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Biomedical subjects

J Wenzel

Publications and source records attributed to J Wenzel.

At least 37 records · Page 2Linked to original sources

Erythropoietin production in healthy volunteers subjected to controlled hypobaric hypoxia: further evidence against a role for adenosine.

AIMS: Objective of this study was to investigate whether adenosine modulates renal erythropoietin production. METHODS: In the present study erythropoietin production was stimulated by hypobaric hypoxia by subjecting healthy volunteers to a simulated altitude of 4000 m in a low pressure chamber for 5.5 h. During exposure to hypoxia the subjects received i.v. in a randomized, single-blind, cross-over fashion the non-specific adenosine antagonist theophylline, the adenosine reuptake inhibitor dipyridamole and placebo. RESULTS: Contrary to the working hypothesis, theophylline did not decrease and dipyridamole did not further boost erythropoietin concentrations. CONCLUSIONS: The results are in agreement with our earlier study using haemorrhage as a controlled physiological stimulus of erythropoietin production, and would question a major role for adenosine as a mediator of renal erythropoietin production.

Adenosine↗

Two-crew operations: stress and fatigue during long-haul night flights.

BACKGROUND: As part of a research program concerning legal aspects of two-pilot operations on long-haul routes, the purpose of the study was to investigate two-crew extended range operations during a flight roster with two consecutive night flights and a short layover. HYPOTHESIS: Present flight time regulations may not be adequate for two-crew minimum operations. METHODS: The study was conducted in cooperation with a German airline company on the route Frankfurt (FRA)-Mahe (SEZ). There were 11 rotations (22 flights) that were investigated by pre-, in- and post-flight data collection each time from the two pilots. Recordings included sleep, taskload, fatigue and stress by measurement of EEG, ECG, motor activity, and subjective ratings. The average actual flight times were 9:15 h (FRA-SEZ) and 9:53 h (SEZ-FRA). All flights took place at night. The layover duration in Mahe was 13:30 h during day-time. RESULTS: During layover, sleep was shortened by 2 h on average compared with 8-h baseline sleep. The two consecutive night duties resulted in a sleep loss of 9.3 h upon return to home base. Inflight ratings of taskload showed moderate grades, but for fatigue ratings an increasing level was observed. Fatigue was more pronounced during the return flight and several pilots scored their fatigue at a critical level. Motor activity, brainwave activity (occurrences of micro-events) and heart rate indicated drowsiness and a low state of vigilance and alertness during both night flights, but these effects were more pronounced during the second flight. CONCLUSIONS: From the findings it is concluded that a duty roster, as conducted in this study, may impose excessive demands on mental and physiological capacity.

Adult↗

Morphological alterations of hippocampal pyramidal neurons heterotopically transplanted into the somatosensory cortex of adult rats: a quantitative Golgi study.

A characteristic feature of hippocampal organization is the laminated termination of extrinsic and intrinsic afferents. At present, it is not known to what extent these layer-specific fiber projections modulate the development and final shape of the dendritic arbor of hippocampal target neurons. In the present study, pieces of late embryonic (E18) rat hippocampus were transplanted heterotopically into a cavity in the somatosensory cortex of 6-8 week-old recipient rats. Here, the transplanted neurons differentiated and survived up to several months in the absence of their specific extrinsic afferents. Moreover, tracing of transplant connections with the carbocyanine dye DiI revealed only a limited projection between the transplant and the host neocortex. Golgi-impregnated transplants were used to analyze the postsynaptic structures (dendrites and spines) of hippocampal pyramidal cells quantitatively. Compared with controls, the transplanted pyramidal neurons showed a significant reduction of apical primary dendrites and basal dendritic branches, i.e. of peripheral dendritic portions that originate farther from the soma. In contrast, the number of basal primary dendrites originating directly from the perikaryon was enhanced. Spine density on the main apical dendritic shaft was significantly lower in all peripheral dendritic segments in transplanted neurons. We conclude from our results that the absence of layer-specific extrinsic afferents that normally terminate on peripheral parts of the dendritic arbor of hippocampal pyramidal neurons caused a reduction of these peripheral dendrites and spines. In contrast, the increase of dendrites and spines near the cell body might be induced by intrinsic fibers that normally terminate on these proximal dendritic portions and are known to sprout under transplant conditions.

Animals↗

The feasibility of Doppler monitoring during EVA.

