Resorufin Enters the Photodynamic Therapy Arena: A Monoamine Oxidase Activatable Agent for Selective Cytotoxicity

A red-absorbing, water-soluble, and iodinated resorufin derivative (R1) that can be selectively activated with a monoamine oxidase (MAO) enzyme was synthesized, and its potential as a photodynamic therapy (PDT) agent was evaluated. R1 showed high ¹O₂ generation yields in aqueous solutions upon addition of MAO isoforms, and it was further tested in cell culture studies. R1 induced photocytotoxicity after being triggered by endogenous MAO enzyme in cancer cells with a much higher efficiency in SH-SY5Y neuroblastoma cells with high MAO-A expression. Additionally, R1 displayed differential cytotoxicity between cancer and normal cells, without any considerable dark toxicity. To the best of our knowledge, R1 marks the first example of a resorufin-based photosensitizer (PS) as well as the first anticancer drug that is activated by a MAO enzyme. Remarkably, the target PDT agent was obtained only in three steps as a result of versatile resorufin chemistry.     

Management of recalcitrant vitiligo in Vogt-Koyanagi-Harada syndrome: Adjuvant ablative fractional laser

The course of dermatologic findings in Vogt-Koyanagi-Harada disease is variable. Herein, we report the remarkable repigmentation of widespread facial vitiligo lesions in an adolescent girl with Vogt-Koyanagi-Harada disease. The patient was treated with a combination of fractional erbium:YAG laser, topical tacrolimus, and phototherapy.     

External beam radiotherapy for localized prostate cancer

Radiotherapy (XRT) is a curative treatment option for prostate cancer (PCa). Recent XRT technologies allow higher dose therapy that lead to increased local control with less adjacent tissue damage. Additionally, receiving neo-adjuvant or adjuvant hormonotherapy (HT) during radiation therapy increases the curative effect. The aim of this paper is to review the current literature and guidelines on external beam radiation therapy for PCa. However, brachytherapy and radiosurgery, a recently evolving relatively new technology for the radiotherapeutic management of localized PCa, are beyond the scope of this paper.     

Selected characteristics of an Ormocer and a conventional hybrid resin composite.

OBJECTIVES: The objective of this in vitro study was to evaluate surface roughness, hardness and wear resistance of an Ormocer (Admira), polymerized by a plasma arc system. A secondary objective was to investigate two placement technique bulk or incremental layers. METHODS: Blocks from Admira and Amelogen (a microhybrid composite) were prepared in cylinders, 3 mm in diameter, and 2 and 5 mm in thickness (bulk or incrementally placed) and polymerized by a plasma arc and a conventional light system. Surface roughness measurements were taken by a Surface Profilometer on the top of the specimens. Vickers hardness measurements, with a load of 600mN were taken on the top and bottom of 2 mm and top, intermediate and bottom of 5 mm thick specimens. For the wear test, specimes (8 mm in diameter and 2 mm in thickness) of Admira, Amelogen and amalgam were tested in a ball-on design, by circular movements of the antagonist (alumina ball; diameter 10 mm) under 10 N load. For the statistical evaluation of the results of surface roughness, microhardness and wear test; a paired samples t-test and Kruskal-Wallis analysis of variance test, were performed. RESULTS: Admira showed highest hardness values in all polymerization types at the top surface and this was statistically significant (p < 0.05). These highest hardness values were obtained with conventional polymerization (81.84 +/- 1.167 VHN). Meanwhile, the wear resistance of Admira was found to be higher than Amelogen (Wd(admira) = 0.024 +/- 0.00149 mm3; Wd(amelogen) = 0.032 +/- 0.00075 mm3). However, Admira demonstrated the highest surface roughness value compared to Amelogen, with plasma arc 5 s (0.65 +/- 0.023 microm). Amelogen was found to have the lowest surface roughness value with conventional 40 s (0.45 +/- 0.012 microm). SIGNIFICANCE: The results indicated that Ormocer, which was developed by Ormocer technology, demonstrated higher microhardness and wear resistance when compared to a hybrid composite; however, the polishability of Ormocer needs further investigation. Also the selection of visible light activated composite resins exhibited higher surface microhardness values when polymerized with conventional rather than with plasma arc.     

