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1.
Neurologia (Engl Ed) ; 39(3): 244-253, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37442425

RESUMO

INTRODUCTION: The relationship between the entorhinal cortex (EC) and the hippocampus has been studied by different authors, who have highlighted the importance of grid cells, place cells, and the trisynaptic circuit in the processes that they regulate: the persistence of spatial, explicit, and recent memory and their possible impairment with ageing. OBJECTIVE: We aimed to determine whether older age causes changes in the size and number of grid cells contained in layer III of the EC and in the granular layer of the dentate gyrus (DG) of the hippocampus. METHODS: We conducted post-mortem studies of the brains of 6 individuals aged 56-87 years. The brain sections containing the DG and the adjacent EC were stained according to the Klüver-Barrera method, then the ImageJ software was used to measure the individual neuronal area, the total neuronal area, and the number of neurons contained in rectangular areas in layer III of the EC and layer II of the DG. Statistical analysis was subsequently performed. RESULTS: We observed an age-related reduction in the cell population of the external pyramidal layer of the EC, and in the number of neurons in the granular layer of the DG. CONCLUSION: Our results indicate that ageing causes a decrease in the size and density of grid cells of the EC and place cells of the DG.


Assuntos
Córtex Entorrinal , Células de Lugar , Humanos , Córtex Entorrinal/fisiologia , Giro Denteado/fisiologia , Hipocampo , Neurônios
2.
Cogn Neurodyn ; 17(2): 385-398, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37007196

RESUMO

People with impaired motor function could be helped by an effective brain-computer interface (BCI) based on a real-time electroencephalogram (EEG) and artificial intelligence algorithms. However, current methodologies for interpreting patient instructions from an EEG are not accurate enough to be completely safe in a real-world situation , where a poor decision would place their physical integrity at risk, such as when traveling in an electric wheelchair in a city. For various reasons, such as the low signal-to-noise ratio of portable EEGs or the effects of signal contamination (disturbances due to user movement, temporal variation of the features of EEG signals, etc.), a long short-term memory network (LSTM) (a type of recurrent neural network) that is able to learn data flow patterns from EEG signals could improve the classification of the actions taken by the user. In this paper, the effectiveness of using an LSTM with a low-cost wireless EEG device in real time is tested, and the time window that maximizes its classification accuracy is studied. The goal is to be able to implement it in the BCI of a smart wheelchair with a simple coded command protocol, such as opening or closing the eyes, which could be executed by patients with reduced mobility. Results show a higher resolution of the LSTM with an accuracy range between 77.61 and 92.14% compared to traditional classifiers (59.71%), and an optimal time window of around 7 s for the task done by users in this work. In addition, tests in real-life contexts show that a trade-off between accuracy and response times is necessary to ensure detection.

3.
J Perinatol ; 43(7): 856-863, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36347968

RESUMO

OBJECTIVE: Assessment of neurobehavior and visual function of newborns with congenital heart disease during the post-operative period to identify infants at risk of neurodevelopmental and visual impairment. STUDY DESIGN: Prospective study that included 45 newborns who underwent cardiac surgery. Newborn Behavioral Observations test (NBO) and "ML Battery of Optotypes" were used for assessment. RESULTS: The median NBO global score was 2.4 [2.1-2.6]. Total days of oral morphine [p = 0.005] and total days of sedation [p = 0.009] were strongly related to abnormal evaluations. Time of cerebral regional oxygen saturation (CrSO2) under 40% during surgery and increased lactate were related to abnormal motor evaluation. Only 14.5% of patients presented pathological results in visual evaluation. CONCLUSIONS: We have demonstrated alterations in attention, autonomic, motor, and oral motor function. Duration of sedative medication, time of CrSO2 under 40% during surgery, and increased lactate are the most important risk factors. No significant visual impairment was detected.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas , Lactente , Humanos , Recém-Nascido , Estudos Prospectivos , Cardiopatias Congênitas/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologia , Lactatos , Oxigênio
4.
J Matern Fetal Neonatal Med ; 35(6): 1213-1218, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32216488

