Medical Literature - 1995

Improved detection of proteolytically cleaved high molecular weight kininogen by immunoblotting using an antiserum against its reduced 47 kDa light chain

Buhler R, Hovinga JK, Aebi-Huber I, Furlan M, Lammle B 5/1995 Blood Coagulation & Fibrinolysis

Several ligand blotting or immunoblotting assays for the detection of single-chain and proteolytically cleaved two-chain high molecular weight kininogen (HK) in whole plasma have been described. Since they may suffer from poor sensitivity for the light chain species of cleaved HK on reduced blots, an antiserum against the reduced and alkylated 47 kDa light chain of HK was raised in rabbits allowing improved immunodetection of HK species on blots of reduced electropherograms. This immunoblotting method is highly specific and sensitive, permitting detection of 0.2 ng single-chain HK or the light chains of 2 ng proteolytically cleaved HK in whole plasma. Thus, this immunoblotting technique is at least 50-100 times more sensitive than ligand blotting with radiolabelled factor XI overlay. A similar cleavage pattern was observed following in vitro activation of normal human plasma by dextran sulphate and after plasma kallikrein-induced proteolysis of purified HK. However, bands of different molecular weights were generated after HK had been cleaved by purified leukocyte elastase. During acute attack in a patient with hereditary angioedema, high levels of in vivo cleaved HK were noticed, whereas concentration of cleaved HK in plasma samples and synovial fluids from patients suffering from various inflammatory conditions were not substantially higher than those in normal plasma. During in vitro cold activation of plasma samples of pregnant women concomitant HK cleavage and plasma kallikrein generation were observed.

May;6(3):223-232

Available online at: journals.lww.com/bloodcoagulation/Abstract/1995/05000/Improved_detection_of_proteolytically_cleaved_high.5.aspx (small fee)

Reduction in transmission of hepatitis C after the introduction of a heat-treatment step in the production of C1-inhibitor concentrate

Cicardi M, Mannucci PM, Castelli R, Rumi MG, Agostoni A 3/1995 Transfusion

BACKGROUND: The transmission of viral infections via protein concentrates made from a large pool of plasma depends on the selection of donors, fractionation process, and virucidal methods. To date, no data are available on the infectivity risk of plasma concentrates of the inhibitor of the first component of complement (C1-INH).

STUDY DESIGN AND METHODS: The prevalence of blood-borne viral infections and levels of transaminases were evaluated in patients treated with a large-pool plasma concentrate of the inhibitor of C1-INH before and after the introduction of virucidal methods. The study included 85 patients with hereditary angioedema and 4 with acquired angioedema. The patients were divided into three groups: 1) 48 untreated patients; 2) 22 patients treated with non-virus-inactivated C1-INH concentrates; and 3) 19 patients treated with virus-inactivated concentrates. Serum samples obtained at various times after the infusion of concentrate were assayed for alanine amino-transferase and tested for hepatitis B surface antigen and antibodies to hepatitis C virus (anti-HCV) and human immunodeficiency virus (anti-HIV); anti-HCV-negative subjects exposed to the concentrate were also tested for HCV RNA.

RESULTS: Prevalences of HCV infection and elevated alanine aminotransferase are significantly lower in patients treated with virus-inactivated concentrates than in those exposed to non-virus-inactivated concentrates. No patients were anti-HIV positive.

CONCLUSION: This study suggests that C1-INH concentrates transmitted HCV, but that the virucidal methods adopted are effective in reducing the infectivity.

Mar;35(3):209-212

Available online at: onlinelibrary.wiley.com/doi/10.1046/j.1537-2995.1995.35395184276.x/pdf (small fee)

Stanozolol as a novel therapeutic agent in dermatology

Helfman T, Falanga V 8/1995 The Journal of the American Academy of Dermatology (JAAD)

Anabolic steroids are synthetic derivatives of testosterone that were developed in the 1950s in an attempt to dissociate the anabolic and androgenic effects of testosterone. The anabolic steroid stanozolol has been particularly helpful because it has one of the largest anabolic/androgenic ratios. In addition, stanozolol has substantial fibrinolytic properties. We discuss the safety profile and the use of stanozolol for a variety of clinical applications. Stanozolol is approved for use in the treatment of hereditary angioedema, but numerous reports have detailed the effectiveness of this agent in the treatment of urticaria, Raynaud’s phenomenon, and, more recently, cryofibrinogenemia and lipodermatosclerosis. Side effects are mostly dose related and are preventable with appropriate follow-up. [References: 32].

Aug;33(2 Pt 1):254-258

Available online at: sciencedirect.com/science/article/pii/0190962295902449 (small fee)

The value of C1 esterase inhibitor in patients with aspirin-sensitive urticaria

Grzelewska-Rzymowska I, Szmidt M, Rozniecki J 9/1995 Journal of Investigational Allergology & Clinical Immunology

The aim of the study was to evaluate the concentration and activity of C1 esterase inhibitor (C1 INH) in patients with aspirin-sensitive urticaria. C1 INH deficiency is the basis of hereditary angioneurotic edema. The study was performed on 32 subjects with aspirin-sensitive urticaria. The value of C1 INH in examined patients was the same as in the control group. There seems to be no coexistence of aspirin-sensitive urticaria and C1 esterase inhibitor deficiency.

Sep-Oct;5(5):272-275

Not available online.

Funding for Canadian Hereditary Angioedema Network has been generously provided by unrestricted grants from:

BioCryst

CSL Behring

Takeda

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