Effects of the Na+/H+-exchange inhibitor Hoe 642 on intracellular pH, calcium and sodium in isolated rat ventricular myocytes

The inhibitors of the Na+/H+-exchange (NHE1) system Hoe 694 and Hoe 642 possess cardioprotective effects in ischaemia/reperfusion. It is assumed that these effects are due to the prevention of intracellular sodium (Nai) and calcium (Cai) overload. The purpose of the present study was to investigate the effects of Hoe 642 on intracellular pH, Na+ and Ca2+ (pHi, Nai and Cai) in isolated rat ventricular myocytes under anoxic conditions or in cells in which oxidative phosphorylation had been inhibited by 1.5 mmol/l cyanide. In cells which were dually loaded with the fluorescent dyes 2, 7-biscarboxyethyl-5,6-carboxyfluorescein (BCECF) and Fura-2, anoxia caused acidification of the cells (from pHi 7.2 to pHi 6.8) and an increase in Cai from about 50 nmol/l to about 1 micromol/l. The decrease in pHi began before the cells underwent hypoxic (rigor) contracture, whereas Cai only began to rise after rigor shortening had taken place. After reoxygenation, pHi returned to its control value and Cai oscillated and then declined to resting levels. It was during this phase that the cells rounded up (hypercontracture). When 10 micromol/l Hoe 642 was present from the beginning of the experiment, pHi and Cai were not significantly different from control experiments. At reoxygenation, pHi did not recover, but Cai oscillated and returned to its resting level. To monitor Nai, the cells were loaded with the dye SBFI. After adding 1.5 mmol/l cyanide or 100 micromol/l ouabain, Nai increased from the initial 8 mmol/l to approximately 16 mmol/l. Hoe 642 or Hoe 694 (10 micromol/l) did not prevent the increase in Nai. In contrast, the blocker of the persistent Na+ current R56865 (10 micromol/l) attenuated the CN--induced rise in Nai. The substance ethylisopropylamiloride was not used because it augmented considerably the intensity of the 380 nm wavelength of the cell's autofluorescence. In conclusion, the specific NHE1 inhibitor Hoe 642 did not attenuate anoxia-induced Cai overload, nor CN--induced Nai and Cai overload. Hoe 642 prevented the recovery of pHi from anoxic acidification. This low pHi maintained after reoxygenation may be cardioprotective. Other possible mechanisms of NHE1 inhibitors, such as prevention of Ca2+ overload in mitochondria, cannot be ruled out. The increase in Nai during anoxia is possibly due to an influx of Na+ via persistent Na+ channels.     

Treatment with the oral growth hormone secretagogue MK-677 increases markers of bone formation and bone resorption in obese young males

The effect of 2 months of treatment with the oral growth hormone (GH) secretagogue MK-677 on markers of bone metabolism was determined in healthy obese male subjects. This was a randomized, double-blind, parallel, placebo-controlled study. Twenty-four healthy obese males, 19-49 years of age, with body mass index > 30 kg/m2 were treated with MK-677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks. MK-677 increased markers of bone formation; a 23% increase in the carboxy-terminal propeptide of type I procollagen levels and a 28% increase in procollagen III peptide levels were seen with as little as 2 weeks of MK-677 treatment (p < 0.01 and p = 0.001 vs. placebo, respectively) while a 15% increase in serum levels of osteocalcin was not detected until 8 weeks of treatment (p < 0.01 vs. placebo). Markers of bone resorption were induced within 2 weeks of treatment with MK-677; serum levels of the carboxy-terminal cross-linked telopeptide of type I collagen were increased 26% at 8 weeks (p = 0.001 vs. placebo), and urine hydroxyproline/creatinine and calcium/creatinine ratios at 8 weeks were increased by 23% (p < 0.05 vs. placebo) and 46% (p < 0.05 vs placebo), respectively, MK-677 increased serum insulin-like growth factor binding protein-5 (IGFBP-5) by 43-44% after 2-8 weeks of treatment (p < 0.01 vs. placebo). Serum IGFBP-4 was increased by 25% after 2 weeks of treatment (p < 0.001 vs. placebo) but no significant change from baseline was observed after 8 weeks of treatment. Plasma interleukin-6 was not significantly changed by active treatment. In conclusion, short-term treatment of healthy obese male volunteers with the GH secretagogue MK-677 increases markers of both bone resorption and formation. Large increases in serum levels of IGF-1 and IGFBP-5 and a transient increase in serum IGFBP-4 were found. Future long-term studies are needed to investigate if prolonged treatment with MK-677 increases bone mass.     

