Acne has a prevalence of over 90% among adolescents and persists into adulthood in approximately 12%–14% of cases with psychological and social implications. Possible outcomes of the inflammatory acne lesions are acne scars which, although they can be treated in a number of ways, may have a negative psychological impact on social life and relationships. The main types of acne scars are atrophic and hypertrophic scars. The pathogenesis of acne scarring is still not fully understood, but several hypotheses have been proposed. There are numerous treatments: chemical peels, dermabrasion/microdermabrasion, laser treatment, punch techniques, dermal grafting, needling and combined therapies for atrophic scars: silicone gels, intralesional steroid therapy, cryotherapy, and surgery for hypertrophic and keloidal lesions. This paper summarizes acne scar pathogenesis, classification and treatment options.
This study examined the pharmacologic characterization of CHF6001 [(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy) phenyl)-2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)ethyl)pyridine 1-oxide], a novel phosphodiesterase (PDE) 4 inhibitor designed for treating pulmonary inflammatory diseases via inhaled administration. CHF6001 was 7-and 923-fold more potent than roflumilast and cilomilast, respectively, in inhibiting PDE4 enzymatic activity (IC 50 5 0.026 6 0.006 nM). CHF6001 inhibited PDE4 isoforms A-D with equal potency, showed an elevated ratio of high-affinity rolipram binding site versus low-affinity rolipram binding site (i.e., .40) and displayed .20,000-fold selectivity versus PDE4 compared with a panel of PDEs. CHF6001 effectively inhibited (subnanomolar IC 50 values) the release of tumor necrosis factor-a from human peripheral blood mononuclear cells, human acute monocytic leukemia cell line macrophages (THP-1), and rodent macrophages (RAW264.7 and NR8383). Moreover, CHF6001 potently inhibited the activation of oxidative burst in neutrophils and eosinophils, neutrophil chemotaxis, and the release of interferon-g from CD4 1 T cells. In all these functional assays, CHF6001 was more potent than previously described PDE4 inhibitors, including roflumilast, UK-500,001 [2-(3,4-difluorophenoxy)-5-fluoro-N-((1S,4S)-4-(2-hydroxy-5-methylbenzamido)cyclohexyl)nicotinamide], and cilomilast, and it was comparable to GSK256066 [6-((3-(dimethylcarbamoyl)phenyl)sulfonyl)-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide]. When administered intratracheally to rats as a micronized dry powder, CHF6001 inhibited liposaccharide-induced pulmonary neutrophilia (ED 50 5 0.205 mmol/kg) and leukocyte infiltration (ED 50 5 0.188 mmol/kg) with an efficacy comparable to a high dose of budesonide (1 mmol/kg i. p.). In sum, CHF6001 has the potential to be an effective topical treatment of conditions associated with pulmonary inflammation, including asthma and chronic obstructive pulmonary disease.
Melasma is a common hypermelanotic disorder affecting the facial area which has a considerable psychological impact on the patient. Managing melasma is a difficult challenge that requires long-term treatment with a number of topical agents, such as rucinol and sophora-alpha. Aims. We aim to compare the combined treatment of skin needling and depigmenting serum with that using depigmenting serum alone in the treatment of melasma, in order to evaluate the use of microneedles as a means to enhance the drug's transdermal penetration. Methods. Twenty patients were treated with combined skin needling and depigmenting serum on one side of the face and with depigmenting serum alone on the other side. The outcome was evaluated periodically for up to two months using the Melasma Area Severity Index score and the Spectrocolorimeter X-Rite 968. Results. The side with combined treatment (skin needling + depigmenting serum) presented a statistically significant reduction in MASI score and luminosity index (L) levels compared to the side treated with depigmenting serum alone, and clinical symptoms were significantly improved. Conclusions. Our study suggests the potential use of combining skin needling with rucinol and sophora-alpha compounds to achieve better results in melasma treatment compared to rucinol and sophora-alpha alone.
The incidence rate of melanoma and non-melanoma skin cancer entities is dramatically increasing worldwide. Exposure to UVB radiation is known to induce basal and squamous cell skin cancer in a dose-dependent way and the depletion of stratospheric ozone has implications for increases in biologically damaging solar UVB radiation reaching the earth’s surface. In humans, arsenic is known to cause cancer of the skin, as well as cancer of the lung, bladder, liver, and kidney. Exposure to high levels of arsenic in drinking water has been recognized in some regions of the world. SCC and BCC (squamous and basal cell carcinoma) have been reported to be associated with ingestion of arsenic alone or in combination with other risk factors. The impact of changes in ambient temperature will influence people’s behavior and the time they spend outdoors. Higher temperatures accompanying climate change may lead, among many other effects, to increasing incidence of skin cancer.
Acrolein (2‐propenal) is a highly reactive α,β‐unsaturated aldehyde and a respiratory irritant that is ubiquitously present in the environment but that can also be generated endogenously at sites of inflammation. Acrolein is abundant in tobacco smoke, which is the major environmental risk factor for chronic obstructive pulmonary disease (COPD), and elevated levels of acrolein are found in the lung fluids of COPD patients. Its high electrophilicity makes acrolein notorious for its facile reaction with biological nucleophiles, leading to the modification of proteins and DNA and depletion of antioxidant defenses. As a consequence, acrolein results in oxidative stress as well as altered intracellular signaling and gene transcription/translation. In pulmonary cells, acrolein, at subtoxic concentrations, can activate intracellular stress kinases, alter the production of inflammatory mediators and proteases, modify innate immune response, induce mucus hypersecretion, and damage airway epithelium. A better comprehension of the mechanisms underlying acrolein effects in the airways may suggest novel treatment strategies in COPD.
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