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81.
Tetrodotoxin binding to normal depolarized frog muscle and the conductance of a single sodium channel. 总被引:4,自引:0,他引:4
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1. We have examined the binding of tritium-labelled and unlabelled tetrodotoxin to frog twitch muscle. Bio-assay as well as radioisotope experiments show a saturable component of tetrodotoxin binding with a binding capacity of about 22 p-mole/g wet wt., and a dissociation constant of about 5 nM. 2. If the observed uptake of tetrodotoxin by muscles represents one-to-one binding of the drug to sodium channels, the channel density is about 380 channels/mum2 of a muscle fibre's surface membrane. On the basis of this result and electrical measurements of sodium conductance in frog muscle, we calculate that the conductance of a single sodium channel is of the order of 10(-12) reciprocal ohms. This is one to two orders of magnitude less than previous estimates. 3. We have looked for an effect of membrane depolarization on saturable tetrodotoxin binding, and have found none. This suggests that there is little molecular interaction between the "gating" portion of the sodium channel molecule, and that which binds tetrodotoxin. 相似文献
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PURPOSE: In order to improve the preparation method for barium examination of the stomach by ranitidine and acetylcysteine use, the effect on the rat gastric mucosa caused by the administration of ranitidine and acetylcysteine was studied. MATERIALS AND METHODS: Rat stomach that had been treated with ranitidine or acetylcysteine at different intervals and examined in vivo was excised and coated with a barium suspension. A radiograph was subsequently taken and evaluated in regard to the removal of gastric mucus and imaging of the areae gastricae (AG). The removal of mucus was assessed by six blind observers. The imaging of AG was estimated as a percentage of the imaged AG area per total gastric corpus. RESULTS: No change was seen on the radiograph with ranitidine preparation, while the mucus was distinctly removed and AG well-imaged in the group studied 15 minutes after the peroral administration of acetylcysteine. CONCLUSION: Proper preparation for barium study of the stomach should involve treatment with a mucolytic agent about 15 minutes before the examination. H2-blockers must be used supplementally in the short term. 相似文献
84.
Dynamic contrast-enhanced magnetic resonance imaging rapidly indicates vessel regression in human squamous cell carcinomas grown in nude mice caused by VEGF receptor 2 blockade with DC101 总被引:3,自引:0,他引:3
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Kiessling F Farhan N Lichy MP Vosseler S Heilmann M Krix M Bohlen P Miller DW Mueller MM Semmler W Fusenig NE Delorme S 《Neoplasia (New York, N.Y.)》2004,6(3):213-223
The purpose of our study was the investigation of early changes in tumor vascularization during antiangiogenic therapy with the vascular endothelial growth factor (VEGF) receptor 2 antibody (DC101) using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). Subcutaneous heterotransplants of human skin squamous cell carcinomas in nude mice were treated with DC101. Animals were examined before and repeatedly during 2 weeks of antiangiogenic treatment using Gd-DTPA-enhanced dynamic T1-weighted MRI. With a two-compartment model, dynamic data were parameterized in "amplitude" (increase of signal intensity relative to precontrast value) and k(ep) (exchange rate constant). Data obtained by MRI were validated by parallel examinations of histological sections immunostained for blood vessels (CD31). Already 2 days after the first DC101 application, a decrease of tumor vascularization was observed, which preceded a reduction of tumor volume. The difference between treated tumors and controls became prominent after 4 days, when amplitudes of treated tumors were decreased by 61% (P =.02). In line with change of microvessel density, the decrease in amplitudes was most pronounced in tumor centers. On day 7, the mean tumor volumes of treated (153 +/- 843 mm(3)) and control animals (596 +/- 384 mm(3)) were significantly different (P =.03). After 14 days, treated tumors showed further growth reduction (83 +/- 93 mm(3)), whereas untreated tumors (1208 +/- 822 mm(3)) continued to increase (P =.02). Our data underline the efficacy of DC101 as antiangiogenic treatment in human squamous cell carcinoma xenografts in nude mice and indicate DCE MRI as a valuable tool for early detection of treatment effects before changes in tumor volume become apparent. 相似文献
85.
One night of total sleep deprivation impairs implicit learning in the serial reaction task,but not the behavioral expression of knowledge 总被引:1,自引:0,他引:1
Implicit sequence learning in the serial reaction task suffers from total sleep deprivation. The authors compared implicit-learning scores in a sleep-deprivation (SD) group (n = 12) and a control group (n = 6). Both groups were tested immediately after learning a 1st sequence; a delayed test was conducted on the next day (after a night without sleep in the SD group). Immediately after the delayed test a 2nd sequence was learned, followed by an immediate test and a delayed test toward the end of the experiment. In the SD group implicit-learning scores were reduced in both tests of the 2nd sequence, but in neither test of the 1st sequence. Thus, 1 night of total sleep deprivation impairs the acquisition of implicit sequence knowledge, but not its behavioral expression. 相似文献
86.
