Summary
Background
TAK‐438 (vonoprazan) is a potassium‐competitive acid blocker that reversibly inhibits gastric H+, K+‐ATPase.
Aim
To evaluate the safety, tolerability, pharmacokinetics and ...pharmacodynamics of TAK‐438 in healthy Japanese and non‐Japanese men.
Methods
In two Phase I, randomised, double‐blind, placebo‐controlled studies, healthy men (Japan N = 60; UK N = 48) received TAK‐438 10–40 mg once daily at a fixed dose level for 7 consecutive days. Assessments included safety, tolerability, pharmacokinetics and pharmacodynamics (intragastric pH).
Results
Plasma concentration–time profiles of TAK‐438 at all dose levels showed rapid absorption (median Tmax ≤2 h). Mean elimination half‐life was up to 9 h. Exposure was slightly greater than dose proportional, with no apparent time‐dependent inhibition of metabolism. There was no important difference between the two studies in AUC0‐tau on Day 7. TAK‐438 caused dose‐dependent acid suppression. On Day 7, mean 24‐h intragastric pH>4 holding time ratio (HTR) with 40 mg TAK‐438 was 100% (Japan) and 93.2% (UK), and mean night‐time pH>4 HTR was 100% (Japan) and 90.4% (UK). TAK‐438 was well tolerated. The frequency of adverse events was similar at all dose levels and there were no serious adverse events. There were no important increases in serum alanine transaminase activity. Serum gastrin and pepsinogen I and II concentrations increased with TAK‐438 dose.
Conclusions
TAK‐438 in multiple rising oral dose levels of 10–40 mg once daily for 7 days was safe and well tolerated in healthy men and caused rapid, profound and sustained suppression of gastric acid secretion throughout each 24‐h dosing interval. Clinicaltrials.gov identifiers: NCT02123953 and NCT02141711.
Silent aspiration of oropharyngeal pathogenic organisms is a significant risk factor causing pneumonia in the elderly. We hypothesized that regular oral hygiene care will affect the presence of ...oropharyngeal bacteria. Professional cleaning of the oral cavity and/or the gargling of a disinfectant liquid solution was performed over a five-month period in three facilities for the dependent elderly. Total oropharyngeal bacteria, streptococci, staphylococci, Candida, Pseudomonas, and black-pigmented Bacteroides species were monitored. The levels of these oropharyngeal bacteria decreased or disappeared after weekly professional oral health care, i.e., cleaning of teeth, dentures, tongue, and oral mucous membrane by dental hygienists. After lunch, gargling with povidone iodine was shown to be less effective than professional oral care. These findings indicate that weekly professional mechanical cleaning of the oral cavity, rather than a daily chemical disinfection of the mouth, can be an important strategy to prevent aspiration pneumonia in the dependent elderly.
Essentials
A consensus methodology for assessing the effects of antiplatelet agents has not been established.
Measuring platelet thrombus formation (PTF) for evaluating antiplatelet effects was ...assessed.
PTF differentially reflected antiplatelet effects compared to other tests.
PTF may be associated with the severity of carotid or intracranial arterial stenosis.
Click to hear a presentation on platelet function testing in the clinic by Gresele and colleagues
Summary
Background
A consensus methodology for assessing the effects of antiplatelet agents has not been established.
Objective
We investigated the usefulness of directly measuring platelet thrombus formation (PTF) using a microchip‐based flow chamber system for evaluating antiplatelet therapy.
Patients/Methods
Platelet thrombus formation in the whole blood of 94 patients with ischemic cerebrovascular disease treated with clopidogrel and/or aspirin was measured in a flow chamber system at a shear rate of 1500 s−1 and was compared with the results of assays for agonist‐induced platelet aggregability, phosphorylation of vasodilator‐stimulated phosphoprotein, platelet p‐selectin expression (PS), and platelet‐monocyte complexes.
Results
In all patients tested, area under the flow pressure curve (AUC10), which represents platelet thrombogenicity, showed weak correlation with platelet aggregation induced by either adenosine diphosphate or collagen. In addition, AUC10 was lower in patients treated with dual antiplatelet therapy (median 79.4) compared with patients treated with aspirin or clopidogrel alone (217.7 and 301.0, respectively), whereas the parameters evaluated by the other assays did not reflect the combined treatment efficacy. In clopidogrel monotherapy patients, AUC10 was associated with the severity of arterial stenosis (R2 = 0.127, β = 1.25), and AUC10 and PS were higher in patients with severe carotid or intracranial arterial stenosis than in those with mild stenosis.
Conclusions
Platelet thrombus formation measurement using a flow‐chamber system was useful for evaluating the efficacy of treatment with aspirin and clopidogrel, both alone and in combination. The present findings indicate that high residual platelet thrombogenicity in patients treated with clopidogrel may be associated with the severity of carotid or intracranial arterial stenosis.
Braid-press forming was developed for manufacturing hollow tube parts made of carbon fiber reinforced thermoplastic (CFRTP) tape. The CFRTP tapes were braided to make a tube, which was consolidated ...under pressure and heat in the press forming process. Internal pressure was applied to the braided CFRTP tube by a silicone rubber rod inserted in the tube using axial compression. The reason for using a silicone rubber rod was to apply a high internal pressure until the molten resin solidified, which cannot be achieved in bladder molding and pultrusion, and to obtain good consolidation quality and high mechanical properties. As a result, up to 7 MPa press pressure was successfully applied and the tube made contained no voids and had good flexural properties. The study of the pressure showed that the higher press pressure (from 4.1 MPa) produced tubes with higher flexural properties. The estimation of wall thickness after press forming using the braiding architecture agreed with the measured value. Subjects to be addressed in future studies are productivity improvements and continuous tube manufacturing by the serial joining of braiding and press forming. It can be concluded that braid-press forming is a desirable method for the manufacturing of tubes for structural applications and can be used in future mass-production.
Aim To investigate the effect of heat treatment on the bending properties of nickel–titanium endodontic instruments in relation to their transformation behaviour.
Methodology Nickel–titanium ...super‐elastic alloy wire (1.00 mm Ø) was processed into a conical shape with a 0.30 mm diameter tip and 0.06 taper. The heat treatment temperature was set at 440 or 500 °C for a period of 10 or 30 min. Nonheat‐treated specimens were used as controls. The phase transformation behaviour was examined using differential scanning calorimetry. A cantilever‐bending test was used to evaluate the bending properties of the specimens. Data were analyed by anova and the Tukey–Kramer test (P = 0.05).
Results The transformation temperature was higher for each heat treatment condition compared with the control. Two clear thermal peaks were observed for the heat treatment at 440 °C. The specimen heated at 440 °C for 30 min exhibited the highest temperatures for Ms and Af, with subsequently lower temperatures observed for specimens heated at 440 °C for 10 min, 500 °C for 30 min, 500 °C for 10 min, and control specimens. The sample heated at 440 °C for 30 min had the lowest bending load values (P < 0.05), both in the elastic range (0.5 mm deflection) and in the super‐elastic range (2.0 mm deflection). The influence of heat treatment time was less than that of heat treatment temperature.
Conclusions Change in the transformation behaviour by heat treatment may be effective in increasing the flexibility of nickel–titanium endodontic instruments.
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