Biomedical subjects

D Ulrich

Publications and source records attributed to D Ulrich.

At least 19 recordsLinked to original sources

PubMed2001

ULBP1, 2, 3: novel MHC class I-related molecules that bind to human cytomegalovirus glycoprotein UL16, activate NK cells.

New members of the extended MHC class I-like family were identified based on their ability to bind human cytomegalovirus glycoprotein UL16 and/or their mutual homology. Soluble UL16 binding proteins (ULBP) competed with each other for binding to NK cells. Treatment of human and mouse NK cells with ULBP led to increased production of cytokines/chemokines, proliferation, cytotoxic activity and up-regulation of activation-associated surface molecules. The presence of ULBP during the stimulation phase of the CTL assay caused increased cytotoxic activity. Addition of soluble recombinant UL16 protein inhibited the biological activities mediated by ULBP, suggesting the existence of a novel mechanism utilized by CMV to evade elimination by the host immune system.

Animals↗

PubMed2001

Burn injuries caused by air bag deployment.

Automobile air bags have gained acceptance as an effective measure to reduce the morbidity and mortality associated with motor vehicle accidents. As more cars have become equipped with them, new problems have been encountered that are directly attributable to the deployment of the bag itself. An increasing variety of associated injuries has been reported, including minor burns. We present two automobile drivers who were involved in front-impact crashes with air bag inflation. They sustained superficial and partial-thickness burns related to the deployment. The evaluation of these cases shows mechanisms involved in burn injuries caused by the air bag system. Most of the burns are chemical and usually attributed to sodium hydroxide in the aerosol created during deployment. Also direct thermal burns from high-temperature gases or indirect injuries due to the melting of clothing, as well as friction burns from physical contact are possible. However, the inherent risks of air bag-related burns are still outweighed by the benefits of preventing potentially life-threatening injuries.

Abdomen↗

PubMed2001

Life threatening burn injuries on holidays: problems of primary care, homeland referral and treatment at a domestic burn centre.

Life threatening burn injuries during vacations abroad raise special problems. Depending on the infrastructure of the country, adequate medical care can be delayed and communication between the patient and the medical staff is frequently impossible due to language barriers. Often the patient finds himself in a critical condition, isolated from supporting relatives and financial difficulties may occur. By summarising three cases referred to our centre, we aim to emphasise particularities of the primary management of burned victims at foreign hospitals, their transport, and following therapy at a domestic burn unit. Primary shock treatment and vital surgical interventions, e.g. escharotomy or treatment of the concomitant trauma, are subject to the facility of the hosting country. After management of the acute phase and initiation of local wound treatment, the next step should be to stabilise and prepare the patient for transport. Aeromedical transportation with physician attendency, as well as contact with a domestic burn centre can be established via responsible organisations. At the domestic hospital, every burn victim from abroad deserves special attention. Wound colonisation with different bacterial species or fungi than the usual spectrum of the centre and the risk of crossinfections should be taken in account of the treating medical team. An structure plan for appropriate and continuing surgical treatment is necessary to prevent deterioration of the patient's condition and to optimise wound closure with autologous skin grafts or allogenic materials.

Adult↗

PubMed2001

[Plasma endotoxin, procalcitonin, C-reactive protein, and organ functions in patients with major burns].

