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Xiaokui Gu, Wei Xue, Yajing Yin, Hongwei Liu, Shaojie Li, Xianyun Sun
Heat Shock Protein 90 (Hsp90) is essential for tumor progression in humans and drug resistance in fungi. However, the roles of its many co-chaperones in antifungal resistance are unknown. In this study, by susceptibility test of Neurospora crassa mutants lacking each of 18 Hsp90/Calcineurin system member genes (including 8 Hsp90 co-chaperone genes) to antifungal drugs and other stresses, we demonstrate that the Hsp90 co-chaperones Sti1 (Hop1 in yeast), Aha1, and P23 (Sba1 in yeast) were required for the basal resistance to antifungal azoles and heat stress...
2016: Frontiers in Microbiology
Ming Li, Inge A M de Graaf, Marina H de Jager, Geny M M Groothuis
Although intestinal P-glycoprotein (P-gp) has been extensively studied in vitro and in animals, its activity and the consequences of P-gp inhibition for drug disposition and toxicity in humans are still difficult to accurately extrapolate from these studies. Moreover, existing in vitro models do not take into consideration that the intestine is heterogeneous with respect to P-gp expression. Recently, we reported rat precision-cut intestinal slices (PCIS) as a physiological ex vivo model to study the regional gradient of P-gp activity and inhibition...
October 19, 2016: Biopharmaceutics & Drug Disposition
Zachery R Reichert, Maha Hussain
The development of metastatic castration-resistant prostate cancer (mCRPC) signals the terminal disease phase. The preceding hormone-dependent disease setting is effectively managed with androgen deprivation therapy. This foundation of treatment has a high rate of biochemical and clinical response and meaningful clinical benefit but is finite in duration as most cancers will progress to castration resistance. Historically, treatment for mCRPC entailed androgen receptor (AR) inhibitors (nilutamide, flutamide, bicalutamide), nonspecific steroidal biosynthesis inhibitors (ketoconazole, itraconazole), steroids (prednisone, diethylstilbesterol, dexamethasone), or palliative chemotherapy (mitoxantrone, estramustine), but none of these strategies impacted survival...
September 2016: Cancer Journal
Juliana Hotta, Wilson Gustavo Cral, Vinicius Tatsuyuji Sakima, Vanessa Soares Lara, Vanessa Migliorini Urban, Karin Hermana Neppelenbroek
BACKGROUND: Antifungal agents incorporated into temporary denture resilient liners as drug carries and delivery have been suggested as an alternative treatment for denture stomatitis. However, to test the in vivo biocompatibility of this protocol, standardization of an intraoral device for optimal drug delivery is required. OBJECTIVE: Standardized criteria were produced to adjust an acrylic intraoral device (IOD) for rats feasible for denture stomatitis treatment by sustained drug-delivery based on minimal inhibitory drug concentrations (MICs) of antifungals for Candida albicans biofilm...
October 13, 2016: Current Drug Delivery
Steven A Lacy, Dale R Miles, Linh T Nguyen
Cabozantinib inhibits receptor tyrosine kinases involved in tumor angiogenesis and metastasis. The capsule formulation (Cometriq(®)) is approved for the treatment of progressive metastatic medullary thyroid cancer at a 140-mg free base equivalent dose. The tablet formulation (Cabometyx™, 60-mg free base equivalent dose) is approved for the treatment of renal cell carcinoma following anti-angiogenic therapy. Cabozantinib displays a long terminal plasma half-life (~120 h) and accumulates ~fivefold by day 15 following daily dosing based on area under the plasma concentration-time curve (AUC)...
October 12, 2016: Clinical Pharmacokinetics
Ramy Sedhom, Sophia Hu, Anupam Ohri, Dorian Infantino, Sara Lubitz
BACKGROUND: Malignant steroid cell tumors of the ovary are rare and frequently associated with hormonal abnormalities. There are no guidelines on how to treat rapidly progressive Cushing's syndrome, a medical emergency. CASE PRESENTATION: A 67-year-old white woman presented to our hospital with rapidly developing signs and symptoms of Cushing's syndrome secondary to a steroid-secreting tumor. Her physical and biochemical manifestations of Cushing's syndrome progressed, and she was not amenable to undergoing conventional chemotherapy secondary to the debilitating effects of high cortisol...
October 12, 2016: Journal of Medical Case Reports
Nicholas M Njuguna, Ken-Ichi Umehara, Felix Huth, Hilmar Schiller, Kelly Chibale, Gian Camenisch
BACKGROUND: The fraction of an absorbed drug metabolized by the different hepatic cytochrome P450 (CYP) enzymes, relative to total hepatic CYP metabolism (fmCYP), can be estimated by measuring the inhibitory effects of presumably selective CYP inhibitors on the intrinsic metabolic clearance of a drug using human liver microsomes. However, the chemical inhibition data are often affected by cross-reactivities of the chemical inhibitors used in this assay. METHODS: To overcome this drawback, the cross-reactivities exhibited by six chemical inhibitors (furafylline, montelukast, sulfaphenazole, ticlopidine, quinidine and ketoconazole) were quantified using specific CYP enzyme marker reactions...
