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12.
目的:研究藏药七十味珍珠丸中汞的5种存在形态和分布.方法:将七十味珍珠丸中汞的形态分为水溶态汞、溶于盐酸的无机汞和有机汞、络合汞、单质汞和残渣态汞,通过电感耦合等离子体原子发射光谱(ICP-AES)法分析5种形态汞的含量和分布.结果:藏药七十味珍珠丸中总汞的93.8%是以惰性汞形式存在的硫化汞,6.18%是与锌、铝、钙... 相似文献
13.
Ortiz-Alvarez O; Cabral D; Prendiville JS; Stringer D; Petty RE; Malleson PN 《Rheumatology (Oxford, England)》1997,36(2):280-284
Two children are reported in whom intestinal pseudo-obstruction was the
initial manifestation of systemic sclerosis. Gastrointestinal symptoms and
skin changes resolved or improved in both children following treatment with
prednisone and penicillamine (case 1) or methotrexate (case 2), although
radiological changes of the gastrointestinal tract persisted at 3 and 2 yr
of follow-up, respectively.
相似文献
14.
Jacqueline AM Smith DL Patil OT Daniels Y-S Ding J-D Gallezot S Henry KHS Kim S Kshirsagar WJ Martin GP Obedencio E Stangeland PR Tsuruda W Williams RE Carson ST Patil 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2015,18(2)
Background:
Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters.Methods:
We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.Results:
TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC50 of 11.7ng/mL and 50.8ng/mL, respectively, consistent with modest selectivity for NET in vivo.Accounting for species differences in protein binding, the projected human NET and SERT plasma EC50 values were 5.5ng/mL and 23.9ng/mL, respectively. A single-dose, open-label PET study (4–20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [11C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [11C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30–40h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC50 for NET was estimated to be 1.21ng/mL, and at doses of greater than 4mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35ng/mL.Conclusions:
These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation. 相似文献15.
16.
The cytoskeleton in Chediak-Higashi syndrome fibroblasts 总被引:2,自引:0,他引:2
The Chediak-Higashi syndrome (CHS) trait is expressed in cultured human skin fibroblasts as an abnormal perinuclear concentration of moderately enlarged lysosomes. The cytoskeleton of CHS fibroblasts appears intact. Microtubules are normal in number and morphology, as assessed by colchicine binding studies, antitubulin immunofluorescence, and electron microscopy. Deformability by shear force is unaltered and microfilaments are abundant. However, CHS lysosomes appear to interact abnormally with the cytoskeleton, since the perinculear aggregation partially disperses after depolymerization of cell microtubules with colchicine. These results suggest that CHS is associated with a defect of either the lysosomal membrane itself or of lysosomal membrane- microtubule interaction. 相似文献
17.
The contribution of von Willebrand factor (vWF)-platelet binding to platelet-collagen interaction was examined in vitro. The binding of vWF to platelets was mediated and regulated by ristocetin. Subthreshold concentrations of ristocetin (less than or equal to 1 mg/mL), insufficient to cause ristocetin-induced platelet aggregation (RIPA), were added to platelet-rich plasma (PRP) prior to the addition of collagen. The collagen-induced platelet aggregation (CIPA) was modified by ristocetin and the degree of alteration was dependent on the ristocetin concentration. Response as a function of ristocetin concentration was designated the Collagen-Platelet Aggregation Response (CoI-PAR). In normal PRP the CoI-PAR was a progressive inhibition followed by decreasing inhibition and then an enhanced response. The enhanced response occurred over a narrow range of ristocetin concentrations (0.8 to 1.0 mg/mL). In the absence of vWF (severe von Willebrand's disease, Type I, vWF less than 1%) the CoI-PAR was a progressive, eventually complete inhibition with no enhanced response (with ristocetin concentrations up to 3.0 mg/mL). With addition of vWF to this PRP an enhanced response was observed at a ristocetin concentration inversely proportional to the vWF level. PRP from a patient with severe Hemophilia A showed a response within the normal range. Subthreshold ristocetin did not cause plasma protein precipitation or platelet release of 3H-serotonin, nor induce micro platelet aggregate formation. Digestion of platelet membrane glycoproteins (GP(s] with chymotrypsin demonstrated that upon removal of GPI, RIPA was absent, CIPA retained and the CoI-PAR was progressive inhibition, with no enhancement. With removal of GPs I, II, and III, RIPA, CIPA, and the CoI-PAR were absent. A dose-response 125I-vWF- platelet binding occurred with increasing ristocetin concentrations which was unchanged by the addition of collagen. These results demonstrated that ristocetin-platelet association inhibited CIPA, and vWF-platelet binding enhanced platelet-collagen adhesion and platelet aggregation. The in vitro-enhanced CIPA represents a vWF-dependent aggregation of sufficient magnitude to overcome the inhibitory effect of ristocetin. These studies demonstrate an influential interaction of ristocetin, vWF, and collagen with the platelet membrane and imply an important hemostatic contribution of vWF-platelet binding in platelet- collagen interaction. 相似文献
18.
