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An. bras. dermatol ; 96(4): 429-435, July-Aug. 2021. tab, graf
Article in English | LILACS | ID: biblio-1285101


Abstract Background: Tacrolimus is used to prevent unaesthetic scars due to its action on fibroblast activity and collagen production modulation. Objectives: To evaluate the action pathways, from the histopathological point of view and in cytokine control, of tacrolimus ointment in the prevention of hypertrophic scars. Methods: Twenty-two rabbits were submitted to the excision of two 1-cm fragments in each ear, including the perichondrium. The right ear received 0.1% and 0.03% tacrolimus in ointment base twice a day in the upper wound and in the lower wound respectively. The left ear, used as the control, was treated with petrolatum. After 30 days, collagen fibers were evaluated using special staining, and immunohistochemistry analyses for smooth muscle actin, TGF-β and VEGF were performed. Results: The wounds treated with 0.1% tacrolimus showed weak labeling and a lower percentage of labeling for smooth muscle actin, a higher proportion of mucin absence, weak staining, fine and organized fibers for Gomori's Trichrome, strong staining and organized fibers for Verhoeff when compared to controls. The wounds treated with 0.03% tacrolimus showed weak labeling for smooth muscle actin, a higher proportion of mucin absence, strong staining for Verhoeff when compared to the controls. There was absence of TGF-β and low VEGF expression. Study limitations: The analysis was performed by a single pathologist. Second-harmonic imaging microscopy was performed in 2 sample areas of the scar. Conclusions: Both drug concentrations were effective in suppressing TGF-β and smooth muscle actin, reducing mucin, improving the quality of collagen fibers, and the density of elastic fibers, but only the higher concentration influenced elastic fiber organization.

Animals , Cicatrix, Hypertrophic/pathology , Cicatrix, Hypertrophic/prevention & control , Cicatrix, Hypertrophic/drug therapy , Ointment Bases , Rabbits , Wound Healing , Tacrolimus , Ear/pathology
Article in English | WPRIM | ID: wpr-922602


OBJECTIVES@#Hypertrophic scar (HS) is the most common pathological scar in clinical practice. During its formation, angiogenesis-related factors show dynamic expression. Modern studies have found that Notch signaling pathway has an extremely important role in maintaining the construction and remodeling of vascular endothelial cells and vascular network. The correlation between Notch signaling pathway and angiogenesis in hypertrophic scar has been rarely reported. This study aims to investigate correlation between Notch signaling pathway and the expression of angiogenic factors in a proliferative scar model.@*METHODS@#A total of 81 Sprague Dawley rats (SPF grade) were randomly assigned into a blank control group, a model group, and a blocker group. In the blocker group, a 2 cm diameter circular scald head was placed on the back of the rats for 10 s at 75 ℃ by using a constant temperature and pressure electrothermal scalding apparatus to form a rat deep II° burn model, and a hyperplastic scar model rat was obtained after natural healing of the wound skin (21 to 23 day epithelialization). A syringe was used to inject a needle from the normal skin around the scar at the 1st, 3rd, 5th, 7th, and 14th days after modeling. The γ-secretase inhibitor was injected locally at 2 mg/kg in a dilution of 0.1 mL at the base of the scar. The rats in the model group was injected with the same amount of saline after modeling; the rats in the blank control group was injected with the same amount of saline. Nine rats in each group was randomly killed by air embolization at the 21st, 28th, and 35th days, respectively. The protein expressions of collagen type I (COL-I) and collagen type III (COL-III) were detected by immunohistochemistry. The protein expressions of vascular endothelial growth factor (VEGF), angiopoietin 1 (Ang1), transforming growth factor-β1 (TGF-β1), and matrix metalloproteinase-2 (MMP-2) were detected by Western blotting.@*RESULTS@#Immunohistochemical results showed that, at the 21st,28th, and 35th days, the protein expressions of COL-I and COL-III in the model group were up-regulated compared with the blank control group (all @*CONCLUSIONS@#In the Sprague Dawley rat proliferative scar model, inhibition of Notch signaling pathway could attenuate the expressions of COL-I and COL-III, reduce traumatic scar proliferation, down-regulate the expressions of VEGF, Ang1, TGF-β1, and MMP-2, and inhibit angiogenesis. The expressions of angiogenesis-related factors appeare to be up-regulated during the formation of proliferative scar. When the Notch signaling pathway is inhibited, the up-regulated angiogenic factors show a decreasing trend and the proliferative scar is alleviated, which suggests that Notch signaling pathway may affect the formation of hyperplastic scar by regulating the expression of angiogenic factors.

