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Growth hormone (GH) is a pituitary protein that exerts pleiotropic roles in vertebrates. The mechanisms regulating GH synthesis and secretion are finely controlled by hypothalamic neuropeptides and other factors. These processes have been considerably studied in mammals but are still poorly understood in other groups. To better understand the pituitary GH regulation during vertebrate phylogeny, we compared the effects of incubating several peptides on cultures of ex-vivo pituitary fragments obtained from representative specimens of reptiles (iguana), birds (chicken) and mammals (rat). The peptides used were: growth hormone-releasing hormone (GHRH), thyrotropin-releasing hormone (TRH), pituitary adenylate cyclase-activating polypeptide (PACAP), ghrelin, gonadotropin-releasing hormone (GnRH), and somatostatin (SST). In rat pituitary cultures, GH secretion was stimulated by GHRH and TRH, while gh mRNA expression was increased by GHRH and PACAP. In the case of chicken pituitaries, GH release was promoted by GHRH, ghrelin, PACAP, and GnRH, although the latter two had a dual effect since at a shorter incubation time they decreased GH secretion; in turn, gh mRNA expression was significantly stimulated by TRH, PACAP, and GnRH. The most intense effects were observed in iguana pituitary cultures, where GH secretion was significantly augmented by GHRH, PACAP, TRH, ghrelin, and GnRH; while gh mRNA expression was stimulated by GHRH, TRH, and PACAP, but inhibited by ghrelin and SST. Also, in the three species, SST was able to block the GHRH-stimulated GH release. Furthermore, it was found that the expression of Pou1f1 mRNA was increased with greater potency by GHRH and PACAP in the iguana, than in chicken or rat pituitary cultures. Additionally, in-silico analysis of the gh gene promoter structures in the three species showed that the reptilian promoter has more Pit-1 consensus binding sites than their avian and mammalian counterparts. Taken together, results demonstrate that pituitary peptide-mediated GH regulatory mechanisms are differentially controlled along vertebrate evolution.
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Resumen Una de las complicaciones durante un evento de síndrome coronario agudo es la presencia de arritmias. Dentro de ellas, las de tipo supraventricular, en especial fibrilación auricular, acarrea un mal pronóstico tanto a corto como a largo plazo y es la causa de situaciones como evento vascular cerebral, arritmias ventriculares y aumento de la mortalidad. Dicha arritmia tiende a aparecer en cierto grupo de población con particulares factores de riesgo durante el evento índice en aproximadamente 10% de los casos. Un tratamiento apropiado en el momento de su aparición, gracias al uso de fármacos que modulan la frecuencia cardiaca, el ritmo y el manejo anticoagulante en los grupos más vulnerables conllevará un desenlace menos sombrío para estos pacientes.
Abstract One of the complications during an acute coronary syndrome event is the presence of arrhythmias. Among them, those of the supraventricular type, especially atrial fibrillation, carry a poor prognosis both in the short and long term, being the cause of situations such as cerebrovascular event, ventricular arrhythmias, and increased mortality. The arrhythmia tends to appear in a certain population group with particular risk factors during the index event in approximately 10% of cases. Appropriate treatment at the time of its onset, thanks to the use of drugs that modulate heart rate, rhythm, and anticoagulant management in the most vulnerable groups, will lead to a less bleak outcome for these patients.
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One of the complications during an acute coronary syndrome event is the presence of arrhythmias. Among them, those of the supraventricular type, especially atrial fibrillation, carry a poor prognosis both in the short and long term, being the cause of situations such as cerebrovascular event, ventricular arrhythmias, and increased mortality. The arrhythmia tends to appear in a certain population group with particular risk factors during the index event in approximately 10% of cases. Appropriate treatment at the time of its onset, thanks to the use of drugs that modulate heart rate, rhythm, and anticoagulant management in the most vulnerable groups, will lead to a less bleak outcome for these patients.
Una de las complicaciones durante un evento de síndrome coronario agudo es la presencia de arritmias. Dentro de ellas, las de tipo supraventricular, en especial fibrilación auricular, acarrea un mal pronóstico tanto a corto como a largo plazo y es la causa de situaciones como evento vascular cerebral, arritmias ventriculares y aumento de la mortalidad. Dicha arritmia tiende a aparecer en cierto grupo de población con particulares factores de riesgo durante el evento índice en aproximadamente 10% de los casos. Un tratamiento apropiado en el momento de su aparición, gracias al uso de fármacos que modulan la frecuencia cardiaca, el ritmo y el manejo anticoagulante en los grupos más vulnerables conllevará un desenlace menos sombrío para estos pacientes.
