Transformation of C18-, C19- and C21-steroids by cultures of Candida albicans.
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Adrenal Cortex Hormones↗
Biomedical subjects
A Wildfeuer
Publications and source records attributed to A Wildfeuer.
Determination of fluconazole concentrations in the prostatic and seminal vesicle fluid (split ejaculate).
The concentrations of fluconazole, a systemic antifungal agent, were determined in the split ejaculate of seven healthy volunteers. Following once-daily oral administration of fluconazole 200 mg over a period of 5 days, the fluconazole levels were determined in ejaculate samples which had been divided into two consecutive fractions upon collection. Simultaneously, a blood sample was drawn for the determination of fluconazole serum levels. It was shown that the fluconazole concentrations determined in both ejaculate fractions corresponded to those found in the serum. As the first fraction of the ejaculate originates in the prostate, the prostatic fluconazole concentrations are likely to be similar to the fluconazole levels found in th ejaculate.
AIDS-Related Opportunistic Infections↗
The in vitro activity of fluconazole against fungi involved in dermal infections.
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Arthrodermataceae↗
Bioavailability of fluconazole in the skin after oral medication.
Fluconazole is an antimycotic drug which until now has been used mostly in the systemic therapy of yeast infections. We have now demonstrated the presence of this drug in various skin structures. After administration of 50 mg of fluconazole per day for 12 days to healthy volunteers, the following mean drug concentrations were measured: serum 1.81 micrograms ml-1, sweat 4.58 micrograms ml-1, dermis-epidermis (without stratum corneum) 2.77 micrograms g-1 and stratum corneum 73 micrograms g-1. Thus, 4 h after the last dose the antimycotic attains a 40-fold higher concentration in the stratum corneum than in serum. One week after ending the oral treatment, 5.8 micrograms g-1 fluconazole was present in stratum corneum. After daily ingestion of 200 mg of fluconazole for 5 days there was a further increase in the mean concentration of fluconazole in stratum corneum, to 127 micrograms g-1. Even 4-5 months after completing the oral treatment, fluconazole was detectable in the head hair and toenails of healthy volunteers. Fluconazole is eliminated from the stratum corneum about 2-3 times more slowly than from serum or plasma. After oral administration fluconazole evidently accumulated rapidly and intensively into the stratum corneum. The concentrations then attained or exceeded the in vitro minimal inhibitory concentrations of fluconazole for most of the dermatophytes and yeasts which are involved in cutaneous mycoses.
Administration, Oral↗
Detection of Candida albicans DNA with a yeast-specific primer system by polymerase chain reaction.
The in vitro and in vivo selectivity and sensitivity of a yeast-specific primer system was investigated. A two-step polymerase chain reaction (PCR) was used: the first amplified a 245-bp fragment of the gene for cytochrome P450L1A1 and the second a product of 193 bp. This nested PCR produced an approximately 1000-fold increase in the sensitivity of the test for Candida albicans DNA compared with the first primer pair. The lower level of sensitivity of the test in physiological saline and tissue homogenate was about 10 C. albicans cells ml-1. On the other hand, the sensitivity of the nested PCR method was reduced by a factor of more than 1000 when C. albicans was fixed with 4% formalin. After i.v. injection of different doses of C. albicans into mice, the yeast could be demonstrated in blood and in six different organs. The nested PCR was to some extent more sensitive than culturing for the detection of the yeast in the specimens of organs such as lung, cardiac muscle, liver, kidneys and brain. In contrast, in blood and spleen the culture was superior to the PCR technique used. Nested PCR is thus a useful additional method for the demonstration of yeasts.
Animals↗
A new pharmaceutical concept for the treatment of oropharyngeal and oesophageal candidosis with fluconazole.
Administration of fluconazole in capsule form has proved effective in the prophylaxis and treatment of mucosal candidosis, particularly in immunosuppressed patients. An additional topical effect in oropharyngeal and oesophageal candidosis might be expected with a fluconazole suspension. This hypothesis was therefore tested in a crossover study in 12 healthy volunteers in whom the concentrations of the antimycotic were measured in saliva and plasma after oral administration of 100 mg fluconazole as either a capsule or a suspension. The time courses of the fluconazole concentrations were very similar with the two formulations in plasma, but significantly different in saliva. Thus, the mean Cmax for fluconazole in saliva of 551 micrograms ml-1 was reached 5 min after ingestion of the suspension, compared with a value of 3 micrograms ml-1 some 4 h after taking the capsule. The mean concentration of the antimycotic in saliva over the observation period (0-96 h) was more than 80% higher with the suspension than with the capsule.
Administration, Oral↗
In vitro evaluation of voriconazole against clinical isolates of yeasts, moulds and dermatophytes in comparison with itraconazole, ketoconazole, amphotericin B and griseofulvin.
