Combination therapy with butyrate and docosahexaenoic acid for keloid fibrogenesis: an in vitro study

Abstract: Background: A single, effective therapeutic regimen for keloids has not been established yet, and the development of novel therapeutic approaches is expected. Butyrate, a short-chain fatty acid, and docosahexaenoic acid (DHA), a ω-3 polyunsaturated fatty acid, play multiple anti-inflammatory and anticancer roles via their respective mechanisms of action. Objective: In this study, we evaluated the antifibrogenic effects of their single and combined use on keloid fibroblasts. Methods: Keloid fibroblasts were treated with butyrate (0-16 mM) and/or DHA (0-100 µM) for 48 or 96 h. Results: Butyrate inhibited cell proliferation, and α-smooth muscle actin (α-SMA) and type III collagen expressions, with inhibition of the transforming growth factor (TGF)-β1 and TGF-β type I receptor expressions and increased prostaglandin E2 with upregulation of cyclooxygenase-1 expression with induction of histone acetylation. DHA inhibited α-SMA, type III collagen, and TGF-β type I receptor expressions. Then, the butyrate/DHA combination augmented the antifibrogenic effects, resulting in additional inhibition of α-SMA, type I and III collagen expressions, with strong disruption of stress fiber and apoptosis induction. Moreover, the butyrate/DHA combination inhibited the cyclooxygenase-2 expression, suggesting stronger anti-inflammatory effect than each monotherapy. Study limitations: Activation in keloid tissue is affected not only by fibroblasts but also by epithelial cells and immune cells. Evaluation of the effects by butyrate and DHA in these cells or in an in vivo study is required. Conclusion: This study demonstrated that butyrate and docosahexaenoic acid have antifibrogenic effects on keloid fibroblasts and that these may exert therapeutic effects for keloid.

Hsp70 Knockdown by siRNA Decreased Collagen Production in Keloid Fibroblasts

PURPOSE: There are currently no consistently effective treatments for the excessive collagen produced by keloid fibroblasts. Previously, we reported that heat shock protein 70 (Hsp70) is up-regulated in keloid fibroblasts and keloid tissue. We, therefore, investigated whether Hsp70 is related to excessive collagen production in keloid fibroblasts. MATERIALS AND METHODS: We inhibited Hsp70 in keloid fibroblasts by RNA interference and examined the resulting collagen expression. Thus, we selected small interfering RNAs (siRNAs) specific for human Hsp70, transfected them into keloid fibroblasts, and evaluated the resulting phenotypes and protein production using real-time polymerase chain reaction (PCR), Western blot, and a collagen assay. RESULTS: The siRNAs dramatically suppressed Hsp70 mRNA expression, resulting in a decrease in collagen production in the keloid fibroblasts compared with controls. The siRNAs did not influence the viability of the keloid fibroblasts. CONCLUSION: Hsp70 overexpression likely plays an important role in the excessive collagen production by keloid fibroblasts. RNA interference has therapeutic potential for the treatment of keloids.

Results of a combination of bleomycin and triamcinolone acetonide in the treatment of keloids and hypertrophic scars / Resultados de uma combinação de bleomicina e triamcinolone acetonide no tratamento de quelóides e cicatrizes hipertróficas

While treatment of keloids and hypertrophic scars normally shows modest results, we found that treatment with bleomycin was more promising. The present study was divided into two parts. In the first part the aim was to show the results using a combination of bleomycin and triamcinolone acetonide per cm2 (BTA). In the second part the objective was to determine the response to both drugs in large keloids that were divided into 1 cm2 squares, treating each square with the dose previously used. In the first part of the study, the clinical response of 37 keloids ranging from 0.3 to 1.8 cm2 treated with BTA were followed up over a period of 1- 2 years. 0.375 IU bleomycin and 4 mg triamcinolone acetonide were injected every 3 months. In the second part of the study we reviewed the clinical response in six patients with large keloids. The monthly dose administered never exceeded 3 IU of bleomycin. The first study showed 36 keloids (97.29%) softening after the first dose. In the second study, 5 showed different responses (the response was complete in the four smaller keloids). The largest keloid needed 9 doses to achieve an improvement of 70%. In conclusion, combined treatment with 0.375 IU of bleomycin and 4mg of triamcinolone acetonide to 1 cm2 was considered to be an acceptable procedure for the treatment of keloids. The best results were obtained in keloids over 1 cm2 or when divided into 1 cm2 square areas. Larger series need to be performed in order to confirm these results..

