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1.
Rev. urug. enferm ; 17(1): 1-9, ene. 2022.
Artículo en Español | LILACS, BDENF, BNUY, BNUY-Enf | ID: biblio-1368515

RESUMEN

En búsqueda de alcanzar mejores resultados en gestión universitaria, la Facultad de Enfermería de la Universidad de la República, ha adoptado cambios en su forma de pensar y hacer gestión. Siguiendo una política central de la Universidad, comenzó un proceso de abandono del trabajo por tareas y empezó a trabajar por objetivos, aplicando la metodología de la Planificación Estratégica. El presente artículo, tiene como objetivo relatar la experiencia en las etapas de diseño, seguimiento y evaluación del primer Plan Estratégico de la Facultad de Enfermería. Se utilizaron como fuente de información informes de catedráticos y datos provenientes de sis-temas administrativos. Se realizaron encuentros de participación colectiva de los distintos grupos de interés que componen la institución (estudiantes, egresados, docentes y funcionarios técnicos, administrativos y de servicio) y encuestas en linea. Como resultado se observó que la elaboración del Plan Estratégico fue un proceso de creación colectiva, lo que propició la incorporación de los objetivos en los respectivos planes operativos anuales de los directivos. El seguimiento y evaluación fueron realizados parcialmente por una unidad académica especializada, creada para tales fines. La evaluación final también supuso una participación importante de todos los grupos de interés de la Facultad. Con respecto a los logros de los objetivos del Plan, se observó un alcance satisfactorio del 80 % , mientras que 11 % se cumplieron parcialmente. Los resultados del proceso y del alcance de los objetivos dan cuenta del beneficio del uso de la metodología de Planificación Estratégica para la gestión de la Facultad.


In search of achieving better results in university management, the Faculty of Nursing of the University of the Republic has adopted changes in its way of thinking and doing management. Following a central policy of the University, a process of abandoning work by tasks began and began to work by objectives, applying the methodology of Strategic Planning. This article aims to report the experience in the stages of design, monitoring and evaluation of the first Strategic Plan of the Faculty of Nursing. Reports from professors and data from administrative systems were used as a source of information. Collective participation meetings were held for the different interest groups that make up the institution (students, graduates, teachers, and technical, administrative, and service officials) and online surveys. As a result, it was observed that the preparation of the Strategic Plan was a process of collective creation, which led to the incorporation of the objectives in the respective annual operating plans of the directors. Monitoring and evaluation were partially carried out by a specialized academic unit created for such purposes. The final evaluation also involved significant participation from all the Faculty's interest groups. Regarding the achievements of the objectives of the Plan, a satisfactory scope of 80 % was observed, while 11 % were partially fulfilled. The results of the process and the scope of the objectives show the benefit of using the Strategic Planning methodology for the management of the Faculty.


Em busca de melhores resultados na gestão universitária, a Faculdade de Enfermagem da Universidade da República tem adotado mudanças em sua forma de pensar e fazer gestão. Seguindo uma política central da Universidade, iniciou-se um processo de abandono do trabalho por tarefas e passou a trabalhar por objetivos, aplicando a metodologia do Planejamento Estratégico Este artigo tem como objetivo relatar a experiência nas etapas de concepção, acompanhamento e avaliação do primeiro Plano Estratégico da Faculdade de Enfermagem. Relatos de professores e dados de sistemas administrativos foram utilizados como fonte de informação. Foram realizadas reuniões de participação coletiva para os diferentes grupos de interesse que compõem a instituição (estudantes, graduados, docentes e técnicos, administrativos e de ser-viço) e pesquisas online. Como resultado, observou-se que a elaboração do Plano Estratégico foi um processo de criação coletiva, o que levou à incorporação dos objetivos nos respectivos planos operacionais anuais dos diretores. O monitoramento e a avaliação foram parcialmente realizados por uma unidade acadêmica especializada criada para esse fim. A avaliação final também contou com a participação significativa de todos os grupos de interesse da Faculdade. Com relação ao cumprimento dos objetivos do Plano, observou-se um alcance satisfatório de 80 %, enquanto 11 % foram parcialmente cumpridos. Os resultados do processo e o alcance dos objetivos mostram o benefício da utilização da metodologia do Planejamento Estratégico para a gestão da Faculdade.