Constrained length minimum inductance gradient coil design

A gradient coil design algorithm capable of controlling the position of the homogeneous region of interest (ROI) with respect to the current-carrying wires is required for many advanced imaging and spectroscopy applications. A modified minimum inductance target field method that allows the placement of a set of constraints on the final current density is presented. This constrained current minimum inductance method is derived in the context of previous target field methods. Complete details are shown and all equations required for implementation of the algorithm are given. The method has been implemented on computer and applied to the design of both a 1:1 aspect ratio (length:diameter) central ROI and a 2:1 aspect ratio edge ROI gradient coil. The 1:1 design demonstrates that a general analytic method can be used to easily obtain very short gradient coil designs for use with specialized magnet systems. The edge gradient design demonstrates that designs that allow imaging of the neck region with a head sized gradient coil can be obtained, as well as other applications requiring edge-of-cylinder regions of uniformity.     

E1A second exon requirements for induction of target cell susceptibility to lysis by natural killer cells: implications for the mechanism of action

Recombinant human granulocyte colony-stimulating factor (G-CSF) at a dose of 1 to 300 micrograms/kg/day was administered intravenously to rats daily for 13 weeks. Serum alkaline phosphatase (ALP) activity increased dose-dependently with leukocytosis. Most of the increased leukocytes were segmented neutrophils, and neutrophil alkaline phosphatase (NAP) scores were elevated markedly. Serum ALP activity correlated very well with the segmented neutrophil counts, and the coefficient of correlation was more than 0.97 in both sexes. Pathological examinations revealed splenomegaly and a marked increase in neutrophils in the red pulp of the spleen. In the spleen, phagocytosis of neutrophils by macrophages was observed. These data indicate that the increased ALP was of neutrophil origin. Serum ALP activity may be increased by the direct release of ALP from the high number of neutrophils into the blood, or by the leakage of ALP into the blood mainly from the spleen where many neutrophils are pooled and destroyed by the macrophage system.     

From ethnographic record to system design

This paper explores the issues involved in moving from ethnographic explorations of work in context to a practical contribution to system design. It does so using the example of an interdisciplinary research project involving sociologists and computer scientists in the domain of air traffic control systems. It forms a pair with another paper (Sommerville et al., 1992) exploring these questions from the perspective of our computer science partners. We characterise ethnography as a research method, and consider the differences between undertaking it for strictly sociological or anthropological purposes by contrast with interdisciplinary and design purposes. We summarise some of our results in ethnographic explications of the work of air traffic controllers, and the sociality which it manifests. We describe the dialogues involved in rendering these observations informative for systems design, and the mutual translations implied in attempting to reconcile sociological with software engineering questions about supporting the work. We conclude by specifying some features of cooperative work which an engineering approach is in danger of overlooking; the ways, and limits, in which ethnographers can form a bridge between users and designers; and some of the conflicts of interest entrained in generating technical change.The research is funded by the UK MRC/SERC/ESRC Cognitive Science/HCI Initiative with the title Social Analysis of Control Systems for HCI Design, grant number SPG 8931598. The computer science partners are Professor Ian Sommerville, Dr Tom Rodden, Dr Pete Sawyer and Mr Richard Bentley. Thanks are due to Val King, Kjeldt Schmidt, Ian Sommerville and Tom Rodden for very helpful comments on earlier drafts of this paper.     

Effect of a direct magnetic field on the interfacial microstructure between molten aluminium and solid iron

Many processing techniques, such as hot dip aluminizing, bimetal formation, liquid metal corrosion, cementing, welding and diffusion bonding, are basically dependent on interfacial reactions [1-3]. It is therefore important to investigate the formation and growth of intermetallic layers at the interface. There have been several studies carried out to examine chemical compositions and growth kinetics of intermetallic layers in the Al-Fe system [4-9]. Most authors have come to an agreement that…     

Rheology and Consolidation of Colloidal Alumina-Coated Silicon Nitride Suspensions

