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1.
Epilepsy Behav ; 156: 109825, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38838461

RESUMO

Correctly diagnosing and classifying seizures and epilepsies is vital to ensure a tailored approach to patients with epilepsy. The ILAE seizure classification consists of two main groups: focal and generalized. Establishing if a seizure is focal or generalized is essential to classify the epilepsy type and the epilepsy syndrome, providing more personalized treatment and counseling about prognosis. EEG is one of the most essential tools for this classification process and further localization of the epileptogenic focus. However, some EEG findings are misleading and may postpone the correct diagnosis and proper treatment. Knowing the most common EEG pitfalls in focal and generalized epilepsies is valuable for clinical practice, avoiding misinterpretations. Some atypical features can be challenging in focal epilepsies, such as secondary bilateral synchrony, focal epileptiform activity induced by hyperventilation and photic stimulation, and non-focal slowing. On the other hand, more than 60 % of persons with idiopathic generalized epilepsies have at least one type of atypical abnormality. In this manuscript, we describe and illustrate some of the most common EEG findings that can make even experienced epileptologists question not only where the epileptogenic focus is but also if the patient has focal or generalized epilepsy. This review summarizes the perils and provide some pearls to assist EEG readers.


Assuntos
Eletroencefalografia , Epilepsias Parciais , Epilepsia Generalizada , Humanos , Eletroencefalografia/métodos , Epilepsia Generalizada/fisiopatologia , Epilepsia Generalizada/diagnóstico , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/diagnóstico , Encéfalo/fisiopatologia
2.
Epilepsy Behav ; 161: 110091, 2024 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-39467450

RESUMO

This manuscript provides practical insights, tips, and lessons particularly valuable for early-career healthcare professionals new to using ketogenic diet therapy (KDT) in clinical practice. The review aims to be accessible, emphasizing actionable knowledge that can be directly applied in a clinical setting. The KDT for epilepsy includes not only the classic KDT but also the modified Atkins diet, the medium-chain triglyceride ketogenic diet, and the low glycemic index treatment. This highly effective non-pharmacological treatment can be rapidly implemented for patients with drug-resistant epilepsy. Identifying suitable candidates and conferring criteria for selecting patients who are likely to benefit ('good responder') from the ketogenic diet is critical for earlier intervention minimizing the burden of seizures and long-term polytherapy. On the other hand, this article outlines conditions where the ketogenic diet may not be appropriate, such as in patients with specific metabolic disorders, representing contraindications or cautions where there are concerns about adherence. Finally, the use of KDT in special settings (e.g., ICU) and how to deal with the most common side effects and abnormal laboratory results are provided based on an updated review and the experience from three level three epilepsy centers.

3.
Epilepsy Behav ; 155: 109762, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636144

RESUMO

OBJECTIVE: To evaluate the clinical predictors of positive genetic investigation in developmental and epileptic encephalopathies, beyond the influence of Dravet Syndrome. METHODS: The study included 98 patients diagnosed with developmental and epileptic encephalopathies. The patients underwent Sanger sequencing of SCN1A, Chromosomal Microarray Analysis, and Whole Exome Sequencing. The association of clinical variables with a positive genetic test was investigated using univariate and multivariate analysis. RESULTS: Genetic diagnosis was identified in 47 (48 %) patients with developmental and epileptic encephalopathies. Beyond Dravet Syndrome influence, first seizure in the context of fever (p < 0.01), seizures precipitated by temperature (p = 0.04), cognitive regression (p = 0.04), hypotonia (p < 0.01), and focal seizures (p = 0.03) increased the chances of a positive genetic investigation. In contrast, atonic seizures (p = 0.01) and generalized discharges on electroencephalogram (p = 0.02) decreased the chances. Dravet Syndrome was positively associated with a genetic developmental and epileptic encephalopathies etiology (p < 0.01), whereas epilepsy with myoclonic-atonic seizures (p = 0.01), developmental and epileptic encephalopathies with spike-wave activation in sleep (p = 0.04), and Lennox-Gastaut syndrome (p = 0.03) were negatively associated. In multivariate analysis, the first seizure in the context of fever (p < 0.01) and hypotonia (p = 0.02) were positively, and atonic seizures (p = 0.01) were negatively and independently associated with a genetic etiology. CONCLUSION: The predictive variables of genetic investigation in developmental and epileptic encephalopathies are first seizure in the context of fever and hypotonia, whereas atonic seizures decrease the chances of finding a genetic cause for developmental and epileptic encephalopathies. Regarding epileptic syndromes, Dravet Syndrome is highly associated with a positive genetic test, whereas epilepsy with myoclonic-atonic seizures, developmental and epileptic encephalopathies with spike-wave activation in sleep, and Lennox-Gastaut syndrome are rarely associated with a positive genetic investigation.


