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71.
Shock-induced modulation of lymphocyte reactivity: suppression, habituation, and recovery 总被引:3,自引:0,他引:3
The present study was designed to evaluate the suppressive effect of different frequencies of signaled-shock presentations on mitogenic reactivity of lymphocytes in Lewis rats, and to assess the recovery of that reactivity at varying times after the shocks. The results showed that the magnitude of decreased reactivity in both the spleen and whole-blood lymphocytes, as determined by mitogenic reactivity to Concanavalin A (Con A), was directly related to the number of shock presentations within a daily session. However, the suppressed reactivity for the spleen cells diminished with repeated sessions of frequent shocks, in contrast to the whole-blood lymphocytes which did not show any habituation. Furthermore, the imposition of different periods of recovery following a single session of frequent shocks showed that the decreased reactivity for the whole-blood lymphocytes extended beyond the immediate period of the shock experience, and took 48 to 96 hours to recover completely. In contrast, the spleen lymphocytes showed complete recovery within 24 hours following the administration of shock. These results establish that the rate of habituation to and recovery from a shock-induced decrease in mitogen reactivity is more rapid for the spleen than whole-blood lymphocytes. 相似文献
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74.
A D Timmis M B Fowler R J Burwood P Gishen R Vincent D A Chamberlain 《BMJ (Clinical research ed.)》1981,283(6292):636-638
Twelve patients with acute myocardial infarction and radiological evidence of pulmonary oedema were observed in whom the left atrial pressure, measured indirectly as pulmonary artery end-diastolic pressure, was not critically increased (range 5-12 mm Hg with reference to sternal angle). Eight of the patients had been treated with frusemide, but only six had responded: hence in at least half of the series diuresis could not account for the anomalous finding. Six patients with low cardiac output were given infusions to expand plasma volume. Appreciable increments in mean values for cardiac index (1.6 to 2.0 1/min/m2), stroke index (18 to 23 ml/beat/m2), mean arterial pressure (65 to 86 mm Hg), and pulmonary artery end-diastolic pressure (8 to 15 mm Hg) were recorded. This group, and the remaining six patients with higher cardiac output, survived to leave hospital. Delay in radiographic clearing after a fall of left atrial pressure was a possible explanation for the relatively low pulmonary artery end-diastolic pressures, especially in the patients treated successfully with diuretics. Other mechanisms, such as alterations in pulmonary vascular permeability, might also have contributed to the syndrome. Pulmonary oedema without a critical increase in the left atrial pressure is unusual in acute myocardial infarction but the therapeutic implications are important. Withdrawal;of diuretics may be indicated, and in some cases expansion of plasma volume may lead to striking clinical improvement. 相似文献
75.
Fenfluramine produced a rapid hyperthermic effect in rats housed in a warm (26–28 °C) environment. Drugs with known activity on serotonin-mediated pathways were the most effective antagonists of this hyperthermia. Among several anti-psychotic agents, clozapine was unique by virtue of its potent and specific antagonism of fenfluramine-induced hyperthermia. It is suggested that this serotonin blocking activity of clozapine may help to account for the lack of extrapyramidal symptoms (EPS) following administration of the drug to man. 相似文献
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77.
Christopher J. Fowler Sandra Holt Gunnar Tiger 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):55-58
Previous studies have demonstrated that fatty acid amide hydrolase, the enzyme responsible for the metabolism of anandamide, is inhibited by the acidic non-steroidal anti-inflammatory drug (NSAID) ibuprofen with a potency that increases as the assay pH is reduced. Here we show that (R) -, (S) - and (R, S) -flurbiprofen, indomethacin and niflumic acid show similar pH-dependent shifts in potency to that seen with ibuprofen. Thus, (S) -flurbiprofen inhibited 2 μM [3 H]anandamide metabolism with IC 50 values of 13 and 50 μM at assay pH values of 6 and 8, respectively. In contrast, the neutral compound celecoxib was a weak fatty acid amide hydrolase inhibitor and showed no pH dependency (IC 50 values ~300 μM at both assay pH). The cyclooxygenase-2-selective inhibitors nimesulide and SC-58125 did not inhibit fatty acid amide hydrolase activity at either pH. The data are consistent with the conclusion that the non-ionised forms of the acidic NSAIDs are responsible for the inhibition of fatty acid amide hydrolase. 相似文献
78.
