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121.
An electrophysiological investigation of the properties of a murine recombinant 5-HT3 receptor stably expressed in HEK 293 cells. 总被引:2,自引:2,他引:0 下载免费PDF全文
1. The pharmacological and biophysical properties of a recombinant 5-HT3 receptor have been studied by use of patch-clamp techniques applied to HEK 293 cells stably transfected with the murine 5-HT3 R-A cDNA. 2. At a holding potential of -60 mV, 77% of cells investigated responded to ionophoretically applied 5-HT with an inward current. Such currents were unaffected by methysergide (1 microM), or ketanserin (1 microM), but were antagonized in a concentration-dependent and reversible manner by the selective 5-HT3 receptor antagonist, ondansetron (IC50 = 440 pM) and the non-selective antagonists (+)-tubocurarine (IC50 = 1.8 nM) and metoclopramide (IC50 50 nM). 3. The 5-HT-induced current reversed in sign (E5-HT) at approximately -2mV and exhibited inward rectification. The influence of extra- and intracellular ion substitutions upon E5-HT indicates the 5-HT-evoked current to be mainly mediated by a mixed monovalent cation conductance. 4. Calcium and magnesium (0.1-10 nM) produced a concentration-dependent, voltage-independent, inhibition of the 5-HT-induced response. Zinc (0.3-300 microM) exerted a biphasic effect with low concentrations enhancing, and high concentrations depressing, the 5-HT-evoked current. 5. Fluctuation analysis of inward currents evoked by a low (1 microM) concentration of 5-HT suggests the current to be mediated by the opening of channels with a conductance of 420 fS. 6. The pharmacological and biophysical properties of the 5-HT3 R-A are similar to those previously described for 5-HT3 receptors native to murine neuroblastoma cell lines, with the exception that the function of the recombinant receptor was enhanced by low concentrations of zinc. This observation suggests that the properties of the native receptor are not completely represented by the 5-HT3 R-A subunit alone. 相似文献
122.
Azithromycin. A review of its antimicrobial activity, pharmacokinetic properties and clinical efficacy. 总被引:18,自引:0,他引:18
Azithromycin is an acid stable orally administered macrolide antimicrobial drug, structurally related to erythromycin, with a similar spectrum of antimicrobial activity. Azithromycin is marginally less active than erythromycin in vitro against Gram-positive organisms, although this is of doubtful clinical significance as susceptibility concentrations fall within the range of achievable tissue azithromycin concentrations. In contrast, azithromycin appears to be more active than erythromycin against many Gram-negative pathogens and several other pathogens, notably Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Urea-plasma urealyticum and Borrelia burgdorferi. Like erythromycin and other macrolides, the activity of azithromycin is unaffected by the production of beta-lactamase. However, erythromycin-resistant organisms are also resistant to azithromycin. Following oral administration, serum concentrations of azithromycin are lower than those of erythromycin, but this reflects the rapid and extensive movement of the drug from the circulation into intracellular compartments resulting in tissue concentrations exceeding those commonly seen with erythromycin. Azithromycin is subsequently slowly released, reflecting its long terminal phase elimination half-life relative to that of erythromycin. These factors allow for a single dose or single daily dose regimen in most infections, with the potential for increased compliance among outpatients where a more frequent antimicrobial regimen might traditionally be indicated. The potential disadvantage of low azithromycin serum concentrations, however, is that breakthrough bacteraemia may occur in patients who are severely ill; nevertheless, animal studies suggest that tissue concentrations of azithromycin are more important than those in serum when treating respiratory and other infections. The clinical efficacy of azithromycin has been confirmed in the treatment of infections of the lower and upper respiratory tracts (the latter including paediatric patients), skin and soft tissues (again including paediatric patients), in uncomplicated urethritis/cervicitis associated with N. gonorrhoeae, Chlamydia trachomatis or U. urealyticum and in the treatment of early Lyme disease. Azithromycin was as effective as erythromycin and other commonly used drugs including clarithromycin, beta-lactams (penicillins and cephalosporins), and quinolone and tetracycline antibiotics in some of the above infections. Some patients with acute exacerbations of chronic bronchitis due to H. influenzae may be refractory to therapy with azithromycin (as is the case with erythromycin) indicating the need for physician vigilance, although it should be noted that azithromycin is of equivalent efficacy to amoxicillin in the treatment of such patients. In the therapy of urethritis/cervicitis associated with C. trachomatis, N. gonorrhoea or U. urealyticum, a single dose azithromycin regimen offers a distinct advantage over currently available pharmacological options, while providing effective therapy.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
123.
