共查询到20条相似文献,搜索用时 0 毫秒
1.
Increased leukocyte adherence to endothelium is recognized to be the first step following the development of unstable angina and cerebrovascular disease. In this paper, the methods to determine leukocyte adherence and the conditions which influence the result of the assay are discussed. We administered aspirin, TxA2 synthetase inhibitor or TxA2 receptor antagonist to healthy volunteers. Leukocyte adherence was inhibited following the administration of these antiplatelet agents. The effect on leukocytes may prevent thrombosis formation. Although the role of the leukocyte adherence in the pathogenesis of thrombosis has not been fully elucidated. Several forms of stimuli may cause expression of adhesive glycoproteins, which have a RGD sequence, on the surface of leukocyte and thus lead to thrombotic formation. 相似文献
2.
Franco Paradisi Chiara D'Onofrio Gabriella Pepe Alda Cifarelli Domenico Piccolo 《International Journal of Clinical & Laboratory Research》1979,9(1):47-60
Summary The uptake of foreign particles by mouse and human macrophages influenced by various metabolic inhibitors was examined in
order to obtain further informations about the energy-dependent mechanisms which are involved in the phagocytic process. The
inhibitors employed were iodoacetate, fluoroacetate, fluoride, malonate, sodium azide, 2-4-dinitrophenol, cycloheximide and
ouabain. These substances were rested on monolayer cultures and the phagocytosis assay was performed by using zymosan suspension
in the nutrient media. The quantitation of phagocytosis was obtained by the direct count of intracellular zymosan particles
(immersion microscopy, 100x) and the results were evaluated and compared by biometrical analysis. The effects of these inhibitors
on phagocytosis and their relation with the metabolic intracellular pathways are discussed. 相似文献
3.
Xuejun Jiang Michael Overholtzer Craig B. Thompson 《The Journal of clinical investigation》2015,125(1):47-54
Autophagy is a catabolic process mediated by incorporation of cellular material into cytosolic membrane vesicles for lysosomal degradation. It is crucial for maintaining cell viability and homeostasis in response to numerous stressful conditions. In this Review, the role of autophagy in both normal biology and disease is discussed. Emphasis is given to the interplay of autophagy with nutrient signaling through the ULK1 autophagy pre-initiation complex. Furthermore, related cellular processes utilizing components of the canonical autophagy pathway are discussed due to their potential roles in nutrient scavenging. Finally, the role of autophagy in cancer and its potential as a cancer therapeutic target are considered. 相似文献
4.
5.
L V Filev A N Tulupov E B Zhiburt I V Volchek A V Bershin 《Klinicheskaia meditsina》1989,67(2):105-108
Antiviral cellular resistance was studied in 32 patients with acute purulent-destructive pulmonary diseases and in 46 normal subjects by determination of monocytes and lymphocytes containing viral inclusions and the coefficient of their viral affection. Parameters of humoral activity and functional monocyte activity were also studied. It has been established that these diseases are attended by the affection of immunocompetent cells which leads to the suppression of their functional activity to reduce anti-infectious cellular defence. Development of an abscess and gangrene in the lung is being investigated taking into consideration not only changes in the quantity of the immunocompetent cells but also the dependence on the degree of their functional activity. 相似文献
6.
Immune cellular interactions during sepsis and septic injury 总被引:2,自引:0,他引:2
The cellular activity generated by PMNs and macrophages in association with diverse cytokines has a profound impact on all major functional responses of host cellular components during sepsis and septic injury. It is the modulation of these cellular interactions and their effect on the continuum between appropriate and inappropriate responses during inflammation that will dictate the outcome of humans with sepsis. 相似文献
7.
Chua AC Graham RM Trinder D Olynyk JK 《Critical reviews in clinical laboratory sciences》2007,44(5-6):413-459
While iron is an essential trace element required by nearly all living organisms, deficiencies or excesses can lead to pathological conditions such as iron deficiency anemia or hemochromatosis, respectively. A decade has passed since the discovery of the hemochromatosis gene, HFE, and our understanding of hereditary hemochromatosis (HH) and iron metabolism in health and a variety of diseases has progressed considerably. Although HFE-related hemochromatosis is the most widespread, other forms of HH have subsequently been identified. These forms are not attributed to mutations in the HFE gene but rather to mutations in genes involved in the transport, storage, and regulation of iron. This review is an overview of cellular iron metabolism and regulation, describing the function of key proteins involved in these processes, with particular emphasis on the liver's role in iron homeostasis, as it is the main target of iron deposition in pathological iron overload. Current knowledge on their roles in maintaining iron homeostasis and how their dysregulation leads to the pathogenesis of HH are discussed. 相似文献
8.
Nearly all stress stimuli (e.g., inflammatory cytokines, glucocorticoids, chemotherapeutics, etc.) induce sphingolipid synthesis, leading to the accumulation of ceramides and ceramide metabolites. While the role of these lipids in the regulation of cell growth and death has been studied extensively, recent studies suggest that a primary consequence of ceramide accumulation is an alteration in metabolism. In both cell-autonomous systems and complex organisms, ceramides modify intracellular signaling pathways to slow anabolism, ensuring that catabolism ensues. These ceramide actions have important implications for diseases associated with obesity, such as diabetes and cardiovascular disease. 相似文献
9.
