Energy analysis of PDT using thermography during the treatment of basal cell carcinoma Publication date: March 2020 Source: Photodiagnosis and Photodynamic Therapy, Volume 29 Author(s): Mirian Denise Stringasci, Ana Gabriela Salvio, Lilian Tan Moriyama, José Dirceu Vollet-Filho, Thereza Cury Fortunato, Vanderlei Salvador Bagnato, Cristina Kurachi Abstract The changes in tissue temperature of basal cell carcinoma lesions were investigated during photodynamic therapy in order to better understand the effects and mechanisms of PDT in tissue. In this study, the monitoring of 40 lesions of basal cell carcinoma was performed during photodynamic therapy. The lesion region becomes thermally evident throughout the procedure, and there is an improved contrast of the lesion edges after the end of the irradiation. The comparison between thermal and fluorescence images showed a correlation between the PpIX evidenced through widefield fluorescence and the temperature gradient of the thermal images after the procedure, indicating that thermography is a potential diagnostic tool to evaluate the selective response of PDT. A model was created to calculate the amount of light energy converted to heat, tissue damage, and other energy transfer processes involved in the PDT. Using this model, it was shown that most of the energy conversion was in photodynamic action (48.7% and 48.3%, in first and second session, respectively), followed by the energy ratio attributable to blood perfusion (37.2%). This is evidence that photodynamic therapy does not generate a significant thermal component, an important aspect of the study of its mechanisms.

5-aminolevulinic acid-based photodynamic therapy associated with Itraconazole successfully treated a case of chromoblastomycosis Publication date: March 2020 Source: Photodiagnosis and Photodynamic Therapy, Volume 29 Author(s): Weijiang Yang, Wentao Zhang, Jiefu Luo, Jinyi Chen, Yang Tan, Xia Lei Abstract Chromoblastomycosis (CBM) is a prevalent implantation fungal infection. Patients with CBM show chronic granulomatous hyperplasia with ulcers and exudation. It may cause incapacity for labor in some severe clinical forms and it is often refractory to antifungal therapies. There is no optimal treatment. Here we report a case of a 71-year-old male farmer with refractory CBM who was successfully treated with 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) and Itraconazole in 2 months. Clinical cure was achieved with no obvious side effects.

Photodynamic therapy inhibits cell growth and enhances the histone deacetylase-mediated viability impairment in Cryptococcus spp. in vitro Publication date: March 2020 Source: Photodiagnosis and Photodynamic Therapy, Volume 29 Author(s): José Athayde Vasconcelos Morais, Mosar C. Rodrigues, Fernanda F. Ferreira, Kunal Ranjan, Ricardo Bentes Azevedo, Marcio J. Poças-Fonseca, Luis A. Muehlmann Abstract Cryptococcosis is a disseminated infection caused mainly by C. neoformans and C. gattii. Limitations for the treatment involve the selection of isolates resistant to conventional antifungal drugs, prolonged treatment time and drugs side effects. This study evaluated the combined effect of histone deacetylase inhibitors (HDACi) and photodynamic therapy (PDT) on the growth of C. neoformans and C. gattii in vitro. Results showed that PDT inhibited yeasts proliferation and enhanced the HDACi-mediated cell viability impairment in Cryptococcus spp.

