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排序方式: 共有101条查询结果,搜索用时 15 毫秒
1.
Frank Lindseth Thomas Lang? Jon Bang Toril A Nagelhus Hernes 《Computer aided surgery》2002,7(4):197-222
2.
Pia Lautala Maija Kivimaa Hannele Salomies Eivor Elovaara Jyrki Taskinen 《Pharmaceutical research》1997,14(10):1444-1448
Purpose. Nitrocatechol COMT inhibitors are a new class of bioactive compounds, for which glucuronidation is the most important metabolic pathway. The objective was to characterize the enzyme kinetics of nitrocatechol glucuronidation to improve the understanding and predicting of the pharmacokinetic behavior of this class of compounds.
Methods. The glucuronidation kinetics of seven nitrocatechols and 4-nitrophenol, the reference substrate for phenol UDP-glucuronosyltrans-ferase activity, was measured in liver microsomes from creosote-treated rats and determined by non-linear fitting of the experimental data to the Michaelis-Menten equation. A new method that combined densitometric and radioactivity measurement of the glucuronides separated by HPTLC was developed for the quantification.
Results. Apparent Km values for the nitrocatechols varied greatly depending on substitution pattern being comparable with 4-nitrophenol (0.11 mM) only in the case of 4-nitrocatechol (0.19 mM). Simple nitrocatechols showed two-fold Vmax values compared with 4-nitrophenol (68.6 nmol min–1 mg–1), while all disubstituted catechols exhibited much lower glucuronidation rate. Vmax/Km values were about 10 times higher for monosubstituted catechols compared to disubstituted ones. The kinetic parameters for COMT inhibitors were in the following order: Km nitecapone >> entacapone > tolcapone; Vmax nitecapone > entacapone > tolcapone; Vmax/Km tolcapone > nitecapone > entacapone.
Conclusions. Nitrocatechols can in principle be good substrates of UGTs. However, substituents may have a remarkable effect on the enzyme kinetic parameters. The different behaviour of nitecapone compared to the other COMT inhibitors may be due to its hydrophilic 5-substituent. The longer elimination half-life of tolcapone in vivo compared to entacapone could not be explained by glucuronidation kinetics in vitro. 相似文献
3.
Riitta Mustonen Eivor Elovaara Antti Zitting Kaija Linnainmaa Harri Vainio 《Archives of toxicology》1989,63(3):203-208
The induction of hepatic peroxisome proliferation and drug metabolizing enzymes and of sister chromatid exchange (SCE) in lymphocytes was studied in male Han/Wistar rats after exposing them for 2 weeks to a commercial chlorophenolate formulation (Ky-5) (100mg/kg/ day), to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD; 0.05–5 g/kg/wk) and to the pure phenoxyacetic acids, 2,4-dichlorophenoxyacetic acid (2,4-D; 100 mg/kg/day) and 2-chloro-4-methylphenoxyacetic acid (MCPA; 100 mg/kg/day). The chlorophenolate formulation and pure 2,4-D and MCPA caused significant increases in the number of peroxisomes in liver cells, although the average size of peroxisomes was not affected, whereas the effect of even the highest dose of 2,3,7,8-TCDD remained small. This finding indicates that dioxin impurities do not account for the peroxisome proliferation induced by chlorophenolate. The relative weight of the liver increased significantly in rats treated with the chlorophenolate formulation and with 2,3,7,8-TCDD (5.0 and 0.5 g/kg). The pattern of induction of xenobiotic metabolizing enzymes showed some differences between chlorophenolate treatment and 2,3,7,8-TCDD treatment. Furthermore, the effects of pure phenoxyacetic acids were different from that seen with chlorophenolate and 2,3,7,8-TCDD. The highest dose of 2,3,7,8-TCDD increased the frequency of SCE in circulating lymphocytes slightly, but significantly. 相似文献
4.
Immunochemical characterization of cytochrome P-450 isozymes responsible for benzene oxidation in the rat liver 总被引:4,自引:0,他引:4
Nakajima Tamie; Elovaara Eivor; Park Sang S.; Gelboin Harry V.; Hietanen Eino; Vainio Hani 《Carcinogenesis》1989,10(9):1713-1717
The contribution of cytochrome P-450 isozymes to benzene metabolismin liver microsomes from fed, fasted, pyrazole-, pbenobarbital(PB)- and ethanol-treated rats and in respective isocaloriccontrols was investigated using monoclonal antibodies (mAbs).Clone 1-7-1 mAb did not inhibit benzene metabolism, whereasclone 2-66-3 inhibited only in PB-induced microsomes at a highconcentration of benzene (6.26 mM), and clone 1-91-3 mAb inhibitedbenzene metabolism in all cases. The degree of inhibition wasas follows: fed isocaloric control PB < fasted < pyrazole ethanol. The pattern of inhibition was similar with clone 1-91-3for low (0.23 mM) and high concentrations of benzene, exceptin PB-induced mkrosomes. Western blot analysis showed that clone1-7-1 mAb did not bind any liver mkrosomal protein in the regionof cytochrome P-450s, whereas with clone 2-66-3 a clear-cutband was seen only in liver microsomes from PB-treated rats,with clone 1-98-1, a band was detected in mkrosomes from alltreated groups, in the following order: PB = isocaloric control< fed < fasted < pyrazole < ethanol. These resultsindicate that (i) cytochromes P-450b,e and P-450J contributeto benzene metabolism in rat liver; (ii) the former has a lowaffinity to benzene and is induced by PB; and (iii) P-450J hasa high affinity to benzene and is induced by 1-day fasting,pyrazole and ethanol, but decreased by PB treatment. 相似文献
5.
