RESUMO
With the aggravation of the global aging process, more and more elderly people are facing the problem of dysphagia. The advantages of three-dimensional (3D) printing in making chewy food are increasingly prominent. In this study, the two-nozzle 3D printer was used to explore the effects of different proportions of buckwheat flour, printing filling ratio, microwave power, and time on the quality of bean-paste buns. The results showed that the bean paste filling containing 6% buckwheat flour had the best antioxidant and sensory properties. When the filling ratio was 21.6%, the microwave power was 560 W, and the time was 4 min, the obtained sample was the most satisfactory. Compared with the microwave-treated and steamed traditional samples, the chewiness of the samples was reduced by 52.43% and 15.14%, respectively, and the final product was easier to chew and swallow.
Assuntos
Fabaceae , Fagopyrum , Farinha , Impressão Tridimensional , Idoso , Humanos , Fabaceae/química , Alimentos , Calefação/métodos , Micro-Ondas , Fagopyrum/química , Farinha/análise , Mastigação , Deglutição , Manipulação de AlimentosRESUMO
Myeloid derived suppressor cells (MDSCs) are a diverse collection of immune cells that suppress anti-tumor immune responses. Decreasing MDSCs accumulation in the tumor microenvironment could improve the anti-tumor immune response and improve immunotherapy. Here, we examine the impact of physiologically relevant thermal treatments on the accumulation of MDSCs in tumors in mice. We found that different temperature-based protocols, including 1) weekly whole-body hyperthermia, 2) housing mice at their thermoneutral temperature (TT, ~30 °C), and 3) housing mice at a subthermoneutral temperature (ST,~22 °C) while providing a localized heat source, each resulted in a reduction in MDSC accumulation and improved tumor growth control compared to control mice housed at ST, which is the standard, mandated housing temperature for laboratory mice. Additionally, we found that low dose ß-adrenergic receptor blocker (propranolol) therapy reduced MDSC accumulation and improved tumor growth control to a similar degree as the models that relieved cold stress. These results show that thermal treatments can decrease MDSC accumulation and tumor growth comparable to propranolol therapy.
Assuntos
Temperatura Alta/uso terapêutico , Células Supressoras Mieloides/imunologia , Neoplasias/imunologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Linhagem Celular Tumoral , Feminino , Resposta ao Choque Térmico/fisiologia , Calefação/métodos , Hipertermia Induzida/métodos , Imunoterapia/métodos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/fisiologia , Microambiente Tumoral/imunologiaRESUMO
Purpose: The aim of this study was to determine whether moderate hyperthermic doses, routinely encountered in the periablational zone during thermal ablation, activate tumor cells sufficiently to secrete pro-tumorigenic factors that can induce increased proliferation.Material and methods: R3230 rat mammary tumor cells and human cancer cell lines, MCF7 breast adenocarcinoma, HepG2 and Huh7 HCC, and HT-29 and SW480 colon adenocarcinoma, were heated in to 45 ± 1 °C or 43 ± 1 °C in vitro for 5-10 min and incubated thereafter at 37 °C for 1.5, 3 or 8 hr (n = 3 trials each; total N = 135). mRNA expression profiles of cytokines implicated in RF-induced tumorigenesis including IL-6, TNFα, STAT3, HGF, and VEGF, were evaluated by relative quantitative real-time PCR. HSP70 was used as control. c-Met and STAT3 levels were assessed by Western blot. Finally, naïve cancer cells were incubated with medium from R3230 and human cancer cells that were subjected to 43-45 °C for 5 or 10 min and incubated for 3 or 8 h at 37 °C in an xCELLigence or incuCyte detection system.Results: Cell-line-specific dose and time-dependent elevations of at least a doubling in HSP70, IL-6, TNFα, STAT3, and HGF gene expression were observed in R3230 and human cancer cells subjected to moderate hyperthermia. R3230 and several human cell lines showed increased phosphorylation of STAT3 3 h post-heating and increased c-Met following heating. Medium of cancer cells subject to moderate hyperthermia induced statistically significant accelerated cell growth of all cell lines compared to non-heated media (p < 0.01, all comparisons).Conclusion: Heat-damaged human tumor cells by themselves can induce proliferation of tumor by releasing pro-tumorigenic factors.
