Relationship between lip skin biophysical and biochemical characteristics with corneocyte unevenness ratio as a new parameter to assess the severity of lip scaling.

OBJECTIVE: Lip skin dryness and chapping are major concerns related to lip skin care in many populations. The distinctive features of lip skin, such as the low water-holding capacity and weak skin barrier, are strongly associated with these problems; however, few studies have examined lip skin characteristics and the mechanisms underlying these issues. This study was conducted to identify the biophysical properties of dry lip skin and molecular targets affecting lip skin physiology. METHODS: Skin hydration, transepidermal water loss and lip skin scaling were evaluated in 40 female subjects. Skin scaling was assessed as a percentage area divided into five categories (G0, G1, G2, G3 and G4) according to the thickness level of tape-stripped corneocytes. The activities and amounts of proteases, cathepsin D and bleomycin hydrolase were measured as markers for the desquamation process and skin hydration, respectively. RESULTS: Skin hydration showed a significantly positive correlation with the percentage area of evenly thin corneocytes (G0) and negative correlations with the percentage areas of slightly thick to severely thick corneocytes (G1-G4). The corneocyte unevenness ratio (CUR) was calculated by dividing the sum of the G1, G2, G3 and G4 values with the G0 value. The CUR was significantly negatively correlated with skin hydration, suggesting that CUR is a new parameter representing the severity of lip scaling. Subjects with lower hydration and higher CUR had higher bleomycin hydrolase activity and lower cathepsin D activity, respectively, than subjects with higher hydration and lower CUR. CONCLUSION: Our study revealed a correlation between lip skin hydration and severity of lip scaling and verified the association of protease activity with the hydration and chapping state of lip skin. These observations provide a basis for further studies of the persistent problem of lip skin dryness and chapping.

OBJECTIF: La sécheresse et la gerçure de la peau des lèvres sont des préoccupations majeures liées aux soins de la peau des lèvres chez de nombreuses populations. Les caractéristiques distinctives de la peau des lèvres, telles que la faible capacité de rétention d'eau et la faible barrière cutanée, sont fortement associées à ces problèmes ; cependant, peu d'études ont examiné les caractéristiques de la peau des lèvres et les mécanismes sous-jacents à ces problèmes. Cette étude a été menée dans le but d'identifier les propriétés biophysiques de la peau sèche des lèvres et les cibles moléculaires affectant la physiologie de la peau des lèvres. MÉTHODES: L'hydratation cutanée, la perte d'eau transépidermique et la desquamation de la peau des lèvres ont été évaluées chez 40 sujets de sexe féminin. La desquamation cutanée a été évaluée en tant que pourcentage de surface, divisée en cinq catégories (G0, G1, G2, G3 et G4) en fonction du niveau d'épaisseur des cornocytes sur la bande adhésive. Les activités et quantités des protéases, de la cathepsine D et de la bléomycine hydrolase ont été mesurées comme marqueurs du processus de desquamation et de l'hydratation cutanée, respectivement. RÉSULTATS: L'hydratation cutanée a montré une corrélation significativement positive avec le pourcentage de surface avec cornocytes uniformément minces (G0), et des corrélations négatives avec les pourcentages de surface avec cornocytes légèrement épais à très épais (G1-G4). Le rapport d'irrégularité des cornocytes (Corneocyte Unevenness Ratio, CUR) a été calculé en divisant la somme des valeurs de G1, G2, G3 et G4 par la valeur de G0. Le CUR était significativement corrélé négativement avec l'hydratation de la peau, ce qui suggère que le CUR est un nouveau paramètre représentant la gravité de la desquamation des lèvres. Les sujets avec une hydratation plus faible et un CUR plus élevé présentaient une activité de la bléomycine hydrolase plus élevée et une activité de la cathepsine D plus faible, respectivement, par rapport aux sujets avec une hydratation plus élevée et un CUR plus faible. CONCLUSION: Notre étude a révélé une corrélation entre l'hydratation de la peau des lèvres et la gravité de la desquamation des lèvres, et a vérifié l'association de l'activité de la protéase avec l'état d'hydratation et de gerçure de la peau des lèvres. Ces observations fournissent une base pour d'autres études sur le problème persistant de la sécheresse et de la gerçure de la peau des lèvres.