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Síndrome Coronariana Aguda , Fibrilação Atrial , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/fisiopatologia , Síndrome Coronariana Aguda/etiologia , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/etiologia , Fatores de RiscoRESUMO
The domestication process of the common bean gave rise to six different races which come from the two ancestral genetic pools, the Mesoamerican (Durango, Jalisco, and Mesoamerica races) and the Andean (New Granada, Peru, and Chile races). In this study, a collection of 281 common bean landraces from Chile was analyzed using a 12K-SNP microarray. Additionally, 401 accessions representing the rest of the five common bean races were analyzed. A total of 2543 SNPs allowed us to differentiate a genetic group of 165 accessions that corresponds to the race Chile, 90 of which were classified as pure accessions, such as the bean types 'Tórtola', 'Sapito', 'Coscorrón', and 'Frutilla'. Our genetic analysis indicates that the race Chile has a close relationship with accessions from Argentina, suggesting that nomadic ancestral peoples introduced the bean seed to Chile. Previous archaeological and genetic studies support this hypothesis. Additionally, the low genetic diversity (π = 0.053; uHe = 0.53) and the negative value of Tajima' D (D = -1.371) indicate that the race Chile suffered a bottleneck and a selective sweep after its introduction, supporting the hypothesis that a small group of Argentine bean genotypes led to the race Chile. A total of 235 genes were identified within haplotype blocks detected exclusively in the race Chile, most of them involved in signal transduction, supporting the hypothesis that intracellular signaling pathways play a fundamental role in the adaptation of organisms to changes in the environment. To date, our findings are the most complete investigation associated with the origin of the race Chile of common bean.
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Phaseolus , Phaseolus/genética , Chile , Argentina , Domesticação , Pool GênicoRESUMO
Treatment for heart failure has experienced a major revolution in recent years, and current evidence shows that a combination of four medications (angiotensin receptor-neprilysin inhibitors + ß-blockers + mineralocorticoid receptor antagonists + sodium.glucose cotransporter 2 inhibitors) offer the greatest benefit to our patients with significant reductions in cardiovascular mortality, heart failure hospitalisations and all-cause mortality. Unfortunately, despite their proven benefits, the implementation of these therapies is still low. Clinical inertia, and unfounded fear of using these drugs might contribute to this. Recently, evidence from randomised clinical trials has shown that intensive implementation of these therapies in patients with heart failure is safe and effective. In this review, we attempt to tackle some of these misconceptions/fears regarding medical therapy for heart failure and discuss the available evidence showing the best strategies for implementation of these therapies.
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Fucosyltransferases (Fut) regulate the fucosylation process associated with tumorogenesis in different cancer types. Ascitic fluid (AF) from patients diagnosed with advanced stage of epithelial ovarian cancer (EOC) is considered as a dynamic tumor microenvironment associated with poor prognosis. Previous studies from our laboratory showed increased fucosylation in SKOV-3 and OVCAR-3, cancer-derived cell lines, when these cells were incubated with AFs derived from patients diagnosed with EOC. In the present work we studied three fucosyltransferases (Fut 2, Fut 4, and Fut 8) in SKOV-3, OVCAR-3 and CAOV-3 cell lines in combination with five different AFs from patients diagnosed with this disease, confirming that all tested AFs increased fucosylation. Then, we demonstrate that mRNAs of these three enzymes were overexpressed in the three cell lines under treatment with AFs. SKOV-3 showed the higher overexpression of Fut 2, Fut 4, and Fut 8 in comparison with the control condition. We further confirmed, in the SKOV-3 cell line, by endpoint PCR, WB, and confocal microscopy, that the three enzymes were overexpressed, being Fut 4 the most overexpressed enzyme compared to Fut 2 and Fut 8. These enzymes were concentrated in vesicular structures with a homogeneous distribution pattern throughout the cytoplasm. Moreover, we found that among the three enzymes, only Fut 4 was located inside the nuclei. The nuclear location of Fut 4 was confirmed for the three cell lines. These results allow to propose Fut 2, Fut 4, and Fut 8 as potential targets for EOC treatment or as diagnostic tools for this disease.