Intrinsic respiratory gating in small-animal CT 总被引:2,自引:0,他引:2
Bartling SH Dinkel J Stiller W Grasruck M Madisch I Kauczor HU Semmler W Gupta R Kiessling F 《European radiology》2008,18(7):1375-1384
Gating in small-animal CT imaging can compensate artefacts caused by physiological motion during scanning. However, all published gating approaches for small animals rely on additional hardware to derive the gating signals. In contrast, in this study a novel method of intrinsic respiratory gating of rodents was developed and tested for mice (n=5), rats (n=5) and rabbits (n=2) in a flat-panel cone-beam CT system. In a consensus read image quality was compared with that of non-gated and retrospective extrinsically gated scans performed using a pneumatic cushion. In comparison to non-gated images, image quality improved significantly using intrinsic and extrinsic gating. Delineation of diaphragm and lung structure improved in all animals. Image quality of intrinsically gated CT was judged to be equivalent to extrinsically gated ones. Additionally 4D datasets were calculated using both gating methods. Values for expiratory, inspiratory and tidal lung volumes determined with the two gating methods were comparable and correlated well with values known from the literature. We could show that intrinsic respiratory gating in rodents makes additional gating hardware and preparatory efforts superfluous. This method improves image quality and allows derivation of functional data. Therefore it bears the potential to find wide applications in small-animal CT imaging. 相似文献
87.
Although opioid therapy has been accepted for the treatment of patients with cancer pain, its use for nonmalignant pain is still regarded as controversial due to concerns about the development of tolerance and psychological dependence. However, recent studies indicate that there is a low incidence of addiction in patients who do not have a history of addictive disorders, and opioid use is increasing for long-term treatment in patients with nonmalignant pain. This paper reviews the results from recent studies that evaluated the efficacy of intrathecal opioid delivery using a number of outcome measures. These studies demonstrate that intrathecal opioid delivery produces short-term relief of specific symptoms and improves long-term outcomes such as patient functioning (measured by increases in activities of daily living [ADLs] and capacity to work), mood, treatment satisfaction, and quality of life, as well as decreases in oral opioid use. Furthermore, these studies showed there was no development of tolerance or addiction in patients who received long-term intrathecal opioid delivery. 相似文献
88.
Sven Almers Göran Granerus Lennart Franzén Magnus Ström 《European journal of nuclear medicine and molecular imaging》1996,23(3):247-255
To compare two technetium-99m scintigraphic techniques —99mTc-labelled antibodies against granulocyte non-specific cross-reacting antigen-95 and99mTc-exametazime labelled leucocytes in ulcerative colitis —23 consecutive patients undergoing colonoscopy were investigated in a prospective and randomized study. In each patient the two scans and colonoscopy and biopsy were performed within 10 days. Scans, endoscopy and histology were independently graded for degree of inflammation in eight different colorectal segments for each patient. Active inflammation in one or more segments was present on endoscopy in 22 patients and on histology in 17 patients. Twenty-two patients had increased uptake on the antibody scan and 21 patients on the exametazime scan. Twelve patients showed the same disease extent with both scan methods (total colitis,n=10; distal colitis,n=2). Compared with endoscopy, sensitivity for inflammation in individual segments was 0.51 for antibody scan and 0.87 for exametazime scan; specificity was 0.67 and 0.55, respectively. The predictive value for presence of inflammation was 0.66 for antibody scan and 0.72 for exametazime; the predictive value for absence of inflammation was 0.52 and 0.77, respectively. Segmental scan uptake of endoscopically or histologically visualized inflammation was consistently lower for antigranulocyte antibodies than for exametazime. It is concluded that in patients with active ulcerative colitis, inflammation is better visualized with99mTc-exametazime labelled leucocytes than with99mTc-labelled antigranulocyte antibodies. The antibody technique offers the advantage of in vivo labelling, but is less reliable than the exametazime method for imaging of colonic inflammation. 相似文献
89.
90.
Integrins αvβ3 and αvβ5 are considered to play an important role in the pathogenesis of breast cancer bone metastases. This study investigates the effects of the αvβ3/αvβ5 integrin-specific inhibitor cilengitide during early metastatic bone colonization. The impact of cilengitide on the migration, invasion and proliferation of MDA-MB-231 human breast carcinoma cells as well as on bone resorption by osteoclasts was investigated in vitro. For in vivo experiments, nude rats were treated with cilengitide for 30 days starting one day after site-specific tumor cell inoculation in the hind leg, and the course of metastatic changes in bone was followed using flat-panel volumetric computed tomography (VCT) and magnetic resonance imaging (MRI). Vascular changes in bone metastases were investigated using dynamic contrast-enhanced (DCE-) MRI-derived parameters amplitude A and exchange rate coefficient kep. In vitro, cilengitide treatment resulted in a decrease in proliferation, migration and invasion of MDA-MB-231 cells, as well as of osteoclast activity. In vivo, the development of bone metastasis in the hind leg of rats was not prevented by adjuvant cilengitide treatment, but cilengitide reduced the volumes of osteolytic lesions and respective soft tissue tumors of developing bone metastases as assessed with VCT and MRI, respectively. DCE-MRI revealed significant changes in the A and kep parameters including decreased relative blood volume and increased vessel permeability after cilengitide treatment indicating vessel remodeling. In conclusion, during early pathogenic processes of bone colonization, cilengitide treatment exerted effects on tumor cells, osteoclasts and vasculature reducing the skeletal lesion size of experimental skeletal metastases. 相似文献