RESUMO

AIM: Cardiopulmonary bypass (CPB) generates a systemic capillary leak syndrome with pulmonary edema. Lung ultrasound (LUS) could be useful to monitor it. Primary objective was to compare sensitivity, specificity, positive and negative predictive values of chest X-ray and LUS to detect pulmonary edema using a new score (LUCAS). Secondary objectives were to evaluate correlation between LUCAS score and respiratory and inotropic support. METHODS: Prospective intervention study including patients <2 months admitted to the Pediatric Intensive Care Unit after CPB. LUS was performed with a lineal probe, screening 3 points in each lung (parasternal, anterolateral and posterior area), pre and post-CPB. Pulmonary edema was evaluated clinically, through LUCAS score and with X-ray. RESULTS: 17 patients were included. LUS achieved higher sensitivity than X-ray to detect pulmonary edema (91.7 versus 44.0%) and greater predictive negative value (88.2 versus 53.3%). There was correlation between higher LUCAS score prior to surgery and longer mechanical ventilation. High values of LUCAS score after surgery correlated with longer CPB time, inotropic support, and FiO2 need. CONCLUSION: LUS detected pulmonary edema better than chest X-ray, with greater sensitivity and negative predictive value. LUCAS score was useful to predict more inotropic support and longer mechanical ventilation.Key notesCardiopulmonary bypass during cardiac surgery, generates a systemic capillary leak syndrome with pulmonary edema.In this prospective study performed in the Pediatric Intensive Care Unit, lung ultrasound detected pulmonary edema better than X-ray, with greater sensitivity and negative predictive value.LUCAS score was useful to predict more inotropic support and longer mechanical ventilation.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Edema Pulmonar , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Humanos , Pulmão/diagnóstico por imagem , Estudos Prospectivos , Edema Pulmonar/diagnóstico por imagem , Edema Pulmonar/etiologia , Ultrassonografia
5.
Chemphyschem ; 23(4): e202100752, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-34931746

RESUMO

The fine structure in the spectral lines of the visible fluorescence of Tb3+ complexes are replaced by a single peak in the case of a singular molecular complex Tb(H3 PTC)3 , where H4 PTC represents perylene-3,4,9,10-tetracarboxylic acid, and its emission wavelength depends on the film thickness. This single peak challenges the old creed that the f-orbital electrons of Tb3+ are always protected from the influence of the surrounding atoms. We perform density functional theory calculations to show that the wavefunction of the ground state is localized and in addition, spin-polarized, and this facilitates fluorescent transitions under UV to the first excited state instead of the fundamental state. We discuss the possibility of making a spintronic device with the molecule, Tb(H3 PTC)3 .

7.
Neurologia (Engl Ed) ; 2021 Sep 13.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34531045

RESUMO

INTRODUCTION: The relationship between the entorhinal cortex and the hippocampus has been studied by different authors, who have highlighted the importance of grid cells, place cells, and the trisynaptic circuit in the processes that they regulate: the persistence of spatial, explicit, and recent memory and their possible impairment with ageing. OBJECTIVE: We aimed to determine whether older age causes changes in the size and number of grid cells contained in layer III of the entorhinal cortex and in the granular layer of the dentate gyrus of the hippocampus. METHODS: We conducted post-mortem studies of the brains of 6 individuals aged 56-87 years. The brain sections containing the dentate gyrus and the adjacent entorhinal cortex were stained according to the Klüver-Barrera method, then the Image J software was used to measure the individual neuronal area, the total neuronal area, and the number of neurons contained in rectangular areas in layer III of the entorhinal cortex and layer II of the dentate gyrus. Statistical analysis was subsequently performed. RESULTS: We observed an age-related reduction in the cell population of the external pyramidal layer of the entorhinal cortex, and in the number of neurons in the granular layer of the dentate gyrus. CONCLUSION: Our results indicate that ageing causes a decrease in the size and density of grid cells of the entorhinal cortex and place cells of the dentate gyrus.

