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https://www.readbyqxmd.com/read/29353398/new-strategies-of-arv-the-road-to-simplification
#1
REVIEW
Rosa de Miguel Buckley, Rocio Montejano, Natalia Stella-Ascariz, Jose R Arribas
PURPOSE OF REVIEW: Simplification of antiretroviral therapy is a strategy aiming to reduce pill burden, drug interactions, and toxicity. This review focuses on the most recent and important studies evaluating a reduction on the number of drugs for HIV treatment, both in naive and virologically suppressed patients. RECENT FINDINGS: Interesting studies have been performed in the past years testing dual therapy and monotherapy, with variable rates of virological control...
January 20, 2018: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/29353278/stereoselective-inhibition-of-renal-basolateral-human-organic-anion-transporter-3-by-lansoprazole-enantiomers
#2
Yugo Hamada, Kenji Ikemura, Takuya Iwamoto, Masahiro Okuda
Lansoprazole, a proton pump inhibitor, potently inhibits human organic anion transporter, hOAT3 (SLC22A8). Lansoprazole has an asymmetric atom in its structure and is clinically administered as a racemic mixture of (R)-and (S)-enantiomers. However, little is known about the stereoselective inhibitory potencies of lansoprazole against hOAT3 and its homolog, hOAT1. In the present study, the stereoselective inhibitory effect of lansoprazole was evaluated using hOAT1-and hOAT3-expressing cultured cells. hOAT1 and hOAT3 transported [14C]p-aminohippurate and [3H]estrone-3-sulfate (ES) with Michaelis-Menten constants of 29...
January 19, 2018: Pharmacology
https://www.readbyqxmd.com/read/29353086/ruthenium-dendrimers-as-carriers-for-anticancer-sirna
#3
Sylwia Michlewska, Maksim Ionov, Marta Maroto-Díaz, Aleksandra Szwed, Aliaksei Ihnatsyeu-Kachan, Svetlana Loznikova, Dzmitry Shcharbin, Marek Maly, Rafael Gomez Ramirez, Francisco Javier de la Mata, Maria Bryszewska
Dendrimers, which are considered as one of the most promising tools in the field of nanobiotechnology due to their structural organization, showed a great potential in gene therapy, drug delivery, medical imaging and as antimicrobial and antiviral agents. This article is devoted to study interactions between new carbosilane-based metallodendrimers containing ruthenium and anti-cancer small interfering RNA (siRNA). Formation of complexes between anti-cancer siRNAs and Ru-based carbosilane dendrimers was evaluated by transmission electron microscopy, circular dichroism and fluorescence...
January 12, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29353085/reactions-of-a-tetranuclear-pt-thiosemicarbazone-complex-with-model-proteins
#4
Tiziano Marzo, Francisco Navas, Damiano Cirri, Antonello Merlino, Giarita Ferraro, Luigi Messori, Adoracion G Quiroga
The tetranuclear Pt complex (PtL)4 (where L2- is the anion derived from para-isopropyl thiosemicarbazone) was first described in A.G. Quiroga et al., J. Med. Chem. 41, 1998, 1399-1408. (PtL)4 manifests antiproliferative properties toward various cancer cell lines being a promising anticancer drug candidate. Yet, details of its reactivity with biomolecules have not been elucidated. To this end, we investigated the reactions of (PtL)4 with a few model proteins, i.e. bovine pancreatic ribonuclease (RNase A), cytochrome c (Cyt c) and hen egg white lysozyme (Lysozyme), through electrospray ionization mass spectrometry and other biophysical methods...
January 10, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29353082/3d-extrusion-printing-of-high-drug-loading-immediate-release-paracetamol-tablets
#5
Shaban A Khaled, Morgan R Alexander, Ricky D Wildman, Martin J Wallace, Sonja Sharpe, Jae Yoo, Clive J Roberts
The manufacture of immediate release high drug loading paracetamol oral tablets was achieved using an extrusion based 3D printer from a premixed water based paste formulation. The 3D printed tablets demonstrate that a very high drug (paracetamol) loading formulation (80% w/w) can be printed as an acceptable tablet using a method suitable for personalisation and distributed manufacture. Paracetamol is an example of a drug whose physical form can present challenges to traditional powder compression tableting...