During extravehicular activities (EVA) outside the spacecraft, astronauts have to work under reduced pressure in a space suit. This pressure reduction induces the risk of decompression sickness (DCS) by the formation of gas bubbles from excess nitrogen dissolved in the organism by breathing air at normal pressure. Under laboratory conditions the gas bubbles moving in the blood stream can be detected by the non-invasive ultrasonic Doppler method. By early detection of excessive bubble formation the development of DCS symptoms may be prevented by early application of preventative measures. The method could also be useful when applied in the space suit in order to compare the results of laboratory tests with operational results, because there is a discrepancy according to the DCS risk of laboratory experiments and actual EVA missions, where no symptoms have been reported yet. A prototype Doppler sensor has been developed and implemented in the Russian Orlan suit. To investigate the feasibility of this method under simulated space conditions, the equipment has been used in a series of 12 thermovacuum chamber tests with suited subjects, where intravenous bubble formation was compared to unsuited control experiments. In more than 50% of the suited tests good Doppler recordings could be achieved. In some cases with unsatisfying results the signal could be improved by breathholding. Although the results do not yet allow any conclusion about a possible difference between suited and unsuited subjects due to the small number of tests performed, the method proved its feasibility for use in EVA suits and should be further developed to enhance the safety of EVA procedures.

Aerospace Medicine↗

Application of the mechanical oscillator technique to the investigation of EVA decompression.

The ultrasonic bubble detection technique has been used as a versatile tool in the investigation of hypobaric decompression procedures for the last two decades. However, this method can only detect relatively large bubbles > 30-50 micrometers (usually in venous blood) and not the very first stages of bubble formation. Recently, the mechanical oscillator technique has been applied in air diving trials in order to detect small blood density changes due to hypothetical fluid shifts. However, sharp density drops were found in the decompression process, and these have been attributed to gas bubble formation. In this study, this method was applied together with Doppler controls to a series of altitude decompressions to 300 and 500 hPa, which represents the range of EVA operational pressures currently used or planned. Six subjects participated in both series; the oscillator sample tube could be pressurized. By the application of pressure on a blood sample containing questionable gas bubbles, these are reduced in volume, like in recompression therapy, and thus the density of the sample is increased. This effect has been shown in all 6 subjects undergoing decompression to 300 hPa, whereas in the 500 hPa series only 3 out of 6 subjects corresponded with gas phase formation immediately after decompression. Typically, Doppler bubbles appeared only after some latency time between 20 and 60 min; after this time, the density effect had nearly vanished. It is concluded that the mechanical oscillator technique represents a complementary research instrument to the Doppler method, because it is able to deliver a quantitative resolution of the early stage of gas phase formation.

Aerospace Medicine↗

Brainstem auditory evoked potentials during a helium-oxygen saturation dive to 450 meters of seawater.

When divers are exposed to extreme atmospheric pressures they may exhibit symptoms of the high pressure nervous syndrome (HPNS). Although clinical HPNS symptoms are well described, little is known about the underlying pathophysiologic mechanisms. Special HPNS signs like vertigo and tremor suggested sensory-motor hyperexcitability resulting from brainstem dysfunction. We therefore studied brainstem auditory evoked potential (BAEP) repeatedly in four divers during an experimental deep helium-oxygen saturation dive to 450 meters of seawater (msw). Wave I (auditory nerve response) latency decreased whereas interpeak latencies (IPLs) I-III and I-V, which indicate respective cochleo-pontine and cochleo-mesencephalic transmission time, prolonged during the dive. IPLs III-V also prolonged the dive, but with greater variability among divers. Two divers showed a marked reversal of the normal attenuation effect of increased stimulus presentation rates on IV and V amplitudes during compression, an effect that subsided during the stay at bottom depth. This finding might indicate a relative enhancement of synaptic excitability and is presumed to be a feature of HPNS. Wave I latency reduction might at least partly be caused by accelerated sound conduction in dense helium. Additionally, an upward shift of middle ear resonance frequencies in helium can induce a basal shift of the main cochlear portion responding to the wide band clicks. This effect may reduce wave I latency due to greater relative input from the basal high frequency-short latency-cochlear neurons. Pressure-induced decrease of nerve conduction velocity, delay of synaptic transmission, and inhibitory modulation of midbrain auditory afferents possibly contributed to observed interpeak latency prolongations. Clinical HPNS signs, such as tiredness, dizziness, postural and intentional hand tremor, ataxia, and opsoclonus, were noted in three divers after reaching 300 msw and continued throughout the 37-h stay at bottom depth.

