Percutaneous penetration of squaric acid and its esters in hairless mouse and human skin in vitro

Summary Squaric acid diethylester and squaric acid dibutylester have been used in contact sensitization therapy of alopecia areata. This study investigated the application of these esters or squaric acid alone to hairless mouse and human skin in vitro to determine squaric acid flux from the various preparations. Measurable amounts of squaric acid were delivered through skin by squaric acid itself, but flux was lower than for that delivered by the two esters. These results support the proposal by Noster that the esters combine with a protein to form an antigen while squaric acid can not and that this explains why the esters are active in contact sensitization and the acid is not. We suggest that the results of previous studies showing that the diethyl ester of squaric acid was a less effective sensitizer than the dibutyl ester may have been due to decomposition of the ethyl ester to squaric acid.     

A retrospective assessment and comparison of the effectiveness of benzoyl peroxide; the combination of topical niacinamide,gallic acid,and lauric acid; and the combination of benzoyl peroxide and erythromycin in acne vulgaris

Acne vulgaris is a chronic inflammatory skin disease that mostly develops during adolescence and continues throughout adulthood. It affects the face, the main location of cosmetic appearance. Despite many developments in acne treatment, various combination therapies are needed to create the best option. Ninety patients were included in this study. We used the global acne grading system (GAGS) and the lesion counting and photographic standards that were used by Hayashi et al., to assess acne severity. The patients were randomly divided into three groups as group 1 (using only 5% BPO, twice a day), group 2 (using only the combination of 5% BPO + 3% erythromycin, twice a day), and group 3 (using only the combination of 4% niacinamide + 1% gallic acid + 1% lauric acid, twice a day). Thirty patients were included in each group. The scores were evaluated at weeks 0, 2, 4 and 8, and compared with each other. As a result of the study, all three treatment types were found to be effective. The combination of 4% niacinamide + 1% gallic acid + 1% lauric acid can be used as an alternative topical treatment for acne vulgaris to prevent resistance against topical antibiotics and the side effects of some other treatments.     

Biological effects and metabolism of 9-cis-retinoic acid and its metabolite 9,13-di-cis-retinoic acid in HaCaT keratinocytes in vitro: comparison with all-trans-retinoic acid

Abstract 9-cis-Retinoic acid (9cRA), a geometric isomer of all-trans-retinoic acid (atRA), is an endogenous high-affinity ligand for retinoid X receptors and retinoic acid receptors activating them with high potency. 9,13-di-cis-Retinoic acid (9,13dcRA) has been described as a major plasma metabolite of 9cRA. In this study, the biological activity and the metabolism of 9cRA and 9,13dcRA were investigated and compared with those of atRA in a retinol-free culture system of HaCaT keratinocytes. 9cRA exhibited a slightly weaker activity overall than atRA in inhibiting cell proliferation, inducing cellular retinoic acid binding protein II (CRABP II) mRNA levels and upregulating cytokeratin 19 expression. 9,13dcRA regulated HaCaT keratinocyte activity only at the highest concentration tested (10^–6 M). In cultures of HaCaT keratinocytes with atRA and 9cRA, rapid intracellular accumulation of atRA was observed within 2 h, and atRA levels were higher with atRA treatment than with 9cRA treatment. 9,13dcRA remained relatively stable in the medium with intracellular 9,13dcRA levels below the level of detection. Taken together, 9cRA seems to be slightly less potent than atRA in regulating the biological activity of HaCaT keratinocytes, while its metabolite 9,13dcRA is effectively inactive at biologically relevant concentrations. Our data suggest a prodrug/drug relationship between 9cRA and atRA in human keratinocytes. 9,13dcRA seems to be a weaker prodrug of atRA or an inactive metabolic derivative. Received: 6 July 2000 / Revised: 8 September 2000 / Accepted: 25 October 2000     

Anti-bacterial and anti-inflammatory properties of capric acid against Propionibacterium acnes: A comparative study with lauric acid