Assuntos
Epilepsias Mioclônicas , Canal de Sódio Disparado por Voltagem NAV1.1 , Humanos , Masculino , Feminino , Criança , Pré-Escolar , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/diagnóstico , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Lactente , Adolescente , Eletroencefalografia , Testes Genéticos , Adulto , Epilepsia/genética , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Adulto Jovem , Sequenciamento do Exoma , Síndrome de Lennox-Gastaut/genética , Síndrome de Lennox-Gastaut/diagnóstico
4.
J Asthma ; 61(9): 1076-1082, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38426671

RESUMO

INTRODUCTION: Reactance inversion (RI) has been associated with impaired peripheral airway function in persistent asthma. However, there is little to no data about the difference between asthmatic children with and without RI. This study aimed to detect clinical and lung function differences in moderate-severe asthmatic children with and without RI. METHODS: This study was conducted between 2021 and 2022 in asthmatic school-age children. Impulse oscillometry (IOS) and spirometry were performed according to ATS/ERS standards. RESULTS: A total of 62 patients, with a mean age of 8.4 years, 54.8% were males and were divided into three groups: group 1 (32.3%) with no RI, group 2 (27.4%) with RI but disappearing after bronchodilator test and group 3 (40.3%) with persistent RI after bronchodilator test. Children in groups 2 and 3 had significantly lower birth weights than in group 1. Group 2 had lower gestational age compared to group 1. FEV1 and FEF25-75 of forced vital capacity were significantly lower in groups 2 and 3. In group 3, R5, AX, R5-20, and R5-R20/R5 ratios were significantly higher. Bronchodilator responses (BDR) in X5c, AX, and R5-R20 were significantly different between groups and lower in group 3. CONCLUSION: RI is frequently found in children with moderate-severe persistent asthma, particularly in those with a history of prematurity or low birth weight. In some patients, RI disappears after the bronchodilator test; however, it, persists in those with the worst pulmonary function. RI could be a small airway dysfunction marker.


Assuntos
Asma , Broncodilatadores , Recém-Nascido de Baixo Peso , Humanos , Asma/fisiopatologia , Asma/tratamento farmacológico , Masculino , Feminino , Criança , Broncodilatadores/uso terapêutico , Broncodilatadores/administração & dosagem , Espirometria , Índice de Gravidade de Doença , Testes de Função Respiratória , Oscilometria , Recém-Nascido
5.
Int J Mol Sci ; 25(13)2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-39000001

RESUMO

Phenolic compounds with a position ortho to the free phenolic hydroxyl group occupied can be tyrosinase substrates. However, ortho-substituted compounds are usually described as inhibitors. The mechanism of action of tyrosinase on monophenols is complex, and if they are ortho-substituted, it is more complicated. It can be shown that many of these molecules can become substrates of the enzyme in the presence of catalytic o-diphenol, MBTH, or in the presence of hydrogen peroxide. Docking studies can help discern whether a molecule can behave as a substrate or inhibitor of the enzyme. Specifically, phenols such as thymol, carvacrol, guaiacol, eugenol, isoeugenol, and ferulic acid are substrates of tyrosinase, and docking simulations to the active center of the enzyme predict this since the distance of the peroxide oxygen from the oxy-tyrosinase form to the ortho position of the phenolic hydroxyl is adequate for the electrophilic attack reaction that gives rise to hydroxylation occurring.


