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OBJECTIVES: Schizophrenia-related psychosis is associated with abnormalities in white matter (WM) microstructure and structural brain dysconnectivity. However, the pathological process underlying such changes is unknown. We sought to investigate the potential association between peripheral cytokine levels and WM microstructure during the acute phase of first-episode psychosis (FEP) in a cohort of drug-naïve patients. METHODS: Twenty-five non-affective FEP patients and 69 healthy controls underwent MRI scanning and blood collection at study entry. After achieving clinical remission, 21 FEP were reassessed; 38 age and biological sex-matched controls also had a second assessment. We measured fractional anisotropy (FA) of selected WM regions-of-interest (ROIs) and plasma levels of four cytokines (IL-6, IL-10, IFN-γ, and TNF-α). RESULTS: At baseline (acute psychosis), the FEP group showed reduced FA relative to controls in half the examined ROIs. Within the FEP group, IL-6 levels were negatively correlated with FA values. Longitudinally, patients showed increments of FA in several ROIs affected at baseline, and such changes were associated with reductions in IL-6 levels. CONCLUSIONS: A state-dependent process involving an interplay between a pro-inflammatory cytokine and brain WM might be associated with the clinical manifestation of FEP. This association suggests a deleterious effect of IL-6 on WM tracts during the acute phase of psychosis.
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Trastornos Psicóticos , Sustancia Blanca , Humanos , Sustancia Blanca/patología , Citocinas , Estudios Longitudinales , Interleucina-6 , Imagen de Difusión Tensora , Encéfalo/patología , AnisotropíaRESUMEN
Temporal lobe epilepsy (TLE) often courses with cognitive deficits, but its underlying neuronal basis remains unclear. Confluent data suggest that epilepsy share pathophysiological mechanisms with neurodegenerative diseases. However, as most studies analyze subjects 60 years old and older, it is challenging to rule out that neurodegenerative changes arise from age-related mechanisms rather than epilepsy in these individuals. To fill this gap, we conducted a neuropathological investigation of the hippocampal formation of 22 adults with mesial TLE and 20 age- and sex-matched controls (both younger than 60 years). Moreover, we interrogated the relationship between these neuropathological metrics and cognitive performance. Hippocampal formation extracted from patients with drug-resistant mesial TLE undergoing surgery and postmortem non-sclerotic hippocampal formation of clinically and neuropathologically controls underwent immunohistochemistry against amyloid ß (Aß), hyperphosphorylated tau (p-tau), and TAR DNA-binding protein-43 (TDP-43) proteins, followed by quantitative analysis. Patients underwent a comprehensive neuropsychological evaluation prior to surgery. TLE hippocampi showed a significantly higher burden of p-tau than controls, whereas Aß deposits and abnormal inclusions of TDP-43 were absent in both groups. Patients with hippocampal sclerosis (HS) type 2 had higher immunostaining for p-tau than patients with HS type 1. In addition, p-tau burden was associated with impairment in attention tasks and seizures frequency. In this series of adults younger than 60 years-old, the increase of p-tau burden associated with higher frequency of seizures and attention impairment suggests the involvement of tau pathology as a potential contributor to cognitive deficits in mesial TLE.
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Epilepsia Refractaria , Epilepsia del Lóbulo Temporal , Adulto , Humanos , Persona de Mediana Edad , Epilepsia del Lóbulo Temporal/patología , Péptidos beta-Amiloides/metabolismo , Hipocampo/metabolismo , Convulsiones/metabolismo , Epilepsia Refractaria/patología , CogniciónRESUMEN
ABSTRACT: Campos, BT, Penna, EM, Rodrigues, JGS, Mendes, TT, Maia-Lima, A, Nakamura, FY, Vieira, ÉLM, Wanner, SP, and Prado, LS. Influence of mental fatigue on physical performance, and physiological and perceptual responses of judokas submitted to the Special Judo Fitness Test. J Strength Cond Res 36(2): 461-468, 2022-Mentally fatigued athletes present impaired aerobic performance, strength endurance, and manual dexterity, despite no changes in anaerobic performance and maximal muscle strength and power. Noteworthy, the effect of mental fatigue on physical performance during high-intensity intermittent tests that require specific motor skills of fighting sports has not been investigated. Therefore, this study aimed to verify whether mental fatigue influences performance and physiological and perceptual responses of judokas subjected to a high-intensity intermittent test designed specifically and validated for judo. Each judoka performed 2 experimental trials-a control trial one and the other one after the induction of mental fatigue. These trials were scheduled in a random and balanced order. In both trials, lactate, glucose, and cortisol concentrations, the heart rate variability, and perceptual variables were collected after the initial treatment and after the Special Judo Fitness Test (SJFT). The initial treatment consisted of a 30-minute cognitive demanding task (Stroop Color test) or watching a movie (control) and was followed by the SJFT. The Stroop Color test increased the perceptions of mental fatigue and effort, without affecting motivation for subsequent testing. Unexpectedly, mentally fatigued athletes did not show reduced performance during the SJFT. Regarding the physiological variables, no significant differences were identified between the 2 experimental conditions. We conclude that physical performance measured during a specific test for judokas is not impaired by a previous 30-minute cognitive task that causes mental fatigue. In addition, this cognitive task did not influence the physiological changes induced by the specific physical test.
