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Search Results: 1 - 10 of 8001 matches for " Helena Parkington "
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TRPM8 and Nav1.8 sodium channels are required for transthyretin-induced calcium influx in growth cones of small-diameter TrkA-positive sensory neurons
Robert J Gasperini, Xu Hou, Helena Parkington, Harry Coleman, David W Klaver, Adele J Vincent, Lisa C Foa, David H Small
Molecular Neurodegeneration , 2011, DOI: 10.1186/1750-1326-6-19
Abstract: Levels of intracellular cytosolic calcium were monitored in dorsal root ganglion (DRG) neurons isolated from embryonic rats using the calcium-sensitive fluorescent indicator Fluo4. An amyloidogenic mutant form of TTR, L55P, induced calcium influx into the growth cones of DRG neurons, whereas wild-type TTR had no significant effect. Atomic force microscopy and dynamic light scattering studies confirmed that the L55P TTR contained oligomeric species of TTR. The effect of L55P TTR was decreased by blockers of voltage-gated calcium channels (VGCC), as well as by blockers of Nav1.8 voltage-gated sodium channels and transient receptor potential M8 (TRPM8) channels. siRNA knockdown of TRPM8 channels using three different TRPM8 siRNAs strongly inhibited calcium influx in DRG growth cones.These data suggest that activation of TRPM8 channels triggers the activation of Nav1.8 channels which leads to calcium influx through VGCC. We suggest that TTR-induced calcium influx into DRG neurons may contribute to the pathophysiology of FAP. Furthermore, we speculate that similar mechanisms may mediate the toxic effects of other amyloidogenic proteins such as the β-amyloid protein of Alzheimer's disease.Protein misfolding is a common feature of many neurodegenerative diseases. In some of these diseases, such as the synucleinopathies and the tauopathies, cytoplasmic proteins aggregate to form intracellular deposits. However, in the amyloidoses, which include Alzheimer's disease (AD), prion diseases and the British and Danish familial dementias, proteinaceous aggregates are observed extracellularly [1-4]. There is increasing evidence that the mechanism of neurotoxicity in these amyloidoses is similar and that it is the conformation of the aggregated protein, rather than its specific amino acid sequence which results in altered membrane permeability to calcium [5]. Therefore, studies on the mechanism of neurotoxicity in one disease may provide insights into the mechanisms involved in other
Comparative Study on the Therapeutic Potential of Neurally Differentiated Stem Cells in a Mouse Model of Multiple Sclerosis
Natalie L. Payne, Guizhi Sun, Daniella Herszfeld, Pollyanna A. Tat-Goh, Paul J. Verma, Helena C. Parkington, Harold A. Coleman, Mary A. Tonta, Christopher Siatskas, Claude C. A. Bernard
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0035093
Abstract: Background Transplantation of neural stem cells (NSCs) is a promising novel approach to the treatment of neuroinflammatory diseases such as multiple sclerosis (MS). NSCs can be derived from primary central nervous system (CNS) tissue or obtained by neural differentiation of embryonic stem (ES) cells, the latter having the advantage of readily providing an unlimited number of cells for therapeutic purposes. Using a mouse model of MS, we evaluated the therapeutic potential of NSCs derived from ES cells by two different neural differentiation protocols that utilized adherent culture conditions and compared their effect to primary NSCs derived from the subventricular zone (SVZ). Methodology/Principal Findings The proliferation and secretion of pro-inflammatory cytokines by antigen-stimulated splenocytes was reduced in the presence of SVZ-NSCs, while ES cell-derived NSCs exerted differential immunosuppressive effects. Surprisingly, intravenously injected NSCs displayed no significant therapeutic impact on clinical and pathological disease outcomes in mice with experimental autoimmune encephalomyelitis (EAE) induced by recombinant myelin oligodendrocyte glycoprotein, independent of the cell source. Studies tracking the biodistribution of transplanted ES cell-derived NSCs revealed that these cells were unable to traffic to the CNS or peripheral lymphoid tissues, consistent with the lack of cell surface homing molecules. Attenuation of peripheral immune responses could only be achieved through multiple high doses of NSCs administered intraperitoneally, which led to some neuroprotective effects within the CNS. Conclusion/Significance Systemic transplantation of these NSCs does not have a major influence on the clinical course of rMOG-induced EAE. Improving the efficiency at which NSCs home to inflammatory sites may enhance their therapeutic potential in this model of CNS autoimmunity.
