A randomized controlled double-blinded split-face prospective clinical trial to assess the efficacy, safety, and tolerability of a novel 3-step routine compared to benzoyl peroxide for the treatment of mild to moderate acne vulgaris.

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.

Application of cantharidin, retinoic acid cream and salicylic acidy in multiple palmoplantar warts.

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.

Topical Silymarin Cream as a Novel Therapy Versus Salicylic Acid Peels in Acne Vulgaris: A Split-Face Clinical Trial.

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.

Therapeutic efficacy and safety of three different modalities in pediatric patients with plantar warts.

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.

An interim internal Threshold of Toxicologic Concern (iTTC) for chemicals in consumer products, with support from an automated assessment of ToxCast™ dose response data.

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.

Effects of irrigation water salinity and salicylic acid on germination and vigor of Mesosphaerum suaveolens (L. ) Kuntze / Efeitos da salinidade da água de irrigação e do ácido salicílico na germinação e no vigor de Mesosphaerum suaveolens (L. ) Kuntze

Salinity is one of the factors that negatively impact plant growth and productivity; therefore, it is necessary to seek solutions that help mitigate the degenerative action of saline stress on crops. The objective of this study was to evaluate the effects of salicylic acid (SA) on the germination and vigor of Mesosphaerum suaveolens (L.) Kuntze seeds subjected to salinity. The experiment was carried out using a completely randomized design, in an incomplete 5 × 5 factorial scheme, with five levels of electrical conductivity of irrigation water (ECw - 0.0, 1.45, 5.00, 8.55, and 10.00 dS m-1) and five doses of SA (0.0, 0.29, 1.00, 1.71, and 2.00 mM), with four replications of 50 seeds, totaling nine combinations generated via a central composite design. The germination percentage, first germination count, germination speed index, average germination time, percentage of abnormal seedlings, shoot, root, and seedling lengths, and total seedling dry mass were evaluated. Salicylic acid attenuated the effect of saline stress on initial growth, mitigating damage to root and shoot lengths. Seed priming with salicylic acid improved germination and seed vigor.(AU)

A salinidade é um dos fatores que promove a inibição no crescimento e produtividade vegetal, sendo necessária a busca por alternativas que auxiliem na mitigação da ação degenerativa do estresse salino às culturas. Objetivou-se com este trabalho avaliar doses de ácido salicílico na germinação e vigor de sementes de Mesosphaerum suaveolens (L.) Kuntze submetidas à salinidade. O experimento foi conduzido em delineamento inteiramente casualizado, em esquema fatorial incompleto 5 x 5, com cinco níveis de condutividade elétrica da água de irrigação (CEa de 0,0; 1,45; 5,00; 8,55 e 10,00 dS m-1) e cinco doses de AS de (0,0; 0,29; 1,00; 1,71 e 2,00 mM L-1), com quatro repetições de 50 sementes, totalizando nove combinações geradas via matriz Composto Central de Box. As variáveis avaliadas foram: porcentagem de germinação, primeira contagem de germinação, índice de velocidade de germinação, tempo médio de germinação, porcentagem de plântulas anormais, comprimento da parte aérea, radícula e plântula e massa seca total de plântulas. O ácido salicílico atenua o efeito do estresse salino sobre o crescimento inicial, mitigando os danos sobre o comprimento de radícula e da parte aérea. O tratamento das sementes com ácido salicílico melhora a germinação e o vigor das sementes.(AU)

Biochemical and physiological responses induced in Mytilus galloprovincialis after a chronic exposure to salicylic acid.

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.

Combined effect of 24-epibrassinolide and salicylic acid mitigates lead (Pb) toxicity by modulating various metabolites in Brassica juncea L. seedlings.

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.

Bioactive food chemicals and gastrointestinal symptoms: a focus of salicylates.

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.

Low-dose 5-fluorouracil in combination with salicylic acid for the treatment of actinic keratoses on the hands and/or forearms - results of a non-interventional study.

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.

Actikerall™ (5-Fluorouracil 0.5% and Salicylic Acid 10%) Topical Solution for Patient-directed Treatment of Actinic Keratoses.

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.

Hormonal and organ-specific dysfunction induced by the interaction between titanium dioxide nanoparticles and salicylic acid in male mice.

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.

Comparative Evaluation of Efficacy and Tolerability of Glycolic Acid, Salicylic Mandelic Acid, and Phytic Acid Combination Peels in Melasma.

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.

A prospective randomized exploratory study comparing the efficacy of once-daily topical 0.5% 5-fluorouracil in combination with 10.0% salicylic acid (5-FU/SA) vs. cryosurgery for the treatment of hyperkeratotic actinic keratosis.