Assuntos
Carcinoma Hepatocelular/radioterapia , Calefação/métodos , Hipertermia Induzida/métodos , Neoplasias Hepáticas/radioterapia , Animais , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , RatosRESUMO
The exploration of an effective method for preventing and treating pressure ulcers (PUs) is a hot topic in medical research. Recently, disputes about the choice of heat and cold therapies have emerged for the prevention and treatment of clinical PUs. The present study was designed to compare the effect of cool and heat therapies on pyroptosis and apoptosis of early-stage PUs in rats. Sixty SD rats of SPF grade were randomly divided into the sham group, model group, heating group, and cooling group. We established a rat model of early-stage PUs by using an ischemia-reperfusion method. At the end of the experiment, the tissue underneath the compressed region was collected for hematoxylin and eosin staining, transmission electron microscopy, immunohistochemistry, immunofluorescence staining, a TdT-mediated dUTP nick-end labeling assay, a Western blot analysis, and a mitochondrial swelling experiment. Our results suggested that the mitochondrial apoptotic pathway and pyroptosis were involved in the formation of early-stage PUs, and local heating increased the PU injury in rats, while local cooling reduced the PU injury in rats. This study showed that heat therapy might not be suitable for the clinical treatment and care of early-stage PUs, while cold therapy may be more appropriate.
Assuntos
Apoptose , Temperatura Baixa , Calefação/métodos , Isquemia/terapia , Úlcera por Pressão/terapia , Piroptose , Traumatismo por Reperfusão/terapia , Animais , Modelos Animais de Doenças , Isquemia/patologia , Masculino , Úlcera por Pressão/patologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologiaRESUMO
Array-induced voltage was used to enhance the extraction of pectin from grapefruit peel. The voltages induced by synchronous alternating magnetic fluxes as stimulus, provided an efficient extraction approach. The dynamics of pectin extraction is described by a pseudo-first-order model. The pectin yield and extraction rate of pectin depended on the vector of the in-phase and reverse-phase voltages. The transposed arrangement of the voltages had no significant influence on the pectin extraction rate. The maximum yield of 10.34%, obtained at 1000 V, a 0° phase difference and a 3 × 3 in-phase voltage array, was 5.74- and 1.3-fold higher than that of the control (0 V) and conventional heating method, respectively. This approach led to a rapid release of pectin with lower neutral sugar content, average molecular weight, Galacturonic acid content, esterification degree, and dynamic viscosity as a result of local heating by the voltage sources (potential hotspots) in the sample solution. Morphological analysis demonstrated the increased extraction of pectin from grapefruit peel by array-induced voltages.
Assuntos
Citrus paradisi/química , Frutas/química , Pectinas/química , Calefação/métodos , Ácidos Hexurônicos/química , Temperatura , ViscosidadeRESUMO
Objectives: The newly developed therapeutic deep heating device can generate deep heat in focal tissue using high-frequency wave stimulation. The objective of this study was to evaluate and compare the effectiveness of this deep heating device (HIPER-500®) with ultrasound in alleviating pain and improving function in patients with shoulder disability. Methods: This noninferiority trial was designed to compare the treatment effect of HIPER-500® to that of SonoStim® (ultrasound) on shoulder pain and disability. Thirty-eight patients with shoulder problems were assigned to either the HIPER-500® or SonoStim® group, and each participated in 10 min therapy sessions, five days a week for two weeks (for a total of ten sessions). Shoulder pain and disability were evaluated using the Visual Analogue Scale (VAS), the University of California at Los Angeles score (UCLA score), the Shoulder Pain and Disability Index (SPADI), and the Constant score in both groups before, immediately after, and four weeks after treatment. Statistical analysis was performed to compare the effects of treatment within and between the groups. Results: A total of 34 patients completed the study. The 18 patients in the HIPER-500® group and 16 patients in the SonoStim® group all showed significant improvements in shoulder pain and function when comparing pretreatment values with the results immediately after treatment and four weeks later. The results before and after treatment did not show a statistically significant difference between the two groups. Conclusions: The newly developed HIPER-500® for high-frequency deep heat therapy showed similar effects to those of SonoStim® for relieving pain and improving physical performance in the patients of this study. HIPER-500® may be a useful modality for treating shoulder pain and improving physical activity in patients with shoulder disease.
