Chlorzoxazone, an SK-type potassium channel activator used in humans, reduces excessive alcohol intake in rats

Background Alcoholism imposes a tremendous social and economic burden. There are relatively few pharmacological treatments for alcoholism, with only moderate efficacy, and there is considerable interest in identifying additional therapeutic options. Alcohol exposure alters SK-type potassium channel (SK) function in limbic brain regions. Thus, positive SK modulators such as chlorzoxazone (CZX), a US Food and Drug Administration–approved centrally acting myorelaxant, might enhance SK function and decrease neuronal activity, resulting in reduced alcohol intake. Methods We examined whether CZX reduced alcohol consumption under two-bottle choice (20% alcohol and water) in rats with intermittent access to alcohol (IAA) or continuous access to alcohol (CAA). In addition, we used ex vivo electrophysiology to determine whether SK inhibition and activation can alter firing of nucleus accumbens (NAcb) core medium spiny neurons. Results Chlorzoxazone significantly and dose-dependently decreased alcohol but not water intake in IAA rats, with no effects in CAA rats. Chlorzoxazone also reduced alcohol preference in IAA but not CAA rats and reduced the tendency for rapid initial alcohol consumption in IAA rats. Chlorzoxazone reduction of IAA drinking was not explained by locomotor effects. Finally, NAcb core neurons ex vivo showed enhanced firing, reduced SK regulation of firing, and greater CZX inhibition of firing in IAA versus CAA rats. Conclusions The potent CZX-induced reduction of excessive IAA alcohol intake, with no effect on the more moderate intake in CAA rats, might reflect the greater CZX reduction in IAA NAcb core firing observed ex vivo. Thus, CZX could represent a novel and immediately accessible pharmacotherapeutic intervention for human alcoholism. Key Words: Alcohol intake; intermittent; neuro-adaptation; nucleus accumbens; SK potassium channel

Stochastic models and simulation of ion channel dynamics

The behaviour of ion channels within cardiac and neuronal cells is intrinsically stochastic in nature. When the number of channels is small this stochastic noise is large and can have an impact on the dynamics of the system which is potentially an issue when modelling small neurons and drug block in cardiac cells. While exact methods correctly capture the stochastic dynamics of a system they are computationally expensive, restricting their inclusion into tissue level models and so approximations to exact methods are often used instead. The other issue in modelling ion channel dynamics is that the transition rates are voltage dependent, adding a level of complexity as the channel dynamics are coupled to the membrane potential. By assuming that such transition rates are constant over each time step, it is possible to derive a stochastic differential equation (SDE), in the same manner as for biochemical reaction networks, that describes the stochastic dynamics of ion channels. While such a model is more computationally efficient than exact methods we show that there are analytical problems with the resulting SDE as well as issues in using current numerical schemes to solve such an equation. We therefore make two contributions: develop a different model to describe the stochastic ion channel dynamics that analytically behaves in the correct manner and also discuss numerical methods that preserve the analytical properties of the model.

Serum bone formation marker correlation with improved osseointegration in osteoporotic rats treated with simvastatin

Objective: Simvastatin has been shown to enhance osseointegration of pure titanium implants in osteoporotic rats. This study aimed to evaluate the relationship between the serum level of bone formation markers and the osseointegration of pure titanium implants in osteoporotic rats treated with simvastatin. Materials and methods: Fifty-four female Sprague Dawley rats, aged 3 months old, were randomly divided into three groups: Sham-operated group (SHAM; n=18), ovariectomized group (OVX; n=18), and ovariectomized with Simvastatin treatment group (OVX+SIM; n=18). Fifty-six days after ovariectomy, screw-shaped titanium implants were inserted into the tibiae. Simvastatin was administered orally at 5mg/kg each day after the placement of the implant in the OVX+SIM group. The animals were sacrificed at either 28 or 84 days after implantation and the undecalcified tissue sections were processed for histological analysis. Total alkaline phosphatase (ALP), bone specific alkaline phosphatase (BALP) and bone Gla protein (BGP) were measured in all animal sera collected at the time of euthanasia and correlated with the histological assessment of osseointegration. Results: The level of ALP in the OVX group was higher than the SHAM group at day 28, with no differences between the three groups at day 84. The level of BALP in the OVX+SIM group was significantly higher than both OVX and SHAM groups at days 28 and 84. Compared with day 28, the BALP level of all three groups showed a significant decrease at day 84. There were no significant differences in BGP levels between the three groups at day 28, but at day 84 the OVX+SIM group showed significantly higher levels than both the OVX and SHAM groups. There was a significant increase in BGP levels between days 28 and 84 in the OVX+SIM group. The serum bone marker levels correlated with the histological assessment showing reduced osseointegration in the OVX compared to the SHAM group which is subsequently reversed in the OVX+SIM group.