8.
J Perinatol ; 40(8): 1185-1192, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32546828

RESUMO

OBJECTIVE: Less invasive surfactant administration (LISA) has proved to safely improve morbidity in extreme preterms with respiratory distress syndrome (RDS). Its effect regarding intraventricular hemorrhage (IVH) remains controversial between most recent systematic reviews. We aimed to evaluate its effect over incidence of severe IVH in this population. STUDY DESIGN: We compared the incidence of IVH in a prospective cohort of consecutively born preterm infants <34 weeks' gestation receiving LISA (n = 108) with a historical cohort receiving surfactant delivery via tracheal tube and managed with mechanical ventilation (n = 100). RESULTS: No significant differences regarding perinatal characteristics were observed between both groups. There was a significant reduction in the incidence of severe IVH in LISA group as compared with the historical group [OR = 0.054 (95% CI 0.01-0.2) p = 0.000. NNT 5]. In addition, a significant trend towards decreased mortality was also observed in the study group [OR = 0.2 (95% CI 0.04-0.9) p = 0.027, NNT 9]. Intervention group infants also showed lower oxygenation requirements during the first 72 h post surfactant administration and a reduced incidence of pneumothorax. They were less frequently intubated [31 infants (28.4%) vs. 100 [100%]; P < 0.001] and required fewer days of mechanical ventilation. However, no significant difference in bronchopulmonary dysplasia incidence was observed between both groups. CONCLUSIONS: LISA approach effectively reduces severe IVH in very low and low birth weight (BW) preterms with RDS. In addition we observe a significant trend towards reduction in both need and duration of MV support, air leak, and overall mortality in the intervention group.


Assuntos
Síndrome do Desconforto Respiratório do Recém-Nascido , Tensoativos , Estudos de Coortes , Feminino , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Estudos Prospectivos , Respiração Artificial , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/prevenção & controle
9.
Clin Neurol Neurosurg ; 194: 105921, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32422545

RESUMO

BACKGROUND: Increasing research reports neurological manifestations of COVID-19 patients. SARS-CoV-2 shares homology with other human coronaviruses that have also had nervous system involvement. OBJECTIVE: To review the neurological aspects of SARS-cov2 and other coronavirus, including transmission pathways, mechanisms of invasion into the nervous system, and mechanisms of neurological disease. METHODS: We conducted a systematic review of articles in PubMed, SCOPUS and EMBASE data bases. Reviewed evidence is presented in sections of this manuscript which includes pathogenesis, neuro-invasion, encephalitis, Guillain-Barré, ADEM, multiple sclerosis, polyneuropathy, and cerebrovascular disease. RESULTS: A total 67 studies were included in the final analysis of experimental studies, case reports, series of cases, cohort studies, and systematic reviews related to neurological manifestations of SARS- CoV-2 and other human coronavirus infections. The SARS-CoV-2 receptor is expressed in the nervous system. Common reported symptoms included hyposmia, headaches, weakness, altered consciousness. Encephalitis, demyelination, neuropathy, and stroke have been associated with COVID-19. Infection through the cribriform plate and olfactory bulb and dissemination through trans-synaptic transfer are some of the mechanisms proposed. Invasion of the medullary cardiorespiratory center by SARS-CoV-2 may contribute to the refractory respiratory failure observed in critically-ill COVID-19 patients. CONCLUSION: An increasing number of reports of COVID-19 patients with neurological disorders add to emergent experimental models with neuro-invasion as a reasonable concern that SARS-CoV-2 is a new neuropathogen. How it may cause acute and chronic neurologic disorders needs to be clarified in future research.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/epidemiologia , Doenças do Sistema Nervoso/diagnóstico por imagem , Doenças do Sistema Nervoso/epidemiologia , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/epidemiologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/virologia , COVID-19 , Infecções por Coronavirus/metabolismo , Humanos , Doenças do Sistema Nervoso/metabolismo , Estudos Observacionais como Assunto/métodos , Pandemias , Pneumonia Viral/metabolismo , SARS-CoV-2
10.
Cancer Lett ; 477: 49-59, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32142919

RESUMO

The prognosis of patients with metastatic rhabdomyosarcoma (RMS), the most common type of soft tissue sarcoma in children, is poor and no strategies have been identified to improve their dismal prognosis. Alpha-9 integrin (ITGA9) plays a particularly crucial role in cancer progression and invasiveness. Despite the consensus on the remarkable pro-oncogenic potential of this protein, the miRNA-mediated regulation of ITGA9 has barely been studied to date. In the present study, miR-7 and miR-324-5p were selected as the best candidates after a screening to find ITGA9 regulators, and their effects on cell proliferation and invasion in RMS are described and characterized for the first time. Interestingly, the overexpression of both miRNA produced a clear impairment of cell proliferation, while miR-7 also induced a remarkable drop in cell invasion. Furthermore, the stable overexpression of both miRNA was found to reduce tumor growth in orthotopic RMS models and miR-7 was able to impair metastatic lung colonization. Consequently, we conclude that miR-7 and miR-324-5p show anti-oncogenic and anti-metastatic potential, thereby opening up the possibility of being used as novel therapeutic tools to avoid RMS progression.


