A GPIIb/IIIa bioreactor for specific treatment of immune thrombocytopenic purpura, an autoimmune disease. Preparation, in vitro characterization, and preliminary proof-of-concept animal studies

Immune thrombocytopenic purpura (ITP) is an autoimmune disease that affects thousands of Americans each year. The resulting thrombocytopenia, which develops from destruction of platelets (PLT) by anti-PLT autoantibodies (APAb), is often associated with hemorrhagic complications. Existing therapies are not effective and are associated with significant morbidity. Recently, a new treatment modality using plasmapheresis with a Protein-A column has shown some clinical promise. Yet, although this method would remove the pathogenic APAb, it would also deplete protective antibodies, thereby weakening the body's self-defense system. Because about 80% of patients with ITP develop APAb against the GPIIb/IIIa antigens on PLT, a novel approach of attaching a GPIIb/IIIa-linked bioreactor with an extracorporeal circuit is suggested herein to achieve highly effective/specific APAb removal and overcome shortcomings of plasmapheresis in treating ITP. A hollow fiber-based bioreactor device was fabricated, and GPIIb/IIIa antigens were immobilized onto the inner lumens of the hollow fibers by using the epichlorohydrin activation method. An optimized bioreactor containing a loading of 1.63 mg GPIIb/IIIa/g fibers and adsorption capacity of 1.9 mg 7E3/g fibers was developed. Preliminary proof-of-concept investigation using a 7E3-induced thrombocytopenic rat model (which mimicked clinical ITP) was carried out. A complete (100%) return of PLT counts to their initial levels was observed in rats within 6 h after the GPIIb/IIIa bioreactor treatment. In addition, a rapid restoration of WBC counts in the treated rats was also found. These preliminary findings shed light of promise of using the GPIIb/IIIa bioreactor approach in achieving highly improved ITP therapy. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48779/1/30470_ftp.pd

Adsorption and Quantum Chemical Studies on the Inhibition Potentials of Some Thiosemicarbazides for the Corrosion of Mild Steel in Acidic Medium

Three thiosemicarbazides, namely 2-(2-aminophenyl)-N phenylhydrazinecarbothioamide (AP4PT), N,2-diphenylhydrazinecarbothioamide (D4PT) and 2-(2-hydroxyphenyl)-N-phenyl hydrazinecarbothioamide (HP4PT), were investigated as corrosion inhibitors for mild steel in H2SO4 solution using gravimetric and gasometric methods. The results revealed that they all inhibit corrosion and their % inhibition efficiencies (%IE) follow the order: AP4PT > HP4PT > D4PT. The %IE obtained from the gravimetric and gasometric experiments were in good agreement. The thermodynamic parameters obtained support a physical adsorption mechanism and the adsorption followed the Langmuir adsorption isotherm. Some quantum chemical parameters were calculated using different methods and correlated with the experimental %IE. Quantitative structure activity relationship (QSAR) approach was used on a composite index of some quantum chemical parameters to characterize the inhibition performance of the studied molecules. The results showed that the %IE were closely related to some of the quantum chemical parameters, but with varying degrees. The calculated/theoretical %IE of the molecules were found to be close to their experimental %IE. The local reactivity has been studied through the Fukui and condensed softness indices in order to predict both the reactive centers and to know the possible sites of nucleophilic and electrophilic attacks

Effect of chromium salts on invertase immobilization onto carboxymethylcellulose-gelatine carrier system

The carboxymethylcellulose-gelatine carrier system was investigated for invertase immobilization. Chromium (III) acetate, chromium (III) sulphate and potassium chromium (III) sulphate were used as cross-linking agents. Effect of carboxymethylcellulose-gelatine ratio and cross-linker concentration on immobilized enzyme activity were analysed. Reusability of immobilized enzyme was also investigated. Maximum immobilized enzyme activities were obtained with cross-linkers chromium (III) sulphate (0.004 mol dm(-3)) and potassium chromium (III) sulphate (0.001 mol dm(-3)) for a carrier composition of carboxymethylcellulose-gelatine ratio 0.111 (w/w) as 78%. (C) 1996 Elsevier Science Limite

Immobilization of glucose oxidase onto gelatin for biosensor construction

The properties of a glucose biosensor made by immobilization of glucose oxidase onto gelatin in a layer of electrochemically deposited polyaniline have been investigated. Glucose oxidase was immobilized within gelatin cross-links with chromium(III) acetate. The glucose oxidase biosensor was developed by forming a polyaniline-deposited electrode surface as support for the immobilized enzyme gel, in order to increase its durability. The polyaniline/gelatin/glucose oxidase biosensor has been characterized using chemical and electrochemical methods. Temperature, pH, cross-linking agent concentration, enzyme concentration, kinetic properties, reusability and the effect of electro-active compounds were among the parameters studied. The response time of the glucose oxidase biosensor is 90 s, the detection limit is below 1 mmol/dm(3) and the sensor can be used 20 times within a 2-month period without losing its stability

Polyacrylamide-gelatine carrier system used for invertase immobilization

Invertase was immobilized into polyacrylamide-gelatin carrier system by chemical cross-linking with chromium (III) acetate, chromium (III) sulphate, and potassium chromium (III) sulphate. The optimum conditions, namely substrate concentration, temperature, and pH were determined. The effect of polyacrylamide-gelatin ratio and cross-linker concentration oil immobilized enzyme activity were analysed. Maximum immobilized enzyme activities were obtained with chromium (III) acetate (0.01 mol dm(-3)), chromium (III) sulphate (0.004 mol dm(-3)) and potassium chromium (III) sulphate (0.001 mol dm(-3)) for 0.177 (w/w) polyacrylamide-gelatin carrier ratio as 79%, 72% and 79%, respectively. The K-m values were 86 and 166 mM for free and immobilized enzyme, respectively. All immobilized samples were used 20 times over a period of 2 months without a considerable loss of activity