Pulmonary Delivery of an Ultra-Fine Oxytocin Dry Powder Formulation: Potential for Treatment of Postpartum Haemorrhage in Developing Countries
Richard J. Prankerd, Tri-Hung Nguyen, Jibriil P. Ibrahim, Robert J. Bischof, Gemma C. Nassta, Livesey D. Olerile, Adrian S. Russell, Felix Meiser, Helena C. Parkington, Harold A. Coleman, David A. V. Morton, Michelle P. McIntosh
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0082965
Abstract: Oxytocin is recommended by the World Health Organisation as the most effective uterotonic for the prevention and treatment of postpartum haemorrhage. The requirement for parenteral administration by trained healthcare providers and the need for the drug solution to be maintained under cold-chain storage limit the use of oxytocin in the developing world. In this study, a spray-dried ultrafine formulation of oxytocin was developed with an optimal particle size diameter (1-5 μm) to facilitate aerosolised delivery via the lungs. A powder formulation of oxytocin, using mannitol, glycine and leucine as carriers, was prepared with a volume-based median particle diameter of 1.9 μm. Oxytocin content in the formulation was assayed using high-performance liquid chromatography-mass spectroscopy and was found to be unchanged after spray-drying. Ex vivo contractility studies utilising human and ovine uterine tissue indicated no difference in the bioactivity of oxytocin before and after spray-drying. Uterine electromyographic (EMG) activity in postpartum ewes following pulmonary (in vivo) administration of oxytocin closely mimicked that observed immediately postpartum (0-12 h following normal vaginal delivery of the lamb). In comparison to the intramuscular injection, pulmonary administration of an oxytocin dry powder formulation to postpartum ewes resulted in generally similar EMG responses, however a more rapid onset of uterine EMG activity was observed following pulmonary administration (129 ± 18 s) than intramuscular injection (275 ± 22 s). This is the first study to demonstrate the potential for oxytocin to elicit uterine activity after systemic absorption as an aerosolised powder from the lungs. Aerosolised oxytocin has the potential to provide a stable and easy to administer delivery system for effective prevention and treatment of postpartum haemorrhage in resource-poor settings in the developing world.
Apparent Solubility of Natural Products Extracted with Near-Critical Carbon Dioxide  [PDF]
Helena Sovová
American Journal of Analytical Chemistry (AJAC) , 2012, DOI: 10.4236/ajac.2012.312A127
Abstract:

The apparent solubility controls the initial stage of supercritical fluid extraction of natural products, which is most important for the process economics. Based on the literature, data on CO2 apparent solubility of volatile substances from different matrices as leaves, flowers, rhizomes and seeds were collected and compared with their thermodynamic solubility. The adsorption isotherm derived by del Valle and Urrego as a modification of the isotherm proposed by Perrut et al. is universal enough to interpret these data as well as the apparent solubility of vegetable oils from seeds, for which it was originally proposed. When the apparent solubility of minor extract components in CO2 is compared with their thermodynamic solubility, their fraction in the extracted mixture should be taken into account.

The Performance as Educator in the Health System: Implications for Brazilian Health Workers Education Process  [PDF]
Alva Helena De Almeida
Creative Education (CE) , 2014, DOI: 10.4236/ce.2014.511106
Abstract:

This paper has the purpose of discussing the performance as health educators in the Brazilian Unified Health System (SUS) and also emphasizing the importance of the educational process for health workforce qualification as well as management device of health systems. This performance has been a strong strategy for SUS implementation process in Brazil.

