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https://www.readbyqxmd.com/read/28545374/modulators-of-the-efflux-pump-cdr1p-of-candida-albicans-mechanisms-of-action-and-chemical-features
#1
Viet-Khoa Tran-Nguyen, Rajendra Prasad, Pierre Falson, Ahcène Boumendjel
The multicomponent primary active ATP-binding cassette transporter Cdr1p in the structure of the pathogenic yeast Candida albicans is among the culprits of antifungal agent resistance reported in recent decades. So far, various potential novel inhibitors/ modulators of this protein have been purified, synthesized, and biologically tested, with results showing their ability to effectively reverse CaCdr1p-mediated drug resistance phenomenon. These compounds are of diverse origins, possess non-identical structural features and adopt different mechanisms of action...
May 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28543298/synthesis-and-preclinical-pharmacokinetic-study-of-dha-10-a-novel-potential-antifungal-pogostone-analogue
#2
Ming Liu, Yanfen Zhou, Jianwei Zhu, Bo Ma, Zheng Fang, Qi Zhang
OBJECTIVES: The emergence of fungal disease calls for the urgency of development of novel drug. In this study, we developed a novel pogostone analogue, DHA-10 and investigated its preclinical pharmacokinetics, tissue distribution, excretion and protein binding rate in rats. METHODS: DHA-10 was synthesized with dehydroacetic acid (DHA) as the starting material and the structure confirmed by NMR and HRMS. The LC-MS/MS was applied to quantitative analysis of DHA-10 concentrations in the biological samples...
May 23, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28540871/clinico-mycological-study-of-dermatophytic-infections-and-their-sensitivity-to-antifungal-drugs-in-a-tertiary-care-center
#3
Soniya Mahajan, Ragini Tilak, Satyendra K Kaushal, Rabindra N Mishra, Shyam S Pandey
BACKGROUND: Worldwide, dermatophytic infections are running a chronic course either due to ineffective treatment or emerging drug resistance. In the past three decades, there has been an increase in incidence and non-responsiveness to conventional antifungals, which suggests that there is a need of antifungal sensitivity testing. AIMS: This study was aimed at identifying clinico-mycological pattern of dermatophytic infections in patients attending thedermatology outpatient department of a tertiary care hospital, and to obtain the sensitivity pattern of isolates against six commonly used oral antifungals (fluconazole, terbinafine, itraconazole, ketoconazole, griseofulvin and voriconazole)...
May 22, 2017: Indian Journal of Dermatology, Venereology and Leprology
https://www.readbyqxmd.com/read/28540147/candida-prosthetic-joint-infection-a-review-of-treatment-methods
#4
REVIEW
Fernando Cobo, Javier Rodríguez-Granger, Antonio Sampedro, Luis Aliaga-Martínez, José María Navarro-Marí
Fungal microorganisms are still a rare cause of bone and joint infections. We report a new case of knee prosthetic joint infection due to Candida albicans in a patient with a previous two-stage right knee arthroplasty for septic arthritis due to S. epidermidis occurred several months ago. Moreover, the treatment in 76 cases of Candida prosthetic joint infection has been discussed. Forty patients were female and mean age at diagnosis was 65.7 (± SD 18) yrs. No risk factors for candidal infection were found in 25 patients...
2017: J Bone Jt Infect
https://www.readbyqxmd.com/read/28539243/synthesis-sar-and-molecular-docking-studies-of-benzo-d-thiazole-hydrazones-as-potential-antibacterial-and-antifungal-agents
#5
Gao-Feng Zha, Jing Leng, N Darshini, T Shubhavathi, H K Vivek, Abdullah M Asiri, Hadi M Marwani, K P Rakesh, N Mallesha, Hua-Li Qin
A series of new benzo[d]thiazole-hydrazones analogues were synthesized and screened for their in vitro antibacterial and antifungal activities. The results revealed that compounds 13, 14, 15, 19, 20, 28 and 30 exhibited superior antibacterial potency compared to the reference drug chloramphenicol and rifampicin. Compounds 5, 9, 10, 11, 12, 28 and 30 were found to be good antifungal activity compared to the standard drug ketoconazole. A preliminary study of the structure-activity relationship (SAR) revealed that the antimicrobial activity depended on the effect of different substituents on the phenyl ring...
