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Biomedical subjects

A Polak

Publications and source records attributed to A Polak.

At least 91 records · Page 5Linked to original sources
PubMed1982

Susceptibility to 5-fluorocytosine and prevalence of serotype in 402 Candida albicans isolates from the United States.

Candida albicans isolates from 402 patients with no prior history of treatment with 5-fluorocytosine were collected at five medical centers from different areas of the United States. Isolates could be separated into four groups based on their minimum inhibitory concentrations (MICs) to 5-fluorocytosine. Group I isolates (60%) had MICs less than or equal to 12.5 micrograms/ml after 7 days, whereas groups II (22%), III (14%), and IV (4%) demonstrated MICs greater than 12.5 micrograms/ml on days 7, 2, and 1, respectively. Serotypes A and B accounted for 50.7 and 49.3%, respectively, of the 398 isolates typed. Serotype B was less prevalent in group I (26%), but predominated in the more resistant groups, groups II (85%), III (86%), and IV (53%). The common practice of identifying as "resistant" those isolates with MICs greater than 12.5 micrograms/ml after 48 h of incubation would yield a resistance rate in the United States of 11.5 to 15.5% in four centers and 35% in the fifth. Although serotype B and small agar disk diffusion zone sizes correlated with poor 5-fluorocytosine susceptibility, their ability to predict tube dilution MICs was limited. The true predictive value of such tests awaits correlation with in vivo studies.

Candida albicans↗
PubMed1982

Combination therapy of experimental candidiasis, cryptococcosis and aspergillosis in mice.

Combination pairs of the major systematic antimycotic drugs, amphotericin B (AmphB), 5-fluorocytosine (5-FC) and ketoconazole (Ktz) were administered to mice with experimental candidiasis, cryptococcosis and aspergillosis at a variety of combination ratios. The 3 mycoses were produced with 3 strains each of Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus, respectively, which were preselected to represent 3 different degrees of 5-FC sensitivity ('normally sensitive', 'moderately resistant', and 'definitely resistant'). The life-prolonging effect of the combinations was compared with the effect of each partner administered alone at the same and at the double dosage. Using the U test of Mann and Whitney and setting limits which on the whole were more rigorous than those of the isobole methods commonly applied to the study of drug interactions, the effects of the concentrations were classified as 'synergistic', 'additive', 'indifferent' or 'antagonistic'. The combination AmphB plus 5-FC was definitely synergistic or definitely additive in all 3 candidiasis models, the most pronounced synergism occurring in the infection with the 'definitely 5-FC-resistant' C. albicans strain; in cryptococcosis produced by any of the 3 C. neoformans strains the effect was definitely additive, but only slightly additive or indifferent in the 3 aspergillosis models. The combination AmphB plus Ktz was slightly synergistic in candidiasis produced by one C. albicans strain, but definitely antagonistic in this mycosis produced by the remaining 2 strains of the same species; the combination was definitely additive or, even, slightly synergistic in the 3 cryptococcus models, but, again, antagonistic in aspergillosis produced by all 3 strains of A. fumigatus. 5-FC plus Ktz was additive or indifferent in the 3 candidiasis models, but throughout indifferent in cryptococcosis and aspergillosis.

Amphotericin B↗
PubMed1982

Oxiconazole, a new imidazole derivative. Evaluation of antifungal activity in vitro and in vivo.

The new imidazole derivative Z-[2,4-dichloro-2-imidazol-1-yl)acetophenone]-O-(2,4-dichlorobenzyl)-oxime nitrate (oxiconazole, Ro 13-8996) is characterized by a broad fungistatic spectrum against the agents of human mycoses in vitro. In addition, fungicidal activity of various degree was found in selected species (Aspergillus fumigatus, Cryptococcus neoformans, Candida albicans and Trichophyton mentagrophytes). Synthesis of DNA was inhibited by subinhibitory concentrations of oxiconazole in parallel to cell multiplication, whereas synthesis of RNA, protein and carbohydrate was decreased to a lesser extent. The most relevant findings was high topical activity in both trichophytosis in the guinea-pig and vaginal candidiasis in the rat. In these 2 models, oxiconazole proved to be more potent than several reference compounds from the group of imidazole antimycotics. Systemic oral activity of oxiconazole was also found in three mouse models, namely in dermal infection with T. mentagrophytes var. quinckeanum, systemic histoplasmosis and, just to a low degree, systemic candidiasis, but the compound proved to be inactive in cryptococcosis and aspergillosis in the mouse. Based on our findings, a clinical evaluation of oxiconazole as a topical antimycotic in human superficial mycosis, seems to be justified.

Animals↗
PubMed1981

The effect of 5-fluorocytosine on the synthesis of 80S ribosomes by pathogenic fungi.

