Potential of hydrogel-forming and dissolving microneedles for use in paediatric populations

Development of formulations and drug delivery strategies for paediatric use is challenging, partially due to the age ranges within this population, resulting in varying requirements to achieve optimised patient outcomes. Although the oral route of drug delivery remains the preferred option, there are problematic issues, such as difficulty swallowing and palatability of medicines specific to this population. The parenteral route is not well accepted by children due to needle-related fear and pain. Accordingly, a plethora of alternative routes of drug administration have been investigated. Microneedles (MN) breach the stratum corneum (SC), the outermost layer of skin, increasing the number of drug substances amenable to transdermal delivery. This strategy involves the use of micron-sized needles to painlessly, and without drawing blood, create transient aqueous conduits in the SC. In this study, polymeric dissolving MN and hydrogel-forming MN were fabricated incorporating two model drugs commonly used in paediatric patients (caffeine and lidocaine hydrochloride). The potential efficacy of these MN for paediatric dosing was investigated via in vitro and in vivo studies. Views pertaining to MN technology were sought amongst school children in Northern Ireland, members of the UK general public and UK-based paediatricians, to determine perceived benefits, acceptance, barriers and concerns for adoption of this technology. In this study, polymeric MN were shown to substantially enhance skin permeability of the model therapeutic molecules in vitro and in vivo. In particular, hydrogel-forming MN led to a 6.1-fold increase in caffeine delivery whilst lidocaine HCl delivery was increased by 3.3-fold using dissolving MN in vitro. Application of caffeine-loaded MN led to a caffeine plasma concentration of 23.87μg/mL in rats at 24h. This research also highlighted a strong consensus regarding MN technology amongst schoolchildren, paediatricians and the general public, regarding potential use of MN in the paediatric population. Overall, 93.6% of general public respondents and 85.9% of paediatricians regarded the use of MN as a positive approach.

Protein Hydrolysis by Immobilized and Stabilized Trypsin

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Alternative drying techniques for the manufacturing of hydrogel-forming and dissolving microneedle arrays.

Dissolving polymeric microneedle arrays and hydrogel-forming microneedle arrays have attracted much attention during recent years due mainly to their biocompatibility and capacity for enhanced drug delivery. Nevertheless, for the production of this type of devices, typically, a drying step is required. Microneedles are prepared following a micromoulding technique using aqueous blends of Gantrez® S-97. Currently, production of microneedles arrays involves a long drying process of 48 hours. Therefore alternative drying methods were investigated including microwave radiation and hot air convection.

Devotional reading and dissolving the self: a critical reading of the late medieval Scottish Legendary using Kristevan theory

The Scottish Legendary is a fourteenth century collection of saints’ lives in Older Scots. The prologue describes the lives as ‘merroure’ (mirror) to readers from which ‘men ma ensample ta’ (people may take example). Thus, the Legendary sets out to reveal how the reader is (mirror) thereby moving her to wish to become how she should be (exemplarity). This dissertation argues that, rather than encouraging devotion to saints along purely dogmatic lines, the Legendary transforms the reader’s selfhood by engaging her affectively, i.e. on an emotional and somatic level. By provoking the reader affectively, the text puts the reader into what Julia Kristeva has described as a ‘semiotic state’ which harks back to the reader’s or listener’s pre-cultural, pre-subjective self (Kristeva, 1984). Thus, the text disrupts the reader’s conception of herself as a complete, hermetic subjectivity, thereby dissolving the boundaries of the reader’s self. The Legendary most powerfully infiltrates the reader’s sense of self along these lines in the moments in which female saints’ bodies are tortured and dismembered. These scenes foreground the permeability of human flesh as well as its powerful influence over selfhood. Such images of abjection are, in Kristeva’s words, ‘opposed to I’; by confronting the reader with the disintegration of subjectivity in abjection, the text incites the reader to likewise experience herself as abject, i.e. disintegrable and permeable (Kristeva 1982). As I shall demonstrate, Kristeva’s psychoanalytic theory of the formation of the self offers a fruitful framework for understanding the processes of self-knowledge through reading that these saints’ lives inspire.

