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1.
J Lipid Res ; 65(3): 100509, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38295984

RESUMO

Alcohol binge drinking allows the translocation of bacterial lipopolysaccharide (LPS) from the gut to the blood, which activates the peripheral immune system with consequences in neuroinflammation. A possible access/direct signaling of LPS to/in the brain has not yet been described under alcohol abuse conditions. Apolipoproteins are compounds altered by alcohol with high affinity to LPS which may be involved in its transport to the brain or in its elimination. Here, we explored the expression of small components of LPS, in its free form or bound to apolipoproteins, in the brain of female and male rats exposed to alcohol binges. Animals received ethanol oral gavages (3 g/kg every 8 h) for 4 days. LPS or its components (Lipid A and core), LPS-binding protein, corticosterone, lipoproteins (HDL, LDL), apolipoproteins (ApoAI, ApoB, and ApoE), and their receptors were measured in plasma and/or in nonperfused prefrontal cortex (PFC) and cerebellum. Brain LipidA-apolipoprotein aggregates were determined by Western blotting and confirmed by co-immunoprecipitation. In animals exposed to alcohol binges: 1) plasma LPS-binding protein was elevated in both sexes; 2) females showed elevations in plasma ApoAI and corticosterone levels; 3) Lipid A formed aggregates with ApoAI in the female PFC and with ApoB in males, the latter showing Toll-like receptor 4 upregulation in PFC but not females. These results suggest that small bacterial components are present within the brain, forming aggregates with different apolipoproteins, depending on the sex, after alcohol binge intoxications. Results may have implications for the crosstalk between alcohol, LPS, and neuroinflammation.


Assuntos
Etanol , Lipopolissacarídeos , Ratos , Masculino , Feminino , Animais , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Doenças Neuroinflamatórias , Lipídeo A/metabolismo , Corticosterona/metabolismo , Apolipoproteínas/metabolismo , Apolipoproteínas E/metabolismo , Encéfalo/metabolismo , Apolipoproteínas B/metabolismo
2.
Eur Child Adolesc Psychiatry ; 28(10): 1395-1405, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30843122

RESUMO

A precise description of the inflammatory response in first-episode psychosis (FEP) by age of onset does not exist. We explored baseline and 6-month follow-up differences in the pro/anti-inflammatory balance in plasma and peripheral blood mononuclear cells in adolescent-onset FEP (≤ 18 y.o., N = 27) and adult-onset FEP (≥ 25 y.o., N = 43) using non-parametric 1-category ANCOVA, with age group as an independent variable and values of pro- and anti-inflammatory markers at baseline and at follow-up as dependent variables. We used a non-parametric repeated-measures mixed-effects model to explore the baseline/6-month change in pro- and anti-inflammatory markers within adolescent- and adult-onset groups, exploring differential trajectories of change by means of the interaction of time by age-of-onset group. Levels of the nuclear transcription factor (NFκB), a master regulator of the inflammatory and oxido/nitrosative status of cells, were higher in adolescent-onset FEP both at baseline and after 6 months. During follow-up, we found further increases in levels of soluble inflammatory markers (PGE2 and NO2-) only in adolescent-onset FEP. In contrast, in adult-onset FEP, the expression of inducible NO synthase (iNOS), which is also pro-inflammatory, tended to decrease, with no further increase in other pro-inflammatory markers. Significant differences in the direction of change by age-of-onset cohort exist only for NFκB (F = 4.165, df = 2, 70.95, p = 0.019). Our results support the existence of changes in the pro/anti-inflammatory balance in FEP depending on the neurodevelopmental stage at illness onset. These results also suggest that inflammation may be a potential therapeutic target in adolescent-onset FEP.


