Photodynamic therapy (PDT) is used for the treatment of malignant tumors. It is based on the interaction of a photosensitizer with light of appropriate wavelength in the presence of molecular oxygen. In recent years, applications of PDT have been extended to conditions other than superficial, early-stage cancers. The therapy leads to inhibition of angiogenesis, and hence has been applied also to the treatment of age-related macular degeneration. Recently, PDT has been reported to potentially reduce cell membrane permeability. In this study, we evaluated the efficacy of PDT, focusing on its ability to regulate cell or tissue functions. In particular, we studied the potential of PDT to reduce acquired resistance to anticancer agents in cell types over-expressing P-glycoprotein (P-gp), a membrane-bound drug efflux transporter. Photofrin®(PF) was used as the photosensitizing agent. Irradiation was performed in the range of 0.5-3.0 J/cm2, which did not lead to any significant cytotoxic effect. The contact between PF and target cells was facilitated by adding PF in (1)a serum-containing culture medium (Protocol 1), and (2)phosphate-buffered saline (Protocol 2). HeLa cells were incubated in these two culture media. A comparative assessment was employed to evaluate the capacity of PDT to reduce acquired resistance to paclitaxel (TXL) in these cells. Although there was no significant reduction in TXL resistance by PDT in Protocol 1, a decrease in drug efflux activity was obtained in Protocol 2, indicating a reduction in TXL resistance. The results of this study suggest that administration of PDT under specific conditions leads to reduction in drug efflux capacity of cells with acquired resistance to anticancer agents.
Tendon rupture is a traumatic injury that is difficult to recover to the condition before injury. In previous studies, histological staining and tensile testing have been widely used to evaluate histological and mechanical healing. However, since both methods are destructive and invasive, it is difficult to apply these methods to clinical diagnosis. If the degree of healing can be visualized nondestructively and noninvasively, new findings may be obtained regarding mechanisms of the tendon healing process. In this study, we used second-harmonic-generation (SHG) microscopy to evaluate the degree of healing of ruptured tendon in a rabbit model. SHG microscopy has high selectivity and high image contrast with respect to the structural maturity, density, and aggregates of collagen molecule, without the need for histological sectioning and staining. Furthermore, since SHG light intensity sensitively reflects the structural maturity of collagen molecule and its aggregates, it has the potential to be a good indicator for the degree of healing of the injured tendon. By comparing the SHG images between 4-week-healing tendons and normal tendons in the animal model, we confirmed that SHG light intensity of the healing tendon was significantly lower than that of the normal tendon, indicating that the collagen structure in the healing tendon is still immature. Furthermore, we performed image analysis based on 2D Fourier transform of the acquired SHG images, and confirmed a significant difference in collagen distribution depending on the sample. These results indicate that SHG microscopy has the unique potential as an indicator of tendon healing.
This study evaluated the effect of pulse arrival time (PAT) on the difference between heart rate variability (HRV) and pulse rate variability (PRV). HRV is the degree of fluctuation in the time intervals between heart beats obtained from ECG, and is a global measure of autonomic nervous system (ANS) function. PRV is obtained from photoplethysmogram (PPG), and several researchers have attempted to use PRV instead of HRV for ANS monitoring, because measuring PPG is easier than measuring ECG. PPG reflects the change in blood volume ejected from the heart. Therefore, there is a strong correlation between the HRV and the PRV, and the PRV is regarded as an acceptable alternative to HRV at rest in ANS evaluation. In this study, we focused on the influence of change of body position on PRV, and we evaluated the effect of PAT on the difference between HRV and PRV. PAT is the sum of pulse transit time (PTT) and the pre-ejection period. Therefore, we used PAT to verify the difference between HRV and PRV. Seven healthy volunteers participated in this experiment. Their ECG and PPG were simultaneously recorded for 5 min before and 5 min after standing up from a chair. The results of the correlation coefficient indicated a strong correlation (r=0.9) between the HRV and the PRV in both sitting and standing positions. In contrast, the results of high-frequency spectral component showed a significant difference while standing, suggesting the influence of PAT on PRV. These results indicate that PRV is not identical to HRV, and that we should pay attention to use PRV instead of HRV for measuring ANS function.