Use of dermograph for improvement of PpIX precursor’s delivery in photodynamic therapy: Experimental and clinical pilot studies Publication date: March 2020 Source: Photodiagnosis and Photodynamic Therapy, Volume 29 Author(s): Michelle Barreto Requena, Pedro Ernesto Russignoli, José Dirceu Vollet-Filho, Ana Gabriela Salvio, Thereza Cury Fortunato, Sebastião Pratavieira, Vanderlei Salvador Bagnato Abstract Background Photodynamic Therapy (PDT) is a treatment for non-melanoma skin cancer. One of the main challenges of topical PDT is to increase the precursor penetration when applied on the lesion. Protoporphyrin IX (PpIX) is an endogenous photosensitizer (PS) widely used, obtained by the administration of precursors such as aminolevulinic acid and methyl aminolevulinate. Aiming for the technique improvement by providing greater PS penetration in skin lesions, we tested a new approach for drug delivery with a minimally invasive technique. A dermograph is a device currently used in aesthetic procedures to promote skin rejuvenation or to micropigmentation. The use of dermograph for drug delivery has not been particularly explored for PDT so far, and the present study explores that approach as its main goal. Methods This study evaluated the PpIX distribution and PDT damage in normal rat skin model; the response of dermograph application in a pilot clinical study was also investigated. Results The animal tests showed that more homogeneous PpIX distribution and greater penetration in the tissue was observed with dermograph when compared to the topical application. Six nodular basal cell carcinoma lesions were treated with PDT using intradermal delivery by dermograph, and no recurrence was observed after 28 months of follow-up. Conclusions The precursor’s penetration improvement and the consequent increase in PpIX distribution in-depth both favor PDT response, providing upgrades concerning problems that hinder the clinical practice acceptance.

Investigating the mechanisms behind extensive death in human cancer cells following nanoparticle assisted photo-thermo-radiotherapy Publication date: March 2020 Source: Photodiagnosis and Photodynamic Therapy, Volume 29 Author(s): Mohammad Mehdi Movahedi, Zahra Alamzadeh, Samira Hosseini-Nami, Ali Shakeri-Zadeh, Gholamreza Taheripak, Amirhossein Ahmadi, Arash Zare-Sadeghi, Habib Ghaznavi, Alireza Mehdizadeh Abstract We have recently reported the synthesis and characterization of gold-coated iron oxide nanoparticle and demonstrated such a nanoparticle (Au@Fe2O3 NP) was able to significantly enhance the lethal effects of photo-thermo-radiotherapy. The purpose of this study was to determine the mechanisms behind such an enhancement by investigating the changes induced in cancer cell viability, proliferation, and morphology as well as monitoring the alteration of some genes which play important role in the process of cell death. Using MTT assay and transmission electron microscopy (TEM), the KB cells viability and morphology were assessed after treating with various combinations of NPs, photothermal therapy (PTT), and radiotherapy (RT). Clonogenic assay was used to assess the proliferation ability of treated KB cells. Nanoparticle internalization into the cells was investigated by TEM and inductively coupled plasma (ICP). During the treatment procedures, temperature changes were monitored using an IR-camera. Furthermore, the changes occurred in Bax, BCL2 and HSP70 genes expression level were measured using real-time PCR. The results showed that combination of NP, PTT, and RT caused more cell death compared to PTT or RT alone. Following such a combination therapy, massive cell injury was detected. We also observed an extensive increase in Bax/Bcl2 ratio and HSP70 expression for the KB cells treated by combination therapy procedure. Our results showed that massive cell injury and apoptosis induction are the main reasons of extensive cell death observed in cancer cells when a nanoparticle assisted photo-thermo-radiotherapy procedure is applied.

Choriocapillary vascular density in central serous chorioretinopathy complicated by choroidal neovascularization Publication date: March 2020 Source: Photodiagnosis and Photodynamic Therapy, Volume 29 Author(s): Gilda Cennamo, Chiara Comune, Federica Mirra, Pasquale Napolitano, Daniela Montorio, Giuseppe de Crecchio Abstract Background To evaluate choriocapillary vascular density (CVD) in eyes with central serous chorioretinopathy (CSC) complicated by choroidal neovascularization (CNV), at baseline and after intravitreal injections (IVR) of Ranibizumab, using optical coherence tomography angiography (OCTA). Methods Twelve eyes of 12 patients were enrolled as group 1 and 12 unaffected fellow eyes formed group 2. Twelve eyes of 12 healthy controls were the control group. Results CVD in Group 1 did not differ before and after treatment. CVD of Group 1 was significantly lower compared with controls at baseline (whole, parafovea and fovea p < 0.05). CVD of controls resulted significantly higher than Group 2 at baseline (whole, parafovea and fovea p < 0.05). There were not significant differences in CVD between Groups 1 and 2 at baseline (p > 0.05). Conclusions OCTA revealed a choriocapillary hypoperfusion that may be responsable for the beginning of this disease and the late development of CNV.

