Role of aspirin-triggered lipoxin A4, aspirin, and salicylic acid in the modulation of the oxidative and inflammatory responses induced by plasma from women with pre-eclampsia.

PROBLEM: Oxidative stress and inflammation are key events leading to pre-eclampsia, involved in several maternal deaths. Low doses of acetylsalicylic acid (ASA) are used in the prevention and treatment of pre-eclampsia. The synthesis of aspirin-triggered lipoxin (ATL) by cyclooxygenase-2 acetylation is an alternative mechanism of ASA, which could explain the effectiveness of ASA treatments. The aim of this study was to evaluate the role of ASA, salicylates, and ATL in the modulation of the oxidative and inflammatory responses induced by plasma from women with pre-eclampsia. METHOD OF STUDY: Plasma from 14 women with pre-eclampsia and 17 normotensive pregnant women was probed for inducing oxidative and inflammatory responses on endothelial cells and U937 promonocytes. The role of ATL, ASA, and salicylic acid (SA) on these events was evaluated. RESULTS: Plasma from women with pre-eclampsia induced TBARS and nitrotyrosine production on endothelial and U937 cells. Pre-treatment with both ATL and ASA decreased the TBARS production, while ATL decreased the nitrotyrosine. Pre-eclamptic plasma augmented the translocation of NF-kB on U937 cells, which decreased by a high dose of ASA and SA. Finally, the pre-eclamptic plasma increased the adhesion of leukocytes-PMN and monocytes-to endothelium, and we were able to determine a state of resolution of inflammation, since ATL decreased the PMN adhesion, and conversely, it increased the monocytes adhesion to endothelium. CONCLUSION: Together, these results suggest that ATL could explain the beneficial actions of ASA and support further research on mechanisms, real efficacy, and rational use of ASA in pre-eclampsia.

Prácticas clave y conocimientos maternos de la -Estrategia AIEPI en el Ambiente Comunitario / Key practices and maternal knowledge regarding the IMCI strategy in a community setting / Práticas-chave e conhecimentos maternos da Estratégia AIEPI no Ambiente Comunitário

Resumen La estrategia de Atención Integral a Enfermedades Prevalentes de la Infancia (AIEPI) busca disminuir la enfermedad y la mortalidad en menores de 5 años, por medio de la implementación de acciones orientadas a una atención idónea, tanto en el ámbito asistencial como en el hogar y en la comunidad. El objetivo fue identificar y clasificar los reportes que se han publicado con respecto a la aplicación de las prácticas clave, y a los conocimientos maternos y de cuidadores de la estrategia AIEPI en el mundo. Se recopilaron publicaciones nacionales e internacionales, escritas en inglés y español, que estuvieran registradas en las bases de datos o fuentes de información Scielo, Bireme, Pubmed, Google académico y tesis académicas. La mayoría de los artículos presentan niveles de evidencia VII y VIII, ya que son estudios de casos y controles y descriptivos. Los estudios relacionados con conocimientos maternos evidencian las falencias que presentan los padres y/o cuidadores de los menores de 5 años, con relación a las acciones y estrategias que deben ejercer frente al manejo apropiado de las enfermedades prevalentes. Con respecto a las prácticas clave, los estudios que hicieron parte de la presente revisión de la literatura coinciden en demostrar su efectividad, en cuanto al mejoramiento de las condiciones de salud y bienestar de los menores de 5 años que son objeto de su aplicación. Los estudios concuerdan en la importancia de adelantar procesos educativos que fortalezcan el conocimiento y la aplicación de las prácticas clave, y de la estrategia en general, tanto en las comunidades como en los profesionales de la salud.

