The alkaloid centcyamine increases expression of klotho and lamin B1, slowing the onset of skin ageing in vitro and in vivo.

BACKGROUND: Klotho is a protein known for its beneficial effects on longevity. Centcyamine is an alkaloid present in certain plants whose extracts have an anti-inflammatory effect. Skin fibroblasts are essential to the formation and structure of the dermis. OBJECTIVE: Centcyamine is an indole-based alkaloid composed of coumaric acid, a resveratrol precursor and methoxytryptamine, which can be both a precursor, or a derivative, of melatonin. Given these building blocks and their well-known bioactivities, it was of interest to explore the potential benefits of using this aryl-alkaloid, in cosmetic skincare applications. METHODS: We tested cultured normal human dermal fibroblasts (NHDF) in vitro to observe how supplementation with centcyamine improves properties of the cells to counteract the effect of ageing. The expression of genes and proteins of interest was quantified. The effect on doubling time and cell function was evaluated following treatment of the cells over several replication cycles. Skin firmness, red spot index and skin isotropy were measured with Dynaskin® , Visia® and Primos® equipment, respectively, and compared over two months in a vehicle-controlled clinical trial on 60 persons. RESULTS: Centcyamine activates the expression of the gene KL and the related protein Klotho in dermal fibroblasts. Moreover, centcyamine slows the replicative ageing process of fibroblasts in culture. These cells retain cellular functions identical to those of young cells: the synthesis of lamin B1, a crucial regulatory protein of proliferation, as well as of collagen I and elastin is retained in aged cells. The clinical data are shown to improve skin isotropy in a majority of subjects, to reduce the red spot intensity and to maintain skin firmness in the treated group vs. the vehicle. CONCLUSION: The alkaloid centcyamine induces changes in the metabolism of the ageing process of human dermal fibroblasts. The up-to-now unobserved implication of both Klotho and lamin B1 to maintain homeostasis of the skin opens new venues for the prevention of age-related changes in skin structure. The in vitro and clinical data, while not demonstrated to be causally related, converge towards a common goal of skin repair and slower ageing processes.

CONTEXTE: Klotho est une protéine connue pour ses effets bénéfiques sur la longévité. Le centcyamine est un alcaloïde présent dans certaines plantes et dont les extraits ont un effet anti-inflammatoire. Les fibroblastes cutanés sont essentiels à la formation et à la structure du derme. OBJECTIF: le centcyamine est un alcaloïde à base d'indole, constitué d'acide coumarique, d'un précurseur du resvératrol et de méthoxytryptamine, qui peut être à la fois un précurseur ou un dérivé de la mélatonine. Compte tenu de ces éléments constitutifs et de leurs bioactivités bien connues, il était intéressant d'étudier les bénéfices potentiels associés à l'utilisation de cet alcaloïde arylé dans des applications en soins cosmétiques de la peau. MÉTHODES: nous avons évalué in vitro des fibroblastes dermiques humains normaux (Normal Human Dermal Fibroblasts, NHDF) en culture pour observer comment une supplémentation en centcyamine améliore les propriétés des cellules à contrer l'effet du vieillissement. L'expression des gènes et des protéines d'intérêt a été quantifiée. L'effet sur le temps de doublement et sur la fonction cellulaire a été évalué après le traitement des cellules pendant plusieurs cycles de réplication. La fermeté de la peau, l'indice des taches rouges et l'isotropie cutanée ont été mesurés, respectivement, à l'aide d'appareils Dynaskin®, Visia® et Primos®, et comparés sur une période de deux mois dans un essai clinique contrôlé par un excipient et mené chez 60 personnes. RÉSULTATS: le centcyamine active l'expression du gène KL et de la protéine apparentée Klotho dans les fibroblastes dermiques. De plus, le centcyamine ralentit le processus de vieillissement réplicatif des fibroblastes en culture. Ces cellules conservent des fonctions cellulaires identiques à celles des cellules jeunes : la synthèse de la lamine B1, une protéine essentielle dans la régulation de la prolifération, ainsi que du collagène I et de l'élastine est maintenue dans les cellules âgées. Les données cliniques montrent une amélioration de l'isotropie cutanée chez une majorité de sujets, une réduction de l'intensité des taches rouges et un maintien de la fermeté de la peau dans le bras traité par rapport à l'excipient. CONCLUSION: l'alcaloïde centcyamine induit, dans les fibroblastes dermiques humains, des modifications du métabolisme impliqué dans le processus de vieillissement. Le rôle jamais observé jusqu'à présent des protéines Klotho et lamine B1 dans le maintien de l'homéostasie de la peau offre de nouvelles possibilités en matière de prévention des modifications de la structure cutanée liées à l'âge. Bien qu'elles n'affichent aucun lien de causalité, les données in vitro et cliniques convergent vers un objectif commun de réparation cutanée et de ralentissement du processus de vieillissement.

