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Biomedical subjects

A Polak

Publications and source records attributed to A Polak.

At least 19 recordsLinked to original sources
PubMed1992

Preclinical data and mode of action of amorolfine.

Amorolfine is an antifungal showing activity against fungi pathogenic to plants, animals and humans. Amorolfine possesses a broad antifungal spectrum including dermatophytes, yeasts, dimorphic fungi and moulds and is not only fungistatic but fungicidal against most species. Amorolfine interferes with ergosterol biosynthesis at two steps: the delta 14 reduction and the delta 7-8 isomerisation. As a consequence of this inhibition the delta 14 sterol ignosterol is accumulated in the cell membrane and ergosterol is depleted. The cell wall thickness is significantly increased and chitin deposits are included inside and outside. In experimental models of systemic mycosis amorolfine shows no significant activity. This lack of systemic activity may be due to strong protein binding and/or rapid metabolism. In models of superficial fungal infection--trichophytosis and vaginal candidosis--amorolfine has a high activity. On a concentration basis amorolfine is more effective in trichophytosis than naftifine and all azoles tested. Amorolfine clears mycotic foci of trichophytosis in the guinea pig in 10 days, while none of the azoles is able to cure these animals. Tolciclate and terbinafine are the only other substances with a curative effect in these experiments. Amorolfine has a long retention time in the horny layer of the skin. In vaginal candidosis 0.1% amorolfine clears the vagina of viable candida cells in rats.

Animals↗
PubMed1990

Melanin as a virulence factor in pathogenic fungi.

The pigment melanin is found universally in nature and is attributed to a variety of functions. In some fungi it is thought to play a decisive role in the determination of virulence. This review examines the experimental evidence which has led to an understanding of the mechanisms by which melanin functions in pathogenic fungi, particularly in plant pathogens, in Cryptococcus neoformans and Wangiella dermatitidis.

Animals↗
PubMed1990

In vitro and in vivo activity of antifungal agents in combination with fleroxacin, a new quinolone.

The in vitro and in vivo interaction of fleroxacin with amphotericin B (Amph B), flucytosine (5-FC) and azoles against Candida albicans strains was tested. In vitro the interaction between fleroxacin and various antifungals was not dependent on the incubation time. Fleroxacin neither enhances nor antagonizes the in vitro activity of Amph B at high concentration (50-100 micrograms/ml). Fleroxacin has a synergistic effect with ketoconazole (KETO), but this is not observed with itraconazole (ITRA) or fluconazole (FLU). In no instance antagonism was observed. The activity of 5-FC was antagonized by fleroxacin being generally reduced by 2-4 dilution steps. In murine candidosis the efficacies of all antifungal drugs were not influenced by addition of 100 mg/kg fleroxacin. Therefore, the effects seen in in vitro tests are most probably not relevant for the clinical use of a combination of fleroxacin with antifungal drugs.

Animals↗
PubMed1989

A new experimental model of localized candidosis for the study of antifungal chemotherapy.

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed and was used to test the efficacy of various antifungal drugs. The results were similar regardless whether cortisone or cyclophosphamide was used for immunosuppression. The highest efficacy was shown by amphotericin B in relatively high doses (2 mg/kg s.c.). The new triazole derivatives also showed good chemotherapeutic activity (fluconazole, ICI 195, 739, SDZ 89-485). Flucytosine was also highly effective despite its short half-life. The model thus gives a valuable indication of the chemotherapeutic efficacy against Candida thrush in humans.

Animals↗
PubMed1989

An acceptable exercise test to study microalbuminuria in type 1 diabetes.