Sepsis is one of the most frequent causes of death after major burn injury. Usually, sepsis appears as a consequence of a gram-negative bacteriaemia with release of endotoxins. In this study, the plasma endotoxin levels of seven patients (three female, four male; average age 51.3 +/- 23.8 years) with burns between 43.5 and 78 % Total Body Surface Area (Abbreviated Burn Severity Index 8 - 12) were determined for five days after thermal trauma every three hours by ELISA and compared with the concentration of procalcitonin (PCT) and C-reactive protein (CRP). A calculation of the Horrowitz-Index (PaO(2)/FiO(2)) and the Pressure-Adjusted Heart Rate (HR x CVP/MAP) took place to show a possible correlation between the endotoxin concentration and the cardiopulmonary organ function. Additionally, we analysed whether operative treatment can influence the level of plasma endotoxin in the early phase after burn injury. At any time after burn trauma, endotoxins could be detected in the plasma of all patients. Between the second and third day, there was a considerable increase in the endotoxin concentration with a maximum after 57 hours of 0.48 +/- 0.32 EU/ml. Two patients with sepsis and death in the further course had a rather distinctive increase. From the fourth day on, occasional episodes of increases in endotoxin concentration were noted. Postoperatively, there was a short increase in plasma endotoxin on the second and fourth day. The plasma endotoxin level showed no correlation with the PCT and CRP or with the oxygenation in the patients' blood. However, a positive correlation could be observed with the Pressure-Adjusted Heart Rate (p = 0.0061; r(2) = 0.212). An explanation for the endotoxin increase after 57 hours could be the translocation of intestinal bacteria, the beginning of bacterial colonisation or decomposition products of the burn wound with protein-protein complexes. Later on, infectious diseases such as pneumonia with gram-negative bacteria are of importance, too. According to the Two-Hit Model, the increase of plasma endotoxin can serve as a trigger and cause a recurrence of systemic inflammation with the changes observed in cardiac organ function, multiple organ dysfunction, and multiple organ failure.

Adult↗

PubMed2001

GABA(B) and NMDA receptors contribute to spindle-like oscillations in rat thalamus in vitro.

Thalamic slice preparations, in which intrathalamic connectivity between the reticular nucleus and relay nuclei is maintained, are capable of sustaining rhythmic burst firing activity in rodents and ferret. These in vitro oscillations occur spontaneously in the ferret and have frequencies (6-10 Hz) within the range of sleep spindles observed in vivo. In the rat, mainly lower frequency (2-4 Hz) oscillations, evoked under conditions of low bath [Mg(2+)] and/or GABA(A) receptor blockade, have been described. Here we show that faster rhythms in the range of 4-9 Hz can be evoked in rat thalamic slices by electrical stimulation of the internal capsule and also occur spontaneously. When bath [Mg(2+)] was 2 mM, these spindle-like oscillations were most common in a brief developmental time window, peaking at postnatal day 12 (P12). The oscillations were almost completely blocked by the GABA(A) receptor antagonist picrotoxin, and, in some cases, the frequency of oscillations was increased by the GABA(B) receptor antagonist CGP-35348. The selective blockade of N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by the antagonists 2-amino-5-phosphonovaleric acid or 1,2,3,4-Tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), respectively, significantly shortened oscillations but did not completely block them. A combination of the two drugs was necessary to abolish oscillatory activity. The barbituate pentobarbital, which enhances GABA(A)R responses, initially slowed and synchronized oscillations before completely blocking them. When bath [Mg(2+)] was reduced from 2 to 0.65 mM, evoked oscillations became more robust and were often accompanied by spontaneously arising oscillations. Under these conditions, GABA(A) receptor blockade no longer inhibited oscillations, but instead converted them into the slow, synchronous rhythms that have been observed in other studies. The effects of GABA(B) or NMDA receptor blockade were more pronounced in 0.65 mM than in 2 mM external [Mg(2+)]. Thus spindle-like oscillations occur in rat thalamic slices in vitro, and we find that, in addition to the previously demonstrated contributions of GABA(A) and AMPA receptors to these oscillations, NMDA and GABA(B) receptors are also involved. The strong influence of external [Mg(2+)] on GABAergic pharmacology and a contribution of NMDA receptors during oscillations suggest a link between the excitability of NMDA receptors and the activation of GABA(B)R-mediated inhibitory postsynaptic currents.

2-Amino-5-phosphonovalerate↗

PubMed2000

Quantitation of Helicobacter pylori in dental plaque samples by competitive polymerase chain reaction.