BackgroundPropionibacterium acnes (P. acnes) is a commensal bacterium which is possibly involved in acne inflammation. The saturated fatty acid, lauric acid (C12:0) has been shown to possess antibacterial and anti-inflammatory properties against P. acnes. Little is known concerning the potential effects of its decanoic counterpart, capric acid (C10:0).ObjectiveTo examine the antibacterial and anti-inflammatory activities of capric acid against P. acnes and to investigate the mechanism of the anti-inflammatory action.MethodsThe antimicrobial activity of fatty acids was detected using the broth dilution method. An evaluation of P. acnes-induced ear edema in mice was conducted to evaluate the in vivo anti-inflammatory effect. To elucidate the in vitro anti-inflammatory effect, human SZ95 sebocytes and monocytic THP-1 cells were treated with P. acnes alone or in the presence of a fatty acid. The mRNA levels and secretion of pro-inflammatory cytokines were measured by qRT-PCR and enzyme immunoassay, respectively. NF-κB activation and MAPK expression were analyzed by ELISA and Western blot, respectively.ResultsLauric acid had stronger antimicrobial activity against P. acnes than capric acid in vitro and in vivo. However, both fatty acids attenuated P. acnes-induced ear swelling in mice along with microabscess and significantly reduced interleukin (IL)-6 and CXCL8 (also known as IL-8) production in P. acnes-stimulated SZ95 sebocytes. P. acnes-induced mRNA levels and secretion of IL-8 and TNF-α in THP-1 cells were suppressed by both fatty acids, which inhibited NF-κB activation and the phosphorylation of MAP kinases.ConclusionOur data demonstrate that both capric acid and lauric acid exert bactericidal and anti-inflammatory activities against P. acnes. The anti-inflammatory effect may partially occur through the inhibition of NF-κB activation and the phosphorylation of MAP kinases.     

Effect of folic or folinic acid supplementation on methotrexate-associated safety and efficacy in inflammatory disease: a systematic review

Background Methotrexate is a folic acid antagonist widely used for the treatment of inflammatory disorders for more than 50 years. Methotrexate is a standard systemic therapy for severe psoriasis and rheumatoid arthritis. Folic acid supplementation has been advocated to limit the toxicity of methotrexate on blood cells, gastrointestinal tract and liver. However, there is still controversy regarding the usefulness of folic acid supplementation. Objectives We sought to assess the evidence for the efficacy of folic acid supplementation in patients treated with methotrexate for inflammatory diseases. We also investigated whether folic acid supplementation may decrease the efficacy of methotrexate. Methods Cochrane and MEDLINE databases were systematically searched. Randomized controlled trials in patients treated with methotrexate for rheumatoid arthritis or psoriasis with or without arthritis were included. Study selection, assessment of methodological quality, data extraction and analysis were carried out by two independent researchers. We selected double‐blind randomized placebo‐controlled trials. Analysis was performed for each subgroup of side‐effects: gastrointestinal, mucocutaneous, haematological and hepatic. Results Six randomized controlled trials met the inclusion criteria, with a total sample of 648 patients. There were 257 patients in the placebo group, 198 patients treated with folic acid, and 193 patients treated with folinic acid. The statistical analysis showed a significant reduction of 35·8% of hepatic side‐effects induced by methotrexate for patients with supplementation with folic or folinic acid (95% confidence interval ?0·467 to ?0·248). There was no statistical difference for mucocutaneous and gastrointestinal side‐effects although there was a trend in favour of supplementation. The effect of supplementation on haematological side‐effects could not be assessed accurately due to a low incidence of these events in the population studied. We were unable to analyse the effect of supplementation on the effectiveness of methotrexate, as markers of activity used in each study were not comparable. Conclusions Supplementation with folic acid is an effective measure to reduce hepatic adverse effects associated with methotrexate treatment. There is no difference between folinic acid and folic acid, but the lower cost of the latter promotes its use.     

Efficacy and safety of serial glycolic acid peels and a topical regimen in the treatment of recalcitrant melasma