Assuntos
Integrinas/genética , MicroRNAs/genética , Rabdomiossarcoma/genética , Rabdomiossarcoma/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Doxiciclina/farmacologia , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos SCID , Fosforilação , RNA Interferente Pequeno , Rabdomiossarcoma/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Ultrasound Obstet Gynecol ; 56(6): 837-849, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31909552

RESUMO

OBJECTIVES: Coarctation of the aorta (CoA) is associated with left ventricular (LV) dysfunction in neonates and adults. Cardiac structure and function in fetal CoA and cardiac adaptation to early neonatal life have not been described. We aimed to investigate the presence of cardiovascular structural remodeling and dysfunction in fetuses with CoA and their early postnatal cardiac adaptation. METHODS: This was a prospective observational case-control study, conducted between 2011 and 2018 in a single tertiary referral center, of fetuses with CoA and gestational age-matched normal controls. All fetuses/neonates underwent comprehensive echocardiographic evaluation in the third trimester of pregnancy and after birth. Additionally, myocardial microstructure was assessed in one fetal and one neonatal CoA-affected heart specimen, using synchrotron radiation-based X-ray phase-contrast microcomputed tomography and histology, respectively. RESULTS: We included 30 fetuses with CoA and 60 gestational age-matched controls. Of these, 20 CoA neonates and 44 controls were also evaluated postnatally. Fetuses with CoA showed significant left-to-right volume redistribution, with right ventricular (RV) size and output dominance and significant geometry alterations with an abnormally elongated LV, compared with controls (LV midventricular sphericity index (median (interquartile range; IQR), 2.4 (2.0-2.7) vs 1.8 (1.7-2.0); P < 0.001). Biventricular function was preserved and no ventricular hypertrophy was observed. Synchrotron tomography and histological assessment revealed normal myocyte organization in the fetal and neonatal specimens, respectively. Postnatally, the LV in CoA cases showed prompt remodeling, becoming more globular (LV midventricular sphericity index (mean ± SD), 1.5 ± 0.3 in CoA vs 1.8 ± 0.2 in controls; P < 0.001) with preserved systolic and normalized output, but altered diastolic, parameters compared with controls (LV inflow peak velocity in early diastole (mean ± SD), 97.8 ± 14.5 vs 56.5 ± 12.9 cm/s; LV inflow peak velocity in atrial contraction (median (IQR), 70.5 (60.1-84.9) vs 47.0 (43.0-55.0) cm/s; LV peak myocardial velocity in atrial contraction (mean ± SD), 5.1 ± 2.6 vs 6.3 ± 2.2 cm/s; P < 0.05). The neonatal RV showed increased longitudinal function in the presence of a patent arterial duct. CONCLUSIONS: Our results suggest unique fetal cardiac remodeling in CoA, in which the LV stays smaller from the decreased growth stimulus of reduced volume load. Postnatally, the LV is acutely volume-loaded, resulting in an overall geometry change with higher filling velocities and preserved systolic function. These findings improve our understanding of the evolution of CoA from fetal to neonatal life. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Coartação Aórtica/fisiopatologia , Coração Fetal/fisiopatologia , Ventrículos do Coração/fisiopatologia , Ultrassonografia Pré-Natal/métodos , Remodelação Ventricular , Adulto , Coartação Aórtica/diagnóstico por imagem , Coartação Aórtica/embriologia , Estudos de Casos e Controles , Ecocardiografia , Feminino , Coração Fetal/diagnóstico por imagem , Idade Gestacional , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/embriologia , Humanos , Recém-Nascido , Gravidez , Estudos Prospectivos , Microtomografia por Raio-X
13.
Rev. argent. dermatol ; 100(4): 21-30, dic. 2019. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1092392

