Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

Insulinomimetic effect on glucose transport by epidermal growth factor when combined with a major histocompatibility complex class I-derived peptide

Peptides derived from the alpha 1-region of the murine H-2Dk molecule enhance glucose uptake in rat adipose cells above the maximum obtained with insulin stimulation alone (Stagsted, J., Reaven, G. M., Hansen, T., Goldstein, A., and Olsson, L. (1990) Cell 62, 297-307). We now describe that epidermal growth factor (EGF) in combination with the same peptides, Dk-(61-85) and Dk-(62-85), stimulates cellular glucose uptake 5-7 times over the basal level, i.e. to 30-50% of the maximal insulin effect. EGF alone increased glucose uptake by only approximately 50% above basal and the peptide alone by 100% above basal. Maximal effect of EGF and peptide was reached in 10-20 min with 30 microM peptide (EC50 10-15 microM) and 50 nM EGF (EC50 1-2 nM). The effect of EGF and peptide on glucose uptake was additive to that of insulin and peptide until the maximal level attained with insulin and peptide was reached. The combined effect of EGF plus peptide on glucose transport was associated with a recruitment of GLUT4 molecules to the plasma membrane. However, the phosphatidylinositol (PI) kinase which is activated by insulin was not activated by EGF plus peptide. Thus, the effect of EGF plus peptide on glucose uptake seems independent of the activity status of the insulin receptor. 125I-Labeled EGF bound specifically to rat adipose cells with an apparent affinity of approximately 2 nM and Bmax approximately 5 x 10(3). However, the major histocompatibility complex (MHC) peptides did not affect EGF-stimulated internalization of EGF receptor, in contrast to their effect on the insulin receptors. Transforming growth factor alpha had an effect similar to EGF on glucose uptake. Three other peptides derived from other parts of murine MHC class I had no effect on glucose uptake in combination with EGF. Thus, EGF in combination with certain MHC class I-derived peptides is insulinomimetic concerning glucose transport and this effect is independent of the insulin receptor activity.     

Investigations of delamination criticality and the transferability of growth criteria

This article describes a study of delamination growth along 0 °/0 °, 0 °/ 5 °, ± 5 °, and 0 °/90 ° interfaces sandwiched between unidirectional carbon fibre/epoxy composite material. Relationships between damage criticality, growth rate and acoustic emission activity for delamination growth have been studied and the transferability of results from laboratory coupons to composite structural elements has been examined. Two types of coupon tests, conventional delamination beams and rigidly loaded single edge notched strips, have been compared for different mode ratios. Comparative tests have been made on buckling-induced delamination in plates. A graphite crack gauge has been used to measure delamination length and growth rate, ranging from 0.05–2000 m/s. Damage growth was also followed using visual, ultrasonic C-scan, X-ray radiography, macro-video and acoustic emission measurements. Empirical evaluations of interlaminar toughness for delamination beams are made using the Irwin-Kies relation. Unstable growth is analysed using elasto-dynamic moving finite elements. Bucklinginduced delamination is analysed using plate/shell FE methods with growth/remeshing algorithms.     

Signal generation and transmission at 40, 80, and 160 Gb/s using a fiber-optical parametric pulse source

Short return-to-zero pulses (/spl sim/2 ps) are generated at bit rates of 40, 80, and 160 Gb/s using a fiber-optical parametric amplifier. The performance of the parametric pulse source is evaluated both back-to-back and in a 110-km transmission link. A receiver sensitivity of -33 dBm back-to-back was achieved after demultiplexing from 160 to 10 Gb/s. The power penalty at 160 Gb/s due to 110-km transmission was less than 2 dB. Very short pulses (0.5 ps) were also achieved when using the parametric amplifier as a compressor.     

A probabilistic model for cleavage fracture with a length scale--parameter estimation and predictions of stationary crack experiments

This study presents a large experimental investigation in the transition temperature region on a modified A508 steel. Tests were carried out on single-edge-notch-bend specimens with three different crack depth over specimen width ratios to capture the strong constraint effect on fracture toughness. Three test temperatures were considered, covering a range of 85 °C. All specimens failed by cleavage fracture prior to ductile tearing. A recently proposed probabilistic model for the cumulative failure by cleavage was applied to the comprehensive sets of experimental data. This modified weakest link model incorporates a length scale, which together with a threshold stress reduce the scatter in predicted toughness distributions as well as introduces a fracture toughness threshold value. Model parameters were estimated by a robust procedure, which is crucial in applications of probabilistic models to real structures. The conformity between predicted and experimental toughness distributions, respectively, were notable at all the test temperatures.     

The Gas-to-Particle Heat Transfer and Hydrodynamics in Spouted Bed Drying of Sawdust

This article presents experimental results for spouted bed drying of sawdust, carried out in a full-scale as well as in a laboratory-scale dryer using air as well as steam as drying media. The aim is to present design parameters for a spouted-bed sawdust dryer that can be used by the industry in designing full-scale dryers. A hydrodynamically stable spouted jet spouted bed was obtained. The heat transfer characteristics of the bed were represented in terms of a volumetric heat transfer coefficient (VHC). When sawdust is dried in a spouted bed, the mean VHC is increasing up to fiber saturation level (20-25% wb) from 40 to 110 W/m³ K. The VHC decreases with the residence time and with an increased static bed height. Gas temperature profiles are also presented for the bottom part of the drying chamber.     

Analysis of molecular determinants in native AMPA receptors

For this study, 194 respondents completed a biographical data sheet, the Templer (1970) Death Anxiety Scale and the Constantinople (1973) Inventory of Psychosocial Development to help assess the relationship among death anxiety, age, and psychosocial maturity. Findings showed that psychosocial maturity was a better predictor of death anxiety than age was. However, both variables were significantly negatively correlated with death anxiety, revealing that as psychosocial maturity and age increase, death anxiety decreases.     

D-lactic acidosis: a treatable encephalopathy in pediatric patients

Isolation of Salmonella from the feces of impounded dogs was carried out to make clear the recent microbiological condition of dogs introduced into our facilities. Salmonella was isolated from 10 out of 283 samples (3.5%). Inparticular, during the first week after introduction, Salmonella was isolated from nine out of 74 dogs (12.2%). The isolation rate during the first week after introduction was significantly higher than that for dogs introduced later. No isolates were detected from dogs reared for more than 3 weeks after introduction. This study indicates that impounded dogs had the highest risk of infecting a person with Salmonella during the first week after introduction into our laboratory animal facilities, and that we need to pay attention to this fact when handling them.