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1.
The presence of 3 different neuropeptide mRNAs with a strict cell-specific expression in vivo was investigated in 13 tumor cell lines from neuroendocrine and in 23 tumor cell lines from non-neuroendocrine origin. Northern blots showed no expression of mRNA for vasopressin (VP) in the 36 tested cell lines. Very low oxytocin (OT) mRNA hybridization signals were detected in the rat pituitary tumor cell line GH4C2 and the rat pancreas tumor cell line RIN5. Both the rat pituitary tumor cell line AtT-20 and the human myeloid leukemia cell line K562, contained proopiomelanocortin (POMC) mRNA. The low incidence of VP, OT and POMC gene expression in the tested tumor cell lines was not influenced by treatments inducing differentiation. In contrast, the cholecystokinin (CCK) gene which is widely present in nervous and endocrine systems was abundantly expressed in the human primitive neuroepithelioma cell line SK-N-MC and its clonal derivative SK-N-MC-IX-C. The results indicate that the expression of neuropeptide genes is very rare in tumor cell lines. The lack of expression in undifferentiated cells agrees with the appearance of expression after day 13 of the embryogenesis when maturation of neurons begins. 相似文献
2.
Lars Bendtsen Rigmor Jensen Jannick Brennum Lars Arendt-Nielsen Jes Olesen 《Cephalalgia : an international journal of headache》1993,13(3):184-191
The duration of the late exteroceptive suppression period (ES2 ) of temporal muscle EMG activity has been reported to be reduced in patients suffering from chronic tension-type headache. Methods of recording and analysing ES2 have varied between centers and reproducibility of results within subjects , although insufficiently studied, has generally been poor. ES2 was investigated in 30 healthy subjects, using a computerized technique of recording, rectifying and averaging the EMG signals. Hour to hour and week to week variations of ES2 durations were calculated, and the influence of pain during a cold pressor test and of sustained muscle contraction on ES2 durations was investigated. The intra-individual variation of ES2 durations was 16.0% from hour to hour and 20.7% from week to week. The inter-individual variation was 36.7%. The present method for analysis of ES2 periods proved to be reliable, as the intra-observer variation was 4.2% and the inter-observer variation 4.6%. ES2 periods were significantly shorter on the first compared to the second day of examination ( p = 0.006) and during experimental pain ( p = 0.0005). We recommend the use of the computerized averaging technique in future studies and caution against the dependence of results upon factors such as conditioning and pain. 相似文献
3.
J. I. Macdonald S. M. Wallace V. Mahachai R. K. Verbeeck 《European journal of clinical pharmacology》1992,42(5):471-474
Summary The pharmacokinetics of diflunisal, a salicylate derivative that undergoes phenolic and acyl glucuronidation as well as sulphate conjugation, has been studied after a single oral dose (250 mg) in patients with cirrhosis (n=5) and in healthy controls (n=5).The plasma clearance of total (bound + unbound) diflunisal was 10.2 ml · min–1 in the control subjects and it was not affected by cirrhosis (10.9 ml · min–1). The plasma protein binding of diflunisal was significantly reduced in cirrhosis; the percentage of unbound diflunisal in plasma was 0.089 in the controls and 0.147 in the patients with cirrhosis. Plasma clearance of unbound diflunisal was significantly impaired in cirrhosis: 11.51 · min–1 in control subjects vs 7.41 · min–1 in cirrhotics.In cirrhotic patients, the unbound partial clearances to the phenolic and acyl glucuronides were both significantly reduced, by approximately 38%. The unbound partial clearance to the sulphate conjugate was not significantly affected by cirrhosis.The results show that both the phenolic and acyl glucuronidation pathways of diflunisal are equally susceptible to the effects of liver cirrhosis. 相似文献
4.
5.
A transient epoxide in equilibrium with its possible isomeric forms, most probably induced easily by neighboring-group assistance of a hydroxy group, and a dihydrodiol formed under the influence of the hydrase enzymic activity and/or by simple hydrolysis were isolated by HPLC and identified by FAB/MS from rat liver microsomal incubation media. 相似文献
6.
Nassim Kamar Karine Sandres-Saune David Ribes Michel Duffaut Jannick Selves Dominique Durand Jacques Izopet Lionel Rostaing 《Journal of clinical virology》2004,31(4):298-303
BACKGROUND: Following renal transplantation (RT), chronic immunosuppression is associated in hepatitis B virus (HBV) (+) patients with a flare-up of the disease, which might be harmful in the long term. OBJECTIVES: We report on the effect of long-term lamivudine therapy given at an initial daily dose of 100mg in 18 HBV (+) RT patients. RESULTS: When lamivudine therapy was commenced, 14 patients (77%) had an increase in their aspartate (AST) and alanine (ALT) aminotransferase levels. During a mean follow-up, under treatment, of 36.5 +/- 3.5 months (up to 66 months), 10 patients (55%) had a sustained partial (HBV DNA < 4 x 10(5)copies/ml) (n = 4) or complete (HBV DNA < 400 copies/ml) (n = 6) virological response. Overall, 12 virological breakthroughs were observed. Of those who were HBe Ag(+) prior to lamivudine therapy (n = 4), one seroconverted to HBe Ab during therapy. At the last follow-up, AST and ALT levels were normal in 13 patients. When liver biopsy was repeated during treatment (n = 15), the virological responders showed a significant decrease in total Knodell score from 10 +/- 0.6 to 7 +/- 1 (P = 0.04), but no significant change in the stage of fibrosis. Conversely, in those patients with high HBV DNA titers, there were no significant changes in the total Knodell score or in the grade of fibrosis. CONCLUSION: In conclusion, lamivudine therapy is safe in HBV(+)ve renal-transplant patients. However, even if the full and partial virological response rates are still high (55%) in the long term, relapse or primary non-responses occur. The implementation of alternative efficient strategies is warranted. 相似文献
7.
