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971.
972.
973.
AIM: To develop an acute tolerant model in describing relationship between diltiazem (Dil) concentrations in plasma and PR intervals on ECG in men. METHOD: Both plasma concentrations of Dil and changes of ECG were simultaneously determined after po Dil 90 mg in 8 men. RESULTS: A two-compartmental pharmacokinetic model with first-order input gave a good fitting for the plasma concentration of Dil. Corresponding pharmacokinetic parameters were estimated: t1/2 beta, 5.9 +/- 1.0 h; MRT, 15.9 +/- 1.0 h; t0, 0.38 +/- 0.07 h; tmax, 2.7 +/- 0.4 h, and Cmax, 161 +/- 60 micrograms.L-1. The good fittings for plasma concentration-effect data were obtained with tolerant model E = S x C/(1 + T/T50). The pharmacodynamic parameters were given as follows: S, 829 +/- 293 s.g-1.L; Kt0, 0.037 +/- 0.024 h-1 and T50, 10 +/- 4 micrograms.L-1. CONCLUSION: Relationship between Dil concentrations in plasma and PR interval changes in men after po 90 mg was described using an acute tolerant model. 相似文献
974.
M Yu L Zhong AK Rishi M Khadeer G Inesi A Hussain L Zhang 《Canadian Metallurgical Quarterly》1998,273(6):3542-3546
High levels of resistance to thapsigargin (TG), a specific inhibitor of intracellular Ca2+ transport ATPases (SERCAs), can be developed in culture by stepwise exposure of mammalian cells to increasing concentrations of TG. We have identified, in two independently selected TG-resistant hamster cell lines of different lineages, mutant forms of SERCA. In the TG-resistant Chinese hamster lung fibroblast cell line DC-3F/TG, a T --> C change at nucleotide 766 introduces a Phe256 --> Leu alteration within the first cytosolic loop of the SERCA. In contrast, in the TG-resistant Syrian hamster smooth muscle cell line DDT/TG 4 microM, a T --> C change at nucleotide 767 introduces a Phe256 --> Ser mutation at that position. When these specific mutations are introduced into a wild-type full-length avian SERCA1 cDNA, transfection experiments reveal that Ca2+ transport function and ATP hydrolytic activity are not altered by such mutations. However, a 4-5-fold resistance to TG inhibition of Ca2+ transport function occurs upon the introduction of either the Phe256 --> Leu or the Phe256 --> Ser mutation into wild-type SERCA1. These specific mutations also render the hydrolytic activity of the ATPase resistant to inhibition by TG. Our results not only implicate amino acid 256 in TG-SERCA interactions, but also demonstrate that specific mutations within SERCA can mediate resistance to TG. 相似文献
975.
976.
胰高血糖素类肽(GLP-1)和葡萄糖依赖性促胰岛素多肽(GIP)为肠内分泌细胞在机体摄入营养时分泌的激素,因其能促进胰岛素的分泌和维持血糖的动态平衡,又被称为肠促胰素。而机体内广泛存在的二肽基肽酶-4(DPP-4)可快速灭活GLP-1和GIP,因此抑制DPP-4的活性可增强GLP-1和GIP激素的活性水平,从而改善2型糖尿病(T2DM)患者的胰岛功能和血糖控制,越来越多基于该靶点的药物被开发出来用于治疗2型糖尿病。本文综述了近年来国内外相关文献,阐述了肠促胰岛素与T2DM之间的关系,并介绍GLP-1发挥效应的机制、以及GLP类降糖药物、DPP-4抑制剂的开发设计原理。 相似文献
977.
Tao Yang Pei Wang Qin Zhou Yingxin Zhong Xiao Wang Jian Cai Mei Huang Dong Jiang 《International journal of molecular sciences》2022,23(15)
Starch–gluten interactions are affected by biopolymer type and processing. However, the differentiation mechanisms for gluten–starch interactions during heating have not been illuminated. The effects of glutens from two different wheat flours (a weak-gluten (Yangmai 22, Y22) and a medium-strong gluten (Yangmai 16, Y16)) on starch’s (S) structural and physicochemical properties during heating and their molecular interactions were investigated in this study. The results showed that gluten hindered the gelatinization and swelling of starch during heating when temperature was below 75 °C, due to competitive hydration and physical barriers of glutens, especially in Y22. Thus, over-heating caused the long-range molecular order and amylopectin branches of starch to be better preserved in the Y22-starch mixture (Y22-S) than in the Y16-starch mixture (Y16-S). Meanwhile, the starch’s degradation pattern during heating in turn influenced the polymerization of both glutens. During heating, residual amylopectin branching points restricted the aggregation and cross-linking of gluten proteins due to steric hindrance. More intense interaction between Y16 and starch during heating mitigated the steric hindrance in starch–gluten networks, which was due to more residual short-range ordered starch and hydrogen bonds involved in the formation of starch–gluten networks in Y16-S during heating. 相似文献
978.
Syed Jawad Ali Shah Haiyang Zhong Qianqian Zhang Huanxiang Liu 《International journal of molecular sciences》2022,23(5)
The formation of neurofibrillary tangles (NFT) with β-sheet-rich structure caused by abnormal aggregation of misfolded microtubule-associated protein Tau is a hallmark of tauopathies, including Alzheimer’s Disease. It has been reported that acetylation, especially K174 located in the proline-rich region, can largely promote Tau aggregation. So far, the mechanism of the abnormal acetylation of Tau that affects its misfolding and aggregation is still unclear. Therefore, revealing the effect of acetylation on Tau aggregation could help elucidate the pathogenic mechanism of tauopathies. In this study, molecular dynamics simulation combined with multiple computational analytical methods were performed to reveal the effect of K174 acetylation on the spontaneous aggregation of Tau peptide 171IPAKTPPAPK180, and the dimerization mechanism as an early stage of the spontaneous aggregation was further specifically analyzed by Markov state model (MSM) analysis. The results showed that both the actual acetylation and the mutation mimicking the acetylated state at K174 induced the aggregation of the studied Tau fragment; however, the effect of actual acetylation on the aggregation was more pronounced. In addition, acetylated K174 plays a major contributing role in forming and stabilizing the antiparallel β-sheet dimer by forming several hydrogen bonds and side chain van der Waals interactions with residues I171, P172, A173 and T175 of the corresponding chain. In brief, this study uncovered the underlying mechanism of Tau peptide aggregation in response to the lysine K174 acetylation, which can deepen our understanding on the pathogenesis of tauopathies. 相似文献
979.
980.
The spray-drying microencapsulation properties of protein isolates from three selected Phaseolus legumes (kidney, red and mung beans; KPI, RPI and MPI), at a specific concentration (6 g/100 mL) and oil/protein ratio (1:1, w/w) were compared with soy protein isolate (SPI). The oil retention efficiency (RE), redispersion and dissolution behavior, as well as microstructure of the spray-dried powders were characterized. The influence of storage at 75% relative humidity for 7 days on these characteristics was also evaluated. The results indicated that the microencapsulation properties (except RE in the KPI case) of the three protein isolates were considerably poorer than SPI, though their emulsifying ability was even superior. The microencapsulating properties of these protein isolates were largely associated with their interfacial properties, especially the interfacial protein concentration. Among the three protein isolates, the spray-dried powders with KPI exhibited highest RE but least redispersion and/or dissolution behavior. The storage resulted in a severe loss of RE and ability to be redispersed and/or dissoluted, with much higher extent observed for the KPI powder. These results suggest that appropriate modifications, especially in interfacial properties, should be conducted on these proteins to warrant their application as wall materials in spray-drying microencapsulation. 相似文献