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https://www.readbyqxmd.com/read/28329693/lanthanide-integrated-supramolecular-polymeric-nanoassembly-with-multiple-regulation-characteristics-for-multidrug-resistant-cancer-therapy
#1
Weihong Jin, Qiwen Wang, Min Wu, Yang Li, Guping Tang, Yuan Ping, Paul K Chu
Cancer treatment can in principle be enhanced by the synergistic effects of chemo- and nucleic acid-based combination therapies but the lack of efficient drug nanocarriers and occurrence of multidrug resistance (MDR) are major obstacles adversely affecting the effectiveness. Herein, a lanthanide-integrated supramolecular polymeric nanoassembly that delivers anticancer drugs and siRNA for more effective cancer therapy is described. This nanotherapeutic system is prepared by loading adamantane-modified doxorubicin (Dox) into polyethylenimine-crosslinked-γ-cyclodextrin (PC) through the supramolecular assembly to form the interior Dox-loaded PC (PCD) followed by electrostatically driven self-assembly of siRNA and PCD to produce the PCD/siRNA nanocomplexes...
March 16, 2017: Biomaterials
https://www.readbyqxmd.com/read/28296768/difficult-clinical-management-of-antituberculosis-dress-syndrome-complicated-by-mrsa-infection-a-case-report
#2
Li Wang, Lin-Feng Li
RATIONALE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe drug-induced hypersensitivity reaction characterized by skin rash, fever, blood abnormalities, and multiple organ involvement. The diagnosis of DRESS syndrome is often delayed because of its variable presentation. Prompt withdrawal of the culprit drug is the definitive treatment. DRESS syndrome induced by antituberculosis drugs has rarely been reported. PATIENT CONCERNS: A 50-year-old man admitted to our hospital with recurrent episodes of progressive rash, fever, eosinophilia, lymphadenopathy, hepatic, and pulmonary involvement were experienced after repeat trials of the same antituberculosis drugs...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28296193/investigating-transporter-mediated-drug-drug-interactions-using-a-physiologically-based-pharmacokinetic-model-of-rosuvastatin
#3
Q Wang, M Zheng, T Leil
Rosuvastatin is a frequently used probe in transporter-mediated drug-drug interaction (DDI) studies. This report describes the development of a physiologically based pharmacokinetic (PBPK) model of rosuvastatin for prediction of pharmacokinetic (PK) DDIs. The rosuvastatin model predicted the observed single (i.v. and oral) and multiple dose PK profiles, as well as the impact of coadministration with transporter inhibitors. The predicted effects of rifampin and cyclosporine (6.58-fold and 5.07-fold increase in rosuvastatin area under the curve (AUC), respectively) were mediated primarily via inhibition of hepatic organic anion-transporting polypeptide (OATP)1B1 (Inhibition constant (Ki ) ∼1...
March 13, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28289911/transcriptomics-as-a-tool-to-discover-new-antibacterial-targets
#4
REVIEW
Ángel Domínguez, Elisa Muñoz, M Carmen López, Miguel Cordero, José Pedro Martínez, Miguel Viñas
The emergence of antibiotic-resistant pathogens, multiple drug-resistance, and extremely drug-resistant strains demonstrates the need for improved strategies to discover new drug-based compounds. The development of transcriptomics, proteomics, and metabolomics has provided new tools for global studies of living organisms. However, the compendium of expression profiles produced by these methods has introduced new scientific challenges into antimicrobial research. In this review, we discuss the practical value of transcriptomic techniques as well as their difficulties and pitfalls...
March 13, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28258008/high-content-screening-of-clinically-tested-anticancer-drugs-identifies-novel-inhibitors-of-human-mrp1-abcc1
#5
Brian G Peterson, Kee W Tan, Bremansu Osa-Andrews, Surtaj H Iram
Multidrug resistance protein 1 (MRP1/ABCC1), an integral transmembrane efflux transporter, belongs to the ATP-binding cassette (ABC) protein superfamily. MRP1 governs the absorption and disposition of a wide variety of endogenous and xenobiotic substrates including various drugs across organs and physiological barriers. Additionally, its overexpression has been implicated in multidrug resistance in chemotherapy of multiple cancers. Here, we describe the development of a high content imaging-based screening assay for MRP1 activity...