May 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28536123/randomized-controlled-trial-of-mineralocorticoid-receptor-blockade-in-children-with-chronic-kidney-allograft-nephropathy
#6
Mara Medeiros, Luis Velásquez-Jones, Ana M Hernández, Guillermo Ramón-García, Saúl Valverde, Yolanda Fuentes, Arindal Vargas, Mauricio Patiño, Rosalba Pérez-Villalva, Juan Antonio Ortega-Trejo, Jonatan Barrera-Chimal, Norma A Bobadilla
BACKGROUND AND OBJECTIVES: We showed that mineralocorticoid receptor blockade (MRB) prevented acute and chronic cyclosporine nephropathy (CsA-Nx) in the rat. The aim of this translational study was to investigate the effect of long-term eplerenone administration on renal allograft function in children with biopsy-proven chronic allograft nephropathy (CAN). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Renal transplant children <18 years, biopsy-proven CAN, and a GFR>40 ml/min per 1...
May 23, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28534445/differential-expression-of-micro-rnas-and-their-predicted-targets-in-renal-cells-exposed-to-amphotericin-b-and-its-complex-with-copper-ii-ions
#7
Joanna Magdalena Gola, Barbara Strzałka-Mrozik, Celina Kruszniewska-Rajs, Jolanta Adamska, Mariusz Gagoś, Urszula Mazurek
MicroRNAs (miRNAs) have been reported to regulate essential biological processes, and their expression was shown to be affected by pathological processes and drug-induced toxicity. Amphotericin B (AmB) can cause liver and kidney injury, but a recently developed complex of AmB with copper (II) ions (AmB-Cu(2+)) exhibits a lower toxicity to human renal cells while retaining a high antifungal activity. The aim of our study was to assess AmB-Cu(2+)- induced changes in the miRNA profile of renal cells and to examine which biological processes are significantly affected by AmB-Cu(2+)...
May 23, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28533240/heterocycle-thiazole-compounds-exhibit-antifungal-activity-through-increase-in-the-production-of-reactive-oxygen-species-in-cryptococcus-neoformans-cryptococcus-gattii-species-complex
#8
Nívea Pereira de Sá, Caroline Miranda de Lima, Cleudiomar Inácio Lino, Paulo Jorge Sanches Barbeira, Ludmila de Matos Baltazar, Daniel Assis Santos, Renata Barbosa de Oliveira, Eleftherios Mylonakis, Beth Burgwyn Fuchs, Susana Johann
Human cryptococcosis can occur as a primary or opportunistic infection and develops as an acute, sub-acute, or chronic systemic infection, involving different organs of the host. Given the limited therapeutic options and the occasional resistance to fluconazole, there is a need to develop novel drugs for the treatment of cryptococcosis. In this report, we describe promising thiazoles 1, 2, 3, and 4 and explore their possible modes of action against Cryptococcus. To this end, we show evidence of interference in the Cryptococcus antioxidant system...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28531175/weekly-high-dose-liposomal-amphotericin-b-l-amb-in-critically-ill-septic-patients-with-multiple-candida-colonization-the-ambidex-study
#9
Elie Azoulay, Jean-François Timsit, Alexandre Lautrette, Stephane Legriel, Adeline Max, Stephane Ruckly, Benoit Misset, Yves Cohen, Michel Wolff
BACKGROUND: To demonstrate the feasibility and safety of weekly high-dose liposomal amphotericin B (L-AmB) (as a pre-emptive antifungal treatment) for 2 weeks in patients with septic shock and Candida colonization. METHODS: Pilot, multicentre, open-label, prospective study conducted in seven French ICUs. Non-immunocompromised patients, receiving mechanical ventilation were eligible if they presented ICU-acquired severe sepsis requiring newly administered antibacterial agents and Candida colonization in at least two sites...
2017: PloS One
https://www.readbyqxmd.com/read/28528783/revelation-and-cloning-of-valinomycin-synthetase-genes-in-streptomyces-lavendulae-acr-da1-and-their-expression-analysis-under-different-fermentation-and-elicitation-conditions
#10
Richa Sharma, Vijaylakshmi Jamwal, Varun P Singh, Priya Wazir, Praveen Awasthi, Deepika Singh, Sumit G Gandhi, Ram A Vishwakarma, Asha Chaubey
Streptomyces species are amongst the most exploited microorganisms due to their ability to produce a plethora of secondary metabolites with bioactive potential, including several well known drugs. They are endowed with immense unexplored potential and substantial efforts are required for their isolation as well as characterization for their bioactive potential. Unexplored niches and extreme environments are host to diverse microbial species. In this study, we report Streptomyces lavendulae ACR-DA1, isolated from extreme cold deserts of the North Western Himalayas, which produces a macrolactone antibiotic, valinomycin...
