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1.
Int Emerg Nurs ; 76: 101501, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39128252

RESUMEN

BACKGROUND: Immobilization is an intervention widely administered to trauma victims and aims to reduce the victim's movements, ensuring the alignment of anatomical structures suspected of being injured. Despite the benefits of immobilization, it is responsible for the occurrence of pressure injuries, increases in intercranial pressure, pain, and discomfort. AIM: To develop an instrument to assess the discomfort caused by immobilization in trauma victims - Discomfort Assessment Scale for Immobilized Trauma Victims (DASITV). METHODS: A sequential mixed-methods design was used, divided into three distinct but complementary phases: (1) Conceptualization Phase - Construction of the DASITV; (2) Focus Group with a Panel of ten Technical Experts in the care of immobilized trauma victims to approve the DASITV proposal; (3) Acceptance of the scale proposal using a modified e-Delphi technique with 30 pre-hospital health professionals. RESULTS: The first phase led to the construction of a scale made up of two sub-scales. The Numerical Discomfort Scale assesses the level of discomfort the person reports from 0 to 10, with 0 being no discomfort and 10 being maximum discomfort. The second evaluation parameter gives the level of pressure in mmHg that the body exerts on the surface where it is immobilized. The combined interpretation of these two sub-scales leads to 4 different possibilities - ordered by level of severity. The Focus Group made it possible to improve the scale, with input from the group of experts and, using the modified e-Delphi technique, a wider group of professionals showed agreement with the DASITV. CONCLUSION: This study allowed us to propose a preliminary scale to assess the discomfort felt by victims of trauma caused by immobilization.

2.
Foods ; 13(13)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38998566

RESUMEN

The extraction of bioactive compounds from wine lees involves a variety of methods, the selection of which is crucial to ensure optimal yields. This systematic review, following PRISMA guidelines and utilizing the Web of Science database, aimed to examine the current state of this field, providing insights for future investigations. The search employed strategies with truncation techniques and Boolean operators, followed by a three-step screening using well-defined eligibility criteria. A bibliometric analysis was conducted to identify authors, affiliations, countries/regions, and research trends. Thirty references were selected for analysis, with Spain standing out as the main source of research on the topic. The majority of studies (66%) focused on the extraction of bioactive compounds from alcoholic fermentation lees, while 33% were directed towards malolactic fermentation lees. Binary mixtures (ethanol-water) were the predominant solvents, with ultrasound being the most used extraction method (31.3%), providing the highest average yields (288.6%) for the various evaluated compounds, especially flavonoids. The potential of wine lees as a source of bioactive compounds is highlighted, along with the need for further research exploring alternative extraction technologies and the combination of methods. Additionally, the importance of "in vitro" and "in vivo" tests to assess the bioactive potential of lees, as well as the use of computational tools to optimize extraction and identify the molecules responsible for bioactive activity, is emphasized.

3.
Front Public Health ; 12: 1334880, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38751579

RESUMEN

Introduction: In today's military landscape, optimizing performance and bolstering physical health and mental resilience are critical objectives. Introducing a 12-week Ashtanga Vinyasa Yoga Supta Method (AVYSM) to the training protocol of military trained Airforce pilots, we aim to assesses the feasibility and impact of the method. Materials and equipment: Borg Scale assesses the intensity level of physical activity during the intervention. Flight simulator data gauges operational performance responses. Postural control responses are measured using a force platform, stress responses are monitored via heart monitor, and handgrip dynamometry will measure strength. Respiratory capacity is assessed using a spirometer, body composition is evaluated using impedance balance, and aviation-related questionnaires are administered before and after the intervention period. Methods: In a randomized controlled trial, the totality of pilots from the "Masters in Military Aeronautics: aviator pilot specialist" course at the Portuguese Air Force Academy (PAA) were randomly assigned to the yoga intervention or the waiting list control groups, with participants providing written informed consent. The control group followed protocolized course classes for 12 weeks, while the intervention group integrated two weekly one-hour yoga sessions into their course. Results: The PAA has approved the implementation of this intervention protocol at Airbase 11 in Beja, highlighting its significance for the organization's policy makers. We hypothesize that this method will enhance operational performance and, subsequently, elevate flight safety. Discussion: This research's potential extends beyond the PAA, as it can be adapted for use in Airforce departments of other nations and various military contexts. Clinical trial registration: Évora University research ethics committee-approval number 21050. Study registered on ClinicalTrials.gov under identifier NCT05821270, registered on April 19, 2023.


