Turbulent boundary layer behavior in an axially symmetric radial diffuser

An investigation of incompressible turbulent boundary layer behavior is an axially symmetrical radial diffuser is presented with experimental results for variable diffuser area ratios

Renal Inhibition of Heme Oxygenase-1 Increases Blood Pressure in Angiotensin II-Dependent Hypertension

The goal of this study was to test the hypothesis that renal medullary heme oxygenase (HO) acts as a buffer against Ang-II dependent hypertension. To test this hypothesis, renal medullary HO activity was blocked using QC-13, an imidazole-dioxolane HO-1 inhibitor, or SnMP, a classical porphyrin based HO inhibitor. HO inhibitors were infused via IRMI catheters throughout the study starting 3 days prior to implantation of an osmotic minipump which delivered Ang II or saline vehicle. MAP was increased by Ang II infusion and further increased by IRMI infusion of QC-13 or SnMP. MAP averaged 113 ± 3, 120 ± 7, 141 ± 2, 153 ± 2, and 154 ± 3 mmHg in vehicle, vehicle + IRMI QC-13, Ang II, Ang II + IRMI QC-13, and Ang II + IRMI SnMP treated mice, respectively (n = 6). Inhibition of renal medullary HO activity with QC-13 in Ang II infused mice was also associated with a significant increase in superoxide production as well as significant decreases in antioxidant enzymes catalase and MnSOD. These results demonstrate that renal inhibition of HO exacerbates Ang II dependent hypertension through a mechanism which is associated with increases in superoxide production and decreases in antioxidant enzymes

Translation of remote control regenerative technologies for bone repair

The role of biomechanical stimuli, or mechanotransduction, in normal bone homeostasis and repair is understood to facilitate effective osteogenesis of mesenchymal stem cells (MSCs) in vitro. Mechanotransduction has been integrated into a multitude of in vitro bone tissue engineering strategies and provides an effective means of controlling cell behaviour towards therapeutic outcomes. However, the delivery of mechanical stimuli to exogenous MSC populations, post implantation, poses a significant translational hurdle. Here, we describe an innovative bio-magnetic strategy, MICA, where magnetic nanoparticles (MNPs) are used to remotely deliver mechanical stimuli to the mechano-receptor, TREK-1, resulting in activation and downstream signalling via an external magnetic array. In these studies, we have translated MICA to a pre-clinical ovine model of bone injury to evaluate functional bone repair. We describe the development of a magnetic array capable of in vivo MNP manipulation and subsequent osteogenesis at equivalent field strengths in vitro. We further demonstrate that the viability of MICA-activated MSCs in vivo is unaffected 48 hrs post implantation. We present evidence to support early accelerated repair and preliminary enhanced bone growth in MICA-activated defects within individuals compared to internal controls. The variability in donor responses to MICA-activation was evaluated in vitro revealing that donors with poor osteogenic potential were most improved by MICA-activation. Our results demonstrate a clear relationship between responders to MICA in vitro and in vivo. These unique experiments offer exciting clinical applications for cell-based therapies as a practical in vivo source of dynamic loading, in real-time, in the absence of pharmacological agents