We studied the influence of 5-fluorocytosine(5FC) on the monomeric 80S ribosomes isolated by gradient ultracentrifugation from Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus and Wangiella dermatitidis. Labelling of the cultures with 32PO4 and [3H]-leucine showed marked inhibition of both ribosomal RNA and ribosomal protein synthesized during the contact of the fungi with the drug. The degree of inhibition was very similar for the synthesis of both ribosomal constituents, (mostly 60-80% each during the initial hours of the contact). This indicates that some ribosomes were still synthesized in the presence of 5FC and that the drug inhibits the synthesis of complete ribosomes to the same extent as the synthesis of ribosomal RNA and protein. By labelling fungi with [14C]-5FC it was shown that in those 80S ribosomes that were still synthesized, large quantities of the drug were incorporated--doubtless as 5-fluorouracil (5FU) in RNA. It can be concluded that RNA containing 5FU is still capable of combining with protein to form complete ribosomes of normal conformation. This is, however, no proof that these ribosomes would have a normal function.

Cell-Free System↗
PubMed1981

The effect of 5-fluorocytosine on the germination of Aspergillus fumigatus and on subsequent nuclear division.

5-Fluorocytosine (5FC) inhibits the germination of the conidia of A. fumigatus. This is different from the lack of effect of 5FC on hyphal formation from blastospores of C. albicans because, unlike C. albicans, A. fumigatus requires DNA synthesis for germination, and this is inhibited by 5FC. A modified fluorescent Feulgen method has been developed to stain fungal nuclei in the presence and absence of 5FC. This method has shown that hyphae treated with 5FC have fewer nuclei than untreated hyphae. During hyphal growth, DNA synthesis and hyphal elongation in A. fumigatus are equally inhibited by 5FC. This is different from the differential effect of 5FC on C. albicans when hyphal elongation continues during an inhibition of DNA synthesis. The equal inhibition in A. fumigatus is clearly not unbalanced growth and so the action of 5FC on A. fumigatus is merely fungistatic.

Aspergillus fumigatus↗
PubMed1980

A study of fifty-eight patients with renal scarring associated with urinary tract infection.

Fifty-eight patients, three male and 55 female, with radiologically apparent renal scarring together with urinary tract infection have been followed for periods from five to 13 years. Control of urinary infection has been attempted by antibacterial treatment and prophylaxis, and radiological appearances, renal function and blood pressure have been monitored. Urinary infection was eliminated in 50 patients (86 per cent), all of whom became symptom-free. Evidence of new renal scarring was not seen, but three patients showed contraction of kidney size and three developed radio-opaque renal calculi. Vesico-ureteric reflux was demonstrated in 20 patients; surgical re-implantation of ureters was carried out in four patients and the indications for this operation are discussed. Of the 12 patients who had a raised serum creatinine at some time during the study only three showed progressive decline in renal function; the serum creatinine returned to normal in seven patients when infection was controlled. Hypertension was more common in patients with bilateral than in those with unilateral scarring, and all patients with evidence of impaired function at any time developed hypertension. We conclude that most patients with scarred kidneys and urinary infection can be rendered symptom-free by control of infection, and that there is some evidence that renal function can be preserved in this way.

Adolescent↗
PubMed1979

The effect of 5-fluorocytosine on the blastospores and hyphae of Candida albicans.

In Candida albicans the continued increase in dry weight, in cell volume and in hyphal length during 5FC treatment is mainly due to increased amount of carbohydrate despite the decreased amounts of nucleic acids. Incorporation studies with 32PO4 (for RNA) in C. albicans and with 3H-thymidine-monophosphate (for DNA) in a thymidine-utilising strain of Saccharomyces cerevisiae have shown that the decreased amounts of nucleic acids were due to an inhibition of synthesis of RNA and DNA by 5FC. Nuclear-staining techniques on the hyphal phase of C. albicans showed that 5FC inhibits nuclear division. The changes in amounts of protein during 5FC treatment do not wholly explain the changes in cell size although 14C-histidine incorporation experiments showed that protein synthesis continued in the presence of 5FC. 14C-glucose incorporation in the presence of 5FC showed an initial accelerated synthesis of carbohydrate with a maintained level of synthesis after 16 h. This abnormal pattern of synthesis correlates with the increase in amount of carbohydrate and in cell size and hyphal elongation. 5FC inhibits DNA synthesis, and all manifestations of unbalanced growth that culminate in the cell volume changes appear to be a consequence of that inhibition.

Candida albicans↗
PubMed1979

Pharmacokinetics of amphotericin B and flucytosine.

