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Biomedical subjects

R S Langer

Publications and source records attributed to R S Langer.

8 recordsLinked to original sources
PubMed1989

Intracerebral drug delivery in rats with lesion-induced memory deficits.

Pharmacological treatments directed at increasing cortical acetylcholine activity in patients with Alzheimer's disease have largely been disappointing, perhaps because denervated areas of brain may not be exposed to adequate amounts of drug. A new method has been developed to enable localized intracerebral delivery of neurotransmitter substances using a polymeric drug delivery system. Microspheres of a polyanhydride sebacic acid copolymer were impregnated with bethanechol, an acetylcholinesterase-resistant cholinomimetic. Twenty rats received bilateral fimbria-fornix lesions, producing cholinergic denervation of the hippocampus and marked impairment in spatial memory. The animals were trained for 2 weeks to run after which they received bilateral intrahippocampal implants of saline (five rats), blank polymer (five rats), or bethanechol-impregnated polymer (10 rats). Following implantation, spatial memory was assessed by radial-maze performance testing for 40 days. Untreated lesioned rats showed persistently poor spatial memory, entering maze arms with near random frequency. Similarly, animals treated with saline and blank polymer did not improve after implantation. Rats treated with bethanechol-impregnated microspheres, however displayed significant improvement within 10 days after implantation; this improvement persisted for the duration of the experiment (p less than 0.05, Student's t-test). Histological analysis of regional acetylcholinesterase staining showed widespread loss of activity throughout the hippocampus bilaterally in all animals. The microsphere implants were visible within the hippocampus, with minimal reactive changes in surrounding brain. It is concluded that intracerebral polymeric drug delivery successfully reversed lesion-induced memory deficits, and has potential as a neurosurgical treatment method for Alzheimer's disease and other neurodegenerative disorders.

Anhydrides↗
PubMed1987

Focal arteriolar insudation. A response of arterioles to chronic nonspecific irritation.

The subcutaneous insertion of sterile, inert plastic pellets over the cremaster muscles of rats induces characteristic focal lesions of the arterioles at a distance from the pellets. These lesions appear with a delay of about 6 hours; by light microscopy they are characterized by a focal dilatation accompanied by endothelial damage and increased permeability. They are more severe if the pellets are loaded with histamine and are inhibited if the pellets are loaded with serotonin. Electron microscopy shows interendothelial gaps; the media is massively infiltrated with blood components and fibrin. The medial smooth muscle cells are stretched and at times necrotic; inflammatory cells are scarce. On the basis of these features the lesion was named focal arteriolar insudation (FAI). Although its pathogenesis is not yet clear, the data at hand suggest that it is caused by endogenous mediators affecting the smooth muscle cells and/or the endothelium. FAI appears to be a specific arteriolar response to chronic nonspecific irritation.

Animals↗
PubMed1986

Sulfur regulation of heparinase and sulfatases in Flavobacterium heparinum.

Sulfur regulation of heparinase synthesis and sulfatase synthesis was studied in Flavobacterium heparinum. Heparinase synthesis was strongly repressed by sulfate and L-cysteine, while the activity of this enzyme showed little or no inhibition by these compounds. Heparinase was synthesized in the absence of heparin when L-methionine was used as the sole sulfur source. The sulfatases produced by F. heparinum, which include the sulfatases involved in heparin catabolism, were also studied. At least some of the sulfatase activity was regulated by sulfur compounds in a manner similar to heparinase regulation. L-Cysteic acid and taurine were not suitable sulfur sources to support the growth of F. heparinum.

Ammonium Sulfate↗
PubMed1979

A single-step immunization by sustained antigen release.

An inert polymer pellet less than 1 mm in diameter, implanted subcutaneously in mice, releases free antigen continuously and enhances antibody formation for over 6 months. The immune response stimulated by sustained antigen delivery is comparable to the secondary response induced by the same total dose of antigen emulsified in complete Freund's adjuvant. The sustained release polymer implants, using antigens over a wide molecular weight range, proved effective in eliciting prolonged antibody formation. The antigens tested included bovine serum albumin, gamma-globulin, and ribonuclease. Superior biocompatibility and release characteristics make the ethylene-vinyl acetate copolymer a promising method for the single-step induction of immunity.

Adjuvants, Immunologic↗
PubMed1979

Oxygen content determined by acrylamide polymerization: screening of anticancer agents, generation of oxyhemoglobin dissociation curves, and potential applications.

Many investigators have endeavored to accurately measure oxygen content produced or consumed from substrates or tissues. Most of the techniques currently available are time consuming or exceedingly complex. Many require expensive apparatus and demand the skills of a highly trained technician. We have deveoloped a rapid and sensitive method of measuring oxygen content or consumption. This method is based upon the time for polymerization of acrylamide gels. The time of acrylamide polymerization is directly proportional to the oxygen content of the test medium. We have used this method to generate oxyhemoglobin dissociation curves which closely resemble those published by Severinghaus and Duvelleroy, as well as those we determined by the conventional Van Slyke analysis. We have also used this method to measure the oxygen consumption of tumor cells and to evaluate the effects of Actinomycin, cyclohexamide and cytosine arabinoside on Walker 256 ascites tumor. The results correlate with the known in vivo effects of these drugs on this tumor cell line. Therefore, because of its sensitivity and adaptability this method may be useful in a variety of clinical and biological situations.

Acrylamides↗
PubMed1976

Mast cells and tumor angiogenesis.

Tumor angiogenesis factor (TAF) elicits a strong vasoproliferative response when implanted upon the chorioallantoic membrane (CAM) of the chick embryo. This response is first observed stereomicroscopically 2-3 days after implantation. A 40-fold increase in mast cell density is observed within the vicinity of this implant by 24 h. Mast cells that have been isolated from retired breeder Sprague-Dawley rats fail to evoke a vascular reaction when implanted on the CAM. An intermediate role for the mast cell in tumor angiogenesis is suggested.

Angiogenesis Inducing Agents↗