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Biomedical subjects

J H Meijer

Publications and source records attributed to J H Meijer.

At least 37 records · Page 2Linked to original sources

Light-induced phase shifts in onset and offset of running-wheel activity in the Syrian hamster.

The effects of light pulses on activity onset and offset were assessed in intergeniculate leaflet- and ventral lateral geniculate nucleus-lesioned Syrian hamsters with a precise onset and offset of circadian wheel-running activity. Light pulses applied to animals in constant darkness during the early subjective night induced phase delays in both activity onset and offset, while light pulses during the late subjective night induced phase advances in the onset and offset of activity. Despite the fact that the direction of onset and offset shifts were similar, differences were found in the magnitude of light-induced phase shifts. Steady state phase delays were larger in the activity onset, while steady state phase advances were largest in the offset of activity. We found phase delays and phase advances within one cycle after the presentation of a light pulse in both activity onset and offset. Differences in magnitude of these immediate phase shifts in activity onset and offset resulted in a compression of activity time for a number of cycles following a light pulse. Similar results were obtained in a selected group of intact animals indicating that intergeniculate leaflet- and ventral lateral geniculate nucleus-lesioned hamsters provide a good model to investigate the effects of light on circadian onset and offset of running-wheel activity.

Animals↗

The effects of electrical stimulation of the optic nerves and anterior optic chiasm on the circadian activity rhythm of the Syrian hamster: involvement of excitatory amino acids.

The circadian pacemaker of the suprachiasmatic nuclei (SCN) is entrained to the environmental light-dark cycle via the retinohypothalamic tract (RHT). It is unknown whether light activates or suppresses firing of the retinal ganglion cells which mediate photic entrainment. We therefore electrically stimulated the optic nerves and the anterior optic chiasm of hamsters with free-running activity rhythms in continuous darkness. These electrical stimulations are thought to induce a release of neurotransmitter at the RHT terminals. Electrical stimulation mimicked the phase dependent shifts induced by light pulses. The phase shifts were significantly larger than the shifts induced by sham stimulation in the same animals or by electrical stimulation in animals with an electrode outside the optic nerves and chiasm. Our results indicate that the retinal ganglion cells which project to the SCN are activated by light. Intraperitoneal administration of MK-801, a non-competitive antagonist of the NMDA-receptor, attenuated the phase delays induced by electrical stimulation in the early subjective night. This suggests that an excitatory amino acid mediates the effects of light upon the circadian pacemaker.

Amino Acids↗

Susceptibility to decubitus ulcer formation.

The hypothesis of blood-flow recovery time after pressure relief was prospectively evaluated as a measure of a patient's susceptibility to develop decubitus ulcers. This blood-flow recovery time was measured using the noninvasive pressure-temperature-time (PTT) method, which uses a 10-minute test-pressure stimulus. The blood-flow response after pressure relief was measured by means of skin-temperature measurements. The evaluation was performed in a group of 109 elderly nursing home patients. A pressure-index was used as a measure for the intensity and duration of pressure and shear forces, to which a patient was exposed, to measure a set of external determinants that are independent of the susceptibility. Both the blood-flow recovery time and the pressure-index were found to correlate significantly with the risk to develop decubitus. A conceptualization of the relationship between the risk, on the one hand, and the susceptibility and the external determinants, on the other hand, is presented, assuming independence (orthogonality) of both sets of determinants. Based on this conceptualization, a three-dimensional risk-relationship was constructed. It is concluded that the blood-flow recovery time can be considered to be a measure for the susceptibility. Further, the conceptualization provides valuable insight into the risk-relationships and forms a base for future research with regard to susceptibility.

Activities of Daily Living↗

Glutamate immunoreactivity in terminals of the retinohypothalamic tract of the brown Norwegian rat.

