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.
{"title":"Juvenile toxicity of atropine sulfate eye drops in young rats.","authors":"Wenqiang Zhang, Wei Yang, Lu Liu, Jinlong Dai, Linyi Wang, Yuankeng Huang, Xialing Lei, Junli Lin, Fafu Zhang, Jianmin Guo","doi":"10.1080/15569527.2024.2432507","DOIUrl":"10.1080/15569527.2024.2432507","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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 PND<sub>21</sub> 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 (PND<sub>21</sub>) to PND<sub>60</sub> 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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"43-49"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2024-12-16DOI: 10.1080/15569527.2024.2438629
Mohsen Farvardin, Payam Peiravian, Mahdi Ravankhah, M Hossein Nowroozzadeh
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.
{"title":"Evaluation of changes in thickness of macular sublayers in patients using Hydroxychloroquine: a cross sectional case-control study and literature review.","authors":"Mohsen Farvardin, Payam Peiravian, Mahdi Ravankhah, M Hossein Nowroozzadeh","doi":"10.1080/15569527.2024.2438629","DOIUrl":"10.1080/15569527.2024.2438629","url":null,"abstract":"<p><strong>Purpose: </strong>To assess changes in the thickness of macular sublayers in individuals taking hydroxychloroquine (HCQ) without any evident toxicity and to review the relevant literature.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>The average age of participants in the case and control groups was 45.6 ± 9.3 and 46.8 ± 11.7 years, respectively (<i>p</i> = 0.831). The percentage of female participants was 91.5% in the case group and 84.0% in the control group (<i>p</i> = 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 (<i>r</i> = 0.344; <i>p</i> = 0.032) and inner Early Treatment Diabetic Retinopathy Study (ETDRS) macular rings (<i>r</i> = 0.303; <i>p</i> = 0.061).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"55-62"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-03-12DOI: 10.1080/15569527.2025.2472156
Malaika Naveed, Tariq Javed, Muhammad Danish Zawar, Uswa Shafqat, Muhammad Babar Taj, Muhammad Wasim, Maryam Batool, Muhammad Amir Zawar
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.
重金属基纳米颗粒在化妆品中的应用一直在稳步增长,因为它们具有非凡的物理化学性质和效益。在这个彻底的回顾中,我们将深入研究各种类型的纳米粒子,如绿色纳米粒子,金属纳米粒子和碳基纳米粒子,特别关注重金属基纳米粒子。这些重金属基纳米颗粒表现出优异的物理和机械性能,使其成为化妆品和个人护理产品的合适材料。银纳米粒子能有效治疗痤疮,并具有很强的抗菌特性,而金纳米粒子具有抗衰老和抗炎特性。ZnO和TiO2纳米颗粒通常用于防晒霜中作为紫外线(UV)过滤器,以防止紫外线- a (UVA)和紫外线- b (UVB)辐射。某些金属,如镍、铬和钴是主要的过敏原,经常引起接触性皮炎和敏感人群的过敏反应。化妆品中大量使用镉、铅、汞和砷(类金属)等材料会带来长期的健康风险,包括致癌性、神经毒性和器官损伤。在化妆品中使用含有重金属的草药提取物,由于其抗氧化特性,进一步提高了个人护理产品的有效性。消费者的意识和监管方面的担忧,尤其是那些对金属过敏的人,对于了解含重金属化妆品的潜在风险至关重要。展望未来,未来的研究工作应该集中在开发更安全、无毒、天然的纳米材料和生物相容性的重金属基纳米颗粒替代品上。
{"title":"Applications of heavy metal-based nanoparticles in cosmetics: a comprehensive review.","authors":"Malaika Naveed, Tariq Javed, Muhammad Danish Zawar, Uswa Shafqat, Muhammad Babar Taj, Muhammad Wasim, Maryam Batool, Muhammad Amir Zawar","doi":"10.1080/15569527.2025.2472156","DOIUrl":"10.1080/15569527.2025.2472156","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"95-112"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-03-07DOI: 10.1080/15569527.2025.2475450
Meryem Altın Ekin, Gul Arıkan, Eren Yagmurlu, Ozlem Ural Fatihoglu, Ali Devebacak, Omer Kartı, Ziya Ayhan, Meltem Soylev Bajin
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.
