Biomedical subjects
Publications and source records attributed to J Kopecek.
The first part of the paper is a review of literature data on the uses of synthetic soluble polymers in medicine. The second part is devoted to a discussion of the trend of investigation of medical polymers with a special attention to the development of new types of carriers of biologically active compounds.
The elimination and retention of a new, fully synthetic plasma prosthesis of Czechoslovak origin under the working name of Duxon (poly[N-(2-hydroxypropyl)methacrylamide]) was investigated in experiments on rabbits by using a 14C-labeled polymer. Results published earlier on elimination have been confirmed and extended. Retention was examined after repeated application. The effect of molecular weight prevailed both in elimination and in retention. Polymers of lower molecular weights, which possess a good therapeutical effect, are not permanently deposited in the organism.
The biocompatibility of three types of hydrophilic poly-(glycol methacrylate) gels--homogeneous, microporous and macroporous--was investigated in an experimental subcutaneous implantation. The occurrence of mucopolysaccharide complexes formed by both hyaluronic acid and chondroitine sulphates was examined in the fibrous tissue which surrounds the implant and penetrates into it in the case of a macroporous polymer. In an early stage of investigation hyaluronic acid prevails, but with proceeding collagenization the chondroitine sulphate part becomes predominant.
The increasing number of lymphocytes with nucleoli synthesizing RNA in the mouse lymph nodes, draining the site of injection of infusion solutions, was used as a marker for their immunogenicity. The percentage of "active" lymphocytes significantly increased 3 days after the administration of preparations based on bovine serum or human haemoglobin which were found immunogenic when testing for antibody formation. Such a reaction was not elicited in mice treated with Physiogel, Dextran and Duxon which do not cause any production of antibodies. The described test may serve as a rapid and economical assay for the immunogenicity of infusion solutions and other substances.
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Between 1964 and 1970 the authors implanted Hydron gel in 62 patients with nose malformations. The cosmetic defects most frequently operated on were the saddle, and scoliosis of the nasal dorsum. By the end of 1973, 39 of the total number of cases were checked again. In two cases, the gel had to be removed shortly after the operation because of local inflammatory changes. No signs of hypersensitivity could be detected. Calcifications were detected by x-ray examination in 54.2% of the cases. Thirty-four of the patients subjected to the checkup were satisfied with the results of their operations. The authors considered the results to be very good in 16 cases, and unsatisfactory in 6 cases. Calcifications detected by x-ray examination did not affect the final cosmetic effect. None of the examined patients had any complaints in connection with long-term application of the gel. Hydron gel seems to be a suitable implant material in plastic operations of the nose.
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The I28 immunoglobulin (Ig)-like module of human cardiac titin, an elastic muscle protein, was used to cross-link acrylamide (AAm) copolymers into hybrid hydrogels. Cross-linking was accomplished through metal coordination bonding between terminal histidine tags (His tags) of the I28 module and metal-chelating nitrilotriacetic acid (NTA)-containing side chains on the copolymer. In solution, the beta-sheet structure of the I28 module unfolded with a transition midpoint of about 58 degrees C as the temperature was elevated. Hydrogels cross-linked with the I28 module demonstrated positive temperature responsiveness; they swelled to 3 times their initial volume at temperatures above the melting temperature of the cross-links. Positive temperature responsiveness is unusual for synthetic hydrogels. The I28 hybrid hydrogels demonstrate that cross-linking synthetic polymers with natural, well-characterized protein modules is a practical strategy for creating new materials with unique environmental responsiveness predictably determined by the mechanical properties of the protein cross-links. These new materials may be useful for controlled chemical delivery.
Cyclosporin A (CsA) was epoxidized with m-chloroperoxybenzoic acid in the presence of sodium carbonate or with tert-butyl hydroperoxide in the presence of dioxomolybdenum iminodiethanoxide. The CsA epoxide was not stable and rearranged into a compound with a more stable five-member ring structure. An amino group containing cyclosporin A derivative (CsA amine) was obtained by the reaction of CsA epoxide with excess ethylenediamine. The yield of the CsA amine was 30--40% based on the CsA. An HPMA copolymer--CsA conjugate was prepared by the reaction of the CsA amine with an HPMA and MA-Gly-Phe-Leu-Gly-ONp copolymer. The content of CsA amine in the conjugate was 8.7 wt %. The CsA amine was released from the copolymer by enzymatic hydrolysis with papain.
Native chymotrypsin and its polyethylene glycol (PEG) conjugates, obtained using the succinimidyl carbonate of methoxy-PEG (SC-PEG) as the amino group modifying reagent, were tested for their activity toward several low and high molecular weight substrates. Tripeptide and tetrapeptide p-nitroanilides either as N alpha-benzyloxycarbonyl derivatives or attached via their N-terminals to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers or to PEG, as well as the proteins albumin and azoalbumin, were used as substrates. Extensively modified chymotrypsin bearing on average of 14 PEG chains per chymotrypsin molecule (PEG14CHT) and a moderately modified one containing 10 PEG chains (PEG10CHT) both degraded the low molecular weight p-nitroanilides at rates comparable to, and in the case of PEG10CHT, greater than, the rates exhibited by the native enzyme. Synthetic high molecular weight substrates and azoalbumin were also degraded by the PEG-modified enzymes. However, rates of such enzymatic reactions were lower for the PEG-enzymes than for the native one. Native albumin, as compared to azoalbumin, resisted degradation by both PEGCHTs yet was readily digested by the native chymotrypsin. The results obtained indicate that substrate-size-dependent specificity of PEG-modified enzymes cannot be explained solely by steric hindrance considerations. The decreased activity of PEG-enzymes toward protein substrates is consistent with the well-documented ability of PEG to exclude proteins from its surroundings and with the influence of protein unfolding on the susceptibility to degradation.