Identification of 19 protein S gene mutations in patients with phenotypic protein S deficiency and thrombosis. Protein S Study Group 总被引:1,自引:1,他引:1
Protein S is a protein C-dependent and independent inhibitor of the coagulation cascade. Deficiency of protein S is an established risk factor for venous thromboembolism. We have used a strategy of specific amplification of the coding regions and intron/exon boundaries of the active protein S gene (PROS1) and direct single-strand solid phase sequencing, to seek mutations in 35 individuals with phenotypic protein S deficiency. Nineteen point mutations (16 novel) in 19 probands (or relatives of probands) with venous thromboembolism are reported here. Fifteen of the 19 mutations were expected to be causal and included 10 missense mutations (Lys9Glu, Glu26Ala, Gly54Glu, Cys145Tyr, Cys200Ser, Ser283Pro, Gly340Asp, Cys408Ser, Ser460Pro, and Cys625Arg). Three of the 15 mutations resulted in premature stop codons (delete T 635 producing a stop codon at position 126, Lys368stop and Tyr595stop) and two were at intron/exon boundaries (+1 G to A in intron d and +3 A to C in intron j). Of the remaining four mutations, three were within intronic sequence and one was a silent mutation within the coding region and did not alter amino acid composition. In two of the 10 missense mutations, reduced plasma protein S activity compared with antigen level suggested the presence of variant (type II) protein S. 相似文献
19.
目的:分析载脂蛋白B(apoB)基因EcoRI、XbaI、MspI位点和载脂蛋白AI(apoAI)基因-75bp、+83bp位点多态性与哈萨克族人冠心病的关系.方法:采用聚合酶链式反应-限制性片段长度多态性分析法检测185例哈萨克族冠心病患者和216例哈萨克族非冠心病对照者的这些位点多态性.结果:①TC、TG及apoA... 相似文献
20.
目的 应用彩色多普勒超声寻找移植肾急性排异反应较为特异的诊断指标.方法 经移植肾穿刺活检证实的急性排异反应患者42例,经长期随访(1年以上)和临床检查证实的功能稳定期患者115例.对两组移植肾长径、宽径、厚径、实质厚度以及主肾动脉和弓状动脉的阻力指数(RI)进行统计学比较;选取肾体积增大,锥体肿大回声减低、RI<0.7、RI≥0.7及RI≥0.8作为诊断标准,按诊断试验评价原则分别计算灵敏度、特异度、误诊率、漏诊率和符合率;并绘制ROC曲线,确定诊断界值.结果 两组的移植肾长径、宽径、厚径及实质厚度差异有统计学意义(P<0.05);急性排异反应组肾内血流灌注减少,肾动脉舒张期血流速度明显下降,RI明显增高,与移植肾功能稳定期比较差异有统计学意义(P<0.05);各诊断标准对应的灵敏度分别为55.30%,55.20%,42.10%,57.90%和31.60%;特异度分别为71.30%、87.10%、25.70%、74.20%、98.20%.结论 肾体积增大、肾锥体肿大、回声减低、RI升高对诊断移植肾急性排异反应有特异性. 相似文献