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Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/metabolismo , Carcinoma Epitelial do Ovário , Líquido Ascítico/metabolismo , Líquido Ascítico/patologia , Galactosídeo 2-alfa-L-Fucosiltransferase , Apoptose , Linhagem Celular Tumoral , Fucosiltransferases/genética , Fucosiltransferases/metabolismo , Microambiente TumoralRESUMO
Introducción: La hipopotasemia es un trastorno hidroelectrolítico frecuente, asociado a enfermedades sistémicas y multifactoriales, cuya forma aguda puede complicarse y causar la muerte, pero en su presentación crónica puede ser un marcador de nefropatía. Objetivo: Caracterizar el perfil del paciente con hipopotasemia no medicamentosa atendidos de emergencia. Métodos: Se revisaron los registros de pacientes mayores de 18 años con diagnóstico de hipopotasemia, ingresados en el hospital en el período de junio 2018 a diciembre de 2019. Se colectaron datos demográficos, antecedentes médicos y evolución postratamiento. Se comparó con 108 pacientes sin hipopotasemia atendidos en el período de estudio. Resultados: Se encontraron 87 casos con edad media de 38,5 años. El 90,8 por ciento eran hombres menores de 50 años, de oficio agricultor (29,9 por ciento), con historia de exposición a plaguicidas y a altas temperaturas ambientales. La mayoría de ellos no tenía historia de enfermedad cardiometabólicas o renal previa. El 48,3 por ciento de todos los pacientes con hipopotasemia (n = 42) tenía creatinina mayor a 1,2 mg/dL y 63 por ciento tenía hiponatremia. La hipopotasemia fue moderada en 39 por ciento y severa en 12 por ciento, los hombres 4,7 veces más afectados que las mujeres. Respecto al grupo sin hipopotasemia y creatinina anormal, tenían mayor frecuencia de enfermedad crónica (92,5 por ciento versus 8 por ciento). Conclusiones: Se encontró hipopotasemia no medicamentosa en varones agricultores, sin enfermedad crónica, pero con datos de nefropatía temprana e hiponatremia, se sugirió la posibilidad de nefropatía mesoamericana. Debe establecerse una alerta epidemiológica regional y un programa de prevención y control(AU)
Introduction: Hypokalemia is a frequent hydroelectrolytic disorder, associated with systemic and multifactorial diseases, whose acute form can be complicated and cause death, but in its chronic presentation it can be a marker of nephropathy. Objective: To characterize the profile of the patient with non-drug hypokalemia seen in an emergency. Methods: The records of patients older than 18 years diagnosed with hypokalemia, admitted to the hospital from June 2018 to December 2019, were reviewed. Demographic data, medical history, and post-treatment evolution were collected. It was compared with 108 patients without hypokalemia seen in the same period. Results: 87 cases with mean age of 38.5 years were studied. 90.8% were men under 50 years of age, who worked as farmers (29.9percent), with history of exposure to pesticides and high ambient temperatures. Most of them had no history of previous cardiometabolic or renal disease. 48.3percent of all patients with hypokalemia (n = 42) had creatinine higher than 1.2 mg/dL and 63percent had hyponatremia. Hypokalemia was moderate in 39% and severe in 12percent, and it was found that men were affected 4.7 times more than women. Regarding the group without hypokalemia and abnormal creatinine, they had higher frequency of chronic disease (92.5percent versus 8percent). Conclusions: Non-drug hypokalemia was found in male farmers, without chronic disease, but with evidence of early nephropathy and hyponatremia. The possibility of Mesoamerican nephropathy was suggested. A regional epidemiological alert and a prevention and control program should be established(AU)
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Humanos , Fazendeiros , Doenças Renais Crônicas Idiopáticas/epidemiologia , HipopotassemiaRESUMO
Introduction: Assessing Health-Related Quality of Life (HRQOL), in addition to evaluating functional status in stroke patients could complement clinician practice. Objective: To assess HRQOL, applying EuroQol-5-dimensions (EQ-5D) in Colombian patients with stroke and correlating its results with the modified Rankin Scale (mRS). Methods: Analytical cross-sectional study in a cohort of ischemic stroke patients in Colombia at three months as a median follow-up (Q1: 1- Q3:3) after their event. We correlated EQ-5D domains, EQ-5D index, mRS with EQ-5D VAS score. We generated a simple linear regression robust model to evaluate the variability between using r2. Results: A total of 91 patients completed the EQ-5D questionnaire, with a mean age of 71.2 years; 59.3% were male. We identified an inverse correlation between EQ-5D VAS and EQ-5D domains with the highest for mobility (rs = -0.69) and the lowest for pain/discomfort (rs -0.52, p<0.001). The r2 ranged from 0.25 (pain/discomfort) to 0.47 (EQ-5D index). Patients with mRS ≥ 3 significantly reduced their EQ-5D VAS score by 25.64 points (95% CI -33.04, -18.24). Variability in EQ-5D VAS scores occurred by EQ-5D index (47%) and by mRS (34%). Conclusions: The correlation between EQ-5D and mRS was favorable. Although EQ-5D and mRS evaluated different spheres on stroke patients, applying the EQ-5D instrument in real-world clinical settings might contribute multidimensional information on how life is affected after a stroke. This kind of information serves to orientate rehabilitation strategies on specific domains such as depression, self-care, anxiety, and pain. This is especially relevant for patients with disabilities (mRS ≥ 3).