Adult↗

Rapid development of somatic spines in stratum granulosum of the adult hippocampus in vitro.

Somatic spines on granule cells have been observed occasionally in the adult rat dentate gyrus in vivo. Here we evaluate the appearance and formation of somatic spines in s. granulosum from adult rat hippocampal slices immediately after slice preparation, 45 min, 3 h, and 5 h later. Initially somatic spines are extremely rare but, after 3 h in vitro, they are readily apparent. Some of these somatic spines form asymmetric synapses that have a spherical vesicle-containing presynaptic bouton and a postsynaptic density. Other somatic spines lack a postsynaptic density and may also lack an apposed presynaptic bouton (free somatic spines) as observed in single thin sections. Both the number of these free somatic spines and the number of somatic spine synapses increase in a time-dependent manner. No somatic spines were observed on CA1 pyramidal cells in the same hippocampal slices. Electrophysiological observations indicate that the formation of somatic spine synapses on granule cells in the hippocampal slice occurs without any apparent granule cell activation. The trigger event for this very rapid synaptogenesis in the adult dentate gyrus remains to be determined.

Animals↗

EVA: European plans.

The current status of European EVA (extravehicular activity) plans is reviewed. The major difference to already existing EVA scenarios in U.S.A. and Soviet Union consists in the adoption of a higher suit pressure, namely 500 hPa. The results of a study concerned with the physiological consequences of this adoption are presented, including recommendations for protective procedures and their necessary experimental validation. A certain discrepancy between laboratory experimental decompression data and EVA operational results is discussed, leading to the identification of several items which may influence space decompression. Microgravity and the influence of the space suit itself are most likely factors in the explanation of this discrepancy, and both experimental procedures and technological developments are proposed to clarify their role for the future design of EVA procedures.

Aerospace Medicine↗

Somatic ribosomal changes induced by long-term potentiation of the perforant path-hippocampal CA1 synapses.

The present study quantified ribosomes, as an ultrastructural marker of neuronal protein synthesis, following long-term potentiation (LTP) in the hippocampal CA1 region in vitro. Sixty min after LTP-inducing, high-frequency stimulation of the perforant path, the total number of ribosomes, the number of polysomes, and the number of membrane-bound ribosomes increased significantly. These increases are a postsynaptic morphological correlate consistent with enhanced protein synthesis following the induction of LTP in the perforant path-CA1 system.

Animals↗

A case of breath holding and ascent-induced circulatory hypotension.

We report a case of transient circulatory depression due to inadvertent apnea of a subject during decompression from a stimulated dive. The dive consisted of exposure to air at 5 bar and subsequent decompression stops. Arterial blood pressure and a lead II ECG were recorded continuously. During decompression from 1.6 to 1.3 bar, the subject inadvertently held his breath. Arterial pressure fell rapidly from 120/80 to 60/53 mmHg within 20 s. Recognizing that the subject held his breath, one of the supervisors ordered him to resume breathing, and arterial blood pressure was restored rapidly. This circulatory depression was probably due to reduced stroke volume such as described for the syncope of ascent: with the subject retaining his breath, the expanding lung volume increased intrathoracic pressure resulting in impaired venous return.

Atmosphere Exposure Chambers↗

Parvalbumin-containing nonpyramidal neurons in intracortical transplants of rat hippocampal and neocortical tissue: a light and electron microscopic immunocytochemical study.

Previous immunocytochemical studies have shown that GABAergic nonpyramidal neurons of the rat hippocampus survive in intracerebral transplants. However, information is still lacking about the dendritic organization and the input synapses of these cells as well as their capacity to express the calcium-binding protein parvalbumin (PARV) under transplant conditions. In the present study, a monoclonal antibody against PARV was used to examine the dendritic morphology and the synaptic organization of parvalbumin-containing GABAergic neurons in hippocampal and dentate transplants. In addition, parvalbumin-containing nonpyramidal neurons were studied in neocortical transplants to compare the differentiation of grafted allocortical and neocortical nonpyramidal neurons. Tissue blocks of hippocampus and fascia dentata and of the parietal neocortex were taken from late embryonic rats (E 21 and E 16, respectively) and were transplanted into a cavity in the somatosensory cortex of young adult rats. After 3.5 or 7 months survival, the recipient brains were fixed by perfusion and immunostained for PARV. As in the hippocampal formation in situ, PARV-containing neurons in the hippocampal transplants were observed within and in the vicinity of the pyramidal and granule cell layer. In neocortical transplants, PARV-immunoreactive cells were distributed in all parts of the transplant with dendrites extending in various directions. In both hippocampal and neocortical transplants, immunoreactive dendrites were smooth and displayed the characteristic regular varicosities known from in situ studies of these cells. Numerous unlabeled terminals as well as a few immunoreactive boutons established synapses on the immunoreactive dendrites. PARV-positive terminals formed the typical pericellular baskets around the immunonegative cell bodies of pyramidal neurons and granule cells in the transplants. They established symmetric synapses with cell bodies and proximal dendrites. Synapses on axon initial segments were absent or rare. Our results demonstrate that allocortical as well as neocortical nonpyramidal neurons transplanted to the neocortex of adult recipients survive transplantation, express the calcium-binding protein parvalbumin, and develop a cell-specific morphology.