Assuntos
Calefação/instrumentação , Terapia por Radiofrequência/instrumentação , Dor de Ombro/terapia , Adulto , Feminino , Calefação/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Terapia por Radiofrequência/métodosRESUMO
Objetivou-se com este trabalho avaliar parâmetros de identidade e qualidade de óleo de abacate produzido nacionalmente, comparativamente a azeite de oliva e óleo de arroz, após aquecimento em bloco digestor ou micro-ondas. Avaliaram-se amostras sem aquecimento (controle) e aquecidas por 1:30 h em bloco digestor ou 3 min em micro-ondas. Determinaram-se a acidez e os índices iodo e refração. Os resultados indicaram que houve aumento de acidez, redução no índice de iodo e índice de refração após o aquecimento. Apesar do maior valor de acidez após o aquecimento, o óleo de abacate sofreu menor elevação em relação ao controle (cerca de 4 vezes) do que as demais amostras. O impacto do aquecimento foi maior no óleo de arroz, seguido do azeite de oliva. O aquecimento por micro-ondas afetou mais a qualidade das amostras que o aquecimento em bloco digestor.
Assuntos
Azeite de Oliva , Calefação/efeitos adversos , Calefação/métodos , Oryza , Persea , Óleos de Plantas/análise , Acidez/análise , Iodo/análise , Micro-Ondas/efeitos adversos , RefratometriaRESUMO
There is currently great interest in replacing fossil-oil with renewable fuels in energy production. Fast pyrolysis bio-oil (FPBO) made of lignocellulosic biomass is one such alternative to replace fossil oil, such as heavy fuel oil (HFO), in energy boilers. However, it is not known how this fuel change will alter the quantity and quality of emissions affecting human health. In this work, particulate emissions from a real-scale commercially operated FPBO boiler plant are characterized, including extensive physico-chemical and toxicological analyses. These are then compared to emission characteristics of heavy fuel-oil and wood fired boilers. Finally, the effects of the fuel choice on the emissions, their potential health effects and the requirements for flue gas cleaning in small-to medium-sized boiler units are discussed. The total suspended particulate matter and fine particulate matter (PM1) concentrations in FPBO boiler flue gases before filtration were higher than in HFO boilers and lower or on a level similar to wood-fired grate boilers. FPBO particles consisted mainly of ash species and contained less polycyclic aromatic hydrocarbons (PAH) and heavy metals than had previously been measured from HFO combustion. This feature was clearly reflected in the toxicological properties of FPBO particle emissions, which showed less acute toxicity effects on the cell line than HFO combustion particles. The electrostatic precipitator used in the boiler plant efficiently removed flue gas particles of all sizes. Only minor differences in the toxicological properties of particles upstream and downstream of the electrostatic precipitator were observed, when the same particulate mass from both situations was given to the cells.
