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1.
Chemistry ; 30(36): e202400890, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38687053

RESUMEN

It is well-known that people suffering from hyperglycemia have a higher propensity to develop Parkinson's disease (PD). One of the most plausible mechanisms linking these two pathologies is the glycation of neuronal proteins and the pathological consequences of it. α-Synuclein, a key component in PD, can be glycated at its fifteen lysine. In fact, the end products of this process have been detected on aggregated α-synuclein isolated from in vivo. However, the consequences of glycation are not entirely clear, which are of crucial importance to understand the mechanism underlying the connection between diabetes and PD. To better clarify this, we have here examined how methylglyoxal (the most important carbonyl compound found in the cytoplasm) affects the conformation and aggregation propensity of α-synuclein, as well as its ability to cluster and fuse synaptic-like vesicles. The obtained data prove that methylglyoxal induces the Lys-Lys crosslinking through the formation of MOLD. However, this does not have a remarkable effect on the averaged conformational ensemble of α-synuclein, although it completely depletes its native propensity to form soluble oligomers and insoluble amyloid fibrils. Moreover, methylglyoxal has a disrupting effect on the ability of α-synuclein to bind, cluster and fusion synaptic-like vesicles.


Asunto(s)
Piruvaldehído , alfa-Sinucleína , alfa-Sinucleína/química , alfa-Sinucleína/metabolismo , Piruvaldehído/química , Piruvaldehído/metabolismo , Humanos , Enfermedad de Parkinson/metabolismo , Agregado de Proteínas/efectos de los fármacos , Conformación Proteica , Glicosilación , Lisina/química , Amiloide/química , Amiloide/metabolismo
2.
J Toxicol Environ Health A ; 86(4): 87-102, 2023 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-36756732

RESUMEN

The aim of this study was to determine the oxidative/antioxidative effects, modulatory and selective potential of α-tocopherol (vitamin E) on antineoplastic drug-induced toxicogenetic damage. The toxicity, cytotoxicity and genotoxicity induced by antineoplastic agents cyclophosphamide (CPA) and doxorubicin (DOX) was examined utilizing as models Saccharomyces cerevisiae, Allium cepa, Artemia salina and human peripheral blood mononuclear cells (PBMCs) in the presence of α-tocopherol. For these tests, concentrations of α- tocopherol 100 IU/ml (67mg/ml), CPA 20 µg/ml, DOX 2 µg/ml were used. The selectivity of α-tocopherol was assessed by the MTT test using human mammary gland non-tumor (MCF10A) and tumor (MCF-7) cell lines. Data showed cytoplasmic and mitochondrial oxidative damage induced by CPA or DOX was significantly diminished by α-tocopherol in S. cerevisiae. In addition, the toxic effects on A. salina and cytotoxic and mutagenic effects on A. cepa were significantly reduced by α-tocopherol. In PBMCs, α-tocopherol alone did not markedly affect these cells, and when treated in conjunction with CPA or DOX, α-tocopherol reduced the toxicogenetic effects noted after antineoplastic drug administration as evidenced by decreased chromosomal alterations and lowered cell death rate. In human mammary gland non-tumor and tumor cell lines, α-tocopherol produced selective cytotoxicity with 2-fold higher effect in tumor cells. Evidence indicates that vitamin E (1) produced anti-cytotoxic and anti-mutagenic effects against CPA and DOX (2) increased higher selectivity toward tumor cells, and (3) presented chemoprotective activity in PBMCs.


Asunto(s)
Antineoplásicos , alfa-Tocoferol , Humanos , alfa-Tocoferol/farmacología , Saccharomyces cerevisiae , Leucocitos Mononucleares , Antineoplásicos/toxicidad , Antineoplásicos/uso terapéutico , Doxorrubicina/toxicidad , Ciclofosfamida/toxicidad , Vitamina E
3.
J Nat Prod ; 85(8): 2044-2051, 2022 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-35969814

RESUMEN

Viral infections affect several million patients annually. Although hundreds of viruses are known to be pathogenic, only a few can be treated in the clinic with available antiviral drugs. Naturally based pharmacotherapy may be a proper alternative for treating viral diseases. Several natural and semisynthetic abietane-type diterpenoids have shown important antiviral activities. In this study, a biological evaluation of a number of either C-18- or C-19-functionalized known semisynthetic abietanes against Zika virus, Dengue virus, Herpes virus simplex type 1, and Chikungunya virus are reported. Semisynthetic abietane ferruginol and its analogue 18-(phthalimid-2-yl)ferruginol displayed broad-spectrum antiviral properties. The scale-up synthesis of this analogue has been optimized for further studies and development. This molecule displayed an EC50 between 5.0 and 10.0 µM against Colombian Zika virus strains and EC50 = 9.8 µM against Chikungunya virus. Knowing that this ferruginol analogue is also active against Dengue virus type 2 (EC50 = 1.4 µM, DENV-2), we can conclude that this compound is a promising broad-spectrum antiviral agent paving the way for the development of novel antivirals.


