In vitro melanogenesis inhibitory effects of N-feruloyldopamine.

Tyrosinase is the rate-limiting enzyme in the melanogenesis process. It remains the most efficient way to downregulate melanin production and improve unsightly pigmentary disorders. The aim of our investigations was to find a structurally characterized molecule with better efficacy than existing molecules without cell toxicity. We focused our investigations on compounds that could act as substrate-mimicking inhibitors of tyrosinase and identified N-feruloyldopamine as the best candidate. In vitro, N-feruloyldopamine inhibited human tyrosinase with higher efficacy than the reference inhibitor arbutin without cell toxicity at least up to 100 µM as measured in cultured normal human epidermal melanocytes (NHEMs). Moreover, the inhibition appeared to be specific to mammalian tyrosinases as shown by a very poor inhibition of mushroom tyrosinase, but a significant decrease of total melanin in B16-F10 cells. The antioxidant capacity assessed using DPPH (1,1-diphenyl-2-picrylhydrazyl) assay was comparable to that of vitamin C and finally, N-feruloyldopamine exerted a significant inhibition of Pmel17 gene expression when used at 100 µM on cultured NHEM. Taken together, these results suggest that N-feruloyldopamine is a serious candidate for in vivo application as complexion-brightening ingredient.

Surface rejuvenating effect of Achillea millefolium extract.

Proopiomelanocortin is a precursor peptide that gives rise to several neuropeptides including adrenocorticotrophic hormone (ACTH) and ß-endorphin. POMC-derived peptides have been shown to be synthesized in human epidermis where they modulate numerous skin functions. Because we previously observed that melanocortin receptor-2 and µ-opioid receptor 1, the respective receptors for ACTH and ß-endorphin decreased with ageing in human epidermis, we have selected an active ingredient (INCI name: Achillea millefolium extract) able to upregulate receptor expressions. The aim of the present work was first to evaluate the effect of A. millefolium extract on the expression pattern of various epidermal differentiation markers ex vivo in normal human skin biopsies using quantitative image analysis and second to evaluate its capacity to rejuvenate the appearance of skin surface in vivo. Results show an improved expression profile of cytokeratin 10, transglutaminase-1 and filaggrin in cultured skin biopsies as well as an increased epidermal thickness. In vivo, a 2-month treatment with A. millefolium extract at 2% significantly improved the appearance of wrinkles and pores compared with placebo. Results were also directionally better than those of glycolic acid that was chosen as reference resurfacing molecule.

Evaluation of the efficacy of a dill extract in vitro and in vivo.

Lysyl oxidase-like (LOXL) is an extracellular enzyme that catalyses the cross-linking between microfibrils and tropoelastin (TE), thereby ensuring elastic fibre functionality. With ageing, LOXL expression decreases, thus participating in the loss of skin elasticity. In a previous study, we showed that a dill seed extract [INCI name: Peucedanum graveolens (Dill) extract] could increase LOXL expression in cultured dermal fibroblasts. Besides, we showed a good correlation between the measurements of skin elasticity obtained in vitro and in vivo using a fully automated bio-tribometer designed to measure the biomechanical properties of soft and complex materials like skin. The aim of this study was to evaluate the ability of the dill extract to improve skin elasticity in vitro and in vivo using different models. Using the bio-tribometer, we first showed that the lateral elasticity of dermis equivalents (DEs) treated with the dill extract at 1% was significantly increased by +29% (P < 0.01) when compared to untreated DEs. In vivo, skin firmness and elastic recovery measured using cutometry methods were also significantly improved compared to placebo in volunteers treated for 56 days with a formula containing 1% of dill extract. Moreover, the clinical evaluation evidenced significant improvements in 'skin elasticity' compared to placebo. A majority of subjects treated with the dill extract also noted significant improvements in skin elasticity, firmness and slackness of the jaw line. Finally, mean wrinkle area and length were also significantly reduced compared to placebo after 84 days as measured using silicone replicas taken from the crow's feet. In summary, this study showed that the dill extract could improve elasticity of DEs in vitro as well as skin biomechanical properties and appearance in vivo. It also highlights the relevance of using the bio-tribometer as an exploratory tool for the measurement of skin elasticity in vitro.

