A. van Bogaert

Examination of G72 and D-amino-acid oxidase as genetic risk factors for schizophrenia and bipolar affective disorder.

A recent study has suggested that the brain-expressed genes for G72 and D-amino-acid oxidase (DAAO) exert an influence on susceptibility to schizophrenia. Our aim was to replicate this finding in German schizophrenic patients and to assess whether G72 and DAAO might also contribute to the development of bipolar affective disorder. We genotyped seven single-nucleotide polymorphisms (SNPs) in the G72 gene and three in the DAAO gene in 599 patients (299 schizophrenic, 300 bipolar) and 300 controls. At G72, individual SNPs and a four-marker haplotype were associated with schizophrenia. The most significant SNP as well as the haplotype were also associated with bipolar affective disorder (BPAD). DAAO was associated with schizophrenia, but not with BPAD. The association of variation at G72 with schizophrenia as well as BPAD provides molecular support for the hypothesis that these two major psychiatric disorders share some of their etiologic background.

Myocardial ultrastructure and haemodynamic reactions during experimental subarachnoid haemorrhage

Abstract The mechanisms governing the haemodynamic, electrocardiographic and ultrastructural changes following subarachnoid haemorrhage are studied. The experiments on dogs show that an increased cellular metabolism due to noradrenaline and to adrenaline, is an essential factor in the haemodynamic reactions in subarachnoid haemorrhage. During the stimulation stage of these hormones, ultrastructural changes appear, indicating an important migration of calcium ions from their store to their point of action. In so far as they influence the action potentials, these movements initially create a “hyperkalaemic” type ECG probably in relation with an associated potassium ion displacement. In the second stage, an “ischaemic” type of ECG change is found which is totally independent of hypoxia, but also caused by the increase in cellular metabolism. This second stage is still reversible. The last or third stage occurs when the hormones deeply disturb the cellular metabolism because of their high dose or because of their prolonged action. At this point irreversible and destructive cellular alterations occur.

Catecholamines in blood and myocardial tissue in experimental subarachnoidal hemorrhage.

The induction of experimental subarachnoidal hemorrhage (ESH) in the dog results in a rise in the adrenaline plasma concentration. The changes in plasma noradrenaline are biphasic: an ‘early noradrena

Effect of hypnorm, chloralosane and pentobarbital on the ultrastructure of the inner membrane of rat heart mitochondria

Rat heart mitochondria were isolated from four groups of animals treated in a different way. The animals of the first group were killed after decapitation (D-group) without previous anaesthesia. The three other groups of animals were anaesthetised with different anaesthetics. The second group (N-group) was anaesthetised with nembutal (sodium pentobarbital), the third group with chloralosane (C-group) and the fourth group with hypnorm (H-group). From these three anaesthetics only nembutal is known to interact with mitochondria. After retrograde perfusion and excision of the heart, mitochondria were prepared from the ventricles by standard methods. After freeze-fracturing the mitochondrial suspension, the intramembrane particle dimension and density on both fracture faces of the inner mitochondrial membrane were measured. The intramembrane particle diameter on the P-face of the inner membrane of the N-group mitochondria was significantly different from D-, C- and H-group mitochondria. Also the density and diameter of the intramembrane particles on the mitochondrial inner membrane of D-group mitochondria compared to C- and H-group mitochondria were significantly different at the 95% level of confidence. Between C- and H-group mitochondria no differences of these parameters were observed. From these results it is clear that, depending on the pretreatment of the animals, a different substructure of the inner membrane of heart mitochondria is obtained.

Influence of Some Hypotensive Drugs on the Effects of Hypothalamic Stimulation

Clonidine, L -α-methyldopa, propranolol as well as noradrenaline, when injected directly into the hypothalamic paraventricular (PV) nucleus area, enhance the activity of this center.

Vascular and noradrenalic reactions in the musculocutaneous bed during hypothalamic stimulation.

When electrical stimulation is applied to the ventromedial hypothalamic zone one observes an increase in systemic blood pressure. There also occur blood pressure variations in the isolated femoral circuit: two distinct phenomena were observed. The early event, being either an increase or a decrease in peripheral resistance, is directly related to the amount of noradrenaline produced locally. The late event is due to catecholamines arriving from the general circulation. Inhibition of local catecholamine release through the baroreceptor reflex and inhibition of ganglionic transmission by a large and sudden increase in adrenaline blood levels do influence the response in the isolated femoral circuit. Moreover the peripheral vasomotor tonus seems to be influenced by yet another mechanism, independent of local catecholamine release. This delicate mechanism depends on the balance between the degree of excitation of hypothalamic pressor (medial) and depressor (lateral) zones.

Arterial and venous responses to hypothalamic stimulation in the dog.

AbstractStimulation of the ventro-medial nucleus of the hypothalamus induces active constriction of both pre- and post-capillary vessels in the dogs hindlimb. Alpha-adrenolytic agents reduce these responses, indicating that they are mediated by the sympathetic nervous system. Stimulation of the paraventricular nucleus dilates both resistance and capacitance vessels. The present study demonstrates that hypothalamic neurones can control venomotor tone.

New Approach of the Cardio-Vascular Depressive Mechanism During Lateral Hypothalamic Stimulation

Paraventricular nucleus stimulation acts directly on the alpha- and beta-adrenoreceptors in heart and arterioles, eliciting arterial hypotension and cardiac chronotropism and inotropism decrease. Efferent pathways follow sympathetic nervous fibres through the medulla and the thoraco-lumbar ganglionic chain. The role of the alpha- and beta-adrenoreceptors in these depressive reactions is discussed.

Absence of a Prostaglandinic Mediator in the Lateral Hypothalamic Cardiovascular Inhibition

The cardio-vascular inhibition elicited by electrical stimulation of the paraventricular nucleus in the lateral hypothalamus of anaesthesized and desafferentiated dogs is not linked with a mediator release like PGE. The effect of this biological agent is not registered in the isolated femoral artery of a receiver, after deviation by a cruised circulation of the arterial blood of a hypothalamic stimulated donor dog. Antipyretics, which are also prostaglandin-synthetase inhibitors, enhance the lateral hypothalamic reactions. As the thermoregulation centre is localized in the same region as the cardio-vascular inhibition centre and because lowering of temperature depends upon vasodilation and decrease in the general cellular metabolism, both functions of the paraventricular nucleus activity, a hypothesis is proposed that thermoregulation and cardio-vascular inhibition centres are a functional and anatomical unity.

Hypothalamic Depressor Reactions in Anaesthetized Dogs After Baroreceptor Exclusion and During Norepinephrine Infusions

The stimulation of the paraventricular hypothalamic centre inhibits the vasoconstriction of the peripheric arterioles and the myocardial effects elicited by endogenous or exogenous increased catecholaminaemia.