Two types of placentitis were studied: ascending and nocardioform placentitis. Although the first diagnosis of nocardioform placentitis was made three decades ago, little is known about the disease, due to the lack of an experimental model. In attempt to develop a research model, Crossiela equi was inoculated through intrauterine, intravenous, intrapharyngeal, and oral routes, but none of the routes resulted in nocardioform placentitis. This may indicate that unidentified factors may play a role in disease pathogenesis and that simple presence of bacteria is not sufficient to induce nocardioform placentitis. The second and major component of this dissertation involved the identification of diagnostic markers for placentitis. Because ascending bacterial placentitis is readily and predictably induced using existing experimental models, this model was used to identify diagnostic markers for placentitis in maternal plasma and fetal fluids. Three potential biomarkers were examined: acute phase inflammatory proteins, steroid hormones produced by the fetoplacental unit, and protein composition of the fetal fluids. Of the three acute phase proteins investigated, serum amyloid A and haptoglobin but not fibrinogen increased in association with experimentally induced ascending placentitis. Androgens and progestins appear to be poor markers for placentitis. Serum estradiol 17β concentrations were reduced in mares with experimentally induced placentitis and appear to be a good marker for placentitis in mares. Different methods were used to study the protein composition of the fetal fluids. Alpha-fetoprotein was characterized as a major protein present in the equine fetal fluids, and this protein was elevated in plasma of mares with placentitis. In another study, using a high-throughput proteomic technique several new proteins were characterized in the amniotic and allantoic fluids of mares carrying normal pregnancies, and several previously uncharacterized proteins were detected in the allantoic fluid of mares with placentitis. Three secreting proteins were elevated in allantoic fluid of mares with experimentally induced ascending placentitis.

La naissance avant terme constitue un important problème de santé périnatale partout dans le monde. Chaque année près de 15 millions de bébés naissent prématurément. Notre laboratoire s’intéresse depuis une décennie à la conception et le développement de nouvelles classes thérapeutiques (appelés agents tocolytiques) capables d’inhiber les contractions utérines et prolonger le temps de gestation. Due à son implication directe dans le déclanchement des contractions utérines, la prostaglandine F2α (FP) est devenue notre cible de choix. Le PDC 113.824 et aza-glycinyl-proline sont apparus comme des inhibiteurs allostériques puissants du récepteur de la prostaglandine F2α, capables de prolonger la durée de gestation chez les souris. Le travail réalisé au cours de ce mémoire a pour objectif d’étudier le tour β nécessaire pour la reconnaissance sur le récepteur de la prostaglandine F2α. Dans la conception de mime peptidique sélectif efficace et puissant, le repliement β est un élément structural essentiel pour le maintien ou l’amélioration de l’activité du mime peptidique. Les études conformationelles du PDC113.824 et l’aza-glycinyl-proline montrent que les squelettes centraux de ces mimes peptidiques pourraient adopter essentiellement un tour β de type I ou II`, ce qui suggère l’implication des deux types de tours dans l’activité biologique. La synthèse de mimes peptidiques adoptant le tour β de type I et II` est devenue une stratégie logique dans la recherche de nouveaux agents tocolytiques. Au cours de ces études quatre analogues du PDC113.824 ont été synthétisés, un azabicyclo[5.3.0]alkanone et un dipeptide macrocyclique (mimes du tours β de type I) pour étudier l’implication du tour β type I. Par la suite la synthèse de glycinyl-proline et le D-alaninyl-proline (des mimes du tour β du type II`) a été réalisée afin de valider l’implication du tour β type II` dans la reconnaissance sur le récepteur. Nous avons utilisé une stratégie de synthèse efficace pour obtenir les deux analogues (azabicyclo [5.3.0]alkanone et dipeptides macrocycles) à partir d’un intermédiaire commun, en procédant par une cyclisation transannulaire diastéréosélective du tétra-peptide. / Preterm birth is a major perinatal health problem. Worldwide each year, more than one baby on ten is born premature, accounting for approximately 15 million babies per year. Pursuing molecules that can delay labour, so called tocolytics, we have targeted the prostaglandin F2α receptor (FP), because of its intimate involvement with the stimulation of uterine contractions leading to birth and preterm birth. Our laboratory has previously demonstrated that PDC-113.824 and azapeptide can modulate FP function by an allosteric mechanism featuring biased signalling, and can delay labour in a mouse model. The objective of the present work is to study the active turn geometry responsible for the modulatory effects of our lead tocolytic agents on the prostaglandin F2α receptor. Crystal structure and computational analyses of indolizidin-2-one amino acid and aza-glycinyl-proline components have shown them to adopt geometry that mimic ideal type I and II’ β-turns suggesting the potential involvement of such turns in the biological activity. To study the relevance of a type I β-turn on activity, we have prepared analogs possessing macrocyclic and pyrroloazepinone dipeptide mimics, because of their reported propensities to mimic type I β-turns. The syntheses of analogs possessing glycinyl-proline and D-alaninyl-proline were conducted to validate the involvement of a type II` β-turn in receptor recognition. In addition, we reported an efficient strategy for preparing the macrocyclic and pyrroloazepinone dipeptide mimics from a common intermediate using a diastereoselective transannular cyclization on a tetrapeptide precursor.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

