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The blood-brain barrier (BBB) is a dynamic interface that regulates the exchange of molecules and cells between the brain parenchyma and the peripheral blood. The BBB is mainly composed of endothelial cells, astrocytes and pericytes. The integrity of this structure is essential for maintaining brain and spinal cord homeostasis and protection from injury or disease. However, in various neurological disorders, such as traumatic brain injury, Alzheimer's disease, and multiple sclerosis, the BBB can become compromised thus allowing passage of molecules and cells in and out of the central nervous system parenchyma. These agents, however, can serve as biomarkers of BBB permeability and neuronal damage, and provide valuable information for diagnosis, prognosis and treatment. Herein, we provide an overview of the BBB and changes due to aging, and summarize current knowledge on biomarkers of BBB disruption and neurodegeneration, including permeability, cellular, molecular and imaging biomarkers. We also discuss the challenges and opportunities for developing a biomarker toolkit that can reliably assess the BBB in physiologic and pathophysiologic states.
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Biomarcadores , Barreira Hematoencefálica , Barreira Hematoencefálica/metabolismo , Humanos , Biomarcadores/metabolismo , AnimaisRESUMO
Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1ß (IL-1ß) for 3 and 24 hours. IL-1ß for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.
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Barreira Hematoencefálica , Laminina , Animais , Barreira Hematoencefálica/diagnóstico por imagem , Barreira Hematoencefálica/metabolismo , Laminina/metabolismo , Doenças Neuroinflamatórias , Células Endoteliais/metabolismo , Inflamação/diagnóstico por imagem , Inflamação/metabolismo , Imageamento por Ressonância Magnética/métodosRESUMO
Sleeve gastrectomy (SG) is the most common bariatric surgery worldwide and has shown to cause de novo or worsen symptoms of gastroesophageal reflux disease (GERD). Esophageal motility and physiology studies are mandatory in bariatric and foregut centers. The predisposing factors in post-SG patients are disruption of His angle, resection of gastric fold and gastric fundus, increased gastric pressure, resection of the gastric antrum, cutting of the sling fibers and pyloric spasm. There are symptomatic complications due to sleeve morphology as torsion, incisura angularis stenosis, kinking and dilated fundus. In this article, we present recommendations, surgical technique and patient selection flow diagram for SG and avoid de novo or worsening GERD.
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Cirurgia Bariátrica , Refluxo Gastroesofágico , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Obesidade Mórbida/complicações , Refluxo Gastroesofágico/diagnóstico , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Estômago , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/métodosRESUMO
Alzheimer's disease (AD) is a chronic neurodegenerative disease and the most frequent cause of progressive dementia in senior adults. It is characterized by memory loss and cognitive impairment secondary to cholinergic dysfunction and N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular neurofibrillary tangles, extracellular plaques composed of amyloid-ß (Aß), and selective neurodegeneration are the anatomopathological hallmarks of this disease. The dysregulation of calcium may be present in all the stages of AD, and it is associated with other pathophysiological mechanisms, such as mitochondrial failure, oxidative stress, and chronic neuroinflammation. Although the cytosolic calcium alterations in AD are not completely elucidated, some calcium-permeable channels, transporters, pumps, and receptors have been shown to be involved at the neuronal and glial levels. In particular, the relationship between glutamatergic NMDA receptor (NMDAR) activity and amyloidosis has been widely documented. Other pathophysiological mechanisms involved in calcium dyshomeostasis include the activation of L-type voltage-dependent calcium channels, transient receptor potential channels, and ryanodine receptors, among many others. This review aims to update the calcium-dysregulation mechanisms in AD and discuss targets and molecules with therapeutic potential based on their modulation.
