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1.
bioRxiv ; 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38352485

RESUMO

The propagation of action potentials along axons is traditionally considered to be reliable, as a consequence of the high safety factor of action potential propagation. However, numerical simulations have suggested that, at high frequencies, spikes could fail to invade distal axonal branches. Given the complex morphologies of axonal trees, with extensive branching and long-distance projections, spike propagation failures could be functionally important. To explore this experimentally in vivo, we used an axonal-targeted calcium indicator to image action potentials at axonal terminal branches in superficial layers from mouse somatosensory cortical pyramidal neurons. We activated axons with an extracellular electrode, varying stimulation frequencies, and computationally extracted axonal morphologies and associated calcium responses. We find that axonal boutons have higher calcium accumulations than their parent axons, as was reported in vitro. But, contrary to previous in vitro results, our data reveal spike failures in a significant subset of branches, as a function of branching geometry and spike frequency. The filtering is correlated with the geometric ratio of the branch diameters, as expected by cable theory. These findings suggest that axonal morphologies contribute to signal processing in the cortex.

2.
J Neurosurg ; : 1-8, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37890180

RESUMO

The prospect of direct interaction between the brain and computers has been investigated in recent decades, revealing several potential applications. One of these is sight restoration in profoundly blind people, which is based on the ability to elicit visual perceptions while directly stimulating the occipital cortex. Technological innovation has led to the development of microelectrodes implantable on the brain surface. The feasibility of implanting a microelectrode on the visual cortex has already been shown in animals, with promising results. Current research has focused on the implantation of microelectrodes into the occipital brain of blind volunteers. The technique raises several technical challenges. In this technical note, the authors suggest a safe and effective approach for robot-assisted implantation of microelectrodes in the occipital lobe for sight restoration.

3.
Sci Rep ; 13(1): 13057, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37567902

RESUMO

The capacity of a physical system to transport and localize energy or information is usually linked to its spatial configuration. This is relevant for integration and transmission of signals as performed, for example, by the dendrites of neuronal cells. Inspired by recent works on the organization of spines on the surface of dendrites and how they promote localization or propagation of electrical impulses in neurons, here we propose a linear photonic lattice configuration to study how the geometric features of a dendrite-inspired lattice allows for the localization or propagation of light on a completely linear structure. We show that by increasing the compression of the photonic analogue of spines and thus, by increasing the coupling strength of the spines with the main chain (the "photonic dendrite"), flat band modes become prevalent in the system, allowing spatial localization in the linear - low energy - regime. Furthermore, we study the inclusion of disorder in the distribution of spines and show that the main features of ordered systems persist due to the robustness of the flat band states. Finally, we discuss if the photonic analog, having evanescent interactions, may provide insight into linear morphological mechanisms at work occurring in some biological systems, where interactions are of electric and biochemical origin.

5.
Brain Spine ; 3: 101736, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37383453

RESUMO

Introduction: Pediatric hydrocephalus is highly prevalent and therefore a major neurosurgical problem in Africa. In addition to ventriculoperitoneal shunts, which have high cost and potential complications, endoscopic third ventriculostomy is becoming an increasingly popular technique especially in this part of the world. However, performing this procedure requires trained neurosurgeons with an optimal learning curve. For this reason, we have developed a 3D printed training model of hydrocephalus so that neurosurgeons without previous experience with endoscopic techniques can acquire these skills, especially in low-income countries, where specific techniques training as this, are relatively absent. Research Question: Our research question was about the possibility to develop and produce a low-cost endoscopic training model and to evaluate the usefulness and the skills acquired after training with it. Material and Methods: A neuroendoscopy simulation model was developed. A sample of last year medical students and junior neurosurgery residents without prior experience in neuroendoscopy were involved in the study. The model was evaluated by measuring several parameters, as procedure time, number of fenestration attempts, diameter of the fenestration, and number of contacts with critical structures. Results: An improvement of the average score on the ETV-Training-Scale was noticed between the first and last attempt (11.6, compared to 27.5 points; p<0.0001). A statistically significant improvement in all parameters, was observed. Discussion and Conclusion: This 3D printed simulator facilitates acquiring surgical skills with the neuroendoscope to treat hydrocephalus by performing an endoscopic third ventriculostomy. Furthermore, it has been shown to be useful to understand the intraventricular anatomical relationships.

