Nucleophilic Diboration Strategy Targeting Diversified 1-Boraphenarene Architectures.

1-Boraphenalenes, a class of boron-doped polyaromatic hydrocarbons, were synthesized by nucleophilic diboration reaction of alkynes. Activation of diboron reagents with a highly basic sp2 -carbanion results in very fast successive C-B bond formations to construct the boracycle. This methodology is characterized by high chemoselectivity, affording a wide variety of 1-boraphenarenes with diverse polar substituents. The endocyclic boron can be arylated conveniently in one pot, and the peripheral boron is available for various chemical transformations. Highly diastereoselective diboration gives pseudo-enantio-enriched boraphenarene, which emits circularly polarized fluorescence (CPL).

Alkynylboration Reaction Leading to Boron-Containing π-Extended cis-Stilbenes as a Highly Tunable Fluorophore.

An unprecedented boron-containing fluorophore, π-extended cis-stilbene, obtained via alkynylboration reaction of alkynamide is reported. Boron-containing π-extended cis-stilbenes emit fluorescence with high quantum yields in the solid state and exhibit aggregation-induced emission enhancement. The broad substrate scope of the alkynylboration reaction offers facile access to electronically diverse structures, enabling fine-tuning of light absorption/emission characteristics. The boron-containing π-extended cis-stilbene with a diphenylamino group displays solvatofluorochromism via an intramolecular charge-transfer transition.

Treatment for crusted scabies: limitations and side effects of treatment with ivermectin.

Skin eruption with mild itching of the hands and feet developed in a man in his 90s 1 month after he was hospitalized following a traffic accident. Scabies was diagnosed in an attending nurse 3 months after the patient's hospitalization, and infection from the patient was suspected. Cornification of the patient's soles and marked hypertrophy of the nails of both feet were observed. After a large number of scabies mites were detected on microscopic examination, crusted scabies was diagnosed. The patient was given oral ivermectin, 6 mg, once per week for 3 weeks, and crotamiton topical ointment containing 30% benzyl benzoate was applied on the body from the neck down. However, because a large number of scabies mites were detected again on microscopic examination, the dose of ivermectin was increased to 12 mg and administered 3 times. One week after the sixth dose of ivermectin was administered, hemorrhagic scabs around the mouth and erosion of the tongue developed. Mucosal drug eruption was suspected, and eruptions around the mouth and on the tongue resolved within 1 week after ivermectin being discontinued. 1% gamma-benzene hexachloride ointment was applied topically on the body from the neck down once a week, crotamiton ointment containing benzyl benzoate was applied daily, and the hypertrophic parts of the nails were removed. The patient subsequently achieved a full recovery.

Functional expression of amyloidogenic human stefins A and B in Pichia pastoris using codon optimization.

Complementary DNAs encoding human stefins A (HSA) and B (HSB) were synthesized using Pichia-preferred codons by overlap extension PCR. The full-length genes were ligated downstream of the glyceraldehyde-3-phosphate dehydrogenase promoter in the Pichia expression vector pGAPZαC and successfully expressed in Pichia pastoris strain X-33. Functional recombinant HSA and HSB proteins were purified from culture medium at yields of 121.3 ± 13.5 (n = 3) and 95.4 ± 4.1 (n = 3) mg/L, respectively. Using this expression strategy, we demonstrated that high levels of bioactive recombinant HSA and HSB can be produced by fermentation in P. pastoris.

Usefulness and pharmacokinetic study of oral terbinafine for hyperkeratotic-type tinea pedis.

To study and establish an optimal administration method of oral antifungal, terbinafine (TBF), for hyperkeratotic-type tinea pedis from the pharmacokinetic point of view, 20 patients with hyperkeratotic-type tinea pedis were given TBF 125 mg once daily for 4 weeks and observed over time for improvement of dermatological symptoms and mycological efficacy. Targeting five of the patients, TBF concentration in the stratum corneum was measured using the LC-MS/MS method. TBF was detected in the stratum corneum of the sole 1 week after beginning the treatment in some cases and reached its peak 1 week after the completion of the treatment with a concentration of 247.8 ng g(-1), which was approximately more than 50 times higher than its minimal inhibitory concentration against dermatophytes. TBF was not detected at 8 weeks post-treatment, although its concentration was 50.73 ng g(-1) at 6 weeks post-treatment. All cases were subjected to analysis for final total efficacy, general safety and usefulness. Its effectiveness rate (effective + markedly effective) was 95% (19/20) with no adverse reactions, including abnormal changes in the laboratory test values, in any patients. From the above, it is noted that TBF showed excellent efficacy and safety for refractory hyperkeratotic-type tinea pedis, and also it was considered as a useful drug to treat cutaneous mycosis, including hyperkeratotic-type tinea pedis, from the pharmacokinetic point of view.

Usefulness and pharmacokinetic study of oral terbinafine for hyperkeratotic type tinea pedis.

