Kelvin Institute

Glasgow, United Kingdom

Kelvin Institute

Glasgow, United Kingdom
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Sutherland H.G.,Kelvin Institute | Griffiths L.R.,Kelvin Institute
Headache | Year: 2017

Migraine is a complex, debilitating neurovascular disorder, typically characterized by recurring, incapacitating attacks of severe headache often accompanied by nausea and neurological disturbances. It has a strong genetic basis demonstrated by rare migraine disorders caused by mutations in single genes (monogenic), as well as familial clustering of common migraine which is associated with polymorphisms in many genes (polygenic). Hemiplegic migraine is a dominantly inherited, severe form of migraine with associated motor weakness. Family studies have found that mutations in three different ion channels genes, CACNA1A, ATP1A2, and SCN1A can be causal. Functional studies of these mutations has shown that they can result in defective regulation of glutamatergic neurotransmission and the excitatory/inhibitory balance in the brain, which lowers the threshold for cortical spreading depression, a wave of cortical depolarization thought to be involved in headache initiation mechanisms. Other putative genes for monogenic migraine include KCKN18, PRRT2, and CSNK1D, which can also be involved with other disorders. There are a number of primarily vascular disorders caused by mutations in single genes, which are often accompanied by migraine symptoms. Mutations in NOTCH3 causes cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary cerebrovascular disease that leads to ischemic strokes and dementia, but in which migraine is often present, sometimes long before the onset of other symptoms. Mutations in the TREX1 and COL4A1 also cause vascular disorders, but often feature migraine. With respect to common polygenic migraine, genome-wide association studies have now identified single nucleotide polymorphisms at 38 loci significantly associated with migraine risk. Functions assigned to the genes in proximity to these loci suggest that both neuronal and vascular pathways also contribute to the pathophysiology of common migraine. Further studies are required to fully understand these findings and translate them into treatment options for migraine patients. © 2017 American Headache Society

Davis F.M.,University of Queensland | Stewart T.A.,University of Queensland | Thompson E.W.,St. Vincent's Institute | Thompson E.W.,University of Melbourne | And 2 more authors.
Trends in Pharmacological Sciences | Year: 2014

The spread of cancer cells to distant organs represents a major clinical challenge in the treatment of cancer. Epithelial-mesenchymal transition (EMT) has emerged as a key regulator of metastasis in some cancers by conferring an invasive phenotype. As well as facilitating metastasis, EMT is thought to generate cancer stem cells and contribute to therapy resistance. Therefore, the EMT pathway is of great therapeutic interest in the treatment of cancer and could be targeted either to prevent tumor dissemination in patients at high risk of developing metastatic lesions or to eradicate existing metastatic cancer cells in patients with more advanced disease. In this review, we discuss approaches for the design of EMT-based therapies in cancer, summarize evidence for some of the proposed EMT targets, and review the potential advantages and pitfalls of each approach. © 2014 Elsevier Ltd.

Lu M.-L.,No117 Hospital Of Pla | He J.,No117 Hospital Of Pla | Lu S.,Kelvin Institute
International Journal of Colorectal Disease | Year: 2015

Purpose: Slow transit constipation is a common disorder in children, which often does not respond well to ordinary treatments. We have conducted a systematic review of reported studies in order to better define the current state of knowledge about electrical stimulation treatment of slow transit constipation in children. Methods: We searched PubMed, Embase, Cochrane Library, BioMed Central, and ISI Web of Knowledge with relevant terms; six studies, all from one center, met the criteria for inclusion. Two trials were randomized clinical trials, and four were prospective studies. The number of subjects included in the studies was 8 to 39, with ages 3 to 18 years. Results: Treatment sessions varied from 20 to 30 min 3 times per week to 1 h daily, and duration of therapy varied from 3 weeks to 6 months. Statistically significant improvements after electrical stimulation therapy were recorded in one to four outcome measures in each of the studies: frequency of defecation, soiling, Bristol Stool Scale, radionuclear transit studies, and quality of life; however, the improvements were of modest degree and of uncertain clinical significance. Quality assessment of the studies found various levels of bias, with attrition bias and reporting bias in all six. Conclusions: This systemic review found moderate support for the effectiveness of electrical stimulation therapy in slow transit constipation in children. However, better-designed studies, with larger and more diverse patient populations followed for longer time periods, will be needed in order to reliably determine the efficacy of electrical stimulation therapy in the treatment of this disorder. © 2015, Springer-Verlag Berlin Heidelberg.