February 28, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28245739/the-conundrum-of-feline-trichomonosis
#6
Jody L Gookin, Katherine Hanrahan, Michael G Levy
Practical relevance: Trichomonosis of the large intestine of the cat was described as a cause of chronic diarrhea over 20 years ago. The trichomonad was identified as Tritrichomonas foetus, with a genotype that is distinct from venereal T foetus of cattle. Clinical challenges: Despite multiple means for diagnosis of the infection, including light microscopy, protozoal culture and PCR amplification using species-specific primers, tests with even greater sensitivity are needed. Feline trichomonosis is resistant to all commonly used antiprotozoal drugs...
March 2017: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/28235673/laquinimod-enhances-central-nervous-system-barrier-functions
#7
Fred Lühder, Hania Kebir, Francesca Odoardi, Tanja Litke, Maike Sonneck, Jorge Ivan Alvarez, Jan Winchenbach, Nadine Eckert, Liat Hayardeny, Ella Sorani, Dmitri Lodygin, Alexander Flügel, Alexandre Prat
Laquinimod is currently being tested as a therapeutic drug in multiple sclerosis. However, its exact mechanism of action is still under investigation. Tracking of fluorescently-tagged encephalitogenic T cells during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, revealed that laquinimod significantly reduces the invasion of pathogenic effector T cells into the CNS tissue. T-cell activation, differentiation and amplification within secondary lymphoid organs after immunization with myelin antigen, their migratory capacity and re-activation within the nervous tissue were either only mildly affected or remained unchanged...
February 22, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28223391/evaluation-of-para-aminosalicylic-acid-pas-as-a-substrate-of-multiple-solute-carrier-slc-uptake-transporters-and-possible-drug-interactions-with-nsaids-in-vitro
#8
Md Masud Parvez, Ho Jung Shin, Jin Ah Jung, Jae-Gook Shin
para-Aminosalicylic acid (PAS) is a second-line anti-tuberculosis drug used to treat multidrug-resistant and extensively drug-resistant tuberculosis for more than 60 years. Renal secretion and glomerular filtration are the major pathways for elimination of PAS. We comprehensively studied PAS transport by using cell lines that overexpressed various transporters, and found that PAS acts as a novel substrate of organic anionic polypeptide (OATP1B1), organic cationic transporters (OCT1 and OCT2), and organic anion transporters (OAT1 and OAT3) but not a substrate of any ATP-binding cassette (ABC) transporters...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28198682/molecular-epidemiology-and-antimicrobial-resistance-phenotypes-of-acinetobacter-baumannii-isolated-from-patients-in-three-hospitals-in-southern-vietnam
#9
Nguyen Tuan Anh, Tran Vu Thieu Nga, Huynh Minh Tuan, Nguyen Si Tuan, Dao Minh Y, Nguyen Van Vinh Chau, Stephen Baker, Ho Huynh Thuy Duong
Multidrug resistance in the nosocomial pathogen Acinetobacter baumannii limits therapeutic options and impacts on clinical care. Resistance against carbapenems, a group of last-resort antimicrobials for treating multidrug-resistant (MDR) A. baumannii infections, is associated with the expression (and over-expression) of carbapenemases encoded by the blaOXA genes. The aim of this study was to determine the prevalence of antimicrobial-resistant A. baumannii associated with infection in three hospitals in southern Vietnam and to characterize the genetic determinants associated with resistance against carbapenems...
January 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28195652/identification-of-the-anti-mycobacterial-functional-properties-of-piperidinol-derivatives
#10
Collette S Guy, Esther Tichauer, Gemma L Kay, Daniel J Phillips, Trisha L Bailey, James Harrison, Christopher M Furze, Andrew D Millard, Matthew I Gibson, Mark J Pallen, Elizabeth Fullam
BACKGROUND AND PURPOSE: Tuberculosis (TB) remains a major global health threat and is now the leading cause of death from a single infectious agent worldwide. The current TB drug regimen is inadequate and new anti-tubercular agents are urgently required to be able to successfully combat the increasing prevalence of drug-resistant TB. The purpose of this study was to investigate a piperidinol compound derivative that is highly active against the Mycobacterium tuberculosis bacillus. EXPERIMENTAL APPROACH: The antibacterial properties of the piperidinol compound and its corresponding bis-Mannich base analogue were evaluated against Mycobacterium smegmatis and Gram-negative organisms...
