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At least 1,423 records · Page 79Linked to original sources
PubMed1977

Fungicidal properties of a chymotrypsin-like cationic protein from human neutrophils: adsorption to Candida parapsilosis.

Human neutrophils contain a chymotrypsin-like cationic protein (CLCP) that binds to the surface of Candida parapsilosis and is preferentially adsorbed by yeasts mixed with unfractionated extracts of neutrophil granules. Adsorption of CLCP to opsonized or nonopsonized yeasts was rapid at pH 4 through 8. Irreversible inhibition of the enzymatic site of CLCP by phenylmethylsulfonylfluoride or N-acetyl-Ala-Ala-Phe-chloromethyl ketone did not affect its adsorption by yeast. Adsorption, highly sensitive to ionic strength, was abrogated by 0.15 M KCl. The number of CLCP molecules adsorbed per yeast cell and the loss of colony-forming units are described by an exponential relationship.

Adsorption↗
PubMed1984

Fungistatic and fungicidal activity of human parotid salivary histidine-rich polypeptides on Candida albicans.

Human parotid saliva histidine-rich polypeptides exerted antifungal activity against Candida albicans at concentrations similar to the known antifungal activity of the imidazole antibiotics. Inhibition of both growth and viability could be demonstrated by optical density monitoring and plating assays. Inhibition of growth was observed to be greatest when the histidine-rich polypeptides were added to the inoculum before addition to the growth media. However, complete inhibition by these polypeptides was still noted during active growth at turbidities of C. albicans corresponding to 10(6) CFU/ml. At higher cell densities, growth was delayed but not halted under the experimental conditions investigated. Candidacidal activity was observed with both growing and nongrowing cells. With respect to the latter, reaction of cells in buffer with the histidine-rich polypeptides for a period of 30 min resulted in killing of greater than 90% of two different strains of C. albicans, whereas a third strain was found to be less susceptible. Moreover, the kinetics of loss of cell viability correlated with the loss of potassium from the cells. In addition to the histidine-rich polypeptides, hen egg white lysozyme, poly-L-lysine, and poly-L-histidine affected C. albicans. Both of the polyamino acids completely inhibited the growth of the yeast whereas lysozyme was not as potent. Where delays in growth were observed for all of these agents, including the histidine-rich polypeptides, turbidities reached those of untreated controls after a 24-h period. Enhanced effects were noted if C. albicans was preincubated with these agents in 0.025 2-(N-morpholino)-ethanesulfonic acid buffer, pH 5.2, before growth in the yeast synthetic medium.

Candida albicans↗
PubMed1987

Fungicidal mechanisms of activated macrophages: evidence for nonoxidative mechanisms for killing of Blastomyces dermatitidis.

The mechanism(s) by which lymphokine-activated peritoneal macrophages kill Blastomyces dermatitidis was studied. Resident peritoneal macrophages from BALB/cByJ mice, when treated overnight with lymph node cells plus concanavalin A, supernatants from concanavalin A-stimulated spleen cells, or recombinant gamma interferon, were then able to kill a virulent B. dermatitidis isolate (ATCC 26199) (at levels of 25% +/- 4%, 28% +/- 8%, and 21% +/- 5%, respectively). Killing was not significantly decreased or enhanced in the presence of superoxide dismutase (450 U/ml), catalase (20,000 U/ml), dimethyl sulfoxide (300 mM), or azide (1 mM). Viable B. dermatitidis elicited a brisk oxidative burst and superoxide anion production in activated macrophages as measured by lucigenin-enhanced chemiluminescence, e.g., 10(4) cpm. However, these responses were not significantly different from those of control macrophages. Luminol-enhanced chemiluminescence responses by activated or control macrophages were meager (less than or equal to 10(2) cpm). These results indicate that activated macrophages kill B. dermatitidis by a mechanism(s) independent of products of the oxidative burst.

Animals↗
PubMed1997

Interleukin-12 (IL-12) and IL-18 synergistically induce the fungicidal activity of murine peritoneal exudate cells against Cryptococcus neoformans through production of gamma interferon by natural killer cells.

