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Itraconazole

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https://www.readbyqxmd.com/read/28088635/mucoadhesive-amorphous-solid-dispersions-for-sustained-release-of-poorly-water-soluble-drugs
#1
Justin S LaFountaine, Leena Kumari Prasad, Dave A Miller, James W McGinity, Robert O Williams
The oral delivery of mucoadhesive patches has been shown to enhance the absorption of large molecules such as peptides. We hypothesized that this mechanism could have utility for poorly soluble small molecules by utilizing a mucoadhesive polymer as the matrix for an amorphous solid dispersion. Binary dispersions of itraconazole and carbomer (Carbopol 71G) were prepared utilizing a thermokinetic mixing process (KinetiSol Dispersing) and the physicochemical properties were investigated by powder x-ray diffraction, calorimetry, and liquid chromatography...
January 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28088354/uncovering-oxysterol-binding-protein-osbp-as-a-target-of-the-anti-enteroviral-compound-ttp-8307
#2
Lucian Albulescu, Joëlle Bigay, Bishyajit Biswas, Marion Weber-Boyvat, Cristina M Dorobantu, Leen Delang, Hilde M van der Schaar, Young-Sik Jung, Johan Neyts, Vesa M Olkkonen, Frank J M van Kuppeveld, Jeroen R P M Strating
The genus Enterovirus (e.g. poliovirus, coxsackievirus, rhinovirus) of the Picornaviridae family of positive-strand RNA viruses includes many important pathogens linked to a range of acute and chronic diseases for which no approved antiviral therapy is available. Targeting a step in the life cycle that is highly conserved provides an attractive strategy for developing broad-range inhibitors of enterovirus infection. A step that is currently explored as a target for the development of antivirals is the formation of replication organelles, which support replication of the viral genome...
January 11, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28087293/first-itraconazole-resistant-aspergillus-fumigatus-clinical-isolate-harbouring-a-g54e-substitution-in-cyp51ap-in-south-america
#3
Florencia Leonardelli, Laura Theill, María Elena Nardin, Daiana Macedo, Catiana Dudiuk, Emilce Mendez, Soledad Gamarra, Guillermo Garcia-Effron
BACKGROUND: A 27-year-old male rural worker was admitted with a fungal keratitis due to an injury involving plant detritus. MATERIALS AND METHODS: Specimens were collected for microscopy examination and culture. The isolate was identified by morphological and molecular criteria. Susceptibility testing was performed using CLSI methods. CYP51A gene was PCR amplified and sequenced. RESULTS: An Aspergillus fumigatus strain resistant to itraconazole (MIC>8μg/ml) was isolated...
January 10, 2017: Revista Iberoamericana de Micología
https://www.readbyqxmd.com/read/28080986/clinical-implications-of-globally-emerging-azole-resistance-in-aspergillus-fumigatus
#4
REVIEW
Jacques F Meis, Anuradha Chowdhary, Johanna L Rhodes, Matthew C Fisher, Paul E Verweij
Aspergillus fungi are the cause of an array of diseases affecting humans, animals and plants. The triazole antifungal agents itraconazole, voriconazole, isavuconazole and posaconazole are treatment options against diseases caused by Aspergillus However, resistance to azoles has recently emerged as a new therapeutic challenge in six continents. Although de novo azole resistance occurs occasionally in patients during azole therapy, the main burden is the aquisition of resistance through the environment. In this setting, the evolution of resistance is attributed to the widespread use of azole-based fungicides...
December 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28080217/synergistic-effects-of-tetrandrine-with-posaconazole-against-aspergillus-fumigatus
#5
Shui-Xiu Li, Yan-Jun Song, Ling Jiang, Ya-Jing Zhao, Hui Guo, Dong-Mei Li, Kun-Ju Zhu, Hong Zhang
In our earlier in vitro and in vivo studies, synergistic effects were observed when itraconazole or voriconazole were combined with tetrandrine (TET) against Aspergillus fumigatus, and the synergistic mechanism was related to inhibition of the drug efflux pump. Posaconazole (PCZ) is a broad-spectrum triazole antifungal agent used for the treatment of diverse fungal infections, including aspergillosis and candidiasis. Herein, the antifungal effects of TET are further investigated in vitro and in vivo alone or combined with PCZ against 20 clinical isolates of A...
