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Biomedical subjects

G Seibert

Publications and source records attributed to G Seibert.

At least 55 records · Page 3Linked to original sources

Cefodizime, an aminothiazolylcephalosporin. I. In vitro activity.

Cefodizime possesses a broad antibacterial spectrum including staphylococci, streptococci and Enterobacteriaceae. Neisseria gonorrhoeae and Haemophilus influenzae are also highly susceptible to cefodizime. Because of its beta-lactamase stability cefodizime is active against bacterial strains producing especially plasmid-coded enzymes. The MICs of cefodizime are slightly higher than those of cefotaxime, but with most Gram-negative bacteria they are lower than those of cefazolin, cefotiam and piperacillin. The in vitro activity of cefodizime is not dependent on inoculum size, or on the pH and composition of the test medium. Cefodizime did not induce in vitro resistance of Staphylococcus aureus or Escherichia coli. Because of its binding properties to PBPs 1A/B and 3, cefodizime leads to filamentation of Gram-negative rods and, at only slightly higher concentrations, to bacteriolysis.

Bacterial Proteins↗

Cefodizime, an aminothiazolylcephalosporin. II. Comparative studies on the pharmacokinetic behavior in laboratory animals.

The pharmacokinetic properties of cefodizime, a new aminothiazolyliminomethoxycephalosporin, were studied in laboratory animals and compared with the pharmacokinetics of another long-acting cephalosporin, ceftriaxone. Both cephalosporin derivatives showed high affinity (33-99%) for serum proteins. High and prolonged blood respectively serum levels of the antibiotics were achieved following subcutaneous and intravenous injection into mice, rats, rabbits, dogs and monkeys. Cefodizime elimination half-lives ranged from 1.17 hours in mice to 3.53 hours in rabbits compared to ceftriaxone half-lives ranging from 0.73 hour in mice to 7.31 hours in rabbits. The antibiotics were well distributed in the body and penetrated into tissues and body fluids to a high degree. Particularly high and prolonged levels were detected in the lungs, liver and kidneys of the experimental animals. Large amounts, approximately 35-55% of the given dose, were recovered in the urine of rabbits and dogs, while the recovery rate in the bile of rabbits was only 0.57% for cefodizime and 1.08% for ceftriaxone.

Animals↗

The in vitro antimicrobial activity of desacetylcefotaxime compared to other related beta-lactams.

Like all other cephalosporins that contain an acetyl side chain in the 3' position, cefotaxime (CTX) is partially desacetylated in vivo. Desacetylcefotaxime (des-CTX) possesses a broad antimicrobial spectrum and high beta-lactamase stability. With the exception of Pseudomonas aeruginosa, Morganella morganii, Bacteroides fragilis, and Staphylococcus aureus, most strains of other species tested usually had mean MICs of des-CTX lower than 1 microgram/ml. Its activity is generally lower than that of the parent compound. It was only against some strains of P. cepacia that des-CTX surpassed the activity of CTX. The activity of des-CTX markedly exceeds the activity of many therapeutically used cephalosporins. This is especially true for Haemophilus influenzae, Neisseria meningitidis, most species of Enterobacteriaceae, and streptococci other than Streptococcus faecalis.

Anti-Bacterial Agents↗

HR 810, a new parenteral cephalosporin with a broad antibacterial spectrum.

3-[(2,3-Cyclopenteno-1-pyridinium)-methyl]-7-[2-syn-methoximino-2-(2-aminothiazol-4-yl)-acetamido]-ceph-3-em-4-carboxylate (HR 810) is a new cephalosporin derivative with an extremely broad antimicrobial spectrum. It is active against all bacterial species of clinical relevance, including strains which are frequently resistant towards cephalosporins of the third generation.

Bacteria↗

Comparison of the antibacterial in vitro and in vivo activity of ofloxacin (HOE 280 DL 8280) and nalidixic acid analogues.

The in vitro and in vivo activity of ofloxacin (DL 8280, HOE 280) was compared with that of other antibacterial compounds. Ofloxacin was found to have a broad antibacterial spectrum which includes both gram-positive and gram-negative aerobic and anaerobic species. Its activity is generally higher than that of pipemidic acid and nalidixic acid. Against staphylococci and streptococci, ofloxacin proved to be more active than norfloxacin. In the case of Enterobacteriaceae and Pseudomonadaceae, ofloxacin and norfloxacin possess comparable activities. Ofloxacin was the most active compound against a number of aerobic isolates which are resistant to cefotaxime and ceftriaxone. Of the compounds compared, ofloxacin was the only one which exhibited reasonable activity against anaerobes. It inhibited all strains of Bacteroides fragilis at a concentration of 3.125 mg/l and the gram-positive anaerobes at 0.5 mg/l. In mice experimentally infected with various gram-positive and gram-negative bacteria, ofloxacin was more active than norfloxacin and pipemidic acid. With the gram-negative pathogens, orally administered ofloxacin was as active as gentamicin used parenterally. We conclude from our studies that ofloxacin could be a valuable therapeutic agent with a variety of indications.

