Search PubMed⌕ Search

Biomedical subjects

D H Brown

Publications and source records attributed to D H Brown.

At least 109 records · Page 6Linked to original sources
PubMed1980

Total serum copper and ceruloplasmin levels following administration of copper aspirinate to rats and guinea-pigs.

Total serum copper and ceruloplasmin oxidase activities have been measured over a 24-h period in rats and guinea-pigs treated with 100 mg/kg body weight of copper (II) aspirinate. In the rat, administration s.c. produced higher total serum copper levels than oral administration at all time intervals studied, whereas in the guinea-pig, oral administration produced the higher level after 1 h and s.c. administration the higher level after 5 h. In both species, the rate of elimination of the additional copper was faster following oral administration. Ceruloplasmin oxidase activity appeared to be inhibited in certain cases but rose in all cases except for orally treated rats after 24 h. The initial rise in serum copper was due mainly to copper present on albumin. The increased albumin copper was detected directly by electrophoresis of serum samples and subsequent determination of the copper level in the portions of the strip which contained proteins. After s.c. administration to the rat, the amount of ultrafilterable copper was raised by a detectable amount. 7 h after s.c. or oral administration of copper aspirinate, the thiol concentration of the serum was reduced in both rats and guinea-pigs. The relationship of these levels to the anti-inflammatory action of copper (II) aspirinate in rats and guinea-pigs is discussed.

Animals↗
PubMed1980

Action of gold salts in some inflammatory and immunological models.

Several gold salts were compared in kaolin-induced rat paw oedema, u.v. erythema in guinea pigs, delayed type hypersensitivity and humoral immunity in mice, and adjuvant-induced arthritis in the rat. In the latter the additional parameters of serum gold and copper levels and lysosomal enzyme activity were determined. In addition, the in vitro inhibition of several lysosomal enzymes derived from mouse macrophages was studied. The gold compounds examined were aurothiomalate, aurothioglucose, triethylphosphine gold chloride (SK & F 36914) and its glucopyranoside derivative (SK & F D-39162), triphenylphosphine gold chloride and sodium gold chloride dihydrate. SK & F 36914 and SK & F D-39162 has significant activity after oral dosage upon paw kaolin and u.v. erythema in rats and guinea pigs, respectively. Gastric swelling also occurred. In Wistar rats, adjuvant arthritis was little affected by the gold salts but in the Lewis rats there was suppression. In both strains there was less elevation in serum copper levels with treatment by SK & F 36914 and SK & F D-39162, but not by aurothiomalate. None of the compounds had any measurable effect on delayed hypersensitivity or humoral antibody levels in mice. The in vitro activities of cathepsin B1 and cathepsin D were inhibited by all the gold compounds. Reactivity of gold compounds with glutathione and cysteine in vitro was dependent on compound solubility and the nature of the gold ligand. Considerable differences exist between the profiles of activity for the different gold salts evaluated. These observations indicate that some gold salts do possess anti-inflammatory activity with a potency similar to that of indomethacin.

Animals↗
PubMed1980

Antiinflammatory effects of some copper complexes.

Copper complexes of a range of ligands have been prepared and evaluated for antiinflammatory activity and irritancy after oral, subcutaneous, and local administration in rats and guinea pigs. The antiinflammatory activities were found to depend on the species used and the route of administration. When nonantiinflammatory ligands were used, the response was generally dose dependent. With D-penicillamine and when the ligands were themselves antiinflammatory in animal models of inflammation--as was the case with flufenamic acid, levamisole, aspirin, L-histidine, and 2-amino-2-thiazoline--differences in antiinflammatory activity were observed between the copper complexes and the free ligands. In some cases, the copper complexes were the more effective. There was a weak correlation between local (subplantar) irritation and the dose of copper but, for four compounds studied in more detail, the response in the local subplantar test and degree of antiinflammatory activity were not related, suggesting that the action of copper is not solely by a counterirritant mechanism. No obvious differences between the activities of copper(I) and copper(II) compounds were observed, suggesting that a common metabolite may be involved in the antiinflammatory action of copper.

Administration, Oral↗
PubMed1980

Plasma zinc and its relationship to clinical symptoms and drug treatment in rheumatoid arthritis.

