Latest medical literature on mycostatin

Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new mycostatin research articles will be listed here shortly after becoming available to us.

Medical research on mycostatin

Successful Nystatin Powder Treatment of Posttraumatic Invasive Aspergillus fumigatus Wound Infection Refractory to Systemic Antifungal Therapy.

J Trauma. 2008 Sep 23;
Volkmer E, Mathonia P, Hummel T, Deiler S, Stengele M, Mutschler W

Quantitative proteomic analysis of macrophage rafts reveals compartmentalized activation of the proteasome and of proteasome-mediated ERK activation in response to lipopolysaccharide.

Mol Cell Proteomics. 2008 Sep 23;
Dhungana S, Merrick BA, Tomer KB, Fessler MB
Lipopolysaccharide (LPS), a glycolipid component of the outer membrane of Gram-negative bacteria, is a potent initiator of the macrophage's innate immune response. LPS triggers downstream signaling by selectively recruiting and activating proteins in cholesterol-rich membrane microdomains called lipid rafts. We applied proteomic analysis to macrophage detergent-resistant membranes (DRMs) during an LPS exposure time course in an effort to identify and validate novel events occurring in macrophage rafts. Following metabolic incorporation in cell culture of heavy isotopes of amino acids Arginine and Lysine (Arg-(13)C(6), Lys-(13)C(6)) or their light counterparts, a SILAC (Stable Isotope Labeling of Amino acids in cell Culture)-based quantitative, liquid chromatography-tandem mass spectrometry proteomics approach was used to profile LPS-induced changes in the lipid raft proteome of RAW 264.7 macrophages. Unsupervised network analysis of the proteomics dataset revealed a marked representation of the ubiquitin-proteasome system, as well as changes in proteasome subunit composition following LPS challenge. Functional analysis of DRMs confirmed that LPS causes selective activation of the proteasome in macrophage rafts and proteasome inactivation outside of rafts. Given previous reports of an essential role for proteasomal degradation of IkappaK-phosphorylated p105 in LPS activation of ERK mitogen-activated protein kinase, we tested for a role of rafts in compartmentalization of these events. Immunoblotting of DRMs revealed proteasome-dependent activation of MEK and ERK specifically occurring in lipid rafts, as well as proteasomal activity upon raft-localized p105 that was enhanced by LPS. Cholesterol extraction from the intact macrophage with methyl-{beta-cyclodextrin was sufficient to activate ERK, recapitulating the LPS IkappaK-p105-MEK-ERK cascade, whereas both it and the alternate raft-disrupting agent nystatin blocked subsequent LPS activation of the ERK cascade. Taken together, our findings indicate a critical, selective role for raft compartmentalization and regulation of proteasome activity in activation of the MEK-ERK pathway.

Novel mucoadhesive extended release tablets for treatment of oral candidosis: "In vivo" evaluation of the biopharmaceutical performance.

J Pharm Sci. 2008 Sep 19;
Llabot JM, Manzo RH, Allemandi DA
Mucoadhesive tablets containing nystatin (10 mg) were evaluated in vivo. The assays were carried out with 12 healthy volunteers and the concentration of nystatin in saliva was determined at different times. Tablets remained attached to the buccal mucosa during 270 min +/- 30 min. No evidence of ulceration or bleeding was observed. Typical appearance of intact human buccal mucosa was seen before and after contact with the tablet. The tablets were well accepted by the volunteers, although most of the volunteers reported a light bitter taste, probably due to nystatin. Concentration of nystatin in saliva was several times higher than MIC over a period of approximately 4.5 h, which was in agreement with the behavior observed in vitro. These results allow us to infer that the administration of these mucoadhesive tablets could be advantageous compared to conventional formulations and mucoadhesive extended-release tablets might produce better therapeutic performance than conventional formulations in the treatment of oral candidosis. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci.

Effect of an antifungal denture liner on the saliva yeast count in patients with denture stomatitis: a pilot study.

J Oral Rehabil. 2008 Sep; 35(9): 664-9
Geerts GA, Stuhlinger ME, Basson NJ
Although in vitro studies on the release of antifungal agents from tissue conditioners have been done, no in vivo research on the topic could be found. The purpose of this study was to determine the in vivo effect of an antifungal agent released from a tissue conditioner on the salivary yeast count. Forty edentulous patients with denture stomatitis caused by Candida albicans were divided in two groups. Group 1 (control) was treated with a tissue conditioner only. Group 2 was treated with a tissue conditioner incorporating 500,000 U nystatin. Oral rinses were performed by both groups before treatment and every second day during treatment for a period of 14 days. Total yeast counts of the oral rinses were performed and the averages and standard deviations for both groups calculated and logarithm-transformed data of the counts over time were statistically analysed using the Wilcoxon signed-rank test. The average oral rinse yeast count of the control group decreased up to day 4. Thereafter, the count increased till the end of the test period. At day 14, the oral rinse yeast level was higher than the pre-treatment level. The average yeast count of the test group decreased up to day 7. Thereafter, the count increased but remained significantly lower (P=0.01) than the control group and did not return to its pre-treatment level. A nystatin-containing short-term denture liner significantly decreases the salivary yeast count of patients with denture stomatitis compared with a liner without nystatin.