October 8, 2016: Drug Metabolism and Personalized Therapy
Peizong Deng, Fangfang Teng, Feilong Zhou, Zhimei Song, Ning Meng, Runliang Feng
Ketoconazole is a broad spectrum imidazole antifungal drug. For the treatment of superficial fungal infections with ketoconazole, it needs to be permeated to deep skin layers. In order to develop topical formulation of ketoconazole for improving its skin deposition and water-solubility, ketoconazole-loaded methoxy poly (ethylene glycol)-b-poly (δ-valerolactone) micelles were developed through thin-film hydration method. Particle size, drug loading capacity, infrared spectrum and x-ray diffraction of drug-loaded micelles were characterized...
October 2, 2016: Journal of Biomaterials Science. Polymer Edition
Ömer Barış Yücel, Emre Salabaş, Bahadır Ermeç, Ateş Kadıoğlu
INTRODUCTION: Priapism, taking its name from God Priapus, is total or partial erection lasting longer than 4 hours independent of sexual stimulus and can result in erectile dysfunction. There are three subtypes of priapism. AIM: To review the three subtypes of priapism, their pathophysiology, current treatment options, and complications. METHODS: The literature including priapism guidelines, review articles, and current trial studies was reviewed and the priapism type of God Priapus was investigated according to the mythology...
September 26, 2016: Sexual Medicine Reviews
Ayman Khalid Johargy
Objective: To determine the antimicrobial susceptibility of the most common bacterial and fungal infections among infected diabetic patients. Methods: This study was conducted at the Umm Al-Qura University, Makkah, Saudi Arabia, from June 2011 to June 2012, and comprised specimens collected from diabetics. Antibiotic susceptibility test using disc diffusion method was performed for bacterial isolates, and antifungal susceptibility test using colorimetric method for candida isolates...
October 2016: JPMA. the Journal of the Pakistan Medical Association
Soraya Eugenia Morales-López, Constanza G Taverna, María Eugenia Bosco-Borgeat, Ivana Maldonado, Walter Vivot, Wanda Szusz, Guillermo Garcia-Effron, Susana B Córdoba
The presence of the cryptic species belonging to the Candida glabrata complex has not been studied in Argentina. We analyzed a collection of 117 clinical isolates of C. glabrata complex belonging to a National Culture Collection of Instituto Nacional de Microbiología "Dr. Carlos G. Malbrán" from Argentina (40 isolates from blood samples, 18 from other normally sterile sites, 20 from vagina, 14 from urine, 7 from oral cavity, 3 from catheter, 1 from a stool sample and 14 isolates whose clinical origin was not recorded)...
September 28, 2016: Mycopathologia
Thais Pandini Figueiredo, Rosymar Coutinho de Lucas, Rodrigo Anselmo Cazzaniga, Carolina Nunes França, Fernando Segato, Rafael Taglialegna, Claudia Maria Leite Maffei
Cryptococcosis is a leading invasive fungal infection in immunocompromised patients. Considering the high prevalence and severity of these infections in immunocompromised patients attended at HC-FMRP-USP, the present research aimed to characterize the clinical isolates of Cryptococcus strains by biochemical and molecular methods and evaluate antifungal susceptibility of clinical isolates. Fifty isolates from 32 HIV-positive patients were obtained at HC-FMRP-USP. Most of the isolates (78.1%) were identified as C...
2016: Revista do Instituto de Medicina Tropical de São Paulo
XiaoMei Zhuang, TianHong Zhang, SiJia Yue, Juan Wang, Huan Luo, YunXia Zhang, Zheng Li, JinJing Che, HaiYing Yang, Hua Li, MingShe Zhu, Chuang Lu
Icotinib (ICO), a novel small molecule and a tyrosine kinase inhibitor, was developed and approved recently in China for non-small cell lung cancer. During screening for CYP inhibition potential in human liver microsomes (HLM), heterotropic activation toward CYP3A5 was revealed. Activation by icotinib was observed with CYP3A-mediated midazolam hydroxylase activity in HLM (∼40% over the baseline) or recombinant human CYP3A5 (rhCYP3A5) (∼70% over the baseline), but not in the other major CYPs including rhCYP3A4...
