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1.
Diabetes Metab Res Rev ; 32(4): 350-65, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26431063

RESUMO

The human insulin receptor (IR) exists in two isoforms that differ by the absence (IR-A) or the presence (IR-B) of a 12-amino acid segment encoded by exon 11. Both isoforms are functionally distinct regarding their binding affinities and intracellular signalling. However, the underlying mechanisms related to their cellular functions in several tissues are only partially understood. In this review, we summarize the current knowledge in this field regarding the alternative splicing of IR isoform, tissue-specific distribution and signalling both in physiology and disease, with an emphasis on the human placenta in gestational diabetes mellitus (GDM). Furthermore, we discuss the clinical relevance of IR isoforms highlighted by findings that show altered insulin signalling due to differential IR-A and IR-B expression in human placental endothelium in GDM pregnancies. Future research and clinical studies focused on the role of IR isoform signalling might provide novel therapeutic targets for treating GDM to improve the adverse maternal and neonatal outcomes.


Assuntos
Diabetes Gestacional/metabolismo , Diabetes Gestacional/patologia , Insulina/metabolismo , Receptor de Insulina/metabolismo , Feminino , Humanos , Gravidez , Isoformas de Proteínas , Transdução de Sinais
2.
Mol Cancer ; 14: 198, 2015 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-26584646

RESUMO

Survivin, a member of the inhibitor of apoptosis family of proteins (IAPs) that controls cell division, apoptosis, metastasis and angiogenesis, is overexpressed in essentially all human cancers. As a consequence, the gene/protein is considered an attractive target for cancer treatment. Here, we discuss recent findings related to the regulation of survivin expression and its role in angiogenesis, particularly in the context of hypoxia. We propose a novel role for survivin in cancer, whereby expression of the protein in tumor cells promotes VEGF synthesis, secretion and angiogenesis. Mechanistically, we propose the existence of a positive feed-back loop involving PI3-kinase/Akt activation and enhanced ß-Catenin-TCF/LEF-dependent VEGF expression followed by secretion. Finally, we elaborate on the possibility that this mechanism operating in cancer cells may contribute to enhanced tumor vascularization by vasculogenic mimicry together with conventional angiogenesis.


Assuntos
Proteínas Inibidoras de Apoptose/metabolismo , Neovascularização Patológica/metabolismo , Hipóxia Celular/genética , Hipóxia Celular/fisiologia , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Inibidoras de Apoptose/genética , Espécies Reativas de Oxigênio/metabolismo , Survivina
3.
Int J Obes (Lond) ; 39(8): 1264-73, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25869606

RESUMO

OBJECTIVE: Human foetal development and growth in an environment of maternal obesity associates with high risk of cardiovascular disease and adverse neonatal outcome. We studied whether supraphysiological gestational weight gain results in human fetoplacental endothelial dysfunction and altered fetoplacental vascular reactivity. METHODS: Primary cultures of human umbilical vein endothelial cells (HUVECs) and umbilical vein rings were obtained from pregnant women (112 total of patients recruited, 7 patients dropped out) exhibiting prepregnancy normal weight that ended with a physiological (pGWG (n=67), total weight gain 11.5-16 kg, rates of weight gain ≤0.42 kg per week) or supraphysiological (spGWG (n=38), total weight gain >16 kg, rates of weight gain >0.42 kg per week) gestational weight gain (reference values from US Institute of Medicine guidelines). Vascular reactivity to insulin (0.1-1000 nmol l(-1), 5 min) in KCl-preconstricted vein rings was measured using a wire myograph. Protein levels of human equilibrative nucleoside transporter 1 (hENT1), total and Ser(1177)- or Thr(495)-phosphorylated endothelial nitric oxide synthase (eNOS) were detected by western blot or immunofluorescence, and adenosine transport (0-250 µmol l(-1) adenosine, 2 µCi ml(-1) [(3)H]adenosine, 20 s, 25 °C) was measured in the presence or absence of 1 µmol l(-1) nitrobenzylthioinosine (hENT1 inhibitor) or 10 µmol l(-1) chlorpromazine (CPZ, endocytosis inhibitor) in HUVECs. RESULTS: spGWG associates with reduced NOS activity-dependent dilation of vein rings (P=0.001), lower eNOS expression and higher Thr(495) (P=0.044), but unaltered Ser(1177)eNOS phosphorylation. hENT1-adenosine maximal transport activity was reduced (P=0.041), but the expression was increased (P=0.001) in HUVECs from this group. CPZ increased hENT1-adenosine transport (P=0.040) and hENT1 plasma membrane accumulation only in cells from pGWG. CONCLUSION: spGWG in women with a normal prepregnancy weight causes lower fetoplacental vascular reactivity owing to the downregulation of eNOS activity and adenosine transport in HUVECs. Maternal spGWG is a detrimental condition for human fetoplacental endothelial function and reducing these alterations could result in a better neonate outcome.


