Cutaneous and Ocular Toxicology最新文献

Objective: Hidradenitis suppurativa (HS), a chronic inflammatory disease that typically manifests after puberty, is characterised by painful nodules, abscesses, draining sinus tracts, and scars in areas rich in apocrine glands such as the axillary and inguinal regions. In recent years, blood-based biomarkers such as the Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR), Monocyte/Lymphocyte Ratio (MLR), Mean Platelet Volume (MPV), Systemic Immune-Inflammation Index (SII) and Pan-Immune-Inflammation Value (PIV) have been used as significant indicators of systemic inflammation. While there are few studies evaluating these biomarkers in HS, the response of these markers to treatment has only been assessed in one study to date. Our study aims to investigate the effect of adalimumab treatment on blood-based systemic inflammation biomarkers in HS, where inflammation plays a significant role.

Methods: The study included 42 adult patients who received adalimumab treatment at our dermatology and venereology clinic between January 2020 and January 2023. Medical records for complete blood count results of the patients were retrospectively reviewed. All systemic inflammation-based biomarkers were calculated from the absolute values of the complete blood count. The SII was calculated with the following formula: (neutrophil count × platelet count/lymphocyte count). The PIV was calculated as follows: (neutrophil count × platelet count × monocyte count/lymphocyte count). Values before the treatment and at the 12th week of treatment were compared.

Results: When the changes in the inflammatory parameters of the patients were examined, it was found that NLR (2.13 ± 0.87 vs 2.26 ± 1.12), PLR (111.01 ± 39.89 vs 99.43 ± 35.34), MLR (0.27 ± 0.11 vs 0.28 ± 0.12), MPV (9.59 ± 0.71 vs 9.70 ± 0.79), SII (680.79 ± 330.18 vs 687.89 ± 442.66), and PIV (552.02 ± 330.71 vs 605.05 ± 415.96) values did not change statistically significantly after treatment (p > 0.05). While there was a significant decrease in platelet count compared to before treatment, no statistically significant difference was found in the other evaluated blood cells.

Conclusion: Adalimumab treatment has not had a significant effect on systemic inflammation markers in HS, an inflammatory disease. More studies are needed to evaluate the effect of adalimumab on these markers in HS.

Purpose: Favipiravir (FAV) used against COVID-19 is an antiviral drug that causes adverse reactions, such as hyperuricaemia, liver damage, and hematopoetic toxicity. The aim of the study was to investigate the systemic and ocular side-effects of FAV in rats, for the first time.Materials and methods: A total of 18 albino male Wistar rats were used in the study. The rats were divided into 3 groups as the healthy group (HG), the group given 50 mg/kg/day favipiravir (FAV50), and the group given 200 mg/kg/d favipiravir (FAV200). These doses were given to the experimental groups for one week. At the end of the experiment histopathological examinations were performed on the conjunctiva and sclera of the eye. In addition, malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), interleukin-1β (IL-1β), and tumor necrosis factor alpha (TNF-α) levels were measured in blood samples taken from rats. Results: Compared to HG, the MDA (1.37 ± 0.61 vs. 4.82 ± 1.40 µmol/mL), IL-1β (2.52 ± 1.14 vs. 6.67 ± 1.99 pg/mL), and TNF-α levels (3.28 ± 1.42 vs. 8.53 ± 3.06 pg/mL) of the FAV200 group were higher. The levels of tGSH (7.58 ± 1.98 vs. 2.50 ± 0.98 nmol/mL) and SOD (13.63 ± 3.43 vs. 3.81 ± 1.43 U/mL) the FAV200 group were lower than the HG (p < 0.05, for all). The degree of damage to the cornea and sclera of the FAV200 group was quite high according to HG (p < 0.001). Conclusions: FAV can cause damage to rat conjunctiva and sclera by increasing oxidant stress and inflammation at high dose.

Purpose: To determine the structure and properties of corneal endothelial cells in children and adolescents with ADHD who received methylphenidate treatment at least six months.

Method: The prospective, observational study included 33 eyes of 33 patients diagnosed with ADHD who received methylphenidate treatment for at least six months, 33 eyes of 33 patients newly diagnosed with ADHD who did not start medication treatment, and 33 eyes of 33 healthy individuals. Average cell density, coefficient of variation, maximum cell area, normal cell area, minimum cell area, average cell area, and hexagonality ratio values were evaluated by non-contact specular microscopy. The parameters recorded in all three groups were compared.