Assuntos
Poluentes Atmosféricos/análise , Calefação/métodos , Material Particulado/análise , Óleos de Plantas/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Polifenóis/química , Pirólise , Finlândia , Combustíveis Fósseis/análise , Óleos Combustíveis/análise , Madeira/químicaRESUMO
AIM: Thermal isoeffective dose (TID) has not been convincingly validated for application to predict biological effects from rapid thermal ablation (e.g., using >55 °C). This study compares the classical method of quantifying TID (derived from hyperthermia data) with a temperature-adjusted method based on the Arrhenius model for predicting cell survival in vitro, after either 'rapid' ablative or 'slow' hyperthermic exposures. METHODS: MTT assay viability data was obtained from two human colon cancer cell lines, (HCT116, HT29), subjected to a range of TIDs (120-720 CEM43) using a thermal cycler for hyperthermic (>2 minutes, <50 °C) treatments, or a novel pre-heated water bath based technique for ablative exposures (<10 seconds, >55 °C). TID was initially estimated using a constant RCEM>43°C=0.5, and subsequently using RCEM(T), derived from temperature dependent cell survival (injury rate) Arrhenius analysis. RESULTS: 'Slow' and 'rapid' exposures resulted in cell survival and significant regrowth (both cell lines) 10 days post-treatment for 240 CEM43 (RCEM>43°C=0.5), while 340-550 CEM43 (RCEM>43°C =0.5) delivered using 'rapid' exposures showed 12 ± 6% viability and 'slow' exposures resulted in undetectable viability. Arrhenius analysis of experimental data (activation energy ΔE = 5.78 ± 0.04 × 105 J mole-1, frequency factor A = 3.27 ± 11 × 1091 sec-1) yielded RCEM=0.42 * e0.0041*T which better-predicted cell survival than using R CEM> 43°C=0.5. CONCLUSIONS: TID calculated using an RCEM(T) informed by Arrhenius kinetic parameters provided a more consistent, heating strategy independent, predictor of cell viability, improving dosimetry of ablative thermal exposures. Cell viability was only undetectable above 305 ± 10 CEM43 using this revised measure.
Assuntos
Morte Celular/fisiologia , Calefação/métodos , Hipertermia Induzida/métodos , HumanosRESUMO
A fast sample preparation procedure based on use of infrared (IR) assisted heating for mineralization of soybean derived samples has been developed for their subsequent multielement analysis by inductively coupled plasma optical emission spectrometry (ICP-OES) and flame atomic absorption spectrometry (FAAS). A cold finger was examined for refluxing of acid vapors to determine its impact on efficiency and economy of digestion. The optimized procedure, based on 1â¯g subsamples, 8â¯mL of HNO3 (65% w/w) and exposure of the mixture to a 500â¯W IR source for 5â¯min without refluxing, permitted accurate determination of all analytes in NIST SRM 1568b (rice flour). Detection limits using ICP-OES were (µg/kg) 97, 1.0, 39, 185, 0.47 and 1200 for Ca, Cu, Fe, K, Mn and P, respectively, and 18 for Zn by FAAS. The IR-assisted digestion approach provided a low cost, easy to use system having great potential for implementation in routine analysis of trace elements in soybean and similar matrices.
Assuntos
Análise de Alimentos/métodos , Glycine max/química , Oligoelementos/análise , Análise de Alimentos/instrumentação , Gases/análise , Calefação/métodos , Raios Infravermelhos , Limite de Detecção , Metais/análise , Fósforo/análise , Espectrofotometria Atômica/métodosRESUMO
Presently we communicate a newly developed method of resonant radiofrequency heating, applicable in hyperthermal therapy. This method uses electron paramagnetic resonance (EPR) to transform the electromagnetic field energy into heat. We report the growth dynamics of the S. cerevisiae yeast cells exposed to EPR heating with superparamagnetic magnetite (Fe3O4) nanoparticles, with only 4% of yeast cells surviving hyperthermia. Given that EPR functions independently of type of the biologic species exposed, and produces spatially localized heating in conjunction with MRI hardware, it may be used in hyperthermal therapy of cancer and other diseases.