{"title":"Predictors of severity in prostaglandin-associated periorbitopathy.","authors":"Meryem Altın Ekin, Gul Arıkan, Eren Yagmurlu, Ozlem Ural Fatihoglu, Ali Devebacak, Omer Kartı, Ziya Ayhan, Meltem Soylev Bajin","doi":"10.1080/15569527.2025.2475450","DOIUrl":"10.1080/15569527.2025.2475450","url":null,"abstract":"<p><strong>Objective: </strong>To determine the predictive factors for severity in prostaglandin-associated periorbitopathy (PAP) using an objective grading system.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 (<i>p</i> < 0.05), the use of bimatoprost (<i>p</i> < 0.05) and travoprost (<i>p</i> < 0.05), and PGA therapy duration >1 year (<i>p</i> < 0.05) were independent risk factors for higher grades of PAP.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"126-134"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: To investigate the potential effects of systemic fingolimod treatment on parameters of the anterior segment of the eye and tear film function tests in patients with multiple sclerosis (MS).
Methods: Forty-eight eyes of 24 individuals who were started on systemic fingolimod treatment for relapsing-remitting MS were prospectively enrolled in this study. Patients underwent examinations immediately before initiation of systemic fingolimod treatment, and at the first and sixth months of treatment. Anterior segment parameters were measured using Sirius Topography. The Schirmer-I test and tear break-up time (TBUT) were recorded during follow-up. Retinal thickness was also analyzed using spectral-domain optical coherence tomography (SD-OCT).
Results: There was no statistically significant difference in retinal thickness measurements between follow-up visits. The central corneal thickness, keratometric values, anterior chamber depth, aqueous humor depth, iridocorneal angle, horizontal anterior chamber tilt and anterior chamber volume values remained similar during follow-up. The Schirmer-I test value was 15.10 ± 2.65 mm at the zeroth month and 17.03 ± 3.61 mm at the sixth month (p = 0.044). The mean TBUT was significantly higher at the six-month visit compared to baseline and the one-month visit (p0-6 < 0.001, p1-6 < 0.001), but there was no statistically significant difference between baseline and month 1 (p0-1 = 0.419).
Conclusion: Systemic use of fingolimod may increase Schirmer I test and TBUT values in MS patients without altering other anterior segment parameters within 6 months.
目的:探讨系统性芬戈莫德治疗对多发性硬化症(MS)患者眼前段参数和泪膜功能测试的潜在影响。方法:本研究前瞻性纳入24例患者的48只眼睛,这些患者开始接受系统性芬戈莫治疗复发-缓解型MS。患者在开始全身性芬戈莫德治疗前,以及在治疗的第一个月和第六个月接受检查。前段参数测量采用天狼星地形。随访期间记录schirmer - 1试验及泪崩时间(TBUT)。使用光谱域光学相干断层扫描(SD-OCT)分析视网膜厚度。结果:随访期间视网膜厚度测量无统计学差异。在随访期间,角膜中央厚度、角膜测量值、前房深度、房水深度、虹膜角膜角、水平前房倾斜和前房容积值保持相似。第0个月的Schirmer-I检验值为15.10±2.65 mm,第6个月的Schirmer-I检验值为17.03±3.61 mm (p = 0.044)。6个月随访时TBUT平均值显著高于基线和1个月随访时(p < 0.01, p < 0.01),但基线和第1个月间差异无统计学意义(p < 0.01 = 0.419)。结论:系统使用芬戈莫德可增加MS患者6个月内Schirmer I试验和TBUT值,但未改变其他前段参数。
