[Three cases of external auditory exostoses in a habitual sauna user].

Exostoses are benign bony excrescences of the external auditory canal, commonly encountered in people who avidly engage in aquatic activities, hence the name "surfer's ear". Exostoses are more prevalent in cold water surfers, and additional years of surfing increase one's risk not only for developing an exostosis but also for developing more severe lesions. Exostoses remain clinically silent until they become large enough to impair the egress of epithelial debris and water from the canal, in which case there may be an associated external otitis and fluctuating hearing loss. Histologically, they demonstrate a laminated structure consistent with a periodic growth pattern. They may also cause a hearing loss by impinging upon the tympanic membrane and manubrium. Symptomatic relief is attained by surgical removal and skin grafting of the epithelially denuded areas of the bony walls of the external auditory canal. We report herein on 3 cases of exostoses which developed in patients who had a habit of taking a cold water bath after a hot sauna for more than 15 years: in spite of the limited time of exposure to cold water stimulation, alternating exposure to the hot environment of the sauna and cold water baths seemed to have acceralated the formation of the exostoses.

Detection of 22 antiepileptic drugs by ultra-performance liquid chromatography coupled with tandem mass spectrometry applicable to routine therapeutic drug monitoring.

The purpose of this study was to develop an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method of 22 antiepileptics for routine therapeutic monitoring. The antiepileptics used in the analyses were carbamazepine, carbamazepine-10,11-epoxide, clobazam, N-desmethylclobazam, clonazepam, diazepam, N-desmethyldiazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, N-desmethylmesuximide, nitrazepam, phenobarbital, phenytoin, primidone, tiagabine, topiramate, valproic acid, vigabatrin and zonisamide. After protein precipitation of 50 µL plasma with methanol, the supernatant was diluted with water or was evaporated to dryness and reconstituted with mobile phase in the case of benzodiazepines. Separation was achieved on an Acquity UPLC BEH C18 column with a gradient mobile phase of 10 mm ammonium acetate containing 0.1% formic acid and methanol at a flow rate of 0.4 mL/min. An Acquity TQD instrument in multiple reaction monitoring mode with ion mode switching was used for detection. All antiepileptics were detected and quantified within 10 min, with no endogenous interference. All the calibration curves showed good linearity in the therapeutic range (r² < 0.99). The precision and accuracy values for intra- and inter-assays were within ±15% except for phenobarbital and tiagabine. A good correlation was observed between the concentration of clinical samples measured by the new method described here and the conventional methods. The values of carbamazepine and phenytoin by UPLC-MS/MS were lower than those detected by the immunoassays, which might be caused by the cross-reaction of antibodies with their metabolites. In conclusion, we developed a simple and selective UPLC-MS/MS method suitable for routine therapeutic monitoring of antiepileptics.

Extracts of Gluconacetobacter hansenii GK-1 induce Foxp3+T cells in food-allergic mice by an IL-4-dependent or IL-4-independent mechanism.

The biological activities of acetic acid bacteria (AAB) as Gram-negative bacteria have attracted our interests, especially in their inhibitory effects on allergic responses. To clarify the underlying mechanism that improves allergic symptoms by ingestion of the AAB Gluconacetobacter hansenii, we examined whether different extracts of heat-killed G. hansenii GK-1 could reduce the interleukin (IL)-4 production of immune cells from food-allergic model of OVA23-3, transgenic mice with ovalbumin (OVA)-specific T-cell-receptor genes. A hot-water extract fraction (FII) of G. hansenii GK-1 significantly decreased the in vitro IL-4 production of spleen cells of OVA23-3 mice compared with those stimulated with OVA alone. The IL-4 inhibitory effect was also observed for FIV (purified lipopolysaccharide (LPS) fraction), but the activity was lower than for FII or LPS from Escherichia coli. Unlike LPS from Escherichia coli, FIV significantly inhibited the LPS-induced IL-6 production of the spleen cells. The addition of FII or FIV to a Foxp3+T cell-inducing culture showed that FII significantly promoted the rate of Foxp3+CD4+T cells of OVA-stimulated mesenteric lymph node cells from recombination-activating-gene (RAG)-2-deficient food-allergic inflammatory OVA23-3 (R23-3) mice with suppression of IL-4 production, while FIV induced Foxp3+T cells from RAG-2-deficient DO11.10 non-inflammatory mice. Structure analysis showed a lack of O-antigen in FIV, which seemed to lead to the weak biological activities of FIV observed. The present study suggests that extracts of G. hansenii GK-1 to inhibit IL-4 production of immune cells and/or promote regulatory T cell differentiation synergistically play important roles in improving allergic symptoms safely as well as normal condition.