Assuntos
Espectroscopia de Ressonância de Spin Eletrônica , Hipertermia Induzida , Nanopartículas de Magnetita , Saccharomyces cerevisiae/crescimento & desenvolvimento , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Calefação/métodos , Temperatura Alta , Hipertermia Induzida/métodos , Nanopartículas de Magnetita/administração & dosagem , Nanopartículas de Magnetita/química , Saccharomyces cerevisiae/citologiaRESUMO
OBJECTIVES: Warming intravenous fluids is essential to prevent hypothermia in patients with trauma, especially when large volumes are administered. Prehospital and transport settings require fluid warmers to be small, energy efficient and independent of external power supply. We compared the warming properties and resistance to flow of currently available battery-operated fluid warmers. METHODS: Fluid warming was evaluated at 50, 100 and 200 mL/min at a constant input temperature of 20°C and 10°C using a cardiopulmonary bypass roller pump and cooler. Output temperature was continuously recorded. RESULTS: Performance of fluid warmers varied with flows and input temperatures. At an input temperature of 20°C and flow of 50 mL/min, the Buddy Lite, enFlow, Thermal Angel and Warrior warmed 3.4, 2.4, 1 and 3.6 L to over 35°C, respectively. However, at an input temperature of 10°C and flow of 200 mL/min, the Buddy Lite failed to warm, the enFlow warmed 3.3 L to 25.7°C, the Thermal Angel warmed 1.5 L to 20.9°C and the Warrior warmed 3.4 L to 34.4°C (p<0.0001). CONCLUSION: We found significant differences between the fluid warmers: the use of the Buddy Lite should be limited to moderate input temperature and low flow rates. The use of the Thermal Angel is limited to low volumes due to battery capacity and low output temperature at extreme conditions. The Warrior provides the best warming performance at high infusion rates, as well as low input temperatures, and was able to warm the largest volumes in these conditions.
Assuntos
Desenho de Equipamento/normas , Hidratação/instrumentação , Calefação/instrumentação , Desenho de Equipamento/métodos , Hidratação/métodos , Hidratação/normas , Calefação/métodos , Calefação/normas , Humanos , Hipotermia/prevenção & controle , Hipotermia/terapia , Estudos Prospectivos , Estatísticas não Paramétricas , Avaliação da Tecnologia Biomédica/métodosRESUMO
To investigate the effect one of the oil products, domestic heating oil (DHO), on freshwater mollusks, Unio tigridis and Viviparous bengalensis were exposed to three DHO concentrations for each species (5.8, 8.7, and 17.4â¯mlâ¯L-1 for mussels; 6.5, 9.7, and 19.5 mlL-1 for snails, respectively). Antioxidant enzymes (superoxide dismutase, catalase), malondialdehyde, acetylcholinesterase and DNA damage in both species tissues were monitored over 21 days. The results showed that both antioxidant enzymes concentration (SOD and CAT) increased in the lowest DHO concentrations (5.8, and 8.7â¯mlâ¯L-1), and then decreased in the highest concentration (17.4â¯mlâ¯L-1) as the same pattern for Unio tigridis, but this not occurred for Viviparous bengalensis. MDA values recorded significantly increased compared to control. No reduction was observed in AChE concentrations in soft tissues of both mollusks may due to that DHO was a non-neurotoxicant to Unio tigridis and Viviparous bengalensis. The results of DNA damage parameters were showed significant differences (p≤ 0.05) between control and DHO concentrations except lowest concentration for each parameter measured in digestive gland of Unio tigridis. As well as, these significant differences were recorded between control and three concentrations of DHO exposure for comet length, and tail length parameters, and between control and highest oil concentration for tail moment in Viviparous bengalensis. DHO has the ability to prevent the reproduction of Viviparous bengalensis snail relation to control, that is what we considered strong evidence of the toxicity properties of DHO on the reproductive status of this species of snails. SOD, CAT, and MDA were useful biomarkers for evaluating the toxicity of DHO in mussel and snails, and comet assay was a good tool to assess the potential genotoxicity of DHO.
