Pharmacokinetics of low doses of colchicine in the leukocytes of Japanese healthy individuals.

The venerable drug colchicine has garnered significant recent attention due to its endorsement by the United States Food and Drug Administration as an anti-inflammatory medication for cardiovascular diseases. However, the administration of this drug at its minimal available dose of 0.5 mg has been associated with certain adverse reactions.

Efficacy and safety of single-dose ivermectin in mild-to-moderate COVID-19: the double-blind, randomized, placebo-controlled CORVETTE-01 trial.

Background: To investigate whether ivermectin inhibits SARS-CoV-2 proliferation in patients with mild-to-moderate COVID-19 using time to a negative COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) test.

Methods: CORVETTE-01 was a double-blind, randomized, placebo-controlled study (August 2020-October 2021) conducted in Japan. Overall, 248 patients diagnosed with COVID-19 using RT-PCR were assessed for eligibility.

Clinical and echocardiographic differences in three different etiologies of severe mitral stenosis.

Background: In our institute, the causes of mitral stenosis (MS) are generally categorized into three main etiologies-rheumatic MS (RMS), degenerative MS with annular and leaflet calcification, and post-clip MS as a consequence of transcatheter mitral valve repair with clips for treating mitral regurgitation. However, clinical differences among the three etiologies are uncertain.

Methods: We retrospectively assessed 293 consecutive patients (53 with RMS, 118 with degenerative MS, and 122 with post-clip MS) who had a three-dimensional (3D) transesophageal echocardiography (TEE) derived mitral valve orifice area (MVA) of ≤1.

Impact of Diastolic Interventricular Septal Flattening on Clinical Outcome in Patients With Severe Tricuspid Regurgitation.

Background Little is known about the impact of diastolic interventricular septal flattening on the clinical outcome in patients with severe tricuspid regurgitation. This study sought to evaluate the association of diastolic interventricular septal flattening with clinical outcome in patients with severe tricuspid regurgitation. Methods and Results We retrospectively studied 407 patients who underwent 2-dimensional transthoracic echocardiography and were diagnosed with severe tricuspid regurgitation between January 2014 and December 2015.

Impact of Systolic Blood Pressure on Heart Failure Symptoms With Moderate Aortic Stenosis.

In patients with moderate aortic stenosis (AS), heart failure (HF) symptoms are often unrelated to the AS severity, and the causes of HF symptoms are often unclear. Hypertension is known as one of the most common comorbidities in degenerative AS. Therefore, we assessed the impact of systolic blood pressure (BP) on HF symptoms in patients with moderate AS.

Exposure of the cytoplasm to low-dose X-rays modifies ataxia telangiectasia mutated-mediated DNA damage responses.

We recently showed that when a low X-ray dose is used, cell death is enhanced in nucleus-irradiated compared with whole-cell-irradiated cells; however, the role of the cytoplasm remains unclear. Here, we show changes in the DNA damage responses with or without X-ray microbeam irradiation of the cytoplasm. Phosphorylated histone H2AX foci, a surrogate marker for DNA double-strand breaks, in V79 and WI-38 cells are not observed in nucleus irradiations at ≤ 2 Gy, whereas they are observed in whole-cell irradiations.

Enhancement patterns detected by multidetector computed tomography are associated with the long-term prognosis of patients with acute myocardial infarction.

The present study investigated the clinical value of myocardial contrast-delayed enhancement (DE) with multidetector computed tomography (MDCT) without iodine re-injection immediately after primary percutaneous coronary intervention (PCI) for predicting future cardiovascular events after acute myocardial infarction (AMI). We performed a prospective study in which 263 consecutive patients with first AMI successfully treated with primary PCI were enrolled. Sixty-four-slice MDCT without the re-injection of contrast medium was performed immediately after PCI.

Arterial stiffening is a crucial factor for left ventricular diastolic dysfunction in a community-based normotensive population.

Background: Left ventricular (LV) diastolic dysfunction is an important underlying hemodynamic mechanism for heart failure. Hypertension reportedly increases aortic stiffness with histological changes in the aorta assessed using aortic pulse wave velocity (PWV) that is associated with LV diastolic dysfunction. The role of hypertension in the relationship between aortic stiffness and LV diastolic dysfunction has not been clarified; therefore, we investigated whether this relation works for normotensive subjects.

Hepatic Adaptation to Therapeutic Doses of Acetaminophen: An Exploratory Study in Healthy Individuals.

Purpose: Acetaminophen (APAP) has hepatotoxic potential when overdosed. Recent studies have reported serum alanine aminotransferase (ALT) elevations that resolve spontaneously with continued use of the drug, referred to as adaptation, in several individuals receiving therapeutic doses of APAP. However, the clinical significance of these ALT elevations remains unclear.

Intervention efficacy for eliminating patient misidentification using step-by-step problem-solving procedures to improve patient safety.

This study aimed to evaluate the efficacy of interventions to reduce patient misidentification incidents classified as level 2 and over (adverse events occurred for patients) with the step-by-step problem-solving method. All incidents related to patient misidentification were selected, and relevant information was collected from the original electronic incident reports. We then conducted an eight-step problem-solving process with the aim of reducing patient misclassification and improving patient safety.

A Drug-Drug Interaction Study to Evaluate the Effect of TAS-303 on CYP3A Activity in the Small Intestine and Liver.