Foreign-body granulomas in the hand can appear secondary to an unrecognized foreign material. In a six-year-old boy, an extensive sterile osteitis of the second metacarpal bone appeared adjacent to a wood splinter. 相似文献
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126.
Michelle Lucinda DeOliveira M.D. Tarcisio Triviño M.D. Ph.D. Gaspar de Jesus Lopes Filho M.D. Ph.D. 《Journal of gastrointestinal surgery》2006,10(8):1140-1143
Carcinoma of the papilla of Vater is classified as periampullary cancer representing 5% of all gastrointestinal tract malignancies.
Early and accurate diagnosis is important for those patients with a tumor of the papilla, as the prognosis is more favorable
than in other periampullary neoplasms. Endoscopically obtained biopsies from suspicious papillae can detect an early tumor,
although even for skilled pathologists it is often difficult to differentiate carcinomas from noninvasive lesions on the basis
of forceps biopsies. The purpose of this study was to assess the preoperative diagnostic accuracy of duodenoscopy appearance
and biopsy in all cases with suspicion of tumor. Thirty patients with suspicion of carcinoma of the papilla of Vater and with
final diagnosis established by pancreatoduodenectomy were included in this retrospective study. In each case, a comparison
was made between endoscopic biopsy and duodenoscopic appearance. Duodenoscopic appearance sensitivity and accuracy for malignancy
were 86% and 83%, respectively, whereas endoscopic biopsy sensitivity and accuracy were 65% and 67%, respectively. Although
preoperative diagnosis of carcinoma of the papilla of Vater is useful for making therapeutic decisions, the diagnostic value
of the endoscopic appearance was superior to endoscopic biopsy in this series.
Presented at the 2003 American Hepato-Pancreato-Biliary Association Congress, Miami, Florida, February 27-March 3, 2003.
Supported by FADA-CAPES/PROP 200J (M.L.D.). 相似文献
127.
Femke M van de Water Johanna M Boleij Janny G P Peters Frans G M Russel Rosalinde Masereeuw 《European journal of pharmaceutical sciences》2007,30(1):36-44
The activity of P-glycoprotein (Pgp/MDR1/ABCB1) and multidrug resistance proteins (MRP/ABCC) influence the pharmacokinetics and bioavailability of many drugs. Few suitable cell lines for the study of drug transport exist. Additional non-human cell lines may help clarify species differences and contribute to the current knowledge of drug transport. The aim of the present study was to characterize three rat epithelial cell lines for transporter expression and activity. Transporter expression was assessed in intestinal IEC-6 and renal GERP and NRK-52E cells using RT-PCR and Western blot analysis. Pgp and Mrp transport activity were analyzed by measuring calcein accumulation and glutathione-S-bimane efflux, respectively. The three cell lines showed Pgp expression and Pgp-dependent transport, both decreasing with culture time after reaching confluency. Besides Pgp, cells expressed Mrp1, Mrp3, Mrp4, and Mrp5, while Mrp2 and Mrp6 were absent. In addition, they showed temperature- and Mrp-dependent efflux of glutathione-S-bimane. Exposure to a panel of different inhibitors showed that this efflux was probably mediated by Mrp4. In conclusion, the three rat epithelial cell lines investigated showed Pgp and Mrp expression and transport. Mrp dependent transport was most likely mediated by Mrp4. In future, these cell lines may be used as in vitro models to study drug transport. 相似文献
128.
129.
K H Calhoun B R Peters C M Stiernberg F B Quinn 《Otolaryngology--head and neck surgery》1988,99(1):76-78
We report a metallic foreign body that entered through the anterior table of the frontal sinus, and rolled down to lodge in the nasofrontal duct. An electromagnet was used to remove the foreign body through a trephination. 相似文献
130.
The radiographic and histological morphology of 38 tumors lesions of the scapula are analyzed. Osteochondromas (n = 12), chondrosarcomas (n = 7), plasmacytomas (n = 4) and Ewing's sarcomas (n = 3) were the most frequent neoplasms. The radiographically determined growth rates allowed an estimate of the dignity in all cases. Benign lesions were only observed in the first five decades of life, and were mostly located in the scapular blade. Most tumors found in the acromion and in the glenoid region and all lesions diagnosed in the 6th to the 8th decades of life were malignant. In 63.2% of cases correct diagnosis of the type of lesion present was possible on radiographic examination. 相似文献