Asunto(s)
Personal Militar , Pilotos , Yoga , Humanos , Masculino , Adulto , Portugal , Femenino
4.
Immunity ; 57(3): 462-477.e9, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38430908

RESUMEN

Inducible nucleosome remodeling at hundreds of latent enhancers and several promoters shapes the transcriptional response to Toll-like receptor 4 (TLR4) signaling in macrophages. We aimed to define the identities of the transcription factors that promote TLR-induced remodeling. An analysis strategy based on ATAC-seq and single-cell ATAC-seq that enriched for genomic regions most likely to undergo remodeling revealed that the transcription factor nuclear factor κB (NF-κB) bound to all high-confidence peaks marking remodeling during the primary response to the TLR4 ligand, lipid A. Deletion of NF-κB subunits RelA and c-Rel resulted in the loss of remodeling at high-confidence ATAC-seq peaks, and CRISPR-Cas9 mutagenesis of NF-κB-binding motifs impaired remodeling. Remodeling selectivity at defined regions was conferred by collaboration with other inducible factors, including IRF3- and MAP-kinase-induced factors. Thus, NF-κB is unique among TLR4-activated transcription factors in its broad contribution to inducible nucleosome remodeling, alongside its ability to activate poised enhancers and promoters assembled into open chromatin.


Asunto(s)
FN-kappa B , Receptor Toll-Like 4 , FN-kappa B/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Nucleosomas , Transducción de Señal , Regulación de la Expresión Génica , Factor de Transcripción ReIA/metabolismo
5.
Int Emerg Nurs ; 71: 101375, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37913691

RESUMEN

BACKGROUND: Acute pain is an important complaint reported by trauma victims, however, the relationship between it and other types of discomfort, such as discomfort caused by cold, discomfort caused by immobilization, and psychological distress such as fear, anxiety, and sadness is limitedly studied and documented. AIM: To assess the relationship between acute trauma pain and other types of suffering in pre-hospital trauma victims. METHODS: This is a prospective multicentre cohort study conducted in Immediate Life Support Ambulances in Portugal. All adult trauma victims with a mechanism of blunt and penetrating injuries, falls, road accidents and explosions, were included. RESULTS: 605 trauma victims were included, mainly male, with a mean age of 53.4 years. Before the intervention of the rescue teams, 90.5 % of the victims reported some level of pain, 39.0 % reported discomfort caused by cold, while 15.7 % felt fear, 8.4 % sadness, 49.8 % anxiety and 4.5 % apathy. Victims with high discomfort caused by cold tend to have higher pain levels. Significantly higher pain intensity were observed in victims with fear and anxiety. Univariate and multivariate analysis indicates that immobilization is associated with increased pain levels. CONCLUSIONS: There is a statistically significant relationship between acute trauma pain, anxiety, fear, cold and immobilization.


Asunto(s)
Dolor Agudo , Heridas y Lesiones , Adulto , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Prospectivos , Estudios de Cohortes , Hospitales , Ansiedad/etiología , Heridas y Lesiones/complicaciones
6.
Children (Basel) ; 10(3)2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36980003

RESUMEN

The purpose of this study was to analyze the relationship between the quality and speed of handwriting and the process characteristics of the handwriting of children in the second grade of elementary school considered as a function of age and gender. A sample of 57 children (mean age 7.25 years, SD 0.43) participated in the study. The Concise Assessment Method for Children's Handwriting (BHK) was used to assess the quality and speed of handwriting. The characteristics of the process of handwriting were assessed using MovAlyzeR® software. The handwriting of boys showed a significantly greater number of strokes and slanted more to the right than the handwriting of girls. Handwriting quality and speed significantly correlated with several process characteristics: the number of strokes, reaction time, duration, relative pen-down duration, average pen pressure, vertical size, horizontal size, road length, and average absolute velocity. This research contributes to the construction of normative values in the process characteristics of the handwriting of elementary school children and provides a promising step towards the early identification of difficulties that can lead to dysgraphia, thus preventing later difficulties in handwriting.