Total plasma zinc levels in patients with rheumatoid arthritis on different therapeutic treatments were determined in conjunction with total serum proteins, serum albumin and globulin, and articular index of joint tenderness, erythrocyte sedimentation rate, rheumatoid factor, serum copper, and serum iron. There were significantly lower zinc levels in patients with rheumatoid arthritis on nonsteroidal anti-inflammatory drugs than in patients on levamisole and penicillamine. Zinc levels correlated positively with serum albumin, and there was an inverse correlation between zinc levels and both ESR and globulin concentration in all rheumatoid patients. However, the correlation coefficient varied in the different treatment groups. The results of this study support the hypothesis that low plasma zinc level in rheumatoid arthritis is one of the nonspecific features of inflammation.

Anti-Inflammatory Agents↗
PubMed1980

Ultrastructure and physical characteristics of proplastids and chloroplasts isolated by zonal centrifugation from Euglena gracilis var. bacillaris.

Proplastids at various stages of development and mature chloroplasts were isolated by zonal centrifugation in a double-sigmoid, sucrose-sorbitol gradient from Euglena gracilis var. bacillaris grown in darkness and subjected to various periods of illumination with white light. Computer programs were used in characterizing physical properties of the isolated organelles and in predicting the location of plastids of different developmental stages in the gradient. The technique permits computation of these parameters in any gradient material. The convoluted nature of the early developing plastids, revealed by electron microscopy, suggests that the frictional coefficients should be taken into account in describing the physical constants of the organelles, since their sedimentation coefficients are lower than would be expected for spherical particles of the same size and density.

Animals↗
PubMed1979

An evaluation of the use of electrophoresis and carbon furnace atomic absorption spectrometry to determine the copper level in separated serum protein fractions.

The results of an evaluation of the use of atomic absorption spectrometry with carbon furnace atomisation to analyse the copper content of individual protein fractions separated by electrophoresis is reported. Albumin copper levels in patients with rheumatoid arthritis were found to be about 1 to 2% of the total serum copper. Both albumin and alpha 2 levels are affected by contamination from residual copper present on the strip. An investigation of this contamination indicated very low blank copper levels in the areas of the strip containing alpha 1 and beta proteins. These results, and the results of analysis of copper in the ultrafiltrate from the same serum samples, are combined to define the copper distribution in a group of patients with rheumatoid arthritis. The determinations that can most readily be carried out by this technique are discussed.

Blood Proteins↗
PubMed1979

Copper distribution and reactivity in serum following administration of cuprous oxide to rats and guinea pigs.

Total serum copper levels produced by the administration of a single dose of cuprous oxide (500 mg/kg) both s.c. and orally to rats and guinea pigs are reported 1, 5, 7 and 24 h after administration, together with caeruloplasmin oxidase activities and changes in the sulphydryl group concentrations. The highest serum copper levels were obtained one hour after oral administration to the guinea pig. Both animal species exhibited increased serum copper levels after s.c. administration and this increase persisted for a longer time than after oral administration. Caeruloplasmin oxidase activity varied in a complex manner and sulphydryl group activity was significantly depressed in all cases except after s.c. administration to the guinea pig. The latter results must be treated cautiously since they may indicate interactions between copper and the test procedures. Analysis of serum fractions separated by electrophoresis indicated that the absorbed copper is mainly transported on albumin. The dissolution of cuprous oxide by amino acids and hydrochloric acid and the absorption of cuprous oxidcations of the results are discussed in terms of their relevance to pharmacological and clinical studies.

Absorption↗
PubMed1979

Time-dose-response studies on cellular immunity.

The time-dose responses to several murine histocompatibility antigens were studied using lymphocytes as an antigen source for immunization and the speed of rejection of skin grafts as an assay of the level of immune responsiveness. It was observed that the weaker the first set response to an antigen the higher the minimal immunizing dose and the lower the tolerizing dose; thus, there was a small "immunizing window." The speed of onset of immune responsiveness and the magnitude of change in it following first antigen contact depended on the "strength" of the antigen. When the antigen was "strong" the level of response increased rapidly following first antigen contact. When the antigen was "weak" a period of tolerance appeared following first antigen contact, which then gave way to a state of immunity; the "weaker" the antigen the longer the interval and the greater the magnitude of tolerance. Increasing the antigen dose tended to magnify and prolong the tolerance. The "weaker" the antigen the longer the interval between first antigen contact and the appearance of immunity. Once established, the level of immunity was not constant. Undulations in the levels of all responses were noted; the "weaker" the antigen the larger the undulations. Possible explanations for the undulations and implications of the time-dose-response curves in immunotherapy are discussed.