Animals , Cicatrix, Hypertrophic/pathology , Endothelial Cells , Matrix Metalloproteinase 2 , Rats , Rats, Sprague-Dawley , Signal Transduction , Transforming Growth Factor beta1 , Vascular Endothelial Growth Factor A
Braz. j. med. biol. res ; 54(8): e11184, 2021. tab, graf
Article in English | LILACS | ID: biblio-1285676


Hypertrophic scar (HS) formation is a common complication that develops after skin injury; however, there are few effective and specific therapeutic approaches for HS. Emodin has previously been reported to inhibit mechanical stress-induced HS inflammation. Here, we investigated the molecular mechanisms underlying the inhibitory effects of emodin on HS formation. First, we conducted in vitro assays that revealed that emodin inhibited M1 and M2 polarization in rat macrophages. We subsequently established a combined rat model of tail HS and dorsal subcutaneous polyvinyl alcohol (PVA) sponge-induced wounds. Rats were treated with emodin or vehicle (DMEM). Tail scar specimens were harvested at 14, 28, and 42 days post-incision and subjected to H&E staining and Masson's trichrome staining. Histopathological analyses confirmed that emodin attenuated HS formation and fibrosis. Macrophages were separated from wound cells collected from the PVA sponge at 3 and 7 days after implantation. Flow cytometry analysis demonstrated that emodin suppressed in vivo macrophage recruitment and polarization at the wound site. Finally, we explored the molecular mechanisms of emodin in modulating macrophage polarization by evaluating the expression levels of selected effectors of the Notch and TGF-β pathways in macrophages isolated from PVA sponges. Western blot and qPCR assays showed that Notch1, Notch4, Hes1, TGF-β, and Smad3 were downregulated in response to emodin treatment. Taken together, our findings suggested that emodin attenuated HS formation and fibrosis by suppressing macrophage polarization, which is associated with the inhibition of the Notch and TGF-β pathways in macrophages.

Animals , Rats , Emodin/pharmacology , Cicatrix, Hypertrophic/pathology , Cicatrix, Hypertrophic/drug therapy , Signal Transduction , Transforming Growth Factor beta , Macrophages
An. bras. dermatol ; 94(2): 164-171, Mar.-Apr. 2019. tab, graf
Article in English | LILACS | ID: biblio-1001151


Abstract BACKGROUND: Tacrolimus, for its activity on modulation of collagen production and fibroblast activity, may have a role in the prevention of hypertrophic scars. OBJECTIVES: Evaluate macroscopic, microscopic, metabolic, laboratory effects and side effects of the use of topical tacrolimus ointment, in different concentrations, in the prevention of hypertrophic scars. METHODS: Twenty-two rabbits were submitted to the excision of 2 fragments of 1 cm of each ear, 4 cm apart, down to cartilage. The left ear of the animals was standardized as control and Vaseline applied twice a day. The right ear received tacrolimus ointment, at concentrations of 0.1% on the upper wound and 0.03% on the lower wound, also applied twice a day. Macroscopic, microscopic, laboratory criteria and the animals' weight were evaluated after 30 days of the experiment. RESULTS: Wounds treated with tacrolimus, at concentrations of 0.1% and 0.03%, when compared to control, showed a lower average degree of thickening (p = 0.048 and p <0.001, respectively). The average of scar thickness and lymphocyte, neutrophil and eosinophil concentrations are lower in the treated wounds compared to the control (p <0.001, p=0.022, p=0.007, p=0.044, respectively). The mean concentration of lymphocytes is lower in wounds treated with a higher concentration of the drug (p=0.01). STUDY LIMITATIONS: experiment lasted only 30 days. CONCLUSIONS: Tacrolimus at the 2 concentrations evaluated reduced the severity of inflammatory changes and positively altered the macroscopic aspect of the scar in the short term. Its use was shown to be safe, with no evidence of systemic or local adverse effects.