In an attempt to improve the colloidal processing of Si₃N₄ ceramics, we studied the rheology and consolidation of colloidal suspensions of Si₃N₄ particles (average particle size 0.7 μm) with small Al₂O₃ particles (average particle size 20 nm). It was found that at pH >7, the viscosity of the mixtures increased and then decreased with an increasing concentration of Al₂O₃. λpotential measurements, optical micrographs, and visible light absorptance measurement suggest that such viscosity behavior is due to clustering of Si₃N₄ particles bridged by the small Al₂O₃ particles. This is also supported by the Derjaquin-Landau-Verwey-Overbeek (DLVO) potential calculations that show the barrier height in the DLVO potential between Al₂O₃ and Si₃N₄ is small. The small barrier height under current experimental conditions stems from the small size of the Al₂O₃ particles. The small barrier height allows the thermal motion of the two kinds of particles to overcome the barrier and attach to each other. The adsorption of small Al₂O₃ particles on Si₃N₄ can occur even when both Al₂O₃ and Si₃N₄ carry the same sign of charges. The adsorption of Al₂O₃ on Si₃N₄ also increases the density of consolidated compacts.     

Chromate leaching from inhibited primers: Part I. Characterisation of leaching

Leaching and characterisation studies have been undertaken on two chromate-inhibited epoxy polyamide primers. Leaching was carried out in 5% (w/v) NaCl solutions at different pH values (1, 3, 5 and 7) and the amount of Cr released into solution was monitored over time. Cr release was initially high, but as the immersion time increased the leaching from the primers slowed. Prior to and after immersion, the primers were characterised by a number of techniques including electron microprobe analysis, X-ray microdiffraction, Raman spectroscopy, and positron annihilation lifetime spectroscopy. The unexposed primers were found to contain the inorganic phases SrCrO₄, BaSO₄ and TiO₂ (anatase or rutile). Upon immersion, water uptake by the primers was observed, together with a decrease in the amount of SrCrO₄ in the primers. These studies provide insights into the mechanism of chromate leaching from inhibited primers.     

Binary and ternary blends of poly(vinyl chloride), hytrel,and a polyurethane

Binary blends of poly(vinyl chloride) and a poly(ether urethane) containing 20 and 40 weight percent, respectively, of poly(vinyl chloride) have been prepared by solution blending from tetrahydrofuran and their degree of mixing investigated using dynamic mechanical analysis. In the polyurethane, transitions were found at ?19°C and ?119°C. The former was attributed to the glass transition and the latter to a Schatzki type of motion of the polyether sequences. This latter transition occurred at a temperature which is higher than the literature value for the low temperature transition in poly(tetrahydrofuran), which is equivalent to the polyether sequence in the polyurethane. This discrepancy is attributed to the influence of neighboring hard segments present because of incomplete segmental phase separation of the polyurethane. For the blends only one very broad transition was observed, indicating that there was substantial mixing of these two polymers. Three ternary blends were prepared, also by solution blending, containing poly(vinyl chloride), Hytrel, and the polyurethane in the ratios 1:1:1, 1:2:1, and 2:1:1, respectively. In the first two blends there was clear evidence of phase separation. It was only in the 2:1:1 blend that an apparently significantly compatible material resulted.     

The estimation of the residual capacity of sealed lead-acid cells using the impedance technique

The problem of estimating the residual usable energy of a lead-acid cell has been intensified by the introduction of fully sealed units. These rely on the recombination of gaseous oxygen produced during overcharge at the positive electrode with the active material at the negative electrode. This introduction has removed the possibility of electrolyte density measurements, third electrode measurements and restricted residual capacity assessments to the two cell terminals. A method for this process is described using a parameter based on a characteristic frequency. The parameter is also a useful measure of cell ageing.Nomenclature R _SOL Ohmic resistance of cell () - Charge-transfer resistance of positive and negative electrodes () - CL Double-layer capacitance of both positive and negative electrodes (F) - Warburg diffusion (S^–1/2) - C _EXT External series capacitor in analogue Fig. 5 (F) - R _EXT External resistor in parallel withC _EXT in the anologue circuit Fig. 5 () - IND Inductor in Fig. 5 representing the geometrical effects of the cell at high frequencies (Henries) - R _IND External resistor in parallel with IND in the analogue circuit Fig. 5 () - Roughness factor allowing for the porosity of both electrodes