In vitro and in vivo efficacy of sulfo-carrabiose, a sugar-based cosmetic ingredient with anti-cellulite properties.

Most of adult women exhibit cellulite on the hips, buttock and thighs. Although extracellular matrix and lymphatic system disorders can increase its appearance, cellulite basically results from an excessive fat storage in the adipose tissue which exerts considerable pressure on the surrounding skin tissue and creates a dimpled irregular appearance. Caffeine, the most widely used anti-cellulite ingredient, favours fat break-down by inhibiting the phosphodiesterase enzyme and encouraging a high intracellular level of cAMP. A series of studies has shown that spermine and spermidine, two ubiquitous polyamines, encouraged fat storage and slowed fat break-down in the adipose tissue. Besides, it was shown that heparan sulfate glycosaminoglycans had a strong affinity for polyamines. To design a new cosmetic ingredient with anti-cellulite properties, we used molecular modelling to screen several ingredients with a structure similar to that of heparan sulfate glycosaminoglycans. This way, we identified sulfo-carrabiose as a potent molecule for trapping spermine and spermidine. These virtual results were first confirmed in tubo where sulfo-carrabiose was shown to dose-dependently inactivate spermine and spermidine. In vitro, adipocytes cultured with sulfo-carrabiose exhibited a significant reduction of lipogenesis and a significant increase of lipolysis. When sulfo-carrabiose was incorporated in a cosmetic formula, significant improvements were observed in thigh circumference, with better results than those obtained with caffeine after 28 days of use. Furthermore, a combination of caffeine and sulfo-carrabiose led to results significantly better than those obtained with caffeine alone. As measured by fringe projection, thigh volume was also significantly reduced after sulfo-carrabiose treatment. Finally, the appearance of cellulite assessed by clinical evaluation was also significantly reduced within 28 days.

On the effects of a plant extract of Orthosiphon stamineus on sebum-related skin imperfections.

Overproduction of sebum is very common and results in an undesirable oily, shiny complexion with enlarged pores. Sebum secretion is basically under the control of 5-α reductase, and more particularly under that of type 1 isozyme. But it is also highly sensitive to environmental factors such as temperature, humidity and food. Moreover, in Asia, the edicts of a flawless facial skin turn oily skin into a major concern for Asian women. We identified Orthosiphon stamineus leaf extract as an interesting ingredient for reducing the oily appearance of skin thanks to its ability to reduce 5-α reductase type 1 expression in normal human epidermal keratinocytes in vitro. This was confirmed ex vivo, where Orthosiphon stamineus leaf extract was shown to reduce 5-α reductase activity as well as the production of squalene, one of the main components of sebum that was used as a tracer of sebum. To evaluate the efficacy of Orthosiphon stamineus leaf extract at reducing sebum-related skin imperfections in vivo, we performed two different clinical studies, one in France on a panel of Caucasian volunteers and the other one in Thailand on a panel of Asian volunteers. Using instrumental techniques as well as clinical evaluation and self-evaluation, we could highlight that an O/W cosmetic formula containing 2% of Orthosiphon stamineus leaf extract could visibly reduce the oily appearance of skin as well as the size of pores, thus leading to a significant improvement of complexion evenness and radiance. Overall, the results obtained were better than those observed with the same formula containing 1% of zinc gluconate, an ingredient frequently used in oily skin care products.

Age-related changes in pro-opiomelanocortin (POMC) and related receptors in human epidermis.

SYNOPSIS: Much effort has been placed in cosmetic research for better understanding of the effects of ageing on skin's appearance, structure, mechanical properties and function. It is now of common knowledge that UV radiations induce pre-mature skin ageing notably in the epidermis where UV radiations induce keratinocyte differentiation. As UV radiations have also been shown to regulate the pro-opiomelanocortin (POMC) peptide family in the skin and because no study has been conducted so far to investigate the age-related changes in POMC and related receptors, we analysed POMC, MC-1R, MC-2R and MOR-1 at mRNA level and MC-1R, MC-2R and MOR-1 at protein level too in primary cultures of normal human keratinocytes obtained from female donors aged from 17 to 75 years old. Regarding the gene expressions, we observed that MC-1R, MC-2R and MOR-1 suffered a dramatic decrease after 50 years of age, whereas POMC increased five-fold. Western blot analysis confirmed these results except for MOR-1 whose expression appeared to decrease at older age, around 70 years old. Immunostainings specific to MC-1R, MC-2R and MOR-1 performed on full-thickness skin biopsies also revealed an intense staining in the basal and spinous layers of a 30-year-old donor, whereas no reactivity could be observed in a 60-year-old one. We conclude that POMC and POMC-related receptors suffer a dramatically disturbed balance with ageing and that this may be implicated in the general process of skin ageing.