May 18, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28528250/antifungal-toxicity-of-linear-geranylphenol-influence-of-oxigenate-substituents
#11
Lautaro Taborga, Maximiliano Sortino, Carrasco Héctor, Estefanía Butassi, Susana Zacchino, Luis Espinoza
Twenty four linear geranylphenols were evaluated for their antifungal properties against ATCC and clinical isolates of Candida albicans and Cryptococcus neoformans. For the analysis of their antifungal behavior the compounds were grouped into two series: (i) compounds with only one geranyl substituent on the benzene ring and (ii) compounds with two geranyl moieties on the benzene ring. Results showed that compounds of series (i) present better antifungal activities than those of series (ii). In addition, within group (i) all compounds showed better activities against C...
May 17, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28527633/anthelmintic-activity-of-cytochrome-p450-inhibitors-miconazole-and-clotrimazole-in-vitro-effect-on-the-liver-fluke-opisthorchis-felineus
#12
Viatcheslav A Mordvinov, Alexander G Shilov, Maria Y Pakharukova
Discovery of drugs for the treatment of opisthorchiasis and schistosomiasis is a high priority. The basic metabolic cytochrome P450 (CYP) system in parasitic flatworms contains a single gene. CYP of the liver fluke Opisthorchis felineus, the causative agent of opisthorchiasis, is important for survival of the worm, so may be a promising target for therapeutics against liver fluke infection. The aims of this study were: (i) to analyse in-vitro anthelmintic activity of various CYP inhibitors using standard motility and mortality assays against juvenile and adult O...
May 17, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28523422/usefulness-of-the-non-conventional-caenorhabditis-elegans-model-to-assess-candida-virulence
#13
Marcelo Ortega-Riveros, Iker De-la-Pinta, Cristina Marcos-Arias, Guillermo Ezpeleta, Guillermo Quindós, Elena Eraso
Invasive candidiasis is caused mainly by Candida albicans, but other Candida species have increasing etiologies. These species show different virulence and susceptibility levels to antifungal drugs. The aims of this study were to evaluate the usefulness of the non-conventional model Caenorhabditis elegans to assess the in vivo virulence of seven different Candida species and to compare the virulence in vivo with the in vitro production of proteinases and phospholipases, hemolytic activity and biofilm development capacity...
May 18, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28522642/influence-of-drug-class-and-healthcare-setting-on-systemic-antifungal-expenditures-in-the-united-states-2005-15
#14
Margaret A Fitzpatrick, Katie J Suda, Charlesnika T Evans, Robert J Hunkler, Frances Weaver, Glen T Schumock
PURPOSE: Overall and specific class trends in systemic antifungal expenditures in various U.S. healthcare settings from 2005 through 2015 were evaluated. METHODS: Systemic antifungal expenditures from January 1, 2005, through December 31, 2015, were obtained from the QuintilesIMS National Sales Perspective database, which provides a statistically valid projection of medication purchases from multiple markets throughout the United States. Summary data for total antifungal expenditures over the entire period are reported, as are growth and the percentage change in expenditures from one year to the next...
May 18, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28522423/sertaconazole-nitrate-loaded-nanovesicular-systems-for-targeting-skin-fungal-infection-in-vitro-ex-vivo-and-in-vivo-evaluation
#15
Menna M Abdellatif, Islam A Khalil, Mahmoud A F Khalil
The aim of this study was to develop different vesicular systems for sertaconazole nitrate and evaluate the ability of targeting deep skin layers to treat dermal fungal infection. Therefore, different phospholipid based nanovesicles, namely liposomes, glycerosomes, transferosmes and ethosomes were prepared and in-vitro evaluated for morphology, entrapment efficiency, vesicle size and zeta potential value, followed by ex-vivo evaluation through skin penetration and permeation. The selected vesicular formula was incorporated into gel base system and assessed by ex-vivo permeation visualization study using confocal laser scanning microscopy (CLSM)...
