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1.
2.
I W Reimann M Jedrychowski R Schulz K H Antonin A Roth P R Bieck 《Arzneimittel-Forschung》1987,37(10):1174-1178
2-Phenylpyrazolo[4,3-c]quinolin-3(5H)-one (CGS 8216) is pharmacologically characterized as benzodiazepine antagonist with low inverse agonistic effects. Single oral doses up to 650 mg and subchronic doses up to 100 mg daily for seven days are well tolerated by young healthy volunteers. Plasma concentrations of CGS 8216 are variable, not dose-related and relatively low considering the doses administered. A high plasma concentration ratio of metabolite vs. parent compound (3:1) points to an extensive gastrointestinal first-pass metabolism. CGS 8216 influences the human electroencephalogram similar to anxiolytic and vigilance enhancing drugs in doses which do not change performance of psychometric tests. CGS 8216 antagonizes the diazepam-induced impairment of alertness. 相似文献
3.
Intramolecular Alkylations of Aromatic Compounds, XVII1): — Synthesis of trans-3,10b-Dimethyl-1,2,3,4,4a,5,6,10b-octahydrobenzo(f)isoquinoline From the cyanhydrine 5b , easily obtained from 4 and trimethylsilyl cyanide, the lactone 6 is prepared, hydrogenation of which gives a mixture of the lactam 7a and the lactone 8 . Compound 7a is reduced to the secondary base 9 , which by treatment with acid is dehydrated to 10 and rearranges to give the isomer 11 , too. Attempted cyclization of the aminoalcohol 12 fails to give 9 or 10 . Rather, the furan 13 is isolated as the final product. N-methylation 10 → 14 and subsequent hydrogenation furnish the 4:1 trans/cis-mixture 2a, b , from which the title compound is separated by column chromatography. From 11 the stereomers 18a, b can be prepared analogously. 相似文献
4.
Inge Reimann Dimitrios Vittas Steen Levin Nielsen Eiliv Svalastoga 《Acta orthopaedica》1989,60(2):185-187
The resorption pattern of synovial fluid through the lymphatic system from normal and synovitic knee joints in rabbits was studied with 99mHechnetium-rhenium-sulfur colloid injected intraarticularly and monitored for 14 hours with a gamma camera.
On the normal side the regional lymph nodes were visualized after I hour and after 14 hours still 75 percent activity remained in the knee. In the synovitic knees no lymphatic transport could be detected; and the radiotracer was unstable with rapid liberation of technetium, which was excreted in the urine. This radiolysis was not found in vitro in synovitic joint fluid.
The lymphatic transport from normal rabbit knees is low. We found a clear difference in lymphatic transport between normal and synovitic knee joints. 相似文献
On the normal side the regional lymph nodes were visualized after I hour and after 14 hours still 75 percent activity remained in the knee. In the synovitic knees no lymphatic transport could be detected; and the radiotracer was unstable with rapid liberation of technetium, which was excreted in the urine. This radiolysis was not found in vitro in synovitic joint fluid.
The lymphatic transport from normal rabbit knees is low. We found a clear difference in lymphatic transport between normal and synovitic knee joints. 相似文献
5.
The liver regulates T-cell homeostasis, induces T-cell tolerance, and supports intrahepatic T-cell responses against hepatotropic pathogens. Many data from clinical and preclinical systems provide supportive evidence for these diverse roles of the liver in modulating peripheral (systemic, mucosal, and intrahepatic) T-cell immunity. Little information is available on the cellular and molecular mechanisms that mediate the dual role of the liver in tolerizing T-cell responses and in supporting intrahepatic priming of T-cell responses. Understanding these immunoregulatory effects in the liver may offer insight into clinically relevant immunopathologies of this organ. 相似文献
6.
James Deschner Birgit Rath-Deschner Susanne Reimann Christoph Bourauel Werner Gtz Soeren Jepsen Andreas Jger 《Annals of anatomy》2007,189(4):326-328
Recent studies have revealed that dynamic biomechanical forces can exert antiinflammatory and antiproteolytic effects on fibrocartitage. Whether the effects of mechanical strain also involve stimulation of the insulin-like growth factor (IGF) system and, therefore, of growth and repair of fibrocartilage has yet to be determined. The objective of this in vitro study was to determine if continuous biophysical strain regulates the gene expression of IGF1, IGF2, IGF1 receptor (IGF1R), insulin receptor substrate (IRS1), and IGF-binding proteins (IGFBP) 3 and 5 in cells from the fibrocartilaginous disc of the temporomandibular joint (TMJ). Rat TMJ disc cells were subjected to continuous biophysical strain (3% and 20%) for 4 and 24 h. Subsequently, RNA was extracted and real-time PCR was performed using an iCycler iQ detection system to analyze the gene expression of the IGF system. The gene expression of IGF1, IGF2, IGF1R, IRS1, IGFBP3, and IGFBP5 was significantly (p < 0.05) inhibited when cells were subjected to continuous biophysical strain, as compared to control at both time points. High strain induced a stronger inhibition of these molecules as compared to strain of Low magnitude. In conclusion, continuous biophysical strain seems to downregulate the expression of the IGF system and may, therefore, reduce the potential of fibrocartilage for growth and repair. 相似文献
7.