Asunto(s)
Humanos , Uruguay , Planificación Estratégica , Investigación en Educación de Enfermería , Educación en Enfermería
2.
Glob Pediatr Health ; 4: 2333794X16685190, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28239625

RESUMEN

To examine gaps in communication versus documentation of weight-management clinical practices, communication was recorded during primary care visits with 6- to 12-year-old overweight/obese Latino children. Communication/documentation content was coded by 3 reviewers using communication transcripts and health-record documentation. Discrepancies in communication/documentation content codes were resolved through consensus. Bivariate/multivariable analyses examined factors associated with discrepancies in benchmark communication/documentation. Benchmarks were neither communicated nor documented in up to 42% of visits, and communicated but not documented or documented but not communicated in up to 20% of visits. Lowest benchmark performance rates were for laboratory studies (35%) and nutrition/weight-management referrals (42%). In multivariable analysis, overweight (vs obesity) was associated with 1.6 more discrepancies in communication versus documentation (P = .03). Many weight-management benchmarks are not met, not documented, or performed without being communicated. Enhanced communication with families and documentation in health records may promote lifestyle changes in overweight children and higher quality care for overweight children in primary care.

3.
Anal Biochem ; 499: 24-33, 2016 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-26836485

RESUMEN

Glutaredoxins catalyze glutathione-dependent disulfide oxidoreductions, particularly reduction of glutathione (GSH)-protein mixed disulfides. Mammalian glutaredoxins are present in the cytosol/nucleus as Grx1 or in mitochondria as Grx2a. Here we describe di-eosin-glutathione disulfide (Di-E-GSSG) as a new tool to study glutaredoxin (Grx) activity. Di-E-GSSG has almost no fluorescence in its disulfide form due to self-quenching, whereas the reduced form (E-GSH) has a large fluorescence emission at 545 nm after excitation at 520 nm. Di-E-GSSG was a very poor substrate for glutathione reductase, but we discovered that the molecule was an excellent substrate for glutaredoxin in a coupled assay system with GSH, nicotinamide adenine dinucleotide phosphate (NADPH), and glutathione reductase or with lipoamide, NADH, and lipoamide dehydrogenase. In addition, Di-E-GSSG was used to glutathionylate the free SH group of bovine serum albumin (BSA), yielding eosin-glutathionylated BSA (E-GS-BSA) readily observed in ultraviolet (UV) light. E-GS-BSA also displayed a quenched fluorescence, and its Grx-catalyzed reduction could be followed by the formation of E-GSH by fluorescence emission using microtiter plates. This way of measuring Grx activity provided an ultrasensitive method that detected Grx1 and Grx2 at picomolar levels. Human Grx1 was readily quantified in 40 µl of plasma and determined to be 680 ± 208 pM in healthy controls.


Asunto(s)
Disulfuros/metabolismo , Eosina Amarillenta-(YS)/química , Fluorescencia , Colorantes Fluorescentes/metabolismo , Glutarredoxinas/metabolismo , Glutatión/metabolismo , Proteína S/metabolismo , Animales , Bovinos , Disulfuros/química , Colorantes Fluorescentes/química , Glutarredoxinas/sangre , Glutarredoxinas/química , Glutatión/química , Humanos , Estructura Molecular , Proteína S/química , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/metabolismo , Espectrometría de Fluorescencia
4.
Acad Pediatr ; 16(3): 260-6, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26514648

RESUMEN

OBJECTIVE: To examine parental perspectives/rankings of the most important weight-management clinical practices and to determine whether preferences/rankings differ when parents disagree that their child is overweight. METHODS: We performed mixed-methods analysis of a 32-question survey of parents of 2- to 18-year-old overweight children assessing parental agreement that their child is overweight, the single most important thing providers can do to improve weight status, ranking American Academy of Pediatrics-recommended clinical practices, and preferred follow-up interval. Four independent reviewers analyzed open-response data to identify qualitative themes/subthemes. Multivariable analyses examined parental rankings, preferred follow-up interval, and differences by agreement with their child's overweight assessment. RESULTS: Thirty-six percent of 219 children were overweight, 42% obese, and 22% severely obese; 16% of parents disagreed with their child's overweight assessment. Qualitative analysis of the most important practice to help overweight children yielded 10 themes; unique to parents disagreeing with their children's overweight assessments was "change weight-status assessments." After adjustment, the 3 highest-ranked clinical practices included, "check for weight-related problems," "review growth chart," and "recommend general dietary changes" (all P < .01); parents disagreeing with their children's overweight assessments ranked "review growth chart" as less important and ranked "reducing screen time" and "general activity changes" as more important. The mean preferred weight-management follow-up interval (10-12 weeks) did not differ by agreement with children's overweight assessments. CONCLUSIONS: Parents prefer weight-management strategies that prioritize evaluating weight-related problems, growth-chart review, and regular follow-up. Parents who disagree that their child is overweight want changes in how overweight is assessed. Using parent-preferred weight-management strategies may prove useful in improving child weight status.