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Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Doença de Alzheimer/patologia , Cálcio/metabolismo , Peptídeos beta-Amiloides/metabolismo , Cálcio da Dieta , Canais de Cálcio Tipo LRESUMO
Adequate iodine nutrition is fundamental for all humans and is critical during pregnancy and lactation due to iodine forms part of the structure of thyroid hormones (THs) and it is required for THs function. Iodine is a scarce micronutrient that must be obtained from the diet. Sufficient iodine can be found in the nature from seafood and given it is not frequently consumed by Chileans, public health policies state that table salt in Chile must be iodized. Health plans must be monitored to determine if the intake of iodine is being appropriated and the population has not fallen in deficiency or excess. The aim of this work was to evaluate iodine intake in 26 women at the third trimester of pregnancy. Pregnant women are resident from El Bosque a low-income County located in Santiago de Chile. These Chilean pregnant women were recruited by nutritionist at the Centros de Salud familiar (CESFAM). A 24 h dietary recall (24 h-DR) was applied to them to evaluate iodine intake. Samples of urine and blood were taken by health professionals to analyze parameters of thyroid function and to measure urine iodine concentration (UIC). The survey analysis showed that the iodine consumption in these pregnant women derived mainly from salt, bread and milk and not from seafood. The survey analysis indicated that iodine intake was above the requirements for pregnant women. However, the average UIC indicated that iodine intake was adequate, suggesting the need to find a better parameter to determine iodine intake in pregnant women.
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Iodo , Terceiro Trimestre da Gravidez , Humanos , Feminino , Gravidez , Iodo/sangue , Iodo/urina , Terceiro Trimestre da Gravidez/sangue , Terceiro Trimestre da Gravidez/urina , Ingestão de Alimentos , Chile , Estudos de Coortes , Pobreza , Glândula Tireoide/fisiologiaRESUMO
Alzheimer's disease (AD) is a frequent and disabling neurodegenerative disorder, in which astrocytes participate in several pathophysiological processes including neuroinflammation, excitotoxicity, oxidative stress and lipid metabolism (along with a critical role in apolipoprotein E function). Current evidence shows that astrocytes have both neuroprotective and neurotoxic effects depending on the disease stage and microenvironmental factors. Furthermore, astrocytes appear to be affected by the presence of amyloid-beta (Aß), with alterations in calcium levels, gliotransmission and proinflammatory activity via RAGE-NF-κB pathway. In addition, astrocytes play an important role in the metabolism of tau and clearance of Aß through the glymphatic system. In this review, we will discuss novel pharmacological and non-pharmacological treatments focused on astrocytes as therapeutic targets for AD. These interventions include effects on anti-inflammatory/antioxidant systems, glutamate activity, lipid metabolism, neurovascular coupling and glymphatic system, calcium dysregulation, and in the release of peptides which affects glial and neuronal function. According to the AD stage, these therapies may be of benefit in either preventing or delaying the progression of the disease.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/terapia , Doença de Alzheimer/metabolismo , Astrócitos/metabolismo , Cálcio/metabolismo , Peptídeos beta-Amiloides/metabolismo , Neurônios/metabolismoRESUMO
Taurine is considered the most abundant free amino acid in the brain. Even though there are endogenous mechanisms for taurine production in neural cells, an exogenous supply of taurine is required to meet physiological needs. Taurine is required for optimal postnatal brain development; however, its brain concentration decreases with age. Synthesis of taurine in the central nervous system (CNS) occurs predominantly in astrocytes. A metabolic coupling between astrocytes and neurons has been reported, in which astrocytes provide neurons with hypotaurine as a substrate for taurine production. Taurine has antioxidative, osmoregulatory, and anti-inflammatory functions, among other cytoprotective properties. Astrocytes release taurine as a gliotransmitter, promoting both extracellular and intracellular effects in neurons. The extracellular effects include binding to neuronal GABAA and glycine receptors, with subsequent cellular hyperpolarization, and attenuation of N-methyl-D-aspartic acid (NMDA)-mediated glutamate excitotoxicity. Taurine intracellular effects are directed toward calcium homeostatic pathway, reducing calcium overload and thus preventing excitotoxicity, mitochondrial stress, and apoptosis. However, several physiological aspects of taurine remain unclear, such as the existence or not of a specific taurine receptor. Therefore, further research is needed not only in astrocytes and neurons, but also in other glial cells in order to fully comprehend taurine metabolism and function in the brain. Nonetheless, astrocyte's role in taurine-induced neuroprotective functions should be considered as a promising therapeutic target of several neuroinflammatory, neurodegenerative and psychiatric diseases in the near future. This review provides an overview of the significant relationship between taurine and astrocytes, as well as its homeostatic and neuroprotective role in the nervous system.
