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Biomedical subjects

Bertha van der Dijs

Publications and source records attributed to Bertha van der Dijs.

At least 19 recordsLinked to original sources
PubMed2006

Central nervous system circuitry involved in the hyperinsulinism syndrome.

Raised plasma levels of insulin, glucose and glucagon are found in patients affected by 'hyperinsulinism'. Obesity, hypertension, mammary plus ovary cysts and rheumatic symptoms are frequently observed in these patients. Sleep disorders and depression are also present in most subjects affected by this polysymptomatic disorder. The simultaneous increases of glucose, insulin and glucagon plasma levels seen in these patients indicate that the normal crosstalk between A cells, B cells and D cells is disrupted. With respect to this, it is well known that glucose excites B cells (which secrete insulin) and inhibits A cells (which secrete glucagon), which in turn excites D cells (which secrete somatostatin). Gastrointestinal hormones (incretins) modulate this crosstalk both directly and indirectly throughout pancreatic and hepatobiliary mechanisms. The above factors depend on autonomic nervous system mediation. For instance, acetylcholine released from parasympathetic nerves excites both B and A cells. Noradrenaline released from sympathetic nerves and adrenaline secreted from the adrenal glands inhibit B cells and excite A cells, which are crowded with beta(2)- and alpha(2)-receptors, respectively. Noradrenaline released from sympathetic nerves also excites A cells by acting at alpha(1)-receptors located at this level. According to this, the excessive release of noradrenaline from these nerves should provoke an enhancement of glucagon secretion which will result in overexcitation of insulin secretion from B cells. That is the disorder seen in the so-called 'hyperinsulinism', in which raised plasma levels of glucose, insulin and glucagon coexist. Taking into account that neural sympathetic activity is positively correlated to the A5 noradrenergic nucleus and median raphe serotonergic neurons, and negatively correlated to the A6 noradrenergic, the dorsal raphe serotonergic and the C1 adrenergic neurons, we postulate that this unbalanced central nervous system circuitry is responsible for the hyperinsulinism syndrome.

Animals↗
PubMed2006

Dorsal raphe vs. median raphe serotonergic antagonism. Anatomical, physiological, behavioral, neuroendocrinological, neuropharmacological and clinical evidences: relevance for neuropharmacological therapy.

Monoaminergic neurons located in the central nervous system (CNS) are organized into complex circuits which include noradrenergic (NA), adrenergic (Ad), dopaminergic (DA), serotonergic (5-HT), histaminergic (H), GABA-ergic and glutamatergic systems. Most of these circuits are composed of more than one and often several types of the above neurons. Such physiologically flexible circuits respond appropriately to both external and internal stimuli which, if not modulated adequately, can trigger pathophysiologic responses. A great deal of research has been devoted to mapping the multiple functions of the CNS circuitry, thereby forming the basis for effective neuropharmacological therapeutic approaches. Such lineal strategies that seek to normalize complex and mixed physiological disorders, however, meet only partial therapeutic success and are often followed by undesirable side effects and/or total failure. In light of these, we have worked to develop possible models of CNS circuitry that are less affected by physiological interaction using the models to design more effective therapeutic approaches. In the present review, we cite and present evidence supporting the dorsal raphe versus median raphe serotonergic circuitry as one model of a reliable paradigm, necessary to the clear understanding and therapy of many psychiatric and even non-psychiatric disturbances.

Animals↗
PubMed2006

Central nervous system circuitry and peripheral neural sympathetic activity responsible for essential hypertension.

Both clinical and experimental studies dealing with patients affected by idiopathic or essential hypertension (EH) are devoted to the great deal of physiological, pharmacological and pathological as well as therapeutical issues of EH. However, most articles devoted to EH do not refer to the central nervous system mechanisms underlying this disease and the channels which allow that these mechanisms are funneled to the peripheral autonomic nervous system and trigger this cardiovascular disorder. In the present review article we attempted to reach this target devoted to the central nervous system circuitry involved in the cardiovascular pathophysiology. We postulated that EH depends on the predominance of the binomial A5 noradrenergic (NA) nucleus + median raphe serotonergic (5-HT) nucleus over the (A6)-NA + dorsal raphe-5HT nuclei. This hypothesis receives additional support from our results obtained throughout the neuropharmacological therapy of this type of neurophysiological disorder. Our therapeutical strategy is addressed to enhance the activity of the (A6)-NA + dorsal raphe-5HT binomial circuitry.

Acetylcholine↗
PubMed2005

Acute effects of tianeptine on circulating neurotransmitters and cardiovascular parameters.