Assuntos
Antioxidantes/metabolismo , Biomarcadores Ambientais , Óleos Combustíveis/toxicidade , Calefação/métodos , Reprodução/efeitos dos fármacos , Caramujos/efeitos dos fármacos , Unio/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Bivalves/efeitos dos fármacos , Catalase/metabolismo , Ensaio Cometa , Dano ao DNA , Água Doce , Malondialdeído/metabolismo , Petróleo , Caramujos/fisiologia , Superóxido Dismutase/metabolismo , Unio/fisiologiaRESUMO
Radio frequency (RF) heating has been successfully used for inactivating microorganisms in agricultural and food products. Athermal (non-thermal) effects of RF energy on microorganisms have been frequently proposed in the literature, resulting in difficulties for developing effective thermal treatment protocols. The purpose of this study was to identify if the athermal inactivation of microorganisms existed during RF treatments. Escherichia coli and Staphylococcus aureus in apple juice and mashed potato were exposed to both RF and conventional thermal energies to compare their inactivation populations. A thermal death time (TDT) heating block system was used as conventional thermal energy source to simulate the same heating treatment conditions, involving heating temperature, heating rate and uniformity, of a RF treatment at a frequency of 27.12â¯MHz. Results showed that a similar and uniform temperature distribution in tested samples was achieved in both heating systems, so that the central sample temperature could be used as representative one for evaluating thermal inactivation of microorganisms. The survival patterns of two target microorganisms in two food samples were similar both for RF and heating block treatments since their absolute difference of survival populations was <1 log CFU/ml. The statistical analysis indicated no significant difference (Pâ¯>â¯0.05) in inactivating bacteria between the RF and the heating block treatments at each set of temperatures. The solid temperature and microbial inactivation data demonstrated that only thermal effect of RF energy at 27.12â¯MHz was observed on inactivating microorganisms in foods.
Assuntos
Escherichia coli/crescimento & desenvolvimento , Sucos de Frutas e Vegetais/microbiologia , Calefação/métodos , Malus/microbiologia , Pasteurização/métodos , Ondas de Rádio , Solanum tuberosum/microbiologia , Staphylococcus aureus/crescimento & desenvolvimento , Alimentos , Microbiologia de Alimentos/métodos , Temperatura Alta , Viabilidade Microbiana/efeitos da radiaçãoRESUMO
This series of nine papers described the operation and pre-clinical assessment of a tobacco heating product THP1.0. This last paper contextualises the pre-clinical assessment data on THP1.0 with data from other next generation products relative to cigarette smoke. The tobacco and nicotine risk continuum is a concept that ranks products according to their potential harm, with cigarettes at the highest risk extreme and Nicotine Replacement Therapy at the least risky extreme. Data generated in pre-clinical studies on THP1.0 and a range of Next Generation Products (NGPs) may provide some initial indication of potential ranking of these products, although importantly, data from such studies are limited and cannot take into consideration several important aspects for risk such as long term product use patterns. In each of the studies, the responses to the emissions from THP1.0 were substantially reduced relative to cigarette smoke. Additionally, responses from THP1.0 were very similar to those from the other NGP emissions. A comparison of the results clearly showed the emissions from all the NGPs were considerably lower than those from cigarettes and all in around the same emissions level. These results show that THP1.0 could have the potential to be a reduced risk product compared to cigarettes, though further studies assessing the exposure, individual and population risk reduction profile would be required to substantiate this potential.
Assuntos
Aerossóis/análise , Sistemas Eletrônicos de Liberação de Nicotina/métodos , Calefação/métodos , Nicotina/análise , Produtos do Tabaco/análise , Aerossóis/administração & dosagem , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Mutagênese/efeitos dos fármacos , Mutagênese/fisiologia , Nicotina/administração & dosagemRESUMO
Radio frequency (RF) heating has been proposed and tested to achieve a required anti-fungal efficacy on various food samples due to its advantage of deeper penetration depth and better heating uniformity. The purpose of this study was to validate applications of RF treatments for controlling Aspergillus parasiticus in corn while maintaining product quality. A pilot-scale, 27.12MHz, 6kW RF heating system together with hot air heating was used to rapidly pasteurize 3.0kg corn samples. Results showed that the pasteurizing effect of RF heating on Aspergillus parasiticus increased with increasing heating temperature and holding time, and RF heating at 70°C holding in hot air for at least 12min resulted in 5-6 log reduction of Aspergillus parasiticus in corn samples with the moisture content of 15.0% w.b. Furthermore, thermal resistance of Aspergillus parasiticus decreased with increasing moisture content (MC) of corn samples. Quality (MC, water activity - aw, protein, starch, ash, fat, fatty acid, color, electrical conductivity and germination rate) of RF treated corn met the required quality standard used in cereal industry. Therefore, RF treatments can provide an effective and rapid heating method to control Aspergillus parasiticus and maintain acceptable corn quality.