Introducción: La evaluación de la Calidad de Vida Relacionada con la Salud (CVRS) y el estado funcional de pacientes con Ataque Cerebrovascular (ACV), podría complementar la práctica clínica. Objetivo: Evaluar la CVRS, aplicando EuroQol-5-dimensiones (EQ-5D) en pacientes colombianos con ACV y correlacionar sus resultados con la escala de Rankin Modificada (mRS). Métodos: Estudio de corte transversal analítico anidado a una cohorte de pacientes con ACV isquémico en Colombia con mediana de 3 meses de seguimiento (Q1: 1- Q3:3) post-ictus. Correlacionamos los dominios del EQ-5D, índice EQ-5D y mRS con la puntuación de EQ-5D VAS. Generamos un modelo de regresión lineal simple para evaluar la variabilidad usando r2. Resultados: Un total de 91 pacientes con una edad media 71,2 años; 59,3 % hombres. Se encontró correlación inversa entre los dominios EQ-5D, mayor para movilidad (rs = -0,69) y menor para dolor/malestar (rs -0,52, p < 0,001). El r2 osciló entre 0,25 (dolor/malestar) y 0,47 (índice EQ-5D). Los pacientes con mRS ≥ 3 redujeron significativamente su puntuación EQ-5D VAS en 25,64 puntos (IC 95%: -33,04; -18,24). La variabilidad en las puntuaciones EQ-5D VAS se produjo por el índice EQ-5D (47 %) y por mRS (34 %). Conclusiones: La correlación entre EQ-5D y mRS fue favorable. Aunque EQ-5D y mRS evalúan diferentes esferas en los pacientes con ACV, la aplicación del EQ-5D en podría aportar información multidimensional sobre cómo se afecta la vida después de un ictus, así como orientar estrategias de rehabilitación en esferas como depresión, autocuidado, ansiedad y dolor; especialmente relevante para pacientes con discapacidades (mRS ≥ 3).
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The Krüppel-like factor 13 (KLF13) has emerged as an important transcription factor involved in essential processes of the central nervous system (CNS). It predominantly functions as a transcriptional repressor, impacting the activity of several signaling pathways with essential roles in the CNS, including the JAK/STAT pathway, which is the canonical mediator of growth hormone (GH) signaling. It is now recognized that GH has important actions as a neurotrophic factor. Therefore, we analyzed the effects of KLF13 on the activity of the JAK/STAT signaling pathway in the hippocampus-derived cell line HT22. Results showed that KLF13 directly regulates the expression of several genes involved in the JAK-STAT pathway, including Jak1, Jak2, Jak3, and Socs1, by associating with their proximal gene promoters. In addition, it was found that in KLF13-deficient HT22 neurons, the expression of Jak1, Stat3, Socs1, Socs3, and Igf1 was dysregulated, exhibiting mRNA levels that went up to 7-fold higher than the control cell line. KLF13 displayed a differential effect on the GH-induced JAK/STAT pathway activity, decreasing the STAT3 branch while enhancing the STAT5 branch. In KLF13-deficient HT22 cells, the activity of the STAT3 branch was enhanced, mediating the GH-dependent augmented expression of the JAK/STAT output genes Socs1, Socs3, Igf1, and Bdnf. Furthermore, GH treatment increased both the nuclear content of KLF13 and Klf13 mRNA levels, suggesting that KLF13 could be part of the mechanisms that maintain the homeostatic state of this pathway. These findings support the notion that KLF13 is a regulator of JAK/STAT activity.
