The effect of selected steroids on the growth, morphology, and sterol contents of Candida albicans

The effect of three selected steroids—decadron, alphadolone acetate and cholic acid salt—on the growth, morphology and sterol content of the yeast and mycelial form of Candida albicans was studied. The effect on growth was measured by dry weight, turbidity and viable count. It was observed that the three steroids promoted the growth of C. albicans. The morphology studies showed two different types of cells: (1) cells which were able to adapt to growth in the presence of exogenous steroids; and (2) cells which were unable to so adapt. Adapted yeast cells were longer and more elongated with a smooth surface. These cells were observed to grow very well and to be involved in cell division especially at high steroid concentrations. The internal structures of these adapted cells were well preserved with distinct intracytoplasmatic structures. [Continues.

Characterization and partial purification of Candida albicans Secretory IL-12 Inhibitory Factor

© 2008 Wang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Evaluation of the ability of a novel miconazole formulation to penetrate nail by using three in vitro nail models

This document is the Accepted Manuscript of the following article: Luisa Christensen, Rob Turner, Sean Weaver, Francesco Caserta, Lisa Long, Mahmoud Ghannoum, and Marc Brown, ‘Evaluation of the Ability of a Novel Miconazole Formulation To Penetrate Nail by Using Three In Vitro Nail Models’, Antimicrobial Agents and Chemotherapy, Vol. 61 (7): e02554-16, July 2017. The final, published version is available online at DOI: https://doi.org/10.1128/AAC.02554-16.In an effort to increase the efficacy of topical medications for treating onychomycosis, several new nail penetration enhancers were recently developed. In this study, the ability of 10% (wt/wt) miconazole nitrate combined with a penetration enhancer formulation to permeate the nail is demonstrated by the use of a selection of in vitro nail penetration assays. These assays included the bovine hoof, TurChub zone of inhibition, and infected-nail models.Peer reviewedFinal Accepted Versio

Oral Cytokine Levels Are More Linked to Levels of Plasma and Oral HIV-1 RNA Than to CD4+ T-Cell Counts in People With HIV.

BackgroundWe determined the levels of 11 soluble immune mediators in oral washings of AIDS Clinical Trials Group A5254 participants with varying degrees of plasma viremia and CD4 T-cell counts to characterize the mucosal immune response at different stages of HIV-1 infection.MethodsA5254 was a multicenter, cross-sectional study in people with HIV (PWH) recruited into 4 strata based on CD4 count and levels of plasma viremia: stratum (St) A: CD4 ≤200 cells/mm3, HIV-1 RNA (viral load [VL]) >1000 cps/mL; St B: CD4 ≤200, VL ≤1000; St C: CD4 >200, VL >1000; St D: CD4 >200, VL ≤1000. Oral/throat washings were obtained from all participants. Soluble markers were tested in oral/throat washings using a multibead fluorescent platform and were compared across strata. Linear regression was used to determine the associations between cytokines and HIV-1 in plasma and oral fluid.ResultsSt A participants had higher levels of interleukin (IL)-1β, IL-6, IL-17, tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ) compared with St B and D (P = .02; P < .0001) but were not different from St C. IL-8, IL-10, and IL-12 were elevated in St A compared with the other 3 strata (P = .046; P < .0001). Linear regression demonstrated that oral HIV-1 levels were associated with IL-1β, IL-6, IL-8, and TNFα production (R > .40; P < .001) when controlling for CD4 count and opportunistic infections.ConclusionsOur results show that high levels of oral HIV-1, rather than low CD4 counts, were linked to the production of oral immune mediators. Participants with AIDS and uncontrolled viremia demonstrated higher levels of pro- and anti-inflammatory soluble immune mediators compared with participants with lower HIV-1 RNA. The interplay of HIV-1 and these immune mediators could be important in the oral health of PWH

Aceros al molibdeno sinterizados con gradiente funcional

Las propiedades que se solicitan a las piezas y productos exigen, la mayoría de las veces, una combinación de materiales que respondan a requerimientos específicos en función de su posición. La fabricación de materiales compuestos y materiales con gradiente funcional proporciona grandes posibilidades de respuesta a las necesidades demandas, tanto de satisfacción de requerimientos como de reducción de materias primas necesarias. En este sentido, satisfacer las propiedades demandadas, de manera localizada geométricamente, puede suponer un ahorro de materias primas y de los residuos relacionados en su fabricación. En el presente estudio de la sinterización a 1120 ºC de un compacto de dos aceros de diferentes composiciones (un acero con un 0,3 % C y un 2 % de cobre y un acero al molibdeno con un 0,7 % carbono y un 2 % de cobre) ofrece unas posibilidades muy atractivas de eficiencia, al reducir en el interior la composición que se requiere en la superficie de las piezas. Se han caracterizado las propiedades mecánicas de este acero sinterizado con gradiente funcional: densidad, variación dimensional, durezas y resistencia mecánica; ilustradas con el análisis de imagen mediante microscopía óptica y electrónica de barrido

Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections

Molds are ubiquitous in the environment, and immunocompromised patients are at substantial risk of morbidity and mortality due to their underlying disease and the resistance of pathogenic molds to currently recommended antifungal therapies. This combination of weakened-host defense, with limited antifungal treatment options, and the opportunism of environmental molds renders patients at risk and especially vulnerable to invasive mold infections such as Aspergillus and members of the Order Mucorales. Currently, available antifungal drugs such as azoles and echinocandins, as well as combinations of the same, offer some degree of efficacy in the prevention and treatment of invasive mold infections, but their use is often limited by drug resistance mechanisms, toxicity, drug-drug interactions, and the relative paucity of oral treatment options. Clearly, there is a need for agents that are of a new class that provides adequate tissue penetration, can be administered orally, and have broad-spectrum efficacy against fungal infections, including those caused by invasive mold organisms. Ibrexafungerp, an orally bioavailable glucan synthase inhibitor, is the first in a new class of triterpenoid antifungals and shares a similar target to the well-established echinocandins. Ibrexafungerp has a very favorable pharmacokinetic profile for the treatment of fungal infections with excellent tissue penetration in organs targeted by molds, such as the lungs, liver, and skin. Ibrexafungerp has demonstrated in vitro activity against Aspergillus spp. as well as efficacy in animal models of invasive aspergillosis and mucormycosis. Furthermore, ibrexafungerp is approved for use in the USA for the treatment of women with vulvovaginal candidiasis. Ibrexafungerp is currently being evaluated in clinical trials as monotherapy or in combination with other antifungals for treating invasive fungal infections caused by yeasts and molds. Thus, ibrexafungerp offers promise as a new addition to the clinician's armamentarium against these difficult-to-treat infections.Experiments reported in this manuscript were funded by Scynexis and support for mucormycosis research was provided by the NIH/NIAID under Contract No. HHSN272201700039I (Task order A34-HHSN27200003).S

Clinical Effects of Gamma-Radiation-Resistant Aspergillus sydowii on Germ-Free Mice Immunologically Prone to Inflammatory Bowel Disease

We report and investigated a case of inadvertent contamination of 125 mice (housed in two germ-free positive-pressurized isolators) with emerging human and coral pathogen Aspergillus sydowii. The infected mice correspond to genetic line SAMP1/YitFc, which have 100% immune predisposition to develop Crohn's disease-like spontaneous pathologies, namely, inflammatory bowel disease (IBD). Pathogen update based on a scoping review of the literature and our clinical observations and experimentation are discussed. The unwanted infection of germ-free mice (immunologically prone to suffer chronic inflammation) with human pathogen A. sydowii resulted in no overt signs of clinical disease over 3-week exposure period, or during DSS-induced colitis experiments. Results and observations suggest that A. sydowii alone has limited clinical effect in immunocompromised germ-free mice or that other commensal microbial flora is required for Aspergillus-associated disease to occur

Candida parapsilosis Characterization in an Outbreak Setting

Candida parapsilosis is an important non-albicans species which infects hospitalized patients. No studies have correlated outbreak infections of C. parapsilosis with multiple virulence factors. We used DNA fingerprinting to determine genetic variability among isolates from a C. parapsilosis outbreak and from our clinical database. We compared phenotypic markers of pathogenesis, including adherence, biofilm formation, and protein secretion (secretory aspartic protease [SAP] and phospholipase). Adherence was measured as colony counts on silicone elastomer disks immersed in agar. Biofilms formed on disks were quantified by dry weight. SAP expression was measured by hydrolysis of bovine albumin; a colorimetric assay was used to quantitate phospholipase. DNA fingerprinting indicated that the outbreak isolates were clonal and genetically distinct from our database. Biofilm expression by the outbreak clone was greater than that of sporadic isolates (p < 0.0005). Adherence and protein secretion did not correlate with strain pathogenicity. These results suggest that biofilm production plays a role in C. parapsilosis outbreaks

The monoclonal antibody Ca37, developed against Candida albicans alcohol dehydrogenase, inhibits the yeast in vitro and in vivo

Candida albicans is a commensal yeast able to cause life threatening invasive infections particularly in immunocompromised patients. Despite the availability of antifungal treatments, mortality rates are still unacceptably high and drug resistance is increasing. We, therefore, generated the Ca37 monoclonal antibody against the C. albicans alcohol dehydrogenase (Adh) 1. Our data showed that Ca37 was able to detect C. albicans cells, and it bound to Adh1 in yeast and Adh2 in hyphae among the cell wall-associated proteins. Moreover, Ca37 was able to inhibit candidal growth following 18h incubation time and reduced the minimal inhibitory concentration of amphotericin B or fluconazole when used in combination with those antifungals. In addition, the antibody prolonged the survival of C. albicans infected-Galleria mellonella larvae, when C. albicans was exposed to antibody prior to inoculating G. mellonella or by direct application as a therapeutic agent on infected larvae. In conclusion, the Ca37 monoclonal antibody proved to be effective against C. albicans, both in vitro and in vivo, and to act together with antifungal drugs, suggesting Adh proteins could be interesting therapeutic targets against this pathogen.Technical and human support provided by the Proteomics Core Facility-SGIker at the UPV/EHU is gratefully acknowledged. We thank the member of the Chartered of Linguists, No 022913 for improving the English in the manuscript. This work was supported by Basque Government (Grant IT1362-19). AA, IB and LMS have received a predoctoral Grant from Basque Government and LAF from UPV/EH

The Artificial Sweetener Splenda Promotes Gut Proteobacteria, Dysbiosis, and Myeloperoxidase Reactivity in Crohn’s Disease–Like Ileitis

We thank John D. Ward and Lindsey N. Kaydo for their technical support and Dr. Wei Xin for the histological scoring of ileitis severity. ARP is an Assistant Professor of Medicine at CWRU School of Medicine. Metagenomic sequencing was conducted in the laboratory of Dr. Skip Virgin at Washington University, School of Medicine, St. Louis, MO. Raw sequencing data files will be available upon request.Peer reviewedPostprin