6.
Res Vet Sci ; 161: 50-61, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37321011

RESUMO

This study investigated the effect of host genetics on the structure and composition of the cecum microbiota of three breeds of guinea pigs: Andina, Inti, and Peru. Fifteen guinea pigs were distributed into three groups according to their breed: Andina (5), Inti (5), and Peru (5). We discovered that four main phyla were shared between the three breeds: Bacteroidota, Firmicutes, Spirochaetota, and Synergistota. Although there were no significant differences in the alpha and beta diversity analysis, we found that the Linear discriminant analysis effect size and the heat tree analysis showed significant differences between the abundance of several taxa present in the cecum microbiome of the three breeds. These results suggest that host genetics could be a factor in the structure and composition of the guinea pig cecum microbiome. In addition, we found unique genera for each breed that have fermentation capacity and, therefore can be analyzed in further studies to determine if there is a functional relationship between them and the breed and its industrial profile.


Assuntos
Microbiota , Animais , Cobaias , Peru , Ceco , Bactérias , Fermentação
7.
Front Microbiol ; 14: 1283738, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38173670

RESUMO

Guinea pigs have historically been used as a food source and are also an important model for studying the human intestines. Fasting is the act of temporarily stopping the intake of food. This process can alter the microbiota of various animals. This study is the first to investigate the impact of fasting on the cecum microbiome of three guinea pig breeds. We investigated the impact of fasting on the microbiome population structure in the cecum of three guinea pig breeds. This was done by sequencing and analyzing the V4 hypervariable region of the 16S rRNA gene in bacterial communities found in cecum mucosa samples. To achieve this, we established two treatment groups (fasting and fed), for each of the three guinea pig breeds: Andina, Inti, and Peru. The study involved twenty-eight guinea pigs, which were divided into the following groups: Andina-fed (five), Andina-fasting (five), Inti-fed (four), Inti-fasting (five), Peru-fed (five), and Peru-fasting (four). The results indicated a significant difference in beta diversity between the treatment groups for the Peru breed (P-value = 0.049), but not for the treatment groups of the Andina and Inti breeds. The dominant phyla across all groups were Firmicutes and Bacteroidetes. We observed variations in the abundance of different taxa in the cecum microbiota when comparing the treatment groups for each breed. Additionally, there was a higher number of unique taxa observed in the fasting groups compared to the fed groups. We discovered that the genus Victivallis was the only one present in all fasting groups across all breeds. Despite the findings, the resilience of the gut microbiome was not challenged in all three breeds, which can lead to disruptive changes that may affect the overall maintenance of the cecum microbiome. Based on the observed differences in the treatment groups of the Peru breed, it can be suggested that fasting has a greater impact on this particular breed.

8.
Cells ; 11(12)2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35740989

RESUMO

Alzheimer's disease (AD) is the most prevalent age-associated neurodegenerative disease. A decrease in autophagy during aging contributes to brain disorders by accumulating potentially toxic substrates in neurons. Rubicon is a well-established inhibitor of autophagy in all cells. However, Rubicon participates in different pathways depending on cell type, and little information is currently available on neuronal Rubicon's role in the AD context. Here, we investigated the cell-specific expression of Rubicon in postmortem brain samples from AD patients and 5xFAD mice and its impact on amyloid ß burden in vivo and neuroblastoma cells. Further, we assessed Rubicon levels in human-induced pluripotent stem cells (hiPSCs), derived from early-to-moderate AD and in postmortem samples from severe AD patients. We found increased Rubicon levels in AD-hiPSCs and postmortem samples and a notable Rubicon localization in neurons. In AD transgenic mice lacking Rubicon, we observed intensified amyloid ß burden in the hippocampus and decreased Pacer and p62 levels. In APP-expressing neuroblastoma cells, increased APP/amyloid ß secretion in the medium was found when Rubicon was absent, which was not observed in cells depleted of Atg5, essential for autophagy, or Rab27a, required for exosome secretion. Our results propose an uncharacterized role of Rubicon on APP/amyloid ß homeostasis, in which neuronal Rubicon is a repressor of APP/amyloid ß secretion, defining a new way to target AD and other similar diseases therapeutically.


