidad celular y la mayor proporción de neuronas no-piramidal/piramidal. Sin embargo, la distribución del componente inhibitorio en estas regiones no se ha descrito. Objetivo: En el presente estudio nos propusimos caracterizar la lámina II de las áreas 10, 24 y 46 del humano, particularmente su componente inhibitorio teniendo en mente su participación en procesos de actividad sostenida relevantes cuando desaparece el estímulo. Métodos: Se utilizaron muestras de cinco sujetos que fallecieron por causas diferentes a enfermedades del sistema nervioso. Se tomaron secciones de las áreas 10, 24 y 46 de Brodmann y se procesaron con los anticuerpos contra NeuN para determinar la población neuronal total y contra Parvalbumina (PV), Calbindina (CB) y Calretinina (CR) para analizar la población de interneuronas. Resultados: Los resultados no mostraron diferencias interhemisféricas entre las áreas. Sin embargo, las tres áreas seleccionadas son significativamente diferentes entre sí en todos los parámetros analizados. El área 46 posee la mayor densidad y tamaño de interneuronas positivas para PV. Conclusiones: La ausencia de asimetrías morfológicas no permite explicar las asimetrías funcionales. La lámina II del área 46 posee el sistema inhibitorio más poderoso. Teniendo en cuenta la arquitectura modular de las capas supragranulares, este sistema inhibitorio subyace a la actividad sostenida, eje fundamental de la memoria operativa.

Adult , Humans , Male , Middle Aged , Interneurons/cytology , Neurons/metabolism , Prefrontal Cortex/cytology , Antigens, Nuclear/metabolism , /metabolism , Calbindins/metabolism , Nerve Tissue Proteins/metabolism , Parvalbumins/metabolism
Cad. saúde pública ; 31(3): 597-606, 03/2015. tab
Article in Portuguese | LILACS | ID: lil-744836


Foi avaliada a associação entre menopausa e insônia e a influência de variáveis socioeconômicas e psicossociais, em estudo transversal com 2.190 funcionárias de uma universidade (Estudo Pró-Saúde), a partir de um questionário autopreenchível com variáveis sobre menopausa, insônia, transtorno mental comum, eventos de vida estressantes, apoio social e variáveis socioeconômicas. Odds ratios foram calculados por meio de regressão logística multivariada, com desfecho politômico. Após ajuste para potenciais confundidoras sociodemográficas, mulheres na menopausa há mais de 60 meses apresentaram maior chance de reportar queixas de sono frequentes (OR entre 1,53 e 1,86) do que as que estavam na menopausa há menos de 60 meses. Após os ajustes, no primeiro grupo, para as variáveis psicossociais, a magnitude dos ORs reduziu para 1,53 (IC95%: 0,92-2,52) para dificuldade em iniciar o sono, 1,81 (IC95%: 1,09-2,98) para dificuldade em manter o sono e 1,71 (IC95%: 1,08-2,73) para queixa geral de insônia. Fatores psicossociais podem mediar a manifestação da insônia em mulheres na menopausa.

This study evaluated the association between insomnia and menopausal status and the influence of socioeconomic and psychosocial variables on this association in a cross-sectional analysis of 2,190 university employees (the Pró-Saúde Study). A self-administered questionnaire was used, covering menopausal status, complaints of insomnia, common mental disorders, stressful life events, social support, and socioeconomic variables. Odds ratios were calculated using logistic regression with a polytomous outcome. After adjusting for potential socio-demographic confounders, women who had entered menopause more than 60 months previously were more likely to report complaints with sleep (OR 1.53-1.86) as compared to women in menopause for less than 60 months. After adjusting for psychosocial variables, in the first group the ORs decreased to 1.53 (95%CI: 0.92-2.52) for difficulty initiating sleep, 1.81 (95%CI: 1.09-2.98) for difficulty maintaining sleep, and 1.71 (95%CI: 1.08-2.73) for general complaints of insomnia. Psychosocial factors can mediate the manifestation of insomnia among menopausal women.

En este estudio se evaluó la asociación entre insomnio y menopausia y la influencia de las variables socioeconómicas y psicosociales, en un estudio transversal con 2.190 mujeres de una universidad (Estudio Pro-Salud), a partir de un cuestionario autoadministrado con variables de la menopausia, insomnio, trastornos mentales, situaciones de estrés vital, apoyo social y variables socioeconómicas. Se calcularon los odds ratio mediante regresión logística multivariante con desenlace politómico. Después de ajustar por factores de confusión sociodemográficos potenciales, las mujeres menopáusicas desde hace más de 60 meses fueron más propensas a reportar quejas frecuentes de sueño (OR entre 1,53 y 1,86) que las menopáusicas hace menos de 60 meses. Después de los ajustes, en el primer grupo, para las variables psicosociales la magnitud de los OR se redujo a 1,53 (IC95%: 0,92-2,52) para la dificultad para iniciar el sueño, un 1,81 (IC95%: 1,09-2,98) para mantener el sueño y un 1,71 (IC95%: 1,08-2,73) para las quejas de insomnio en general. Los factores psicosociales pueden mediar en la manifestación del insomnio en las mujeres menopáusicas.

