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Biomedical subjects

R A Fromtling

Publications and source records attributed to R A Fromtling.

At least 55 records · Page 3Linked to original sources
PubMed1985

Norfloxacin versus trimethoprim-sulphamethoxazole: efficacy in a model of ascending urinary tract infection in normal and streptozotocin-induced diabetic mice.

A model of ascending urinary tract infection due to an isolate of Escherichia coli was developed in normal and streptozotocin-induced mice to compare the efficacy of norfloxacin and trimethoprim-sulphamethoxazole. Norfloxacin and trimethoprim-sulphamethoxazole both were effective in reducing the number of colony forming units of E. coli from the kidneys of normal experimentally-infected mice, although norfloxacin yielded a greater quantitative reduction of colony forming units. Norfloxacin was substantially more effective than trimethoprim-sulphamethoxazole in reducing the number of colony forming units from kidney homogenates when the test animals were diabetic. This study supports the initiation of clinical trials to evaluate norfloxacin in diabetic patients.

Animals↗
PubMed1985

Chemiluminescence as a tool for the evaluation of antimicrobial agents: a review.

Chemiluminescence is a measure of the respiratory burst of phagocytic immune cells following stimulation by antigen. Measurement of chemiluminescence by scintillation counters set in the out of coincidence mode or by instruments designed specifically to measure chemiluminescence is an accurate, reproducible means of evaluating the immune potential of chemiluminescence emiting cell populations. One area under recent investigation has been the study of the effect of antimicrobial agents on the ability of various immune cell populations to emit chemiluminescence. This technique permits the investigator to test the effect of a drug on the activity of immune cell populations. The purpose of this review is to describe chemiluminescence, the basic kinetics of the response following stimulation with various antigens, and the reported effects of antimicrobial agents on chemiluminescence which have appeared in the literature.

Animals↗
PubMed1984

In vitro antifungal activities of Bay n 7133 and Bay L 9139, two new orally absorbed antifungal imidazole derivatives, against pathogenic yeasts.

Bay n 7133 and Bay L 9139 (Bayer AG, Wuppertal, Fed. Rep. Germany) are new, orally absorbable, antifungal imidazole derivatives. In vitro, Bay n 7133 was comparable to ketoconazole and miconazole when tested against isolates of Candida albicans and Cryptococcus neoformans. Bay L 9139 also was active against these organisms but to a lesser degree than the other imidazoles. LY 121019, an analog of echinocandin B, was also tested. It proved to be the most active antimycotic against C. albicans but the least active against C. neoformans. Optimal results were obtained in tests employing Kimmig's agar, a medium previously described for use in susceptibility tests with antifungal agents.

Antifungal Agents↗
PubMed1984

Cryptococcus neoformans: in vivo protection of mice by pretreatment with pyran copolymer.

Synthetic polyanions have been shown to alter host resistance to infection. The anticryptococcal effect of pyran copolymer was assessed in vivo and in vitro. Pretreatment with pyran copolymer significantly extended mean survival in mice lethally infected with Cryptococcus neoformans when compared to untreated animals (p less than 0.01). The anticryptococcal effect of peritoneal exudate cells (PEC) elicited by 10% thioglycollate or pyran copolymer (25 mg/kg) was assessed in vitro. Initial percent phagocytosis of both encapsulated and non-encapsulated isolates of C. neoformans was greatest in the pyran elicited PEC. Significant killing of C. neoformans in vitro was observed only in pyran-activated PEC cultures combined with non-encapsulated cells of C. neoformans, although pyran PEC did inhibit initial growth of phagocytized encapsulated yeast cells. The protection of pyran copolymer pretreated mice from infection with C. neoformans, but the absence of significant killing of encapsulated yeast in vitro suggest a complex mechanism of host defense which may involve an activation of the reticuloendothelial system by pyran copolymer.

Animals↗
PubMed1984

Immunotoxic effects of diethylstilbestrol on host resistance: comparison with cyclophosphamide.