Assuntos
Doença de Alzheimer , Proteínas Relacionadas à Autofagia , Neuroblastoma , Doenças Neurodegenerativas , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Proteínas Relacionadas à Autofagia/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Camundongos Transgênicos , Neuroblastoma/metabolismo , Doenças Neurodegenerativas/metabolismo , Neurônios/metabolismo
9.
World Neurosurg ; 163: e593-e609, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35430399

RESUMO

BACKGROUND: Stereoscopy has been demonstrated to be a useful method of education in the field of anatomy because it allows users to see, in a simulation, the anatomical structures in their actual volume and depth. METHODS: Cadaveric specimens preserved under formaldehyde using the Thiel and Klinger techniques have been dissected and photographed in the medical school anatomy laboratory (University Miguel Hernández) for the past 10 years. The photographic material and technique required to capture and project stereoscopic photographs have been described in different fields of surgical neuroanatomy. We used the results from a survey completed by the participants of different training courses to evaluate the utility of the 3-dimensional (3D) method. RESULTS: A large database of photographs taken of different anatomical regions and approaches of neurosurgical interest was obtained. We have presented some examples in the form of pairs of photographs in 2-dimensional (2D) format, with explanatory labels, paired with the corresponding 3D photograph in anaglyph format. The survey showed that the lectures that had included 3D photographs were significantly better accepted than the lectures with conventional 2D photographs. CONCLUSIONS: The teaching of basic, academic, and clinical neuroanatomy through the projection of stereoscopic photographs can be useful. The methods of image capture and stereoscopic projection in neuroanatomy, once combined with the necessary theoretical and practical knowledge, can be reproduced at other centers of neuroanatomy teaching.


Assuntos
Anatomia , Imageamento Tridimensional , Simulação por Computador , Humanos , Imageamento Tridimensional/métodos , Neuroanatomia/educação
10.
Science ; 375(6576): 82-86, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34762487

RESUMO

Dendritic spines mediate most excitatory neurotransmission in the nervous system, so their function must be critical for the brain. Spines are biochemical compartments but might also electrically modify synaptic potentials. Using two-photon microscopy and a genetically encoded voltage indicator, we measured membrane potentials in spines and dendrites from pyramidal neurons in the somatosensory cortex of mice during spontaneous activity and sensory stimulation. Spines and dendrites were depolarized together during action potentials, but, during subthreshold and resting potentials, spines often experienced different voltages than parent dendrites, even activating independently. Spine voltages remained compartmentalized after two-photon optogenetic activation of individual spine heads. We conclude that spines are elementary voltage compartments. The regulation of voltage compartmentalization could be important for synaptic function and plasticity, dendritic integration, and disease states.


Assuntos
Espinhas Dendríticas/fisiologia , Células Piramidais/fisiologia , Córtex Somatossensorial/fisiologia , Potenciais de Ação , Animais , Potenciais da Membrana , Camundongos , Optogenética , Técnicas de Patch-Clamp , Córtex Somatossensorial/citologia , Sinapses/fisiologia , Potenciais Sinápticos
11.
Childs Nerv Syst ; 37(11): 3475-3484, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34240241

RESUMO

The use of cerebrospinal fluid (CSF) shunts remains a fundamental therapeutic modality in the management of hydrocephalus. Nowadays, neurosurgeons have an arsenal of different shunt technologies on their hands, with several companies producing many different configurations of them. The greatest difficulty of treating a child with hydrocephalus is to deal with a brain that will enormously change its size and hydrodynamic conditions and a body that will multiply its height and weight in a short time. Detailed knowledge of the hydrodynamic properties of shunts is mandatory for any neurosurgeon and much more for those taking care of pediatric patients. It is necessary to know that these properties of the valve may influence the evolution of the patient after shunting and it is recognized that a patient physiology-specific valve selection may yield better outcomes and decrease complications. This article provides a summary of the most common available CSF valves and overdrainage control devices, their technology, and possible combinations. The objective is to offer a quick overview of the armamentarium to facilitate the recognition of the implanted device and improve the selection of the most suitable valve for each patient.


