Sensory irritation to methylparaben is caused by its low metabolism in the skin.

Sensitive skin is a well- known skin condition showing sensory irritation to daily used products such as cosmetics or pharmaceuticals, possibly containing sensory irritants. Methylparaben (MP), widely used as a preservative, is a representative sensory irritant and hydrolyzed in the skin. We aimed to clarify the relationship between MP sensory irritation and MP hydrolysis. First, we investigated the percutaneous penetration and hydrolysis of MP by using an ex vivo pig skin system and confirmed that topically applied MP was immediately hydrolyzed to p-hydroxybenzoic acid (PHBA). We next evaluated whether MP or PHBA causes sensory irritation using a well-used stinging test in human skin and found that MP, but not PHBA, induced irritation. Additionally, MP, but not PHBA, increased intracellular calcium in cultured TRPA1-expressed HEK293 cells, supporting the stimulatory activity of MP. Five and 10 individuals with sensitive and non-sensitive skin, respectively, were selected by a questionnaire and stinging test. In their biopsied skin samples, MP hydrolytic activity was significantly lower in sensitive than non-sensitive skin. Finally, we examined the activity of carboxylesterase (CES), which promptly hydrolyzes MP to PHBA. By using specific inhibitors of CES and CES2, we found that CES1 was responsible for MP metabolism. Our study suggests that low skin metabolism of topical agents is one of the causes of skin sensory irritation and resultant sensitive skin.

Control of cell adhesion and proliferation utilizing polysaccharide composite film scaffolds.

We have developed polysaccharide composite films made of anionic polysaccharides and chitosan (CHI) by utilizing hot press techniques. In order to demonstrate the versatility of these films as cell scaffolds, the present study investigated the adhesion and proliferation of fibroblasts on composite films prepared by using various kinds of anionic polysaccharides and that were modified with proteins. Cells were spread on heparin/CHI and alginic acid/CHI films and grew well, whereas those on chondroitin sulfate C (CS)/CHI and hyaluronic acid/CHI films were round in shape. The differences in adhesion and proliferation behaviors of cells could be explained by the differences in the biochemical function of the anionic polysaccharides and the physical properties of the films such as morphology, storage modulus, ζ-potentials, and swelling ratios. Among them, the number of cells on CS/CHI films remained almost unchanged. The mechanisms underlying growth suppression on CS/CHI films were investigated by using an integrin stimulator, the TNIIIA2 peptide, and platelet-derived growth factor-B. It was indicated that the growth suppression was due to the lack of fibronectin-integrin growth signaling. The surface modification of CS/CHI films with fibronectin promoted the adhesion and proliferation of cells. These results show that the chemical and physical properties of the polysaccharide composite films, which resulted from the chemical species of anionic polysaccharides or surface modifications of the films, can modulate cell adhesion and proliferation properties thereon.

Histological study of deposited cementum in human deciduous teeth with pathological root resorption.

Physiological root resorption is a characteristic feature of human deciduous teeth. Pathological root resorption due to apical periodontitis, dental trauma or excessive orthodontic force is also observed in deciduous roots. The root resorption is not continuous, and has resting periods. In the resting period, cementum deposits in resorbed root surface. The deposited cementum in permanent teeth has been reported in detail. However, the deposited cementum in deciduous teeth is unclear. The present study examined apices of roots of human deciduous incisors with apical periodontitis and roots of sound deciduous incisors by light and transmission electron microscopy. Root dentin and original cementum had a severe irregular caved surface. Cementum was partially deposited on the caved root surfaces. The deposited cementum had made the caved root surface relatively flat. The cementum was lax and had some defects. The deposited cementum was belt-like in shape and had a stratified structure. Each layer had various structures consisting of abundant microfibrils and fine granular materials, microfibrils, granular materials, and collagen fibrils, a few fibrils and granular materials and a relatively homogeneous structure. The original cementum had many collagen fibrils, such as intrinsic and extrinsic fibers, and no granular materials or homogeneous structure. Therefore, structure of the deposited cementum was very different from that of original cementum in deciduous teeth and from that of deposited cementum in permanent teeth.