Cutaneous and Ocular Toxicology最新文献

Purpose: To investigate the toxicity of repeated simultaneous intrastromal and intracameral injections of voriconazole in corneal endothelial cells in a rabbit model.

Methods: Thirty-six eyes of 18 New Zealand white rabbits (six eyes per group) were divided into 6 groups according to the concentration of voriconazole (Group A, 0%; Group B, 0.05%; Group C, 0.1%; Group D, 0.25%; Group E, 0.5%; Group F, 1%). A combination of intrastromal and intracameral voriconazole injections were administrated to the eyes of each group three times on days 0, 3, and 7. Corneal clouding grades and central corneal thickness (CCT) were examined on days 0, 3, 7, 10, and 14. The endothelial cell counts (ECC) were measured on days 0 and 14. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were performed on day 14.

Results: Group F (1%) showed more severe corneal clouding than the other groups (Groups A-E) from day 7 (p < 0.05, respectively). There were no significant differences in CCT and ECC among the six groups at any time point (p > 0.05, respectively). SEM revealed blurring of the cell border and loss of microvilli at concentrations ≥0.25% (Groups D-F). TEM revealed microstructural changes in endothelial cells at concentrations ≥0.1% (Groups C-F), and multiple vacuoles were observed at a concentration of 1% voriconazole (Group F).

Conclusions: Repeated simultaneous intrastromal and intracameral voriconazole injections at a concentration of 0.1% or higher induced microstructural endothelial damage in rabbit corneal endothelial cells.

Purpose: This study aimed to investigate the effect of sodium fluorescein on the choroidal vascularity index (CVI).

Materials and methods: In this cross-sectional study, a total of 27 eyes of 27 mild nonproliferative diabetic retinopathy patients (without maculopathy and any systemic disease) who performed fluorescein angiography (FA) procedure were included. Choroidal parameters such as choroidal thickness (CT), total choroidal area (TCA), luminal area (LA), stromal area (SA), LA/SA, and CVI were examined with the optical coherence tomography and binarization technique at baseline and 5th, 15th, and 30th minutes after FA. The values of the parameters before and after the procedure were compared.

Results: At baseline, the mean values of the TCA, LA, SA, LA/SA, and CVI were 0.44 ± 0.14mm2, 0.29 ± 0.09 mm2, 0.15 ± 0.05 mm2, 1.87 ± 0.19. Five minutes later to FA, the mean values of the TCA, LA, SA, LA/SA, and CVI were 0.43 ± 0.13 mm2, 0.28 ± 0.08 mm2, 0.15 ± 0.05 mm2, 1.82 ± 0.20, and 0.64 ± 0.03, respectively. There was a significant decrease in LA and CVI values 5 minutes after FA (p:0.002 and p:0.021, respectively). On the other hand, the mean, nasal, subfoveal, and temporal CT were 279.22 ± 93.40 μm, 289.78 ± 91.17 μm, 267.44 ± 95.71 μm before FA and 270.33 ± 90.34 μm, 279.67 ± 90.01 μm, 261.82 ± 95.82 μm 5 minutes after FA (p = 0.960, p = 0.952, and p = 0.991, respectively). Although there was a reduction in the value of CT, there was not a statistically significant difference between before and after FA.

Conclusions: This study shows that there was a significant decrease in LA and CVI values 5 minutes after FA in patients with mild nonproliferative diabetic retinopathy.

Numerous adverse effects on human health have been reported in epidemiological studies of oleoresin capsicum (OC) and other riot control agents (RCAs). Importantly, the daunting risk of such RCAs can be neutralized by optimizing the desired concentration of such agents for mob dispersal. Hence, a nonlethal riot control combinational formulation (NCF) was prepared for dispersing rioters without imparting fatal outcomes. However, for desired utilization of NCF, it is essential to recognize its extent of potential toxicity. Therefore, the current investigation evaluated the dermal toxicity of NCF using experimental animals in compliance with the OECD guidelines. Additionally, few essential metal ions were analyzed and found non -significantly different in the test rats as compared to control rats. Moreover, abnormal dermal morphology and lesions ultrastructural tissue defects were not noticed as evinced by different studies like ultrasonography, histology, and scanning electron microscopy (SEM) respectively. Further, Doppler ultrasonography exhibited non-significantly different blood flow velocity in both groups, whereas miles test demonstrated a significantly increased Evans blue concentration in test rats compared to the control rats, which might be due to an initial increase in blood flow via an instant action of the NCF at the cutaneous sensory nerve endings. However, our results demonstrated NCF can produce initial skin irritating and sensitizing effects in guinea pigs and rabbits without the antecedence of acute toxicity (≤2000 mg/kg) in Wistar rats.

