Phototoxic Risk Research Articles

Two Small Molecule Drugs with Topical Applications, Diflunisal and Naphazoline, and Their Potentially Toxic Photodegradants: Analysis by Chemical and Biological Methods.

Because of their topical application in patients and meaningful UV/VIS absorptive properties, the degradation and potential toxicity under irradiation of diflunisal (DIF) and naphazoline (NAF) were studied. In addition, the impact of pH on their photostability was examined, showing the highest degradation of acidic DIF at pH 1 and 13 and the highest degradation of basic NAF at pH below 7. An LC-UV analysis and chemical tests showed the first-order kinetics for their degradation and generation of reactive oxygen species (ROS). A UPLC-HRMS/MS analysis allowed us to identify four degradants of DIF (from DD-1 to DD-4) and six degradants of NAF (from ND-1 to ND-6). When Toxtree software was used, a high class III of toxicity was observed for DD-2, DD-3, and DD-4, and for all the NAF degradants. Furthermore, the ND-2 product, i.e., 2-[(1-methylnaphthalen-2-yl)methyl]-4,5-dihydro-1H-imidazole, was shown to present medium mutagenic and high tumorigenic effects according to OSIRIS Property Explorer. In addition, two in vitro tests on BALB/c 3T3 mouse fibroblasts showed a phototoxic effect of DIF and NAF at the lowest concentrations tested, i.e., 5 µg/mL. Thus, our present results could be useful to design further phototoxicity studies for DIF and NAF to minimize the risk of phototoxicity due to their photodegradation.

Efficient generation of high-contrast Bessel light sheets: a flexible method for improved imaging.

Light-sheet fluorescence microscopy plays a pivotal role in the field of biological 3D imaging. Among its various implementations, non-diffracting light sheets have garnered significant attention due to their remarkable ability to achieve a favorable balance between field of view and resolution. However, the presence of noticeable side-lobe effects in the non-diffracting light sheets poses challenges, including decreased contrast and an increased risk of phototoxicity. While amplitude modulation-based methods effectively suppress side-lobe influences, their transmission efficiency remains suboptimal. To address these limitations, this article introduces an approach based on phase modulation, facilitating the convenient and flexible generation of light sheets that effectively suppress side-lobe effects while maintaining high transmission efficiency. Importantly, our method enables rapid determination of optimal phase parameters, successfully suppressing the peak intensity of the first and second side lobes to levels exceeding 98% and 99%, respectively. Subsequently, experimental results substantiate the light sheet's exceptional contrast-enhancing capabilities.

Method for optimizing imaging parameters to record neuronal and cellular activity at depth with bioluminescence.

Optical imaging has accelerated neuroscience in recent years. Genetically encoded fluorescent activity sensors of calcium, neurotransmitters, and voltage are commonly used for optical recording of neuronal activity. However, fluorescence imaging is limited to superficial regions for in vivo activity imaging, due to photon scattering and absorbance. Bioluminescence imaging offers a promising alternative for achieving activity imaging in deeper brain regions without hardware implanted within the brain. Bioluminescent reporters can be genetically encoded and produce photons without external excitation. The use of enzymatic photon production also enables prolonged imaging sessions without the risk of photobleaching or phototoxicity, making bioluminescence suitable for non-invasive imaging of deep neuronal populations. To facilitate the adoption of bioluminescent activity imaging, we sought to develop a low cost, simple in vitro method that simulates in vivo conditions to optimize imaging parameters for determining optimal exposure times and optical hardware configurations to determine what frame rates can be captured with an individual lab's imaging hardware with sufficient signal-to-noise ratios without the use of animals prior to starting an in vivo experiment. We developed an assay for modeling in vivo optical conditions with a brain tissue phantom paired with engineered cells that produce bioluminescence. We then used this assay to limit-test the detection depth versus maximum frame rate for bioluminescence imaging at experimentally relevant tissue depths using off-the-shelf imaging hardware. We developed an assay for modeling in vivo optical conditions with a brain tissue phantom paired with engineered cells that produce bioluminescence. With this method, we demonstrate an effective means for increasing the utility of bioluminescent tools and lowering the barrier to adoption of bioluminescence activity imaging. We demonstrated an improved method for optimizing imaging parameters for activity imaging in vivo with bioluminescent sensors.