Enquanto normalmente o tratamento de queloides e cicatrizes hipertróficas mostra resultados moderados, o tratamento com bleomicina revelou resultados mais promissores. Este estudo foi dividido em duas partes. Na primeira parte, o objetivo foi mostrar os resultados da utilização de uma combinação de bleomicina e acetonido de triancinolona por cm2 (BAT). Na segunda parte, o objetivo foi determinar a resposta aos dois medicamentos em queloides grandes, que foram divididos em quadrados de 1 cm2, tratando cada quadrado com a dose utilizada anteriormente. Na primeira parte do estudo, a resposta clínica de 37 queloides de 0,3 to 1,8 cm2 tratados com BAT foi monitorada por um período de 1 a 2 anos. Injeções de 0,375 UI de bleomicina e 4 mg de acetonido de triancinolona foram aplicadas a cada 3 meses. Na segunda parte do estudo, revisamos a resposta clínica em 6 pacientes com queloides grandes. A dose mensal administrada nunca excedeu 3 UI de bleomicina. O primeiro estudo mostrou que 36 queloides (97,29%) amoleceram após a primeira dose. No segundo estudo, 5 mostraram diferentes respostas (a resposta foi completa nos quatro queloides menores). O queloide maior necessitou de 9 doses para apresentar melhora de 70%. Concluindo, o tratamento combinado com 0,375 UI de bleomicina e 4 mg de acetonido de triancinolona por cm2foi considerado um procedimento aceitável para o tratamento de queloides. Os melhores resultados foram obtidos em queloides com mais de 1 cm2 ou divididos em áreas de 1cm2. Estudos mais amplos deveriam ser realizados, para confirmar esses resultados.

Comparison of intralesional verapamil with intralesional triamcinolone in the treatment of hypertrophic scars and keloids.

BACKGROUND: The calcium channel blocker, verapamil stimulates procollagenase synthesis in keloids and hypertrophic scars. AIM: To study the effect of verapamil in the treatment of hypertrophic scars and keloids and to evaluate the effect of verapamil on the rate of reduction of hypertrophic scars and keloids in comparison with triamcinolone. METHODS: The study was a randomized, single blind, parallel group study in which 54 patients were allocated to to receive either verapamil or triamcinolone. Drugs were administered intralesionally in both groups. Improvement of the scar was measured using modified Vancouver scale and by using a centimeter scale serially till the scar flattened. RESULTS: There was a reduction in vascularity, pliability, height and width of the scar with both the drugs after 3 weeks of treatment. These changes were present at one year of follow-up after stopping treatment. Scar pigmentation was not changed desirably by either drug. Length of the scars was also not altered significantly by either drug. The rate of reduction in vascularity, pliability, height and width of the scar with triamcinolone was faster than with verapamil. Adverse drug reactions were more with triamcinolone than with verapamil. CONCLUSION: Intralesional verapamil may be a suitable alternative to triamcinolone in the treatment of hypertrophic scars and keloids.

effect of different concentrations of topical vitamin E on cosmetic appearance of hypertrophic and keloid scars

There are a few clinical trials on human that show the effect of topical vitamin E on keloid and hypertrophic scars. In this investigation we try to study this effect and also show the effect of the concentrations which have not been considered yet in improving hypertrophic scar and keloid healing. In a double-blind randomized clinical trial, 32 patients who had hypertrophic scar from 12 weeks ago were given three ointments including placebo and ointments contaning injectional vitamin E [d-a tocopheryl] with different concentrations [300Iu/mg and 600Iu/mg]. The scars size, erythema and hardness were evaluated by patients and physicians after 1, 4 and 12 weeks. Data was analyzed using ANOVA and Kruskal Walis tests. After 12 weeks there were no signs or symptoms of dermatitis and rash. Comparison of the scar size after 1 week showed difference between the high concentrated ointment with the others and in the 12[th] week all of the ointments were different [p<0.001]. Evaluation of the scar erythema, in the 1[th], 4[th] and 12[th] week showed significant difference between vitamin ointments and placebo [p<0.001], also scar hardness in the 12[th] week was significantly different between groups [p<0.001], but in the first and 4[th] week no difference was detected in hardness. This study shows that topical vitamin E has good effects on keloid and hypertropic scars. Their effect in decreasing size and erythema is more considerable than scar hardness

