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Background: The SkinMedica Acne Treatment Platform (SM Regimen) was formulated to treat acne without overdrying the skin. We evaluated efficacy and tolerability of the SM Regimen (including a novel 1% salicylic acid Acne Clarifying Cleanser and 2% salicylic acid Acne Treatment Lotion) versus a prescription formulation (Rx Regimen; including adapalene 0.1%/benzoyl peroxide 2.5%) in a diverse population of adults with mild to moderate facial acne., Methods: This single-center, double-blind, randomized study enrolled adults (18-45 years) with Fitzpatrick skin types (FST) I-VI. SM Regimen or Rx Regimen was applied topically to the entire face for 12 weeks. Assessments were conducted at 24 and 48 h and 4, 8, and 12 weeks., Results: Subjects (SM Regimen, n = 31; Rx Regimen, n = 23) were primarily female (90.7%) with mean age of 28.6 years; 53.8% had FST IV-VI. Efficacy was comparable between regimens. The SM regimen resulted in significant improvements versus baseline in mean Investigator's Global Assessment of acne severity from 48 h through week 12 (p ≤ 0.001), as well as significant and sustained improvements from baseline in total acne lesion count, global postinflammatory hyperpigmentation/postinflammatory erythema, and oiliness. The SM Regimen was well tolerated at all time points, with mean scores below mild for all parameters; the Rx Regimen caused significantly more tightness/dry feeling at week 4 versus SM Regimen (p = 0.008). Subjects (> 96%) reported high satisfaction with the SM Regimen at all time points., Conclusions: The SM Regimen reduced acne severity and skin oiliness, evening out skin tone without overdrying or irritating the skin., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Chloasma is a common skin hyperpigmentation condition, with treatment options ranging from topical agents to advanced interventions such as chemical peels and laser therapy. Salicylic acid, including its supramolecular form (SSA), has shown promise in managing chloasma. However, to date, no multicentre randomized controlled trial of SSA for chloasma is available., Objectives: The purpose of this study was to assess the efficacy and safety of 30% SSA combined with 10% niacinamide in treating -chloasma., Methods: This multicentre (n = 15), randomized, double-blind, parallel placebo-controlled trial (Clinical trial registration number: ChiCTR2200065346) enrolled and randomized 300 participants (1 : 1) to either 30% SSA treatment or placebo, with 150 allocated to treatment and 150 to placebo in the full analysis set, and 144 to treatment and 147 to placebo in the per-protocol set. A Visia® Skin Analysis System was used at each visit to assess the degree of improvement in chloasma lesions. The primary endpoint was the effective rate after 16 weeks, assessed using the modified Melasma Area and Severity Index (mMASI) score [(pretreatment score - post-treatment score)/pretreatment score × 100%]., Results: The total mMASI score, overall score on the Griffiths 10-point scale, and Griffiths 10 score for the left and the right sides of the face were significantly lower in the 30% SSA group than in the placebo group (all P < 0.001). One study of drug-related adverse events (AEs) and one study of drug-unrelated AEs were reported in the 30% SSA group. No AE was reported in the placebo group., Conclusions: Among our patients, 30% SSA combined with 10% niacinamide was shown to be effective and safe for treating chloasma., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Allergic contact dermatitis (ACD) to salicylic acid (SA) is widely unreported. Furthermore, cross-reactivity between SA and other salicylates has not been reported despite well-documented in-group salicylate cross-reactivity., Objective: To describe our clinic's experience patch testing to SA, highlighting seven cases of relevant reactions and concomitant reactivity with other salicylates., Methods: Results of patch testing to 5% SA in petrolatum between 1 January 2020, and 9 February 2024, are reported. Seven cases of relevant reactions to SA are detailed., Results: A total of 489 patients (27.5%) were tested to SA, 21 of which were positive: 7 doubtful (+/-), 14 weak positive (+), and no strong/extreme positive reactions. Four irritant reactions were documented. Of the 14 weak positive (+) reactions, 7 had definite or probable clinical relevance, 5 of which also reacted to other salicylates., Conclusions: ACD to SA is likely underreported due to a lack of testing. In our experience, testing SA 5% petrolatum is tolerable without significant irritation. Cross-reactivity between SA and other salicylates is probable. Though SA appears to be the primary sensitizer in some cases, more studies are needed to understand its possible role as a marker for salicylate allergy., (© 2024 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Objective: Salicylic acid (SA) has been used for treatment of acne of different severity levels. However, there are few researches about the safety and efficacy for treatment of mild to moderate acne, and the improvement of the skin condition by using 2% supramolecular salicylic acid (SSA) compared to Davuwen Adapaline gel., Methods: A multicenter, randomized, assessor-blind and parallel-controlled study was conducted. A total of 500 patients (trial group: 249, control group: 251) with mild to moderate (grade I-II) facial acne vulgaris were recruited in this study over a 16-week trial period. Patients in the trial group were treated with Broda 2% SSA hydrogel, while control group treated with Davuwen Adapaline gel once a day. The number of inflammatory papules, comedones, and pustules were counted and the rate of lesion reduction was calculated pre- and post-treatment. Then, the skin physiological indicators, including L*a*b*, TEWL, skin sebum and hydration were measured. Statistical analysis was conducted using SAS 9.4. Significance was set at p = 0.05., Results: At the end of 12 weeks' therapy, the regression and markedly improvement rate of the trail group and the control group were 51.01% and 43.10% respectively, and there was no significant difference in the improvement rate between two groups (p = 0.0831). Although, there was no difference in adverse events rate between two groups, the adverse events rate of the trail group was 0.40%, a little lower than the control group (0.80%). Moreover, there was a significant difference in the numbers of pores at T1 between two groups., Conclusion: Both 2% SSA and Adapaline gel were equally effective in the treatment of mild to moderate acne vulgaris. 2% SSA is worth the clinical promotion and application in mild to moderate acne vulgaris., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Adult acne vulgaris affects up to 43-51% of individuals. While there are numerous treatment options for acne including topical, oral, and energy-based approaches, benzoyl peroxide (BPO) is a popular over the counter (OTC) treatment. Although BPO monotherapy has a long history of efficacy and safety, it suffers from several disadvantages, most notably, skin irritation, particularly for treatment naïve patients. In this prospective, randomized, controlled, split-face study, we evaluated the comparative efficacy, safety, and tolerability of a novel 3-step azelaic acid, salicylic acid, and graduated retinol regimen versus a common OTC BPO-based regimen over 12 weeks. A total of 37 adult subjects with self-reported mild to moderate acne vulgaris were recruited. A total of 21 subjects underwent a 2-week washout period and completed the full study with 3 dropping out due to product irritation from the BPO routine, and 13 being lost to follow-up. Detailed tolerability surveys were conducted at Week 4. Additional surveys on tolerability and product preferences were collected monthly, at Week 4, Week 8, and Week 12. A blinded board-certified dermatologist objectively scored the presence and type of acne lesions (open or closed comedones, papules, pustules, nodules, and cysts) at baseline, Week 4, Week 8, and Week 12. Patients photographed themselves and uploaded the images using personal mobile phones. Detailed Week 4 survey results showed across 25 domains of user-assessed product performance, the novel routine outperformed the BPO routine in 19 (76%) which included domains in preference (e.g. "I would use this in the future) and performance ("my skin improved" and "helped my acne clear up faster"). Users of the novel routine reported less facial redness, itching, and burning, though differences did not reach statistical significance. In terms of efficacy, both products performed similarly, reducing total acne lesions by 36% (novel routine) and 40% (BPO routine) by Week 12. Overall, accounting for user preferences and tolerability the novel routine was more preferred than the BPO routine in 79% of domains (22/28). Differences in objective acne lesion reduction were not statistically significant (p = 0.97). In a randomized split-face study, a 3-step azelaic acid, salicylic acid, and graduated retinol regimen delivered similar acne lesion reduction, fewer user dropouts, greater user tolerability, and higher use preference compared to a 3-step BPO routine based in a cohort of participants with mild-to-moderate acne vulgaris., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Multiple palmoplantar warts, caused by human papillomavirus (HPV) infection, were investigated for clinical efficacy using cantharidin, retinoic acid cream, and salicylic acid cream., Methods: A total of 110 patients with multiple palmoplantar warts were enrolled. The experimental group (54 cases) received a 1:1:1 combination (CRS) of 0.25% cantharidin, 0.1% retinoic acid cream, and 5% salicylic acid, applied with pressurized encapsulation for 8 h every night, three times per week. The control group (56 cases) underwent conventional liquid nitrogen freezing. Monthly follow-ups assessed cure rate, effective rate, dermatological life quality index (DLQI), visual analog scale (VAS), and cost, with evaluations conducted after 3 months., Results: The treatment group exhibited a cure rate of 85.19% and a total effective rate of 96.30%, surpassing the control group with rates of 39.29% and 51.79%, respectively (p < 0.05). The treatment group's DLQI score (1.84 ± 1.06) was significantly lower than the control group's score (6.04 ± 1.78) (p = 0.0005). Additionally, the treatment group's VAS score (1.84 ± 1.06) was notably lower than the control group's score (8.56 ± 1.07) (p < 0.0001). The treatment group's total cost (43.20 ± 2.85) was markedly lower than the control group's cost (206.38 ± 90.81), with a statistically significant difference (p < 0.0001)., Conclusion: The combination of cantharidin, retinoic acid cream, and salicylic acid with local encapsulation is a safe, effective, economical, and convenient treatment method for multiple palmoplantar warts, exhibiting few side effects and showing promise., (© 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Objective: To observe the efficacy and safety of supramolecular salicylic acid monotherapy and supramolecular nicotinamide in the treatment of chloasma., Methods: A total of 28 female patients with chloasma diagnosed in the dermatology outpatient department of our hospital were randomly divided into an experimental group and a control group, with 14 cases in each group. All patients were treated with 30% supramolecular salicylic acid every 2 weeks, for a total of 8 treatments. The experimental group was treated with 10% supramolecular nicotinamide once in the morning and once in the evening, and the control group was a blank control. Before each exfoliation treatment, subjects were photographed with a VISIA skin detector, and skin image analysis and modified melasma area and severity index (MASI) score were performed., Results: According to the MMASI decrease rate (%) before and after treatment, the effective rate of the experimental group was 64.29%, and the effective rate of the control group was 14.29%. The results of the GriffithS10 and VISIA were improved. During the whole treatment, there was one mild adverse reaction in both groups., Conclusion: Salicylic acid stripping combined with nicotinamide in the treatment of chloasma is safe and effective, can improve skin conditions, and can be widely applied in clinical practice., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Acne vulgaris is a common dermatological condition that greatly impacts patients' self-confidence. Ongoing research is conducted to explore new treatment modalities. Silymarin owns special characteristics that qualify it as a possible treatment for acne vulgaris., Objective: We evaluated the efficacy and safety of silymarin cream as a new therapeutic option against salicylic acid peels in the treatment of mild to moderate acne vulgaris., Methods: A split-face, comparative, Quasi-experimental clinical trial included 30 patients with acne vulgaris. Salicylic acid 30% peels were applied as an office procedure to one half of the face every 2 weeks for 3 months. Topical silymarin 1.4% cream was prescribed as a home treatment, twice daily, to the other half of the face for 3 months. The results were evaluated using the Global Acne Grading System (GAGS), photographic evaluation, and patient self-assessment scale. The adverse effects during treatment were recorded. The sample size was calculated by Stata/IC 16.1., Results: After treatment, a significant reduction of GAGS was noted on both sides of the face, with an insignificant difference between both treatments. The comparative photographic evaluation and patient self-assessment scale were also insignificant. Hyperpigmentation was recorded in 2 cases on the salicylic acid-treated side. No side effects for silymarin cream were observed., Conclusion: Topical silymarin cream 1.4% showed comparable results to Salicylic acid 30% peels. It can be considered a promising safe treatment modality for mild to moderate acne vulgaris., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Inflammatory and non-inflammatory acne lesions constitute a significant clinical challenge in acne subjects., Aim: To evaluate the efficacy and safety of a facial serum and a mask containing salicylic acid and lipohydroxy acid for improving skin conditions., Methods: This randomized controlled trial included adults with comedones, post-inflammatory erythema (PIE) and/or hyperpigmentation (PIH) in Shanghai, China in July 2021. Participants were randomly assigned 1:1 to receive the study Serum + Mask or serum alone for 8 weeks. Acne severity, comedones, papules, pustules, PIE, PIH, skin pores, skin tone evenness, sebum secretion, skin hydration, and trans-epidermal water loss were evaluated at T0d, T1d, T7d, T14d, T28d, and T56d., Results: Eighty-three participants were included, including 41 and 42 in the Serum + Mask and Serum groups, respectively. Acne severity, density of skin pores, skin tone evenness, PIH foci on face, PIE foci on nose, intensity of PIE and PIH, closed comedones on face, open comedones on nose, sebum secretion, and skin hydration were significantly improved from baseline after 8 weeks of treatment in both groups (all p < 0.05). Addition of the mask improved the number of closed comedones (-6.56 ± 0.39 vs. -5.19 ± 0.44, p = 0.022) and acne severity (-0.39 ± 0.08 vs. -0.12 ± 0.09, p = 0.026) substantially more than using the serum alone. No adverse reaction was reported in either group., Conclusions: The study serum improved skin conditions by regulating skin barrier function and achieving a balance of skin hydration and sebum secretion, removing comedones and improving PIE and PIH. Addition of the mask accelerated the effects without compromising safety., (© 2023 L'Oreal. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