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Rendimiento Atlético , Artes Marciales , Prueba de Esfuerzo , Humanos , Fatiga Mental , Aptitud Física , Rendimiento Físico FuncionalRESUMEN
INTRODUCTION: Reduction in functional capacity is a negative clinical outcome of chronic obstructive pulmonary disease (COPD). Studies have shown association between inflammatory and oxidative stress biomarkers and functional capacity. However, it is unclear whether these biomarkers are associated with outcomes of functional capacity. Therefore, the aim of this study was to evaluate whether plasma biomarkers of inflammation and oxidative stress are predictors of the 6-min walking test (6MWT)-derived outcomes. METHODS: Twenty COPD patients were assessed on three consecutive days with different clinical measures, including functional capacity, and blood sampling. Plasma concentrations of IL-6, IL-8, TNF-É, IL-10 and soluble TNF-É receptors (sTNFR1 and sTNFR2) were determined by immunoassays. Oxidative stress was evaluated by determining lipid peroxidation products based on the enzymatic activity of superoxide dismutase (SOD) and catalase, and total antioxidant capacity of plasma. Functional capacity was assessed considering the six-minute walking distance (6MWD) and the estimate of six-minute walking work (6MWW). The association between biomarkers (i.e. inflammation and oxidative stress) and functional exercise capacity was investigated through the Pearson's correlation coefficient. To identify the determinants of the 6MWT, multiple linear stepwise regression analyses were performed with adjustment for age, sex and GOLD classification. RESULTS: Patients were predominantly male (65%), with mean age of 64 years and moderate airflow obstruction and impaired functional capacity. There were positive correlations between SOD activity and 6MWD (r = 0.520; p = 0.02) and 6MWW (r = 0.554; p = 0.01), as well as a negative correlation between sTNF-R1 and 6MWD (r = -0.437; p = 0.05). SOD was an independent determinant of the functional capacity, explaining 23% of the variability of 6MWD (p = 0.019) and 27% of the variability of 6MWW (p = 0.011). sTNF-R1 levels were associated with 6MWD and, together with SOD explained 40% of variability in 6MWD (p = 0.005). CONCLUSION: SOD activity was an independent determinant of performance in the 6MWT, and together with sTNFR1 explained 40% of the variations in walking distance in COPD patients. SOD activity and sTNFR1 levels might be seen as potential biomarkers of the functional capacity in patients with COPD.
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Enfermedad Pulmonar Obstructiva Crónica , Caminata , Biomarcadores , Prueba de Esfuerzo , Tolerancia al Ejercicio , Humanos , Masculino , Estrés Oxidativo , Prueba de PasoRESUMEN
Alzheimer's disease (AD) is associated with memory impairment and altered peripheral metabolism. Mounting evidence indicates that abnormal signaling in a brain-periphery metabolic axis plays a role in AD pathophysiology. The activation of pro-inflammatory pathways in the brain, including the interleukin-6 (IL-6) pathway, comprises a potential point of convergence between memory dysfunction and metabolic alterations in AD that remains to be better explored. Using T2-weighted magnetic resonance imaging (MRI), we observed signs of probable inflammation in the hypothalamus and in the hippocampus of AD patients when compared to cognitively healthy control subjects. Pathological examination of post-mortem AD hypothalamus revealed the presence of hyperphosphorylated tau and tangle-like structures, as well as parenchymal and vascular amyloid deposits surrounded by astrocytes. T2 hyperintensities on MRI positively correlated with plasma IL-6, and both correlated inversely with cognitive performance and hypothalamic/hippocampal volumes in AD patients. Increased IL-6 and suppressor of cytokine signaling 3 (SOCS3) were observed in post-mortem AD brains. Moreover, activation of the IL-6 pathway was observed in the hypothalamus and hippocampus of AD mice. Neutralization of IL-6 and inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling in the brains of AD mouse models alleviated memory impairment and peripheral glucose intolerance, and normalized plasma IL-6 levels. Collectively, these results point to IL-6 as a link between cognitive impairment and peripheral metabolic alterations in AD. Targeting pro-inflammatory IL-6 signaling may be a strategy to alleviate memory impairment and metabolic alterations in the disease.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Péptidos beta-Amiloides/metabolismo , Animales , Hipocampo/diagnóstico por imagen , Hipocampo/metabolismo , Humanos , Interleucina-6 , Ratones , Placa AmiloideRESUMEN