Islam N.,Queensland University of Technology | Islam N.,Kelvin Institute | Ferro V.,University of Queensland
Nanoscale | Year: 2016

The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed. Although chitosan has wide applications in terms of formulations and routes of drug delivery, this review is focused on pulmonary delivery of drug-encapsulated nanoparticles of chitosan and its derivatives. In addition, the controversial toxicological effects of chitosan nanoparticles for lung delivery will also be discussed. © 2016 The Royal Society of Chemistry.

Walshe J.,Queensland Eye Institute | Harkin D.G.,Queensland Eye Institute | Harkin D.G.,Queensland University of Technology | Harkin D.G.,Kelvin Institute
Experimental Eye Research | Year: 2014

The routine cultivation of human corneal endothelial cells, with the view to treating patients with endothelial dysfunction, remains a challenging task. While progress in this field has been buoyed by the proposed existence of progenitor cells for the corneal endothelium at the corneal limbus, strategies for exploiting this concept remain unclear. In the course of evaluating methods for growing corneal endothelial cells, we have noted a case where remarkable growth was achieved using a serial explant culture technique. Over the course of 7 months, a single explant of corneal endothelium, acquired from cadaveric human tissue, was sequentially seeded into 7 culture plates and on each occasion produced a confluent cell monolayer. Sample cultures were confirmed as endothelial in origin by positive staining for glypican-4. On each occasion, small cells, closest to the tissue explant, developed into a highly compact layer with an almost homogenous structure. This layer was resistant to removal with trypsin and produced continuous cell outgrowth during multiple culture periods. The small cells gave rise to larger cells with phase-bright cell boundaries and prominent immunostaining for both nestin and telomerase. Nestin and telomerase were also strongly expressed in small cells immediately adjacent to the wound site, following transfer of the explant to another culture plate. These findings are consistent with the theory that progenitor cells for the corneal endothelium reside within the limbus and provide new insights into expected expression patterns for nestin and telomerase within the differentiation pathway. © 2014 Elsevier Ltd.

Christian P.G.,University of Queensland | Harkin D.G.,Institute of Health and Biomedical Innovation | Schmid K.L.,Kelvin Institute
Current Eye Research | Year: 2014

Purpose: GABA antagonists inhibit experimental myopia in chick and GABA receptors have been localized to chick sclera and the retinal pigment epithelium (RPE). The RPE and the choroid alter scleral DNA and glycosaminoglycan (GAG) content in vitro; opposite effects have been observed for tissues from myopic and hyperopic eyes. The aim was to determine the effect of GABAergic agents on the DNA and GAG content of chick scleral fibroblasts directly and in co-culture with ocular tissues from myopic and hyperopic chick eyes. Materials and Methods: Primary cultures of fibroblastic cells expressing vimentin and α-smooth muscle actin were established. GABAergic agents were added separately (i) to the culture medium of the scleral cells and (ii) to the culture medium of the scleral cells with the addition of posterior eye cup tissue (retina, RPE, retina+RPE, choroid+RPE) to cell culture inserts. Ocular tissues were obtained from chick eyes wearing+15D (lens-induced hyperopia, LIH) or -15D lenses (lens-induced myopia, LIM) for three days (post-hatch day 5-8) (n=12). GAG and DNA content of scleral fibroblasts were measured. Results: GABA agents had a small direct effect on scleral cell GAG and DNA content but a larger effect was measured when GABA agents were added to the culture medium with myopic and hyperopic RPE and choroid+RPE tissues. GABA agonists increased (p=0.002) whereas antagonists decreased (p=0.0004) DNA content of scleral cells; effects were opposite for scleral GAG content. GABA agents significantly altered the effect of both LIM and LIH tissues (p=0.0005) compared to control; the effects were greater for LIM tissue versus LIH tissue co-culture (p=0.0004). Conclusion: GABAergic agents affect the DNA and GAG content of scleral fibroblasts both directly and when co-cultured with ocular tissues. GABA antagonists that prevent myopia development in chick model could act via a scleral mechanism utilizing the RPE/choroid. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.