Assuntos
Aspergillus/efeitos da radiação , Grão Comestível/microbiologia , Calefação/métodos , Pasteurização/métodos , Ondas de Rádio , Zea mays/microbiologia , ÁguaRESUMO
The use of non-invasive radiofrequency (RF) energy to induce mild thermal and non-thermal effects in cancer tissue is under study as an adjuvant to chemo, radio or immuno therapy. This study examines cell specific sensitivities to RF exposure and the potential of nanoparticles to elevate heating rates or enhance biological effects. Increases in the heating rate of water in an RF field operating at 13.56MHz (0.004-0.028°C/s) were positively correlated with concentration of hybrid nanoparticles (1-10mg/ml) consisting of water soluble malonodiserinolamide [60]fullerene (C60-ser) conjugated to the surface of mesoporous silica nanoparticles (SiO2-C60). The heating rate of highly conductive cell culture media (0.024°C/s) was similar to that of the highest concentration of nanoparticles in water, with no significant increase due to addition of nanoparticles at relevant doses (<100µg/ml). With respect to cell viability, anionic (SiO2 and SiO2-C60) or neutral (C60) nanoparticles did not influence RF-induced cell death, however, cationic nanoparticles (4-100µg/ml) caused dose-dependent increases in RF-induced cell death (24-42% compared to RF only). The effect of cell type, size and immortalization on sensitivity of cells to RF fields was examined in endothelial (HUVEC and HMVEC), fibroblast (primary dermal and L939) and cancer cells (HeLa and 4T1). While the state of cellular immortalization itself did not consistently influence the rate of RF-induced cell death compared to normal cell counter parts, cell size (ranging from 7 to 30µm) negatively correlated with cell sensitivity to RF (21-97% cell death following 6min irradiation). In summary, while nanoparticles do not alter the heating rate of biologically-relevant solutions, they can increase RF-induced cell death based on intrinsic cytotoxicity; and cells with smaller radii, and thereby greater surface membrane, are more susceptible to cell damage in an RF field than larger cells. STATEMENT OF SIGNIFICANCE: The ability of nanoparticles to either direct heating or increase susceptibility of cancer cells to radiofrequency (RF) energy remains controversial, as is the impact of cell attributes on susceptibility of cells to RF-induced cell death. This manuscript examines the impact of nanoparticle charge, size, and cellular localization on RF-induced cell death and the influence of nanoparticles on the heating rates of water and biologically-relevant media. Susceptibility of immortalized or primary cells to RF energy and the impact of cell size are also examined. The ability to selectively modulate RF heating rates in specific biological locations or in specific cell populations would enhance the therapeutic potential of RF therapy.
Assuntos
Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Fulerenos/administração & dosagem , Calefação/métodos , Hipertermia Induzida/métodos , Nanopartículas/administração & dosagem , Ondas de Rádio , Relação Dose-Resposta a Droga , Células HeLa , Humanos , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Doses de Radiação , Radiossensibilizantes/administração & dosagemRESUMO
OBJECTIVES: The objective is to design heating protocols to completely damage PC3 tumors after a single magnetic nanoparticle hyperthermia session with minimal collateral thermal damage, based on microCT image generated tumor and mouse models. METHODS: Tumor geometries and volumetric heat generation rate distributions that are generated from microCT scans in our previous study are imported into COMSOL 4.3® multiphysics for heat transfer simulations and heating protocol design using the Arrhenius damage model. Then, parametric studies are performed to evaluate how significantly the infusion rate affects the protocol design and its resulted collateral thermal damage. RESULTS: The simulated temperature field in the generated tumor geometry and volumetric heat generation rate distribution are reasonable and correlates well with the amount of the total thermal energy deposited into the tumors. The time needed for complete thermal damage is determined to be approximately 12min or 25min if one uses the Arrhenius integral Ω equal to 1 or 4 as the damage threshold, when the infusion rate is 3µL/min. The heating time increases 26% or 91% in the higher infusion rate groups of 4 or 5µL/min, respectively. Collateral thermal damage to the surrounding tissue is also assessed. Although the two larger infusion rate groups can still cause thermal damage to the entire tumor, the collateral thermal damage would have exceeded the design criterion of 5%, while the assessment criterion is acceptable only in the infusion rate group of 3µL/min. Based on the results of this study, we identify an injection strategy and heating protocols to be implemented in future animal experiments to evaluate treatment efficacy for model validation.