Assuntos
Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase , Fenóis , Monofenol Mono-Oxigenase/química , Monofenol Mono-Oxigenase/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Fenóis/química , Fenóis/metabolismo , Especificidade por Substrato , Domínio Catalítico
6.
Brain ; 145(6): 1962-1977, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34957478

RESUMO

Focal cortical dysplasia is a highly epileptogenic cortical malformation with few treatment options. Here, we generated human cortical organoids from patients with focal cortical dysplasia type II. Using this human model, we mimicked some focal cortical dysplasia hallmarks, such as impaired cell proliferation, the presence of dysmorphic neurons and balloon cells, and neuronal network hyperexcitability. Furthermore, we observed alterations in the adherens junctions zonula occludens-1 and partitioning defective 3, reduced polarization of the actin cytoskeleton, and fewer synaptic puncta. Focal cortical dysplasia cortical organoids showed downregulation of the small GTPase RHOA, a finding that was confirmed in brain tissue resected from these patients. Functionally, both spontaneous and optogenetically-evoked electrical activity revealed hyperexcitability and enhanced network connectivity in focal cortical dysplasia organoids. Taken together, our findings suggest a ventricular zone instability in tissue cohesion of neuroepithelial cells, leading to a maturational arrest of progenitors or newborn neurons, which may predispose to cellular and functional immaturity and compromise the formation of neural networks in focal cortical dysplasia.


Assuntos
Epilepsia , Malformações do Desenvolvimento Cortical do Grupo I , Malformações do Desenvolvimento Cortical , Encéfalo , Humanos , Recém-Nascido , Neurônios
7.
Environ Res ; 217: 114776, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36403656

RESUMO

The excessive contamination of drinking water sources by pesticides has a pernicious impact on human health and the environment since only 0.1% of pesticides is utilized effectively to control the and the rest is deposited in the environment. Filtration by polymeric membranes has become a promising technique to deal with this problem; however, the scientific community, in the need to find better pesticide retention results, has begun to meddle in the functionalization of polymeric membranes. Given the great variety of membrane, polymer, and nanomaterial synthesis methods present in the market, the possibilities of obtaining membranes that adjust to different variables and characteristics related to a certain pesticide are relatively extensive, so it is expected that this technology will represent one of the main pesticide removal strategies in the future. In this direction, this review focused on, - the main characteristics of the nanomaterials and their impact on pristine polymeric membranes; - the removal performance of functionalized membranes; and - the main mechanisms by which membranes can retain pesticides. Based on these insights, the functionalized polymeric membranes can be considered as a promising technology in the removal of pesticides since the removal performance of this technology against pesticide showed a significant increase. Obtaining membranes that adjust to different variables and characteristics related to a certain pesticide are relatively extensive, so it is expected that functionalized membrane technology will represent one of the main pesticide removal strategies in the future.


Assuntos
Nanoestruturas , Praguicidas , Humanos , Praguicidas/análise , Filtração , Polímeros , Tecnologia
8.
Environ Monit Assess ; 195(12): 1496, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37982889

RESUMO

This investigation examines the transport of metal- and pesticide-polluted dust emitted by one of the most relevant agricultural areas of Northwestern Mexico. In the contaminated area, an excessive water extraction of the aquifer and seawater intrusion caused the abandonment of fields, which are pollutant-loaded dust emitters. We used air mass forward trajectories (HYSPLIT) model to obtain particle trajectories in the wind and the use of banned pesticides as geochemical tracers for dust transported by wind. Fifty dust samples from 10 agriculture fields and 26 roof dust of a city close to the agricultural area were analyzed for their contents of zirconium, lead, arsenic, zinc, copper, iron, manganese, vanadium, and titanium, by portable X-ray fluorescence. Nine pesticides were analyzed in the roof dust and agricultural soil samples by gas chromatography. Results show that the distribution of metals was significantly different between active and abandoned fields. Arsenic-lead-copper was mainly concentrated in abandoned fields, while zinc-iron-manganese-titanium was dominant in active fields. Two potential sources of metal contamination were found by principal component analysis (PCA): (I) a mixture of traffic and agricultural sources and (II) a group related to agricultural activities. The occurrence of banned pesticides in dust deposited on roofs collected at nearby cities confirms the atmospheric transport from the agricultural area. The HYSPLIT results indicated that the dust emitted from agricultural fields can reach up to the neighboring states of Sonora, Mexico, and the USA. The impacts that these emissions can have on human health should be studied in future research.