Assuntos
Adenosina/metabolismo , Endotélio Vascular/metabolismo , Óxido Nítrico/metabolismo , Obesidade/fisiopatologia , Placenta/irrigação sanguínea , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Aumento de Peso , Adulto , Transporte Biológico , Chile , Feminino , Humanos , Recém-Nascido , Obesidade/complicações , Circulação Placentária , Gravidez , Gestantes , Transdução de Sinais , Veias Umbilicais/citologia
4.
J Hum Nutr Diet ; 26(1): 56-70, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23078460

RESUMO

BACKGROUND: Nutrition may be a risk factor for unipolar depression. We aimed to review the association between dietary variables and the risk of depression. METHODS: Fifteen databases were searched up to May 2010. Only longitudinal studies for which outcomes were unipolar depression and/or depressive symptoms in adults were eligible for inclusion. Eleven studies were included and critically evaluated. Participants were in the age range 18-97 years and the study sample size was in the range 526-27 111. Follow-up ranged from 2 to 13 years. The diversity of dietary variables and nonlinear associations precluded formal meta-analysis and so a narrative analysis was undertaken. RESULTS: Variables inversely associated with depression risk were the consumption of nutrients such as folate, omega-3 fatty acids and monounsaturated fatty acids; foods such as olive oil and fish; and a diet rich in fruits, vegetables, nuts and legumes. Some of these associations varied by sex and some showed a nonlinear association. CONCLUSIONS: At the study level, weaknesses in the assessment of exposure and outcome may have introduced bias. Most studies investigated a cohort subgroup that may have resulted in selection bias. At the review level, there is a risk of publication bias and, in addition, narrative analyses are more prone to subjectivities than meta-analyses. Diet may potentially influence the risk of depression, although the evidence is not yet conclusive. Strengthening healthy-eating patterns at the public health level may have a potential benefit. Robust prospective cohort studies specially designed to study the association between diet and depression risk are needed.


Assuntos
Depressão/etiologia , Transtorno Depressivo/etiologia , Dieta/efeitos adversos , Depressão/prevenção & controle , Transtorno Depressivo/prevenção & controle , Dieta/normas , Gorduras na Dieta , Ácidos Graxos , Feminino , Ácido Fólico , Humanos , Masculino , Metanálise como Assunto
5.
Rev Med Chil ; 140(4): 503-6, 2012 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-22854697

RESUMO

BACKGROUND: Arterial gasometry is considered the gold standard for establishing a diagnosis of respiratory failure of any etiology. However, there are some circumstances in which it loses specificity, making necessary to consider other tests such as pulse oximetry to adequately determine hypoxemia. We report a 67 years old patient with sudden hypoacusia, right hemiparesis and polypnea. His laboratory exams on admission, showed extreme hypoxemia in several readings, without correlation to the patient's clinical condition nor the pulse oximetry, and a leukocytosis of 800.000 cells x ml, with many immature cells. Chronic myeloid leukemia was diagnosed and treatment with hydroxyurea was initiated, achieving normalization in the arterial gases in accordance with the fall of the white cell count. Interpretation of laboratory findings according to the general clinical context of the patient allowed to suspect a spurious hypoxemia, saving the patient from unnecessary and risky interventions.