To evaluate the usefulness of host resistance assays for measurement of immunotoxicologic effects of chemicals, the immunosuppressive effects of exposure to diethylstilbestrol (DES) were compared with the effects of treatment with the known immunosuppressive drug cyclophosphamide (CPS). A panel of six host resistance models was evaluated, including infection with the bacterium Listeria monocytogenes, herpes simplex virus type 2 (HSV-2), and encephalomyocarditis virus (EMC), the yeast Cryptococcus neoformans, the parasite Naegleria fowleri, and transplantation of the B16F10 melanoma tumor. The results demonstrate a general correlation between the effects of CPS and DES on host resistance. Acute treatment with CPS (200 mg/kg) markedly depressed resistance to the microbial infections with L. monocytogenes and HSV, and exposure to DES usually also decreased resistance in a dose dependent manner. Moreover, CPS had no marked effect on resistance to N. fowleri and EMC virus, and exposure to DES also had a neglible or slight effect. There were, however, two model systems in which the effects of CPS and DES diverged. Whereas treatment with DES produced no significant effect on resistance to C. neoformans, acute treatment with CPS prior to the fungal infection produced a marked increase in resistance. Also, while treatment with CPS markedly increased B16F10 lung metastases, treatment with DES significantly decreased the incidence and number of lung metastases. The data support the general validity of host resistance assays, particularly with models of short disease course, for measuring immunosuppression. However, the results also emphasize the complexity of interpreting effects of environmental chemicals on host resistance, because of the interplay of such factors as relative times of exposure to the chemical in relation to pathogenesis of infection, the length of the disease course, the nature of the operative host defense mechanisms, and the compensatory recovery of these mechanisms.

Amebiasis↗
PubMed1984

Comparative pathogenicity of auxotrophic mutants of Candida albicans.

An induced mutant of Candida albicans with greatly decreased virulence for mice is described. The mutant was one of five auxotrophic mutants obtained by ultraviolet irradiation of a clinical isolate (strain MY 1044). The five mutants included two methionine auxotrophs, one methionine-cysteine auxotroph, one temperature-sensitive serine auxotroph, and one auxotroph with unknown growth requirements. Each of the mutants produced normal mycelium and had a normal profile of susceptibility to four antifungal drugs. The virulence of each mutant was compared with the parent strain by LD50 determination in mice. Four of the five auxotrophs exhibited LD50's that were not significantly different from the parent strain (mean LD50 = 7.5 x 10(5) cells). However, the temperature-sensitive serine auxotroph was significantly less virulent than the parent strain (LD50 greater than 10(7) cells), even though it grew well in vivo and in mouse serum at 37 degrees C in vitro. Use of this mutant in conjunction with its "isogenic" parent should help to elucidate true virulence factors in C. albicans.

Animals↗
PubMed1984

Antibacterial efficacy of norfloxacin, trimethoprim-sulfamethoxazole, and gentamicin in experimentally-infected normal and streptozotocin-induced diabetic mice.

Systemic bacterial infections due to Escherichia coli MB 2884, Proteus mirabilis MB 3125 and Klebsiella pneumoniae MB 4005 were well controlled by treatment with norfloxacin both in normal and streptozotocin-induced diabetic mice. similar observations were made when trimethoprim-sulfamethoxazole was used against susceptible pathogens. Systemic infection due to Pseudomonas aeruginosa MB 4700 was well controlled by norfloxacin and gentamicin in normal mice; this infection was more refractory to treatment by both drugs in diabetic animals. These observations suggest that norfloxacin may be an effective drug in the treatment of bacterial infections which may occur under diabetic conditions, and further investigation is warranted.

Animals↗
PubMed1984

In vitro effect of pH and glucose concentration on the antibacterial activity of norfloxacin in urine.

The in vitro effect of pH and glucose concentration on the antibacterial activity of norfloxacin in urine was studied. Norfloxacin effectively inhibited the growth of four gram-negative pathogens in urine in vitro at pH values of 6.0, 7.0, and 8.0. The antibacterial activity of norfloxacin in urine was reduced severalfold at pH 6, but minimum inhibitory concentrations (MICs) at this pH remained clinically significant. Glucose at concentrations of 200 mg/dl and 400 mg/dl (simulating glucosuria of diabetes) did not significantly affect the antibacterial activity of norfloxacin when tested against clinical isolates of Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, or Pseudomonas aeruginosa. Norfloxacin appears to be a highly effective antibiotic in vitro under conditions which simulate normal and diabetic states.