Animals , Mice , Cerebral Cortex/metabolism , Drosophila Proteins/metabolism , Microfilament Proteins/metabolism , Microtubules/metabolism , Neurogenesis , Neurons/metabolism , Pseudopodia/metabolism , Actins/metabolism , Cell Line, Tumor , Cells, Cultured , Cerebral Cortex/embryology , Drosophila , Drosophila Proteins/genetics , /metabolism , Growth Cones/metabolism , Mutation , Microfilament Proteins/genetics , RNA Interference
Braz. dent. j ; 26(1): 86-88, Jan-Feb/2015. graf
Article in English | LILACS | ID: lil-735838


This paper presents a case of osteonecrosis of the jaw related to zoledronic acid (5 mg) administered once yearly to treat osteoporosis. A 79-year-old woman who has been treated for osteoporosis for 5 years with 5 applications of zoledronic acid was referred for evaluation. The patient had been submitted to dental implant placement and there was no osseointegration. On clinical examination, suppuration and exposed bone on the alveolar ridge were observed. Radiographic examination revealed an osteolytic area and bone sequestration. Both clinical and radiological features were suggestive of osteonecrosis. The treatment consisted of surgery to remove the affected bone completely. The patient is asymptomatic at 9 months after surgery. Dentists and oral surgeons should be alert to the possibility of osteonecrosis related to the use of once-yearly injections of zoledronic acid for the treatment of postmenopausal osteoporosis.

O presente estudo teve como objetivo apresentar um caso de osteonecrose dos maxilares associada ao uso de ácido zoledrônico (5 mg) administrado uma vez ao ano para tratar a osteoporose. Uma mulher de 79 anos de idade estava em tratamento de osteoporose por 5 anos com 5 aplicações do ácido zoledrônico foi encaminhada para nossa avaliação. A paciente tinha sido submetida à colocação de implante dental e não houve osseointegração. Ao exame clínico, supuração e osso exposto no rebordo alveolar foram observados. Os exames radiográficos revelaram uma área osteolítica e sequestro ósseo. Ambos os aspectos clínicos e radiográficos eram sugestivos de osteonecrose. O tratamento consistiu de cirurgia para remover todo o osso afetado. A paciente está assintomática há 9 meses (desde a cirurgia). Cirurgiões-dentistas e cirurgiões orais devem estar atentos para a possibilidade de osteonecrose relacionada ao uso de injeções anuais de ácido zoledrônico para tratamento da osteoporose pós-menopausa.

Female , Humans , Pregnancy , Brain/pathology , Cell Differentiation , Encephalitis/pathology , Pregnancy Complications, Infectious/pathology , Brain/metabolism , Encephalitis/metabolism , Fetus/metabolism , Fetus/pathology , Glial Fibrillary Acidic Protein/metabolism , Neuroglia/metabolism , Neurons/metabolism , Pregnancy Complications, Infectious/metabolism , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A/metabolism
Salud pública Méx ; 57(1): 4-13, ene.-feb. 2015. tab
Article in English | LILACS | ID: lil-736456


Objective. To describe food expenditure and consumption of foods prepared away from home among Mexican adults. Materials and methods. Data were from 45 241 adult participants in the National Health and Nutrition Survey 2006, a nationally-representative, cross-sectional survey of Mexican households. Descriptive statistics and multivariable linear and logistic regression were used to assess the relationship between location of residence, educational attainment, socioeconomic status and the following: 1) expenditure on all food and at restaurants, and 2) frequency of consumption of comida corrida or restaurant food and street food. Results. Food expenditure and consumption of food prepared away from home were positively associated with socioeconomic status, educational attainment, and urban vs. rural residence (p<0.001 for all relationships in bivariate analyses). Conclusions. Consumption of food prepared outside home may be an important part of the diet among urban Mexican adults and those with high socioeconomic status and educational attainment.

Objetivo. Describir los gastos en alimentos y el consumo de alimentos preparados fuera de casa en población mexicana. Material y métodos. Los datos fueron de 45 241 adultos mexicanos en la Encuesta Nacional de Salud y Nutrición de 2006, representativa al nivel nacional. Se utilizaron estadísticas descriptivas y regresión linear y logística para estimar la relación entre el lugar de residencia, el nivel educativo y el nivel socioeconómico, con el gasto en todos los alimentos y en restaurantes, y con la frecuencia de consumo de comida corrida, en restaurantes y de la calle. Resultados. El gasto en alimentos y el consumo de alimentos preparados se asociaron positivamente con el nivel socioeconómico, el nivel educativo y la residencia rural (p<0,001 para todas las relaciones). Conclusiones. El consumo de alimentos preparados puede ser una parte importante de la dieta de los adultos urbanos y de aquéllos con altos niveles socioeconómicos y educativos.

Animals , Cricetinae , Female , Humans , Male , Mice , G Protein-Coupled Inwardly-Rectifying Potassium Channels/chemistry , Neurodegenerative Diseases/pathology , Spinal Cord/metabolism , Tyrosine/chemistry , Anisomycin/chemistry , Antibodies/chemistry , Behavior , Blotting, Western , Cell Line , Cell Line, Tumor , CHO Cells , DNA , Dose-Response Relationship, Drug , Electrophysiology , Enzyme-Linked Immunosorbent Assay , G Protein-Coupled Inwardly-Rectifying Potassium Channels/physiology , GTP-Binding Proteins/metabolism , Heart Atria/metabolism , Heart Ventricles/cytology , Heart Ventricles/pathology , Immunoblotting , Immunohistochemistry , Inflammation , Microscopy, Confocal , Microscopy, Fluorescence , Muscle Cells/metabolism , Neurons/metabolism , Phosphorylation , Protein Structure, Tertiary , Plasmids/metabolism , Stress, Physiological , Sciatic Nerve/metabolism , Spinal Cord/pathology , Xenopus laevis