Capítulo I: Para evaluar el efecto sinérgico de IL-12/IL-18 y M-CSF/GM-CSF en la diferenciación de los monocitos y su impacto en el estallido respiratorio y el metabolismo del colesterol de los monocitos derivados en macrófagos, los monocitos fueron diferenciados durante 7 días en presencia de la combinación de la granulocyte-macrophage colony-stimulating factor (GM-CSF) y macrophage colonystimulating factor (M-CSF) o la interleucina 12 (IL-12) e IL-18 para producir respectivamente la M / GM-Ф y IL12/IL18- Ф. Como control, los monocitos fueron diferenciados sólo con M-CSF, GM-CSF, IL-12 e IL-18 para producir respectivamente la M-Ф, GM-Ф, IL12-Ф y IL18-Ф. El análisis de muestras de cuatro donantes de monocitos demostró una diferencia en el metabolismo del colesterol y el estallido respiratorio de las subpoblaciones de macrófagos. Los M/GM-Ф y IL12/IL18-Ф estimulados producieron alto nivel de H2O2 y mieloperoxidasa, y generaron gran cantidad de HOCl en respuesta al PMA. Por el contrario, mostraron bajos niveles de enzima antioxidante catalasa. Además intensificaron la oxidación de LDL y acumularon de forma espontánea gran cantidad de colesterol cuando incubado con la lipoproteína de baja densidad nativa. Los resultados sugieren que las vías M-CSF/GM-CSF o IL12/IL18 podría ser algunas señales sinérgica crítica experimentado por los monocitos / macrófagos durante su diferenciación in-vivo, en el que su potencial aterogénico o su capacidad de oxidar el LDL aumenta. Capítulo II: Estudios recientes muestran que el rebote de la carga del VIH-1 después de largos períodos de interrupciones del tratamiento (IT), resulta en un estallido de biomarcadores de la enfermedad arterial coronaria (CAD). Hemos investigado si las interrupciones cortas inducen un estallido de estos biomarcadores, si los niveles de estos biomarcadores vuelven a la basal durante la reintroducción del tratamiento y si los estallidos eran relacionados con el número de interrupciones. Los biomarcadores de CAD CRP, CXCL8, dímero-D, MMP-9 y los lípidos plasmáticos fueron medidos a partir de muestras de plasma almacenadas de 21 sujetos con infección crónica por el VIH-1 sometidos en un estudio de evaluación de seis ciclos de "2 semanas de interrupción" / "4 semanas reintroducción" de la terapia antirretrovirales. Los sujetos fueron agrupados en aquellos con un rebote de la carga viral después de interrumpir el tratamiento y los que no sufrieron del rebote. Los niveles de CRP, MMP-9, CXCL8, dímero-D y los triglicéridos aumentaron significativamente después de cada IT en los pacientes con el rebote de la carga viral. Los cambios de incremento medio en los sujetos sin rebote de la carga viral eran muy bajos en comparación con la basal y sin interés clínico como los valores se mantuvieron entre los rangos plasmáticos normales. Ningún efecto tiempo se observó durante la IT a la excepción de la CRP. Todos los biomarcadores volvieron a los niveles basales después de cada reinicio del tratamiento. Los resultados sugieren que las IT antirretroviral de tan sólo dos semanas son asociadas con un estallido de relevancia clínica de los biomarcadores de CAD aguda, que indica la importancia de la adherencia al tratamiento. / We organized the thesis into two chapters: Chapter I: To evaluate the synergic effect of IL-12/IL-18 and M-CSF/GM-CSF on monocytes differentiation and their impact on the respiratory burst and cholesterol metabolism of monocytes-derived macrophages, monocytes were differentiated for 7 days in the presence of both granulocyte-macrophage colonystimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) or Interleukin-12 (IL- 12) and IL-18 to produce respectively M/GM-Ф and IL12/IL18-Ф. As control, monocytes were differentiated only with M-CSF, GM-CSF, IL-12 and IL-18 to produce respectively M-Ф, GM-Ф, IL12- Ф and IL18-Ф. Samples analyses of four monocytes donors demonstrated a differential in the cholesterol metabolism and respiratory burst of macrophage subpopulations. Stimulated M/GM-Ф and IL12/IL18-Ф produce high level of H2O2 and myeloperoxidase; and generate significant amount of HOCl in response to PMA. In contrast, they show low levels of anti-oxidant enzyme catalase. Moreover they intensify LDL oxidation and spontaneously accumulate significant amount of cholesterol when incubated with unmodified low-density lipoprotein. The results suggest that M-CSF/GM-CSF or IL12/IL18 pathways might be some critical synergic signals experienced by monocytes/macrophages during their differentiation in-vivo; in which their atherogenic potential or their capacity to oxidize LDL increase. Chapter II: Recent studies show that HIV-1 load rebound after long periods of treatment interruptions (TI), results in a burst of coronary artery disease (CAD) biomarkers. We investigate whether short interruptions induce a burst of these biomarkers, whether their levels return to the baseline during treatment resumption and if the burst were related to the number of interruptions. CAD biomarkers CRP, CXCL8, D-dimer, MMP-9 and plasma lipids were measured from stored plasma samples of 21 chronically HIV-1 infected subjects enrolled in a study evaluating six cycles of “2 weeks off” / “4 weeks on” antiretroviral therapy. Subjects were clustered into those with a viral load rebound after stopping treatment and those without. The levels of CRP, MMP-9, CXCL8, D-dimer and triglycerides rose significantly after each TI in subjects with viral load rebound. Changes of means increment in subjects without viral load rebound were too low relative to the baseline and without clinical interest as values stayed between the normal plasma ranges. No times effect was observed during TI except for CRP. All biomarkers return to baseline levels after each treatment resumption. The results suggest that antiretroviral TI as short as two weeks are associated with a clinically relevant burst of acute CAD biomarkers, that indicating the importance of adhering to treatment.