Abstract The Integrated Management of Childhood Illness (IMCI) strategy aims to reduce disease and mortality among children under five years of age through the implementation of actions aimed at providing adequate care at the medical, home and community levels. The objective was to identify and classify the reports that have been published regarding the application of key practices and the knowledge that mothers and caregivers have regarding the IMCI strategy in the world. To this end, national and international publications were collected which were written in English or Spanish and registered in databases or information sources such as Scielo, Bireme, Pubmed, Google Scholar and academic theses. The evidence levels of most papers were VII and VIII because they were case, controls and descriptive studies. The studies on maternal knowledge showed the shortcomings of parents and/or caregivers of children under five years of age concerning the actions and strategies that should be applied to appropriately manage prevalent diseases. Regarding key practices, the studies considered in this literature review are consistent in demonstrating their effectiveness in improving the health and welfare conditions among children under five years of age, on whom they are applied. The studies also agree on the importance of advancing educational processes which strengthen the knowledge and application of the key practices as well as the strategy in general, for both communities and healthcare professionals.

Resumo A estratégia de Assistência Integral a Doenças Prevalentes da Infância (AIEPI) visa diminuir doenças e a mortalidade em menores de 5 anos, por meio da implantação de ações destinadas a um atendimento idôneo, tanto no plano assistencial quanto no lar e na comunidade. O propósito foi identificar e classificar os relatórios que têm sido publicados sobre a aplicação das práticas-chave, e sobre os conhecimentos maternos e de protetores da estratégia AIEPI no mundo. Foram coletadas publicações nacionais e internacionais, escritas em inglês e espanhol, que estivessem registradas nas bases de dados ou fontes de informação Scielo, Bireme, Pubmed, Google acadêmico e teses acadêmicas. A maioria dos artigos apresentam níveis de evidência VII e VIII, pois são estudos de casos e controles e descritivos. Os estudos relacionados com conhecimentos maternos evidenciam as falhas que apresentam os pais e/ou pessoas encarregadas do cuidado dos menores de 5 anos, com relação às ações e estratégias que devem exercer diante do controle apropriado das doenças prevalentes. Com relação às práticas-chave, os estudos que fizeram parte desta revisão da literatura coincidem em demonstrar a sua efetividade, quanto à melhora das condições de saúde e bem-estar dos menores de 5 anos que são objeto da sua aplicação. Os estudos concordam na importância de se desenvolver processos educativos que fortaleçam o conhecimento e a aplicação das práticas-chave, e da estratégia em geral, tanto nas comunidades quanto nos profissionais da saúde.

Expresión del fenotipo Duffy negativo en mujeres afrodescendientes y su relación con la preeclampsia / Expression of the Duffy negative phenotype in women of African descent and their relation to pre-eclampsia

La preeclampsia (PE) es una complicación del embarazo que trae consigo algunas consecuencias negativas para la madre y el feto: en la madre provoca principalmente hipertensión y proteinuria, mientras que en el feto puede presentarse trombocitopenia, alteración en el desarrollo del sistema nervioso central y circulatorio, y restricción del crecimiento intrauterino, lo cual se considera el factor de riesgo principal de muerte fetal en nacimientos producto de una PE severa. En la preeclampsia se presenta una disfunción endotelial relacionada con placentación anormal, estado de estrés oxidativo y proceso inflamatorio sistémico, que lleva a la activación de neutrófilos y monocitos. Se ha considerado a la interleucina-8 (IL-8) como un posible candidato desencadenante por ser quimioatrayente y activador de leucocitos; en la circulación sanguínea, la IL-8 se une a un receptor de quimiocina multiespecífico de alta afinidad denominado DARC, que es idéntico al antígeno del grupo sanguíneo Duffy. Este receptor regula los niveles plasmáticos de IL-8, uniéndose a esta quimiocina, pero cuando hay una mutación en la región promotora del gen se altera la expresión de DARC, lo que conlleva a que la IL-8 de los factores genéticos involucrados en la activación de los neutrófilos y de los monocitos, y por ende, en la disfunción endotelial presentada durante este síndrome hipertensivo, especialmente en la población afrodescendiente.