Asunto(s)
Actitud Frente a la Salud , Disentimientos y Disputas , Padres , Prioridad del Paciente , Obesidad Infantil/terapia , Atención Primaria de Salud , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Renta , Masculino , Sobrepeso/terapia , Pediatría , Encuestas y Cuestionarios
5.
BBA Clin ; 4: 14-20, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26966682

RESUMEN

The possible beneficial effects of coenzyme Q10 (CoQ10) supplementation on disease progression and oxidant status in diabetes remains debated. In the present study, patients with type 1 and type 2 diabetes were treated with oral CoQ10, 100 mg twice daily for 12 weeks. We assessed total antioxidant capacity, intra- and extracellular levels of the redox regulating protein glutaredoxin 1 (Grx1), CoQ10, oxidized LDL-cholesterol, lipid profile and HbA1c. We have previously shown that extracellular Grx1 is increased in patients with type 2 diabetes compared to healthy subjects. In the present study, CoQ10 treatment significantly decreased serum Grx1 activity as well as total antioxidant capacity independent of type of diabetes, indicating an improvement to a less oxidized extracellular environment. The effect on serum Grx1 activity was more prominent in patients not on statin treatment. Conversely, intracellular Grx1 activity as well as mRNA levels increased independent of statin treatment. There was a significant improvement in oxidized LDL-cholesterol and lipid profile, with a tendency to improved metabolic control (HbA1c). Additionally, we describe for the first time that CoQ10 is a direct substrate for glutathione, and that Grx1 catalyzes this reaction, thus presenting a novel mechanism for CoQ10 reduction which could explain our findings of an increased intracellular Grx1. In conclusion, 12 weeks CoQ10 treatment significantly improved the extracellular redox balance and lipid profile, indicating that prolonged treatment may have beneficial effects also on clinical outcome in diabetes.

6.
Pediatrics ; 134(5): 892-9, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25311599

RESUMEN

OBJECTIVE: To examine pediatrician weight-management communication with overweight Latino children and their parents and whether communication differs by pediatrician-patient language congruency. METHODS: Mixed-methods analysis of video-recorded primary care visits with overweight 6- to 12-year-old children. Three independent reviewers used video/transcript data to identify American Academy of Pediatrics-recommended communication content and establish communication themes/subthemes. Language incongruence (LI) was defined as pediatrician limited Spanish proficiency combined with parent limited English proficiency (LEP). Bivariate analyses examined associations of LI with communication content/themes. RESULTS: The mean child age (N = 26) was 9.5 years old; 81% were obese. Sixty-two percent of parents had LEP. Twenty-seven percent of pediatricians were Spanish-proficient. An interpreter was used in 25% of LI visits. Major themes for how pediatricians communicate overweight included BMI, weight, obese, chubby, and no communication (which only occurred in LI visits). The pediatrician communicated child overweight in 81% of visits, a weight-management plan in 50%, a culturally relevant dietary recommendation in 42%, a recommendation for a follow-up visit in 65%, and nutrition referral in 50%. Growth charts were used in 62% of visits but significantly less often in LI (13%) versus language-congruent (83%) visits (P < .001). CONCLUSIONS: Many overweight Latino children do not receive direct communication of overweight, culturally sensitive dietary advice, or follow-up visits. LI is associated with a lower likelihood of growth chart use. During primary care visits with overweight Latino children, special attention should be paid to directly communicating child overweight, formulating culturally sensitive weight-management plans, and follow-up. With LEP families, vigilance is needed in providing a trained interpreter and using growth charts.