AIM: To establish a competitive PCR (cPCR) assay for quantitation of H pylori organisms in dental plaque samples. METHODS: The cPCR co-amplified target H pylori DNA and a known amount of internal standard template in the same tube with the same primers directed to 0.86 kb DNA of H pylori. The internal standard was a synthesised DNA bearing the same primer recognition sites at two ends and a non-homologous core sequence as the target DNA fragment. Quantitation was based on determination of the relative, not absolute, amounts of the differently sized and [32P]-dCTP labelled products derived from H pylori DNA and the competitive internal standard after gel electrophoresis separation. RESULTS: A significant correlation between known amounts of H pylori added to dental plaque samples and the results of the cPCR was found, and a standard line was developed which allowed quantitation of H pylori in the plaque samples. cPCR was performed on supragingival plaque samples from 10 adult patients with H pylori infection in the stomach, and from five adults and six children without H pylori infection in the stomach. The ranges of H pylori numbers were 1-213 (median 25), 6-76 (10), and 4-94 (14) cells/mg of dental plaque in the three groups, respectively. CONCLUSIONS: cPCR is useful for quantitation of H pylori in supragingival dental plaque samples; however, the number of the organisms in dental plaque samples seems very low.

Adolescent↗

PubMed2000

Dendrosomatic voltage and charge transfer in rat neocortical pyramidal cells in vitro.

Most excitatory synapses on neocortical pyramidal cells are located on dendrites, which are endowed with a variety of active conductances. The main origin for action potentials is thought to be at the initial segment of the axon, although local regenerative activity can be initiated in the dendrites. The transfer characteristics of synaptic voltage and charge along the dendrite to the soma remains largely unknown, although this is an essential determinant of neural input-output transformations. Here we perform dual whole-cell recordings from layer V pyramidal cells in slices from somatosensory cortex of juvenile rats. Steady-state and sinusoidal current injections are applied to characterize the voltage transfer characteristics of the apical dendrite under resting conditions. Furthermore, dendrosomatic charge and voltage transfer are determined by mimicking synapses via dynamic current-clamping. We find that around rest, the dendrite behaves like a linear cable. The cutoff frequency for somatopetal current transfer is around 4 Hz, i.e., synaptic inputs are heavily low-pass filtered. In agreement with linearity, transfer resistances are reciprocal in opposite directions, and the centroids of the synaptic time course are on the order of the membrane time constant. Transfer of excitatory postsynaptic potential (EPSP) charge, but not peak amplitude, is positively correlated with membrane potential. We conclude that the integrative properties of dendrites in infragranular neocortical pyramidal cells appear to be linear near resting membrane potential. However, at polarized potentials charge transferred is voltage-dependent with a loss of charge at hyperpolarized and a gain of charge at depolarized potentials.

Animals↗

PubMed1999

The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23.

The vitronectin receptor, alphavbeta3 integrin, plays an important role in tumor cell invasion, angiogenesis, and phagocytosis of apoptotic cells. CD47, a member of the multispan transmembrane receptor family, physically and functionally associates with vitronectin receptor (VnR). Although vitronectin (Vn) is not a ligand of CD47, anti-CD47 and beta3 mAbs suppress Vn, but not fibronectin (Fn) binding and function. Here, we show that anti-CD47, anti-beta3 mAb and Vn, but not Fn, inhibit sCD23-mediated proinflammatory function (TNF-alpha, IL-12, and IFN-gamma release). Surprisingly, anti-CD47 and beta3 mAbs do not block sCD23 binding to alphav+beta3+ T cell lines, whereas Vn and an alphav mAb (clone AMF7) do inhibit sCD23 binding, suggesting the VnR complex may be a functional receptor for sCD23. sCD23 directly binds alphav+beta3+/CD47(-) cell lines, but coexpression of CD47 increases binding. Moreover, sCD23 binds purified alphav protein and a single human alphav chain CHO transfectant. We conclude that the VnR and its associated CD47 molecule may function as a novel receptor for sCD23 to mediate its proinflammatory activity and, as such, may be involved in the inflammatory process of the immune response.

Animals↗

PubMed1999

Tissue stresses and strain in trabeculae of a canine proximal femur can be quantified from computer reconstructions.