Assuntos
Hipóxia/etiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucocitose/complicações , Idoso , Gasometria , Humanos , Hipóxia/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Contagem de Leucócitos , Masculino , Oximetria
6.
Rev Clin Esp (Barc) ; 222(1): 44-53, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34629305

RESUMO

OBJECTIVE: Systematically analyse the characteristics and impact of peer assisted learning programmes implemented in undergraduate health education. METHODS: Following the PRISMA protocol, we searched the electronic indexed databases WoS and SCOPUS; original studies reporting peer assisted learning in health science careers were included in the systematic review. Among them, the studies between 2010 and January 2020 were selected, and information regarding programme structures and principal results was subsequently extracted. RESULTS: A total of 47 studies were included in the review. The most frequent programme characteristics were the near-peer teaching modality, lecture classes, clinical laboratories and peer tutor training. The main findings identified were benefits in tutors' confidence and knowledge, better student comprehension and a more comfortable learning environment in comparison with that established by academic tutors. CONCLUSION: Peer assisted learning programmes have shown qualitative benefits in the learning environment, generation of support networks and confidence in knowledge acquired. Nonetheless, quantitative benefits measured as improvements in marks are inconclusive. Future studies are needed to standardise the methodologies used to determine which characteristics are the most positive in the learning process.


Assuntos
Aprendizagem , Grupo Associado , Estudantes de Ciências da Saúde , Humanos , Avaliação de Programas e Projetos de Saúde , Estudantes de Ciências da Saúde/psicologia , Universidades
9.
J Phys Chem B ; 112(30): 9006-12, 2008 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-18593152

RESUMO

A thermostimulated sol-gel transition in a system prepared by mixing a ZrOCl(2) acidified solution to a hot H(2)SO(4) aqueous solution was studied by dynamic rheological measurements and quasi-elastic light scattering. The effect of temperature and of molar ratio R(S) = [Zr]/[SO(4)] on the gelation kinetics was analyzed using the mass fractal aggregate growth model. This study shows that the linear growth of aggregates occurs at the early period of transformation, while bidimensional growth occurs at the advanced stage. The bidimensional growth can be shifted toward monodimensional growth by decreasing the aggregation rate by controlling the temperature and/or molar ratio R(S). EXAFS and Raman results gave evidence that the linear chain growth is supported by covalent sulfate bonding between primary building blocks. At the advanced stage of aggregation, the assembly of linear chains through hydrogen bonding gave rise to the growth of bidimensional particles.

10.
Rev Chilena Infectol ; 24(4): 270-5, 2007 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-17728913

RESUMO

Dental caries is a transmissible infectious disease in which Streptococcus mutans is a principal protagonist. Although it is widely believed that pregnancy is harmful to teeth, the effect of pregnancy on the development of caries is not clear. Considering this situation, the aim of the present study was to evaluate the levels of infection and to differentiate bacterial species with cariogenic potential in pregnant women from the Araucania region in Chile, by bacteriological and molecular analysis. In this work, we evaluated 51 pregnant women aged 15 to 40 years. The results show that 100% of women are infected by mutans streptococci Group, and 70.6% exhibited high levels of infection (> 500.000 cfu/mL). The molecular analysis shows that Streptococcus mutans and Streptococcus sobrinus frequencies were 92.1% and 1.9%, respectively. In conclusion, our data suggest that pregnant women are a high risk group for caries development.


Assuntos
Cárie Dentária/microbiologia , Complicações Infecciosas na Gravidez/microbiologia , Streptococcus mutans/genética , Streptococcus sobrinus/genética , Adolescente , Adulto , Chile , Índice CPO , Feminino , Humanos , Gravidez , Fatores de Risco , Streptococcus mutans/isolamento & purificação , Streptococcus sobrinus/isolamento & purificação
11.
Rev. clín. esp. (Ed. impr.) ; 222(1): 44-53, ene. 2022. tab, ilus
Artigo em Espanhol | IBECS (Espanha) | ID: ibc-204615