Assuntos
Derivações do Líquido Cefalorraquidiano , Hidrocefalia , Cateteres , Criança , Humanos , Hidrocefalia/cirurgia , Lactente , Próteses e Implantes , Tecnologia
13.
Cell Rep ; 30(13): 4505-4517.e5, 2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-32234483

RESUMO

TRPM8 is the main ion channel responsible for cold transduction in the somatosensory system. Nerve terminal availability of TRPM8 determines cold sensitivity, but how axonal secretory organelles control channel delivery remains poorly understood. Here we examine the distribution of TRPM8 and trafficking organelles in cold-sensitive peripheral axons and disrupt trafficking by targeting the ARF-GEF GBF1 pharmacologically or the small GTPase RAB6 by optogenetics. In axons of the sciatic nerve, inhibition of GBF1 interrupts TRPM8 trafficking and increases association with the trans-Golgi network, LAMP1, and Golgi satellites, which distribute profusely along the axonal shaft. Accordingly, both TRPM8-dependent ongoing activity and cold-evoked responses reversibly decline upon GBF1 inhibition in nerve endings of corneal cold thermoreceptors. Inhibition of RAB6, which also associates to Golgi satellites, decreases cold-induced responses in vivo. Our results support a non-conventional axonal trafficking mechanism controlling the availability of TRPM8 in axons and cold sensitivity in the peripheral nervous system.


Assuntos
Axônios/metabolismo , Temperatura Baixa , Organelas/metabolismo , Canais de Cátion TRPM/metabolismo , Animais , Axônios/efeitos dos fármacos , Complexo de Golgi/efeitos dos fármacos , Complexo de Golgi/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Células HEK293 , Células HeLa , Humanos , Masculino , Mentol/farmacologia , Camundongos , Optogenética , Organelas/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismo , Termorreceptores/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo
14.
Clín. investig. arterioscler. (Ed. impr.) ; 32(1): 1-7, ene.-feb. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-187001

RESUMO

Introducción y objetivos: La haptoglobina es una proteína implicada en la protección frente al daño oxidativo producido por el hierro de la hemoglobina. Esta proteína es polimórfica, con 3 isomorfas prevalentes en la población. Los portadores de la isoforma Hp2-2 tienen una menor capacidad antioxidante, y en la población con diabetes, un mayor riesgo de enfermedad vascular subclínica y de complicaciones cardiovasculares. Nuestro objetivo fue evaluar si dicha isomorfa se asocia con un mayor riesgo de arteriosclerosis carotídea en sujetos con y sin diabetes, libres de enfermedad cardiovascular. Pacientes y métodos: Estudio realizado en una población de entre 45 y 74años de edad seleccionada aleatoriamente del área noroeste de Madrid. Los participantes fueron caracterizados en cuanto a su estatus glucémico mediante una sobrecarga oral de glucosa y la determinación de la concentración de Hb1Ac. A todos ellos se les determinó el fenotipo de la haptoglobina mediante un ensayo inmunoenzimático y la presencia de arteriosclerosis carotídea mediante ecografía. Resultados: De los 1.256 participantes incluidos en el presente análisis (edad media 61,6 ± 6 años, 41,8% varones), la distribución de las isoformas de la haptoglobina fue la siguiente: Hp1-1: 13,3%, Hp1-2: 48,5% y Hp2-2: 38,2%. En comparación con los sujetos Hp1-1 y Hp1-2, aquellos con el fenotipo Hp2-2 tuvieron una mayor prevalencia de dislipemia (53,3% vs 43%, p < 0,0001) e hipertensión arterial (39,2% vs 32,2%, p = 0,012), y recibieron con más frecuencia tratamiento con estatinas (31,5% vs 21,6%, p < 0,0001) y con antihipertensivos (38,4% vs 30,8%, p = 0,006). Los portadores de la isoforma Hp2-2 tuvieron una mayor prevalencia de placas carotídeas (OR: 1,35; IC 95%: 1,07-1,69; p = 0,011), sin diferencias en dicha prevalencia en función del estatus glucémico. No existieron diferencias en el grosor íntima-media entre los diferentes fenotipos. La relación del fenotipo Hp2-2 con la presencia de placas en carótida fue independiente de la edad, del sexo, de la presencia de factores de riesgo (dislipemia, hipertensión y diabetes), de la concentración de colesterol LDL, proteína C reactiva y ácido úrico, de la presión arterial y del tratamiento con estatinas y antihipertensivos (OR: 1,31; IC 95%: 1,01-1,70; p = 0,044). Conclusión: Los sujetos con el fenotipo Hp2-2 de la haptoglobina tienen una mayor prevalencia de arteriosclerosis carotídea, que es independiente de la presencia de otros factores de riesgo cardiovascular y de su estatus glucémico


