Pharmacokinetics and pharmacodynamics of prasugrel in healthy Japanese subjects

AbstractThis randomized double-blind and placebo-controlled study assessed the pharmacodynamics and pharmacokinetics of prasugrel in healthy adult Japanese male subjects after single (n = 50) and multiple (n = 40) oral administration. With a single administration of prasugrel (2–30 mg), the plasma concentration of the active metabolite increased rapidly, reached a maximum at 30 min after administration, and then decreased rapidly within 4 h. The 5 mg and higher doses prevented ADP-induced platelet aggregation in a dose-dependent manner. Further analyses showed that 30 mg prasugrel exhibited the peak inhibition, and 20 mg prasugrel showed a nearly equivalent effect. With multiple doses (2.5–10 mg), the pharmacokinetic parameters on Day 1 and Day 7 were similar, and no accumulation attributable to multiple dosing was observed. The inhibitory effect on ADP-induced platelet aggregation increased with doses from 2.5 to 7.5 mg, and reached the peak level at 7.5 mg. Regarding safety, all of the drug-related adverse events observed were mild, and there were no clinically significant bleeding-related adverse events. This study indicates that a single oral administration of prasugrel at a dose of up to 30 mg and a maintenance dose of up to 10 mg are tolerated in Japanese healthy subjects

Study on surface degradation of LCFA-GGBF geopolymers by partial water absorption and silane impregnation techniques

When the pore solution becomes supersaturated in Portland cement hardened bodies due to evaporation of moisture, temperature change and so on, salts dissolved in the pore solution precipitate and the surface whitening (efflorescence) and surface roughening may occur. Similar phenomena also occur in hardened geopolymer (GP) (Fig.1). Formation process and resultant minerals are different from those of Portland cement and there are a few studies on GP so far on these events. In this paper, efflorescence and surface roughening were studied using low calcium coal fly ash (LCFA) / ground granulated blast furnace-slag (GGBS) type GP. Primarily, these phenomena were studied by partial water immersion technique (Fig.2). Subsequently, surface impregnation technique by a silane was performed and effective results were obtained as follows: (1) Since efflorescence and surface roughening were promoted in the refrigerator rather than in the constant temperature room (20°C, 60%RH), deterioration of the surface layer of GP is more likely to proceed as the temperature and humidity are lower. In addition, repetition of temperature change promotes deterioration of the surface layer. (2) Efflorescence and surface roughening of GP impairs not only aesthetic appearance of the structure but also sometimes lowers proof stress, so certain measures are necessary. (3) Efflorescence and surface roughening of GP can be suppressed by increasing the GGBS substitution rate (Fig.3). (4) Adjustment of the concentration of alkaline solution may suppress efflorescence and surface roughening. (5) The silane-based surface impregnating material for OPC concrete has the effect of reducing the rate of efflorescence and surface roughening of GP. Please click Additional Files below to see the full abstract

Outcome of Endoscopy-Assisted Microscopic Extended Transsphenoidal Surgery for Suprasellar Adult Craniopharyngiomas

Craniopharyngiomas are difficult to treat. The extended transsphenoidal approach has recently been described in several small series. We describe the usefulness of microscopy-assisted angled endoscopy for visualizing vital structures such as tumor attachment or tumor invasion to the pituitary stalk to achieve confident radical tumor removal. Between 2006 and 2010, 15 patients underwent the microscopy-assisted extended transsphenoidal approach for resection of entirely suprasellar craniopharyngiomas. Fourteen patients had the transinfundibular type, and one had the transinfundibular type with extension to the third ventricle. We observed color change within the pituitary stalk by endoscopy. The pituitary stalk was cut intentionally in 10 patients because of suspected tumor invasion surrounding the stalk. Total removal was accomplished in nine patients. Pathological specimens from the pituitary stalk showed tumor invasion spreading over the surface of the pituitary stalk, shown by a discolored pituitary stalk, and this was essential for confident radical tumor removal. Even after stalk resection, postoperative diabetes insipidus was minimal when a bright signal on T1 in the posterior lobe was not observed with preoperative magnetic resonance imaging. Confident radical tumor removal is possible with the introduction of the endoscopy-assisted microscopic extended transsphenoidal approach

Production of overdense plasmas by launching 2,45 GHz electron cyclotron waves in a helical device

For production of low temperature plasmas with low collisionality, 2.45GHz microwave power up to 20kW is injected perpendicularly to the toroidal field at very low toroidal field BtComment: 12th International Congress on Plasma Physics, 25-29 October 2004, Nice (France

Pregnenolone Sulfate Potentiates the Inwardly Rectifying K+ Channel Kir2.3

BACKGROUND:Neurosteroids have various physiological and neuropsychopharmacological effects. In addition to the genomic effects of steroids, some neurosteroids modulate several neurotransmitter receptors and channels, such as N-methyl-D-aspartate receptors, gamma-aminobutyric acid type A (GABA(A)) receptors, and sigma(1) receptors, and voltage-gated Ca(2+) and K(+) channels. However, the molecular mechanisms underlying the various effects of neurosteroids have not yet been sufficiently clarified. In the nervous system, inwardly rectifying K(+) (Kir) channels also play important roles in the control of resting membrane potential, cellular excitability and K(+) homeostasis. Among constitutively active Kir2 channels in a major Kir subfamily, Kir2.3 channels are expressed predominantly in the forebrain, a brain area related to cognition, memory, emotion, and neuropsychiatric disorders. METHODOLOGY/PRINCIPAL FINDINGS:The present study examined the effects of various neurosteroids on Kir2.3 channels using the Xenopus oocyte expression assay. In oocytes injected with Kir2.3 mRNA, only pregnenolone sulfate (PREGS), among nine neurosteroids tested, reversibly potentiated Kir2.3 currents. The potentiation effect was concentration-dependent in the micromolar range, and the current-voltage relationship showed inward rectification. However, the potentiation effect of PREGS was not observed when PREGS was applied intracellularly and was not affected by extracellular pH conditions. Furthermore, although Kir1.1, Kir2.1, Kir2.2, and Kir3 channels were insensitive to PREGS, in oocytes injected with Kir2.1/Kir2.3 or Kir2.2/Kir2.3 mRNA, but not Kir2.1/Kir2.2 mRNA, PREGS potentiated Kir currents. These potentiation properties in the concentration-response relationships were less potent than for Kir2.3 channels, suggesting action of PREGS on Kir2.3-containing Kir2 heteromeric channels. CONCLUSIONS/SIGNIFICANCE:The present results suggest that PREGS acts as a positive modulator of Kir2.3 channels. Kir2.3 channel potentiation may provide novel insights into the various effects of PREGS

Installation of the superconducting gravimeter CT(#043) at Syowa Station, Antarctica

During the wintering period of the 44th Japanese Antarctic Research Expedition (JARE-44: February 2003 to January 2004), a new superconducting gravimeter CT(#043) with a cryocooler was installed and tested to replace the former TT70(#016) at Syowa Station, Antarctica. The CT(#043) has design sensitivity of 1nGal (1×10^(-11)m/s^2) to study the Earth\u27s dynamics in tidal and longer-period bands. A new type of diaphragm was used to effectively isolate the vibration from the refrigerator cold-head and to prevent solid air contamination from entering the Dewar. A real-time remote monitoring system including a Web camera for diagnostics from Japan has also been installed