[On the biological effectiveness of pharmaceutical parathyroid hormone preparations].
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Animals↗
Biomedical subjects
B Lemmer
Publications and source records attributed to B Lemmer.
Decrease in adenylate cyclase activity antecedes neurofibrillary tangle formation.
In previous studies, the formation of cAMP was seen to be significantly reduced in various brain regions in Alzheimer patients. Recently, a staging system was introduced in which Alzheimer-related. histopathological changes were classified according to the pattern of alterations rather than their density. In this study, we examined the degree of correlation between these stages and the postmortem activity of the CAMP-generating enzyme adenylate cyclase. Our findings suggest that forskolin-stimulated adenylate cyclase activity is significantly decreased before major neurofibrillary changes develop. Early impairment of postreceptor signalling could have potentially important consequences for drug treatment and/or for the development of neurofibrillary changes.
Adenylyl Cyclases↗
Stereospecific and circadian-phase-dependent kinetic behavior of d,l-, l-, and d-propranolol in plasma, heart, and brain of light--dark-synchronized rats.
In light--dark-synchronized male rats, the kinetic behavior of d,l-, l-, and d-propranolol after single (1.78 and 8.89 mg/kg) or multiple drug administration (6 X 8.89 mg/kg) was studied in plasma, heart, and brain both in the light period (L) and in the dark period (D). With either dosage regimen the kinetics of racemic propranolol displayed a temporal dependency, elimination half-lives in plasma, heart, and brain being shorter during D than during L. This was observed with the stereoisomers only after single drug application with no circadian phase dependency at steady-state concentrations. On the other hand, the kinetic behavior of l- and d-propranolol exhibited pronounced stereospecificity in that t1/2 Beta, Vdbeta, plasma clearance, and drug accumulation in heart and brain were greater for l-propranolol than for the d-isomer. Stereospecific differences in t1/2 beta and elimination rate were more pronounced during D. In the light of the flow-dependent hepatic extraction of propranolol it is unlikely that daily variations in microsomal liver enzyme activity are responsible for the chronopharmacokinetics of propranolol. It is assumed that daily variations in liver blood flow, which is more effectively reduced by beta-receptor blockade in the period of increased sympathetic tone during D, are mainly responsible for the chronopharmocokinetics of the therapeutically used d,l-propranolol.
Animals↗
Effects of inhibitors of the catecholamine synthesis on motor activity in the rat during light and darkness.
Under controlled conditions of light and darkness (12:12 hrs) the influence of inhibitors of the tyrosine-hydroxylase (alpha-MT) and dopamine-beta-hydroxylase (FLA 63) on motor activity were investigated in male Wistar rats at different times of the day. Simultaneously, turnover experiments of the cerebral noradrenaline and dopamine were performed, which revealed diurnal variations within 24 hrs of a day. Both inhibitors showed clear-cut chronopharmacological differences in influencing motor activity, and a phase shift between the darkness-induced increase in motor activity and the maximum turnover rate of the cerebral dopamine was observed.
Animals↗
Circadian rhythm of soluble interleukin-2 receptor in healthy individuals.
The cytokine levels of soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6) and tumor-necrosis-factor alpha (TNF-alpha) were studied in 12 healthy volunteers at 11 different times of day. TNF-alpha levels were below the detection limit, and IL-6 levels were at baseline values of the respective assay used. Interindividual variations were found for the plasma levels of sIL-2R (179-524 U/ml). Shedded IL-2 receptors displayed a pronounced circadian phase-dependency (p less than 0.0001) with a peak value at 12:29 h and a trough at 4:14 h when a complex cosine function (period lengths: 24 h plus 12 h) was fitted to the data. These findings may be of importance when using sIL-2R as a diagnostic tool as well as in controlling efficacy of drug treatment.
Adult↗
Transition training.
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Community Health Services↗
Chronopharmacology: a new perspective in pharmacology.
Vital signs and several constituents of the serum and urine exhibit a circadian rhythm, and the same is true for the onset of several diseases. The rhythmic changes in the blood volume, functions of the liver and kidney, etc., have implications for drug availability, and the circadian changes should be taken into account in pharmacokinetic studies. These changes are the subject of chronopharmacokinetics. In addition to the circadian rhythm in changes in drug absorption, elimination and bioavailability, a rhythm of the intensity of drug effects and side-effects may also be observed: this is the domain of chronopharmacodynamics. Several examples demonstrate that chronopharmacokinetic and chronopharmacodynamic results support the view that the temporal organization of the organism is an important variable influencing the action of drugs.
Animals↗
Membrane effects of drugs interfering with adrenergic mechanisms.
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1-Propanol↗
Evidence for a circadian-phase-dependency in 3H-dihydroalprenolol binding and cyclic AMP content in heart ventricles of L-D-synchronized rats.
Receptor binding studies with 3H-dihydroalprenolol (3H-DHA, spec. act. 90-102 Ci/mmol) were performed in heart ventricular membranes of light-dark-synchronized (L: 7-19 h, D: 19-7 h) male rats, which were sacrificed either at 08:00 h or 20:00 h. Saturation, competition and kinetic studies revealed two specific 3H-DHA binding sites--being specific for mainly beta 1-adrenoceptors--which were abolished after addition of the guanine nucleotide Gpp(NH)p. In control experiments, i.e. in the absence of the guanine nucleotide, circadian-phase-dependent differences in the KD and Bmax values were observed. Total number of binding sites was about 40% higher in the 20:00 h-ventricles than in the 08:00 h-ventricles. Pretreatment with isoprenaline further decreased and catecholamine-depletion further increased Bmax values. In accordance with these findings a significant circadian rhythm in the ventricular cAMP content with a maximum at 20:00 h and a minimum at 08:00 h was observed.
Alprenolol↗