Asunto(s)
Peso Corporal/etnología , Comunicación , Hispánicos o Latinos/etnología , Sobrepeso/etnología , Pediatría/métodos , Relaciones Médico-Paciente , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Sobrepeso/diagnóstico , Sobrepeso/terapia , Padres
7.
Acta Diabetol ; 51(2): 225-32, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23836328

RESUMEN

Oxidative stress induced by hyperglycemia is a key factor in the pathogenesis of diabetes complications. Glutaredoxin 1(Grx1) is a cytosolic redox protein that catalyzes GSH-dependent thiol redox reactions and reversible protein S-glutathionylation. In humans, Grx1 antigen has previously been detected in plasma; however, it has hitherto been unclear if plasma Grx1 is enzymatically active, which would indicate an extracellular function of the protein. Given that glucose overload damages cells through oxidative stress responses, we investigated whether postprandial hyperglycemia induces changes in extracellular Grx1 in patients with abnormal glucose tolerance and healthy subjects. Using a novel sensitive fluorescent substrate assay, we demonstrated that plasma Grx consists of active protein. Grx antigen, activity and total antioxidant capacity were significantly elevated in patients compared to healthy subjects. In response to oral glucose tolerance test, Grx activity and antioxidant capacity increased significantly in healthy volunteers, however, not to the high levels of the patients. In conclusion, these results indicate an extracellular function of plasma Grx in blood glucose metabolism. Thus, Grx may be a marker of increased oxidative stress during hyperglycemia in healthy subjects and may be a risk marker of progression toward diabetes onset.


Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Intolerancia a la Glucosa/sangre , Glutarredoxinas/sangre , Adulto , Western Blotting , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Oxidación-Reducción , Estrés Oxidativo/fisiología , Espectrometría de Fluorescencia , Estadísticas no Paramétricas , Adulto Joven
8.
Anal Biochem ; 449: 139-46, 2014 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-24374250

RESUMEN

Thioredoxin (Trx) is a protein disulfide reductase that, together with nicotinamide adenine dinucleotide phosphate (NADPH) and thioredoxin reductase (TrxR), controls oxidative stress or redox signaling via thiol redox control. Human cytosolic Trx1 has Cys32 and Cys35 as the active site and three additional cysteine residues (Cys62, Cys69, and Cys73), which by oxidation generates inactive Cys62 to Cys69 two-disulfide Trx. This, combined with TrxR with a broad substrate specificity, complicates assays of mammalian Trx and TrxR. We sought to understand the autoregulation of Trx and TrxR and to generate new methods for quantification of Trx and TrxR. We optimized the synthesis of two fluorescent substrates, di-eosin-glutathione disulfide (Di-E-GSSG) and fluorescein isothiocyanate-labeled insulin (FiTC-insulin), which displayed higher fluorescence on disulfide reduction. Di-E-GSSG showed a very large increase in fluorescence quantum yield but had a relatively low affinity for Trx and was also a weak direct substrate for TrxR, in contrast to GSSG. FiTC-insulin was used to develop highly sensitive assays for TrxR and Trx. Reproducible conditions were developed for reactivation of modified Trx, commonly present in frozen or oxidized samples. Trx in cell extracts and tissue samples, including plasma and serum, were subsequently analyzed, showing highly reproducible results and allowing measurement of trace amounts of Trx.


Asunto(s)
Pruebas de Enzimas/métodos , Eosina Amarillenta-(YS)/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Colorantes Fluorescentes/metabolismo , Disulfuro de Glutatión/análogos & derivados , Reductasa de Tiorredoxina-Disulfuro/metabolismo , Tiorredoxinas/metabolismo , Animales , Línea Celular Tumoral , Eosina Amarillenta-(YS)/metabolismo , Fluoresceína-5-Isotiocianato/análisis , Colorantes Fluorescentes/análisis , Disulfuro de Glutatión/metabolismo , Humanos , Insulina/metabolismo , Oxidación-Reducción
9.
Proc Natl Acad Sci U S A ; 110(50): 20057-62, 2013 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-24277839

