The Experts below are selected from a list of 672 Experts worldwide ranked by ideXlab platform
Toshiaki Sunaga - One of the best experts on this subject based on the ideXlab platform.
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Quantitative analysis of antiatherosclerotic effect of nifedipine in cholesterol-fed rabbits
Cardiovascular Drugs and Therapy, 1990Co-Authors: Yhukou Ohta, Naoaki Higuchi, Sei Emura, Toshinobu Takashima, Kazuhisa Oogushi, Hiroaki Kato, Keizo Ohmori, Toshiaki SunagaAbstract:Reports concerning the effect of slow calciumchannel blockers on experimental atherosclerosis are controversial. We examined the antiatherosclerotic effect of nifedipine (40 mg/day for 16 weeks) on aorta of rabbits on diets containing 0.3%, 0.5%, and 1.0% cholesterol. There were no significant differences in levels of serum lipids with or without nifedipine in the same cholesterol-fed rabbits. The results obtained show that nifedipine suppressed the extent of lipid deposition and surface involvement (S.I) in aorta in 0.3% cholesterol-fed rabbits, whereas nifedipine only tended to suppress S.I. in 0.5% cholesterol-fed rabbits and had no effect in 1.0% cholesterol-fed rabbits. The log dose-response relationship of S.I. was obtained by plotting the concentration of cholesterol in the feed or the “integrated value” of the total serum cholesterol (TC), i.e., the cumulative sum of the serum TC values obtained at each week. The log, Doseresponse Curve was shifted in parallel with the right in nifedipine groups. The Lineweaver-Burk plot constructed from the dose-response Curve had the same points crossing the ordinate with or without nifedipine. These results suggested that nifedipine suppressed S.I. in a competitive manner with cholesterol on the specific binding site of lipid deposition. Electron-microscopic findings also demonstrated that fat droplets in smooth muscle cells, extracellular matrix containing collagen, and elastic fibers decreased in nifedipinetreated rabbits.
Michael C. Harrass - One of the best experts on this subject based on the ideXlab platform.
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Regulatory use of ecotoxicity statistics: a US perspective
Ecotoxicology, 1996Co-Authors: Michael C. HarrassAbstract:A variety of regulatory requirements for ecotoxicity test data exist in the US and each of these is able to specify what test protocols and endpoints are used. General practice is to calculate regression Curve endpoints, usually EC_50 values, for acute tests, and hypothesis test endpoints (e.g. NOEC, LOEC) for chronic studies. However, tests of wastewater effluents often use a hypothesis test endpoint which has been derived using site-specific information to represent a pass-fail standard for compliance. Field work, such as site assessments, tends to use hypothesis tests, but such work does not seek the Doseresponse Curve sought in standard laboratory tests. The risk-based approaches being developed use cither type of endpoint, but this seems to be an accommodation to existing data; preference is for dose-response Curves, not just a single ECx value. Endpoints are only one component of the conventional paradigm of environmental protection. Experience with various tests and endpoints suggest several perspectives: quality is critical, test species must be reliable and relevant, extrapolations will dominate decisions, and basing environmental decisions on the most sensitive endpoint of the most sensitive species may not remain a feasible paradigm for protecting ecological systems.
Fang Xiao - One of the best experts on this subject based on the ideXlab platform.
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The effect of dexamethasone on the contraction of isolated guinea-pig tracheal smooth muscle in vitro
Chinese Pharmacological Bulletin, 1995Co-Authors: Fang XiaoAbstract:The effect of Dex on isolated tion was studied in vitro.CaCl2 and histamine caused significant tracheal smooth muscle contraction and PD was 3.9 and 5.92 respectively.After incubated with Dex, the Doseresponse Curve of CaCl2 and His was significantly depressed was PD’and 4. 74 and 6. 67. Dex could also inhibited isoguinea-pig tracheal smooth muscle contraclated tracheal strips contraction induced by Ach 3×10-6 mol·L-1 and PGF2a 3 mmol·L-1. IC50 were 2.4×10-5 mol· L-1 and 4.26×10-4 mol· l-1. Dex had significant dilated effect on tracheal smooth muscle.
