RESUMEN
Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease due to axonal damage of the corticospinal secondary to an inflammatory response against infected T-cells. In the present work, we aimed to evaluate biomarkers of neurodegeneration and neuroinflammation in the definition of HAM/TSP prognosis. Neurofilament light (NfL) and phosphorylated heavy (pNfH) chains, total Tau protein, cellular prion protein (PrPc), inflammatory chemokines, and neopterin were quantified in paired cerebrospinal fluid (CSF) and serum samples from HAM/TSP patients (n=21), HTLV-1 asymptomatic carriers (AC) (n=13), and HTLV-1 seronegative individuals with non-inflammatory non-degenerative neurological disease (normal-pressure hydrocephalus) (n=9) as a control group. HTLV-1 proviral load in peripheral blood mononuclear cells and the expression of chemokine receptors CCR4, CCR5, and CXCR3 in infected CD4+ T-cells (HTLV-1 Tax+ cells) were also assessed. CSF levels of Tau, NfL, and pNfH were similar between groups, but PrPc and neopterin were elevated in HAM/TSP patients. Most individuals in the control group and all HTLV-1 AC had CSF/serum neopterin ratio < 1.0, and two-thirds of HAM/TSP patients had ratio values > 1.0, which positively correlated with the speed of disease progression and pNfH levels, indicating active neuroinflammation. HAM/TSP patients showed high serum levels of CXCR3-binding chemokines (CXCL9, CXCL10, and CXCL11) and elevated CSF levels of CCL2, CCL3, CCL4, CCL17, CXCL5, CXCL10, and CXCL11. Indeed, CXCL10 concentration in CSF of HAM/TSP patients was 5.8-fold and 8.7-fold higher in than in HTLV-1 AC and controls, respectively, and correlated with CSF cell counts. HAM/TSP patients with typical/rapid disease progression had CSF/serum CXCL10 ratio > 1.0 and a higher frequency of CXCR3+Tax+CD4+ T-cells in blood, which indicated a positive gradient for the migration of infected cells and infiltration into the central nervous system. In conclusion, the slow progression of HAM/TSP abrogates the usefulness of biomarkers of neuronal injury for the disease prognosis. Thus, markers of inflammation provide stronger evidence for HAM/TSP progression, particularly the CSF/serum neopterin ratio, which may contribute to overcome differences between laboratory assays.
Asunto(s)
Citocinas , Virus Linfotrópico T Tipo 1 Humano/patogenicidad , Mediadores de Inflamación , Degeneración Nerviosa , Proteínas del Tejido Nervioso , Enfermedades Neurodegenerativas/diagnóstico , Paraparesia Espástica Tropical/diagnóstico , Adulto , Anciano , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Estudios Transversales , Citocinas/sangre , Citocinas/líquido cefalorraquídeo , Progresión de la Enfermedad , Femenino , Interacciones Huésped-Patógeno , Humanos , Mediadores de Inflamación/sangre , Mediadores de Inflamación/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Neopterin/sangre , Neopterin/líquido cefalorraquídeo , Proteínas del Tejido Nervioso/sangre , Proteínas del Tejido Nervioso/líquido cefalorraquídeo , Enfermedades Neurodegenerativas/sangre , Enfermedades Neurodegenerativas/líquido cefalorraquídeo , Enfermedades Neurodegenerativas/virología , Paraparesia Espástica Tropical/sangre , Paraparesia Espástica Tropical/líquido cefalorraquídeo , Paraparesia Espástica Tropical/virología , Valor Predictivo de las Pruebas , PronósticoRESUMEN
BACKGROUND: Stress precipitates mood disorders, characterized by a range of symptoms present in different combinations, suggesting the existence of disease subtypes. Using an animal model, we previously described that repetitive stress via restraint or immobilization induced depressive-like behaviors in rats that were differentially reverted by a serotonin- or noradrenaline-based antidepressant drug, indicating that different neurobiological mechanisms may be involved. The forebrain astrocyte protein aldolase C, contained in small extracellular vesicles, was identified as a potential biomarker in the cerebrospinal fluid; however, its specific origin remains unknown. Here, we propose to investigate whether serum small extracellular vesicles contain a stress-specific protein cargo and whether serum aldolase C has a brain origin. METHODS: We isolated and characterized serum small extracellular vesicles from rats exposed to restraint, immobilization, or no stress, and their proteomes were identified by mass spectrometry. Data available via ProteomeXchange with identifier PXD009085 were validated, in part, by western blot. In utero electroporation was performed to study the direct transfer of recombinant aldolase C-GFP from brain cells to blood small extracellular vesicles. RESULTS: A differential proteome was identified among the experimental groups, including aldolase C, astrocytic glial fibrillary acidic protein, synaptophysin, and reelin. Additionally, we observed that, when expressed in the brain, aldolase C tagged with green fluorescent protein could be recovered in serum small extracellular vesicles. CONCLUSION: The protein cargo of serum small extracellular vesicles constitutes a valuable source of biomarkers of stress-induced diseases, including those characterized by depressive-like behaviors. Brain-to-periphery signaling mediated by a differential molecular cargo of small extracellular vesicles is a novel and challenging mechanism by which the brain might communicate health and disease states to the rest of the body.