February 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28192112/multiple-blood-brain-barrier-transport-mechanisms-limit-bumetanide-accumulation-and-therapeutic-potential-in-the-mammalian-brain
#11
Kerstin Römermann, Maren Fedrowitz, Philip Hampel, Edith Kaczmarek, Kathrin Töllner, Thomas Erker, Douglas H Sweet, Wolfgang Löscher
There is accumulating evidence that bumetanide, which has been used over decades as a potent loop diuretic, also exerts effects on brain disorders, including autism, neonatal seizures, and epilepsy, which are not related to its effects on the kidney but rather mediated by inhibition of the neuronal Na-K-Cl cotransporter isoform NKCC1. However, following systemic administration, brain levels of bumetanide are typically below those needed to inhibit NKCC1, which critically limits its clinical use for treating brain disorders...
February 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28187754/extended-spectrum-beta-lactamase-producing-organisms-causing-urinary-tract-infections-in-sri-lanka-and-their-antibiotic-susceptibility-pattern-a-hospital-based-cross-sectional-study
#12
M M P S C Fernando, W A N V Luke, J K N D Miththinda, R D S S Wickramasinghe, B S Sebastiampillai, M P M L Gunathilake, F H D S Silva, R Premaratna
BACKGROUND: Extended Spectrum Beta- Lactamase producing organisms causing urinary tract infections (ESBL-UTI) are increasing in incidence and pose a major burden to health care. While ESBL producing Klebsiella species seem to account for most nosocomial outbreaks, ESBL-producing E. coli have been isolated from both hospitalized and non-hospitalized patients. Although 95-100% ESBL organisms are still considered sensitive to meropenem, rapid emergence of carbapenem resistance has been documented in many countries...
February 10, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28176533/simultaneous-assay-of-multiple-antibiotics-in-human-plasma-by-lc-ms-ms-importance-of-optimizing-formic-acid-concentration
#13
Feng Chen, Zhe-Yi Hu, S Casey Laizure, Joanna Q Hudson
AIM: Optimal dosing of antibiotics in critically ill patients is complicated by the development of resistant organisms requiring treatment with multiple antibiotics and alterations in systemic exposure due to diseases and extracorporeal drug removal. Developing guidelines for optimal antibiotic dosing is an important therapeutic goal requiring robust analytical methods to simultaneously measure multiple antibiotics. METHODS: An LC-MS/MS assay using protein precipitation for cleanup followed by a 6-min gradient separation was developed to simultaneously determine five antibiotics in human plasma...
March 2017: Bioanalysis
https://www.readbyqxmd.com/read/28175954/multiple-resistance-to-carcinogens-and-xenobiotics-p-glycoproteins-as-universal-detoxifiers
#14
REVIEW
Thomas Efferth, Manfred Volm
The detoxification of toxic substances is of general relevance in all biological systems. The plethora of exogenous xenobiotic compounds and endogenous toxic metabolic products explains the evolutionary pressure of all organisms to develop molecular mechanisms to detoxify and excrete harmful substances from the body. P-glycoprotein and other members of the ATP-binding cassette (ABC) transporter family extrude innumerous chemical compounds out of cells. Their specific expression in diverse biological contexts cause different phenotypes: (1) multidrug resistance (MDR) and thus failure of cancer chemotherapy, (2) avoidance of accumulation of carcinogens and prevention of carcinogenesis in healthy tissues, (3) absorption, distribution, metabolization and excretion (ADME) of pharmacological drugs in human patients, (4) protection from environmental toxins in aquatic organisms (multi-xenobiotic resistance, MXR)...
February 7, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28138373/resistance-of-candida-albicans-biofilms-to-drugs-and-the-host-immune-system
#15
REVIEW
Doblin Sandai, Yasser M Tabana, Ahmad El Ouweini, Ishola Oluwaseun Ayodeji
BACKGROUND: Candida albicans is a commensal fungus that resides on mucosal surfaces and in the gastrointestinal and genitourinary tracts in humans. However, it can cause an infection when the immune system of the host is impaired or if a niche becomes available. Many C. albicans infections are due to the organism's ability to form a biofilm on implanted medical devices. A biofilm represents an optimal medium for the growth of C. albicans as it allows cells to be enclosed by a self-produced extracellular matrix (ECM)...
