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201.
A novel approach for the potential on-line determination of the enantiomeric excess (ee) of an M3 antagonist drug substance combining attenuated total reflectance infrared (ATR-IR) spectroscopy, guest-host complexes, and chemometric data analysis is described. Chiral recognition through a formation of diastereomeric complexes was measured by ATR-IR. Small changes on the IR spectra reflect the interaction between the guest (M3) and host (chiral selector). These changes are measured as a function of M3 enantiomer excess. The standard error of prediction is 1.3 ee%. The prediction results based on the IR method were in good agreement with the gravimetric method. The robustness of the calibration model was evaluated by varying the concentration of the chiral selector, the pH of the solution, and the organic solvents. The stability of the calibration model was also demonstrated through measuring different sets of samples on different days. 相似文献
202.
Mie Ø. Pedersen Agnete Larsen Milena Penkowa 《Progress in histochemistry and cytochemistry》2009,44(1):29-64
The antiapoptotic, antioxidant, proliferative, and angiogenic effects of metallothionein (MT)-I+II has resulted in increased focus on their role in oncogenesis, tumor progression, therapy response, and patient prognosis. Studies have reported increased expression of MT-I+II mRNA and protein in various human cancers; such as breast, kidney, lung, nasopharynx, ovary, prostate, salivary gland, testes, urinary bladder, cervical, endometrial, skin carcinoma, melanoma, acute lymphoblastic leukemia (ALL), and pancreatic cancers, where MT-I+II expression is sometimes correlated to higher tumor grade/stage, chemotherapy/radiation resistance, and poor prognosis. However, MT-I+II are downregulated in other types of tumors (e.g. hepatocellular, gastric, colorectal, central nervous system (CNS), and thyroid cancers) where MT-I+II is either inversely correlated or unrelated to mortality. Large discrepancies exist between different tumor types, and no distinct and reliable association exists between MT-I+II expression in tumor tissues and prognosis and therapy resistance. Furthermore, a parallel has been drawn between MT-I+II expression as a potential marker for prognosis, and MT-I+II's role as oncogenic factors, without any direct evidence supporting such a parallel. This review aims at discussing the role of MT-I+II both as a prognostic marker for survival and therapy response, as well as for the hypothesized role of MT-I+II as causal oncogenes. 相似文献
203.
Enhancement of nickel and lead accumulation and their toxic growth-inhibitory effects on amaranth seedlings in the presence of calcium 总被引:1,自引:0,他引:1
The effects of Ni(NO3)2 and Pb(NO3)2 on Amaranthus sp. L. root growth and the effect of calcium on heavy metal (HM) accumulation in the growing root zone and root growth inhibition were studied. The seeds were germinated in the Pb(NO3)2 solutions at concentrations of 50, 100, 200, 500 and 700 μM or Ni(NO3)2 solutions at concentrations of 10, 50, 70, 100, and 500 μM in the presence of 100 μM Ca(NO3)2 or without it. HM toxicity was assesses in 7 days after seed sowing by the root length. Distribution of HM over the tissues of the growing root part was examined histochemically. Ni was more toxic to root growth than Pb. In the presence of Ca, Ni and Pb accumulation in the amaranth root growing part increased markedly, and this enhanced their growth-inhibitory of action. A comparison of results obtained in this work and available from the literature permitted a conclusion that the routes of HM penetration into the root differ in different plant species, and this determines ambiguity of protective Ca action. 相似文献
204.
205.
Sai Chetan K Sukuru Florian Nigsch Jean Quancard Martin Renatus Rajiv Chopra Natasja Brooijmans Dmitri Mikhailov Zhan Deng Allen Cornett Jeremy L Jenkins Ulrich Hommel John W Davies Meir Glick 《Protein science : a publication of the Protein Society》2010,19(11):2096-2109
We present here a comprehensive analysis of proteases in the peptide substrate space and demonstrate its applicability for lead discovery. Aligned octapeptide substrates of 498 proteases taken from the MEROPS peptidase database were used for the in silico analysis. A multiple‐category naïve Bayes model, trained on the two‐dimensional chemical features of the substrates, was able to classify the substrates of 365 (73%) proteases and elucidate statistically significant chemical features for each of their specific substrate positions. The positional awareness of the method allows us to identify the most similar substrate positions between proteases. Our analysis reveals that proteases from different families, based on the traditional classification (aspartic, cysteine, serine, and metallo), could have substrates that differ at the cleavage site (P1–P1′) but are similar away from it. Caspase‐3 (cysteine protease) and granzyme B (serine protease) are previously known examples of cross‐family neighbors identified by this method. To assess whether peptide substrate similarity between unrelated proteases could reliably translate into the discovery of low molecular weight synthetic inhibitors, a lead discovery strategy was tested on two other cross‐family neighbors—namely cathepsin L2 and matrix metallo proteinase 9, and calpain 1 and pepsin A. For both these pairs, a naïve Bayes classifier model trained on inhibitors of one protease could successfully enrich those of its neighbor from a different family and vice versa, indicating that this approach could be prospectively applied to lead discovery for a novel protease target with no known synthetic inhibitors. 相似文献
206.