[Toxicity and efficacy of chemotherapy dependent on circadian time of cytostatic drug administration]. / Toksycznosc i skutecznosc chemioterapii w zaleznosci od pory dnia podawania cytostatyków.

A prospective, controlled study was carried out in order to evaluate efficacy and toxicity of chemotherapy based on cisplatin in dependence on the circadian rhythm of drugs administration in patients with testicular and ovarian cancer. The study included 80 patients (40 with testicular cancer and 40 with ovarian cancer), divided into two groups (A and B). The cytostatics were administered in the evening in the group A and in the morning in the group B. The response rates and the 3-years survival rates were comparable in both groups. However the patients in the group A presented less haematological and renal side effects, while nausea and vomiting were milder. Chronotherapy may appear to be a method improving the tolerance of chemotherapy based on cisplatin.

[Late hematologic status after chemotherapy observed in patients 3 to 10 years after treatment]. / Pózne powiklania hematologiczne po leczeniu chemicznym obserwowane u pacjentów w 3 do 10 lat po leczeniu.

The aim of the present study is the evaluation of late hematological complication in patients who received aggressive chemotherapy, and were observed 3, 5 and 10 years after treatment was completed. In the group of 35 patients, besides high percent of early hematological complications, there was only one case of anemia grade 2 (acc. to WHO score). We concluded that the hematological recovery after aggressive chemotherapy was satisfactory. No secondary hematological malignancies have been found.

[Results of adjuvant therapy with the preparation Poly-a Poly-u in patients with malignant melanoma during a 10-year observation]. / Wyniki adjuwantnej terapii preparatem Poly-A Poly-U u chorych na czerniaka zlosliwego w 10-letniej obserwacji.

During 10 years patients with malignant melanoma were followed up after radical removal of primary tumour and metastatic regional lymph nodes, the half of whom was given immunomodulation with the preparation Poly-A Poly-U in a controlled clinical trial. It was found that the performed immunomodulation exerted slight effect on the course of malignant melanoma causing later development of recurrence, less dynamic course of the disease, longer asymptomatic periods in relation to the control group. No effect of the drug administration was observed on longterm survival.

[A rare case of dissemination of anaplastic oligodendroma outside the central nervous system]. / Rzadki przypadek rozsiewu anaplastycznego skapodrzewiaka poza osrodkowy uklad nerwowy.

A rare case is reported of primary brain tumour with histological features of anaplastic oligodendroglioma, with metastases outside the central nervous system. Of interest is a short remission after treatment with cyclophosphamide and vepesid which shows that this type of tumour is sensitive in a way to chemotherapy.

[Role of chemotherapy in the treatment of anaplastic thyroid cancer --personal observations]. / Rola chemioterapii w leczeniu anaplastycznego raka tarczycy--doswiadczenia wlasne.

Results of chemotherapy applied in 23 patients with anaplastic thyroid cancer are presented. Chemotherapy combined with local treatment is a suggested therapy for treatment the locally advanced anaplastic thyroid cancer.

[Assessment of causes for delayed treatment in patients with malignant neoplasms ]. / Ocena przyczyn opóznionego leczenia chorych na nowotwory zlosliwe.

Investigation of the causes of delay in the treatment of patients with malignant neoplasms indicates that medium time of delay caused by patient has been 7 months, and caused by physician 9 months. Investigations indicate also that time of waiting for admission to the Oncology Center has been averaging 3 weeks. It has been found that every 9-th patient has been under non medical care for average period of 7 months.