Diffused light attenuation at 664 nm for PDT in salted cadaver brain Publication date: March 2020 Source: Photodiagnosis and Photodynamic Therapy, Volume 29 Author(s): Emiyu Ogawa, Jiro Akimoto, Shinjiro Fukami, Shogo Hayashi, Michihiro Kohno, Marika Doi, Risa Hamada, Haruna Nakazawa, Aki Miyashita, Tsunenori Arai Abstract Background We investigated light attenuation at 664 nm, which is the excitation wavelength of photodynamic therapy (PDT) using talaporfin sodium, in a salted cadaver brain. Estimation of therapeutic lesions is important to ensure the effectiveness and safety of brain tumor PDT. Previously reported optical properties of the human brain vary widely. In this study, we measured the light attenuation in brain tissue using a practical method. We employed a salted cadaver brain, in which the mechanical and optical properties can be maintained as close as possible to those under operative conditions. Methods A neuroendoscope was inserted into the brain until the cerebral ventricle was reached. A thin cylindrical diffuser probe was advanced 10 mm from the endoscope tip. By another path from the brain surface, an optical fiber for measurement was inserted into a puncture needle, and a pair of needles was used to puncture the tissue and reach the same cerebral ventricle in which the endoscope tip was positioned. The attenuation of light intensities in the frontal lobe and cerebellum was measured by varying the bundle tip position. The starting positions of the bundle were confirmed by the endoscopic view. The measured light intensity attenuations were fitted with an exponential curve. Results The following attenuation coefficients were obtained: 0.20 ± 0.05 mm−1 in the cerebrum and 0.27 ± 0.05 mm−1 in the cerebellum. Conclusion As conventional spectroscopic measurement may overestimate attenuation in the whole tissue, in situ measurement using the withdrawal technique might be appropriate for measurement of inhomogeneous biological tissues.

Evaluation of a pulsed xenon ultraviolet light device for reduction of pathogens with biofilm-forming ability and impact on environmental bioburden in clinical laboratories Publication date: March 2020 Source: Photodiagnosis and Photodynamic Therapy, Volume 29 Author(s): Li-hua Chen, Yu Li, Yong Qi, Shan-ni Wang, Chang-qing Gao, Yong Wu Abstract Background Biofilm-forming organisms can persist on surfaces in hospital clinical laboratories and potentially lead to nosocomial infections. Therefore, effective decontamination procedures are essential for reducing infections. In this study, we investigated an alternative to often ineffective manual cleaning methods, a pulsed xenon ultraviolet (PX-UV) light device. We evaluated PX-UV effect on biofilm formation ability of pathogens and also evaluated PX-UV effectiveness on environmental bioburden in clinical laboratories. Methods We selected and identified P. aeruginosa PA47, Staphylococcus aureus B1, and K. pnenumoniae CR52 from clinic isolates. Biofilm-forming ability and effectiveness of PX-UV in killing these biofilm forming strains on surfaces was evaluated. The central laboratory, the clinical microbiology laboratory, and the clinical immunology laboratory were chosen for testing environmental bioburden. Air samples and high-touch surface specimens in the three laboratories were obtained before and after routine manual cleaning, and after 6 min of PX-UV disinfection. The cultured microbes were then identified with MALDI- TOF-MS. Results We found that P. aeruginosa PA47, Staphylococcus aureus B1, and K. pnenumoniae CR52 were able to form robust biofilms, and that PX-UV significantly reduced colony counts of these strains on all surfaces tested. PX-UV reduced the bioburden of air samples and eliminated bioburden on surfaces. All microbes identified in the clinical laboratories were pathogenic and consisted of cocci, rods, and fungi. Conclusions The PX-UV device effectively reduced pathogens with biofilm-forming ability on surfaces, and the environmental bioburden was also significantly reduced by PX-UV. PX-UV is a viable option for protecting staff and decreasing rates of laboratory-acquired infections.