Introduction and objectives: Haptoglobin is a protein involved in the protection against oxidative damage caused by iron in haemoglobin. This protein is polymorphic, with 3 isomorphs prevalent in the population. The carriers of the Hp2-2 isoform have a lower antioxidant capacity and, in the population with diabetes, an increased risk of subclinical vascular disease and cardiovascular complications. The objective of this study was to evaluate whether this isomorphy is associated with an increased risk of carotid arteriosclerosis in subjects with and without diabetes, and free of cardiovascular disease. Patients and methods: A study was conducted in a population between 45 and 74years of age, randomly selected from the northwest area of Madrid. The participants were characterised in terms of their glycaemic status by oral glucose overload and the determination of the concentration of Hb1Ac. The haptoglobin phenotypes in all of them were determined by means of an immunoenzymatic assay, and the presence of carotid arteriosclerosis by ultrasound. Results: Of the 1,256 participants included in the present analysis (mean age 61.6 ± 6 years, 41.8% males), the distribution of the isoforms of haptoglobin was as follows: Hp1-1: 13.3%, Hp1-2: 48.5%, and Hp2-2: 38.2%. In comparison with subjects Hp1-1 and Hp1-2, those with the Hp2-2 phenotype had a higher prevalence of dyslipidaemia (53.3% vs 43%; P < .0001) and arterial hypertension (39.2% vs. 32.2%, P = .012), and they more frequently received treatment with statins (31.5% vs 21.6%, P < .0001), and with antihypertensive agents (38.4% vs 30.8%, P = .006). The carriers of the Hp2-2 isoform had a higher prevalence of carotid plaques (OR: 1.35, 95%CI: 1.07-1.69, P = .011), with no differences in that prevalence as regards the glycaemic status. There were no differences in the intima-media thickness between the different phenotypes. The relationship of the Hp2-2 phenotype with the presence of plaques in the carotid was independent of age, gender, presence of risk factors (dyslipidaemia, hypertension and diabetes), the concentration of LDL-cholesterol, C-reactive protein and uric acid, blood pressure, and treatment with statins, and hypertensive drugs (OR: 1.31, 95% CI 1.01-1.70, P = .044). Conclusion: Subjects with the Hp2-2 phenotype of haptoglobin have a higher prevalence of carotid arteriosclerosis, which is independent of the presence of other cardiovascular risk factors and their glycaemic status


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Haptoglobinas/análise , Doenças Vasculares/sangue , Arteriosclerose/diagnóstico por imagem , Isoformas de Proteínas/análise , Doenças Vasculares/metabolismo , Haptoglobinas/metabolismo , ELISPOT , Isoformas de Proteínas/provisão & distribuição , Hiperlipidemias/epidemiologia , Fatores de Risco , Estudos Prospectivos , Antropometria , Modelos Logísticos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
15.
Clin Investig Arterioscler ; 32(1): 1-7, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31221534

