[Pharmaokinetics of beta-escin after administration of various Aesculus extract containing formulations]. / Pharmakokinetik von beta-Aescin nach Gabe verschiedener Aesculus-Extrakt enthaltender Formulierungen.

With a specific radioimmunoassay the pharmacokinetics and relative bioavailability of escin was measured after administration of different formulations containing Aesculus-extract. Of special interest was the relative bioavailability of escin after administration of a newly developed film-coated tablet with sustained release in comparison to a reference formulation. In a cross-over steady-state study in 24 volunteers bioequivalence of test and reference preparation could be demonstrated. The 90% confidence interval of the AUC (O-tau) was 98.3 to 120.9%.

Afferent connections of the nucleus centralis amygdalae. A horseradish peroxidase study and literature survey.

The central nucleus of the amygdala has been shown to be involved in cardiovascular regulation and the integration of arousal. In this study, the afferent input was investigated in cat by microinjecting horseradish peroxidase (HRP) into the central nucleus and examining retrogradely-labelled cells in the brain. Retrograde labelling was found in the cortex next to the sulcus ectosylvius anterior, fissura lateralis Sylvii, sulcus rhinicus anterior and posterior, sulcus suprasylvius, and pyriform and entorhinal cortices as well as in the insula and claustrum. Each of the sub-nuclei of the amygdaloid complex exhibited retrogradely-labelled perikarya. Labelled cells were also found in the diagonal band of Broca, nucl. lateralis septi, and nucl. proprius striae terminalis (bed nucl. of stria terminalis). In the hypothalamus the area preoptica medialis and lateralis, nucl. dorsomedialis, paraventricularis, periventricularis, arcuatus and mammilaris medialis were labelled. The nucl. subthalamicus, zona incerta, peripeduncular system, substantia nigra, and nucl. interpeduncularis contained HRP-marked cells. In the thalamus labelled cells were observed in the nucl. reuniens, nucl. centroposterior lateralis, nucl. latero-posterior, nucl. posterior, nucl. centro-anterior, antero-dorsalis, antero-medialis, antero-lateralis, centrum mdianum, nucl. reticularis, nucl. rhomboideus, nucl. parafascicularis and subfascicularis. The area tegmentalis Tsai and the corpora geniculata also contained labelled cells. In the brain stem, HRP-marked cells could be detected in the brachium colliculi inferioris, aqueductal grey matter, locus coeruleus, nucl. parabrachialis, in various nuclei of the formatio reticularis, in the nucl. retrofascialis, nucl. solitarius, nucl. commissuralis, nucl. ambiguus and nucl. dorsalis n. vagi. The results were compared to other neuroanatomical studies and to functional studies of the amygdala.

Cardiovascular changes during arousal elicited by stimulation of amygdala, hypothalamus and locus coeruleus.

Experiments were performed in chronically operated cats first awake and thereafter anesthetized with pentobarbitone, 16-20 mg/kg i.v. Stimulation of the central amygdala in awake cats elicited an arousal reaction seen in cortical and hippocampal EEG, and in muscle activity of dorsal neck muscles. Concomitantly therewith were autonomic system reactions resulting in a decrease in aortic blood flow distal to the renal arteries, an increase in arterial blood pressure, a tachycardia during, and a short-lasting bradycardia at the end of stimulation. In slightly anesthetized cats the cardiovascular reactions were found to be qualitatively similar. If the postero-lateral hypothalamus or the locus coeruleus complex were stimulated in cats first awake and thereafter anesthetized, similar arousal reactions and similar cardiovascular changes were obtained as with amygdaloid stimulations. However, the onset and magnitude of the response were more abrupt and more marked than those obtained by amygdaloid stimulations. Recordings of single unit activity within the central amygdala during spontaneously occurring changes in the level of arousal showed that amygdaloid units (n = 10) discharged at a rate of 7-14 impulses/sec during wakefulness whereas during slow wave sleep (n = 5) the discharge was only 2-9 impulses/sec. The hypothesis is put forward that the amygdala integrates behavioral and cardiovascular changes during arousal.

Absence of sympathetic cholinergic vasodilatation in cats during early stages of affective behaviour elicited by stimulation of central amygdala, postero-lateral hypothalamus and locus coeruleus.

1. Stimulation of the central amygdala, postero-lateral hypothalamus and locus coeruleus in cats resulted in a sustained increase in arterial pressure, an increase in heart rate, with a poststimulation bradycardia and an increase in peripheral resistance (vasoconstriction in the vessels of the hindlimbs). The behavioural pattern was characterized by an alerting reaction. Increased stimulus intensities resulted in rage reactions if the amygdala or the hypothalamus were stimulated. 2. Stimulation of the basal amygdala resulted in a cardiovascular pattern characterized by a sympathetic cholinergic vasodilatation. The concomitantly observed behaviour was characterized by alerting, anxious behaviour, eventually resulting in defence. 3. Alerting was not necessarily linked to sympathetic cholinergic vasodilatation. 4. The cardiovascular pattern including sustained vasoconstriction of the vessels of the hindlimbs was supposed to be of greater importance for the induction of hypertension than the cardiovascular pattern, including sympathetic cholinergic vasodilatation.