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Laminin, a non-collagenous glycoprotein present in the brain extracellular matrix, helps to maintain blood-brain barrier (BBB) integrity and regulation. Neuroinflammation can compromise laminin structure and function, increasing BBB permeability. The aim of this paper is to determine if neuroinflammation-induced laminin functional changes may serve as a potential biomarker of alterations in the BBB. The 38 publications included evaluated neuroinflammation, BBB disruption, and laminin, and were assessed for quality and risk of bias (protocol registered in PROSPERO; CRD42020212547). We found that laminin may be a good indicator of BBB overall structural integrity, although changes in expression are dependent on the pathologic or experimental model used. In ischemic stroke, permanent vascular damage correlates with increased laminin expression (ß and γ subunits), while transient damage correlates with reduced laminin expression (α subunits). Laminin was reduced in traumatic brain injury and cerebral hemorrhage studies but increased in multiple sclerosis and status epilepticus studies. Despite these observations, there is limited knowledge about the role played by different subunits or isoforms (such as 411 or 511) of laminin in maintaining structural architecture of the BBB under neuroinflammation. Further studies may clarify this aspect and the possibility of using laminin as a biomarker in different pathologies, which have alterations in BBB function in common.
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Barreira Hematoencefálica , Laminina , Biomarcadores/metabolismo , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Humanos , Laminina/metabolismo , Doenças NeuroinflamatóriasRESUMO
Zoonotic larvae of the family Anisakidae found in several fish species represent a serious risk in public health since they may cause food-borne anisakidosis in humans. Chile has culinary preferences including eating raw fish in many traditional preparations. In the present study, a total of 180 fish specimens representing three different fish species, i.e., Chilean hake (Merluccius gayi), snoek (Thyrsites atun), and sea bream (Brama australis), were caught at central coast of Chile. Parasitological examination was performed on musculature and abdominal cavity for subsequent extraction and quantification of anisakid larvae. Estimation of infection parameters, such as prevalence, was performed indicating 100% (CI: 0.94-1.0) prevalence of anisakid L3 in Chilean hakes and snoeks. Moreover, sea breams reached a prevalence of 35% (CI: 0.23-0.48). Prevalence of anisakid larvae in muscle was also analyzed showing values of 18.6% (CI: 0.097-0.309) in Chilean hakes, 15% (CI: 0.07-0.26) in snoeks, and 1.7% (CI: 0-0.089) in sea breams. Meanwhile, prevalence of anisakid larvae in internal organs showed highest values for peritoneum (100% and 83.3%) for snoeks and Chilean hakes, respectively, for liver (96.7%) and gonads (86.6%) in Chilean hakes, and for intestine (98.3%) in snoeks. Molecular analysis of collected anisakid L3 unveiled presence of two potentially zoonotic nematode species, i.e., Pseudoterranova cattani and Anisakis pegreffii. P. cattani was found in Chilean hakes and snoeks being the first molecular host species report for Chilean snoeks. Besides, A. pegreffii was also identified in these species being the first molecular report on this regard. These findings are relevant for better understanding of epidemiology of anisakiasis in Chilean coasts and for public health issues considering potential risk of human population due to its culinary preferences in eating raw fish.
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Anisaquíase , Anisakis , Ascaridoidea , Doenças dos Peixes , Gadiformes , Perciformes , Animais , Anisaquíase/epidemiologia , Anisaquíase/veterinária , Anisakis/genética , Ascaridoidea/genética , Chile/epidemiologia , Doenças dos Peixes/epidemiologia , Peixes , Humanos , Larva/genética , PrevalênciaRESUMO
Adequate iodine nutrition is crucial for all mammals by playing his starring role as a component of thyroid hormones, which are key regulators of cellular processes for life such as differentiation, growth, function, and metabolism. Deficiency or excess of iodine in the diet are worldwide highly frequent conditions that are responsible of health problems like hypothyroidism, hypothyroxinemia, goiter, thyroiditis, hyperthyroidism, and autoimmune thyroid diseases among others. The incorporation of iodine in salt or other nutrients resolved the consequences of severe iodine deficiency like goiter, cretinism. However, this strategy in several countries led to other ailments like Hashimoto autoimmune thyroiditis, hyperthyroidism, and hypothyroidism. The goal of this review is to analyze and discuss the different aspects of iodine nutrition for human health comprising its biological role through thyroid hormones, pathogen control, and the regulation of the intestinal microbiota.