RESUMO

Objetivo: Analizar sistemáticamente las características y los impactos de los programas e iniciativas de aprendizaje asistido por pares realizados en estudios universitarios en ciencias de la salud en los cursos de pregrado. Métodos: Siguiendo el protocolo PRISMA, se realizó una búsqueda en las bases de datos indexadas en WoS y SCOPUS, con todos los trabajos originales que reportan aprendizaje asistido por pares en estudios universitarios en ciencias de la salud. Se seleccionaron artículos originales entre enero de 2010 y enero de 2020, analizando la información sobre las características de los programas y los principales resultados e impactos de los estudios. Resultados: Se incluyeron 47 estudios en la revisión. Las características de los programas más representadas fueron la utilización de la modalidad aprendizaje entre pares próximos, el uso de clases teóricas, laboratorios clínicos y la capacitación a los tutores pares. Los principales impactos identificados son los beneficios en la confianza y en el conocimiento de los tutores, la mejor comprensión de los contenidos y la mayor comodidad en comparación con los tutores académicos en los estudiantes. Conclusión: Los programas de aprendizaje asistido por pares han demostrado beneficios cualitativos relativos al ambiente de aprendizaje, la generación de redes de apoyo y la confianza en los conocimientos adquiridos. Sin embargo, los beneficios cuantitativos, medidos como mejoría en las calificaciones, no son concluyentes. Se necesitan futuros estudios que busquen indagar sobre las metodologías utilizadas para detectar qué características impactan más positivamente sobre el proceso de aprendizaje (AU)


Objective: Systematically analyse the characteristics and impact of peer assisted learning programmes implemented in undergraduate health education. Methods: Following the PRISMA protocol, we searched the electronic indexed databases WoS and SCOPUS; original studies reporting peer assisted learning in health science careers were included in the systematic review. Among them, the studies between 2010 and January 2020 were selected, and information regarding programme structures and principal results was subsequently extracted. Results: A total of 47 studies were included in the review. The most frequent programme characteristics were the near-peer teaching modality, lecture classes, clinical laboratories and peer tutor training. The main findings identified were benefits in tutors’ confidence and knowledge, better student comprehension and a more comfortable learning environment in comparison with that established by academic tutors. Conclusion: Peer assisted learning programmes have shown qualitative benefits in the learning environment, generation of support networks and confidence in knowledge acquired. Nonetheless, quantitative benefits measured as improvements in marks are inconclusive. Future studies are needed to standardise the methodologies used to determine which characteristics are the most positive in the learning process (AU)


Assuntos
Humanos , Aprendizagem , Grupo Associado , Estudantes de Ciências da Saúde , Universidades
12.
Rev. ANACEM (Impresa) ; 15(1): 33-41, 2021. tab
Artigo em Espanhol | LILACS | ID: biblio-1283060

RESUMO

INTRODUCCIÓN: El Concurso Nacional de Ingreso al Sistema Nacional de Servicio de Salud (CONISS) es una de las modalidades más conocidas para acceder a una especialización médica en Chile. Se basa en la evaluación de 5 rubros diferentes y en los últimos años no ha sido capaz de cubrir la demanda de los postulantes haciendo necesario un mejor conocimiento de este. El objetivo del estudio es describir los resultados del concurso CONISS de los últimos 4 años según las universidades de los participantes. Material y método: Estudio observacional, corte transversal, descriptivo. Asociación de puntajes obtenidos por los estudiantes con su respectiva universidad, obteniéndose datos de la página de superintendencia de Salud y utilizándose software Microsoft Excel® para su procesamiento. Resultados: El total de egresados fue de 6.092, provenientes de 22 universidades chilenas. Destaca la Pontificia Universidad Católica de Chile por liderar en el rubro 1 y el puntaje total durante los 4 años y la Universidad Pedro de Valdivia por encontrarse en el último puesto. Los rubros 4 y 5 fueron los que más se completaron. Las universidades con mejor desempeño en el rubro 1 fueron también las que obtuvieron mejor desempeño en el puntaje final. Discusión: El rubro 1 es el que posee mayor importancia en el resultado final del concurso y no se encuentra estandarizado entre universidades quedando sujeto al criterio de cada institución. No completar el resto de los rubros representa una desventaja comparativa pues la mayoría tiene buenos puntajes, pero estos resultados se ven limitados en gran medida por las calificaciones.