COVID-19 in solid organ transplant recipients: a single-center experience

Solid organ transplant (SOT) recipients may be at risk for severe COVID-19. Data on the clinical course of COVID-19 in immunosuppressed patients are limited, and the effective treatment strategy for these patients is unknown. We describe our institutional experience with COVID-19 in SOT. Demographic, clinical, and treatment data were extracted from the electronic patient files. A total of 23 SOT transplant recipients suffering from COVID-19 were identified (n = 3 heart; n = 15 kidney; n = 1 kidney-after-heart; n = 3 lung, and n = 1 liver transplant recipient). The presenting symptoms were similar to nonimmunocompromised patients. Eighty-three percent (19/23) of the patients required hospitalization, but only two of these were transferred to the intensive care unit. Five patients died from COVID-19; all had high Clinical Frailty Scores. In four of these patients, mechanical ventilation was deemed futile. In 57% of patients, the immunosuppressive therapy was not changed and only three patients were treated with chloroquine. Most patients recovered without experimental antiviral therapy. Modification of the immunosuppressive regimen alone could be a therapeutic option for SOT recipients suffering from moderate to severe COVID-19. Pre-existent frailty is associated with death from COVID-19.     

Nonlinear analysis of heart rate variability of healthy subjects and patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is one of the causes of mortality worldwide with an increasing prevalence. Heart rate variability (HRV) reflects the regulation mechanism of the cardiac activity by the autonomic nervous system. The assessment of HRV by using nonlinear methods is more sensitive for the detection of complexity when compared to linear methods. This study aims to get information about the autonomic dysfunction occurred in patients with COPD by analysing the complexity of HRV. Electrocardiogram signals recorded from healthy subjects, patients with moderate COPD and severe COPD (eight subjects per group) were analysed. The HRV signals were acquired from ECG signals. Signals were reconstructed in the phase space and largest Lyapunov exponent (LLE), correlation dimension, Hurst exponent and approximate entropy (ApEn) values were calculated. It has seen that for the patients with COPD LLE, correlation dimension, Hurst exponent and ApEn values were less than control group. According to this, HRV complexity decreases in the presence of COPD. However, there is no significant difference between COPD groups and the severity of COPD has no effect on the chaoticity of the system. The results revealed that autonomic dysfunction occurred in patients with COPD is associated with reduced HRV complexity.     

Patients with Behcet's disease carry a higher risk for microvascular involvement in active disease period

BACKGROUND: Behcet's disease (BD) is characterized with remissions and exacerbations. However, to date, there is no study to investigate a possible association of disease activity (active versus inactive disease period) with cardiovascular complications. METHODS: Forty patients with BD were evaluated in both active and in inactive disease period. For the control group 45 healthy volunteers, age and sex matched, were registered. Subjects with at least a 15-day lesion-free period were regarded in inactive disease period, and subjects with any oral, skin, and/or genital lesion was regarded as in active disease period. In each subject coronary diastolic peak flow velocities (DPFV) were measured at baseline and after dipyridamole infusion (0.84 mg/kg over 6 minutes) using an Acuson Sequoia C256 echocardiography system. Coronary flow reserve (CFR) was defined as the ratio of hyperemic to baseline DPFV. RESULTS: CFR values were significantly lower in BD patients compared to the controls (2.57+/-0.50 versus 2.87+/-0.53, P = 0.006). In active disease period, basal DPFV (24.6+/-7.5 versus 27.3+/-6.6, P = 0.019) was significantly higher than in the inactive disease period. In the active disease period hyperemic DPFV (61.7+/-14.9 versus 56.8+/-16.7, P = 0.015) values decreased significantly. Therefore, in the active disease period CFR significantly decreased from 2.57+/-0.50 to 2.09+/-0.46, P<0.001. The only independent predictor of CFR within the active disease period was the disease duration (beta = -0.384, P = 0.012). CONCLUSION: Within the active disease period, coronary microvascular function is more prominently impaired in BD patients. Therefore, BD patients are possibly more vulnerable to cardiovascular manifestations when they are in an active disease period.