November 2016: Jundishapur Journal of Microbiology
https://www.readbyqxmd.com/read/28137234/mycobacterial-dna-replication-as-a-target-for-antituberculosis-drug-discovery
#16
Renata Płocińska, Małgorzata Korycka-Machała, Przemysław Płociński, Jarosław Dziadek
Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, is a leading infectious disease organism, causing millions of deaths each year. This serious pathogen has been greatly spread worldwide and recent years have observed an increase in the number of multi-drug resistant and totally drug resistant M. tuberculosis strains (WHO report, 2014). The danger of tuberculosis becoming an incurable disease has emphasized the need for the discovery of a new generation of antimicrobial agents...
January 30, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28089718/cathelicidin-antimicrobial-peptide-from-alligator-mississippiensis-has-antibacterial-activity-against-multi-drug-resistant-acinetobacter-baumanii-and-klebsiella-pneumoniae
#17
Stephanie M Barksdale, Evelyn J Hrifko, Monique L van Hoek
Alligator mississippiensis (American alligator), a member of order Crocodilia, lives in bacteria-laden environments but is not often known to succumb to bacterial infections. Their serum has been shown to have antibacterial activity beyond that of human serum, and it is believed that this activity is partially due to cationic antimicrobial peptides (CAMPs). CAMPs are produced by many organisms as part of the innate immune system. CAMPs are attractive possible therapies against multi-drug resistant bacteria, such as those found in biofilm-infected war wounds, because they seldom cause genetic resistance in bacteria and are effective against antibiotic resistant bacteria...
January 13, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28089172/metal-oxide-nanoparticles-as-antimicrobial-agents-a-promise-for-the-future
#18
REVIEW
Azhwar Raghunath, Ekambaram Perumal
Microbial infectious diseases are a global threat to human health. Excess and improper use of antibiotics has created antimicrobial-resistant microbes that can defy clinical treatment. The hunt for safe and alternate antimicrobial agents is on in order to overcome such resistant micro-organisms, and the birth of nanotechnology offers promise to combat infectious organisms. Over the past two decades, metal oxide nanoparticles (MeO-NPs) have become an attractive alternative source to combat microbes that are highly resistant to various classes of antibiotics...
February 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28072493/patterns-of-infections-aetiological-agents-and-antimicrobial-resistance-at-a-tertiary-care-hospital-in-northern-tanzania
#19
Happiness Houka Kumburu, Tolbert Sonda, Blandina Theophil Mmbaga, Michael Alifrangis, Ole Lund, Gibson Kibiki, Frank M Aarestrup
OBJECTIVE: To determine the causative agents of infections and their antimicrobial susceptibility at a tertiary care hospital in Moshi, Tanzania, to guide optimal treatment. METHODS: A total of 590 specimens (stool (56), sputum (122), blood (126) and wound swabs (286)) were collected from 575 patients admitted in the medical and surgical departments. The bacterial species were determined by conventional methods, and disc diffusion was used to determine the antimicrobial susceptibility pattern of the bacterial isolates...
January 10, 2017: Tropical Medicine & International Health: TM & IH
https://www.readbyqxmd.com/read/28062543/multiple-slc-and-abc-transporters-contribute-to-the-placental-transfer-of-entecavir
#20
Zhiyuan Ma, Xi Yang, Ting Jiang, Mengru Bai, Caihong Zheng, Su Zeng, Dongli Sun, Huidi Jiang
Entecavir (ETV), a nucleoside analogue with high efficacy against hepatitis B virus, is recommended as a first-line antiviral drug for the treatment of chronic hepatitis B. However, scant information is available on the use of ETV in pregnancy. To better understand the safety of ETV in pregnant women, we aimed to demonstrate whether ETV could permeate placental barrier and the underlying mechanism. Our study showed that small amount of ETV could permeate across placenta in mice. ETV accumulation in activated or non-activated BeWo cells (treated with or without forskolin) was sharply reduced in the presence of 100 μM of adenosine, cytidine and in Na+ free medium, indicating that nucleoside transporters possibly mediate the uptake of ETV...
January 6, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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