Evidence for superantigen involvement in insulin-dependent diabetes mellitus aetiology

Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease whose onset is believed to be triggered by unknown environmental factors acting on a predisposing genetic background. Islet-infiltrating T (IIT) cells from two IDDM patients, who had died at the onset of the disease from brain swelling as a complication of ketoacidosis, were analysed. The results provided evidence for the involvement of a pancreatic islet cell membrane-bound superantigen as a diabetes aetiopathogenetic factor. There was a selective expansion of a T-cell receptor (TCR) variable segment of the beta-chain (V beta 7) in these IIT cells in association with unselected V alpha-chain segments; extensive junctional diversity of the TCR V beta 7 chains; and evidence of positive selection, after exposure to diabetic islet cell membrane preparations, of V beta 7+ T-cell clones among peripheral blood lymphocytes from non-diabetic individuals.     

Endothelin-1 infusion inhibits plasma insulin responsiveness in normal men

OBJECTIVES: Elevated plasma endothelin (ET)-1 levels have been described in insulin-resistant states such as syndrome X, obesity, non-insulin-dependent diabetes mellitus, and in some studies in essential hypertension. To investigate whether increases in circulating ET-1 to levels observed in insulin-resistant states can modulate insulin levels and/or insulin sensitivity in humans, we assessed these variables during low, non-pressor-dose ET-1 compared with placebo infusion. DESIGN: In a randomized, single blind, crossover design, 10 lean normotensive male subjects received either an intravenous infusion of subpressor doses of ET-1 dissolved in polygeline or a control infusion of polygeline only (placebo). Using dynamic assessment by the minimal model approach with the modified frequent sampling intravenous glucose tolerance test (FSIGT) the following and other parameters were measured: insulin sensitivity; acute insulin response to glucose (AIR(G)) calculated as the average of the three peak values between 2 and 5 min after injection of glucose from which the basal insulin levels were subtracted; the initial area under the curve (AUC(1-19)) from insulin values between time 0 and 19 min and the first-phase insulin secretion (phi1) from insulin kinetics parameters. RESULTS: ET-1 infusion reduced AIR(G) (to 34.85 +/- 4.27 compared with 49.3 +/- 6.9 microU/ml during placebo, P=0.017) and the acute C-peptide response to glucose (to 2.33 +/- 0.41 compared with 3.1 +/- 0.44 ng/ml, P=0.018), decreased plasma insulin levels during the FSIGT compared with placebo (analysis of variance P<0.0001) and decreased the AUC(1-19) (to 2.1 +/- 0.2 compared with 2.9 +/- 0.3 U/l per 20 min, P<0.01) while phi1 tended to be lower. S1 measured during ET-1 infusion was unaltered (11.11 +/- 1.91 x 10(-4) versus 10.88 +/- 2.11 10(-4)/min per mU per l, NS). CONCLUSIONS: These findings demonstrate that an increase in circulating ET-1 to levels observed in insulin-resistant states acutely diminishes the insulin secretory response but does not significantly modify insulin sensitivity.     

Correlations between blood pressure, blood volume and plasma renin during therapy with diuretics in essential hypertension. Comparison between the mineralocorticoid antagonist spironolactone and the "loop" diuretic mefruside

35 patients with benign essential hypertension were treated for 6 weeks with high doses of the mineralocorticoid-antagonist spironolactone (400 mg/day), or with the "loop-diuretic" mefruside (mean maximal dose 110 mg/day). Spironolactone caused greater reductions in blood pressure and blood volume and a more marked increase in plasma renin activity (PRA) than mefruside (p less than 0.05). It appears possible that he weaker antihypertensive effect of mefruside may relate partly to its lesser influence on circulatory volume. With both diuretics, mean decreases in blood pressure were greater in patients with low pre-therapeutic PRA than in patients with normal or high PRA. However, the diuretic-induced changes in blood pressure did not correlate with the associated variations in blood volume or PRA. Thus, the increased blood pressure sensitivity to diuretics in patients with low-renin essential hypertension did not appear to be volume or renin-dependent. Under normal conditions, the maintenance of a constant blood pressure during volume depletion may partly depend on compensatory activation of the sympathetic nervous system. Moreover, patients with low-renin essential hypertension have been found to have decreased adrenergic activity. It seems possible, therefore, that the marked blood pressure sensitivity to diuretic treatment in such patients may be the result of an impaired compensatory sympathetic response to sodium and volume depletion. Analysis of the literature suggests that the diuretic furosemide, a structural relative of mefruside, may also have less blood pressure lowering efficacy in patients with essential hypertension than the distally-acting thiazides, chlorthalidone or spironolactone. Consideration of possible differences in the blood pressure reducing potential of certain diuretics thus appears to be necessary in planning the pharmacotherapy of essential hypertension.     