Asunto(s)
Virus Chikungunya , Virus , Infección por el Virus Zika , Virus Zika , Abietanos/farmacología , Antivirales , Humanos , Replicación Viral , Infección por el Virus Zika/tratamiento farmacológico
4.
Adicciones ; 33(2): 121-136, 2021 Mar 31.
Artículo en Inglés, Español | MEDLINE | ID: mdl-32677691

RESUMEN

The objective was to evaluate the risk of presenting an alcohol use disorder (AUD) in outpatient psychiatric units and compare it with drug addiction outpatient units and with healthy controls in the same administrative health area. An observational, descriptive, multicenter study was carried out in which a total of 1054 participants were evaluated. Data were obtained by means of the camouflaged CAGE questionnaire, which consists of 4 basic questions camouflaged with 8 other questions about healthy lifestyle habits. Cut-off points 1 and 2 were considered.Of the total number of participants, 588 were psychiatric outpatients, 153 outpatients from addiction centers and 313 healthy individuals. The mean age of the total sample was 45.8 years and the percentage of men was 53.2%. Of the total sample, 38.3% scored ≥1, as did 34.2% of psychiatric patients, 72.5% of drug addicts and 29.4% of healthy people. The ≥2 cut-off was reached by 26.6% of the total sample, 22.6% of psychiatric patients, 64.7% of drug addicts and 15.3% of healthy subjects. The participants with the highest percentage of ≥1 scores were men (48.8%), those younger than 30 years (50%), those with a diagnosis of alcohol use disorder (95.9%) and ADHD (83.3%).Psychiatric patients are at a higher risk of having an AUD than the healthy subjects, although lower than those who are drug addicts, and the CAGE questionnaire is a simple and useful tool to detect the risk patients have to suffer the condition under study.


El objetivo fue evaluar el riesgo de presentar un trastorno por uso de alcohol (TUA) en las consultas psiquiátricas ambulatorias y compararlo con las consultas de drogodependencias y con individuos sanos de la misma zona de salud. Se realizó un estudio observacional, descriptivo, multicéntrico, en el que fueron incluidos un total de 1054 participantes. Se utilizó el cuestionario CAGE camuflado para la obtención de los datos, que consta de 4 preguntas básicas camufladas con otras 8 preguntas sobre hábitos de vida saludables. Se consideraron los puntos de corte de 1 y 2.Del total de participantes, 588 eran pacientes psiquiátricos ambulatorios, 153 de los centros de drogodependencias ambulatorios y 313 sanos. La edad media de la muestra fue de 45,8 años y el porcentaje de hombres fue del 53,2%. El 38,3% de los participantes presentaron una puntuación ≥1, el 34,2% en las consultas psiquiátricas, el 72,5% en las de drogodependencias y el 29,4% en sanos. El 26,6% presentaron una puntuación ≥2, el 22,6% en las consultas psiquiátricas, el 64,7% en las de drogodependencias y el 15,3% en sanos. Los que presentaron mayor porcentaje de puntuación ≥1 fueron los hombres (48,8%), los menores de 30 años (50%), y los que tenían un diagnóstico de trastorno por uso de alcohol (95,9%) y de TDAH (83,3%).Los pacientes psiquiátricos presentan un mayor riesgo de presentar un TUA que los individuos sanos, aunque menor que los drogodependientes, siendo el cuestionario CAGE una herramienta sencilla y útil para detectar el riesgo de presentarlos.


Asunto(s)
Alcoholismo , Consumidores de Drogas , Trastornos Relacionados con Sustancias , Alcoholismo/diagnóstico , Alcoholismo/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Grupos de Población , Trastornos Relacionados con Sustancias/diagnóstico , Trastornos Relacionados con Sustancias/epidemiología , Encuestas y Cuestionarios
5.
Neuroendocrinology ; 110(11-12): 1042-1054, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31945763

RESUMEN

Linaclotide is a synthetic peptide approved by the FDA for the treatment of constipation-predominant irritable bowel syndrome and chronic constipation. Linaclotide binds and activates the transmembrane receptor guanylate cyclase 2C (Gucy2c). Uroguanylin (UGN) is a 16 amino acid peptide that is mainly secreted by enterochromaffin cells in the duodenum and proximal small intestine. UGN is the endogenous ligand of Gucy2c and decreases body weight in diet-induced obese (DIO) mice via the activation of the thermogenic program in brown adipose tissue. Therefore, we wanted to evaluate whether oral linaclotide could also improve DIO mice metabolic phenotype. In this study, we have demonstrated that DIO mice orally treated with linaclotide exhibited a significant reduction of body weight without modifying food intake. Linaclotide exerts its actions through the central nervous system, and more specifically, via Gucy2c receptors located in the mediobasal hypothalamus, leading to the activation of the sympathetic nervous system to trigger the thermogenic activity of brown fat stimulating energy expenditure. These findings indicate for first time that, in addition to its effects at intestinal level to treat irritable bowel syndrome with constipation and chronic constipation, linaclotide also exerts a beneficial effect in whole body metabolism.


