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Evaluation of Pazopanib Phase Behavior Following pH-Induced Supersaturation.

Salts of weakly basic active pharmaceutical ingredients are widely used to improve aqueous solubility and/or dissolution rate. However, these compounds are prone to precipitation due to the lower solubility of the un-ionized species at the higher pH in the intestinal region, and this can result in poor and/or variable absorption. The goal of this study was to investigate the degree of supersaturation achieved following dissolution of different amounts of pazopanib hydrochloride at low pH, followed by rapid pH increase. Using pH solubility profiles, phase boundaries were defined for crystalline and amorphous free base forms. The resultant phase diagram was used to rationalize the observed supersaturation and phase behavior of pazopanib following pH adjustment. In the presence of a crystallization inhibitor, hydroxypropylmethyl cellulose (HPMC), the degree of supersaturation was found to be very high, approximately 600-fold, at pH 6.5. At a dose equivalent to the clinical dose, the maximum free drug concentration observed at pH 6.5 was dictated by the amorphous solubility. Solutions that exceeded the amorphous solubility upon pH increase were found to undergo glass-liquid phase separations (GLPS) with the formation of amorphous colloidal drug-rich particles. Microscopic observations confirmed that HPMC delayed the appearance of pazopanib free base crystals. The phase behavior upon pH change is thus well predicted by the phase diagram, after taking into consideration the initial dose, the extent of supersaturation generated upon pH change, and the presence or absence of a crystallization inhibitor.

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Prognostic value of quantitative ctDNA levels in non small cell lung cancer patients.

Circulating tumor DNA (ctDNA) levels correlate well with tumor bulk. In this paper we aim to estimate the prognostic value of the dynamic quantification of ctDNA levels.

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Huaiqihuang Granules () reduce proteinuria by enhancing nephrin expression and regulating necrosis factor κB signaling pathway in adriamycin-induced nephropathy.

To investigate the effects of Huaiqihuang Granules (, HQH), a mixture of Chinese herbs including Trametes robiniophila Murr, Fructus Lycii and Polygonatum sibiricum, on adriamycininduced nephropathy (ADRN) in rats and its underlying mechanisms.

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IGF-1R Signaling Phospho- TGF beta induced factor 2 AKT PKB Signaling Phospho AMPK Signaling Phospho-Sp ErbB Her Signaling Phosph ERK Signaling Phospho-Spe GPCR Signaling to MAPK ER NF-kB II Phospho-Specific p53 Signaling Phospho-Spe T-Cell Receptor Signaling TGF-Beta Signaling Phosph Goat Anti-Human Tissue Fa

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5Alpha-Reduced Steroids Are Major Metabolites in the Early Equine Embryo Proper and Its Membranes.

Steroid production and metabolism by early conceptuses are very important for the establishment and maintenance of pregnancy in horses. Our earlier work suggested the possible formation of 5alpha-reduced steroids in equine conceptuses. We have now demonstrated the formation of 5alpha-reduced metabolites of androstenedione, testosterone, and progesterone by the embryo and its membranes. A total of 44 conceptuses were collected from 26 mares between 20 and 31 days of pregnancy. Tissues from the embryo proper and from the separated components of the conceptus (bilaminar and trilaminar trophoblast, allantois) were incubated with tritium-labeled substrates. 5Alpha-reduced metabolites (5alpha-dihydro- and 3beta,5alpha-tetrahydro- steroids) as radiolabeled products were identified from a series of chromatographic steps using four solvent systems for high-performance liquid chromatography. Use of a 5alpha-reductase inhibitor confirmed the metabolites were indeed 5alpha-reduced steroids. For the embryo, the only products from androstenedione were 5alpha-dihydroandrostenedione and 3beta,5alpha-tetrahydroandrostenedione, with no evidence of more polar metabolites; there was some 3beta,5alpha-tetrahydrotestosterone but no 5alpha-dihydrotestosterone from testosterone, and formation of androstenedione was followed by the production of 5alpha-dihydroandrostenedione and 3beta,5alpha-tetrahydroandrostenedione. The major 5alpha-reduced product from progesterone was 3beta,5alpha-tetrahydroprogesterone, with lesser amounts of 5alpha-dihydroprogesterone. For the membranes, reductions to tetrahydro, 5alpha-reduced steroids were prominent in most instances, but also present were considerable amounts of products more polar than the substrates. The well-recognized activity of some 5alpha-reduced steroids--for example, 5alpha-dihydrotestosterone in male sexual differentiation--provokes interest in their even earlier appearance, as seen in this study, and suggests a possible role for them in early embryonic development in horses and, more generally, in other species.

