Cutaneous and Ocular Toxicology最新文献

Purpose: To examine effects of topical antiglaucoma drops on ocular surface (OS)and meibomian glands(MG) in relation to drug type, number of drugs and drug intensity.

Methods: This was a cross-sectional case study of 93 patients with glaucoma treated with topical anti-glaucoma drugs for more than 1 year. According to drug type we formed two groups; Group 1: Prostaglandin containing drops(monotherapy and combination therapy), Group 2:Non -PGA therapy.According to drug number, we formed three groups; Group 1:One active drug compound, Group 2: Two active drug compounds, Group 3:Three or more active drug compounds.We formed 2 groups accrding to drug intensity index (DII); Group 1: DII was < 50, Group 2: DII ≥ 50.Conjonctival hyperemia, ocular surface staining, tear break-up time (TBUT), and eyelid signs representing meibomian gland disease (eyelid vascularity, irregularity, nature of meibum and the Marx line score) have been compared between groups.

Results: Prostaglandin containing drops group showed significantly worse results in comparison of TBUT, conjonctival hyperemia, ocular surface staining, lid margin vascularity, meibum quality, and Marx line score.Çonjonctival hyperemia, and lid margin vascularity were observed to be significantly higher in those using eye drops containing two or more active compounds.When the DII is increased only lid margin irregularity, and meibum quality are getting worse, significantly.

Conclusion: Our results showed that the main factor contrubuting to OSD and MGD were prostaglandin analog therapy as a drug type. Management of ocular surface disease in glaucomatous patients is important when trying to reduce further ocular morbidity.

Purpose: The aim of this study is to evaluate the therapeutic potential of systemic glatiramer acetate (GA), a drug used in the treatment of multiple sclerosis (MS), in an imiquimod-induced psoriasis mouse model, given the common immunopathogenic mechanisms between the two diseases.

Materials and methods: Fifty-four adult female BALB/c mice (16-18 weeks old) were divided into nine groups (6 mice each). A psoriasis-like model was induced in eight groups by application of 5% imiquimod cream for seven days. Systemic treatments included methotrexate (2 mg/kg/week), saline (1 mL/kg/day) and GA at doses ranging from 50 to 100 mcg, administered subcutaneously either during or after the induction phase. Clinical severity was assessed using the modified Psoriasis Area and Severity Index (mPASI), while histopathological and immunohistochemical analyses were performed to assess inflammation and cytokine expression, focusing on TNF-α, IL-1β and IL-17.

Results: The highest mPASI scores were observed in the untreated psoriasis group, whereas the healthy control and mice treated with 50 mcg GA, especially after induction, showed the lowest scores. Statistically significant improvements in histopathological scores were observed (p < 0.05). GA treatment at 50 mcg resulted in the most favourable cytokine profile, with TNF-α and IL-17 levels comparable to the healthy group and a similar trend observed for IL-1β expression.

Conclusions: Among the doses tested, 50 mcg GA administered after model induction was the most effective in reducing clinical severity and inflammatory cytokine expression. These findings suggest that GA is a promising systemic therapeutic agent for psoriasis.

Introduction: This study explores the wound healing potential of Chitligsan (CHG), a novel formulation derived from the enzymatic and fossil-based components of Sahara soil, in nanosuspension-based gel and spray forms. Using a full-thickness wound model in Wistar rats, CHG's efficacy was compared with saline (control) and terramycin treatments.

Methods: A total of 48 rats were divided into four groups: Control (saline), Spray (CHG spray), Gel (CHG gel), and Terramycin pomad. Wound areas were measured at days 3, 7, 14, and 21.

Results: By day 21, CHG spray reduced wound size to 0.08 ± 0.01 cm², while the gel achieved 0.09 ± 0.01 cm², outperforming both control (0.34 ± 0.02 cm²) and terramycin (0.14 ± 0.05 cm², p < 0.05). Histopathological analysis demonstrated superior epithelial regeneration, dense collagenization, and minimal inflammation in CHG-treated groups compared to others. The nanoscale size of CHG particles (89.6 ± 0.26 nm) and their stable zeta potential (-26.1 ± 1.5 mV) contributed to enhanced bioavailability and wound healing efficiency. Morphological and FTIR analyses confirmed the stability and compatibility of the nanosuspension.

Conclusions: This study highlights CHG's potential as a biocompatible and effective wound care solution, offering significant advantages in granulation tissue formation and keratinization compared to conventional treatments.

Purpose: With the increasing use of diode lasers emitting in the visible light spectrum, concerns about their potential to dazzle and cause eye damage have grown. This study aims to determine the maximum safe exposure levels and evaluate the retinal damage and dazzling effects caused by red, green, blue, and synthetic white lasers.

Materials and methods: A chinchilla grey rabbit model was used for experimentation. Lasers with wavelengths of 635 nm (red), 520 nm (green), and 456 nm (blue), along with their combined output as synthetic white light, were directed at the rabbits' eyes for 0.2 s. Retinal damage was assessed using a fundus camera at 1 h and 24 h post-irradiation. Histological analysis was conducted to evaluate tissue changes. The dazzling effect was measured by recording the b-wave recovery time in the electroretinogram 0.1 s after laser exposure.

