PubMed Health⌕ Search

Biomedical subjects

G Seibert

Publications and source records attributed to G Seibert.

At least 37 records · Page 2Linked to original sources
PubMed1990

Comparative chemotherapeutic activity of cefpirome and imipenem in experimental infections.

In systemic and local infections, the therapeutic efficacy of cefpirome was compared to that of imipenem and cefotaxime. Murine septicemia induced with methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains responded well to cefpirome and imipenem therapy, the ED50 values ranged from 0.8 to 28.40 mg/kg and 0.5 to 15.58 mg/kg, respectively. The carbapenem also displayed high efficacy against Enterococci and was more potent than cefpirome. Cefotaxime, however, exhibited lower activity or proved to be inactive against these strains. With ED50 values of 0.03 to 31.33 mg/kg, cefpirome was the most active of the three antibiotics in protecting mice challenged with Enterobacteriaceae. The corresponding ED50 values of imipenem and cefotaxime ranged from 0.72 to 70.95 mg/kg and 0.06 to 66.30 mg/kg, respectively. Despite distinctly lower in vitro activity against the infecting organism, cefpirome showed efficacy similar to imipenem in the treatment of subcutaneous S. aureus abscesses in mice. It was more effective than imipenem and cefotaxime against experimental Klebsiella pneumonia in mice and the Escherichia coli infected granuloma pouch in rats.

Abscess↗
PubMed1987

Formation of transmural complement pores in serum-sensitive Escherichia coli.

The binding of C9 at 0 and 37 degrees C to viable Escherichia coli K-12 cells carrying C5b-8 complexes was quantified. At low temperature, limited average binding of only 1 to 1.4 molecules of C9 per C8 molecule occurred, whereas 6 to 8 C9 molecules were bound per C8 molecule at 37 degrees C. Despite incorporation of C9 into C5b-9 complexes at 0 degrees C, these terminal complexes caused no loss of bacterial viability even when present in very large numbers (1,000 to 1,500 per CFU) on the bacterial cells. In contrast, generation of 50 to 100 C5b-9 complexes carrying multiple C9 molecules per CFU caused loss of viability. The failure of C5b-81C91 complexes to generate transmural pores was confirmed by measurements of o-nitrophenyl-beta-D-galactoside influx into the cells. Whereas treatment of C5b-8-laden cells with C9 at 32 degrees C caused virtually instantaneous influx of the marker, almost no influx was registered in cells receiving C9 at 0 degrees C. When cells carrying C5b-7 were brought into the stationary phase and given C8 and C9 at 32 degrees C, a C9-dependent disruption of the outer membrane permeability barrier immediately occurred as demonstrated by cleavage of a chromogenic substrate by periplasmic beta-lactamase. In sharp contrast, o-nitrophenyl-beta-D-galactoside influx was markedly retarded over a prolonged period, with abrupt permeability increases of the inner membrane toward this molecule being noted just before bacterial cell division occurred. We conclude that killing of E. coli requires binding of C5b-9 complexes containing C9 oligomers to the outer membrane and suggest that formation of pores in the inner membrane occurs when these complexes are "hit" by transiently forming zones of bioadhesion. Formation of the latter may be a dynamic process that is accentuated during cell division and quiescent during the stationary phase.

Blood Bactericidal Activity↗
PubMed1987

HRE 664, a new parenteral penem. II. Evaluation of the pharmacokinetic behavior and the chemotherapeutic activity in animals.

The pharmacokinetic and chemotherapeutic properties of the new penem antibiotic HRE 664 (Fig. 1) were evaluated in experimental animals. High and sustained blood and serum levels were achieved following parenteral injection in mice, rats, dogs and monkeys. Half-lives ranged from 27 to 40 minutes in the various species tested. The antibiotic was well distributed in the rodents and penetrated well into tissues and body fluids. At 30 minutes after subcutaneous administration to mice (50 mg/kg), concentrations of between 12.4 and 35.9 micrograms/g were measured in the lungs, liver, heart and kidneys, that is 33 approximately 95% of the corresponding level in murine blood (37.7 micrograms/ml). In experimentally induced infections in mice, HRE 664 displayed good chemotherapeutic activity particularly against septicemias caused by methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains and on abscess formation induced by Bacteroides fragilis. Most of the cephalosporins and other beta-lactam antibiotics exhibited low efficacy against these strains of bacteria.

