Using the suppression subtractive hybridization technique, we isolated a novel kinase, IKK-i, whose message is drastically induced by lipopolysaccharide (LPS) in mouse macrophage cell line RAW264.7. The predicted protein contains kinase domain its N-terminus, which shares 30% identity to that of IKK-α or IKK-β. C-terminal portion leucine zipper and potential helix-loop-helix domain, as case IKK-i expressed mainly immune cells, response proinflammatory cytokines such tumor necrosis factor-α,...

Onychomycosis is a common fungal nail infection in adults that difficult to treat. The vitro antifungal activity of efinaconazole, novel triazole antifungal, was evaluated recent clinical isolates Trichophyton rubrum, mentagrophytes, and Candida albicans, causative onychomycosis pathogens. In comprehensive survey 1,493 isolates, efinaconazole MICs against T. rubrum mentagrophytes ranged from ≤ 0.002 0.06 μg/ml, with 90% inhibited (MIC90) at 0.008 0.015 respectively. Efinaconazole 105 C....

ABSTRACT The mechanism of action efinaconazole, a new triazole antifungal, was investigated with Trichophyton mentagrophytes and Candida albicans . Efinaconazole dose-dependently decreased ergosterol production accumulated 4,4-dimethylsterols 4α-methylsterols at concentrations below its MICs. induced morphological ultrastructural changes in T. hyphae that became more prominent increasing drug concentrations. In conclusion, the primary efinaconazole is blockage biosynthesis, presumably...

ABSTRACT Onychomycosis is a common fungal nail disease that difficult to treat topically due the deep location of infection under densely keratinized plate. Keratin affinity topical drugs an important physicochemical property impacting therapeutic efficacy. To be effective, must penetrate bed and retain their antifungal activity within matrix, both which are adversely affected by keratin binding. We investigated these properties for efinaconazole, new onychomycosis, compared with those...

Onychomycosis is difficult to treat topically due the deep location of infection under densely keratinized nail plate. In order obtain an in vitro index that relevant clinical efficacy topical anti-onychomycosis drugs, we profiled five drugs: amorolfine, ciclopirox, efinaconazole, luliconazole, and terbinafine, for their permeabilities, keratin affinities, anti-dermatophytic activities presence keratin. Efinaconazole ciclopirox permeated full-thickness human nails more deeply than...

The ∼50 Myr old Izu–Bonin–Mariana (IBM) arc consists mostly of Oligocene middle and lower crust that underlies the upper crust; these units are in turn covered by Quaternary volcanic rocks. Seismic imaging, forearc geology, Ocean Drilling Program drilling magnetic anomalies suggest most IBM was created Eocene–Oligocene times. However, remnants this have never been found at northern end arc, where it is colliding with Honshu (Izu collision zone). Two batholiths zone (the Tanzawa tonalites...

The therapeutic efficacy of KP-103, a novel topical triazole, in guinea pig tinea unguium model was investigated. Experimental and pedis were produced by inoculation Trichophyton mentagrophytes SM-110 between the toes hind paw pigs. One percent solution (0.1 ml) amorolfine, or terbinafine topically applied to nails whole sole an infected foot once daily for 30 consecutive days, also orally administered at dose 40 mg/kg body weight starting on day 60 postinfection. fungal burdens plantar skin...

The present study investigates the expression of VLA-4 on thymocytes at various stages maturation and their capacity to adhere thymic stromal cells. Whole were stained with anti-CD4 anti-CD8, as well anti-VLA-4 antibodies. Flow microfluorometric analyses revealed that a) most CD4-8- (double negative DN) CD4-8intermediate thymocyte populations expressed large amounts VLA-4, b) levels considerably markedly reduced CD4+8+ positive DP) single (SP) (CD4+8- or CD4-8+) populations, respectively....

A two-step chemical procedure to separate Sr from whole igneous rock sample has been developed for the analysis of isotopes by thermal ionization mass spectrometry (TIMS). Firstly, a Sr-bearing fraction and REE are separated major elements decomposed solution using H+ form cation-exchange chromatography. Then is purified in second column extraction chromatography specific resin. For small amounts (< 0.1 mg) obtained micro-milling, only step separation applied, directly separating solution....