Increased plasma levels of interleukin-6 (IL-6) in response to acute hypoglycemia have been well documented. Aiming to study the interaction between IL-6 and counter-regulatory hormones during hypoglycemic stress we conducted an exploratory single center study involving 26 adult patients undergoing insulin tolerance test. Insulin-induced hypoglycemia elicited a significant dynamic response of IL-6, adrenaline, noradrenaline, GH, prolactin, ACTH and serum and salivary cortisol (P < 0.001 for all variables). Patients with insufficient HPA axis response had lower hypoglycemia-induced IL-6 increase (median: 0.88 pg/mL) compared with individuals with intact HPA axis response (2.03 pg/mL, P = 0.007). IL-6 maximal increase correlated with the maximal increase of serum cortisol (rs = 0.48; P = 0.013), salivary cortisol (rs = 0.66; P = 0.012), plasma ACTH (rs = 0.48; P = 0.013) and with the increase in procedure-related symptoms of anxiety and hypoglycemia (rs = 0.57; P = 0.003). In conclusion, hypoglycemic stress-induced IL-6 increase is associated with activation of the HPA axis, suggesting that IL-6 response to hypoglycemic stress may be regarded as part of the counter-regulatory response, possibly contributing to the maintenance of glucose homeostasis.
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BACKGROUND: Stroke is a major cause of death and disability worldwide. Among its complications, post-stroke depression (PSD) leads to a significant burden. The diagnosis of PSD is complex, and there are no biomarkers that can assist in its early identification and adequate management. OBJECTIVE: The aim of the present study is to investigate peripheral biomarkers in the acute phase of stroke and their potential association with depressive symptoms. METHODS: We evaluated 60 patients in the acute phase of stroke by using standardized instruments of psychiatric and neurological assessment (Mini International Neuropsychiatric Interview-Plus- MINI-Plus, Hospital Anxiety and Depression Scale-HADS, and National Institutes of Health Stroke Scale-NIHSS) and measured peripheral biomarkers. RESULTS: In multivariate analysis, low peripheral levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and higher NIHSS scores were associated with PSD. The severity of depressive symptoms was inversely correlated with sTREM-1 and glial cell-derived neurotrophic factor (GDNF) levels. CONCLUSION: This is the first study indicating an association between sTREM-1 and PSD. Our results may point to the involvement of glial mechanisms in the manifestation of depressive symptoms after stroke.
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Depresión/sangre , Depresión/diagnóstico , Factor Neurotrófico Derivado de la Línea Celular Glial/sangre , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/diagnóstico , Receptor Activador Expresado en Células Mieloides 1/sangre , Anciano , Biomarcadores/sangre , Estudios Transversales , Depresión/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Accidente Cerebrovascular/complicacionesRESUMEN
PURPOSE: The physiological role of arginine vasopressin (AVP) in the acute stress response in humans and especially in children is unclear. The aim of this study was to explore the interaction between copeptin, a well-established surrogate marker of AVP release, and anterior pituitary hormone activation in response to acute hypoglycemic stress in children and adolescents. METHODS: We conducted an exploratory single center study involving 77 children and adolescents undergoing insulin-induced hypoglycemia. Blood levels of copeptin, ACTH, cortisol, GH, prolactin, interleukin-6 (IL-6), adrenaline and noradrenaline were determined at baseline and after insulin-induced hypoglycemia. RESULTS: Basal plasma levels of copeptin (median: 5.2 pmol/L) increased significantly after hypoglycemia (median 9.7 pmol/L; P < 0.0001). Subjects with insufficient HPA axis response or severe GH deficiency had lower hypoglycemia-induced copeptin increase (median: 2.3 pmol/L) compared with individuals with intact pituitary response (median: 5.2 pmol/L, P = 0.02). Copeptin increase correlated significantly with the maximal increase of ACTH (rs = 0.30; P = 0.010), cortisol (rs = 0.33; P = 0.003), prolactin (rs = 0.25; P = 0.03), IL-6 (rs = 0.35; P = 0.008) and with BMI-SDS (rs = - 0.28, P = 0.01). In multivariate regression analysis, prolactin increase was the only independent variable associated with copeptin increase (P = 0.0004). CONCLUSION: Our data indicate that: (1) hypoglycemic stress elicits a marked copeptin response in children and adolescents, pointing out its role as an acute stress marker in this population; (2) stress-induced AVP/copeptin release is associated with anterior pituitary activation, mainly a prolactin response.