RESUMO

INTRODUCTION AND OBJECTIVES: Haptoglobin is a protein involved in the protection against oxidative damage caused by iron in haemoglobin. This protein is polymorphic, with 3 isomorphs prevalent in the population. The carriers of the Hp2-2 isoform have a lower antioxidant capacity and, in the population with diabetes, an increased risk of subclinical vascular disease and cardiovascular complications. The objective of this study was to evaluate whether this isomorphy is associated with an increased risk of carotid arteriosclerosis in subjects with and without diabetes, and free of cardiovascular disease. PATIENTS AND METHODS: A study was conducted in a population between 45 and 74years of age, randomly selected from the northwest area of Madrid. The participants were characterised in terms of their glycaemic status by oral glucose overload and the determination of the concentration of Hb1Ac. The haptoglobin phenotypes in all of them were determined by means of an immunoenzymatic assay, and the presence of carotid arteriosclerosis by ultrasound. RESULTS: Of the 1,256 participants included in the present analysis (mean age 61.6±6years, 41.8% males), the distribution of the isoforms of haptoglobin was as follows: Hp1-1: 13.3%, Hp1-2: 48.5%, and Hp2-2: 38.2%. In comparison with subjects Hp1-1 and Hp1-2, those with the Hp2-2 phenotype had a higher prevalence of dyslipidaemia (53.3% vs 43%; P<.0001) and arterial hypertension (39.2% vs. 32.2%, P=.012), and they more frequently received treatment with statins (31.5% vs 21.6%, P<.0001), and with antihypertensive agents (38.4% vs 30.8%, P=.006). The carriers of the Hp2-2 isoform had a higher prevalence of carotid plaques (OR: 1.35, 95%CI: 1.07-1.69, P=.011), with no differences in that prevalence as regards the glycaemic status. There were no differences in the intima-media thickness between the different phenotypes. The relationship of the Hp2-2 phenotype with the presence of plaques in the carotid was independent of age, gender, presence of risk factors (dyslipidaemia, hypertension and diabetes), the concentration of LDL-cholesterol, C-reactive protein and uric acid, blood pressure, and treatment with statins, and hypertensive drugs (OR: 1.31, 95%CI 1.01-1.70, P=.044). CONCLUSION: Subjects with the Hp2-2 phenotype of haptoglobin have a higher prevalence of carotid arteriosclerosis, which is independent of the presence of other cardiovascular risk factors and their glycaemic status.


Assuntos
Arteriosclerose/epidemiologia , Doenças das Artérias Carótidas/epidemiologia , Espessura Intima-Media Carotídea , Haptoglobinas/metabolismo , Idoso , Arteriosclerose/sangue , Doenças das Artérias Carótidas/sangue , Feminino , Glucose/metabolismo , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Isoformas de Proteínas , Fatores de Risco
16.
BMC Biol ; 17(1): 71, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31514747

RESUMO

As a "holy grail" of neuroscience, optical imaging of membrane potential could enable high resolution measurements of spiking and synaptic activity in neuronal populations. This has been partly achieved using organic voltage-sensitive dyes in vitro, or in invertebrate preparations yet unspecific staining has prevented single-cell resolution measurements from mammalian preparations in vivo. The development of genetically encoded voltage indicators (GEVIs) and chemogenetic sensors has enabled targeting voltage indicators to plasma membranes and selective neuronal populations. Here, we review recent advances in the design and use of genetic voltage indicators and discuss advantages and disadvantages of three classes of them. Although genetic voltage indicators could revolutionize neuroscience, there are still significant challenges, particularly two-photon performance. To overcome them may require cross-disciplinary collaborations, team effort, and sustained support by large-scale research initiatives.


Assuntos
Corantes Fluorescentes/química , Proteínas Luminescentes , Neurônios/fisiologia , Canais de Ânion Dependentes de Voltagem , Animais , Membrana Celular/metabolismo , Proteínas Luminescentes/química , Proteínas Luminescentes/genética , Rodopsina/química , Rodopsina/genética , Análise de Célula Única/métodos , Canais de Ânion Dependentes de Voltagem/química , Canais de Ânion Dependentes de Voltagem/genética
17.
F1000Res ; 8: 1717, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32832071

RESUMO

Background: Bladder adenocarcinoma (AC) is a scarce histological variant and there are few studies on its proper management. No previous case reports present the management of a urachal tumor and the incidental finding of bladder adenocarcinoma. Clinical case: We present the case of a young woman with nonspecific symptoms, who presented with a prior history of dysuria, bladder tenesmus, suprapubic pain and urinary urgency for one year, which had been treated as recurrent urinary tract infection. A partial cystectomy plus extended lymphadenectomy was scheduled. We found a bladder tumor with characteristics of a urachal tumor and the pathological report indicated a primary bladder AC. The patient had a complete recovery at one year of follow-up. Conclusions: A patient can present with a tumor with urachal characteristics; however, the pathology report can show primary AC. The decision to perform partial cystectomy was an appropriate option for the location of this tumor, with optimal surgical results. Still, a long-term follow-up is necessary. More specific management guidelines are required for the treatment of AC.


