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Acne is one of the most prevalent skin conditions seen by dermatologists. Acne scars are a frequent complication of acne that may negatively impact on person's physical, mental and social well-being, as although active acne can persist for a decade or more, acne scars may persist for a lifetime. Although a wide range of treatments are currently being used, there is a lack of high-quality evidence on which is the most effective treatment for acne scars, especially for those with huge severity. Therefore, based on personal experience of various clinical scenarios, the present study aimed to provide both patients and health care providers insights about the suitability of different new techniques for treating acne scars to better improve the quality of life of patients suffering from this condition.
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BACKGROUND: Hyaluronic acid (HA), a naturally occurring polysaccharide, is used in the production of dermal fillers for esthetic purposes. As it has a few days of half-life in human tissues, HA-based dermal filler is chemically modified to increase its lifetime in the body. The most common modification used in commercial HA-based filler is the cross-linking of HA chains using 1,4-butanediol diglycidyl ether (BDDE) as cross-linking agent. Residual, or unreacted, BDDE is considered nontoxic when it is <2 parts per million (ppm); therefore, the quantification of residual BDDE in the final dermal filler is mandatory to ensure the safety of the patients. MATERIALS AND METHODS: The present study describes the detection and characterization of one by-product of the cross-linking reaction between BDDE and HA in alkaline conditions by combining both liquid chromatography and mass spectroscopy (LC-MS). RESULTS: After different analyses, it was found that the alkaline conditions and the high temperatures employed to sterilize the HA-BDDE hydrogel promote the formation of this new by-product, a "propene glicol-like" compound. LC-MS analysis confirmed that this by-product have the same monoisotopic mass as that of BDDE, a different retention time (tR), and also a different UV absorbance (λ=200 nm) pattern. Unlike BDDE, it was observed in the LC-MS analysis that this by-product had a higher detection at 200 nm in the same assay conditions. CONCLUSION: These results suggest that this new compound does not have an epoxide on its structure. The discussion is open to assess the risk of this new by-product found in the production of HA-BDDE hydrogels (HA dermal fillers) for commercial purposes.
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INTRODUCTION: Silanol (organic silicon) has been used for decades in the treatment of skin photoaging as it stabilizes and maintains skin structures through hydrogen bonding electrostatic interaction with extracellular matrix (ECM) proteins or glycosaminoglycans. Organic silicon-based products are often presented as silanol derivatives which are currently associated to other structural molecules such as orthohydroxybenzoate, carboxymethyl theophylline alginate, ascorbate, acetyltyrosine, sodium lactate or mannuronate. Consequently, organic silicon formulations may differ substantially between the medical devices available on the market, which may result in additional effect on the skin. Therefore, there is a real need for a better characterization of the products in terms of their action on human skin and in vitro skin model. MATERIALS AND METHODS: In this in vitro study, the effect of RRS® Silisorg was analyzed. RRS® Silisorg is a dermal implant (CE Class III medical device) containing monomethylsilanol mannuronate associated to an antioxidant resveratrol. Skin fibroblast viability and capacity to induce the production of key ECM genes were evaluated in the presence of different concentrations of RRS® Silisorg. The key ECM genes selected were collagen type I, elastin and hyaluronan synthase type 2 (HAS2), which is the cellular enzyme responsible for high-molecular weight hyaluronic acid (HA) production. Viability was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and expression was quantified by quantitative polymerase chain reaction. RESULTS: RRS® Silisorg increased fibroblast gene expression of HAS2 in the first 24 hours, 25 times in the presence of 1 mg/mL of solution, followed by a collagen type I gene expression (4.7 times) and elastin expression (2.5 times) increase after 48 hours. CONCLUSION: These results demonstrate that the silanol-based medical device RRS® Silisorg sustains HA, collagen and elastin production in human skin fibroblasts in vitro.
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Mesotherapy/biorevitalization with hyaluronic acid (HA) is a treatment approach currently used for skin rejuvenation. Various products with a wide range of polycomponent formulations are available on the market. Most of these formulations contain noncross-linked HA in combination with a biorevitalization cocktail, formed by various amounts of vitamins, minerals, amino acids, nucleotides, coenzymes, and antioxidants. Although ingredients are very similar among the different products, in vitro and clinical effects may vary substantially. There is a real need for better characterization of these products in terms of their action on human skin or in vitro skin models. In this study, we analyzed the effect of the RRS(®) (Repairs, Refills, Stimulates) HA injectable medical device on human skin fibroblasts in vitro. Skin fibroblast viability and its capacity to induce the production of key extracellular matrix were evaluated in the presence of different concentrations of RRS HA injectable. Viability was evaluated through colorimetric MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and key extracellular matrix genes, type I collagen and elastin, were quantified by quantitative polymerase chain reaction. Results demonstrated that RRS HA injectable could promote human skin fibroblast viability (+15%) and increase fibroblast gene expression of type I collagen and elastin by 9.7-fold and 14-fold in vitro, respectively. These results demonstrate that mesotherapy/biorevitalization products can, at least in vitro, effectively modulate human skin fibroblasts.