INTRODUCTION: The National Entrance Contest to the National Health Service System (CONISS) is one of the best known modalities to access a medical specialization in Chile. It is based on the evaluation of 5 different areas (items) and in recent years it has not been able to meet the demand of the applicants, making it necessary to know more about the subject. The objective of the study is to describe the results of the CONISS by university for the last 4 years. Material and method: Observational, cross-sectional, descriptive study. Association of scores obtained by students with their respective university, obtaining data from the Superintendency of Health page and using Microsoft Excel® software for processing. Results: The total number of graduates was 6,092, from 22 Chilean universities. The Pontificia Universidad Católica de Chile stands out for leading in item 1 and the total score during the 4 years and "Pedro de Valdivia" University for being in the last position. Items 4 and 5 were the most completed. The universities with the best performance in item 1 were also the ones that obtained the best performance in the final score. Discussion: Item 1 is the one that has the greatest importance in the final result of the contest and is not standardized among universities, being subject to the criteria of each institution. Not achieving the other items implies a comparative disadvantage as most participants have good scores, but these results are largely limited by grades.


Assuntos
Humanos , Estudantes de Medicina , Universidades/estatística & dados numéricos , Avaliação Educacional , Chile , Programas de Pós-Graduação em Saúde , Estudo Observacional , Desempenho Acadêmico , Medicina
13.
Curr Mol Med ; 16(1): 23-32, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26695697

RESUMO

To sustain tumor growth, the cancer cells need to adapt to low levels of oxygen (i.e., hypoxia) in the tumor tissue and to the tumor-associated acidic microenvironment. In this phenomenon, the activation of the sodium/proton exchanger 1 (NHE1) at the plasma membrane and the hypoxia-inducible factor (HIF) are critical for the control of the intracellular pH (pHi) and for hypoxia adaptation, respectively. Interestingly, both of these mechanisms end in sustaining cancer cell proliferation. However, regulatory mechanisms of pHi in human ovary tissue and in malignant ascites are unknown. Additionally, a potential role of NHE1 in the modulation of H(+) efflux in human ovarian cancer cells is unknown. In this review, we discussed the characteristics of tumor microenvironment of primary human ovarian tumors and tumor ascites, in terms of pHi regulatory mechanisms and oxygen level. The findings described in the literature suggest that NHE1 may likely play a role in pHi regulation and cell proliferation in human ovarian cancer, potentially involving HIF2α activation. Since ovarian cancer is the fifth cause of prevalence of women cancer in Chile and is usually of late diagnosis, i.e., when the disease jeopardizes peritoneal cavity and other organs, resulting in reduced patient survival, new efforts are required to improve patient-life span and for a better understanding of the pathophysiology of the disease. The potential advantage of the use of amiloride and amiloride-derivatives for cancer treatment in terms of NHE1 expression and activity is also discussed as a therapeutic approach in human ovarian cancer.


Assuntos
Neoplasias Ovarianas/metabolismo , Animais , Proliferação de Células/fisiologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Oxigênio/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Microambiente Tumoral/fisiologia
14.
Rev. enferm. neurol ; 20(2): 126-138, may.-ago. 2021.
Artigo em Espanhol | LILACS | ID: biblio-1368366