De Souza P.L.,University of New South Wales | Russell P.J.,Kelvin Institute | Kearsley J.H.,St George Hospital Cancer Care Center | Howes L.G.,Griffith University
Nutrition Reviews | Year: 2010

Isoflavones are phytoestrogens that have pleiotropic effects in a wide variety of cancer cell lines. Many of these biological effects involve key components of signal transduction pathways within cancer cells, including prostate cancer cells. Epidemiological studies have raised the hypothesis that isoflavones may play an important role in the prevention and modulation of prostate cancer growth. Since randomized phase III trials of isoflavones in prostate cancer prevention are currently lacking, the best evidence for this concept is presently provided by case control studies. However, in vitro data aremuch more convincing in regard to the activity of a number of isoflavones, and have led to the development of genistein and phenoxodiol in the clinic as potential treatments for cancer. In addition, the potential activity of isoflavones in combination with cytotoxics or radiotherapy warrants further investigation. This review focuses on the clinical pharmacology of isoflavones and its relevance to their development for use in the prevention of prostate cancer, and it evaluates some of the conflicting data in the literature. © 2010 International Life Sciences Institute.

Barker C.J.,Kelvin Institute | Gillett A.,Australia Zoo Wildlife Hospital | Polkinghorne A.,Kelvin Institute | Timms P.,Kelvin Institute
Veterinary Microbiology | Year: 2013

As a dietary source, the foliage of Eucalyptus spp. is low in available protein and carbohydrate while containing polyphenolic compounds that interfere with enzymatic digestion. To overcome this, the koala ( Phascolarctos cinereus) has evolved a range of anatomical and physiological adaptations to assist with digestion and absorption of nutrients from this food source. Microbial fermentation of partially digested eucalyptus leaves is thought to be critical in this process, however, little is known about the composition and diversity of microorganisms that are associated with digestive health in this native species. In this study, we performed 16S rRNA gene pyrosequencing of caecum, colon and faecal pellet samples from two wild, free ranging, Queensland koalas. Our results reveal a highly complex and diverse ecosystem with considerable intra-individual variation. Although samples were dominated by sequences from the Bacteroidetes and Firmicutes phyla there was considerable variation at the genus level. This study is the first non-culture based microbiota analysis, using 454-amplicon pyrosequencing, and provides preliminary data to expand our understanding of the koala hindgut. © 2013 Elsevier B.V.

Mathur A.,Kelvin Institute | Atchison D.A.,Kelvin Institute
Journal of Cataract and Refractive Surgery | Year: 2010

Purpose: To measure the effect of spherical intraocular lens (IOL) implantation and conventional myopic laser in situ keratomileusis (LASIK) on peripheral ocular aberrations. Setting: Visual and Ophthalmic Optics Laboratory, School of Optometry, and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. Methods: Peripheral aberrations were measured using a modified commercial Hartmann-Shack aberrometer across 42 degrees × 32 degrees of the central visual field after spherical IOL implantation and after conventional LASIK for myopia. The results were compared with those in an age-matched emmetropic group and an age-matched myopic control group, respectively. Results: The rate of quadratic change in spherical equivalent (SE) refraction, higher-order root-mean-square (RMS) aberrations, and total RMS aberrations across the visual field was greater and the amount of spherical aberration higher in the IOL group than in the emmetropic control group. However, coma trends were similar in the 2 groups. The rate of quadratic change in SE refraction, higher-order RMS aberrations, and total RMS aberrations was greater across the field and the amount of spherical aberration higher in the LASIK group than in the myopic control group. The trend in coma across the field in the LASIK group was opposite that in the other groups. Conclusions: Spherical IOL implantation and conventional myopic LASIK increased ocular peripheral aberrations, causing a significant increase in spherical aberration across the visual field. Laser in situ keratomileusis reversed the sign of the rate of change in coma across the field relative to that in the other groups. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. © 2010 ASCRS and ESCRS.

Momot K.I.,Kelvin Institute
European Biophysics Journal | Year: 2011

We used Monte Carlo simulations of Brownian dynamics of water to study anisotropic water diffusion in an idealised model of articular cartilage. The main aim was to use the simulations as a tool for translation of the fractional anisotropy of the water diffusion tensor in cartilage into quantitative characteristics of its collagen fibre network. The key finding was a linear empirical relationship between the collagen volume fraction and the fractional anisotropy of the diffusion tensor. Fractional anisotropy of the diffusion tensor is potentially a robust indicator of the microstructure of the tissue because, to a first approximation, it is invariant to inclusion of proteoglycans or chemical exchange between free and collagen-bound water in the model. We discuss potential applications of Monte Carlo diffusion-tensor simulations for quantitative biophysical interpretation of magnetic resonance diffusion-tensor images of cartilage. Extension of the model to include collagen fibre disorder is also discussed. © 2010 European Biophysical Societies' Association.

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