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Arginina Vasopresina/sangre , Glicopéptidos/sangre , Hipoglucemiantes/sangre , Prolactina/sangre , Adolescente , Niño , Preescolar , Femenino , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Masculino , Sistema Hipófiso-Suprarrenal/metabolismoRESUMEN
Temporal lobe epilepsy (TLE) is usually associated with hippocampal sclerosis (HS), characterized by gliosis and neuronal loss, mainly in the cornus ammonis (CA). Regardless the type of HS, gliosis is associated with neuronal loss. Indeed, glial reactivation seems to induce both neuronal and glial apoptosis. Anti-apoptotic mechanisms are also activated in order to contain the cell death in chronic epilepsy. However, the role of the intrinsic apoptosis pathway in human TLE is unclear, mainly in relation to glial death. The purpose of this study was to evaluate the reactive gliosis areas in parallel with Bcl-2/Bax ratio and active caspase 3 immunoreactivity in hippocampi of TLE patients in comparison with control hippocampi. We also sought to investigate whether the levels of these markers were correlated with TLE clinical parameters. Paraffin-embedded sclerotic and control hippocampi were collected for immunohistochemical analyses of glial fibrillary acidic protein (GFAP), human leucocyte antigen DR (HLA-DR), neuronal nuclei protein (NeuN), Bax, Bcl-2 and active caspase 3. Sclerotic hippocampi presented higher immunoreactivity areas of GFAP and HLA-DR than controls, with similar values in HS types 1 and 2. Bcl-2 protein expression was increased in epileptic hippocampi, while Bax expression was similar to controls. Despite Bcl2/Bax ratio increase, granular neurons and glia exhibited active caspase 3 expression in TLE hippocampi, while controls did not show staining for the same marker. In conclusion, glial and neuronal death is increased in sclerotic hippocampi, independently of HS type, and co-localized with gliosis. Furthermore, Bcl-2/Bax ratio increase does not prevent expression of active caspase 3 by glia and granular neurons in TLE.
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Epilepsia del Lóbulo Temporal/patología , Neuroglía/patología , Neuronas/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Adolescente , Adulto , Apoptosis , Epilepsia del Lóbulo Temporal/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuroglía/metabolismo , Neuronas/metabolismoRESUMEN
Heavy episodic drinking or binge drinking during adolescence may elicit serious neurotoxic consequences in cerebral areas (e.g., the prefrontal cortex, i.e., PFC) and the hippocampus, delay the maturation of the brain and increase the probability of drug abuse and dependence. The endocannabinoid system plays an important role in neuroprotection by reducing oxidative stress and neuroinflammation. In the present study, we aimed to investigate whether URB597, an inhibitor of the metabolic enzyme of the endocannabinoid anandamide (AEA), altered the effects of acute and chronic alcohol administration beginning during rat adolescence on recognition memory, neuroinflammation and brain-derived neurotrophic factor (BDNF) levels. The animals received intraperitoneal injections of URB597 (0.3 mg/Kg) or vehicle followed by the oral administration of ethanol (3 or 6 g/Kg) or distilled water for 3 consecutive days in one week (acute binging) or over 4 weeks (chronic binging). The groups were submitted to the novel object recognition task, and their PFCs and hippocampi were removed for analyses of the cytokine and BDNF levels. URB597 potentiated long-term memory after the 3 mg/Kg acute alcohol administration. The chronic binge alcohol administration increased the interferon (IFN)-γ and tumor necrosis factor (TNF)-α levels in the PFC and hippocampus and the interleukin (IL)-10 and BDNF levels in the PFC, and these effects were prevented by URB597. Our results indicate that the neuromodulation facilitated by AEA can reduce the neuroimmune response induced by the chronic administration of alcohol beginning in adolescence in rats.