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Janus Quinases , Transdução de Sinais , Janus Quinases/genética , Janus Quinases/metabolismo , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Heart failure (HF) is usually accompanied by cardiovascular and non-cardiovascular comorbidities, which may significantly impact its prognosis. In this study we aimed to characterize the comorbidity profile and its impact in mortality in patients with HF diagnosis from the Colombian Heart Failure Registry (RECOLFACA). METHODS: RECOLFACA enrolled adult patients with HF diagnosis from 60 centers in Colombia during the period 2017-2019. The primary outcome was all-cause mortality. A Cox proportional hazards regression model was used to assess the impact of the comorbidities in mortality. A p-value of <0.05 was considered significant. RESULTS: From the total 2528 patients included in the registry, 2514 patients (58% males, mean age 68 years) had information regarding comorbidity diagnoses. 2321 patients (92.3%) reported at least one comorbidity. Arterial hypertension was the most frequent individual diagnosis (72%; n = 1811), followed by anemia (30.1%, n = 726). The most frequently observed coexisting comorbidities were coronary disease (CHD) with dyslipidemia, and chronic kidney disease (CKD) with type 2 Diabetes Mellitus (T2DM). Different patterns of comorbidity coexistence were observed when comparing HF patients by sex and left-ventricular ejection fraction (LVEF) classification. The only comorbidities that were significantly associated with mortality after multivariate adjustment were T2DM (HR 1.45. 95% CI 1.01-2.12), anemia (HR 1.48. 95% CI 1.02-2.16), and CHD (HR 1.59. 95% CI 1.09-2.33). CONCLUSION: Multiple comorbidities were frequently observed in the patients from the RECOLFACA. T2DM, anemia and CHD were significantly associated with a higher risk of mortality, highlighting the importance of promoting an optimal follow-up and control of these conditions.
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Anemia , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Masculino , Adulto , Humanos , Idoso , Feminino , Colômbia/epidemiologia , Volume Sistólico , Função Ventricular Esquerda , América Latina , Comorbidade , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Doença Crônica , Sistema de RegistrosRESUMO
We use 395 nm ultraviolet radiation to excite the matrix of barium hafnate doped with europium ions to develop an optical temperature sensor. Luminescent analysis as a function of temperature was performed in the physiological range. The Emission spectra showed significant variations in luminescent intensity at all transitions, obtaining a relative sensitivity of 1574.3/T2, when the temperature of the material increases from 289.7 to 323.8 K. The 5D0 -> 7F2 transition presented the better temperature resolution (1.1 × 102 K).
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Európio , Raios Ultravioleta , Temperatura , Fluorescência , LuminescênciaRESUMO
AIM: The aim of this study was to determine the sagittal position of the upper incisor considering Andrews' analysis based on the position of the forehead in Peruvian individuals with different skeletal relationships. MATERIALS AND METHODS: This retrospective, cross-sectional study included 212 lateral head radiographs of Peruvian individuals (males: 85, mean age 21.38 ± 6.88, and females: 127, mean age 21.18 ± 6.95), with different skeletal relationships (Class I group = 96, Class II group = 57, Class III group = 59). The values of the ANB, SNA, SNB angles as well as the forehead anterior limit line (FALL) and goal anterior limit line (GALL) points were identified in the radiographs, and then a vertical line was drawn in each point to determine if the upper incisor was positioned forward (protruded), backward (retruded) or within (adequate) these lines. Two trained and calibrated investigators performed all the measurements. The Chi-square test was used to evaluate associations. A p-value < 0.05 was considered statistically significant. RESULTS: Overall, the sagittal position of the upper incisor showed a significant association with the sagittal skeletal relationship (p = 0.001). The upper incisors showed an adequate position (41.7%), protruded position (56.10%), and retruded position (42.40%), for Class I, II, and III skeletal relationships, respectively, as highest percentages in each Class. Statistical significance was found for females only (p = 0.005). CONCLUSION: Skeletal Class I mainly showed an adequate position of the upper central incisor, whereas for Class II a protruded position was most frequently found, and Class III presented a retruded position. CLINICAL SIGNIFICANCE: Andrews' analysis based on the position of the forehead in Peruvian individuals is a valuable tool for orthodontic diagnosis. How to cite this article: Bazán-Mendoza JR, Arias-Modesto PB, Ruíz-Mora GA, et al. Sagittal Position of the Upper Incisor in Relation to the Forehead in Peruvian Individuals with Different Skeletal Relationships. J Contemp Dent Pract 2023;24(11):821-825.