Abscess↗
PubMed1987

The in vitro activity of the combination of cefotaxime and HRE 664.

Cefotaxime (CTX) and HRE 664 (a novel penem antibiotic) possess complementary in vitro properties. Differences can be observed in their antibacterial spectra, their beta-lactamase stability and -inhibition, and their affinity to penicillin-binding proteins. These differences suggested that combinations of the cephalosporin and the penem antibiotic would be advantageous and should be studied. The fractional inhibitory concentration values of checkerboard studies confirmed that CTX and HRE 664 act synergistically against various Gram-positive and Gram-negative bacteria. Fixed combinations containing 80% CTX and 20% HRE 664 possess broader antibacterial spectra and in certain cases higher antibacterial activities than each of the components alone. The combinations had improved activity against Staphylococci including methicillin-resistant strains, beta-lactamase producing strains of Enterobacter sp. and Bacteroides fragilis. The combination as well as the single antibiotics had only limited activity against Pseudomonas aeruginosa.

Anti-Bacterial Agents↗
PubMed1987

HRE 664, a new parenteral penem. I. Antibacterial activity in vitro.

The new penem antibiotic HRE 664 displays potent antibacterial activity in vitro against a broad spectrum of clinically relevant bacterial strains including Gram-negative and Gram-positive aerobes and anaerobes. With an MIC 90% of 0.43 micrograms/ml, it is also active against methicillin-resistant staphylococci. HRE 664 is extremely stable against beta-lactamases, it binds preferentially to the penicillin-binding proteins 2, 3, 5 and 6 of Escherichia coli.

Anti-Bacterial Agents↗
PubMed1986

Chemotherapeutic effects of ofloxacin (HOE 280) and other quinolone-carboxylic derivates in the treatment of experimental lung infections due to Klebsiella pneumoniae DT-S in mice.

The chemotherapeutic activity of ofloxacin (HOE 280), a new pyridone-carboxylic acid derivative, was compared with that of other drugs in the same group, including norfloxacin, ciprofloxacin, enoxacin and in some cases pipemidic acid and nalidixic acid. The test model used was experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice. In the treatment of pneumonic mice, ofloxacin was 4 to 18 times more effective than norfloxacin and enoxacin and in most cases slightly more effective than ciprofloxacin. Pipemidic acid and nalidixic acid showed only low activity or proved to be inactive. In studies on the bactericidal activity of the compounds in vivo, ofloxacin produced a more pronounced effect than ciprofloxacin. With norfloxacin and enoxacin, a bactericidal effect in the infected tissue of the animals was only observed during the first hours after treatment.

Animals↗
PubMed1986

Properties of an inducible beta-lactamase from Proteus vulgaris.

The inducible beta-lactamase of the clinical Proteus vulgaris isolate 4917/81 was highly purified by column chromatography and by FPLC (cation ion exchange column). Molecular weight of the enzyme amounted 33,000 daltons, as revealed by SDS-electrophoresis. The enzyme was not inhibited by p-chloromercuribenzoate, but by low concentrations of oxacillin and clavulanic acid. The enzyme inactivated not only penicillin derivatives (including ureidopenicillins), but also first-generation cephalosporins and above all oxime-cephalosporins such as cefuroxime, cefotaxime and related derivatives. Turnover rates of these agents were mainly influenced by the nature of substitution in 3' position of the cephalosporin nucleus. Breakdown was not detectable in compounds which were substituted in 6 alpha or 7 alpha position, respectively. The enzyme proved to be very sensitive to the nature of 6 alpha or 7 alpha substituent, as revealed by the study of enzyme kinetics; no turnover could be detected for the penem Sch29 482, imipenem, latamoxef, and aztreonam.

Anti-Bacterial Agents↗
PubMed1986

Comparative effects of cefpirome (HR 810) and other cephalosporins on experimentally induced pneumonia in mice.