Assuntos
Biomarcadores/sangue , Inflamação/metabolismo , Transtornos Psicóticos/etiologia , Adolescente , Adulto , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Adulto Jovem
3.
Br J Pharmacol ; 175(24): 4464-4479, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30248186

RESUMO

BACKGROUND AND PURPOSE: Chronic alcohol consumption alters the gut-brain axis, but little is known about alcohol binge episodes on the functioning of the intestinal barrier. We investigated the influence of ethanol binges on bacterial translocation, gut inflammation and immunity, and tight junction (TJ) structure and the ability of the biolipid oleoylethanolamide (OEA) to prevent ethanol binge-induced intestinal barrier dysfunction. EXPERIMENTAL APPROACH: OEA was injected i.p. before repeated ethanol administration by oral gavage. Plasma, spleen, liver and mesenteric lymph nodes (MLN) were collected in sterile conditions for determination of bacterial load. Immune/inflammatory parameters, TJ proteins and apoptotic markers were determined in colonic tissue by RT-PCR and Western blotting. TJ ultrastructure was examined by transmission electron microscopy. KEY RESULTS: Ethanol binges induced bacterial translocation to the MLN (mainly) and spleen. Colonic tissues showed signs of inflammation, and activation of innate (Toll-like receptor-4) and adaptive (IgA) immune systems and TJ proteins (occludin and claudin-3) were decreased after ethanol binges. Pretreatment with OEA reduced intestinal inflammation and immune activation and partially preserved the TJ structure affected by alcohol binges but had no effect on alcohol-induced apoptosis. Ultrastructural analyses of colonic TJs revealed dilated TJs in all ethanol groups, with less electron-dense material in non-pretreated rats. The protective effects of i.p. OEA did not reduce bacterial translocation to the MLN. However, intragastric OEA administration significantly reduced plasma LPS levels and bacterial translocation to the MLN. CONCLUSION AND IMPLICATIONS: OEA-based pharmacotherapies could potentially be useful to treat disorders characterized by intestinal barrier dysfunction, including alcohol abuse.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Endocanabinoides/farmacologia , Etanol/administração & dosagem , Etanol/efeitos adversos , Mucosa Intestinal/efeitos dos fármacos , Ácidos Oleicos/farmacologia , Alcoolismo/fisiopatologia , Animais , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/prevenção & controle , Mucosa Intestinal/metabolismo , Masculino , Ratos , Ratos Wistar
4.
Rev. Hosp. Clin. Univ. Chile ; 29(1): 48-59, 20180000. Graf., Ilus., Tab.
Artigo em Espanhol | LILACS | ID: biblio-980187

RESUMO

Manual wheelchair is one the most used mobility device in people that is unable to walk. It enhances functional independence in non ambulant people, but it costs a great energy expenditure and is a source of painful musculoskeletal injuries. The most frequently affected joint in manual wheelchair users is the shoulder (rotator cuff tendinopathy and subacromial impingement). In this review, we aim to describe the risk factors and biomechanical issues that make wheelchair users more prone to develop shoulder pain. Further, we discuss potencial approaches for the prevention and early treatment of these injuries. (AU)


Assuntos
Humanos , Masculino , Feminino , Cadeiras de Rodas/efeitos adversos , Lesões do Ombro , Cadeiras de Rodas/estatística & dados numéricos
5.
Psychol Med ; 46(10): 2133-44, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27055381

RESUMO

BACKGROUND: Cognitive deficits are present from the onset of psychosis and are considered a core feature of the disorder. Increasing evidence suggests that cognitive function is associated with inflammatory processes. This study evaluated the association between cognition and inflammatory biomarkers in first-episode psychosis (FEP), in order to identify cognitive phenotypes from inflammatory expression profiles. METHOD: A case-control study of 92 FEP patients and 80 matched controls was used. Neurocognitive assessment, including verbal ability, sustained attention, verbal memory, working memory and executive function, was performed. The expression of pro- and anti-inflammatory mediators of the main intracellular inflammatory pathway was measured in peripheral blood mononuclear cells and plasma. RESULTS: FEP patients performed worse in all cognitive domains compared to controls and had higher expression of pro-inflammatory mediators and lower expression of anti-inflammatory mediators. In the FEP group, cognition and psychopathology were associated with inflammation. Hierarchical regression analysis showed that association between the anti-inflammatory prostaglandin 15d-PGJ2 and sustained attention on one hand, and COX-2 expression and executive function on the other, were statistically significant. CONCLUSIONS: Our study provides evidence for an association between anti-inflammatory biomarkers and cognition in FEP. The identification of a subgroup of patients based on these measures could be useful to guide treatment programmes by providing tools to select a personalized treatment approach, but longitudinal studies are needed before. In the future, establishment of biomarkers linked to cognition would be useful to monitor the course of cognitive impairment, but substantially more data will be required. Determination of IκBα, the inhibitory protein of the pro-inflammatory transcription factor NFκB, could be useful in early phases to assess clinical severity.


