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排序方式: 共有116条查询结果,搜索用时 62 毫秒
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Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with beta-amyloid 总被引:6,自引:0,他引:6
Cribbs DH Ghochikyan A Vasilevko V Tran M Petrushina I Sadzikava N Babikyan D Kesslak P Kieber-Emmons T Cotman CW Agadjanyan MG 《International immunology》2003,15(4):505-514
The role of adjuvant on the T(h)1 and T(h)2 immune responses to Abeta-immunotherapy (Abeta(42 )peptide) was examined in wild-type mice. Fine epitope analysis with overlapping oligomers of the Abeta(42) sequence identified the 1-15 region as a dominant B cell epitope. The 6-20 peptide was recognized only weakly by antisera from mice administrated with Abeta(42) peptide formulated in complete Freund's adjuvant (CFA), alum or TiterMax Gold (TMG). However, mice immunized with Abeta(42) mixed with QS21 induced a significant antibody response to the 6-20 peptide. The only T cell epitope found was within the 6-28 sequence of Abeta(42). QS21 and CFA induced the strongest humoral response to Abeta, alum was intermediate, and TMG the weakest adjuvant. Analysis of antibody isotypes specific for Abeta indicates that alum induces primarily T(h)2-type immune response, whereas TMG, CFA and QS21 shift the immune responses toward a T(h)1 phenotype. Stimulation of splenocytes from Abeta-immunized mice with Abeta(40) peptide induced strikingly different cytokine expression profiles. QS21 and CFA induced significant IFN-gamma, IL-4 and tumor necrosis factor-alpha expression, whereas alum induced primarily IL-4 production. As T(h)1-type immune responses have been implicated in many autoimmune disorders, whereas T(h)2-type responses have been shown to inhibit autoimmune disease, the choice of adjuvant may be critical for the design of a safe and effective immunotherapy for Alzheimer's disease. 相似文献
3.
B Davit K Reynolds R Yuan F Ajayi D Conner E Fadiran B Gillespie C Sahajwalla S M Huang L J Lesko 《Journal of clinical pharmacology》1999,39(9):899-910
Recent advances in in vitro metabolism methods have led to an improved ability to predict clinically relevant metabolic drug-drug interactions. To address the relationships of in vitro metabolism data and in vivo metabolism outcomes, the Office of Clinical Pharmacology and Biopharmaceutics in the Center for Drug Evaluation and Research, Food and Drug Administration, evaluated a number of recently approved new drug applications. The goal of these evaluations was to determine the contribution of in vitro metabolism data in (1) predicting in vivo drug-drug interactions, (2) determining the need to conduct an in vivo drug-drug interaction study, and (3) incorporating findings into drug product labeling. Ten cases are presented in this article. They fall into two major groups: (1) in vitro data were predictive of in vivo results, and (2) in vitro data were not predictive of in vivo results. Discussion of these cases highlights factors limiting predictability of in vivo metabolic interactions from in vitro metabolism data. The integration of these findings into drug product labeling is also discussed. 相似文献
4.
Increased flow and shear stress enhance in vivo transforming growth factor-beta1 after experimental arterial injury 总被引:2,自引:0,他引:2
Song RH Kocharyan HK Fortunato JE Glagov S Bassiouny HS 《Arteriosclerosis, thrombosis, and vascular biology》2000,20(4):923-930
We have previously demonstrated that high-flow (HF) conditions inhibit experimental intimal hyperplasia. We hypothesized that such flow conditions may alter transforming growth factor-beta1 (TGF-beta1) after mural injury. The right common carotid artery (CCA) was balloon-injured in 54 New Zealand White male rabbits. Flow was thereafter preserved (normal flow [NF]), reduced by partial outflow occlusion (low flow [LF]), or increased by ligation of the left CCA (HF). Four sham-operated animals served as uninjured controls. Mean blood flow and pressure in the right CCA were measured before and after flow modulation and before euthanasia (3, 7, and 14 days). TGF-beta1 mRNA and protein levels in the right CCA were determined by Northern and ELISA analyses at each time point. At 7 and 14 days, intimal hyperplasia was quantified, and the transmural localization of TGF-beta1 was determined by immunohistochemical analysis. Mean flow was reduced from 22+/-1 to 10+/-3 mL/min in the LF group and increased to 34+/-2 mL/min in the HF group (P<0.001). Blood pressure was not different among the flow groups for all time points. Wall shear stress was markedly decreased in the LF group to 14+/-4 dyne/cm(2) and increased in the HF group to 63+/-6 dyne/cm(2) at 7 days compared with values in uninjured controls (39+/-2 dyne/cm(2), P<0.001) and the NF group (44+/-7 dyne/cm(2), P<0.001). At 14 days, wall shear stress was similar among the flow groups. The intima-to-media ratio was 5- and 2-fold greater in the LF group than in the HF and NF groups at 14 days. mRNA levels for TGF-beta1 and its active ligand were increased in the HF group by at least 2- and 3-fold, respectively, at 3 and 7 days compared with levels in uninjured controls and the LF group (P<0.05) but were not different among the flow groups at 14 days. TGF-beta1 preferentially localized in the abluminal vascular smooth muscle cells of the HF arterial segments. Flow- and shear-mediated release of TGF-beta1 may therefore play a role in abrogating the proliferative and migratory response of vascular smooth muscle cells in the early stages after mural injury. 相似文献
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6.