January 15, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29353039/cetylpyridinium-chloride-as-a-novel-inhibitor-of-hepatitis-b-viral-capsid-assembly
#6
Hyun Wook Seo, Joon Pyung Seo, Yoon Jun Kim, Guhung Jung
Hepatitis B virus (HBV) infection is a major risk factor for chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC) worldwide. While multiple hepatitis B drugs have been developed, development of drug resistance during treatment or weak efficacies observed in some cases have limited their application. Therefore, there is an urgent need to develop better pharmacological agents for HBV-infected individuals. Here, we identified cetylpyridinium chloride (CPC) as a novel inhibitor of HBV. Using computational analysis of CPC-nucleocapsid proteins, microscale thermophoresis analysis of CPC binding to viral nucleocapsids, and in vitro nucleocapsid formation assays, we found that CPC interacts with dimeric viral nucleocapsid protein (known as core protein or HBcAg)...
January 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29352964/c24-hydroxylated-stigmastane-derivatives-as-liver-x-receptor-agonists
#7
Francisco Fermin Castro Navas, Gianluca Giorgi, Daniela Maggioni, Manuela Pacciarini, Vincenzo Russo, Maura Marinozzi
Phytosterols are stucturally correlated to the endogenous ligands of Liver X Receptor (LXR), a ligand-activated nuclear receptor that has emerged as an attractive drug target due to its ability to integrate metabolic and inflammatory signaling. Natural and semi-synthetic phytosterol derivatives characterized by the presence of side-chain oxygenated functions have shown to be able to modulate LXR activity. Here, we describe the efficient synthesis of four stigmastane derivatives, endowed with a hydroxyl group at C24 position, namely (24R)- and (24S)-stigmasta-5,28-diene-3β,24-ols (also referred to as saringosterols, 10a and 10b) and (24R)- and (24S)-stigmasta-5-ene-3β,24-ols (11a and 11b), starting from the readily available stigmasterol...
January 15, 2018: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/29352931/effects-of-chitosan-quaternary-ammonium-salt-on-the-physicochemical-properties-of-sodium-carboxymethyl-cellulose-based-films
#8
Beibei Wang, Xiaodeng Yang, Congde Qiao, Yan Li, Tianduo Li, Chunlin Xu
The effects of N-(2-hydroxyl)-propyl-3-trimethylammonium chitosan chloride (HTCC) on the physicochemical properties of sodium carboxymethyl cellulose (CMC)-based films were investigated. The prepared HTCC/CMC film-forming solutions (FFSs) with varying mass ratios exhibited shear-thinning behavior and typical pseudo-plasticity. The highest apparent viscosity and lowest crossover frequency was obtained for the HTCC/CMC FFS with a mass ratio of 10%, due to the formation of the strongest intermolecular interactions, which also led to the best mechanical properties...
March 15, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29352886/aldehyde-functionalized-chitosan-montmorillonite-films-as-dynamically-assembled-switchable-chemical-release-bioplastics
#9
Jamal Chabbi, Oumayma Jennah, Nadia Katir, Mohamed Lahcini, Mosto Bousmina, Abdelkrim El Kadib
Temporal release of synergistic and/or complementary chemicals (e.g.: drugs) is recognized as extremely challenging because of their frequently intertwined kinetic delivery and presently, straightforward concepts enabling to circumvent this bottleneck are missing in the open literature. In this framework, we report herein on aldehyde-functionalized, transparent and flexible chitosan-montmorillonite hybrid films that act as a new generation of eco-friendly, controlled-chemical release bioplastics. These dynamically-assembled nanomaterials are designed by a ternary assembly from biowaste derived chitin biopolymer, aromatic aldehydes and layered clay nanoparticles...
March 1, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29352622/anaesthesia-for-caesarean-section-in-a-patient-with-parkinson-s-disease
#10
V D Ward
Parkinson's disease is prevalent worldwide but mainly affects the elderly and is rarely seen in women of child-bearing age. The clinical signs and symptoms, the physiological changes of pregnancy, and drug interactions, pose unique challenges for the anaesthetic management of patients with Parkinson's disease who present for delivery. A 36-year-old primigravid woman at 36 weeks' gestation, with Parkinson's disease, presented for pre-anaesthesia assessment prior to elective caesarean section. Her Parkinson's disease had been diagnosed four years previously and was treated with Sinemet (levodopa/carbidopa) and pramipexole...