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In 1913, a distinctive clinical entity of acute genital ulcer occurring in an adolescent girl with a non-venereal infectious aetiology was described by Lipschütz. Since the initial description, several aetiologies have been discussed, and among them, paratyphoid fever is very uncommon. After her return from a trip, a 25-year-old girl developed high fever and diarrhoea. Examination of the vulva revealed a genital ulcer. The rest of the general examination was normal. Blood cultures identified Salmonella paratyphi A, and a diagnosis of Lipschütz's ulcer associated with paratyphoid fever was made. Bacteriaemia was then treated with antibiotics and the vulvar ulceration rapidly disappeared. Lipschütz described a distinctive clinical entity of acute genital ulcers occurring in adolescents. To our knowledge, we report herein the second case associated with proved paratyphoid fever. The authors thus recommend that typhoid or paratyphoid fever should be included in the differential diagnosis of genital ulcerations.
Assuntos
Febre Paratifoide/diagnóstico , Úlcera/diagnóstico , Doenças da Vulva/diagnóstico , Adulto , Diagnóstico Diferencial , Diarreia/etiologia , Feminino , Humanos , Febre Paratifoide/complicações , Febre Paratifoide/patologia , Salmonella paratyphi A/isolamento & purificação , Úlcera/complicações , Úlcera/patologia , Doenças da Vulva/complicações , Doenças da Vulva/patologiaRESUMO
UNLABELLED: The widespread use of TNFalpha antagonists in recent years has led to the recognition of paradoxical adverse effects, defined as the onset or exacerbation of disorders that are usually improved by TNFalpha antagonists. Cutaneous psoriasis is an example, of which several cases have been reported. OBJECTIVE: To identify cases of psoriasis onset or exacerbation during TNFalpha antagonist therapy and to look for potential predictive factors. METHODS: We retrospectively reviewed cases of psoriasis onset or exacerbation during TNFalpha antagonist therapy. For each case we recorded the following data: age, sex, underlying disease, nature of the TNFalpha antagonist, effectiveness in improving the underlying disease, history of psoriasis in the patient or family, time to psoriasis development, type of psoriasis (confirmed by an experienced dermatologist), concomitant treatments, whether the TNFalpha antagonist was stopped or continued, and the outcome of the psoriasis. These data were compared to those in the literature. RESULTS: We identified 12 patients, six men and six women, with a mean age of 45.5 years. The TNFalpha antagonist was adalimumab in four patients, etanercept in six patients, and infliximab in two patients. The underlying disease was ankylosing spondylitis in six cases, rheumatoid arthritis in four, and psoriatic arthritis in two. Mean time from treatment initiation to psoriasis was 4.1 months (range, 1-15 months). A previous history of psoriasis in the patient was noted in six cases, including four of the six patients taking etanercept. TNFalpha antagonist therapy was effective on the underlying disease in 11 of the 12 patients. The drug was discontinued in five patients, of whom four experienced resolution of their psoriasis. In the remaining seven patients, the drug was continued and the skin lesions remained unchanged. Most of the patients had psoriasis vulgaris (plaque psoriasis); palmoplantar pustulosis was a feature in five patients. DISCUSSION: Over 40 cases of psoriasis onset or exacerbation during TNFalpha antagonist therapy have been reported in the literature. The prevalence of this adverse effect has been estimated at 1.5-5% of patients taking TNFalpha antagonists. The findings from our case series are consistent with data in the literature. Psoriasis is a class effect that has been reported with all the currently available TNFalpha antagonists. The skin lesions develop within the first few months of therapy. Patients with a wide range of underlying diseases can be affected. Palmoplantar pustulosis is a common feature. A previous history of psoriasis seems more common in patients who experience psoriasis onset or exacerbation during etanercept therapy (four of six patients in our study and 55% in the literature); thus, previous psoriasis may be a risk factor for psoriasis exacerbation during etanercept therapy.