Assuntos
Arsênio , Praguicidas , Humanos , Cobre , Manganês , Titânio , Arizona , Monitoramento Ambiental , Agricultura , Metais , Zinco , Ferro , Poeira
9.
Sensors (Basel) ; 23(1)2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36616940

RESUMO

The evaluation of the biogenic amines (BAs) profile of different types of craft beers is herein presented. A previously developed and validated analytical method based on ion-pair chromatography coupled with potentiometric detection was used to determine the presence of 10 BAs. Good analytical features were obtained for all amines regarding linearity (R2 values from 0.9873 ± 0.0015 to 0.9973 ± 0.0015), intra- and inter-day precision (RSD lower than 6.9% and 9.7% for beer samples, respectively), and accuracy (recovery between 83.2-108.9%). Detection and quantification limits range from 9.3 to 60.5 and from 31.1 to 202.3 µg L-1, respectively. The validated method was applied to the analysis of four ale beers and one lager craft beer. Ethylamine, spermidine, spermine, and tyramine were detected in all analyzed samples while methylamine and phenylethylamine were not detected. Overall, pale ale beers had a significantly higher total content of BAs than those found in wheat pale and dark samples. A general least square regression model showed a good correlation between the total content of BAs and the brewing process, especially for Plato degree, mashing, and fermentation temperatures. Knowledge about the type of ingredients and manufacturing processes that contribute to higher concentrations of these compounds is crucial to ensuring consumer safety.


Assuntos
Cerveja , Aminas Biogênicas , Cerveja/análise , Aminas Biogênicas/análise , Cromatografia Líquida de Alta Pressão/métodos , Espermidina/análise , Espermina/análise
10.
Int J Neuropsychopharmacol ; 24(9): 734-748, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34165516

RESUMO

BACKGROUND: Minocycline (MIN) is a tetracycline with antioxidant, anti-inflammatory, and neuroprotective properties. Given the likely involvement of inflammation and oxidative stress (IOS) in schizophrenia, MIN has been proposed as a potential adjuvant treatment in this pathology. We tested an early therapeutic window, during adolescence, as prevention of the schizophrenia-related deficits in the maternal immune stimulation (MIS) animal model. METHODS: On gestational day 15, Poly I:C or vehicle was injected in pregnant Wistar rats. A total 93 male offspring received MIN (30 mg/kg) or saline from postnatal day (PND) 35-49. At PND70, rats were submitted to the prepulse inhibition test. FDG-PET and T2-weighted MRI brain studies were performed at adulthood. IOS markers were evaluated in frozen brain tissue. RESULTS: MIN treatment did not prevent prepulse inhibition test behavioral deficits in MIS offspring. However, MIN prevented morphometric abnormalities in the third ventricle but not in the hippocampus. Additionally, MIN reduced brain metabolism in cerebellum and increased it in nucleus accumbens. Finally, MIN reduced the expression of iNOS (prefrontal cortex, caudate-putamen) and increased the levels of KEAP1 (prefrontal cortex), HO1 and NQO1 (amygdala, hippocampus), and HO1 (caudate-putamen). CONCLUSIONS: MIN treatment during adolescence partially counteracts volumetric abnormalities and IOS deficits in the MIS model, likely via iNOS and Nrf2-ARE pathways, also increasing the expression of cytoprotective enzymes. However, MIN treatment during this peripubertal stage does not prevent sensorimotor gating deficits. Therefore, even though it does not prevent all the MIS-derived abnormalities evaluated, our results suggest the potential utility of early treatment with MIN in other schizophrenia domains.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Encefalopatias Metabólicas/tratamento farmacológico , Minociclina/farmacologia , Malformações do Sistema Nervoso/patologia , Transtornos do Neurodesenvolvimento/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Inibição Pré-Pulso/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Animais , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Encefalopatias Metabólicas/etiologia , Modelos Animais de Doenças , Feminino , Imageamento por Ressonância Magnética , Masculino , Minociclina/administração & dosagem , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/etiologia , Transtornos do Neurodesenvolvimento/induzido quimicamente , Transtornos do Neurodesenvolvimento/imunologia , Tomografia por Emissão de Pósitrons , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/imunologia , Ratos , Ratos Wistar , Esquizofrenia/induzido quimicamente , Esquizofrenia/imunologia
11.
Eur J Neurol ; 28(3): 1056-1081, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33180965