A quantitative assessment of bone tissue stresses and strains is essential for the understanding of failure mechanisms associated with osteoporosis, osteoarthritis, loosening of implants and cell-mediated adaptive bone-remodeling processes. According to Wolff's trajectorial hypothesis, the trabecular architecture is such that minimal tissue stresses are paired with minimal weight. This paradigm at least suggests that, normally, stresses and strains should be distributed rather evenly over the trabecular architecture. Although bone stresses at the apparent level were determined with finite element analysis (FEA), by assuming it to be continuous, there is no data available on trabecular tissue stresses or strains of bones in situ under physiological loading conditions. The objectives of this project were to supply reasonable estimates of these quantities for the canine femur, to compare trabecular-tissue to apparent stresses, and to test Wolff's hypothesis in a quantitative sense. For that purpose, the newly developed method of large-scale micro-FEA was applied in conjunction with micro-CT structural measurements. A three-dimensional high-resolution computer reconstruction of a proximal canine femur was made using a micro-CT scanner. This was converted to a large-scale FE-model with 7.6 million elements, adequately refined to represent individual trabeculae. Using a special-purpose FE-solver, analyses were conducted for three different orthogonal hip-joint loading cases, one of which represented the stance-phase of walking. By superimposing the results, the tissue stress and strain distributions could also be calculated for other force directions. Further analyses of results were concentrated on a trabecular volume of interest (VOI) located in the center of the head. For the stance phase of walking an average tissue principal strain in the VOI of 279 strain was found, with a standard deviation of 212 microstrain. The standard deviation depended not only on the hip-force magnitude, but also on its direction. In more than 95% of the tissue volume the principal stresses and strains were in a range from zero to three times the averages, for all hip-force directions. This indicates that no single load creates even stress or strain distributions in the trabecular architecture. Nevertheless, excessive values occurred at few locations only, and the maximum tissue stress was approximately half the value reported for the tissue fatigue strength. These results thus indicate that trabecular bone tissue has a safety factor of approximately two for hip-joint loads that occur during normal activities.

Animals↗

PubMed1999

Tissue stresses and strain in trabeculae of a canine proximal femur can be quantified from computer reconstructions.

A quantitative assessment of bone tissue stresses and strains is essential for the understanding of failure mechanisms associated with osteoporosis, osteoarthritis, loosening of implants and cell- mediated adaptive bone-remodeling processes. According to Wolff's trajectorial hypothesis, the trabecular architecture is such that minimal tissue stresses are paired with minimal weight. This paradigm at least suggests that, normally, stresses and strains should be distributed rather evenly over the trabecular architecture. Although bone stresses at the apparent level were determined with finite element analysis (FEA), by assuming it to be continuous, there is no data available on trabecular tissue stresses or strains of bones in situ under physiological loading conditions. The objectives of this project were to supply reasonable estimates of these quantities for the canine femur, to compare trabecular-tissue to apparent stresses, and to test Wolff's hypothesis in a quantitative sense. For that purpose, the newly developed method of large-scale micro-FEA was applied in conjunction with micro-CT structural measurements. A three-dimensional high-resolution computer reconstruction of a proximal canine femur was made using a micro-CT scanner. This was converted to a large-scale FE-model with 7.6 million elements, adequately refined to represent individual trabeculae. Using a special-purpose FE-solver, analyses were conducted for three different orthogonal hip-joint loading cases, one of which represented the stance-phase of walking. By superimposing the results, the tissue stress and strain distributions could also be calculated for other force directions. Further analyses of results were concentrated on a trabecular volume of interest (VOI) located in the center of the head. For the stance phase of walking an average tissue principal strain in the VOI of 279 strain was found, with a standard deviation of 212 microstrain. The standard deviation depended not only on the hip-force magnitude, but also on its direction. In more than 95% of the tissue volume the principal stresses and strains were in a range from zero to three times the averages, for all hip-force directions. This indicates that no single load creates even stress or strain distributions in the trabecular architecture. Nevertheless, excessive values occurred at few locations only, and the maximum tissue stress was approximately half the value reported for the tissue fatigue strength. These results thus indicate that trabecular bone tissue has a safety factor of approximately two for hip-joint loads that occur during normal activities.

Animals↗

PubMed1999

Load transfer analysis of the distal radius from in-vivo high-resolution CT-imaging.

