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Purpose: Radioiodine (I131) therapy is the treatment mainstay for several benign and malignant thyroid disorders, however I131 is known to cause DNA damage and liberation of thyroidal self-antigens inducing secondary immunoreactivity. The exact mechanisms underpinning cellular death and subsequent induction of autoimmune thyroid disease following I131 treatment have not yet been fully elucidated. This manuscript aims to review the literature concerning the effects of I131 on the thyroid gland.Conclusion: The effects of I131 on malignant thyroid cells appears to depend on absorbed dose with the literature demonstrating a clear initial delay in the triggering of apoptosis in response to I131-mediated cellular damage. Some studies also observed necrotic cellular death following high-dose I131 treatment. Liberation of thyroidal self-antigen following I131 treatment helps to explain phenomena such as the subsequent induction of autoimmune thyroid disease. The clinical utility of cytokines and autoantibodies for prognostication of hypothyroidism and treatment failure following I131 remains uncertain and further appropriately-powered studies are required to clarify their role. The potential role of other cell death mechanisms activated after treatment with I131 should also be explored in order to fully delineate the thyroidal response.
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Radioisótopos do Iodo/uso terapêutico , Doenças da Glândula Tireoide/radioterapia , Dano ao DNA , Humanos , Doenças da Glândula Tireoide/genética , Glândula Tireoide/metabolismo , Glândula Tireoide/efeitos da radiaçãoRESUMO
BACKGROUND: Though the management of malignancies has improved vastly in recent years, many treatment options lack the desired efficacy and fail to adequately augment patient morbidity and mortality. It is increasingly clear that patient response to therapy is unique to each individual, necessitating personalised, or 'precision' medical care. This demand extends to thyroid cancer; ~ 10% patients fail to respond to radioiodine treatment due to loss of phenotypic differentiation, exposing the patient to unnecessary ionising radiation, as well as delaying treatment with alternative therapies. METHODS: Human thyroid tissue (n = 23, malignant and benign) was live-sliced (5 mm diameter × 350-500 µm thickness) then analysed or incorporated into a microfluidic culture device for 96 h (37 °C). Successful maintenance of tissue was verified by histological (H&E), flow cytometric propidium iodide or trypan blue uptake, immunohistochemical (Ki67 detection/ BrdU incorporation) and functional analysis (thyroxine [T4] output) in addition to analysis of culture effluent for the cell death markers lactate dehydrogenase (LDH) and dead-cell protease (DCP). Apoptosis was investigated by Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Differentiation was assessed by evaluation of thyroid transcription factor (TTF1) and sodium iodide symporter (NIS) expression (western blotting). RESULTS: Maintenance of gross tissue architecture was observed. Analysis of dissociated primary thyroid cells using flow cytometry both prior to and post culture demonstrated no significant change in the proportion of viable cells. LDH and DCP release from on-chip thyroid tissue indicated that after an initial raised level of release, signifying cellular damage, detectable levels dropped markedly. A significant increase in apoptosis (p < 0.01) was observed after tissue was perfused with etoposide and JNK inhibitor, but not in control tissue incubated for the same time period. No significant difference in Ki-67 positivity or TTF1/NIS expression was detected between fresh and post-culture thyroid tissue samples, moreover BrdU positive nuclei indicated on-chip cellular proliferation. Cultured thyroid explants were functionally viable as determined by production of T4 throughout the culture period. CONCLUSIONS: The described microfluidic platform can maintain the viability of thyroid tissue slices ex vivo for a minimum of four days, providing a platform for the assessment of thyroid tissue radioiodine sensitivity/adjuvant therapies in real time.
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Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/instrumentação , Dispositivos Lab-On-A-Chip , Técnicas de Cultura de Tecidos/instrumentação , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologiaRESUMO
Power output limitation is one of the main challenges that needs to be addressed for full-scale applications of the Microbial Fuel Cell (MFC) technology. Previous studies have examined electrochemical performance of different cathode electrodes including the development of novel iron based electrocatalysts, however the long-term investigation into continuously operating systems is rare. This work aims to study the application of platinum group metals-free (PGM-free) catalysts integrated into an air-breathing cathode of the microbial fuel cell operating on activated sewage sludge and supplemented with acetate as the carbon energy source. The maximum power density up to 1.3 Wm-2 (54 Wm-3) obtained with iron aminoantipyrine (Fe-AAPyr) catalyst is the highest reported in this type of MFC and shows stability and improvement in long term operation when continuously operated on wastewater. It also investigates the ability of this catalyst to facilitate water extraction from the anode and electroosmotic production of clean catholyte. The electrochemical kinetic extraction of catholyte in the cathode chamber shows correlation with power performance and produces a newly synthesised solution with a high pH > 13, suggesting caustic content. This shows an active electrolytic treatment of wastewater by active ionic and pH splitting in an electricity producing MFC.