R. K. Verbeeck J. I. Macdonald S. M. Wallace R. J. Herman 《European journal of clinical pharmacology》1995,47(6):519-523
The effect of probenecid on the pharmacokinetics of diflunisal and its glucuronide and sulphate conjugates was studied in 8 healthy volunteers. Diflunisal 250 mg b. d. was administered p. o. for 15 days and its steady state pharmacokinetics was evaluated on Day 16 after the last dose (control phase). Probenecid 500 mg b. d. was co-administered throughout the entire study period in the treatment phase of the study.The steady state plasma concentration of diflunisal was significantly higher during the probenecid treatment phase as compared to the control phase (104.0 vs. 63.1 g·ml–1). This was the result of a significant decrease in the plasma clearance of diflunisal from 5.8 (control) to 3.4 ml·min–1 (probenecid co-administration). The metabolite formation clearances of both glucuronides were significantly decreased by probenecid, -45 % and -54 % for the phenolic and acyl glucuronide, respectively. The metabolite formation clearance of the sulphate conjugate was not affected by probenecid co-administration.Steady state plasma concentrations of the sulphate and glucuronide conjugates of diflunisal were 2.5- to 3.1-fold higher during probenecid co-administration, due to a significant reduction in the renal clearance of the three diflunisal conjugates. Probenecid also reduced the plasma protein binding of diflunisal, but only to a minor extent; the unbound plasma fraction of diflunisal at steady state averaged between 5 and 30 % higher during probenecid co-administration. 相似文献
8.
BACKGROUND: Sevoflurane is metabolized by cytochrome P450 and produces inorganic fluoride. The anhepatic phase of liver transplantation provides a useful tool to study the extrahepatic metabolism of drugs. The authors therefore studied the extrahepatic metabolism of sevoflurane by measuring the fluoride production in children receiving sevoflurane solely during the anhepatic phase of orthotopic liver transplantation. METHODS: Children with end-stage liver disease undergoing orthotopic liver transplantation were studied. Anesthesia was provided with isoflurane, sufentanil, and pancuronium. In one group, isoflurane was replaced by sevoflurane as soon as the liver was removed from the patient and maintained until reperfusion of the new liver. Arterial blood samples were drawn at induction, before removal of the liver, 15 min and 30 min after the beginning of the anhepatic phase, at the unclamping of the new liver, and finally 60 and 120 min after the unclamping. Plasma fluoride concentrations were determined by ion-selective electrode. RESULTS: No differences between the two groups (n = 10) regarding age, weight, duration of the anhepatic phase, or basal level of inorganic fluoride were found. The fluoride concentration increased significantly as soon as sevoflurane was introduced; it remained stable in the group receiving isoflurane. The peak fluoride concentration was also significantly higher in the first group (mean +/- SD: 5.5 +/- 0.8 microM (sevoflurane group) versus 1.4 +/- 0.5 microM (isoflurane group) P < 0.05). CONCLUSIONS: These results demonstrate the existence of an extrahepatic metabolism of sevoflurane at least in children with end-stage liver disease. 相似文献
9.
10.
Giang E Dorner M Prentoe JC Dreux M Evans MJ Bukh J Rice CM Ploss A Burton DR Law M 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(16):6205-6210
Hepatitis C virus (HCV) infects ~2% of the world's population. It is estimated that there are more than 500,000 new infections annually in Egypt, the country with the highest HCV prevalence. An effective vaccine would help control this expanding global health burden. HCV is highly variable, and an effective vaccine should target conserved T- and B-cell epitopes of the virus. Conserved B-cell epitopes overlapping the CD81 receptor-binding site (CD81bs) on the E2 viral envelope glycoprotein have been reported previously and provide promising vaccine targets. In this study, we isolated 73 human mAbs recognizing five distinct antigenic regions on the virus envelope glycoprotein complex E1E2 from an HCV-immune phage-display antibody library by using an exhaustive-panning strategy. Many of these mAbs were broadly neutralizing. In particular, the mAb AR4A, recognizing a discontinuous epitope outside the CD81bs on the E1E2 complex, has an exceptionally broad neutralizing activity toward diverse HCV genotypes and protects against heterologous HCV challenge in a small animal model. The mAb panel will be useful for the design and development of vaccine candidates to elicit broadly neutralizing antibodies to HCV. 相似文献