La tasa de nacimientos prematuros en 184 países afiliados a la OMS va de 5 a 18%, por eso, en las metas ampliadas, estableció que deberá reducirse la tasa de mortalidad neonatal por parto prematuro en 50% en el periodo 2010-2025 en los países con tasa ≥ 5 x 1,000 nacidos vivos, lo que evitaría que 550,000 prematuros mueran cada año para el 2025. La recomendación principal de la OMS para evitar la muerte neonatal es: la aplicación del Método mamá Canguro, es por ello que se realizó el trabajo de investigación titulado: “Experiencias de las enfermeras frente a la aplicación del método mamá canguro en recién nacidos prematuros en un hospital local, Chiclayo, 2021”; con el objetivo de describir, analizar y comprender las experiencias de las enfermeras frente a la aplicación del método mamá canguro. La investigación fue de tipo cualitativo, con metodología descriptiva. Los sujetos de estudio fueron las enfermeras del servicio de neonatología; el tamaño de la muestra se determinó con la técnica de saturación; los datos se obtuvieron mediante la entrevista semiestructurada. Se obtuvo como resultado 3 categorías: Beneficios del método mamá canguro, experiencias afectivas ante la aplicación del método mamá canguro, e inexperiencia y temor del método mamá canguro ante un hijo prematuro. Conclusión: Las enfermeras, experimentan sentimientos muy profundos al ver a las madres realizar éste método, asimismo se confirma que uno de los beneficios del método mamá canguro es la mejora del desarrollo del niño prematuro de una forma muy rápida y eficaz. / The rate of premature births in 184 countries affiliated with the WHO ranges from 5 to 18%, therefore, in the expanded goals, it was established that the neonatal mortality rate due to premature birth should be reduced by 50% in the period 2010-2025 in the countries with a rate ≥ 5 x 1,000 live births, which would prevent 550,000 premature babies from dying each year by 2025. The main recommendation of the WHO to avoid neonatal death is: the application of the Kangaroo Mother Method, which is why the research work titled: “Nurses' experiences regarding the application of the kangaroo mother method in premature newborns in a local hospital, Chiclayo, 2021”; with the objective of describing, analyzing and understanding the experiences of nurses regarding the application of the kangaroo mother method. The research was qualitative, with descriptive methodology. The study subjects were the nurses of the neonatology service; the sample size was determined with the saturation technique; The data were obtained through the semi-structured interview. The result was 3 categories: Benefits of the kangaroo mother method, affective experiences with the application of the kangaroo mother method, and inexperience and fear of the kangaroo mother method when faced with a premature child. Conclusion: Nurses experience very deep feelings when seeing mothers perform this method. It is also confirmed that one of the benefits of the kangaroo mother method is the improvement of the development of premature children in a very fast and effective way.

Este trabajo de investigación se basa en la necesidad de desarrollar una solución que permita una monitorización eficiente de la actividad uterina en primigestas con la finalidad de identificar posibles anomalías que ponen en riesgo la salud de la madre y el feto. Al realizarse una revisión detallada de la literatura, se pudo identificar la oportunidad de implementar una solución con sensores de bajo costo y una técnica para medir contracciones uterinas mediante impulsos eléctricos del sistema nervioso llamada “electromiografía”. Esto en conjunto con una aplicación móvil, que permitirá monitorear las contracciones de la gestante y alertar a ella y a su obstetra de posibles parámetros irregulares, cubre la brecha de investigaciones en mobile health enfocada en el electrodiagnóstico. Del mismo modo, la solución propuesta permitirá hacer uso eficiente de los recursos del centro de salud en el que está implementado al tener conocimiento del estado de salud de la madre en tiempo real. Para desarrollar nuestra solución, hemos considerado los aspectos tecnológicos, médicos y legales que permitan garantizar la alineación correcta con las necesidades de todas las partes interesadas. / The following research work is based on the need to develop a solution that allows efficient monitoring of uterine activity with the determination to identify possible abnormalities that may put the health of the mother and fetus at risk. Conducting a detailed review of the literature, the opportunity to implement a low-cost sensor solution and a technique to measure uterine contractions using electrical impulses from the nervous system called "electromyography" was identified. This together with a mobile application to monitor the contractions of the pregnant woman and alert her and her obstetrician of possible irregular parameters, covers the gap of research on mobile health issues focused on electrodiagnostic. At the same time, the proposed solution makes efficient use of the resources of the health center in which it is implemented by knowing the mother's health state in real-time. To develop our solution, we have considered the technological, medical, and legal aspects to guarantee a correct alignment with the needs of all stakeholders. / Trabajo de investigación

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