S. S. Hernes E. Hagen H. Quarsten B. Bjorvatn P. S. Bakke 《European journal of clinical microbiology & infectious diseases》2014,33(3):359-364
We tested the hypothesis that the results of real-time polymerase chain reaction (PCR) analyses for respiratory viruses would reduce antibiotic treatment and length of stay in elderly patients hospitalized with respiratory infections. Within 24 h of hospital admission, a total of 922 patients aged ≥60 years were interviewed for symptoms of ongoing respiratory tract infection. Symptomatic patients were swabbed for oropharyngeal/nasopharyngeal presence of viral pathogens immediately by members of the study group. During a 2-month period, non-symptomatic volunteers among interviewed patients were swabbed as well (controls). Oropharyngeal/nasopharyngeal swabs were analyzed with real-time PCR for nine common respiratory viruses. A total of 147 out of 173 symptomatic patients and 56 non-symptomatic patients (controls) agreed to participate in the study. The patients were allocated to three cohorts: (1) symptomatic and PCR-positive (S/PCR+), (2) symptomatic and PCR-negative (S/PCR?), or (3) non-symptomatic and PCR-negative (control). There were no non-symptomatic patients with a positive PCR result. A non-significant difference in the frequency of empiric antibiotic administration was found when comparing the S/PCR+ to the S/PCR? cohort; 16/19 (84 %) vs. 99/128 (77 %) (χ2?=?0.49). Antibiotic treatment was withdrawn in only two patients in the S/PCR+ cohort after receiving a positive viral diagnosis. The length of stay did not significantly differ between the S/PCR+ and the S/PCR? groups. We conclude that, at least in our general hospital setting, access to early viral diagnosis by real-time PCR had little impact on the antimicrobial treatment or length of hospitalization of elderly patients. 相似文献
6.
Neuronavigation by intraoperative three-dimensional ultrasound: initial experience during brain tumor resection 总被引:28,自引:0,他引:28
Unsgaard G Ommedal S Muller T Gronningsaeter A Nagelhus Hernes TA 《Neurosurgery》2002,50(4):804-12; discussion 812
OBJECTIVE: Three-dimensional (3-D) ultrasound is an intraoperative imaging modality used in neuronavigation as an alternative to magnetic resonance imaging (MRI). This article summarizes 4 years of clinical experience in the use of intraoperative 3-D ultrasound integrated into neuronavigation for guidance in brain tumor resection. METHODS: Patients were selected for inclusion in the study on the basis of the size and location of their lesion. Preoperative 3-D MRI data were registered and used for planning as in other conventional neuronavigation systems. Intraoperative 3-D ultrasound images were acquired three to six times, and tumor resection was guided on the basis of these updated 3-D images. RESULTS: Intraoperative 3-D ultrasound represents a good solution to the problem of brain shift in neuronavigation because it easily provides an updated, and hence more accurate, map of the patient's true anatomy in all phases of the operation. Ultrasound makes it possible to follow the progression of the operation, and it improves the radicality of tumor resection by detecting tumor tissue that would remain if the imaging technology had not been used (in 53% of the cases). Integration of 3-D ultrasound with navigation technology solves the orientation problem experienced previously with two-dimensional ultrasound in neurosurgery. The technology makes it possible to directly compare intraoperative ultrasound and MRI data regarding visualization of the lesion. Ultrasound image quality is useful for guiding surgical procedures. CONCLUSION: Intraoperative 3-D ultrasound seems to provide a time- and cost-effective way to update high-quality 3-D maps used in neuronavigation. 相似文献
7.
3D ultrasound-based navigation for radiofrequency thermal ablation in the treatment of liver malignancies 总被引:9,自引:0,他引:9
Sjølie E Langø T Ystgaard B Tangen GA Nagelhus Hernes TA Mårvik R 《Surgical endoscopy》2003,17(6):933-938
BACKGROUND: The aim of the study was to compare three methods for ultrasound-based guidance of a radiofrequency probe into liver tumors in a model setup. METHODS: The liver model tumors were placed inside excised calf livers, and the radiofrequency probe was guided into the center using either a new 3D navigation method or two conventional 2D methods-freehand scanning and a method based on a biopsy guide. We performed 54 experiments, measuring the physical distance (all methods) and image distance (3D method only) from the tip of the probe to the center of the tumors. RESULTS: Based on the physical measurements alone, the biopsy-based guiding performed better than both the 2D freehand and the 3D navigation method. However, the 3D image measurements showed that the tip of the probe was better positioned in the center of the model tumors for the 3D navigation method as compared to the physical measurement results for the 2D methods. CONCLUSION: Although it was easier to position the radiofrequency probe accurately using the 3D image display technique, movement of the model tumor during 3D navigation is a challenge. 相似文献
8.
