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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    FEMS microbiology letters 244 (2005), S. 0 
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Antifungal activity of histatin 3 against two Candida albicans clinical isolates was determined in assays containing rabbit submandibular gland saliva. Histatin 3 inhibited the cell growth and germination of both isolates dose-dependently (10–100 μg ml−1) with maximum inhibition occurring after 60 min incubation. Adding fresh histatin 3 after 60 min caused further reduction in the viable cell count. Higher histatin 3 concentrations (50–100 μg ml−1) and prolonged exposure to peptide were required to inhibit germination. Histatin 3 was rapidly degraded in rabbit submandibular gland saliva and this may explain why fresh addition of histatin 3 increases candidacidal activity.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1574-695X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Pathogenesis of invasive candidiasis may involve regulatory activities of Th2 immunity on phagocytic host defenses. The effects of interleukin (IL)-4 on antifungal capacity of human mononuclear phagocytes against Candida albicans were studied. Incubation of adherent mononuclear leukocytes from healthy donors with IL-4 (1–5 ng ml−1) at 37°C for 2–4 days suppressed uptake of C. albicans blastoconidia in the presence of human serum (P≤0.01), and anti-IL-4 inhibited its suppressive effect. The effect of IL-4 was protein synthesis-dependent. Interferon-γ (0.25–25 ng ml−1), granulocyte-macrophage colony-stimulating factor (CSF, 20 ng ml−1), macrophage-CSF (15 ng ml−1) but not IL-10 (100 ng ml−1) somewhat counteracted the suppressive effect of IL-4. In contrast, mannose receptor-mediated uptake of blastoconidia in the absence of serum was increased by IL-4. Killing of conidia was decreased after incubation of morphonuclear leukocytes with IL-4 for 2 days (P〈0.05). While superoxide anion production in response to phorbol myristate acetate was decreased by IL-4 (P〈0.05), it was not altered in response to blastoconidia and pseudohyphae. Morphonuclear leukocyte-induced pseudohyphal damage also remained unaltered. These findings suggest that IL-4 plays its detrimental role in invasive candidiasis by predominantly suppressing uptake and killing of blastoconidia by morphonuclear leukocytes. Anti-IL-4, IFN-γ, GM-CSF and M-CSF appear to counteract suppression of morphonuclear leukocyte phagocytic activity suggesting new approaches to the management of disseminated candidiasis.
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    FEMS immunology and medical microbiology 31 (2001), S. 0 
    ISSN: 1574-695X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: We investigated the effects of human interleukin-13 (IL-13) on human monocytes’ (MNC) activities against Candida albicans, an important human pathogen. Increased phagocytosis of blastoconidia was observed after incubation with 50 U ml−1 of IL-13 for 4 h or 48 h in the presence or absence of serum. The latter effect was inhibited by anti-IL-13 monoclonal antibody or mannose. Incubation of MNC with 50 U ml−1 of IL-13 for 2 h significantly enhanced superoxide anion production in response to phorbol myristate acetate. IL-13 did not, however, alter the damage caused by MNC to hyphae, whereas it suppressed killing of blastoconidia. IL-13 has variable effects on MNC activities and may play an important immunoregulatory role against C. albicans.
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  • 5
    ISSN: 1574-695X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The responses of rabbit pulmonary alveolar macrophages (PAMs) and elutriated human monocytes (EHMs) to Penicillium marneffei, an emerging dimorphic fungus that may cause fatal disease in human immunodeficiency virus-infected patients, were studied. PAMs and EHMs comparably phagocytosed conidia of two P. marneffei strains in the presence of serum. Electron microscopy showed intraphagosomal destruction of conidia after 12 h. Serum-opsonized conidia elicited significantly more superoxide anion (O2−) release from EHMs compared to non-opsonized conidia, but equivalent O2− amounts to that elicited by serum-opsonized Aspergillus fumigatus conidia. Macrophage colony-stimulating factor (M-CSF) significantly enhanced phagocytosis of P. marneffei conidia by PAMs and EHMs, as shown by light microscopy. Moreover, M-CSF enhanced O2− production by EHMs in response to both serum-opsonized (P〈0.001) and non-opsonized (P=0.03) conidia of A. fumigatus as well as conidia of the P. marneffei isolates (P〈0.001 and 0.03). We conclude that M-CSF enhances phagocytosis and oxidative metabolism of mononuclear phagocytes suggesting a potential role for this cytokine in host defense against pulmonary and disseminated P. marneffei infection.
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  • 6
    ISSN: 1573-904X
    Keywords: amphotericin B ; liposomes ; pharmacokinetics ; tissue distribution ; toxicity ; toxicokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Amphotericin B (AmB) in small, unilamellar liposomes (AmBisome ®) has an improved therapeutic index, and altered pharmacokinetics. The repeat-dose safety and toxicokinetic profiles of AmBisome were studied at clinically relevant doses. Methods. Beagle dogs (5/sex/group) received intravenous AmBisome (0.25, 1,4, 8, and 16 mg/kg/day), empty liposomes or vehicle for 30 days. AmB was determined in plasma on days 1, 14, and 30, and in tissues on day 31. Safety parameters included body weight, clinical chemistry, hematology and microscopic pathology. Results. Seventeen of twenty animals receiving 8 and 16 mg/kg were sacrificed early due to weight loss caused by reduced food intake. Dose-dependent renal tubular nephrosis, and other effects characteristic of conventional AmB occurred at 1 mg/kg/day or higher. Although empty liposomes and AmBisome increased plasma cholesterol, no toxicities unique to AmBisome were revealed. Plasma ultrafiltrates contained no AmB. AmBisome achieved plasma levels 100-fold higher than other AmB formulations. AmBisome kinetics were non-linear, with clearance and distribution volumes decreasing with increasing dose. This, and nonlinear tissue uptake, suggest AmBisome disposition was saturable. Conclusions. AmBisome has the same toxic effects as conventional AmB, but they appear at much higher plasma exposures. AmBisome's non-linear pharmacokinetics are not associated with increased risk, as toxicity increases linearly with dosage. Dogs tolerated AmBisome with minimal to moderate changes in renal function at doses (4 mg/kg/day) producing peak plasma concentrations of 18−94 µg/mL.