{"title":"Effects of systemic fingolimod treatment on anterior segment parameters and tear film functions.","authors":"Atike Burcin Tefon Aribas, Semra Mungan, Feyza Dicle Işik, Gokhan Celik, Gonul Vural, Ersin Kasım Ulusoy, Nilay Yuksel","doi":"10.1080/15569527.2024.2432508","DOIUrl":"10.1080/15569527.2024.2432508","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the potential effects of systemic fingolimod treatment on parameters of the anterior segment of the eye and tear film function tests in patients with multiple sclerosis (MS).</p><p><strong>Methods: </strong>Forty-eight eyes of 24 individuals who were started on systemic fingolimod treatment for relapsing-remitting MS were prospectively enrolled in this study. Patients underwent examinations immediately before initiation of systemic fingolimod treatment, and at the first and sixth months of treatment. Anterior segment parameters were measured using Sirius Topography. The Schirmer-I test and tear break-up time (TBUT) were recorded during follow-up. Retinal thickness was also analyzed using spectral-domain optical coherence tomography (SD-OCT).</p><p><strong>Results: </strong>There was no statistically significant difference in retinal thickness measurements between follow-up visits. The central corneal thickness, keratometric values, anterior chamber depth, aqueous humor depth, iridocorneal angle, horizontal anterior chamber tilt and anterior chamber volume values remained similar during follow-up. The Schirmer-I test value was 15.10 ± 2.65 mm at the zeroth month and 17.03 ± 3.61 mm at the sixth month (<i>p</i> = 0.044). The mean TBUT was significantly higher at the six-month visit compared to baseline and the one-month visit (<i>p</i><sub>0-6</sub> < 0.001, <i>p</i><sub>1-6</sub> < 0.001), but there was no statistically significant difference between baseline and month 1 (<i>p</i><sub>0-1</sub> = 0.419).</p><p><strong>Conclusion: </strong>Systemic use of fingolimod may increase Schirmer I test and TBUT values in MS patients without altering other anterior segment parameters within 6 months.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"50-54"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-02-22DOI: 10.1080/15569527.2025.2467620
Zhengrui Liao, Shiwen Wen, Lee-Hoon Ho, Thuan-Chew Tan
Purpose: This study examined a plant extract (PE) foundation's safety, antioxidant and protective properties. To offer a scientific foundation for the viability of creating 'skincare makeup' and improve the comprehension of cosmetic compositions' efficacy evaluations.
Methods: Cellular assays tested six different concentrations (up to 5%) of the PE for cell viability levels and reactive oxygen species (ROS) levels of human immortalised epidermal cells (HaCaTs). The identified non-cytotoxic concentration (0.5% PE) was then tested by gene assays. A commercial foundation containing 0.5% PE (PEF0.5) was tested for safety, skin protective effectiveness, and user satisfaction.
Results: Compared to the control groups, 0.5% PE had a significant inhibitory effect on the expression level of MMP-1 but promoted the expression of COL1A1, COL3A1, ELN, and AQP3. PEF0.5 significantly (p < 0.05) reduced wrinkles and transepidermal water loss (TEWL) while improving hydration, glossiness, and elasticity for 14 and 28 days. Interestingly, sebum was reduced by PEF0.5 at 28 days without any negative consequences for 28 days. No significant (p > 0.05) differences were detected in the foundation's effectiveness and usability.
Conclusion: Applying PEF0.5 for 28 days may improve the skin barrier function, as indicated by skin TEWL, hydration, wrinkle, elasticity, and sebum content, without any adverse effects.
