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161.
7-(1,7-双取代-1,4-二氢-4-酮-1,8-萘啶-3-甲酰氨基)头孢菌素的合成 总被引:1,自引:0,他引:1
本文报道了以1,7-双取代-1,4-二氢-4-酮-1,8-萘啶-3-羧酸,用混合酸酐法与7-ACA,7-ADCA,7-ACT和7-ACD缩合,合成了24个1,7-双取代-1,4-二氢-4-酮-1,8-萘啶-3-甲酰胺头孢菌素衍生物,通过葡聚糖凝胶(Sephadex LH-20)及离心薄层层析纯化精制,得到纯品。体外抑菌试验结果表明:大多数新头孢菌素衍生物对革兰氏阳性菌具有较好的抗菌作用。尚有一些新头孢菌素衍生物对某些革兰氏阴性菌具有中等敏感程度。 相似文献
162.
Calpain inhibition prevents sinusoidal endothelial cell apoptosis in the cold ischemic rat liver. 总被引:7,自引:0,他引:7
BACKGROUND: Cold preservation of the liver followed by reperfusion results in sinusoidal endothelial cell (SEC) apoptosis. Calpain-like activity is dramatically increased during reperfusion and inhibition of calpains results in lower graft injury and longer survival. Recently, calpains have been implicated in inducing apoptosis. Our aim was to determine the effect of calpain inhibition on SEC apoptosis. METHODS: Livers were stored in the University of Wisconsin solution for 24 hr (survival conditions) and 40 hr (nonsurvival conditions) and ex vivo reperfused for 1 hr at 37 degrees C. Calpain-like activity was inhibited in some experiments using an i.p. injection of a selective inhibitor 2 hr before explantation. Apoptosis was quantified using the terminal deoxynucleotidyl trans. ferase-mediated dUTP nick end-labeling assay. Cross-inhibition by the inhibitor was determined for caspases 1 and 3. RESULTS: Apoptosis of exclusively the SEC was a key feature of reperfusion injury after both storage periods in University of Wisconsin solution after 1 hr normothermic reperfusion. Inhibition of calpain activity with Cbz-Val-Phe methyl ester resulted in a 50% reduction of apoptotic SEC in the 40-hr preserved liver, and an almost complete abrogation of SEC apoptosis after 24 hr preservation. Only minimal cross-inhibition of caspases was determined at high concentrations in vitro by the calpain inhibitor. CONCLUSION: Apoptosis of exclusively SEC is a key feature of reperfusion injury partially mediated through calpain-dependent processes. Calpain inhibition reduces the number of apoptotic SEC. Based on these data and our previous work, calpain inhibition may prove to be useful in clinical transplantation. 相似文献
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165.
Ming Zhao Yan‐Fang Xian Siu‐Po Ip Harry HS Fong Chun‐Tao Che 《Phytotherapy research : PTR》2010,24(9):1414-1416
A new protoberberine alkaloid, 3‐hydroxy‐2‐methoxy‐9,10‐methylenedioxy‐8‐oxo‐protoberberine, along with three known compounds, was isolated from Rhizoma Coptidis. The new compound displayed weak antispasmodic activity against acetylcholine‐induced contraction in isolated guinea‐pig ileum with an IC50 of 83.7 μm . Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
166.
Renal functional status in Mycobacterium leprae infected mice can be best studied by examining the enzymatic status of brush border membrane vesicles from proximal convoluted tubule. The role of vaccination in modulation of the renal status brought by the disease has been studied using this technique. The characteristic marker enzymes of renal brush border membrane--namely alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl transpeptidase decreased significantly (p less than 0.01) in due course in M. leprae infection over a period of 9 months. The combined vaccine (BCG + M. leprae) may have a protective effect on renal abnormalities only in the initial stages of infection as indicated by a significant rise in enzymatic levels. However, no significant (p greater than 0.05) protective effect of vaccine was found in a more advanced disease state after 9 months in infected mice. 相似文献
167.
P T Horn J D Kohli L I Goldberg 《The Journal of pharmacology and experimental therapeutics》1982,223(2):462-468
Effects of the (R) and (S) enantiomers of sulpiride, a potent dopamine (DA) antagonist, on ganglionic transmission were studied in anesthetized dogs. The pre- and postganglionic nerves of cardiac sympathetic ganglia were stimulated electrically, and heart rate was monitored as a measure of ganglionic transmission and sympathetic nerve activity. The heart rate was free from influence of the central nervous system. (R)- And (S)-sulpiride injected i.a. close to the blood supply of the ganglia did not alter basal heart rate, but facilitated ganglionic transmission as demonstrated by an increase in the tachycardia induced by preganglionic nerve stimulation. The (R) enantiomer was 4 times more active than the (S) enantiomer in this respect. Neither enantiomer affected the tachycardia induced by postganglionic nerve stimulation. Norepinephrine and DA injected i.a. caused inhibition of the tachycardia induced by preganglionic nerve stimulation. The inhibitory effect of both catecholamines was antagonized by the sulpiride enantiomers (R)-sulpiride was about 4-fold more potent than (S)-sulpiride in antagonizing DA, whereas (S)-sulpiride was more active against norepinephrine. The sulpiride enantiomers affected neither the tachycardia induced by i.a. administration of acetylcholine nor the bradycardia induced by vagal nerve stimulation. Thus, cholinesterase inhibition and ganglionic stimulation were excluded. These data are, therefore, consistent with the hypothesis that the facilitatory action of the sulpiride enantiomers is related to the antagonism of catecholamines. Positive correlation between the activity of the (R) enantiomer to facilitate ganglionic transmission and to antagonize DA suggests that DA is a physiologically released catecholamine modulating transmission in the cardiac sympathetic ganglia of the dog. 相似文献
168.