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  • 7
    ISSN: 1573-904X
    Keywords: amphotericin B ; liposomes ; pharmacokinetics ; toxicokinetics ; tissue distribution ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Amphotericin B in small, unilamellar liposomes (AmBisome) is safer and produces higher plasma concentrations than other formulations. Because liposomes may increase and prolong tissue exposures, the potential for drug accumulation or delayed toxicity after chronic AmBisome was investigated. Methods. Rats (174/sex) received intravenous AmBisome (1, 4, or 12 mg/kg), dextrose, or empty liposomes for 91 days with a 30-day recovery. Safety (including clinical and microscopic pathology) and toxicokinetics in plasma and tissues were evaluated. Results. Chemical and histopathologic changes demonstrated that the kidneys and liver were the target organs for chronic AmBisome toxicity. Nephrotoxicity was moderate (urean nitrogen [BUN] ≤51 mg/dl; creatinine unchanged). Liposome-related changes (vacuolated macrophages and hypercholesterolemia) were also observed. Although plasma and tissue accumulation was nonlinear and progressive (clearance and volume decreased, half-life increased with dose and time), most toxic changes occurred early, stabilized by the end of dosing, and reversed during recovery. There were no delayed toxicities. Concentrations in liver and spleen greatly exceeded those in plasma; kidney and lung concentrations were similar to those in plasma. Elimination half-lives were 1-4 weeks in all tissues. Conclusions. Despite nonlinear accumulation, AmBisome revealed predictable hepatic and renal toxicities after 91 days, with no new or delayed effects after prolonged treatment at high doses that resulted in plasma levels 〉200 μg/ml and tissue levels 〉3000 μg/g.
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  • 8
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 7 (1961), S. 53-61 
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: This paper summarizes an experimental study of turbulent diffusion downstream of a line source of heat. Mean temperature profiles in the core of nearly fully developed pipe flow were measured at four mean velocities, from Uc = 72.6 to 160 ft./sec. Hot-wire anemometer surveys showed that the turbulence in the axial core was nearly homogeneous and isotropic. The objective was to find empirical relations between the anemometer (Eulerian) specification of the turbulence and the Lagrangian statistical properties which determine diffusion.The diffusion results agreed with predictions of G. I. Taylor's theory of diffusion by continuous movements; the eddy diffusivity increased from zero at the heat source to a constant, asymptotic value far downstream. The Lagrangian correlation coefficients inferred from the diffusion data had shapes similar to the Eulerian correlations over most of the range of time and space. Empirical relations were found to relate the coordinates of the Lagrangian and Eulerian correlation coefficients over the range of this experiment. In addition preliminary measurements are reported for a general Eulerian correlation which is a function of both space and time; the results indicate that a special case of this new Eulerian function may be a fair approximation of the Lagrangian correlation.
    Additional Material: 10 Ill.
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  • 9
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 8 (1962), S. 48-52 
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: This investigation was undertaken to determine the rate controlling step in the reduction of iron oxides with hydrogen and carbon monoxide. For the reduction of porous hematite pellets, and bars it was found that the reduction rate is controlled by the counterdiffusion of reactant gas and product gas between the reaction zone and the main gas stream.The reduction specimens were spheres ranging in size from 1.5- to 4.4-cm. diameter and 5.1- by 7.6-cm. bars either 0.69 or 1.24 cm. thick. They were prepared from electrolytic iron powder, partially oxidized in a rotary kiln. The final oxidation of the specimens to hematite was accomplished by firing them at 1,149°C. in an oxidizing atmosphere. The bulk density was 3.5 g./cc. The specific surface area was 0.08 sq.m./g. and the void faction was 0.31. The oxide specimens were reduced in streams of pure hydrogen or carbon monoxide at temperatures between 700° and 1,200°C. The reduction was followed by measuring the sample weight during the reaction. Reduction rates were studied at system pressures of 1 and 2 at.The samples reduced step by step, to magnetite, to wüstite, and finally to iron. A shell of reduction, clearly visible in sections of partially reduced specimens, moved concentrically into the core of the samples. Ahead of the receding interface the specimens were known to be pervious to the reactant gases. This led to the conclusion that the gas composition at the interface was in equilibrium with the oxide phases present.Except for the removal of the last portions of oxygen at the lower reduction temperatures, the course of the reduction followed Fick's first law of diffusion. Values of the diffusion co-efficients, determined from the experimental data, were in close agreement with values predicted from empirical equations. Varying the total pressure of the system had no effect on the rate of reduction, which is consistent with the equations developed from Fick's law for the diffusion-controlled reaction under investigation.It is speculated that the retarding of the reduction reaction at the lower reduction temperatures is due to the entrapment of oxide inside shells of iron, which are impervious to the reducing gas. Reduction of the trapped oxide then proceeds by solid state diffusion in a manner proposed by Edström (6).
    Additional Material: 5 Ill.
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  • 10
    Publication Date: 1987-06-15
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
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