Assuntos
Disfunção Cognitiva , Ciclo-Oxigenase 2/metabolismo , Função Executiva/fisiologia , Inflamação , Prostaglandina D2/análogos & derivados , Transtornos Psicóticos , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Disfunção Cognitiva/imunologia , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Inflamação/imunologia , Inflamação/fisiopatologia , Masculino , Prostaglandina D2/metabolismo , Transtornos Psicóticos/imunologia , Transtornos Psicóticos/fisiopatologia , Adulto Jovem
6.
Neurosci Biobehav Rev ; 64: 134-47, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26905767

RESUMO

The innate immunity is a stereotyped first line of defense against pathogens and unspecified damage signals. One of main actors of innate immunity are the Toll-like receptors (TLRs), and one of the better characterized members of this family is TLR-4, that it is mainly activated by Gram-negative bacteria lipopolysaccharide. In brain, TLR-4 organizes innate immune responses against infections or cellular damage, but also possesses other physiological functions. In the last years, some evidences suggest a role of TLR-4 in stress and stress-related neuropsychiatric diseases. Peripheral and brain TLR-4 activation triggers sickness behavior, and its expression is a risk factor of depression. Some elements of the TLR-4 signaling pathway are up-regulated in peripheral samples and brain post-mortem tissue from depressed and suicidal patients. The "leaky gut" hypothesis of neuropsychiatric diseases is based on the existence of an increase of the intestinal permeability which results in bacterial translocation able to activate TLR-4. Enhanced peripheral TLR-4 expression/activity has been described in subjects diagnosed with schizophrenia, bipolar disorder and in autistic children. A role for TLR-4 in drugs abuse has been also proposed. The therapeutic potential of pharmacological/genetic modulation of TLRs signaling pathways in neuropsychiatry is promising, but a great preclinical/clinical scientific effort is still needed.


Assuntos
Transtornos Mentais/imunologia , Receptor 4 Toll-Like/metabolismo , Animais , Humanos
7.
Rev. esp. patol. torac ; 28(1): 9-15, ene. 2016. tab
Artigo em Espanhol | IBECS | ID: ibc-149672

RESUMO

OBJETIVOS: 1- Valorar la adherencia al tratamiento nebulizado con colistimetato de sodio-Promixín® con dispositivo Ineb® en pacientes con bronquiectasias (BQ) no fibrosis quística (FQ) colonizadas por Pseudomonas aeruginosa; 2- Identificar un perfil de paciente incumplidor. MÉTODO: Estudio multicéntrico, observacional, prospectivo, de corte transversal, de una cohorte de adultos tratados al menos durante 6 meses con colistimetato de sodio (Promixin®) administrado con el nebulizador Ineb®. Se obtuvieron los registros del tratamiento nebulizado (plataforma informática Insight®), datos de función pulmonar, cultivos de esputo y número de agudizaciones antes y después del tratamiento. Se analizó la adherencia global, el manejo del nebulizador y la adherencia real. Se define a los pacientes con mala adherencia terapéutica como aquellos con una adherencia global o real ≤80%. RESULTADOS: La muestra inicial fue de 126 pacientes, considerándose no válidos para su análisis 20 de ellos, siendo seleccionados 106 pacientes con BQ no FQ, 47 de causa postinfecciosa (44,3%), 13 EPOC (12,3%), 12 discinesia ciliar (11,3%), 17 otras causas(16%) y 17 idiopáticas (16%). La edad media fue de 64,0 ± 14,6 años, 57 varones (53,8%) y 49 mujeres (46,2%), 61 procedentes de hospitales terciarios (57,5%) y 45 de comarcales (42,5%). La adherencia global fue del 86,7 ± 19,3% y en el 73,6% de los casos ≥80%. El 96,6 ± 7,8% de los pacientes manejaron adecuadamente el nebulizador, con unos tiempos de nebulización de 6,3 ± 3,4 minutos. La adherencia real fue del 84,4 ± 20,2% y en el 75,5% de los casos ≥80%. No hubo diferencias en cuanto al sexo, edad, función pulmonar, causa de las BQ no FQ y exacerbaciones previas para ninguna de estas variables. CONCLUSIÓN: En nuestra población el manejo del nebulizador y la adherencia, global y real, es muy buena. El escaso número de pacientes no adherentes no nos ha permitido definir el perfil del incumplidor