Chromium as an Environmental Pollutant: Insights on Induced Plant Toxicity
Helena Oliveira
Journal of Botany , 2012, DOI: 10.1155/2012/375843
Abstract: In the past decades the increased use of chromium (Cr) in several anthropogenic activities and consequent contamination of soil and water have become an increasing concern. Cr exists in several oxidation states but the most stable and common forms are Cr(0), Cr(III) and Cr(VI) species. Cr toxicity in plants depends on its valence state. Cr(VI) as being highly mobile is toxic, while Cr(III) as less mobile is less toxic. Cr is taken up by plants through carriers of essential ions such as sulphate. Cr uptake, translocation, and accumulation depend on its speciation, which also conditions its toxicity to plants. Symptoms of Cr toxicity in plants are diverse and include decrease of seed germination, reduction of growth, decrease of yield, inhibition of enzymatic activities, impairment of photosynthesis, nutrient and oxidative imbalances, and mutagenesis. 1. Introduction Chromium (Cr) is the 17th most abundant element in the Earth’s mantle [1]. It occurs naturally as chromite (FeCr2O4) in ultramafic and serpentine rocks or complexed with other metals like crocoite (PbCrO4), bentorite Ca6(Cr,Al)2(SO4)3 and tarapacaite (K2CrO4), vauquelinite (CuPb2CrO4PO4OH), among others [2]. Cr is widely used in industry as plating, alloying, tanning of animal hides, inhibition of water corrosion, textile dyes and mordants, pigments, ceramic glazes, refractory bricks, and pressure-treated lumber [1]. Due to this wide anthropogenic use of Cr, the consequent environmental contamination increased and has become an increasing concern in the last years [3]. Chromium exists in several oxidation states, but the most stable and common forms are Cr(0), the trivalent Cr(III), and the hexavalent Cr(VI) species. Cr(0) is the metallic form, produced in industry and is a solid with high fusion point usually used for the manufacturing of steel and other alloys. Cr(VI) in the forms of chromate ( C r O 4 2 ? ), dichromate ( C r O 4 2 ? ), and CrO3 is considered the most toxic forms of chromium, as it presents high oxidizing potential, high solubility, and mobility across the membranes in living organisms and in the environment. Cr(III) in the forms of oxides, hydroxides, and sulphates is less toxic as it is relatively insoluble in water, presents lower mobility, and is mainly bound to organic matter in soil and aquatic environments. Moreover, Cr(III) forms tend to form hydroxide precipitates with Fe at typical ground water pH values. At high concentrations of oxygen or Mn oxides, Cr(III) can be oxidized to Cr(VI) [4, 5]. As Cr(VI) and Cr(III) present different chemical, toxicological, and
Among Synthetic, Supramolecular and Theoretical Chemistry Stabilization of Short-lived Species in “Molecular’ or ‘Supramolecular Flasks’
Helena Dodziuk
International Journal of Molecular Sciences , 2002, DOI: 10.3390/i3070814
Abstract: The recent advances in the syntheses of short-lived species inside cages of ‘molecular’ or ‘supramolecular flasks’ lead their more involved studies. Moreover, they open prospects for much closer and fruitful cooperation among organic synthetic, theoretical and supramolecular chemists that will allow one to obtain and study numerous, exciting highly strained molecules, ions and/or radicals.