This dissertation examined the relationship between maternal stressful life events and urogenital infection in preterm birth. A systematic literature review revealed ambivalent findings concerning the relationship between maternal stress and infection during pregnancy; the effects of this relationship on pregnancy outcome were not examined in the reviewed studies. The current study employed a biobehavioral model consisting of maternal stressful life events (illness among family members, divorced, moved, became homeless, partner lost job, mom lost job, argued with partner more than usual, partner did not want the child, inability to pay bills, got in a physical fight, partner went to jail, close friend/relative had a bad problem with drinking or drug use, and close friend/relative died) and urogenital infection (genital warts, herpes, chlamydia, gonorrhea, pelvic inflammatory disease, syphilis, Group B streptococcus, bacterial vaginosis, trichomoniasis, yeast infection, urinary tract infection, and other infection) to examine the relationship between these variables in preterm birth. Data from 1,647 respondents of the 2005 Florida Pregnancy Risk Assessment Monitoring System survey were analyzed using descriptive statistics, chi-square and student t- tests, analysis of variance, and structural equation modeling (SEM). Of the respondents, 42% were White, 37.8% had preterm deliveries, and the mean age was 27.1 years. White mothers who became homeless (p = 0.021) or had a partner in jail (p = 0.041) during the 12 months prior to delivery had more preterm deliveries as compared to full-term deliveries. Other non-White mothers who had an ill family member (p = 0.010) had fewer preterm deliveries. In general, mothers diagnosed with Group B streptococcus during pregnancy (p = 0.031) had fewer preterm deliveries. Black mothers diagnosed with herpes (p = 0.006) had fewer preterm deliveries. SEM revealed a significant relationship between maternal stress and infection, in general (p < 0.001), and among White (p < 0.001), Black (p < 0.001), and Hispanic (p < 0.001) mothers. The interaction between these variables was not significant, in general, or among racial/ethnic groups. Results of this study indicate that culturally tailored prevention programs designed to help women cope with multiple risk factors may prove beneficial in reducing preterm birth rates.

No description available.

Reproduction de : Thèse d'exercice : Médecine : Nancy 1 : 2003. / Thèse : 03NAN1119. Titre provenant de l'écran-titre.

Reproduction de : Thèse d'exercice : Médecine spécialisée : Nancy 1 : 2002. / Thèse : 02NAN11026. Titre provenant de l'écran-titre.

Reproduction de : Thèse d'exercice : Médecine spécialisée : Nancy 1 : 2001. / Thèse : 01NAN11163. Titre provenant de l'écran-titre.

Thesis (Ph. D.)--Open University. BLDSC no. DXN075774.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 64-69).

Chronic microbial infections result from persistent host colonization that is not cleared via the immune response or therapeutics. Within the host, microbes can undergo adaptive evolution, whereby beneficial traits promoting persistence arise due to selection; these traits can therefore affect disease outcomes and treatment strategies. The Gram-negative opportunistic pathogen Pseudomonas aeruginosa is the primary cause of chronic, fatal respiratory infections in individuals with the heritable disease cystic fibrosis (CF). The goal of this dissertation is to identify adaptations that allow P. aeruginosa to persist in the host during chronic CF lung infection. To achieve this goal, P. aeruginosa was chronologically sampled from 3 CF patients, ranging from the first infecting bacterium (the ancestor) to ~40,000 generations post-infection. By comparing gene expression profiles of ancestral and evolved isolates sampled from multiple patients, I identified 24 parallel gene expression changes that occurred over time within each lineage, suggesting that these traits are beneficial to the bacterium. Because most of these traits had unknown physiological roles, I sought to characterize their biological significance. I used a gain-of-function genetic screen and discovered that a subset of these genes enhance biofilm formation, a sessile mode of growth proposed to be important during chronic CF lung infection. I showed that enhanced biofilm formation is due to increased production of the exopolysaccharide Psl, which is traditionally viewed as less critical for maintaining chronic infections than other virulence factors. Lastly, I demonstrated that a majority (~72%) of chronic P. aeruginosa isolates produce more Psl than their corresponding ancestor, suggesting that this exopolysaccharide is important during chronic infection and an adaptive trait. / text

published_or_final_version / Nursing Studies / Master / Master of Nursing