Isolation, characterization and long term preservation of mutant strains of Xanthophyllomyces dendrorhous.

J Basic Microbiol. 2008 Sep 12;
Baeza M, Retamales P, Sepúlveda D, Lodato P, Jiménez A, Cifuentes V
The yeast Xanthophyllomyces dendrorhous is biotechnologically important due to its ability to produce the pigment astaxanthin, but is poorly understood at the genetic level. This is mainly because its preservation is difficult and many of the mutants obtained are unstable. The objectives of the present work were (i) the mutagenesis X. dendrorhous and, (ii) isolation of mutants with auxotrophic markers suitable for genetic studies of the carotenogenesis pathway and sexual cycle. Additionally, two kinds of preservation methods at the laboratory level were tested for the storage of strains. A collection of X. dendrorhous mutants affected in the production of carotenoid pigments or development of sexual structures and auxotrophic requirements were isolated by treatment with N-methyl-N'-nitro-N-nitrosoguanidine and the antibiotic nystatin. From a detailed analysis about the requirements of auxotrophic mutants the ARG7, ARG3 and PRO3 loci can be defined in this yeast. Among the methods assayed for the long-term preservation of X. dendrorhous strains, the dehydrated gelatin drop method showed the highest recovery of viable yeast after storage for 65 months. No changes in auxotrophic properties and in macro or micro morphology were observed after applying the latter method. ((c) 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

Mechanisms for Recycling and Biosynthesis of Endogenous Cannabinoids Anandamide and 2-Arachidonylglycerol.

J Neurochem. 2008 Sep 6;
Placzek EA, Okamoto Y, Ueda N, Barker EL
The mechanisms of endogenous cannabinoid biosynthesis are not completely understood. We hypothesized that anandamide could be recycled by the cell to form new endocannabinoid molecules and released into the extracellular space. We determined that new endocannabinoids derived from exogenous anandamide or arachidonic acid were synthesized and released from RBL-2H3 cells in response to ionomycin. Treatment of RBL-2H3 cells with nystatin and progesterone, agents that disrupt organization of lipid raft/caveolae, resulted in the attenuation of anandamide and 2-arachidonyl glycerol synthesis and/or release in response to stimulation with ionomycin suggesting a role for these membrane microdomains in endocannabinoid biosynthesis. Furthermore, anandamide synthesis may be independent of N-acyl phosphatidylethanolamine phospholipase D as expression of the enzyme was not detected in RBL-2H3 cells. We also established that extracellular calcium is necessary for endocannabinoid biosynthesis because release of intracellular calcium stores alone does not promote endocannabinoid biosynthesis. Next, we examined the role of calcium as a "switch" to activate the synthesis of anandamide and simultaneously reduce uptake. Indeed, [(3)H] anandamide uptake was reduced in the presence of calcium. Our findings suggest a mechanism indicative of calcium-modulated activation of anandamide synthesis and simultaneous termination of uptake.

Clathrin- and caveolae-independent entry of feline infectious peritonitis virus in monocytes depends on dynamin.

J Gen Virol. 2008 Sep; 89(Pt 9): 2147-56
Van Hamme E, Dewerchin HL, Cornelissen E, Verhasselt B, Nauwynck HJ
Feline infectious peritonitis virus (FIPV), a coronavirus that causes a lethal chronic disease in cats, enters feline monocytes via endocytosis. In this study, the pathway of internalization is characterized by evaluating the effect of chemical inhibitors and/or expression of dominant-negative (DN) proteins on the percentage of internalized virions per cell and infection. Further, co-localization studies were performed to determine the involvement of certain cellular internalization proteins. FIPV is not internalized through a clathrin-mediated pathway, as chlorpromazine, amantadine and DN eps15 did not influence virus uptake and FIPV did not co-localize with clathrin. The caveolae-mediated pathway could be excluded based on the inability of genistein and DN caveolin-1 to inhibit virus uptake and lack of co-localization between FIPV and caveolin-1. Dynamin inhibitory peptide and DN dynamin effectively inhibited virus internalization. The inhibitor strongly reduced uptake to 20.3+/-1.1% of uptake in untreated cells. In the presence of DN dynamin, uptake was 58.7+/-3.9% relative to uptake in untransduced cells. Internalization of FIPV was slightly reduced to 85.0+/-1.4 and 87.4+/-6.1% of internalization in control cells by the sterol-binding drugs nystatin and methyl-beta-cyclodextrin, respectively. Rho GTPases were inhibited by Clostridium difficile toxin B, but no effect was observed. These results were confirmed with infection studies showing that infection was not influenced by chlorpromazine, amantadine and genistein, but was significantly reduced by dynamin inhibition and nystatin. In conclusion, these results indicate that FIPV enters monocytes through a clathrin- and caveolae-independent pathway that strongly depends on dynamin and is slightly sensitive to cholesterol depletion.