Results: The average age of children in the ADHD + MPH, ADHD, and control groups is 9 ± 1.7, 8.9 ± 2.3, and 8.9 ± 1.8 years, respectively. (p > 0.05) The average MPH treatment dose is 0.94 ± 0.19 mg/kg, the average daily MPH intake is 34.12 ± 14.04 mg, and the average duration of use of MPH is 24.03 ± 12.46 months. Central corneal thickness (CCT) was measured as an average of 540.45 ± 31.23 in the ADHD + MPH group, 540.61 ± 29.69 in the ADHD group, and 546.58 ± 27.72 in the control group. (p = 0.499) The average coefficient of variation (CV) values were measured as 25.48 ± 4.22 in the ADHD + MPH group, 26.12 ± 3.48 in the ADHD group, and 26.12 ± 3.64 in the control group. (p = 0.491) The average hexagonality ratio (%) (HEX) values were measured as 69.45 ± 8.41 in the ADHD + MPH group, 68.21 ± 6.82 in the ADHD group, and 68.91 ± 7.97 in the control group. (p = 0.892) No statistically significant difference was observed between all three groups in terms of all parameters.

Conclusion: Methylphenidate treatment administered for at least six months with a diagnosis of ADHD did not have a toxic effect on the corneal endothelium.

Objective: Chemotherapy induced alopecia (CIA) is one of the most common side effects in cancer patients, however; it doesn't have an effective pharmacological treatment yet. In this study we aimed to research the protective effect of newly developed HDDPiW-jSB solution on docetaxel (DTX) -induced rat alopecia model.

Material and methods: Docetaxel (10 mg/kg/week) was administered to the 6-8 months old rats for three weeks. HDDPiW-jSB solution was applied once or twice a week for 4 weeks beginning prior to one week before DTX. Rat hair follicles were evaluated with hematoxylin-eosin and immune-histochemical staining.

Results: In the first stage of this study, alopecia was successfully developed by DTX (10 mg/kg/three times) application. In the second stage of the study, application of HDDPiW-jSB solution, did not change the study parameters significantly on control group. The solution improved the anagen hair follicle count and Bcl-2 levels in the skin samples of DTX-induced alopecic rat groups, especially when applied twice weekly. Additionally, level of Caspase 3 was decreased. HDDPiW-jSB solution was safe when applied on the skin.

Conclusion: Topical HDDPiW-jSB solution could be effective and safe for the protection of DTX-induced alopecia in rat models.

Purpose: To study the effects of the anti-IL-23A antibody risankizumab on the IL-36γ/IL-23A/IL-17A signalling cascade we used a newly developed 3D skin model consisting of primary human keratinocytes, fibroblasts and γδ-T-cells.

Methods: In this in vitro study we developed new full-thickness 3D skin models containing normal human epidermal keratinocytes (NHEK), normal human dermal fibroblasts (NHDF) and IL-23A responsive and IL-17A producing γδ-T-cells. The effects of IL-36γ stimulation with and without risankizumab treatment on IL-23A and IL-17A expression were examined at the RNA and protein levels.

Results: In preliminary monolayer experiments stimulation of γδ-T-cells with IL-23A promoted the IL-17A expression that was inhibited after risankizumab treatment. Using 3D skin models containing γδ-T-cells, we found that stimulation with IL-36γ significantly increased not only IL-23A but also IL-17A expression. These effects were inhibited by concomitant treatment with risankizumab.

Conclusions: Our results showed that blockade of IL-23A has inhibitory effects on the IL-36γ/IL-23A feedforward loop. Our newly developed 3D skin model containing IL-23A responsive and IL-17A producing γδ-T-cells enables molecular analysis of targeted therapies aimed at the IL-36γ/IL-23A/IL-17A signalling cascade in psoriasis.

Purpose: Although the inflammatory and anti-inflammatory effects of isotretinoin (ISO) treatment in patients with acne vulgaris have been discussed in the literature in recent years, no sensitive and specific marker has been found in studies so far. Neutrophil/HDL (high-density lipoprotein) (NHR), lymphocyte/HD L(LHR), platelet/HDL (PHR), and lymphocyte/monocyte (LMR) are new biomarkers related to inflammation. Triglyceride/HDL (TG/HDL), LDL/HDL, and total cholesterol/HDL have been shown to be cardiometabolic risk factors predicting both cardiovascular disease risk and metabolic risk, rather than just a simple dyslipidemia scale. To our knowledge, the relationship between these parameters and ISO treatment has never been studied before. We aimed to evaluate the immuno-inflammatory response of ISO treatment in patients with acne vulgaris with NHR, LHR, PHR, LMR, TG/HDL, LDL/HDL, and total cholesterol/HDL parameters.