Animals↗

Human brainstem auditory-evoked potentials in deep experimental diving to pressures up to 62.5 bar.

The neural mechanisms underlying the high pressure neurologic syndrome (HPNS), which limit man's safe advance to extreme diving depths, are still unclear. This work was aimed at a better understanding of HPNS through study of brainstem auditory-evoked potentials (BAEP). BAEP were repeatedly recorded within 2 experimental chamber dives, Titan VIII (2 divers, maximum depth of 560 msw, compression time to bottom 109 h) and Titan XI (3 divers, maximum depth of 615 msw, compression time to bottom 240 h). Prolongation of the IV/V-complex occurred in 2 divers upon reaching 525 msw during Titan VIII compression and was accompanied by vestibular disturbances and amplitude increases of finger tremor. Both categories of changes--clinical signs and IV/V delay--gradually diminished during a 4-day stay at 545 msw, suggesting that they depended on excessive compression rates and insufficient acclimation time. Longer holding times at intermittent depths during Titan XI clearly reduced both HPNS symptoms and magnitude of prolongation of IV/V latencies. Wave I and wave III latency did not significantly change, pointing to a suppression of pontomesencephalic transmission. We infer that pressure suppresses synaptic transmission or triggers an increase of cortical or subcortical efferent inhibitory modulation of upper pontine and midbrain auditory afferents. Postdive controls revealed no persistent changes of BAEP measures in either the Titan VIII or XI divers.

Adult↗

[Morphometric-stereological study of hippocampal long term potentiation with special consideration of the analysis of variance with two-way hierarchical classification].

Regarding the hippocampal formation and especially the external two thirds of it's dentate molecular layer a lot of possible morphological changes after long-term potentiation (LTP) have been described in literature. The present morphometric-stereological study of vesicles in axo-spino-dendritic synapses of the inner third of the molecular layer was done under the aspect of heterosynaptic influences following LTP. Because of the hierarchical link of the three analytic levels (test-group, animal, synapse), for statistical interpretation we used the analysis of variance with two-way hierarchical classification. Between the 3 groups (passive control, active control, LTP-group) we found no significant differences. Because of the great differences between the vesicles even within a single synapse we subsequently investigated the middle third of the molecular layer, i.e. the terminal area of the stimulated perforant path. No differences between the three groups we found here either. There was no confirmation for the expected greater homogenization of the synapses based on the uniform input. As a result of this study pure morphological studies without selective staining of specific population of synapses are considered inadvisable. Only with the help of selective staining in the area of the synapses possible differences between the groups may be found.

Analysis of Variance↗

The influence of long-term potentiation on the spatial relationship between astrocyte processes and potentiated synapses in the dentate gyrus neuropil of rat brain.

The influence of long-term potentiation (induced by repeated high-frequency stimulation of the perforant pathway) on the distribution pattern of astrocyte processes in the neuropil of the hippocampal dentate area containing the potentiated synapses was investigated by quantitative electronmicroscopy. It has been found that significant changes occurred in the ramification of astrocyte processes as well as in their topographic relation to synaptic complexes. When comparing the results obtained in LTP animals with active control or sham-operated animals, we found significant higher numerical density, but smaller volume, higher surface density and closer apposition of astrocyte processes to the synaptic clefts, boutons terminaux or spines in the potentiated synapses containing neuropil. The glial reaction to synaptic activation has been seen most pronounced 8 h after the LTP induction. The results are pointing to a participation of the glia cells in the maintenance of the LTP effect as well as to a metabolic coupling between synaptic transmission and glia function for equilibrating the homeostasis by clearing the extracellular space next to the transmission zones.