OBJECTIVE: 1) Assess adherence to nebulized treatment with colistimethate sodium-Promixin® using an Ineb® nebulizer in patients with bronchiectasis (BQ) but without cystic fibrosis (CF) colonized by Pseudomonas aeruginosa; 2) Identify a noncompliant patient profile. METHOD: A multi-center, observational, prospective, transversal study, with a cohort of adults treated for at least six months with colistimethate sodium (Promixin®) administered with an Ineb® nebulizer. Registers of nebulized treatment were obtained (Insight® IT platform), pulmonary lung function, sputum culture and number of exacerbations prior to and after the treatment. Global adherence was analyzed, as well as handling the nebulizer and real adherence. Patients with poor therapeutic adherence were defined as those with a global or real adherence of ≤80%. RESULTS: The initial sample included 126 patients, 20 of which were considered not valid for the analysis; 106 patients with BQ non-CF, 47 were post-infectious causes(44.3%), 13 COPD (12.3%), 12 ciliary dyskinesia(11.3%), 17 other causes (16%) and 17 idiopathic (16%). The mean age was 64.0 ± 14.6 years; 57 males (53.8%) and 49 females (46.2%), 61 were from tertiary hospitals (57.5%) and 45 from local hospitals (42.5%). Global adherence was 86.7 ± 19.3% and in 73.6% of the cases ≥80%. 96.6 ± 7.8% of the patients adequately handled the nebulizer, with nebulization times of 6.3 ± 3.4 minutes. Real adherence was 84.4 ± 20.2% and in 75.5% of the cases ≥80%. No differences were seen in terms of sex, age, pulmonary function, cause of BQ non-CF and prior exacerbations for none of these variables. CONCLUSION: In our population, handling the nebulizer and adherence, both global and real, is very good. The limited number of patients who failed to adhere has hindered our defining a non-compliant profile


Assuntos
Humanos , Antibacterianos/administração & dosagem , Bronquiectasia/tratamento farmacológico , Infecções por Pseudomonas/complicações , Sprays Orais , Pseudomonas aeruginosa/patogenicidade , Adesão à Medicação/estatística & dados numéricos
8.
Schizophr Bull ; 42(1): 142-51, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26130821