January 12, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28070489/acute-disseminated-histoplasmosis-with-atypical-lymphocytosis-in-an-immunocompetent-host
#6
Ayman Elbadawi, Hamdy M A Ahmed, Hussain Adly, Mohamed A Elkhouly, Samar Abohamed, Ann R Falsey
65 year-old-male presented with a one-week history of high grade fever, fatigue and confusion which began abruptly two days after a cystoscopy procedure. Past medical history included pulmonary sarcoidosis diagnosed by mediastinal lymph biopsy, diabetes and hypertension. On admission he was febrile and confused with stable vital signs. Initial workup included negative Head CT and lumbar puncture. Blood work revealed normal metabolic and liver function tests with progressive anemia, thrombocytopenia and atypical lymphocytosis of 15-20%...
2017: IDCases
https://www.readbyqxmd.com/read/28070050/-clinical-comparative-analysis-for-pulmonary-histoplasmosis-and-progressive-disseminated-histoplasmosis
#7
Yan Zhang, Xiaoli Su, Yuanyuan Li, Ruoxi He, Chengping Hu, Pinhua Pan
To compare clinical features, diagnosis and therapeutic effect between pulmonary histoplasmosis and progressive disseminated histoplasmosis.
 Methods: A retrospective analysis for 12 cases of hospitalized patients with histoplasmosis, who was admitted in Xiangya Hospital, Central South University during the time from February 2009 to October 2015, was carried out. Four cases of pulmonary histoplasmosis and 8 cases of progressive disseminated histoplasmosis were included. The differences of clinical features, imaging tests, means for diagnosis and prognosis were analyzed between the two types of histoplasmosis...
December 28, 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28065821/an-evaluation-of-the-utility-of-lvdp-dt40-qa-interval-lvdp-dtmin-and-tau-as-indicators-of-drug-induced-changes-in-contractility-and-lusitropy-in-dogs
#8
Michael K Pugsley, Brian Guth, Alan Y Chiang, Jennifer M Doyle, Michael Engwall, Jean-Michel Guillon, Peter K Hoffmann, John E Koerner, Scott W Mittelstadt, Jennifer Beck Pierson, Eric I Rossman, R Dustan Sarazan, Stan Parish
INTRODUCTION: The importance of drug-induced effects on the inotropic state of the heart is well known.Unlike hemodynamic and cardiac electrophysiological methods, which have been routinely used in drug safety testing for years, the non-clinical assessment of drug effects on myocardial contractility is used less frequently with no established translation to humans. The goal of these studies was to determine whether assessment of alternate measures of cardiac inotropy could detect drug-induced changes in the contractile state of the heart using drugs known to have clinically relevant positive and negative effects on myocardial contractility...
January 5, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28062431/disseminated-histoplasmosis-presenting-as-diabetic-keto-acidosis-in-an-immunocompetent-patient
#9
Negin Niknam, Prashant Malhotra, Angela Kim, Seth Koenig
Histoplasma capsulatum causes a spectrum of manifestations from asymptomatic to fatal disseminated disease. Disseminated histoplasmosis is mostly seen in endemic areas among immunocompromised patients such as those with AIDS. Here, we present a patient living in a non-endemic area with previously undiagnosed diabetes mellitus, who presented with septic shock and diabetic ketoacidosis (DKA), and was ultimately diagnosed with disseminated histoplasmosis. The patient rapidly recovered on administration of intravenous liposomal amphotericin followed by oral itraconazole...
January 6, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28062320/melanised-fungal-infections-in-kidney-transplant-recipients-contributions-to-optimize-the-clinical-management
#10
Daniel Wagner de Castro Lima Santos, Luis Fernando Aranha Camargo, Sarah Santos Gonçalves, Marília Marufuji Ogawa, Jane Tomimori, Milvia Maria Simões E Silva Enokihara, José Osmar Medina Pestana, Arnaldo Lopes Colombo
OBJECTIVES: This is a retrospective and observational study addressing clinical and therapeutic aspects of melanised fungal infections in kidney transplant recipients. METHODS: We retrospectively reviewed medical records of all patients admitted between January 1996 and December 2013 in a single institution who developed infections by melanised fungi. RESULTS: We reported 56 patients aging between 30 and 74 years with phaeohyphomycosis or chromoblastomycosis (0...
