Uric Acid as a predictor of adverse maternal and perinatal outcomes in women hospitalized with preeclampsia.

OBJECTIVE: Elevated serum uric acid is commonly observed in women with preeclampsia, but its utility in predicting adverse outcomes has recently been disputed. Our goal was to analyze data from a large cohort of women with preeclampsia to determine the utility of serum uric acid in predicting adverse maternal and perinatal outcomes. METHODS: Data were obtained from an ongoing international prospective study of women admitted to hospital with preeclampsia (Pre-eclampsia Integrated Estimate of RiSk). Univariate logistic regression was used to determine the relationship between serum uric acid concentration (both absolute and gestational-age corrected [Z score]) and adverse outcomes (maternal and perinatal). Analyses were conducted to compare cohorts of women with preeclampsia as defined by hypertension and proteinuria versus hypertension and hyperuricemia. RESULTS: Uric acid Z score was associated with adverse perinatal outcome (OR 1.5; 95% CI 1.4 to 1.7) and had a point estimate > 0.7 (area under the curve receiver operating characteristic 0.72; 95% CI 0.69 to 0.74). Serum uric acid concentration also showed a significant association with adverse maternal outcomes, but the point estimate was < 0.7. No significant differences were observed between groups in which preeclampsia was defined by hypertension and proteinuria and by hypertension and hyperuricemia. CONCLUSION: In women admitted to hospital with preeclampsia, the serum uric acid concentration, corrected for gestational age via a Z score, is clinically useful in predicting adverse perinatal outcomes but not maternal outcomes.

Objectif : Bien qu'un taux sérique élevé d'acide urique soit couramment constaté chez les femmes qui présentent une prééclampsie, son utilité pour ce qui est de la prévision des issues indésirables a récemment été remise en question. Nous avions pour objectif d'analyser les données issues d'une importante cohorte de femmes présentant une prééclampsie, afin de déterminer l'utilité du taux sérique d'acide urique pour ce qui est de la prévision des issues indésirables maternelles et périnatales. Méthodes : Les données ont été tirées d'une étude prospective internationale toujours en cours qui porte sur des femmes hospitalisées présentant une prééclampsie (Pre-eclampsia Integrated Estimate of RiSk). Une régression logistique univariée a été utilisée pour déterminer la relation entre la concentration sérique en acide urique (tant absolue que corrigée en fonction de l'âge gestationnel [score Z]) et les issues indésirables (maternelles et périnatales). Des analyses ont été menées pour comparer des cohortes de femmes présentant une prééclampsie définie par l'hypertension et la protéinurie à des cohortes de femmes présentant une prééclampsie définie par l'hypertension et l'hyperuricémie. Résultats : Le score Z quant à l'acide urique était associé à des issues périnatales indésirables (RC, 1,5; IC à 95 %, 1,4 - 1,7) et comptait une estimation ponctuelle > 0,7 (surface sous la courbe de la fonction d'efficacité de l'observateur, 0,72; IC à 95 %, 0,69 - 0,74). Une association significative a également été constatée entre la concentration sérique en acide urique et des issues indésirables maternelles; toutefois, l'estimation ponctuelle était < 0,7. Aucune différence significative n'a été constatée entre les groupes « prééclampsie définie par l'hypertension et la protéinurie ¼ et « prééclampsie définie par l'hypertension et l'hyperuricémie ¼. Conclusion : Bien que la concentration sérique en acide urique (corrigée en fonction de l'âge gestationnel par l'intermédiaire d'un score Z) soit utile sur le plan clinique pour ce qui est de la prévision des issues indésirables périnatales chez les femmes hospitalisées présentant une prééclampsie, elle ne compte pas une utilité semblable en ce qui concerne les issues indésirables maternelles.

Herpes simplex virus type 1-encoded glycoprotein C contributes to direct coagulation factor X-virus binding.

The HSV1 (herpes simplex virus type 1) surface has been shown recently to initiate blood coagulation by FVIIa (activated Factor VII)-dependent proteolytic activation of FX (Factor X). At least two types of direct FX-HSV1 interactions were suggested by observing that host cell-encoded tissue factor and virus-encoded gC (glycoprotein C) independently enhance FVIIa function on the virus. Using differential sedimentation to separate bound from free 125I-ligand, we report in the present study that, in the presence of Ca2+, FX binds directly to purified wild-type HSV1 with an apparent dissociation constant (K(d)) of 1.5+/-0.4 muM and 206+/-24 sites per virus at saturation. The number of FX-binding sites on gC-deficient virus was reduced to 43+/-5, and the remaining binding had a lower K(d) (0.7+/-0.2 microM), demonstrating an involvement of gC. Engineering gC back into the deficient strain or addition of a truncated soluble recombinant form of gC (sgC), increased the K(d) and the number of binding sites. Consistent with a gC/FX stoichiometry of approximately 1:1, 121+/-6 125I-sgC molecules were found to bind per wild-type HSV1. In the absence of Ca2+, the number of FX-binding sites on the wild-type virus was similar to the gC-deficient strain in the presence of Ca2+. Furthermore, in the absence of Ca2+, direct sgC binding to HSV1 was insignificant, although sgC was observed to inhibit the FX-virus association, suggesting a Ca2+-independent solution-phase FX-sgC interaction. Cumulatively, these data demonstrate that gC constitutes one type of direct FX-HSV1 interaction, possibly providing a molecular basis for clinical correlations between recurrent infection and vascular pathology.

NeuroDevNet: Training the next generation of Canadian developmental neurobiologists.

Enhancing Canadian capacity in the research and treatment for neurodevelopmental disorders is central to NeuroDevNet's mission. Building on the notion that it takes a network of scientists, clinicians, and educators to train the next generation researchers, NeuroDevNet brings together the diversity of expertise from across Canada to provide multifaceted, cross-disciplinary training opportunities for our trainees. Our Program provides for a diverse training experience that fosters the development of active young researchers with a collaborative focus and an eye toward the bidirectional translation of knowledge between the bench and the bedside. With funding from the NCE of Canada, as well as public and private partnerships, we offer fellowship and internship opportunities to trainees that encourage collaborative interactions, interdisciplinary exchanges and knowledge translation. This program will enhance the development and integration of NeuroDevNet as well as the Canadian community caring for the health and wellbeing of its citizens with neurodevelopmental disorders.