We examined the ability of interleukin-12 (IL-12) and IL-18 to induce the production of gamma interferon (IFN-gamma) and nitric oxide (NO) by murine peritoneal exudate cells (PEC) and to stimulate the growth-inhibitory activity of these cells against Cryptococcus neoformans. PEC produced IFN-gamma and NO when stimulated with a combination of IL-12 and IL-18 but little or no IFN-gamma or NO when either cytokine was used alone. PEC anticryptococcal activity was mediated by IFN-gamma and NO production, since it was completely inhibited by a neutralizing anti-IFN-gamma monoclonal antibody (MAb) and N(G)-monomethyl-L-arginine, a competitive inhibitor of NO synthesis, respectively. To identify the IFN-gamma-producing cells among PEC stimulated with IL-12 and IL-18, we depleted NK cells, gammadelta T cells, or CD4+ T cells by treating PEC with specific Abs and complement. NK cell depletion strongly suppressed IFN-gamma production and almost completely inhibited NO production and anticryptococcal activity, while depletion of other cells had no such influence. Alternatively, purified NK cells by two cycles of glass adherence and magnetic separation with anti-CD3, -CD4, -CD8, and -B220 MAbs produced a greater amount of IFN-gamma by stimulation with IL-12 and IL-18 than unseparated non-glass-adherent PEC. Our results demonstrated that IL-12 and IL-18 synergistically induced NO-dependent anticryptococcal activity of PEC by stimulating NK cells to produce IFN-gamma.

Animals↗
PubMed1990

Environmental and biological monitoring of exposure to ethylenebisdithiocarbamate fungicides and ethylenethiourea.

Exposure of workers to ethylenebisdithiocarbamates (EBDCs; maneb or mancozeb) in 29 potato farms was evaluated during the control of potato late blight. Concentrations of EBDCs and ethylenethiourea (ETU), an impurity and degradation product in EBDC formulations, in ambient air were evaluated during pesticide application. Biological monitoring of exposure to EBDCs was carried out by measuring the concentrations of ETU, a metabolite of EBDCs, in urine for 22 days after the end of the exposure. The estimated inhaled doses of ETU and EBDCs during the average four hour application period were 0.07 and 1.8 micrograms/kg, respectively. Only 1-10% of ETU on the clothes reached the skin. The creatinine corrected concentrations of ETU in urine were 0.1-2.5 micrograms/mmol creatinine 24 hours after exposure ended. The estimated half life for eliminating ETU through the kidneys was close to 100 hours. These results indicate that the measurement of ETU in urine is suitable for biological monitoring of exposure to EBDCs.

Agriculture↗
PubMed1980

Vulvo-vaginal candidosis and its treatment with the new fungicidal substance econazole.

Thirty-five patients suffering from vulvo-vaginal candidosis were treated with econazole vaginal suppositories for 3 consecutive days, on a once-a-day schedule. In 80% of the cases clinical symptoms subsided and the mycological findings became negative. No side-effects were observed or reported, and the tolerability was excellent.

Candidiasis, Vulvovaginal↗
PubMedDate not supplied

Actin gene-targeted RT-PCR could be a useful method for evaluating in vitro fungicidal activity against dermatophytes.

This study examined the effects of the antifungal agents amorolfine hydrochloride (AMF) and bifonazole (BFZ) on actin mRNA expression determined by reverse transcription-polymerase chain reaction (RT-PCR) amplification, and the morphology of Trichophyton mentagrophytes. In AMF-treated cultures, the hyphal cells of T. mentagrophytes exhibited concentration- and/or time-dependent progressively degenerative morphological damage. Those cultures exhibiting severe and necrotic morphological changes (such as crushed, bent and flattened hyphal cells) did not express actin mRNA. In BFZ-treated cultures, similar morphological changes were seen in the hyphae of T. mentagrophytes, but these changes were milder than observed in the AMF-treated samples, and actin gene fragments were amplified in all of these samples. These results indicate that actin gene-targeted RT-PCR could be a useful tool for testing the susceptibility of dermatophytes to antifungal agents in vitro.

Actins↗
PubMed2004

Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity.

The balance of arginine metabolism via nitric oxide synthase (NOS) or arginase is an important determinant of the inflammatory response of murine macrophages and dendritic cells. Here we analyzed the expression of the isoform arginase I in human myeloid cells. Using healthy donors and patients with arginase I deficiency, we found that in human leukocytes arginase I is constitutively expressed only in granulocytes and is not modulated by a variety of proinflammatory and anti-inflammatory stimuli in vitro. We demonstrate that arginase I is localized in azurophil granules of neutrophils and constitutes a novel antimicrobial effector pathway, likely through arginine depletion in the phagolysosome. Our findings demonstrate important differences between murine and human leukocytes with respect to regulation and function of arginine metabolism via arginase.

Animals↗