Christopher J. Fowler Gunnar Tiger María L. López-Rodríguez Alma Viso Silvia Ortega-Gutiérrez José A. Ramos 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):225-231
Arachidonoyl-serotonin inhibits in a mixed-type manner the metabolism of the endocannabinoid anandamide by the enzyme fatty acid amidohydrolase. In the present study, compounds related to arachidonoyl-serotonin have been synthesised and investigated for their ability to inhibit anandamide hydrolysis by this enzyme in rat brain homogenates. Removal of the 5-hydroxy from the serotonin head group of arachidonoyl-serotonin produced a compound (N-arachidonoyltryptamine) that was a 2.3-fold weaker inhibitor of anandamide hydrolysis, but which also produced its inhibition by a mixed-type manner (Ki(slope) 1.3 µM; Ki(intercept) 44 µM). Replacement of the amide linkage in this compound by an ester group further reduced the potency. In contrast, replacement of the arachidonoyl side chain by a linolenoyl side chain did not affect the observed potency. N-(Fur-3-ylmethyl) arachidonamide (UCM707), N-(fur-3-ylmethyl)linolenamide and N-(fur-3-ylmethyl)oleamide inhibited anandamide hydrolysis with pI50 values of 4.53, 5.36 and 5.25, respectively. The linolenamide derivative was also found to be a mixed-type inhibitor. It is concluded that the 5-hydroxy group of arachidonoyl-serotonin contributes to, but is not essential for, inhibitory potency at fatty acid amidohydrolase. 相似文献
79.
P. J. Gerard J. R. F. Barringer J. G. Charles S. V. Fowler J. M. Kean C. B. Phillips A. B. Tait G. P. Walker 《BioControl》2013,58(2):149-162
Biological control systems are integral to New Zealand’s success as a nation reliant on exporting quality agricultural, forestry and horticultural products. The likely impacts of climate change projections to 2090 on one weed and four invertebrate management systems in differing production sectors were investigated, and it was concluded that most natural enemies will track the changing distributions of their hosts. The key climate change challenges identified were: disparities in natural enemy capability to change distribution, lack of frosts leading to emergence of new pests and additional pest generations, non-target impacts from range and temperature changes, increased disruptions caused by extreme weather events, disruption of host-natural enemy synchrony, and insufficient genetic diversity to allow evolutionary adaptation. Five classical biological control systems based on the introduced species Longitarsus jacobaeae, Cotesia kazak, Aphelinus mali, Microctonus aethiopoides and Microctonus hyperodae are discussed in more detail. 相似文献
80.
Environmental effects on population growth are often quantified by coupling environmental covariates with population time series, using statistical models that make particular assumptions about the shape of density dependence. We hypothesized that faulty assumptions about the shape of density dependence can bias estimated effect sizes of temporally autocorrelated covariates. We investigated the presence of bias using Monte Carlo simulations based on three common per capita growth functions with distinct density dependent forms (θ-Ricker, Ricker and Gompertz), autocorrelated (coloured) ‘known’ environmental covariates and uncorrelated (white) ‘unknown’ noise. Faulty assumptions about the shape of density dependence, combined with overcompensatory intrinsic population dynamics, can lead to strongly biased estimated effects of coloured covariates, associated with lower confidence interval coverage. Effects of negatively autocorrelated (blue) environmental covariates are overestimated, while those of positively autocorrelated (red) covariates can be underestimated, generally to a lesser extent. Prewhitening the focal environmental covariate effectively reduces the bias, at the expense of the estimate precision. Fitting models with flexible shapes of density dependence can also reduce bias, but increases model complexity and potentially introduces other problems of parameter identifiability. Model selection is a good option if an appropriate model is included in the set of candidate models. Under the specific and identifiable circumstances with high risk of bias, we recommend prewhitening or careful modelling of the shape of density dependence. 相似文献