Prevention of osteoporotic bone fractures requires accurate diagnostic methods to detect the increase in bone fragility at an early stage of osteoporosis. However, today's bone fracture risk prediction, primarily based on bone density measurement, is not sufficiently precise. There is increasing evidence that, in addition to bone density, also the bone microarchitecture and its mechanical loading conditions are important factors determining the fracture risk. Recently, it has been shown that new high-resolution imaging techniques in combination with new computer modeling techniques based on the finite-element (FE) method can account for these additional factors. These techniques might provide information that is more relevant for the prediction of bone fracture risk. So far, however, these new imaged-based FE techniques have not been feasible in-vivo. The objectives of this study were to quantify the load transfer through the trabecular network in a distal radius using a computer model based on in-vivo high-resolution images and to determine if common regions of fractures can be explained as a result of high tissue loading in these regions. The left distal radius and the two adjacent carpal bones of a healthy volunteer were imaged using a high-resolution three-dimensional CT system providing an isotropic resolution of 165 microm. The bone representation was converted into a FE-model that was used to calculate stresses and strains in the trabecular network. The two carpal bones were loaded using different load ratios (for each load case 1000 N in total) representing impact forces on the hand either in near-neutral position or ulnar/radial deviation. The load transfer through the trabecular network of the radius was characterized by the tissue strain energy density (SED) distribution for all load cases. It was found that the distribution of the tissue loading depends on the ratio of the forces acting on the carpal bones. For all load cases the higher SED values (on average: 0.02 +/- 0.08 (S.D.) N mm(-2)) are found in a 10 mm region adjacent to the articular surface which corresponds well with the region where Colles- or Chauffeur-fractures occur. We expect that, eventually, this new approach can lead to a better prediction of the fracture risk than methods based on bone density alone since it accounts for the bone microstructure as well as its loading conditions.

Carpal Bones↗

PubMed1999

The ability of three-dimensional structural indices to reflect mechanical aspects of trabecular bone.

Bone mineral density (BMD) and bone microarchitecture are important determinants for the mechanical properties of cancellous bone. Although BMD alone is a good predictor of average mechanical properties of cancellous bone, there remains unexplained variation in mechanical properties that might be due to missing information regarding bone microarchitecture. Recent developments in three-dimensional (3D) structural analysis have provided possibilities for measuring a variety of structural indices to characterize bone microarchitecture. The objectives of this study were to calculate structural indices and elastic constants of human cancellous bone from different skeletal sites and to investigate the predictive value of different 3D structural indices for the elastic properties of bone. A total of 237 cancellous bone samples taken from the iliac crest, lumbar spine, femoral head, and calcaneus were imaged with a 3D microcomputed tomography (microCT) system. The segmented 3D images were used to calculate BV/TV, BS/TV, Tb.Th, Tb.Sp, Tb.N, and MII ratio and for microstructural finite-element (microFE) analysis to calculate Young's moduli, shear moduli, and Poisson's ratios. A subgroup of "critical" specimens within each site was selected to represent specimens that could not be identified as osteoporotic or normal on the basis of BMD measurement alone. For these "critical" specimens, structural indices and elastic constants were correlated by means of linear multivariate regression analysis. It was found that the elastic constants clearly correlated better when one of the 3D structural indices was included as independent variable than when BV/TV was the only independent variable. Each of the examined structural indices could improve the correlation: the R2 values were maximally increased from 53% (BV/TV alone) to 82% (BV/TV and MIL ratio). The most effective indices, however, were not the same for the different skeletal sites. Even better correlations were found when more than one of the 3D structural indices were included as independent variables: the R2 values were maximally increased from 53% (BV/TV alone) to 92% (BV/TV, Tb.Sp, and MIL ratio). The prediction of elastic constants for cancellous bone samples is clearly improved when BV/TV is supplemented with 3D structural indices. These results suggest that the determination of mechanical properties of bone and the diagnosis of osteoporosis can be improved if, in addition to BMD, the 3D bone microarchitecture is assessed in vivo.

Adult↗

PubMed1998

Dendritic low-threshold calcium currents in thalamic relay cells.