To determine the efficacy of supramolecular salicylic acid combined with doxycycline on acne, totally 70 patients with acne treated in our dermatology department from May 2020 to May 2021 were enrolled and randomized (1:1) into control or experimental groups using the random number table method. The control group was given doxycycline for oral administration while the experimental group was given oral doxycycline combined with supramolecular salicylic acid for topical administration. The overall effective rate of treatment was significantly higher in the experimental group versus control group (97.14% vs. 82.86%, P<0.05). Patients in the control group had significantly longer mean acne regression time after treatment versus experimental group (P<0.05). After treatment, patients in the experimental group had significantly lower self-rating depression scale (SDS) scores and self-perceived burden (SPB) scores than the control group, while Short Form 36-item health survey (SF-36) scores were significantly higher than the control group (P<0.05). The overall incidence of adverse reactions was significantly lower in the experimental group versus control group (5.71% vs. 17.14%, P<0.05). Supramolecular salicylic acid in combination with doxycycline in the treatment of patients with acne is an optimal option, as it could better promote acne regression, reduce the level of depression and reduce the patient's self-perceived burden.

To evaluate the efficacy of topical 30% salicylic acid plus minocycline in moderate to severe acne. One hundred patients with moderate to severe acne from February 2020 to February 2021 were retrospectively analyzed. They were assigned (1:1) to receive either topical 30% salicylic acid plus minocycline (combination group) or minocycline (mono therapy group). The acne scores, physician subjective and objective scores, efficacy, quality of life, incidence of adverse reactions, recurrence and satisfaction in both groups were compared. The combination group had lower Global Acne Grading System (GAGS) scores, erythema scores and papulopustular scores than the mono therapy group. Combined therapy was associated with lower erythema absolute value and erythema index, more skin water content and less transcutaneous water loss versus minocycline. Higher efficacy, acne symptoms scores, and quality of life were observed with combination therapy versus mono therapy (P<0.05). The two groups had a similar incidence of adverse reactions and recurrence. Combination therapy showed a higher appearance satisfaction versus mono therapy. The efficacy of topical 30% salicylic acid plus minocycline for moderate to severe acne was better versus minocycline.

Introduction: Seborrheic dermatitis (SD) is a chronic, relapsing, inflammatory disorder of the head and trunk., Objectives: To explore the potential of a 1% Selenium disulphide (SeS2)-based shampoo to prevent relapses of scalp SD (SSD) following corticosteroid/salicylic acid (TCS/SA) treatment., Materials & Methods: After a 2-week treatment with TCS/SA, adult patients with moderate-to-severe SSD received either the SeS2-based shampoo or its vehicle for eight weeks in a randomized, double-blinded fashion. Visits took place at baseline, weeks 2, 6 and 10. SSD severity was assessed based on erythema, flakes and pruritus; patients assessed the severity of pruritus. Global investigator and patient satisfaction were assessed at week 10., Results: Forty-eight adults were included. After four and eight weeks of post TCS/SA maintenance regimen, 8.1% and 16.7% in the SeS2, and 41.7% and 54.2% in the vehicle group relapsed, respectively. First median time-to-relapse in the vehicle group was 56 days; this was not reached for SeS2. After two weeks of TCS/SA, the prevalence of patients with no pruritus was 29.2% in the SeS2 group, and 41.7% in the vehicle group; it increased to 76.2% with SeS2 and to 57.1% with the vehicle at the end of the study. The clinical benefit of treatment with TCS/SCA was maintained in the SeS2 group only. Investigators and patients were highly satisfied with the efficacy of SeS2. Tolerance to SeS2 was excellent, with no reported adverse events., Conclusion: The SeS2-based shampoo significantly reduces the time-to-relapse of moderate-to-severe SSD flares. Its tolerance was excellent, with no reported adverse events.

