Incidence, prevalence, and treatment of Moyamoya disease in Japan: A population-based descriptive study.

BACKGROUND: Moyamoya disease (MMD) is characterized by progressive stenosis or occlusion of the terminal portions of the bilateral internal carotid arteries. A Japanese survey in 2003 reported an incidence and prevalence of MMD of 0.54 and 6.03 per 100,000 people, respectively, showing an upward trend over previous surveys. An update to these estimates is therefore warranted. Additionally, evidence is lacking on trends in revascularization and antiplatelet therapy in MMD patients. METHODS: We conducted a population-based descriptive study using a Japanese claims database. From fiscal year (FY) 2015 to 2019, we standardized the incidence and prevalence estimates of MMD to the 2015 Japanese census population by age and sex. We also estimated the 1-year cumulative incidence of revascularization among incident MMD patients and the proportion of prevalent MMD patients receiving antiplatelet therapy in each FY. RESULTS: The age-standardized male-to-female ratio of both incident and prevalent MMD patients was approximately 1:2. Standardized incidence and prevalence of MMD per 100,000 population increased slightly from 1.8 to 2.4 and 14.7 to 17.6, respectively. The 1-year cumulative incidence of revascularization among incident MMD patients varied between 21.9 % and 28.9 %. Among prevalent MMD patients, 36.6 % to 39.0 % received antiplatelet therapy. CONCLUSIONS: The incidence and prevalence of MMD in Japan from FY 2015 to 2019 were higher than those estimated in 2003. The trends in revascularization and antiplatelet therapy identified in this study will be useful in further improving the quality of MMD clinical practice.

Urinary Excretion of Nadolol as a Possible In Vivo Probe for Drug Interactions Involving P-Glycoprotein.

Nadolol is a hydrophilic and nonselective ß-adrenoceptor blocker with a bioavailability of 30%, relatively longer half-life, negligible metabolism, and predominant renal excretion. Previous studies have reported that nadolol is a substrate of P-glycoprotein, and the coadministration with itraconazole, a typical P-glycoprotein inhibitor, results in elevated plasma concentrations and cumulative urinary excretion of nadolol. In this study, we assessed whether measurements of urinary-excreted nadolol can be an alternative method of plasma pharmacokinetics for P-glycoprotein-mediated drug interactions in humans. We reanalyzed the pooled data set of plasma concentration and urinary excretion of nadolol from our previous clinical studies in a total of 32 healthy Japanese adults. The area under the plasma concentration-time curve from 0 to infinity (AUC0-∞ ) of nadolol in individual subjects was significantly correlated with the maximum plasma concentration (r = 0.80, P < .01) and the cumulative amount excreted into urine (Ae ) at 4 (r = 0.51, P = .01), 8 (r = 0.63, P < .01), 24 (r = 0.75, P < .01), and 48 (r = 0.77, P < .01) hours. Significant correlations were also observed between the AUC and Ae during the same respective periods. In the drug interactions of nadolol with itraconazole, rifampicin, a well-known P-glycoprotein inducer, or grapefruit juice, there were significant correlations between the differences in AUC0-48 and those in Ae, 0-48 from the controls in individual subjects. These results suggest that the measurements of urinary excretion of nadolol can be employed as a sensitive and reliable alternative to plasma pharmacokinetics for the evaluation of P-glycoprotein-mediated drug interactions.

Polyoxometalate-Assisted, One-Pot Synthesis of a Pentakis[(triphenylphosphane)gold]ammonium(2+) Cation Containing Regular Trigonal-Bipyramidal Geometries of Five Bonds to Nitrogen.

Novel intercluster compounds consisting of pentakis[(triphenylphosphane)gold]ammonium(2+) cation (1) and Keggin polyoxometalate (POM) anions, i.e., {[Au(PPh3)]5(µ5-N)}3[α-PM12O40]2 (1-PW for M = W; 1-PMo for M = Mo), were synthesized in 30-36% yield by one-pot reaction of the protonic acid form of the Keggin POMs, H3[α-PM12O40]·nH2O (n = 13 for M = W; n = 15 for M = Mo) with monomeric (triphenylphosphane)gold(I) carboxylate [Au(RS-pyrrld)(PPh3)] [RS-Hpyrrld = (RS)-2-pyrrolidone-5-carboxylic acid] in the presence of aqueous NH3 at a molar ratio of 2:15:x (x = 3 for 1-PW; x = 7.5 for 1-PMo). These compounds resulted from the nitrogen-centered phosphanegold(I) clusterization of in situ generated monomeric phosphanegold(I) units, [Au(PPh3)]+ or [Au(L)(PPh3)]+ (L = NH3 or solvent), during the carboxylate elimination of [Au(RS-pyrrld)(PPh3)] in the presence of the Keggin POMs and aqueous NH3. The products 1-PW and 1-PMo were characterized by elemental analysis, Fourier transform infrared, thermogravimetric and differential thermal analyses (TGA/DTA), X-ray crystallography, and solid-state cross-polarization magic-angle-spinning (CPMAS) (31P and 15N) and solution (31P{1H} and 1H) NMR spectroscopy. The lattice contained three independent {[Au(PPh3)]5(µ5-N)}2+ cations, of which two took regular trigonal-bipyramidal (TBP) geometries and the third took a distorted, square-pyramidal (SP) geometry. These geometries are in contrast to those reported by Schmidbaur's group for {[Au(PPh3)]5(µ5-N)}2+ cations as BF4 salts. Density functional theory and ONIOM calculations for {[(L3P)Au]nN}(n-3)+ (L = H or Ph; n = 4-6) showed that the pentacoordinate cluster is energetically most stable and its TBP structure is only 1.6 kcal mol-1 more stable than its SP structure, in accordance with the experimental facts.

MicroRNA-1 targets Slug and endows lung cancer A549 cells with epithelial and anti-tumorigenic properties.

MicroRNA-1 (miR-1) has recently been suggested to function as a tumor suppressor. Its functional relevance was assessed by exploring structural and tumorigenic properties of lung cancer A549 cells stably transduced with retrovirus containing pre-miR-1. A549 cells overexpressing miR-1 exhibited a significant morphological change from a mesenchymal to an epithelial phenotype characterized by cell polarization and intercellular junctions. The cells showed increased expression of E-cadherin, which colocalized with cortical actin filaments and vinculin to form typical adherens junction at the apical regions of intercellular borders. Additionally, they exhibited occludin-positive tight junctions at similar apical regions. Moreover, their migratory and invasive activities were inhibited, and their sensitivity to doxorubicin was increased slightly compared to control mock-infected cells. These structural and tumorigenic properties induced by miR-1 were associated with the reduced expression of Slug, which was a transcriptional repressor of E-cadherin or an inducer of epithelial-to-mesenchymal transition. Consistently, Slug was identified as a miR-1 target by bioinformatics and a luciferase reporter assay with plasmids containing luciferase-Slug 3'UTR. Collectively, the data presented here suggest that re-expression of miR-1 may be an effective therapy that prevents cancer malignancy by converting cells from a mesenchymal phenotype to an epithelial phenotype via the downregulation of Slug.