ABSTRACT. Objective. Kawasaki disease (KD) is an acute febrile vasculitic syndrome in children. CD40 ligand (CD40L) has been implicated in certain types of vasculitis. We proposed that CD40L expression might be correlated with coronary artery lesions in KD.Methods. Blood samples were collected from 43 patients with KD before intravenous immunoglobulin (IVIG) treatment and 3 days afterward. Forty-three agematched febrile children with various diseases were studied in parallel as controls. CD40L expression on Tcells and platelets were detected by flow cytometry, and soluble CD40L (sCD40L) levels were measured by enzyme-linked immunosorbent assay.Results. We found that CD40L expression on CD4 ؉ T-cells was significantly higher in patients with KD than in the febrile control (FC) group (28.69 ؎ 1.17% vs 4.37 ؎ 0.36%). CD40L expression decreased significantly 3 days after IVIG administration (28.69 ؎ 1.17% vs 13.53 ؎ 0.55%). CD40L expression on platelets from patients with KD was also significantly higher than in the FC group (8.20 ؎ 0.41% vs 1.26 ؎ 0.12%) and decreased after IVIG therapy. sCD40L levels were also significantly higher in KD patients with those of FC (9.69 ؎ 0.45 ng/mL vs 2.25 ؎ 0.19 ng/mL) but were not affected by IVIG treatment 3 days afterward (9.69 ؎ 0.45 ng/mL vs 9.03 ؎ 0.32 ng/mL). More interesting, we found that in KD patients, CD40L expression on CD4 ؉ T-cells and platelets but not on CD8 ؉ T-cells or sCD40L was correlated with the occurrence of coronary artery lesions.Conclusions. CD40L might play a role in the immunopathogenesis of KD. IVIG therapy might downregulate CD40L expression, resulting in decrease of CD40L-mediated vascular damage in KD. This implicates that modulation of CD40L expression may benefit to treat KD vasculitis. Pediatrics 2003;111:e140 -e147. URL: http://www. pediatrics.org/cgi/content/full/111/2/e140; Kawasaki disease, intravenous immunoglobulin, CD40 ligand, soluble CD40L.ABBREVIATIONS. KD, Kawasaki disease; CD40L, CD40 ligand; IgG, immunoglobulin G; sCD40L, soluble CD40L; FC, febrile controls; IVIG, intravenous immunoglobulin; CAL, coronary artery lesions; FITC, fluorescein isothiocyanate; PE, phycoerythrin; PBS, phosphate-buffered saline; PRP, platelet-rich plasma; IL, interleukin; TSST-1, toxic shock syndrome toxin-1. K awasaki disease (KD) is an acute multisystem vasculitic syndrome of unknown cause that occurs in infants and children. 1 Evidence increasingly suggests that immunoregulatory activation with vascular endothelial inflammation may be involved in the immunopathogenesis of KD. 2 The acute stage of KD is associated with overactivation of numerous immunologic parameters, such as immune-competent cell activation, 3-5 cytokines, 6 nitric oxide production, 7 autoantibody production, 8 and adhesion molecule expression. 9 Pathologic examination of acute coronary arteritis in the acute stage of KD showed that KD vascular lesion formation is an activated T-lymphocyte-dependent process characterized by transmural infiltration of activated T-lymphocytes, with CD8ϩ T...
Infants passively exposed to morphine or heroin through their addicted mothers usually develop characteristic withdrawal syndrome of morphine after birth. In such early life, the central nervous system exhibits significant plasticity and can be altered by various prenatal influences, including prenatal morphine exposure. Here we studied the effects of prenatal morphine exposure on postsynaptic density protein 95 (PSD-95), an important cytoskeletal specialization involved in the anchoring of the NMDAR and neuronal nitric oxide synthase (nNOS), of the hippocampal CA1 subregion from young offspring at postnatal day 14 (P14). We also evaluated the therapeutic efficacy of dextromethorphan, a widely used antitussive drug with noncompetitive antagonistic effects on NMDARs, for such offspring. The results revealed that prenatal morphine exposure caused a maximal decrease in PSD-95 expression at P14 followed by an age-dependent improvement. In addition, prenatal morphine exposure reduced not only the expression of nNOS and the phosphorylation of cAMP responsive element-binding protein at serine 133 (CREB(Serine-133)), but also the magnitude of long-term depression (LTD) at P14. Subsequently, the morphine-treated offspring exhibited impaired performance in long-term learning and memory at later ages (P28-29). Prenatal coadministration of dextromethorphan with morphine during pregnancy and throughout lactation could significantly attenuate the adverse effects as described above. Collectively, the study demonstrates that maternal exposure to morphine decreases the magnitude of PSD-95, nNOS, the phosphorylation of CREB(Serine-133), and LTD expression in hippocampal CA1 subregion of young offspring (e.g., P14). Such alterations within the developing brain may play a role for subsequent neurological impairments (e.g., impaired performance of long-term learning and memory). The results raise a possibility that postsynaptic density proteins could serve an important role, at least in part, for the neurobiological pathogenesis in offspring from the morphine-addicted mother and provide tentative therapeutic strategy.
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