Background: Acne tarda (AT) is typically known as adult acne and most preferably affected 25-45 age groups. Used isotretinoid monotherapy is not effective and also produces side effects from long treatment., Aim: The present study assesses the effectiveness of combined treatment of oral isotretinoid with topical chemical peeling (20% salicylic and 10% mandelic acid known as SM peeling) by a comparative double-blind randomized single-center interventional open-label study., Materials and Methods: A total fifty-eight participants AT outpatients (25-45 age groups) attending for diagnosis in two groups and effectiveness of proposed combined treatments were determined at baseline and follow-up within 4-week interval. Briefly group A (n = 28) received 0.5 mg/kg of oral isotretinoin once daily for 16 weeks and group B (n = 30) received the same oral dose, addition with SM peeling every 4 weeks interval for 16 weeks. After 4 weeks, treatment efficacy was assessed based on Michelson's acne severity index (MASI) and visual analog scale (VAS), further validated using statistical tools., Results: Based on MASI and VAS scores, combined treatment was significantly effective than the monotherapy. The pre- and post-treatment analyses of response to scarring, inflammatory components at baseline and at the end of treatment were also statistically significant with p > 0.008., Conclusion: The above investigation revealed that the combination of oral isotretinoin with SM peeling was highly effective and could be used as newer therapy against AT without any serious side effects., (© 2022 Wiley Periodicals LLC.)

Multiple approaches are used to treat acne scars, but some are expensive, ineffective, and cause complications. We aimed to evaluate the efficacy and safety of ultra-pulsed CO 2 fractional laser combined with 30% supramolecular salicylic acid in the treatment of acne scars in a prospective split-face control study. Twenty patients with facial symmetrical acne scars were enrolled. One side of face was randomly treated with 30% supramolecular salicylic acid, and two sides were treated with ultra-pulsed CO 2 fractional laser. The Echelle d'evaluation clinique des cicatrices d'acne (ECCA) scale was used to evaluate the clinical efficacy before and 3 months after treatment, and a quartile scale was used to self-evaluate the improvement of patients. A visual analog scale was used to record pain scores after each treatment, and side effects and other adverse reactions on the face were recorded. All the patients completed treatment and follow-up. There was statistical difference in ECCA scores of bilateral facial acne scars after three treatments (p < 0.001). ECCA scores on the combined side were lower after three treatments than those on the laser side (p = 0.003). The patient satisfaction quartile scale on the combined side was higher than that on the laser side alone (p = 0.015). Ultra-pulsed CO 2 fractional laser combined with 30% supramolecular salicylic acid has better efficacy in the treatment of acne scars than laser alone, and patient self-assessment of combined treatment has a greater degree of improvement in acne scars, and does not increase patient pain scores and related adverse reactions., (© 2022 Wiley Periodicals LLC.)

Background: Acne vulgaris (AV) is a common dermatosis. For moderate to severe AV, isotretinoin is the first-line treatment. Chemical peeling with supramolecular salicylic acid (SSA) was developed with water solubility and advanced skin penetration properties. In the present study, we investigated the efficacy and safety of oral low-dose isotretinoin combined with 30% SSA chemical peeling., Methods: Thirty-three moderate-to-severe acne patients were enrolled and received oral low-dose (0.2-0.4 mg/kg/d) isotretinoin and were then randomly assigned to receive 30% SSA or not on each side of the face with 2-week intervals for four sessions. Photos, the number of lesions, GAGS score, skin indices (melanin, erythema, pore, and texture), hydration, and transepidermal water loss (TEWL) were assessed at 0, 2, 4, 6, and 10 weeks. Side effects, efficacy, and satisfactory rates were recorded., Results: A total of 29 patients completed the study. Oral isotretinoin combined with SSA decreased response time compared to isotretinoin monotherapy, with significantly improved GAGS score, count of lesions, and efficacy (%) at 4-6 weeks. Skin indices of melanin, erythema, pore, and texture evaluated at week 10 were improved as well. Oral isotretinoin with or without SSA was effective by the lesion clearance; only SSA significantly improved the TEWL. All the side effects were temporary and tolerable, and no adverse effects were observed., Conclusion: Oral low-dose isotretinoin combined with 30% SSA is safe and effective, which advanced the onset of action and improves lesion clearance., (© 2022 the International Society of Dermatology.)

Human papillomavirus infection is relatively common in communities. Thus, determining an effective and painless treatment method, especially in pediatric patients is of utmost importance. This study aimed to compare the outcomes of three different methods of treating plantar warts in pediatric patients. Children with verruca plantaris treated with a salicylic acid-lactic acid combination once daily (SA/LA 1), a salicylic acid-lactic acid combination applied in three to seven layers under occlusion every 3 days (SA/LA 2), or a combination of 5-fluorouracil (0.5%) and salicylic acid (10%) (SA/5-FU) were evaluated retrospectively. Treatment responses and recurrence rates were also evaluated after a minimum of 4 months. Among the 98 children with verruca plantaris, 19 were treated with SA/LA 1, 53 were treated with SA/LA 2, and 18 were treated with SA/5-FU; the eight patients who received cryotherapy were excluded. The mean treatment duration was significantly shorter in the SA/LA 2 group than in the SA/LA 1 group and the SA/5-FU group. (p = 0.000 for both) Application of a salicylic acid-lactic acid combination in multiple layers under occlusion is a safe, painless, and effective treatment method for plantar warts in children., (© 2021 Wiley Periodicals LLC.)

Background: Acne vulgaris is a common and chronic skin disease that impacts on physical and psychological perceptions. Combination therapy with topical retinoids and antimicrobial agent is considered the preferred approach for most of the subjects affected by mild-to-moderate acne. A correct therapeutic management should include a prolonged treatment to ensure therapeutic success and to prevent recurrences. The aim of this study was to evaluate the efficacy and tolerability of a new topical gel formulation that combines retinol encapsulated in glycospheres and hydroxypinacolone retinoate, associated with an anti-microbial peptide (BIOPEP-15) salicylic acid, glycolic acid, and niacinamide as monotherapy in mild acne vulgaris., Methods: A 2-month prospective study was conducted at the Unit of Dermatology of the Federico II University. Twenty-five patients aged from 14 to 30 years with mild acne of the face (GAGS score ≤ 18) were consecutively enrolled. Each patient was asked to apply the gel formulation once daily in the evening for 8 weeks. The number of acne lesions with VISIA camera system, the global acne grading system (GAGS) score, trans epidermal water loss (TEWL), skin colorimetry (X-rite Spectrocolorimeter), reflectance confocal microscopy exam were evaluated at baseline, after 4 and 8 weeks of treatment for each patient. Tolerability and safety of the product were also evaluated., Results: Twenty-five female patients with a median age of 23.4 were enrolled. Twenty-two (88%) completed the 2-month treatment period visits. At baseline the total acne lesion number, mean (SD), was 5.5 (4) and the GAG score 9 (4). A significant (P=0.001) reduction in number of total acne lesions was observed at week 4 (-57%) and at week 8 (-80%). All patients presented a significant reduction of the GAGS score values: -42% at week 4 and -78% at week 8, confirming the clinical efficacy of the product. At baseline TEWL was 10.2 g/m 2 /h (1.3) and 10.7 (1.4) at week 8, thus showing that the gel did not impair the skin barrier function. Skin colorimetry was significantly (P=0.0015) reduced by the treatment in comparison with baseline (62 vs. 58). Efficacy of the gel formulation was also confirmed with RCM exams, showing a reduction of dermal inflammation and exocytosis, and an improvement of infundibular hyperkeratinization. We observed that adherence to treatment correlated positively with the improvement of the single parameters. Moreover, side effects such as erythema, dryness, and excessive xerosis were not reported, resulting in a complete adherence to the treatment., Conclusions: Our findings provide favorable evidences of the efficacy and safety of this new product as a first line treatment in patients with mild acne, or, as a maintenance therapy for prolonged periods after the suspension of a systemic treatment. Furthermore, the tolerability of this topical product and the absence of any side effects increased the adherence to the therapy.