Rygh OM Selbekk T Torp SH Lydersen S Hernes TA Unsgaard G 《Acta neurochirurgica》2008,150(10):1033-1042
Objective The purpose of the study was to compare the ability of navigated 3D ultrasound to distinguish tumour and normal brain tissue
at the tumour border zone in subsequent phases of resection.
Materials and methods Biopsies were sampled in the tumour border zone as seen in the US images before and during surgery. After resection, biopsies
were sampled in the resection cavity wall. Histopathology was compared with the surgeon’s image findings.
Results Before resection, the tumour border was delineated by ultrasound with high specificity and sensitivity (both 95%). During
resection, ultrasound had acceptable sensitivity (87%), but poor specificity (42%), due to biopsies falsely classified as
tumour by the surgeon. After resection, sensitivity was poor (26%), due to tumour or infiltrated tissue in several biopsies
deemed normal by ultrasound, but the specificity was acceptable (88%).
Conclusions Our study shows that although glioblastomas are well delineated prior to resection, there seem to be overestimation of tumour
tissue during resection. After resection tumour remnants and infiltrated brain tissue in the resection cavity wall may be
undetected. We believe that the benefits of intraoperative ultrasound outweigh the shortcomings, but users of intraoperative
ultrasound should keep the limitations shown in our study in mind. 相似文献
9.
Melatonin modulates allergic lung inflammation 总被引:3,自引:0,他引:3
Eivor Martins Jr Ana Paula Ligeiro de Oliveira Ana Maria Fialho de Araujo Wothan Tavares de Lima José Cipolla-Neto & Luis Fernando B. P. Costa Rosa 《Journal of pineal research》2001,31(4):363-369
Asthma is an inflammatory lung disease characterized by cell migration, bronchoconstriction and hyperresponsiveness, and can be induced, as an experimental model, by ovalbumin sensitization followed by a challenge. In addition to the well-known immunostimulatory effects of melatonin, research has identified some of its anti-inflammatory properties. In this study, we evaluated the influence of pinealectomy and melatonin administration on cell migration in an experimental model of allergic airway inflammation. We evaluated, in pinealectomized rats treated or not with melatonin, cell migration into the bronchoalveolar fluid, the number of cells and their proliferative activity in the bone marrow, and plasma corticosterone levels. Pinealectomy reduces, 24 hr after the challenge, the total cell number count in the lung and bone marrow cell proliferation, without changing the number of cells in the bone marrow or in the peripheral blood. This fact suggests that melatonin is important in the control of cell recruitment from the bone marrow and the migration of those cells to the lung. Melatonin administration to pinealectomized rats seems to restore the ability of cells to migrate from the bone marrow to the bronchoalveolar fluid. So, the development of specific inhibitors of melatonin would benefit patients with asthma. 相似文献
10.
Eivor Wiking MD Nuha Saleh-Stattin PhD Sven-Erik Johansson PhD Jan Sundquist MD PhD 《Scandinavian journal of caring sciences》2009,23(2):290-297
Our knowledge of the immigrant patient’s experiences and reflections regarding consultations in primary health care where interpreters are used is limited. Thus, the primary aim was to explore these experiences and reflections. The second aim was to study whether demographic and migration‐related factors are associated with the patient’s satisfaction with the consultation and feeling of consolation given by the general practitioner (GP). The third aim was to analyse whether these feelings are related to the time from the booking to the consultation, to self‐reported health, symptoms and the patient’s experiences. A questionnaire was distributed to 78 consecutive immigrant patients from Chile, Iran and Turkey at 12 primary healthcare centres around Stockholm. The respondents were asked about their background and health status, while open‐ended questions focused on their experiences and comments regarding the consultation and cross‐cultural communication in general. Ethical approval was obtained. The respondents consisted of 52 patients, 16 from Chile, nine from Iran and 27 from Turkey. Most of the answers concerned communication problems because of language and cultural differences between the GP and the patient and the GP’s ability to listen. Therefore, the importance of having a competent interpreter for a satisfactory consultation was stressed. Many of the respondents also felt that the GP’s ability to listen to them and understand them is crucial in the consultation. Background facts, including demographic and migration‐related factors, health status and factors related to the consultation, did not seem to be associated with the patient’s satisfaction and the feeling of consolation. One limitation is that the sample is small and not equally distributed. The use of authorized interpreters during the consultation is essential. The consultation must be based on a patient‐centred strategy and adjusted to the patient’s educational level. Cultural competence is needed when meeting immigrant patients. 相似文献