Anti-Bacterial Agents↗
PubMed1984

Effects of diethylstilbestrol and cyclophosphamide on the pathogenesis of experimental Cryptococcus neoformans infections.

Treatment of mice with a single dose of cyclophosphamide 24 h before challenge with Cryptococcus neoformans increased host survival, whereas treatment with 10 daily exposures of cyclophosphamide, starting 2 days before challenge, markedly reduced survival in mice challenged on the second day of drug treatment. Treatment with 14 daily exposures of diethylstilbestrol before challenge with C. neoformans did not markedly affect host survival. A correlation was sought between the distribution of radiolabeled C. neoformans and host survival. Radiolabeled C. neoformans administered intravenously was cleared rapidly from the blood of naive mice and accumulated in the lungs, liver and kidney within 1 h. The radiolabeled yeasts were subsequently cleared from the lungs. The distribution of radiolabeled C. neoformans among organs was generally the same in control mice and mice treated with diethylstilbestrol of various cyclophosphamide regimens after 3 or 24 h. The distribution of C. neoformans measured as colony forming units was generally in agreement with results from radioactivity measurements for animals sacrificed 3 or 24 h after challenge. One week after challenge, C. neoformans colonies were grown from the brain, liver and kidneys. C. neoformans was found in the brain within 1 h after i.v. challenge, suggesting that the central nervous system disease in mice challenged i.v. resulted from a primary infection of the brain.

Animals↗
PubMed1983

In vitro antibacterial activity of norfloxacin compared with eight other antimicrobial agents.

The antibacterial activity of norfloxacin, an organic acid structurally related to nalidixic acid, was compared with that of the oral cephalosporins cefaclor and cephalexin, and with that of nalidixic acid, cinoxacin, amikacin, ampicillin, trimethoprim alone and the combination of trimethoprim and sulfamethoxazole. Agar dilution studies were performed with a total of 398 clinical isolates of gram-negative bacteria. Norfloxacin was found to be the most active drug studied against each of the different groups of organisms tested. MIC90 values for norfloxacin were as follows: Citrobacter spp., 2 micrograms/ml; Enterobacter spp., 0.13 micrograms/ml; Escherichia coli, 0.06 micrograms/ml; Klebsiella spp., 0.13 micrograms/ml; Proteus spp., 0.06 micrograms/ml; Salmonella spp., 1 microgram/ml; Serratia spp., 0.13 micrograms/ml; and Pseudomonas spp., 2 micrograms/ml. MIC90 values for the other drugs were 4 micrograms/ml or greater and many organisms were totally resistant to one or more of the other drugs (MIC greater than 128 micrograms/ml). Cross resistance between norfloxacin and the related drugs nalidixic acid and cinoxacin was not observed.

Anti-Bacterial Agents↗
PubMed1983

In-vitro inhibitory activities of 2 new orally absorbable imidazole derivatives: BAY n 7133 and BAY 1 9139.

The inhibitory activities of 2 new orally absorbed antifungal imidazole derivatives, BAY n 7133 and BAY 1 9139, were compared in vitro with those of ketoconazole and miconazole. Clinical isolates of pathogenic fungi tested included 35 yeasts, 62 dimorphic fungal pathogens, 37 filamentous fungi and 31 dermatophytes. LY 121019, a semisynthetic analog of echinocandin B, was included in tests with the pathogenic yeasts. Both BAY n 7133 and BAY 1 9139 were found to be broad spectrum antifungal agents. The spectra of these newer compounds were comparable to those of ketoconazole and miconazole; however only BAY n 7133 resembled these latter 2 imidazoles quantitatively in terms of the degree of antifungal activity as indicated by measurable MICs. In contrast, the spectrum of LY 121019 appeared to be confirmed only to isolates of Candida.

Antifungal Agents↗
PubMed1983

Immunization of mice with stable, acapsular, yeast-like mutants of Cryptococcus neoformans.