Asunto(s)
Astrocitos/metabolismo , Moléculas de Adhesión Celular Neuronal/sangre , Proteínas de la Matriz Extracelular/sangre , Vesículas Extracelulares/metabolismo , Fructosa-Bifosfato Aldolasa/sangre , Proteína Ácida Fibrilar de la Glía/sangre , Proteínas del Tejido Nervioso/sangre , Serina Endopeptidasas/sangre , Estrés Psicológico/sangre , Animales , Biomarcadores/sangre , Moléculas de Adhesión Celular Neuronal/genética , Proteínas de la Matriz Extracelular/genética , Vesículas Extracelulares/genética , Fructosa-Bifosfato Aldolasa/genética , Proteína Ácida Fibrilar de la Glía/genética , Masculino , Proteínas del Tejido Nervioso/genética , Mapas de Interacción de Proteínas/fisiología , Ratas , Ratas Sprague-Dawley , Proteína Reelina , Restricción Física/efectos adversos , Restricción Física/psicología , Serina Endopeptidasas/genética , Estrés Psicológico/genética , Estrés Psicológico/psicología , Sinaptofisina/sangre , Sinaptofisina/genéticaRESUMEN
BACKGROUND: Cocaine and amphetamine-regulated transcript (CART) is an endogenous antioxidant present since the embryonic period. CART is activated by high levels of dopamine and might be of interested in understanding the changes in the REDOX system associated with crack/cocaine intake. The goal of this study was to determine whether exposure to crack in utero is associated with increased CART levels. METHODS: In this cross-sectional study with consecutive sampling, we compared the umbilical cord blood (UCB) CART levels (µg/mL) of newborns exposed to crack/cocaine in utero (EN, n = 57) to levels in non-exposed newborns (NEN, n = 99). In addition, we compared serum CART levels between EN and NEN mothers, in the immediate postpartum period. Potential confounders, such as perinatal data (e.g., weight, Apgar, etc.), psychopathology (DSM-IV), and use of drugs other than crack (ASSIST) were assessed. RESULTS: According to general linear model analysis, the adjusted mean CART was significantly higher in EN (0.180, 95% CI 0.088-0.272) than in NEN (0.048, 95% CI 0.020-0.076; p < 0.002; d = 0.68). The difference in CART levels between EN and NEN mothers was not significant (p ≥ 0.05). CONCLUSION: The increase in CART levels in EN UBC suggests a response to crack/cocaine-induced oxidative stress during gestational period, as a potential attempt of neuroprotection. In adult women in puerperium, however, this endogenous antioxidant recruitment does not seem to operate.
Asunto(s)
Cocaína Crack/farmacología , Sangre Fetal/metabolismo , Proteínas del Tejido Nervioso/sangre , Adulto , Estudios Transversales , Femenino , Humanos , Recién Nacido , Masculino , Periodo Posparto , EmbarazoRESUMEN
OBJECTIVE: To investigate serum nesfatin-1 levels at 24-28 weeks of pregnancy in women newly diagnosed with gestational diabetes and determine the association of nesfatin-1 with several metabolic parameters. SUBJECTS AND METHODS: Forty women newly diagnosed with gestational diabetes at 24-28 weeks of pregnancy and 30 healthy pregnant women matched in age and gestational week were included in this cross-sectional study. Serum nesfatin-1 levels were analyzed using ELISA, and the relationship between nesfatin-1 and several metabolic parameters were assessed. RESULTS: Serum nesfatin-1 levels were found to be lower in women with gestational diabetes compared to the pregnant women in the control sample (p = 0.020). Multiple linear regression analysis revealed that nesfatin-1 was lower in participants with gestational diabetes independently from gestational age, BMI, HOMA-IR, fasting plasma glucose, and age. In correlation analysis, the only variable that was found to have a statistically significant correlation with nesfatin-1 was gestational age (p = 0.015, r = 0.30). CONCLUSION: Lower nesfatin-1 levels in women with gestational diabetes compared to the control group at 24-28 weeks of gestation draws attention to nesfatin-1 levels in gestational diabetes and motivates further research in this area.