Hyaluronic acid: in vitro and in vivo analysis, biochemical properties and histological and morphological evaluation of injected filler.

BACKGROUND: No human model has emerged as an accepted standard to evaluate tissue filler longevity. OBJECTIVES: To validate a human model adequate to compare soft tissue filler degradation and tissue reaction. MATERIALS AND METHODS: We evaluated in 18 patients the persistence of hyaluronic acid (HA) filler injected into labial tissue analyzing hyaluronidase (HYAL) activity by means of in vitro and in vivo tests, MRI and histological and ultra-structural examination at 3 and 6 months postop. RESULTS: MRI examination revealed the presence of HA filler in a clear hyperintense area. Histology demonstrated fibroblast activation. The amount and the degradation rate of HYAL and HA did not show a linear correlation. CONCLUSION: MRI demonstrated the presence of HA in lip tissue even after 6 months. Biopsies at 3 months revealed tissue maturation and at 6 months confirmed the ability of HA to reorganize and integrate the extracellular matrix. The absence of linear correlation between HYAL and HA revealed that the result clinically is probably dependent on systemic factors which can determine HYAL activity and therefore HA longevity.

Roles of BMP signaling pathway in lip and palate development.

Cleft lip with or without cleft palate (CLP) and cleft palate only (CP) are severe disruptions affecting orofacial structures. Patients with orofacial clefts require complex interdisciplinary care, which includes nursing, plastic surgery, maxillofacial surgery, otolaryngology, speech therapy, audiology, psychological and genetic counseling, orthodontics and dental treatment, among others. Overall, treatment of clefts of the lip and palate entails a significant economic burden for families and society. Therefore, prevention is the ultimate objective and this will be facilitated by a complete understanding of the etiology of this condition. Here we review the current concepts regarding the genetic and environmental factors contributing to orofacial clefts and emphasize on the roles of BMP signaling pathway components in the normal and aberrant development of the lip and palate.

Indoleamine 2,3-dioxygenase expression in early keratocyte neoplasia of the lower lip correlates to the degree of cell atypia.

Actinic cheilitis (AC) is an early keratocyte neoplasia with inflammation that occurs in the lip vermillion with the potential to develop into invasive squamous cell carcinoma (SCC). The expression of the intracellular enzyme indoleamine 2,3-dioxygenase (IDO) by antigen-presenting cells and/or tumor cells has been described to arrest T cell proliferation by degrading the essential amino acid tryptophan from the environment. The expression of IDO in AC may support cancer progression by inhibiting T cell-mediated rejection responses. The aim of this study was to identify the cellular nature and extent of IDO expression in early keratocye neoplasia of the lower lip (n=25), and to correlate IDO expression to the severity of epithelial atypia (KIN I°- KIN III°) and to the extent of actinic inflammation. The expression of IDO was analyzed together with expression markers for T-cells (CD3), myeloid DCs (S100, CD11c), macrophages (CD68, CD11c), and Langerhans cells (CD1a) by immunohistochemistry and immunofluorescence analysis. Analyses showed that IDO was expressed in myeloid S100(+) CD11c(+) DCs. The expression of IDO correlated significantly with the degree of epithelial atypia (P=0.0005) but not to the extent of inflammation (P=0.4283). Expression of IDO in early atypic skin epithelial conditions might be a predictor to promote carcinogenesis.

Increased mast cell density and protease content in actinic cheilitis.

BACKGROUND: Actinic cheilitis (AC) is a pre-malignant lesion caused by ultraviolet (UV) radiation and characterized by epithelial and connective tissue alterations. Mast cells (MCs), key contributors to solar elastosis in murine UV-irradiated skin, were characterized in order to assess their potential contribution to connective tissue degeneration in AC. METHODS: Actinic cheilitis (n = 15) and normal lip (n = 8) biopsies were stained immunohistochemically for tryptase and enzymehistochemically for chymase to determine MC density and protease content. MC subpopulations (i.e. MC(T) containing only tryptase, and MC(TC) containing chymase and tryptase) and their distribution were also determined. RESULTS: Mast cells and their proteases were increased in AC as compared with normal lip (P < 0.0001), and appeared degranulated especially around elastotic areas. MC(T) predominated over MC(TC) in AC and normal lip (P < 0.05). However, in AC MC(T) were increased in the epithelium/connective junction and connective area (P < 0.05), while in normal lip MC(T) predominated in connective and submucosal areas (P < 0.05). CONCLUSION: The results suggest that increased MC density and protease content may contribute to elastosis formation in AC. In addition, changes in MC(T) distribution may favor AC malignization.

