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Singhal P Gaur A Behl V Gautam A Varshney B Paliwal J Batra V 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,852(1-2):293-299
A simple, sensitive and rapid liquid chromatography/tandem mass spectrometric (LC-MS/MS) method was developed and validated for quantification of chloroquine, an antimalarial drug, in plasma using its structural analogue, piperazine bis chloroquinoline as internal standard (IS). The method is based on simple protein precipitation with methanol followed by a rapid isocratic elution with 10 mM ammonium acetate buffer/methanol (25/75, v/v, pH 4.6) on Chromolith SpeedROD RP-18e reversed phase chromatographic column and subsequent analysis by mass spectrometry in the multiple reaction monitoring mode (MRM). The precursor to product ion transitions of m/z 320.3-->247.2 and m/z 409.1-->205.2 were used to measure the analyte and the IS, respectively. The assay exhibited a linear dynamic range of 2.0-489.1 ng/mL for chloroquine in dog plasma. The limit of detection (LOD) and lower limit of quantification (LLOQ) were 0.4 and 2.0 ng/mL, respectively in 0.05 mL plasma. Acceptable precision and accuracy were obtained for concentrations over the standard curve range of 2.0-489.1 ng/mL. A run time of 2.0 min for a sample made it possible to achieve a throughput of more than 400 plasma samples analyzed per day. The validated method was successfully used to analyze samples of dog plasma during non-clinical study of chloroquine. 相似文献
44.
The ability to sense and respond to the environment is a hallmark of living systems. These processes occur at the levels of the organism, cells and individual molecules. Sensing of extracellular changes could result in a structural or chemical alteration in a molecule, which could in turn trigger a cascade of intracellular signals or regulated trafficking of molecules at the cell surface. These and other such processes allow cells to sense and respond to environmental changes. Often, these changes and the responses to them are spatially and/or temporally localized, and visualization of such events necessitates the use of high-resolution imaging approaches. Here we discuss optical imaging approaches and tools for imaging individual events at the cell surface with improved speed and resolution. 相似文献
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Shreyasi Asthana Zaved Hazarika Parth Sarathi Nayak Jyoti Roy Anupam Nath Jha Bibekanand Mallick Suman Jha 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(1):153-166
Background
Injection localized amyloidosis is one of the most prevalent disorders in type II diabetes mellitus (TIIDM) patients relying on insulin injections. Previous studies have reported that nanoparticles can play a role in the amyloidogenic process of proteins. Hence, the present study deals with the effect of zinc oxide nanoparticles (ZnONP) on the amyloidogenicity and cytotoxicity of insulin.Methods
ZnONP is synthesised and characterized using XRD, Zeta Sizer, UV-Visible spectroscope and TEM. The characterization is followed by ZnONP interaction with insulin, which is studied employing fluorescence spectroscopes, isothermal titration calorimetry and molecular dynamics simulations. The interaction leads insulin conformational rearrangement into amyloid-like fibril, which is studied using thioflavin T dye binding assay, circular dichroism spectroscopy and TEM, followed by cytotoxicity propensity using Alamar Blue dye reduction assay.Results
Insulin has very weak interaction with ZnONP interface. Insulin at studied concentration forms amorphous aggregates at physiological pH, whereas in presence of ZnONP interface amyloid-like fibrils are formed. While the amyloid-like fibrils are cytotoxic to MIN6 and THP-1 cell lines, insulin and ZnONP individual solutions and their fresh mixtures enhance the cells proliferation.Conclusions
The presence of ZnONP interface enhances insulin fibrillation at physiological pH by providing a favourable template for the nucleation and growth of insulin amyloids.General significance
The studied protein-nanoparticle system from protein conformational dynamics point of view throws caution over nanoparticle use in biological applications, especially in vivo applications, considering the amyloidosis a very slow but non-curable degenerative disease. 相似文献47.
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Mongin Alexander A.; Reddi Jyoti M.; Charniga Carol; Kimelberg Harold K. 《American journal of physiology. Cell physiology》1999,276(5):C1226
Volume-dependent anion channels permeable forCl and amino acids arethought to play an important role in the homeostasis of cell volume.Astrocytes are the main cell type in the mammalian brain showing volumeperturbations under physiological and pathophysiological conditions. Weinvestigated the involvement of tyrosine phosphorylation in hyposmoticmedium-induced[3H]taurine andD-[3H]aspartaterelease from primary astrocyte cultures. The tyrosine kinase inhibitorstyrphostin 23 and tyrphostin A51 partially suppressed thevolume-dependent release of[3H]taurine in adose-dependent manner with half-maximal effects at ~40 and 1 µM,respectively. In contrast, the release ofD-[3H]aspartatewas not significantly affected by these agents in the sameconcentration range. The inactive analog tyrphostin 1 hadno significant effect on the release of both amino acids. The dataobtained suggest the existence of at least two volume-dependent anionchannels permeable to amino acids in astrocyte cultures. One of thesechannels is permeable to taurine and is under the control of tyrosinekinase(s). The other is permeable to both taurine and aspartate, butits volume-dependent regulation does not require tyrosine phosphorylation. 相似文献
50.
Kurukulasuriya R Sorensen BK Link JT Patel JR Jae HS Winn MX Rohde JR Grihalde ND Lin CW Ogiela CA Adler AL Collins CA 《Bioorganic & medicinal chemistry letters》2004,14(9):2047-2050
Biaryl amides derived from a reported series of ureas 1 were evaluated and found to be potent human glucagon receptor antagonists. The benzofuran analogue 6i was administered in Sprague-Dawley rats and blocked the effects of an exogenous glucagon challenge. 相似文献