RESUMO

RESUMEN Los efectos nocivos de la radiación solar han sido reportados, pero casi no se ha estudiado la población laboral de Latinoamérica. Este es un estudio transversal analítico realizado en ocho países. Las preguntas sobre protección solar se tomaron de trabajos previos; además, se preguntó por las características laborales; ambos datos se cruzaron para obtener datos estadísticos de asociación. De los 3.222 trabajadores encuestados, el 71% (2270) tenía piel mestiza. Hubo asociación del enrojecimiento de la piel según la cantidad de horas de exposición solar directa (p<0,001) e indirecta (p<0,001). El 47% (995) usaban protector/bloqueador solar, el 54% (1150) usaban ropa adecuada y el 50% (1056) usaban alguna gorra o sombrero; siendo estadísticamente diferente el medio de adquisición de dichos equipos. El 21% (446) no usaba ninguno de los equipos de protección personal ante los efectos del sol. Concluimos que es alarmante el bajo porcentaje de trabajadores que reciben adecuada protección contra los efectos de la radiación solar. Esto podría generar problemas a corto, mediano y largo plazo entre los empleados, lo que podría aumentar la morbi-mortalidad y el riesgo de cáncer de piel.


ABSTRACT The harmful effects of solar radiation have been reported, but the work population in Latin America has hardly been studied. The objective is describe the type of sun protection they use and find associations according to their characteristics in Latin American workers. The methodology isCross-sectional analytical study carried out in 8 countries, the questions of sun protection were taken from previous work, in addition, asked about the labor characteristics; Both were crossed to obtain association statistics. Our results: Of the 3.222 workers surveyed, 71% (2270) had mestizo skin. There was association of skin redness according to the number of hours of direct (p <0.001) and indirect sun exposure (p <0.001). 47% (995) wore the sunscreen / protector, 54% (1150) wore appropriate clothing and 50% (1056) wore a cap or hat; statistically different according to the means of acquisition of such equipment (p value <0.001 for all three cases). 21% (446) did not wear any personal protective equipment to the effects of the sun. It is alarming that the low percentage of workers who receive adequate protection against the effects of solar radiation can cause problems in the short, medium and long term among employees. This could increase morbidity and mortality and the risk of skin cancer. It is important to do more research in this regard, as this issue is of utmost importance because of the changes that have occurred in radiation levels, which could generate a public health problem in this work group.

14.
Rev Neurol (Paris) ; 175(10): 705-723, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31521394

RESUMO

Observational epidemiological studies provide valuable information regarding naturally occurring protective factors observed in populations with very low prevalences of vascular disease. Between 1935 and 1965, the Italian-American inhabitants of Roseto (Pennsylvania, USA) observed a traditional Italian diet and maintained half the mortality rates from myocardial infarction compared with neighboring cities. In the Seven Countries Study, during 40years (1960-2000) Crete maintained the lowest overall mortality rates and coronary heart disease fatalities, which was attributed to strict adherence to the Mediterranean diet. In the French Three-City Study, a ten-year follow-up (2000-2010) showed that higher consumption of olive oil was associated with lower risk of death, as well as protection from cognitive decline and stroke. A large number of population-based studies and intervention trials have demonstrated that the Mediterranean diet is associated with lower prevalence of vascular disease, obesity, arthritis, cancer, and age-associated cognitive decline. Many of these effects are the result of consumption of fruits, seeds, legumes and vegetables but olive oil is the chief dietary fat in Mediterranean countries and the main source of monounsaturated fatty acids, as well as an important source of beneficial polyphenols and other antioxidants. Considering the critical role of vascular factors in the pathogenesis of late-onset Alzheimer disease it seems appropriate to focus on disease modification through proven dietary therapy. The authors base their hypothesis on meta-analyses of epidemiological data, numerous experimental studies, and a comprehensive review of the mechanisms of action of extra-virgin olive oil and its components in the prevention of vascular disease. In addition, extra-virgin olive oil has had positive effects on experimental animal models of Alzheimer disease. We therefore propose that extra-virgin olive oil is a promising tool for mitigating the effects of adverse vascular factors and may be utilized for potential prevention of late-onset Alzheimer disease.


Assuntos
Doença de Alzheimer/prevenção & controle , Azeite de Oliva/uso terapêutico , Idade de Início , Doença de Alzheimer/dietoterapia , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/etiologia , Animais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Dieta Mediterrânea/história , História do Século XX , História do Século XXI , Humanos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidade , Estados Unidos/epidemiologia
15.
BMC Pediatr ; 19(1): 326, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506079

RESUMO

BACKGROUND: Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. METHODS: Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). DISCUSSION: The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children's neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD. TRIAL REGISTRATION: NCT02996630 , on 4th December 2016 (retrospectively registered).