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Bócio , Hipertireoidismo , Hipotireoidismo , Iodo , Animais , Humanos , MicronutrientesRESUMO
Neurodegenerative diseases are characterized by increased permeability of the blood-brain barrier (BBB) due to alterations in cellular and structural components of the neurovascular unit, particularly in association with neuroinflammation. A previous screening study of peptide ligands to identify molecular alterations of the BBB in neuroinflammation by phage-display, revealed that phage clone 88 presented specific binding affinity to endothelial cells under inflammatory conditions in vivo and in vitro. Here, we aimed to identify the possible target receptor of the peptide ligand 88 expressed under inflammatory conditions. A cross-link test between phage-peptide-88 with IL-1ß-stimulated human hCMEC cells, followed by mass spectrometry analysis, was used to identify the target of peptide-88. We modeled the epitope-receptor molecular interaction between peptide-88 and its target by using docking simulations. Three proteins were selected as potential target candidates and tested in enzyme-linked immunosorbent assays with peptide-88: fibronectin, laminin subunit α5 and laminin subunit ß-1. Among them, only laminin subunit ß-1 presented measurable interaction with peptide-88. Peptide-88 showed specific interaction with laminin subunit ß-1, highlighting its importance as a potential biomarker of the laminin changes that may occur at the BBB endothelial cells under pathological inflammation conditions.
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Barreira Hematoencefálica , Células Endoteliais/metabolismo , Inflamação/metabolismo , Laminina/metabolismo , Animais , Bacteriófago M13 , Biomarcadores , Células Cultivadas , Reagentes de Ligações Cruzadas , Fibronectinas/metabolismo , Ontologia Genética , Humanos , Interleucina-1beta/farmacologia , Modelos Moleculares , Simulação de Acoplamento Molecular , Biblioteca de Peptídeos , Ligação Proteica , Conformação Proteica , Mapeamento de Interação de Proteínas , RatosRESUMO
En Chile, la obesidad y el sobrepeso han presentado un constante incremento, en las últimas décadas. Cifras del Ministerio de Salud (MINSAL) dan cuenta de un aumento de prevalencia, desde un 61% en 2003, hasta una preocupante estimación de 74% de la población adulta, en 2019 según la Organización para la Cooperación y el Desarrollo Económicos (OCDE). La Organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO por sus siglas en inglés) estimó que 4 millones de adultos chilenos padecían de obesidad en 2019, situando a Chile como el país latinoamericano con el más alto índice de la condición. El porcentaje de la población adulta, en edad reproductiva, que presenta obesidad, se estima en 9 -18% para hombres y 12 -28% para mujeres. El exceso de grasa corporal tiene serias consecuencias adversas, para el potencial fértil y la capacidad reproductiva de las parejas, comprometiendo fecundidad y determinando infertilidad, trastornos de la ovulación, función sexual y peores resultados en técnicas de reproducción asistida y pronóstico obstétrico
In Chile, excess weight and obesity have shown a steady increase over the last decades. Data from the ministry of health (MINSAL) show a rise in prevalence from 61% in 2003 to an alarming 74% of the adult population by 2019 according to the Organization for Economic Cooperation and Development (OCDE). The United Nations Food and Agriculture Organization (FAO) estimates that 4 million adult Chileans suffered obesity in 2019, placing Chile as the country in Latin America with the highest incidence of the condition. The percentage of reproductive age adults that suffer obesity is estimated in 9-18% for men and 12-28% for women. The excess body fat has serious detrimental effects on fertility potential and the reproductive capacity of couples compromising fecundity and causing anovulatory infertility and sexual dysfunction as well as poorer results in assisted reproductive technologies and obstetric outcome
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Humanos , Masculino , Feminino , Infertilidade/epidemiologia , Obesidade/epidemiologia , Infertilidade/etiologia , Infertilidade/terapia , Obesidade/complicações , Obesidade/terapiaRESUMO
Research on violence in Mexico and Latin America suggests that, in part, due to state attempts to fight organized crime and the widespread availability of firearms, violence and homicides in general have experienced a recent shift from expressive to instrumental. Despite this transformation, however, socioeconomically disadvantaged young males continue to be overwhelmingly present in homicide events. We argue that both the use of a firearm and demographic and traditional socioeconomic factors should independently predict instrumental homicide; however, the association between the use of a firearm and instrumentality should be moderated by the level or category of these traditional characteristics (i.e., socioeconomic status, age, and gender). Our findings are broadly consistent with these claims. We show that the relationship between the use of a firearm and instrumental homicides is larger for homicides involving disadvantaged males as victims because this group is more at risk of suffering homicidal violence to begin with, despite the fact that independently (i.e., with no interactions), higher socioeconomic status, age, and female victimhood are positively associated with instrumentality. We discuss the implications of these findings for research on Latin American violence and the expressive/instrumental distinction.