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Goat Anti-Human, Mouse AR Rat TGF-beta-inducible ea Rat TGF-beta-inducible ea Angiogenesis (Human) Anti Angiogenesis (Human) Anti Angiogenesis (Mouse) Anti Apoptosis (Human) Antibod Atherosclerosis (Human) A Atherosclerosis (Mouse) A Chemokine (Human) Antibod Cytokine (Human) Antibody Cytokine (Human) Antibody

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A cationic surfactant-decorated liquid crystal sensing platform for simple and sensitive detection of acetylcholinesterase and its inhibitor.

In this paper, construction of the liquid crystal (LC)-based sensing platform for simple and sensitive detection of acetylcholinesterase (AChE) and its inhibitor using a cationic surfactant-decorated LC interface was demonstrated. A change of the optical images of LCs from bright to dark appearance was observed when the cationic surfactant, myristoylcholine chloride (Myr), was transferred onto the aqueous/LC interface, due to the formation of a stable surfactant monolayer at the interface. A dark-to-bright change of the optical appearance was then observed when AChE was transferred onto the Myr-decorated LC interface. The sensitivity of this new type of LC-based sensor is 3 orders of magnitude higher in the serum albumin solution than that only in the buffer solution. Noteworthy is that the AChE LC sensor shows a very high sensitivity for the detection of the enzyme inhibitor, which is around 1 fM. The constructed low-cost LC-based sensor is quite simple and convenient, showing high promise for label-free detection of AChE and its inhibitors.

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Caspase-3 Inhibitor Z-DEV Caspase-3 Inhibitor Z-DEV Caspase-Family Inhibitor Caspase-Family Inhibitor Caspase-6 Inhibitor Z-VEI Caspase-6 Inhibitor Z-VEI Caspase-1 Inhibitor Z-YVA Caspase-1 Inhibitor Z-YVA Caspase-8 Inhibitor Z-IET Caspase-8 Inhibitor Z-IET Caspase-2 Inhibitor Z-VDV Caspase-2 Inhibitor Z-VDV

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Stability of Dabigatran Etexilate in Manufacturer's Blister Pack, Unit-Dose Packaging, and Community Pharmacy Blister Pack.

Dabigatran, a direct thrombin inhibitor, is indicated for the prevention and treatment of venous thromboembolism and for stroke prophylaxis in atrial fibrillation. The manufacturer recommends that dabigatran etexilate be retained in the original packaging until administration. Currently, no information exists about the stability of dabigatran etexilate outside its original packaging.

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Micheliolide derivative DMAMCL inhibits glioma cell growth in vitro and in vivo.

There is no highly effective chemotherapy for malignant gliomas to date. We found that dimethylaminomicheliolide (DMAMCL), a selective inhibitor of acute myeloid leukemia (AML) stem/progenitor cells, inhibited the growth of glioma cells.

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Cultrex In Vitro Angiogen MarkerGeneTM in vivo lacZ anti HSV (II) gB IgG1 (mo anti HCMV IE pp65 IgG1 (m anti HCMV gB IgG1 (monocl CELLKINES Natural Human I CELLKINES INTERLEUKIN 2 ( CELLKINES INTERLEUKIN 2 ( Human Insulin-like Growth Human Insulin-like Growth Jurkat Cell Extract (Indu Jurkat Cell Extract (Indu

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Effect of fasudil hydrochloride on the post-thaw viability of cryopreserved porcine adipose-derived stem cells.

