Photothermal therapy (PTT) using a photo-absorbent in the near-infrared (NIR) region is an effective methodology for local cancer treatment. Before PTT using a NIR absorbent is executed, the operator generally determines the two parameters of fluence rate and irradiation time. However, even if the irradiation parameters are unchanged, the therapeutic effect of PTT is often different for individual tumors. Hence, we examined the therapeutic effect of PTT using a NIR absorbent (ICG lactosome) while changing two parameters (fluence rate and irradiation time) in various combinations. As a result, there was no robust correlation between those parameters and the therapeutic effect. Compared to those parameters, we found that a more reliable determinant was maintenance of the tumor temperature above 43 °C during NIR irradiation. To reconfirm the significance of the determinant, we developed a new system that can regulate the temperature at the NIR irradiation site at a constant level. By using the new system, we verified the treatment outcomes for tumors in which the NIR absorbent had accumulated. All of the tumors that had been kept at 43 °C during NIR irradiation were cured, while none of the tumors that had been kept at a temperature below 41 °C were cured. In conclusion, PTT using a NIR absorbent with thermal dosimetry is a highly reliable treatment for cancer.
Although noradrenaline and adrenaline are some of the most important neurotransmitters in the central nervous system, the effects of noradrenergic/adrenergic modulation on the striatum have not been determined. In order to explore the effects of adrenergic receptor (AR) agonists on the striatal firing patterns, we used optogenetic methods which can induce continuous firings. We employed transgenic rats expressing channelrhodopsin-2 (ChR2) in neurons. The medium spiny neuron showed a slow rising depolarization during the 1-s long optogenetic striatal photostimulation and a residual potential with 8.6-s half-life decay after the photostimulation. As a result of the residual potential, five repetitive 1-sec long photostimulations with 20-s onset intervals cumulatively increased the number of spikes. This 'firing increment', possibly relating to the timing control function of the striatum, was used to evaluate the AR modulation. The β-AR agonist isoproterenol decreased the firing increment between the 1st and 5th stimulation cycles, while the α-AR agonist phenylephrine enhanced the firing increment. Isoproterenol and adrenaline increased the early phase (0-0.5s of the photostimulation) firing response. This adrenergic modulation was inhibited by the β-antagonist propranolol. Conversely, phenylephrine and noradrenaline reduced the early phase response. β-ARs and α-ARs work in opposition controlling the striatal firing initiation and the firing increment.
Flexible materials are important for the development of neural probes in recording stable signals (spikes) in vivo. Here, we present inkjet-printed, flexible neural probes for spike recording by using polymeric thin films. The neural probes were constructed from 400 nm-thick poly(D,L-lactic acid) nanofilms, inkjet-printed lines consisting of Au and poly(3,4-ethylenedioxythiophene):polystyrenesulfonate nanoinks, and fluoropolymer layers. Microelectrodes were exposed by cutting the edge with a razor. The 6 μm-thick probes were connected to the external amplifiers by gradual increase of stiffness with thickness-dependent manner. The probe was formed into a needle shape, which recorded spikes from mouse thalamus in vivo.
Laser hyperthermia is a powerful therapeutic modality that suppresses the growth of proliferative lesions. In hyperthermia, the optimal temperature range is dependent on the disease; thus, a temperature-driven laser output control system is desirable. Such a laser output control system, integrated with a thermal sensor circuit based on thermography, has been established. In this study, the feasibility of the developed system was examined by irradiating mouse skin. The system is composed of a thermograph, a thermal sensor circuit (PC and microcontroller), and an infrared laser. Based on the maximum temperature in the laser-irradiated area acquired every 100 ms during irradiation, the laser power was controlled such that the maximum temperature was maintained at a preset value. Temperature-controlled laser hyperthermia using the thermal sensor circuit was shown to suppress temperature fluctuations during irradiation (SD ∼ 0.14 ∘ C) to less than 1/10 of those seen without the thermal sensor circuit (SD ∼ 1.6 ∘ C). The thermal sensor circuit was able to satisfactorily stabilize the temperature at the preset value. This system can therefore provide noncontact laser hyperthermia with the ability to maintain a constant temperature in the irradiated area.
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