Animals↗

European EVA decompression sickness risks.

For the first manned flight of Hermes there will be a capability of performing EVA. The European EVA Space Suit will be an anthropomorphic system with an internal pressure of 500 hPa of pure oxygen. The pressure reduction from the Hermes cabin pressure of 1013 hPa will induce a risk for Decompression Sickness (DCS) for the EVA crewmember if no adequate protective procedures are implemented. Specific decompression procedures have to be developed. From a critical review of the literature and by using knowledge gained from research conducted in the past in the fields of diving and aerospace medicine safe protective procedures are proposed for the European EVA scenario. An R factor of 1.2 and a tissue half-time (t1/2) of 360 minutes in a single-tissue model have been identified as appropriate operational values. On the basis of an acceptable risk level of approximately 1%, oxygen prebreathing times are proposed for (a) direct pressure reduction from 1013 hPa to a suit pressure of 500 hPa, and (b) staged decompression using a 700 hPa intermediate stage in the spacecraft cabin. In addition, factors which influence individual susceptibility to DCS are identified. Recommendations are also given in the areas of crew selection and medical monitoring requirements together with therapeutic measures that can be implemented in the Hermes scenario. A method for demonstration of the validity of proposed risks and procedures is proposed.

Aerospace Medicine↗

Heterosynaptic changes in number and shape of the transmission zones of axo-spino-dendritic synapses in the central nervous system following long-term potentiation.

Regarding the hippocampal formation and especially the external two thirds of it's dentate molecular layer a lot of possible morphological changes after long-term potentiation (LTP) have been described in literature. The present morphometric-stereological study of axo-spino-dendritic synapses from the inner third of the molecular layer was done under the aspect of heterosynaptic influences following LTP. We were looking for differences in the number of transmission zones, in the total length of the transmission zone and in the qualitative shape of the single transmission membrane. Because of the hierarchical link of the three analytic levels (test-group, animal, synapse), for statistical interpretation we used the analysis of variance with two-way hierarchical classification. We detected large differences between the single synapses but not significant differences between the 3 groups (passive control, active control, LTP-group). Our quantitative studies showed the same results also in the middle third of the molecular layer (Grabs et al. 1991). Pure morphological studies should be done under selective staining of specified population of synapses to differ in stimulated and non-stimulated synapses. Only with the help of selective staining in the area of the synapses possible differences between the groups may be found.

Animals↗

Spinules in axospinous synapses of the rat dentate gyrus: changes in density following long-term potentiation.

Following high frequency stimulation of the perforant path the density of axospinous synapses from the middle third of the molecular layer of the rat dentate gyrus did not change significantly. By contrast, within this synaptic population the density of axospinous synapses containing synaptic spinules increased markedly. We interpret these results in terms of a structural modification related to enhanced synaptic efficacy.

Animals↗

Interactions between imipramine and morphine on motility in rats: possible relation to antidepressant effects?

The aim of the present study was to evaluate whether morphine and the more modern antidepressant drug imipramine have common effects on behavior after both acute and chronic administration, and, in particular, to establish whether they act synergistically. In rats, morphine (15 mg/kg i.p.) produced a pronounced hypokinesia, followed by locomotor activation and stereotyped behavior. After repeated administration (eight times), tolerance to the hypokinesia developed, whereas locomotor activation and stereotypies occurred earlier and were more pronounced. Subacute pretreatment with imipramine (twice daily 10 mg/kg i.p. for eight days) enhanced and prolonged hypokinesia and delayed the manifestation of stereotypies and locomotor activation. In contrast, chronic treatment with imipramine (for 29 days) no longer inhibited morphine-induced stereotypies and locomotor activation, but seemed to enhance them when they were tested in rats repeatedly treated with morphine. When the same rats were tested with morphine (15 mg/kg) seven days after withdrawal of morphine and imipramine, morphine produced increased stereotypies and a slight enhancement of locomotion. The experimental conditions used excluded the possibility that conditioning phenomena might explain the enhancement of (probably dopamine-mediated) behavior. Furthermore, the results demonstrated that 1) acute administration of morphine and subacute administration of imipramine may act in a synergistic way, and 2) repeated administration of morphine and chronic treatment with imipramine also act synergistically, although contrary to the acute actions of both drugs. These interactions might be of therapeutic or toxicological relevance.

Animals↗