The chemotherapeutic efficacy of cefpirome (HR 810), a new polar aminothiazolylcephalosporin and that of ceftazidime, cefotaxime, cefoperazone, latamoxef and cefodizime were examined against experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice. When compared in terms of MIC values against the infecting organism and the pharmacokinetic pattern, cefpirome showed equal activity and a similar pharmacokinetic behavior to ceftazidime and cefotaxime in mice. Trials to assess the bactericidal activity in vivo, however, showed that cefpirome displayed a more marked bactericidal effect in pneumonic mice than the other cephalosporins tested. Only cefodizime, a cephalosporin with extremely high and prolonged blood and tissue levels in experimental animals exerted chemotherapeutic effects similar to cefpirome. After cefpirome or cefodizime medication (50 mg/kg), the viable counts in the lungs of experimental animals fell steadily to 1/10,000 of the pretreatment level and, in contrast to the reference compounds, no regrowth of the challenge organisms could be observed with both drugs. Moreover, with ED50s ranging from 1.1 to 59.1 mg/kg in treatment studies, cefpirome as well as cefodizime were two to ten times more effective than ceftazidime and cefotaxime, whereas cefoperazone and latamoxef were considerably less effective.

Animals↗
PubMed1985

Utilisation of the European Retrieval Carrier Eureca for life science research.

Eureca, the European Retrieval Carrier, is a reusable free-flying platform, which will be launched to 500 km altitude and retrieved by the Shuttle. up to 6 months later at 300 km. The first mission of Eureca is dedicated to research in the fields of life sciences and material sciences. The experimental hardware of the first mission will consist of a variety of processing chambers for crystal growth and equipment for biological investigations viz plant growth and protein crystallization, and there is the possibility to perform experiments in the field of exobiology. The Eureca mission offers the opportunity for long time exposure of material and of terrestrial origin to the unique environment of space or to selected factors of it, such as the radiation environment, the space vacuum, extreme temperatures and microgravity conditions.

Biological Science Disciplines↗
PubMed1985

Antibacterial and antifungal activity of Avarone and Avarol.

The sesquiterpenoid hydroquinone and quinone, Avarol and Avarone, were previously found to be potent antitumor agents (Müller et al., 1984). In the present study it is reported that in aqueous solution (pH 7.2), in the presence of dimethylsulfoxide, Avarol is converted to Avarone. Avarone and to a smaller extent also Avarol were active against a variety of grampositive bacterial species. The highest activity was determined for Streptococcus pneumoniae and Erysipelothrix rhusiopathiae (MIC 0.781 mg/l). The antibacterial activity can be augmented 2 to 4-fold by lowering the pH in the culture medium from 7.0 to 6.0. The efficiency of Avarone and Avarol was abolished in the presence of serum. No antibacterial activity was determined in gramnegative bacterial species. In addition, Avarol and to a smaller extent also Avarone displayed an antifungal activity on Trichophyton species and Microsporum canis (MIC: 15.6-62.5 mg/l), while Avarone and not Avarol was active on Aspergillus niger, no activity was found against Candida species. These data indicate that the antitumor agents Avarol/Avarone display also antibacterial- and antifungal activities against a limited range of microorganisms.

Bacteria↗
PubMed1985

Potent antileukemic activity of the novel cytostatic agent avarone and its analogues in vitro and in vivo.

Avarone and avarol are novel cytostatic agents which have potent antileukemic activity both in vitro and in vivo (mice). Cell culture experiments revealed that the cytostatic activity of these two compounds on L5178Y mouse lymphoma cells was 13- to 14-fold higher than that determined for HeLa cells and 40- to 43-fold higher than that for human melanoma cells. Nontumor cells (human fibroblasts and human gingival cells) were highly resistant against the two compounds. The inhibitory potency of avarone on L5178Y cells (50% inhibitory concentration, 0.62 microM) was significantly higher than the avarol activity (50% inhibitory concentration, 0.93 microM). Modification of the molecule at the quinone ring or the double bond in the terpenoid skeleton resulted in a significant loss of activity. In vivo studies with L5178Y cells in the ascites of mice confirmed the strong antileukemic effect determined in vitro. At doses of 10 mg/kg given i.p. once daily for 5 days to mice bearing approximately 10(8) leukemia cells, avarone was found to be curative in about 70% of the mice (20% for avarol). The optimal daily i.p. dose of avarone increased life span over controls by 146% when treatment was begun 1 day after tumor implantation and by 87% when treatment was delayed until day 8. Avarol, although active, was less effective. Based on the determined log10 kill values, avarone can be classified as a highly active and avarol as a markedly active cytostatic agent. The efficacy of the two compounds is also emphasized by the therapeutic index of 11.7 for avarone and of 4.5 for avarol. The two agents were determined not to be either direct mutagens or premutagens in the Ames test.

