Impaired thermoregulatory function during dynamic exercise in multiple sclerosis

INTRODUCTION: Impairments in sudomotor function during passive whole-body heating have been reported in multiple sclerosis (MS), a demyelinating disease of the CNS that disrupts autonomic function. However, the capability of the thermoregulatory system to control body temperature during exercise has never been assessed in MS. Thus, the aim of the present study was to test the hypothesis that thermoregulatory function is impaired in MS patients compared to healthy controls (CON) exercising at similar rates of metabolic heat production. METHODS: Sweating and skin blood flow responses were compared between 12 individuals diagnosed with relapsing-remitting MS (9 females, 3 males) and 12 sex-, age-, mass- and BSA-matched healthy controls during a single bout of cycling exercise (rate of metabolic heat production: ~4.5 W/kg) for 60 min in a climate-controlled room (25 °C, 30% RH). RESULTS: Individuals with MS exhibited an attenuated increase in cumulative whole-body sweat loss after 30 min (MS: 72 ± 51; CON: 104 ± 37 g, p=0.04) and 60 min (MS: 209 ± 94; CON: 285 ± 62 g, p=0.02), as well as lower sweating thermosensitivity (MS: 0.49 ± 0.26; CON: 0.86 ± 0.30 mg/cm2/min/°C, p=0.049). Despite evidence for thermoregulatory dysfunction, there were no differences between MS and CON in esophageal or rectal temperatures at 30 or 60 min time points (p>0.05). Cutaneous vasculature responses were also not different in MS compared to CON (p>0.05). CONCLUSION: Taken together, MS blunts sweating responses during exercise while cutaneous vasculature responses are preserved. Altered mechanisms of body temperature regulation in persons with MS may lead to temporary worsening of disease symptoms and limit exercise tolerance under more thermally challenging conditions.Accepted manuscrip

An experimental design approach to the chemical characterisation of pectin polysaccharides extracted from Cucumis melo Inodorus

Extracted pectins have been utilised in a number of applications in both the food and pharmaceutical industries where they are generally used as gelling agents, thickeners and stabilisers, although a number of pectins have been shown to be bioactive. These functional properties will depend upon extraction conditions. A statistical experimental design approach was used to study the effects of extraction conditions pH, time and temperature on pectins extracted from Cucumis melo Inodorus. The results show that the chemical composition is very sensitive to these conditions and that this has a great influence on for example the degree of branching. Higher temperatures, lower pHs and longer extraction times lead to a loss of the more acid labile arabinofuranose residues present on the pectin side chain. The fitting of regression equations relating yield and composition to extraction conditions can therefore lead to tailor-made pectins for specific properties and/ or applications

The Liquidus Temperature for Methanol-Water Mixtures at High Pressure and Low Temperature, with Application to Titan

Methanol is a potentially important impurity in subsurface oceans on Titan and Enceladus. We report measurements of the freezing of methanol-water samples at pressures up to 350~MPa using a volumetric cell with sapphire windows. For low concentrations of methanol, the liquidus temperature is typically a few degrees below the corresponding ice freezing point, while at high concentrations it follows the pure methanol trend. In the Ice-III regime, we observe several long-lived metastable states. The results suggest that methanol is a more effective antifreeze than previously estimated, and might have played an important role in the development of Titan's subsurface ocean

Consensus virtual screening approaches to predict protein ligands

In order to exploit the advantages of receptor-based virtual screening, namely time/cost saving and specificity, it is important to rely on algorithms that predict a high number of active ligands at the top ranks of a small molecule database. Towards that goal consensus methods combining the results of several docking algorithms were developed and compared against the individual algorithms. Furthermore, a recently proposed rescoring method based on drug efficiency indices was evaluated. Among AutoDock Vina 1.0, AutoDock 4.2 and GemDock, AutoDock Vina was the best performing single method in predicting high affinity ligands from a database of known ligands and decoys. The rescoring of predicted binding energies with the water/butanol partition coeffcient did not lead to an improvement averaged over all receptor targets. Various consensus algorithms were investigated and a simple combination of AutoDock and AutoDock Vina results gave the most consistent performance that showed early enrichment of known ligands for all receptor targets investigated. In case a number ligands is known for a specific target, every method proposed in this study should be evaluated

Neuropeptide F regulates courtship in Drosophila through a male-specific neuronal circuit.