Local Treatment of Vulvovaginal Candidosis : General and Practical Considerations.

Drugs. 2008; 68(13): 1787-1802
das Neves J, Pinto E, Teixeira B, Dias G, Rocha P, Cunha T, Santos B, Amaral MH, Bahia MF
Vulvovaginal candidosis is a common worldwide female medical problem, occurring mostly in women of childbearing age. Currently available options for the treatment of this condition include local and oral (systemic) therapy. Both alternatives have been considered equally effective in the treatment of uncomplicated vulvovaginal candidosis, although oral regimens are often preferred by physicians and women. However, local treatment presents several advantageous and unique features that may favour this therapeutic approach. The availability of numerous antifungal drugs and products for topical administration makes the selection quite challenging as this task is mostly based on personal experience or anecdotal data. Also, recent advances have been made in topical antifungal formulations and there is an increasing availability of over-the-counter products. Therefore, a review of both general and practical considerations related to the local treatment of vulvovaginal candidosis is timely.In summary, azoles and short-term regimens are usually recommended for the local treatment of vulvovaginal candidosis, with nystatin and boric acid considered as second-line alternatives. Unconventional approaches may also be regarded as suitable in patients refractory to usual treatments. In addition to the susceptibility of implicated Candida spp. to the antifungal agents, this choice should take into consideration other important issues such as particular situations (e.g. pregnancy, menopause, drug hypersensitivity), women's preferences, and the availability, particularities and cost of antifungal formulations.

Mediation by calcium/calmodulin-dependent protein kinase II of suppression of GABA(A) receptors by NMDA.

Sci China C Life Sci. 2000 Dec; 43(6): 655-62
Wang D, Lü H, Xu T
Using nystatin-perforated whole-cell recording configuration, the modulatory effect of N-methyl-D-aspartate (NMDA) on gamma-aminobutyric acid (GABA)-activated whole-cell currents was investigated in neurons freshly dissociated from the rat sacral dorsal commissural nucleus (SDCN). The results showed that: (i) NMDA suppressed GABA-and muscimol (Mus)-activated currents (I(gaba) and I(Mus)), respectively in the Mg(2+)-free external solution containing 1 mumol/L glycine at a holding potential (V ( H )) of -40 mV in SDCN neurons. The selective NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acid (APV, 100 gammamol/L), inhibited the NMDA-evoked currents and blocked the NMDA-induced suppression of I(gaba); (ii) when the neurons were incubated in a Ca(2+)-free bath or pre-loaded with a membrane-permeable Ca(2+) chelator, BAPTA AM (10 mumol/L), the inhibitory effect of NMDA on I(GAba) disappeared. Cd(2+) (10 mumol/L) or La(3+) (30 mumol/L), the non-selective blockers of voltage-dependent calcium channels, did not affect the suppression of I(gaba) by NMDA application; (iii) the suppression of I(GAba) by NMDA was inhibited by KN-62, a calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor. These results indicated that the inhibition of GABA response by NMDA is Ca(2+)-dependent and CaMKII is involved in the process of the Ca(2+)-dependent inhibition.

Species distribution and in vitro antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis.

BMC Microbiol. 2008; 8: 135
Hamza OJ, Matee MI, Moshi MJ, Simon EN, Mugusi F, Mikx FH, Helderman WH, Rijs AJ, van der Ven AJ, Verweij PE
BACKGROUND: In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis. METHODS: A total of 296 clinical oral yeasts were isolated from 292 HIV-infected patients with oropharyngeal candidiasis at the Muhimbili National Hospital, Dar es Salaam, Tanzania. Identification of the yeasts was performed using standard phenotypic methods. Antifungal susceptibility to fluconazole, itraconazole, miconazole, clotrimazole, amphotericin B and nystatin was assessed using a broth microdilution format according to the guidelines of the Clinical and Laboratory Standard Institute (CLSI; M27-A2). RESULTS: Candida albicans was the most frequently isolated species from 250 (84.5%) patients followed by C. glabrata from 20 (6.8%) patients, and C. krusei from 10 (3.4%) patients. There was no observed significant difference in species distribution between patients with primary and recurrent oropharyngeal candidiasis, but isolates cultured from patients previously treated were significantly less susceptible to the azole compounds compared to those cultured from antifungal naïve patients. CONCLUSION: C. albicans was the most frequently isolated species from patients with oropharyngeal candidiasis. Oral yeast isolates from Tanzania had high level susceptibility to the antifungal agents tested. Recurrent oropharyngeal candidiasis and previous antifungal therapy significantly correlated with reduced susceptibility to azoles antifungal agents.