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41.
Luis G Sevillano Concepción P Melero Esther Caballero Fernando Tomé Lionel G Lelièvre K?thi Geering Gilles Crambert Rosalía Carrón Manuel Medarde Arturo San Feliciano 《Journal of medicinal chemistry》2002,45(1):127-136
Several hydroindenic derivatives (7a-methyl-2,3,5,6,7,7a-hexahydro-1H-indenes), bearing an amidinohydrazone at C-5 and different moieties at C-1, have been synthesized and evaluated for their inotropic and chronotropic effects on right- and left-guinea-pig-atria activity. Three of them showed the same profile as digoxin, although with lower potency. The effect on Na(+),K(+)-ATPase (NKA) was also evaluated for these three compounds, observing that two of them, with the same absolute configuration as natural cardenolides, are also NKA inhibitors, while the compound with the opposite configuration lacks such an effect. More interestingly, both active compounds act without affecting the cardiac rhythm. This could be related to the selective inhibition of the human alpha2beta1 isozyme (associated with the inotropic effect) with respect to the alpha1beta1 isozyme (associated with the maintenance of basal ionic levels in the cell and the toxic effect of cardenolides). 相似文献
42.
In vivo phosphorylation of the Na,K-ATPase alpha subunit in sciatic nerves of control and diabetic rats: effects of protein kinase modulators. 总被引:3,自引:0,他引:3 下载免费PDF全文
I Borghini K Geering A Gjinovci C B Wollheim W F Pralong 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(13):6211-6215
The phosphorylation state of the Na,K-ATPase alpha subunit has been examined in 32P-labeled sciatic nerves of control and streptozotocin-treated diabetic rats. Intact nerves were challenged with protein kinase (PK) modulators and alpha-subunit 32P labeling was analyzed after immunoprecipitation. In control nerves, the PKC activator phorbol 12-myristate 13-acetate (PMA) had little effect on alpha-subunit 32P labeling. In contrast, staurosporine, a PKC inhibitor, and extracellular calcium omission decreased it. In Ca(2+)-free conditions, PMA restored the labeling to basal levels. The cAMP-raising agent forskolin reduced the 32P labeling of the alpha subunit. The results suggest that nerve Na,K-ATPase is tonically phosphorylated by PKC in a Ca(2+)-dependent manner and that PKA modulates the phosphorylation process. In nerves of diabetic rats, PMA increased 32P labeling of the alpha subunit. In contrast to staurosporine or extracellular calcium omission, the decreased state of phosphorylation seen with forskolin was no longer significant in diabetic nerves. No change in the level of alpha-subunit isoforms (alpha 1 or alpha 2) was detected by Western blot analysis in such nerves. In conclusion, the altered effect of PK activators on Na,K-ATPase phosphorylation state is consistent with the view that a defect in PKC activation exists in diabetic nerves. 相似文献
43.
The esterases of Aedes aegypti were studied in the ovary before and during a gonotrophic cycle and also in fully embryonated eggs by means of disc electrophoresis. During oogenesis no significacant changes can be observed besides a marked increase in the total esterase activity. A different esterase pattern is found in eggs after embryogenesis. The electrophoretic mobility of some esterase bands is highly increased in the ovary compared to other organs. One esterase fraction in the ovary and two in the fertilized egg were identified as acetylcholinesterases. All other enzymes are carboxylesterases. The results are compared to those of previous authors and are discussed in view of possible functions of esterases during reproduction. 相似文献
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Abstract A total of 282 patient histories and occlusal analyses made by students for instructional purposes were evaluated. An attempt was made to correlate the slide from centric relation to centric occlusion (maximum intercuspation), and occlusal interferences in eccentric movements, to pain and/or symptoms of functional disturbances of the masticatory system. A slide in combination with balancing interference(s) was found almost twice as frequently in patients with pain and/or symptoms compared to patients with no symptoms. Neither the amount nor the direction of the slide was correlated with the pain and/or symptoms. The balancing interferences tended to be located on the pain and/or symptom side. 相似文献
46.
The most common form of neutrophil death is apoptosis. In the present study, we report surprising differences in the molecular mechanisms used for caspase activation between FAS/CD95-stimulated and TNF receptor 1 (TNFR1)-stimulated neutrophils. Whereas FAS-induced apoptosis was followed by caspase-8 activation and required Bid to initiate the mitochondrial amplification loop, TNF-α-induced apoptosis involved class IA PI3Ks, which were activated by MAPK p38. TNF-α-induced PI3K activation resulted in the generation of reactive oxygen species, which activated caspase-3, a mechanism that did not operate in neutrophils without active NADPH oxidase. We conclude that in neutrophils, proapoptotic pathways after TNFR1 stimulation are initiated by p38 and PI3K, but not by caspase-8, a finding that should be considered in anti-inflammatory drug-development strategies. 相似文献
47.
1. With a constant plasma concentration of Ampicillin the ratio of concentration in the cerebrospinal fluid to concentration in the plasma reaches a constant value after 2 hrs in patients with and without serous meningitis. 2. Patients without serous meningitis have a value of 0.025, patients with serous meningitis a value of 0.061. 3. From this it can be calculated that Ampicillin passes two and a half times faster through inflamed meningeal membranes than unaffected membranes. 相似文献
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49.
Serologic approaches to the study of cancer in animals and in man 总被引:13,自引:0,他引:13
50.
A soluble antigen of the mammary tumor virus 总被引:6,自引:0,他引:6