Assuntos
Hipertermia Induzida/métodos , Nanopartículas de Magnetita/uso terapêutico , Modelos Biológicos , Neoplasias/terapia , Temperatura , Microtomografia por Raio-X/métodos , Animais , Linhagem Celular Tumoral , Simulação por Computador , Modelos Animais de Doenças , Calefação/métodos , Temperatura Alta , Humanos , Hipertermia Induzida/instrumentação , CamundongosRESUMO
Passive heat therapy (repeated hot tub or sauna use) reduces cardiovascular risk, but its effects on the mechanisms underlying improvements in microvascular function have yet to be studied. We investigated the effects of heat therapy on microvascular function and whether improvements were related to changes in nitric oxide (NO) bioavailability using cutaneous microdialysis. Eighteen young, sedentary, otherwise healthy subjects participated in 8 wk of heat therapy (hot water immersion to maintain rectal temperature ≥38.5°C for 60 min/session; n = 9) or thermoneutral water immersion (sham, n = 9), and participated in experiments before and after the 8-wk intervention in which forearm cutaneous hyperemia to 39°C local heating was assessed at three microdialysis sites receiving 1) Lactated Ringer's (Control), 2) N(ω)-nitro-l-arginine (l-NNA; nonspecific NO synthase inhibitor), and 3) 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), a superoxide dismutase mimetic. The arm used for microdialysis experiments remained out of the water at all times. Data are means ± SE cutaneous vascular conductance (CVC = laser Doppler flux/mean arterial pressure), presented as percent maximal CVC (% CVCmax). Heat therapy increased local heating plateau from 42 ± 6 to 53 ± 6% CVCmax (P < 0.001) and increased NO-dependent dilation (difference in plateau between Control and l-NNA sites) from 26 ± 6 to 38 ± 4% CVCmax (P < 0.01), while no changes were observed in the sham group. When data were pooled across all subjects at 0 wk, Tempol had no effect on the local heating response (P = 0.53 vs. Control). There were no changes at the Tempol site across interventions (P = 0.58). Passive heat therapy improves cutaneous microvascular function by improving NO-dependent dilation, which may have clinical implications.
Assuntos
Hipertermia Induzida/métodos , Microcirculação/fisiologia , Óxido Nítrico/metabolismo , Comportamento Sedentário , Fenômenos Fisiológicos da Pele , Pele/irrigação sanguínea , Vasodilatação/fisiologia , Adulto , Feminino , Calefação/métodos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Hyperthermia generated with various energy sources including microwave has been widely studied for cancer treatment. However, the potential damage due to nontargeted heating of normal tissue is a major hurdle to its widespread application. Fullerene is a potential agent for improving cancer therapy with microwave hyperthermia but is limited by its poor solubility in water for biomedical applications. Here we report a combination therapy for enhanced cancer cell destruction by combining microwave heating with C60-PCNPs consisting of fullerene (C60) encapsulated in Pluronic F127-chitosan nanoparticles (PCNPs) with high water solubility. A cell culture dish integrated with an antenna was fabricated to generate microwave (2.7 GHz) for heating PC-3 human prostate cancer cells either with or without the C60-PCNPs. The cell viability data show that the C60-PCNPs alone have minimal cytotoxicity. The combination of microwave heating and C60-PCNPs is significantly more effective than the microwave heating alone in killing the cancer cells (7.5 versus 42.2% cell survival). Moreover, the combination of microwave heating and C60-PCNPs is significantly more destructive to the cancer cells than the combination of simple water-bath heating (with a similar thermal history to microwave heating) and C60-PCNPs (7.5 versus 32.5% survival) because the C60 in the many nanoparticles taken up by the cells can absorb the microwave energy and convert it into heat to enhance heating inside the cells under microwave irradiation. These data suggest the great potential of targeted heating via fullerene for enhanced cancer treatment by microwave hyperthermia.