Immune responses, including lymphocyte transformation and protection, were evaluated in a new model of experimental murine cryptococcosis. Newly developed, genetically stable, acapsular mutants of Cryptococcus neoformans were used to immunize C3H/HeN mice. Intraperitoneal and subcutaneous routes of immunization without adjuvant were studied. Spleen cells and pooled popliteal and inguinal lymph node cells responded significantly to heat-killed, whole-cell C. neoformans antigen but not to Candida albicans antigen in lymphocyte transformation assays. No significant difference in lymphocyte transformation response to antigens was observed between intraperitoneally and subcutaneously immunized animals. Mean survival time of immunized mice was extended significantly in comparison to controls following intravenous challenge with virulent C. neoformans. Degree of protection was independent of route of immunization but dependent upon the magnitude of the challenge inoculum. This model should prove valuable in the study of immunoregulation of cryptococcosis and vaccine development.

Animals↗
PubMed1983

Ethanol-cephalosporin antibiotic interactions: an animal model for the detection of disulfiram (Antabuse)-like effects.

Disulfiram (Antabuse)-like reactions occurring in patients undergoing antibacterial therapy with certain cephalosporin antibiotics, and after ingestion of ethanol, are well documented. A murine model is described which may prove useful in the detection of compounds likely to produce this effect. Eight cephem compounds (moxalactam, cefamandole, cefmetazole, cefonicid, cefmenoxime, cefoperazone, cefotiam, ceforanide) each carrying an N-methyltetrazolethiol substituent in the 3-position of the dihydrothiazine ring of the parent antibiotic were capable of inducing a disulfiram-like reaction in the test animals. Evidence is presented which strongly suggests a direct relationship between N-methyltetrazolethiol and related heterocyclic thiols and the ability to induce this reaction.

Animals↗
PubMed1983

A new polyene with antimycotic activity produced by a streptomycete from the rhizosphere of an indoor plant.

From the rhizosphere of a potted Sanseviera trifasciata, a Streptomyces griseus strain with a broad antifungal activity was isolated; in the soil of this plant, a sole hyphomycete, Aspergillus niger, was found in pure culture at 37 degrees C. This streptomycete produced a polyene, belonging to the pentaene group. It was found to inhibit, in vitro, the growth of all the 123 strains tested; the strains belonging to the genera Aspergillus, Cryptococcus, Candida, Trichophyton, Epidermophyton, Microsporum, Penicillium and Mucor. An antimycotic activity of this substance was also found to be present after i.v. administration to white mice infected with Cr. neoformans. Toxicological tests will have to show if this polyene could be considered as a candidate antimycotic drug. The soil of potted indoor plants is discussed as a possible habitat for streptomycetes with defined antifungal activities.

Animals↗
PubMed1982

Decreased virulence in stable, acapsular mutants of cryptococcus neoformans.

Six acapsular strains of Cryptococcus neoformans obtained by chemical mutagenesis failed to produce a capsule in vivo and were avirulent in mice following high dose intramuscular, intraperitoneal or intravenous inoculation. Peritoneal granulomas were observed in all animals inoculated with the acapsular mutants. These granulomas were characterized by a large central mass consisting of intact, degenerating and necrotic yeast cells. This was surrounded by concentric layers of a broad band of histiocytes, a narrow band of fibroblasts, and around the periphery, a mass of lymphocytes and plasma cells. These isolates did not revert to an encapsulated or virulent state after more than a year of subculturing or 18 passages through mice.

Animals↗
PubMed1982

Cryptococcal capsular polysaccharide clearance in nonimmune mice.

Clearance of cryptococcal polysaccharide (CP) from tissues and body fluids of nonimmune mice was studied. Mice were injected intravenously only with one mg of purified CP, and serum, urine and tissues were obtained from each animal at various intervals for a period of 84 days. Tissue extracts, serum and urine were tested for CP content by enzyme-linked immunosorbent assay (ELISA) and latex agglutination. High concentrations of CP were detected by both assays one-half hour after injection in blood (serum), liver, spleen, kidney and lung (extracts). The duration of ELISA detectable CP was longest (70 days) in liver and spleen and shortest (14 days) in lung extract. By 14 days after injection, concentration of CP in the blood fell below that found in the liver and spleen. CP remained detectable (titers 32-64) after all other extracts became negative. These results indicate that CP is stored in tissues (binding mechanism and site unknown), and that the liver and spleen possess greater storage capacity than other tissues. Antibody (IgM) to CP appeared in low titer on the 14th day and thereafter.

Animals↗