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Biomedical subjects

H Hof

Publications and source records attributed to H Hof.

At least 145 records · Page 8Linked to original sources

Antibacterial activity of GO 10213, a nitroimidazole derivative.

Compound GO 10213, a 5-nitroimidazole substituted at the 2 position, is more active against aerobic, microaerophilic, and anaerobic bacteria than metronidazole. The MICs for Salmonella typhimurium (2 to 128 micrograms/ml), Campylobacter spp. (0.06 to 16 micrograms/ml) and Bacteroides spp. (0.03 to 0.25 micrograms/ml) are definitely lower than those of metronidazole. Niridazole, a 5-nitrothiazole, is still more active.

Antitrichomonal Agents↗

Effect of different nitroheterocyclic compounds on aerobic, microaerophilic, and anaerobic bacteria.

The antibacterial activities of different nitroheterocyclic compounds were assessed by an agar dilution method against aerobic, microaerophilic, and anaerobic bacteria. Nitronaphthofurans inhibited the multiplication of aerobic bacteria at low concentrations (MIC for 50% of strains tested [MIC50], 1 mg/liter). Under anaerobic growth conditions the MICs were found to be even lower. The rough, DNA repair-deficient mutants of Salmonella typhimurium were more susceptible, whereas nitroreductase-deficient strains were resistant. Microaerophilic campylobacter isolates could be divided into two groups, one of which was as susceptible as aerobic bacteria (MIC50, 1 mg/liter) and the other of which was more highly susceptible (MIC50, 0.015 mg/liter). All anaerobic bacteria tested were susceptible to nitronaphthofurans (MIC50, 0.125 mg/liter). Nitrothiazole exerted antibacterial activities similar to those of the nitronaphthofurans. Metronidazole, a nitroimidazole derivative, and nitrofurans were definitely less active. Nitrobenzofurans showed relatively high MICs.

Anti-Bacterial Agents↗

[Pathogenicity of Listeria].

20 different Listeria strains which hitherto have been all classed with the same serovar 3 of L. monocytogenes because of common surface markers, differ markedly in respect to their pathogenic capacities. Some strains are virulent, because they are able to multiply within a normal, adult mouse. Others show only weak virulence, since they survive within the host for several days. Multiplication, however, does not occur. Still other strains are rapidly eliminated and thus avirulent. These characteristics are still more pronounced in the compromised host. The avirulent strains are even not able to multiply in mice deprived of macrophage function, in T-lymphocyte-deficient mice or in newborn mice. These avirulent strains have to be classified into the new species of L. innuocua because of biochemical markers, whereby the absence of hemolysin production is crucial. Whereas priming of protective immunity is only possible by strains of high and intermediate virulence of L. monocytogenes, boosting of pre-existing immunity could also be achieved by the avirulent strain of L. innocua.

Animals↗

[Double infection with Yersinia enterocolitica 0:3 and 0:9].

An unusual case of Yersiniosis was observed in a 20-year-old woman. Except for an extraordinarily severe onset the clinical course was not remarkable. But two different strains of Yersinia were repeatedly isolated. While strain serotype 0:9 was demonstrated only transiently and gave an only weak immune reaction, serotype 0:3 persisted longer and stimulated a strong immune reaction. But both strains had similar virulence characteristics in different tests, such as plasmid demonstration, autoagglutination, growth on Ca-deficient agar, and in mice.

Adult↗

Therapeutic activities of nitrothiazole derivatives in experimental infections with Salmonella typhimurium and Bacteroides fragilis.

The antibacterial activities of niridazole (AmbilharR) and 12 other newly synthesized nitrothiazole derivatives were examined. Most of these compounds were active in vitro against Salmonella typhimurium (MICs 1-4 mg/l) and Bacteroides fragilis (MICs 0.015-0.03 mg/l). A therapeutic effect as determined by a reduction of bacterial counts per spleen of mice infected with Salm. typhimurium could only be achieved with those agents which displayed a similar side chain as niridazole, i.e. an imidazolidinone ring. Other nitrothiazole derivatives with a cleaved imidazolidinone ring as the side chain, although active in vitro, could not exert a reduction of bacterial counts in vivo. Similar results were obtained in mice infected with Bact. fragilis. Whereas niridazole and another nitrothiazole derivative with an imidazolidinone ring in the side chain were able to reduce the bacterial counts in a subcutaneous abscess, the derivative with a laminar side chain was inactive in vivo, although highly active in vitro.

Abscess↗

Murine model for therapy of listeriosis in the compromised host. IV. Cotrimoxazole.

Mice infected with a cotrimoxazole-susceptible strain of Listeria monocytogenes (MIC 0.25 mg/l) were highly protected by a short-lived therapy with this drug. The excellent activity of ampicillin, however, was not achieved. Only the combination of trimethoprim and sulfamethoxazole gave sufficient protection. In dextran sulfate-treated mice, highly susceptible to listeria infection, cotrimoxazole showed also good activity. In the nude, athymic mouse, however, when the deficient immune system did not afford assistance to the elimination of bacteria, only transient reduction of bacterial counts occurred.