The mammalian circadian pacemaker of the suprachiasmatic nucleus (SCN) is entrained to the environmental light-dark cycle via a retinal projection, the retinohypothalamic tract (RHT). Several studies suggest that an excitatory amino acid, possibly glutamate, is involved in photic entrainment. However, it has not yet been established whether glutamate is a transmitter of the RHT itself. We have now identified terminals of the RHT in the SCN of brown Norwegian rats by intravitreous injections of horse radish peroxidase conjugated to cholera toxin. To detect glutamate immunoreactivity (IR), post-embedding immunocytochemistry was performed with polyclonal antibodies which were visualized for electron microscopy with colloidal gold particles. Retinal terminals had a significantly 82% higher glutamate-IR than their post-synaptic dendrites and a significantly 76% higher glutamate-IR than non-retinal terminals. These observations provide ultrastructural evidence that glutamate is a transmitter of the RHT.

Animals↗

The effects of glutamate on membrane potential and discharge rate of suprachiasmatic neurons.

The suprachiasmatic nucleus (SCN) is a major pacemaker for circadian rhythms in mammals. Photic entrainment of the circadian pacemaker is mediated by the retinohypothalamic tract (RHT). Most likely, excitatory amino acids function as neurotransmitters in this pathway. We have now investigated the effect of glutamate on the membrane potential of cultured SCN cells of the rat with the aid of the patch clamp technique. It was found that 1 mM glutamate depolarizes the cells by about +44 mV. In spontaneously active neurons, the glutamate induced depolarization caused either an increase in discharge or a depolarization block. We then investigated the effect of 1 mM glutamate on SCN discharge in the acutely prepared hypothalamic slice of the hamster. In most cells glutamate induced an increase in discharge whilst in a few cells discharge was suppressed. Both series of experiments indicate that glutamate in the used dosage was effective and its effect reversible. The data are discussed with respect to the failure of 1 mM glutamate injections to mimic the effect of light on the circadian activity rhythm of the hamster.

Animals↗

The relation between light-induced discharge in the suprachiasmatic nucleus and phase shifts of hamster circadian rhythms.

The role of neurophysiological activation of suprachiasmatic nucleus (SCN) cells in phase shifting the circadian pacemaker of the hamster was investigated in a combined behavioural and electrophysiological study. An electrophysiological study examined the relation between the pattern of light presentation and the induced discharge rate in the SCN. Behavioural experiments examined the relation between the pattern of light presentation and the magnitude of phase shift induced. The combination of these results provides an indirect assay of the relations between induced neural discharge in the SCN and phase shifts of the circadian activity rhythm. The data indicate that the magnitude of phase shifts is monotonically, but not linearly, related to photically induced changes in discharge rate.

Action Potentials↗

Aspartate injections into the suprachiasmatic region of the Syrian hamster do not mimic the effects of light on the circadian activity rhythm.

The excitatory amino acids glutamate and aspartate are thought to be involved in the photic entrainment of the circadian pacemaker of the suprachiasmatic nuclei (SCN). When applied to the SCN region glutamate imitates the effects of dark pulses on the circadian activity rhythm rather than those of light. We have now injected aspartate into the SCN region of Syrian hamsters. These injections mimicked the effects of dark pulses as well, in so far as slight advances of the activity rhythm were obtained during the subjective day. However, the mean phase shift was not significantly different from the shift obtained with control injections. It is concluded that (1) aspartate has little or no effect on the phase of the circadian activity rhythm and (2) none of the putative transmitters of the photic afferents of the SCN produces the effects of light upon injection.

Animals↗

Influence of high and low sodium dialysis on blood volume preservation.