Animals↗
PubMed1984

Differential stimulation of lymphocyte cell growth in vitro by cephalosporins.

The in vitro effect of three cephalosporins (cefodizime, cefotaxime, and ceftizoxime) on the growth of the following lymphocytes or their derivatives was tested: L 5178y mouse lymphoma cells, Molt-4 cells, and murine splenic lymphocytes. Within the concentration range of 0.1 to 50 microM, the cephalosporins had no effect on L 5178y cell growth. However, Molt-4 cell growth was significantly stimulated by 0.3 to 20 microM cefotaxime and cefodizime but was not influenced by ceftizoxime. Binding studies with [14C]cefotaxime revealed that the Molt-4 cells responding to the drug bind this cephalosporin to their cell surface (1.9 X 10(5) molecules per cell); no significant binding was observed in the assays with L 5178y cells. Determinations of the extractable activities of DNA-synthesizing enzymes from cefodizime-treated Molt-4 cells showed a direct correlation between cell growth and DNA polymerase alpha as well as terminal deoxynucleotidyl transferase activity; the DNA polymerase beta activity remained unchanged. Cefodizime (0.15 to 50 microM) which was added to mouse spleen cell cultures significantly increased [3H]thymidine incorporation into lymphocytes. This stimulatory effect was less pronounced in concanavalin A-stimulated cultures. These findings suggest that some cephalosporins display a growth-stimulating influence on some lymphocyte populations.

Animals↗
PubMed1984

Cefodizime, an aminothiazolyl cephalosporin. III. Therapeutic activity against experimentally induced pneumonia in mice.

The activity of the aminothiazolyliminomethoxy cephalosporin cefodizime (HR 221) was compared to that of cefotaxime, cefuroxime and cefazolin in experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice. Cefodizime exhibited high and long-acting levels in the blood and lung homogenates of infected mice; the blood and tissue concentrations obtained with the other cephalosporins tested were low by comparison. In the treatment of experimental Klebsiella pneumonia, cefodizime was superior to cefotaxime and cefuroxime. Counts of the number of viable bacteria present in the infected tissue showed that cefodizime exerted a more marked bactericidal effect than cefotaxime or cefuroxime. Hardly any therapeutic activity was seen with cefazolin.

Animals↗
PubMed1984

Cefodizime, an aminothiazolyl cephalosporin. IV. Influence on the immune system.

Studies concerning the activity of cefodizime (HR 221), on certain aspects of the immune response, were conducted. It was found that lymphocytes from Balb/c mice treated with 3 and 30 mg/kg/day of cefodizime display increased responsiveness to B-cell mitogens and specific antigens. Also, the amount of antigen specific antibody producing plaque forming cells was increased in these mice and was accompanied by a rise in the specific IgG haemagglutinin titer. These effects were not observed in lymphocytes obtained from NMRI mice that had been treated with cefodizime. Peritoneal macrophages from NMRI mice, treated with cefodizime prior to harvesting of the cells, contained increased levels of lysosomal enzymes, developed enhanced chemiluminescent reaction to stimuli and showed elevated pinocytosis rates. Furthermore, NMRI mice treated with cefodizime during the immunization, developed enhanced DTH-reaction, when challenged with the antigen (SRBC). The prophylactic treatment of Balb/c mice with cefodizime (2 X 30 mg/kg/day ip for 4 days) significantly prolonged the mean survival time of the animals after intravenous infection with Candida albicans 200/175 (16.7 days as against 3.5 days in the case of the controls). This stimulatory effect of cefodizime on the host defence system was not observed for NMRI mice. Treatment with latamoxef or cefoperazone under the same experimental conditions did not reduce the susceptibility of mice to C. albicans. The protective activity of cefodizime against C. albicans in Balb/c mice, may be due to the immuno-stimulatory activity of this agent.

Animals↗