The Study on Timolol and Its Potential Phototoxicity Using Chemical, In Silico and In Vitro Methods.

Timolol (TIM) is a non-selective ß-adrenergic receptor antagonist used orally for the treatment of hypertension and heart attacks, and topically for treating glaucoma; lately, it has also been used in some specific dermatological problems. In the present study, its photodegradation and potential risk of phototoxicity were examined using chemical, in silico and in vitro methods. The UV/VIS irradiated solutions of TIM at pH 1-13 were subjected to LC-UV and UPLC-HRMS/MS analyses showing pseudo first-order kinetics of degradation and several degradation products. The structures of these photodegradants were elucidated by fragmentation path analysis based on high resolution (HR) fragmentation mass spectra, and then used for toxicity evaluation using OSIRIS Property Explorer and Toxtree. Potential risk of phototoxicity was also studied using chemical tests for detecting ROS under UV/VIS irradiation and in vitro tests on BALB/c 3T3 mouse fibroblasts (MTT, NRU and Live/Dead tests). TIM was shown to be potentially phototoxic because of its UV/VIS absorptive properties and generation ROS during irradiation. As was observed in the MTT and NRU tests, the co-treatment of fibroblasts with TIM and UV/VIS light inhibited cell viability, especially when concentrations of the drug were higher than 50 µg/mL.

Potential consequences of phototoxicity on cell function during live imaging of intestinal organoids.

Live imaging visualizes the structure, dynamics, and function of cells and tissues to reveal the molecular mechanisms, and has contributed to the advancement of life science. In live imaging, it has been well known that there is a trade-off between higher-resolution analysis and cell damage caused by light illumination, i.e., phototoxicity. However, despite the risk of unknowingly distorting experimental results, phototoxicity is an unresolved issue in live imaging because overall consequences occurring inside cells due to phototoxicity remains unknown. Here, we determined the molecular process of phototoxicity-induced cell damage systematically under low- and high-dose light illumination conditions by analyzing differential gene expression using RNA-sequencing in a three-dimensional organoid of small intestinal epithelial cells, enteroid. The low-dose light illumination already induced various abnormalities in functional molecules involved in the response to reactive oxygen species generated by the excitation of fluorescent dyes, intracellular metabolism, mitosis, immune responses, etc., at mRNA expression level. Together with the behavior toward apoptosis caused by high-dose light illumination, the light dose-dependent progression of intracellular damage was revealed. About visible impairment of intestinal epithelial function, failures in both the structure-forming ability of enteroids and Paneth cell granule secretion were observed under high-dose light illumination, while the drug efflux was not disturbed despite abnormal drug efflux transporter mRNA expression. Based on the gene expression profiles, we comprehensively clarified phenomena in the cells at mRNA level that cannot be recognized both morphologically and functionally during live imaging, further providing a new insight into the risk of phototoxicity. This study warns from the aspect of mRNA expression that awareness of phototoxic artifacts is needed when analyzing cellular function and the mechanism in live imaging.

Deep learning-based photodamage reduction on harmonic generation microscope at low-level optical power.

The trade-off between high-quality images and cellular health in optical bioimaging is a crucial problem. We demonstrated a deep-learning-based power-enhancement (PE) model in a harmonic generation microscope (HGM), including second harmonic generation (SHG) and third harmonic generation (THG). Our model can predict high-power HGM images from low-power images, greatly reducing the risk of phototoxicity and photodamage. Furthermore, the PE model trained only on normal skin data can also be used to predict abnormal skin data, enabling the dermatopathologist to successfully identify and label cancer cells. The PE model shows potential for in-vivo and ex-vivo HGM imaging.

