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Adsorption reactions of various cations on clay minerals have different effects on their environmental behaviors depending on the molecular-scale adsorption structure. Some cations ...form outer-sphere complexes via hydration, while others create inner-sphere complexes through dehydration. This preference dictates their environmental impact. However, the factors controlling these complex formations remain unclear. Furthermore, research on the adsorption preferences of radium (Ra) is lacking. Thus, this study conducted the first EXAFS study of Ra2+ adsorbed on clay minerals and showed that Ra2+ forms inner-sphere complexes on vermiculite, which can be surprising because Ra2+ is a divalent cation and prefers to be hydrated. In order to investigate the factors controlling the complex formations, this study conducted systematic EXAFS measurements and DFT calculations for alkali and alkaline earth metal cations. The results showed the importance of the size-matching effect between the adsorbed cation and the cavity of the tetrahedral sheets and that the complex formation can be estimated by the combination of the ionic radius and hydration enthalpy of the adsorbed cation. Furthermore, this study also analyzed environmental core samples. Their results showed the fixation of Ra2+ by clay minerals and the controlling factors can effectively predict cation environmental behavior.
Macrolides are reported to reduce exacerbation of chronic inflammatory respiratory disease, such as chronic obstructive pulmonary disease (COPD), and also show anti-inflammatory effects in vitro and ...in vivo. However the anti-inflammatory efficacies of current macrolides are relatively weak. Here we found that a novel macrolide/fluoroketolide solithromycin (CEM-101) showed superior anti-inflammatory effects to macrolides in current clinical use. The effects of solithromycin (SOL) on lipopolysaccharide-induced TNFα (tumor necrosis factor α) and/or CXCL8 (C-X-C motif chemokine ligand 8; interleukin-8) release, phorbol 12-myristate 13-acetate-induced MMP9 (matrix metalloproteinase 9) activity and NF-κB (nuclear factor-κB) activity under conditions of oxidative stress have been evaluated and compared with the effects of erythromycin, clarithromycin, azithromycin, and telithromycin in macrophage-like PMA-differentiated U937 cells and peripheral blood mononuclear cells (PBMC) obtained from COPD patients. We also examined effect of SOL on cigarette smoke-induced airway inflammation in mice. SOL exerted superior inhibitory effects on TNFα/CXCL8 production and MMP9 activity in monocytic U937 cells. In addition, SOL suppressed TNFα release and MMP9 activity in PBMC from COPD patients at 10 µM, which is 10 times more potent than the other macrolides tested. Activated NF-κB by oxidative stress was completely reversed by SOL. SOL also inhibited cigarette smoke-induced neutrophilia and pro-MMP9 production in vivo, although erythromycin did not inhibit them. Thus, SOL showed better anti-inflammatory profiles compared with macrolides currently used in the clinic and may be a promising anti-inflammatory and antimicrobial macrolide for the treatment of COPD in future.
We investigated changes in blood pressure (BP) and metabolic adverse effects, especially elevation of uric acid (UA), after treatment with a thiazide-like diuretic (TD) in patients with essential ...hypertension. Furthermore, the role of genetic factors in the elevation of UA by TD was assessed by a 500 K SNP DNA microarray. The subjects included 126 hypertensive patients (57 women and 69 men, mean age 59 ± 12 years) who registered for the GEANE (Gene Evaluation for ANtihypertensive Effects) study. After one month of the nontreatment period, TD, indapamide, angiotensin II receptor antagonist valsartan, and Ca channel blocker amlodipine were administered to all patients for 3 months each in a randomized crossover manner. BP, renal function, serum UA level, and electrolytes were measured at baseline and at the end of each treatment period. Single nucleotide polymorphisms (SNPs) associated with UA elevation after treatment with indapamide were investigated by a genome-wide association study (GWAS). Indapamide significantly decreased both office and home BP levels. Treatment with indapamide also significantly reduced the estimated glomerular filtration rate and serum potassium and increased serum UA. Patients whose UA level increased more than 1 mg/dl showed significantly higher baseline office SBP and plasma glucose and showed greater decline in renal function compared with those who showed less UA increase (<1 mg/dl). Some SNPs strongly associated with an increase in UA after treatment with indapamide were identified. This study is the first report on SNPs associated with UA elevation after TD treatment. This information may be useful for the prevention of adverse effects after treatment with TD.
Aim of the Study: Interleukin (IL)-10 is an anti-inflammatory cytokine, but its role in cigarette smoke (CS)-induced inflammation and chronic obstructive pulmonary disease (COPD) has not been fully ...elucidated. The purpose of this study was to investigate the effect of IL-10 deficiency on CS-induced pulmonary inflammation in mice in vivo and in vitro. Materials and Methods: IL-10-deficient and wild-type control mice with a C57BL6/J genetic background were exposed to CS, and inflammatory cells in bronchoalveolar lavage fluid (BALF) and mRNA of cytokines in lung were evaluated with enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). Results: During 12 days of daily CS exposure to wild-type mice, neutrophil counts in BAL fluid and tumor necrosis factor (TNF)-α mRNA expression were increased, peaked at day 8, and then declined on day 12 when the level of IL-10 reached its peak. In IL-10-deficient mice, neutrophil recruitment and TNF-α mRNA levels induced by CS exposure were significantly greater than those in wild-type mice. Keratinocyte-derived chemokine (KC; murine ortholog of human CXCL8) and granulocyte macrophage colony-stimulating factor (GM-CSF) mRNA levels or matrix metalloproteinase(MMP)-9 protein levels were not correlated with neutrophil count. Conclusions: IL-10 had a modulatory effect on CS-induced pulmonary neutrophilic inflammation and TNF-α expression in mice in vivo and therefore appears to be an important endogenous suppressor of airway neutrophilic inflammation.