Asunto(s)
Tejido Adiposo Pardo/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Agonistas de la Guanilato Ciclasa C/farmacología , Hipotálamo/efectos de los fármacos , Obesidad/tratamiento farmacológico , Péptidos/farmacología , Receptores de Enterotoxina/efectos de los fármacos , Termogénesis/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Dieta Alta en Grasa , Masculino , Ratones , Ratones Endogámicos C57BL
6.
Int J Eat Disord ; 53(6): 964-971, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32333613

RESUMEN

BACKGROUND: Patients with eating disorders (ED) are very sensitive and responsive to psychosocial stress. Stress response includes changes in immune cell distribution and may be modulated by the capability to cope with stressors. Thus, the present study sought to analyze the association between coping strategies and immune response (natural killer [NK] cell redistribution following psychosocial stress) in patients with anorexia nervosa (AN) and bulimia nervosa (BN) and healthy controls (HC). METHOD: Twenty-four AN patients, 29 BN patients, and 58 HC were studied. A multidimensional assessment tool, the COPE Inventory, was used to assess coping strategies. The number of NK cells was quantified in peripheral blood before and after the application of the Trier Social Stress Test (TSST). Potentially mediating variables, such as weight status, severity of eating pathology, depression, anxiety, and impulsivity were controlled. RESULTS: The three groups differed in intensity and direction of cell redistribution: The TSST was followed in BN patients by a significant decrease in the number of NK cells, whereas HC displayed a moderate decrease and AN a clear increase. Specific correlations between coping strategies and NK cell mobilization were found, especially in BN patients (positive for "planning" and negative for "substance abuse"). CONCLUSION: Recognition and subsequent modification of the dysfunctional coping strategies used by patients with ED could contribute to improving their immune status, strengthening their resilience and increasing their ability to overcome the disease.


ANTECEDENTES: Los pacientes con trastornos de la conducta alimentaria (TCA) son muy sensibles y respondedores ante el estrés psicosocial. La respuesta al estrés incluye cambios en la distribución de las células inmunes y parece estar modulada por la capacidad de afrontamiento del individuo. En este contexto, el objetivo del presente estudio fue analizar la asociación entre estrategias de afrontamiento y redistribución tras el estrés de las células agresoras naturales (natural killer, NK) en pacientes de sexo femenino con anorexia nervosa (AN) y bulimia nervosa (BN), y controles sanos (CS). MÉTODO: Treinta y cuatro pacientes con AN, 29 pacientes con BN y 58 CS fueron estudiados. Para evaluar las estrategias de afrontamiento se utilizó un instrumento multidimensional, el Inventario COPE. El número de células NK en sangre periférica fue cuantificado antes y después de la aplicación del Trier Social Stress Test (TSST). Las posibles variables mediadoras, como el estado ponderal, la gravedad de la patología alimentaria, depresión, ansiedad e impulsividad fueron control. RESULTADOS: Los tres grupos difirieron en la intensidad y la dirección de la redistribución de células NK: el TSST fue seguido de una notable reducción en el número de células NK en las pacientes con BN, de una disminución moderada en las CS y de un claro incremento en las pacientes con AN. Se encontraron correlaciones específicas entre estrategias de afrontamiento y movilización de células NK, especialmente en las pacientes con BN (positiva para "planificación" y negativa para "abuso de sustancias"). CONCLUSIÓN: El reconocimiento y la modificación consiguiente de las estrategias de afrontamiento disfuncionales utilizadas por las pacientes con TCA pueden contribuir a mejorar su estado inmunológico, incrementando su resistencia y su capacidad para superar la enfermedad.


Asunto(s)
Adaptación Psicológica/fisiología , Trastornos de Alimentación y de la Ingestión de Alimentos/complicaciones , Células Asesinas Naturales/metabolismo , Estrés Psicológico/psicología , Adulto , Bulimia Nerviosa/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Femenino , Humanos , Adulto Joven
7.
Public Health Nutr ; 23(1): 13-21, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31511116