Melasma is a common acquired disorder of facial hyperpigmentation. In this study we investigated the efficacy and safety of a combined treatment regimen including serial glycolic acid peels, topical azelaic acid cream and adapalene gel in the treatment of recalcitrant melasma. Twenty-eight patients with recalcitrant melasma were enrolled in a prospective, randomized, controlled trial lasting 20 weeks. The patients of the group receiving chemical peels underwent serial glycolic acid peels in combination with topical azelaic acid 20% cream (b.i.d.) and adapalene 0.1% gel (q.i.d., applied at night). The control group received only topical treatment including topical azelaic acid and adapalene. The clinical improvement was assessed with the Melasma Area Severity Index (MASI) at baseline and monthly during the 20-week treatment period. The results showed a prominent decrease in MASI scores at the end of the treatment in both groups, although the results were better in the group receiving chemical peels (P=0.048). All patients tolerated the topical agents well with minimal irritation observed in the first few weeks of the therapy. Three patients in the glycolic acid peel group developed a mild-degree postinflammatory hyperpigmentation with total clearance at the end of the treatment period. Therefore, the present study suggests that combined treatment with serial glycolic acid peels, azelaic acid cream and adapalene gel should be considered as an effective and safe therapy in recalcitrant melasma.     

Efficacy and safety of a facial serum and a mask containing salicylic acid and lipohydroxy acid in acne management: A randomized controlled trial

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.     

Long-term systemic therapy with dimethylfumarate and monoethylfumarate (Fumaderm®) in psoriasis

Objective The aim of this study was to assess the clinical efficacy of long-term (> 6 months) oral fumarate maintenance treatment regimen and to determine its adverse effect profile. Background We previously showed the efficacy of oral fumarate treatment in psoriasis. However, little is known about long-term maintenance therapy with oral fumarates. Because of concern about renal toxicity and/or other potentially hazardous adverse effects, their role in the long-term management of psoriasis is still controversial and limited. Methods Clinical data and laboratory parameters of 83 psoriasis patients who were treated with oral fumarates during an uninterrupted period of 6 or more months, were collected and subsequently analysed. Results In 31 of the 83 patients the oral fumarate therapy was discontinued preliminarily (<6 months) because of intolerable adverse effects (9 patients), lack of clinical efficacy (16 patients), insurance refunding problems (4 patients) and lost to follow-up (2 patients), A major improvement of the psoriasis was present in 41 of the 83 patients. Long-term oral fumarate maintenance therapy was accompanied by subjective adverse effects, mainly flushing (28 patients) and gastrointestinal upset (15 patients) and by a relative lymphocytopenia (35 patients). Conclusion Oral fumarates are effective well tolerated drugs suitable for long-term management of psoriasis. However, this systemic therapy still has to be considered experimental and should only be performed under strictly controlled conditions. The cause and the clinical relevance of the relative lymphocytopenia, which occurs in a high percentage of patients during long-term oral fumarate maintenance treatment regimen are unknown and still have to be determined.     

Perioral contact urticaria from sorbic acid and benzoic acid in a salad dressing

Contact urticaria was observed in a kindergarten in 18 of 20 children following the intake and accidental perioral application of a mayonnaise salad cream. In healthy adult controls, stinging tests and closed 20 minute patch test with the salad dressing were positive in 9 out of 12 and 4 out of 10 cases respectively. Twenty minute patch tests with the different components of the salad dressing were positive only so sorbic acid (SA) and benzoic acid (BA). Urticaria was provoked by inunction of the salad dressing periorally in two healthy boys. Serial 20 minute closed patch testing with varying concentrations of SA in 91 patients and BA in 41 patients gave almost identical results: positive reactions in two thirds of the patients with the highest concentrations. The response was only partially blocked by anti-histamine applied locally before testing. Non-immunologic mechanisms are probably responsible for the transient reaction, and no restriction in the extensive use of SA or BA as preservatives in food should be considered.     

Contact urticaria from Synthetic cassia oil and sorbic acid limited to the face

A patient with contact urticaria with skin and respiratory symptoms was found to be sensitive to both sorbic acid and synthetic oil of cassia. The contact urticaria was only elicitable on intact skin of the face by open testing. The source of the patient's contactants was her shampoo and toothpaste.     

Acquired partial lipodystrophy treated with poly-L-lactic acid and hyaluronic acid fillers: a case report

Acquired partial lipodystrophy (APL), also known as Barraquer-Simons syndrome, is a rare disorder characterized by progressive fat loss in the upper body. Use of poly-L-lactic acid and hyaluronic acid (HA) fillers for the treatment of APL is neither approved by the Food and Drug Administration nor described in the literature. Herein, we describe a case of APL that achieved significant improvement in facial volume following treatment with combination poly-L-lactic acid and HA fillers.     