Domino Cross-Scholl Reaction of Tetracene with Molecular Benzene: Synthesis, Structure, and Mechanism.

A domino-type multiple C-H functionalization of tetracene with molecular benzene is reported. Under the typical conditions of the Scholl reaction, a domino reaction occurs between tetracene and six molecules of benzene in one pot to furnish an aromatic compound with a curved π-system. This reaction sequence involves oxidative cross-dehydrogenative coupling/annulation and Friedel-Crafts-type reactions. Eight C-C bonds are formed via this intermolecular domino reaction without mediation by a metal or the assistance of a specific substituent.

Ossiculoplasty with a cartilage-connecting hydroxyapatite prosthesis for tympanosclerotic stapes fixation.

Many cases of tympanosclerotic stapes fixation are accompanied by fixation or erosion of malleus and/or incus. This status of the ossicular chain is one of the reasons that ossiculoplasty for tympanosclerotic stapes fixation is more difficult than that for otosclerosis. We conducted a retrospective review of seven patients who were operated on for tympanosclerotic stapes fixation between 2002 and 2006. All of the patients had abnormal conditions of the malleus and/or incus and underwent stapedectomy and total ossiculoplasty with hydroxyapatite prosthesis (Apaceram T-7 type), which has a planar-like head portion that contacts a piece of cartilage. Postoperative hearing results were assessed in all seven patients after at least 1 year. The postoperative air-bone gap (ABG) was closed within 10 dB in two of seven patients, and was less than 20 dB in six of seven patients. The mean postoperative ABG was closed within 10 dB at 1 and 2 kHz and less than 20 dB at low frequencies (0.25 and 0.5 Hz). There was almost no hearing improvement at high frequencies (4 and 8 kHz). There were no patients with postoperative sensorineural hearing loss. The present study shows that stapedectomy and total ossiculoplasty with cartilage-connecting hydroxyapatite prosthesis is effective and safe for stapes fixation accompanied by fixation or erosion of the malleus and/or incus.

Highly Active NaTaO3 -Based Photocatalysts for CO2 Reduction to Form CO Using Water as the Electron Donor.

Doped NaTaO3 (NaTaO3 :A, where A=Mg, Ca, Sr, Ba, or La) has arisen as a highly active photocatalyst for CO2 reduction to simultaneously form CO, H2 , and O2 using water as the electron donor when used with an Ag cocatalyst, under UV irradiation, and with 1 atm (0.1 MPa) of CO2 . The ratio of the number of reacted electrons/holes was almost unity, indicating that water was consumed as the electron donor. A liquid-phase reduction method for loading of the Ag cocatalyst was superior to photodeposition and impregnation methods. The Ag cocatalyst-loaded NaTaO3 :Ba was the most active photocatalyst in water with no required additives. The addition of bases, such as hydrogencarbonate, was effective to enhance the CO formation for Mg-, Ca-, Sr-, Ba-, and La-doped NaTaO3 photocatalysts with an Ag cocatalyst. Ca- and Sr-doped NaTaO3 photocatalysts showed especially high activity along with the Ba-doped photocatalyst in the aqueous NaHCO3 solution. The selectivity for the CO formation [CO/(CO+H2 )] on Ca-, Sr-, and Ba-doped NaTaO3 photocatalysts with Ag cocatalyst reached around 90 %.

Postoperative Submandibular Gland Swelling following Craniotomy under General Anesthesia.

Objective. Reporting of a rare case of postoperative submandibular gland swelling following craniotomy. Case Report. A 33-year-old male underwent resection for a brain tumor under general anesthesia. The tumor was resected via a retrosigmoid suboccipital approach and the patient was placed in a lateral position with his face down and turned to the right. Slight swelling of the right submandibular gland was observed just after the surgery. Seven hours after surgery, edematous change around the submandibular gland worsened and he required emergent reintubation due to airway compromise. The cause of submandibular gland swelling seemed to be an obstruction of the salivary duct due to surgical positioning. Conclusion. Once submandibular swelling and edematous change around the submandibular gland occur, they can worsen and compromise the air way within several hours after operation. Adequate precaution must be taken for any predisposing skull-base surgery that requires strong cervical rotation and flexion.

Impact of P-glycoprotein and breast cancer resistance protein on the brain distribution of antiepileptic drugs in knockout mouse models.