Eye burns due to the accidental application of pharmacological or nonpharmacological substances packaged in plastic dropper bottles have been described for more than three decades and continue to occur. These burns can cause potentially serious corneal injuries. We report the case of a patient who mistakenly applied salicylic acid to the right eye after confusing it with an eye lubricant, which caused him a severe corneal burn. Fortunately, after aggressive medical and surgical management (including oxygen therapy and amniotic membrane grafting), the visual results were good. We suggest conducting educational campaigns and taking legislative measures in our country to avoid packaging corrosive substances in this type of dropper bottle to reduce the risk of accidental burns.

Objective: Antibiotics and retinoids have been used for acne vulgaris for decades. Though effective, each has its own drawbacks. Chemical peels have been used for treatment of acne vulgaris with inadequate clinical evidence. We sought to determine the efficacy and safety of Jessner's solution (JS) in comparison with salicylic acid (SA) 30% in the management of acne vulgaris and postacne hyperpigmentation in patients with colored skin., Methods: A total of 36 subjects (94.5% Fitzpatick Type IV-V) were recruited in this randomized double-blinded, split-face, controlled trial. Each side of the face was randomly assigned for treatment with either JS or SA. Subjects were treated once fortnightly for a total of three sessions. Lesion counting, Michaelsson acne score (MAS), photographs, and postacne hyperpigmentation index (PAHPI) were used to objectively assess the improvement. Complications were assessed during each visit. Statistical analysis was conducted using SPSS v22.0. Significance was set at P = 0.05., Results: At the end of therapy, significant reduction in inflammatory, noninflammatory lesions, MAS, and PAHPI scores (P < 0.001, respectively) were noted in comparison to baseline. Mixed model analysis revealed no significant outcome difference between the two groups. Patients who reported good and very good outcome were 76.4% (JS) and 85.3% (SA). Burning, stinging sensation, and exfoliation were the common complications reported. Postinflammatory hyperpigmentation was reported only once in the JS arm., Conclusion: Both JS and SA were equally effective in the treatment of acne vulgaris and reducing postacne hyperpigmentation in patients with colored skin., (© 2020 the International Society of Dermatology.)

Additional non-animal methods are urgently needed to meet regulatory and animal welfare goals. TTC is a broadly used risk assessment tool. TTC based on external dose has limited utility for multi-route exposure and some types of structure activity relationship assessments. An internal TTC (iTTC), where thresholds are based on blood concentration, would extend the applicability of TTC. While work is on-going to develop robust iTTC thresholds, we propose an interim conservative iTTC. Specifically, an interim iTTC of 1 μM, supported by the published experience of the pharmaceutical industry, a literature review of non-drug chemical/receptor interactions, and analysis of ToxCast™ data. ToxCast™ data were used to explore activity versus the 1 μM interim iTTC and recommendations for the analysis and interpretation of HTS data. Test concentration-based points of departure were classified to identify quality of fit to the Hill Model. We identified, for exclusion from the approach, estrogen receptor and androgen receptor targets as potent chemical/receptor interactions potentially associated with low dose exposure to non-pharmaceutical active ingredients in addition to the original TTC exclusions. With these exclusions, we conclude that a 1 μM plasma concentration is unlikely to be associated with significant biological effects from chemicals not intentionally designed for biological activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Riehl's melanosis is a chronic, refractory disorder, which can adversely affect patient's quality of life. Intense pulse light, neodymium-doped yttrium aluminum garnet laser, hydroquinone, tranexamic acid have been reported to treat this disease, but there have been few reports on the effectiveness of other treatments., Aim: To assess the efficacy and safety of triple combination therapy with salicylic acid chemical peels, oral glycyrrhizin compound, and vitamin C for Riehl's melanosis., Patients/methods: Three patients diagnosed with Riehl's melanosis were enrolled. All patients were treated with glycyrrhizin compound (150 mg/d), vitamin C (100 mg/d), and salicylic acid 30% peels once every 2 weeks. Clinical photographs and VISIA were used to assess the efficacy., Results: All patients received obvious improvement and reported no obvious side effects., Conclusion: Triple combination therapy with salicylic acid peels, oral glycyrrhizin compound, and vitamin C is a safe and effective modality for Riehl's melanosis., (© 2019 Wiley Periodicals, Inc.)

Background: Glycolic acid (GA) and salicylic acid (SA) peels have been used separately for acne treatment, not as a sequential peel., Aim: To evaluate the efficacy and safety of sequential peeling with 70% GA and 20% SA as a monotherapy and as an adjuvant to systemic doxycycline in treatment of mild to moderate acne and the effect on serum interleukin (IL) 17 and tissue IL-1α., Patients/methods: Forty-five mild to moderate acne vulgaris patients were randomly assigned into three groups. Group [A] underwent sequential application of 70% GA followed by 20% SA biweekly for three months. Group [B] underwent sequential peeling and doxycycline PO100 mg BD for 1 month followed by 100 OD for 2 months. Group [C] received oral doxycycline. Acne grading, lesion counting, and patient satisfaction were assessed. Serum samples and perilesional skin biopsies were obtained at onset and 2 weeks after finishing the treatment for assessment of serum IL-17 and tissue IL-1α., Results: All groups showed statistically significant decrease in acne grading and lesion count, increase in patient satisfaction, and decrease in serum IL-17 and tissue IL-1 α after treatment. There was no significant difference between the 3 groups before or after treatment, except regarding patient satisfaction after treatment, which was significantly higher in groups [A] and [B] than group [C] (P = .001)., Conclusions: This study recommends using sequential GA 70% and SA 20% peels in the treatment of mild or moderate acne vulgaris as a new cost-effective mode, with low-down time and potential safety, in noncompliant patients on medical therapy., (© 2019 Wiley Periodicals, Inc.)

Background: Chemical peels have become a popular modality in the treatment of acne vulgaris (AV). Mandelic acid (MA) is a new emerging peeling agent for AV owing to its antibacterial and anti-inflammatory properties. Hence, it is worthwhile to evaluate the effectiveness and safety profile of this newer agent and to compare it with an older established peeling agent, salicylic acid (SA) in the treatment of AV., Objective: Comparison between therapeutic efficacy and safety of 45% MA peel with 30% SA peel in Indian patients suffering from mild-to-moderate facial AV., Methods: A total of 50 patients suffering from mild-to-moderate AV were randomly divided into two groups, with one receiving 30% SA peels and the other receiving 45% MA peels at an interval of 2 weeks for six sessions. Total duration of the study was 12 weeks. Michaelsson acne scores (MAS) and clinical photographs were used to evaluate the efficacy of therapy objectively. Adverse effects of both the agents were also noted at each visit., Results: Both agents showed almost equal efficacy in improving mild-to-moderate AV. Salicylic acid was found better in treating noninflammatory lesions, while MA had an upper hand in treating inflammatory lesions. Overall, there was no significant difference between the two peels in improving MAS and percentage decrease in MAS. However, adverse effects were lesser with MA peels., Conclusion: About 45% MA peel was found to be equally effective as 30% SA peel in mild-to-moderate facial AV. However, safety and tolerability of MA peel were better than SA peel., (© 2019 Wiley Periodicals, Inc.)

Background: Melasma is an acquired hyperpigmentation, often involving the face, and a source of distress for the affected individuals. Although treatment is challenging and frequently a multimodality approach, topical applications are the mainstay of therapy., Objective: Due to the frequent relapses, a therapy both acting rapidly and suitable for long-term use, with fewer adverse effects should be administered. In our outpatient clinic, we treated the melasma patients with a previously unreported triple combination which was empirically formulated with lesser amount of active components, regarding the balance between long-term use and safety., Methods: Sixty-eight female patients with melasma who referred to our hospital dermatology clinic in the years 2016-2017 were retrospectively recruited. They all had completed 6-month treatment with a prescribed cream mixture comprised of azelaic acid (4%), hydroquinone (1.6%), methylprednisolone aceponate (0.04%), and salicylic acid (2%). The outcomes were evaluated both instrumentally (Melanin Index/MI) and by patients (Patient Self-Assessment Scale/PSAS)., Results: Adverse effects declared by the patients were transient irritation in three and mild hypertrichosis in two. Both the MI and PSAS values were found extremely significant at the end of 6th month, compared with initial values. Approximately 62% of total decrease in MI was realized in the first 3 months., Conclusion: The triple combination containing active ingredients with lesser concentrations than proposed, and with the addition of 2% salicylic acid, may be promising as a quite effective and safe protocol in treatment of melasma for longer durations., (© 2019 Wiley Periodicals, Inc.)