Topical aminolaevulinic acid- and aminolaevulinic acid methyl ester-based photodynamic therapy with red and violet light: influence of wavelength on pain and erythema

Background Photodynamic therapy (PDT) is based on the combination of an exogenously administered precursor of photosensitizer [protoporphyrin IX (PpIX)] synthesis and exposure to light. Choosing the optimal wavelength is important. Red light penetrates deeper into tissue, while violet light is more efficient in activating PpIX but does not penetrate so deeply. Objectives We studied PpIX formation and the PDT effect after application to human skin of creams containing aminolaevulinic acid (ALA) and aminolaevulinic acid methyl ester (MAL). The aim of the study was to investigate whether the wavelength of the light used has an influence on pain sensations during topical PDT with the different prodrugs. Methods ALA cream (10%) and MAL cream (10%) were topically applied on the skin of 10 healthy volunteers. After 24 h the application site was exposed to 8 mW cm⁻² violet laser or to 100 mW cm⁻² red laser light. The erythema index was monitored up to 24 h after light exposure. For the first time the pain during topical ALA‐ and MAL‐PDT was assessed by measuring the time taken for pain to occur. Also, for the first time, the intensities of the light sources were calibrated so as to have the same relative quantum efficiency. Results The pain sensation during ALA‐PDT with red light came 22 s sooner than during ALA‐PDT with violet light, which is statistically significant (P < 0·05). Moreover, ALA‐PDT with red light gave stronger and more persistent erythema than ALA‐PDT with violet light. ALA induced about three times more PpIX than MAL. No statistically significant differences were found for erythema, or for the time for pain to occur, in the case of MAL‐PDT with red vs. violet light. Conclusions Topical ALA‐PDT with violet light allows longer exposure times before pain is induced and gives less erythema as compared with topical ALA‐PDT with red light.     

Contact allergy to atranorin in lichens and perfumes

Atranorin, one of the most common lichen substances, gave positive patch test reactions in eight subjects (1 %) in a routine series. These subjects also reacted to fumarprotocetraric acid and some of them to evernic acid. Stictic acid and usnic acid gave negative reactions. The lichen oak moss Evernia prunastri and an oak moss perfume gave positive reactions. Thin-layer chromatography and a spot test indicated that atranorin is present in oak moss perfumes which are made from oak moss and tree moss. Contact with oak moss perfumes and lichens in nature may cause atranorin allergy. None of the eight subjects had a history of light sensitivity or atopy and none had chronic facial eczema.     

熊果酸和齐墩果酸抗性器官和呼吸系肿瘤作用

熊果酸和齐墩果酸是化学立体结构相同的同分异构体。它们广泛存在于各种植物之中,是一类生物活性广、毒副作用甚低的活性成分。具有促进机体免疫功能和广谱抗肿瘤作用,如具有抗乳腺癌、抗宫颈癌、子宫内膜癌、抗前列腺癌和抗鼻咽癌、抗肺癌等作用。熊果酸和齐墩果酸对肿瘤细胞既有选择性细胞毒作用、引起肿瘤细胞坏死,又有诱导凋亡和分化作用。本文综述它们的抗性器官和呼吸系肿瘤作用及机制研究进展。     

Linoleic acid and α-linolenic acid lightens ultraviolet-induced hyperpigmentation of the skin

Abstract This study was conducted to evaluate the effects of unsaturated fatty acids on ultraviolet-induced hyperpigmentation of the skin. An efficient lightening effect was observed following topical application of linoleic acid or α-linolenic acid to UV-stimulated hyperpigmented dorsal skin of brownish guinea pigs. The number of melanocytes in the treated skin was similar to the number in the skin of the pigmented control, indicating that the pigment-lightening effect was not due to depletion of melanocytes. In vitro experiments using cultured murine melanoma cells showed that melanin production was inhibited most effectively by α-linolenic acid, followed by linoleic acid and then by oleic acid. Furthermore, the turnover of the stratum corneum, which plays an important role in the removal of melanin pigment from the epidermis, was accelerated by linoleic acid and by α-linolenic acid. Taken together, the results suggest that the pigment-lightening effects of linoleic acid and α-linolenic acid are, at least in part, due to suppression of melanin production by active melanocytes, and to enhanced desquamation of melanin pigment from the epidermis. Received: 8 October 1997