铅对小鼠血液和肝肾影响的实验性初步观察 总被引:3,自引:0,他引:3
用全血细胞分析仪检测染毒小鼠新鲜血样,再用日立7020生化分析仪,配合试剂盒法对血清进行检测,研究铅对血液与肝肾功能的影响,结果表明:100mg/kg浓度的醋酸铅对小鼠的血液有显著影响,白细胞数目(WBC),淋巴细胞数目(Lymph),中性粒细胞数目(Gran)等指标显著增加(P〈0.05),此外对血小板凝血系统功能显著影响,血小板数目(PLT)等指标下降极显著(P〈0.01),对血红细胞(RBC),血红蛋白(HGB)等指标影响不显著(P〉0.05)。肝肾功能性指标:谷丙转氨酶(AIJT),谷草转氨酶(AST)尿素氮(UREA)肌酐(CREA)生化酶显著偏离正常值(P〈0.05)。表明铅对肝脏肾脏功能有显著的破坏。对检测结果做了进一步的分析讨论。 相似文献
207.
The objective of this study was to investigate the influence of microbial phytase and calcium supplementation to diets for
growing pigs on the retention of lead in the kidney, liver, muscle, brain, and bone (phalanx 1). The experiments were carried
out with barrows over the body weight range from 17 to 50 kg. The average lead concentration of the diets was 1.45 mg/kg dry
matter. Diets were prepared with or without a supplement of 800 units of microbial phytase. The calcium concentration in the
diets was 6.53 or 13.4 g/kg dry matter. The addition of microbial phytase showed an increase of lead concentration in bone.
By increasing the calcium concentration to 13.4 g/kg dry matter, it was possible to avoid the phytase-induced increase of
lead retention in bone. 相似文献
208.
Using municipal biosolids in combination with other residuals to restore metal-contaminated mining areas 总被引:4,自引:1,他引:3
Brown Sally L. Henry Charles L. Chaney Rufus Compton Harry DeVolder Pam S. 《Plant and Soil》2003,249(1):203-215
High metal waste materials from historic mining at the Bunker Hill, Idaho (ID) Superfund site was amended with a range of materials including municipal biosolids, woody debris, wood ash, pulp and paper sludge, and compost. The existing soil or waste material has elevated metal concentrations with total Zn, Pb and Cd ranging from 6000 to 14700, 2100 to 27000 and 9 to 28 mg kg–1, respectively. Surface application of certain amendments including biosolids mixed with wood ash resulted in significant decreases in subsoil acidity as well as subsoil extractable metals. This mixture was sufficient to restore a plant cover to the contaminated areas. At the Bunker Hill site, a surface application of high N biosolids (44 or 66 tons ha–1) in combination with wood ash (220 tons ha–1) with or without log yard debris (20% by volume) or pulp and paper sludge (44 tons ha–1) was able to restore a vegetative cover to the metal contaminated materials for 2 years following amendment application. Plant biomass in 1999 was 0.01 mg ha–1 in the control versus a mean of 3.4 tons ha–1 in the residual amended plots. Metal concentrations of the vegetation indicated that plants were within normal concentrations for the 2 years that data were collected. Surface application of amendments was also able to reduce Ca(NO3)2 extractable Zn in the subsoil from about 50 mg kg–1in the control to less than 4 mg kg–1in two of the treatments. Use of conventional amendments including lime alone and microbial stimulants were not sufficient to support plant growth. These results indicate that surface application of biosolids in combination with other residuals is sufficient to restore a vegetative cover to high metal mine wastes. 相似文献
209.
Polyphosphate bodies containing lead were induced in laboratory cultures of Diatoma tenue var. elongatum Lyngb. by the addition of phosphorus and 0.05 μg-atoms/l Pb to P deficient medium. Morphometric analysis of cells exposed to Pb showed a significant decrease in number of mitochondria with a concomitant increase in their volume and an increase in membranous organelles in the vacuole compared to phosphorus starved and phosphorus sufficient controls. Exposure of cultures to 0.08 μg-atoms/l copper resulted in reduction of the number of polyphosphate bodies formed during luxury uptake but no other significant morphological changes in cellular organelles. Ecological implications of the interactions between nutrients and low level trace metal contamination are discussed. 相似文献
210.
The influence of dietary iron deficiency on acute nickel, lead or cadmium toxicity as reflected by the induction of hepatic, renal and intestinal metallothionein (MT), disposition of the metals, and alterations in hematological parameters was investigated in rats. The administration of cadmium induced the hepatic, renal and intestinal MT while that of nickel or lead induced hepatic MT only. However, dietary iron deficiency did not influence the cadmium induced tissue MT but enhanced the ability of nickel or lead to restore the normal synthesis of renal and intestinal MT lowered under the influence of reduced body iron status. The accumulation of lead in liver and kidney and that of cadmium enhanced in liver only, while tissue deposition of nickel remained unaffected by iron deficiency. The induction of hepatic MT by three metals appears related to the concomitant rise in the hepatic zinc, calcium and iron levels in normal rats. However, dietary iron deficiency increased the hepatic zinc in response to nickel or cadmium and that of heptic calcium in response to lead. 相似文献