Tianeptine is a serotonin-uptake enhancer drug whose antidepressant effectiveness is based on its ability to reduce rather than increase serotonin availability at the synaptic cleft. This paradoxical neuropharmacological mechanism has raised doubt among neuropharmacologists and psychiatrists as to the role of tianeptine as a trusty-reliable antidepressant drug. This controversial issue led us to investigate the acute effects of a single, oral dose (12.5 mg) of this drug on circulating neurotransmitters and cardiovascular parameters in 50 healthy subjects. The drug provoked a striking and significant reduction of plasma noradrenaline (NA) and plasma serotonin (f-5-HT) while it increased plasma dopamine (DA) and platelet serotonin (p-5-HT) concentrations within the 4-h study period. No adrenaline (Ad) changes were registered. The NA/Ad ratio and the f-5-HT/p-5-HT ratio showed significant reduction throughout the test. Finally, although diastolic blood pressure (DBP) showed significant decrease, neither systolic blood pressure (SBP) nor heart rate (HR) showed significant change. These findings are consistent with the postulation that tianeptine reduces both neural sympathetic activity and parasympathetic activity without affecting adrenal sympathetic activity, enabling us to discuss the possible mechanisms involved in the antidepressant effects of tianeptine. The well-known fact that major depressed patients always show raised NA plus lower than normal p-5-HT levels, both disorders which are normalized by tianeptine, gives neurochemical support to the clinical improvement triggered by the drug in these patients. Summarizing, the results presented in this study demonstrate that tianeptine triggers significant reduction of circulating noradrenaline and plasma serotonin while increasing circulating dopamine and platelet serotonin. Other possible neuropharmacological effects are also discussed.

Administration, Oral↗
PubMed2005

Neurochemical, neuroautonomic and neuropharmacological acute effects of sibutramine in healthy subjects.

Sibutramine is a neuropharmacological drug that exerts central (CNS) and peripheral effects including noradrenaline (NA), and serotonin (5-HT) uptake inhibition. In addition, the drug is able to induce release from DA axons. We measured levels of circulating neurotransmitters in 20 healthy subjects during supine-resting (fasting) state before and after 15 mg of oral sibutramine. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were also monitored. Sibutramine triggered sustained and progressive increase of NA, NA/Ad ratio and DBP. Slight increases of DA were also registered between the 60 and 240 min periods. The rise in DA tended to fade progressively, reaching basal level at 360 min period. Diastolic blood pressure, but neither SBP nor HR, showed significant increases that correlated positively with NA/Ad ratios. Slight but significant negative correlation was also found between DBP and DA. This correlation tended to fade throughout the trial to show no significance at the 360 min period. Although neither plasma serotonin (f-5HT) nor platelet serotonin (p-5HT) values showed significant variation throughout the trial, the f-5HT/p-5HT ratio showed significant decrease throughout. Significant negative correlation was found between f-5HT/p-5HT ratio and NA/Ad ratio. Our results indicate that sibutramine stimulates neural sympathetic activity but not adrenal sympathetic activity in healthy individuals. Further, sibutramine lowers parasympathetic activity. The moderate rise in diastolic blood pressure triggered by sibutramine would be associated with CNS-NA enhancement plus parasympathetic inhibition.

Antidepressive Agents↗
PubMed2004

Circulating neurotransmitters during the different wake-sleep stages in normal subjects.

We investigated the changes of circulating neurotransmitters during the wake-sleep cycle in order to find possible correlations with the activity of central neurocircuitry functioning. Noradrenaline (NA), adrenaline (Ad), dopamine (DA), platelet serotonin (p-5HT), plasma serotonin (f-5HT) and plasma tryptophan (TRP) were assessed during the morning (supine resting + 1-min orthostasis + 5-min exercise) and at night (supine resting + slow wave sleep (SWS) + REM sleep). Only NA increased in the plasma during short-lasting (1-min) orthostasis morning waking period. Both NA and Ad rose during moderate exercise. The nocturnal results demonstrated that whereas Ad dropped during the supine resting, NA did not fall until SWS period. Although DA did not show significant changes during the nocturnal test, the NA/DA ratio showed significant reduction. The analysis of correlations supports the postulation that this finding reflects the DA modulatory role on neural sympathetic activity. Both f-5HT and p-5HT values were lower during sleep cycle than wake periods. However, they showed progressive rises during sleep stages. Conversely, the f-5HT/p-5HT ratio showed significantly greater values during the SWS period than during supine resting and REM periods. These findings are consistent with the postulation that f-5HT/p-5HT ratio is positively associated with parasympathetic activity during the sleep-cycle. We concluded that the profile of sleep-cycle circulating neurotransmitters differs from that obtained during waking periods. According to the above, we attempted to correlate the profile of circulating neurotransmitters with the very well-known central neurocircuitry functioning during wake-sleep cycle, in experimental mammals.

Adolescent↗