RESUMO

Introducción: la estrategia de atención integrada a las enfermedades prevalentes de la infancia (AIEPI), avanza en el concepto de integralidad de la atención de la salud, siendo una herramienta práctica, en los servicios de salud y hogar, establece máxima validez a las preocupaciones de la comunidad y del personal de salud. Objetivo: conocer la promoción de la salud a través de prácticas claves en la atención integrada a las enfermedades prevalentes de la infancia (AIEPI), en profesores de educación prebásica. Material y métodos: investigación descriptiva en población de 59 técnicos y profesionales adscritos a jardines infantiles y salas cuna, en la ciudad de Temuco, que corresponden a 23 salas cuna, que ejercen actividades laborales con lactantes de 6-12 meses. Recolección de información, y instrumento de prácticas claves propuestas por AIEPI OMS/OPS, el análisis se trabajó con estadística descriptiva e inferencia estadística, apoyándose en el software SPSS versión 24 en español. La investigación cumplió los criterios de rigor ético de Ezequiel Emanuel y la aprobación del Comité de Ética acreditado de la Universidad Mayor. Resultados: 59 personas, de sexo femenino, personal de atención en la guardería de jardines infantiles y salas cuna. La edad promedio de 40 años, promedio de 8 años de ejercicio técnico profesional. El 78% del personal de atención en la guardería, posee una jornada laboral de 9 horas diarias. Respecto a las conductas en lactancia materna un 78 %, "siempre" realiza fomento del amamantamiento y un 72,9 % "siempre" fomenta los beneficios de la lactancia materna; no obstante, en cuanto al fomento de la técnica de acople, "a veces" fomenta la técnica un 39,8 %. De la inmunización un 64,4 % del personal parvulario, "siempre fomenta la vacunación del PNI", por otro lado, un 71 % de la muestra "siempre fomenta la administración de vacunas de campaña (influenza)". De la conducta por cuadro respiratorio, un 69,5 % de la población, "siempre reconoce los signos y síntomas que alertan de un cuadro respiratorio". Conclusión: en la comunidad educativa, el uso de la estrategia desarrolla un actuar más efectivo, identificando actitudes de promoción. El tener la posibilidad de contacto diario; permite a la comunidad de prebásica dirigir su mirada hacia los problemas más relevantes y proponer estrategias para la solución en conexión con el sector salud


Introduction: the strategy of Integrated Attention to Prevalent Childhood Diseases (IMCI), advances in the concept of comprehensive health care, being a practical tool, in health and home services, giving maximum validity to concerns of the community and health personnel. Objective: to know the promotion of health through key practices in Integrated Attention to Prevalent Childhood Illnesses (IMCI), in pre-basic education teachers. Material and Methods: Descriptive research in a population of 59 technicians and professionals assigned to Kindergartens and Nursery Rooms, in the city of Temuco, corresponding to 23 Nursery Rooms, who carry out work activities with infants aged 6-12 months. Information collection and key practices instrument proposed by IMCI WHO / PAHO. The analysis was carried out with descriptive statistics and statistical inference, relying on the SPSS software version 24 in Spanish. The research met the criteria of ethical rigor of Ezequiel Emanuel and the approval of the accredited Ethics Committee of the Universidad Mayor. Results: 59 people, female, nursery care personnel from Kindergartens and Nursery Rooms. The average age of 40 years, average of 8 years of professional technical practice. 78% of the kindergarten staff have a 9-hour workday. Regarding breastfeeding behaviors, 78% "always" promote breastfeeding and 72.9% "always" promote the benefits of breastfeeding, however, regarding the promotion of the coupling technique, "a times", 39.8% promote the technique. Of the immunization, 64.4% of the kindergarten staff "always promote the PNI vaccination", on the other hand, 71% of the sample "always promote the administration of field vaccines (Influenza)". Of the behavior due to respiratory symptoms, 69.5% of the population "always recognize the signs and symptoms that warn of a respiratory condition". Conclusion: in the educational community, the use of the strategy develops a more effective action, identifying attitudes of promotion. Having the possibility of daily contact; allows the pre-basic community to direct its gaze towards the most relevant problems and propose strategies for the solution in connection with the health sector.


Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Lactente , Atenção Integrada às Doenças Prevalentes na Infância , Promoção da Saúde , Saúde da Criança , Enfermagem
15.
Placenta ; 36(8): 895-902, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26055528

RESUMO

INTRODUCTION: Maternal hypercholesterolemia and hypertriglyceridemia during pregnancy is correlated with fetoplacental endothelial dysfunction and atherosclerotic lesions in fetal arteries. Few studies have reported the distribution of the concentrations of maternal total cholesterol (TCh), lipoprotein cholesterol and triglycerides during pregnancy. Therefore, we determined maternal lipid concentration during pregnancy and established the percentiles over which fetoplacental endothelial dysfunction is observed. METHODS: A lipoprotein profile was determined for 249 pregnant Chilean women in each trimester of pregnancy in cross-sectional and longitudinal lipid determination studies. Distribution percentiles for TCh, high-, low- and very-low-density lipoprotein (HDL, LDL, and vLDL, respectively) cholesterol and triglycerides were estimated. The reactivity of human umbilical vein rings to the calcitonin gene-related peptide (0.1-1000 nmol/L, 5 min) and sodium nitroprusside (10 µmol/L, 5 min) was measured (wire myography) in KCl-preconstricted vessels. RESULTS: Maternal lipoproteins and triglyceride concentrations increased over time from preconception to the 3rd trimester of pregnancy. Newborn umbilical blood lipoprotein and triglyceride concentrations were lower than those in maternal circulation. Changes in maternal HDL correlated with newborn HDL concentration; however, no correlation between maternal lipoprotein concentrations and newborn weight was found. Maternal TCh and LDL concentrations were inversely correlated with the maximal dilation, but the >75th percentile of maternal TCh and LDL concentrations (>291 and >169 mg/dL, respectively) correlated with reduced calcitonin gene-related peptide sensitivity of the vein rings. DISCUSSION AND CONCLUSION: We identified percentiles for maternal TCh and LDL concentrations over which abnormal endothelium-dependent human fetoplacental vascular response is observed.


Assuntos
LDL-Colesterol/sangue , Veias Umbilicais/fisiologia , Adolescente , Adulto , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , HDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Nitroprussiato/farmacologia , Gravidez , Estudos Retrospectivos , Triglicerídeos/sangue , Veias Umbilicais/efeitos dos fármacos , Vasodilatadores/farmacologia , Adulto Jovem
16.
Placenta ; 36(3): 287-96, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25573092

RESUMO

INTRODUCTION: Preeclampsia is associated with impaired placental vasodilation and reduced endothelial nitric oxide synthase (eNOS) activity in the foetoplacental circulation. Adenosine and insulin stimulate vasodilation in endothelial cells, and this activity is mediated by adenosine receptor activation in uncomplicated pregnancies; however, this activity has yet to be examined in preeclampsia. Early onset preeclampsia is associated with severe placental vasculature alterations that lead to altered foetus growth and development, but whether late-onset preeclampsia (LOPE) alters foetoplacental vascular function is unknown. METHODS: Vascular reactivity to insulin (0.1-1000 nmol/L, 5 min) and adenosine (1 mmol/L, 5 min) was measured in KCl-preconstricted human umbilical vein rings from normal and LOPE pregnancies using a wire myograph. The protein levels of human cationic amino acid transporter 1 (hCAT-1), adenosine receptor subtypes, total and Ser¹¹77- or Thr495-phosphorylated eNOS were detected via Western blot, and L-arginine transport (0-1000 µmol/L L-arginine, 3 µCi/mL L-[³H]arginine, 20 s, 37 °C) was measured in the presence or absence of insulin and adenosine receptor agonists or antagonists in human umbilical vein endothelial cells (HUVECs) from normal and LOPE pregnancies. RESULTS: LOPE increased the maximal L-arginine transport capacity and hCAT-1 and eNOS expression and activity compared with normal conditions. The A(2A) adenosine receptor (A(2A)AR) antagonist ZM-241385 blocked these effects of LOPE. Insulin-mediated umbilical vein ring relaxation was lower in LOPE pregnancies than in normal pregnancies and was restored using the A(2A)AR antagonist. DISCUSSION AND CONCLUSIONS: The reduced foetoplacental vascular response to insulin may result from A(2A)AR activation in LOPE pregnancies.