American Society for Clinical Oncology 39th Annual Meeting, Chicago, Illinois, USA, 31 May to 3 June 2003: Breast cancer neoadjuvant and adjuvant chemotherapy – prognostic and predictive markers
Helena Earl
Breast Cancer Research , 2003, DOI: 10.1186/bcr647
Abstract: The American Society of Clinical Oncology (ASCO) Annual Meeting is a leading educational and scientific event for oncologists, clinical researchers, academics and other health care professionals involved in multidisciplinary cancer care. This year the congress was held in Chicago, Illinois, from May 31 to June 3. The theme for the 39th annual meeting was 'Commitment, care, compassion: honouring people with cancer'. The goal of the meeting was to promote communication among cancer related medical specialities and the exchange of ideas arising from ongoing advances in oncology. This encompassed the areas of pathophysiology, diagnosis and management, and included innovations in therapies. For the first time this year, an oral presentation session was devoted to pharmacogenomics. A wide range of translational scientific research relevant to breast cancer was covered as well as new clinical data pertinent to breast oncology management.Worldwide, many research groups are concentrating on breast cancer gene expression and molecular profiling, and this area was given significant coverage at the ASCO meeting. The first presentation in the meeting's plenary session, given by Lajos Pusztai from the MD Anderson group, dealt with the predictive nature of profiling in terms of response to chemotherapy. Their group described the use of gene expression profiling in predicting complete pathological response (pCR) to neoadjuvant chemotherapy with a paclitaxel and anthracycline combination (abstract #1 [1]). In 21 patients the overall accuracy of response prediction based on a group of five genes (three oestrogen sulphotransferases, nuclear factor 1/A, and histone acetyltransferase) was 81% and the positive predictive value for pCR was 75%, with an overall specificity of 93%, although sensitivity fell to 50%.The group from Baylor College (abstract #32 [1]) presented their work on gene expression patterns for de novo and acquired resistance to docetaxel. Twenty-four patients had paired
Cancer of the Breast – a new edition of a classic reference text
Helena Earl
Breast Cancer Research , 2004, DOI: 10.1186/bcr764
Abstract: The review of epidemiology was excellent, and presumably the next edition will include the emerging evidence from the Million Woman Study on hormone replacement therapy (HRT) and breast cancer risk. As a working clinician, I particularly enjoyed the excellent coverage of nutrition and breast disease (chapter 9), prevention (chapter 12), and exercise and weight control in prevention and rehabilitation (chapter 13). These provided a comprehensive review of evidence in the subject areas I am so often challenged on by my patients and friends, but of which I am relatively ignorant. 'What is your opinion, Doctor, of a healthy life-style to reduce the risk of breast cancer or breast cancer recurrence?' There was also a very comprehensive and up to date review of both hormone therapy and chemotherapy by authors of international repute, which I could not fault.The coverage of molecular and biological aspects of breast cancer was on the whole very good, thorough, up to date and readable, and again provides an excellent reference text. I enjoyed the chapter on the genetic basis for the emergence and progression of breast cancer (10), and the molecular biology of breast cancer (11), although the latter needs some good illustrations to improve its comprehensibility. The chapter on cellular kinetics (19) was interesting but probably too long and somewhat outdated. The chapter on growth rates (21) definitely had too few pictures, and as this is an important and interesting area of research, and pertinent to the general breast cancer researcher, it needs to be re-interpreted in a more readable style. Too many mathematical equations in a text usually lead to inattention in the reader, and this important information needs to be better presented.Where did the book disappoint? The chapter that covered prognosis (22) really needs to be separated and expanded to include information on the promise of the emerging technologies of molecular profiling, proteomics, and bio-informatics. Pregna
Orienta??o sexual em uma escola: recortes de corpos e de gênero
Altmann, Helena;
Cadernos Pagu , 2003, DOI: 10.1590/S0104-83332003000200012
Abstract: this article deals with sexual orientation in a municipal grade school (grades 5th to 8th) in rio de janeiro, brazil. the reflections about how a school develops this work are investigated from the perspective of the emergence of an image of gender during the making up of an ethnographic study. the fact that a larger number of girls than boys allowed themselves to be interviewed leads one to question who talks about these subjects with the adolescents and how the topic of sexuality is approached, limited and inserted into the school. it can be said that there are two central topics around which sex education classes are organized: pregnancy and std/aids, to which are linked the forms of prevention - the condom and birth control methods. this is followed by a discussion of issues about how the feminine and masculine bodies are viewed, which is in turn related to the historical process of the female body's medicalization. finally, a few issues about some paradoxes confronted by the adolescents in relation to birth control.
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