RESUMEN
The possible relationship between periodontal disease resulting from the infection of gingival tissue by the Gram-negative bacterium Porphyromonas gingivalis (P. gingivalis) and the development of neuroinflammation remains under investigation. Recently, P. gingivalis lipopolysaccharide (LPS) was reported in the human brain, thus suggesting it might activate brain microglia, a cell type participating in neuroinflammation. We tested the hypothesis of whether in vitro exposure to ultrapure P. gingivalis LPS may result in classical and alternative activation phenotypes of rat microglia, with the concomitant release of cytokines and chemokines, as well as superoxide anion (O2-), thromboxane B2 (TXB2), and matrix metalloprotease-9 (MMP-9). After an 18-h exposure of microglia to P. gingivalis LPS, the concentration-dependent responses were the following: 0.1-100 ng/mL P. gingivalis LPS increased O2- generation, with reduced inflammatory mediator generation; 1000-10,000 ng/mL P. gingivalis LPS generated MMP-9, macrophage inflammatory protein 1α (MIP-1α/CCL3), macrophage inflammatory protein-2 (MIP-2/CXCL2) release and significant O2- generation; 100,000 ng/mL P. gingivalis LPS sustained O2- production, maintained MMP-9, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) release, and triggered elevated levels of MIP-1α/CCL3, MIP-2/CXCL2, and cytokine-induced neutrophil chemoattractant 1 (CINC-1/CXCL-1), with a very low release of lactic dehydrogenase (LDH). Although P. gingivalis LPS was less potent than Escherichia coli (E. coli) LPS in stimulating TXB2, MMP-9, IL-6 and interleukin 10 (IL-10) generation, we observed that it appeared more efficacious in enhancing the release of O2-, TNF-α, MIP-1α/CCL3, MIP-2/CXCL2 and CINC-1/CXCL-1. Our results provide support to our research hypothesis because an 18-h in vitro stimulation with ultrapure P. gingivalis LPS resulted in the classical and alternative activation of rat brain microglia and the concomitant release of cytokines and chemokines.
Asunto(s)
Lipopolisacáridos/farmacología , Microglía/efectos de los fármacos , Porphyromonas gingivalis/metabolismo , Animales , Células Cultivadas , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/aislamiento & purificación , Metaloproteinasa 9 de la Matriz/metabolismo , Microglía/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fenotipo , Ratas , Superóxidos/metabolismo , Tromboxano B2/metabolismoRESUMEN
BACKGROUND: Peak gonadotropin-releasing hormone or agonist (GnRHa) stimulated luteinizing hormone (LH) testing with leuprolide acetate (LA) is commonly used to document suppression during therapy for central precocious puberty (CPP). The objective of the study was to investigate suitability of using basal LH levels to monitor GnRHa treatment and to determine optimal transition from 1-month to 3-month LA formulations via a post hoc analysis of a randomized, open-label, 6-month study. METHODS: A total of 42 children with CPP, pretreated with 7.5-, 11.25-, or 15-mg 1-month LA formulations were randomized to 11.25- or 30-mg 3-month LA. Basal LH/peak-stimulated LH levels were measured at weeks 0, 4, 8 and 12. Positive/negative predictive values and sensitivities/specificities were determined for basal LH vs. LH-stimulation results. RESULTS: Pretreatment with any 1-month formulation for the most part did not affect continuation of suppression after transitioning to 3-month formulation (mean peak-stimulated LH levels remained < 4 IU/L). Basal LH predicted suppression escape (basal LH-level cutoff ≥ 0.6 IU/L predicted 70% of those failing suppression). Tolerability was similar, regardless of dose. CONCLUSIONS: Our data indicate that a basal level of <0.60 IU/L is adequate for monitoring suppression approximately two-thirds of the time. Furthermore, the effectiveness and safety of 3-month LA treatments are not influenced by previous CPP therapies.
Asunto(s)
Monitoreo de Drogas , Hormona Liberadora de Gonadotropina/agonistas , Leuprolida/administración & dosificación , Hormona Luteinizante/sangre , Pubertad Precoz/tratamiento farmacológico , Sustancias para el Control de la Reproducción/administración & dosificación , Niño , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/efectos adversos , Preparaciones de Acción Retardada/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Hormona Folículo Estimulante Humana/antagonistas & inhibidores , Hormona Folículo Estimulante Humana/sangre , Hormona Folículo Estimulante Humana/metabolismo , Humanos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Leuprolida/efectos adversos , Leuprolida/uso terapéutico , Hormona Luteinizante/antagonistas & inhibidores , Hormona Luteinizante/metabolismo , Masculino , Microesferas , Ovario/efectos de los fármacos , Ovario/metabolismo , Pubertad Precoz/sangre , Sustancias para el Control de la Reproducción/efectos adversos , Sustancias para el Control de la Reproducción/uso terapéutico , Estudios Retrospectivos , Testículo/efectos de los fármacos , Testículo/metabolismoRESUMEN
This group of Vermont community health nurses from different agencies collaborated to develop a competence validation framework for maternal and child health nursing in the practice areas of perinatal client teaching, breastfeeding, and prenatal, postpartum, and newborn nursing care. The framework is based on the work of Benner, using the "competent" level of nursing practice, and delineates three parameters of competence: technical skills, interpersonal skills, and critical thinking skills. Learning resource materials, including newborn and maternal assessment guidelines, were developed for each competence area. The four competence validation tools were successfully tested for validity and reliability as well as efficiency and effectiveness by nurses in all 13 home health agencies and 12 public health district offices in Vermont. This system of competence validation is now used to support a consistently high quality of care for all recipients of Vermont's Healthy Babies, Kids, and Families services, and is available for use in other care settings.