RESUMEN

OBJECTIVE: The purpose of this study was to analyse the reliability and validity of a semi-quantitative FFQ to assess food group consumption in South American children and adolescents. DESIGN: The SAYCARE (South American Youth/Child cARdiovascular and Environmental) study is an observational, multicentre, feasibility study performed in a sample of 3- to 18-year-old children and adolescents attending private and public schools from six South American countries. Participants answered the FFQ twice with a two-week interval and three 24-h dietary recalls. Intraclass and Spearman's correlations, weighted Cohen's kappa (κw), percentage of agreement and energy-adjusted Pearson's correlation coefficients were calculated. SETTING: Seven cities in South America (Buenos Aires, Lima, Medelin, Montevideo, Santiago, Sao Paulo and Teresina). SUBJECTS: A sample of 200 children and 244 adolescents for reliability analyses and 252 children and 244 adolescents for validity analyses were included. RESULTS: Depending on the food group, for children and adolescents, reliability analyses resulted in Spearman's coefficients from 0·47 to 0·73, intraclass correlation coefficients from 0·66 to 0·99, κw coefficients from 0·35 to 0·63, and percentage of agreement between 72·75 and 83·52 %. In the same way, validity analyses resulted in Spearman's coefficients from 0·17 to 0·37, energy-adjusted Pearson's coefficients from 0·17 to 0·61, κw coefficients from 0·09 to 0·24, and percentages of agreement between 45·79 and 67·06 %. CONCLUSION: The SAYCARE FFQ achieved reasonable reliability and slight-moderate validity for almost all food groups intakes. Accordingly, it can be used for the purpose of ranking the intake of individuals within a population.


Asunto(s)
Fenómenos Fisiológicos Nutricionales Infantiles , Encuestas sobre Dietas/normas , Dieta/métodos , Adolescente , Fenómenos Fisiológicos Nutricionales de los Adolescentes , Niño , Preescolar , Registros de Dieta , Ingestión de Energía , Conducta Alimentaria , Femenino , Humanos , Masculino , Recuerdo Mental , Evaluación Nutricional , Reproducibilidad de los Resultados , América del Sur
8.
Int J Food Sci Nutr ; 71(5): 529-539, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31694434

RESUMEN

Studies have shown synergistic and independent effects of leucine and resveratrol (RSV) as possible therapeutic agents to ameliorate metabolic disorders. Thus, the objective of this study was to investigate the effects of supplementation with leucine and RSV, alone and in combination, on metabolic changes in white adipose tissue of neonatally STZ-induced diabetic rats. After weaning, the rats were treated with trans-resveratrol (0.6 mg/kg/dose) and/or leucine (1.35 mg/kg/dose) administered orally. The animals were euthanized at age 16 weeks for blood analyses. Subcutaneous (SC), periepididymal (PE) and retroperitoneal (RP) fat pads were weighed. Adipocytes from PE and RP pads were isolated for morphometric analysis. Long-term supplementation with RSV promoted adiposity recovery, prevented hypoinsulinemia and improved the metabolic profile of the diabetic rats. However, some of these effects were impaired when RSV was associated with leucine. The diabetic rats supplemented with leucine alone showed no significant improvement in metabolic disorders.


Asunto(s)
Tejido Adiposo Blanco/metabolismo , Glucemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Interacciones Farmacológicas , Hipoglucemiantes/farmacología , Leucina/farmacología , Resveratrol/farmacología , Adipocitos , Tejido Adiposo , Adiposidad , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Suplementos Dietéticos , Frutas/química , Hipoglucemiantes/uso terapéutico , Insulina/sangre , Resistencia a la Insulina , Leucina/uso terapéutico , Masculino , Fitoterapia , Ratas , Resveratrol/uso terapéutico
9.
Eur Eat Disord Rev ; 28(6): 724-738, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32770610

RESUMEN

OBJECTIVES: The study aimed to examine whether dissociation and attitudes towards change were associated with the psychopathology in patients with eating disorders (EDs) at 1-year follow-up. METHOD: The study included 110 females with anorexia nervosa and bulimia nervosa (48 and 62 respectively). At the beginning of the study and 1 year later, they were assessed by means of the following questionnaires: Dissociative Experiences Scale, Attitudes Towards Change (ACTA), State-Trait Anxiety Inventory, Rosenberg Self-Esteem Scale, Beck Depression Inventory, Eating Attitude Test, Bulimic Investigatory Test Edinburgh and Body Shape Questionnaire (BSQ). RESULTS: No statistically significant differences were found between both diagnostic groups regarding dissociation scores. The ACTA at baseline, specifically for patients in the contemplation stage, mediate the effect of dissociation on the psychopathological outcome. DISCUSSION: These findings suggest that dissociation might be a transdiagnostic feature related to the EDs outcome. The psychotherapeutic framework must take it into account, particularly in patients in the contemplation stage.