The in vitro activity of KP-103, a novel triazole derivative, against pathogenic fungi that cause dermatomycoses and its therapeutic efficacy plantar tinea pedis cutaneous candidiasis guinea pigs were investigated. MICs determined by broth microdilution method with morpholinepropanesulfonic acid-buffered RPMI 1640 medium for Candida species Sabouraud dextrose dermatophytes an agar dilution C Malassezia furfur. KP-103 was the most active all drugs tested albicans (geometric mean [GM] MIC,...

A fully automated open-column resin-bed chemical-separation system, named COLUMNSPIDER, has been developed. The system consists of a programmable micropipetting robot that dispenses chemical reagents and sample solutions into an resin bed for elemental separation. After the initial set up columns, reagents, beakers separated components, all separation procedures are automated. As many as ten samples can be eluted in parallel single run. Many procedures, such radiogenic isotope ratio analyses...

Efinaconazole is a novel triazole antifungal drug for the topical treatment of onychomycosis, nail infection caused mainly by dermatophytes. We assessed potential efinaconazole to induce resistance in dermatophytes continuous exposure Trichophyton rubrum strains vitro (12 passages) and guinea pig onychomycosis model (8 weeks). There was no evidence development tested under experimental conditions used.

Use of oral antifungals in the treatment onychomycosis is commonplace; but their use can be limited by safety and patient concerns. Due to broader margins, topical (efinaconazole, tavaborole, ciclopirox) are a useful option mild-to-moderate USA, antifungal activity has yet directly compared. This study aims identify important factors contributing vivo efficacies three antifungals. Minimum inhibitory concentrations (MICs) were determined Clinical Laboratory Standards Institute (CLSI) M38-A2...

2-Aryl-1-azolyl-3-(substituted amino)-2-butanol derivatives I were prepared by ring-opening reaction of epoxides II with excess amine, and their antifungal activities evaluated as topical agents. Azolyl-cyclic amine a methylene group showed extremely strong activity broad spectrum in vitro. In general, anti-Trichophyton mentagrophytes most the agents are substantially reduced addition keratin (a major constituent keratinized tissue). However, triazole derivative (2R, 3R)-2-(2,...

To reduce the immunogenicity of β-lactoglobulin (BLG), we prepared wild-type bovine BLG variant A (wt) and three site-specifically glycosylated BLGs (D28N, D137N/A139S, P153A), expressed them in methylotrophic yeast Pichia pastoris by fusion cDNA to sequence coding for α-factor signal peptide from Saccharomyces cerevisiae. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE) analysis indicated that were conjugated with a ∼4 kDa high-mannose chain. Each retained ∼80%...

To evaluate the combination effects of anti-onychomycosis drugs, minimum inhibitory concentrations topical (efinaconazole, luliconazole, and tavaborole) oral (itraconazole terbinafine) drugs for Trichophyton rubrum interdigitale (8 each, with a total 16 strains) were determined using microdilution checkerboard technique based on Clinical Laboratory Standard Institute guidelines. No antagonism was observed between against all tested strains. Efinaconazole terbinafine exerted synergistic...

The mechanism of transport KP-736, a novel cephalosporin with 1,5-dihydroxy-4-pyridone moiety at the C-7 position, into Escherichia coli K-12 cell was investigated by determining susceptibilities iron mutants to KP-736. tonB mutant showed higher degree resistance indicating that KP-736 incorporated E. cells via tonB-dependent system. product exbB gene also necessary for maximal antibacterial potency Cir-lacking and Fiu-lacking moderate level However, lacking any one proteins FepA, FecA,...

Four isolectins were isolated from bulbs of Croccus sativum (saffron), using affinity chromatography on mannan-Sepharose 4B, gel filtration and ion-exchange column in the presence 8 M urea. The relative molecular masses these lectins determined by to be approximately 48 kDa. On polyacrylamide electrophoresis, kDa obtained, suggesting that are hexamers. No carbohydrates detected lectins. agglutinated yeasts Saccharomyces cerevisiae at a minimum concentration 30 micrograms/ml, however, they...

The therapeutic efficacy of KP-103, a triazole derivative, for 10 guinea pigs with interdigital tinea pedis or corporis was investigated. Topical KP-103 solution (0.25 to 1%) dose-dependently effective in treating both dermatophytoses. A 1% KP-103-treatment rendered all infected skins culture-negative on day-2 posttreatment. high negative-culture rate obtained solutions butenafine and lanoconazole but not neticonazole solution. follow up study performed day-30 day-9 posttreatment...