微藻光合放氢的生理生化调控及生物技术研究

氢能将是主宰未来世界的主要能源之一，氢能的研究开发已经成为世界各国能源研究的重要方向。微藻光合制氢，因其无污染、可再生，成为生物制氢领域最有应用前景的研究方向之一。 本论文选取模式植物莱茵衣藻、经济藻种钝顶螺旋藻作为实验材料，对微藻光合放氢的生理生化过程调控及相关生物技术进行综合研究。获得的主要成果如下： （1）建立起微藻两步法放氢的技术平台和批次培养的回馈监控模式;同时，运用离子色谱追踪整个放氢过程中的离子变化，我们的实验结果证明对于衣藻两步法放氢而言，乙酸的存在是必要条件之一。这个结果与文献报道不尽相同，值得进一步深入地研究。 （2）筛选出一株联合固氮菌，摸索出藻菌共培养的培养基合适配置和活性控制条件;在两步法放氢的基础上，充分利用藻菌之间的优势互补，设计构建藻菌共培养放氢体系，与两步法放氢比较，该体系能提前12小时进入放氢状态，提高单位叶绿素放氢效率1倍左右，延长体系稳定时间近20小时。 （3）利用固定化技术获得高产氢效率，去固定化后持续产氢是我们设计出微藻连续放氢的一个特点。同时，摸索出衣藻放氢过程中的间歇进料进流程序，使连续放氢时间可达3周左右。 （4）实验证明两步法放氢技术，并不适用于螺旋藻;同时，在摸索建立螺旋藻的藻菌共培养放氢体系过程中，发现非致病性肺炎克雷伯氏杆菌培养液可以破碎螺旋藻细胞，这种全新的提取藻蓝蛋白的方法，具有节约成本，便于操作，温和均匀的独特优势。 （5）在连续放氢体系中加入适量蔗糖做底物和引物，剩余存活的菌可以继续利用提取藻蓝蛋白后剩余螺旋藻藻渣和放氢后死亡的衣藻进行发酵放氢，可获得更高产率的氢气，之后继续利用光合细菌进一步放氢，形成连续放氢网络，这一步还在探索之中。 作为一项应用基础研究，从三角瓶里的实验到工厂化生产还有很长的路，希望本实验的工作能为以后同类研究提供一些有用的信息和启发。

Dissolving views, memory and sensory experience: The Cosmopoligraphicon or the ‘World in Many Pictures’ in Melbourne, Australia, in 1855

While magic lanterns and dissolving views were a global phenomenon in the nineteenth century, scholars are only starting to examine in depth their social dimensions. This article seeks to extend our understanding of dissolving views by analysing the audience sensory experience in a specific historical context – gold rush Melbourne in 1855. It argues that while a Melbourne audience admired the technological wonder of the magic lantern and the dissolving views, their sensory experience was informed by the colonial social context. The audiences appear to have delighted in immersing themselves in the dissolving views, both learning about the world and reacquainting themselves with parts of the (old) world they had left behind. This article further argues that dissolving views were more than a visual spectacle: they actively engaged the senses in ways that gave emotional meanings to the dissolving views and linked a Melbourne gold rush audience with the world left behind, yet still accessible remotely through memory and sensory imagination.

Stone baby: An exploration of affect and trauma in visual art

Stone Baby: An Exploration of Affect and Trauma in Visual Art was held at the Block, QUT Creative Industries Precinct on August 27-28, 2014. At the conclusion of my Masters project, this exhibition was a showcase of the outcomes of my material and digital explorations in the form of installation, sculpture and film. My primary motivation can be described as a relational and ethical attempt to find a balance between the erotic and the aggressive. This is experienced in the self as feelings of attraction and repulsion in response to the new and unknown "other". Consequently creative practice is necessarily a complex affair that is experienced as a completely immersive and self-contained psychological space. It is within this space that both physical sensation and raw emotion are able to tangibly and conceptually interact with psychoanalytic theory, and concrete materials video and sound.

Transducer and base compliance alter the in situ 6 dof force measured from muscle during an isometric contraction in a multi-joint limb.

