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Biomedical subjects

B Ekström

Publications and source records attributed to B Ekström.

At least 37 records · Page 2Linked to original sources

Isolation and characteristics of human urinary sialoglycoproteins.

Three sialoglycoproteins (S1, S2, and S3) have been isolated from normal human urine by ultrafiltration, zone electrophoresis, gel chromatography, and ion-exchange chromatography. The average yields per litre of urine were 0.39 mg (S1), 0.40 mg (S2), and 1.9 mg (S3). The isolated substances were homogeneous on ultracentrifugation both at neutral and acid pH with sedimentation coefficients of 3.6 S (S1), 2.4S (S2), and 0.93S (S3). Equilibrium ultracentrifugation gave molecular weights of 77900 (S1), 37000 (S2), and 5300 (S3). All three components were rich in carbohydrate (64 to 76%) and contained 28 to 35% of sialic acid. Alkaline borohydride degradation of component S3 yielded two sialylated oligosaccharides which were partially characterized. The origin of the isolated substances is unknown. The molecular size of S3 (Stokes' radius of 2.0 nm) is compatible with passage from the blood by glomerular filtration whereas the size of S1 (Stokes' radius of 6.5 nm) would suggest a renal origin.

Chemical Phenomena↗

Structural studies on the carbohydrate portion of human alpha 1-microglobulin.

Human alpha 1-microglobulin has been shown to have three N-glycosidically linked carbohydrate chains of the following structure: (formula: see text) This structure was established by sugar and methylation analysis before and after removal of the N-acetylneuraminic acid residue and by using specific chemical degradation techniques such as Smith degradation, chromium trioxide oxidation and trifluoroacetolysis.

Alpha-Globulins↗

alpha 1-Microglobulin.

A new low-molecular weight plasma protein was discovered and isolated from human urine by Ingemar Beggård. He named it alpha 1-microglobulin. The protein has a molecular weight of 26,000, contains about 20% carbohydrate, is electrophoretically heterogenous, carries a brown-coloured, unidentified substance, and is present in serum in free, as well as in high molecular weight complexes. alpha 1-Microglobulin seems to interfere with the in vitro response of lymphocytes to some antigens. The site of synthesis of alpha 1-microglobulin is unclear.

Alpha-Globulins↗

Synergistic activity of co-trimazine and co-trimoxazole in the urine.

Co-trimazine (sulphadiazine, 410 mg + trimethoprim, 90 mg) is a new drug combination developed especially for use in the treatment of urinary tract infections. In cross-over experiments in volunteers receiving daily doses of co-trimazine (2 X 500 mg and 1 X 1000 mg), co-trimoxazole (2X960 mg), or nitrofurantoin (3X50 mg), the degree of antibacterial activity of co-trimazine in the urine was at least as high as that of co-trimoxazole and much higher and more consistent than that of nitrofurantoin. In further cross-over experiments in volunteers receiving co-trimazine 2X1000 mg or co-trimoxazole 2X960 mg for four days no or only slight activity was found in the urine against a sulphonamide-resistant Group D streptococcus, but distinct synergistic activity between the components was found against four Escherichia coli strains sensitive to trimethoprim and sensitive or resistant to sulphonamides. Against three of the latter strains the degree of activity in the urine was higher after co-trimazine than after cotrimoxazole. The synergistic action of trimethoprim and sulphonamide in the urine appeared greater with the former than with the latter combination.

Drug Combinations↗

Development of sulphonamide-trimethoprim combinations for urinary tract infections. Part I: Comparison of the antibacterial effect of sulphonamides alone and in combination with trimethoprim.

Plasma half life and in vitro activity were major criteria for selection of sulphonamides which are likely to give a strong synergistic action with trimethoprim in vivo. On the basis of literature data six sulphonamides, sulphadiazine, sulphachloropyridazine, sulphamethoxazole, sulphaisodimidine, sulphamerazine and sulphamethomidine appeared particularly suitable for combination with trimethoprim. An investigation of the activity in vitro of these compounds and their combinations with the latter against clinically isolated, sulphonamide-sensitive Klebsiella-Enterobacter and Escherichia coli strains showed optimal synergy at trimethoprim-sulphonamide ratios between 1:10 and 1:40, but that appreciable mutual potentiation occurred within a rather broad range of concentration ratios. Limited experiments indicated that synergy occurs less frequently and is less pronounced against sulphonamide resistant bacteria. The different sulphonamides behaved rather similarly in their combinations with trimethoprim, and in order to find the best sulphonamide, detailed comparisons of the pharmacokinetic properties of the different combinations are necessary.

Bacteria↗

Antibacterial activity of co-trimazine in vitro and in vivo.

Co-trimazine is a new drug combination especially designed for the treatment of urinary tract infections. It consists of trimethoprim (90 mg) and sulphadiazine (410 mg). When combined in vitro, the components show high activity and a high frequency of synergy against urinary tract pathogens. After oral absorption sulphadiazine has a serum half-life similar to that of trimethoprim and is excreted in active form into the urine to a much higher degree than sulphamethoxazole. The ratio of the concentrations of trimethoprim and sulphadiazine in the urine following co-trimazine is favourable for a strong synergistic action between the compounds. In cross-over studies in volunteers receiving repeated daily doses of co-trimazine, either 500 mg twice daily or 1000 mg once daily, it was found that antibacterial activity in the urine was at least as high as that provided by co-trimoxazole (2 x 960 mg) and considerably higher and more uniform than that given by nitrofurantion (3 x 50 mg).

