Search results for "SoMe"

Organic solvent vapor effects on phase transition of α and β tegafur upon grinding with solvent additives.

2012

Abstract Solvent effects on α tegafur (5-fluoro-1-(tetrahydro-2-furyl)uracil) phase transition to β tegafur during grinding with solvent additive, as well as phase transition in samples exposed to 95% relative solvent vapor pressure has been studied in this research. Samples containing 0.5% and 0.1% of β tegafur in α and β tegafur mixture, as well as samples of pure α tegafur were ground with different solvent additives, and conversion degrees depending on the solvent were determined using PXRD method. Samples with α and β tegafur weight fraction of 1:1 were exposed to 95% relative solvent vapor pressure, and phase transition rates were determined. Solubility of α tegafur, solvent sorption …

Effects of gadolinium and cadmium on the electrically evoked release of 45calcium from the isolated rat neurohypophysis.

1988

Isolated neural lobes of the rat pituitary gland were fixed by their stalks to a platinum wire electrode. They were loaded with 45calcium and then superfused with radioactivity-free Krebs-solution. The efflux of 45calcium into the superfusion medium was determined. After 54–60 min of superfusion the spontaneous outflow of 45calcium was 2.03%/min of the tissue 45calcium. It was not affected by cadmium (Cd2+, 0.03-3 mmol/1), but reduced by 40% in the presence of 1 mmol/1 gadolinium (Gd3). Electrical stimulation with pulses of 15 Hz (3 times for 1 min with intervals of 1 min) evoked a 45calcium release of 14.4% of the tissue radioactivity. The evoked release of 45calcium was reduced by 80% in …

New Lipid Modulating Drugs: The Role of Microsomal Transport Protein Inhibitors

2011

Microsomal triglyceride transfer protein (MTP) is involved in the synthesis of very low density lipoprotein in the liver. Its deficiency results in abetalipoproteinemia. MTP inhibitors target the assembly and secretion of apolipoprotein B-containing lipoproteins. These agents may potentially play a role, alone or in combination, in the treatment of hypercholesterolemia or hypertriglyceridemia. Clinical applications of MTP inhibitors initially focused primarily on high-dose monotherapy in order to produce substantial reductions in LDL-cholesterol levels but these proved to induce significant hepatic steatosis and transaminase elevations. However, likely orphan indications for MTP inhibitors,…

Calcium-dependent conformational changes of membrane-bound Ebola fusion peptide drive vesicle fusion

2003

AbstractThe fusogenic subdomain of the Ebola virus envelope glycoprotein is an internal sequence located ca. 20 residues downstream the N-terminus of the glycoprotein transmembrane subunit. Partitioning of the Ebola fusion peptide into membranes containing phosphatidylinositol in the absence of Ca2+ stabilizes an α-helical conformation, and gives rise to vesicle efflux but not vesicle fusion. In the presence of millimolar Ca2+ the membrane-bound peptide adopts an extended β-structure, and induces inter-vesicle mixing of lipids. The peptide conformational polymorphism may be related to the flexibility of the virus–cell intermembrane fusogenic complex.

Absolute Humidity Influences the Seasonal Persistence and Infectivity of Human Norovirus

2014

ABSTRACT Norovirus (NoV) is one of the main causative agents of acute gastroenteritis worldwide. In temperate climates, outbreaks peak during the winter season. The mechanism by which climatic factors influence the occurrence of NoV outbreaks is unknown. We hypothesized that humidity is linked to NoV seasonality. Human NoV is not cultivatable, so we used cultivatable murine norovirus (MNV) as a surrogate to study its persistence when exposed to various levels of relative humidity (RH) from low (10% RH) to saturated (100% RH) conditions at 9 and 25°C. In addition, we conducted similar experiments with virus-like particles (VLPs) from the predominant GII-4 norovirus and studied changes in bin…

Efficacy and tolerability of a fixed dose combination of cortex phospholipid liposomes and cyanocobalamin for intramuscular use in peripheral neuropa…

2019

Peripheral neuropathies are frequently encourtered in clinical practice and are assiociated with a major impairment in quality of life . Howewvwr, their management reamans poor, and current therapies are often burdened with major side effects and can present poor efficacy on pain and functionality. Therefore, it has been suggested that the combination of two or more different drugs may improve analgesis efficacy and reduce side effects. Tricortin 1000 is formulated with 12 mg of Brain cortex phospholipid liposomes + 1000 microgrammi of Cyanocobalamin injectable (PL+ CNCb1) for intramuscolar use and is indicated in the tratment of poly-algo-neuropathic syndromes. This combination exerts a ma…

Solvent-Enhanced Diastereo- and Regioselectivity in the PdII-Catalyzed Synthesis of Six- and Eight-Membered Heterocycles viacis-Aminopalladation

2009

The Pd(II)-catalyzed intramolecular oxidative cyclization of tosyl-protected cis- and trans-N-allyl-2-aminocyclohexanecarboxamides was examined, and efficient syntheses of cyclohexane-fused pyrimidin-4-ones and 1,5-diazocin-6-ones were developed. In the course of the research, a marked solvent effect was observed on both the regio- and diastereoselectivity. Additionally, a novel Pd(II)-mediated domino oxidation, oxidative amination reaction was discovered. Our experimental and theoretical findings suggest that the reactions proceed via a cis-aminopalladation mechanism.

PML nuclear body-residing proteins sequentially associate with HPV genome after infectious nuclear delivery.

2019

Subnuclear promyelocytic leukemia (PML) nuclear bodies (NBs) are targeted by many DNA viruses after nuclear delivery. PML protein is essential for formation of PML NBs. Sp100 and Small Ubiquitin-Like Modifier (SUMO) are also permanently residing within PML NBs. Often, large DNA viruses disassemble and reorganize PML NBs to counteract their intrinsic antiviral activity and support establishment of infection. However, human papillomavirus (HPV) requires PML protein to retain incoming viral DNA in the nucleus for subsequent efficient transcription. In contrast, Sp100 was identified as a restriction factor for HPV. These findings suggested that PML NBs are important regulators of early stages o…

2019

Negative image-based (NIB) screening is a rigid molecular docking methodology that can also be employed in docking rescoring. During the NIB screening, a negative image is generated based on the target protein’s ligand-binding cavity by inverting its shape and electrostatics. The resulting NIB model is a drug-like entity or pseudo-ligand that is compared directly against ligand 3D conformers, as is done with a template compound in the ligand-based screening. This cavity-based rigid docking has been demonstrated to work with genuine drug targets in both benchmark testing and drug candidate/lead discovery. Firstly, the study explores in-depth the applicability of different ligand 3D conformer…

A Molecular Dynamics-Shared Pharmacophore Approach to Boost Early-Enrichment Virtual Screening: A Case Study on Peroxisome Proliferator-Activated Rec…

2016

Molecular dynamics (MD) simulations can be used, prior to virtual screening, to add flexibility to proteins and study them in a dynamic way. Furthermore, the use of multiple crystal structures of the same protein containing different co-crystallized ligands can help elucidate the role of the ligand on a protein's active conformation, and then explore the most common interactions between small molecules and the receptor. In this work, we evaluated the contribution of the combined use of MD on crystal structures containing the same protein but different ligands to examine the crucial ligand-protein interactions within the complexes. The study was carried out on peroxisome proliferator-activat…