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Armas de Fogo , Homicídio , Feminino , Hispânico ou Latino , Humanos , Masculino , México/epidemiologia , ViolênciaRESUMO
Diabetes and related neurological complications are serious worldwide public health problems. The increasing number of affected individuals make it necessary to implement novel nutritional and therapeutic interventions. The tree Moringa oleifera (MO) has been used as a food source and for traditional medicine purposes due to possible antihyperglycemic, antioxidant, anti-inflammatory, and lipid regulating properties. These properties may be explained by the presence of numerous phytochemicals in the leaves, fruits, roots and, oil of the tree. The evidence for acute antihyperglycemic effects of MO extract on diabetic animal models seems to be robust, but more chronic and long-term studies are needed. In contrast, the hypoglycemic effects of MO on humans are not as clear. The scarce number of human studies, together with a diverse range of methodologies and MO doses, may explain this. In addition, evidence regarding changes in insulin levels due to MO intervention is ambiguous, both in animal and human studies. Therefore, more structured studies are needed to clarify if MO has an effect on insulin levels or activity.
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Hipoglicemiantes/farmacologia , Insulina/sangue , Moringa oleifera , Compostos Fitoquímicos/farmacologia , Preparações de Plantas/farmacologia , Animais , Glicemia/efeitos dos fármacos , HumanosRESUMO
Alzheimer's disease (AD) is the leading cause of dementia worldwide. It compromises patients' daily activities owing to progressive cognitive deterioration, which has elevated direct and indirect costs. Although AD has several risk factors, aging is considered the most important. Unfortunately, clinical diagnosis is usually performed at an advanced disease stage when dementia is established, making implementation of successful therapeutic interventions difficult. Current biomarkers tend to be expensive, insufficient, or invasive, raising the need for novel, improved tools aimed at early disease detection. AD is characterized by brain atrophy due to neuronal and synaptic loss, extracellular amyloid plaques composed of amyloid-beta peptide (Aß), and neurofibrillary tangles of hyperphosphorylated tau protein. The visual system and central nervous system share many functional components. Thus, it is plausible that damage induced by Aß, tau, and neuroinflammation may be observed in visual components such as the retina, even at an early disease stage. This underscores the importance of implementing ophthalmological examinations, less invasive and expensive than other biomarkers, as useful measures to assess disease progression and severity in individuals with or at risk of AD. Here, we review functional and morphological changes of the retina and visual pathway in AD from pathophysiological and clinical perspectives.
