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排序方式: 共有443条查询结果,搜索用时 15 毫秒
31.
Z Gao Z Li S P Baker R D Lasley S Meyer E Elzein V Palle J A Zablocki B Blackburn L Belardinelli 《The Journal of pharmacology and experimental therapeutics》2001,298(1):209-218
Several potent and selective A2A adenosine receptor agonists are currently available. These compounds have a high affinity for the A2A receptor and a long duration of action. However, in situations where a short duration of action is desired, currently available A2A receptor agonists are less than ideal. From a series of recently synthesized A2A receptor agonists, two agonists (CVT-3146 and CVT-3033) with low affinity were selected for further characterization as selective and short-acting coronary vasodilators. Both compounds were selective for the A2A adenosine receptor (AdoR) versus the A1, A2B, and A3AdoR in binding and functional studies. CVT-3146 and CVT-3033 appeared to be weak partial agonists to cause cAMP accumulation in PC12 cells, but were full and potent agonists to cause coronary vasodilation, a response that has a very large A2A receptor reserve. However, the durations of action of CVT-3146 and CVT-3033 were remarkably shorter than those of the high-affinity agonists CGS21680 or WRC0470, presumably due to the relative lower affinity of CVT-3146 and CVT-3033 for the A2A receptor. Indeed, an inverse relationship was found between the affinity of the various agonists for the A2A receptor and the duration of their actions. These data indicate that low-affinity agonists can produce a response that is of equivalent magnitude but more rapid in termination than that caused by a high-affinity agonist. Hence, the low-affinity A2A agonists CVT-3146 and CVT-3033 may prove to be superior to currently available high-affinity agonists as coronary vasodilators during myocardial imaging with radionuclide agents. 相似文献
32.
Troels K. Bergmann Tore B. Stage Jan Stenvang Palle Christophersen Thomas A. Jacobsen Nicklas L. Roest Peter M. Vestlev Nils Brünner 《Basic & clinical pharmacology & toxicology》2020,127(4):329-337
SCO‐101 (Endovion) was discontinued 20 years ago as a new drug under development against sickle cell anaemia. Data from the phase 1 studies remained unpublished. New data indicate that SCO‐101 might be efficacious as add‐on therapy in cancer. Thus, we report the results from the four phase 1 trials performed between 2001 and 2002. Adult volunteers received SCO‐101 or placebo in four independent trials. Adverse events were recorded, and SCO‐101 was determined for pharmacokinetic analysis. Ninety‐two volunteers completed the trials. The most remarkable adverse effect was a transient and dose‐dependent increase in unconjugated bilirubin. Plasma SCO‐101 elimination was approximately log linear, with apparent oral clearances of between 315 and 2103 mL/h for single doses, and between 121 and 2433 mL/h at steady state following oral administration. There was a marked decrease in clearance with increasing dose, and for repeated dose versus single dose. Tmax was greater, and Cmax and AUC∞ were lower in the fed state compared to the fasted state. Exposure was equivalent in males and females and for African Americans and Caucasians. In conclusion, SCO‐101 appears to be a safe drug with a predictable PK profile. Its efficacy as add‐on to standard anticancer drugs has yet to be defined. 相似文献
33.
L Vico D Chappard C Alexandre S Palle P Minaire B V Morukov A S Rakhmanov V S Oganov 《Annales de biologie clinique》1987,45(2):145-151
Bone biopsies of iliac crests, performed at the beginning and the end of a decubitus period of 120 days, were studied in 20 healthy volunteers men. The purpose of this experiment is to simulate the bony alterations of astronauts. The bony mass of all bed-ridden patients remained constant. In strictly immobilized patients, the rate of bony mineralization is decreased and the osteoclastic resorption activity is stimulated. In bed-ridden patients subjected to preventive physical exercises, the bony formation and resorption are increased. When prevention is administered with the use of a diphosphonate, the osteoid and osteoclastic parameters are decreased. When both types of prevention are administered, the osteoid parameters and the resorption activity are decreased but less markedly than in patients treated with diphosphonate alone. 相似文献
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Voltage- and Ca(2+)-dependent K(+) channels in the membrane of both T and B lymphocytes are important for the cellular immune response. In the current issue of the European Journal of Immunology, Reich et al. demonstrate that selective blockade of the intermediate-conductance Ca(2+)-activated K(+) channel (the IK channel encoded by the KCNN4 gene) prevents cytokine production in the spinal chord and ameliorates the development of EAE caused by injection of myelin oligodendrocyte glycoprotein (MOG)(35-55) in mice. These data renew the focus on the IK channel as a potential target for the development of new immune-suppressant drugs for the treatment of autoimmune diseases. 相似文献
37.
Rotavirus particles can survive storage in ambient tropical temperatures for more than 2 months 下载免费PDF全文
Typing and in vitro cultivation of rotavirus-positive human stool samples stored unintentionally at ambient tropical temperatures for 2 1/2 months showed that rotavirus is stable and may still be infectious in vitro. This indicates that stool specimen collection for rotavirus studies can be performed in areas and settings where reliable cold storage is not available. The retained infectivity of rotavirus particles underscores the need for safe systems for disposal of feces, in particular in developing countries where rotavirus is a major cause of childhood mortality. 相似文献
38.
By surveying a filtered, high-quality set of SNPs in the human genome, we have found that SNPs positioned 1, 2, 4, 6, or 8 bp apart are more frequent than SNPs positioned 3, 5, 7, or 9 bp apart. The observed pattern is not restricted to genomic regions that are known to cause sequencing or alignment errors, for example, transposable elements (SINE, LINE, and LTR), tandem repeats, and large duplicated regions. However, we found that the pattern is almost entirely confined to what we define as "periodic DNA." Periodic DNA is a genomic region with a high degree of periodicity in nucleotide usage. It turned out that periodic DNA is mainly small regions (average length 16.9 bp), widely distributed in the genome. Furthermore, periodic DNA has a 1.8 times higher SNP density than the rest of the genome and SNPs inside periodic DNA have a significantly higher genotyping error rate than SNPs outside periodic DNA. Our results suggest that not all SNPs in the human genome are created by independent single nucleotide mutations, and that care should be taken in analysis of SNPs from periodic DNA. The latter may have important consequences for SNP and association studies. 相似文献
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Lipopolysaccharide from S. typhosa, injected intraperitoneally into Swiss albino mice, produced acute thymic involution—maximal at 48 hours after injection, followed by regeneration that was complete within 5 to 7 days. Using tissues fixed and embedded for electron microscopy, cell counts were made with the light microscope and cytological details were examined in electron micrographs. The cellular events of involution and regeneration were similar to those produced by injection of adrenal glucocorticoids, but it remains to be determined whether or not endotoxin acts on the thymus by inciting adrenal cortical secretion. Involution appeared to be the result of both the death of small lymphocytes and reduced lymphopoiesis in the thymus. Within 48 hours, macrophages had cleared away the cellular debris and medullary epithelial cells showed signs of hypertrophy and increased putative secretory activity. Subsequently, large lymphocytes proliferated at an accelerated rate in the subcapsular cortex, the cortex grew in width by the accumulation of small lymphocytes, and regeneration ceased when the thymus had reached its former size. These observations provide circumstantial evidence for the hypothesis that in regeneration, medullary epithelial cells increase their production of a lymphopoietic hormone which stimulates mitotic proliferaton of cortical lymphocytes. 相似文献