7.
Children (Basel) ; 10(3)2023 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-36980119

RESUMEN

This article describes the translation and cultural adaptation process of the WRITIC (Writing Readiness Inventory Tool in Context) into European Portuguese. We examined the content and convergent validity, test-retest, and interrater reliability on the norm-referenced subdomain of the Portuguese (PT) WRITIC Task Performance (TP). To establish content validity, we consulted six experts in handwriting. Internal consistency was found with 70 children, test-retest reliability with 65, inter-rater reliability with 69, and convergent validity with 87. All participants were typically developing kindergarten children. Convergent validity was examined with the Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery™VMI-6) and the Nine Hole Peg-Test (9-HPT). On content validity, we found an agreement of 93%, a good internal consistency with Cronbach's alpha of 0.72, and an excellent test-retest and inter-rater reliability with ICCs of 0.88 and 0.93. Correlations with Beery™VMI-6 and 9-HPT were moderate (r from 0.39 to 0.65). Translation and cross-cultural adaptation of WRITIC into European Portuguese was successful. WRITIC-PT-TP is stable over time and between raters; it has excellent internal consistency and moderate correlations with Beery™VMI-6 and 9-HPT. This analysis of the European Portuguese version of WRITIC gives us the confidence to start the implementation process of WRITIC-PT in Portugal.

8.
Immunother Adv ; 2(1): ltac010, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36284839

RESUMEN

Macrophages are immune cells that are widespread throughout the body and critical for maintaining tissue homeostasis. Their remarkable plasticity allows them to acquire different phenotypes, becoming able either to fight infection (M1-like, classically activated macrophages) or to promote tissue remodeling and repair (M2-like, alternatively activated macrophages). These phenotypes are induced by different cues present in the microenvironment. Among the factors that might regulate macrophage activation are mediators produced by different branches of the nervous system. The regulation exerted by the sympathetic nervous system (SNS) on macrophages (and the immune system in general) is becoming a subject of increasing interest, indeed a great number of articles have been published lately. Catecholamines (noradrenaline and adrenaline) activate α and ß adrenergic receptors expressed by macrophages and shape the effector functions of these cells in contexts as diverse as the small intestine, the lung, or the adipose tissue. Activation of different subsets of receptors seems to produce antagonistic effects, with α adrenergic receptors generally associated with pro-inflammatory functions and ß adrenergic receptors (particularly ß2) related to the resolution of inflammation and tissue remodeling. However, exceptions to this paradigm have been reported, and the factors contributing to these apparently contradictory observations are still far from being completely understood. Additionally, macrophages per se seem to be sources of catecholamines, which is also a subject of some debate. In this review, we discuss how activation of adrenergic receptors modulates macrophage effector functions and its implications for inflammatory responses and tissue homeostasis.

9.
JBI Evid Synth ; 20(11): 2743-2750, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36081390

RESUMEN

OBJECTIVE: The objective of this review is to identify the level of discomfort caused by immobilization as reported by trauma victims, and to map all the interventions in the prehospital context where they have been implemented and evaluated in order to reduce discomfort in adult victims of trauma. INTRODUCTION: Immobilization is a cause of discomfort for trauma victims, which has important implications for the deterioration of vital signs and quality of life. However, discomfort caused by immobilization remains an under-explored topic by the scientific community. INCLUSION CRITERIA: This scoping review will consider studies of adult victims of trauma, aged 18 years or over, in prehospital emergency care. Studies that focus on interventions designed to reduce immobilization discomfort, implemented and evaluated by health professionals, of any form, duration, frequency, and dose will be considered. METHODS: An initial search of PubMed and CINAHL will be undertaken, followed by a second search for published and unpublished studies without time restrictions, in major health care-related electronic databases. Studies in English, French, Spanish, and Portuguese will be included. Data extraction will be performed independently by 2 reviewers in a tabular format and will include details about the level of discomfort, interventions, populations, study methods, and outcomes of interest. A narrative synthesis will accompany the results and will describe how they relate to the review objectives. REVIEW REGISTRATION NUMBER: OSF https://osf.io/4scg5/.