Animals , Male , Rabbits , Tacrolimus/therapeutic use , Calcineurin Inhibitors/therapeutic use , Ointments , Urea/blood , Serum Albumin/analysis , Serum Albumin/drug effects , Administration, Topical , Tacrolimus/administration & dosage , Tacrolimus/pharmacology , Cicatrix, Hypertrophic/pathology , Cicatrix, Hypertrophic/prevention & control , Lymphocyte Count , Creatinine/blood , Alanine Transaminase/drug effects , Alanine Transaminase/blood , Disease Models, Animal , Ear, External/pathology , Erythema/pathology , Calcineurin Inhibitors/administration & dosage , Calcineurin Inhibitors/pharmacology , Inflammation/pathology , Inflammation/prevention & control
An. bras. dermatol ; 93(2): 268-270, Mar.-Apr. 2018. graf
Article in English | LILACS | ID: biblio-887174


Abstract: This study describes a case of a 19-year-old patient with seven asymptomatic lesions on the chest, measuring between 0.5 to 1cm in diameter, with no history of trauma in the region. The immunohistochemical evaluation was positive for vimentin and smooth muscle actin, determining Dermatomyofibroma as definitive diagnosis. Dermatomyofibroma is a benign skin tumor, with a myofibroblastic origin, prevalent in young women. It usually presents as a single lesion, with very few reports of multiple lesions.

Humans , Female , Young Adult , Skin Neoplasms/pathology , Myofibroma/pathology , Biopsy , Immunohistochemistry , Cicatrix, Hypertrophic/pathology , Fibroblasts/pathology
An. bras. dermatol ; 92(4): 474-477, July-Aug. 2017. tab, graf
Article in English | LILACS | ID: biblio-887001


Abstract: Background: Surgical sutures, wound tension, additional skin incisions and other factors may result in recurrence of tumor-like scar. Objective: To investigate the role of wound natural healing therapy in tumor-like hypertrophic scar. Methods: In this study, tumor-like hypertrophic scars of 47 cases were excised completely and the residual wounds were treated with natural healing. The short-term and long-term effects of treatment were evaluated. Results: All cases were successfully cured by natural healing therapy. The healing time of the maximum wound (80mm × 20mm) and the minimal wound (5mm× 5mm) was 25 days and 7 days respectively. The size of new skin scars ranged from 3mm to 11 mm. Clinical followed-up was performed in 34 cases for 36 months. Among them, no recurrence happened in 31 cases and new scar size ranged from 2mm to 8mm, while local recurrence happened in 3 cases whose scar size were less than 5 mm. Study Limitations: The cure rate of the therapy was 91.2%. Conclusion: The wound natural healing therapy is effective in treating tumor-like hypertrophic scar, which can prevent recurrence and has good cosmetic results.

Male , Female , Child , Adolescent , Adult , Middle Aged , Aged , Young Adult , Wound Healing/physiology , Cicatrix, Hypertrophic/surgery , Wound Closure Techniques , Postoperative Period , Recurrence , Surgical Wound Infection/etiology , Sutures/adverse effects , Suture Techniques/adverse effects , Treatment Outcome , Cicatrix, Hypertrophic/pathology , Cicatrix, Hypertrophic/prevention & control , Preoperative Period
Clinics ; 69(8): 565-573, 8/2014. graf
Article in English | LILACS | ID: lil-718189


Scar formation is a consequence of the wound healing process that occurs when body tissues are damaged by a physical injury. Hypertrophic scars and keloids are pathological scars resulting from abnormal responses to trauma and can be itchy and painful, causing serious functional and cosmetic disability. The current review will focus on the definition of hypertrophic scars, distinguishing them from keloids and on the various methods for treating hypertrophic scarring that have been described in the literature, including treatments with clearly proven efficiency and therapies with doubtful benefits. Numerous methods have been described for the treatment of abnormal scars, but to date, the optimal treatment method has not been established. This review will explore the differences between different types of nonsurgical management of hypertrophic scars, focusing on the indications, uses, mechanisms of action, associations and efficacies of the following therapies: silicone, pressure garments, onion extract, intralesional corticoid injections and bleomycin. .