RESUMO

Previous studies have indicated systemic deregulation of the proinflammatory or anti-inflammatory balance in individuals with first-episode psychosis (FEP) that persists 12 months later. To identify potential risk/protective factors and associations with symptom severity, we assessed possible changes in plasma levels of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) and their receptors in peripheral blood mononuclear cells (PBMCs). Expression of the 2 forms of BDNF receptors (active TrkB-FL and inactiveTrkB-T1) in PBMCs of FEP patients changed over time, TrkB-FL expression increasing by 1 year after diagnosis, while TrkB-T1 expression decreased. The TrkB-FL/TrkB-T1 ratio (hereafter FL/T1 ratio) increased during follow-up in the nonaffective psychosis group only, suggesting different underlying pathophysiological mechanisms in subgroups of FEP patients. Further, the expression of the main NGF receptor, TrkA, generally increased in patients at follow-up. After adjusting for potential confounders, baseline levels of inducible isoforms of nitric oxide synthase, cyclooxygenase, and nuclear transcription factor were significantly associated with the FL/T1 ratio, suggesting that more inflammation is associated with higher values of this ratio. Interestingly, the FL/T1 ratio might have a role as a predictor of functioning, a regression model of functioning at 1 year suggesting that the effect of the FL/T1 ratio at baseline on functioning at 1 year depended on whether patients were treated with antipsychotics. These findings may have translational relevance; specifically, it might be useful to assess the expression of TrkB receptor isoforms before initiating antipsychotic treatment in FEPs.


Assuntos
Transtornos Psicóticos Afetivos/tratamento farmacológico , Antipsicóticos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator de Crescimento Neural/metabolismo , Transtornos Psicóticos/tratamento farmacológico , Receptor trkA/metabolismo , Receptor trkB/metabolismo , Adolescente , Adulto , Transtornos Psicóticos Afetivos/imunologia , Transtornos Psicóticos Afetivos/metabolismo , Estudos de Casos e Controles , Ciclo-Oxigenase 2/imunologia , Ciclo-Oxigenase 2/metabolismo , Feminino , Humanos , Inflamação , Leucócitos Mononucleares/metabolismo , Estudos Longitudinais , Masculino , NF-kappa B/imunologia , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/imunologia , Óxido Nítrico Sintase Tipo II/metabolismo , Prognóstico , Prostaglandina D2/análogos & derivados , Prostaglandina D2/imunologia , Prostaglandina D2/metabolismo , Isoformas de Proteínas , Transtornos Psicóticos/imunologia , Transtornos Psicóticos/metabolismo , Análise de Regressão , Transdução de Sinais , Adulto Jovem
9.
Int J Neuropsychopharmacol ; 18(3)2014 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-25522409

RESUMO

BACKGROUND: Alterations in the innate immune/inflammatory system have been proposed to underlie the pathophysiology of psychotic disease, but the mechanisms implicated remain elusive. The main agents of the innate immunity are the family of toll-like receptors (TLRs), which detect circulating pathogen-associated molecular patterns and endogenous damage-associated molecular patterns (DAMPS). Current antipsychotics are able to modulate pro- and anti-inflammatory pathways, but their actions on TLRs remain unexplored. METHODS: This study was conducted to elucidate the effects of paliperidone (1mg/Kg i.p.) on acute (6 hours) and chronic (6 hours/day during 21 consecutive days) restraint stress-induced TLR-4 pathway activation and neuroinflammation, and the possible mechanism(s) related (bacterial translocation and/or DAMPs activation). The expression of the elements of a TLR-4-dependent proinflammatory pathway was analyzed at the mRNA and protein levels in prefrontal cortex samples. RESULTS: Paliperidone pre-treatment prevented TLR-4 activation and neuroinflammation in the prefrontal cortices of stressed rats. Regarding the possible mechanisms implicated, paliperidone regulated stress-induced increased intestinal inflammation and plasma lipopolysaccharide levels. In addition, paliperidone also prevented the activation of the endogenous activators of TLR-4 HSP70 and HGMB-1. CONCLUSIONS: Our results showed a regulatory role of paliperidone on brain TLR-4, which could explain the therapeutic benefits of its use for the treatment of psychotic diseases beyond its effects on dopamine and serotonin neurotransmission. The study of the mechanisms implicated suggests that gut-increased permeability, inflammation, and bacterial translocation of Gram-negative microflora and HSP70 and HGMB1 expression could be potential adjuvant therapeutic targets for the treatment of psychotic and other stress-related psychiatric pathologies.