Ampicillin↗

[Mutagenic activity of nitrothiazole compounds].

The mutagenic activities of different nitrothiazole derivatives were examined by the Ames-test. Such nitrothiazoles which display pronounced antibacterial properties against aerobic as well as anaerobic bacteria exert strong mutagenic activities. Thereby, both base pair substitution and frame-shift mutation occur. Reduction of the nitro-group of the nitrothiazoles by bacterial nitroreductases is a prerequisite for these mutagenic activities. In contrast, nitrothiazole derivatives which are unable to inhibit bacterial multiplication are also not mutagenic.

Chemical Phenomena↗

Effects of cyclosporin A on experimental infection with Listeria monocytogenes.

The effects of cyclosporin A on primary and secondary infection of mice with Listeria monocytogenes was studied both at the microbiological and the histomorphological level. This drug, when given in a dose of 100 mg/kg/day, was found to inhibit the development of protective immunity after primary infection as well as the expression of acquired immunity to challenge infection as determined by counting of bacterial numbers in the spleen. The manifestation of delayed type hypersensitivity was also impaired. When the cellular immune system was functionally intact, the formation of granulomas composed of macrophages and lymphocytes enabled the animals to overcome the Listeria infection. In mice treated with cyclosporin A protective granulomatous reaction during secondary infection did not occur. Instead numerous necropurulent lesions developed in the reticuloendothelial organs, such as spleen and liver, of animals unable to control the lethal infection.

Animals↗

Virulence of different strains of Listeria monocytogenes serovar 1/2a.

Different strains of Listeria monocytogenes serovar 1/2a were used to infect mice. A smooth, haemolytic strain multiplied in the spleen of normal adult mice and induced a long-lasting immunity to subsequent challenge infection. When the animals were treated with dextran sulphate (DS) Listeriae multiplied more rapidly and death followed within a few days. When normal baby mice were infected with this organism, fatal infection occurred. In nude mice a chronic infection developed. Secondly, a rough, haemolytic strain was used to infect mice. In normal adult mice no multiplication of this strain was observed. This holds true also for DS-treated animals. In nude mice the bacteria were eliminated slowly. Normal baby mice could only be killed if the infective dose was increased. This strain was considered to be intermediate in virulence. The infection stimulated a considerable immune response in mice, although to a lesser degree than the smooth, haemolytic Listeria strain. Thirdly, a smooth, non-haemolytic strain of L. monocytogenes serovar 1/2a was used. The bacteria were rapidly eliminated in normal, in DS-treated and in nude animals. Normal baby mice did not develop fatal disease, so it was considered that this strain of L. monocytogenes serovar 1/2a was avirulent. This variant was found to be non-immunogenic. A boosting of immunity of animals by this avirulent Listeria strain was, however, found to be possible. A reasonable explanation for the rapid elimination of avirulent L. monocytogenes serovar 1/2a from mice cannot be presented at this time. Whereas it is known that the macrophage system and the T-lymphocytes play an essential role in the resistance to virulent Listeriae, there is no increased susceptibility of the avirulent bacteria to these defence mechanisms. Other bacterial properties, such as serum sensitivity and lysozyme susceptibility, are likewise considered to be unimportant.

Animals↗

Failure of cephalosporins to cure experimental listeriosis.

In vitro, 15 strains of various serotypes of Listeria monocytogenes were found to be susceptible to cefazedone and cephalotin. Other cephalosporins, such as cefotaxime, were much less active. In spite of their relatively good in vitro activities, however, neither cefazedone nor cephalotin reduced the bacterial counts in mice infected with a virulent strain of L. monocytogenes. In contrast, ampicillin was active both in vitro and in vivo. Cephalosporins should not be used clinically for treating listeriosis.

Ampicillin↗

Antibacterial activities of nitrothiazole derivatives.

A new group of chemical agents with pronounced antibacterial activities is presented. Different nitrothiazole derivatives, but not all, exhibit antibacterial activities similar to that of niridazole (AmbilharR), a nitrothiazolyl-imidazolidinone. Certain aerobic bacteria are moderately susceptible to these agents. The efficacy of these agents is almost comparable to that of ampicillin and tetracyline. It is much better than the efficacy of nitrofuran derivatives, the nitroimidazole derivatives being inactive. The mode of action of the nitrothiazole derivatives is bactericidal. Against anaerobic bacteria the nitrothiazole derivatives are unique, since the extremely low MIC's are not approached by any other of the nitro-compounds nor by any other of the common antibiotics tested, such as clindamycin, ampicillin and tetracycline. It is suggested that the nitrogroup of the nitrothiazole ring moiety represents the chemical structure responsible for their excellent antibacterial activities.

Anti-Bacterial Agents↗

Antibacterial activities of nitrothiazole against Campylobacter jejuni and Campylobacter coli.