Asunto(s)
Proteínas de Unión al Calcio/sangre , Proteínas de Unión al ADN/sangre , Diabetes Gestacional/sangre , Proteínas del Tejido Nervioso/sangre , Adulto , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Casos y Controles , Estudios Transversales , Diabetes Gestacional/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Ayuno/sangre , Femenino , Edad Gestacional , Prueba de Tolerancia a la Glucosa , Humanos , Nucleobindinas , EmbarazoRESUMEN
The lentil lectin glycoprotein enzyme-linked immunoelectrotransfer blot (LLGP EITB, reported sensitivity 99% and specificity 100%) is used as a serologic marker of exposure to Taenia solium in pigs. However, only a limited number of parasites have been evaluated for cross reactivity. Pigs may host other related cestode infections, including Taenia hydatigena, which have not been formally evaluated for cross-reactions. We investigated a corral in Tumbes, Peru, a region where a cysticercosis elimination demonstration project was completed in 2012. In this corral, 14/19 (73.7%) 6-8-week-old piglets were reactive to GP50 on LLGP EITB, and all had circulating Taenia sp. antigens. From eight necropsied piglets; four were infected with T. hydatigena metacestodes whereas none had evidence of T. solium infection. Two resident dogs were subsequently confirmed to have T. hydatigena taeniasis. These results suggest GP50 cross-reactivity in T. hydatigena-infected pigs, although controlled experimental infection is needed to confirm this hypothesis.
Asunto(s)
Antígenos Helmínticos/sangre , Cisticercosis/diagnóstico , Cisticercosis/veterinaria , Proteínas del Tejido Nervioso/sangre , Taenia/aislamiento & purificación , Animales , Anticuerpos Antihelmínticos/sangre , Biomarcadores/sangre , Reacciones Cruzadas , Cisticercosis/sangre , Perros/parasitología , Interacciones Huésped-Parásitos , Perú , Sensibilidad y Especificidad , Porcinos/parasitología , Enfermedades de los Porcinos/sangre , Enfermedades de los Porcinos/diagnóstico , Enfermedades de los Porcinos/parasitología , Taenia/clasificaciónRESUMEN
ABSTRACT Objective To investigate serum nesfatin-1 levels at 24-28 weeks of pregnancy in women newly diagnosed with gestational diabetes and determine the association of nesfatin-1 with several metabolic parameters. Subjects and methods Forty women newly diagnosed with gestational diabetes at 24-28 weeks of pregnancy and 30 healthy pregnant women matched in age and gestational week were included in this cross-sectional study. Serum nesfatin-1 levels were analyzed using ELISA, and the relationship between nesfatin-1 and several metabolic parameters were assessed. Results Serum nesfatin-1 levels were found to be lower in women with gestational diabetes compared to the pregnant women in the control sample (p = 0.020). Multiple linear regression analysis revealed that nesfatin-1 was lower in participants with gestational diabetes independently from gestational age, BMI, HOMA-IR, fasting plasma glucose, and age. In correlation analysis, the only variable that was found to have a statistically significant correlation with nesfatin-1 was gestational age (p = 0.015, r = 0.30). Conclusion Lower nesfatin-1 levels in women with gestational diabetes compared to the control group at 24-28 weeks of gestation draws attention to nesfatin-1 levels in gestational diabetes and motivates further research in this area.
