High-mobility group box 1 (HMGB1) protein has been demonstrated to play an important role in chronic inflammatory diseases including rheumatoid arthritis, and systemic lupus erythematosus. This study investigated the association between extracellular HMGB1 expression and disease activity, and clinical features of Behcet's disease (BD). Extracellular HMGB1 expression in the sera of 42 BD patients was measured and was compared to that of 22 age- and sex-matched healthy controls. HMGB1 expression was significantly increased in BD patients compared to healthy controls (78.70 +/- 20.22 vs 10.79 +/- 1.90 ng/mL, P = 0.002). In addition, HMGB1 expression was significantly elevated in BD patients with intestinal involvement compared to those without (179.61 +/- 67.95 vs 61.89 +/- 19.81 ng/mL, P = 0.04). No significant association was observed between HMGB1 concentration and other clinical manifestations, or disease activity. It is suggested that extracellular HMGB1 may play an important role in the pathogenesis of BD.
Adult ; Aged ; Behcet Syndrome/genetics/*metabolism/pathology ; Extracellular Space/metabolism ; Female ; HMGB1 Protein/genetics/*metabolism ; Humans ; Inflammation ; Intestinal Diseases/blood/genetics ; Male ; Middle Aged ; Young Adult

OBJECTIVETo study the clinical features and ABCG5/ABCG8 gene mutations of three pedigrees of phytosterolemia presented with macrothrombocytopenia and hemolysis.

METHODSErythrocyte and platelet morphology were examined under light microscope. Plasma sterol levels were measured by high pressure/performance liquid chromatography method. All of ABCG5 and ABCG8 exons and intron-exon boundaries were directly sequenced to identify mutations, the corresponding gene mutation sites of three families members and healthy individuals were detected.

RESULTSAll the patients presented macrothrombocytopenia, hemolysis, splenomegaly and xanthomas. The blood smears showed large platelets, some as large as erythrocytes, and abnormal erythrocyte shapes, such as stomatocytes. Plasma concentrations of phytosterols, especially sitosterol were markedly elevated (30 fold) in the affected patients. Four mutations were identified in these three pedigrees, ABCG5 C20896T (R446X) and A20883G, ABCG8 del43683-43724 and del1938C-1939G/ins1938T. The latter three were novel mutations reported for the first time.

CONCLUSIONSPhytosterolemia associated with macrothrombocytopenia and hemolysis is a new subtype of this disease. Plasma phytosterols and related gene analysis should be performed when ever an unexplained macrothrombocytopenia, especially combined with haemolysis or/and stomatocytosis.

ATP Binding Cassette Transporter, Sub-Family G, Member 5 ; ATP Binding Cassette Transporter, Sub-Family G, Member 8 ; ATP-Binding Cassette Transporters ; genetics ; Adult ; Blood Platelets ; cytology ; DNA Mutational Analysis ; Erythrocytes, Abnormal ; Female ; Hemolysis ; genetics ; Humans ; Hypercholesterolemia ; genetics ; pathology ; Intestinal Diseases ; genetics ; pathology ; Lipid Metabolism, Inborn Errors ; genetics ; pathology ; Lipoproteins ; genetics ; Male ; Middle Aged ; Mutation ; Pedigree ; Phytosterols ; adverse effects ; blood ; genetics ; Platelet Count ; Thrombocytopenia ; genetics ; pathology

OBJECTIVETo discuss the effect of matrine on nitric oxide (NO) and asymmetric methylarginine (ADMA) metabolism pathways in serum and tissues of mice with lipopolysaccharide (LPS) -induced intestine tissue inflammation.

METHODKunming mice were randomly divided into five groups: the normal control group, the LPS group and matrine (80, 40, 20 mg x kg(-1) x d(-1)) groups. The mice were intragastrically administered with drugs for 3 d (distilled water of the same volume for the normal control group and the LPS group). One hour after the last intragastrical administration, normal saline or LPS (1 mg x kg(-1)) were intraperitoneally injected. Twelve hours later, serum and tissues were collected to determine NO and ADMA levels and observe the pathological changes of intestinal tissues. The Western blot method was adopted to detect the protein expressions of arginine methyltransferases 1 (PRMT1) and dimethylarginine dimethylaminohydrolase 2 (DDAH2) in intestinal tissues.

RESULTCompared with the model group, matrine (80, 40, 20 mg x kg(-1) x d(-1)) groups showed lower NO content in serum and tissues, higher ADMA level in serum and increased PRMT1 expression in intestinal tissues, but without effect on DDAH2 expression.

CONCLUSIONMatrine could inhibit LPS-induced intestine tissue inflammation in mice. Its action mechanism is related to the decreased NO content in serum and tissues and increased ADMA level in serum and PRMT1 expression in intestinal tissues.

Alkaloids ; administration & dosage ; Animals ; Arginine ; analogs & derivatives ; blood ; metabolism ; Humans ; Inflammation ; Intestinal Diseases ; drug therapy ; enzymology ; immunology ; metabolism ; Intestines ; drug effects ; enzymology ; immunology ; metabolism ; Lipopolysaccharides ; adverse effects ; Male ; Mice ; Nitric Oxide ; blood ; metabolism ; Protein-Arginine N-Methyltransferases ; genetics ; metabolism ; Quinolizines ; administration & dosage