Patients often request treatment of their burdensome cutaneous warts. However, a safe and effective treatment for cutaneous warts is lacking. This study evaluates treatment outcome, side effects, and patient satisfaction after topical application of cantharidin 1% podophyllin 2% salicylic acid 30% (CPS1) solution in a large series of children and adults with cutaneous warts. Fifty-two children and 83 adults with warts, treated with CPS1 solution between October 2012 and October 2014, were included. Complete clearance of warts occurred in 86.5% of children and 62.7% of adults treated with CPS1 solution (p < .01). Resolution of warts was partial in 3.9 and 24.1% and absent in 9.6 and 13.2% of children and adults respectively. Side effects were present in 41.2% of children and 46.3% of adults (p = .7). Most common side effects were blistering, pain, and burning sensation. No serious adverse events occurred. On a 10-point scale, median patient satisfaction score was 9.0 (interquartile range 7.8-10.0) and 8.0 (interquartile range 5.1-9.7) for children and adults respectively (p < .01). CPS1 solution is a safe and promising treatment modality with a high clearance and high patient satisfaction rate for the management of cutaneous warts, particularly in children., (© 2019 The Authors. Dermatologic Therapy published by Wiley Periodicals, Inc.)

A vast variety of substances currently reaches the aquatic environment, including newly developed chemicals and products. Lack of appropriate analytical methods for trace determinations in aquatic ecosystem compartments and lack of information regarding their toxicity explains existing regulation gaps. However, suspicion of their toxicity assigned them as Contaminants of Emerging Concern (CECs). Among CECs are Pharmaceuticals including Salicylic Acid (SA), which is the active metabolite of acetylsalicylic acid (ASA; aspirin). The aim of the present study was to evaluate the potential effects of SA on the mussel Mytilus galloprovincialis. For this, organisms were exposed for 28 days to different concentrations of SA (0.005; 0.05; 0.5 and 5 mg/L), resembling low to highly polluted sites, after which different physiological and biochemical parameters were evaluated to assess organism's respiration rate, neurotoxic, metabolic and oxidative stress status. Our results clearly showed that SA strongly reduced the respiration capacity of mussels. Also, SA inhibited the activity of superoxide dismutase (SOD) and catalase (CAT) enzymes, but increased the activity of glutathione peroxidase (GPx) and glutathione-S-transferases (GSTs), which prevented the occurrence of lipid peroxidation (LPO). Nevertheless, oxidative stress was confirmed by the strong decrease of the ratio between reduce glutathione (GSH) and oxidized (GSSG) glutathione in contaminated mussels. Moreover, neurotoxicity was observed in mussels exposed to SA. Overall, this study demonstrates the metabolic, neurotoxic and oxidative stress impacts of SA in M. galloprovincialis, which may result in negative consequences at the population level., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Combined azelaic acid (AA) and salicylic acid (SA) have not been previously used for acne. Objective: To compare the efficacy of this combination versus trichloroacetic acid (TCA) 25% peel in acne. Methods: Thirty-four patients were included in this trial. Patients received four sessions 2 weeks apart. The combined solution was applied to one side of the face, while TCA was applied to the other. Our outcomes were physician-reported clinical improvement, dermoscopic assessment of the erythema and patient's satisfaction. Results: After two sessions, a significant clinical improvement was observed in non-inflammatory lesions in the TCA-treated side-treated TCA and in inflammatory lesions in the SA/AA-treated side. At the end, both modalities led to significant improvement, with no significant difference in between. Patients reported more discomfort with the TCA-treated side. There was no significant different clinical improvement in both treated sides as regards SPT. Erythema improved in both sides. Patients were more satisfied by the SA/AA-treated side. Conclusion: Chemical peeling is effective in controlling mild-moderate acne in SPT III-IV. Combined SA 20% and AA 20% are recommended at early stage of treatment if patients have more inflammatory lesions, while TCA is recommended if patients have more non-inflammatory lesions.

The purpose of the study was to investigate the changes of Ca 2+ /calmodulin-dependent protein kinases II (CaMKII)/cAMP response element-binding protein (CREB) signaling pathway in a rat tinnitus model. Eighteen Wistar rats were randomly divided into three groups: normal control (NC), normal saline (NS), and tinnitus model (TM) groups. Tinnitus model was induced by intraperitoneal injection of salicylate. The concentration of intracellular calcium level in auditory cortex cells was determined using Fura-2 acetoxymethyl ester (Fura-2 AM) method with fluorospectrophotometer. Expressions of calmodulin (CaM), N-methyl-D-aspartate receptor 2B subunit (NR2B), calcium-calmodulin kinase II (CaMKII), and cAMP response element-binding protein (CREB) were detected with Western blot. Tinnitus model was successfully established by the intraperitoneal administration of salicylate in rats. Compared with rats in NC and NS groups, salicylate administration significantly elevated CaM, NR2B, phospho-CaMKII and phospho-CREB expression in auditory cortex from tinnitus model group (p < 0.05), and the free intracellular Ca 2+ concentrations (p < 0.05). Our data reveal that salicylate administration causes tinnitus symptoms and elevates Ca 2+ /CaMKII/CREB signaling pathway in auditory cortex cells. Our study likely provides a new understanding of the development of tinnitus.

The known metallotherapeutic [Ag(salH)] 2 (AGSAL-1) of salicylic acid (salH 2 ), was used for the development of new efficient silver based material for wounds healing. AGSAL-1 was characterized by spectroscopic techniques and X-ray crystallography. The wound healing epithelialization of AGSAL-1 was investigated by the means of scratch assay against immortalized human keratinocytes (HaCaT) cells. The anti-inflammatory activity of AGSAL-1 was evaluated by monitoring the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX). The antibacterial activity of AGSAL-1 was evaluated against bacterial species which colonize wounds, such as: Pseudomonas aeruginosa (PAO1), Staphylococcus epidermidis and Staphylococcus aureus, by the means of Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and their Inhibition Zone (IZ). Moreover, the influence of AGSAL-1 against the formation of biofilm of PAO1 and St. aureus was also evaluated by the mean of Biofilm Elimination Concentration (ΒΕC). A hydrogel material CMC@AGSAL-1, based on the dispersion of AGSAL-1 in to carboxymethyl cellulose (CMC) was tested for its antimicrobial activity. Molecular Docking was performed, to explore the molecular interaction of AGSAL-1 with (i) the transcriptional regulator of PAO1, LasR. (ii) the mevalonate pathway for the biosynthesis of isoprenoids which is essential for gram-positive bacteria St. epidermidis and St. aureus. The toxicity of AGSAL-1 was examined against the HaCaT cells. Its genotoxicity was evaluated using Allium cepa model, in vivo. No genotoxicity was detected, indicating that AGSAL-1 is a candidate towards the development on a new efficient medication of the silver based metallodrugs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The present study demonstrated the combined effect of 24-epibrassinolide and salicylic acid against lead (Pb, 0.25, 0.50, and 0.75 mM) toxicity in Brassica juncea seedlings. Various parameters including water status, metal uptake, total water- and lipid-soluble antioxidants, metal chelator content (total thiols, protein-bound thiols, and non-protein-bound thiols), phenolic compounds (flavonoids, anthocyanins, and polyphenols), and organic acids were studied in 10-day-old seedlings. Dry matter content and the heavy metal tolerance index were reduced by 42.24 and 52.3%, respectively, in response to Pb treatment. Metal uptake, metal-chelating compounds, phenolic compounds, and organic acids were increased in Pb-treated seedlings as compared to control plants. The treatment of Pb-stressed seedlings with combination of EBL and SA resulted in enhancement of heavy metal tolerance index by 40.07%, water content by 1.84%, and relative water content by 23.45%. The total water- and lipid-soluble antioxidants were enhanced by 21.01 and 2.21%, respectively. In contrast, a significant decline in dry weight, metal uptake, thiol, and polyphenol contents was observed following the application of 24-epibrassinolide and salicylic acid. These observations indicate that Pb treatment has an adverse effect on B. juncea seedlings. However, co-application of 24-epibrassinolide and salicylic acid mitigates the negative effects of Pb, by lowering Pb metal uptake and enhancing the heavy metal tolerance index, water content, relative water content, antioxidative capacities, phenolic content, and organic acid levels.

