Investigation of partially myristoylated carboxymethyl chitosan, an amphoteric-amphiphilic chitosan derivative, as a new material for cosmetic and dermal application.

BACKGROUND: Cationic amphiphilic chitosan derivatives can form polymeric micelles, which are useful cosmetic materials, but they form polyion complexes with anionic polymers, which can cause formulation difficulties. AIMS: This study aimed to evaluate the usefulness of partially myristoylated carboxymethyl chitosan, an amphoteric-amphiphilic chitosan derivative, as a new material for cosmetics in the absence of a surfactant comprising an anionic polymer. METHODS: An anionic polymer and 1,2-decanediol (an antimicrobial agent)-containing partially myristoylated carboxymethyl chitosan nanoemulsified lotion and glabridin (an antimelanogenic agent)-containing partially myristoylated carboxymethyl chitosan polymeric micelle were prepared using a pressure homogenization method. The release of interleukin-1α, cell viability, and melanogenesis inhibition was evaluated on a human skin model. Antimicrobial activity was evaluated using agar dilution method. RESULTS: A mixture of partially myristoylated carboxymethyl chitosan and carboxyvinyl polymer did not form a polyion complex, but it formed a hydrophilic gel. The anionic polymer-containing partially myristoylated carboxymethyl chitosan nanoemulsified formulation was stable, with no decrease in cell viability and horny layer exfoliation, which are typically observed with Tween 60. Compared with the formulation with methyl paraben (0.2%), the formulation to which 1,2-decanediol (0.05%) was added improved the antibacterial activity against methicillin-resistant Staphylococcus aureus and Propionibacterium acnes; however, no interleukin-1α upregulation was observed. The glabridin-containing partially myristoylated carboxymethyl chitosan polymeric micelles enhanced melanogenesis inhibition and percutaneous glabridin delivery to the epidermis compared with conventional emulsified micelles. CONCLUSIONS: These results suggest that partially myristoylated carboxymethyl chitosan-forming polymeric micelles, in combination with 1,2-decanediol and glabridin, may be useful for surfactant-free cosmetic emulsions.

Building brain capital.

Brains are indispensable drivers of human progress. Why not invest more heavily in them? We seek to place Brain Capital at the center of a new narrative to fuel economic and societal recovery and resilience.

Acute infantile encephalopathy predominantly affecting the frontal lobes.

To establish a novel subtype of acute infantile encephalopathy, the clinical and radiologic features of nine infants with acute encephalopathy involving the bilateral frontal lobes were examined. These patients had convulsive status epilepticus with hyperpyrexia followed by a prolonged impairment of consciousness for 2-20 days. After the recovery of consciousness, all the patients manifested regression of verbal function and lack of spontaneity. Some of them also exhibited stereotypic movements, instability of mood, or catalepsy. Transient postictal edema in both frontal lobes was suggested by diffusion-weighted magnetic resonance imaging. Attenuated cerebral perfusion in the frontal lobes was demonstrated by single-photon emission computed tomography at the tenth day after onset or subsequently. Serial studies disclosed atrophic changes in the frontal lobes. All patients manifested regression or retardation of motor and verbal functions. The recovery of intellectual deficit was slower and less prominent than that of motor dysfunction. These unique features suggest that the frontal lobes are the focus of this novel subtype of acute encephalopathy, which we propose to call acute infantile encephalopathy predominantly affecting the frontal lobes.

[Etiology and management of neonatal seizures--successful treatment by midazolam].

Etiology and management of neonatal seizures was retrospectively studied in 39 patients, who were admitted in our neonatal intensive care unit. Midazolam was administered to 22 patients by intravenous bolus injection (0.15 +/- 0.08 mg/kg) and/or continuous intravenous infusion (0.33 mg +/- 0.11 mg/kg/hr), both of which were judged as effective in 71% and 76% of the patients, respectively. Seven patients showed decrease of blood pressure possibly related with administration of midazolam, but five of them were managed by decreasing dose of the drug or observation of clinical pictures. We consider that midazolam is effective and relatively safe for the management of neonatal seizures.

Mitf-D, a newly identified isoform, expressed in the retinal pigment epithelium and monocyte-lineage cells affected by Mitf mutations.

Microphthalmia-associated transcription factor (Mitf) regulates the differentiation of melanocytes, optic cup-derived retinal pigment epithelium (RPE), and some types of bone marrow-derived cells. Mitf consists of at least five isoforms with different N-termini, each of which is encoded by a separate exon 1. Here we identified a novel isoform, termed mouse Mitf-D/human MITF-D, that is expressed in RPE, macrophages, and osteoclasts affected by the Mitf mutations, but not expressed in other Mitf target cells, including melanocyte-lineage cells and natural killer cells. The initiation Met of MITF-D is located in the downstream domain (B1b domain) that is shared by other MITF isoforms. The 5'-untranslated region of MITF-D mRNA is encoded by the newly identified first exon of the MITF gene, termed exon 1D, which is located 3 kb upstream of the exon encoding the B1b domain. Thus, the MITF gene generates multiple isoforms with different expression patterns by using the alternative promoters in a cell-dependent manner, thereby providing the molecular basis for the phenotypic variability seen in the MITF/Mitf mutants.

Polyamidoamine dendrimers as novel potential absorption enhancers for improving the small intestinal absorption of poorly absorbable drugs in rats.

Effects of polyamidoamine (PAMAM) dendrimers on the intestinal absorption of poorly absorbable drugs were examined by an in situ closed loop method in rats. 5(6)-Carboxyfluorescein (CF), fluorescein isothiocyanate-dextrans (FDs) with various molecular weights, calcitonin and insulin were used as model drugs of poorly absorbable drugs. The absorption of CF, FD4 and calcitonin from the rat small intestine was significantly enhanced in the presence of PAMAM dendrimers. The absorption-enhancing effects of PAMAM dendrimers for improving the small intestinal absorption of CF were concentration and generation dependent and a maximal absorption-enhancing effect was observed in the presence of 0.5% (w/v) G2 PAMAM dendrimer. However, G2 PAMAM dendrimer had almost no absorption-enhancing effect on the small intestinal absorption of macromolecular drugs including FD10 and insulin. Overall, the absorption-enhancing effects of G2 PAMAM dendrimer in the small intestine decreased as the molecular weights of drug increased. However, G2 PAMAM dendrimer did not enhance the intestinal absorption of these drugs with different molecular weights in the large intestine. Furthermore, we evaluated the intestinal membrane damage with or without G2 PAMAM dendrimer. G2 PAMAM dendrimer (0.5% (w/v)) significantly increased the activities of lactate dehydrogenase (LDH) and the amounts of protein released from the intestinal membranes, but the activities and amounts of these toxic markers were less than those in the presence of 3% Triton X-100 used as a positive control. Moreover, G2 PAMAM dendrimer at concentrations of 0.05% (w/v) and 0.1% (w/v) did not increase the activities and amounts of these toxic markers. These findings suggested that PAMAM dendrimers at lower concentrations might be potential and safe absorption enhancers for improving absorption of poorly absorbable drugs from the small intestine.