11 research outputs found
Lymph act, TCR αβ, TCR γδ cells in peripheral blood in children with juvenile idiopathic arthritis
Characterization of human hepatic and extrahepatic UDP-glucuronosyltransferase (UGTs) enzymes involved in the metabolism of classical cannabinoids
Congenital localized scleroderma
OBJECTIVES: Juvenile localized scleroderma (JLS) usually has its onset during later childhood. This report describes the clinical and serologic features of six children with congenital localized scleroderma (CLS).
STUDY DESIGN: A large, multinational study was conducted among pediatric rheumatology and dermatology centers by collecting information on demographics, family history, triggering environmental factors, clinical features, laboratory reports, and treatment of patients with JLS. Patients with onset at birth were carefully examined.
RESULTS: Among 750 patients with JLS, 6 patients (0.8%) had scleroderma-related lesions at birth. Female-to-male ratio was 2:1. All patients had linear scleroderma, in four involving the face with en coup de sabre appearance. Two patients were misdiagnosed as having skin infection, one nevus, one salmon patch, and two undefined skin lesions. The mean diagnostic delay was 3.9 years. In comparison with the group of 733 patients with late-onset JLS, CLS presented a significantly more prolonged disease duration at diagnosis and a higher frequency of en coup de sabre subtypes.
CONCLUSIONS: Congenital localized scleroderma is a rare and probably underestimated condition in neonates. The linear subtype was the exclusive manifestation of the disease. CLS should be included in the differential diagnosis of infants with cutaneous erythematous fibrotic lesions to avoid functional and aesthetic sequelae and to allow prompt therapy
Identification of Hydroxywarfarin Binding Site in Human UDP Glucuronosyltransferase 1A10: Phenylalanine 90
Characterization of Human Hepatic and Extrahepatic UDP-Glucuronosyltransferase Enzymes Involved in the Metabolism of Classic Cannabinoids
Tetrahydrocannabinol (Δ9-THC), the primary psychoactive
ingredient in marijuana, is subject to cytochrome P450 oxidation and
subsequent UDP-glucuronosyltransferase (UGT)-dependent glucuronidation. Many
studies have shown that CYP2C9 and CYP3A4 are the primary enzymes responsible
for these cytochrome P450-dependent oxidations, but little work has been done
to characterize phase II metabolic pathways. In this study, we test the
hypothesis that there are specific human UGTs responsible for classic
cannabinoid metabolism. The activities of 12 human recombinant UGTs toward
classic cannabinoids [cannabinol (CBN), cannabidiol (CBD),
(–)-Δ8-THC, (–)-Δ9-THC,
(±)-11-hydroxy-Δ9-THC (THC-OH), and
(–)-11-nor-9-carboxy-Δ9-THC (THC-COOH)] were evaluated
using high-performance liquid chromatography-tandem mass spectrometry and
labeling assays. Despite activity by UGT1A1, 1A3, 1A8, 1A9, 1A10, and 2B7
toward CBN, CBD, THC-OH, and THC-COOH, only selected UGTs demonstrate
sufficient activity for further characterization of steady-state kinetics. CBN
was the most recognized substrate as evidenced by activities from hepatic
UGT1A9 and extrahepatic UGT1A7, UGT1A8, and UGT1A10. These results may reflect
the introduction of an aromatic ring to Δ9-THC, leading to
favorable π stacking with phenylalanines in the UGT active site. Likewise,
oxidation of Δ9-THC to THC-OH results in UGT1A9 and UGT1A10
activity toward the cannabinoid. Further oxidation to THC-COOH surprisingly
leads to a loss in metabolism by UGT1A9 and UGT1A10, while creating a
substrate recognized by UGT1A1 and UGT1A3. The resulting glucuronide of
THC-COOH is the main metabolite found in urine, and thus these hepatic enzymes
play a critical role in the metabolic clearance of cannabinoids. Taken
together, glucuronidation of cannabinoids depends on upstream processing
including enzymes such as CYP2C9 and CYP3A4
Characterization of Human Hepatic and Extrahepatic UDP-Glucuronosyltransferase Enzymes Involved in the Metabolism of Classic Cannabinoids
ABSTRACT: Tetrahydrocannabinol (⌬ 9 -THC), the primary psychoactive ingredient in marijuana, is subject to cytochrome P450 oxidation and subsequent UDP-glucuronosyltransferase (UG
Performance of Birmingham Vasculitis Activity Score and disease extent index in childhood vasculitides.
OBJECTIVES: To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) v3 and the Disease Extent Index (DEI) for the assessment of disease activity in 4 primary childhood (c-) systemic vasculitides. METHODS: Patients fulfilling the EULAR/PRINTO/PRES (Ankara) c-vasculitis classification criteria for Henoch-Schönlein purpura (HSP), childhood (c) polyarteritis nodosa (c-PAN), c-Wegener's granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) with disease duration at the time of diagnosis ≤3 months were extracted from the PRINTO database. The performance of the BVAS and DEI were examined by assessing convergent validity, the pattern of disease involvement, and responsiveness. We also evaluated alternative unweighted scoring methods for both tools. RESULTS: The analysis set included 796 patients with 669 HSP, 80 c-PAN, 25 c-WG and 22 c-TA. The median age at diagnosis was 6.9 years (6.6-12) and median delay in making the diagnosis from the onset of signs/symptoms was 0.01 (0.003-0.027) years. A strong correlation was found between the BVAS and DEI (rs=0.78) while correlation with the physician global assessment was moderate (rs=0.48) with BVAS and poor with DEI (rs=0.25). Both the BVAS and DEI sub-scores and total scores were able to descrive the disease involvement in the 4 childhood vasculitides. Responsiveness was large (>1.5) for both tools. The performance characteristics of the BVAS and DEI with the unweighted methods were comparable. CONCLUSIONS: This study demonstrates that both the BVAS and DEI are valid tools for the assessment of the level of disease activity in a large cohort of childhood acute and chronic vasculitides