Assuntos
Desenvolvimento Infantil , Ensaios Clínicos como Assunto , Cardiopatias Congênitas/complicações , Transtornos do Neurodesenvolvimento/etiologia , Biomarcadores/sangue , Ecocardiografia , Feminino , Idade Gestacional , Cardiopatias Congênitas/sangue , Humanos , Lactente , Imageamento por Ressonância Magnética , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Prognóstico , Estudos Prospectivos
17.
Redox Biol ; 24: 101187, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30965198

RESUMO

Erythropoietin is a glycoproteic hormone that regulates hematopoiesis by acting on its specific receptor (EpoR). The expression of EpoR in the central nervous system (CNS) suggests a role for this hormone in the brain. Recently, we developed a new Epo variant without hematopoietic activity called EpoL, which showed marked neuroprotective effects against oxidative stress in brain ischemia related models. In this study, we have evaluated the neuroprotective effects of EpoL against oxidative stress induced by chronic treatment with Aß. Our results show that EpoL was neuroprotective against Aß-induced toxicity by a mechanism that implicates EpoR, reduction in reactive oxygen species, and reduction in astrogliosis. Furthermore, EpoL treatment improved calcium handling and SV2 levels. Interestingly, the neuroprotective effect of EpoL against oxidative stress induced by chronic Aß treatment was achieved at a concentration 10 times lower than that of Epo. In conclusion, EpoL, a new variant of Epo without hematopoietic activity, is of potential interest for the treatment of diseases related to oxidative stress in the CNS such as Alzheimer disease.


Assuntos
Eritropoetina/farmacologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Proteínas Recombinantes/farmacologia , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/farmacologia , Animais , Sinalização do Cálcio , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Eritropoetina/genética , Eritropoetina/isolamento & purificação , Cabras , Leite , Fármacos Neuroprotetores/isolamento & purificação , Fragmentos de Peptídeos/química , Multimerização Proteica , Espécies Reativas de Oxigênio/metabolismo , Receptores da Eritropoetina/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação
18.
Vaccine ; 37(10): 1340-1349, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30711318

RESUMO

Proliferative enteropathy, caused by Lawsonia intracellularis, represents a threat for swine industry. Current vaccines are effective but difficult to obtain and scaled up, because of demanding bacterial culture conditions. In this work, a subunit vaccine candidate against L. intracellularis was developed and its efficacy was evaluated in vivo, alone or co-formulated with pig recombinant IFN-α. The vaccine formulation contains three chimeric antigens: two outer membrane proteins and a secreted one, which were engineered by adding T epitopes using bioinformatics tools. After simultaneously expressing the three antigens in E. coli, its immunogenicity was tested in mice and pigs. Antigens co-formulated with porcine IFN-α were also assayed in the last species. Immune response was assessed by ELISA and qPCR, and histopathological studies of intestinal epithelial tissue were performed after challenge. Mice and pigs showed an increased IgG response against chimeric antigens. Particularly, there were significant differences in the antibody response when porcine IFN-α was co-administrated with L. intracellularis antigens. Besides, mRNAs from il12 and cd4 marker were detected during the first week after immunization of pigs, suggesting a Th1-type cellular immune response. The significant enhancement of oas2 gene expression indicates the effect exerted by porcine IFN-α. Post-mortem histopathological analysis post-challenge revealed damage only into epithelial cells of the gastrointestinal tract from animals of the negative control group. Injuries were related to atrophy of the intestinal villi, where a decrease of globet cells and a greater migration of lymphocytes were observed. Overall, our results demonstrated that the vaccine candidate elicited significant humoral and cellular immune responses. Besides, histopathological analysis suggested that vaccinated animals were protected against experimental L. intracellularis infection. This research constitutes a step forward to the generation of the first recombinant chimeric vaccine against L. intracellularis, representing a faster, easier and cost effective approach to counteract the porcine proliferative enteropathy.


