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21.
选择性环氧化酶—2抑制剂的研究现状及应用评价 总被引:3,自引:1,他引:2
选择性环氧化酶(COX)-2抑制剂可有效地治疗炎症,同时避免或减轻由于抑制COX-1而导致的毒副作用。有乐观的临床应用前景,但其不良反应亦不容忽视,寻找临床评价好的选择性COX-2抑制剂是当前非甾体类抗类药物研究的重点。 相似文献
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One of the consequences of increased intracellular calcium in response to a variety of physiological stimuli is the calcium activation of cytosolic proteases. Unlike lysosomal proteases with broad specificity, these calcium-activated neutral proteases show limited proteolysis of a restricted set of substrate proteins suggesting they may play a regulatory role in cellular physiology. In this study we show that the neural cell adhesion molecules NCAM-180 and N-cadherin are substrates for such endogenous calcium-activated neutral proteases. In contrast, a third neural cell adhesion molecule G4/L1 was not susceptible to calcium-activated proteolysis. The threshold for activation of NCAM and N-cadherin proteolysis is in the micromolar range of calcium suggesting that NCAM and N-cadherin are substrates for a mu-type calpain (calpain I). The site recognized by this protease is within intracellular domains of NCAM-180 and N-cadherin which are important for their interaction with cytoskeletal components. These results suggest that calcium-activated proteolysis at these sites in vivo could disrupt the linkage between extracellular ligand binding to these adhesion molecules and the normal intracellular effectors of such extracellular binding events. 相似文献
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The effects of intracellular Ca2+ (Ca2+i) on K+ currents in hippocampal cells were examined using acutely isolated cells obtained from adult guinea pigs. Whole-cell voltage-clamp recordings were carried out in a configuration that allowed a continuous perfusion of the intracellular medium. Recording media were made to block inward currents and allowed selective activation of K(+)-dependent outward currents. Voltage-dependent outward currents consisted of an initial rapidly decaying component followed by a sustained component. The time constant of decay of the transient current was about 25 msec, and previous studies (Numann et al., 1987) showed that the kinetic and pharmacological properties of this current closely resembled the A current recorded in invertebrate neurons (Connor and Stevens, 1971; Thompson, 1982). Intracellular perfusion of hippocampal cells with a solution containing elevated Ca2+ (about 4.5 x 10(-4) M) elicited outward currents at the holding potential (-45 to -55 mV) and produced changes in voltage-dependent K+ currents. The transient outward current (IA) activated by depolarization was suppressed with increases in Ca2+i. Delayed, sustained K+ currents were greatly potentiated. Data also showed that, among the 3 effects elicited by Ca2+i, suppression of IA was most sensitive to Ca2+i elevation. Previous results (Numann et al., 1987) showed that IA had a lower threshold (about -45 mV) than sustained currents (about -40 mV). By using low levels of depolarization (-40 mV), IA can be selectively activated, and the suppressive effect of Ca2+i on IA was confirmed on the kinetically isolated IA.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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The effect of the traditional Chinese medicinal herbs enema and enteric-coated capsules in the treatment of ulcerative colitis (UC) were compared in 260 cases. The immune complexes and the dynamic change of autoantibodies were monitored in 28 out of the 260 cases before and after treatment. The following results were observed. (1) There was no significant difference in the total effective rate between the enema group and the oral capsule group (93.3% and 87.5% respectively), but the recovery rates of purulent hemafecia, mucusfecia and erosion accompanying colitis, etc. in the former group were higher than those in the latter (P less than 0.01). (2) The circulating immune complexes were found 43 times above the normal range in 17 cases with positive rate 60.7%, and tended to decrease as the condition became better after treatment. Antinuclear antibodies were determined by the indirect fluorescent immune method and the indirect enzyme labelling method and the positive rates were 53.6% and 64.7% respectively, both being much higher than those in the controls (P less than 0.01). 相似文献
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OBJECTIVES: To explore the morphological and functional findings of transvaginal sonography (TVS) in the diagnosis and management of distal ureteral calculi. METHODS: We retrospectively reviewed the imaging studies in seven cases of distal ureteral calculi (study group) and 20 cases of female volunteers without urinary tract infection (control group). All 27 patients had undergone TVS for assessment of the lower urinary tract. The variables measured on ultrasound included the presence or absence of distal ureteral calculi, the size and location of a calculus if present, the presence or absence of the ureter jet phenomenon, morphological changes of the ureteral papilla and adjoining tissue, and the height of the ureteral papilla, as well as vascular changes seen on Doppler imaging. RESULTS: In the controls, 80% of the ureteral papillae were triangular and 20% trapezoidal. The average (+/-SD) height of the ureteral papillae was 3.5 +/- 0.7 mm on the right and 3.6 +/- 0.9 mm on the left. There was no statistically significant difference between the heights of the right and left papillae (P = 0.619). In the study group, echogenic stones were identified in all seven patients and a hypoechogenic tubular structure connected to the involved papilla was identified in 6/7 patients. The average height of the involved papilla was 6.7 +/- 1.6 mm. Ureteric jets were visible in all patients in both the study and control groups. CONCLUSION: In patients with distal ureteral calculi, TVS provides a rapid, non-invasive and repeatable means of assessing the morphology and function of the distal ureter. 相似文献
29.