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.

Salicylic acid induces mitochondrial injury by inhibiting ferrochelatase heme biosynthesis activity.

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.

Comparative evaluation of topical calcipotriol versus coal tar and salicylic acid ointment in chronic plaque psoriasis.

BACKGROUND: Calcipotriol is a newer topical treatment option available for plaque psoriasis and coal tar being one of the oldest treatment and still in use. AIMS: To evaluate and compare the differences in terms of efficacy, safety and relapse with Calcipotriol 0.005% (50 mcg/gm) and 6% coal tar and 3% salicylic ointment in patients with Plaque psoriasis. SETTING and DESIGNS: Study conducted on 60 patients of plaque psoriasis, who attended the skin OPD in our hospital. METHODS: The patients with mild to moderate plaque psoriasis were selected. 60 patients were enrolled for the study after obtaining informed consent. Subjects were asked to apply Calcipotriol 0.005% (50 mcg/gm) (Heximar Win care) twice a day on the right side plaques and on left side plaques, Petroleum jelly (Vaseline) in the morning and 6% coal tar and 3% salicylic ointment (Protar® Percos) at nighttime. PASI score was used to assess the reponse to therapy at 2nd, 4th, 6th and 8th week. After treatment subjects were observed for 6 weeks for any relapse. STATISTICAL ANALYSIS: It was done by paired t-test and independent sample t-test. CONCLUSIONS: The results showed that statistically significant difference was seen in the mean percentage reduction of PASI score between both the groups, at all the assessment visits, 2, 4, 6, and 8 weeks, the mean percentage reduction at 2 weeks for calcipotriol being 21±12.06 and for coal tar being 13.44±11.19 (P=0.000), at 4 weeks for calcipotriol was 40±16.71 and for coal tar 25±99 (P=0.000), at 6 weeks for calcipotriol was 53.99+-22.43 and for coal tar 41±21.23 (P=0.002), at 8 weeks for calcipotriol was 62.73±24.04 and for coal tar was 51.53±23.27 (P=0.11). Relapse was seen in 5/60 (8.3%) of patients on calcipotriol treated side and 9/60 (15%) of patients with coal tar treated side. Thus it can be concluded that calcipotriol cream is more efficacious when compared with coal tar and does have a quick response. It is well tolerated and acceptable cosmetically.

Tolerance and efficacy of a product containing ellagic and salicylic acids in reducing hyperpigmentation and dark spots in comparison with 4% hydroquinone.

Hydroquinone (HQ) is the benchmark prescription agent for skin lightening. However, HQ use is recently banned in Europe and in parts of Asia because of potential long-term consequences, including carcinogenesis when orally consumed. This has resulted in development of alternative skin-lightening agents with comparable efficacy to HQ, but better safety profiles. This study examined the skin-lightening ability of a topical product containing 0.5% ellagic acid and 0.1% salicylic acid and compared its efficacy with that of a prescription generic 4% HQ product. Fifty-four multiethnic subjects were randomly assigned to use the topical test formulation or generic 4% HQ twice daily for 12 weeks to evaluate product tolerability and efficacy. Under the conditions of this double-blinded clinical study, the test product demonstrated comparable tolerance and efficacy to that of a benchmark product 4% HQ, as assessed by clinical grading, physical measurement of spot size using image analysis, and questionnaire response analysis. This study suggests that this new product provided comparable skin depigmentation benefit to the benchmark product. In addition, the product appears to have better esthetics (texture, pleasantness to use, skin feel) than the 4% HQ product.

Single-center, open-label study of a proprietary topical 0.5% salicylic acid-based treatment regimen containing sandalwood oil in adolescents and adults with mild to moderate acne.

BACKGROUND: A proprietary topical blend of salicylic acid and highly purified sandalwood oil from Australia was used in this open-label study in adolescents and adults with mild to moderate facial acne. METHODS: The investigational regimen consisted of a foaming cleanser, an acne serum, a spot treatment, and a mask. Patients applied the treatment regimen as directed for 8 weeks. The primary efficacy measure was the percentage of patients assessed as improved, much improved, or very much improved according to the Global Aesthetic Improvement Scale (GAIS) ratings at week 8. Severity was rated using the Evaluator's Global Severity Scores (EGSS) at baseline and weeks 2, 4, and 8. Tolerability was assessed at baseline and weeks 2, 4, and 8 by asking patients to rate the severity of itching, scaling, erythema, burning, dryness, and stinging. Patients were also asked to complete an acne questionnaire. RESULTS: 89.4% (42/47) met the primary end point determined by the GAIS of improved (66%), much improved (19%), or very much improved (4%). Notable reductions in lesion counts were observed in patients with more severe or inflamed lesions. Tolerability was queried at all visits. No itching, scaling, or erythema was reported after initial application. Symptoms of intolerability peaked at week 2; however, most events were mild to moderate and were typically reported with use of the mask component. Intolerance decreased by week 4 and by week 8. The treatment regimen was well tolerated by patients. CONCLUSIONS: Results from this study support the use of a proprietary investigational regimen in patients with mild to moderate acne and warrant further investigation to determine whether longer-term therapy (ie, beyond 8 weeks) results in enhanced efficacy with minimal side effects, leading to continued patient compliance and skin improvement.