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Benzamidas/farmacología , Consumo Excesivo de Bebidas Alcohólicas , Encéfalo/efectos de los fármacos , Carbamatos/farmacología , Envejecimiento , Amidohidrolasas/antagonistas & inhibidores , Animales , Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Citocinas/efectos de los fármacos , Citocinas/metabolismo , Masculino , Ratas , Ratas WistarRESUMEN
Abstract Objective: Posterior urethral valve is the most common lower urinary tract obstruction in male children. A high percentage of patients with posterior urethral valve evolve to end‐stage renal disease. Previous studies showed that cytokines, chemokines, and components of the renin-angiotensin system contribute to the renal damage in obstructive uropathies. The authors recently found that urine samples from fetuses with posterior urethral valve have increased levels of inflammatory molecules. The aim of this study was to measure renin-angiotensin system molecules and to investigate their correlation with previously detected inflammatory markers in the same urine samples of fetuses with posterior urethral valve. Methods: Urine samples from 24 fetuses with posterior urethral valve were collected and compared to those from 22 healthy male newborns at the same gestational age (controls). Renin-angiotensin system components levels were measured by enzyme‐linked immunosorbent assay. Results: Fetuses with posterior urethral valve presented increased urinary levels of angiotensin (Ang) I, Ang‐(1‐7) and angiotensin‐converting enzyme 2 in comparison with controls. ACE levels were significantly reduced and Ang II levels were similar in fetuses with posterior urethral valve in comparison with controls. Conclusions: Increased urinary levels of angiotensin‐converting enzyme 2 and of Ang‐(1‐7) in fetuses with posterior urethral valve could represent a regulatory response to the intense inflammatory process triggered by posterior urethral valve.
Resumo Objetivo: A válvula de uretra posterior é a obstrução do trato urinário inferior mais comum em crianças do sexo masculino. Uma alta porcentagem de pacientes com válvula de uretra posterior evolui para doença renal em estágio final. Estudos anteriores mostraram que citocinas, quimiocinas e componentes do sistema renina-angiotensina contribuem para o dano renal em uropatias obstrutivas. Recentemente, descobrimos que amostras de urina de fetos com válvula de uretra posterior tinham níveis aumentados de moléculas inflamatórias. O objetivo deste estudo foi medir as moléculas de renina-angiotensina e investigar sua correlação com marcadores inflamatórios previamente detectados nas mesmas amostras de urina de fetos com válvula de uretra posterior. Métodos: Amostras de urina de 24 fetos com válvula de uretra posterior foram coletadas e comparadas com amostras de urina de 22 recém-nascidos saudáveis de mesma idade gestacional (controles). Os níveis dos componentes de SRA foram medidos por ensaio de imunoabsorção enzimática. Resultados: Os fetos com válvula de uretra posterior apresentaram níveis urinários aumentados de angiotensina (Ang) I, Ang-(1-7) e enzima conversora de angiotensina 2 em comparação com os controles. Os níveis de enzima conversora de angiotensina eram significativamente menores e os níveis de Ang II eram semelhantes nos fetos com válvula de uretra posterior em comparação com os controles. Conclusões: O aumento dos níveis urinários de enzima conversora de angiotensina 2 e de Ang-(1-7) em fetos com válvula de uretra posterior poderia representar uma resposta regulatória ao intenso processo inflamatório desencadeado pela válvula de uretra posterior.
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Humanos , Masculino , Femenino , Embarazo , Recién Nacido , Fragmentos de Péptidos/orina , Uretra/anomalías , Enfermedades Uretrales/orina , Angiotensina I/orina , Angiotensina II/orina , Peptidil-Dipeptidasa A/orina , Feto/anomalías , Uretra/embriología , Enfermedades Uretrales/diagnóstico , Enfermedades Uretrales/embriología , Biomarcadores/orina , Estudios de Casos y Controles , Técnicas de InmunoadsorciónRESUMEN
The growing elderly population world widely prompts the need for studies regarding aged brain and its susceptibility to neurodegenerative diseases. It has been shown that aged brain exhibits several alterations, including neuroinflammation, which prone this organ to neurodegenerative processes. Metabotropic glutamate receptor 5 (mGlu5 receptor) has a role in neuronal cell loss and inflammation. Although the relevance of mGlu5 receptor in different diseases has been investigated, its involvement in normal brain aging remains unclear. In the present study, we used the mGlu5 receptor knockout (mGluR5-/-) mice, a model of Huntington's Disease (BACHD), and the double mutant mice (mGluR5-/-/BACHD), at the ages of 2, 6 and 12 months, to investigate whether mGlu5 receptor has a role in brain aging. We demonstrated that mGluR5-/- mice exhibit diminished number of neurons at 12 months of age in the cortex and striatum, similarly to what was observed in the case of BACHD and mGluR5-/-/BACHD mice. In addition, ablation of mGlu5 receptor increased the number of astrocytes and microglia in BACHD and wild type (WT) mice in an age-dependent manner in the cortical region, but not in the striatum. Interestingly, 12-month-old mGluR5-/- mice induced microglia activation, evidenced by increased CD68 expression and diminished number of microglia ramifications in skeleton analyses. Importantly, the presence of mutant huntingtin and the absence of mGlu5 receptor promoted decreased levels of fractalkine expression in aged mice, which could account for the decreased levels of microglia activation in these mice. Together, our data provide evidence that mGlu5 receptor plays a role in brain aging by modulating different cell types in the central nervous system (CNS).