Assuntos
Adenocarcinoma/diagnóstico , Úraco/patologia , Neoplasias da Bexiga Urinária/diagnóstico , Adenocarcinoma/patologia , Adulto , Cistectomia , Feminino , Humanos , Neoplasias da Bexiga Urinária/patologia
18.
J Clin Lipidol ; 12(4): 1039-1046.e3, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29773421

RESUMO

BACKGROUND: The R46L variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been related to lipid levels and cardiovascular disease. OBJECTIVE: To evaluate the influence of this polymorphism on subclinical vascular disease and erectile dysfunction (ED). METHODS: We analyzed the association of the PCSK9 rs11591147 single-nucleotide polymorphism with lipid levels, intima-media thickness (IMT), and the ankle-brachial index, in 1188 adults free of cardiovascular disease, randomly selected from the population. In 473 male participants, we also investigated its relationship with ED. The association of the R46L polymorphism with lipid levels was also assessed in 2 cohorts of 1103 prepuberal children and 830 adolescents. RESULTS: The prevalence of the T allele was 2.9% in adults. Low-density lipoprotein cholesterol (LDL-cholesterol) levels did not vary according to this polymorphism (134 ± 32 vs 134 ± 31 mg/dL, for the TT + GT vs GG carriers, respectively, P = .931). Despite equal LDL-cholesterol levels, adults carrying the T allele had a lower mean common carotid IMT (0.685 ± 0.09 vs 0.723 ± 0.127 mm; P = .035), a lower maximum common carotid IMT (0.819 ± 0.11 vs 0.865 ± 0.159 mm; P = .040), and, in males, a lower prevalence of ED (36.8% vs 61%: P = .036), than GG carriers. Prevalence of the T allele was 3.2% in both cohorts of children. They had lower levels of LDL-cholesterol than GG subjects (100 vs 109 mg/dL; P = .060, for prepuberal children, and 85 vs 99 mg/dL; P = .010 for adolescents). CONCLUSION: In our population, an association between the PCSK9 R46L variant and LDL-cholesterol levels is observed in children. In adults, although its association with lipid levels is not evident, there is a significant relationship between the PCSK9 R46L variant and markers of subclinical atherosclerosis, including IMT and ED.


Assuntos
LDL-Colesterol/sangue , Disfunção Erétil/genética , Pró-Proteína Convertase 9/genética , Doenças Vasculares/genética , Adolescente , Idoso , Alelos , Apolipoproteínas B/sangue , Espessura Intima-Media Carotídea , Criança , Estudos de Coortes , Diabetes Mellitus Tipo 2/patologia , Disfunção Erétil/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estado Pré-Diabético , Doenças Vasculares/patologia
19.
Curr Opin Cell Biol ; 53: 9-14, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29631154

RESUMO

Although translation of cytosolic proteins is well described in axons, much less is known about the synthesis, processing and trafficking of transmembrane and secreted proteins. A canonical rough endoplasmic reticulum or a stacked Golgi apparatus has not been detected in axons, generating doubts about the functionality of a local route. However, axons contain mRNAs for membrane and secreted proteins, translation factors, ribosomal components, smooth endoplasmic reticulum and post-endoplasmic reticulum elements that may contribute to local biosynthesis and plasma membrane delivery. Here we consider the evidence supporting a local secretory system in axons. We discuss exocytic elements and examples of autonomous axonal trafficking that impact development and maintenance. We also examine whether unconventional post-endoplasmic reticulum pathways may replace the canonical Golgi apparatus.