January 3, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28057172/substrate-specificity-of-human-cytochrome-p450-cyp-2c-subfamily-and-effect-of-azole-antifungal-agents-on-cyp2c8
#11
Toshiro Niwa, Yurie Imagawa
PURPOSE: The metabolic activities of aminopyrine N-demethylation and tolbutamide methylhydroxylation by the human hepatic cytochrome P450 (P450 or CYP) 2C subfamily were compared and the effects of azole antifungal agent on the drug-metabolizing activity of CYP2C8 were investigated. METHODS: Aminopyrine N-demethylation and tolbutamide methylhydroxylation by CYP2C8, CYP2C9, and CYP2C19 were determined by the previous reported methods. The effects of five azole antifungal agents, fluconazole, itraconazole, ketoconazole, miconazole, and voriconazole, on the aminopyrine N-demethylation activity by CYP2C8 were investigated...
October 2016: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28053212/multilocus-phylogeny-and-antifungal-susceptibility-of-aspergillus-section-circumdati-from-clinical-samples-and-description-of-a-pseudosclerotiorum-sp-nov
#12
J P Z Siqueira, D A Sutton, J Gené, D García, N Wiederhold, S W Peterson, J Guarro
A multilocus phylogenetic study was carried out to assess species identity of a set of 34 clinical isolates from Aspergillus section Circumdati from the USA, and to determine their in vitro antifungal susceptibility against eight antifungal drugs. The genetic markers used were ITS, BenA, CaM and RPB2, and the drugs tested were amphotericin B, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, micafungin, and terbinafine. The most common species sampled was A. westerdijkiae (29.4%), followed by a novel species, which was described here as A...
January 4, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28052853/activity-of-a-long-acting-echinocandin-cd101-and-seven-comparator-antifungal-agents-tested-against-a-global-collection-of-contemporary-invasive-fungal-isolates-in-the-sentry-2014-antifungal-surveillance-program
#13
Michael A Pfaller, Shawn A Messer, Paul R Rhomberg, Mariana Castanheira
The activity of CD101 and comparators was evaluated against 606 invasive fungal isolates collected worldwide during 2014 using the CLSI method. All C. albicans (n=251), C. tropicalis (n=51), C. krusei (n=16), and C. dubliniensis (n=11) were inhibited by ≤0.12 μg/ml of CD101 and were susceptible or wild type to other echinocandins. Five C. glabrata (n=100) displayed CD101 MIC values of 1-4 μg/ml, elevated caspofungin (2->8 μg/ml), anidulafungin (2-4 μg/ml), and micafungin (2-4 μg/ml) MICs, and carried mutations on fks1/fks2 C...
January 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28052140/a-novel-zn2-cys6-transcription-factor-atrr-plays-a-key-role-in-an-azole-resistance-mechanism-of-aspergillus-fumigatus-by-co-regulating-cyp51a-and-cdr1b-expressions
#14
Daisuke Hagiwara, Daisuke Miura, Kiminori Shimizu, Sanjoy Paul, Ayumi Ohba, Tohru Gonoi, Akira Watanabe, Katsuhiko Kamei, Takahiro Shintani, W Scott Moye-Rowley, Susumu Kawamoto, Katsuya Gomi
Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To elucidate mechanisms underlying azole resistance, we identified a novel transcription factor that is required for normal azole resistance in Aspergillus fungi including A. fumigatus, Aspergillus oryzae, and Aspergillus nidulans...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28050634/damage-resistance-protein-dap-contributes-to-azole-resistance-in-a-sterol-regulatory-element-binding-protein-srba-dependent-way
#15
Jinxing Song, Pengfei Zhai, Ling Lu
The targeting of stress-response regulators has emerged as a powerful strategy to enhance azole drug efficacy and to abrogate azole drug resistance. Previously, we reported that a damage resistance protein (Dap) family, composed of DapA, DapB, and DapC, could respond to azole stress stimuli in Aspergillus fumigatus, although the exact response mechanisms remain unknown. In this study, RNA-seq analysis found that a total of 180 genes are induced by azole in a dapA-dependent manner. These genes are involved in oxidation-reduction, metabolic processes, and transmembrane transport...