Use of in silico and in vitro methods as a potential new approach methodologies (NAMs) for (photo)mutagenicity and phototoxicity risk assessment of agrochemicals

The increased use of agrochemicals raises concerns about environmental, animal, and mainly human toxicology. The development of New Approach Methodologies (NAMs) for toxicological risk assessment including new in vitro tests and in silico protocols is encouraged. Although agrochemical mutagenicity testing is well established, a complementary alternative approach may contribute to increasing reliability, with the consequent reduction of false-positive results that lead to unnecessary use of animals in follow-up in vivo testing. Additionally, it is unreasonable to underestimate the phototoxic effects of an accidental dermal exposure to agrochemicals during agricultural work or domestic application in the absence of adequate personal protection equipment, especially in terms of photomutagenicity. In this scenario, we addressed the integration of in vitro and in silico techniques as NAMs to assess the mutagenic and phototoxic potential of agrochemicals. In the present study we used the yno1 S. cerevisiae strain as a biomodel for in vitro assessment of agrochemical mutagenicity, both in the absence and in the presence of simulated sunlight. In parallel, in silico predictions were performed using a combination of expert rule-based and statistical-based models to assess gene mutations and phototoxicity. None of the tested agrochemicals showed mutagenic potential in the two proposed approaches. The Gly and 2,4D herbicides were photomutagenic in the in vitro yeast test despite the negative in silico prediction of phototoxicity. Herein, we demonstrated a novel experimental approach combining both in silico and in vitro experiments to address the complementary investigation of the phototoxicity and (photo)mutagenicity of agrochemicals. These findings shed light on the importance of investigating and reconsidering the photosafety assessment of these products, using not only photocytotoxicity assays but also photomutagenicity assays, which should be encouraged.

An "IgG-hitchhiking" approach for rapid tumor accumulation and clearance of photosensitizers.

Photodynamic therapy (PDT) has been widely used for the local treatment of a variety of cancer. To improve the therapeutic effect, delicate nanoparticles loading photosensitizers (PSs) have been designed to improve the accumulation of PSs in tumor. Different from the anti-cancer drugs for chemotherapy or immunotherapy, the delivery of PSs requires rapid tumor accumulation followed by quick elimination to reduce the potential risk of phototoxicity. However, owing to the nature of prolonged blood circulation of the nanoparticles, the conventional nanoparticulate delivery systems may decelerate the clearance of PSs. Here, we present a tumor-targeted delivery approach termed "IgG-hitchhiking" strategy through a self-assembled PSs nanostructure, according to the intrinsic binding between the photosensitizer pheophorbide A (PhA) and immunoglobulin (IgG). We utilize the intravital fluorescence microscopic imaging to uncover that the nanostructures (IgG:PhA NPs) increase the extravasation of PhA into tumor within the first hour post intravenous injection compared with free PhA, correlating with an improved efficacy of PDT. After 1 h post-injection, a quick decrease in the PhA amount in the tumor is observed, while the tumor IgG level is continuously increasing. The disparity of the tumor distribution between PhA and IgG allows the quick elimination of the PSs for minimized skin phototoxicity. Our results provide a direct evidence of the enhanced accumulation and elimination of the PSs in the tumor microenvironment through the "IgG-hitchhiking" approach. This strategy presents a promising tumor-targeted delivery approach for the PSs in lieu of the existing strategy for enhanced PDT with minimal toxicity in clinic.

Traditional analogue vs. three-dimensional digital visualization used in ophthalmic surgery

The visualization of the surgical process remains a topical issue in cataract surgery. The review presents the history of visualization technique in ophthalmic surgery and compares the main current analogue and 3D digital technologies. The advent of 3D imaging systems in clinical practice has helped solve many issues associated with the use of standard analogue microscopes. These issues include limited focus and field of vision, the need to use a large amount of light, which increases the risk of iatrogenic retinal phototoxicity, the surgeon's attachment to the microscope and, consequently, a high load on the surgeon's visual apparatus when using eyepieces, as well as on their back and neck muscles.

