Urinary sulfated bile acid analysis for the early detection of biliary atresia in infants

Background: Measurement of urinary sulfated bile acid (USBA) is a non‐invasive method to detect bile congestion. Our aim was to evaluate the feasibility of USBA analysis for the early detection of biliary atresia (BA). Methods: We determined the USBA‐to‐creatinine ratio (USBA/cr) in 1148 infants at 10–40 days after birth. All infants were followed until the 3‐ to 4‐month postnatal routine health check. The cutoff value for USBA/cr was 55.0 µmol/g creatinine. Results: Among the infants tested, 47 (4.10%) had USBA/cr ratios that exceeded the cutoff value. Two of these 47 infants had liver disease; one was diagnosed with neonatal hepatitis syndrome, and the other was diagnosed with BA. The BA patient underwent USBA analysis for the first time on day 18 after birth and hepatoportoenterostomy on day 49. No other infants were diagnosed with hepatobiliary disease during the follow‐up period. Conclusion: This USBA analysis provided the correct assessment without fail and identified a case of BA. This approach could be used for the screening and early detection of BA when the false‐positive rate is decreased by improving the methods for sample collection and urine storage.     

Lectin‐like oxidized low‐density lipoprotein receptor 1 mediates leukocyte infiltration and articular cartilage destruction in rat zymosan‐induced arthritis

Objective

The relationship between rheumatoid arthritis and atherosclerosis has been recognized for >20 years. This study aimed to elucidate the roles of oxidized low‐density lipoprotein (ox‐LDL; one of the main pathogenic factors of atherosclerosis) and its endothelial receptor, lectin‐like ox‐LDL receptor 1 (LOX‐1), in arthritic joints using a rat zymosan‐induced arthritis (ZIA) model.

Methods

LOX‐1 expression and ox‐LDL accumulation in arthritic joints were detected by immunohistochemistry using specific mouse anti–LOX‐1 and anti–ox‐LDL monoclonal antibodies, respectively. To elucidate the effects of the expressed LOX‐1 on arthritis, ZIA rats were treated with anti–LOX‐1 antibody or normal mouse IgG. The severity of arthritis was analyzed by joint swelling. Cell infiltration, synovial hyperplasia, and proteoglycan losses were also determined by histologic scoring. Proinflammatory cytokine and nitrite levels in serum and joint fluid were also measured.

Results

Immunohistochemical study of ZIA demonstrated LOX‐1 expression on synovial endothelium and postcapillary venules at 6 hours after the induction of inflammation, with maximum expression detected at 24 hours. LOX‐1 was also expressed weakly on both joint cartilage and synovium. Ox‐LDL, a ligand of LOX‐1, was also detected in articular chondrocytes. Administration of anti–LOX‐1 antibody, which blocks LOX‐1 activity, suppressed joint swelling (by 33.5%), leukocyte infiltration, and joint nitrite accumulation at 24 hours, as well as cartilage destruction at 7 days, compared with control rats.

Conclusion

LOX‐1 induction in arthritic joints might play a role in promoting joint inflammation and cartilage destruction by mediating leukocyte infiltration into the arthritic joints of ZIA rats.