RESUMO

BACKGROUND AND PURPOSE: Minocycline is a broad-spectrum antibiotic, effective as a chronic treatment for recurrent bacterial infections. Beyond its antibiotic action, minocycline also has important anti-inflammatory, antioxidant and antiapoptotic properties. Its efficacy has therefore been evaluated in many neurodegenerative and psychiatric diseases that have an inflammatory basis. Our aim was to review preclinical and clinical studies performed in neurological and psychiatric diseases whose treatment involved the use of minocycline and thereby to discern the possible beneficial effect of minocycline in these disorders. METHODS: Completed and ongoing preclinical studies and clinical trials of minocycline for both neurodegenerative diseases and psychiatric disorders, published from January 1995 to January 2020, were identified through searching relevant databases (https://www.ncbi.nlm.nih.gov/pubmed/, https://clinicaltrials.gov/). A total of 74 preclinical studies and 44 clinical trials and open-label studies were selected. RESULTS: The results of the nearly 20 years of research identified are diverse. While minocycline mostly proved to be effective in animal models, clinical results showed divergent outcomes, with positive results in some studies counterbalanced by a number of cases with no significant improvements. Specific data for each disease are further individually described in this review. CONCLUSIONS: Despite minocycline demonstrating antioxidant and anti-inflammatory effects, discrepancies between preclinical and clinical data indicate that we should be cautious in analyzing the outcomes. Improving and standardizing protocols and refining animal models could help us to determine if minocycline really is a useful drug in the treatment of these pathologies.


Assuntos
Transtornos Mentais , Doenças Neurodegenerativas , Animais , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Humanos , Transtornos Mentais/tratamento farmacológico , Minociclina/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico
12.
Sensors (Basel) ; 21(17)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34502770

RESUMO

A supramolecular atropine sensor was developed, using cucurbit[6]uril as the recognition element. The solid-contact electrode is based on a polymeric membrane incorporating cucurbit[6]uril (CB[6]) as an ionophore, 2-nitrophenyl octyl ether as a solvent mediator, and potassium tetrakis (4-chlorophenyl) borate as an additive. In a MES-NaOH buffer at pH 6, the performance of the atropine sensor is characterized by a slope of (58.7 ± 0.6) mV/dec with a practical detection limit of (6.30 ± 1.62) × 10-7 mol/L and a lower limit of the linear range of (1.52 ± 0.64) × 10-6 mol/L. Selectivity coefficients were determined for different ions and excipients. The obtained results were bolstered by the docking and spectroscopic studies which demonstrated the interaction between atropine and CB[6]. The accuracy of the potentiometric analysis of atropine content in certified reference material was evaluated by the t-Student test. The herein proposed sensor answers the need for reliable methods providing better management of this hospital drug shelf-life while reducing its flush and remediation costs.


Assuntos
Atropina , Polímeros , Eletrodos , Humanos , Ionóforos , Potenciometria
13.
Environ Geochem Health ; 42(2): 499-511, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31372863

RESUMO

Arsenic exposure in adults has been associated with increased serum matrix metalloproteinase-9 (MMP-9), a biomarker which is associated with chronic respiratory disease, lung inflammation, cardiovascular disease and cancer. The objective of this study was to evaluate the association between serum MMP-9 levels in children, urinary arsenic, arsenic chronic daily intake (CDI) and arsenic exposure from playground dust. This cross-sectional study examined 127 children from five elementary schools, in Hermosillo, Sonora, Mexico. Arsenic was analyzed in the dust using a portable X-ray fluorescence (XRF) analyzer. Total urinary arsenic was determined by inductively coupled plasma/optical emission spectrometry. Serum was analyzed for MMP-9 using ELISA. Arsenic levels in playground dust averaged 16.9 ± 4.6 mg/kg. Urinary arsenic averaged 34.9 ± 17.1 µg/L. Arsenic concentration in playground dust was positively associated with serum MMP-9 levels in crude analyses and after adjustment (P < 0.01), MMP-9 and CDI were positively associated only after adjustment (P < 0.01), and no association was found between MMP-9 and urinary arsenic. In conclusion, our study showed an association in children between serum MMP-9 levels and playground dust arsenic concentrations. Therefore, exposure to arsenic in dust where children spend significant time may manifest toxic effects.