Adipose-derived stem cells (ADSCs) are of interest for regenerative medicine as they are isolated easily and can differentiate into multiple cell lineages. Recently, it was reported that a Rho-associated kinase (ROCK) inhibitor Y-27632 could enhance the post-thaw viability and physiological function of cryopreserved BMSC.

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Macrophage Colony Stimula Macrophage Colony Stimula Human Cord Blood CD34+ Ce Rat Anti-Porcine SWC6 Nul Stemez hN2 Human Neuron D Porcine Red Blood Cells, Porcine Red Blood Cells, Porcine Red Blood Cells, LumiSTEM 96 iPS MSC deriv Ondansetron hydrochloride Ofloxacin CAS Number [824 Ondansetron hydrochloride

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Hepatic basolateral efflux contributes significantly to rosuvastatin disposition II: characterization of hepatic elimination by basolateral, biliary, and metabolic clearance pathways in rat isolated perfused liver.

Basolateral efflux clearance (CLBL) contributes significantly to rosuvastatin (RSV) elimination in sandwich-cultured hepatocytes (SCH). The contribution of CLBL to RSV hepatic elimination was determined in single-pass isolated perfused livers (IPLs) from wild-type (WT) and multidrug resistance-associated protein 2 (Mrp2)-deficient (TR(-)) rats in the absence and presence of the P-glycoprotein and breast cancer resistance protein (Bcrp) inhibitor, elacridar (GF120918); clearance values were compared with SCH. RSV biliary clearance (CLBile) was ablated almost completely by GF120918 in TR(-) IPLs, confirming that Mrp2 and Bcrp primarily are responsible for RSV CLBile. RSV appearance in outflow perfusate was attributed primarily to CLBL, which was impaired in TR(-) IPLs. CLBL was ≈ 6-fold greater than CLBile in the linear range in WT IPLs in the absence of GF120918. Recovery of unchanged RSV in liver tissue increased in TR(-) compared with WT (≈ 25 versus 6% of the administered dose) due to impaired CLBL and CLBile. RSV pentanoic acid, identified by high-resolution liquid chromatography-tandem mass spectroscopy, comprised ≈ 40% of total liver content and ≈ 16% of the administered dose in TR(-) livers at the end of perfusion, compared with ≈ 30 and 3% in WT livers, consistent with impaired RSV excretion and "shunting" to the metabolic pathway. In vitro-ex vivo extrapolation between WT SCH and IPLs (without GF120918) revealed that uptake clearance and CLBL were 4.2- and 6.4-fold lower, respectively, in rat SCH compared with IPLs; CLBile translated almost directly (1.1-fold). The present IPL data confirmed the significant role of CLBL in RSV hepatic elimination, and demonstrated that both CLBL and CLBile influence RSV hepatic and systemic exposure.

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Isolation and analysis of linker histones across cellular compartments.

Analysis of histones, especially histone H1, is severely limited by immunological reagent availability. This paper describes the application of cellular fractionation with LC-MS for profiling histones in the cytosol and upon chromatin. First, we show that linker histones enriched by cellular fractionation gives less nuclear contamination and higher histone content than when prepared by nuclei isolation. Second, we profiled the soluble linker histones throughout the cell cycle revealing phosphorylation increases as cells reach mitosis. Finally, we monitored histone H1.2-H1.5 translocation to the cytosol in response to the CDK inhibitor flavopiridol in primary CLL cells treated ex vivo. Data shows that all H1 variants translocate in response to drug treatment with no specific order to their cytosolic appearance. The results illustrate the utility of cellular fractionation in conjunction with LC-MS for the analysis of histone H1 throughout the cell.

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