Asunto(s)
Anorexia Nerviosa/complicaciones , Anorexia Nerviosa/terapia , Bulimia Nerviosa/complicaciones , Bulimia Nerviosa/terapia , Trastornos Disociativos/etiología , Trastornos de Alimentación y de la Ingestión de Alimentos/complicaciones , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Psicopatología/métodos , Adulto , Anorexia Nerviosa/psicología , Actitud , Bulimia Nerviosa/psicología , Trastornos Disociativos/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Femenino , Humanos , Masculino , Resultado del Tratamiento , Adulto Joven
10.
Medicina (Kaunas) ; 55(6)2019 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-31216737

RESUMEN

Background and objective: The assessment of physical fitness has become a necessary issue in epidemiological studies, since a reduction in fitness is directly associated with early mortality. Therefore, the development of simple, accurate, and inexpensive methods is necessary to measure physical fitness. This study aimed to determine the reliability and validity of the criteria and constructs of the International Fitness Scale (IFIS), Portuguese version, in Brazilian pediatric populations. Methods: A total of 190 children aged 3-10 years and 110 adolescents aged 11-17 years were enrolled in an observational study of reliability and validity. For reliability, the participants completed a questionnaire twice (with an interval of 15 days). To test the criterion validity, we analyzed the agreement between the questionnaire and physical tests (20-m shuttle run test, handgrip strength, standing long jump tests, 4 × 10-m shuttle run test, and back-saver sit and reach test), and the construct validity was estimated by agreement between the questionnaire and high blood pressure. The reliability was analyzed by kappa coefficients. The agreement between the testing and retesting of the questionnaire was evaluated by kappa coefficients. We applied a 2 × 2 table to estimate the specificity, sensitivity, and accuracy of the questionnaire. Results: The mean age of the children was 6.7 years (n = 190), and for the adolescents it was 14.6 years (n = 110). The questionnaire reliability showed an almost perfect score (κ ≥ 0.93 in children and κ ≥ 0.88 in adolescents). The questionnaire showed moderate criterion validity (κ ≥ 0.40 in children and adolescents) as well as moderate construct validity (κ ≥ 0.40) in the components of general conditioning, cardiorespiratory capacity, muscular strength, and speed/agility in children and in the components of cardiorespiratory capacity, muscle strength, and speed/agility in adolescents. The questionnaire was a sensitive method for measuring physical fitness. Conclusions: The Portuguese version of the IFIS is a reliable and valid method for measuring physical fitness in pediatric populations.


Asunto(s)
Aptitud Física/psicología , Autoinforme , Adolescente , Análisis de Varianza , Antropometría/métodos , Brasil , Niño , Preescolar , Prueba de Esfuerzo/métodos , Prueba de Esfuerzo/normas , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Masculino , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
11.
Mult Scler ; 24(10): 1337-1346, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-28741976

RESUMEN

OBJECTIVE: The primary objective of this real-world study was to describe the response to fampridine and changes of gait parameters in multiple sclerosis (MS) patients' walking disability (Expanded Disability Status Scale (EDSS): 4-7) after treatment with fampridine for 2 weeks as recommended by the European Medicines Agency (EMA) and compare it with the overall physician's judgement. METHODS: A total of 211 adult MS patients were analyzed using a multimodal gait assessment including the timed 25-foot walk test (T25FW), 2-minute walking test (2-MWT), 12-item Multiple Sclerosis Walking Scale (MSWS-12), the GAITRite electronic walkway system, and the patients' clinical global impression (CGI). Multimodal gait assessment was compared with the clinician's impression of overall improvement after 2 weeks. RESULTS: In total, 189 subjects were included, of which 133 (70.37%) were responders to fampridine (RF), according to physician's judgement. Looking at independent multimodal gait assessment, RFs showed improvement of 12.60% in the T25FW, 19.25% in the 2-MWT, 21.12% in the MSWS-12, and 6.54% in their Functional Ambulation Profile (FAP) score. The combination of the T25FW and the MSWS-12 would offer the best sensitivity and specificity for determining response to fampridine according to both neurologists' and patients' classification. CONCLUSION: This study provides new information on the use of fampridine in a real-world setting with a large patient sample on the potential benefit of using more definitive responder criteria to fampridine for the clinical setting.


Asunto(s)
4-Aminopiridina/uso terapéutico , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Esclerosis Múltiple/tratamiento farmacológico , Bloqueadores de los Canales de Potasio/uso terapéutico , Adulto , Anciano , Femenino , Trastornos Neurológicos de la Marcha/etiología , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Resultado del Tratamiento
12.
Eur Eat Disord Rev ; 26(3): 207-216, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29464867

RESUMEN

OBJECTIVE: Clinical research on cortisol response to stress in patients with eating disorders has provided controversial and even contradictory results. As this might be the consequence of the inclusion in the studies of heterogeneous clinical populations, 3 highly selected samples were studied. METHODS: Dexamethasone suppression test was performed on 15 restricting anorexia nervosa patients without history of bulimia nervosa (BN), 17 BN patients with normal weight and no history of anorexia nervosa, and 22 healthy controls. Three days later, the Trier Social Stress Test was applied, and 8 saliva samples were collected along the trial for cortisol assessment. RESULTS: When the patients were considered as a single group, a slightly blunted cortisol response to stress was observed, but when the 3 groups were considered separately, the blunted response was observed only in the BN patients. DISCUSSION: The results support the association between blunted cortisol response and bulimic features.