Background: As an in situ carcinoma, actinic keratoses should be treated early. Previous studies on the efficacy of a low-dose 0.5% 5-fluorouracil solution in combination with 10% salicylic acid (low-dose 5-FU/SA) are mostly related to lesions appearing on the head and face. In contrast, actinic keratoses (AK) lesions of the upper extremities are considered to be difficult to treat., Objective: The efficacy of low-dose 5-FU/SA in the treatment of actinic keratoses on the hands and/or forearms was studied for the first time in this non-interventional study (NIS) under practical conditions in a large patient population. In addition to the clinical course during therapy and a follow-up period, the length of application and adherence were documented., Methods: As part of this NIS, 649 patients with AK were treated at 207 centres with low-dose 5-FU/SA. The data of the study were recorded at baseline, optionally during an intermediate examination, at the end of therapy and during a final assessment., Results: The average number of AK lesions decreased during the entire observation period by 92%. Side-effects were documented only rarely in the form of local skin reactions (2%). The attending physicians assessed the efficacy, tolerability and safety of the therapy as being predominantly very good or good (in each case ≥90%)., Conclusion: AK lesions on the hands and/or forearms were effectively treated with low-dose 5-FU/SA under routine conditions in dermatological practice and the treatment was well tolerated., (© 2016 European Academy of Dermatology and Venereology.)

Bioactive food chemicals are substances present in food that are capable of interacting with living cells causing changes in physiological functions. Salicylic acid (SA), a plant hormone involved in plant immune response, is one such bioactive food chemical. Aspirin, a commercially available SA, might play beneficial roles in cardiovascular health and colon cancer. It may also cause urticaria, angioedema, asthma, and gastrointestinal symptoms in SA-sensitive individuals. Dietary SA might exert similar beneficial effects and/or may induce similar symptoms in hypersensitive individuals. Food-related SA sensitivity in relation to gastrointestinal symptoms is not well documented besides a few self-reported questionnaires and the knowledge that low doses of aspirin (equivalent of high dietary intake) can cause gastrointestinal injury. The only direct evidence that suggests benefits of reducing dietary SA was reported in asthmatic individuals. Although SA sensitivity in relation to gut symptoms in susceptible individuals is accepted by clinicians, the detection of this disease remains a challenge because of the complicated nature of dietary challenges and the risk of oral aspirin provocation tests in patients with severe hypersensitivity reactions. Given the non-IgE mediated nature of the disease, in vitro assays like basophil activation may have failed to produce reliable results. However, given the simplicity of this assay, further studies need to be formulated to firmly establish its reliability. Formulation of proper dietary strategies for symptom control is also impossible given the controversial and scant nature of the data on SA content of food. This issue needs to be resolved to formulate proper dietary strategies for effective symptom control., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Chemical peeling is a well-identified therapeutic modality for acne vulgaris (AV). Jessner's solution (JS) is a known peeling agent for acne since more than 100 years. Salicylic acid (SA) peel is a well-established peeling agent for acne. There is paucity of literature comparing the current peeling agents of choice, that is, SA with the older peeling agents, that is, JS for acne., Objective: To compare the efficacy and safety of 30% SA vs. JS peels in treatment of mild-to-moderate facial acne in Indian patients., Materials and Method: A total of 40 patients with mild-to-moderate AV were enrolled for 12 weeks and were randomly divided into two groups: group 1, 30% SA peels and group 2, JS peels were performed 2 weeks apart with total of six peels in 12-week duration. Clinical improvement was assessed objectively using Michaelsson acne scores (MAS) and clinical photographs. Side effects were observed at each visit., Results: At the end of therapy, improvement in MAS and percentage decrease in MAS were significantly higher in group 1 as compared to group 2. Likewise, decrease in mean comedone counts in group 1 was significantly higher as compared to group 2. However, there was no statistically significant difference in the decrease in mean papule and pustule counts between the two groups. Both the groups tolerated the peels well., Conclusion: Thus, 30% SA peels were more effective than JS peels in treatment of noninflammatory lesions, that is, comedones and in overall improvement of mild-to-moderate facial acne vulgaris., (© 2016 Wiley Periodicals, Inc.)

Background: Postinflammatory hyperpigmentation (PIH) is an acquired hyperpigmentation that involves areas of prior cutaneous inflammation. In addition to prevention, there are a variety of medications and procedures used to treat PIH., Aim of the Work: The aim of this work was to evaluate the efficacy, tolerability, and safety of salicylic acid peeling in comparison with topical tretinoin in the treatment of PIH., Patients and Methods: This study included forty-five patients with PIH lesions. The patients were divided into three groups, group I was treated with salicylic acid peeling 20-30%, group II was treated with topical tretinoin 0.1%, and group III was treated with combination of salicylic acid peel and topical tretinoin. The patients were assessed clinically to evaluate the efficacy, tolerability, and safety of the treatment. Dermoscopy was carried out to the recurrent or nonimproved cases only., Results: Combination of salicylic acid peel and topical tretinoin treatment showed significant clinical improvement of PIH than each treatment alone with no complications. There was no significant difference in the recurrence rate between the three groups. There was nonsignificant difference between the efficacy of the treatment and the PIH type in the studied groups. There was nonsignificant difference between the efficacy of the treatment and the duration of the PIH except for group III., Conclusion: Combination treatment modality is believed to be preferred in the treatment of PIH due to its higher efficacy than single treatment alone, with well tolerability, less side effects, and low recurrence rate., (© 2016 Wiley Periodicals, Inc.)

Acne vulgaris treatments usually cause sensitivity, teratogenicity and bacterial resistance. Investigations of other therapeutic techniques, such as phototherapy, are highly relevant. Thus, we compared the effectiveness of two Acne vulgaris treatments in adolescents: peeling with salicylic acid (SA) and phototherapy. Teens were randomly divided into: group I, treatment with SA peels (10%) and group II, treatment with phototherapy (blue LED and red laser lights). Photographs were taken before and after ten sessions of each treatment, carried out weekly, and compared. To compare the differences between the treatments, the Student t-test was used. P values < 0.05 were considered significant. Both techniques are effective therapies for the treatment of acne in teenagers since the number of comedones, papules and pustules decreased significantly at the end of the session. However, when the two treatments were compared, phototherapy showed a significant difference in reducing the number of pustules. The combined use of red and blue lights due to their anti-inflammatory and wound-healing properties is a more efficient alternative for treating Acne vulgaris in relation to SA and proves more reliable and without side effects, improving the adolescents' skin health.

The aim of our study was to evaluate the efficacy and safety of topical cantharidin-podophylotoxin-salicylic acid (CPS) treatment of recalcitrant plantar warts (RPW). This study was carried out in a health center in the city of A Coruña (Spain) between January and December 2013. A total of 75 patients completed all the stages of the research process. Information related to treatment with CPS and adverse effects was abstracted from medical records. Of 93 potential patients identified, 75 had at least one follow-up visit or telephone call after treatment and were included in this study. Patients experienced an average of 5.4 visits until complete resolution of their plantar wart occurred, although CPS was not applied at every visit. Fifty-four patients required one application to eliminate the wart and 21 patients required two applications/patient. Seventy-seven percent of patients experienced blistering - an expected therapeutic side effect. All patients experienced some form of an adverse event, the most common being pain (81.3%) and significant blistering (15%). Other side effects were rare (18.7%) and included pruritus, possible mild infection, significant irritation, and bleeding. All patients reported treatment, supporting our results that CPS is a safe and efficacious treatment modality for RPW and should be considered when symptomatic infection necessitates treatment., (© 2016 Wiley Periodicals, Inc.)