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Testa , Incisivo , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Incisivo/diagnóstico por imagem , Testa/diagnóstico por imagem , Testa/anatomia & histologia , Estudos Retrospectivos , Estudos Transversais , Peru , Cefalometria , MaxilaRESUMO
Phenol is used in the manufacturing process of phenolic resins from which residues remain that must be sent for confinement. For that reason, in this study, the wastewater of a resin factory was analyzed to isolate the bacteria present, identify them by molecular methods and finally evaluate their impact on bioremediation treatment. A total of 15 bacteria were isolated, of these, eight belong to the genus Bacillus spp. All bacteria were individually multiplied and inoculated in clusters in 15 L reactors which were carefully monitored for pH, electrical conductivity, chemical oxygen demand and temperature. The acquired data were analyzed using ANOVA with repeated measurements. The first test revealed that native bacterial communities reduce the phenol content by up to 20% and COD by 49%, which is significant with respect to the reactor not being inoculated with bacteria. Furthermore, when a mathematical model was applied to the reactors, it was shown that the bacteria require an adaptation time of approximately 100 h. A second test where the inoculation was interspersed with the addition of lime as a flocculant showed that, even though the reduction in phenol and COD was lower than in the previous test, the difference between treatments and control is statistically significant (α ≤ 0.05).
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Fenol , Águas Residuárias , Fenol/química , Biodegradação Ambiental , Águas Residuárias/microbiologia , Fenóis , Bactérias , Reatores Biológicos/microbiologia , Eliminação de Resíduos Líquidos/métodosRESUMO
Several motor, sensory, cognitive, and behavioral dysfunctions are associated with neural lesions occurring after a hypoxic injury (HI) in preterm infants. Growth hormone (GH) expression is upregulated in several brain areas when exposed to HI conditions, suggesting actions as a local neurotrophic factor. It is known that GH, either exogenous and/or locally expressed, exerts neuroprotective and regenerative actions in cerebellar neurons in response to HI. However, it is still controversial whether GH can cross the blood-brain barrier (BBB), and if its effects are exerted directly or if they are mediated by other neurotrophic factors. Here, we found that in ovo microinjection of Cy3-labeled chicken GH resulted in a wide distribution of fluorescence within several brain areas in the chicken embryo (choroid plexus, cortex, hypothalamus, periventricular areas, hippocampus, and cerebellum) in both normoxic and hypoxic conditions. In the cerebellum, Cy3-GH and GH receptor (GHR) co-localized in the granular and Purkinje layers and in deep cerebellar nuclei under hypoxic conditions, suggesting direct actions. Histological analysis showed that hypoxia provoked a significant modification in the size and organization of cerebellar layers; however, GH administration restored the width of external granular layer (EGL) and molecular layer (ML) and improved the Purkinje and granular neurons survival. Additionally, GH treatment provoked a significant reduction in apoptosis and lipoperoxidation; decreased the mRNA expression of the inflammatory mediators (TNFα, IL-6, IL-1ß, and iNOS); and upregulated the expression of several neurotrophic factors (IGF-1, VEGF, and BDNF). Interestingly, we also found an upregulation of cerebellar GH and GHR mRNA expression, which suggests the existence of an endogenous protective mechanism in response to hypoxia. Overall, the results demonstrate that, in the chicken embryo exposed to hypoxia, GH crosses the BBB and reaches the cerebellum, where it exerts antiapoptotic, antioxidative, anti-inflammatory, neuroprotective, and neuroregenerative actions.
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Proteínas Aviárias/metabolismo , Hormônio do Crescimento/metabolismo , Fármacos Neuroprotetores , Animais , Barreira Hematoencefálica/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cerebelo/metabolismo , Embrião de Galinha , Galinhas/metabolismo , Humanos , Hipóxia/metabolismo , Recém-Nascido , Recém-Nascido Prematuro , Mediadores da Inflamação/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-6/metabolismo , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The abnormal implantation of the trophoblast during the first trimester of pregnancy precedes the appearance of the clinical manifestations of preeclampsia (PE), which is a hypertensive disorder of pregnancy. In a previous study, which was carried out in a murine model of PE that was induced by NG-nitro-L-arginine methyl ester (L-NAME), we observed that the intravenous administration of fibroblast growth factor 2 (FGF2) had a hypotensive effect, improved the placental weight gain and attenuated the fetal growth restriction, and the morphological findings that were induced by L-NAME in the evaluated tissues were less severe. In this study, we aimed to determine the effect of FGF2 administration on the placental gene expression of the vascular endothelial growth factor (VEGFA), VEGF receptor 2 (VEGFR2), placental growth factor, endoglin (ENG), superoxide dismutase 1 (SOD1), catalase (CAT), thioredoxin (TXN), tumor protein P53 (P53), BCL2 apoptosis regulator, Fas cell surface death receptor (FAS), and caspase 3, in a Sprague Dawley rat PE model, which was induced by L-NAME. The gene expression was determined by a real-time polymerase chain reaction using SYBR green. Taking the vehicle or the L-NAME group as a reference, there was an under expression of placental VEGFA, VEGFR2, ENG, P53, FAS, SOD1, CAT, and TXN genes in the group of L-NAME + FGF2 (p < 0.05). The administration of FGF2 in the murine PE-like model that was induced by L-NAME reduced the effects that were generated by proteinuria and the increased BP, as well as the response of the expression of genes that participate in angiogenesis, apoptosis, and OS. These results have generated valuable information regarding the identification of molecular targets for PE and provide new insights for understanding PE pathogenesis.