Osteoblast cell response to surface-modified carbon nanotubes

In order to investigate the interaction of cells with modified multi-walled carbon nanotubes (MWCNTs) for their potential biomedical applications, the MWCNTs were chemically modified with carboxylic acid groups (–COOH), polyvinyl alcohol (PVA) polymer and biomimetic apatite on their surfaces. Additionally, human osteoblast MG-63 cells were cultured in the presence of the surface-modified MWCNTs. The metabolic activities of osteoblastic cells, cell proliferation properties, as well as cell morphology were studied. The surface modification of MWCNTs with biomimetic apatite exhibited a significant increase in the cell viability of osteoblasts, up to 67.23%. In the proliferation phases, there were many more cells in the biomimetic apatite-modified MWCNT samples than in the MWCNTs–COOH. There were no obvious changes in cell morphology in osteoblastic MG-63 cells cultured in the presence of these chemically-modified MWCNTs. The surface modification of MWCNTs with apatite achieves an effective enhancement of their biocompatibility.     

Monitoring of ethylene by a pulsed quantum cascade laser

We report on the development and performance of a gas sensor based on a quantum cascade laser operating at a wavelength of approximately 10 microns to measure ethylene (C2H4) concentrations by use of a rotational component of the fundamental nu 7 band. The laser is thermoelectrically cooled and operates in a pulsed mode. The influence of pulse-to-pulse fluctuations is minimized by use of a reference beam and a single detector with time discriminating electronics. Gas absorption is recorded in a 100-m optical path-length astigmatic Herriott cell. With a 10-kHz pulse repetition rate and an 80-s total acquisition time, a noise equivalent sensitivity of 30 parts per billion has been demonstrated. The sensor has been applied to monitor C2H4 in vehicle exhaust as well as in air collected in a high-traffic urban tunnel.     

Influence of oxygen and water related surface defects on the dye sensitized TiO2 solar cell

Oxygen- and water-related surface defects on porous TiO₂ (anatase) can be well controlled by the oxygen and water partial pressures and therefore such defects are of technological relevance for dye sensitized TiO₂ solar cells. We investigated the action of oxygen and water-related surface defects in situ by impedance spectroscopy, photoconductivity, photoluminescence, and optical transmission as well as by characterizing solar cells which were prepared under respective conditions. Oxygen loss from the TiO₂ surface leads to electrical doping by Ti³⁺/oxygen donor states. Such defects create recombination paths for injected electrons back into the electrolyte. Pre-treatment of porous TiO₂ by chemisorption of water increases the open circuit voltage of the solar cells without altering the short circuit current. Water-related surface defects decrease the saturation current of the diode, probably by raising the barrier height at the TiO₂/electrolyte interface.     

Crazing and the creep behaviour of PMMA in methanol

A considerable increase in strain was observed when crazes formed during tensile creep tests on poly(methyl methacrylate) (PMMA) specimens immersed in methanol. A model of craze growth from surface flaws is proposed which is based on craze growth kinetics, and which shows good correlation with the measured time and stress dependent behaviour.     

Retrieval of atmospheric ozone profiles from an infrared quantum cascade laser heterodyne radiometer: results and analysis

Following the recent development of a ground-based prototype quantum cascade laser heterodyne radiometer operating in the midinfrared, atmospheric ozone profile retrievals from a solar occultation measurement campaign performed at the Rutherford Appleton Laboratory on 21 September 2006 are presented. Retrieval is based on the optimal estimation method. High resolution (0.0073 cm(-1)) atmospheric spectra recorded by the laser heterodyne radiometer and covering a microwindow (1033.8-1034.5 cm(-1)) optimized for atmospheric ozone measurements were used as measurement vectors. As part of the evaluation of this novel instrument, a comprehensive analysis of the retrievals is presented, demonstrating the high potential of quantum cascade laser heterodyne radiometry for atmospheric sounding. Vertical resolutions of 2 km near the ground and about 3 km in the stratosphere were obtained. The information content of the retrieval was found to be up to 48 bits, which is much higher than any other passive ground-based instrument. Frequency mismatches of several absorption peaks between the forward model and experimental spectra have been observed and significantly contribute to the retrieval noise error in the upper-troposphere lower-stratosphere region. Retrieved ozone vertical profiles were compared to ozonesonde data recorded at similar latitudes. The agreement is generally excellent except for the 20 to 25 km peak in ozone concentration, where ozonesonde data were found to be 20% lower than the amount retrieved from the laser heterodyne radiometer spectra. Quantum cascade laser based heterodyne radiometry in the midinfrared has been demonstrated to provide high spectral resolution and unprecedented vertical resolution for a passive sounder in a highly compact and mechanically simple package.