Asunto(s)
Anorexia Nerviosa , Bulimia Nerviosa , Hidrocortisona , Adulto , Anorexia Nerviosa/metabolismo , Bulimia , Bulimia Nerviosa/metabolismo , Humanos , Hidrocortisona/metabolismo , Saliva , Estrés Psicológico
13.
Actas Esp Psiquiatr ; 46(5): 183-91, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30338775

RESUMEN

INTRODUCTION: Patients with bipolar disorder (BD) have a comorbid substance use with high frequency. Our study aims to establish a relationship between substance use and BD, in terms of greater diagnostic difficulty, a worse prognosis and changes in pharmacological prescription. METHODS: The sample consisted of 394 subjects over twenty years were hospitalized with a diagnosis of BD in acute psychiatry unit of a general hospital (10.6% of total of 3,704 patients). The medical records were analyzed for demographic, clinical and family group relating to data subjects. RESULTS: Complete data were obtained from 319 patients. Of these 165 (51.7%) had a history of drug consumption (abuse/dependence). This was more frequent in men (79.7% vs. 34.2%), in patients under 65 years (58.4% vs. 16.7%) and BD type I compared to type II (55% vs. 35%). Consumers substance patients had an age of onset of the disease earlier and more diagnostic difficulties. Regarding treatment, receiving discharge more mood stabilizers and antipsychotics than nonusers, and higher doses of most of them. CONCLUSIONS: The cases of dual pathology were detected in more than half of the sample, being the most serious and poorer prognosis patients, besides presenting a debut earlier disease. BD / substance use association was more common in men and in patients under 65 years.


Asunto(s)
Trastorno Bipolar/complicaciones , Trastornos Relacionados con Sustancias/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Niño , Diagnóstico Dual (Psiquiatría) , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
14.
Physiol Genomics ; 49(12): 712-721, 2017 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-28986396

RESUMEN

Emerging evidence suggests that both systemic and white adipose tissue-renin-angiotensin system components influence body weight control. We previously demonstrated that higher angiotensin-converting enzyme (ACE) gene expression is associated with lower body adiposity in a rodent model. In this study, we tested the hypothesis that a higher ACE gene dosage reduces fat accumulation by increasing energy expenditure and modulating lipolysis and glucose incorporation into lipids in adipocytes. After a 12 wk follow-up period, transgenic mice harboring three ACE (3ACE) gene copies displayed diminished WAT mass, lipid content in their carcasses, adipocyte hypotrophy, and higher resting oxygen uptake (V̇o2) in comparison with animals with one ACE gene copy (1ACE) after long fasting (12 h). No differences were found in food intake and in the rates of lipolysis and glucose incorporation into lipids in adipocytes. To assess whether this response involves increased angiotensin II type I receptor (AT1R) activation, AT1R blocker (losartan) was used in a separate group of 3ACE mice with body weight and adiposity comparable to that in the other 3ACE animals. We suggest that fasting-induced lower adiposity observed in animals with 3ACE gene copies might be associated with a higher expense of energy reserves; this response did not involve AT1R activation.


Asunto(s)
Glucosa/metabolismo , Tejido Adiposo/metabolismo , Adiposidad/genética , Adiposidad/fisiología , Metabolismo Energético/genética , Metabolismo Energético/fisiología , Lipólisis
15.
J Neuroinflammation ; 14(1): 41, 2017 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-28231856

RESUMEN

BACKGROUND: Growing evidence emphasizes the relevance of sphingolipids for metabolism and immunity of antigen-presenting cells (APC). APCs are key players in balancing tolerogenic and encephalitogenic responses in immunology. In contrast to the well-known prominent effects of sphingosine-1-phosphate (S1P) on lymphocyte trafficking, modulatory effects on APCs have not been fully characterized. METHODS: Frequencies and activation profiles of dendritic cell (DC) subtypes, monocytes, and T cell subsets in 35 multiple sclerosis (MS) patients were evaluated prior and after undergoing fingolimod treatment for up to 24 months. Impact of fingolimod and S1P on maturation and activation profile, pro-inflammatory cytokine release, and phagocytotic capacity was assessed in vitro and ex vivo. Modulation of DC-dependent programming of naïve CD4+ T cells, as well as CD4+ and CD8+ T cell proliferation, was also investigated in vitro and ex vivo. RESULTS: Fingolimod increased peripheral slanDC count-CD1+ DC, and monocyte frequencies remained stable. While CD4+ T cell count decreased, ratio of Treg/Th17 significantly increased in fingolimod-treated patients over time. CD83, CD150, and HLADR were all inhibited, but CD86 was upregulated in DCs after incubation in the presence of fingolimod. Fingolimod but not S1P was associated with reduced release of pro-inflammatory cytokines from DCs and monocytes in vitro and ex vivo. Fingolimod also inhibited phagocytic capacity of slanDCs and monocytes. After fingolimod, slanDCs demonstrated reduced potential to induce interferon-gamma-expressing Th1 or IL-17-expressing Th17 cells and DC-dependent T cell proliferation in vitro and in fingolimod-treated patients. CONCLUSIONS: We present the first evidence that S1P-directed therapies can act additionally as immunomodulators that decrease the pro-inflammatory capabilities of APCs, which is a crucial element in DC-dependent T cell activation and programming.


