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Janiczek‐Dolphin, N.; Cook, J.; Thiboutot, D.; Harness, J.; Clucas, A.
doi: 10.1111/j.1365-2133.2010.09878.xpmid: 20518779
SummarySebum excretion has generally been accepted as an important factor in the development of acne vulgaris. However, the relationship of sebum excretion and acne outcome has not yet been clearly demonstrated quantitatively. The objective of this analysis was to explore the correlation of sebum and acne by combining data from studies of various acne treatments that have demonstrated effects on both sebum excretion and acne outcome. Acne measures included total lesion count, inflammatory lesion count and acne severity grade. For each acne measure, data were pooled and analysed at the 3‐ and 4‐month endpoints, when sebum reduction has generally equilibrated and efficacy in acne is approaching the maximum effect for most treatments. A linear model was used to describe the percentage reduction in each acne measure as a function of percentage reduction in sebum excretion. Slope values were similar for the three acne parameters and all were significantly different from zero (P <0·025), suggesting a significant correlation of sebum and acne. The projected sebum reduction required to achieve 50% reduction in acne measures ranged from 30% to 50%. The results shown here suggest that the collective data across multiple studies may provide a useful generalization of the association of sebum reduction and acne outcome. As the relationship apparently remains consistent regardless of the treatment, it can be inferred that extrapolation to novel exploratory treatments may be valid.
Ohguchi, K.; Itoh, T.; Akao, Y.; Inoue, H.; Nozawa, Y.; Ito, M.
doi: 10.1111/j.1365-2133.2010.09825.xpmid: 20426787
SummaryBackground SIRT1, an NAD+‐dependent histone/protein deacetylase, controls a broad range of cellular functions.Objectives We examined if SIRT1 is involved in the regulation of matrix metalloproteinase (MMP) expression in human dermal fibroblasts.Methods We studied the effect of inhibition of SIRT1 by specific inhibitor and small interfering RNA (siRNA) on MMP‐1 and MMP‐3 expression in human dermal fibroblasts.Results Treatment with a potent and selective inhibitor of SIRT1, EX‐527, increased the basal expression levels of MMP‐1 and MMP‐3 proteins. Knockdown of endogenous SIRT1 by siRNA led to increased expression of MMP‐1 and MMP‐3 at both mRNA and protein levels. SIRT1 knockdown also upregulated MMP protein induction caused by an inflammatory cytokine, interleukin (IL)‐1β. Moreover, treatment with a SIRT1 activator, resveratrol, significantly suppressed IL‐1β‐mediated induction of MMP‐1, which was attenuated by pretreatment with EX‐527. Finally, MMP‐1 promoter activity was increased by EX‐527 in cells treated with or without IL‐1β.Conclusions Our findings suggest that SIRT1 exerts a negative regulatory role in the production of MMP‐1 and MMP‐3 in human dermal fibroblasts.
Levi, K.; Kwan, A.; Rhines, A.S.; Gorcea, M.; Moore, D.J.; Dauskardt, R.H.
doi: 10.1111/j.1365-2133.2010.09937.xpmid: 20633012
SummaryBackground Emollient molecules are widely used in skin care formulations to improve skin sensory properties and to alleviate dry skin but little is understood regarding their effects on skin biomechanical properties.Objectives To investigate the effects of emollient molecules on drying stresses in human stratum corneum (SC) and how these stresses are related to SC components and moisture content.Methods The substrate curvature method was used to measure the drying stresses in isolated SC following exposure to selected emollient molecules. While SC stresses measured using this method have the same biaxial in vivo stress state and moisture exchange with the environment, a limitation of the method is that moisture cannot be replenished by the underlying skin layers. This provides an opportunity to study the direct effects of emollient treatments on the moisture content and the components of the SC. Attenuated total reflectance Fourier transform infrared spectroscopy was used to determine the effects of emollient molecules on SC lipid extraction and conformation.Results Emollient molecules resulted in a complex SC drying stress profile where stresses increased rapidly to peak values and then gradually decreased to significantly lower values compared with the control. The partially occlusive treatments also penetrated into the SC where they caused extraction and changes in lipid conformation. These effects together with their effects on SC moisture content are used to rationalize the drying stress profiles.Conclusions Emollient molecules have dramatic effects on SC drying stresses that are related to their effects on intercellular lipids and SC moisture content.