Asunto(s)
Servicios Médicos de Urgencia , Calidad de Vida , Literatura de Revisión como Asunto
10.
Nanomaterials (Basel) ; 12(18)2022 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-36144933

RESUMEN

Inflammasomes are cytosolic complexes composed of a Nod-like receptor, NLR, the adaptor protein, ASC, and a proteolytic enzyme, caspase-1. Inflammasome activation leads to caspase-1 activation and promotes functional maturation of IL-1ß and IL-18, two prototypical inflammatory cytokines. Besides, inflammasome activation leads to pyroptosis, an inflammatory type of cell death. Inflammasomes are vital for the host to cope with foreign pathogens or tissue damage. Herein, we show that quantum-dot-based iron oxide nanoparticles, MNP@QD, trigger NLRP3 inflammasome activation and subsequent release of proinflammatory interleukin IL-1ß by murine bone marrow-derived dendritic cells (BMDCs). This activation is more pronounced if these cells endocytose the nanoparticles before receiving inflammatory stimulation. MNP@QD was characterized by using imaging techniques like transmission electron microscopy, fluorescence microscopy, and atomic force microscopy, as well as physical and spectroscopical techniques such as fluorescence spectroscopy and powder diffraction. These findings may open the possibility of using the composite MNP@QD as both an imaging and a therapeutic tool.

11.
Tuberculosis (Edinb) ; 136: 102254, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36126496

RESUMEN

In our laboratory, Mycobacterium caprae has poor growth in standard medium (SM) 7H9-OADC supplemented with pyruvate and Tween-80. Our objectives were to identify mutations affecting M. caprae metabolism and use this information to design a culture medium to improve its growth. We selected 77 M. caprae genomes and sequenced M. caprae NLA000201913 used in our experiments. Mutations present in >95% of the strains compared to Mycobacterium tuberculosis H37Rv were analyzed in silico for their deleterious effects on proteins of metabolic pathways. Apart from the known defect in the pyruvate kinase, M. caprae has important lesions in enzymes of the TCA cycle, methylmalonyl cycle, B12 metabolism, and electron-transport chain. We provide evidence of enzymatic redundancy elimination and epistatic mutations, and possible production of toxic metabolites hindering M. caprae growth in vitro. A newly designed SM supplemented with l-glutamate allowed faster growth and increased final microbial mass of M. caprae. However, possible accumulation of metabolic waste-products and/or nutritional limitations halted M. caprae growth prior to a M. tuberculosis-like stationary phase. Our findings suggest that M. caprae relies on GABA and/or glyoxylate shunts for in vitro growth in routine media. The newly developed medium will improve experiments with this bacterium by allowing faster growth in vitro.


Asunto(s)
Mycobacterium bovis , Mycobacterium tuberculosis , Genómica , Ácido Glutámico , Glioxilatos , Mycobacterium bovis/genética , Mycobacterium tuberculosis/genética , Polisorbatos , Piruvato Quinasa , Piruvatos , Ácido gamma-Aminobutírico
12.
Artículo en Inglés | MEDLINE | ID: mdl-35897511

RESUMEN

Heart rate variability (HRV) and performance response during emergency flight maneuvers were analyzed. Two expert pilots (ages 35 and 33) and two rookie pilots (ages 25) from the Portuguese Air Force participated in this case-control report study. Participants had to complete the following emergency protocols in a flight simulator: (1) take-off engine failure, (2) flight engine failure close to the base, (3) flight engine failure far away from the base, and (4) alternator failure. The HRV was collected during all these maneuvers, as well as the performance data (the time it took to go through the emergency protocol and the subjective information from the flight simulator operator). Results regarding autonomic modulation showed a higher sympathetic response during the emergency maneuvers when compared to baseline. In some cases, there was also a higher sympathetic response during the emergency maneuvers when compared with the take-off protocol. Regarding performance data, the expert pilots accomplished the missions in less time than the rookie pilots. Autonomic modulation measured from HRV through portable devices can easily relay important information. This information is relevant since characterizing these maneuvers can provide helpful information to design training strategies to improve those psychophysiological responses.


Asunto(s)
Personal Militar , Pilotos , Adulto , Urgencias Médicas , Frecuencia Cardíaca , Humanos , Análisis y Desempeño de Tareas
13.
Front Immunol ; 13: 910022, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35844531

RESUMEN

Adjuvants are essential for vaccine development, especially subunit-based vaccines such as those containing recombinant proteins. Increasing the knowledge of the immune response mechanisms generated by adjuvants should facilitate the formulation of vaccines in the future. The present work describes the immune phenotypes induced by Poly (I:C) and Montanide ISA 720 in the context of mice immunization with a recombinant protein based on the Plasmodium vivax circumsporozoite protein (PvCSP) sequence. Mice immunized with the recombinant protein plus Montanide ISA 720 showed an overall more robust humoral response, inducing antibodies with greater avidity to the antigen. A general trend for mixed Th1/Th2 inflammatory cytokine profile was increased in Montanide-adjuvanted mice, while a balanced profile was observed in Poly (I:C)-adjuvanted mice. Montanide ISA 720 induced a gene signature in B lymphocytes characteristic of heme biosynthesis, suggesting increased differentiation to Plasma Cells. On the other hand, Poly (I:C) provoked more perturbations in T cell transcriptome. These results extend the understanding of the modulation of specific immune responses induced by different classes of adjuvants, and could support the optimization of subunit-based vaccines.