Wen-Ni Chang Jen-Ning Tsai Bing-Hung Chen Huei-Sheng Huang Tzu-Fun Fu 《Drug metabolism and disposition》2007,35(11):2127-2137
Serine hydroxymethyltransferase (SHMT) provides activated one-carbon units required for the biosynthesis of nucleotides, protein, and methyl group by converting serine and tetrahydrofolate to glycine and N(5),N(10)-methylenetetrahydrofolate. It is postulated that SHMT activity is associated with the development of methotrexate resistance and the in vivo activity of SHMT is regulated by the binding of N(5)-CHO-THF, the rescue agent in high-dose methotrexate chemotherapy. The aim of this study is to advance our understanding of the folate-mediated one-carbon metabolism in zebrafish by characterizing zebrafish mitochondrial SHMT. The cDNA encoding zebrafish mitochondrial SHMT was cloned, overexpressed in Escherichia coli, and purified with a three-step purification protocol. Similarities in structural, physical, and kinetic properties were revealed between the recombinant zebrafish mitochondrial SHMT and its mammalian orthologs. Surprisingly, leucovorin significantly inhibits the aldol cleavage of serine catalyzed by zebrafish cytosolic SHMT but inhibits to a lesser extent the reaction catalyzed by the mitochondrial isozyme. This is, to our knowledge, the first report on zebrafish mitochondrial folate enzyme as well as the differential inhibition of leucovorin on these two SHMT isoforms. Western blot analysis revealed tissue-specific distribution with the highest enrichment present in liver for both cytosolic and mitochondrial SHMTs. Intracellular localization was confirmed by confocal microscopy for both mitochondrial and cytosolic SHMTs. Unexpectedly, the cytosolic isoform was observed in both nucleus and cytosol. Together with the previous report on zebrafish cytosolic SHMT, we suggest that zSHMTs can be used in in vitro assays for folate-related investigation and antifolate drug discovery. 相似文献
30.
Yulu Miao Mingxia Zhang Yulin Nie Wan Zhao Bin Huang Zhengming Jiang Shaoxiong Yu Zhibin Huang Hongjin Fu 《中国神经再生研究》2007,2(2):126-128
BACKGROUND: Besides local changes of cranial parenchymal cells, hemorrhage, etc., severe traumatic brain injuries also cause the changes of total body fluid and various functions, and the changes of lymphocytes and T lymphocyte subsets should be paid more attention to. OBJECTIVE: To reveal the changing laws of T lymphocyte subsets after severe traumatic brain injury, and compare with mild to moderate brain injury. DESIGN: A comparative observation. SETTINGS: Department of Neurosurgery, Longgang District Buji People's Hospital of Shenzhen City; Central Laboratory of Shenzhen Hospital of Prevention and Cure for Chronic Disease. PARTICIPANTS: All the subjects were selected from the Department of Neurosurgery, Longgang District Buji People's Hospital of Shenzhen City from August 2002 to August 2005. Thirty patients with severe brain injury, whose Glasgow coma score (GCS) was ≤ 8 points, were taken as the experimental group, including 21 males and 9 females, aging 16 - 62 years. Meanwhile, 30 patients with mild traumatic brain injury were taken as the control group (GCS ranged 14- 15 points), including 18 males and 12 females, aging 15 -58 years. All the subjects were in admission at 6 hours after injury, without disease of major organs before injury Informed consents were obtained from all the patients or their relatives. METHODS: (1) The T lymphocytes and the subsets in peripheral blood were detected with immunofluorescent tricolor flow cytometry at l, 3, 7 and 14 days after injury in both groups. (2) The conditions of pulmonary infections were observed at 4 days after injury. The differences of measurement data were compared with the t test. MAIN OUTCOME MEASURES: Changes of T lymphocytes subsets at 1 - 14 days after severe and mild or moderate traumatic injury. RESULTS: Finally, 28 and 25 patients with mild to moderate traumatic brain injury, whereas 25 and 21 patients with severe traumatic brain injury were analyzed at 7 and 14 days respectively, and the missed ones died due to the development of disease. (1) Changes of T lymphocyte subsets: At 1 and 3 days after injury, CD3, CD4, CD8, CD4/CD8 began to decrease, whereas CD8 increased in the experimental group, which were very significantly different from those in the control group (t =2.77 - 3.26, P 〈 0.01), and began to recover at 7 days, which were significantly different from those in the control group (t = 2.06 - 2.24, P 〈 0.05), and generally recovered to the normal levels at 14 days (P 〉 0.05). (2) Conditions of pulmonary infections: At 4 days after injury, the rate of pulmonary infection was significantly different between the experimental group and control group [73% (22/30), 0, x2=37.29, P 〈 0.01]. CONCLUSION: Patients with severe traumatic brain injury suffer from damages of cellular immune function at early period (within 7 days), and they are easily to be accompanied by pulmonary infections. 相似文献