Refractory epilepsy is reportedly associated with an overexpression of ATP-binding cassette transporters such as P-glycoprotein (Pgp) and breast cancer resistance protein (Bcrp). In this study, we examined the contribution of Pgp and Bcrp to the brain distribution of 12 antiepileptic drugs (AEDs) in Mdr1a/1b(-/-) and Mdr1a/1b(-/-)/Bcrp(-/-) mice within a therapeutic concentration range. The blood concentrations were sequentially determined, and the brain concentrations were measured at 60 min after intravenous administration. The plasma concentration profiles for each AED in the Mdr1a/1b(-/-) mice were equivalent to those in the wild-type mice. In contrast, the plasma concentration profiles of phenytoin, lamotrigine, topiramate, tiagabine, and levetiracetam in the Mdr1a/1b(-/-)/Bcrp(-/-) mice were significantly lower than the corresponding ones in the wild-type mice. The brain-to-plasma concentration ratio (Kpbrain) values of phenytoin, topiramate, and tiagabine in the Mdr1a/1b(-/-) mice were significantly higher than the corresponding ones in the wild-type mice. In contrast, the Kpbrain values of phenobarbital, clobazam, zonisamide, gabapentin, tiagabine, and levetiracetam in the Mdr1a/1b(-/-)/Bcrp(-/-) mice were significantly higher than the corresponding ones in Mdr1a/1b(-/-) mice. The Kpbrain values of the 12 AEDs in the Mdr1a/1b(-/-)/Bcrp(-/-) mice, but not wild-type mice, significantly correlated with the corresponding molecular weight values. These findings suggest that both Pgp and Bcrp restrict brain access for several AEDs. Taken together, information on the contribution of each transporter may be useful in the development of strategic treatments of refractory epilepsy.

Development of a two-dimensional high-performance liquid chromatography system coupled with on-line reduction as a new efficient analytical method of 3-nitrobenzanthrone, a potential human carcinogen.

3-Nitrobenzanthrone (3-NBA) is an extremely strong mutagen and carcinogen in rats inducing squamous cell carcinoma and adenocarcinoma. We developed a new sensitive analytical method, a two-dimensional HPLC system coupled with on-line reduction, to quantify non-fluorescent 3-NBA as fluorescent 3-aminobenzanthrone (3-ABA). The two-dimensional HPLC system consisted of reversed-phase HPLC and normal-phase HPLC, which were connected with a switch valve. 3-NBA was purified by reversed-phase HPLC and reduced to 3-ABA with a catalyst column, packed with alumina coated with platinum, in ethanol. An alcoholic solvent is necessary for reduction of 3-NBA, but 3-ABA is not fluorescent in the alcoholic solvent. Therefore, 3-ABA was separated from alcohol and impurities by normal-phase HPLC and detected with a fluorescence detector. Extracts from surface soil, airborne particles, classified airborne particles, and incinerator dust were applied to the two-dimensional HPLC system after clean-up with a silica gel column. 3-NBA, detected as 3-ABA, in the extracts was found as a single peak on the chromatograms without any interfering peaks. 3-NBA was detected in 4 incinerator dust samples (n=5). When classified airborne particles, that is, those <1.1, 1.1-2.0, 2.0-3.3, 3.3-7.0, and >7.0 µm in size, were applied to the two-dimensional HPLC system after purified using a silica gel column, 3-NBA was detected in those particles with particle sizes <1.1 and 1.1-2.0 µm and the particle-size distribution ratios were 84% and 16%, respectively. This is the first report on the particle-size distribution of 3-NBA in airborne particles and the detection of 3-NBA in incinerator dust.

Incidence of external auditory canal exostoses in competitive surfers in Japan.

OBJECTIVE: The objective of this study was to demonstrate the prevalence and severity of external auditory canal exostoses in a population of competitive surfers in Japan. The authors used a "surfing index," the product of the period (years) as an active surfer and the frequency (number of surfing days per week), to predict external auditory exostoses formation. STUDY DESIGN: Cross-sectional study. SETTING: A total of 5 surfing competitions that were held in Miyazaki, Japan. MATERIALS AND METHODS: The ear canals of 373 surfers with an average age of 33.1 years (range, 11-80 years) were examined with an otoscope. The severity of exostosis was classified into 4 groups, ranging from grade 0 to 3, according to otoscopic findings. Subjects also completed a questionnaire detailing their surfing habits. RESULTS: There was a 59.8% overall prevalence of exostoses in 373 surfers. The incidences of grade 1, 2, and 3 exostoses were 118 (31.6%), 71 (19.0%), and 34 (9.1%), respectively. The prevalences of grade 2 and 3 exostoses were higher in surfers with a surfing index of more than 20 (P < .0001). CONCLUSIONS: The authors determined that a positive association exists between the surfing index and the severity of exostoses. The findings suggest that it is possible to assume the likelihood of exostosis formation from the surfing index, and this may be of help to spread awareness of exostosis among surfers.