Asunto(s)
Adyuvantes Inmunológicos , Anticuerpos Antiprotozoarios , Adyuvantes Inmunológicos/farmacología , Adyuvantes Farmacéuticos , Animales , Sistema Inmunológico , Inmunidad , Ratones , Aceite Mineral , Poli I-C , Proteínas Recombinantes
14.
J Pers Med ; 11(9)2021 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-34575710

RESUMEN

Numerous of our daily activities are performed within multitask or dual task conditions. These conditions involve the interaction of perceptual and motor processes involved in postural control. Age-related changes may negatively impact cognition and balance control. Studies identifying changes related to dual-task actions in older people are need. This study aimed to determine the effects of different types of dual-tasking on the balance control of healthy older adults. The sample included 36 community-living older adults, performing two tests-a sway test and a timed up-and-go test-in three conditions: (a) single motor task; (b) dual motor task; and (c) dual motor task with cognitive demands. Cognitive processes (dual-task and cognition) affected static balance, increasing amplitude (p < 0.001) and frequency (p < 0.001) of the center of mass displacements. Dynamic balance revealed significant differences between the single motor condition and the other two conditions during gait phases (p < 0.001). The effect of dual-tasking in older adults suggests that cognitive processes are a main cause of increased variability in balance and gait when under an automatic control. During sit-to-stand, turning, and turn-to-sit movements under dual-tasking, the perceptive information becomes the most important focus of attention, while any cognitive task becomes secondary.

15.
Nutr Cancer ; 73(4): 642-651, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32406264

RESUMEN

There is a strong correlation between obesity and cancer. Here, we investigated the influence of IL-6 and gut microbiota of obese mice in melanoma development. We first evaluated B16F10 melanoma growth in preclinical models for obesity: mice deficient for leptin (ob/ob) or adiponectin (AdpKO) and in wild-type mice (WT, C57BL/6J) fed a high-fat diet (HFD; 60% kcal from fat) for 12 weeks. The survival rates of ob/ob and HFD-fed mice were lower than those of their respective controls. AdpKO mice also died earlier than WT control mice. We then verified the involvement of IL-6 signaling in obese mice that were inoculated with melanoma cells. Both ob/ob and AdpKO mice had higher circulating IL-6 levels than wild-type mice. Melanoma tumor volumes in IL-6 KO mice fed an HFD were reduced compared to those of WT mice subjected to the same diet. Also evaluated the effect of microbiota in tumor development. Cohousing and fecal matter transfer experiments revealed that microbiota from ob/ob mice can stimulate tumor development in lean WT mice. Taken together, our data show that in some conditions IL-6 and the gut microbiota are key mediators that link obesity and melanoma.


Asunto(s)
Microbioma Gastrointestinal , Melanoma , Animales , Dieta Alta en Grasa/efectos adversos , Interleucina-6 , Leptina , Ratones , Ratones Endogámicos C57BL , Ratones Obesos
16.
Cell Rep ; 28(12): 3120-3130.e5, 2019 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-31533035

RESUMEN

Noradrenaline (NE), the main neurotransmitter released by sympathetic nerve terminals, is known to modulate the immune response. However, the role of the sympathetic nervous system (SNS) on the development of autoimmune diseases is still unclear. Here, we report that the SNS limits the generation of pathogenic T cells and disease development in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). ß2-Adrenergic receptor (Adrb2) signaling limits T cell autoimmunity in EAE through a mechanism mediated by the suppression of IL-2, IFN-γ, and GM-CSF production via inducible cAMP early repressor (ICER). Accordingly, the lack of Adrb2 signaling in immune cells is sufficient to abrogate the suppressive effects of SNS activity, resulting in increased pathogenic T cell responses and EAE development. Collectively, these results uncover a suppressive role for the SNS in CNS autoimmunity while they identify potential targets for therapeutic intervention.