Asunto(s)
Clorhidrato de Fingolimod/farmacología , Inmunidad Innata/efectos de los fármacos , Factores Inmunológicos/farmacología , Activación de Linfocitos/efectos de los fármacos , Esclerosis Múltiple , Adulto , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Relación Dosis-Respuesta a Droga , Femenino , Citometría de Flujo/métodos , Humanos , Inmunidad Innata/inmunología , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Esclerosis Múltiple/inmunología , Adulto Joven
16.
Acta Paediatr ; 106(3): 489-496, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27935112

RESUMEN

AIM: Gaining weight has been directly associated with an increased probability of developing high blood pressure (HBP) and metabolic abnormalities. We examined the independent and combined effects of overweight, obesity and abdominal obesity on blood pressure in adolescents. METHODS: This cross-sectional school-based study evaluated 869 adolescents (53.4% girls) from 14 to 19 years of age, and the data were collected in 2013 in the city of Imperatriz, Maranhão, Brazil. The outcome was HBP. The independent variables were overweight and obesity classified by body mass index, abdominal obesity classified by the waist-to-height ratio and the combination of obesity and overweight and abdominal obesity. The potential confounding variables were age, the socio-economic status of the family, parental education, type of school and physical activity levels. RESULTS: The prevalence ratios of HBP were higher when male and female adolescents were overweight (1.61-3.11), generally obese (3.20-4.70), had abdominal obesity (2.18-3.02) and were both generally obese and had abdominal obesity (3.28-5.16) compared with normal weight adolescents. CONCLUSION: Obesity or abdominal obesity increased the risk of HBP in adolescents aged 14-19. However, adolescents who were both generally obese and had abdominal obesity showed an even higher risk of having HBP.


Asunto(s)
Presión Sanguínea , Hipertensión/epidemiología , Obesidad Abdominal/epidemiología , Obesidad Infantil/epidemiología , Adolescente , Brasil/epidemiología , Estudios Transversales , Femenino , Humanos , Hipertensión/etiología , Masculino , Obesidad Abdominal/complicaciones , Obesidad Infantil/complicaciones , Adulto Joven
17.
Actas Esp Psiquiatr ; 44(3): 93-6, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27254401

RESUMEN

INTRODUCTION: Pharmacotherapy for the management of obesity is primarily aimed at weight loss, weight loss maintenance and risk reduction (reduction in body fat, risk factors for cardiovascular disease and the incidence of diabetes mellitus). Among drugs that have been evaluated for weight loss include antidepressants (fluoxetine) and antiepileptic (topiramate). MATERIAL AND METHODS: We analyzed eating behavior and weight loss in a sample of morbid obesity patients before bariatric surgery. The patients suffering eating disturbances symptoms were grouped into three groups: one group received 40 mg of flouxetine/day (Group A); another group received topiramate 200 mg/day (Group B); and the third group of patients were treated with fluoxetine 40 mg and 200 mg of topiramate/day (Group C). RESULTS: Patients treated with fluoxetine plus topiramate lost more weight at 3 and 6 months before surgery. CONCLUSIONS: The use of the psychopharmaceutical drug (fluoxetine and topiramate) in morbid obese patients with eating disorders could represent a new approach to the management of eating behavior before bariatric surgery.


Asunto(s)
Fármacos Antiobesidad/administración & dosificación , Cirugía Bariátrica , Conducta Alimentaria/efectos de los fármacos , Fluoxetina/administración & dosificación , Fructosa/análogos & derivados , Obesidad Mórbida/tratamiento farmacológico , Obesidad Mórbida/cirugía , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Adulto , Quimioterapia Combinada , Femenino , Fructosa/administración & dosificación , Humanos , Masculino , Cuidados Preoperatorios , Topiramato
18.
J Pineal Res ; 58(3): 251-61, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25626464