Preeclampsia (PE) is a complication of pregnancy that brings some negative consequences for both mother and fetus. It specially causes hypertension and proteinuria in mothers; while in fetuses it causes thrombocytopenia, development alterations of the central nervous and circulatory system; also intrauterine growth restriction may occur. This last factor is regarded as the main risk factor for fetal death in births as a result of severe PE. There is endothelial dysfunction in preeclampsia related to abnormal placentation, state of oxidative stress and systemic inflammatory process that leads to the activation of neutrophils and monocytes. Interleukin-8 (IL-8) is considered as a possible trigger candidate, since this chemokine is a chemoattractant and leukocyte activator. In the bloodstream, interleukin-8 binds to a high affinity multispecific-chemokine receptor called DARC, which is identical to the Duffy blood group antigen. This receptor regulates plasma levels of IL-8 by binding to chemokine. But, when there is a mutation in the gene promoter region, DARC expression is altered, and IL-8 inefficiently binds to receptor. This mutation results in Duffy negative phenotype, which is present in most of African descendants. This literature review is intended to address the role of IL-8 as neutrophil chemo-attractant, the importance of Duffy blood system and the possible association between ethnicity and preeclampsia.

Lipoxinas inducidas por la aspirina: una alternativa para modular los procesos proinflamatorios en la preeclampsia / Aspirin induced lipoxins: alternative to modulate proinflammatory processes in preeclampsia

La preeclampsia es un síndrome hipertensivo que se presenta a partir de la semana 20 de gestación. El objetivo de este trabajo es describir la producción y los mecanismos de acción de las lipoxinas inducidas por la aspirina y proponerlas como una alternativa adecuada para modular los procesos oxidativos característicos de la preeclampsia y los ciclos proinflamatorios que inician con la cascada de activación del factor nuclear-kappa B, y en consecuencia de sus productos. La preeclampsia se caracteriza por la producción de sustancias proinflamatorias, que inducen la activación de células endoteliales, directa o indirectamente, a través de la activación previa de los monocitos, los cuales pueden generar especies reactivas de oxígeno y expresar moléculas de adhesión que median la interacción con el endotelio, contribuyendo a su estado de disfunción, activación e inducción de la cascada de señalización del factor nuclear-kappa B. La aspirina por su parte, induce la producción de lipoxinas que inhiben la activación del factor nuclear-kappa B mediante el bloqueo de la proteína quinasa IkB, necesaria para desencadenar la activación de la vía canónica y no canónica de este factor nuclear.

Preeclampsia is a hypertensive syndrome that occurs after the 20th weeks of gestation. The objective of this review was to describe the mechanisms of production and action of aspirin- triggered lipoxins in order to consider them as a suitable alternative to modulate oxidative processes, which are characteristic of preeclampsia and proinflammatory cycles starting with cascade activation of nuclear factor-kappa B, consequently of their products. Preeclampsia is characterized by the production of proinflammatory substances that induce directly or indirectly endothelial cell activation,, through prior activation of monocytes, which can generate reactive oxygen species and expression of adhesion molecules that mediate interacting with the endothelium, contributing to its dysfunction, activation and induction of signaling cascade nuclear factor-kappa B. Aspirin induces lipoxin, which inhibits the activation of nuclear factor-kappa B by blocking IkB protein kinase, necessary to trigger the activation of canonical and non-canonical pathway of this nuclear factor.

[Evaluation of atypical semen parameters in individuals whose couples had a history of early recurrent embryo death: in search for a reference value]. / Evaluación de parámetros seminales no convencionales en individuos cuyas parejas presentan muerte embrionaria temprana recurrente: en busca de un valor de referencia.

INTRODUCTION: Previous studies related alterations in non-conventional seminal parameters with recurrent early embryonic death for one couple. A reference standard of clinical assessment is required for the management of these kinds of patients. OBJECTIVE: Normal semen parameters were established based on functional tests including lipid peroxidation of sperm membranes, antioxidant capacity of seminal plasma and integrity of sperm chromatin to compare with men whose partners have recurrent early embryonic death. These parameters set reference values to identify subfertile individuals whose condition can be attributed to altered semen parameters. MATERIALS AND METHODS: The conventional and non-conventional semen parameters of 47 samples of semen were evaluated. Thirty-six samples were from subfertile individuals whose partners had a history of early recurrent embryo death, and 11 samples were from individuals with recent evidence of normal fertility. RESULTS: By discriminant analysis, the two groups were classified as follows: a value below 0.50 for 86.1% of individuals in the group of recurrent early embryonic death, and a value above 0.50 to classify 81.8% of individuals in the group of recent fertility. CONCLUSIONS: This reference value of 0.5 based on the results of sperm tests can identify infertile male patients whose partners have a history of early embryonic death. This will aid the physician to suggest treatments more focused on the possible cause of subfertility.

