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Biomedical subjects

R Langer

Publications and source records attributed to R Langer.

At least 487 records · Page 27Linked to original sources
PubMed1987

New approaches for anticoagulation in extracorporeal therapy.

The need to fully heparinize patients undergoing extracorporeal therapy often leads to hemorrhagic complications. Two approaches have been used to solve this problem. The first involves full heparinization of blood entering the extracorporeal device followed by the elimination of heparin from the blood returned to the patient using an immobilized heparinase reactor system. Animal studies have demonstrated the successful elimination of heparin's anticoagulant activity using this reactor. The second approach uses very low molecular weight (VLMW) heparins with improved properties. Although low molecular weight heparins and heparinoids have been successfully used in hemodialysis, these preparations are polydisperse mixtures. New VLMW heparins are described which are pure, monodisperse, structurally defined drugs and show improved pharmacokinetics and greater specificity than heparin. The separation of ATIII and HCII mediated activity against factors IIa and Xa may permit extracorporeal therapy with only partial anticoagulation resulting in increased antithrombotic activity with decreased hemorrhagic side-effects. Finally, these VLMW heparins suggest certain desirable structural characteristics in the design blood compatible non-thrombotic synthetic polymers for use in extracorporeal devices.

Enzymes, Immobilized↗
PubMed1987

Determination of conjugated and total bilirubin in serum of neonates, with use of bilirubin oxidase.

A new, simple, and rapid assay for conjugated bilirubin that does not require serum-matrix standards was developed by using the enzyme bilirubin oxidase (EC 1.3.3.5). This procedure can also be modified to measure total bilirubin. Measurements from these assays were compared with results obtained with the Sigma 605 (Jendrassik-Gróf method), Sigma 550/551 (Walters-Gerarde method), and Kodak Ektachem (BuBc) bilirubin assays. The one-year study involved serum specimens from 283 infants younger than 30 days. Linear-regression analysis of data for conjugated bilirubin collected by this assay and by the Kodak Ektachem assay yielded a slope of 0.975, an intercept of 0.088, an Syx of 1.47 mg/L, and a correlation coefficient of 0.94 for a total of 49 specimens. Correlation was also good (r = 0.95) between results for total bilirubin by this assay and both the Sigma 605 and the Kodak Ektachem methods.

Bilirubin↗
PubMed1986

Single-step immunization using a controlled release, biodegradable polymer with sustained adjuvant activity.

The use of a biodegradable polymer for antigen delivery based on poly(CTTH-iminocarbonate) (IUPAC nomenclature: poly[oxyimidocarbonyloxy-p-phenylene [2-(hexyloxycarbonyl)ethylene]imino[2-[1-(benzyloxy)formamido]- 1-oxotrimethylene]-p-phenylene]) was investigated. This polymer was selected since its primary degradation product, N-benzyloxycarbonyl-L-tyrosyl-L-tyrosine hexyl ester (CTTH) was found to be as potent an adjuvant as complete Freund's adjuvant and muramyl dipeptide, when measuring the serum antibody response to bovine serum albumin (BSA) in male CD-1 mice over 56 weeks. BSA released from subcutaneously implanted polymeric antigen delivery devices made of poly(CTTH-iminocarbonate) resulted in significantly higher (P less than 0.006) anti-BSA antibody titers than devices made of poly(bisphenol A-iminocarbonate).

Adjuvants, Immunologic↗
PubMed1986

Removal of the anticoagulant activities of the low molecular weight heparin fractions and fragments with flavobacterial heparinase.

Recently, the development of low molecular weight heparin fractions and fragments (LMHF) as potential antithrombotic agents has gained increased attention. However, the lack of antagonists to neutralize the anticoagulant effects of these drugs may seriously exclude them from possible uses in extracorporeal therapy. This is mainly because of the concern that the high dosage of the drugs employed in extracorporeal therapy could lead to serious bleeding risks. Our earlier work has demonstrated that immobilized heparinase can remove polydisperse heparin both in vitro and in vivo. To examine whether such a system may be used as a novel approach to neutralize the anticoagulant effects of LMHF, different LMHF were tested using heparinase. In vitro data showed that both the APTT and anti-FXa activities of the LMHF including Kabi 2165, PK 10169, Cy 216 and CY 222 were nearly completely eliminated by heparinase in less than 20 min. This study suggests that an immobilized heparinase system may be an useful element for the acceptance of the LMHF for their use in extracorporeal therapy.

Anticoagulants↗
PubMed1986

Purification and partial amino acid sequence of a bovine cartilage-derived collagenase inhibitor.