November 21, 2017: International Journal of Obstetric Anesthesia
https://www.readbyqxmd.com/read/29352473/the-impact-of-mk-467-on-plasma-drug-concentrations-sedation-and-cardiopulmonary-changes-in-sheep-treated-with-intramuscular-medetomidine-and-atipamezole-for-reversal
#11
M Adam, M R Raekallio, T Keskitalo, J M Honkavaara, M Scheinin, M Kajula, S Mölsä, O M Vainio
The effect of MK-467, a peripheral α2 -adrenoceptor antagonist, on plasma drug concentrations, sedation and cardiopulmonary changes induced by intramuscular (IM) medetomidine was investigated in eight sheep. Additionally, the interactions with atipamezole (ATI) used for reversal were also evaluated. Each animal was treated four times in a randomized prospective crossover design with 2-week washout periods. Medetomidine (MED) 30 μg/kg alone or combined in the same syringe with MK-467 300 μg/kg (MMK) was injected intramuscular, followed by ATI 150 μg/kg (MED + ATI and MMK + ATI) or saline intramuscular 30 min later...
January 19, 2018: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29352472/the-bioequivalence-of-a-single-intravenous-administration-of-the-anesthetic-alfaxalone-in-cyclodextrin-versus-alfaxalone-in-cyclodextrin-plus-preservatives-in-cats
#12
K Pasloske, M G Ranasinghe, S Sauer, J Hare
To demonstrate the bioequivalence of alfaxalone in cyclodextrin (Reference Product) to a formulation of alfaxalone in cyclodextrin also containing the preservatives ethanol, chlorocresol, and benzethonium chloride (Test Product) when administered for the purpose of inducing anesthesia in the cat. Blinded, single-dose, randomized, two-period, two-sequence, cross-over bioequivalence study with a 7-day washout period between treatments. Twenty-four (12 neutered males and 12 intact females), healthy, adult cats weighing 4...
January 19, 2018: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29352450/carrier-mediated-uptake-of-clonidine-in-cultured-human-lung-cells
#13
Marc Le Vée, Elodie Jouan, Olivier Fardel
The lung is a preferential organ site for accumulation of lipophilic basic amine drugs, so-called pneumophilic drugs and belonging to various pharmacological classes, which can result in lung toxicity. In order to investigate the mechanism involved in such pulmonary accumulation of drugs, uptake of clonidine, used here as a prototypical basic amine drug, was characterized in cultured human lung cells. Clonidine accumulation in lung alveolar A549 cells was found to be temperature- and pH-dependent; it was saturable, with a Michaelis-Menten affinity constant (Km) value of 569...
January 19, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29352409/recent-perspectives-on-the-molecular-basis-of-biofilm-formation-by-pseudomonas-aeruginosa-and-approaches-for-treatment-and-biofilm-dispersal
#14
REVIEW
Sinosh Skariyachan, Vaishnavi Sneha Sridhar, Swathi Packirisamy, Supreetha Toplar Kumargowda, Sneha Basavaraj Challapilli
Pseudomonas aeruginosa, a Gram-negative, rod-shaped bacterium causes widespread diseases in humans. This bacterium is frequently related to nosocomial infections such as pneumonia, urinary tract infections (UTIs) and bacteriaemia especially in immunocompromised patients. The current review focuses on the recent perspectives on biofilms formation by these bacteria. Biofilms are communities of microorganisms in which cells stick to each other and often adhere to a surface. These adherent cells are usually embedded within a self-produced matrix of extracellular polymeric substance (EPS)...
January 19, 2018: Folia Microbiologica
https://www.readbyqxmd.com/read/29352320/high-level-production-and-purification-in-a-functional-state-of-an-extrasynaptic-gamma-aminobutyric-acid-type-a-receptor-containing-%C3%AE-4%C3%AE-3%C3%AE-subunits
#15
Xiaojuan Zhou, Rooma Desai, Yinghui Zhang, Wojciech J Stec, Keith W Miller, Youssef Jounaidi
The inhibitory γ-aminobutyric acid type A receptors are implicated in numerous physiological processes, including cognition and inhibition of neurotransmission, rendering them important molecular targets for many classes of drugs. Functionally, the entire GABAAR family of receptors can be subdivided into phasic, fast acting synaptic receptors, composed of α-, β- and γ-subunits, and tonic extrasynaptic receptors, many of which contain the δ-subunit in addition to α- and β-subunits. Whereas the subunit arrangement of the former group is agreed upon, that of the αβδ GABAARs remains unresolved by electrophysiological and pharmacological research...