Assuntos
Arginina/metabolismo , Endotélio Vascular/metabolismo , Resistência à Insulina , Insulina/metabolismo , Pré-Eclâmpsia/metabolismo , Receptor A2A de Adenosina/metabolismo , Veias Umbilicais/metabolismo , Adenosina/metabolismo , Antagonistas do Receptor A2 de Adenosina/farmacologia , Adulto , Transporte Biológico/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Hipoglicemiantes/uso terapêutico , Técnicas In Vitro , Insulina/farmacologia , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/patologia , Gravidez , Terceiro Trimestre da Gravidez , Receptor A2A de Adenosina/química , Transdução de Sinais/efeitos dos fármacos , Veias Umbilicais/efeitos dos fármacos , Veias Umbilicais/patologia , Adulto Jovem
17.
Food Funct ; 5(7): 1564-72, 2014 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-24855655

RESUMO

Alpha-linolenic acid (ALA) is an essential n-3 PUFA; its n-3 LCPUFA derivatives EPA and DHA, which have diverse beneficial effects, are scarce in the human diet. In recent years nontraditional vegetable oils rich in ALA (up to 45%) have been developed as new alternatives to increase ALA consumption. This work evaluated the accretion of ALA, EPA and DHA into the phospholipids extracted from erythrocytes, liver, kidney, small intestine, heart, quadriceps and the brain in rats fed sunflower (SFO), canola (CO), Rosa canina (RCO), sacha inchi (Plukenetia volubilis, SIO) and chia (Salvia hispánica, ChO) oils. Five experimental groups (n = 12 per group) were fed for 21 days with SFO (1% ALA), CO (10% ALA), RCO (33% ALA), SIO (49% ALA), and ChO (64% ALA). SIO and ChO allowed higher ALA accretion in all tissues, except the brain, and a reduction in the content of arachidonic acid in all tissues except the brain. EPA was increased in erythrocytes, liver, kidney, small intestine, heart and quadriceps, but not in the brain. DHA was increased in the liver, small intestine and brain tissues. Our results demonstrate that ALA, when provided in significant amounts, can be converted into n-3 LCPUFA, mostly DHA in the liver and brain. It is suggested that oils rich in ALA, such as SIO and ChO, are good sources for obtaining higher tissue levels of ALA, also allowing its selective conversion into n-3 LCPUFA in some tissues of the rat.


Assuntos
Euphorbiaceae/química , Óleos de Plantas/farmacologia , Rosa/química , Salvia/química , Ácido alfa-Linolênico/farmacologia , Animais , Ácido Araquidônico/análise , Ácido Araquidônico/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ácidos Docosa-Hexaenoicos/análise , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/análise , Ácido Eicosapentaenoico/farmacologia , Coração/efeitos dos fármacos , Coração/fisiologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Fosfolipídeos/metabolismo , Ratos , Ratos Wistar , Ácido alfa-Linolênico/análise
20.
Curr Mol Med ; 13(2): 266-81, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23228128

RESUMO

Caveolins are a family of membrane proteins required for the formation of small plasma membrane invaginations called caveolae that are implicated in cellular trafficking processes. In addition to this structural role, these scaffolding proteins modulate numerous intracellular signaling pathways; often via direct interaction with specific binding partners. Caveolin-1 is particularly well-studied in this respect and has been attributed a large variety of functions. Thus, Caveolin-1 also represents the best-characterized isoform of this family with respect to its participation in cancer. Rather strikingly, available evidence indicates that Caveolin-1 belongs to a select group of proteins that function, depending on the cellular settings, both as tumor suppressor and promoter of cellular traits commonly associated with enhanced malignant behavior, such as metastasis and multi-drug resistance. The mechanisms underlying such ambiguity in Caveolin-1 function constitute an area of great interest. Here, we will focus on discussing how Caveolin-1 modulates cell death and survival pathways and how this may contribute to a better understanding of the ambiguous role this protein plays in cancer.


Assuntos
Caveolina 1/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Neoplasias/genética , Neoplasias/genética , Animais , Antineoplásicos/uso terapêutico , Cavéolas/efeitos dos fármacos , Cavéolas/metabolismo , Caveolina 1/metabolismo , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Metástase Neoplásica , Proteínas de Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Transdução de Sinais/efeitos dos fármacos
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