May 15, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28516956/selective-bet-bromodomain-inhibition-as-an-antifungal-therapeutic-strategy
#16
Flore Mietton, Elena Ferri, Morgane Champleboux, Ninon Zala, Danièle Maubon, Yingsheng Zhou, Mike Harbut, Didier Spittler, Cécile Garnaud, Marie Courçon, Murielle Chauvel, Christophe d'Enfert, Boris A Kashemirov, Mitchell Hull, Muriel Cornet, Charles E McKenna, Jérôme Govin, Carlo Petosa
Invasive fungal infections cause significant morbidity and mortality among immunocompromised individuals, posing an urgent need for new antifungal therapeutic strategies. Here we investigate a chromatin-interacting module, the bromodomain (BD) from the BET family of proteins, as a potential antifungal target in Candida albicans, a major human fungal pathogen. We show that the BET protein Bdf1 is essential in C. albicans and that mutations inactivating its two BDs result in a loss of viability in vitro and decreased virulence in mice...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28516493/diagnosis-and-treatment-of-dermatophytosis-in-dogs-and-cats-clinical-consensus-guidelines-of-the-world-association-for-veterinary-dermatology
#17
REVIEW
Karen A Moriello, Kimberly Coyner, Susan Paterson, Bernard Mignon
BACKGROUND: Dermatophytosis is a superficial fungal skin disease of cats and dogs. The most common pathogens of small animals belong to the genera Microsporum and Trichophyton. It is an important skin disease because it is contagious, infectious and can be transmitted to people. OBJECTIVES: The objective of this document is to review the existing literature and provide consensus recommendations for veterinary clinicians and lay people on the diagnosis and treatment of dermatophytosis in cats and dogs...
June 2017: Veterinary Dermatology
https://www.readbyqxmd.com/read/28515716/antifungal-activity-of-the-biphosphinic-cyclopalladate-c7a-against-candida-albicans-yeast-forms-in-vitro-and-in-vivo
#18
Julian E Muñoz, Diego C P Rossi, Kelly Ishida, Cristina C Spadari, Marcia S C Melhem, Daniel M Garcia, Antonio C F Caires, Carlos P Taborda, Elaine G Rodrigues
Vulvovaginal and invasive candidiasis are frequent conditions in immunosuppressed individuals caused by Candida albicans and non-albicans Candida spp. Fluconazole and Amphotericin B are the main drugs used to fight the infection. However, resistance to fluconazole and other azole antifungal drugs is an important clinical problem that encourages the search for new therapeutic alternatives. In this work, we evaluate the antifungal activity of the biphosphinic cyclopalladate C7a in the in vitro and in vivo model...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28515217/an-analytical-and-clinical-evaluation-of-the-pathonostics-aspergenius%C3%A2-assay-for-the-detection-of-invasive-aspergillosis-and-resistance-to-azole-antifungal-drugs-direct-from-plasma-samples
#19
P Lewis White, Raquel B Posso, Rosemary A Barnes
With the proposal to include Aspergillus PCR in the revised EORTC/MSG definitions for fungal disease, commercially manufactured assays may be required to provide standardisation and accessibility. The PathoNostics AsperGenius® assay represents one such test that has the ability to detect a range of Aspergillus species and azole-resistance in A. fumigatus Performance has been validated when testing BAL and serum specimens, but recent evidence suggests that testing plasma may enhance sensitivity over serum. It was decided to evaluate the analytical and clinical performance of the PathoNostics AsperGenius® assay when testing plasma...
May 17, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28513771/species-distribution-and-antifungal-susceptibility-patterns-of-candida-isolates-from-a-public-tertiary-teaching-hospital-in-the-eastern-cape-province-south-africa
#20
P Mnge, B I Okeleye, S D Vasaikar, T Apalata
Candida species are the leading cause of invasive fungal infections, and over the past decade there has been an increased isolation of drug resistant Candida species. This study aimed to identify the species distribution of Candida isolates and to determine their unique antifungal susceptibility and resistance patterns. During a cross-sectional study, 209 Candida isolates (recovered from 206 clinical samples) were collected and their species distribution was determined using ChromAgar Candida. The Vitek-2 system (Biomerieux, South Africa) was used to determine minimum inhibitory concentrations (MICs) to azoles (fluconazole, voriconazole), echinocandins (caspofungin, micafungin), polyenes (amphotericin B) and flucytosine...
May 15, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
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