Asunto(s)
Humanos , Femenino , Embarazo , Adulto , Proteínas de Unión al Calcio/sangre , Diabetes Gestacional/sangre , Proteínas de Unión al ADN/sangre , Proteínas del Tejido Nervioso/sangre , Ensayo de Inmunoadsorción Enzimática , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Casos y Controles , Estudios Transversales , Ayuno/sangre , Edad Gestacional , Diabetes Gestacional/diagnóstico , Nucleobindinas , Prueba de Tolerancia a la GlucosaRESUMEN
Membrane neuronal glycoprotein M6a is highly expressed in the brain and contributes to neural plasticity promoting neurite growth and spine and synapse formation. We have previously showed that chronic stressors alter hippocampal M6a mRNA levels in rodents and tree shrews. We now show that M6a glycoprotein can be detected in mouse blood. M6a is a transmembrane glycoprotein and, as such, unlikely to be free in blood. Here we demonstrate that, in blood, M6a is transported in extracellular vesicles (EVs). It is also shown that M6a-containing EVs are delivered from cultured primary neurons as well as from M6a-transfected COS-7 cells. Released EVs containing M6a can be incorporated into COS-7 cells changing its phenotype through formation of membrane protrusions. Thus, M6a-containing EVs might contribute to maintain cellular plasticity. M6a presence in blood was used to monitor stress effects. Chronic restraint stress modulated M6a protein level in a sex dependent manner. Analysis of individual animals indicated that M6a level variations depend on the stressor applied. The response to stressors in blood makes M6a amenable to further studies in the stress disorder field.
Asunto(s)
Vesículas Extracelulares/metabolismo , Glicoproteínas de Membrana/sangre , Proteínas del Tejido Nervioso/sangre , Estrés Fisiológico , Animales , Transporte Biológico , Biomarcadores , Células COS , Chlorocebus aethiops , Vesículas Extracelulares/ultraestructura , Femenino , Técnica del Anticuerpo Fluorescente , Hipocampo/metabolismo , Masculino , Glicoproteínas de Membrana/líquido cefalorraquídeo , Glicoproteínas de Membrana/genética , Ratones , Proteínas del Tejido Nervioso/líquido cefalorraquídeo , Proteínas del Tejido Nervioso/genética , Neuronas/metabolismo , Factores SexualesRESUMEN
Most biomarker candidates arising from proteomic studies of psychiatric disorders have not progressed for use in clinical studies due to insufficient validation steps. Here we describe a selective reaction monitoring mass spectrometry (SRM-MS) approach that could be used as a follow-up validation tool of proteins identified in blood serum or plasma. This protocol specifically covers the stages of peptide selection and optimization. The increasing application of SRM-MS should enable fast, sensitive, and robust methods with the potential for use in clinical studies involving sampling of serum or plasma. Understanding the molecular mechanisms and identifying potential biomarkers for risk assessment, diagnosis, prognosis, and prediction of drug response goes toward the implementation of translational medicine strategies for improved treatment of patients with psychiatric disorders and other debilitating diseases.
Asunto(s)
Biomarcadores/sangre , Química Encefálica , Espectrometría de Masas/métodos , Trastornos Mentales/sangre , Proteínas del Tejido Nervioso/sangre , Humanos , Espectrometría de Masas/instrumentación , Fragmentos de Péptidos/sangre , Plasma , SueroAsunto(s)
Antígenos de Neoplasias/sangre , Autoanticuerpos/sangre , Ataxia Cerebelosa/complicaciones , Encefalitis/complicaciones , Enfermedad de Hashimoto/complicaciones , Pérdida Auditiva/etiología , Proteínas del Tejido Nervioso/sangre , Adulto , Ataxia Cerebelosa/diagnóstico , Ataxia Cerebelosa/inmunología , Encefalitis/diagnóstico , Encefalitis/inmunología , Enfermedad de Hashimoto/diagnóstico , Enfermedad de Hashimoto/inmunología , Humanos , MasculinoRESUMEN
BACKGROUND: Meteorin (METRN) is a recently described neutrophic factor with angiogenic properties. This is a nested case-control study in a longitudinal cohort study that describes the serum profile of METRN during different periods of gestation in healthy and preeclamptic pregnant women. Moreover, we explore the possible application of METRN as a biomarker. METHODS AND FINDINGS: Serum METRN was measured by ELISA in a longitudinal prospective cohort study in 37 healthy pregnant women, 16 mild preeclamptic women, and 20 healthy non-pregnant women during the menstrual cycle with the aim of assessing serum METRN levels and its correlations with other metabolic parameters. Immunostaining for METRN protein was performed in placenta. A multivariate logistic regression model was proposed and a classifier model was formulated for predicting preeclampsia in early and middle pregnancy. The performance in classification was evaluated using measures such as sensitivity, specificity, and the receiver operating characteristic (ROC) curve. In healthy pregnant women, serum METRN levels were significantly elevated in early pregnancy compared to middle and late pregnancy. METRN levels are significantly lower only in early pregnancy in preeclamptic women when compared to healthy pregnant women. Decision trees that did not include METRN levels in the first trimester had a reduced sensitivity of 56% in the detection of preeclamptic women, compared to a sensitivity of 69% when METRN was included. CONCLUSIONS: The joint measurements of circulating METRN levels in the first trimester and systolic blood pressure and weight in the second trimester significantly increase the probabilities of predicting preeclampsia.