Terapia de cicatriz hipertrófica e quelóide em mucosa bucal: relato de caso clínico / Hypertophic cicatrix and keloid therapy in oral mucosa: caso report

O presente trabalho aborda as características clínicas e histopatológicas das cicatrizes hipertróficas e quelóides, além do tratamento proposto atualmente na literatura. É relatado ainda, um caso clínico de cicatriz hipertrófica em mucosa interna de lábio superior, onde se utilizou, intralesionalmente, o acetato de triamcinolona como terapia

Queloides auriculares: tratamiento quirúrgico y comprensivo / Surgical and comprenssive treatment of ear lobe keloids

Los queloides son el resultado de un proceso de cicatrización patológico, en el que los fibroblastos sintetizan colágeno en forma excesiva. Aunque se han descrito algunos factores predisponentes, su etiología es desconocida. Los queloides auriculares se asocian al empleo de aros, piercing, traumatismos, quemaduras y cirugías. Además de las repercusiones estéticas y psicológicas, suelen causar dolor, prurito y parestesias. Su manejo es controvertido, habiéndose descrito modalidades quirúrgicas y no quirúrgicas de tratamiento. Aunque ninguna de ellas es efectiva en todos los casos, su asociación parece tener mejores resultados. Se presenta una serie de 9 pacientes, con 13 queloides auriculares, en los que empleamos cirugía y comprensión, como pilares del tratamiento. Finalmente proponemos un algoritmo terapéutico.

Self-adhesive silicone gel sheet: a treatment for hypertrophic scars and keloids.

An open clinical trial was conducted to assess the effect of self-adhesive silicone gel sheet (SASGS) for the treatment of hypertrophic scars and keloids in Thai people. Patients were instructed to apply the SASGS to the scars as long as possible, but not less than 12 hours per day for at least 8 weeks. The subjective results of the treatment were evaluated by the patients. The scars were evaluated for color, height, weight before and after treatment at 4 and 8 weeks. Eighteen patients with 18 hypertrophic scars or keloids were recruited into the study. Their ages ranged from 6 to 33 years (mean 21 years). The average duration of the scars was 5.7 years. Twelve patients (66.67%) stated good results. All of the 18 patients wanted to continue the treatment with SASGS. Heights of the scars were reduced in 12 lesions (66.67%) after treatment for 8 weeks (P = 0.058). Weights of the lesions were decreased in 10 lesions (55.55%) but were not statistically different (P = 0.090). Seven lesions (36.84%) were improved in color. Two patients (11.11%) developed erythematous rash around the lesions which subsided after withdrawal of the treatment. The long term follow-up for the recurrence and the mechanism of action of this treatment should be studied further.

use of common insulin syringe for intralesional steroid injection in hypertrophic scars and keloids

A technique of delivering intralesional steroid injection in hypertrophic scars and keloids is described using the ubiquitous insulin syringe with fixed needle

Principais características das cicatrizes queloideanas / Brief accout of the clinical and histological features of keloids, their treatment

Breve relato das características clínicas e histológicas dos quelóides, sua diferenciaçäo das cicatrizes hipertróficas e os vários métodos de tratamento

Cicatriz queloide: dimetil-sulfóxido más diacetato de triamcinolona: una alternativa en su manejo / Keloids cicatrix: dimetil-sulfoxide with triamcinolone acetonide: at alternative in its management

En ocho pacientes con cicatriz queloide se realizó un estudio abierto, prospectivo y experimental con aplicación tópica de dimetil-sulfóxido, más diacetato de triamcinolona; en algunos, además, se practicó cirugía parcial. Los resultados son alentadores.