Assuntos
Antipsicóticos/uso terapêutico , Encéfalo/metabolismo , Encefalite , Isoxazóis/uso terapêutico , Pirimidinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Estresse Fisiológico/fisiologia , Receptor 4 Toll-Like/metabolismo , Animais , Antipsicóticos/farmacologia , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Encefalite/etiologia , Encefalite/patologia , Encefalite/prevenção & controle , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Isoxazóis/farmacologia , Lipopolissacarídeos/sangue , Lipopolissacarídeos/farmacologia , Masculino , Óxido Nítrico Sintase Tipo II , Nitritos/metabolismo , Palmitato de Paliperidona , Pirimidinas/farmacologia , Ratos , Ratos Wistar , Restrição Física/efeitos adversos , Receptor 4 Toll-Like/genética
11.
Rev. esp. patol. torac ; 26(2): 89-96, abr.-jun. 2014. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-126673

RESUMO

OBJETIVO: el objetivo primario es valorar la adherencia al tratamiento nebulizado con colistimetato de sodio-Promixín®con dispositivo I-neb® en pacientes con bronquiectasias (BQ) colonizadas por Pseudomonas aeruginosa y la identificación de un perfil de incumplidor. El impacto, en términos de función pulmonar, frecuencia de exacerbaciones y resultados en la microbiología del esputo, son objetivos secundarios. PACIENTES Y MÉTODO: estudio multicéntrico, observacional, retrospectivo, de corte transversal, de una cohorte de adultos tratados al menos durante 3 meses. Se obtuvieron los registros del tratamiento nebulizado, datos de función pulmonar, culti-vos de esputo y número de agudizaciones antes y después del tratamiento. Se analizó la duración media del tratamiento, la adherencia global, el manejo del nebulizador y la adherencia real.RESULTADOS: fueron seleccionados 29 pacientes, 18 con BQ por fibrosis quística (FQ). La edad fue de 41,4 ± 22,4 años y el FEV1 al inicio fue de 67,7 ± 18,1%, sin cambios tras el tratamiento. En todos los pacientes se redujo el número de exacerbaciones. La duración media de la nebulización fue de 7,2 ± 3,5 min. El 95 ± 8,5% de los pacientes manejaron adecuadamente el nebulizador, independientemente del sexo, edad o patología de base. Existieron diferencias significativas en adherencia global y real según la enfermedad de base, a favor de los pacientes con BQ no FQ.CONCLUSIÓN: en nuestra población, la respuesta clínica al tra-tamiento, el manejo del nebulizador y la adherencia fue muy buena, sin cambios en la función pulmonar, a pesar de que sí los hubo en la flora microbiológica. Los pacientes jóvenes son los más incumplidores


OBJECTIVE: First of all, adherence to a nebulized treatment with colistimethate sodium-Promixín® using an I-neb® device was assessed in patients with bronchiectasis (BQ) colonized by Pseudomonas aeruginosa to identify patient noncompliance profiles. The impact, in terms of pulmonary function, frequency of exacerbations and the microbiological results of sputum were secondary objectives. PATIENTS AND METHOD: This was a multicenter, observational, retrospectivestudy, with a cross-section adult cohort treated du-ring at least three (3) months. The registers for the nebulized treatment were obtained, as well as pulmonary function, spu-tum cultures and number of exacerbations prior to and after treatment. The average treatment duration was analyzed, as was global adherence, handling of the nebulizer and real adherence.RESULTS: 29 patients were selected, 18 with BQ due to Cys-tic Fibrosis (CF). The age range was 41.4 ± 22.4 years and the initial FEV1 was 67.7 ± 18.1%, without changes after the treatment. The number of exacerbations was reduced in all patients. The average duration of the nebulizationwas from 7.2 ± 3.5 minutes. 95 ± 8.5% of the patients adequately mana-ged the nebulizer, independently of gender, age or underlying pathology. There were significant differences in global and real adherence depending on the underlying disease, which favored BQ patients without CF. CONCLUSION: In our population, the clinical response to the treatment, handling of the nebulizer and adherence was very good, without changes in pulmonary function, despite the fact that there were changes in the microbiological flora. Young patients complied worse