The in vitro activity of voriconazole (UK-109, 496), a new antifungal triazole derivative, against 650 clinical isolates of yeasts, moulds and dermatophytes was compared with that of itraconazole, ketoconazole, amphotericin B and griseofulvin. The geometric means of the minimum inhibitory concentrations (MICs) of voriconazole were 0.05 microgram ml-1 against yeasts (n = 187), 0.58 microgram ml-1 against moulds (n = 260) and 0.08 microgram ml-1 against dermatophytes (n = 203). The overall activity of voriconazole against yeasts and moulds was good, being similar to that of itraconazole, ketoconazole and amphotericin B. Voriconazole was highly effective against Aspergillus fumigatus (mean MIC 0.23 microgram ml-1) and other Aspergillus species and showed noteworthy activity (mean MICs 0.08-0.78 microgram ml-1) against emerging and less common clinical isolates of opportunistic moulds, such as Alternaria spp., Cladosporium spp., Acremonium spp., Chrysosporium spp. and Fusarium spp. On the other hand, voriconazole was less active in vitro than the comparative agents studied against various species of zygomycetes, such as Mucor spp., Rhizopus spp. and Absidia spp. Voriconazole and the other two azoles, itraconazole and ketoconazole, were more active than griseofulvin in vitro against most dermatophytes tested.
Amphotericin B↗
Josamycin concentration in human ejaculate and its influence on sperm motility--a contribution to antibiotic therapy in andrological patients.
The concentration of josamycin was determined in the split ejaculate of 5 volunteers after oral administration for several days. One aim of this investigation was to examine the penetration of the macrolide antibiotic into the prostate and the seminal vesicles. 2.23 +/- 1.8 micrograms/ml josamycin was found in fraction I of the ejaculate, consisting mostly of prostatic secretion, and 1.56 +/- 1.37 micrograms/ml josamycin in fraction II comprising mainly secretions from the seminal vesicles. The concentrations of josamycin found in both fractions of the ejaculate are clearly comparable with serum levels of the antibiotic. Josamycin thus attains concentrations in the prostate and seminal vesicles which are effective against Mycoplasma and Chlamydia, pathogens of increasing importance in infections of the urogenital tract. In vitro studies on samples from 30 andrological patients showed that josamycin (0.5 micrograms/ml) did not impair, but even increased the motility of spermatozoa (p less than or equal to 0.01). On the basis of these results josamycin is recommended for the treatment of andrological patients. In particular, the specific antibacterial spectrum also indicates the use of this antibiotic for treatment of the partner when children are desired. The usual precautionary measures for pregnancy must then be adhered to.
Administration, Oral↗
Effect of anti-rheumatic drugs on the release of lysosomal enzymes from human leukocytes.
The release of lysosomal enzymes from human polymorphonuclear neutrophils (PMN) into the extracellular medium was selectively induced by the phagocytosis of zymosan particles. The "in vitro" effect on the release of lysosomal enzymes was determined for eight different substances used in the therapy of rheumatoid arthritis. Prednisolone and the three non-steroidal anti-rheumatic agents indomethacin, diclofenac and benoxaprofen only inhibited the release of various lysosomal enzymes at the elevated concentrations of 20-200 micrograms/ml. Of the four drugs examined which are used in basis therapy, Chloroquine and Levamisole exhibited the most clear-cut inhibition of the enzymes (at 20-200 micrograms/ml). The effect of gold salts was uncertain and D-penicillamine only inhibited the release of myeloperoxidase. The release of lysosomal enzymes from neutrophils is then largely resistant to anti-rheumatic agents--at least in the range of therapeutic concentrations. On the basis of these experimental results it seems questionable whether the relatively weak inhibition of lysosomal enzymes observed "in vitro" can contribute to the anti-rheumatic efficacy in patients of the drugs examined.
Anti-Inflammatory Agents↗
Effects of non-steroidal anti-inflammatory drugs on human leucocytes.
The action of 4 non steroidal anti-inflammatory drugs (NSAID) on the function of human polymorphonuclear neutrophils (PMN), monocytes and lymphocytes has been investigated and compared to that of prednisolone. Benoxaprofen and diclofenac inhibited the chemotaxis of leucocytes in a dose-dependent fashion in vitro whereas acetylsalicylic acid and indomethacin were inactive or effective on the migration of these cells at high concentrations only. Benoxaprofen did not reduce significantly (variance analysis, p = 0.05) the chemotactic locomotion of PMN or monocytes isolated from volunteers after repeated oral administration of the drug. The other function of the leucocytes investigated, which are essential for the defense of the host, were not suppressed by NSAID at therapeutic concentrations. From these experimental results it was concluded that Nsaid have a differing spectrum of biological activities and can act selectively on functions of leucocytes. However, the relevance of these findings to the effect of drugs on the inflammatory process is still unclear.
Anti-Inflammatory Agents↗
[Effect of piroxicam on the structure and function of joint cartilage].
Experimental studies on the dog were performed to investigate possible deleterious effects of non steroidal anti-inflammatory agents, in particular piroxicam, on healthy articular cartilage. Piroxicam, diclofenac, and indomethacin were administered orally to beagles over an 8-week period. Control animals received empty capsules during the same period. A variety of morphological investigations were carried out on the tissues of the knee joint following treatment. Macroscopically and at light microscopical level no differences in the structure of cartilage or synovial membrane were detected between control and test animals. Similarly, with the transmission electron microscope, no structural changes were observed between control and test groups (piroxicam-treated). The incorporation of radioactively labeled sulfur into cartilage proteoglycans was similar in piroxicam-treated and control dogs. Related studies involving the addition of piroxicam to isolated chondrocytes in vitro showed that the proliferative capacity and proteoglycan synthesis of chondrocytes were unaffected by this antirheumatic agent. It is concluded that piroxicam exerts no damaging effect on normal cartilage in the knee joint of the dog.
Animals↗