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Envejecimiento/metabolismo , Encéfalo/metabolismo , Mediadores de Inflamación/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Receptor del Glutamato Metabotropico 5/deficiencia , Envejecimiento/genética , Envejecimiento/patología , Animales , Encéfalo/patología , Enfermedad de Huntington/genética , Enfermedad de Huntington/metabolismo , Enfermedad de Huntington/patología , Inflamación/metabolismo , Inflamación/patología , Ratones , Ratones de la Cepa 129 , Ratones Noqueados , Ratones Transgénicos , Microglía/metabolismo , Microglía/patología , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/patología , Receptor del Glutamato Metabotropico 5/genéticaAsunto(s)
Albuminuria/etiología , Albuminuria/orina , Anemia de Células Falciformes/complicaciones , Peptidil-Dipeptidasa A/orina , Factores de Edad , Albuminuria/diagnóstico , Anemia de Células Falciformes/diagnóstico , Enzima Convertidora de Angiotensina 2 , Biomarcadores , Niño , Susceptibilidad a Enfermedades , Humanos , Sistema Renina-AngiotensinaRESUMEN
OBJECTIVES: The immune system has an important role in the development of systemic lupus erythematosus (SLE) and chronic periodontitis (CP). Altered cytokines levels characterise both diseases and contributes to periodontal tissue damage in CP and to macrocomplexes deposition with connective tissue destruction in SLE. This study aimed to evaluate the production of salivary cytokines in patients with SLE and its association with periodontal status. METHODS: The sample comprised 70 SLE patients and 70 paired controls. SLE activity and damage were scored using Systemic Lupus Erythematosus Disease Activity Index 2000 and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Subjects were classified as without or with CP. Salivary concentrations of IL-33, MMP2/TIMP2, RANK and OPG were measured by ELISA, while IL-2, IFNγ, TNFα, IL-4, IL-6, IL-10 and IL-17A were determined by Cytometric Bead Array. Linear regression models analysed association among SLE, CP and salivary cytokines. RESULTS: IL-6 and IL-17A concentrations were significantly higher in SLE/CP patients than controls/CP. Concentrations of IL-6, IL-17A and IL-33 were increased in SLE/CP individuals when compared to SLE without CP. Multivariate model revealed association of cumulative dose of corticoids with periodontal damage and of IL-33 salivary concentration with SLE activity. CONCLUSIONS: Our findings suggest that long-term therapy with corticoids would contribute with periodontal destruction in SLE patients. Moreover, the increased levels of IL-6, IL-17A and IL-33 in saliva of SLE subjects with CP may signal it as possible inflammatory pathways in this process.
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Periodontitis Crónica/inmunología , Citocinas/análisis , Lupus Eritematoso Sistémico/inmunología , Saliva/inmunología , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , HumanosRESUMEN
OBJECTIVE: Posterior urethral valve is the most common lower urinary tract obstruction in male children. A high percentage of patients with posterior urethral valve evolve to end-stage renal disease. Previous studies showed that cytokines, chemokines, and components of the renin-angiotensin system contribute to the renal damage in obstructive uropathies. The authors recently found that urine samples from fetuses with posterior urethral valve have increased levels of inflammatory molecules. The aim of this study was to measure renin-angiotensin system molecules and to investigate their correlation with previously detected inflammatory markers in the same urine samples of fetuses with posterior urethral valve. METHODS: Urine samples from 24 fetuses with posterior urethral valve were collected and compared to those from 22 healthy male newborns at the same gestational age (controls). Renin-angiotensin system components levels were measured by enzyme-linked immunosorbent assay. RESULTS: Fetuses with posterior urethral valve presented increased urinary levels of angiotensin (Ang) I, Ang-(1-7) and angiotensin-converting enzyme 2 in comparison with controls. ACE levels were significantly reduced and Ang II levels were similar in fetuses with posterior urethral valve in comparison with controls. CONCLUSIONS: Increased urinary levels of angiotensin-converting enzyme 2 and of Ang-(1-7) in fetuses with posterior urethral valve could represent a regulatory response to the intense inflammatory process triggered by posterior urethral valve.