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OBJECTIVES: These studies aimed to assess the short-term (12-hour, single use) and long-term (four weeks, continuous use) efficacy of a new Dual Zinc plus Arginine dentifrice against intra-oral halitosis versus a negative control. METHODS: Two clinical studies were conducted to assess the dentifrice: a four-week, continuous use parallel design versus a negative control and a single use crossover design versus a negative control. Both studies used organoleptic and hedonic odor judge scores measured 12 hours overnight after product use as the primary efficacy variable. Additionally, the single use study employed SIFT-MS to quantify the intra-oral concentration of volatile sulfur compounds as a complementary measure of efficacy. RESULTS: In both studies, the Dual Zinc plus Arginine dentifrice provided statistically significant improvements in breath quality across all measures versus a negative control. CONCLUSIONS: Improvements in breath quality were attributed to the effects of zinc cations delivered by the uniquely formulated dentifrice.
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Arginina , Dentifrícios , Halitose , Zinco , Análise de Variância , Arginina/uso terapêutico , Dentifrícios/uso terapêutico , Halitose/terapia , Humanos , Zinco/uso terapêuticoRESUMO
The use of ceramics as low cost membrane materials for Microbial Fuel Cells (MFCs) has gained increasing interest, due to improved performance levels in terms of power and catholyte production. The catholyte production in ceramic MFCs can be attributed to a combination of water or hydrogen peroxide formation from the oxygen reduction reaction in the cathode, water diffusion and electroosmotic drag through the ion exchange membrane. This study aims to evaluate, for the first time, the effect of ceramic wall/membrane thickness, in terms of power, as well as catholyte production from MFCs using urine as a feedstock. Cylindrical MFCs were assembled with fine fire clay of different thicknesses (2.5, 5 and 10 mm) as structural and membrane materials. The power generated increased when the membrane thickness decreased, reaching 2.1 ± 0.19 mW per single MFC (2.5 mm), which was 50% higher than that from the MFCs with the thickest membrane (10 mm). The amount of catholyte collected also decreased with the wall thickness, whereas the pH increased. Evidence shows that the catholyte composition varies with the wall thickness of the ceramic membrane. The possibility of producing different quality of catholyte from urine opens a new field of study in water reuse and resource recovery for practical implementation.
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The diagnosis and treatment of breast cancer can adversely affect quality of life. Here the aim was to determine the effects of reflexology on host defences and endocrine function in women with early breast cancer. Six weeks after surgery for early breast cancer, 183 women were randomly assigned to self-initiated support (SIS), SIS plus foot reflexology, or SIS plus scalp massage. Peripheral blood mononuclear cells and serum were isolated at T1 (6 weeks post surgery; baseline), T2 and T3 (4 and 10 weeks post completion of intervention, respectively). Lymphocyte phenotyping found that CD25(+) cells were significantly higher in the massage group compared with the SIS group at T3. The percentage of T cells, and more specifically the T helper subset expressing IL4, decreased significantly in the massage group compared with the SIS group at T3. This change was accompanied by an increase in the percentage of CD8(+) T cytotoxic cells expressing IFNγ in the massage group. Natural killer and lymphokine activated killer cell cytotoxicity measurements, serum levels of cortisol, prolactin and growth hormone, and flow cytometric assessment of their corresponding receptors all revealed no significant differences between the three groups of patients. This study provides evidence that the immunological balance of patients can be altered in a potentially beneficial manner by massage. The original trial was registered with the International Standard Randomised Controlled Trial Registry (ISRCTN87652313).
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Ischemia-reperfusion injury (IRI) occurs following coronary artery revascularization. Reactive oxygen species (ROS) were initially thought to play a role in the pathogenesis of this injury. However, the evidence for this is inconclusive. Recent studies involving ischemic preconditioning have identified ROS as potential mediators for the cardioprotective effects observed following this technique. Furthermore, cardiac studies involving IRI and the use of hyperbaric oxygen (HBO) have demonstrated the ability of HBO to induce cardioprotection and to attenuate IRI. This review suggests the possible role for HBO as a new drug in the arena of myocardial revascularization and cellular protection. While there is mounting clinical evidence for this, a methodological understanding of HBO's cellular mechanisms of actions appears to be lacking. As such, this article attempts to draw the similarity between HBO and other protective oxidative stress mechanisms and then to speculate in an evidence-based manner its possible cellular mechanistic role as a drug via the generation of ROS.