The absorption of flucytosine from the digestive tract is very good but minimal with amphotericin B. For this reason, amphotericin B has to be injected intravenously. Fungistatic levels are achieved rapidly with flucytosine and slowly with amphotericin B, since the dose has to be increased slowly. Distribution of flucytosine in other body fluids is high, whereas with amphotericin B it is poor. Flucytosine is excreted mainly via the kidney without metabolism, whereas amphotericin B is eliminated mainly by metabolism. Therefore, amphotericin B dosage does not have to be adapted to kidney function, which is the case for flucytosine. The half-life of flucytosine is short (hours), that of amphotericin B is long (days); flucytosine is haemodialysable, whereas amphotericin B, probably owing to the high protein binding, is not.

Amphotericin B↗
PubMed1979

A family with massive acute vitamin D intoxication.

Acute massive vitamin D overdosage occurred in a family after eating food cooked in a nut oil containing 5 million units of vitamin D3/ml. The plasma vitamin D was 55 and 60 i.u./ml in the father and mother respectively, and 9.6 i.u./ml in their 11-month-old infant (normal range, 0--1.6 i.u/ml). All the family presented with symptoms of hypercalcaemia and the infant responded quickly to prednisone. After steroids had failed to control the hypercalcaemia in the parents, neutral phosphate was successful, although necessary for 9 months. Before phosphate therapy it was shown that both parents were in strongly negative calcium balance, indicating that the vitamin D was mobilizing calcium from bone. Eleven years later all 3 patients are well but a renal biopsy in one of them shows persistent nephrocalcinosis.

Acute Disease↗
PubMed1978

Mode of action of the 2-nitroimidazole derivative benznidazole.

Using cultures of Trypanosoma cruzi cells in a liquid medium, the mode of action of the 2-nitroimidazole derivative benznidazole was examined. Benznidazole inhibits protein synthesis and RNA synthesis in T. cruzy. The DNA synthesis is only slightly decreased and no effect on the aerobic respiration of T. cruzi was observed.

Animals↗
PubMed1978

Synergism of polyene antibiotics with 5-fluorocytosine.

The synergism of 5-FC with 4 polyene antibiotics, amphotericin B (amph. B), candicidin, trichomycin and nystatin were investigated in 3 in vitro models measuring the fungistatic and fungicidal activity as well as the development of resistant mutants. In these 3 models candicidin and trichomycin exerted a higher synergistic effect than amph. B or nystatin. In vivo (systemic treatment of septicemic candidiasis of the mouse) the combination of 5-FC with amph. B was, however, the most effective. Only with this combination a complete cure (culturally negative) was observed. For topical treatment of Candida vaginitis in rats, the combination of 5-FC with candicidin proved the most active. As far as the biochemical basis of synergism is concerned in Candida albicans in the presence of polyene antibiotics, the incorporation of fluorinated pyrimidines was increased and the reduction of uptake of histidine by 5-FC alone, significantly enhanced. These effects could not be observed in Cryptococcus neoformans. The release of amino acids, phosphate and potassium caused by polyenes was significantly more pronounced in cells pretreated with 5-FC. Thus, the interaction between 5-FC and the polyenes may, in fact be, mutual.

Amino Acids↗
PubMed1977

Early diastolic murmurs in end-stage renal failure.

An early diastolic murmur thought to indicate functional aortic regurgitation was heard in 7 of 74 consecutive patients with end-stage renal failure assessed for chronic intermittent haemodialysis and transplantation. In all 7 cases the murmur was transient and related to episodes of hypertension and fluid overload and disappeared on correction of these factors. In a further 2 patients aortic regurgitation resulted from a structural abnormality of the aortic valve. Thus, an early diastolic murmur is not uncommon in this situation and does not necessarily indicate organic aortic valve disease which might preclude selection for haemodialysis and transplantation.

Adolescent↗
PubMed1977

The influence of 5-fluorocytosine on nucleic acid synthesis in Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus.

5-Fluorocytosine (5-FC) has a rapid inhibitory effect on the synthesis of RNA and DNA in the yeast and hyphal form of Candida albicans. 5-FC has a less marked effect on the RNA and DNA content of sensitive strains of Cryptococcus neoformans and has no effect on the nucleic acid content of Aspergillus fumigatus nor of resistant strains of C. albicans and C. neoformans. 5-FC has a slower inhibitory effect on yeast cell number increase and no effect on hyphal length of hyphal phase C. albicans over a 7-h incubation period. Rapidly growing yeasts of C. albicans and C. neoformans decrease in volume and in dry weight per cell. 5-FC prevents this decrease in sensitive strains. These results have been discussed with respect to the known metabolic pathway of 5-FC, the fungistatic and fungicidal action of 5-FC and the development of resistance to 5-FC.

Aspergillus fumigatus↗