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121.
Potent, orally active inhibitors of lipoprotein-associated phospholipase A(2): 1-(biphenylmethylamidoalkyl)-pyrimidones. 总被引:4,自引:0,他引:4
Helen F Boyd Stephen C M Fell Deirdre M B Hickey Robert J Ife Colin A Leach Colin H Macphee Kevin J Milliner Ivan L Pinto D Anthony Rawlings Stephen A Smith Ian G Stansfield Steven J Stanway Colin J Theobald Caroline M Whittaker 《Bioorganic & medicinal chemistry letters》2002,12(1):51-55
A series of 1-(biphenylmethylamidoalkyl)-pyrimidones has been designed as nanomolar inhibitors of recombinant lipoprotein-associated phospholipase A(2) with high potency in whole human plasma. 5-(Pyrazolylmethyl) derivative 16 and 5-(methoxypyrimidinylmethyl) derivative 27 demonstrated excellent pharmacodynamic profiles which correlated well with their pharmacokinetic effects. 相似文献
122.
Norman M. Ursula Smith A. Ian Hickey Michael J. 《International journal of peptide research and therapeutics》2001,8(3-5):195-199
Summary The zinc metalloendopeptidases EC 3.4.24.15 (EP 24.15) and EC 3.4.24.16 (EP 24.16) are closely related ubiquitous enzymes,
which have well-defined in vitro activities in generation and degradation of a range of specific peptide targets. Despite
this, little is known regarding their roles in whole animal physiology. One of the peptides degraded by these enzymes in vitro
is bradykinin, a mediator with potent effects on the vasculature at both systemic and local levels. This review summarises
the work that has examined the role of EP 24.15/24.16 in regulation of the vascular effects of bradykinin in vivo. This work
was made possible by the development of a specific stable inhibitor of these enzymes, JA-2. Use of this inhibitor has shown
that EP 24.15/24.16 are capable of regulating responses induced by exogenous bradykinin. This effect was observed at a systemic
level with an increase in the hypotensive effect of intravenous bradykinin. Further work is required to determine whether
these enzymes also regulate bradykinin produced endogenously. 相似文献
123.
A low-frequency response analysis of three Grass model 7 polygraphs was undertaken. Observed error was generally found to fall within the manufacturer's stated range of +5 to -10% of DC signal height over the frequency range of human respiration (0.1-3 Hz), but this was not the case for frequencies greater than 6 Hz under certain circumstances. The magnitude of error was seen to vary directly with frequency and indirectly with pen-deflection amplitude and paper speed. The pen-oscillograph apparatus was the predominant source of low-frequency error, and this is probably due to pen inertia and pen friction on the writing surface. Two schemes to reduce such error are presented. 相似文献
124.
D R Hickey K Jayaraman C T Goodhue J Shah S A Fingar J M Clements Y Hosokawa S Tsunasawa F Sherman 《Gene》1991,105(1):73-81
Genes encoding tuna, pigeon, and horse cytochromes c were constructed with synthetic oligodeoxyribonucleotides having preferred codons and portions of the iso-1-cytochrome c-encoding gene from the yeast Saccharomyces cerevisiae. The genes were ligated into an expression vector, which contains the normal 5'- and 3'-untranslated regions of the yeast iso-1-cytochrome c gene, and were integrated in single copy into the chromosome. Yeast strains were also constructed with multiple integrated copies of the pigeon gene. The heterologous and normal mRNA levels of the single-copy strains were equivalent. Although the N-terminal methionines were completely cleaved in the heterospecific proteins, the levels of trimethylation of Lys72 and acetylation of N-terminal glycines ranged from 39-78% and 10-70%, respectively. Horse cytochrome c was produced at a nearly normal level, whereas the pigeon and tuna cytochromes c were produced at approx. 40% of the normal levels. The levels of the cytochromes c and growth of the mutant yeast strains indicated that the heterospecific cytochromes c had approx. 50% specific activity in vivo. 相似文献
125.
Three main preventive principles against milk fever were evaluated in this literature review, and the efficacy of each principle was estimated from the results of controlled investigations. Oral calcium drenching around calving apparently has a mean efficacy of 50%–60% in terms of milk fever prevention as well as prevention of milk fever relapse after intravenous treatment with calcium solutions. However, some drenches have been shown to cause lesions in the forestomacs. When using the DCAD (dietary cation-anion difference) principle, feeding rations with a negative DCAD (measured as (Na + K) – (Cl + S)) significantly reduce the milk fever incidence. Calculating the relative risk (RR) of developing milk fever from controlled experiments results in a mean RR between 0.19 and 0.35 when rations with a negative versus positive DCAD are compared. The main drawback from the DCAD principle is a palatability problem. The principle of feeding rations low in calcium is highly efficient in milk fever prevention provided the calcium intake in the dry period is kept below 20 g per day. Calculating the relative risk (RR) of developing milk fever from controlled experiments results in a very low mean RR (between 0 and 0.20) (daily calcium intake below versus above 20 g/d). The main problem in implementing the low-Ca principle is difficulties in formulating rations sufficiently low in calcium when using commonly available feeds. The use of large doses of vitamin D metabolites and analogues for milk fever prevention is controversial. Due to toxicity problems and an almost total lack of recent studies on the subject this principle is not described in detail. A few management related issues were discussed briefly, and the following conclusions were made: It is important to supply the periparturient cow with sufficient magnesium to fulfil its needs, and to prevent the dry cows from being too fat. Available information on the influence of carbohydrate intake, and on the effect of the length of the dry period and prepartum milking, is at present insufficient to include these factors in control programmes. 相似文献
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127.
McArley Tristan. J. Hickey Anthony J. R. Wallace Lisa Kunzmann Andreas Herbert Neill. A. 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2019,189(3-4):399-411
Journal of Comparative Physiology B - Decreased oxygen (O2) availability (hypoxia) is common in rock pools and challenges the aerobic metabolism of fishes living in these habitats. In this study,... 相似文献
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