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Angiotensina II/orina , Angiotensina I/orina , Feto/anomalías , Fragmentos de Péptidos/orina , Peptidil-Dipeptidasa A/orina , Uretra/anomalías , Enfermedades Uretrales/orina , Enzima Convertidora de Angiotensina 2 , Biomarcadores/orina , Estudios de Casos y Controles , Femenino , Humanos , Técnicas de Inmunoadsorción , Recién Nacido , Masculino , Embarazo , Uretra/embriología , Enfermedades Uretrales/diagnóstico , Enfermedades Uretrales/embriologíaRESUMEN
Whole-body vibration (WBV) has gained prominence in the rehabilitation of individuals with chronic obstructive pulmonary disease (COPD) because it is a safe and low intensity exercise that promises beneficial effects on physical performance and quality of life. However, its effects on plasma cytokine levels in COPD are still unclear. The aim of the current study was to investigate the acute effects of WBV on inflammatory biomarkers in people with COPD. Twenty-six participants, COPD people (n=13) and healthy controls (n=13), were included. Both groups performed WBV at amplitude of 2 mm and frequency of vibration of 35 Hz, during six series of 30 seconds. They were assessed for lung function, body composition, 6-minute walking test (6MWT), handgrip strength test, plasma concentrations of interleukin (IL), IL-6, IL-8, and IL-10, and soluble tumor necrosis factor alpha (TNF-α) receptors (sTNFR-1 and sTNFR-2). People with COPD had moderate disease [forced expiratory volume in the first second (FEV1) = 58.1%], as well as a worse performance in the 6MWT. The plasma cytokine profile at rest showed that participants with COPD had higher levels of IL-8 and lower levels of IL-10. After one session of WBV, we found an increased plasma IL-10 level in the COPD group, with similar levels for healthy controls. One session of WBV modified the plasma IL-10 level. No effects were found on the other investigated cytokines.
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OBJECTIVE: Stroke is a major public health problem worldwide, and its neuropsychiatric sequelae are frequent and disabling. Furthermore, there is evidence that these sequelae impair recovery. Brazil has the highest stroke rates in Latin America, but data on the frequency of neuropsychiatric disorders in these patients are scarce. This study aimed to identify mental disorders among in-hospital patients with acute ischemic stroke. METHODS: The Mini International Neuropsychiatric Interview-Plus (MINI-Plus) was applied to 60 patients during the first week of hospitalization. RESULTS: Psychiatric disorders were diagnosed in 55% of the patients. A wide range of neuropsychiatric disorders have been identified, mainly mood and anxiety disorders. Specifically, we identified major depression (26.7%), alcohol abuse or dependence (11.7%), specific phobia (8.3%), generalized anxiety disorder (6.7%), psychosis (5.0%), social phobia (3.3%), adjustment disorder (3.3%) and panic disorder (1.7%). CONCLUSION: Psychiatric comorbidity should be evaluated as part of the rehabilitation of stroke patients and should be carefully examined by physicians.
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Trastornos Mentales/epidemiología , Accidente Cerebrovascular/epidemiología , Enfermedad Aguda , Anciano , Trastornos de Ansiedad/complicaciones , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/epidemiología , Brasil/epidemiología , Estudios Transversales , Trastorno Depresivo/complicaciones , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/epidemiología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Entrevista Psicológica , Masculino , Trastornos Mentales/complicaciones , Trastornos Mentales/diagnóstico por imagen , Persona de Mediana Edad , Morbilidad , Factores Socioeconómicos , Accidente Cerebrovascular/complicaciones , Factores de TiempoRESUMEN
Whole body vibration training (WBVT) has been identified as an alternative intervention to improve exercise capacity and quality of life of patients with chronic obstructive pulmonary disease (COPD). However, the effect of WBVT on inflammatory-oxidative biomarkers remains unknown. The aim of this trial was to investigate the effects of WBVT on quality of life and physical and inflammatory-oxidative parameters in patients with COPD. Twenty patients were equally divided into 1) an intervention group (IG) that performed the WBVT, and 2) a control group (CG) that did not receive any intervention. Intervention consisted in performing static squatting on a vibrating platform, in six series of 30 s, 3 days/wk, for 12 wk. Patients were evaluated for plasma levels of IL-6, IL-8, IFN-γ, soluble receptors of TNF-α; white cell count; plasma levels of oxidant and antioxidant markers; 6-min walking distance (6MWD); peak oxygen uptake (VÌo2peak); handgrip strength; quality of life; timed 5-chair sit-to-stand (5STS); and timed get-up and go test (TUG). After WBVT, patients from IG showed a significant increase in the 6MWD, VÌo2peak, and handgrip strength ( P < 0.05). Furthermore, patients from the IG reached minimal clinically important difference regarding quality of life. No significant differences were found in 5STS, TUG, inflammatory-oxidative biomarkers, and white cell count in the IG. The CG did not show significant improvement in all assessments ( P > 0.05). Taken together, our results demonstrated that the WBVT induced clinically significant benefits regarding exercise capacity, muscle strength, and quality of life in patients with COPD that were not related to inflammatory-oxidative biomarker changes. NEW & NOTEWORTHY Whole body vibration training is a new option for nonpharmacological treatment of chronic obstructive pulmonary disease (COPD). This study showed the potential of this training to improve exercise capacity, quality of life, and muscle strength in patients with COPD. Furthermore, to our knowledge this was the first study showing that vibration exercise does not modify the plasma levels of inflammatory-oxidative biomarkers, suggesting that the beneficial effects on physical measures and quality of life are independent of changes in biomarkers.