Humans , Cicatrix, Hypertrophic/therapy , Keloid/therapy , Wound Healing , Bleomycin/therapeutic use , Injections, Intralesional , Cicatrix, Hypertrophic/etiology , Cicatrix, Hypertrophic/pathology , Adrenal Cortex Hormones/therapeutic use , Silicone Gels/therapeutic use , Gravity Suits , Keloid/pathology
Braz. j. med. biol. res ; 44(5): 402-410, May 2011. ilus
Article in English | LILACS | ID: lil-586506


Basic fibroblast growth factor (bFGF) regulates skin wound healing; however, the underlying mechanism remains to be defined. In the present study, we determined the effects of bFGF on the regulation of cell growth as well as collagen and fibronectin expression in fibroblasts from normal human skin and from hypertrophic scars. We then explored the involvement of mitochondria in mediating bFGF-inducedeffects on the fibroblasts. We isolated and cultivated normal and hypertrophic scar fibroblasts from tissue biopsies of patients who underwent plastic surgery for repairing hypertrophic scars. The fibroblasts were then treated with different concentrations of bFGF (ranging from 0.1 to 1000 ng/mL). The growth of hypertrophic scar fibroblasts became slower with selective inhibition of type I collagen production after exposure to bFGF. However, type III collagen expression was affected in both normal and hypertrophic scar fibroblasts. Moreover, fibronectin expression in the normal fibroblasts was up-regulated after bFGF treatment. bFGF (1000 ng/mL) also induced mitochondrial depolarization in hypertrophic scar fibroblasts (P < 0.01). The cellular ATP level decreased in hypertrophic scar fibroblasts (P < 0.05), while it increased in the normal fibroblasts following treatment with bFGF (P < 0.01). These data suggest that bFGF has differential effects and mechanisms on fibroblasts of the normal skin and hypertrophic scars, indicating that bFGF may play a role in the early phase of skin wound healing and post-burn scar formation.

Humans , Cicatrix, Hypertrophic/pathology , Collagen Type I/metabolism , Collagen Type III/metabolism , /pharmacology , Fibroblasts/drug effects , Fibronectins/metabolism , Skin/cytology , Cells, Cultured , Cicatrix, Hypertrophic/metabolism , Collagen Type I/ultrastructure , Collagen Type III/ultrastructure , Fibroblasts/metabolism , Fibroblasts/ultrastructure , Fibronectins/ultrastructure , Microscopy, Electron, Transmission , Membrane Potential, Mitochondrial/drug effects , Membrane Potential, Mitochondrial/physiology , Reverse Transcriptase Polymerase Chain Reaction , Skin/metabolism , Up-Regulation , Wound Healing
Clinics ; 66(11): 1949-1954, 2011. ilus
Article in English | LILACS | ID: lil-605877


OBJECTIVE: After burn injuries, scarred skin lacks elasticity, especially in hypertrophic scars. Topical treatment with tretinoin can improve the appearance and quality of the skin (i.e., texture, distensibility, color, and hydration). The objective of this prospective study was to examine the effects of treatment with 0.05 percent tretinoin for one year on the biomechanical behavior and histological changes undergone by facial skin with post-burn scarring. Setting: Tertiary, Institutional. METHOD: Fifteen female patients who had suffered partial thickness burns with more than two years of evolution were selected. Skin biopsies were obtained initially and after one year of treatment. The resistance and elastance of these skin biopsies were measured using a mechanical oscillation analysis system. The density of collagen fibers, elastic fibers, and versican were determined using immunohistochemical analysis. RESULTS: Tretinoin treatment significantly lowered skin resistance and elastance, which is a result that indicates higher distensibility of the skin. However, tretinoin treatment did not significantly affect the density of collagen fibers, elastic fibers, or versican. CONCLUSION: Topical tretinoin treatment alters the mechanical behavior of post-burn scarred skin by improving its distensibility and thus leads to improved quality of life for patients.