Thijs Devriendt Davit Chokoshvili Maddalena Favaretto Pascal Borry PhD 《Drug testing and analysis》2018,10(5):802-806
The Athlete Biological Passport (ABP) refers to the collection of data related to an individual athlete. The ABP contains the Haematological Module and the Steroidal Module, which are used for the longitudinal monitoring of variables in blood and urine, respectively. Based on changes in these variables, a statistical model detects outliers which indicate doping use and guide further targeted testing of the athlete. Presently, athletes can access their data of the Haematological Module in the Anti‐Doping Administration and Management System (ADAMS). However, granting athletes access to this data has been a matter of debate within the anti‐doping community. This article investigates whether an athlete has a right to access the contents of their ABP profile. We approached this discussion by comparing the nature of ABP data with that of forensic and medical data and touched on important concerns with ABP data disclosure to athletes such as potentially allowing for the development of alternative doping techniques to circumvent detection; and making athletes vulnerable to pressure by the media to publicly release their data. Furthermore, given that ABP data may contain medically relevant information that can be used to diagnose disease, athletes may over‐interpret its medical significance and wrongly see it as a free health check. We argue that safeguarding the integrity of the ABP system must be seen as the most essential element and thus a departure from immediate data disclosure is necessary. Two different strategies for delayed data disclosure are proposed which diminish the chances of ABP data being misused to refine doping techniques. 相似文献
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8.
MRI at 7 Tesla has been used to investigate the accumulation of manganese in the occipital cortex of common marmoset monkeys (Callithrix jacchus) after administering four fractionated injections of 30 mg/kg MnCl2 · 4H2O in the tail vein. We found a statistically significant decrease in T1 in the primary (V1) and secondary (V2) areas of the visual cortex caused by an accumulation of manganese. The larger T1 shortening in V1 (ΔT1 = 640 ms) relative to V2 (ΔT1 = 490 ms) allowed us to robustly detect the V1/V2 border in vivo using heavily T1‐weighted MRI. Furthermore, the dorso‐medial (DM) and middle‐temporal (MT) areas of the visual pathway could be identified by their T1‐weighted enhancement. We showed by comparison to histological sections stained for cytochrome oxidase (CO) activity that the extent of V1 is accurately identified throughout the visual cortex by manganese‐enhanced MRI (MEMRI). This provides a means of visualizing functional cortical regions in vivo and could be used in longitudinal studies of phenomena such as cortical plasticity, and for non‐destructive localization of cortical regions to guide in the implementation of functional techniques. Published in 2009 by John Wiley & Sons, Ltd. 相似文献
9.
Davit S Senkaya I Ercan AK Kan II Ozkan H 《Cardiovascular surgery (London, England)》2002,10(6):579-585
Coronary by-pass on a beating heart may provide a safer form of surgical revascularization by avoiding the well-documented side effects of cardiopulmonary by-pass. In addition, off-pump bypass is suggested to be a good alternative to on-pump especially in high risk patients. This study reviews the feasibility of coronary by-pass on the beating heart in all patients referred to surgery. Two hundred and ninety-four patients operated on the beating heart were prospectively followed and compared to the control group of 100 consecutive patients operated with the conventional method. There were no significant differences between the groups with respect to risk factors, except the incidence of chronic obstructive pulmonary disease and ejection fraction which were higher in the conventional group, whereas peripheral vascular disease was higher in the beating heart group. There was more distal anastomosis in the conventional group. Postoperative inotrope requirement, peak creatine phosphokinase- MB, ventilation time, blood loss in the first 24 h, transfusion needs, new atrial fibrillation and length of hospital stay were significantly lower in the beating heart operations. However, there were no significant differences between the groups in terms of neurological complications, chest infection, intraaortic balloon pump usage and mortality. In conclusion, multivessel off pump coronary by-pass is feasible with the same or better results as it is observed in the conventional technique when postoperative bleeding, neurogenic complications, arrythmias, hospital stay, overall morbidity and mortality are compared. 相似文献
10.
Polli JE Cook JA Davit BM Dickinson PA Argenti D Barbour N García-Arieta A Geoffroy JM Hartauer K Li S Mitra A Muller FX Purohit V Sanchez-Felix M Skoug JW Tang K 《The AAPS journal》2012,14(3):627-638
This summary workshop report highlights presentations and over-arching themes from an October 2011 workshop. Discussions focused on best practices in the application of biopharmaceutics in oral drug product development and evolving bioequivalence approaches. Best practices leverage biopharmaceutic data and other drug, formulation, and patient/disease data to identify drug development challenges in yielding a successfully performing product. Quality by design and product developability paradigms were discussed. Development tools include early development strategies to identify critical absorption factors and oral absorption modeling. An ongoing theme was the desire to comprehensively and systematically assess risk of product failure via the quality target product profile and root cause and risk analysis. However, a parallel need is reduced timelines and fewer resources. Several presentations discussed applying Biopharmaceutics Classification System (BCS) and in vitro-in vivo correlations in development and in post-development and discussed both resource savings and best scientific practices. The workshop also focused on evolving bioequivalence approaches, with emphasis on highly variable products (HVDP), as well as specialized modified-release products. In USA, two bioequivalence approaches for HVDP are the reference-scaled average bioequivalence approach and the two-stage group-sequential design. An adaptive sequential design approach is also acceptable in Canada. In European Union, two approaches for HVDP are a two-stage design and an approach to widen C (max) acceptance limits. For some specialized modified-release products, FDA now requests partial area under the curve. Rationale and limitations of such metrics were discussed (e.g., zolpidem and methylphenidate). A common theme was the benefit of the scientific and regulatory community developing, validating, and harmonizing newer bioequivalence methodologies (e.g., BCS-based waivers and HVDP trial designs). 相似文献