Haemodialysis has a profound effect on fluid balance. Since fluid is initially withdrawn from the intravascular compartment, hypovolaemia is a frequent complication. A fluid shift from the overhydrated interstitium towards the intravascular compartment can counteract hypovolaemia. However, a fast decline in extracellular osmolality may cause an increase in the intracellular volume, reducing the available amount of fluid to compensate for the hypovolaemia. To overcome this problem, the use of alternating high and low sodium dialysate is advocated. In this study six patients were studied during standard haemodialysis (HD) and during dialysis with alternating high and low sodium dialysate (HLSD). Changes in intracellular fluid volume (IFV) and extracellular fluid volume (EFV) of tissue and blood were measured by means of a non-invasive electrical conductivity method. Changes in blood volume (BV) were studied by serial erythrocyte counts. Plasma sodium concentration was determined at regular intervals. The distribution volume of sodium during the high and low sodium episodes of HLSD was calculated according to a mathematical model. HLSD led to fluctations in plasma sodium concentration that induced changes in red cell volume, but not in IFV. Distribution of sodium was largely confined to blood. BV was better preserved during HLSD than during HD, probably due to a higher mean plasma sodium concentration. Postdialysis sodium concentration however, was not significantly different between HLSD and HD. These data suggest that the better BV preservation during HLSD results from an induced osmotic gradient across the capillary wall, rather than from an osmotic gradient across the cell membrane.

Blood Volume↗

The two-oscillator circadian system of tree shrews (Tupaia belangeri) and its response to light and dark pulses.

The wheel-running activity rhythm of tree shrews (tupaias; Tupaia belangeri) housed in constant darkness (DD) phase-advanced following a 3-hr light pulse at circadian time (CT) 21. Dark pulses of 3 hr presented to tupaias in bright constant light (LL) did not induce significant phase shifts of the free-running activity rhythm, irrespective of the CT. In dim LL, tupaias showed simultaneous splitting of their circadian rhythm of wheel-running activity, nest-box activity, and feeding behavior. Light pulses of 6 hr and 2300 lux were presented to 13 tupaias with split wheel-running activity rhythms. These light pulses induced immediate phase shifts in the two components of the split rhythm in opposite directions. No differences were observed between the light-pulse phase response curves of the two components. Equally large immediate phase advances were induced in both components by light pulses of 230 lux, but not by 23 lux. The final phase shifts were small at all CTs. In two tupaias, activity rhythms transiently split and re-fused. Analysis of the relative position of the components in one of these indicates asymmetry in the coupling between the components.

Animals↗

Physiological basis for photic entrainment.

The suprachiasmatic nuclei of the hypothalamus contain a major circadian pacemaker. The most important external stimulus that affects the circadian pacemaker is the environmental light-dark cycle. The effects of light and darkness on the pacemaker at various phases of the circadian cycle have been well documented. In this paper these effects are summarized briefly. A number of pharmacological and neurophysiological studies will then be presented that are related to the processing of light information by the circadian system. It will be considered whether these studies have increased insight in the behavioral responsiveness to light.

Animals↗

Photically responsive neurons in the hypothalamus of a diurnal ground squirrel.

The suprachiasmatic nuclei (SCN) function as a circadian pacemaker. Entrainment to the external light-dark cycle is mediated by the retina which gives rise to both direct and indirect projections to the SCN. The hypothalamic targets of the retinohypothalamic tract (RHT) were investigated in thirteen-lined ground squirrels (Spermophilus tridecemlineatus) following WGA-HRP injections. The results indicate that retinal fibers project to the entire SCN. Extracellular single-unit activity was recorded in and near the SCN of thiopental sodium anesthetized squirrels while the eyes were photically stimulated. A small population of hypothalamic cells were responsive to retinal illumination. About half of these cells were activated by light while the others were light-suppressed. The majority of these cells responded in a sustained way to light pulses. Light intensities of at least 1000 lux appeared necessary to induce a sustained response to light. No differences in light responsiveness were observed between visual cells inside and outside the SCN. The visual properties of SCN cells have previously been investigated in hamsters and rats, both nocturnal species. Hypothalamic cells in all 3 species were similar in that they showed predominantly sustained responses to retinal illumination. The diurnal squirrel differed from the other two species in that there was a higher proportion of photically suppressed cells in the squirrel, and in that higher light intensities were required to stimulate photically responsive neurons.

Action Potentials↗

Hamster circadian rhythms are phase-shifted by electrical stimulation of the geniculo-hypothalamic tract.