Background: Nanomaterials coating gained much concern in orthopedic implants and cosmetics. Drug combination may be a promising strategy for treating multi-factorial diseases. Titanium dioxide (TDN) nanoparticles are being widely used in many industries as well as in medicine and pharmacology. Therefore, increased human and environmental exposure can be expected, which has put TDN under toxicological scrutiny, and it is necessary to address the potential health and safety implications of nanomaterials used in nanomedicine. The toxicity of titanium oxide nanoparticles (TDN) and salicylic acid (SA) separately or in combination was studied for 21 days., Methods: The liver and kidney biomarker were determined, and hormones and oxidative stress levels were detected in mice., Results: The intraperitoneal (i.p.) injection of TDN and SA in combination had a potential toxicological effect on major organs and hormonal homeostasis of mice. TDN and SA could antagonistically interact to affect the liver and kidney functions. No synergistic damage was observed in the liver function of mice that were treated with both TDN and SA as compared to the SA group. TDN acted as a synergistic agent to SA in the case of total cholesterol and total proteins levels. SA acted as antagonistic to the effect of TDN when injected together in mice because the effect on kidney functions is less than that predicted on the basis of the additive. The effect of co-administration of SA and TDN on the following hormones; triiodothyronine, thyroxine, estradiol II and insulin various among additive, potentiation, antagonistic and no effect, respectively as compared to TDN group. The interaction of TDN and SA was also found to induce oxidative stress as indicated by the increase in lipid peroxidation (LPO) levels. The decrease in the level of the reduced glutathione in the co-treated group indicated that there were no synergistic damages. SA and TDN co-administration could induce a potential increase in LPO levels in liver, kidney, and spleen but not in heart tissue. These results have not suggested that TDN and SA have a synergistic sub-chronic toxicity in mice after i.p. administration. SA may decrease the toxicity of TDN to some degree that could be related to the potentiation chemical reaction between SA and TDN., Conclusions: Our results suggested that the damage observed in mice treated with TDN and SA is organ-specific and associated with hormonal homeostasis and oxidative damage.

Background: The aim of this paper was to evaluate efficacy and tolerability of a topical gel (ACNAID TM gel medical device) containing 3% hydrogen peroxide (HPO), 1.5% salicylic acid (SA) and 4% D-panthenol (D-p) in the treatment of mild-moderate acne, comparing it with a previous formulation (ACNAID TM gel Cosmetic) containing 4% HPO, 0.5% SA, 4% D-p., Methods: Twenty patients of both sex with mild-moderate acne have been selected. The topical gel was applied twice a day for 60 days. Evaluations included: Global Acne Grading System (GAGS); lesions count; photographic assessment; a questionnaire to assess the tolerability. The results have been compared with those obtained in a previous study conducted with the formulation containing 4% HPO, 0.5% SA, 4% D-p., Results: The GAGS score showed a reduction of 43% from T0 to T1 and of 61% from T0 to T2. Count of lesions: comedones reduction of 62% from T0 to T1 and of 95% from T0 to T2; papules reduction of 49% from T0 to T1 and of 68% from T0 to T2; pustules reduction of 75% from T0 to T1 and of 100% from T0 to T2. Digital images showed a significant reduction of acne lesions. At T2 the tolerability of the topical product was excellent according to 83% of patients and good according to 17% of patients., Conclusions: The topical gel has demonstrated to be effective and safe for treatment of mild to moderate acne. No patients reported side effects. These results are superior to those obtained in the previous study.

WRKY transcription factors play a central role not only in plant growth and development but also in plant stress responses. However, the role of WRKY transcription factors in herbivore-induced plant defenses and their underlying mechanisms, especially in rice, remains largely unclear. Here, we cloned a rice WRKY gene OsWRKY45, whose expression was induced by mechanical wounding, by infestation of the brown planthopper (BPH, Nilaparvata lugens) and by treatment with jasmonic acid (JA) or salicylic acid (SA). The antisense expression of OsWRKY45 (as-wrky) enhanced BPH-induced levels of H₂O₂ and ethylene, reduced feeding and oviposition preference as well as the survival rate of BPH, and delayed the development of BPH nymphs. Consistently, lower population densities of BPH on as-wrky lines, compared to those on wild-type (WT) plants, were observed in field experiments. On the other hand, as-wrky lines in the field had lower susceptibility to sheath blight (caused by Rhizoctonia solani) but higher susceptibility to rice blast (caused by Magnaporthe oryzae) than did WT plants. These findings suggest that OsWRKY45 plays important but contrasting roles in regulating the resistance of rice to pathogens and herbivores, and attention should be paid if OsWRKY45 is used to develop disease or herbivore-resistant rice.

Actinic keratosis (AK), a common cutaneous lesion with the potential to transform into squamous cell carcinoma, has traditionally been treated with ablative and/or surgical procedures. Recently, a topical formulation combining 0.5% 5-fluorouracil with 10% salicylic acid (5-FU-SA) was introduced in Europe under the trade name Actikerall™ for the treatment of grade I/II AKs. In a single randomized phase III trial, 5-FU-SA was shown to be superior to diclofenac 3% gel in hyaluronic acid, as measured by the histological clearance of one defined lesion (72% vs. 59.1%) and by complete clinical clearance (55.4% vs. 32.0%). 5-FU-SA should be applied once daily to a total area of up to 25 cm(2), which may include the lesion(s) and a small area of surrounding skin (rim of healthy skin should not exceed 0.5 cm), for up to 12 weeks. The most common side effects are local inflammation and pruritus at the application site, and no serious adverse effects have been reported to date. Now commercially available in Canada, 5-FU-SA represents a patientapplied therapeutic option for the treatment of both overt and subclinical AKs.

Background: Melasma is acquired symmetric hypermelanosis characterized by light-to-deep brown pigmentation over cheeks, forehead, upper lip, and nose. Treatment of this condition is difficult and associated with high recurrence rates. Chemical peels have become a popular modality in the treatment of melasma., Objective: To compare the therapeutic efficacy and tolerability of glycolic acid (35%) versus salicylic-mandelic (SM) acid (20% salicylic/10% mandelic acid) versus phytic combination peels in Indian patients with melasma., Materials and Methods: Ninety patients diagnosed with melasma were randomly assigned into 3 groups of 30 patients each. Group A received glycolic acid (GA-35%) peel, Group B received SM acid, and Group C received phytic combination peels. Each group was primed with 4% hydroquinone and 0.05% tretinoin cream for 4 weeks before treatment. Chemical peeling was done after every 14 days in all groups until 12 weeks. Clinical evaluation using melasma area and severity index (MASI) score and photography was recorded at every visit and follow-up was done until 20 weeks., Results: There was a decrease in MASI score in all 3 groups but it was statistically significantly lower in Group A than Group C (p = .00), and it was also statistically significantly lower in Group B than Group C (p = .00) but there was no statistically significant difference between Groups A and B (p = .876). Objective response to treatment evaluated by reduction in MASI scoring after 12 weeks was 62.36% reduction in GA group, 60.98% reduction in SM group, and 44.71% in phytic acid group., Conclusion: It is concluded that GA (35%) and SM acid peels are both equally efficacious and a safe treatment modality for melasma in Indian skin, and are more effective than phytic acid peels. Salicylic-mandelic peels are better tolerated and more suitable for Indian skin.

Background: Actinic keratoses (AKs) are clinically significant and require therapy. Efficacy of low-dose (0.5%) 5-fluorouracil with 10% salicylic acid (5-FU/SA) has been shown in randomized comparative trials of hyperkeratotic lesions of various grades., Objectives: To evaluate the efficacy, tolerability and safety of low-dose 5-FU/SA topical solution vs. cryosurgery in patients with moderate/severe (grade II/III) hyperkeratotic AKs (NCT01358851)., Methods: In an exploratory, open, randomized study, patients with histologically confirmed moderate/severe hyperkeratotic AKs on the face/forehead or bald scalp received 6 weeks of once-daily topical 0.5% 5-FU/SA, or up to two cryosurgery treatments (3 weeks apart). Histological outcomes were determined from punch biopsies. Clinical, cosmetic and tolerability outcomes were also assessed., Results: Sixty-six patients received treatment (33 per arm). The baseline total number of lesions was 266 (8.1/patient) in the 0.5% 5-FU/SA and 263 (8.0/patient) in the cryosurgery group. Most (74.5%) lesions were grade II (grade III, 25.5%). Mean change in lesion count from baseline to Day 98 was -5.2 and -5.7 lesions per patient for 0.5% 5-FU/SA and cryotherapy groups respectively. Histological AK clearance rates on Day 98 were 62.1% and 41.9% respectively. At 6-month posttreatment follow-up, recurrence of cleared lesions (no clinically visible lesions in treatment area) occurred in 39.4% of 0.5% 5-FU/SA and 84.8% of cryosurgery patients. Drug-related adverse events (AEs), including local skin reactions considered 'severe' by the investigator, were reported in 24.2% of 0.5% 5-FU/SA and 6.1% of cryosurgery patients. All drug-related AEs were skin reactions., Conclusions: Although the study was not powered to explore statistical differences in clinical efficacy between treatments, a short (6-week) schedule of topical treatment with 0.5% 5-FU/SA achieved greater histological clearance and lower recurrence of grade II/III hyperkeratotic AKs than cryosurgery. AE incidence across both treatment groups was relatively low and AEs were generally mild or moderate. Clinical trials.gov identifier: NCT01358851., (© 2014 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of the European Academy of Dermatology and Venereology.)