Turbulence characteristics of a small subtropical estuary during and after some moderate rainfall

In natural estuaries, scalar diffusion and dispersion are driven by turbulence. In the present study, detailed turbulence measurements were conducted in a small subtropical estuary with semi-diurnal tides under neap tide conditions. Three acoustic Doppler velocimeters were installed mid-estuary at fixed locations close together. The units were sampled simultaneously and continuously at relatively high frequency for 50 h. The results illustrated the influence of tidal forcing in the small estuary, although low frequency longitudinal velocity oscillations were observed and believed to be induced by external resonance. The boundary shear stress data implied that the turbulent shear in the lower flow region was one order of magnitude larger than the boundary shear itself. The observation differed from turbulence data in a laboratory channel, but a key feature of natural estuary flow was the significant three dimensional effects associated with strong secondary currents including transverse shear events. The velocity covariances and triple correlations, as well as the backscatter intensity and covariances, were calculated for the entire field study. The covariances of the longitudinal velocity component showed some tidal trend, while the covariances of the transverse horizontal velocity component exhibited trends that reflected changes in secondary current patterns between ebb and flood tides. The triple correlation data tended to show some differences between ebb and flood tides. The acoustic backscatter intensity data were characterised by large fluctuations during the entire study, with dimensionless fluctuation intensity I0b =Ib between 0.46 and 0.54. An unusual feature of the field study was some moderate rainfall prior to and during the first part of the sampling period. Visual observations showed some surface scars and marked channels, while some mini transient fronts were observed.

A review of road traffic noise indicators and their correlation with the LA10(18hour)

This paper outlines a study to determine the correlation between the LA10(18hour) and other road traffic noise indicators. It is based on a database comprising of 404 measurement locations including 947 individual days of valid noise measurements across numerous circumstances taken between November 2001 and November 2007. This paper firstly discusses the need and constraints on the indicators and their nature of matching a suitable indicator to the various road traffic noise dynamical characteristics. The paper then presents a statistical analysis of the road traffic noise monitoring data, correlating various indicators with the LA10(18hour) statistical indicator and provides a comprehensive table of linear correlations. There is an extended analysis on relationships across the night time period. The paper concludes with a discussion on the findings.

Analysis of multiple shared channel cooperative routing in OFDM based wireless networks

Diversity techniques have long been used to combat the channel fading in wireless communications systems. Recently cooperative communications has attracted lot of attention due to many benefits it offers. Thus cooperative routing protocols with diversity transmission can be developed to exploit the random nature of the wireless channels to improve the network efficiency by selecting multiple cooperative nodes to forward data. In this paper we analyze and evaluate the performance of a novel routing protocol with multiple cooperative nodes which share multiple channels. Multiple shared channels cooperative (MSCC) routing protocol achieves diversity advantage by using cooperative transmission. It unites clustering hierarchy with a bandwidth reuse scheme to mitigate the co-channel interference. Theoretical analysis of average packet reception rate and network throughput of the MSCC protocol are presented and compared with simulated results.

Ergodic capacity of the exponentially correlated slotted amplify and forward relay channel

In this paper we analyze the performance degradation of slotted amplify-and-forward protocol in wireless environments with high node density where the number of relays grows asymptotically large. Channel gains between source-destination pairs in such networks can no longer be independent. We analyze the degradation of performance in such wireless environments where channel gains are exponentially correlated by looking at the capacity per channel use. Theoretical results for eigenvalue distribution and the capacity are derived and compared with the simulation results. Both analytical and simulated results show that the capacity given by the asymptotic mutual information decreases with the network density.

Patterns of correlation between vehicle occupant seat pressure and anthropometry

Seat pressure is known as a major factor of seat comfort in vehicles. In passenger vehicles, there is lacking research into the seat comfort of rear seat occupants. As accurate seat pressure measurement requires significant effort, simulation of seat pressure is evolving as a preferred method. However, analytic methods are based on complex finite element modeling and therefore are time consuming and involve high investment. Based on accurate anthropometric measurements of 64 male subjects and outboard rear seat pressure measurements in three different passenger vehicles, this study investigates if a set of parameters derived from seat pressure mapping are sensitive enough to differentiate between different seats and whether they correlate with anthropometry in linear models. In addition to the pressure map analysis, H-Points were measured with a coordinate measurement system based on palpated body landmarks and the range of H-Point locations in the three seats is provided. It was found that for the cushion, cushion contact area and cushion front area/force could be modeled by subject anthropometry,while only seatback contact area could be modeled based on anthropometry for all three vehicles. Major differences were found between the vehicles for other parameters.

Analysis of rural MUSA-MIMO-OFDM uplink channel capacity

Multi-user single antenna multiple-input multiple-output orthogonal frequency division multiplexing (MUSA-MIMO-OFDM) is a promising technology to improve the spectrum efficiency of fixed wireless broadband access systems in rural areas. This letter investigates the capacity of MUSA-MIMO-OFDM uplink channel by theoretical, simulation, and empirical approaches considering up to six users. We propose an empirical capacity formula suitable for rural areas. Characteristics of channel capacity temporal variations and their relationship with the wind speed, observed in a rural area, are also presented in this letter.