Materials and methods: In this study, 153 patients who received oral ISO treatment for at least 3 months with a diagnosis of moderate-severe acne vulgaris were evaluated retrospectively. Patients were given oral isotretinoin at a dose of 0.5-1 mg/kg. Pre and post-treatment leukocyte (WBC), neutrophil (NE), lymphocyte (LY), platelet (PLT), red cell distribution width (RDW), plateletcrit (PCT), neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), mean platelet volume (MPV), monocyte/lymphocyte (MLR), LMR, total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, MHR, NHR, LHR, PHR, TG/HDL, total cholesterol/HDL, LDL/HDL parameters were evaluated.

Results: It was found that post-treatment WBC and MPV values increased statistically significantly; NLR, neutrophil, and PCT values, on the other hand, decreased significantly (p < 0.05). No statistically significant change was detected in PLR, MLR, LMR, MHR, NHR, LHR, PHR, lymphocyte, monocyte, platelet, and RDW parameters (p > 0.05). It was determined that post-treatment total cholesterol, triglyceride, VLDL, and LDL levels increased statistically significantly; however, the HDL level decreased significantly (p < 0.05). Levels of total cholesterol/HDL, TG/HDL, and LDL/HDL were also found to increase statistically significantly (p < 0.05).

Conclusion: Our study suggests that the MPV and NLR ratio as biomarkers can be used as indicators of atherosclerosis-related inflammation due to ISO treatment, but the MHR, NHR, LHR, PHR, MLR, LMR ratios cannot be used. Moreover, we believe that the ratios of TG/HDL, LDL/HDL, and total cholesterol/HDL offer a new contribution as indicators of cardiovascular risk and systemic inflammation related to ISO treatment.

Purpose: To compare the thickness of the retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GC-IPL) in smoker and nonsmoker diabetics without diabetic retinopathy.

Materials and methods: Patients with diabetes were divided into two groups according to their smoking status: Group 1 consisted of 38 smoker diabetics who had chronically smoked more than 20 cigarettes per day for more than five years; Group 2 consisted of 38 nonsmoker diabetics. After a detailed ophthalmologic examination, the mean and regional (superior, supratemporal, inferior, inferotemporal, temporal, nasal, superonasal, and inferonasal) RNFL and GC-IPL thicknesses were measured with spectral-domain optic coherence tomography (SD-OCT) and compared between groups.

Results: The mean age was 54.7 ± 10.5 and 51.2 ± 9.7 years in the smoker and nonsmoker groups, respectively (p = 0.14). Gender, duration of diabetes, and the mean axial length were similar between groups (p:0.43, p:0.54, p: 0.52, respectively). Mean RNFL thickness was 89.1 ± 8.0 µm in the smoker group and 93.4 ± 7.0 µm in the nonsmoker group, and it was significantly thinner in the smoker group (p = 0.01). The temporal RNFL thickness in the smoker group was thinner than in the nonsmoker group (p = 0.02). There was no difference in superior, inferior, and nasal RNFL thicknesses between the groups (p = 0.31, p = 0.12, p = 0.39, respectively). The mean macular GC-IPL thickness of the smoker and nonsmoker groups was 78.53 ± 15.74 µm and 83.08 ± 5.85 µm, respectively (p = 0.09). Superior, superonasal, inferonasal, inferior, inferotemporal, and superotemporal quadrant GC-IPL thicknesses were similar between the groups (p = 0.07, p = 0.60, p = 0.55, p = 0.77, p = 0.71, p = 0.08, respectively). The groups showed no difference in minimum GC-IPL thickness (p = 0.43). There was a significant negative correlation between smoking exposure and mean, inferior quadrant RNFL thicknesses in the smoker group (p = 0.04, r= -0.32, and p = 0.01, r= -0.39, respectively).

Conclusion: Mean RNFL thickness was significantly thinner in smoker diabetics. Although not statistically significant, especially mean, superior, and superotemporal GC-IPL was thinner in smoker diabetics. The results suggest a potential association between the coexistence of diabetes and smoking with alterations in RNFL and GC-IPL thickness.