Asunto(s)
Encefalomielitis Autoinmune Experimental/inmunología , Inmunidad Celular , Esclerosis Múltiple/inmunología , Receptores Adrenérgicos beta 2/inmunología , Transducción de Señal/inmunología , Sistema Nervioso Simpático/inmunología , Linfocitos T/inmunología , Animales , Citocinas/genética , Citocinas/inmunología , Encefalomielitis Autoinmune Experimental/patología , Ratones , Ratones Noqueados , Esclerosis Múltiple/genética , Esclerosis Múltiple/patología , Receptores Adrenérgicos beta 2/genética , Transducción de Señal/genética , Sistema Nervioso Simpático/patología , Linfocitos T/patología
17.
Hig. Aliment. (Online) ; 33(288/289): 657-661, abr.-maio 2019. tab
Artículo en Portugués | LILACS, VETINDEX | ID: biblio-1482016

RESUMEN

O objetivo deste trabalho foi desenvolver e avaliar a qualidade microbiológica e aceitabilidade de geleias mistas funcionais de manga “Tommy-Atkins” e maracujá (Passiflora edulis f. flavicarpa) enriquecidas com 0,5%, 1,0% e 3% de sementes de chia (Salvia hispânica). A caracterização sensorial utilizou os critérios: aparência, cor, aroma, consistência, sabor, doçura e impressão global. As características microbiológicas mantiveram-se dentro dos padrões estabelecidos pela legislação. A interpretação dos dados estatísticos da análise sensorial revelou que, para um nível de 5% de significância (p<0,05), o acréscimo de chia influenciou significativamente nos aspectos visuais. Porém, mesmo com adição das sementes o produto apresentou boa aceitação, indicando que a adição de chia é estratégica para o desenvolvimento deste alimento funcional.


Asunto(s)
Humanos , Alimentos Fortificados , Comportamiento del Consumidor , Mermeladas de Frutas , Microbiología de Alimentos , Salvia , Alimentos Funcionales , Mangifera , Passiflora
18.
Anticancer Agents Med Chem ; 19(3): 389-401, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30417795

RESUMEN

BACKGROUND: BRN2 transcription factor is associated with the development of malignant melanoma. The cytotoxic activities and cell death mechanism against B16F10-Nex2 cells were determined with synthetic peptide R18H derived from the POU domain of the BRN2 transcription factor. OBJECTIVE: To determine the cell death mechanisms and in vivo activity of peptide R18H derived from the POU domain of the BRN2 transcription factor against B16F10-Nex2 cells. METHODS: Cell viability was determined by the MTT method. C57Bl/6 mice were challenged with B16F10-Nex2 cells and treated with R18H. To identify the type of cell death, we used TUNEL assay, Annexin V and PI, Hoechst, DHE, and determination of caspase activation and cytochrome c release. Transmission electron microscopy was performed to verify morphological alterations after peptide treatment. RESULTS: Peptide R18H displayed antitumor activity in the first hours of treatment and the EC50% was calculated for 2 and 24h, being 0.76 ± 0.045 mM and 0.559 ± 0.053 mM, respectively. After 24h apoptosis was evident, based on DNA degradation, chromatin condensation, increase of superoxide anion production, phosphatidylserine translocation, activation of caspases 3 and 8, and release of extracellular cytochrome c in B16F10-Nex2 cells. The peptide cytotoxic activity was not affected by necroptosis inhibitors and treated cells did not release LDH in the extracellular medium. Moreover, in vivo antitumor activity was observed following treatment with peptide R18H. CONCLUSION: Peptide R18H from BRN2 transcription factor induced apoptosis in B16F10-Nex2 and displayed antitumor activity in vivo.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Proteínas de Homeodominio/química , Melanoma/tratamiento farmacológico , Melanoma/patología , Factores del Dominio POU/química , Péptidos/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Melanoma/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Estructura Molecular , Péptidos/síntesis química , Péptidos/química , Relación Estructura-Actividad
20.
Rev. Bras. Med. Fam. Comunidade (Online) ; 12(39): 1-6, jan.-dez. 2017.
Artículo en Portugués | ColecionaSUS, LILACS | ID: biblio-848270