Ene I. Ette 《Computers in biology and medicine》1996,26(6):505-512
There is no method available to compare the fit of two non-hierarchical non-linear mixed effects models, although the common practice is to select the model with the lower objective function. Bootstrapping the log-likelihood differences (LLDs) of non-hierarchical models and constructing a bootstrap confidence interval on the LLDs is proposed for comparing the goodness-of-fit of such models. This is illustrated with different parameterizations of clearance models for an anti-infective agent in a longitudinal pharmacokinetic study which are compared. Additive and exponential models of creatinine clearance as a predictor of clearance are used as examples. 相似文献
8.
9.
Effects of omalizumab, a humanized monoclonal anti-IgE antibody, on nasal reactivity to allergen and local IgE synthesis. 总被引:2,自引:0,他引:2
Jonathan Corren David Diaz-Sanchez Andrew Saxon Yamo Deniz James Reimann Don Sinclair Teresa Davancaze Daniel Adelman 《Annals of allergy, asthma & immunology》2004,93(3):243-248
BACKGROUND: Treatment with omalizumab has been shown to reduce serum free IgE concentrations and to have beneficial effects on allergic airway disease. However, its effect on IgE synthesis is unknown. OBJECTIVE: To determine whether omalizumab therapy affects nasal reactivity to allergen and local IgE production. METHODS: Nineteen patients with perennial allergic rhinitis were treated with intravenous omalizumab every 2 weeks for 26 weeks in an open-label study. Serum free and total IgE concentrations were measured at baseline and every 2 weeks throughout the study. Nasal challenge to dust mite allergen was performed at baseline and after 12 and 24 weeks of treatment. Nasal lavage fluid obtained before and after each nasal challenge was evaluated for mite-specific antibodies, plaque-forming cells, and productive epsilon messenger RNA (mRNA). RESULTS: During treatment, serum free IgE concentrations were decreased by 97% to 99%, and the nasal response to allergen challenge was significantly reduced on days 80 and 164. The postchallenge increase in nasal lavage mite specific IgE was significantly reduced by treatment with omalizumab on day 168. IgE plaque-forming cells and productive epsilon mRNA were not significantly affected by omalizumab treatment. CONCLUSIONS: Omalizumab treatment markedly reduced serum free IgE and the clinical response to nasal allergen challenge. However, the absence of an effect on IgE-secreting B cells and epsilon mRNA in nasal lavage fluid suggests that omalizumab treatment for 6 months does not significantly modulate synthesis of nasal IgE. 相似文献
10.
Inflammatory bowel disease in scid mice is initiated by transplantation of CD4(+) T-cells from immunocompetent syngenic donor mice. As the disease progresses, immunoglobulin (Ig)-containing cells appear in the gut lamina propria, suggesting that locally accumulating Ig may play a role in disease development. In the present work we have investigated the relationship between disease progression and patterns or levels of Ig isotypes in the feces of scid mice suffering from an ongoing colitis. The data clearly showed that the severity or progression of the disease did not influence the levels of IgA, IgG1, IgG2a, IgG2b, and IgG3, whereas the level of fecal IgM increased during the course of colitis. The presence of the serum protein alpha-1-antitrypsin in fecal extracts from diseased mice suggests that some of the fecal Ig has leaked through the inflamed epithelial membrane into the gut lumen. Finally, Ig-containing cells were observed in mesenteric lymph nodes and in the spleen, suggesting that the fecal Ig is produced both systemically and locally in the gut wall. In conclusion, the present results demonstrate that the level of IgM increases as colitis progresses. Also, the five remaining major Ig isotypes are increased in the gut lumen of scid mice with colitis, but the individual Ig types vary randomly during the course of the disease. Thus, it is unlikely that immunoglobulins are involved in the immunopathogenesis of this model of colitis. 相似文献