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1.
Phys Med Biol ; 64(6): 065016, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30736017

RESUMO

This study presents an investigation of human skin exposure to obliquely incident electromagnetic waves at frequencies from 6 GHz to 1 THz. We aim to clarify the relationship between the power density and the skin surface temperature elevation under various exposure conditions. A Monte Carlo simulation was conducted to assess the transmittance and surface temperature elevation considering the variation of skin tissue thickness. For the case of TM wave injection, transmittance increases with increasing incidence angle from the normal incidence because of the Brewster effect. The normal incidence is confirmed as the worst-case exposure condition when the incident power density is defined in an area normal to the propagation direction. In addition, we investigated the power density required to obtain the equivalent temperature elevation over the skin surface. The analysis shows that the incident power density defined in the direction normal to the skin surface may underestimate the temperature elevation when TM waves are incident over the normal incidence up to the maximum transmittance angle. Our results also show that the power density inside the skin surface strongly correlates with the surface temperature elevation but less dependent on the frequency and independent of the oblique incidence angle and polarization. The findings of this study are expected to be valuable for discussing how to use the different definitions of power density based on dosimetric characteristics as measures in safety guidelines to protect humans from excessive temperature elevation by millimeter and submillimeter-wave exposure.


Assuntos
Temperatura Corporal/efeitos da radiação , Campos Eletromagnéticos/efeitos adversos , Exposição à Radiação/análise , Pele/efeitos da radiação , Humanos , Modelos Biológicos , Método de Monte Carlo , Doses de Radiação
2.
EBioMedicine ; 39: 562-574, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30502055

RESUMO

BACKGROUND: We have previously reported that xeno-transplanted human ESC-derived retinas are able to mature in the immunodeficient retinal degeneration rodent models, similar to allo-transplantations using mouse iPSC-derived retina. The photoreceptors in the latter developed outer segments and formed synapses with host bipolar cells, driving light responses of host retinal ganglion cells. In view of clinical application, here we further confirmed the competency of human iPSC-derived retina (hiPSC-retina) to mature in the degenerated retinas of rat and monkey models. METHODS: Human iPSC-retinas were transplanted in rhodopsin mutant SD-Foxn1 Tg(S334ter)3LavRrrc nude rats and two monkeys with laser-induced photoreceptor degeneration. Graft maturation was studied by immunohistochemistry and its function was examined by multi-electrode array (MEA) recording in rat retinas and visually-guided saccade (VGS) in a monkey. FINDINGS: A substantial amount of mature photoreceptors in hiPSC-retina graft survived well in the host retinas for at least 5 months (rat) to over 2 years (monkey). In 4 of 7 transplanted rat retinas, RGC light responses were detected at the grafted area. A mild recovery of light perception was also suggested by the VGS performance 1.5 years after transplantation in that monkey. INTERPRETATION: Our results support the competency of hiPSC-derived retinas to be clinically applied for transplantation therapy in retinal degeneration, although the light responses observed in the present models were not conclusively distinguishable from residual functions of degenerating host retinas. The functional analysis may be further elaborated using other models with more advanced retinal degeneration.


Assuntos
Fatores de Transcrição Forkhead/genética , Células-Tronco Pluripotentes Induzidas/transplante , Lasers/efeitos adversos , Degeneração Retiniana/terapia , Animais , Células Cultivadas , Modelos Animais de Doenças , Eletrorretinografia , Haplorrinos , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Mutação , Ratos , Ratos Nus , Retina/citologia , Retina/patologia , Retina/fisiopatologia , Degeneração Retiniana/etiologia , Degeneração Retiniana/fisiopatologia , Rodopsina/genética
3.
Proc Natl Acad Sci U S A ; 113(1): E81-90, 2016 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-26699487

RESUMO

Retinal transplantation therapy for retinitis pigmentosa is increasingly of interest due to accumulating evidence of transplantation efficacy from animal studies and development of techniques for the differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells into retinal tissues or cells. In this study, we aimed to assess the potential clinical utility of hESC-derived retinal tissues (hESC-retina) using newly developed primate models of retinal degeneration to obtain preparatory information regarding the potential clinical utility of these hESC-retinas in transplantation therapy. hESC-retinas were first transplanted subretinally into nude rats with or without retinal degeneration to confirm their competency as a graft to mature to form highly specified outer segment structure and to integrate after transplantation. Two focal selective photoreceptor degeneration models were then developed in monkeys by subretinal injection of cobalt chloride or 577-nm optically pumped semiconductor laser photocoagulation. The utility of the developed models and a practicality of visual acuity test developed for monkeys were evaluated. Finally, feasibility of hESC-retina transplantation was assessed in the developed monkey models under practical surgical procedure and postoperational examinations. Grafted hESC-retina was observed differentiating into a range of retinal cell types, including rod and cone photoreceptors that developed structured outer nuclear layers after transplantation. Further, immunohistochemical analyses suggested the formation of host-graft synaptic connections. The findings of this study demonstrate the clinical feasibility of hESC-retina transplantation and provide the practical tools for the optimization of transplantation strategies for future clinical applications.