Evaluación de parámetros seminales no convencionales en individuos cuyas parejas presentan muerte embrionaria temprana recurrente: en busca de un valor de referencia / Evaluation of atypical semen parameters in individuals whose couples had a history of early recurrent embryo death: in search for a reference value}

Introducción. En estudios previos se relacionaron las alteraciones en los parámetros espermáticos no convencionales con la presencia de muerte embrionaria temprana recurrente de la pareja; debido a esto, se planteó la necesidad de establecer un valor de referencia de utilidad clínica para el manejo de estos pacientes. Objetivo. Evaluar los parámetros seminales convencionales y las pruebas funcionales de lipoperoxidación de las membranas espermáticas, capacidad antioxidante del plasma seminal e integridad de la cromatina espermática, en individuos cuyas parejas presentan muerte embrionaria temprana recurrente, con el fin de obtener un valor de referencia y poder identificar aquellos individuos en quienes la disminución de la fertilidad se pueda demostrar con estas pruebas. Materiales y métodos. Se evaluaron los parámetros espermáticos convencionales y no convencionales de 47 muestras de semen, de las cuales, 36 pertenecían al grupo de individuos con disminución de la fertilidad por historia de muerte embrionaria temprana recurrente en sus parejas, y 11 muestras de individuos sanos con fertilidad reciente. Resultados. Mediante el análisis discriminante se obtuvo una función que permitió clasificar los dos grupos analizados así: un valor menor de 0,50 para el 86,1 % de los individuos del grupo de muerte embrionaria temprana recurrente y un valor mayor de 0,50 para clasificar el 81,8 % de los individuos del grupo de fertilidad reciente. Conclusiones. Este valor de referencia de 0,5, basado en los resultados de los análisis espermáticos y utilizando el análisis discriminante, permitiría categorizar a los pacientes que consulten por historia de muerte embrionaria temprana en sus parejas y le ayudaría al médico a sugerir un tratamiento más enfocado en la posible causa de la disminución de la fertilidad.

Introduction. Previous studies related alterations in non-conventional seminal parameters with recurrent early embryonic death for one couple. A reference standard of clinical assessment is required for the management of these kinds of patients. Objective. Normal semen parameters were established based on functional tests including lipid peroxidation of sperm membranes, antioxidant capacity of seminal plasma and integrity of sperm chromatin to compare with men whose partners have recurrent early embryonic death. These parameters set reference values to identify subfertile individuals whose condition can be attributed to altered semen parameters. Materials and methods. The conventional and non-conventional semen parameters of 47 samples of semen were evaluated. Thirty-six samples were from subfertile individuals whose partners had a history of early recurrent embryo death, and 11 samples were from individuals with recent evidence of normal fertility. Results. By discriminant analysis, the two groups were classified as follows: a value below 0.50 for 86.1% of individuals in the group of recurrent early embryonic death, and a value above 0.50 to classify 81.8% of individuals in the group of recent fertility. Conclusions. This reference value of 0.5 based on the results of sperm tests can identify infertile male patients whose partners have a history of early embryonic death. This will aid the physician to suggest treatments more focused on the possible cause of subfertility.

Assessment of sperm factors possibly involved in early recurrent pregnancy loss.