目的:研究植物提取物(PE)基质的安全性、抗氧化性和防护性。为创造“护肤彩妆”的可行性提供科学依据,提高对化妆品成分功效评估的理解。方法:细胞试验测试了六种不同浓度(最高5%)的PE对人永生化表皮细胞(HaCaTs)的细胞活力水平和活性氧(ROS)水平的影响。鉴定出的非细胞毒浓度(0.5% PE)通过基因分析进行检测。我们测试了含有0.5% PE (PEF0.5)的商用粉底的安全性、皮肤保护效果和用户满意度。结果:与对照组相比,0.5% PE对MMP-1的表达水平有显著抑制作用,但对COL1A1、COL3A1、ELN、AQP3的表达有促进作用。基金会的有效性和可用性PEF0.5差异显著(p p > 0.05)。结论:PEF0.5涂抹28天,可改善皮肤的TEWL、水合、抗皱、弹性、皮脂含量等指标的屏障功能,无不良反应。
{"title":"Benefits of incorporating plant extracts into a commercially available foundation for daily skin use.","authors":"Zhengrui Liao, Shiwen Wen, Lee-Hoon Ho, Thuan-Chew Tan","doi":"10.1080/15569527.2025.2467620","DOIUrl":"10.1080/15569527.2025.2467620","url":null,"abstract":"<p><strong>Purpose: </strong>This study examined a plant extract (PE) foundation's safety, antioxidant and protective properties. To offer a scientific foundation for the viability of creating 'skincare makeup' and improve the comprehension of cosmetic compositions' efficacy evaluations.</p><p><strong>Methods: </strong>Cellular assays tested six different concentrations (up to 5%) of the PE for cell viability levels and reactive oxygen species (ROS) levels of human immortalised epidermal cells (HaCaTs). The identified non-cytotoxic concentration (0.5% PE) was then tested by gene assays. A commercial foundation containing 0.5% PE (PEF0.5) was tested for safety, skin protective effectiveness, and user satisfaction.</p><p><strong>Results: </strong>Compared to the control groups, 0.5% PE had a significant inhibitory effect on the expression level of MMP-1 but promoted the expression of COL1A1, COL3A1, ELN, and AQP3. PEF0.5 significantly (<i>p</i> < 0.05) reduced wrinkles and transepidermal water loss (TEWL) while improving hydration, glossiness, and elasticity for 14 and 28 days. Interestingly, sebum was reduced by PEF0.5 at 28 days without any negative consequences for 28 days. No significant (<i>p</i> > 0.05) differences were detected in the foundation's effectiveness and usability.</p><p><strong>Conclusion: </strong>Applying PEF0.5 for 28 days may improve the skin barrier function, as indicated by skin TEWL, hydration, wrinkle, elasticity, and sebum content, without any adverse effects.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"82-94"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2024-08-24DOI: 10.1080/15569527.2024.2387596
Hans A Raabe, Gertrude-Emilia Costin, David G Allen, Anna Lowit, Marco Corvaro, Lindsay O'Dell, Julie Breeden-Alemi, Kathryn Page, Monique Perron, Tara Flint Silva, Walter Westerink, Elizabeth Baker, Kristie Sullivan
Background: Test methods to inform hazard characterization and labeling of pesticides to protect human health are typically conducted using laboratory animals, and for skin irritation/corrosion the rabbit Draize test is currently required by many regulatory agencies. Although the Draize test is generally regarded to provide protective classifications for human health, new approach methodologies (NAMs) have been developed that offer more human relevant models that circumvent the uncertainty associated with species differences that exist between rabbits and humans. Despite wide applicability and use of these test methods across a broad range of chemicals, they have not been widely adopted for testing pesticides and pesticidal formulations. One of the barriers to adoption of these methods in this sector is low concordance with results from the Draize rabbit test, particularly for chemicals within the mild to moderate irritation spectrum.
Methods: This review compares and contrasts the extent to which available models used in skin irritation testing mimic the anatomy and physiology of human skin, and how each aligns with the known key events leading to chemically-induced adverse skin irritation and corrosion. Doing so fully characterizes the human relevance of each method.
Results: As alternatives to the rabbit Draize test, several protocols using ex vivo, in chemico, and in vitro skin models are available as internationally harmonized test guidelines. These methods rely on a variety of models of human skin, including excised rodent skin, synthetic biochemical models of barrier function, cell culture systems, and reconstructed human tissue models. We find these models exhibit biological and mechanistic relevance aligned with human skin irritation responses. Further, recent retrospective analyses have shown that the reproducibility of the Draize test is less than 50% for mild and moderate responses, with many of the replicate predictions spanning more than one category (e.g., a moderate response reported in one study followed by a non-irritant response reported in another study).