Creutzfeldt--Jakob Disease in Recipients of Human Growth Hormone in the United Kingdom: A Clinical and Radiographic Study 总被引:1,自引:0,他引:1
MARKUS HS; DUCHEN LW; PARKIN EM; KURTZ AB; JACOBS HS; COSTA DC; HARRISON MJ 《QJM : monthly journal of the Association of Physicians》1992,82(1):43-51
In the past 3 years there have been five further cases, in additionto one case reported in 1985, of Creutzfeldt-Jakob disease inrecipients of human growth hormone in the United Kingdom. Theclinical findings of two of these cases are described, demonstratinga typical presentation with a predominantly cerebellar syndromeat onset which is not commonly a presenting feature of sporadicCreutzfeldt-Jakob disease. In one case a 99mTc hexamethylpropylenaminesingle photon emission tomographic scan showed marked impairmentof tracer uptake in the basal ganglia and cerebral cortex ata time when the clinical picture was predominantly cerebellar.This technique may be useful in early diagnosis. In the othercase post mortem examination of the brain showed prominent amyloiddeposition in the cerebellum, which has not been described previouslyin pituitary-hormone related Creutzfeldt-Jakob disease. Thepreviously published cases of growth hormone-related Creutzfeldt-Jakobdisease are reviewed and reasons for the particular clinicalpattern seen are discussed. 相似文献
169.
A human monocyte-like cell line, U937, when grown in continuous culture, does not secrete lysosomal enzymes or migrate towards chemotactic factors. When the cells are stimulated by lymphokines, however, they develop the ability both to migrate directionally and to secrete enzymes in response to several types of chemoattractants. The development, by stimulated cells, of chemotactic and secretory responses to one class of chemoattractants, the N- formylated peptides, is accompanied by the appearance on the cells of specific binding sites for these substances. Using tritiated N-formyl- methionyl-leueyl-phenylalanine (fMet-Leu-[(3)H]Phe) as a ligand, it was determined that unstimulated U937 cells possess no detectable binding sites. However, after stimulation with lymphocyte culture supernates for 24, 48, and 72 h, they developed 4,505 (+/-) 1,138, 22,150(+/-) 4,030, and 37,200 (+/-) 8,000 sites/cell, respectively. The dissociation constants for the interaction of fMet-Leu-[SH]Phe with the binding sites were approximately the same regardless of stimulation time and ranged between 15 and 30 nM. The binding of fMet-Leu-[(3)H]Phe by stimulated U937 cells was rapid and readily reversed by the addition of a large excess of unlabeled peptide. The affinity of a series of N-formylated peptides for binding to U937 cells exactly reflected the potency of the peptides in inducing lysosomal enzyme secretion and chemotaxis. The availability of a continuous human monocytic cell line that can be induced to express receptors for N-formylated peptides will provide a useful tool not only for the characterization of such receptors but also for the delineation of regulatory mechanisms involved in cellular differentiation and the chemotactic response. 相似文献
170.
In vitro low-level resistance to azoles in Candida albicans is associated with changes in membrane lipid fluidity and asymmetry 总被引:8,自引:0,他引:8
Kohli A Smriti Mukhopadhyay K Rattan A Prasad R 《Antimicrobial agents and chemotherapy》2002,46(4):1046-1052
The present study tracks the development of low-level azole resistance in in vitro fluconazole-adapted strains of Candida albicans, which were obtained by serially passaging a fluconazole-susceptible dose-dependent strain, YO1-16 (fluconazole MIC, 16 microg ml(-1)) in increasing concentrations of fluconazole, resulting in strains YO1-32 (fluconazole MIC, 32 microg ml(-1)) and YO1-64 (MIC, 64 microg ml(-1)). We show that acquired resistance to fluconazole in this series of isolates is not a random process but is a gradually evolved complex phenomenon that involves multiple changes, which included the overexpression of ABC transporter genes, e.g., CDR1 and CDR2, and the azole target enzyme, ERG11. The sequential rise in fluconazole MICs in these isolates was also accompanied by cross-resistance to other azoles and terbinafine. Interestingly, fluorescent polarization measurements performed by using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene revealed that there was a gradual increase in membrane fluidity of adapted strains. The increase in fluidity was reflected by observed change in membrane order, which was considerably decreased (decrease in fluorescence polarization values, P value) in the adapted strain (P value of 0.1 in YO1-64, compared to 0.19 in the YO1-16 strain). The phospholipid composition of the adapted strain was not significantly altered; however, ergosterol content was reduced in YO1-64 from that in the YO1-16 strain. The asymmetrical distribution of phosphatidylethanolamine (PE) between two monolayers of plasma membrane was also changed, with PE becoming more exposed to the outer monolayer in the YO1-64 strain. The results of the present study suggest for the first time that changes in the status of membrane lipid phase and asymmetry could contribute to azole resistance in C. albicans. 相似文献