A modified test for studying the response of urinary albumin excretion (UAV) to exercise in diabetic patients is described. It is designed to produce a standardized increase in pulse rate (by 90-110%) rather than a standardized workload. Thirty-three normotensive Type 1 diabetic patients with normal pre-exercise UAV (less than 10 micrograms min-1) on the day of the test were compared with 25 non-diabetic subjects matched for age and sex. The patients developed a significantly greater increase in the median UAV (p less than 0.05) and systolic blood pressure (p less than 0.01) during exercise, despite the use of lower workloads (p less than 0.05). During exercise, the albumin excretion in the patients was not related to their heart rate, blood pressure, workload or fall in blood glucose; nor was it related to duration of diabetes, glycosylated haemoglobin or insulin dose. An exercise UAV greater than 15 micrograms min-1 was found in 10 of the 33 patients; it was significantly correlated (p less than 0.01) with the frequency of previous overnight microalbuminuria (greater than 10 micrograms min-1), and was associated with a greater progression of microalbuminuria (p less than 0.05) over a mean period of 24 months. Retinol-binding protein excretion rate was also measured as an indicator of proximal tubular function and did not increase in either group.

Adult↗
PubMed1989

Loss of melanin in Wangiella dermatitidis does not result in greater susceptibility to antifungal agents.

Melanized wild-type and melanin-deficient (Mel-) strains of Wangiella dermatitidis (Kano) McGinnis were tested for in vitro susceptibility to amphotericin B, flucytosine, amorolfine, ketoconazole, fluconazole, terbinafine, and itraconazole by using an agar dilution technique. Although the MICs of itraconzole obtained with seven of the eight Mel- strains were lower than those obtained with the melanized wild-type strains, there was no such trend observed with fluconazole, the other triazole tested. Furthermore, there was no apparent difference in MICs when comparing the melanized wild-type and the Mel-strains for the other drugs tested. Thus, no consistent increase in in vitro antifungal activity was found to be associated with a specific class of drug. Therefore, melanin does not appear to confer protection against some of the more important antifungal agents.

Antifungal Agents↗
PubMed1989

Fungus dose-dependent primary pulmonary aspergillosis in immunosuppressed mice.

We report on a model of primary pulmonary aspergillosis occurring after intranasal instillation of concentrated suspensions of conidia of Aspergillus fumigatus in immunocompromised mice. Unconcentrated suspensions of inoculum contained ca. 2 x 10(7) conidia per ml (1x). These suspensions were concentrated by centrifugation, adjusted to give ca. 2 x 10(8) (10x) or 2 x 10(9) (100x) conidia per ml, and delivered in 30-microliters droplets to the nares of anesthetized mice. Mice were untreated or injected with cortisone acetate (CA) or cyclophosphamide (CY) in various dosage regimens. It was not possible to obtain mortality of more than 50% with sublethal immunosuppressive treatment and 1x fungus. In contrast, mortality followed a fungus dose response in mice receiving sublethal immunosuppression with either CA or CY. Mortality rates of up to 100% were obtained with 100x fungus and a single dose of CY (200 mg/kg) or CA (250 mg/kg) or three alternate doses (125 mg/kg per day) of CA prior to infection. This model is applicable to the study of acute, fatal primary pulmonary aspergillosis and chemotherapy trials.

Animals↗
PubMed1989

Mel- mutants of Wangiella dermatitidis in mice: evaluation of multiple mouse and fungal strains.

Melanin-deficient mutants of Wangiella dermatitidis were studied by comparing a spontaneous mutant (Mel 3) with the parental wild type (wt) in four strains of mice and by comparing various UV-induced mutants in a single strain of mouse. Mice were inoculated intravenously with 3 x 10(6), 1 x 10(7), 3 x 10(7) or 1 x 10(8) yeast-like cells and mortality assessed at the end of 20 days. Neuropathology was evaluated in methenamine-silver stained brain sections of the different strains of mice injected with either wt or Mel 3 (1 x 10(7) cells per mouse). In general, both fungus strain related and mouse strain related differences in mortality were observed. The DBA/2J mouse was the most susceptible to fatal infection with all fungus strains. In the other strains of mice, however, the melanin deficient mutants were significantly less virulent than the wt at a concentration of less than or equal to 3 x 10(7) cells per mouse. No obvious trend was seen in the numbers of brain lesions in different strains of mice with respect to wt vs. Mel 3. However, invasive hyphal forms did seem to be associated with virulence.