Results: The maximum safe power density levels for red, green, blue, and synthetic white lasers were found to be 140, 60, 35, and 55 mJ/cm², respectively. Exposures exceeding these thresholds resulted in visible retinal damage, including white-coagulated spots, hemorrhages, and corresponding histopathological changes. At an exposure level of 12.0 mJ/cm², the b-wave recovery times for green, blue, and synthetic white light were 9.0, 8.0, and 7.8 s, respectively, while no dazzling effect was observed with the red laser.

Conclusions: The synthetic white light laser exhibited slightly inferior safety compared to the green laser but was significantly safer than the blue laser, with fewer dazzling effects. These findings provide valuable insights for the safe use of visible light lasers.

Purpose: This study aimed to biochemically and histopathologically evaluate the protective and therapeutic effects of elamipretide and methylprednisolone on methanol poisoning-induced brain, optic nerve, and retinal toxicity.

Method: In this study, 40 male Wistar Albino rats were divided into six groups: healthy control (HC), methotrexate (MTX, 0.3 mg/kg/d for 7 d), methotrexate + methanol (MTX-M, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8), methotrexate + methanol + methylprednisolone (MTX-M-MPZ, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + MPZ 1 mg/kg/d for 3 d), methotrexate + methanol + elamipretide (MTX-M-E, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + elamipretide 5 mg/kg/d for 3 d), and methotrexate + methanol + methylprednisolone + elamipretide (MTX-M-MPZ-E, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + MPZ 1 mg/kg/d + Elamipretide 5 mg/kg/d for 3 d). The rats were euthanized 8 h after the last drug administration. Histopathological and biochemical evaluations were performed on serum, caudatoputamen, and ocular tissues. Retinal degeneration was assessed using a scoring system where higher scores indicate less degeneration, with a score of 5 representing normal structure and 1 reflecting severe degeneration.

Results: In the MTX-M-MPZ-E group, the retinal degeneration score was higher than in MTX-M group (p = 0.002). The apoptosis index in the retina was highest in MTX-M group, while it was lower in MTX-M-MPZ-E group compared to MTX-M group (p = 0.018). In addition, the apoptosis index in the caudatoputamen was lower in MTX-M-MPZ-E group compared to MTX-M group (p = 0.009).

Conclusion: Combined elamipretide and methylprednisolone treatment improved optic nerve and retinal degeneration, reduced neuronal degeneration in the caudatoputamen, decreased oxidative stress and lipid peroxidation, and reduced apoptosis in the retina and caudatoputamen.

Introduction/objective: Anti-VEGF (Vascular endothelial growth factor) agents have revolutionized ophthalmotherapy and are vital for various retinal disease treatment in ophthalmic practice. Ophthalmology has witnessed an explosion in the number of intravitreal injections delivered to patients over the past years. The rising popularity of anti-VEGF drugs came along with concerns about its safety in clinical use. The aim of this focused review is to critically analyze currently available findings on systemic safety.

Materials and methods: A literature search was conducted using PubMed, Web of Science, and Google Scholar databases for studies published from January 2012 to February 2025. The reference lists of meta-analyses and selected studies were also reviewed. Eighty four articles of high or medium clinical relevance were selected for review. The exclusion criteria included non-English language publications, articles directly unrelated to the review topic, commentaries, conference abstracts.

Results: Systemic safety concern in intraocular pharmacotherapy by antiangiogenic agents has a strong body of clinical evidence, resulting in plenty of peer reviewed clinical articles. It is certainly becoming recognized that anti-VEGF agents, despite given intraocularly, have the potential to cause systemic adverse events, such as cardiovascular, renal, neurological.

Conclusions: Accumulating evidence obviate the need to raise medical professionals' awareness about systemic risk profile in patients with eye diseases treated by anti-VEGF, paying a special attention on patients with diabetes and older patients with multimorbidity. Early identification and prompt management of patients with undesirable systemic side effects secondary to intraocular pharmacotherapy by angiogenics can lessen disease severity, and help achieve earlier resolution.

Objectives: This study was to investigate the effects of atropine sulphate eye drops (ASED)on the development of partial systems in young rats and their toxic reactions following repeated eye-drop administration over a period of 40 days.

Methods: SD rats of 20 days old were randomly assigned to control group, 0.01, 0.02, and 0.04% ASED groups, with 60 females and 25 males per group. ASED was given by eye drops from PND₂₁ onwards and normal saline was given in the control group at 10 μL/eye once a day for 40 days, in both right and left eyes. Rats of ASED groups were instilled with eye drops at the 10 μL/day per eye, from postnatal day 21 (PND₂₁) to PND₆₀ for 40 consecutive days. The clinical observation, body weight, food intake, physical development, physiological development, reproductive development, ophthalmic examination, intraocular pressure, and axial length of the rats were examined during the study period.