Purpose: Riot control agents (RCAs) such as CS, CN, CR, PAVA, and OC, etc., are already in use and has produced numerous health risks, including skin burns, dermatitis, gastrointestinal issues, impairment of respiratory variables, conjunctivitis, etc., and even prolonged and repeated exposure may cause death. Therefore, there is a demand and need for non-lethal, non-toxic RCAs that can effectively control riots without resulting in fatal outcomes. This study was carried out to evaluate the health risks related to a novel formulation made from isolated Tragia involucrata leaf hair lining, that can be used as the best suitable non-lethal RCAs.Methods: According to the OECD guidelines, studies on acute dermal toxicity, dermal irritation/corrosion, and skin sensitisation were carried out. Wistar rats were used in an acute dermal toxicity study, and the results indicated no mortality, morbidity, or abnormal food-and-water intake, biochemical parameters, or histopathological examination findings. A study on dermal irritation in Rabbits produced moderate erythema and the effect was instantaneous and resolved within 72 hrs of post-exposure. A skin sensitisation test was conducted on Guinea pig.Results: The results showed that the formulation had moderate skin-sensitizing properties after the application of the challenge dose. Patchy erythema was seen, and it went away 30 hrs after the gauze patch was removed.Conclusion: The preclinical results did not produce any indication of severe toxicity which supports it to be used as a natural RCAs in the future.

Purpose: To investigate the effect of oral isotretinoin therapy on central macular thickness (CMT) thickness and choroidal thickness (CT) using optical coherence tomography (OCT).

Methods: CT and CMT thickness of 43 eyes were evaluated at baseline, the third, and sixth month of isotretinoin therapy by spectral-domain OCT. For assessment of CT, OCT measurements were obtained at the fovea with six additional measurements at adjacent locations (at 500-1000 µm temporal to the fovea and 500-1000 µm nasal to the fovea).

Results: Forty-three eyes from 43 patients with acne vulgaris, including 33 females (76.7%), who had a mean age of 24.81 ± 6.60 years, completed the study. The mean CMT was 231.49 ± 19.52 at the baseline and significantly decreased to 229.0 ± 19.57 (p = 0.02) and 229.28 ± 18.83 after three and six months, respectively (p < 0.03). The change in the macular thicknesses measured at four quadrants and choroidal thicknesses were not statistically significant during the study (p > 0.05).

Conclusion: The result of our study demonstrated choroidal thickness change is not significant in patients with acne vulgaris after systemic isotretinoin therapy during six months of follow-up. The decreased CMT amount was 2.2 microns; even if statistically significant, this amount is clinically insignificant.

Objective: This study aims to investigate possible preventive effect of ATP on optic nerve damage caused by amiodarone in rats.

Material and method: Thirty albino male Wistar rats weighing between 265 and 278 g were used in the study. Before the experiment, the rats were housed at 22 °C in a 12-h light/dark cycle under appropriate condition. The rats were equally divided into five groups of six animals each: healthy group, 50 mg/kg amiodarone (AMD-50), 100 mg/kg amiodarone (AMD-100), 25 mg/kg ATP + 50 mg/kg amiodarone (ATAD-50), and 25 mg/kg ATP + 100 mg/kg amiodarone (ATAD-100). At the end of 14th day, the animals were sacrificed using cardiac puncture under deep thiopental anaesthesia, and optic nerve tissues were harvested to measure superoxide dismutase (SOD), total glutathione (tGSH), malondialdehyde (MDA), and catalase (CAT) levels.

Results: The MDA levels were found to be significantly higher in the AMD-50 and AMD-100 groups compared to the healthy group (p ˂ 0.001). There was also a significant difference between the AMD-50 and ATAD-50 groups, and between the AMD-100 and ATAD-100 groups regarding MDA levels (p ˂ 0.001). tGSH, SOD, and CAT levels were significantly lower in the AMD-50 and AMD-100 groups compared to the healthy group (p ˂ 0.001). ATP was found to partially inhibit amiodarone-induced optic neuropathy.

Conclusion: The biochemical and histopathological results of this study demonstrated that amiodarone at high doses caused more severe optic neuropathy inducing oxidative damage, but ATP could relatively antagonise these negative effects on the optic nerve. Therefore, we believe that ATP may be beneficial in preventing amiodarone-induced optic neuropathy.

Purpose: The complement system is considered to play an important role in the progression of myopia, whereas the influence of complement activation on the human scleral fibroblasts (HSFs) remains unknown. Hence, the effect of complement 3a (C3a) on HSFs was investigated in this study.

Methods: HSFs were cultured with exogenous C3a at 0.1 μM for various periods following different measurement protocols, and cells without C3a treatment served as negative control (NC). Cell viability was investigated using the MTS assay after 3 days of C3a treatment. Cell proliferation was evaluated by the 5-Ethynyl-20-Deoxyuridine (EdU) assay following C3a stimulation for 24 hours. Apoptosis was assessed by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining following C3a stimulation for 48 hours and the stained cells were analysed using flow cytometry. The levels of type I collagen and matrix metalloproteinase-2 (MMP-2) were analysed using ELISA following C3a stimulation for 36 and 60 hours. The level of CD59 were analysed using western blot following C3a stimulation for 60 hours.