Adolescent , Adult , Female , Humans , Young Adult , Burns/complications , Cicatrix, Hypertrophic/drug therapy , Elasticity/drug effects , Facial Injuries/drug therapy , Keratolytic Agents/therapeutic use , Tretinoin/therapeutic use , Administration, Topical , Biomechanical Phenomena/drug effects , Cicatrix, Hypertrophic/pathology , Cicatrix, Hypertrophic/physiopathology , Facial Injuries/pathology , Facial Injuries/physiopathology , Prospective Studies , Skin/drug effects , Skin/pathology , Skin/physiopathology , Treatment Outcome
Indian J Dermatol Venereol Leprol ; 2007 Sep-Oct; 73(5): 336-9
Article in English | IMSEAR | ID: sea-52460


Keloids are the result of excessive fibroblast proliferation and then over-abundant collagen deposition. There is no method able to guarantee absolute success in the therapeutic approach to keloids. Our case report involves a female patient with six lesions treated with a 32P-patch brachyradiotherapy. Pre-treatment and adjuvant treatment of the lesions were performed with thiomucase, 5-fluoruracil, procaine and triamcinolone. Taking into account the activity contained in each of the patches and the total radiation dose to be administered according to clinical practice, dosimetric calculations were done for each lesion. Separate silicone patches with chromic [32P]phosphate were designed for each lesion based on these calculations. Total remission was achieved in three treated lesions. The other lesions did not achieve total remission yet, but their sizes are diminishing. The differences observed in treatment outcome may be related with lesion features, adjuvant treatments and/or treatment schedule.

Aged, 80 and over , Brachytherapy/methods , Cicatrix, Hypertrophic/pathology , Female , Humans , Keloid/pathology , Phosphorus Radioisotopes/therapeutic use , Radiation Dosage , Skin/pathology
Egyptian Journal of Surgery [The]. 2006; 25 (4): 221-230
in English | IMEMR | ID: emr-187250


Aim: Keloid [KD] and Hypertrophic [HS] scars affected patients and frustrated physicians. This study aimed to analyze clinical, anatomical site and specific morphological characteristics of KD and HS scars that might help understanding their pathophysiology and to reach to the appropriate management

Methods: Total of 125 patients [keloid [n=57], hypertrophic [n=63] and combined [n=5] scars] were recruited from Plastic and Reconstructive Surgery unit at King Abdulaziz University Hospital, Jeddah, Saudi Arabia during period [2000-2005]. Patients were clinically assessed. Seventy-three KD and 87 HS were evaluated morphologically

Results: Abnormal scars were more in females than males [p<0.01], Saudi than non-Saudi [p<0.05], healthy than with co- morbid patient [p<0.000], brown than white, black colored [p<0.000], patients with negative than positive family history [p<0.000]. Commonest age of KD and HS were [20-29 and 10-19 years, respectively]. Commonest etiology of keloid, combined keloid and hypertrophic scars was burn while hypertrophic scar was trauma. Commonest symptoms were pruritus. Keloids, hypertrophic scars were mostly single. Commonest site of keloid was chest [21.9%] while for hypertrophy scars were face [26.4%]. KD and HS showed different morphological appearance in different anatomical areas

Conclusion: Keloid and hypetrophic scars are not uncommon in Saudi Arabia. We demonstrated that female, young age, brown color has significant effect on clinical presentation of keloid and hypertrophic scarring

Humans , Male , Female , Cicatrix, Hypertrophic/pathology , Diagnosis, Differential , Keloid , Cicatrix, Hypertrophic/diagnosis , Hospitals, University
Rev. chil. dermatol ; 16(1): 42-6, 2000. ilus, tab
Article in Spanish | LILACS | ID: lil-274563


Con la finalidad de prevenir o mejorar la apariencia de las cicatrices hipertróficas, sean éstas de origen quirúrgico o traumático, se ha desarrollado una gran variedad de tratamientos, tanto tópicos como sistémicos. Estas lesiones son notoriamente recurrentes y su manejo es poco satisfactorio. Ninguna medida en forma individual ha probado ser efectiva en evitar el proceso de la cicatrización hipertrófica (CH), con excepción tal vez de la silicona. El presente trabajo tiene como objetivo revisar la evidencia disponible en estudios prospectivos, controlados, descritos en la literatura acerca de la utilidad de la silicona en el tratamiento de las cicatrices hipertróficas

Humans , Male , Female , Cicatrix, Hypertrophic/therapy , Silicone Gels/therapeutic use , Cicatrix, Hypertrophic/pathology , Cicatrix, Hypertrophic/prevention & control , Silicone Gels/administration & dosage , Silicone Gels/pharmacology