To study and establish an optimal administration method of oral antifungal, terbinafine (TBF), for hyperkeratotic type tinea pedis, from the pharmacokinetic point of view, 20 patients with hyperkeratotic type tinea pedis were given TBF 125 mg once daily for 4 weeks and observed over time for improvement in dermatological symptoms and mycological efficacy. Targeting five of the patients, TBF concentration in the stratum corneum was measured using the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. TBF was detected in the stratum corneum of the sole 1 week after beginning the treatment in some cases and reached its peak 1 week after the completion of the treatment with a concentration of 247.8 ng g(-1), which was approximately more than 50 times higher than its minimal inhibitory concentration against dermatophytes. TBF was not detected at 8 weeks post-treatment, although its concentration was 50.73 ng g(-1) at 6 weeks post-treatment. Its effectiveness rate (effective + markedly effective) was 95% (19/20) with no adverse reactions, including abnormal changes in the laboratory test values, in any patient. These results suggest that TBF is a useful drug to treat hyperkeratotic tinea pedis from the pharmacokinetic point of view.

Systemic lupus erythematosus-associated cutaneous cryptococcosis treated successfully with an intermittent 3-day on/off cycle of itraconazole.

We describe a case of systemic lupus erythematosus (SLE)-associated cutaneous cryptococcosis. A 32-year-old woman with SLE and lupus nephritis presented with the erythematous maculae on the chest and the extremities, in which encapsulated yeasts were revealed, and was diagnosed with secondary cutaneous cryptococcosis. We administered fluconazole (FLCZ) and then itraconazole (ITCZ) instead of amphotericin B (AMPH-B) to avoid the risk of renal toxicity of AMPH-B in the patient. While treatment with FLCZ was not particularly effective, repeated intermittent administration of ITCZ on a "3-day on/off cycle" (i.e. medication on 3 consecutive days and suspension for the next 3 days in turn) achieved complete remission of the cryptococcosis.

Usefulness of itraconazole for sporotrichosis in Japan: study of three cases and literature comparison of therapeutic effects before and after release on the market.

Potassium iodide, itraconazole (ITCZ), and terbinafine are widely known as oral antifungal agents for the treatment of sporotrichosis. Although potassium iodide has been used as the antifungal agent of first choice in Japan due to its high efficacy, its use is not covered by the health insurance programs. In this report, we present the disease course of 3 patients with sporotrichosis in which ITCZ was remarkably effective. By reviewing cases reported in the past, we found sufficient therapeutic effects of ITCZ against sporotrichosis. We also conducted a simple comparison of the efficacy of ITCZ in clinical trials with that of its post-market release; finding the latter to be lower. This seems to be attributable to the problem of compliance or the administration method.

Molecular weight-dependent gene transfection activity of unmodified and galactosylated polyethyleneimine on hepatoma cells and mouse liver.

To optimize a receptor-mediated and cell-selective gene transfer with polyethyleneimine (PEI)-based vector, we synthesized three galactosylated PEIs (Gal-PEI) with different molecular weights (PEI(1800), PEI(10,000), and PEI(70,000)) and investigated their potential as a targetable vector to asialoglycoprotein receptor-positive cells. All PEI derivatives formed complexes with plasmid DNA (pDNA), whereas the particle size of the complex became smaller on increasing the molecular weight of PEI. Transfection efficiency in HepG2 cells with PEI was highest with PEI(1800); efficiency was next highest with PEI(10,000), although the cellular association was similar. After galactosylation, Gal(19)-PEI(10,000)/pDNA and Gal(120)-PEI(70,000)/pDNA showed considerable agglutination with a galactose-recognizing lectin, but Gal(9)-PEI(1800) did not, suggesting that galactose units on the Gal(9)-PEI(1800)-pDNA complex are not sufficiently available for recognition. Gal(19)-PEI(10,000)-pDNA and Gal(120)-PEI(70,000)-pDNA complexes showed galactose-inhibitable transgene expression in HepG2 cells. Transfection efficiency was greatest with Gal(19)-PEI(10,000)/pDNA, a result that highlights the importance of obtaining a balance between the cytotoxicity and the transfection activity, both of which are found to be a function of the molecular weight of PEI. After intraportal injection, however, Gal(153)-PEI(70,000)/pDNA having a low N/P ratio was most effective, suggesting that additional variables, such as the size of the complex, are important for in vivo gene transfer to hepatocytes.

[Monthly cycles of 1-week therapy with itraconazole for patients with Tinea pedis].

Monthly cycles of 1-week therapy with oral itraconazole at 200 mg daily for tinea pedis was assessed to determine its acceptability to patients. Thirty-four patients (17 men and 17 women) with intractable tinea pedis, with informed consent, took 200 mg of itraconazole once daily for one week over a month period until mycological studies showed negative results for up to 4 months. The overall mycological effectiveness was about 80% after this therapy. Information was also gathered on the influence of this therapy on the patients quality of life by questionnaires. Nineteen (70%) among the 27 patients who answered the questionnaire preferred this 1-week administration of itraconazole over a month-long period compared with continuous daily therapy. Twenty-two (81%) preferred this therapy over topical treatment. We recommend to this therapy be added for the treatment of intractable tinea pedis.