2018: PloS One
https://www.readbyqxmd.com/read/29352246/u-box-ubiquitin-ligase-ppil2-suppresses-breast-cancer-invasion-and-metastasis-by-altering-cell-morphology-and-promoting-snai1-ubiquitination-and-degradation
#16
Zhaojun Jia, Miao Wang, Shujing Li, Xiahui Li, Xiao-Yan Bai, Zhaowei Xu, Yangyang Yang, Bowen Li, Yanan Li, Huijian Wu
Metastasis is the leading cause of breast cancer fatalities. To develop new therapeutic strategies, the mechanisms underlying breast cancer invasion and metastasis need to be further investigated. Peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) is a U-box-type E3 ubiquitin ligase belonging to the cyclophilin family. Proteins within this family are the major cytosolic binding proteins of the immunosuppressant drug cyclosporine A (CsA). Although PPIL2 has been reported to potentially be involved in cell migration, its role in breast cancer is still unclear...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352161/the-action-of-a-negative-allosteric-modulator-at-the-dopamine-d2-receptor-is-dependent-upon-sodium-ions
#17
Christopher J Draper-Joyce, Ravi Kumar Verma, Mayako Michino, Jeremy Shonberg, Anitha Kopinathan, Carmen Klein Herenbrink, Peter J Scammells, Ben Capuano, Ara M Abramyan, David M Thal, Jonathan A Javitch, Arthur Christopoulos, Lei Shi, J Robert Lane
Sodium ions (Na+) allosterically modulate the binding of orthosteric agonists and antagonists to many class A G protein-coupled receptors, including the dopamine D2 receptor (D2R). Experimental and computational evidences have revealed that this effect is mediated by the binding of Na+ to a conserved site located beneath the orthosteric binding site (OBS). SB269652 acts as a negative allosteric modulator (NAM) of the D2R that adopts an extended bitopic pose, in which the tetrahydroisoquinoline moiety interacts with the OBS and the indole-2-carboxamide moiety occupies a secondary binding pocket (SBP)...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352067/sandwich-cultured-hepatocytes-for-mechanistic-understanding-of-hepatic-disposition-of-parent-drugs-and-metabolites-by-transporter-enzyme-interplay
#18
Norikazu Matsunaga, Yukina Fukuchi, Haruo Imawaka, Ikumi Tamai
Functional interplay between transporters and drug-metabolizing enzymes is currently one of the hottest topics in the field of drug metabolism and pharmacokinetics. Uptake transporter-enzyme interplay is important to determine intrinsic hepatic clearance based on the extended clearance concept. Enzyme-efflux transporter interplay, which includes both sinusoidal (basolateral) and canalicular efflux transporters, determines the fate of metabolites formed in the liver. As sandwich-cultured hepatocytes (SCHs) maintain metabolic activities and form a canalicular network, the whole interplay between uptake/efflux transporters and drug-metabolizing enzymes can be investigated simultaneously...
January 19, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29351899/web-based-survey-application-to-collect-contextually-relevant-geographic-data-with-exposure-times-application-development-and-feasibility-testing
#19
Abby Rudolph, Karin Tobin, Jonathan Rudolph, Carl Latkin
BACKGROUND: Although studies that characterize the risk environment by linking contextual factors with individual-level data have advanced infectious disease and substance use research, there are opportunities to refine how we define relevant neighborhood exposures; this can in turn reduce the potential for exposure misclassification. For example, for those who do not inject at home, injection risk behaviors may be more influenced by the environment where they inject than where they live...
January 19, 2018: JMIR Public Health and Surveillance
https://www.readbyqxmd.com/read/29351860/microtubule-dynamics-moving-toward-a-multi-scale-approach
#20
REVIEW
Mahya Hemmat, Brian T Castle, David J Odde
Microtubule self-assembly dynamics serve to facilitate many vital cellular functions, such as chromosome segregation during mitosis and synaptic plasticity. However, the detailed atomistic basis of assembly dynamics has remained an unresolved puzzle. A key challenge is connecting together the vast range of relevant length-time scales, events happening at time scales ranging from nanoseconds, such as tubulin molecular interactions (Å-nm), to minutes-hours, such as the cellular response to microtubule dynamics during mitotic progression (μm)...
January 16, 2018: Current Opinion in Cell Biology
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