IVF bovine oocyte classification and selection.

The current technology for in vitro fertilization (IVF) has a long history of merely 40 years. The addition of all live births from either fresh or frozen oocytes transferred from a single oocyte collection is known as the IVF productivity rate. The ability to select the best quality eggs is the key to minimizing the number of oocytes generated, procedural cycles for potential failed attempts, and lowering cost and maximize efficiencies. The current standard for egg selection is based on defined morphological criteria. Technicians usually look for an identifiable pattern such as cytoplasm, perivitelline space, zona pellucida, size, etc. Concomitantly oocyte is also screened using genetic analysis that enhances selectivity. However, the same selection procedure is not possible for oocytes. It also has been shown that eggs with similar morphology performance might have drastically different metabolism. Here we proposed a solution where we focus on developing advanced non-invasive imaging methods to map the energy metabolism of oocytes using fluorescent lifetime imaging (FLIM). Combining multiphoton excitation, hyperspectral imaging, and machine learning approach to minimize instrumenting costs, minimize laser exposure to the bovine oocyte, and maximize predictably results for oocyte selection whether fresh or frozen. Hyperspectral imaging (HI) offers the capability of collecting intensity of autofluorescence signals from the oocytes with less laser exposure minimizing the risk of photo-toxicity. Using the phasor approach to HI enables the use of multiparametric analysis of the emission in the range of 350-500 nm range (in the range of emission of metabolic cofactors in oocytes). Complete profiling of the entire egg in three-dimensional space shows its morphological and metabolic features is then generated, showing significant differences for super-stimulation with follicle stimulating hormone, in-vitro maturation, IVF, and in-vitro culture produced oocytes.

ABCG2 Polymorphisms and Predictive Fluoroquinolone Phototoxicity in Nondomestic Felids

Fluoroquinolones are a widely used class of chemotherapeutics within veterinary medicine, prized for their broad-spectrum bactericidal activity. These drugs present a known risk of retinal phototoxicity in domestic cats (Felis catus); therefore, using lower doses and alternative antibiotic classes is encouraged in this species. This adverse drug effect of fluoroquinolones, and enrofloxacin specifically, has been determined to be species-specific in domestic felids. Four feline-specific missense variants in ABCG2 result in four amino acid changes (E159M, S279L, H283Q, and T644I) that are unique to the domestic cat compared with multiple other nonfeline mammalian species. These changes alter the ABCG2 protein involved with the cellular transmembrane transport of drugs, including fluoroquinolones, making the protein functionally defective in domestic cats. The predisposition to fluoroquinolone-mediated phototoxicity in nondomestic felids was explored in this study. At least eight nondomestic felids share the four ABCG2 missense variants with domestic cats, and eleven other felids shared at least three of the four domestic cat variants. Taken together, these results suggest the genetic potential for nondomestic felids to also experience fluoroquinolone-induced retinal phototoxicity; therefore, cautions similar to those for domestic cats should be followed for these drugs in the entire feline taxon.

A proposed NAM-based tiered phototoxicity testing and human risk assessment framework for agrochemicals

Phototoxicity testing is required by European regulations for agrochemicals with UV/visible molar extinction/absorption coefficient (MEC) higher than 10 L x mol−1 x cm−1 in the 290–700 nm wavelength range. Furthermore, regulations identify a need of considering human exposure in case of positive results. While in vitro OECD test guidelines are available for hazard characterisation, there is no guidance on how to utilise positive results in human exposure risk assessments. Our goal was to take a first step towards developing a NAM based tiered testing approach and a framework for non-dietary acute human dermal risk assessment for phototoxicity to agrochemicals. The proposed framework can be divided into a few steps: 1) use the OECD updated MEC values of 1000 L x mol−1 x cm−1 as trigger for phototoxicity testing; 2) establish a reference concentration (RfC) from in vitro phototoxicity studies using BMC approach, 3) estimate potential exposure to skin, target organ for phototoxicity, using EFSA exposure models, product specific labels and skin penetration values, and 4) phototoxicity risk assessment; 5) refinement to RfC and/or exposure estimates can be considered. Finally, case studies of a nematicide and an herbicide active substance are provided to illustrate the proposed framework.