Conclusions: Based on this comparative evaluation, we recommend top-down and bottom-up testing strategies that use the most human relevant in vitro test methods for skin irritation and corrosion classification of pesticides and pesticide formulations. To further discriminate among mild and non-irritant formulations, optimization of a cytokine release protocol and subsequent analyses of reference formulation test results is recommended.
{"title":"Human relevance of in vivo and in vitro skin irritation tests for hazard classification of pesticides.","authors":"Hans A Raabe, Gertrude-Emilia Costin, David G Allen, Anna Lowit, Marco Corvaro, Lindsay O'Dell, Julie Breeden-Alemi, Kathryn Page, Monique Perron, Tara Flint Silva, Walter Westerink, Elizabeth Baker, Kristie Sullivan","doi":"10.1080/15569527.2024.2387596","DOIUrl":"10.1080/15569527.2024.2387596","url":null,"abstract":"<p><p><b>Background:</b> Test methods to inform hazard characterization and labeling of pesticides to protect human health are typically conducted using laboratory animals, and for skin irritation/corrosion the rabbit Draize test is currently required by many regulatory agencies. Although the Draize test is generally regarded to provide protective classifications for human health, new approach methodologies (NAMs) have been developed that offer more human relevant models that circumvent the uncertainty associated with species differences that exist between rabbits and humans. Despite wide applicability and use of these test methods across a broad range of chemicals, they have not been widely adopted for testing pesticides and pesticidal formulations. One of the barriers to adoption of these methods in this sector is low concordance with results from the Draize rabbit test, particularly for chemicals within the mild to moderate irritation spectrum.</p><p><p><b>Methods:</b> This review compares and contrasts the extent to which available models used in skin irritation testing mimic the anatomy and physiology of human skin, and how each aligns with the known key events leading to chemically-induced adverse skin irritation and corrosion. Doing so fully characterizes the human relevance of each method.</p><p><p><b>Results:</b> As alternatives to the rabbit Draize test, several protocols using <i>ex vivo, in chemico</i>, and <i>in vitro</i> skin models are available as internationally harmonized test guidelines. These methods rely on a variety of models of human skin, including excised rodent skin, synthetic biochemical models of barrier function, cell culture systems, and reconstructed human tissue models. We find these models exhibit biological and mechanistic relevance aligned with human skin irritation responses. Further, recent retrospective analyses have shown that the reproducibility of the Draize test is less than 50% for mild and moderate responses, with many of the replicate predictions spanning more than one category (<i>e.g.</i>, a moderate response reported in one study followed by a non-irritant response reported in another study).</p><p><p><b>Conclusions:</b> Based on this comparative evaluation, we recommend top-down and bottom-up testing strategies that use the most human relevant <i>in vitro</i> test methods for skin irritation and corrosion classification of pesticides and pesticide formulations. To further discriminate among mild and non-irritant formulations, optimization of a cytokine release protocol and subsequent analyses of reference formulation test results is recommended.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"1-21"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-03-08DOI: 10.1080/15569527.2025.2475444
Ayşegül Tel Kankılıç, Ömer Karakoyun, Erhan Ayhan
Objective: In recent years, the frequency of use of biological agents in the treatment of many dermatological diseases has been increasing. While effective, these treatments may carry the risk of hepatitis B virus (HBV) reactivation, particularly in patients with underlying or resolved HBV infection. Data on the risk of reactivation—especially with newer IL-23 antagonists that treat psoriasis vulgaris such as risankizumab and guselkumab, and IL-17 antagonists such as ixekizumab and secukinumab—remain limited. The aim of this study was to investigate HBV seroprevalence in patients with psoriasis using biological drug therapy and to investigate the frequency of reactivation and the importance of prophylactic treatment in this patient group at risk of HBV reactivation.
