Vascular α1A Adrenergic Receptors as a Potential Therapeutic Target for IPAD in Alzheimer’s Disease

Drainage of interstitial fluid from the brain occurs via the intramural periarterial drainage (IPAD) pathways along the basement membranes of cerebral capillaries and arteries against the direction of blood flow into the brain. The cerebrovascular smooth muscle cells (SMCs) provide the motive force for driving IPAD, and their decrease in function may explain the deposition of amyloid-beta as cerebral amyloid angiopathy (CAA), a key feature of Alzheimer's disease. The α-adrenoceptor subtype α1A is abundant in the brain, but its distribution in the cerebral vessels is unclear. We analysed cultured human cerebrovascular SMCs and young, old and CAA human brains for (a) the presence of α1A receptor and (b) the distribution of the α1A receptor within the cerebral vessels. The α1A receptor was present on the wall of cerebrovascular SMCs. No significant changes were observed in the vascular expression of the α1A-adrenergic receptor in young, old and CAA cases. The pattern of vascular staining appeared less punctate and more diffuse with ageing and CAA. Our results show that the α1A-adrenergic receptor is preserved in cerebral vessels with ageing and in CAA and is expressed on cerebrovascular smooth muscle cells, suggesting that vascular adrenergic receptors may hold potential for therapeutic targeting of IPAD.</p

On the Pulsed and Transitional Behavior of an Electrified Fluid Interface

Journal of Fluids Engineering Copyright © 2009 by ASME SEPTEMBER 2009, Vol. 131 / 091202-1Transient modes of an electrified fluid interface are investigated, specifically, (a) intermittent or pulsed cone-jet mode and (b) smooth and abrupt transitions of the interface in response to a step voltage. These modes were studied experimentally by capturing the motion of the interface and measuring the emitted ion current (via electrospray) as they occur. The observed phenomena are described using an analytical model for the equilibrium of an electrified fluid interface, and the effect of operational parameters on the transient modes is discussed. Pressure, which is related to the supplied flow rate, significantly influences the behavior of the transient modes. It is useful to understand transient modes so they can be avoided in applications that require a stable electrospray. However, with improved knowledge, the modes studied here can assist in the development of specialized applications. DOI: 10.1115/1.3203203NSER

Application of an Equilibrium Model for an Electrified Fluid Interface—Electrospray Using a PDMS Microfluidic Device

An experimental investigation of an electrified fluid interface is presented. The experimental findings are related to a previously developed analytical model of Gubarenko , which is used to determine when a fluidic interface under electrical stress is in equilibrium, and to observations reported in the literature. The effect of key parameters on causing the interface to rupture, form, and maintain an electrospray is investigated. The experimental results reveal the dependence of interface shape on operational parameters, the impact of the interface apex angle on equilibrium, the conditions that cause either dripping mode or cone-jet mode, and the structure of operational domains. This paper confirms predictions made using the analytical model, including the range of parameters that cause the onset and steadiness of a quasi-equilibrium (electrospray) state of the interface. Testing is performed using an electrospray emitter chip fabricated from two layers of Polydimethylsiloxane and one layer of glass. The model and experimental results assist in design decisions for electrospray emitters. Applications of electrified interfaces (electrosprays) are found in mass spectrometry, microfluidics, material deposition, and colloidal thrusters for propulsion

Interfacial Targeting of Sessile Droplets Using Electrospray

We report on the use of electrospray atomization to deliver nanoparticles and surfactant directly to the surface of sessile droplets. The particles delivered to the target droplet remained adsorbed at its interface since they arrived solvent-free. Upon complete evaporation, the interface of the target drop was mapped to the underlying substrate, forming a nanoparticle deposit. The use of electrospray permitted the exploration of the interfacial particle transport and the role of surfactants in governing particle motion and deposit structure. When no surfactant was present in the sprayed solution, there was no observable convection of the interfacial particles. When Tween 80, a high-molecular-weight surfactant, was added to the sprayed solution, the surface flow was similarly suppressed. Only when small surfactants (e.g., sodium dodecyl sulfate) were present in the sprayed solution was Marangoni flow, directed toward the droplet apex, induced at the interface. This flow drove the interfacial particles to the apex of the target droplet, creating a particle-dense region at the center of the final deposit. We found that small surfactants were capable of desorbing from the interface at a sufficiently high rate relative to the evaporation time scale of the target droplet. Once inside the drop, the desorbed surfactant was convected to the contact line where it accumulated, inducing a surface tension gradient and a solutal Marangoni flow. Numerical modeling using the lattice Boltzmann–Brownian dynamics method confirmed this mechanism of particle transport and its relationship to deposit structure. The use of sacrificial targets combined with electrospray may provide a unique capability for building colloidal monolayers with organized structure in a scalable way

Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial

Background Rosiglitazone is a thiazolidinedione that reduces insulin resistance and might preserve insulin secretion. The aim of this study was to assess prospectively the drugs ability to prevent type 2 diabetes in individuals at high risk of developing the condition