Cleft lip: a histochemical and ultrastructural analysis of lip muscles.

AIMS: In order to evaluate the pathogenesis of cleft-lip in relation to both the anatomical and structural anomalies of the mesenchymal tissues, the authors concluded that the presence of structural anomalies in the examined tissues could not explain the malformation, but might be a consequence of it. Delayed muscular development, asymmetrical distribution of the muscular fibres and their anomalous insertion suggest that the anatomical/functional loss clinically detectable in the orbicular muscle could be the result of a perinatal dysmorphological process rather than of a simple mesenchymal hypoplasia. METHODS: Schendel et al. suggested that a metabolic defect in the mitochondrial function could cause a deficiency in cell migration and proliferation responsible for the malformation in question. To establish whether the pathogenesis of the cleft-lip is associated with an alteration in mitochondrial functionality, eight patients affected by unilateral cleft-lip were subjected to a biopsy of the orbicular muscle during the course of reparative surgery. RESULTS: The results obtained showed: 1) a great variation in the size of muscle fibres; 2) the absence of ragged red fibres; 3) a normal oxidative function in the muscle fibres examined; 4) the absence of typologically significant groupings positive for myofibral ATPases. Furthermore, the morphology of the mitochondria was preserved in all cases and neither inclusions nor morphological or volumetric changes were detected. CONCLUSIONS: This preliminary data did not confirm the constant presence of mitochondrial pathology responsible for the malformation in question. In our opinion, the growth deficiency of the maxillary segment could be ascribed to the cicatrization of the surgical repair of the cleft-lip.

Neutral endopeptidase (EC 3.4.24.11) in labial salivary glands in healthy controls and in patients with Sjögren's syndrome.

OBJECTIVE: Neuropeptides from nerve fibres can cause neurogenic inflammation. The potency of these peptides in vitro has led to the hypothesis that enzyme degradative systems are operative in vivo to limit their action. To consider this question neutral endopeptidase (NEP) in labial salivary glands in patients with Sjögren's syndrome was studied. METHODS: Synthesis of NEP mRNA in situ in labial salivary glands was studied using the reverse transcriptase polymerase chain reaction (RT-PCR). Immunohistochemical staining was used to localise the NEP enzyme protein and its neuropeptide substrates and fluorophotometry to measure the corresponding enzyme activities in saliva. RESULTS: NEP was found in nerve fibres and in perivascular, periductal, and periacinar axon terminal varicosities. Double labelling of PGP 9.5 and NEP confirmed this neuronal localisation of NEP. Although some fibroblast-like cells and occasional intravascular neutrophils were NEP positive, NEP mRNA was not found in labial salivary glands. Patients with Sjögren's syndrome and healthy controls did not have nerves containing NEP or neuropeptides (vasoactive intestinal peptide, substance P, or calcitonin gene related peptide (CGRP)) in lymphocyte foci. Salivary NEP activity was not decreased in patients compared with controls. CONCLUSION: NEP in labial salivary glands is almost totally of neuronal origin and plays a part in proteolytic modulation of neuropeptides in salivary glands and saliva. These regulatory interactions seem to be altered in focal lymphocyte accumulations in Sjögren's syndrome.

The significance of amylase in forensic investigations of body fluids.

Amylase levels in body fluids are reported, and it is shown that high amylase levels may occasionally occur in body fluids other than saliva. Low amylase levels are reported in a saliva component which has been previously described as being rich in blood group active material. The use of amylase activity in the localisation and identification of saliva is discussed in detail and guidelines for the interpretation of results are proposed.