Assuntos
Arsênio/toxicidade , Poeira , Biomarcadores Ambientais , Poluentes Ambientais/toxicidade , Metaloproteinase 9 da Matriz/sangue , Adolescente , Arsênio/urina , Criança , Pré-Escolar , Estudos Transversais , Poeira/análise , Exposição Ambiental/análise , Poluentes Ambientais/urina , Feminino , Humanos , Masculino , México , Instituições Acadêmicas
14.
J Artif Organs ; 22(1): 14-28, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30006787

RESUMO

End-stage renal disease is a growing health problem with increasing prevalence and high health care costs. Patients suffering from end-stage renal disease exhibit higher morbidity and mortality rates compared to the general population. These patients, who are treated using hemodialysis, typically suffer from anemia, inflammation, and oxidative stress. Inadequate dialyzer membrane biocompatibility exacerbates these negative side effects. Modifications of the composition of hemodialysis membranes have improved their biocompatibility and improve the patients' quality of life. Recently, the use of dialyzer membranes coated with bioactive compounds has also been proposed to further ameliorate dialysis-associated problems. Based on a survey of the current literature, application of bioactive membranes decreases the inflammation and oxidative stress of patients treated with hemodialysis.


Assuntos
Materiais Biocompatíveis , Falência Renal Crônica/terapia , Membranas Artificiais , Diálise Renal/efeitos adversos , Antioxidantes/administração & dosagem , Celulose , Humanos , Inflamação/etiologia , Inflamação/prevenção & controle , Estresse Oxidativo , Proteínas Secretadas Inibidoras de Proteinases , Qualidade de Vida , Ácido Tióctico/administração & dosagem , Vitamina E/administração & dosagem
15.
FASEB J ; 31(2): 544-555, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28148778

RESUMO

The observation of acetylcholinesterase (AChE) type H (AChEH), which is the predominant AChE variant in visceral organs and immune cells, in lipid rafts of muscle supports functional reasons for the raft targeting of glypiated AChEH The search for these reasons revealed that liver AChE activity is mostly confined to rafts and that the liver is able to make N-extended AChE variants and target them to rafts. These results prompted us to test whether AChE and muscarinic receptors existed in the same raft. Isolation of flotillin-2-rich raft fractions by their buoyancy in sucrose gradients, followed by immunoadsorption and matrix-assisted laser desorption ionization-time of flight-mass spectrometry application, gave the following results: 1) most hepatic AChE activity emanates from AChE-H mRNA, and its product, glypiated AChEH, accumulates in rafts; 2) N-extended N-AChE readthrough variant, nonglypiated N-AChEH, and N-AChE tailed variant were all identified in liver rafts; and 3) M3 AChRs were observed in rafts, and coprecipitation of raft-confined N-AChE and M3 receptors by using anti-M3 antibodies showed that enzyme and receptor reside in the same raft unit. A raft domain that harbors tightly packed muscarinic receptor and AChE may represent a molecular device that, by means of which, the intensity and duration of cholinergic inputs are regulated.-Montenegro, M. F., Cabezas-Herrera, J., Campoy, F. J., Muñoz-Delgado, E., Vidal, C. J. Lipid rafts of mouse liver contain nonextended and extended acetylcholinesterase variants along with M3 muscarinic receptors.


Assuntos
Acetilcolinesterase/classificação , Acetilcolinesterase/metabolismo , Regulação Enzimológica da Expressão Gênica/fisiologia , Variação Genética , Microdomínios da Membrana/fisiologia , Receptor Muscarínico M3/metabolismo , Animais , Encéfalo/enzimologia , Fígado/enzimologia , Camundongos , Miocárdio/enzimologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor Muscarínico M3/genética
16.
Epilepsy Behav ; 82: 164-169, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29649723