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Fator 2 de Crescimento de Fibroblastos , Pré-Eclâmpsia , Animais , Modelos Animais de Doenças , Feminino , Fator 2 de Crescimento de Fibroblastos/farmacologia , Expressão Gênica , Humanos , NG-Nitroarginina Metil Éster/efeitos adversos , Placenta/metabolismo , Fator de Crescimento Placentário/genética , Fator de Crescimento Placentário/metabolismo , Pré-Eclâmpsia/induzido quimicamente , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/genética , Gravidez , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase-1/genética , Proteína Supressora de Tumor p53/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Prenatal hypoxic−ischemic (HI) injury inflicts severe damage on the developing brain provoked by a pathophysiological response that leads to neural structural lesions, synaptic loss, and neuronal death, which may result in a high risk of permanent neurological deficits or even newborn decease. It is known that growth hormone (GH) can act as a neurotrophic factor inducing neuroprotection, neurite growth, and synaptogenesis after HI injury. In this study we used the chicken embryo to develop both in vitro and in vivo models of prenatal HI injury in the cerebral pallium, which is the equivalent of brain cortex in mammals, to examine whether GH exerts neuroprotective and regenerative effects in this tissue and the putative mechanisms involved in these actions. For the in vitro experiments, pallial cell cultures obtained from chick embryos were incubated under HI conditions (<5% O2, 1 g/L glucose) for 24 h and treated with 10 nM GH, and then collected for analysis. For the in vivo experiments, chicken embryos (ED14) were injected in ovo with GH (2.25 µg), exposed to hypoxia (12% O2) for 6 h, and later the pallial tissue was obtained to perform the studies. Results show that GH exerted a clear anti-apoptotic effect and promoted cell survival and proliferation in HI-injured pallial neurons, in both in vitro and in vivo models. Neuroprotective actions of GH were associated with the activation of ERK1/2 and Bcl-2 signaling pathways. Remarkably, GH protected mature neurons that were particularly harmed by HI injury, but was also capable of stimulating neural precursors. In addition, GH stimulated restorative processes such as the number and length of neurite outgrowth and branching in HI-injured pallial neurons, and these effects were blocked by a specific GH antibody, thus indicating a direct action of GH. Furthermore, it was found that the local expression of several synaptogenic markers (NRXN1, NRXN3, GAP-43, and NLG1) and neurotrophic factors (GH, BDNF, NT-3, IGF-1, and BMP4) were increased after GH treatment during HI damage. Together, these results provide novel evidence supporting that GH exerts protective and restorative effects in brain pallium during prenatal HI injury, and these actions could be the result of a joint effect between GH and endogenous neurotrophic factors. Also, they encourage further research on the potential role of GH as a therapeutic complement in HI encephalopathy treatments.
Assuntos
Hormônio do Crescimento Humano , Hipóxia-Isquemia Encefálica , Fármacos Neuroprotetores , Animais , Animais Recém-Nascidos , Embrião de Galinha , Galinhas/metabolismo , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento Humano/uso terapêutico , Hipóxia/tratamento farmacológico , Hipóxia-Isquemia Encefálica/metabolismo , Isquemia/tratamento farmacológico , Mamíferos/metabolismo , Fatores de Crescimento Neural/uso terapêutico , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
A genotyping by sequencing (GBS) approach was used to analyze the organization of genetic diversity in V. pubescens and V. chilensis. GBS identified 4675 and 4451 SNPs/INDELs in two papaya species. The cultivated orchards of V. pubescens exhibited scarce genetic diversity and low but significant genetic differentiation. The neutrality test yielded a negative and significant result, suggesting that V. pubescens suffered a selective sweep or a rapid expansion after a bottleneck during domestication. In contrast, V. chilensis exhibited a high level of genetic diversity. The genetic differentiation among the populations was slight, but it was possible to distinguish the two genetic groups. The neutrality test indicated no evidence that natural selection and genetic drift affect the natural population of V. chilensis. Using the Carica papaya genome as a reference, we identified critical SNPs/INDELs associated with putative genes. Most of the identified genes are related to stress responses (salt and nematode) and vegetative and reproductive development. These results will be helpful for future breeding and conservation programs of the Caricaceae family.