RESUMEN

Embryonic development depends on complex and precisely orchestrated signaling pathways including specific reduction/oxidation cascades. Oxidoreductases of the thioredoxin family are key players conveying redox signals through reversible posttranslational modifications of protein thiols. The importance of this protein family during embryogenesis has recently been exemplified for glutaredoxin 2, a vertebrate-specific glutathione-disulfide oxidoreductase with a critical role for embryonic brain development. Here, we discovered an essential function of glutaredoxin 2 during vascular development. Confocal microscopy and time-lapse studies based on two-photon microscopy revealed that morpholino-based knockdown of glutaredoxin 2 in zebrafish, a model organism to study vertebrate embryogenesis, resulted in a delayed and disordered blood vessel network. We were able to show that formation of a functional vascular system requires glutaredoxin 2-dependent reversible S-glutathionylation of the NAD(+)-dependent protein deacetylase sirtuin 1. Using mass spectrometry, we identified a cysteine residue in the conserved catalytic region of sirtuin 1 as target for glutaredoxin 2-specific deglutathionylation. Thereby, glutaredoxin 2-mediated redox regulation controls enzymatic activity of sirtuin 1, a mechanism we found to be conserved between zebrafish and humans. These results link S-glutathionylation to vertebrate development and successful embryonic angiogenesis.


Asunto(s)
Sistema Cardiovascular/embriología , Glutarredoxinas/metabolismo , Glutatión/metabolismo , Neovascularización Fisiológica/fisiología , Transducción de Señal/fisiología , Sirtuina 1/metabolismo , Animales , Western Blotting , Cartilla de ADN/genética , Técnicas de Silenciamiento del Gen , Glutarredoxinas/genética , Células HeLa , Humanos , Espectrometría de Masas , Microscopía Confocal , Oxidación-Reducción , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/genética , Imagen de Lapso de Tiempo , Pez Cebra
10.
Free Radic Biol Med ; 50(7): 811-20, 2011 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-21215310

RESUMEN

Alterations in mitochondrial structure and function are a hallmark of cancer cells compared to normal cells and thus targeting mitochondria has emerged as an novel approach to cancer therapy. The mitochondrial thioredoxin 2 (Trx2) system is critical for cell viability, but its role in cancer biology is not well understood. Recently some cationic triphenylmethanes such as brilliant green (BG) and gentian violet were shown to have antitumor and antiangiogenic activity with unknown mechanisms. Here we demonstrate that BG killed cells at nanomolar concentrations and targeted mitochondrial Trx2, which was oxidized and degraded. HeLa cells were more sensitive to BG than fibroblasts. In HeLa cells, Trx2 down-regulation by siRNA resulted in increased sensitivity to BG, whereas for fibroblasts, the same treatments had no effect. BG was observed to accumulate in mitochondria and cause a rapid and dramatic decrease in mitochondrial Trx2 protein. With a redox Western blot method, we found that treatment with BG caused oxidation of both Trx1 and Trx2, followed by release of cytochrome c and apoptosis-inducing factor from the mitochondria into the cytosol. Moreover, this treatment resulted in an elevation of the mRNA level of Lon protease, a protein quality control enzyme in the mitochondrial matrix, suggesting that the oxidized Trx2 may be degraded by Lon protease.


Asunto(s)
Apoptosis/efectos de los fármacos , Violeta de Genciana/farmacología , Mitocondrias/metabolismo , Compuestos de Amonio Cuaternario/farmacología , Tiorredoxinas/antagonistas & inhibidores , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Factor Inductor de la Apoptosis/análisis , Factor Inductor de la Apoptosis/metabolismo , Cationes/química , Supervivencia Celular/efectos de los fármacos , Citocromos c/análisis , Citocromos c/metabolismo , Fibroblastos , Violeta de Genciana/química , Violeta de Genciana/uso terapéutico , Células HeLa , Humanos , Neoplasias/tratamiento farmacológico , Oxidación-Reducción , Proteasa La/metabolismo , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/uso terapéutico , ARN Interferente Pequeño/farmacología , Especies Reactivas de Oxígeno/metabolismo , Tiorredoxinas/biosíntesis , Compuestos de Tritilo/química , Compuestos de Tritilo/farmacología , Compuestos de Tritilo/uso terapéutico , Regulación hacia Arriba
11.
Biochem J ; 433(2): 303-11, 2011 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-21029046

