A report of the Sixth Annual Meeting of the International Society for the Prevention of Tobacco Induced Diseases (ISPTID)

The Sixth meeting of the International Society for the Prevention of Tobacco Induced Diseases (ISPTiD) was held in Little Rock, Arkansas on November 2–4, 2007 and has brought together 140 participants, scientists and experts in this specialized field from 30 countries across the World. The central theme of the conference was the "Translational Approaches to the Prevention of Tobacco Induced Diseases". Discussions held during the three days meeting's sessions (including poster session and platform discussion) promoted a better understanding of the connection between tobacco use and associated medical and health consequences. The Sixth Annual meeting of ISPTiD served as another successful step toward decrease in the huge sociological and economical burden that the entire World is facing with this addiction. The proceedings of the meeting were published in the conference booklet, the ISPTiD global web site and Cancer Database abstract web site. Funds generated from this meeting helped in part to establish the society's Journal "Tobacco Induced Diseases "into the major scientific journal index PubMed database and BioMed Central. The meeting set the tone for next the Annual meeting in Kyoto, Japan for the year 2008 with the theme "Tobacco free future"

Na+–K+ pump cycle during β-adrenergic stimulation of adult rat cardiac myocytes

The mechanisms underlying the increase in Na+–K+ pump current (Ip) caused by adrenergic stimulation were investigated in cultured adult rat cardiac myocytes using the whole-cell patch-clamp technique at 31–33 °C.In myocytes perfused internally with 50 mm Na+ (0 Ki+, 20 nM Ca2+, caesium aspartate solution) and externally with 5.4 mm Ko+, noradrenaline (NA) and isoprenaline (Iso) (1–50 μm) stimulated Ip by 40–45 %.Na+-dependent transient Ip measurements with 0 mm Ki+ and 0 mm Ko+ revealed no change in the total charge transferred by the Na+–K+ pump during the conformational change, suggesting that the pump site density was not changed by adrenergic stimulation (2630 ± 370 pumps μm−2 in control and 2540 ± 190 pumps μm−2 in the presence of 10 μm NA).With saturating Nai+ or Ko+ (150 and 15–20 mm, respectively), Ip was still stimulated by NA and Iso. Thus, there was no indication that adrenergic activation of the Na+–K+ pump was mediated by accumulation of Nai+ and Ko+ or changes in the Na+–K+ pump affinity for Nai+ and Ko+.Both Ip and its increase under adrenergic stimulation were found to depend on [K+]i. While steady-state Ip decreased from 2.2 ± 0.1 to 1.2 ± 0.1 pA pF−1 (P < 0.05), the stimulation of Ip by 10 μm Iso increased from 0.38 ± 0.04 to 0.67 ± 0.06 pA pF−1 (P < 0.05) with an increase in [K+]i from 0 to 100 mm.Under conditions that cause the Ip-Vm (membrane potential) relationship to express a positive slope ([Na+]o, 150 mm; [K+]o, 5.4 mm) or a negative slope ([Na+]o, 0; [K+]o, 0.3 mm) Iso stimulated Ip with no change in the shape of Ip-Vm curves. Thus, adrenergic stimulation of the Na+–K+ pump was not due to an alteration of voltage-dependent steps of the pump cycle.Simulation of these data with a six-step model of the Na+–K+ pump cycle suggested that in rat ventricular myocytes a signal from adrenergic receptors increased the Na+–K+ pump rate by modulating the rate of K+ de-occlusion and release by the pump

Changes in Mechanical Properties of Rat Bones under Simulated Effects of Microgravity and Radiation†

AbstractThe aim of this study was to determine the changes in elasticity and lattice structure in leg bone of rats which were: 1) under Hind-Limb Suspension (HLS) by tail for 2 weeks and 2) exposed to a total radiation of 10 Grays in 10 days. The animals were sacrificed at the end of 2 weeks and the leg bones were surgically removed, cleaned and fixed with a buffered solution. The mechanical strength of the bone (elastic modulus) was determined from measurement of bending of a bone when under an applied force. Two methodologies were used: i) a 3-point bending technique and ii) classical bending where bending is accomplished keeping one end fixed. Three point bending method used a captive actuator controlled by a programmable IDEA drive. This allowed incremental steps of 0.047mm for which the force is measured. The data is used to calculate the stress and the strain. In the second method a mirror attached to the free end of the bone allowed a reflected laser beam spot to be tracked. This provided the displacement measurement as stress levels changed. Analysis of stress vs. strain graph together with solution of Euler-Bernoulli equation for a cantilever beam allowed determination of the elastic modulus of the leg bone for (i) control samples, (ii) HLS samples and (iii) HLS samples with radiation effects. To ascertain changes in the bone lattice structure, the bones were cross-sectioned and imaged with a 20 keV beam of electrons in a Scanning Electron Microscope (SEM). A backscattered detector and a secondary electron detector in the SEM provided the images from well-defined parts of the leg bones. Elemental compositions in combination with mechanical properties (elastic modulus and lattice structure) changes indicated weakening of the bones under space-like conditions of microgravity and radiation

Sub-cellular Electrical Heterogeneity Revealed by Loose Patch Recording Reflects Differential Localization of Sarcolemmal Ion Channels in Intact Rat Hearts

The cardiac action potential (AP) is commonly recoded as an integral signal from isolated myocytes or ensembles of myocytes (with intracellular microelectrodes and extracellular macroelectrodes, respectively). These signals, however, do not provide a direct measure of activity of ion channels and transporters located in two major compartments of a cardiac myocyte: surface sarcolemma and the T-tubule system, which differentially contribute to impulse propagation and excitation-contraction (EC) coupling. In the present study we investigated electrical properties of myocytes within perfused intact rat heart employing loose patch recording with narrow-tip (2 μm diameter) extracellular electrodes. Using this approach, we demonstrated two distinct types of electric signals with distinct waveforms (single peak and multi-peak AP; AP1 and AP2, respectively) during intrinsic pacemaker activity. These two types of waveforms depend on the position of the electrode tip on the myocyte surface. Such heterogeneity of electrical signals was lost when electrodes of larger pipette diameter were used (5 or 10 μm), which indicates that the electric signal was assessed from a region of &lt;5 μm. Importantly, both pharmacological and mathematical simulation based on transverse (T)-tubular distribution suggested that while the AP1 and the initial peak of AP2 are predominantly attributable to the fast, inward Na+ current in myocyte's surface sarcolemma, the late components of AP2 are likely representative of currents associated with L-type Ca2+ channel and Na+/Ca2+ exchanger (NCX) currents which are predominantly located in T-tubules. Thus, loose patch recording with narrow-tip pipette provides a valuable tool for studying cardiac electric activity on the subcellular level in the intact heart