Co-existing proteinase 3-antineutrophil cytoplasmic antibody-associated vasculitis with immunoglobulin A nephropathy

No abstract available.

Vascular Aneurysms: A Perspective.

Aneurysms develop as a result of chronic inflammation of vascular bed, where progressive destruction of structural proteins, especially elastin and collagen of smooth muscle cells has been shown to manifest. The underlying mechanisms are an increase in local production of proinflammatory cytokines and subsequent increase in proteases, especially matrix metalloproteinases (MMPs) that degrade the structural proteins. The plasminogen system: urokinase-type PA (u-PA), tissue-type PA (t-PA) and plasminogen activator inhibitor-1 (PAI-1) and the MMPs system-MMPs and TIMPs contribute to the progression and development of aneurysms. Recent studies suggest that aneurysms may be genetically determined. To date, most observable candidate genes for aneurysm (elastin, collagen, fibrillin, MMPs and TIMPs) have been explored with little substantiation of the underlying cause and effect. Recently, overexpression of the MMP-2 gene has been suggested as an important phenomenon for aneurysm formation. Along with MMPs, matrix formation also depends on JNK (c-Jun N-terminal kinase) as its activation plays important role in downregulating several genes of matrix production. Under stress, activation of JNK by various stimuli, such as angiotensin II, tumor necrosis factor-α and interleukin-1β has been noted significantly in vascular smooth muscle cells. Several therapeutic indications corroborate that inhibition of MMP-2 and JNK is useful in preventing progression of vascular aneurysms. This review deals with the role of proteases in the progression of vascular aneurysm.

Clinical application of anti-proteinase 3 capture ELISA in diagnosis of Wegener's granulomatosis / 临床检验杂志

Objective To investige the sensitivity and specificity of anti-proteinase 3 (PR3) capture ELISA in diagnosis of Wegener's granulomatosis (WG),and the correlation between the capture ELISA and indirect immunofluorescence assay (IIF).Methods Anti-PR3 antibody and anti-neutrophil cytoplasmic antibody (cANCA) in sera from 72 patients with WG,206 healthy blood donors and 24 patients with autoimmune diseases were detected by classic ELISA,capture ELISA and IIF.Results The sensitivities of classic ELISA and capture ELISA for detection of anti-PR3 in WG diagnosis were 73.6% and 87.5% respectively.The specificities of both the ELISAs were identical (100%).Detection of anti-PR3 by ELISA or IIF alone led to the serological hit rate of 87.5% and 84.7% for WG respectively,but the combination of capture ELISA and IIF increase the hit rate up to 91.6%.Conclusions The sensitivity of anti-PR3 capture ELISA as well as its correlation with IIF is prior to classic anti-PR3 ELISA.The combined detection of anti-PR3 capture ELISA and IIF may increase the diagnosis rate of clinically suspected WG.

Clinical application of antiproteinase 3 antibodies in Wegener's granulomatosis and other vasculitis patients / 中华风湿病学杂志

Objective To investgate prevalence and clinical significance of antiproteinase 3(PR3)an- tibodies in Wegener's granulomatosis(WG)and other vasculitis patients.Methods One hundred and eleven systemic vasculitis patients with WG(9 cases,including 21 serums of tracking WG patients)and other systemic vasculitis(102 cases),403 secondnary vasculitis CTD(SLE 213 cases,RA 135 cases),nephritis 62 cases,30 healthy subjects were examined for anti-PR3 and anti-MPO antibody by enzyme-linked immunosorbent assay (ELISA)and ANCA by indirect immunofluorescence(IIF)was performed.Result Anti-PR3 positive were 23 in 588 serums of patients.The prevalence of anti-PR3 positive was WG(16/21,71.4 %),other systemic vas- culitis were not found anti-PR3,SLE(6/213,2.8%),RA(1/135,0.7%).In particular,the prevalence of anti- PR3 and cANCA with WG tended to be higher in the patients with other systemic and secondnary vasculitis (P＜0.05).The sensitivity and specificity of anti-PR3 for diagnosis of WG were 71.42% and 98.58%.The sensi- tivity and specificity of combination anti-PR3 and cANCA were 61.90% and 99.82%.Anti-PR3 and cANCA are associated with treament of WG.Conclusion Anti-PR3 antibody has high specificity for diagnosis of RA. Detection of anti-PR3 and cANCA at the same time can improve the specificity considerably.As sensitive markers of WG,anti-PR3 antibody may be useful for diagonosis and early treament.Anti-PR3 also may be useful for activity and relapse of WG.

Effect of Camostat Mesylate on Chemical Compositions of Bile and Crystallization in Gallbladder Stone Patients

BACKGROUND: It has been well demonstrated that trypsin inhibitor can stimulate the secretion of cholecystokinin. Camostat mesylate (C20H22N4O5 CH3SO3H) is a synthetic trypsin inhibitor. We demonstrated the effect of camostat mesylate on the chemical composition of bile and the crystallization in gallbladder-stone patients. METHODS: Gallbladder bile sample from 22 patients with GB stones were analyzed. In 11 patients, camostat mesylate (Foy-pan ) was administered orally in a dosage of 600 mg per day for more than 5 days, and the results of the bile analysis were compared to those of 11 controls. RESULTS: The total protein concentration in the camostat group was lower than that in control group (0.21+/-0.10 vs 0.24+/-0.06 g/dl) but the difference was not significant (p=0.41). The total bile acid concentration in the camostat group was significantly lower than that in the control group (5.47+/-1.56 vs 6.85+/-1.32 g/dl, p=0.04). The concentrations of cholesterol and phospholipid were lower in the camostat group (0.35 +/- 0.19 vs 0.44 +/- 0.11 g/dl, 2.10 +/- 1.19 vs 2.92 +/- 0.93, respectively), but the differences were not statistically significant (p=0.20, p=0.09, respectively). The total lipid concentration which reflects the concentrated magnitude of the bile, was significantly lower in the camostat group (7.93 +/- 2.87 vs 10.20 +/- 2.01 g/dl, p=0.04). The cholesterol saturation index didn't demonstrate a significant difference between the two groups (1.06 +/- 0.27 vs 0.95 +/- 0.31, p=0.38). Crystallization in the bile from cholesterol stone patients, was observed every day for 7 days. Crystallizations was less frequent in the camostat group, but the difference was not statistically significant (1/6 vs 4/8, p=0.39). DISIDA (disofenin iminediacetate) scans were performed in 3 healthy volunteers to observe the changes in the radioactivities and the volumes of the gallbladders before and after the administrations of camostat. The peak radioactivities, the transittime to the peak radioactivity, and the gallbladder volume at the peak radioactivity in the scan after the administration of camostat were lower than in the corresponding values before the administration. CONCLUSIONS: Camostat mesylate lowers the concentration of all bile components. We assume that the effects of Camostat mesylate are mediated by CCK, which enhances gallbladder motility and limits the concentrating function of the gallbladder.