RESUMEN

Human GLRX5 (glutaredoxin 5) is an evolutionarily conserved thiol-disulfide oxidoreductase that has a direct role in the maintenance of normal cytosolic and mitochondrial iron homoeostasis, and its expression affects haem biosynthesis and erythropoiesis. We have crystallized the human GLRX5 bound to two [2Fe-2S] clusters and four GSH molecules. The crystal structure revealed a tetrameric organization with the [2Fe-2S] clusters buried in the interior and shielded from the solvent by the conserved ß1-α2 loop, Phe69 and the GSH molecules. Each [2Fe-2S] cluster is ligated by the N-terminal activesite cysteine (Cys67) thiols contributed by two protomers and two cysteine thiols from two GSH. The two subunits co-ordinating the cluster are in a more extended conformation compared with iron-sulfur-bound human GLRX2, and the intersubunit interactions are more extensive and involve conserved residues among monothiol GLRXs. Gel-filtration chromatography and analytical ultracentrifugation support a tetrameric organization of holo-GLRX5, whereas the apoprotein is monomeric. MS analyses revealed glutathionylation of the cysteine residues in the absence of the [2Fe-2S] cluster, which would protect them from further oxidation and possibly facilitate cluster transfer/acceptance. Apo-GLRX5 reduced glutathione mixed disulfides with a rate 100 times lower than did GLRX2 and was active as a glutathione-dependent electron donor for mammalian ribonucleotide reductase.


Asunto(s)
Glutarredoxinas/química , Proteínas Hierro-Azufre/química , Multimerización de Proteína , Cristalografía por Rayos X , Disulfuros/química , Disulfuros/metabolismo , Glutarredoxinas/metabolismo , Humanos , Proteínas Hierro-Azufre/metabolismo , Modelos Moleculares , Oxidación-Reducción , Unión Proteica , Estructura Cuaternaria de Proteína
12.
J Clin Invest ; 120(12): 4220-35, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21084748

RESUMEN

Selenium, a trace element that is fundamental to human health, is incorporated into some proteins as selenocysteine (Sec), generating a family of selenoproteins. Sec incorporation is mediated by a multiprotein complex that includes Sec insertion sequence-binding protein 2 (SECISBP2; also known as SBP2). Here, we describe subjects with compound heterozygous defects in the SECISBP2 gene. These individuals have reduced synthesis of most of the 25 known human selenoproteins, resulting in a complex phenotype. Azoospermia, with failure of the latter stages of spermatogenesis, was associated with a lack of testis-enriched selenoproteins. An axial muscular dystrophy was also present, with features similar to myopathies caused by mutations in selenoprotein N (SEPN1). Cutaneous deficiencies of antioxidant selenoenzymes, increased cellular ROS, and susceptibility to ultraviolet radiation-induced oxidative damage may mediate the observed photosensitivity. Reduced levels of selenoproteins in peripheral blood cells were associated with impaired T lymphocyte proliferation, abnormal mononuclear cell cytokine secretion, and telomere shortening. Paradoxically, raised ROS in affected subjects was associated with enhanced systemic and cellular insulin sensitivity, similar to findings in mice lacking the antioxidant selenoenzyme glutathione peroxidase 1 (GPx1). Thus, mutation of SECISBP2 is associated with a multisystem disorder with defective biosynthesis of many selenoproteins, highlighting their role in diverse biological processes.


Asunto(s)
Mutación , Proteínas de Unión al ARN/genética , Selenoproteínas/deficiencia , Adulto , Anciano , Secuencia de Aminoácidos , Animales , Azoospermia/genética , Secuencia de Bases , Niño , Preescolar , Codón sin Sentido , ADN/genética , Femenino , Pérdida Auditiva Sensorineural/genética , Humanos , Resistencia a la Insulina/genética , Masculino , Ratones , Persona de Mediana Edad , Modelos Moleculares , Datos de Secuencia Molecular , Distrofias Musculares/genética , Mutación Missense , Linaje , Trastornos por Fotosensibilidad/genética , Proteínas de Unión al ARN/química , Proteínas de Unión al ARN/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Selenocisteína/metabolismo , Selenoproteínas/metabolismo , Homología de Secuencia de Aminoácido , Espermatogénesis/genética , Linfocitos T/inmunología
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