In septic shock (SS), hydrogen peroxide (H2O2) and other reactive oxygen species (ROS) are released by inflammatory cells and have been implicated in tissue damage and inflammation. Recently, H2O2 has been established as an important signaling molecule and an important component of SS. The pathways involved in this process are not completely understood, but the formation of hydroperoxides (HPs), arachidonic acid (AA) metabolites and potassium (K+) channels have been implicated. In this study, we used a canine carotid ring preparation as a bioassay to determine the role of peroxyacetic acid (POX), a hydroperoxide (HP), in causing vasodilation and elucidate the subsequent pathways involved. We removed internal carotid artery segments from dogs and placed them in an organ bath. The segments were preconstricted after which we added POX to the preparation. We found that POX produced an endothelium and nitric oxide independent vasodilation in the carotid artery ring preparation. This decrease in tension could be prevented by high concentrations of K+ in the bath. This suggested that K+ channels were involved in POX’s action. Further investigation showed that the particular K+ channels implicated were the combination of small (SKCa) and intermediate conductance calcium activated K+ channels (IKCa). In addition we found that the prostaglandin H synthase (PGHS) inhibitor, indomethacin, could block POX’s mechanism of action. This finding indicates that PGHS takes part in the vasodilation caused by POX. Our results suggest that HPs that are released from inflammatory cells in sepsis could stimulate the PGHS pathway leading to prostaglandin synthesis and subsequently activating SKCa and IKCa to produce vasodilation. Inhibition of this pathway may be important component in the treatment of SS.

No description available.

No description available.

Spatial and temporal variations in channel morphology, near-bed velocity, shear stress, bedload transport rate, pebble tracer movement, and bedload and bed material size distribution were measured in seven different channel patterns in two gravel-bed rivers in the Scottish Highlands (the Dubhaig and Feshie) and a proglacial stream in Norway (the Lyngsdalselva). The results showed that there were discernible links between the channel processes and changes which were consistent for all river types. 169 shear stress estimates from velocity profiles with changing discharge showed that Keller's (1971) velocity-reversal hypothesis holds true in different channel patterns of gravel-bed rivers and can be extended to include subunits of the pool/riffle cycle. At discharges near bankfull there is a decrease in the flow strength and amount of bedload movement from the poolhead down to the pooltail (and then riffle). On a broader scale 72 Helley-Smith bedload samples and the movement of over 3700 pebble tracers showed that the entrainment of different size fractions from heterogeneous bed material is inefficient and is overpredicted by the traditional bedload transport equations. Empirical analyses showed that when the armour is mobile/broken large and small particles have almost equal mobility as first proposed by Parker et al. (1982) and Andrews (1983). However for the majority of flow conditions the armour is static and entrainment is selective to a greater or lesser degree depending on the availability of appropriate-sized sediment at the surface and from bank erosion. The magnitude and direction of flow strength and bedload transport helps to explain the location and mode of channel development as revealed by repeated levelling and mapping. The accelerating convergent/decelerating divergent cells of flow alter the channel morphology in predictable ways. The positions of these cells can change with increasing discharge as the channel becomes generally, rather than locally, competent to move coarse sediment. The rates of bank erosion and volumetric scour and fill decreased from the active multi-braided system through to the stable straight channel type.

Excitable cells display dynamically regulated changes in the properties of ion currents during development. These changes are crucial for the proper maturation of cellular excitability, and therefore have the potential to affect more sophisticated functions, including neural circuits, movements, and behaviors. Zebrafish skeletal muscle is an excellent model for studying the development of ion channels and their contributions to excitability. They possess distinguishable populations of red and white muscle fibers, whose biological functions are well understood. The main objectives of this thesis were: (1) To characterize the development of muscle excitability by examining properties of voltage-gated sodium and potassium currents expressed in embryonic and larval zebrafish during the first week of development. (2) To elucidate some of the mechanisms by which ion current development might be controlled, beginning with activity-dependent and phosphorylation-dependent mechanisms. These objectives were approached using whole-cell electrophysiological techniques to examine the voltage-dependent and kinetic properties of voltage-gated sodium and potassium currents in intact zebrafish skeletal muscle preparations. Mutant sofa potato zebrafish, which lack functional nicotinic acetylcholine receptors, were then utilized to determine whether synaptic activity at the neuromuscular junction is required for proper ion current development. Finally, protein kinases were activated pharmacologically in order to determine whether they were able to modulate ion currents during development. The results revealed that properties of ion currents undergo a developmental progression, including increased current density, accelerated kinetics, and shifts in voltage-dependence; these developments correlated well with the maturation of muscle action potentials and the movements and behaviors they mediate. Sofa potato mutants were found to be deficient in certain aspects of ion current development, but other aspects appeared to be unaffected by a lack of synaptic activity. Protein kinase A demonstrated the ability to drastically reduce potassium current density; however the effects of PKA were similar at all developmental stages. Overall, these findings provide novel insight into the roles played by voltage-gated currents during the development of excitability in zebrafish skeletal muscle, and expand the rapidly growing body of knowledge about ion channel function in general. / Physiology, Cell & Developmental Biology

Thesis (Ph. D.)--University of Hawaii at Manoa, 1990. / Includes bibliographical references (leaves 135-153) / Microfiche. / xi, 153 leaves, bound ill. 29 cm

In the skeletal muscle cell membrane, the voltage gated chloride channel, CIC-1, maintains as unusually high resting membrane conductance and thereby prevents myotonic skeletal muscle disease. Protein crystallization experiments with bacterial CIC proteins, provide the information for the three dimensional (3D) structure of CIC chloride channels. / Thesis (PhDBiomedicalScience)--University of South Australia, 2003.

Bibliography: p. 159-171. / xviii, 171 p., [61] leaves of plates : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 1996?

Drawdown is the lowering of the water level, and can refer to the groundwater, or the level of a river. In this thesis it will generally refer to a river going from a high flow condition to a lower flow condition. The rate of drawdown is expressed as either the change in flow per unit time, or the change in stage per unit time. The later is of most importance in terms of bank stability. (For complete abstract open document)

Thesis (M.S. - Hydrology and Water Resources)--University of Arizona. / Includes bibliographical references (leaves 99-104).