Rodent-borne pathogenic hantaviruses cause two severe and often lethal zoonotic diseases: hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. Currently, no US FDA-approved therapeutics or vaccines are available for HFRS/HCPS. Infections with hantaviruses are not lytic, and it is currently not known exactly why infections in humans cause disease. A better understanding of how hantaviruses interfere with normal cell functions and activation of innate and adaptive immune responses might provide clues to future development of specific treatment and/or vaccines against hantavirus infection. In this article, the current knowledge regarding immune responses observed in patients, hantavirus interference with cellular proteins and signaling pathways, and possible approaches in the development of therapeutics are discussed. 相似文献
10.
11.
Z Darzynkiewicz 《Pharmacology & therapeutics》1983,21(2):143-188
12.
13.
Totah RA Allen KE Sheffels P Whittington D Kharasch ED 《The Journal of pharmacology and experimental therapeutics》2007,321(1):389-399
Methadone is administered as a racemate, although opioid activity resides in the R-enantiomer. Methadone disposition is stereoselective, with considerable unexplained variability in clearance and plasma R/S ratios. N-Demethylation of methadone in vitro is predominantly mediated by cytochrome P450 CYP3A4 and CYP2B6 and somewhat by CYP2C19. This investigation evaluated stereoselectivity, models, and kinetic parameters for methadone N-demethylation by recombinant CYP2B6, CYP3A4, and CYP2C19, and the potential for interactions between enantiomers during racemate metabolism. CYP2B6 metabolism was stereoselective. CYP2C19 was less active, and stereoselectivity was opposite that for CYP2B6. CYP3A4 was not stereoselective. With all three isoforms, enantiomer N-dealkylation rates in the racemate were lower than those of (R)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (R-methadone) or (S)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (S-methadone) alone, suggesting an enantiomeric interaction and mutual metabolic inhibition. For CYP2B6, the interaction between enantiomers was stereoselective, with S-methadone as a more potent inhibitor of R-methadone N-demethylation than R-of S-methadone. In contrast, enantiomer interactions were not stereoselective with CYP2C19 or CYP3A4. For all three cytochromes P450, methadone N-demethylation was best described by two-site enzyme models with competitive inhibition. There were minor model differences between cytochromes P450 to account for stereoselectivity of metabolism and enantiomeric interactions. Changes in plasma R/S methadone ratios observed after rifampin or troleandomycin pretreatment in humans in vivo were successfully predicted by CYP2B6- but not CYP3A4-catalyzed methadone N-demethylation. CYP2B6 is a predominant catalyst of stereoselective methadone metabolism in vitro. In vivo, CYP2B6 may be a major determinant of methadone metabolism and disposition, and CYP2B6 activity and stereoselective metabolic interactions may confer variability in methadone disposition. 相似文献
14.
15.
Yang H Kim SK Kim M Reche PA Morehead TJ Damon IK Welsh RM Reinherz EL 《The Journal of clinical investigation》2005,115(2):379-387
The EGF-like domain of smallpox growth factor (SPGF) targets human ErbB-1, inducing tyrosine phosphorylation of certain host cellular substrates via activation of the receptor's kinase domain and thereby facilitating viral replication. Given these findings, low molecular weight organic inhibitors of ErbB-1 kinases might function as antiviral agents against smallpox. Here we show that CI-1033 and related 4-anilinoquinazolines inhibit SPGF-induced human cellular DNA synthesis, protein tyrosine kinase activation, and c-Cbl association with ErbB-1 and resultant internalization. Infection of monkey kidney BSC-40 and VERO-E6 cells in vitro by variola strain Solaimen is blocked by CI-1033, primarily at the level of secondary viral spreading. In an in vivo lethal vaccinia virus pneumonia model, CI-1033 alone promotes survival of animals, augments systemic T cell immunity and, in conjunction with a single dose of anti-L1R intracellular mature virus particle-specific mAb, fosters virtually complete viral clearance of the lungs of infected mice by the eighth day after infection. Collectively, these findings show that chemical inhibitors of host-signaling pathways exploited by viral pathogens may represent potent antiviral therapies. 相似文献
16.