Asunto(s)
Péptidos y Proteínas de Señalización Intercelular/sangre , Proteínas del Tejido Nervioso/sangre , Preeclampsia/sangre , Adulto , Antropometría , Estudios de Casos y Controles , Árboles de Decisión , Femenino , Humanos , Inmunohistoquímica , Modelos Logísticos , Placenta/metabolismo , Embarazo , Trimestres del Embarazo/sangre , Factores de Riesgo , Adulto JovenRESUMEN
Objective. To evaluate technical efficiency and potential presence of scale and scope economies in Mexican private medical units (PMU) that will improve management decisions. Materials and methods. We used data envelopment analysis methods with inputs and outputs for 2 105 Mexican PMU published in 2010 by the Instituto Nacional de Estadística y Geografía from the "Estadística de Unidades Médicas Privadas con Servicio de Hospitalización (PEC-6-20-A)" questionnaire. Results. The application of the models used in the paper found that there is a marginal presence of economies of scale and scope in Mexican PMU. Conclusions. PMU in Mexico must focus to deliver their services on a diversified structure to achieve technical efficiency.
Objetivo. Evaluar la eficiencia técnica y la presencia de potenciales economías de escala y alcance en unidades médicas privadas (UMP) mexicanas, de forma que sea posible establecer planes para la mejora de su gestión. Material y métodos. Se utilizó el método de Análisis Envolvente de Datos con información de insumos y productos para 2 105 UMP del año 2010 publicada por el Instituto Nacional de Estadística y Geografía a través del cuestionario denominado "Estadística de Unidades Médicas Privadas con Servicio de Hospitalización (PEC-6-20-A)". Resultados. La aplicación de los modelos encuentra una presencia marginal de economías de escala y alcance en las UMP mexicanas. Conclusiones. La operación de las UMP en México debe enfocarse a prestar servicios bajo un modelo diversificado para alcanzar mejores niveles de eficiencia técnica.
Asunto(s)
Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factor Natriurético Atrial/sangre , Proteínas del Tejido Nervioso/sangre , Disfunción Ventricular Izquierda/diagnóstico , Biomarcadores/sangre , Cateterismo Cardíaco , Estudios Transversales , Fragmentos de Péptidos/sangre , Valor Predictivo de las Pruebas , Precursores de Proteínas/sangreRESUMEN
Nesfatin-1 is an anorexigenic neuropeptide derived by post-translational cleavage from the N-terminus region DNA binding/EF-hand/acidic amino acid rich region (NEFA)/nucleobindin2 (NucB2) protein through proteolytic prohormone convertases. This neuropeptide was originally localized in different appetite controlling areas such as the hypothalamic paraventricular nucleus, arcuate nucleus, supraoptic nucleus, lateral hypothalamic area, and nucleus tractus solitarius. The objective of this study was to determine the expression and the changes that occur to mRNA and protein of NucB2 and Nesfatin-1 serum levels during gestation. This study utilized molecular and immunological approaches to investigate the expression and regulation of NucB2/Nesfatin-1 protein throughout gestation in rat fed under ad libitum and food restricted conditions (30% nutrient restriction). NucB2 was immunolocalized in the amnion and decidua of the rat placenta. Nesfatin-1 serum levels were measured by radioimmunoassay on gestational days 12, 16, 19 and 21, showing a significant (p<0.01) decrease in serum levels after day 12 until the end of gestation in rats fed ad libitum. These results were correlated with the analysis of NucB2 mRNA, with a significant (p<0.01) reduction observed in both the mRNA and protein of NucB2 during the gestational days 12, 16 and 21. It was also observed that food restriction decreases Nesfatin-1 serum levels and NucB2 placental expression at day 16 of gestation when compared to pregnant rats fed ad libitum. This study illustrates for the first time through molecular and immunological approaches the NucB2 expression and regulation on rat placenta and that this peptide is regulated throughout pregnancy. Consistent with previous reports, our results provide additional evidence supporting the role of NucB2 protein as an anorexigenic peptide that may contribute to the regulation of feeding behavior and energy homeostasis. NucB2/Nesfatin-1 might play an important metabolic role during pregnancy and fetal development and its energy balance mediating role should be studied in various physiological and pathological conditions throughout gestation.