Niridazole (Ambilhar) and three other newly synthesized nitrothiazole derivatives were highly active against 19 microaerophilic campylobacters (minimum concentration required to inhibit 50% of strains [MIC50], 0.0075 to 0.015 mg/liter). There were, however, considerable differences in the susceptibility among strains tested, and one nitrothiazole derivative was rather inactive (MIC50, 2 mg/liter). Nitroimidazole derivatives, such as metronidazole and tinidazole, were less active (MIC50, 2 and 4 mg/liter, respectively). The nitrofuran derivatives, such as nitrofurazone and nitrofurantoin, were also less active (MIC50, 1 mg/liter). Niridazole and another potent nitrothiazole derivative killed the campylobacters rapidly at low concentrations. In contrast, much higher concentrations of metronidazole were required to achieve bactericidal values.

Anti-Bacterial Agents↗

Murine model for therapy of listeriosis in the compromised host. III. The effect of rifampicin.

10 different strains of Listeria monocytogenes tested in vitro were found to be susceptible to rifampicin showing minimal inhibitory concentrations between 0.0075 and 0.06 microgram/ml. Mice infected with a virulent strain of L. monocytogenes were treated with this antibiotic. Bacterial counts rapidly declined. In dextran sulfate-treated animals, deprived of their macrophage system and consequently highly susceptible to Listeria infection, rifampicin was able to protect the animals. Furthermore, nude athymic mice, chronically infected with L. monocytogenes, were also nearly cured. A few remaining bacteria, however, started to multiply after cessation of therapy, so that a relapse was noted. Development of resistance of L. monocytogenes to rifampicin during treatment was not observed.

Animals↗

The role of macrophages in acquired cell-mediated immunity to Toxoplasma gondii.

Mice immunized by primary infection with an avirulent strain of Toxoplasma gondii were protected against challenge infection with a highly virulent strain, even though macrophages were eliminated either by dextran sulfate or by carbon ink. This findings differs strikingly from previous results obtained in similar experiments with other intracellular pathogens such as Listeria monocytogenes and Salmonella typhimurium. It is therefore concluded that the macrophage population, which plays an essential role in the cell-mediated immunity to reinfection with L. monocytogenes and S. typhimurium, is not of primary importance in cell-mediated immunity to reinfection with T. gondii.

Animals↗

Course of infection and development of immunity in experimental infection of mice with Listeria serotypes.

NMRI mice were experimentally infected with Listeria monocytogenes serotypes 1/2b, 3a, 4b, and 4d and Listeria innocua serotype 6b by different means. The course of infection was monitored, using bacteriological and histological methods. The following typical features of experimental infection with the various L. monocytogenes and L. innocua serotypes were observed. (i) On the basis of the mean lethal dose, L. monocytogenes 4b, 4d, and 1/2b proved to be mouse pathogenic, although to different degrees, L. monocytogenes 3a and L. innocua can be regarded as nonpathogenic for NMRI mice. The virulence of L. monocytogenes serotype 4d was increased 1,000-fold after adaptation to mice. (ii) Primary infection with any serotype of L. monocytogenes or L. innocua resulted in protection against a lethal challenge with the most virulent serotype, 4b. This protective immunity could be transferred by spleen cells. Compared with the duration of immunity achieved by infection with L. monocytogenes serotype 4b, the protection induced by infection with L. innocua was short lived and dose dependent. The data obtained also suggest that immunity after experimental infection with any serotype of L. monocytogenes or L. innocua is produced only when the animal host is filled with bacteria. (iii) The distribution of the germs in the internal organs of the mouse shortly after infection was dependent on the route of infection rather than on the serotype used. (iv) The main difference among the Listeria serotypes tested was their ability to multiply within the host and to induce a granulomatous inflammation. The results indicate that mouse pathogenicity and virulence of Listeria spp. cannot be defined only by the capacity of the bacteria to infect or kill conventional mice. Such a definition should include an analysis of the immune system of the host, a kinetic study of experimental infection, and a histomorphological evaluation of the lesions induced.

Adaptation, Physiological↗

Cloned hemolysin genes from Escherichia coli that cause urinary tract infection determine different levels of toxicity in mice.

After intraperitoneal injection of mice with Escherichia coli strains isolated from patients with urinary tract infections, the mortality due to hemolytic (Hly+) and nonhemolytic (Hly-) isolates was 77 and 40%, respectively. Deletion of the chromosomal hemolysin (hly) determinant in an E. coli O6:K15:H31 urinary tract infection strain led to a significant reduction in toxicity for mice, and its reintroduction on a recombinant plasmid partially restored the original toxicity. Although introduction of the cloned plasmid pHly152-encoded hly determinant into the Hly- E. coli O6 mutant strain increased toxicity by only a marginal degree, transformation with the cloned chromosomal hly determinants from two E. coli strains of serotypes O18ac:K5:H- and O75:K95:H? resulted in markedly greater toxicity, even exceeding that of the original Hly+ E. coli O6 wild-type strain.

Animals↗