Recent years have seen increased attention to the needs and support of siblings of children with chronic illness, and reports of intervention studies on siblings are gradually increasing worldwide. ...In Japan, the basic policy approved by the Cabinet in 2021 of The Basic Law for Child and Maternal Health and Development stipulates promoting support for the siblings of children with chronic illness, medical care, and disabilities. Simultaneously, practical reports are emerging. However, reports on the actual state of sibling support at medical institutions in Japan are limited. This study aimed to describe the actual state of support for siblings of children with illness in Japanese medical institutions using a cross-sectional design. Responses were obtained from 207 of 484 registered training facilities for Board-Certified Pediatricians of the Japan Pediatric Society through anonymous questionnaires investigating the actual state of siblings' support. Descriptive statistics were calculated, and the state of siblings' support was described. Fifty-two participants (25.1%) answered that the entire ward, including two outpatient departments, provided siblings' support, while 37 (17.9%) answered some staff made an effort, and 117 (56.5%) did not. Support mentioned included conversing with siblings, actively speaking to siblings, calling siblings' names, and counseling care through the parents. Of the 45 cases (21.7%) where siblings were invited to events and gatherings, 10 (22.2%) were siblings-centered events. Some cases involved collaboration with local sibling support groups such as non-profit organizations. This study clarified the actual state of siblings' support, and further expansion of this support is required.
The purpose of the present study was to investigate oral bioavailability of an immediate release tablet containing wet-milled crystals of a poorly water-soluble drug, cilostazol, and to establish in ...vitro–in vivo correlation. Sub-micron sized cilostazol (median diameter: 0.26 μm) was successfully prepared using a beads-mill in water in the presence of a hydrophilic polymer and an anionic surfactant. The milled suspension was solidified with a sugar alcohol as a water-soluble carrier by spray-drying method. The co-precipitate was compressed into an immediate release tablet with common excipients. Oral bioavailability of the wet-milled cilostazol tablet in male beagle dogs was 13-fold higher than the hammer-milled commercial tablet in fasted condition. Food did not increase the oral bioavailability of the wet-milled tablet, while 4-fold increase was found for the commercial tablet. Irrespective to the bioavailability enhancement, in vitro dissolution rate of the wet-milled tablet was even slower than the commercial tablet by the compendial method (USP Apparatus 2). On the other hand, a good correlation was found between the dissolution profiles obtained by a flow-through cell method (USP Apparatus 4, closed-loop system without outlet filter) using a large volume of water and sodium lauryl sulfate (SLS) solution at the concentration lower than the critical micellar concentration (cmc) as dissolution media corresponding to the fasted and fed conditions, respectively.
Purpose
Pulmonary vein (PV) isolation using balloon ablation was developed as a technique for patients with paroxysmal atrial fibrillation (PAF). While most studies examined cryoballoon ablation ...(CBA), there have also been many reports on hot balloon ablation (HBA). We aimed to evaluate the clinical characteristics and outcomes between HBA and CBA.
Methods
In a total of 103 consecutive patients with PAF who underwent catheter ablation, 60 propensity score–matched (30 CBA and 30 HBA) patients were enrolled. The procedural differences and clinical outcomes between the two groups were analyzed.
Results
The requirement for additional touch-up ablation was more frequent in the left superior pulmonary vein (LSP) in the HBA group than in the CBA group. Pre-procedural computed tomography (CT) images showed that a thicker left pulmonary vein ridge and larger cross-sectional area of the LSPV were significantly associated with residual PV potentials after HBA. However, post-procedural CT images showed that PV stenosis (> 25%) was higher in the HBA group (33%) than in the CBA group (0%). PV stenosis after HBA was observed most frequently in the right superior PV (50%). The atrial fibrillation/atrial tachycardia–free survival rate during follow-up (365 ± 102 days) was similar between the two groups (CBA vs. HBA, 83% vs. 90%).
Conclusions
Although both balloon modalities can relieve atrial arrhythmia after the procedure, careful attention is required during HBA procedures, especially for the right superior PV, to avoid PV stenosis.
Introduction: The cardio-ankle vascular index (CAVI) was developed in Japan and is a blood pressure-independent index of arterial stiffness from the origin of the aorta to the ankle. In recent years, ...it has been studied by many researchers worldwide, and it is strongly anticipated that it will play a role as a predictive factor for arteriosclerotic diseases. The objective of this study was to examine the benefits of using CAVI as a predictor of cardiovascular events in high-risk patients. Methods and Design: This prospective multicenter study to evaluate the usefulness of the CAVI to predict cardiovascular events in Japan (CAVI-J) is a cohort study with central registration. Participants (n = 3,000) will be scheduled to enroll and data will be collected for up to 5 years from entry of participants into the study. To be eligible to participate in the CAVI-J study, individuals have to be aged between 40 and 74 years and have at least one of the following risk factors for arteriosclerosis: (1) type 2 diabetes mellitus; (2) high-risk hypertension; (3) metabolic syndrome; (4) chronic kidney disease (stage 3), or (5) history of coronary artery disease or noncardiogenic cerebral infarction. The primary endpoints of this study are cardiovascular death, nonfatal myocardial infarction, and stroke. The secondary endpoints are composite cardiovascular events including all cause death, angina pectoris with revascularization, new incidence of peripheral artery disease, abdominal aortic aneurysm, aortic dissection, heart failure requiring hospitalization, and deterioration in renal function. The cutoff for CAVI against the incidence of cardiovascular events will be determined.
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