Absorption↗

Comparative in vivo activity of bacampicillin and amoxycillin.

Bacampicillin is an orally well-absorbed pro-drug of ampicillin giving high in vivo levels of the latter. Its therapeutic activity was compared with that of amoxycillin in two experimental infection models in mice. The animals were infected with suspensions of Escherichia coli III and Haemophilus influenzae 22863 intraperitoneally and treated orally four hours afterwards with one of the two compounds. The antibacterial activity of the compounds was determined as CD50 values or by making viable counts in the blood and in organ homogenates of the animals. Ampicillin and amoxycillin had the same inhibitory but different bactericidal activity against the test strains. Both compounds appeared to have similar therapeutic activity and were found to cause a rapid decrease of the bacterial counts in the animals. Bacampicillin appeared to give a more rapid bactericidal activity than amoxycillin against the Haemophilus influenzae strain, whereas amoxycillin initially appeared more bactericidal against the Escherichia coli infection.

Amoxicillin↗

Evaluation of amino penicillins in experimental infections in mice.

The therapeutic activity of bacampicillin compared to that of ampicillin and amoxycillin was evaluated against experimental infections in mice. Median curative doses (CD50) were determined in groups of animals challenged with bacterial suspensions injected intraperitoneally together with mucin and treated orally with the penicillins. When treated directly after the infection bacampicillin was slightly more active than ampicillin, whereas it was significantly more active than ampicillin and at least as active as amoxycillin when the treatment was instituted not until four hours after infection. Bacterial counts made on various organ homogenates from infected animals four hours after the infection showed that a generalized infection with high bacterial concentrations had developed. Penicillin administration caused a significant reduction in the bacterial counts and the bactericidal activity in vivo obtained after administration of bacampicillin appeared as good as that of amoxycillin.

Administration, Oral↗

Antibody reactivity in penicillin-sensitive patients determinated with different penicillin derivatives.

35 individuals showing reactions to penicillin of anaphylactic shock, angioedema or urticaria were investigated. Their skin sensitivity was analysed using 16 different penicillin derivatives. In addition, the content of circulating reagins against the penicilloyl structure in the patient's sera were analysed using RAST. 17 of the patients had negative skin reactions and RAST results to all substances tested. The other 18 were skin test-positive to at least one derivative but showed markedly heterogeneous patterns of skin reactivity. 14 had positive reactions against penicilloyl structures accompanied by anti-penicilloyl reagins. Four patients showed doubtful reactions only to penicillin or penicilloate and/or penilloate. These patients also had very low levels of reagins against penicilloyl in their sera. Positive skin test results using monovalent penicillin derivatives such as penicillin, penicilloate, penilloate, penicilloyl amide, penicilloyl-formyl-lysine, penicillamine, which cannot form a multivalent antigen with penicillyol specificity, indicated formation of other derivatives of importance in penicillin allergy, e.g., penicillamine protein conjugates. Three patients showed skin reactions to ampicillin polymer and two to benzyl-penicillin polymer. The skin tests performed with the penicillin derivatives used do not seem to give more information on the sensitivity of the patients than does the RAST using penicilloyl structures.

Adolescent↗

Synthesis and antibacterial properties of methylsulfinyl and methylsulfonyl analongs of some nitrofurans.

The sulfoxides 5-methylsulfinyl-2-furaldehyde semicarbazone (2) and 1-[(5-methylsulfinyl-2-fufurylidene)amino]hydantoin (3) as well as the sulfones 1-[(5-methylsulfonyl-2-furfurylidene)animo]hydantoin (1) and 1-(5-methylsulfonly-2-furyl)-2-(6-amino-3-p-ridazyl)ethylene hydrochloride (4) have been prepared and tested for antibacterial activity against a number of gram-negative and gram-positive organisms. The compounds are much less active than the corresponding 5-nitrofuran derivatives, possibly because their reduction potentials are too negative for them to interfere with reductive enzyme systems within the bacteria.

Anti-Bacterial Agents↗

Bacampicillin: a new orally well-absorbed derivative of ampicillin.

Bacampicillin (proposed international nonproprietary name), 1'-ethoxycarbonyloxyethyl 6-(d-alpha-aminophenylacetamido)penicillanate, is a new orally well-absorbed penicillin, highly active in vivo due to rapid transformation into ampicillin. The compound is stable in vitro at gastric pH and hydrolyzed slowly to ampicillin at neutral pH but very rapidly in the presence of biological fluids, e.g., tissue homogenates or serum. In vivo the transformation into ampicillin is so rapid that no unchanged compound could be detected in the blood after oral administration of bacampicillin to rats, dogs, and humans. On oral administration to mice, rats, and dogs, bacampicillin was found to be better absorbed than ampicillin, giving higher and earlier peak blood levels of ampicillin. The bioavailability of bacampicillin in rats and dogs was three to four times higher than that of an equimolar amount of ampicillin. On oral administration to rats, bacampicillin was found to give higher levels of ampicillin in organs such as the kidney, liver, and spleen than ampicillin itself. In "tissue cages" in rats, higher transudate levels of antibiotic were found after oral administration of bacampicillin than after ampicillin. On oral treatment of experimentally infected mice, bacampicillin was found to be more active than ampicillin.

Ampicillin↗