Animals↗
PubMed1988

Urinary albumin excretion in healthy adult subjects: reference values and some factors affecting their interpretation.

A conventional radioimmunoassay has been used to measure urinary albumin concentration in overnight, recumbent and daytime, ambulant samples from 127 healthy, normotensive volunteers (mean age 33.3 yr SD 12.4; 59 males, 68 females). Reference values were obtained for urine albumin concentration (mg/l), albumin/creatinine ratio (mg/mmol), and albumin excretion rate (microgram/min). The frequency distributions of these variables were positively skewed, but became Gaussian on logarithmic transformation of the data. Albumin excretion was significantly higher in daytime, ambulant samples than in overnight, recumbent samples (p less than 0.001). Surface area was not correlated with urine albumin concentration but it was negatively correlated with urine albumin/creatinine ratio (p less than 0.05) due to the association between surface area and creatinine excretion. Urine albumin concentration was negatively correlated with age, but this was due to a higher urine flow rate in older subjects. There was no significant association with sex or with mean arterial blood pressure in the normal range. Two repeated measurements showed that variability was high and comparable for urine albumin concentration, albumin/creatinine ratio and albumin excretion rate: it was not significantly less in overnight, recumbent than in day-time, ambulant samples.

Adolescent↗
PubMed1988

Ro 15-0216: a nitroimidazole compound active in vitro against human and animal pathogenic African trypanosomes.

In vitro systems for the continuous cultivation of Trypanosoma brucei brucei, T. b. gambiense, T. b. rhodesiense, T. congolense and T. vivax were used to determine the antitrypanosomal activity of the 2-substituted nitroimidazole Ro 15-0216. For all trypanosome species, the concentration which inhibited parasite growth by 50% (IC50 value) was established: 0.0957 microgram ml-1 (T. b. brucei TC221), 0.1327 microgram ml-1 (T. b. gambiense STIB 754-A), 0.0450 microgram ml-1 (T. b. rhodesiense STIB 704-BABA), 0.0896 microgram ml-1 (T. congolense ILNat 3.1) and 0.0109 microgram ml-1 (T. vivax ILRAD 1392). The IC50 value of its major metabolite Ro 19-9638 was 0.0341 microgram ml-1 (T. b. rhodesiense STIB 704-BABA). Furthermore, minimum exposure times required to render T. b. brucei non-infective for mice as well as preventing their growth in vitro have been established to be three, four, six and ten hours at drug concentrations of 30, 10, 3 and 1 microgram ml-1, respectively.

Acetanilides↗
PubMed1988

Side-room tests to screen for microalbuminuria in diabetes mellitus.

Three side-room tests (latex bead immunoagglutination test, LBT; 25% sulphosalicylic acid test, SST; microalbutest, MAT) for the detection of microalbuminuria in diabetics are described and their screening potential and practicability assessed. One hundred insulin-dependent diabetics attending a diabetic clinic provided an early morning urine sample (Albustix-negative) which was subjected to each of the three tests, and urinary albumin concentration (UA) was assayed by RIA. Tests were assessed in random order by two trained operators using a semiquantitative grading scale with 100% concordance between 10 observers. All test results greater than or equal to trace +ve were sufficiently sensitive (sensitivity greater than or equal to 90%) in detecting UA greater than 15 mg/l, but MAT exhibited a significantly reduced specificity (69%) and positive predictive value (58%). For a reference UA greater than 30 mg/l, LBT and SST results greater than or equal to trace +ve and MAT results greater than or equal to +ve showed a sensitivity of 100%, a specificity greater than 85% and a positive predictive value greater than 60%. Reagent shelf-life was shortest with LBT. SST involved centrifugation or filtration. Technical skill required was highest with LBT and lowest with MAT. Costs were slightly higher with LBT than SST and were not available for MAT.

Albuminuria↗