The low-threshold calcium current (IT) underlies burst generation in thalamocortical (TC) relay cells and plays a central role in the genesis of synchronized oscillations by thalamic circuits. Here we have combined in vitro recordings and computational modeling techniques to investigate the consequences of dendritically located IT in TC cells. Simulations of a reconstructed TC cell were compared with the recordings obtained in the same cell to constrain the values of its passive parameters. T-current densities in soma and proximal dendrites were then estimated by matching the model to voltage-clamp recordings obtained in dissociated TC cells, which lack most of the dendrites. The distal dendritic T-current density was constrained by recordings in intact TC cells, which show 5-14 times larger peak T-current amplitudes compared with dissociated cells. Comparison of the model with the recordings of the same cell constrained further the T-current density in dendrites, which had to be 4.5-7.6 times higher than in the soma to reproduce all experimental results. Similar conclusions were reached using a simplified three-compartment model. Functionally, the model shows that the same amount of T-channels can lead to different bursting behaviors if they are exclusively somatic or distributed throughout the dendrites. In conclusion, this combination of models and experiments shows that dendritic T-currents are necessary to reproduce low-threshold calcium electrogenesis in TC cells. Dendritic T-current may also have significant functional consequences, such as an efficient modulation of thalamic burst discharges by corticothalamic feedback.

Action Potentials↗

PubMed1998

Comparison of two sample preparation techniques for sniffing experiments with broccoli (Brassica oleracea var. italica Plenck).

The suitability of the headspace solid phase microextraction (HSSPME) for gas chromatography-olfactometry (GC-O) with aroma extract dilution analysis in comparison to the dynamic head space sampling on a Tenax trap was tested exemplarily by the aroma volatiles of fresh broccoli. A high number of odour sensations in qualitative olfactometry was registered with both sample preparation techniques. The key aroma compounds of the fresh broccoli material are represented by high flavour dilution factors with dynamic head space sampling and headspace SPME. The SPME method has found to be a convenient and fast technique suitable especially for qualitative GC-O. The adsorption selectivity of the fiber and the substance discrimination have to be taken into account for quantitative use like aroma extract dilution analysis.

Brassica↗

PubMed1998

Finite element analysis of trabecular bone structure: a comparison of image-based meshing techniques.

In this study, we investigate if finite element (FE) analyses of human trabecular bone architecture based on 168 microm images can provide relevant information about the bone mechanical characteristics. Three human trabecular bone samples, one taken from the femoral head, one from the iliac crest, and one from the lumbar spine, were imaged with micro-computed tomography (micro-CT) using a 28 microm resolution. After reconstruction the resolution was coarsened to 168 microm. First, all reconstructions were thresholded and directly converted to FE-models built of hexahedral elements. For the coarser resolutions of two samples, this resulted in a loss of trabecular connections and a subsequent loss of stiffness. To reduce this effect, a tetrahedral element meshing based on the marching cubes algorithm, as well as a modified hexahedron meshing, which thresholds the image such that load carrying bone mass is preserved, were employed. For each sample elastic moduli and tissue Von Mises stresses of the three different 168 microm models were compared to those from the hexahedron 28 microm model. For one sample the hexahedron meshing at 168 microm produced excellent results. For the other two samples the results obtained from the hexahedral models at 168 microm resolution were poor. Considerably better results were attained for these samples when using the mass-compensated or tetrahedron meshing techniques. We conclude that the accuracy of the FE-models at 168 microm strongly depends on the bone morphology, in particular its trabecular thickness. A substantial loss of trabecular connections during the hexahedron meshing process indicates that poor FE results will be obtained. In this case the tetrahedron or mass-compensated hexahedron meshing techniques can reduce the loss of connections and produce better results than the plain hexahedron meshing techniques.

Algorithms↗

PubMed1998

Mechanical analysis of bone and its microarchitecture based on in vivo voxel images.