Results: The MTS assay revealed that cell viability was attenuated by 13% and 8% after C3a for 2 and 3 days, respectively (P < 0.05). The EdU assay demonstrated a 9% decrease in proliferation rate for the C3a-treated cells after 24 hours (P < 0.05). The apoptosis analysis revealed an increased percentage of cells in early apoptosis (P = 0.02) and total apoptosis (P = 0.02) in the C3a-treated group. Compared with NC group, the level of MMP-2 was increased by 17.6% (P = 0.002), whereas the levels of type I collagen and CD59 were respectively decreased by 12.5% (P = 0.024) and 21.6% (P = 0.044) with C3a treatment for 60 hours.

Conclusions: These results indicated that C3a-induced complement activation is potentially involved in inducing myopic-associated scleral extracellular matrix remodelling via mediating the proliferation and function of HSFs.

Purpose: Acne vulgaris is a very prevalent dermatological condition, especially among adolescents and young adults up to 25 years old, classifying it as juvenile acne. One of the most effective treatments for severe acne is isotretinoin, a derivative of retinoic acid. Despite its high efficacy, this drug has been linked to several side effects including psychiatric adverse alterations, such as anxiety, depression and even suicide. With this systematic review we aim to determine if it is possible to establish a causal relation between oral isotretinoin in the treatment of juvenile acne and the appearance of psychiatric adverse effects.

Materials and methods: We searched two distinct databases, PubMed and Web of Science, and considered the work published between January 2000 and November 2021.

Results: Out of the 599 identified articles, we included 19 studies in this systematic review. Globally, the results we found do not support an association between the use of isotretinoin for acne treatment and mental side effects and the safety of this drug appears to be assured. However, the individual characteristics of each adolescent and their environment should be considered; the personal and family history of mental disorders are pointed out as red flags we should look out for when treating these patients.

Conclusion: Despite this being a highly debated topic, especially among the dermatology community, more studies with larger populations and randomised controlled trials are necessary to increase the strength of the evidence presented.

Purpose: The study aimed to investigate the electrophysiological effects of hyperbaric oxygen treatment (HBOT) on the retina after ten sessions in healthy eyes.

Methods: This prospective, interventional study evaluated forty eyes of twenty patients who were treated with HBOT of ten sessions with the diagnosis of an extraocular health problem. All patients underwent a complete ophthalmologic examination, including assessments of best-corrected visual acuity (BCVA), slit-lamp and pupil-dilated fundus examinations, full-field electroretinography (ffERG) measurements before and after HBOT within 24 h of the 10th session. The ffERG was recorded according to the International Society for Clinical Electrophysiology of Vision protocol using the RETI-port system.

Results: The mean age of patients was 40.5 years ranging from 20 to 59 years. Thirteen patients were administered HBOT for avascular necrosis, six patients for sudden hearing loss, and one patient for chronic osteomyelitis of the vertebra. BCVA acuity was 20/20 in all eyes. The mean spherical refractive was 0.56 dioptre (D), and the mean cylindrical refractive error was 0.75 D. Dark-adapted b-wave amplitude in 3.0 ERG was the only variable for the b-wave that showed a statistically significant decrease (p = 0.017). The amplitude of the a-waves in dark-adapted 10.0 ERG and light-adapted 3.0 ERG reduced significantly (p = 0.024, p = 0.025). The amplitude of N 1-P 1 in light-adapted 30 Hz Flicker ERG also demonstrated a statistically significant decrease (p = 0.011). Implicit times did not differ significantly in any of the ffERG data (p > 0.05).

Conclusions: HBOT caused the deterioration of a-wave and b-wave amplitudes in ffERG after ten treatment sessions. The results showed that photoreceptors were adversely affected in the short term after HBOT treatment.

Purpose: To evaluate the vascular structure of the choroid and each retinal layer in patients with breast cancer on tamoxifen therapy and compare them with healthy subjects.

Materials and methods: 124 eyes of 62 patients with breast cancer who were on tamoxifen therapy (group 1) and 80 eyes of 40 healthy controls (group 2) were included in this prospective cohort study. The structure of the choroid was evaluated using enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT) and choroidal binarisation. Spectral-domain OCT (SD-OCT) was performed to analyse the peripapillary nerve fibre layer thickness (pRNFL) and each retinal layer thickness. A subgroup analysis was performed based on chemotherapy history in Group 1. All parameters were compared between Group 1 and the healthy controls and between the subgroups of Group 1.

Results: The subfoveal choroidal thickness and temporal and nasal directions were increased in Group 1 when compared with Group 2 (p < 0.05, each comparison). Choroidal vascularity index was significantly decreased in Group 1 compared with Group 2 (63.15 ± 3.11% and 65.37 ± 4.63%, p < 0.001). There were no significant differences in each retinal layer, pRNFL thickness, and choroid structural parameters between the subgroups of Group 1.

Conclusions: Increased choroidal thickness may be the initial finding of subclinical tamoxifen-induced retinopathy. Patients with breast cancer undergoing tamoxifen therapy may be screened prior to tamoxifen therapy and followed during treatment by SD-OCT.