Assuntos
Axônios/metabolismo , Organelas/metabolismo , Transporte Proteico , Animais , Membrana Celular/metabolismo , Citosol/metabolismo , Retículo Endoplasmático/metabolismo , Complexo de Golgi/metabolismo , Humanos , Processamento de Proteína Pós-Traducional , Sistemas de Translocação de Proteínas
20.
Clín. investig. arterioscler. (Ed. impr.) ; 30(2): 49-55, mar.-abr. 2018. tab
Artigo em Espanhol | IBECS | ID: ibc-172066

RESUMO

Objetivo: Evaluar si existen diferencias en el perfil de factores de riesgo asociados con el grosor íntima-media (GIM) y la presencia de placas carotídeas. Métodos: Estudio transversal de base poblacional, en 1.475 sujetos de entre 45 y 75años de edad, seleccionados de forma aleatoria de los registros de Atención Primaria del área noroeste de Madrid. Se les realizó una exploración física, una analítica y se les determinó el GIM en carótida común y la presencia de placas mediante ecografía. Resultados: El GIM medio de la población fue de 0,725±0,132mm. El 47% presentaban placas carotídeas. En el análisis multivariante, los factores relacionados con el GIM fueron: edad (β0,227, p<0,0001), sexo (β0,104, p<0,0001), presencia de hipertensión (β0,082, p=0,002), diabetes (β0,130, p<0,0001) y tabaquismo activo (β0,107, p<0,0001), presión arterial sistólica (PAS) (β0,219, p<0,0001) y concentración de colesterol LDL (β0,074, p=0,003), y de forma inversa, presión arterial diastólica (PAD) (β−0,124, p=0,001) y concentraciones de colesterol HDL (β−0,111, p<0,0001) y triglicéridos (β−0,060, p=0,028). La presencia de placas se asoció de forma directa con edad (OR1,08; IC95%: 1,05-1,10), sexo (OR1,95; IC95%: 1,52-2,51), tabaquismo activo (OR2,75; IC95%: 1,92-3,95), antecedente de hipertensión (OR1,58; IC95%: 1,22-2,04) y de diabetes (OR1,84; IC95%: 1,31-2,58), consumo de estatinas (OR1,56; IC95%: 1,19-2,04) y PAS (OR1,03; IC95%: 1,02-1,05), y de forma inversa con PAD (OR0,98; IC95%: 0,96-0,99). Conclusión: Los factores de riesgo asociados con el GIM y la presencia de placas son similares, un dato que apoya el continuo entre la hipertrofia de la capa muscular y el desarrollo de arteriosclerosis (AU)


Objective: To evaluate whether there were any differences in the risk factor profile associated with either the intima-media thickness (IMT) or the presence of carotid plaques. Methods: Cross-sectional study in 1475 subjects between 45 and 75years, randomly selected from the population of the Northwest area of Madrid (Spain). They had a physical exam, blood analysis, and ultrasound measurement of the IMT and of the presence of plaques. Results: Mean IMT was 0.725±0.132mm. Forty seven percent of the participants had carotid plaques. In multivariate analysis, factors directly associated with the IMT were, age (β0.227, P<.0001), sex (β0.104, P<.0001), presence of hypertension (β0.082, P=.002), diabetes (β0.130, P<.0001) and current smoking (β0.107, P<.0001), systolic blood pressure (SBP) (β0.219, P<.0001) and LDL-cholesterol levels (β0.074, P=.003), and inversely, diastolic blood pressure (DBP) (β−0.124, P=.001), HDL-cholesterol (β−0.111, P<.0001) and triglyceride levels (β−0.060, P=.028). The presence of plaques was directly associated with age (OR1.08; 95%CI: 1.05-1.10), sex (OR1.95; 95%CI: 1.52-2.51), current smoking (OR2.75; 95%CI: 1.92-3.95), history of hypertension (OR1.58; 95%CI: 1.22-2.04) or diabetes (OR1.84; 95%CI: 1.31-2.58), statin treatment (OR1.56; 95%CI: 1.19-2.04) and SBP (OR1.03; 95%CI: 1.02-1.05), and inversely with DBP (OR0.98; 95%CI: 0.96-0.99). Conclusion: Factors associated with the IMT and the presence of plaques are similar, a finding that support a continuum between muscular layer hypertrophy and arteriosclerosis development (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Espessura Intima-Media Carotídea , Fatores de Risco , Atenção Primária à Saúde , Doenças das Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Estudos Transversais/métodos , Ultrassonografia Mamária/métodos , Análise Multivariada , Estudos Prospectivos , Antropometria/métodos , Análise de Variância , Análise de Regressão , Artérias Carótidas/anormalidades
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