Inclusion complexes of salicylic acid (SA) and acetylsalicylic acid (aspirin, ASA) with polysaccharide arabinogalactan (AG) from larch wood Larix sibirica and Larix gmelinii were synthesized using mechanochemical technology. In the present study, we have investigated physicochemical properties of the synthesized complexes in solid state and in aqueous solutions as well as their anti-aggregation and ulcerogenic activity. The evidence of the complexes formation was obtained by nuclear magnetic resonance (NMR) relaxation technique. It was shown that in aqueous solution the molecules of SA and ASA are in fast exchange between the complex with AG macromolecules and solution. The stability constant of aspirin complex was calculated. It was shown that mechanochemically synthesized complexes are more stable when compared to the complex obtained by mixing solutions of the components. Complexes of ASA show two-fold increase of anti-platelet effect. It allows to reduce the dose of the antithrombotic drug and its ulcerogenic activity. These results substantiate the possibility to design new preparations on the basis of ASA with increased activity and safety.

Introduction: Plantar warts often are refractory to any treatment and can last for decades in adults. Recalcitrant warts are defined as those that have persisted for more than two years, or after at least two treatment modalities., Methods: A total of 15 consecutive patients with recalcitrant plantar warts were included in this preliminary study. The treatment consisted of applying one to two sessions that comprised compounding 1% cantharidin, 5% of podophyllotoxin, and 30% salicylic acid (CPS), with an interval between applications of four weeks., Results: With treatment and subsequent follow-up for six months, there was complete eradication of lesions in 15 patients, eight (53.3%) required a single application of the solution, and seven (46.7%) two applications, with no side effects. Patient satisfaction related to treatment was measured by a visual analog scale (VAS) of 10 cm in length, with an average score 9.73 ± 0.46, and all said they would proceed with the treatment again if necessary., Conclusions: Topical treatment by compounding is safe, effective, and a promising therapeutic modality when applied in recalcitrant plantar warts.

Objective: This study was designed to establish a low dose salicylate-induced tinnitus rat model and to investigate whether central or peripheral auditory system is involved in tinnitus., Methods: Lick suppression ratio (R), lick count and lick latency of conditioned rats in salicylate group (120 mg/kg, intraperitoneally) and saline group were first compared. Bilateral auditory nerves were ablated in unconditioned rats and lick count and lick latency were compared before and after ablation. The ablation was then performed in conditioned rats and lick count and lick latency were compared between salicylate group and saline group and between ablated and unablated salicylate groups., Results: Both the R value and the lick count in salicylate group were significantly higher than those in saline group and lick latency in salicylate group was significantly shorter than that in saline group. No significant changes were observed in lick count and lick latency before and after ablation. After ablation, lick count and lick latency in salicylate group were significantly higher and shorter respectively than those in saline group, but they were significantly lower and longer respectively than those in unablated salicylate group., Conclusion: A low dose of salicylate (120 mg/kg) can induce tinnitus in rats and both central and peripheral auditory systems participate in the generation of salicylate-induced tinnitus.

The biggest hurdle in the treatment of acne vulgaris is patient non-compliance that is due in large part to poor tolerability to common acne medications. As such, new acne treatments must be developed that balance good anti-acne efficacy with excellent tolerability in order to ensure patient adherence and by extension ensure good clinical outcomes. The goal of the present study was to determine the tolerability and efficacy of a novel skin care system, composed of a cleanser, containing 1% salicylic acid and botanical ingredients, and a treatment gel, containing 1% salicylic acid, 10% buffered glycolic acid and botanical ingredients for the treatment of mild acne. In this single-center, open-label clinical study, 25 male and female volunteers used the test cleanser and test gel twice daily over six weeks. Tolerability assessments showed that the skin care regimen was very well tolerated by all study volunteers. Acne severity was significantly reduced by two acne grades at six weeks. Inflammatory lesion counts were significantly reduced, on average, by 59.06% (P ≤ 0.0001), 91.62% (P ≤ 0.0001), 90.85% (P ≤ 0.0001) and by 98.55% (P ≤ 0.0001) at weeks 1, 2, 4, and 6, respectively. Non-inflammatory lesion counts were reduced, on average, by 13.54% (ns), 38.95% (P ≤ 0.0001), 44.48% (P ≤ 0.0001), and by 56.10% (P ≤ 0.0001) at weeks 1, 2, 4, and 6, respectively. Standardized photography also demonstrated a progressive reduction in acne lesions over time. In conclusion, results of the present study suggest that the tested skin care regimen offers rapid acne clearance and excellent tolerability that together may help to improve patient adherence as well as treatment outcome.

Topical salicylic acid is often used in dermatologic conditions because of its keratolytic, bacteriostatic, fungicidal, and photoprotective properties. The bioavailability of salicylic acid differs depending on the vehicle used and pH of transcellular fluids. Although rare, salicylic acid toxicity (salicylism) can occur from topical application. Physicians should be mindful of the potential for salicylism or even death from topically applied salicylic acid., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: This study was performed to explore the mechanism underlying tinnitus by investigating the changes in the synaptic ribbons and RIBEYE expression in cochlear inner hair cells in salicylate-induced tinnitus., Methods: C57BL/6J mice were injected with salicylate (350 mg/kg) for 10 days and grouped. Behavioral procedures were performed to assess whether the animals experienced tinnitus. The specific presynaptic RIBEYE protein and non-specific postsynaptic glutamate receptor 2&3 protein in basilar membrane samples were examined by immunofluorescent labeling. RT-PCR and Western blot assays were used to examine RIBEYE expression. Serial sections were used to build three-dimensional models using 3ds MAX software to evaluate the changes in the synaptic ribbons., Results: The administration of salicylate increased false positives in the behavioral procedure from 3 d to 10 d. The membrane profiles of inner hair cells in all mice were intact. The number of synaptic ribbons in the salicylate group increased on the 7(th) d and decreased on the 9(th) and 10(th) d. mRNA and protein expression of RIBEYE were initially up-regulated and later down-regulated by injecting salicylate for 10 consecutive days., Conclusion: This change in the ribbon synapses of cochlear inner hair cells in salicylate-induced mice might serve as a compensatory mechanism in the early stages of ototoxicity and contribute to tinnitus later. The alteration of RIBEYE expression could be responsible for the changes in the morphology of ribbon synapses and for salicylate-induced tinnitus., (© 2014 S. Karger AG, Basel.)

Salicylic acid is a classic nonsteroidal anti-inflammatory drug. Although salicylic acid also induces mitochondrial injury, the mechanism of its antimitochondrial activity is not well understood. In this study, by using a one-step affinity purification scheme with salicylic acid-immobilized beads, ferrochelatase (FECH), a homodimeric enzyme involved in heme biosynthesis in mitochondria, was identified as a new molecular target of salicylic acid. Moreover, the cocrystal structure of the FECH-salicylic acid complex was determined. Structural and biochemical studies showed that salicylic acid binds to the dimer interface of FECH in two possible orientations and inhibits its enzymatic activity. Mutational analysis confirmed that Trp301 and Leu311, hydrophobic amino acid residues located at the dimer interface, are directly involved in salicylic acid binding. On a gel filtration column, salicylic acid caused a shift in the elution profile of FECH, indicating that its conformational change is induced by salicylic acid binding. In cultured human cells, salicylic acid treatment or FECH knockdown inhibited heme synthesis, whereas salicylic acid did not exert its inhibitory effect in FECH knockdown cells. Concordantly, salicylic acid treatment or FECH knockdown inhibited heme synthesis in zebrafish embryos. Strikingly, the salicylic acid-induced effect in zebrafish was partially rescued by FECH overexpression. Taken together, these findings illustrate that FECH is responsible for salicylic acid-induced inhibition of heme synthesis, which may contribute to its antimitochondrial and anti-inflammatory function. This study establishes a novel aspect of the complex pharmacological effects of salicylic acid.