An inhibitor of mammalian collagenase from bovine scapular cartilage has been purified to homogeneity. The inhibitor, extracted from cartilage using 2 M NaCl, was applied to an A-1.5m gel filtration column. Inhibitor eluted at an apparent Mr of 28,000. Further purification was achieved by ion exchange chromatography, gel filtration, and reverse-phase high performance liquid chromatography. A purification of greater than 1,000-fold was achieved. The inhibitor was judged homogeneous by the appearance of a single band on a silver-stained 15% sodium dodecyl sulfate-polyacrylamide gel. Reduced inhibitor had an Mr of 27,400, unreduced inhibitor had an Mr of 23,900. NH2-terminal sequence data were obtained for the first 45 residues. The bovine cartilage-derived inhibitor exhibits greater than 65% homology over the first 23 residues with a collagenase inhibitor purified from human skin fibroblasts maintained in cell culture. This is the first demonstration that collagenase inhibitors extracted directly from tissue may be similar to those obtained from culture medium.

Amino Acid Sequence↗
PubMed1986

Bioerodible polyanhydrides as drug-carrier matrices. II. Biocompatibility and chemical reactivity.

The biocompatibility of bioerodible polyanhydrides and toxicology of the polymer breakdown products were assessed. Poly-[bis (p-carboxy-phenoxy) propane anhydride] (PCPP), Poly(terephthalic acid anhydride) (PTA), and their copolymers with sebacic acid were tested. The polymers did not provoke inflammatory responses in the corneas of rabbits over a six week implantation period. Subcutaneous implantation studies of PCPP in rats over a six month period showed no evidence of inflammatory cells and only slight tissue encapsulation by layers of fibroblastic cells. The degradation products of the polymers were nonmutagenic, noncytotoxic, and had a low teratogenic potential. The in vitro growth of mammalian cells on the polymers was unaffected as measured by cell morphology and cell growth rate. The chemical reactivity of the polyanhydrides with reactive model drugs, para substituted anilines, was also examined. Amides were formed when the drugs were injection molded with the polyanhydrides at 120 degrees C. However, no reaction was observed using compression molding at room temperature. No reaction occurred between the polymer and the drug during the hydrolytic degradation of the matrix at 37 degrees C.

Anhydrides↗
PubMed1986

Primary (isolated) bilateral pulmonary hypoplasia: a comparative study of radiologic findings and autopsy results.

Comparative radiologic/pathologic study of 45 newborns with primary and secondary pulmonary hypoplasia is presented and 43 cases were proven at autopsy. From 9 cases with primary pulmonary hypoplasia, 7 could be identified by 3 independent observers on chest radiographs. The roentgen criteria of primary pulmonary hypoplasia are evaluated and should serve in future to diagnose this condition clinically.

Humans↗
PubMed1986

Polyanhydrides for controlled release of bioactive agents.

This report is a review of the development of a drug delivery system based on biorodible polyanhydrides. With the water labile anhydride linkage, a wide range of matrix degradation and drug release rates can be obtained from these drug-carriers. In addition to monolithic formulations, the feasibility of an injectable system by microencapsulation is demonstrated. The possibility of enhancing the release externally by an ultrasonic source has also been explored. The polymers tested showed good tissue biocompatibility and their breakdown products showed no adverse toxicological effects. Preliminary in vivo results confirmed the efficacy of these devices.

Anhydrides↗
PubMed1986

Poly(iminocarbonates) as potential biomaterials.

Poly(iminocarbonates), based on diphenols such as hydroquinone or Bisphenol A were synthesized. Poly(iminocarbonates) degraded under physiological conditions. Compression moulded discs of poly-(hydroquinone-iminocarbonate) showed near zero-order release for low loadings (1%, w/w) of Eosin Y. Poly(Bisphenol A-iminocarbonate) formed transparent films and strong fibres. It is a tough polymer with high tensile strength. Under physiological conditions complete erosion of a thin film of poly(Bisphenol A-iminocarbonate) required about 200 d. The release profile for p-nitroaniline from solvent cast films of poly(Bisphenol A-iminocarbonate) was characterized by a lag period (20 d), followed by near zero-order release for 90 d. Initial toxicological studies revealed no inflammatory cell response after implantation in the corneas of rabbits or subcutaneously in mice.

Animals↗
PubMed1986

Comparative studies of heparin and heparin fragments: distribution and toxicity in the rat.

To control blood levels of heparin during extracorporeal therapy, the use of a blood filter containing heparinase, a heparin-specific enzyme that cleaves heparin to small fragments with less anticoagulant activity, has been proposed. These fragments have anti-factor Xa activity but no anti-thrombin activity. The potential toxicity of heparin fragments as compared to heparin was examined in rats by identifying presumptive sites of drug-related toxicity by whole-body autoradiography and by histological examination of major organs. Radioautograms of rats sacrificed 5 hr after dosing with [35S]heparin fragments indicated no potential targets different from what was observed in rats dosed with [35S]heparin. In addition, the faster urinary clearance of heparin fragments resulted in a lower concentration of these fragments than of heparin in all common target organs. No hemorrhages or other lesions were found in rats injected intravenously with heparin fragments (100 mg/kg) and sacrificed after 5 hr. In addition, no mortality or delayed toxic effects were observed in a similar group of animals sacrificed 2 weeks after dosing. In contrast, 80% of rats injected with heparin (100 mg/kg) showed hemorrhages of the lungs at the time of necropsy.

Animals↗