RESUMEN

Melatonin, the main hormone produced by the pineal gland, is secreted in a circadian manner (24-hr period), and its oscillation influences several circadian biological rhythms, such as the regulation of clock genes expression (chronobiotic effect) and the modulation of several endocrine functions in peripheral tissues. Assuming that the circadian synchronization of clock genes can play a role in the regulation of energy metabolism and it is influenced by melatonin, our study was designed to assess possible alterations as a consequence of melatonin absence on the circadian expression of clock genes in the epididymal adipose tissue of male Wistar rats and the possible metabolic repercussions to this tissue. Our data show that pinealectomy indeed has impacts on molecular events: it abolishes the daily pattern of the expression of Clock, Per2, and Cry1 clock genes and Pparγ expression, significantly increases the amplitude of daily expression of Rev-erbα, and affects the pattern of and impairs adipokine production, leading to a decrease in leptin levels. However, regarding some metabolic aspects of adipocyte functions, such as its ability to synthesize triacylglycerols from glucose along 24 hr, was not compromised by pinealectomy, although the daily profile of the lipogenic enzymes expression (ATP-citrate lyase, malic enzyme, fatty acid synthase, and glucose-6-phosphate dehydrogenase) was abolished in pinealectomized animals.


Asunto(s)
Tejido Adiposo Blanco/metabolismo , Ritmo Circadiano/genética , Expresión Génica/genética , Proteínas Circadianas Period/metabolismo , Glándula Pineal , Animales , Ritmo Circadiano/fisiología , Expresión Génica/fisiología , Masculino , Proteínas Circadianas Period/genética , Glándula Pineal/enzimología , Glándula Pineal/fisiología , Glándula Pineal/cirugía , Ratas , Ratas Wistar
19.
Eur Eat Disord Rev ; 23(3): 185-92, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25766414

RESUMEN

The study was aimed at analysing the reciprocal relationships of several clinical and neurobiological items in order to predict alcohol misuse in patients with bulimia nervosa (BN). Seventy BN patients and 70 healthy controls were assessed for depression, impulsivity, borderline personality traits and self-defeating behaviours using specific scales; serum cortisol and 24-hour urinary excretion of serotonin and 5-hydroxiindolacetic acid were also assessed. The study confirmed the implications of these clinical factors for alcohol misuse in BN patients, but the results suggested that depressive symptoms and hypercortisolism could lie behind these relationships.


Asunto(s)
Alcoholismo/complicaciones , Bulimia Nerviosa/complicaciones , Bulimia Nerviosa/psicología , Hidrocortisona/metabolismo , Neurobiología , Serotonina/orina , Ácido Acético/orina , Adolescente , Adulto , Alcoholismo/psicología , Trastorno de Personalidad Limítrofe , Depresión/complicaciones , Depresión/psicología , Trastorno Depresivo/complicaciones , Trastorno Depresivo/psicología , Femenino , Humanos , Hidrocortisona/sangre , Conducta Impulsiva , Indoles/orina , Masculino , Modelos Psicológicos , Serotonina/metabolismo , Adulto Joven
20.
Actas Esp Psiquiatr ; 43(3): 91-8, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25999156

RESUMEN

INTRODUCTION: The aim of the study was to identify the relationship between perceived rearing styles and the clinical expression of Eating Disorders (ED). METHODS: One hundred and ninety-six patients diagnosed of an ED and 127 healthy student as controls selected from the Nursing College were evaluated for general psychopathology (STAI, BDI II, RSE), and for abnormal eating attitudes (EAT, EDI-II, BITE). The EMBU (‘my memories of upbringing’) was administered for the assessment of perceived parental rearing styles and was used a questionnaire to assess familial variables. RESULTS: In relation to the control group, patients with ED perceived greater rejection, overprotection and less warmth than the controls. Patients who perceived greater paternal favoritism, maternal overprotection and low paternal emotional warmth, showed higher levels of anxiety. Paternal affection and maternal attitudes of rejection, overprotection and favoritism were related to lower self-esteem. Regarding abnormal eating attitudes, body dissatisfaction inversely correlated with paternal emotional care and maternal favoritism. The EDI subscales: ineffectiveness, perfectionism and ascetism were associated to parental rejection. Maternal rejection also related with drive for thinness, interoceptive awareness and impulse regulation. Perceived emotional warmth was related with perfectionism. Bulimia subscale and BITE scores were inversely associated to paternal overprotection and affection, and scored significantly higher in paternal favoritism and rejection from both parents. CONCLUSIONS: Perceived parental bonding is different in the various subtypes of EDs. Patients diagnosed of Bulimia Nervosa or Eating Disorders Not Otherwise Specified perceived greater rejection, less affection and a greater overprotection than Anorexia Nervosa patients and controls.


Asunto(s)
Crianza del Niño , Trastornos de Alimentación y de la Ingestión de Alimentos/etiología , Relaciones Padres-Hijo , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Femenino , Humanos , Padres , Autoinforme , Adulto Joven
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