Animals↗
PubMed1979

Serum copper and its relationship to clinical symptoms in rheumatoid arthritis.

Total serum copper and ultrafilterable copper levels in patients with rheumatoid arthritis were determined and related to articular index, erythrocyte sedimentation rate (ESR), and serum iron concentration. Relationships were found between serum copper and ESR, and between ultrafilterable copper and articular index. The relationship between serum copper and serum iron was found to be a drug-dependent.

Arthritis, Rheumatoid↗
PubMed1978

Comparison of gold levels and distribution in guinea pig serum.

Serum levels after oral administration of 30 mg/kg of sodium aurothiomalate (Myocrisin), triethylphosphine gold chloride, or triphenylphosphine gold chloride to guinea pigs indicated that all were orally absorbed. However, the serum gold level of triethylphosphine gold chloride was three to four times that of Myocrisin or triphenylphosphine gold chloride and was comparable with the serum level produced when the same dose of Myocrisin was injected intramuscularly. A comparative time-course study between intramuscular administration of Myocrisin and oral administration of triethylphosphine gold chl;ride indicated that during the first 24 hours after intramuscular injection of Myocrisin, a large fraction of the gold was not protein-bound, whereas all detectable gold in serum after oral administration of triethylphosphine gold chloride was protein-bound. Gold levels in the separated protein fractions indicate that the gamma-globulin level after oral administration of triethylphosphine gold chloride is approximately three times higher after 24 hours than with intramuscular Myocrisin.

Administration, Oral↗
PubMed1978

A comparison of tissue gold levels in guinea-pigs after treatment with myocrisin injected intramuscularly and triethylphosphine gold chloride and myocrisin administered orally.

A comparative study of tissue gold levels produced in guinea-pigs after the oral administration of either triethylphosphine gold chloride or Myocrisin (sodium aurothiomalate) or after the injection of Myocrisin intramuscularly is reported. Gold concentrations were determined 5, 24 and 168 hours after administration in stomach, small intestine, large intestine, kidney, liver and spleen and 5 and 24 hours after administration in skin, adrenals, heart, lung and brain. In gastrointestinal tissues, tissue gold concentrations were highest with triethylphosphine gold chloride. The stomach gold level 5 hours after oral administration of triethylphosphine gold chloride is particularly high and, taken in conjunction with the other gastrointestinal gold levels measured, suggests that a stomach rather than an intestinal absorption mechanism may predominate. A more extensive time-course study on kidney and liver is reported and the possible relationship between tissue concentration and toxicity is discussed.

Administration, Oral↗
PubMed1978

Structure of the polysaccharide formed by incubating glycogen with D-[14C]glucose in the presence of the glycogen debranching enzyme [amylo-(1 linked to 6)-glucosidase-4-alpha-glucanotransferase].

[14C]Glycogen has been synthetized in vitro by incubating D-[14C]glucose with rabbit-liver glycogen in the presence of a pure preparation of the glycogen debranching enzyme [amylo-(1 linked to 6)-glucosidase-4-alpha-glucanotransferase]. The course of the reaction has been monitored and 14C-products isolated after 30 min and 5 h. The distribution of D-[14C]glucose groups in the polysaccharides has been determined by debranching the molecules with a crystalline isoamylase from Pseudomonas. The quantities of unlabeled and 14C-linear unit chains containing D-[14C]glucose at their reducing ends have been determined by paper chromatography followed by enzymic degradation and analysis. In the 30-min product, between 65 and 85% of the D-[14C]glucose groups were covered by unlabeled groups because of transferase action. In the 5-h product, the extent of covering approached 100%. Extensive redistribution of unlabeled groups also was found to have occurred, even in the early stages of the reaction. It is concluded that the D-[14C]glucose incorporation assay for amylo-(1 linked to 6)-glucosidase, as ordinarily carried out, is probably not specific just for the hydrolytic action of this enzyme, but that it depends indirectly on its transferase activity as well.

Animals↗