Assuntos
Humanos , Monitoramento de Medicamentos/métodos , Antibacterianos/administração & dosagem , Bronquiectasia/tratamento farmacológico , Pseudomonas aeruginosa/patogenicidade , Sprays Orais , Cooperação do Paciente , Adesão à Medicação , Estudos Retrospectivos
13.
Br J Pharmacol ; 171(11): 2814-26, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24467609

RESUMO

BACKGROUND AND PURPOSE: Stress exposure produces excitotoxicity and neuroinflammation, contributing to the cellular damage observed in stress-related neuropathologies. The endocannabinoids provide a homeostatic system, present in stress-responsive neural circuits. Here, we have assessed the possible regulatory role of cannabinoid CB2 receptors in stress-induced excitotoxicity and neuroinflammation. EXPERIMENTAL APPROACH: We used wild type (WT), transgenic overexpressing CB2 receptors (CB2xP) and CB2 receptor knockout (CB2-KO) mice exposed to immobilization and acoustic stress (2 h·day(-1) for 4 days). The CB2 receptor agonist JWH-133 was administered daily (2 mg·kg(-1), i.p.) to WT and CB2-KO animals. Glutamate uptake was measured in synaptosomes from frontal cortex; Western blots and RT-PCR were used to measure proinflammatory cytokines, enzymes and mediators in homogenates of frontal cortex. KEY RESULTS: Increased plasma corticosterone induced by stress was not modified by manipulating CB2 receptors. JWH-133 treatment or overexpression of CB2 receptors increased control levels of glutamate uptake, which were reduced by stress back to control levels. JWH-133 prevented the stress-induced increase in proinflammatory cytokines (TNF-α and CCL2), in NF-κB, and in NOS-2 and COX-2 and in the consequent cellular oxidative and nitrosative damage (lipid peroxidation). CB2xP mice exhibited anti-inflammatory or neuroprotective actions similar to those in JWH-133 pretreated animals. Conversely, lack of CB2 receptors (CB2-KO mice) exacerbated stress-induced neuroinflammatory responses and confirmed that effects of JWH-133 were mediated through CB2 receptors. CONCLUSIONS AND IMPLICATIONS: Pharmacological manipulation of CB2 receptors is a potential therapeutic strategy for the treatment of stress-related pathologies with a neuroinflammatory component, such as depression.


Assuntos
Lobo Frontal/metabolismo , Inflamação/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Estresse Psicológico/metabolismo , Animais , Canabinoides/farmacologia , Quimiocina CCL2/genética , Corticosterona/sangue , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Ácido Glutâmico/metabolismo , Masculino , Camundongos Endogâmicos ICR , Camundongos Transgênicos , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Nitritos/metabolismo , Receptor CB2 de Canabinoide/agonistas , Sinaptossomos/metabolismo , Fator de Necrose Tumoral alfa/genética
14.
J Clin Psychol ; 70(1): 1-17, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23801539

RESUMO

OBJECTIVE: The literature on later age of onset (LAO) in women with eating disorders is scarce. We compared the severity of eating disorders, eating disorder subtype, and personality profiles in a clinical sample of consecutively assessed women with eating disorders with later age of onset (LAO, > = 25 years) to women with typical age of onset (TAO, <25 years). METHOD: All eating disorder patients met the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria and were admitted to the Eating Disorder Unit of the University Hospital of Bellvitge in Barcelona, Spain. Ninety-six patients were classified as LAO and 759 as TAO. ASSESSMENT: Measures included the Eating Attitude Test-40 (EAT-40), Eating Disorders Inventory-2 (EDI-2), Bulimic Investigatory Test Edinburgh (BITE), Symptom Checklist Revised (SCL-90-R), and the Temperament and Character Inventory-Revised (TCI-R), as well as other clinical and psychopathological indices. RESULTS: LAO individuals reported significantly fewer weekly vomiting episodes, fewer self-harming behaviours, less drug abuse, and lower scores on the BITE symptoms, the EDI-2 drive for thinness, and the TCI-R harm avoidance scales than TAO individuals. Conversely, the LAO group reported more current and premorbid obesity than the TAO group. CONCLUSION: LAO eating disorder patients in this sample presented with milder symptomatology and less extreme personality traits. Premorbid obesity may be more relevant to LAO than TAO eating disorders and should be routinely assessed and considered when planning treatment.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Obesidade/epidemiologia , Personalidade/fisiologia , Adulto , Fatores Etários , Idade de Início , Comorbidade , Transtornos da Alimentação e da Ingestão de Alimentos/classificação , Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Inventário de Personalidade , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Espanha/epidemiologia , Adulto Jovem
17.
Gynecol Obstet Invest ; 72(2): 117-22, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21372552