Asunto(s)
Proteínas de Unión al Calcio/sangre , Proteínas de Unión al ADN/sangre , Regulación del Desarrollo de la Expresión Génica/fisiología , Proteínas del Tejido Nervioso/sangre , Placenta/metabolismo , Embarazo/metabolismo , Factores de Edad , Análisis de Varianza , Animales , Proteínas de Unión al Calcio/genética , Proteínas de Unión al ADN/genética , Ayuno/sangre , Femenino , Mucosa Gástrica/metabolismo , Edad Gestacional , Proteínas del Tejido Nervioso/genética , Nucleobindinas , Placenta/embriología , ARN Mensajero/metabolismo , Radioinmunoensayo , Ratas , Ratas Sprague-Dawley , Estómago/embriologíaRESUMEN
Nesfatin-1 is a recently identified anorexigenic peptide that has been implicated in appetite regulation, weight loss and/or malnutrition. Anorexia and malnutrition are common features of chronic kidney disease (CKD) that predispose patients to worse outcomes. However, the reasons for the occurrence of anorexia in CKD patients are not fully elucidated. The aim of this study was to investigate the association between nesfatin-1 and protein intake and body composition in patients undergoing hemodialysis (HD). Twenty five HD patients from a private Clinic in Rio de Janeiro, Brazil were studied and compared with 15 healthy subjects that were matched for body mass index (BMI), % body fat mass (by anthropometrics) and age. Appetite was measured using a specific questionnaire, and food intake was evaluated based on 3-day food records. Nesfatin-1 levels were measured by ELISA and leptin, TNF-α and IL-6 levels were determined by a multiplex assay kit. Serum nesfatin-1 levels did not differ between HD patients (0.16±0.07ng/mL) and healthy subjects (0.17±0.10ng/mL). Nesfatin-1 levels showed significant negative correlations with protein intake (r=-0.42; p=0.03), but did not associate with inflammatory markers or appetite scores. Combining patients and controls, we observed positive correlations with BMI (r=0.33; p=0.03), % body fat (r=0.35; p=0.03), leptin (r=0.45; p=0.006) and the triceps skinfold thickness (r=0.36; p=0.02). In multivariate analysis % body fat was the main determinant of nesfatin-1 variance. In conclusion, nesfatin-1 levels did not differ between HD patients and healthy subjects and negatively correlated with protein intake. This pathway is likely not dysregulated in uremia.
Asunto(s)
Adiposidad , Proteínas de Unión al Calcio/sangre , Proteínas de Unión al ADN/sangre , Ingestión de Alimentos , Mediadores de Inflamación/sangre , Fallo Renal Crónico/sangre , Proteínas del Tejido Nervioso/sangre , Diálisis Renal , Adipoquinas/sangre , Adulto , Apetito , Composición Corporal , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Fallo Renal Crónico/terapia , Leptina/sangre , Masculino , Persona de Mediana Edad , Nucleobindinas , Estado Nutricional , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Increased plasma osmolality by food intake evokes augmentation of plasma oxytocin (OT). Ovarian steroids may also influence the balance of body fluids by acting on OT neurones. Our aim was to determine if estrogen influences the activity of OT neurones in paraventricular nucleus (PVN) and supraoptic nucleus (SON) under different osmotic situations. Ovariectomized rats (OVX) were treated with either estradiol (E(2)) or vehicle and were divided into three groups: group I was fed ad libitum, group II underwent 48âh of fasting, and group III was refed after 48âh of fasting. On the day of the experiment, blood samples were collected to determine the plasma osmolality and OT. The animals were subsequently perfused, and OT/FOS immunofluorescence analysis was conducted on neurones in the PVN and the SON. When compared to animals which were fasted or fed ad libitum, the plasma osmolality of refed animals was higher, regardless of whether they were treated with vehicle or E(2). We observed neural activation of OT cells in vehicle- or E(2)-treated OVX rats refed after 48âh of fasting, but not in animals fed ad libitum or in animals that only underwent 48âh of fasting. Finally, the percentage of neurones that co-expressed OT and FOS was lower in both the PVN and the SON of animals treated with E(2) and refed, when compared to vehicle-treated animals. These results suggest that E(2) may have an inhibitory effect on OT neurones and may modulate the secretion of OT in response to the increase of osmolality induced by refeeding.