Methods: This retrospective study included 219 patients (aged 18-92) with psoriasis vulgaris who were treated with at least one biological drug treatment for at least 3 months at Dicle University Dermatology Clinic between 1 January 2018 and 30 June 2024. HBV serological markers (HBsAg, anti-HBcIgG, anti-HBs) and laboratory test results were evaluated. Patients were divided into five groups based on HBV serological: natural immune, chronic HBV infection, isolated anti-HBcIgG positivity, vaccinated and susceptible. These serological tests were repeated every 6 months during follow-up. Patients who did not meet the above-mentioned criteria or had incomplete test results were excluded from the study. Screening for hepatitis B reactivation was performed only in those with a positive anti-HBc IgG test who were at risk of reactivation. This was defined as either: Those who had a positive HBV DNA test prior to biological treatment and had an increase of >1 log10İU/mL in HBV DNA titre during biological treatment use; or those who initially tested negative for HBV DNA prior to starting biological treatment but became HBV DNA–positive during treatment were considered to have HBV reactivation.
Results: Of the 219 psoriasis vulgaris patients, 102 (46.6%) females and 117 (53.4%) males. The distribution biological agents uses was as follows: 87 (39.7%) secucinumab, 29 (13.2%) ixekizumab, 47 (21.5%), guselkizumab, and 56 (25.6%) risankizumab. Patients were categorized into five (5) groups based on HBV serology and among these groups, 46 (21%) patients (10 with secucinumab and risakizumab, 12 with ixekizumab, and 14 with guselkizumab) were found to be at risk of hepatitis B reactivation (anti-HBc IgG test positive). It was observed that 40 (86.96%) of these 46 patients at risk of hepatitis B reactivation used prophylaxis, and no reactivation developed. No significant ALT or AST elevation was detected in all patients during their biological treatment
Conclusion: IL-23 antagonist such as rizankizumab and guzelkumab, as well as IL-17 antagonists like secukinumab and ixekizumab, have been reported to carry a risk of
{"title":"Risk of HBV reactivation in psoriasis vulgaris patients receiving biological agent therapy.","authors":"Ayşegül Tel Kankılıç, Ömer Karakoyun, Erhan Ayhan","doi":"10.1080/15569527.2025.2475444","DOIUrl":"10.1080/15569527.2025.2475444","url":null,"abstract":"<p><strong>Objective: </strong>In recent years, the frequency of use of biological agents in the treatment of many dermatological diseases has been increasing. While effective, these treatments may carry the risk of hepatitis B virus (HBV) reactivation, particularly in patients with underlying or resolved HBV infection. Data on the risk of reactivation—especially with newer IL-23 antagonists that treat psoriasis vulgaris such as risankizumab and guselkumab, and IL-17 antagonists such as ixekizumab and secukinumab—remain limited. The aim of this study was to investigate HBV seroprevalence in patients with psoriasis using biological drug therapy and to investigate the frequency of reactivation and the importance of prophylactic treatment in this patient group at risk of HBV reactivation.</p><p><strong>Methods: </strong>This retrospective study included 219 patients (aged 18-92) with psoriasis vulgaris who were treated with at least one biological drug treatment for at least 3 months at Dicle University Dermatology Clinic between 1 January 2018 and 30 June 2024. HBV serological markers (HBsAg, anti-HBcIgG, anti-HBs) and laboratory test results were evaluated. Patients were divided into five groups based on HBV serological: natural immune, chronic HBV infection, isolated anti-HBcIgG positivity, vaccinated and susceptible. These serological tests were repeated every 6 months during follow-up. Patients who did not meet the above-mentioned criteria or had incomplete test results were excluded from the study. Screening for hepatitis B reactivation was performed only in those with a positive anti-HBc IgG test who were at risk of reactivation. This was defined as either: Those who had a positive HBV DNA test prior to biological treatment and had an increase of >1 log10İU/mL in HBV DNA titre during biological treatment use; or those who initially tested negative for HBV DNA prior to starting biological treatment but became HBV DNA–positive during treatment were considered to have HBV reactivation.</p><p><strong>Results: </strong>Of the 219 psoriasis vulgaris patients, 102 (46.6%) females and 117 (53.4%) males. The distribution biological agents uses was as follows: 87 (39.7%) secucinumab, 29 (13.2%) ixekizumab, 47 (21.5%), guselkizumab, and 56 (25.6%) risankizumab. Patients were categorized into five (5) groups based on HBV serology and among these groups, 46 (21%) patients (10 with secucinumab and risakizumab, 12 with ixekizumab, and 14 with guselkizumab) were found to be at risk of hepatitis B reactivation (anti-HBc IgG test positive). It was observed that 40 (86.96%) of these 46 patients at risk of hepatitis B reactivation used prophylaxis, and no reactivation developed. No significant ALT or AST elevation was detected in all patients during their biological treatment</p><p><strong>Conclusion: </strong>IL-23 antagonist such as rizankizumab and guzelkumab, as well as IL-17 antagonists like secukinumab and ixekizumab, have been reported to carry a risk of ","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"113-117"},"PeriodicalIF":1.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Photoaging is characterised by cutaneous changes caused by exposure to ultraviolet light over time. Quercetin is a bioflavanoid with antioxidant, antineoplastic, and anti-inflammatory effects. This study investigated the therapeutic effects of topical quercetin on photoaging, a phenomenon not previously studied in ultraviolet A (UVA)-induced photoaging.