Assuntos
Células-Tronco Embrionárias Humanas/citologia , Retina/citologia , Retina/transplante , Degeneração Retiniana/cirurgia , Animais , Diferenciação Celular , Cobalto/toxicidade , Modelos Animais de Doenças , Haplorrinos , Humanos , Células Fotorreceptoras/patologia , Primatas , Ratos , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/patologia
4.
Inflamm Regen ; 36: 2, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29259675

RESUMO

Rodent studies have recently demonstrated substantial integration of transplanted photoreceptors, with potential synaptic connection and functional restoration. Consequently, photoreceptor transplantation therapy for retinitis pigmentosa is attracting a growing interest in the field of translational research. Differentiation strategies for the formation of three-dimensional (3D) retinal tissue that are suitable for graft preparation have also been introduced via the use of human embryonic stem cells (hESCs) and human induced pluripotent stem cells. We have recently shown that hESC-derived retinal tissue (hESC-retina) can survive, mature, and potentially integrate with host secondary neurons following transplantation into two established primate models of retinal degeneration. Our data demonstrated the feasibility of deploying hESC-retina transplantation as a new remedy with which to restore the vision of patients with end-stage retinal degenerative diseases. In the present mini-review, we provide a short introduction of photoreceptor transplantation research.

5.
Phys Med Biol ; 55(16): 4647-59, 2010 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-20671356

RESUMO

The present study describes theoretical parametric analysis of the steady-state temperature elevation in one-dimensional three-layer (skin, fat and muscle) and one-layer (skin only) models due to millimeter-wave exposure. The motivation of this fundamental investigation is that some variability of warmth sensation in the human skin has been reported. An analytical solution for a bioheat equation was derived by using the Laplace transform for the one-dimensional human models. Approximate expressions were obtained to investigate the dependence of temperature elevation on different thermal and tissue thickness parameters. It was shown that the temperature elevation on the body surface decreases monotonically with the blood perfusion rate, heat conductivity and heat transfer from the body to air. Also revealed were the conditions where maximum and minimum surface temperature elevations were observed for different thermal and tissue thickness parameters. The surface temperature elevation in the three-layer model is 1.3-2.8 times greater than that in the one-layer model. The main reason for this difference is attributed to the adiabatic nature of the fat layer. By considering the variation range of thermal and tissue thickness parameters which causes the maximum and minimum temperature elevations, the dominant parameter influencing the surface temperature elevation was found to be the heat transfer coefficient between the body surface and air.


Assuntos
Temperatura Cutânea , Pele/patologia , Temperatura Corporal , Simulação por Computador , Capacitância Elétrica , Impedância Elétrica , Temperatura Alta , Humanos , Modelos Biológicos , Modelos Teóricos , Propriedades de Superfície , Temperatura , Condutividade Térmica
6.
Biomed Eng Online ; 8: 20, 2009 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-19775447

RESUMO

BACKGROUND: Because the possibility of millimeter wave (MMW) exposure has increased, public concern about the health issues due to electromagnetic radiation has also increased. While many studies have been conducted for MMW exposure, the effect of dielectric permittivities on skin heating in multilayer/heterogeneous human-body models have not been adequately investigated. This is partly due to the fact that a detailed investigation of skin heating in a multilayer model by computational methods is difficult since many parameters are involved. In the present study, therefore, theoretical analyses were conducted to investigate the relationship between dielectric permittivities and MMW-induced skin heating in a one-dimensional three-layer model (skin, fat, and muscle). METHODS: Approximate expressions were derived for the temperature elevation and temperature difference in the skin due to MMW exposure from analytical solutions for the temperature distribution. First, the power absorption distribution was approximated from the analytical solution for a one-layer model (skin only). Then, the analytical expression of the temperature in the three-layer model was simplified on the basis of the proposal in our previous study. By examining the approximate expressions, the dominant term influencing skin heating was clarified to identify the effects of the dielectric permittivities. Finally, the effects of dielectric permittivities were clarified by applying partial differentiation to the derived dominant term. RESULTS: Skin heating can be characterized by the parameters associated with the dielectric permittivities, independently of morphological and thermal parameters. With the derived expressions, it was first clarified that skin heating correlates with the total power absorbed in the skin rather than the specific absorption rate (SAR) at the skin surface or the incident power density. Using Debye-type expression we next investigated the effect of frequency dispersion on the complex relative permittivity of tissue. The parametric study on the total power absorbed in the skin showed that skin heating increases as the static permittivity and static conductivity decrease. In addition, the maximum temperature elevation on the body surface was approximately 1.6 times that of the minimum case. This difference is smaller than the difference caused by the thermal and morphological parameters reported in our previous study. CONCLUSION: This paper analytically clarified the effects of dielectric permittivities on the thermally steady state temperature elevation and the temperature difference in the skin of a one-dimensional three-layer model due to MMW exposure.


Assuntos
Modelos Biológicos , Temperatura Cutânea/fisiologia , Temperatura Cutânea/efeitos da radiação , Animais , Simulação por Computador , Relação Dose-Resposta à Radiação , Capacitância Elétrica , Impedância Elétrica , Humanos , Micro-Ondas , Doses de Radiação
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