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Muhammad Naeem Khan Muhammad Rasul Jan Jasmin Shah Sang Hak Lee Young Ho Kim 《Luminescence》2013,28(6):915-921
A highly sensitive and simple method for identifying sulpiride in pharmaceutical formulations and biological fluids is presented. The method is based on increased chemiluminescence (CL) intensity of a luminol–H2O2 system in response to the addition of Cr (III) under alkaline conditions. The CL intensity of the luminol–H2O2–Cr (III) system was greatly enhanced by the addition of sulpiride and the CL intensity was proportional to the concentration of sulpiride in a sample solution. Various parameters affecting the CL intensity were systematically investigated and optimized for determination of the sulpiride in a sample. Under the optimum conditions, the CL intensity was proportional to the concentration of sulpiride in the range of 0.068–4.0 µg/mL, with a good correlation coefficient of 0.997. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 8.50 × 10‐6 µg/mL and 2.83 × 10‐5 µg/mL, respectively. The method presented here produced good reproducibility with a relative standard deviation (RSD) of 2.70% (n = 7). The effects of common excipients and metal ions were studied for their interference effect. The method was validated statistically through recovery studies and successfully applied for the determination of sulpiride in pure form, pharmaceutical preparations and spiked human plasma samples. The percentage recoveries were found to range from 99.10 to 100.05% for pure form, 98.12 to 100.18% for pharmaceutical preparations and 97.9 to 101.4% for spiked human plasma. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
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Kwangkook Lee Shenyan Gu Lei Jin Thi Tuc Nghi Le Luisa W. Cheng Jasmin Strotmeier Anna Magdalena Kruel Guorui Yao Kay Perry Andreas Rummel Rongsheng Jin 《PLoS pathogens》2013,9(10)
Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and cause the fatal disease botulism, a flaccid paralysis of the muscle. BoNTs are released together with several auxiliary proteins as progenitor toxin complexes (PTCs) to become highly potent oral poisons. Here, we report the structure of a ∼760 kDa 14-subunit large PTC of serotype A (L-PTC/A) and reveal insight into its absorption mechanism. Using a combination of X-ray crystallography, electron microscopy, and functional studies, we found that L-PTC/A consists of two structurally and functionally independent sub-complexes. A hetero-dimeric 290 kDa complex protects BoNT, while a hetero-dodecameric 470 kDa complex facilitates its absorption in the harsh environment of the gastrointestinal tract. BoNT absorption is mediated by nine glycan-binding sites on the dodecameric sub-complex that forms multivalent interactions with carbohydrate receptors on intestinal epithelial cells. We identified monosaccharides that blocked oral BoNT intoxication in mice, which suggests a new strategy for the development of preventive countermeasures for BoNTs based on carbohydrate receptor mimicry. 相似文献
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Kenneth W. Able Mark J. Wuenschel Thomas M. Grothues James M. Vasslides Peter M. Rowe 《Environmental Biology of Fishes》2013,96(5):661-675
The fishes of the energetic surf zone of exposed ocean beaches are poorly known, especially along the U.S. east coast. We investigated the role that surf zones in southern New Jersey have as habitat by describing the young-of-the-year fishes caught by seines within the surf zone from May through October in 1998, 1999, 2005 and 2006. In addition, we investigated the nursery role of these surf zones by examining abundance, growth, and inferred survival during the summer for the dominant locally (New Jersey) and southern (south of Cape Hatteras) spawned species. At least three southern species, i.e. bluefish Pomatomus saltatrix (Cohort I), white mullet Mugil curema, and Florida pompano Trachinotus carolinus successfully use New Jersey surf zones as nurseries during the summer. It is clear that bluefish (Cohort I) contributes to the adult population and it is likely for the other southern species. Ultimately, the nursery contribution of surf zones and other habitats at the northern limits of the range of southern species depends on whether surviving juveniles can successfully emigrate to overwinter habitats and complete their life history. 相似文献
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Birte Arlt Guido Mastrobuoni Jasmin Wuenschel Kathy Astrahantseff Angelika Eggert Stefan Kempa Hedwig E. Deubzer 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):1282
The small-molecule inhibitor of phosphoglycerate dehydrogenase, NCT-503, reduces incorporation of glucose-derived carbons into serine in vitro. Here we describe an off-target effect of NCT-503 in neuroblastoma cell lines expressing divergent phosphoglycerate dehydrogenase (PHGDH) levels and single-cell clones with CRISPR-Cas9-directed PHGDH knockout or their respective wildtype controls. NCT-503 treatment strongly reduced synthesis of glucose-derived citrate in all cell models investigated compared to the inactive drug control and independent of PHGDH expression level. Incorporation of glucose-derived carbons entering the TCA cycle via pyruvate carboxylase was enhanced by NCT-503 treatment. The activity of citrate synthase was not altered by NCT-503 treatment. We also detected no change in the thermal stabilisation of citrate synthase in cellular thermal shift assays from NCT-503-treated cells. Thus, the direct cause of the observed off-target effect remains enigmatic. Our findings highlight off-target potential within a metabolic assessment of carbon usage in cells treated with the small-molecule inhibitor, NCT-503. 相似文献
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Francesco Addabbo Qiuying Chen Dhara P. Patel May Rabadi Brian Ratliff Frank Zhang Jean-Francois Jasmin Michael Wolin Michael Lisanti Steven S. Gross Michael S. Goligorsky 《PloS one》2013,8(6)
Endothelial Cell Dysfunction (ECD) is a recognized harbinger of a host of chronic cardiovascular diseases. Using a mouse model of ECD triggered by treatment with L-Nω-methylarginine (L-NMMA), we previously demonstrated that renal microvasculature displays a perturbed protein profile, including diminished expression of two key enzymes of the Krebs cycle associated with a Warburg-type suppression of mitochondrial metabolism. We hypothesized that supplementation with L-glutamine (GLN), that can enter the Krebs cycle downstream this enzymatic bottleneck, would normalize vascular function and alleviate mitochondrial dysfunction. To test this hypothesis, mice with chronic L-NMMA-induced ECD were co-treated with GLN at different concentrations for 2 months. Results confirmed that L-NMMA led to a defect in acetylcholine-induced relaxation of aortic rings that was dose-dependently prevented by GLN. In caveolin-1 transgenic mice characterized by eNOS inactivation, L-NMMA further impaired vasorelaxation which was partially rescued by GLN co-treatment. Pro-inflammatory profile induced by L-NMMA was blunted in mice co-treated with GLN. Using an LC/MS platform for metabolite profiling, we sought to identify metabolic perturbations associated with ECD and offset by GLN supplementation. 3453 plasma molecules could be detected with 100% frequency in mice from at least one treatment group. Among these, 37 were found to be differentially expressed in a 4-way comparison of control vs. LNMMA both with and without GLN. One of such molecules, hippuric acid, an “uremic toxin” was found to be elevated in our non-uremic mice receiving L-NMMA, but normalized by treatment with GLN. Ex vivo analysis of hippuric acid effects on vasomotion demonstrated that it significantly reduced acetylcholine-induced vasorelaxation of vascular rings. In conclusion, functional and metabolic profiling of animals with early ECD revealed macrovasculopathy and that supplementation GLN is capable of improving vascular function. Metabolomic analyses reveal elevation of hippuric acid, which may further exacerbate vasculopathy even before the development of uremia. 相似文献
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