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Doença de Alzheimer/fisiopatologia , Retina/fisiopatologia , Transtornos da Visão/fisiopatologia , Vias Visuais/fisiopatologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Progressão da Doença , Humanos , Placa Amiloide/metabolismo , Placa Amiloide/fisiopatologia , Retina/metabolismo , Transtornos da Visão/diagnóstico , Transtornos da Visão/metabolismo , Vias Visuais/metabolismo , Proteínas tau/metabolismoRESUMO
Status epilepticus is a medical emergency with elevated morbidity and mortality rates, and represents a leading cause of epilepsy-related deaths. Though status epilepticus can occur at any age, it manifests more likely in children and elderly people. Despite the common prevalence of epileptic disorders, a complete explanation for the mechanisms leading to development of self-limited or long lasting seizures (as in status epilepticus) are still lacking. Apart from neurons, research evidence suggests the involvement of immune and glial cells in epileptogenesis. Among glial cells, astrocytes represent an ideal target for the study of the pathophysiology of status epilepticus, due to their key role in homeostatic balance of the central nervous system. During status epilepticus, astroglial cells are activated by the presence of cytokines, damage associated molecular patterns and reactive oxygen species. The persistent activation of astrocytes leads to a decrease in glutamate clearance with a corresponding accumulation in the synaptic extracellular space, increasing the chance of neuronal excitotoxicity. Moreover, major alterations in astrocytic gap junction coupling, inflammation and receptor expression, facilitate the generation of seizures. Astrocytes are also involved in dysregulation of inhibitory transmission in the central nervous system and directly participate in ionic homeostatic alterations during status epilepticus. In the present review, we focus on the functional and structural changes in astrocytic activity that participate in the development and maintenance of status epilepticus, with special attention on concurrent inflammatory alterations. We also include potential astrocytic treatment targets for status epilepticus.
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Resumen: El compromiso simultáneo del arco aórtico y aorta descendente proximal, ya sea por disección o aterosclerosis, constituye uno de los mayores desafíos que puede enfrentar un cirujano cardiovascular. La prótesis híbrida Thoraflex, introducida en los últimos años, ha resultado ser una importante ayuda para el tratamiento quirúrgico de esta compleja y grave patología. Esta consiste en un tubo protésico de Dacron con 4 ramas, para el reemplazo del arco aórtico y sus troncos braquiocefálicos y perfusión corporal distal, y una endoprótesis que queda como "trompa de elefante suspendida" en la aorta descendente proximal. Presentamos en esta oportunidad nuestra experiencia inicial en 4 pacientes, 3 con disección aórtica crónica y una con un aneurisma aterosclerótico, usando la prótesis híbrida Thoraflex.
Abstract: Atherosclerotic aneurysm or dissection of the aortic arch and proximal descending thoracic aorta is one of the major challenges for a cardiovascular surgeon. The new hybrid prosthesis Thoraflex has become an important devise to simplify the surgical treatment of this very complex and technically demanding aortic pathology. This hybrid prosthesis consists of a 4-branched arch graft with a stent-graft at the distal end. The proximal part is a gelatin-coated woven polyester prosthesis. The stented section is a self-expanding endoprosthesis constructed of thin-walled polyester and nitinol ring stents that is left in the proximal descending aorta as a "frozen elephant trunk". We present our initial experience with the Thoraflex prosthesis in four patients, three of them with chronic aortic dissection and one with an atherosclerotic aneurysm.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/métodos , Procedimentos Endovasculares/métodos , Dissecção Aórtica/cirurgia , Aorta Torácica/cirurgia , Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Dissecção Aórtica/diagnóstico por imagemRESUMO
Background Situation awareness (SA) is defined in three levels: SA1 is the perception of the elements in a specific context, SA2 is the comprehension of their meaning, and SA3 is the projection of their status. Purpose To analyze the possible association of a genetic polymorphism in the serotonin transporter ( SLC6A4) gene and performance on the Situational Awareness test (SAtest). Methods SAtest was applied to a sample of 230 healthy Colombian subjects, using the Psychology Experiment Building Language platform and a functional polymorphism in the SLC6A4 gene was genotyped by polymerase chain reaction. Results In the SA1 level, s/s genotype carriers had worse accuracy, in comparison with s/l and l/l genotypes. At SA2 level, l/l genotype carriers had better accuracy than s/s and s/l individuals and that in the SA3 level, l/l carriers also had better accuracy. These associations were significant after correction for multiple testing. Conclusions It is possible that l/l carriers have a better ability to perceive and focus their attention on the elements of their environment and to have the capacity to understand and predict what will happen with those elements. This is the first genetic study of SA performance in healthy participants. Additional investigations of other genes could contribute to the understanding of the molecular correlates of SA in healthy subjects and in neuropsychiatric patients.