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We aimed to describe and compare characteristics and outcomes of patients with a worsening heart failure episode included in the RECOLFACA registry during 2017-2019 vs population from VICTORIA trial. 2528 patients were included, 1890 (74.8%) had an ejection fraction <45% and a worsening episode. VICTORIA population was similar to RECOLFACA patients in mean age (67.3 vs 66.9 years), ejection fraction (28.9% vs 28.4%), the prevalence of COPD (17.1% vs 15.7%), and the median eGFR (61.5 vs 61.4 mL/min/1.73m2). RECOLFACA patients were mostly women, with a lower prevalence of atrial fibrillation, diabetes mellitus, and coronary artery disease. The 1-year heart failure hospitalization rate was 29.6% in the placebo group of VICTORIA, compared to 26.9% in RECOLFACA. Patients enrolled in the RECOLFACA that met the VICTORIA definition had more similar characteristics and outcomes compared to the VICTORIA population. There is an opportunity to improve this unmet need with the use of vericiguat.
Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Idoso , Colômbia , Feminino , Humanos , Masculino , Sistema de Registros , Volume SistólicoRESUMO
Carbon nanotubes (CNTs) have been proposed as nanovehicles for drug or antigen delivery since they can be functionalized with different biomolecules. For this purpose, different types of molecules have been chemically bonded to CNTs; however, this method has low efficiency and generates solvent waste. Candida antarctica lipase is an enzyme that, in an organic solvent, can bind a carboxylic to a hydroxyl group by esterase activity. The objective of this work was to functionalize purified CNTs with insulin as a protein model using an immobilized lipase of Candida antarctica to develop a sustainable functionalization method with high protein attachment. The functionalized CNTs were characterized by scanning electron microscope (SEM), Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzymatic functionalization of insulin on the surface of the CNTs was found to have an efficiency of 21%, which is higher in conversion and greener than previously reported by the diimide-activated amidation method. These results suggest that enzymatic esterification is a convenient and efficient method for CNT functionalization with proteins. Moreover, this functionalization method can be used to enhance the cellular-specific release of proteins by lysosomal esterases.
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Introducción: A pesar de que actualmente la radiografía panorámica es un instrumento auxiliar de diagnóstico de uso común, desafortunadamente sus beneficios no se aprovechan en su totalidad y su empleo se limita al uso en determinadas áreas de la odontología y en ocasiones se omiten hallazgos que pueden tener un significado clínico importante. Material y métodos: Estudio transversal y descriptivo de una muestra aleatoria de 500 estudios de imagen (radiografías panorámicas) durante el periodo de enero a mayo de 2018 analizadas por expertos estandarizados y empleando estadística descriptiva básica mediante el paquete estadístico Excel. Resultados: Se incluyeron 500 estudios, 67% correspondió a mujeres en un rango de cinco a 91 años de edad con una mediana de 43 años, 48% presentó alteraciones siendo las más frecuentas pérdida del proceso alveolar 45%, alteraciones en articulación temporomandibular 34%, y calcificación del ligamento estilohioideo 31%. Conclusión: Se reportaron hallazgos clínico-radiográficos significativos, resaltando la necesidad de un análisis cuidadoso de los métodos auxiliares de diagnóstico que permitan visualizar de manera contextual el tratamiento odontológico de los pacientes y/o reportar al especialista correspondiente otro tipo de hallazgos (AU))
Introduction: Although panoramic radiography is currently a commonly used diagnostic auxiliary instrument, unfortunately its benefits are not fully exploited and its use is limited to use in certain areas of Dentistry and eventually findings that may have important clinical significance are omitted. Material and methods: Crosssectional and descriptive study of a random sample of 500 imaging studies (panoramic radiographs) during the period from January to May 2018, analyzed by standardized experts and using basic descriptive statistics using the Excel statistical package. Results: 500 studies were included corresponding to 67% women and an age range from five to 91 years of age with a median of 43 years, 48% presented alterations, the most frequent being loss of the alveolar process 45%, alterations in the temporomandibular joint 34%, and calcification of the hyoid ligament 31%. Conclusion: In this study significant clinical-radiographic findings are reported, highlighting the need for a careful analysis of auxiliary diagnostic methods that allow visualize the dental treatment of the patients and / or report other findings to the corresponding specialist (AU)