The suprachiasmatic nuclei (SCN) contain the major pacemaker for mammalian circadian rhythms. The SCN receive photic input both directly, via the retinohypothalamic tract (RHT), and indirectly, via the geniculohypothalamic tract (GHT), which originates in cells in the intergeniculate leaflet (IGL) and anterior portions of the ventral lateral geniculate nucleus (vLGN). We tested whether electrical stimulation of the GHT would induce phase shifts in wheel-running activity rhythms of Syrian hamsters housed in continuous darkness or continuous illumination. In both lighting conditions, electrical stimulation of the GHT induced mainly phase advances when given during the late subjective day and small phase delays when given during the late subjective night and early subjective day. Stimulation in the thalamus outside the GHT failed to produce similar phase shifts. Repeated daily stimulation had only a weak entraining effect on the activity rhythm. Activation of GHT neurons appears to influence the pacemaker for activity rhythms in a phase-dependent manner.

Animals↗

Method for the measurement of susceptibility to decubitus ulcer formation.

A method for measuring the susceptibility of a patient to develop decubitus ulcers is described and initially evaluated. It is based on an indirect, noninvasive measurement of the transient regional blood flow response after a test pressure load which simulates the external stimulus for pressure-sore formation. This method was developed to determine the individual risk of a patient and to study the subfactors which contribute to the susceptibility. This would also offer the possibility of evaluating the effect of preventive treatment aimed at reducing the susceptibility. The method was found to discriminate between preselected elderly patients at risk on the one hand, and non-risk patients and healthy young adults on the other hand. No differences in blood flow responses were found between the non-risk elderly patients and the healthy young adults. This suggests that age per se is not a factor in the formation of pressure sores. In the risk group the recovery time after pressure relief was found to be three times as long as the duration of the pressure exercise. This indicates that the recovery time after pressure exercise may be as important as the period of pressure exercise in deducing the risk of developing decubitus ulcers.

Adult↗

Measurement of transcellular fluid shift during haemodialysis. Part 1. Method.

A method is presented to measure transcellular fluid shifts during haemodialysis based on a simplified model of the electrical admittance of biological tissues. It allows for the measurement of intracellular and extracellular conductivities and their ratios. The method is noninvasive, clean and harmless, and can be easily computerised in order to be performed continuously. A typical example is given of a recording during haemodialysis.

Body Fluids↗

Measurement of transcellular fluid shift during haemodialysis. Part 2. In vitro and clinical evaluation.

A method to measure intra- and extracellular conductivity is evaluated. In vitro experiments show that these two variables can be measured separately. The conductivity appears to depend on the concentration and fluid volume of the compartment concerned. In vitro variation of the intracellular volume of blood by dilution and by shrinking and swelling of blood cells is detectable by this method. In vivo too the method seems to detect intra- and extracellular fluid volumes separately. The course of these two variables during different strategies of haemodialysis is determined.

Body Fluids↗

Pulmonary shunting after cardiopulmonary bypass.

The effect of cardiopulmonary bypass (CPB) on pulmonary function was investigated in 32 adult patients, including 23 patients undergoing coronary artery bypass grafting and nine patients undergoing heart-valve replacement. Clinical indicators for pulmonary insufficiency, such as chest X-ray, gas exchange and lung function tests were measured. Transthoracic electrical impedances were measured, and the mean specific thoracic impedance (RHO) was calculated. (RHO is an accurate indicator for the intrathoracic fluid content; low RHO values correspond with high intrathoracic fluid content.) Significant postoperative decreases in RHO were paralleled by a significant impairment of gas exchange. Chest X-rays demonstrated accumulation of intrathoracic fluid. Lung function tests showed significant postoperative decreases in lung volumes and vital capacity. These findings are consistent with the concept that CPB provokes an inflammatory reaction in the lung. The non-invasive RHO measurement proved to be simple and in good agreement with clinical indicators. This method may be a real asset in the prevention and treatment of pulmonary dysfunction after CPB. The possibility of calibrating RHO with respect to absolute values of intrathoracic fluid content should be investigated.

Cardiography, Impedance↗