Rower JE Meditz A Gardner EM Lichtenstein K Predhomme J Bushman LR Klein B Zheng JH Mawhinney S Anderson PL 《Antimicrobial agents and chemotherapy》2012,56(6):3011-3019
The cellular pharmacology of zidovudine (ZDV) and lamivudine (3TC) in vivo is not completely understood. This prospective longitudinal study investigated the relationship between HIV-1 serostatus, sex, race, and time on therapy with intracellular and plasma ZDV and 3TC concentrations. Of 20 HIV-seronegative and 23 HIV-seropositive volunteers enrolled, 16 (8 women) and 21 (5 women) completed all 12 study days, respectively. Volunteers began ZDV-3TC therapy (plus a third active drug in HIV-seropositive volunteers), and steady-state concentrations (C(ss)) were determined after days 1, 3, 7, and 12. A repeated-measures mixed model was utilized. HIV-seronegative status was associated with 22% (95% confidence interval [CI], 0%, 50%) and 37% (15%, 67%) higher C(ss) estimates compared to those of HIV-seropositive individuals for intracellular ZDV-TP and 3TC-TP levels, respectively. African-Americans had 36% (8%, 72%) higher ZDV-TP estimates than non-African-Americans. Sex was not associated with ZDV-TP or 3TC-TP (P > 0.19). Women had 36% (4%, 78%) higher plasma ZDV, but the effect was lessened when normalized by lean body weight (5% [-19%, 38%]; P = 0.68). Plasma 3TC was 19% (0%, 41%) higher in HIV-seropositive volunteers and 22% (0%, 48%) higher in African American volunteers, but these effects were not significant when corrected for creatinine clearance (7% [-9%, 20%] and -5% [-26%, 12%] for HIV serostatus and race, respectively; P > 0.35). These results suggest that HIV-seropositive status decreases and African American race elevates the cellular triphosphates of ZDV and 3TC. This information extends knowledge of ZDV and 3TC cellular pharmacology in vivo and provides new leads for future cellular pharmacology studies aimed at optimizing HIV prevention/treatment with these agents. 相似文献
17.
乙型肝炎病毒基因型与耐药病毒株的相关性研究 总被引:1,自引:1,他引:0
目的研究乙型肝炎病毒(HBV)基因型与耐药病毒株产生的相关性。方法征集340例接受拉米夫定治疗1年以上的慢性乙型肝炎(CHB)患者为研究对象。采集血样经离心分离血浆,进行HBV DNA定量检测,再进行基因测序和基因分型。结果基因测序和基因型分析结果为:A型16例(4.7%),B型112例(32.9%),C型148例(43.5%),D型44例(12.9%),B/C混合型20例(5.9%)。其中发生YMDD耐药突变的基因型分别是:A型4例(25.0%),B型20例(18.5%),C型64例(42.1%),D型8例(18.2%),B/C混合型4例(20.0%)。结论 HBV基因型C发生YMDD耐药突变的频率较高,HBV基因型与YMDD突变可能存在相关性。 相似文献
18.
C N Serhan T Takano K Gronert N Chiang C B Clish 《Clinical chemistry and laboratory medicine》1999,37(3):299-309
Eicosanoids are known to play important roles in inflammation. Recent findings have given rise to several new concepts regulating the generation of eicosanoids, illustrated in Figure 1. Lipoxins (LX) are trihydroxytetraene-containing eicosanoids that are generated within vascular lumen by platelet-leukocyte interactions and at mucosal surfaces by leukocyte-epithelial cell interactions. During these cell-cell interactions, transcellular biosynthetic pathways are used as major routes, and thus, in humans, LX are formed in vivo during multicellular responses such as inflammation, atherosclerosis, and thrombosis. This branch of the eicosanoid cascade generates specific tetraene-containing products that appear to function as stop signals, since they inhibit key steps in leukocyte-mediated inflammation. Of special interest, it appears that aspirin also functions in part via production of novel epimers of lipoxins or 15-epi-lipoxins (Figure 1). Here, we review recent developments on the cellular interactions of these novel anti-inflammatory mediators. 相似文献
19.
20.
Hot Bun Béatrice Disdier Claude Aubert and Jacques Catalin 《Fundamental & clinical pharmacology》1999,13(5):577-581
Cytochrome P450 expression in liver is influenced by several factors, including species, sex and strain. We compared metabolism formation of clozapine in different species (rat, mouse, guinea-pig, dog, monkey and man) so as to choose between species to further validate interaction studies. Liver microsomes of male and female Sprague-Dawley rats, hairless rats, OF1 mice, Balb C mice and Dunkin-Hartley albino guinea-pigs, male beagle dogs, male cynomolgus monkeys and man were used to investigate in vitro metabolism of clozapine. This process was dependent on the presence of NADPH and on the presence of microsome protein. In addition, we observed the formation of desmethyl- and N-oxide metabolites, with the rate of formation of each of these compounds varying with species, sex and strain of microsomes incubated. The desmethyl- and N-oxide metabolites formed were statistically greater in male than in female rats, mice in the two strains studied, as well as for the guinea-pigs. Levels of desmethyl clozapine formed were high for the rats and no significant difference in clozapine biotransformation was observed between Sprague-Dawley and hairless rats. For man, the formation of metabolites of clozapine was comparable with guinea-pig, dog and monkey. In addition, we screened the effect of 52 molecules, representative of 11 different therapeutic classes, on the metabolism of clozapine by rat liver microsomes. We found that most of the calcium channel blockers (diltiazem, felodipine, isradipine, lacidipine, nicardipine and nitrendipine), antifungals (ketoconazole, miconazole) and two anticancer drugs (paclitaxel, teniposide) caused more than 50% inhibition of clozapine metabolism in vitro. The extent of inhibition was increased in a concentration-dependant manner. Complementary clinical and pharmacokinetic studies should be performed to confirm these results. 相似文献