Asymmetric, amphiphilic RGD conjugated phthalocyanine for targeted photodynamic therapy of triple negative breast cancer

Targeted photodynamic therapy (TPDT) is considered superior to conventional photodynamic therapy due to the enhanced uptake of photosensitizers by tumor cells. In this paper, an amphiphilic and asymmetric cyclo-Arg-Gly-Asp-d-Tyr-Lys(cRGDyK)-conjugated silicon phthalocyanine (RSP) was synthesized by covalently attaching the tripeptide Arg-Gly-Asp (RGD) to silicone phthalocyanine in the axial direction for TPDT of triple-negative breast cancer (TNBC). RSP was characterized by spectroscopy as a monomer in physiological buffer. Meanwhile, the modification of RSP with RGD led to a high accumulation of the photosensitizer in TNBC cells overexpressing ανβ3 integrin receptors which can bind RGD, greatly reducing the risk of phototoxicity. In vitro photodynamic experiments showed that the IC50 of RSP was 295.96 nM in the 4T1 cell line, which caused significant apoptosis of the tumor cells. The tumor inhibition rate of RSP on the orthotopic murine TNBC achieved 74%, while the untargeted photosensitizer exhibited no obvious tumor inhibition. Overall, such novel targeted silicon phthalocyanine has good potential for clinical translation due to its simple synthesis route, strong targeting, and high therapeutic efficacy for TPDT treatment of TNBC.

Enhancing Entangled Two-Photon Absorption for Picosecond Quantum Spectroscopy

Entangled two-photon absorption (ETPA) is known to create photoinduced transitions with extremely low light intensity, reducing the risk of phototoxicity compared to classical two-photon absorption. Previous works have predicted the ETPA cross-section, σe, to vary inversely with the product of entanglement time (Te) and entanglement area (Ae), i.e., σe ∼ 1/AeTe. The decreasing σe with increasing Te has limited ETPA to fs-scale Te, while ETPA applications for ps-scale spectroscopy have been unexplored. However, we show that spectral-spatial coupling, which reduces Ae as the SPDC bandwidth (σf) decreases, plays a significant role in determining σe when Te > ∼100 fs. We experimentally measured σe for zinc tetraphenylporphyrin at several σf values. For type-I ETPA, σe increases as σf decreases down to 0.1 ps-1. For type-II SPDC, σe is constant for a wide range of σf. With a theoretical analysis of the data, the maximum type-I σe would occur at σf = 0.1 ps-1 (Te = 10 ps). At this maximum, σe is 1 order of magnitude larger than fs-scale σe and 3 orders of magnitude larger than previous predictions of ps-scale σe. By utilizing this spectral-spatial coupling, narrowband type-I ETPA provides a new opportunity to increase the efficiency of measuring nonlinear optical signals and to control photochemical reactions requiring ps temporal precision.

Анализ результатов хирургического лечения макулярных разрывов методом перевернутого лоскута внутренней пограничной мембраны с применением 3D визуализации