TAS-303 (4-piperidinyl 2,2-diphenyl-2-[propoxy-1,1,2,2,3,3,3-d ] acetate hydrochloride) is a novel selective noradrenaline reuptake inhibitor being developed for the treatment of stress urinary incontinence. An in vitro study and a physiologically based pharmacokinetic model simulation showed that TAS-303 had inhibitory potential against cytochrome P450 (CYP) 3A. This open-label, single-group study investigated the effect of TAS-303 on CYP3A activity by evaluating the pharmacokinetics (PK) of single-dose oral simvastatin 5 mg or intravenous midazolam 1 mg after repeated oral administration of TAS-303 3 mg in 12 healthy participants.

A 3-Part Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DSP-6952 in Healthy Japanese Subjects and Those With ≤3 Spontaneous Bowel Movements per Week.

We hypothesized that DSP-6952, a partial agonist of the 5-hydroxytryptamine type-4 receptor and a gastrointestinal prokinetic agent, can induce natural bowel movements by enhancing gastrointestinal motility and colonic transit in patients with chronic constipation and irritable bowel syndrome with constipation. This 3-part phase 1 study evaluated the safety, tolerability, and pharmacokinetic and pharmacodynamic profiles of DSP-6952. Eighty-eight Japanese subjects (64 healthy volunteers and 24 subjects with spontaneous bowel movements ≤3 times/wk) were randomized to DSP-6952 or placebo.

SOCIOEMOTIONAL AND BEHAVIORAL PROBLEMS IN TODDLERS WITH LANGUAGE DELAY.

Toddlers with language delay are at risk for persistent developmental and behavioral difficulties; however, the association between socioemotional/behavior problems and language in young children is not well understood. This study explored socioemotional/behavior problems in a unique sample of toddlers with language delays using a measure developed explicitly for this age group. Toddlers identified by 18 months with receptive and expressive language delay (LD; n = 30) or typical development (TD; n = 61) were evaluated at 18 and 24 months of age using the Infant-Toddler Social and Emotional Assessment (ITSEA) and the Mullen Scales of Early Learning.

Effect of single and multiple doses of elobixibat, an ileal bile acid transporter inhibitor, on chronic constipation: A randomized controlled trial.

Aims: Elobixibat is a minimally absorbed ileal bile acid transporter inhibitor. This study aimed to investigate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of elobixibat in Japanese patients with chronic constipation.

Methods: This study consisted of single-dose and multiple-dose tests with a dose-escalating design.

Prefrontal Activation During Executive Tasks Emerges Over Early Childhood: Evidence From Functional Near Infrared Spectroscopy.

Functional Near Infrared Spectroscopy (fNIRS) is a brain imaging technique that is well-suited for use in young children, making it particularly useful for investigating the neural bases of the development of executive functions. In the present study, children (ages 4-10) underwent fNIRS while completing response inhibition and working memory tasks. While both tasks were associated with increases in oxyhemoglobin and decreases in deoxyhemoglobin, we found that strength of activation increased with age and with improvements in task performance.

Population Pharmacokinetic-Pharmacodynamic Analysis to Compare the Effect of Moxifloxacin on QT Interval Prolongation Between Healthy Korean and Japanese Subjects.

Purpose: The goal of this study was to evaluate the moxifloxacin-induced QT interval prolongation in healthy male and female Korean and Japanese volunteers to investigate interethnic differences.

Methods: This multicenter, randomized, double-blind, placebo-controlled, 2-way crossover study was conducted in healthy male and female Korean and Japanese volunteers. In each period, a single dose of moxifloxacin or placebo 400 mg was administered orally under fasting conditions.

Inflammatory responses following intramuscular and subcutaneous immunization with aluminum-adjuvanted or non-adjuvanted vaccines.

Aluminum-adjuvanted vaccines are administered through an intramuscular injection (IM) in the US and EU, however, a subcutaneous injection (SC) has been recommended in Japan because of serious muscle contracture previously reported following multiple IMs of antibiotics. Newly introduced adjuvanted vaccines, such as the human papillomavirus (HPV) vaccines, have been recommended through IM. In the present study, currently available vaccines were evaluated through IM in mice.

In vivo kinetics of indoxyl sulfate in humans and its renal interaction with angiotensin-converting enzyme inhibitor quinapril in rats.

Indoxyl sulfate (IS) is an organic anion uremic toxin that accumulates in patients with chronic kidney disease (CKD). The aims of this study were to examine the kinetic profiles of IS in humans at a steady state after multiple doses of L-Trp, a precursor of IS, and the in vivo interaction of IS with the angiotensin-converting enzyme inhibitor quinapril, whose active metabolite is a substrate of organic anion transporter 3 (OAT3) in rats. First, 12-h kinetics after single doses of Trp (2, 4, and 8 g) were examined in two healthy volunteers.

Safety, tolerability and pharmacokinetics of TAS-108, a novel anti-oestrogen, in healthy post-menopausal Japanese women: a phase I single oral dose study.

TAS-108 is a novel steroidal anti-oestrogen, expected to be useful for the treatment of breast cancer. The present study was conducted to investigate the safety, tolerability and pharmacokinetics of TAS-108 following the administration at a single oral dose of 40 mg to up to 120 mg in 12 post-menopausal women and the effect of food on the pharmacokinetics of the drug. All adverse events were mild and involved transient symptoms that resolved without therapeutic intervention.