RESUMO

In this study, we aimed to evaluate the attentional and executive functions in patients with benign childhood epilepsy with centrotemporal spikes (BCECTS) with and without attention-deficit hyperactivity disorder (ADHD) compared with controls and compared with patients with ADHD without epilepsy. We evaluated 12 patients with BCECTS and ADHD (66.7% boys; mean age of 9.67years); 11 children with non-ADHD BCECTS (63.6% boys; mean age of 11.91years); 20 healthy children (75% boys; mean age of 10.15years); and 20 subjects with ADHD without epilepsy (60% boys; mean age of 10.9years). We used a comprehensive battery of neuropsychological tests to evaluate attentional and executive functions in their broad domains. Patients with BCECTS and ADHD had worse performance in Conners' Continuous Performance Test II (reaction time standard error [p=0.008], variability [p=0.033], perseverations [p=0.044] and in reaction time interstimuli interval [p=0.016]). Patients with ADHD showed worse performance in Trail Making Test B errors [p=0.012]. In conclusion, patients with BCECTS and ADHD had worse executive and attentional performance compared with controls than non-ADHD patients with BCECTS. Regardless of the presence of epilepsy, ADHD also negatively impacted executive and attentional functions but in different executive subdomains compared with patients with epilepsy.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Epilepsia Rolândica/psicologia , Função Executiva/fisiologia , Adolescente , Atenção/fisiologia , Estudos de Casos e Controles , Criança , Cognição/fisiologia , Eletroencefalografia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Tempo de Reação , Teste de Sequência Alfanumérica
17.
Exp Parasitol ; 189: 28-33, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29673623

RESUMO

The presence of free-living amoebae of the genera Naegleria, Acanthamoeba and Balamuthia, which contain pathogenic species for humans and animals, has been demonstrated several times and in different natural aquatic environments in the northwest of Mexico. With the aim of continuing the addition of knowledge about immunology of pathogenic free-living amoebae, 118 sera from children and adolescents, living in three villages, were studied. Humoral IgG response against B. mandrillaris, N. fowleri and Acanthamoeba sp. genotype T4, was analyzed in duplicate to titers 1: 100 and 1: 500 by enzyme-linked immunosorbent assay (ELISA). Children and adolescents ages ranged between 5 and 16 years old, with a mean of 9 years old, 55% males. All tested sera were positive for the 1: 100 dilution, and in the results obtained with the 1: 500 dilution, 116 of 118 (98.3%) were seropositive for N. fowleri, 101 of 118 (85.6%) were seropositive for Acanthamoeba sp. genotype T4, and 43 of 118 (36.4%) were seropositive for B. mandrillaris. The statistical analysis showed different distributions among the three communities and for the three species of pathogenic free-living amoebae, including age. Lysed and complete cells used as Balamuthia antigens gave differences in seropositivity.


Assuntos
Acanthamoeba/imunologia , Anticorpos Antiprotozoários/sangue , Balamuthia mandrillaris/imunologia , Infecções Protozoárias do Sistema Nervoso Central/epidemiologia , Naegleria fowleri/imunologia , Adolescente , Amebíase/epidemiologia , Amebíase/imunologia , Infecções Protozoárias do Sistema Nervoso Central/imunologia , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Criança , Pré-Escolar , Ecossistema , Encefalite/epidemiologia , Encefalite/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , México/epidemiologia , População Rural
18.
Int J Neuropsychopharmacol ; 20(12): 988-993, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29016806

RESUMO

Background: Glutamatergic neurotransmission has emerged as a novel target in antidepressant drug development, with a critical role of the ventral anterior cingulate cortex. We recently reported that blockade of the astrocytic glutamate transporter GLT-1 with dihydrokainic acid in infralimbic cortex (rodent equivalent of ventral anterior cingulate cortex), but not in the adjacent prelimbic cortex, evoked robust antidepressant-like effects through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation and increased serotonin release. Methods: 2-deoxy-2-[18F]-fluoro-D-glucose-positron emission tomography and computed tomography in 36 male Wistar rats microinfused bilaterally in prelimbic cortex or infralimbic cortex with dihydrokainic acid or vehicle. Results: Dihydrokainic acid microinfusion in infralimbic cortex and prelimbic cortex evoked dramatically different regional patterns of subcortical activity. In infralimbic cortex, dihydrokainic acid selectively affected midbrain areas, whereas in prelimbic cortex it affected the basal ganglia, the thalamus, and both superior and inferior colliculi. Conclusions: These results highlight the differential connectivity of infralimbic and prelimbic cortex with subcortical brain regions and support the involvement of infralimbic cortex-midbrain pathway in the antidepressant-like effects of dihydrokainic acid.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/farmacologia , Transportador 2 de Aminoácido Excitatório/metabolismo , Ácido Caínico/análogos & derivados , Animais , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Transportador 2 de Aminoácido Excitatório/antagonistas & inibidores , Fluordesoxiglucose F18 , Ácido Caínico/farmacologia , Masculino , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Tomografia por Emissão de Pósitrons , Ratos , Ratos Wistar , Tomógrafos Computadorizados
19.
Epilepsy Behav ; 72: 173-177, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28622557