Methods: A total of 40 rats were randomly categorised into 5 groups, each comprising 8 rats. A photoaging model was induced by applying UVA to the dorsal region of all rats, except for the negative control group. Topical 0.1% retinoic acid was applied to one UVA group, topical 0.3% quercetin to another UVA group, and both agents were applied in combination to yet another UVA group 5 days a week for 8 weeks. Subsequently, wrinkle values were measured, reactive oxygen species (ROS) and matrix metalloproteinase-1 (MMP-1) levels were analysed, and histopathological parameters were examined.
Results: The wrinkle value of the UVA group was found to be significantly higher than that of the UVA + Quercetin group. Collagen damage was lower in the UVA + Quercetin group than in the UVA group, although this difference was not statistically significant. Compared with the UVA + Retinoic Acid group, the UVA + Quercetin group exhibited a more significant decrease in inflammation. MMP-1 values were considerably higher in the UVA + Retinoic Acid and UVA + Quercetin + Retinoic Acid groups as well as in the UVA + Quercetin group compared with the control and UVA groups.
Conclusion: The present study showed that quercetin can be utilised in the treatment of photoaging, especially when combined with retinoic acid.
{"title":"Photoprotective effects of quercetin on photoaging-induced rats.","authors":"Betul Kizilkan, Betul Sereflican, Ayhan Cetinkaya, Selma Erdogan Duzcu, Cevher Altug, Jehat Kizilkan","doi":"10.1080/15569527.2024.2442584","DOIUrl":"10.1080/15569527.2024.2442584","url":null,"abstract":"<p><strong>Purpose: </strong>Photoaging is characterised by cutaneous changes caused by exposure to ultraviolet light over time. Quercetin is a bioflavanoid with antioxidant, antineoplastic, and anti-inflammatory effects. This study investigated the therapeutic effects of topical quercetin on photoaging, a phenomenon not previously studied in ultraviolet A (UVA)-induced photoaging.</p><p><strong>Methods: </strong>A total of 40 rats were randomly categorised into 5 groups, each comprising 8 rats. A photoaging model was induced by applying UVA to the dorsal region of all rats, except for the negative control group. Topical 0.1% retinoic acid was applied to one UVA group, topical 0.3% quercetin to another UVA group, and both agents were applied in combination to yet another UVA group 5 days a week for 8 weeks. Subsequently, wrinkle values were measured, reactive oxygen species (ROS) and matrix metalloproteinase-1 (MMP-1) levels were analysed, and histopathological parameters were examined.</p><p><strong>Results: </strong>The wrinkle value of the UVA group was found to be significantly higher than that of the UVA + Quercetin group. Collagen damage was lower in the UVA + Quercetin group than in the UVA group, although this difference was not statistically significant. Compared with the UVA + Retinoic Acid group, the UVA + Quercetin group exhibited a more significant decrease in inflammation. MMP-1 values were considerably higher in the UVA + Retinoic Acid and UVA + Quercetin + Retinoic Acid groups as well as in the UVA + Quercetin group compared with the control and UVA groups.</p><p><strong>Conclusion: </strong>The present study showed that quercetin can be utilised in the treatment of photoaging, especially when combined with retinoic acid.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"63-71"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-03-20DOI: 10.1080/15569527.2025.2478416
Nur Demir, Hasine Gozde Dalkılıc, Tugba Falay Gur, Belma Kayhan, Sukru Sevincli, Burce Can Kuru, Murat Sonmez
Purpose: Cosmetic botulinum toxin A (BoNT-A) injections are increasing worldwide. Adverse effects need to be evaluated in more detail for BoNT-A regulations. This study aims to assess the anticholinergic effect of BoNT-A on accommodation amplitude (AA) after upper face application.