Male courtship is provoked by perception of a potential mate. In addition, the likelihood and intensity of courtship are influenced by recent mating experience, which affects sexual drive. Using Drosophila melanogaster, we found that the homolog of mammalian neuropeptide Y, neuropeptide F (NPF), and a cluster of male-specific NPF (NPFM) neurons, regulate courtship through affecting courtship drive. Disrupting NPF signaling produces sexually hyperactive males, which are resistant to sexual satiation, and whose courtship is triggered by sub-optimal stimuli. We found that NPFM neurons make synaptic connections with P1 neurons, which comprise the courtship decision center. Activation of P1 neurons elevates NPFM neuronal activity, which then act through NPF receptor neurons to suppress male courtship, and maintain the proper level of male courtship drive

Development of mucoadhesive sprayable gellan gum fluid gels

The nasal mucosa provides a potentially good route for local and systemic drug delivery. However, the protective feature of the nasal cavity make intranasal delivery challenging. The application of mucoadhesive polymers in nasal drug delivery systems enhances the retention of the dosage form in the nasal cavity. Several groups have investigated using low acyl gellan as a drug delivery vehicle but only limited research however, has been performed on high acyl gellan for this purpose, despite its properties being more conducive to mucoadhesion. High acyl gellan produces highly elastic gels below 60 °C which make it difficult to spray using a mechanical spray device. Therefore, in this study we have tried to address this problem by making fluid gels by introducing a shear force during gelation of the gellan polymer. These fluid gel systems contain gelled micro-particles suspended in a solution of un-gelled polymer. These systems can therefore behave as pourable viscoelastic fluids. In this study we have investigated the rheological behavior and mucoadhesion of fluid gels of two different types of gellan (high and low acyl) and fluid gels prepared from blends of high and low acyl gellan at a 50:50 ratio. The results demonstrated that by preparing fluid gels of high acyl gellan, the rheological properties were sufficient to spray through a standard nasal spray device. Moreover fluid gels also significantly enhance both high acyl and low acyl gellan mucoadhesion properties

Helping and servicing regional small businesses: an evaluation of the Business Grow Program in the South West region of Western Australia

In October 1997 the Edith Cowan University was invited to evaluate the performance of the Business Grow Program. The program commenced on July 1, 1995, and its evaluation, scheduled to be completed by April 1998, has been undertaken to assess the performance of the Program since its instigation. The evaluation team has relied substantially on information provided by small business owners, local government representatives, industry associations, and the manager of the Program. The evaluation team would like to thank Kate Loughton for her assistance in facilitating the administration of this project. The evaluation was undertaken by Small and Medium Enterprise Research Centre (SMERC). The team consisted of Dr Xueli (Charles) Huang, Post-Doctoral Research Fellow at SMERC, Associate Professor Alan Brown, Director of SMERC, Barry Chapman, Graduate and Higher Degree Coordinator, and Robyn Morris, Senior Lecturer in Faculty of Business and Head of Business Program, Bunbury campus. SMERC is the principal research centre in the Faculty of Business at Edith Cowan University and harnesses the SME expertise of the staff in the Faculty

Development of component and system level test methods to characterize manual wheelchair propulsion cost

The current approach to manual wheelchair design lacks a sound and objective connection to metrics for wheelchair performance. The objective of this research was three-fold: 1) to characterize the inertial and resistive properties of different wheelchair components and configurations, 2) to characterize the systems-level wheelchair propulsion cost, and 3) to model wheelchair propulsion cost as a function of measured component and configuration properties. Scientific tools developed include 1) a series of instruments and methodologies to evaluate the rotational inertia, rolling resistance, and scrub torque of wheelchair casters and drive wheels on various surface types, and 2) a wheelchair-propelling robot capable of measuring propulsion cost across a collection of maneuvers representative of everyday wheelchair mobility. This suite of tools were used to demonstrate the variance manifested in the resistive properties of 8 casters and 4 drive wheels, and the impact/tradeoffs of these components (as well as mass and weight distribution) on system-level wheelchair propulsion cost. Coupling these findings with a theoretical framework describing wheelchair dynamics resulted in two empirical models linking system propulsion cost to component resistive properties. The outcomes of this research empower clinicians and users to make more informed wheelchair selections, as well as offer manufacturers a basis by which to optimize their wheelchair designs.Ph.D