RESUMEN

Introduction: Assessment of serum uric acid is frequently done in Primary Health Care, although not scientifically recommended. The subsequent therapeutic approach is often a clinical challenge, particularly in the case of asymptomatic hyperuricemia (AH). The aim of this study was to review the evidence on AH treatment. Methods: A research was conducted on Medline and evidence-based medical sites for articles published between April 2012 and April 2016 in English, Spanish or Portuguese using the keywords "hyperuricemia" and "asymptomatic conditions". Results: Five articles met the inclusion criteria: one meta-analysis (MA), three systematic reviews (SR) and one original study (OS). MA and OS recommend treatment of AH, for the prevention of renal dysfunction and for the prevention of cardiovascular events (CV), respectively. Two SR do not recommend treatment of AH and one says that pharmacological treatment should be considered after an individual assessment of risk/benefit ratio, particularly in the prevention of gout in subjects with serum uric acid above 9 mg/dL. Conclusion: Very limited scientific data are available on the pharmacologic treatment of AH, with limitations and controversial results. The clinical significance of AH and its causal relationship with occurrence of acute attacks of gout, renal dysfunction and cardiovascular disease are still uncertain. There is no scientific evidence to support the pharmacological treatment of HA in asymptomatic patients (SOR B). Further studies, that are methodologically robust and oriented to the patient are needed.


Introducción: La evaluación de los niveles de ácido úrico es una práctica frecuente en los Cuidados de Salud Primarios, pero no hay evidencia científica. El enfoque terapéutico posterior es frecuentemente un desafío clínico, particularmente en el caso de la hiperuricemia asintomática (HA). Objetivo: Revisar la evidencia sobre la relevancia del tratamiento de la HA. Métodos: Búsqueda de normas de orientación clínica, revisiones sistemáticas (RS), meta-análisis (MA) y estudios originales (EO) en la MEDLINE y otros lugares de Medicina Basada en la Evidencia, publicados desde abril/2012 hasta abril/2016, en inglés, español y portugués. Términos MeSH: "hyperuricemia" e "asymptomatic conditions". Resultados: Cinco estudios cumplían los criterios de inclusión: una MA, tres RS y un EO. La MA y el EO recomiendan el tratamiento de la HA, para la prevención de la disfunción renal y de problemas cardiovasculares (CV), respectivamente. Dos RS no recomiendan el tratamiento de la HA y una recomienda una decisión individualizada para valores de uricemia superiores a 9mg/dL, particularmente para la prevención de la gota. Conclusiones: La evidencia científica disponible es escasa, con limitaciones, y controversia, en lo que se refiere a la institución del tratamiento farmacológico. La importancia clínica de la HA y su relación causal con la ocurrencia de ataques agudos de gota, disfunción renal y las enfermedades cardiovasculares siguen siendo inciertas. No hay evidencia científica que justifique el tratamiento farmacológico de la HA en pacientes asintomáticos (SOR B). Son necesarios más estudios, metodológicamente robustos y orientados al paciente.


Introdução: A avaliação dos níveis séricos de ácido úrico é realizada com frequência nos Cuidados de Saúde Primários, porém sem evidência científica que a justifique. A abordagem terapêutica subsequente constitui frequentemente um desafio clínico, particularmente no caso da hiperuricemia assintomática (HA). O objetivo desta revisão foi rever a evidência sobre a pertinência do tratamento da HA. Métodos: Pesquisa de normas de orientação clínica (NOC), revisões sistemáticas (RS), meta-análises (MA) e estudos originais (EO) no Medline e outros sítios de Medicina Baseada na Evidência, publicados desde abril de 2012 até abril de 2016, em inglês, espanhol e português. Termos MeSH: "hyperuricemia" e "asymptomatic conditions". Resultados: Cinco estudos cumpriam os critérios de inclusão: uma MA, três RS e um EO. A MA e o EO recomendam o tratamento da HA, para a prevenção da disfunção renal e para prevenção de eventos cardiovasculares (CV), respetivamente. Duas RS não recomendam o tratamento da HA e uma recomenda uma decisão individualizada para valores de uricemia acima de 9mg/dL, particularmente para a prevenção da gota. Conclusões: A evidência científica disponível é escassa, com limitações, e controversa no que diz respeito à instituição de tratamento farmacológico. O significado clínico da HA e sua relação causal com ocorrência de crises agudas de gota, disfunção renal e doença cardiovascular ainda são incertos. Não existe evidência científica que justifique o tratamento farmacológico da HA em doentes assintomáticos (SOR B). São, por isso, necessários mais estudos, metodologicamente robustos e orientados para o paciente.


Asunto(s)
Atención Primaria de Salud , Ácido Úrico , Hiperuricemia , Enfermedades Asintomáticas , Revisión , Metaanálisis
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