Methods: Twenty patients aged between 20 and 45 years were recruited in this prospective, interventional study. Abobotulinum toxin A of 500 units was diluted with 3 ml saline and injected into the forehead, glabellar and periorbital area. AA was measured with both the push-up and minus-lens techniques before and after two weeks of the injections. T-test for normally distributed variables was applied for the comparison of the results.
Results: The study group comprised 18 women and 2 men with a mean age of 33.9 ± 8.59. AA decreased significantly after two weeks of the injection. In the push-up test, AA was 9.18 ± 4.72 D before BoNT-A injection and decreased to 7.11 ± 3.02 D after the injection (p < 0.001). In the minus lens test, AA reduced from 5.86 ± 2.24 D to 5.24 ± 2.06 D after BoNT-A injection (p < 0.001). Refraction did not change in any of the participants.
Conclusion: The present study showed that cosmetic upper face BoNT-A injections reduced AA. However, this reduction did not result in any significant symptomatic effects in the patients. These findings suggest that while BoNT-A injection has a measurable impact on the ciliary muscle or its parasympathetic innervation, it may not lead to noticeable clinical outcomes.
{"title":"Accommodation amplitude change after cosmetic use of the botulinum toxin in the upper face.","authors":"Nur Demir, Hasine Gozde Dalkılıc, Tugba Falay Gur, Belma Kayhan, Sukru Sevincli, Burce Can Kuru, Murat Sonmez","doi":"10.1080/15569527.2025.2478416","DOIUrl":"10.1080/15569527.2025.2478416","url":null,"abstract":"<p><strong>Purpose: </strong>Cosmetic botulinum toxin A (BoNT-A) injections are increasing worldwide. Adverse effects need to be evaluated in more detail for BoNT-A regulations. This study aims to assess the anticholinergic effect of BoNT-A on accommodation amplitude (AA) after upper face application.</p><p><strong>Methods: </strong>Twenty patients aged between 20 and 45 years were recruited in this prospective, interventional study. Abobotulinum toxin A of 500 units was diluted with 3 ml saline and injected into the forehead, glabellar and periorbital area. AA was measured with both the push-up and minus-lens techniques before and after two weeks of the injections. T-test for normally distributed variables was applied for the comparison of the results.</p><p><strong>Results: </strong>The study group comprised 18 women and 2 men with a mean age of 33.9 ± 8.59. AA decreased significantly after two weeks of the injection. In the push-up test, AA was 9.18 ± 4.72 D before BoNT-A injection and decreased to 7.11 ± 3.02 D after the injection (p < 0.001). In the minus lens test, AA reduced from 5.86 ± 2.24 D to 5.24 ± 2.06 D after BoNT-A injection (p < 0.001). Refraction did not change in any of the participants.</p><p><strong>Conclusion: </strong>The present study showed that cosmetic upper face BoNT-A injections reduced AA. However, this reduction did not result in any significant symptomatic effects in the patients. These findings suggest that while BoNT-A injection has a measurable impact on the ciliary muscle or its parasympathetic innervation, it may not lead to noticeable clinical outcomes.</p>","PeriodicalId":11023,"journal":{"name":"Cutaneous and Ocular Toxicology","volume":" ","pages":"135-139"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}