Asunto(s)
Biomarcadores/metabolismo , Ejercicio Físico/fisiología , Inflamación/metabolismo , Estrés Oxidativo/fisiología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Anciano , Anciano de 80 o más Años , Prueba de Esfuerzo/métodos , Tolerancia al Ejercicio/fisiología , Femenino , Volumen Espiratorio Forzado/fisiología , Fuerza de la Mano/fisiología , Humanos , Inflamación/fisiopatología , Masculino , Persona de Mediana Edad , Fuerza Muscular/fisiología , Calidad de Vida , VibraciónRESUMEN
To what extent the cognitive impairment of rheumatoid arthritis (RA) is modulated by autoimmune and/or inflammatory activity is largely unknown. The aim of this study was to investigate the role of peripheral inflammation on cognitive functions of patients with active (Ac-), controlled (Co-) RA and healthy controls. In a cross-sectional study, 102 RA patients and 30 matched healthy controls were recruited. B and T cell subsets were immunophenotyped by flow cytometry. Plasma cytokines and neurotrophins were measured by flow cytometry and ELISA, respectively. Cognitive performance, depression and stress were evaluated by structured clinical interviews. Generalized linear modeling (GzLM) was used to compare differences between groups and multiple linear regression models were used to explore the predictive value of immune variables on cognitive performance. RA patients had overall cognitive impairment. Of note, the Ac-RA had the poorest performance on digit span (DST) and N-back when compared to Co-RA and control group (DST 9.9 ± 2.1, 12.9 ± 4.2, 15.5 ± 4.7, respectively; N-back 49.2 ± 8.3, 55.5 ± 11.1, 60.8 ± 9.1, respectively, all p < 0.0001). RA patients had expansions of immature B cells (Ac-RA 11.2 ± 7.1, Co-RA: 9 ± 5.7, control 5.9 ± 2.1) and plasma cells (Ac-RA 5.2 ± 2.5, Co-RA 6.9 ± 3.7, control 2.8 ± 1.7) as compared to controls, all p < 0.05. RA patients (controlled and active disease) had higher plasma levels of TNF, IL-2, IL-4, IL-6 and IL-10 than controls (all p < 0.002). RA patients had higher BDNF levels (Ac-RA 17,354.4 ± 5357.3, Co-RA 13,841.2 ± 5953.7, control 11,543.3 ± 3772), but lower GDNF levels [median (interquartile range) Ac-RA 0 pg/ml (0.0), Co-RA 0 pg/ml (4.6) and control 4.7 pg/ml (18.1)] than controls (all p < 0.05). RA patients had global cognitive impairment, which was associated with disease activity and immune changes.
Asunto(s)
Artritis Reumatoide/complicaciones , Disfunción Cognitiva/complicaciones , Citocinas/metabolismo , Subgrupos Linfocitarios/inmunología , Factores de Crecimiento Nervioso/metabolismo , Adulto , Anciano , Artritis Reumatoide/inmunología , Artritis Reumatoide/psicología , Disfunción Cognitiva/inmunología , Disfunción Cognitiva/psicología , Estudios Transversales , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
OBJECTIVE: Stroke is a major public health problem worldwide, and its neuropsychiatric sequelae are frequent and disabling. Furthermore, there is evidence that these sequelae impair recovery. Brazil has the highest stroke rates in Latin America, but data on the frequency of neuropsychiatric disorders in these patients are scarce. This study aimed to identify mental disorders among in-hospital patients with acute ischemic stroke. METHODS: The Mini International Neuropsychiatric Interview-Plus (MINI-Plus) was applied to 60 patients during the first week of hospitalization. RESULTS: Psychiatric disorders were diagnosed in 55% of the patients. A wide range of neuropsychiatric disorders have been identified, mainly mood and anxiety disorders. Specifically, we identified major depression (26.7%), alcohol abuse or dependence (11.7%), specific phobia (8.3%), generalized anxiety disorder (6.7%), psychosis (5.0%), social phobia (3.3%), adjustment disorder (3.3%) and panic disorder (1.7%). CONCLUSION: Psychiatric comorbidity should be evaluated as part of the rehabilitation of stroke patients and should be carefully examined by physicians.