RESUMO

AIMS: To measure endometrial volume and endometrial-subendometrial vascularization by 3-D power Doppler ultrasound in patients undergoing cycles of artificial insemination with ovarian stimulation, to evaluate their relationship with patients' age and pregnancy development. METHODS: We included patients with primary and secondary infertility of one year of evolution. We measured vascular indexes and endometrial volume by 3-D power Doppler ultrasound. RESULTS: Seventy-nine consecutive cycles were studied. Endometrial volume average was 4.7 ± 2.66 ml. We did not find any difference between the endometrial volumes in women who did versus did not become pregnant (9 vs. 70 women, respectively). The endometrial vascular index was significantly higher in patients aged between 31 and 33 years old. In patients between the ages of 31 and 33, both the endometrial flow index (FI; p = 0.017) and the endometrial vascular FI (p = 0.013) were higher. At the subendometrial area, the vascular FI was lower in women older than 33 years old (p = 0.024), while the FI was higher in patients that achieved pregnancy (p = 0.047). CONCLUSIONS: Endometrial volumes were independent of pregnancy development. Endometrial and subendometrial vascularization FIs were significantly higher in younger women. The subendometrial FI was significantly higher in patients who achieved pregnancy.


Assuntos
Implantação do Embrião , Endométrio/irrigação sanguínea , Endométrio/diagnóstico por imagem , Imageamento Tridimensional , Infertilidade Feminina/diagnóstico por imagem , Ultrassonografia Doppler , Adulto , Endométrio/patologia , Feminino , Humanos , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez , Adulto Jovem
20.
Psychol Med ; 40(12): 2001-11, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20214841

RESUMO

BACKGROUND: The same executive dysfunctions and alterations in neuroimaging tests (both functional and structural) have been found in obsessive-compulsive patients and their first-degree relatives. These neurobiological findings are considered to be intermediate markers of the disease. The aim of our study was to assess verbal and non-verbal memory in unaffected first-degree relatives, in order to determine whether these neuropsychological functions constitute a new cognitive marker for obsessive-compulsive disorder (OCD). METHOD: Recall and use of organizational strategies in verbal and non-verbal memory tasks were measured in 25 obsessive-compulsive patients, 25 unaffected first-degree relatives and 25 healthy volunteers. RESULTS: First-degree relatives and healthy volunteers did not show differences on most measures of verbal memory. However, during the recall and processing of non-verbal information, deficits were found in first-degree relatives and patients compared with healthy volunteers. CONCLUSIONS: The presence of the same deficits in the execution of non-verbal memory tasks in OCD patients and unaffected first-degree relatives suggests the influence of certain genetic and/or familial factors on this cognitive function in OCD and supports the hypothesis that deficits in non-verbal memory tasks could be considered as cognitive markers of the disorder.


Assuntos
Transtorno Obsessivo-Compulsivo/genética , Transtorno Obsessivo-Compulsivo/fisiopatologia , Adulto , Biomarcadores , Estudos de Casos e Controles , Transtornos Cognitivos/fisiopatologia , Feminino , Humanos , Masculino , Transtornos da Memória/fisiopatologia , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/psicologia
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