Animals↗

The cooperation of cefotaxime and desacetyl-cefotaxime with respect to antibacterial activity and beta-lactamase stability.

Desacetyl-cefotaxime, the main metabolite of cefotaxime, possesses a broad antibacterial spectrum. Its activity is lower than that of cefotaxime, but significantly surpasses that of cefazolin against gram-negative bacteria. The beta-lactamase stability of desacetyl-cefotaxime is higher than that of the parent compound. This beta-lactamase stability might be responsible for the synergistic effects of cefotaxime and desacetyl-cefotaxime occasionally seen in in vitro combination studies.

Bacteria↗

Purification and characterization of a cephalosporinase from E. coli.

The isolation and properties of a beta-lactamase from E. coli are described, which hydrolyses the Cephalosporins of the third generation. The enzyme has been brought to high purity by precipitation with (NH4)2SO4, gel chromatography and affinity chromatography on Cephalosporin C bound to agarose. The enzyme has been characterized by evaluation of its molecular weight 39 000, isoelectric point (pH 7.2), pH-optimum (pH 8.4) and substrate profile. It accepts Ceftizoxime, Cefamandole, Cefazolin and Cefotaxime as substrates, but shows nearly no activity on Penicillin G, Cefoxitin and the Desacetylmetabolite of Cefotaxime.

Cephalosporinase↗

Purification of a nuclease from human serum.

The purification procedure for a nuclease from human serum is described. It includes ammonium sulfate precipitation, chromatography on DEAE-Sephadex and on Sephacryl-S 200, and preparative electrophoresis. The enzyme purified about 2000-fold, is homogeneous in a sodium dodecyl sulfate electrophoretic system, where it has a mol. wt of 78,000. The pH optimum lies around pH 6.5; it is a sugar-nonspecific endonuclease.

Deoxyribonucleases↗

Tubercidin metabolism in mouse L5178y cells in vivo and in vitro.

Tubercidin (7-deazaadenosine) is a strong inhibitor of cell proliferation in mouse L5178y cells. Radioactive tubercidin is incorporated into DNA and RNA. Poly(A)-containing RNA shows the highest specific radioactivity. The amount of low molecular weight 4S and 5S RNA is diminished to some extent under the influence of the compound. Tubercidin triphosphate is a potent inhibitor of DNA-dependent DNA polymerases alpha and beta, and the DNA-dependent RNA polymerases I, II, and III, although the efficiency of its incorporation is lower than of dATP and ATP. Tubercidin triphosphate also seems to be a good substrate for the Mg2+-dependent poly(A) polymerase.

Animals↗

Single-step separation of major and rare ribonucleosides and deoxyribonucleosides by high-performance liquid cation-exchange chromatography for the determination of the purity of nucleic acid preparations.

A method is described for the separation of 13 major and minor ribo- and deoxyribonucleosides in a single chromatographic run using high-performance liquid chromatography on strongly acidic cation-exchange columns. The method proved useful for the routine determination of small amounts of ribonucleic acid impurities in deoxyribonucleic acid preparations and vice versa. About 3% or even less of nucleic acid contamination in a given sample can be easily detected and quantitatively determined under the conditions used.

Chromatography, High Pressure Liquid↗

Endoribonuclease IV. 2. Further investigation on the specificity.

The poly(A)-specific endoribonuclease IV produces oligo(A) fragments of a chain length of 10 AMP nucleotides. One enzyme molecule performs 1700 cleavages per min; the cleavages occur randomly. The endoribonuclease IV is a nuclear enzyme which is present in the oviduct of quails in a concentration of 40 000 enzyme molecules per cell. Poly(A) segments on mRNA are selectively hydrolyzed by endoribonuclease IV; the poly(A)-free part of the RNA is not affected. After incubation with the enzyme, a residual oligo(A) stretch of 5 AMP nucleotides remains on poly(A)-rich RNA. The endoribonuclease IV does not disintegrate the polyribosomal complex after incubation in vitro and the enzyme has also no influence on the translational capacity of a cell-free protein-synthesizing system.

Animals↗

The conservation of poly-A-containing RNA during the dormant state of the moss Polytrichum commune.

The moss Polytrichum commune can be dried to less than 2% of free water and kept for some weeks without losing its viability. Upon rehydration of the moss, protein synthesis starts about 60 minutes before incorporation of radioactive precursors into RNA can be observed. Pulse labeled total RNA and poly-A-containing RNA do not show quantitative or qualitative alterations during desiccation up to 20 days.

Drug Stability↗