Purpose. Analysis of results of inverted internal limiting membrane (ILM) flap technique using 3D visualization for surgical treatment of macular holes (MH). Material and methods. 21 people with stage 3 or 4 MH. Visometry and optical coherence tomography (OCT) were performed before surgery, on the 3rd day and 1 month after surgery. All patients underwent a three-port 27G vitrectomy with using NGENUITY 3D visualization system (Alcon, USA). After vitrectomy and ILM staining, the ILM flap was formed in the form of single monoblock with wide base, which was turned over and placed on the MH area. The operation was completed by fluid/air exchange. Results. MH closure on the 3rd day after surgery was observed in 19 (90.5%) of 21 patients. In 2 patients, MH closure was absent; in these cases, a second operation was performed with silicone oil tamponade. One month after the operation, according to OCT datas, complete MH closure was noted in all patients. The average value of the best corrected visual acuity by this observation period was 0.3, which was 6 times higher than the initial (0.05) visual acuity. The use of 3D visualization system allowed us to reduce the level of endoillumination by up to 15% and to reduce the exposure time of the endovitreal dye to 15 seconds to reduce the risks of retinal phototoxicity. Conclusion. The proposed inverted ILM flap technique made it possible to achieve MH closure in 90.5% of cases. The experience of using NGENUITY 3D visualization system has shown high efficiency and safety by reducing the risk of iatrogenic phototoxicity. Key words: macular hole, inverted flap, internal limiting membrane, 3D visualization, NGENUITY.

An approach to evaluate metabolite-related phototoxicity with combined use of photochemical properties and skin deposition

Some chemicals have been reported to cause metabolite-related phototoxicity, and this study aimed to verify the applicability of photosafety assessment based on photochemical and pharmacokinetic properties to evaluate the metabolite-related phototoxicity risk. The phototoxic risk of imipramine (IMI) and its metabolite, desipramine (DMI), was evaluated by photochemical and pharmacokinetic analyses. IMI and DMI were found to have similar photoreactivities based on the generation of reactive oxygen species. The skin concentrations of IMI and DMI reached maximal levels at approximately 1 and 4 h, respectively, after oral administration of IMI (10 mg/kg), and DMI showed high skin deposition compared with IMI. According to the results, DMI was identified as a contributor to phototoxicity induced by orally-taken IMI. In in vivo phototoxicity testing, ultraviolet A irradiation from 3 to 6 h after oral administration of IMI (100 mg/kg) caused more potent phototoxic reactions compared with that from 0 to 3 h, and DMI yielded by metabolism of IMI would be associated with phototoxic reactions caused by orally-administered IMI. In addition to the data on IMI, a parent chemical, photochemical and pharmacokinetic profiling of its metabolite, DMI, led to reliable phototoxicity prediction of orally-administered IMI. Thus, characterization of the photosafety of metabolites would generate reliable information on the phototoxicity risk of parent chemicals, and the proposed strategy may facilitate comprehensive photosafety assessment of drug candidates in pharmaceutical development.

Lux study: Contribution of a three-dimensional, high dynamic range, ultra-high-definition heads-up visualization system to a significant delivered light intensity decrease during different types of ocular surgeries

To explore the hypothesis that using a large, three-dimensional (3D), ultra-high-definition (4K), heads-up display (HUD) system in a real-life setting may be associated with a significant reduction in light intensity (LI) delivered during various types of eye surgery. Single center, post-learning curve observational study of 142 independent consecutive cases: 73 cataracts and 69 vitrectomies (VR). For each group, the only variable setting was the LI. The LI delivered by each source was calibrated in lumens (lm). In the VR group, the delivered LI dramatically decreased from the 80% reference to 27.8%±13.2% (P<0.0001) (4.3 to 1.5lm). Among these surgeries, 91.3% needed 40% or less LI (2.3lm). The corneal transparency and quality of pupil dilation showed some correlation with the results. In the cataract group, the difference was even more spectacular, from 80% to 15%±11.3% (P<0.0001) (2.5 to 0.3lm). Among these surgeries, 80.8% required less than 20% LI (0.5lm). The surgical time, LI variations and type of cataract seemed to influence the results, down to 9.6%±5.4% (P<0.0001) (0.22lm) for nuclear cataracts, which represented 63% of the cataract sample. The digital signal amplification with this HUD system allows comfortable posterior as well as anterior segment surgery despite the decrease in incident light, suggesting an unprecedented reduction in the risk of phototoxicity compared to conventional systems as well as a likely improvement in patient comfort.

Tetracyclines and photosensitive skin reactions: A narrative review.