Size effect of platinum nanoparticles in simulated anticancer photothermal therapy Publication date: March 2020 Source: Photodiagnosis and Photodynamic Therapy, Volume 29 Author(s): J. Depciuch, M. Stec, B. Klebowski, A. Maximenko, E. Drzymała, J. Baran, M. Parlinska-Wojtan Abstract Platinum nanoparticles (Pt NPs) with properties including damage of DNA, enzmatic activity and possibility of light absorption in the biological range could find application as effective photosensitizers in photothermal anticancer therapy (PTT). The photothermal properties of Pt NPs depend on their shape, size and crystalline structure. Therefore, in this paper the effect of Pt NPs size on photothermal efficiency is determined. For this purpose, spherical, crystalline 80 nm PtI NPs and 2 nm PtII NPs were synthesized and characterized by transmission electron microscopy (TEM), selected area diffraction patterns (SAED) and X-ray diffraction (XRD). The possibilities of using Pt NPs in PTT were investigated using two colon cancer cell lines: SW480 and SW620, which were cultured with both Pt NPs and irradiated by two, 650 nm and 808 nm lasers. Microscopy images of cells and MTS assay showed, that the PTT is the most effective when 2 nm nanoparticles and the 650 nm laser were used. The mortality of cells was around 62% for SW480 and 70% for SW620. Furthermore, higher temperatures after irradiation of Pt NPs by lasers were observed for the 2 nm Pt NPs for both wavelengths. Consequently, the values of photothermal efficiency are higher by approximately 5% and 6% for 2 nm Pt NPs, than for 80 nm ones, which were irradiated by 650 and 808 nm lasers, respectively. Moreover, the results obtained from experimental data corresponded with Mie theory.

Effect of photodynamic therapy on gingival inflammation in patients with thalassemia Publication date: March 2020 Source: Photodiagnosis and Photodynamic Therapy, Volume 29 Author(s): Dhafer Al Asmari, Muhammad Khalil Khan Abstract Background To evaluate the role of photodynamic therapy (PDT) as an adjunct to full-mouth ultrasonic scaling (FMUS) in reducing inflammation and gingival crevicular fluid (GCF) levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in thalassemia major (TM) patients with gingivitis. Materials and methods Thirty patients were randomized into two groups; Group A: PDT + FMUS and Group B: FMUS alone. Clinical periodontal parameters including plaque index (PI), gingival index (GI), bleeding on probing (BoP) and probing depth (PD) were measured. Levels of IL-6 and TNF-α were estimated using enzyme linked immunosorbent assay. All measurements were performed at baseline (T0), 6 weeks (T6) and 12 weeks (T12), respectively. Results For PI and GI, the reduction in Group A (p < 0.001) was higher than Group B (p < 0.05) at T12. Intra-group comparison between T6 and T12 showed statistical significance in both the groups (p < 0.01). The inter-group mean differences (Δ0-6 and Δ0-12) for both deltas showed statistical significance (p = 0.01). For BoP, no significant differences were seen until the end of T12 in both groups. The BoP in Group A reduced by a significant margin at T6 and remained less high by the end of T12 compared with group B (p = 0.02). Significant reduction in both IL-6 and TNF-α from T0 to T6 were seen in both groups. However, only for TNF-α that the intra-group differences were statistically significantly different from T0 to T12. The GCF levels of TNF-α in Group A remained less high by the end of T12 compared with group B (p < 0.05). Conclusion The adjunctive role of PDT in the reduction of clinical and immunological signs of inflammation in TM patients seem to be effective in the short term.