The Vitiligo Impact Patient Scale (VIPs): Development and Validation of a Vitiligo Burden Assessment Tool.

Vitiligo has a major impact on health-related quality of life. Although a few vitiligo-specific quality of life instruments exist, there is no specific vitiligo burden tool. We developed and validated a specific vitiligo burden tool according to skin phototype. In total, 301 patients completed 35 items of the Vitiligo Impact Patient scale, of whom 235 were of skin phototype I to III and 66 of phototype IV to VI. The dimensionality of the items was evaluated using factor analyses, with results suggesting three factors in fair- and dark-skinned patients ("Psychological effects on daily life," "Relationships and Sexuality," and "Economic Constraints, Care & Management of Disease"). Unidimensionality was confirmed by higher order factor analysis. Cronbach's α were high-and intradimensional coherences all demonstrated good reliability (α > 0.8). The final instrument consists of 29 items (19 items common to all patients, 3 specific to fair skin, and 7 to dark skin). The test-retest reliability demonstrated very good reproducibility. The intraclass correlation of each dimension was greater than 0.90 for each population. External validity was confirmed by the correlation coefficients and Bland and Altman plots of the Vitiligo Impact Patient scale-Fair Skin and Vitiligo Impact Patient scale-Dark Skin versus the Short-Form-12, PVC Metra, Body Image States Scale, and Daily Life Quality Index assessment tools.

Impact of liposomal doxorubicin-based adjuvant chemotherapy on autonomy in women over 70 with hormone-receptor-negative breast carcinoma: A French Geriatric Oncology Group (GERICO) phase II multicentre trial.

RATIONALE: Breast cancer is a disease of ageing. Functional independence in elderly patients, measured with the Katz activities of daily living (ADL) scale, predicts overall survival and the need for welfare support. Few prospective studies have examined the feasibility of adjuvant chemotherapy and its impact on autonomy in women over 70 years of age with high-risk breast cancer. This multicentre phase II trial was designed to assess the impact of adjuvant anthracycline-based chemotherapy on these patients' autonomy. DESIGN AND METHODS: In a two-stage Fleming design, women aged ≥70 years with histologically proven hormone-receptor-negative early breast cancer and a significant risk of recurrence (pN+ or "high risk" pN0) received 4 cycles of nonpegylated liposomal doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks postoperatively, on an outpatient basis. The primary endpoint was the change in the ADL score during chemotherapy. Secondary endpoints include comprehensive geriatric, quality-of-life and acceptability assessments, tolerability, and long-term outcome. The results for the primary endpoint and other scales at completion of adjuvant chemotherapy are reported here, while long-term follow-up is not yet complete. RESULTS: Forty patients (median age 75 [70-82]) were enrolled between February 2006 and November 2007. Chemotherapy had no deleterious impact on ADL, cognition, mental status, or the frequency of comorbidities. In contrast, the number of patients at risk of malnutrition, based on the Mini Nutritional Assessment, more than doubled between baseline and the end of chemotherapy, rising from 15% to 38%. Quality-of-life deteriorated in terms of social and role functioning, likely owing to fatigue, loss of appetite, nausea and vomiting. Treatment acceptability was good. The main adverse effect was neutropenia, 15% of the patients experiencing febrile neutropenia. No cardiac toxicity or toxic deaths occurred. CONCLUSION: This study demonstrates the feasibility of an adjuvant chemotherapy regimen combining nonpegylated liposomal doxorubicin and cyclophosphamide in fit elderly women <85 years with breast cancer. Although chemotherapy had an impact on social and role functioning, autonomy was not impaired and toxicity was acceptable. Special attention should be paid to nutritional status before and after treatment.