Tetracyclines are a group of broad‐spectrum antibiotics largely employed in infectious, dermatological and surgical fields. Some adverse events may occur during treatment, including photosensitivity reactions, which are divided in phototoxic or photoallergic. We performed a systematic search on Pubmed, Cochrane and Embase from database inception to August 9, 2020 aim to summarize all available papers on photosensitive reactions related to tetracyclines in all clinical settings where they are used on human being. On the basis of our inclusion criteria, we selected only randomized controlled trials, open comparative trials and prospective cohort studies performed on both volunteers and patients, moreover we included a pharmacovigilance register. Thirty‐eight articles met inclusion criteria, describing photo‐sensitive effects due to doxycycline, minocycline, tetracycline, lymecycline, sarecycline, demethylchlortetracycline, chlortetracycline and metacycline, across six diagnoses (acne, Lyme disease, Gulf Veteran Illness, adbominal aortic aneurysms, traveler's diarrhea and pterygium) and several volunteers who were deliberately exposed to natural or artificial light sources. Not all drugs belonging to tetracyclines class are available to date, moreover the studies included lacked a homogeneous design and most of them involved a scarce number of patients, including reactions induced in volunteers during photo‐testing. Available data on incidence, severity and clinical relevance of tetracyclines‐related photo‐sensitive reactions are scarce, heterogeneous and weak. What we can extrapolate is that some tetracyclines are more often related to phototoxic skin reactions than others and some of those seem to have a very low risk of phototoxicity.

3D Imaging Restoration of Spinning-Disk Confocal Microscopy Via Deep Learning

Due to the multipoint excitation and simultaneous detection strategy applied, spinning-disk confocal microscopy (SDCM) results in an increased imaging speed compared to conventional confocal microscopy. Additionally, the super-resolution radial fluctuations (SRRF) approach can further improve the imaging resolution of SDCM in 3D imaging at the cost of imaging time due to the large amounts of data acquisition and the increased risk of photo-bleaching and photo-toxicity due to the multiple excitations. Here, we propose a deep learning-based method for 3D SDCM, where the neighboring pixels in $z$ -scanning slices are taken into account for 3D reconstruction. Consequently, high-quality imaging slices can be reconstructed directly from the SDCM stacks with a single scan. The image quality achievable with this SRRF-Deep method is comparable with the SRRF method, whereas it achieves image reconstruction about 30 times faster using 100 times fewer images. Thus, practicality of the SDCM system can be significantly improved in 3D imaging.

Photodegradation of the H1 Antihistaminic Topical Drugs Emedastine, Epinastine, and Ketotifen and ROS Tests for Estimations of Their Potent Phototoxicity.

In this study, important H1 antihistaminic drugs, i.e., emedastine (EME), epinastine (EPI), and ketotifen (KET), were irradiated with UV/Vis light (300–800 nm) in solutions of different pH values. Next, they were analyzed by new high performance liquid chromatography (HPLC) methods, in order to estimate the percentage of degradation and respective kinetics. Subsequently, ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) was used to identify their photodegradation products and to propose degradation pathways. In addition, the peroxidation of linoleic acid and generation of singlet oxygen (SO) and superoxide anion (SA) were examined, together with the molar extinction coefficient (MEC) evaluation, to estimate their phototoxic risk. The photodegradation of all EME, EPI, and KET followed pseudo first-order kinetics. At pH values of 7.0 and 10.0, EPI was shown to be rather stable. However, its photostability was lower at pH 3.0. EME was shown to be photolabile in the whole range of pH values. In turn, KET was shown to be moderately labile at pH 3.0 and 7.0. However, it degraded completely in the buffer of pH 10.0. As a result, several photodegradation products were separated and identified using the UPLC-MS/MS method. Finally, our ROS assays showed a potent phototoxic risk in the following drug order: EPI < EME < KET. All of these results may be helpful for manufacturing, storing, and applying these substantial drugs, especially in their ocular formulations.