Khan, S.; Muzaffar, S.; Tariq, M.; Khan, A.; Basit, S.; Ahmad, W.
doi: 10.1111/j.1365-2133.2010.09881.xpmid: 20518786
SummaryBackground Palmoplantar keratodermas (PPKs) are a group of highly heterogeneous diseases causing hyperkeratosis of the palms and soles. They can be inherited in an autosomal recessive, dominant, mitochondrial or possibly X‐linked recessive fashion. The present study describes clinical and molecular genetic analysis of a consanguineous Pakistani family showing a severe form of PPK inherited in an autosomal recessive manner.Objectives To map the gene responsible for an autosomal recessive form of PPK.Methods Human genome scan using polymorphic microsatellite markers was performed to localize the disease gene. Eleven candidate genes, located in the linkage interval, were screened to identify the potential sequence variants.Results All five affected members of the family showed severe bilateral involvement of palms and soles with minor nail involvement, severe fissuring with bleeding, painful walking, and problems in grasping. Linkage analysis in the family mapped a novel locus for the disease on chromosome 3q27.2‐q29. The candidate region flanked by markers D3S1530 and D3S1272 spans 28·22 cM, which corresponds to a physical distance of 11·63 Mb. The maximum two‐point LOD score of 3·13 at θ = 0·00 was obtained with marker D3S2748 along the disease locus. DNA sequence analysis of 11 candidate genes, located in the linkage interval, failed to detect functional sequence variants.Conclusions A novel locus for an autosomal recessive form of PPK was mapped on chromosome 3q27.2‐q29 in a consanguineous Pakistani family. Failure to detect pathogenic sequence variants in the 11 candidate genes suggests either that the variants are located in the regulatory regions of the genes or that another unknown gene, responsible for the disease, is present in the region.
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doi: 10.1111/j.1365-2133.2010.09874.xpmid: 20518783
SummaryBackground Vascular‐type Ehlers–Danlos syndrome (vEDS) is a severe autosomal dominant inherited disorder resulting from mutations within the α1 type III collagen gene (COL3A1). The majority of published mutations are base changes leading to the substitution of single glycine residues within the triple‐helical domain of type III collagen. Although clinical characteristics and mutations in the COL3A1 gene have been analysed for some patients from Europe and America, similar analyses have not yet been performed for Japanese patients with vEDS.Objectives To analyse the genetic and phenotypic findings in Japanese patients with vEDS.Methods We analysed the clinical features of 20 unrelated individuals with vEDS. To quantify type III collagen production, the fibroblasts were cultured with 3H‐proline, and the radiolabelled collagenous proteins were analysed using sodium dodecyl sulphate–polyacrylamide gel electrophoresis and fluorography. Mutations in COL3A1 were detected by sequence analysis of cDNA from patients’ fibroblasts and subsequently by a genomic DNA sequence analysis.Results Thin and translucent skin with extensive bruising and hypermobility of the small joints were observed in about 90% of the patients, whereas the prevalence of serious clinical findings such as rupture/dissection/aneurysm of the arteries (30%) or rupture of the gastrointestinal tract (25%) was relatively low. Sequence analyses of the COL3A1 gene demonstrated heterozygous point mutations leading to glycine substitution in only nine patients (45%), while heterozygous splice‐site mutations at the junction of the triple‐helical exons were observed in the remaining 11 patients (55%). The average type III collagen production level in the cultured dermal fibroblasts was 14·6% of the normal value. The types of complication were not associated with specific mutations in COL3A1.Conclusion The analysis in the present series revealed a low frequency of patients presenting with serious clinical findings such as arterial rupture/arterial dissection/aneurysm and perforation or rupture of the gastrointestinal tract, and revealed a higher prevalence of splice‐site mutations at the junction of the triple‐helical exons than of glycine substitution mutations in COL3A1.