January 3, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28045862/comparing-azole-plasma-trough-levels-in-lung-transplant-recipients-percentage-of-therapeutic-levels-and-intra-patient-variability
#16
Stelzer Daniela, Weber Alexandra, Ihle Franziska, Matthes Sandhya, Ceelen Felix, Zimmermann Gregor, Kneidinger Nikolaus, Schramm Rene, Winter Hauke, Zoller Michael, Vogeser Michael, Behr Juergen, Neurohr Claus
BACKGROUND: This study compared therapeutic azole plasma trough levels (APL) of the azole antimycotics itraconazole (ITR), voriconazole (VOR), and posaconazole (POS) in lung transplant recipients and analyzed the influencing factors. In addition, intra-patient variability for each azole was determined. METHODS: From July 2012 to July 2015, 806 APL of ITR, VOR, POS liquid (POS-Liq), and POS tablets (POS-Tab) were measured in 173 patients of the Munich Lung Transplantation (LTx) Program...
December 29, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28042367/the-upside-of-bias-a-case-of-chronic-meningitis-due-to-sporothrix-schenckii-in-an-immunocompetent-host
#17
Christine Hessler, Carol A Kauffman, Felicia C Chow
Chronic meningitis of unknown etiology is a vexing illness for patients and clinicians. Identification of the correct pathogen can be challenging and time consuming, leading to delays in appropriate treatment. Although Sporothrix schenckii is a recognized and treatable cause of chronic meningitis, neurologists and infectious diseases physicians may not regularly evaluate for Sporothrix infection. We describe an immunocompetent patient with chronic meningitis who partially responded to empiric fluconazole. Prompted by a recent culture-confirmed case of meningeal sporotrichosis, we tested for S schenckii antibodies from the cerebrospinal fluid, which were positive...
January 2017: Neurohospitalist
https://www.readbyqxmd.com/read/28040821/over-the-counter-and-natural-remedies-for-onychomycosis-do-they-really-work
#18
Pierre Halteh, Richard K Scher, Shari R Lipner
Onychomycosis is a fungal infection of the nail unit that may lead to dystrophy and disfigurement over time. It accounts for up to 50% of all nail conditions, with toenails affected more commonly than fingernails. Onychomycosis may affect quality of life and increase the prevalence and severity of foot ulcers in patients with diabetes. Available oral agents approved by the US Food and Drug Administration (FDA) for the treatment of onychomycosis include terbinafine and itraconazole, which have demonstrated good efficacy but are associated with the risk of systemic side effects and drug-drug interactions...
November 2016: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28040409/antifungal-effects-of-phytocompounds-on-candida-species-alone-and-in-combination-with-fluconazole
#19
REVIEW
Mengjiao Lu, Tao Li, Jianjian Wan, Xiuyun Li, Lei Yuan, Shujuan Sun
Invasive fungal infections caused by Candida spp. remain the most predominant nosocomial fungal infections. Owing to the increased use of antifungal agents, resistance of Candida spp. to antimycotics has emerged frequently, especially to fluconazole (FLC). To cope with this issue, new efforts have been dedicated to discovering novel antimycotics or new agents that can enhance the susceptibility of Candida spp. to existing antimycotics. The secondary metabolites of plants represent a large library of compounds that are important sources for new drugs or compounds suitable for further modification...
December 15, 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28034694/single-jugular-vein-cannulated-rats-may-not-be-suitable-for-intravenous-pharmacokinetic-screening-of-high-logp-compounds
#20
Nilesh Gaud, Anoop Kumar, Muralikrishna Matta, Prashant Kole, Srikanth Sridhar, Sandhya Mandlekar, Vinay K Holenarsipur
Rat is commonly used for pharmacokinetic screening during pharmaceutical lead optimization. To handle the large number of compounds, rats with a single jugular vein cannulation are commonly utilized for intravenous pharmacokinetic studies, where the same cannula is used both for dose administration and blood sampling. We demonstrate that the single cannula method is not suitable for all compounds, especially for high logP compounds. We propose an alternative dual cannulation technique in which two cannulas are placed in the same jugular vein, thus avoiding an additional surgery...
December 26, 2016: European Journal of Pharmaceutical Sciences
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