Although musculoskeletal models are commonly used, validating the muscle actions predicted by such models is often difficult. In situ isometric measurements are a possible solution. The base of the skeleton is immobilized and the endpoint of the limb is rigidly attached to a 6-axis force transducer. Individual muscles are stimulated and the resulting forces and moments recorded. Such analyses generally assume idealized conditions. In this study we have developed an analysis taking into account the compliances due to imperfect fixation of the skeleton, imperfect attachment of the force transducer, and extra degrees of freedom (dof) in the joints that sometimes become necessary in fixed end contractions. We use simulations of the rat hindlimb to illustrate the consequences of such compliances. We show that when the limb is overconstrained, i.e., when there are fewer dof within the limb than are restrained by the skeletal fixation, the compliances of the skeletal fixation and of the transducer attachment can significantly affect measured forces and moments. When the limb dofs and restrained dofs are matched, however, the measured forces and moments are independent of these compliances. We also show that this framework can be used to model limb dofs, so that rather than simply omitting dofs in which a limb does not move (e.g., abduction at the knee), the limited motion of the limb in these dofs can be more realistically modeled as a very low compliance. Finally, we discuss the practical implications of these results to experimental measurements of muscle actions.

Characterization of light and heavy hydrated magnesium carbonates using thermal analysis

Upon heating, hydrated magnesium carbonates (HMCs) undergo a continuous sequence of decomposition reactions. This study aims to investigate the thermal decomposition of various commercially produced HMCs classified as light and heavy, highlight their differences, and provide an insight into their compositions in accordance with the results obtained from thermal analysis and microstructure studies. An understanding of the chemical compositions and microstructures, and a better knowledge of the reactions that take place during the decomposition of HMCs were achieved through the use of SEM, XRD, and TG/differential thermal analysis (DTA). The quantification of their CO 2 contents was provided by TG and dissolving the samples in HCl acid. Results show that variations exist within the microstructure and decomposition patterns of the two groups of HMCs, which do not exactly fit into the fixed stoichiometry of the known HMCs in the MgO-CO2-H2O system. The occurrence of an exothermic DTA peak was only observed for the heavy HMCs, which was attributed to their high CO2 contents and the relatively delayed decomposition pattern. © 2013 Akadémiai Kiadó, Budapest, Hungary.

Recovering a lost inheritance : The marital economy and its absence from the Prehistory of Economics in Britain

Roberts, Michael. 'Recovering a lost inheritance: the marital economy and its absence from the Prehistory of Economics in Britain', in: 'The Marital Economy in Scandinavia and Britain 1400-1900', (Eds) Argen, Maria., Erickson, Amy Louise., Farnham: Ashgate, 2005, pp.239-256 RAE2008

In vitro study on the cell adhesion ability of immobilized lactobacilli on natural supports

The aim of the present study was to investigate the effect of probiotic immobilization onto wheat grains, both wet and freeze dried, on the adhesion properties of the probiotic cells and make comparisons with wet and freeze dried free cells. Lactobacillus casei ATCC 393 and Lactobacillus plantarum NCIMB 8826 were used as model probiotic strains. The results showed satisfactory adhesion ability of free cells to a monolayer of Caco-2 cells (> 1000 CFU/100 Caco-2 cells for wet cells). Cell immobilization resulted in a significant decrease in adhesion, for both wet and freeze dried formulations, most likely because immobilized cells did not have direct access to the Caco-2 cells, but it still remained in adequate levels (> 100 CFU/100 Caco-2 cells for wet cells). No clear correlation could be observed between cell adhesion and the hydrophobicity of the bacterial cells, measured by the hexadecane adhesion assay. Most notably, immobilization enhanced the monolayer integrity of Caco-2 cells, demonstrated by a more than 2-fold increase in transepithelial electrical resistance (TEER) compared to free cells. SEM micrographs ascertained the adhesion of both immobilized and free cells to the brush border microvilli. Finally, the impact of the food matrix on the adhesion properties of probiotic bacteria and on the design of novel functional products is discussed.

Theoretical modeling and experimental validation of surface stress in thrombin aptasensor

Adsorption of target molecules on the immobilized microcantilever surface produced beam displacement due to the differential surface stress generated between the immobilized and non-immobilized surface. Surface stress is caused by the intermolecular forces between the molecules. Van der Waals, electrostatic forces, hydrogen bonding, hydrophobic effect and steric hindrance are some of the intermolecular forces involved. A theoretical framework describing the adsorption-induced microcantilever displacement is derived in this paper. Experimental displacement of thrombin aptamer-thrombin interactions was carried out. The relation between the electrostatic interactions involved between adsorbates (thrombin) as well as adsorbates and substrates (thrombin aptamer) and the microcantilever beam displacement utilizing the proposed mathematical model was quantified and compared to the experimental value. This exercise is important to aid the designers in microcantilever sensing performance optimization.

