[Results following coronary revascularization. 478 patients in a detailed follow-up].
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Biomedical subjects
P Ahlström
Publications and source records attributed to P Ahlström.
Felodipine versus placebo in stable effort-induced angina pectoris in patients inadequately controlled with metoprolol--a dose-finding study.
We compared the antianginal and antiischemic effect and tolerability of four different doses of felodipine extended-release (ER) tablets with placebo in patients with stable effort-induced angina pectoris treated with beta-blocker [metoprolol controlled release (CR) 100 mg once daily, o.d.]. Seventy-five patients were enrolled in the study. At the end of a 2-week single-blind period, all patients performed two exercise tests. If total exercise time did not vary by > 15% between the two tests and both tests were limited by anginal discomfort and concomitant ST depression of at least 1 mm, the patients were randomized to double-blind treatment (66 patients). Each patient received three of the following treatments: felodipine 2.5, 5, 10, or 20 mg, or placebo. The treatments were given o.d. in a cross-over, balanced incomplete block design with three of 3-week treatment periods. Exercise tests were performed 12 and 24 h after dose intake at the end of each treatment period. Fifty-nine patients completed the study. Twelve hours after dose administration, 10 and 20 mg felodipine increased time to onset of anginal pain by 60 and 63 s on the average, respectively, as compared with placebo (p = 0.001). Time to 1-mm ST depression was prolonged by 29 s after 10 mg (p = 0.14) and by 30 s after 20 mg (p = 0.13) felodipine. Time to end of exercise was increased by 28 s (p = 0.07) and 15 s (p > 0.20), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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Molecular dynamics simulation of a phospholipase A2-substrate complex.
We have used knowledge of the three-dimensional structure of phospholipids and phospholipases A2 together with biochemical data, computer graphics modelling and a 48 ps molecular dynamics simulation to predict the structure of a phospholipase A2-substrate complex. There is remarkable similarity between this predicted structure of enzyme-substrate complex and the structure that can be deduced from the observed enzyme-inhibitor complex. Molecular dynamics simulation highlights the importance of the calcium-ion in substrate binding and the persistence of the His-48 to water-hydrogen bond is compatible with the proposed role of this water molecule as the nucleophile in catalysis.
Animals↗
The kinetics of calcium binding to calmodulin: Quin 2 and ANS stopped-flow fluorescence studies.
The rate of calcium dissociation from bovine testis calmodulin was measured by fluorescence stopped-flow using the calcium indicator Quin 2 or the fluorescence probe 8-anilinonaphthalene sulphonate. Two processes are resolved with Quin 2 corresponding to dissociation from the high affinity sites (kdiss 2 to 9 s-1 for T = 11 to 28 degrees C) and from the low affinity sites (kdiss 293 to 550 s-1 for T = 11 to 19 degrees C). These rates and the activation parameters as determined for the slow process delta H not equal to = 59 +/- 10 kJ X mol-1 and delta S not equal to = 30 +/- 30 JK-1 X mol-1 are in good agreement with values determined from the 43Ca NMR exchange rates. These experiments provide confirmation that the calcium induced conformational change cannot be resolved kinetically from the calcium binding or dissociation, and by inference this conformational change is not a rate-limiting process in the function of calmodulin.
Aminoquinolines↗
[Differention of the neural tube. Experimental study in chick and quail embryos].
In order to study the possible influence of adjacent structures upon differentiation and proliferation of the chick spinal cord, a piece of neural tube of chick embryos incubated for 2 days (stages 12-14 of HAMBURGER and HAMILTON) was extirpated and replaced by an equal graft from a donor embryo of the same age. The grafts were rotated 90 or 180 degrees around their longitudinal axis. The examination of the serial histological sections and the analysis of the distribution of mitotic density in the rotated spinal cord of embryos fixed 2-8 days after the operation led to the following results: the differences in morphogenesis and histogenesis between dorsal and ventral sectors of the spinal cord are already determined in 2-day-old chick embryos. The reversal of the neural tube at this time has no effect either upon the typical differentiation or the characteristic distribution of the mitotic cells in the spinal cord.
Animals↗
Cyclic AMP and adenylate cyclase in the inner ear.
The activity of adenylate cyclase and the steady state levels of cyclic AMP (cAMP) were determined in stria vascularis (SV) and organ of Corti (OC) of the guinea pig cochlea. The activities are 12 and 19 pmoles/mg dry weight/minute for OC and SV, respectively. The activity was increased two to four-fold by NaF. The base level of cAMP is 4.2 and 4.4 nmoles/g dry weight in OC and SV, respectively. In contrast to brain, neither ischemia nor barbiturates produced major changes of the steady state levels of cAMP. No in vitro effect of cAMP upon the state of activation of glycogen phosphorylase was noticeable in either tissue. cAMP did not exert a significant in vitro inhibition of strial Na+K+-ATPase. Perilymphatic perfusion of cAMP (10-3 M) and of theophylline (5 times 10-3 M) did not produce changes in the endolymphatic potential (EP), but dibutyryl cAMP (10-3 M) led to a significant increase of EP. The alpha adrenergic blocking agent, phentolamine, produced very complex changes of the cochlear potentials. A possible role of catecholamines and cAMP in the secretory phenomena of the SV and in the transduction and/or transmission processes of the auditory sense organ are discussed.
Action Potentials↗