RESUMO

RATIONALE: Benign Epilepsy of Childhood with Centrotemporal Spikes (BECTS) and temporal lobe epilepsy (TLE) represent two distinct models of focal epilepsy of childhood. In both, there is evidence of executive dysfunction. The purpose of the present study was to identify particular deficits in the executive function that would distinguish children with BECTS from children with TLE. METHODS: We prospectively evaluated 19 consecutive children and adolescents with TLE with hippocampal sclerosis (HS) (57.9% male; mean 11.74years [SD 2.05]; mean IQ 95.21 [SD 15.09]), 19 with BECTS (36.8% male; mean 10.95years [SD 2.33]; mean IQ 107.40 [SD 16.01]), and 21 age and gender-matched controls (33.3% male; mean 11.86years [SD 2.25]; mean IQ 108.67 [15.05]). All participants underwent a neuropsychological assessment with a comprehensive battery for executive and attentional functions. We used ANOVA and chi-square to evaluate differences on demographic aspects among groups (BECTS, TLE-HS, and control groups). Group comparisons on continuous variables were complemented by MANOVA and Bonferroni posthoc comparisons. RESULTS: Patients with BECTS had worse performance than controls in: Matching Familiar Figures Test, time (p=0.001); Matching Familiar Figures Test, time×errors index (p<0.001); Verbal Fluency for foods (p=0.038); Trail Making Test, part B time (p=0.030); Trail Making Test, part B number of errors (p=0.030); and WCST, number of categories achieved (p=0.043). Patients with BECTS had worse performance than patients with TLE-HS on Matching Familiar Figures Test, time (p=0.004), and Matching Familiar Figures Test, time×errors index (p<0.001). Patients with TLE-HS had worse performance than controls on the following tests: Verbal Fluency for foods (p=0.004); Wisconsin Card Sorting Test, the number of categories achieved (p<0.001); and Wisconsin Card Sorting Test, the number of perseverative errors (p=0.028). Patients with TLE-HS had worse performance than patients with BECTS on Digit Backward (p=0.002); and the Wisconsin Card Sorting Test, the number of perseverative errors (p<0.001). CONCLUSIONS: Patients with TLE and BECTS present distinct cognitive profiles. Patients with TLE-HS had worse performance in mental flexibility, concept formation, and working memory compared to BECTS. Patients with BECTS had worse inhibitory control compared to children with TLE-HS. Both TLE-HS and BECTS had a higher number of errors on an inhibitory control test. However, patients with BECTS had a slower mental processing even when compared to patients with TLE-HS. Rehabilitation programs for children with epilepsy must include children with benign epilepsies and must take into account the epileptic syndrome and its particular neurocognitive phenotype.


Assuntos
Potenciais de Ação/fisiologia , Epilepsia Rolândica/diagnóstico por imagem , Epilepsia Rolândica/psicologia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/psicologia , Função Executiva/fisiologia , Adolescente , Criança , Formação de Conceito/fisiologia , Epilepsia Rolândica/fisiopatologia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Humanos , Masculino , Memória de Curto Prazo/fisiologia , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Testes Neuropsicológicos , Estudos Prospectivos , Teste de Sequência Alfanumérica
20.
J Org Chem ; 81(8): 3296-302, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26991893

RESUMO

The application of organoboron compounds as light-absorbing or light-emitting species in areas as relevant as organic electronics or biomedicine has motivated the search for new materials which contribute to the progress of those applications. This article reports the synthesis of four-coordinate boron complexes based on the unexplored 7-(azaheteroaryl)indole ligands. An easy synthetic approach has enabled the fine-tuning of the electronic structure of the organoboron species by modifying a heteroaromatic component in the conjugated system. Furthermore, a comprehensive characterization by X-ray diffraction, absorption and emission spectroscopy, both in solution and in the solid state, cyclic voltammetry, and computational methods has evidenced the utility of this simple strategy. Large Stokes shifts have been achieved in solid thin-films which show a range of emitted light from blue to orange. The synthesized compounds have been used as biocompatible fluorophores in cell bioimaging.

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