September 22, 2016: Biochemical Pharmacology
Sandeep Kumar, Pawan Kaur, Manju Bernela, Ruma Rani, Rajesh Thakur
The objective of the present study was to prepare ketoconazole loaded chitosan-gellan gum (CSGG) nanoparticles and to evaluate them for antifungal activity against Aspergillus niger. Ketoconazole loaded CSGG nanoparticles were prepared by electrostatic complexation technique using chitosan (CS) as cationic polymer and gellan gum (GG) as anionic polymer with ketoconazole as drug. It was observed that the effect of gellan gum on particle size was more pronounced in comparison to chitosan and increase in its concentration resulted in a significant increase in particle size but decrease in zeta potential...
September 20, 2016: International Journal of Biological Macromolecules
Y L Gong, Z C Yang, S P Yin, M X Liu, C Zhang, X Q Luo, Y Z Peng
Objective: To analyze the distribution and drug resistance of pathogen isolated from severely burned patients with bloodstream infection, so as to provide reference for the clinical treatment of these patients. Methods: Blood samples of 162 severely burned patients (including 120 patients with extremely severe burn) with bloodstream infection admitted into our burn ICU from January 2011 to December 2014 were collected. Pathogens were cultured by fully automatic blood culture system, and API bacteria identification panels were used to identify pathogen...
September 20, 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
Catherine A Outerbridge, Stephen D White, Verena K Affolter
OBJECTIVE: To describe a case of testicular neoplasia and alopecia universalis in a dog, and successful treatment of the latter with ciclosporin. ANIMAL: Twelve-year-old intact male wirehaired fox terrier. METHODS: Castration, skin biopsy for histopathology, lymphocyte immunophenotyping and clonality analysis of the canine T-cell receptor gamma locus (TCRγ) rearrangement. RESULTS: The dog presented with symmetrical generalized alopecia...
September 19, 2016: Veterinary Dermatology
Susanne Johansson, Boel Löfberg, Maria Aunes, Helen Lunde, Lars Frison, Nils Edvardsson, Marie Cullberg
The objectives were to estimate and compare, in silico and in vivo, the effects of a strong and a moderate CYP3A4 inhibitor on AZD1305 pharmacokinetics. In silico, simulations were performed with the computer software Simcyp, and the predicted outcome was compared with the results observed in healthy male subjects. In silico, the geometric mean plasma exposure of AZD1305 + ketoconazole showed a 7.1-fold higher AUC and a 4.4-fold higher Cmax compared with AZD1305 alone. Coadministration with verapamil gave a 1...
September 2016: Clinical Pharmacology in Drug Development
Nan Shu, Mengyue Hu, Zhaoli Ling, Peihua Liu, Fan Wang, Ping Xu, Zeyu Zhong, Binbin Sun, Mian Zhang, Feng Li, Qiushi Xie, Xiaodong Liu, Li Liu
Liver injury is a common adverse effect of atorvastatin. This study aimed to investigate atorvastatin-induced hepatotoxicity in diabetic rats induced by high-fat diet combined with streptozotocin. The results showed that 40 mg/kg atorvastatin was lethal to diabetic rats, whose mean survival time was 6.2 days. Severe liver injury also occurred in diabetic rats treated with 10 mg/kg and 20 mg/kg atorvastatin. The in vitro results indicated that atorvastatin cytotoxicity in hepatocytes of diabetic rats was more severe than normal and high-fat diet feeding rats...
2016: Scientific Reports
Srinivasan Periasamy, Chuan-Teng Liu, Se-Ping Chien, Ying-Chien Chen, Ming-Yie Liu
Ketoconazole (KCZ) is the most commonly used systemic antifungal drug. However, long-term treatment of KCZ induces hepatic injury. Oxidative stress is involved in KCZ-induced hepatic injury. Oxidative stress plays an important role in apoptosis-associated hepatic damage. Sesame oil is rich in potent antioxidants and antifungal constituents. It attenuates hepatic injury by inhibiting oxidative stress. Thus, sesame oil may protect against KCZ-induced oxidative stress, apoptosis and hepatic damage. The aim of the present study was to investigate the protective effect of sesame oil as a nutritional supplement on KCZ-induced hepatic injury in mice...
August 25, 2016: Journal of Nutritional Biochemistry
V M C Oliveira, S S F Santos, C R G Silva, A O C Jorge, M V P Leão
AIMS: The study investigated whether the interaction with Lactobacillus rhamnosus (ATCC7469) interfere with the expression of virulence factors by Candida albicans (ATCC18804). METHODS AND RESULTS: These microorganisms were grown in biofilms for 24, 48 and 72 h, Candida was isolated and the expression of the major virulence factors were investigated. The production of phospholipase, protease and hemolysin were observed in appropriate media; observation of germ tubes formation in serum; biofilm formation, after growth in microtiter plates and reading in spectrophotometer...
September 8, 2016: Journal of Applied Microbiology
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