The effect of solid-state forms on the topical delivery of roxithromycin

MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2016The skin is a very accessible and convenient route of administration for topical and systemic drugs (Williams, 2003:1). The only problem most formulators face is overcoming the barrier function of the stratum corneum, which has proved to be quite a challenge (Varun et al., 2012:632). This being said, the topical/transdermal route still holds many advantages over other routes of administration, with the most obvious being no first-pass effect from the liver and being a non-invasive, painless route of administration (Washington et al., 2001:187). The skin itself is affected by many diseases and one of the most common, from which a large number of the population suffers, is acne (Bershad, 2001:279). Acne vulgaris is a chronic inflammatory disease which affects the pilosebaceous units found in the dermis layer of the skin and the micro-organism which accumulates in these sebaceous glands and causes the inflammation, is known as Propionibacterium acnes. Topical antibiotics have a direct affect against P. acnes found in the sebum glands and in this way reduce the acne inflammation (Williams et al., 2012:361, 364). The antibiotics used today for the treatment of acne have been reported to be up to 60% resistant to the acne causing bacteria (P. acnes) (Scheinfeld et al., 2003:43). In the recent past, trials have been conducted on newer antibiotics for acne treatment, one in particular is roxithromycin (Oschsendorf, 2006:830). Roxithromycin is a macrolide antibiotic which has a bacteriostatic effect on P. acnes which accumulates in the dermis, but its poor solubility has been a major drawback for topical drug formulation (Gollnick, 2003:1585; Medsafe, 2014). For optimal skin penetration, a compound must preferably have an aqueous solubility above 1 mg/ml (Williams, 2003:37) and roxithromycin was reported to have a solubility of only 0.0335 mg/ml at 25 °C, which is below the optimal solubility for topical penetration (Aucamp et al., 2013:26; Williams, 2003:37). It has previously been proved that by using amorphous forms of a compound, along with its changed crystal lattice, can result in improved drug properties including increased solubility (Biradar et al., 2006:22; Purohit & Venugopalan, 2009:883). Patents from Liebenberg et al. (2013) and Liebenberg & Aucamp (2013) proved the glassy amorphous form of roxithromycin and the chloroform desolvated amorphous form had improved solubilities in comparison to the crystalline monohydrate form. Another area of research that has shown much growth is that of vesicle carrier systems, which have the ability to improve therapeutic activity of drugs by increasing the topical delivery of especially poorly soluble drugs such as roxithromycin (Bansal et al., 2012:704). Niosomes are used as an alternative to liposomes in current years as it overcomes the chemical instability, high cost and lack of purity of phospholipids (Jadon et al., 2009:1186). Niosomes are liposomes which are prepared using non-ionic surfactants instead of phospholipids and ufosomes are liposomes made from fatty acids (Bansal et al., 2012:710; Williams, 2003:128-129). Provesicular systems, such as proniosomes and pro-ufosomes, are prepared in order to overcome the stability problems that vesicular carriers face (Bansal et al., 2012:706, 709). The aim of this study was to determine if the two amorphous forms of roxithromycin, namely the glassy form and the chloroform desolvate, coupled with better solubility would have better topical diffusion. These three solid-state forms were each encapsulated into four chosen vesicle systems namely, niosomes, proniosomes, ufosomes and pro-ufosomes and the delivery of the two amorphous forms were compared to that of the crystalline monohydrate form to determine if an increase in topical delivery took place. The target area for the active pharmaceutical ingredient (API) was the dermis, as this is the area where P. acnes accumulates (Gollnick, 2003:1585). The optimisation and characterisation of amorphous forms entrapped in vesicles proved that all carrier systems were well formed and had optimal properties for topical delivery. An accurate and reliable high performance liquid chromatography (HPLC) method of analysis was developed and validated for the analysis of roxithromycin samples during experiments. The release studies showed that the API was successfully released from all carrier systems, with niosomes and proniosomes having superior release over the ufosomes and pro-ufosomes. The reason for this was that the API had higher affinity (and therefore less release) for the ingredients used to make ufosomes and pro-ufosomes (Agarwal et al., 2001:49; Dayan, 2005:74). The topical diffusion studies showed that there was no API concentration detected in the stratum corneum, which meant the API successfully penetrated the barrier. There was practically no API found in the receptor phase of the Franz cells which indicated that there was no systemic absorption and that the vesicle systems aided in drug targeting. An API concentration was found in the epidermis-dermis of all vesicle systems, which proved the intended target area for roxithromycin was successfully reached. The vesicle systems which assisted in the delivery of roxithromycin and its amorphous forms, from highest to lowest diffused concentration, were niosomes, ufosomes, proniosomes and pro-ufosomes. The total concentration was more dependent on the carrier type than the solid-state form, as there was no obvious leading roxithromycin form. Nevertheless, when the solid-state forms were grouped together, regardless of what carrier systems they were delivered in, the amorphous forms had higher epidermis-dermis concentrations than the roxithromycin monohydrate. This suggests the amorphous forms retained their increased solubilities while entrapped and resulted in improved topical delivery.Master

An evaluation of photoengraved microelectrodes for extracellular single-unit recording.

Miaoetectiodes fabricated using integrated-circuit technology are shown to be suitable for extracellular single-unit recording, and the factors influencing electrode-cell coupling are discussed. Electrode tip size as well as location is found to be critical in recording high spike amplitudes, suggesting that the paths for current flow in central nervous system (CNS) tissue may be extremely small. A. Starr was with the Department of Neurology, Stanford University, Stanford, Calif. He is now with the Department of Neurology, University of California College of Medicine, Irvine, Calif. Copyright © 1973 by The Institute of Electrical and Electronics Engineers, Inc

An evaluation of photoengraved microelectrodes for extracellular single-unit recording.

Miaoetectiodes fabricated using integrated-circuit technology are shown to be suitable for extracellular single-unit recording, and the factors influencing electrode-cell coupling are discussed. Electrode tip size as well as location is found to be critical in recording high spike amplitudes, suggesting that the paths for current flow in central nervous system (CNS) tissue may be extremely small. A. Starr was with the Department of Neurology, Stanford University, Stanford, Calif. He is now with the Department of Neurology, University of California College of Medicine, Irvine, Calif. Copyright © 1973 by The Institute of Electrical and Electronics Engineers, Inc