Low-dose 5-fluorouracil in combination with salicylic acid as a new lesion-directed option to treat topically actinic keratoses: histological and clinical study results.

BACKGROUND: Actinic keratoses (AKs) arise after chronic sun exposure. Because long-term ultraviolet (UV) damage may induce proliferation of atypical keratinocytes, treatment of AKs is recommended. OBJECTIVES: To compare 5-fluorouracil 0·5%/salicylic acid 10·0% [low-dose 5-FU/SA (Actikerall®)] with diclofenac 3% in hyaluronic acid (diclofenac HA) and vehicle for the treatment of AKs. METHODS: This was a randomized, placebo-controlled, double-blind, parallel-group, multicentre trial. Patients received topical low-dose 5-FU/SA once daily, its vehicle or diclofenac HA twice daily for a maximum of 12 weeks. The final evaluation was at week 20. The primary objectives were to demonstrate the histological clearance rate of one predefined lesion. The secondary objectives were the improvement of treated lesions, tolerability and safety. RESULTS: There were 470 patients with 4-10 AK lesions each (grade I or II) on the face/forehead or bald scalp included in the study. Low-dose 5-FU/SA was superior to diclofenac HA (P < 0·01) and vehicle (P < 0·0001) for histological clearance of one representative lesion 8 weeks post-treatment. In 72·0%, 59·1% and 44·8% of patients in the low-dose 5-FU/SA, diclofenac HA and vehicle groups, respectively, the week-20 biopsy revealed no AKs. Significantly more lesions were cleared with low-dose 5-FU/SA (74·5%) compared with diclofenac HA (54·6%; P < 0·001) or vehicle (35·5%; P< 0·001). Low-dose 5-FU/SA was superior in terms of complete clinical clearance: 55·4%, vs. diclofenac HA (32·0%, P < 0·001) and vehicle (15·1%P < 0·001). Application-site disorders (mainly burning and inflammation) were more frequent with low-dose 5-FU/SA but mainly of mild to moderate intensity. CONCLUSIONS: Topical low-dose 5-FU/SA demonstrated higher histological and clinical clearance rates vs. diclofenac HA or vehicle. Low-dose 5-FU/SA is an effective lesion-directed treatment for AKs.

Efficacy and safety of a new topical keratolytic treatment for localized hyperkeratosis in adults.

BACKGROUND: Palmoplantar keratoderma (PPK) is a heterogeneous group of skin disorders characterized by symmetrical diffuse or patchy areas of hyperkeratosis on the palms and soles. This study aimed to evaluate the efficacy and safety of a topical keratolytic treatment for localized hyperkeratosis. METHODS: International, randomized, vehicle-controlled, double-blind, intra-individual comparative study. RESULTS: Clinical signs assessed by the investigator significantly improved in both group from baseline to day 10 and day 21 (P<0.001). Mean improvement was significantly more marked on the treated side than the control side (except pruritus) at day 10 for hyperkeratosis (-0.58 ± 0.59 versus -0.41 ± 0.51, P=0.009), desquamation (-0.62 ± 0.69 versus -0.47 ± 0.67, P=0.042) and dryness (-0.75 ± 0.67 versus -0.57 ± 0.67, P=0.014). At day 21, dryness (-1.16 ± 0.80 versus -1.00 ± 0.79, P=0.036) was significantly improved but only a trend for hyperkeratosis (-0.86 ± 0.76 versus -0.72 ± 0.72, P=0.158) and desquamation (-0.83 ± 0.85 versus -0.65 ± 0.85, P=0.057) was observed. Tolerance was considered to be good or very good in more than 92 percent patients. Both patients and investigators were satisfied in more than 84 percent of cases with the topical keratolytic treatment efficacy. Safety profile was highly satisfactory. CONCLUSION: This topical keratolytic treatment represents a valuable first-line option for mild to moderate hyperkeratosis.