Results: ASED at concentrations of 0.01, 0.02, 0.04%, dose levels of 0.002, 0.004, 0.008 mg/day per rat, had no toxicological effects on the clinical observation, body weight, food intake, physical development, physiological development, reproductive development, ophthalmic examination, intraocular pressure, and axial length in rats.

Conclusion: The no-observed-adverse-effect-level (NOAEL) of ASED in young SD rats equivalent to human over 2 years old was 0.008 mg/day at a concentration of 0.4 mg/mL.

Purpose: To assess changes in the thickness of macular sublayers in individuals taking hydroxychloroquine (HCQ) without any evident toxicity and to review the relevant literature.

Methods: This prospective case-control study examined 47 adults on HCQ without evident toxicity on spectral-domain optical coherence tomography (SD-OCT) and visual field tests, as well as 25 healthy controls. Macular thickness in different sublayers was measured using SD-OCT. The thickness of combination layers and the variability of sublayers were also recorded. Data were compared between the case and control groups, and the correlation between cumulative HCQ use and outcome measures was analysed.

Results: The average age of participants in the case and control groups was 45.6 ± 9.3 and 46.8 ± 11.7 years, respectively (p = 0.831). The percentage of female participants was 91.5% in the case group and 84.0% in the control group (p = 0.927). In the case group, the average duration of HCQ use was 5.1 ± 5.2 years, with a mean cumulative dose of 301 ± 365 g. No significant differences were found in the visual field mean deviation or pattern standard deviation between patients with HCQ use of <5-years vs. ≥5-years. Additionally, there were no statistically significant differences in various retinal thickness measurements between the case and control groups. However, a significant association was observed between the cumulative dose of HCQ and the thickness of the outer retinal layer (ORL) in both the outer (r = 0.344; p = 0.032) and inner Early Treatment Diabetic Retinopathy Study (ETDRS) macular rings (r = 0.303; p = 0.061).

Conclusions: No significant difference in macular sublayer thickness was found between patients taking HCQ without evident toxicity and the control group. A weak direct association was observed between the cumulative dose of HCQ and the ORL thickness. These findings suggest that analysing macular sublayer thickness may not be useful in detecting the earliest signs of presumed HCQ toxicity in individuals without classical sign of toxicity on qualitative SD-OCT or visual field test.

The utilisation of heavy metal-based nanoparticles in cosmetic products has been steadily increasing because of their extraordinary physicochemical properties and benefits. In this thorough review, we will delve into the various types of nanoparticles, such as green nanoparticles, metallic nanoparticles, and carbon-based nanoparticles, with a special focus on heavy metal-based nanoparticles. These heavy metal-based nanoparticles exhibit exceptional physical and mechanical properties, making them suitable materials for cosmetic and personal care products. Silver nanoparticles effectively treat acne and have strong antimicrobial properties, while gold nanoparticles have anti-ageing and anti-inflammatory properties. ZnO and TiO2 nanoparticles are commonly used in sunscreens as ultraviolet (UV) filters to protect against ultraviolet-A (UVA) and ultraviolet-B (UVB) radiation. Certain metals like nickel, chromium, and cobalt are major allergens, frequently causing contact dermatitis and allergic reactions in sensitive individuals. Extensive use of materials such as cadmium, lead, mercury, and arsenic (metalloid) in cosmetics poses long-term health risks, including carcinogenicity, neurotoxicity, and organ damage. The utilisation of herbal extracts containing heavy metals in cosmetics further improves the effectiveness of personal care products due to their antioxidant properties. Consumer awareness and regulatory concerns, especially among those with metal allergies, are crucial for understanding the potential risks associated with heavy metal-containing cosmetics. Looking ahead, future research efforts should concentrate on the development of safer, non-toxic, natural nanomaterials and biocompatible alternatives to heavy metal-based nanoparticles.

Objective: To determine the predictive factors for severity in prostaglandin-associated periorbitopathy (PAP) using an objective grading system.

Methods: The study included patients diagnosed with glaucoma or ocular hypertension who had used a topical prostaglandin analog (PGA) unilaterally for at least three months. Clinical characteristics and PAP signs were compared based on the types of PGAs used. The severity of PAP signs was categorised according to an objective grading system. Univariate and multivariate logistic regression analyses were performed to identify risk factors for different grades of PAP.

Results: Among the 86 patients included in the study, 24 (27.9%) used bimatoprost, 35 (40.7%) used latanoprost, and 27 (31.4%) used travoprost. The most commonly observed feature of PAP was orbital fat atrophy (48.8%), followed by deepening of the upper eyelid sulcus (38.4%), involution of dermatochalasis (32.6%), and enophthalmos (26.7%). Fifty-eight patients (67.4%) exhibited at least one periorbital change associated with PGA use. Multivariate logistic regression analysis revealed that age >60 years (p < 0.05), the use of bimatoprost (p < 0.05) and travoprost (p < 0.05), and PGA therapy duration >1 year (p < 0.05) were independent risk factors for higher grades of PAP.

Conclusion: Older age, longer duration of PGA therapy, and the use of bimatoprost and travoprost were significant and independent predictors of severe PAP in patients with glaucoma. Patients with these risk factors should be identified and managed to prevent the development of severe PAP.