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Atenção/fisiologia , Conscientização/fisiologia , Compreensão/fisiologia , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: Adequate function of the nervous system depends on the balance of glianeuron complex interactions. Astrocytes, in particular, are key elements in this process due to the significant participation of these cells in essential properties of the nervous system such as neuroinflammation, regulation of neurotransmitters, release of gliotransmitters and control of synaptic plasticity, among others. Astrocytes express the receptor for advanced glycation end products (RAGE) which is very important in the recognition of endogenous molecules released in the context of infection, physiological stress or chronic inflammation. RAGE can bind several advanced glycation end products, S100 proteins, HMGB1, amyloid-ß and other additional DAMP molecules. The nuclear factorkappa B (NF-κB) transcription pathway is the main intracellular signaling pathway activated by the RAGE receptor, inducing an increase in the expression and release of proinflammatory cytokines. Due to its numerous interactions, RAGE is suspected to be involved in various physiological and pathological processes. CONCLUSION: It is plausible that a prolonged exposure to RAGE ligands or abnormally increased concentrations of some ligands may induce lengthy periods of intracellular proinflammatory activation, which may induce the appearance of reactive astrocytes involved in the development and/or progression of neurodegenerative disorders. Blocking or reducing the duration of activation of RAGE/NF-κB signaling in astrocytes may become an important therapeutic alternative for the treatment of neurodegenerative disorders in the future.
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Astrócitos/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais/fisiologia , Animais , Anti-Inflamatórios/administração & dosagem , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Gliose/tratamento farmacológico , Gliose/metabolismo , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacosRESUMO
Alzheimer disease (AD) is a frequent and devastating neurodegenerative disease in humans, but still no curative treatment has been developed. Although many explicative theories have been proposed, precise pathophysiological mechanisms are unknown. Due to the importance of astrocytes in brain homeostasis they have become interesting targets for the study of AD. Changes in astrocyte function have been observed in brains from individuals with AD, as well as in AD in vitro and in vivo animal models. The presence of amyloid beta (Aß) has been shown to disrupt gliotransmission, neurotransmitter uptake, and alter calcium signaling in astrocytes. Furthermore, astrocytes express apolipoprotein E and are involved in the production, degradation and removal of Aß. As well, changes in astrocytes that precede other pathological characteristics observed in AD, point to an early contribution of astroglia in this disease. Astrocytes participate in the inflammatory/immune responses of the central nervous system. The presence of Aß activates different cell receptors and intracellular signaling pathways, mainly the advanced glycation end products receptor/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, responsible for the transcription of pro-inflammatory cytokines and chemokines in astrocytes. The release of these pro-inflammatory agents may induce cellular damage or even stimulate the production of Aß in astrocytes. Additionally, Aß induces the appearance of oxidative stress (OS) and production of reactive oxygen species and reactive nitrogen species in astrocytes, affecting among others, intracellular calcium levels, NADPH oxidase (NOX), NF-κB signaling, glutamate uptake (increasing the risk of excitotoxicity) and mitochondrial function. Excessive neuroinflammation and OS are observed in AD, and astrocytes seem to be involved in both. The Aß/NF-κB interaction in astrocytes may play a central role in these inflammatory and OS changes present in AD. In this paper, we also discuss therapeutic measures highlighting the importance of astrocytes in AD pathology. Several new therapeutic approaches involving phenols (curcumin), phytoestrogens (genistein), neuroesteroids and other natural phytochemicals have been explored in astrocytes, obtaining some promising results regarding cognitive improvements and attenuation of neuroinflammation. Novel strategies comprising astrocytes and aimed to reduce OS in AD have also been proposed. These include estrogen receptor agonists (pelargonidin), Bambusae concretio Salicea, Monascin, and various antioxidatives such as resveratrol, tocotrienol, anthocyanins, and epicatechin, showing beneficial effects in AD models.