Prevention of osteoporotic fractures requires accurate methods to detect the increase in bone fragility at an early disease stage as well as effective therapies to reduce the risk of bone fractures. Presently the prediction of the patient-specific bone fracture risk is primarily based on bone density, since this is the only parameter which can routinely be measured in vivo. However, these predictions might not always be precise because the fracture risk is also determined by the bone microarchitecture and the bone's loading conditions. The aim of this paper is to introduce and evaluate new methods which could contribute to a better quantification of bone fracture risk. Recently, a new approach, combining computational engineering methods (finite element (FE) method) and 3D high-resolution imaging techniques, has been introduced which can account not only for bone density but also for microarchitecture and loading conditions. High-resolution imaging techniques allow acquisition of 3D images of the bone microarchitecture, whereas FE methods applied to these images allow very precise calculation of the mechanical properties of bone. However, such a detailed FE analysis was not feasible for bone in vivo mainly because the resolution was not sufficient to measure the bone microarchitecture. It is shown here, from preliminary results, that the FE approach based on high-resolution images from a new CT scanner now allows prediction of the mechanical behavior of peripheral bones in vivo. It is expected that, eventually, the FE approach will lead to a better patient-specific fracture risk prediction than earlier methods based on bone density alone. Hence, with this new approach, it might be possible to detect the increase in bone fragility at an early stage of osteoporosis and it might also be possible to evaluate treatments more accurately.

Biomechanical Phenomena↗

PubMed1997

Nucleus-specific chloride homeostasis in rat thalamus.

Synchronous thalamic network activity occurring during slow wave sleep and paroxysmal discharges critically depends on the ability of thalamocortical relay cells and inhibitory neurons of the nucleus reticularis thalami (nRt) to fire bursts of action potentials. Inhibitory synaptic potentials (IPSPs) originating from nRt cells are crucial in deinactivating T-channels and thus promoting burst firing in relay cells, but the functional role of intra-nRt IPSPs is less well understood. A major factor that regulates the net effects of IPSP generation is the chloride equilibrium potential (ECl). Here we applied the perforated patch-clamp technique, using the cation-selective ionophore gramicidin to assess the reversal potential of chloride in nRt and relay cells in brain slices. We found that the reversal potential of GABA-induced membrane currents (EGABA) was significantly more hyperpolarized in relay (-81 +/- 2.6 mV), as compared with nRt cells (-71 +/- 2.5 mV). EGABA was not significantly different from the reversal potential of evoked IPSCs (EIPSC; -82 +/- 4.4 mV) in relay cells. In both relay and reticular neurons the chloride gradient was collapsed partially by the chloride cation cotransport blocker furosemide, suggesting an active chloride extrusion mechanism in thalamic neurons. Given the relatively hyperpolarized resting potentials (approximately -70 mV) reported for nRt and relay cells during in vitro thalamic oscillations, we conclude that under these conditions GABAA IPSPs lead to significant hyperpolarization in relay cells. By contrast, intra-nRt inhibition essentially would be shunting, i.e., would produce minimal membrane polarization but still could reduce the amplitude of excitatory events.

2-Amino-5-phosphonovalerate↗

PubMed1997

GABA(A)-receptor-mediated rebound burst firing and burst shunting in thalamus.

The role of gamma-aminobutyric acid-A (GABA(A))-receptor-mediated inhibitory postsynaptic potentials (IPSPs) in 1) generating rebound burst firing and 2) burst inhibition in thalamocortical (TC) relay cells and inhibitory neurons of nucleus reticularis thalami (nRt) was investigated. Experimental data from previous studies were used to generate artificial synaptic responses in neurons via a computer-driven dynamic clamp. On average, in nRt neurons trains of six or more 10-nS GABA(A) IPSPs generated rebound bursts of action potentials with a mean delay of 605 +/- 32 (SE) ms. In contrast, 10 IPSPs were required for rebound bursts in relay cells, and these occurred with a significantly shorter delay of 327 +/- 35 ms. Ca2+-dependent burst responses could be shunted by single IPSPs. Half-maximal burst inhibition was obtained in nRt cells when IPSP conductance was 1.5 times the whole cell input conductance. Burst shunting in TC cells was less effective and required a synaptic- to input-conductance ratio of 3. The relative time window of IPSP burst shunting was broader in nRt (approximately 20 ms) than TC cells (approximately 10 ms). We conclude that in nRt cells GABA(A)-dependent rebound burst responses would occur with a latency that is incompatible with pacemaking of fast (>3-Hz) thalamic rhythm generation such as spindles, yet burst inhibition is powerful. Therefore a likely role for reciprocal intra-nRt connectivity is to mediate lateral inhibition between nRt cells.

Animals↗