OBJECTIVE: To evaluate and compare standard sperm parameters, lipid peroxidation of sperm plasma membranes, antioxidant capacity of seminal plasma, and sperm chromatin integrity in ejaculates from men whose partners have a history of recurrent pregnancy loss and from a control group of men with recent fertility. DESIGN: Descriptive study. SETTING: Reproduction Program, University of Antioquia, Medellín, Colombia. PATIENT(S): Twenty-three couples with history of recurrent pregnancy loss and 11 men with recent fertility. INTERVENTION(S): Semen samples from control men and men whose partner had a history of recurrent pregnancy loss were examined for differences in semen parameters, lipid peroxidation, antioxidant capacity, DNA fragmentation index, and sperm preparation. MAIN OUTCOME MEASURE(S): Migration-sedimentation method was used to collect motile spermatozoa from fresh ejaculates for examination for semen parameters. RESULT(S): Men from the control group had spermatozoa with higher percentage of normal sperm morphology, concentration, progressive motility, and antioxidant capacity compared with men from the recurrent pregnancy loss group, who had spermatozoa with higher teratozoospermia and higher lipid peroxidation. Motile sperm fractions from both groups had spermatozoa with better sperm parameters compared with freshly ejaculated sperm. CONCLUSION(S): This study strengthens the current literature associating sperm quality with recurrent pregnancy loss, and emphasizes the importance of evaluating male factor by tests such as lipid peroxidation and measuring antioxidant capacity of seminal plasma in addition to conventional sperm parameters.

Role of male factor in early recurrent embryo loss: do antioxidants have any effect?

OBJECTIVE: To evaluate whether increasing antioxidant intake in men with high levels of DNA damage or lipid peroxidation improves gestational results in couples with history of recurrent embryo loss. DESIGN: Descriptive study (case series). SETTING: Early recurrent embryo loss program at the University of Antioquia, Medellín, Colombia. PATIENT(S): Seventeen men whose spouses had a history of two or more embryo losses before 12 weeks of gestation. INTERVENTION(S): Male partners with increased DNA fragmentation index (%DFI) or high thiobarbituric acid reactive substances (TBARS) were instructed to consume a diet rich in antioxidants or commercial multivitamins containing beta-carotene, vitamin C, vitamin E, and zinc for at least 3 months. MAIN OUTCOME MEASURE(S): Pregnancy outcome was recorded in the spouses of men with increased %DFI or TBARS who received antioxidant supplementation. RESULTS: Of the 17 men, 9 (53%) presented with an increased %DFI or TBARS. They were started on an antioxidant supplementation regimen. Of these nine men, six of their spouses became pregnant. All couples whose male partners accepted antioxidant supplementation achieved a successful pregnancy. CONCLUSIONS: Our study demonstrates the benefits of an increased intake of antioxidant-rich food or antioxidant supplements by men who show high levels of sperm DNA fragmentation or lipid peroxidation, which could result in an improvement in gestational outcomes in couples with history of recurrent embryo losses.

[Early embryo death: does the male factor play a role?]. / Muerte embrionaria temprana: tiene influencia el factor masculino?

OBJECTIVE: To discuss the possible role of the male factor in early embryo death. METHOD: A detailed bibliographic review has been put together to establish which alterations in spermatozoa can be associated with early embryo death. RESULTS: Before the fusion between plasma membranes of the sperm and the oocyte occurs, both germ cells must undergo a maturation process that allows successful fertilization and embryo development. The study of couples with early embryo loss is usually approached from the side of the woman due to the obvious relationship that exists between the female and the developing embryo. However, it is not illogical to suppose that a genetic or epigenetic alteration of the sperm could have important consequences on these losses due to the necessary contribution of the male gamete not only to embryonic but also to placental development. On the other hand, spermatozoa have certain characteristics such as a highly compact DNA, they undergo apoptosis and the seminal plasma contains antioxidants that protect the structural and functional integrity of the germ cell. These factors assure fertilization and embryo development. Nevertheless, epigenetic alterations of the sperm such as altered chromatin packing, mistakes in imprinting, absence or alteration of the centrosome, telomeric shortening and absence of sperm RNA, could affect functions leading to early embryo loss. CONCLUSIONS: Knowledge concerning sperm intervention previous to embryo development will provide the basis for better understanding and for possible diagnosis and treatment of diverse reproductive alterations in men that could impede embryo development.