Piezoelectric biosensors for real-time monitoring of hybridization and detection of hepatitis C virus

The piezoelectric quartz crystal resonators modified with oligonucleotide probes were used for detection of hepatitis C virus (HCV) in serum. The gold electrodes on either rough or smooth surface crystals were modified with a self-assembled monolayer of cystamine. After activation with glutaraldehyde, either avidin or streptavidin were immobilized and used for attachment of biotinylated DNA probes (four different sequences). Piezoelectric biosensors were used in a flow-through setup for direct monitoring of DNA resulting from the reverse transcriptase-linked polymerase chain reaction (RT-PCR) amplification of the original viral RNA. The samples of patients with hepatitis C were analyzed and the results were compared with the standard RT-PCR procedure (Amplicor test kit of Roche, microwell format with spectrophotometric evaluation). The piezoelectric hybridization assay was completed in 10 min and the same sensing surface was suitable for repeated use. (C) 2004 Elsevier B.V. All rights reserved.

Radiography, computed tomography and magnetic resonance imaging at 0.5 Tesla of mechanically inducedosteoarthritis in rabbit knees

In the present experimental study we assessed induced osteoarthritis data in rabbits, compared three diagnostic methods, i.e., radiography (XR), computed tomography (CT) and magnetic resonance imaging (MRI), and correlated the imaging findings with those obtained by macroscopic evaluation. Ten young female rabbits of the Norfolk breed were used. Seven rabbits had the right knee immobilized in extension for a period of 12 weeks (immobilized group), and three others did not have a limb immobilized and were maintained under the same conditions (control group). Alterations observed by XR, CT and MRI after the period of immobilization were osteophytes, osteochondral lesions, increase and decrease of joint space, all of them present both in the immobilized and non-immobilized contralateral limbs. However, a significantly higher score was obtained for the immobilized limbs (XT: P = 0.016, CT: P = 0.031, MRI: P = 0.0156). All imaging methods were able to detect osteoarthritis changes after the 12 weeks of immobilization. Macroscopic evaluation identified increased thickening of joint capsule, proliferative and connective tissue in the femoropatellar joint, and irregularities of articular cartilage, especially in immobilized knees. The differences among XR, CT and MRI were not statistically significant for the immobilized knees. However, MRI using a 0.5 Tesla scanner was statistically different from CT and XR for the non-immobilized contralateral knees. We conclude that the three methods detected osteoarthritis lesions in rabbit knees, but MRI was less sensitive than XR and CT in detecting lesions compatible with initial osteoarthritis. Since none of the techniques revealed all the lesions, it is important to use all methods to establish an accurate diagnosis.

Leucine and HMB differentially modulate proteasome system in skeletal muscle under different sarcopenic conditions

In the present study we have compared the effects of leucine supplementation and its metabolite β-hydroxy-β-methyl butyrate (HMB) on the ubiquitin-proteasome system and the PI3K/Akt pathway during two distinct atrophic conditions, hindlimb immobilization and dexamethasone treatment. Leucine supplementation was able to minimize the reduction in rat soleus mass driven by immobilization. On the other hand, leucine supplementation was unable to provide protection against soleus mass loss in dexamethasone treated rats. Interestingly, HMB supplementation was unable to provide protection against mass loss in all treatments. While solely fiber type I cross sectional area (CSA) was protected in immobilized soleus of leucine-supplemented rats, none of the fiber types were protected by leucine supplementation in rats under dexamethasone treatment. In addition and in line with muscle mass results, HMB treatment did not attenuate CSA decrease in all fiber types against either immobilization or dexamethasone treatment. While leucine supplementation was able to minimize increased expression of both Mafbx/Atrogin and MuRF1 in immobilized rats, leucine was only able to minimize Mafbx/Atrogin in dexamethasone treated rats. In contrast, HMB was unable to restrain the increase in those atrogenes in immobilized rats, but in dexamethasone treated rats, HMB minimized increased expression of Mafbx/Atrogin. The amount of ubiquitinated proteins, as expected, was increased in immobilized and dexamethasone treated rats and only leucine was able to block this increase in immobilized rats but not in dexamethasone treated rats. Leucine supplementation maintained soleus tetanic peak force in immobilized rats at normal level. On the other hand, HMB treatment failed to maintain tetanic peak force regardless of treatment. The present data suggested that the anti-atrophic effects of leucine are not mediated by its metabolite HMB.