Ruth Gallily - One of the best experts on this subject based on the ideXlab platform.
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Mycoplasma capricolum membranes induce tumor necrosis factor α by a mechanism different from that of lipopolysaccharide
Cancer Immunology Immunotherapy, 1990Co-Authors: Talia Sher, Shlomo Rottem, Ruth GallilyAbstract:Heat-inactivated (60°C, 45 min) Mycoplasma capricolum strain JR cells activate murine macrophages to secrete high levels of tumór necrosis factor α (TNFα) and to lyse tumor target cells efficiently. Fractionation of the intact M. capricolum cells, obtained from cells harvested at the exponential phase of growth, shows that their capacity to induce TNFα secretion by macrophage resides exclusively in the membrane fraction. The macrophage-mediated cytolysis following activation by M. capricolum membranes was significantly inhibited by specific anti-recombinant murine TNFα antibodies. M. capricolum membranes are a potent inducer of TNFα as the commonly used bacterial lipopolysaccharide, indicated by their Doseresponse Curve for macrophage activation. Our study further showed that M. capricolum membranes and lipopolysaccharide synergize to augment TNFα secretion by C57BL/6-derived macrophages markedly. Moreover, lipopolysaccharide-unresponsive C3H/HeJ-derived macrophages, were pronouncedly activated by M. capricolum membranes, which do not contain lipopolysaccharide. These findings suggest that the mechanism by which M. capricolum membranes activate macrophages differs from that of lipopolysaccharide. Results of preliminary experiments show that human monocytes as well secrete TNFα following activation by M. capricolum membranes. Thus, in contrast with the prohibitive toxicity of lipopolysaccharide to animals and humans, M. capricolum membranes, which contain no lipopolysaccharide and are nontoxic in nature, may be of therapeutic value in the treatment of cancer.
Rc Ferreira - One of the best experts on this subject based on the ideXlab platform.
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Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial
'Public Library of Science (PLoS)', 2016Co-Authors: Todd J, Evangelou M, Aj Cutler, Ml Pekalski, Nm Walker, He Stevens, Porter L, Dj Smyth, Db Rainbow, Rc FerreiraAbstract:Background Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. Methods and Findings To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+ CD4+ CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five preassigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2 , in order to model the Doseresponse Curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = −0.052, 0.254) and 0.497 × 106 IU/m2 (SE = 0.092, 95% CI = 0.316, 0.678), respectively. On analysis of secondary outcomes, using a highly sensitive IL-2 assay, the observed plasma concentrations of the drug at 90 min exceeded the hypothetical Treg-specific therapeutic window determined in vitro (0.015–0.24 IU/ml), even at the lowest doses (0.040 × 106 and 0.045 × 106 IU/m2 ) administered. A rapid decrease in Treg frequency in the circulation was observed at 90 min and at day 1, which was dose dependent (mean decrease 11.6%, SE = 2.3%, range 10.0%–48.2%, n = 37), rebounding at day 2 and increasing to frequencies above baseline over 7 d. Teffs, natural killer cells, and eosinophils also responded, with their frequencies rapidly and dose-dependently decreased in the blood, then returning to, or exceeding, pretreatment levels. Furthermore, there was a dose-dependent down modulation of one of the two signalling subunits of the IL-2 receptor, the β chain (CD122) (mean decrease = 58.0%, SE = 2.8%, range 9.8%–85.5%, n = 33), on Tregs and a reduction in their sensitivity to aldesleukin at 90 min and day 1 and 2 post-treatment. Due to blood volume requirements as well as ethical and practical considerations, the study was limited to adults and to analysis of peripheral blood only. Conclusions The DILT1D trial results, most notably the early altered trafficking and desensitisation of Tregs induced by a single ultra-low dose of aldesleukin that resolves within 2–3 d, inform the design of the next trial to determine a repeat dosing regimen aimed at establishing a steady-state Treg frequency increase of 20%–50%, with the eventual goal of preventing T1D