Assuntos
Antígenos de Bactérias/imunologia , Vacinas Bacterianas/imunologia , Infecções por Desulfovibrionaceae/veterinária , Imunogenicidade da Vacina , Doenças dos Suínos/prevenção & controle , Animais , Antígenos de Bactérias/administração & dosagem , Vacinas Bacterianas/administração & dosagem , Infecções por Desulfovibrionaceae/prevenção & controle , Escherichia coli/genética , Escherichia coli/imunologia , Fezes/microbiologia , Feminino , Imunidade Celular , Interferon-alfa/administração & dosagem , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Lawsonia (Bactéria) , Camundongos , Camundongos Endogâmicos C57BL , Suínos , Células Th1/imunologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia
19.
J Perinatol ; 39(4): 547-553, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30723276

RESUMO

OBJECTIVE: Intraventricular hemorrhage (IVH) is a common complication in extremely preterm infants. We aimed to demonstrate that umbilical cord milking (UCM) would reduce the incidence of IVH in this at risk population. STUDY DESIGN: We compared the incidence of IVH in a prospective cohort of consecutively born preterm infants <32 weeks' gestation receiving UCM (n = 33) with a historical cohort that underwent immediate cord clamping (ICC) (n = 36). RESULTS: No significant differences regarding perinatal characteristics were present between both groups except for chorioamnionitis and preterm rupture of membranes which were more frequent in the UCM group. There was a significant reduction in the incidence of IVH in the UCM group as compared to the ICC group (UCM vs. ICC = 12 vs. 33%, p = 0.037; OR = 0.276 (95% CI 0.079-0.967; p = 0.033; NNT = 4.7) and a reduction in the number of transfusions (UCM vs. ICC = 56 vs. 30%, p = 0.035; OR = 0.348 (0.129-0.938; p = 0.033; NNT = 3.8). UCM was safe for mothers (similar decrease in maternal hemoglobin) and offspring. CONCLUSION: UCM significantly reduced the incidence of IVH in preterm infants < 32 weeks' gestation without associated complications for mother or offspring.


Assuntos
Hemorragia Cerebral Intraventricular/prevenção & controle , Recém-Nascido Prematuro , Cordão Umbilical , Adulto , Transfusão de Sangue , Circulação Cerebrovascular , Estudos de Coortes , Constrição , Feminino , Idade Gestacional , Humanos , Incidência , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Circulação Placentária , Gravidez , Estudos Prospectivos , Risco
20.
Pediatr Obes ; 14(3): e12476, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30362284

RESUMO

BACKGROUND: The sequence of prenatal growth restraint and postnatal catch-up growth leads to a thicker intima-media and more pre-peritoneal fat by age 3-6 years. OBJECTIVES: To study whether carotid intima-media thickness (cIMT) and pre-peritoneal fat differ already between catch-up small-for-gestational-age (SGA) infants and appropriate-for-gestational-age (AGA) controls in late infancy (ages 1 and 2 years) and whether such differences - if any - are accompanied by differences in cardiac morphology and function. METHODS: Longitudinal assessments included body height and weight; fasting glucose, insulin, Insulin-like growth factor (IGF-I), high-molecular-weight adiponectin; body composition (by absorptiometry); cIMT, aortic IMT, pre-peritoneal fat partitioning (by ultrasound); cardiac morphometry and function (by echocardiography) in AGA and SGA infants at birth, at age 1 year (N = 87), and again at age 2 years (N = 68). RESULTS: Catch-up SGA infants had already a thicker cIMT than AGA controls at ages 1 and 2 years, and more pre-peritoneal fat by age 2 years (all p values between <0.01 and <0.0001); all cardiac and endocrine-metabolic results were similar in AGA and SGA infants at ages 1 and 2 years. CONCLUSIONS: From late infancy onwards, catch-up SGA infants have a thicker cIMT and more pre-peritoneal fat than AGA controls, but their cardiac morphology and function remain reassuringly similar.


Assuntos
Gordura Abdominal/fisiologia , Espessura Intima-Media Carotídea/estatística & dados numéricos , Desenvolvimento Infantil/fisiologia , Coração/fisiologia , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Adiponectina/sangue , Glicemia/fisiologia , Composição Corporal/fisiologia , Estatura , Peso Corporal , Pré-Escolar , Ecocardiografia/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Estudos Longitudinais , Masculino , Gravidez , Estudos Prospectivos
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