Asunto(s)
Ingestión de Alimentos , Estradiol/metabolismo , Hipotálamo Anterior/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Oxitocina/metabolismo , Equilibrio Hidroelectrolítico , Animales , Femenino , Hipotálamo Anterior/citología , Proteínas del Tejido Nervioso/sangre , Neuronas/citología , Concentración Osmolar , Ovariectomía , Oxitocina/sangre , Núcleo Hipotalámico Paraventricular/citología , Núcleo Hipotalámico Paraventricular/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Wistar , Núcleo Supraóptico/citología , Núcleo Supraóptico/metabolismo , Transmisión SinápticaRESUMEN
Lymphocytes from human peripheral blood exhibit a series of markers of neurotransmitters, such as specific receptors and transporters. A reduction of serotonin transporters and an increase of them has been reported after treatment with fluoxetine in depressed patients. The aim of this study was to determine if the administration of an antidepressant with a different mechanism of action, such as mirtazapine, could produce a similar effect. Twenty eight patients (age 41.40+/-2.45) were diagnosed following the criteria for major depression by the Structured Clinical Interview for Disorders of Axis I of the American Psychiatric Association. Severity was measured by Hamilton Scale and by Beck Inventory for Depression, scores of 30.88+/-7.48 and 30.24+/-10.88, respectively, prior to treatment. Samples from control subjects were obtained alternating with patients before and after the administration of the antidepressant: twenty eight and twenty four, respectively (age 38.80+/-2.95). Mirtazapine was given in a dose of 30 mg/day for 6 weeks. Blood lymphocytes were isolated by density gradient from patients and controls before and after treatment. There was a partial response according to clinical evaluation and scores of the Scale and the Inventory. Serotonin transporters were labeled with [3H] paroxetine. Number of sites (B(max)) were 10.86+/-2.60 and 12.58+/-2.71 fmol/10(6) cells for both groups of controls. The depressed patients had a significant reduction of serotonin transporters in their lymphocytes before treatment and an increase after it, with B(max) values of 6.52+/-0.49 and 15.61+/-0.49 fmol/10(6) cells, respectively. There were no significant differences in the affinity for the ligand. Concentrations of serotonin or noradrenaline in lymphocytes were not modified before the treatment, although there was a significant decrease after taking 30 mg/day of the antidepressant for 6 weeks. Mirtazapine, not being a serotonin reuptake inhibitor, did increase the number of transporters in lymphocytes of major depression patients, indicating a complex mechanism, not only directly related to the transporter, but involved in the therapeutic response.
Asunto(s)
Antidepresivos Tricíclicos/farmacología , Trastorno Depresivo Mayor/metabolismo , Linfocitos/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Mianserina/análogos & derivados , Mianserina/farmacología , Proteínas del Tejido Nervioso/metabolismo , Adulto , Antidepresivos de Segunda Generación/metabolismo , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Trastorno Depresivo Mayor/sangre , Femenino , Humanos , Ácido Hidroxiindolacético/metabolismo , Cinética , Linfocitos/efectos de los fármacos , Masculino , Glicoproteínas de Membrana/sangre , Proteínas de Transporte de Membrana/sangre , Persona de Mediana Edad , Mirtazapina , Proteínas del Tejido Nervioso/sangre , Norepinefrina/metabolismo , Paroxetina/metabolismo , Escalas de Valoración Psiquiátrica , Serotonina/metabolismo , Proteínas de Transporte de Serotonina en la Membrana PlasmáticaRESUMEN
Patients with idiopathic pulmonary arterial hypertension usually undergo acute vasodilator tests with nitric oxide (NO) for haemodynamic evaluation and therapeutical planning. The aim of this study was to evaluate the link between the variation of N-terminal (NT)-pro-brain natriuretic peptide (BNP) levels and haemodynamic parameters during the acute vasodilator test. A total of 22 idiopathic pulmonary arterial hypertension patients who underwent acute vasodilator tests were studied. Blood samples were collected at baseline and after 30 and 60 min of NO inhalation. NT-pro-BNP levels were measured in each sample. A receiver-operating characteristic curve was used to evaluate the capability of the NT-pro-BNP level variation during NO inhalation in recognising nonresponders. To distinguish responders from nonresponders, the increase of the NT-pro-BNP (0% as cut-off value) determined a 50% specificity and 100% sensitivity (positive predictive value of 38% and a negative predictive value of 100%). These results suggest that N-terminal-pro-brain natriuretic peptide was able to distinguish nonresponder patients with the acute vasodilator test. N-terminal-pro-brain natriuretic peptide may be an interesting additional biological tool in the evaluation of idiopathic pulmonary arterial hypertension patients.
Asunto(s)
Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/diagnóstico , Proteínas del Tejido Nervioso/sangre , Fragmentos de Péptidos/sangre , Adulto , Biomarcadores/sangre , Pruebas de Provocación Bronquial , Broncodilatadores , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Péptido Natriurético Encefálico , Óxido Nítrico , Sensibilidad y EspecificidadRESUMEN
The gold standard serodiagnostic assay for cysticercosis and neurocysticercosis, diseases caused by the metacestode of Taenia solium, uses lentil lectin-purified glycoprotein (LLGP) in a Western blot assay. We tested two antigens derived from LLGP, synthetic TS18var1 (sTS18var1) and recombinant GP50 antigen (rGP50), in an enzyme-linked immunosorbent assay (ELISA) using serum and cerebrospinal fluid (CSF) samples. The sensitivity for serum and CSF was 94.7% and 100% for rGP50 and 90.4% and 90.2% for sTS18var1, respectively. The specificity for serum and CSF samples was 93.8% and 100% for rGP50 and 90.3% and 98.0% for sTS18var1, respectively. The use of these antigens individually or combined as a diagnostic antigen cocktail eliminates the need for purification of antigens from parasite material and offers the advantage of using a simple and quantitative ELISA format.
Asunto(s)
Proteínas del Tejido Nervioso/sangre , Neurocisticercosis/diagnóstico , Taenia/inmunología , Teniasis/diagnóstico , Animales , Anticuerpos/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Proteínas del Tejido Nervioso/genética , Neurocisticercosis/sangre , Neurocisticercosis/inmunología , Proteínas Recombinantes/sangre , Valores de Referencia , Sensibilidad y Especificidad , Pruebas Serológicas , Teniasis/sangre , Teniasis/inmunologíaRESUMEN
OBJECTIVE: To verify whether the serum levels of N-Terminal ProBNP fraction (ProBNP) allow us to identify with accuracy the clinical functional status of patients with heart failure (HF), because the clinical diagnosis of this syndrome is based basically on clinical data when the complementary tests have lower specificity. METHODS: Sixty-nine patients with a history of HF were studied. Their mean age of was 53.5 years and 78.3% were males. All underwent clinical and echocardiographic evaluations and a test to determine the serum dosage of ProBNP. According to clinical manifestation, patients were in the following functional classes (FC), 14% FC I, 40.6% FC II, 28.1% FC III, and 23.4% FC IV. The mean ejection fraction (EF) was 0.28. RESULTS: ProBNP did not differ according to age, sex, and cause of cardiopathy. No correlation existed between EF and the ProBNP serum level. ProBNP levels were significantly lower in patients in FC I than those in FC II (42 vs 326.7 pmol/L; P=0.0001), and in FC II than those in FC III (P=0.01). ProBNP levels did not differ statically between FC III and IV patients (888.1 vs 1082.8 pmol/L; P=0.25). ProBNP values greater than 100 pmol/L identify patients with decompensated HF with a sensitivity of 98%. CONCLUSION: ProBNP values over 100 pmol/L were indicative of HF, and patients with advanced HF had values over 270 pmol/L. A ProBNP dosage test was an excellent auxiliary in the clinical characterization of patients with HF.