Thiazolidinediones and Edema: Recent Advances in the Pathogenesis of Thiazolidinediones-Induced Renal Sodium Retention

Thiazolidinediones (TZDs) are one of the major classes of antidiabetic drugs that are used widely. TZDs improve insulin resistance by activating peroxisome proliferator-activated receptor gamma (PPARγ) and ameliorate diabetic and other nephropathies, at least, in experimental animals. However, TZDs have side effects, such as edema, congestive heart failure, and bone fracture, and may increase bladder cancer risk. Edema and heart failure, which both probably originate from renal sodium retention, are of great importance because these side effects make it difficult to continue the use of TZDs. However, the pathogenesis of edema remains a matter of controversy. Initially, upregulation of the epithelial sodium channel (ENaC) in the collecting ducts by TZDs was thought to be the primary cause of edema. However, the results of other studies do not support this view. Recent data suggest the involvement of transporters in the proximal tubule, such as sodium-bicarbonate cotransporter and sodium-proton exchanger. Other studies have suggested that sodium-potassium-chloride cotransporter 2 in the thick ascending limb of Henle and aquaporins are also possible targets for TZDs. This paper will discuss the recent advances in the pathogenesis of TZD-induced sodium reabsorption in the renal tubules and edema

The relation between mindfulness and the fatigue of women with breast cancer: path analysis

Background: Although fatigue is a common and distressing symptom in cancer survivors, the mechanism of fatigue is not fully understood. Therefore, this study aims to investigate the relation between the fatigue and mindfulness of breast cancer survivors using anxiety, depression, pain, loneliness, and sleep disturbance as mediators. Methods: Path analysis was performed to examine direct and indirect associations between mindfulness and fatigue. Participants were breast cancer survivors who visited a breast surgery department at a university hospital in Japan for hormonal therapy or regular check-ups after treatment. The questionnaire measured cancer-related-fatigue, mindfulness, anxiety, depression, pain, loneliness, and sleep disturbance. Demographic and clinical characteristics were collected from medical records. Results: Two-hundred and seventy-nine breast cancer survivors were registered, of which 259 answered the questionnaire. Ten respondents with incomplete questionnaire data were excluded, resulting in 249 participants for the analyses. Our final model fit the data well (goodness of fit index = .993; adjusted goodness of fit index = .966; comparative fit index = .999; root mean square error of approximation = .016). Mindfulness, anxiety, depression, pain, loneliness, and sleep disturbance were related to fatigue, and mindfulness had the most influence on fatigue (β = − .52). Mindfulness affected fatigue not only directly but also indirectly through anxiety, depression, pain, loneliness, and sleep disturbance. Conclusions: The study model helps to explain the process by which mindfulness affects fatigue. Our results suggest that mindfulness has both direct and indirect effects on the fatigue of breast cancer survivors and that mindfulness can be used to more effectively reduce their fatigue. It also suggests that health care professionals should be aware of factors such as anxiety, depression, pain, loneliness, and sleep disturbance in their care for fatigue of breast cancer survivors. Trial registration: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN number. 000027720) on June 12, 2017

LIPUS effect on lateral tooth movement

Introduction: Because mechanical stimulation of the periodontal ligament (PDL) by low-intensity pulsed ultrasound (LIPUS) has been shown to increase the speed of bone remodeling, the aim of this study was to examine the effects of LIPUS stimulation on the rate of tooth movement and bone remodeling during lateral tooth movement. Methods: Twelve-week-old Wistar rats were divided into two groups. The LIPUS group received experimental tooth movement with LIPUS stimulation, and the tooth movement (TM) group had experimental tooth movement without LIPUS. For the LIPUS and TM groups, the upper right first molars were moved labially with fixed appliances. LIPUS exposure was placed in the region corresponding to the right maxillary first molar. Three days after tooth movement, tartrate-resistant acid phosphatase (TRAP) was examined. Fourteen days after tooth movement, the intermolar width, bone mineral content (BMC), and bone volume fraction (BV/TV) were examined by micro computed tomography (micro-CT), and newly formed bone was measured histomorphometrically. Results: The number of TRAP-positive cells at the compressed region was obviously greater in the LIPUS group. The intermolar width was significantly greater in the LIPUS group than in the TM group. The alveolar bone around the maxillary first molar showed no differences in BMC or BV/TV between the LIPUS and TM groups. The LIPUS group exhibited a significantly greater amount of newly formed alveolar bone than the TM group. Conclusions: The present study provides evidence of the beneficial effects of LIPUS on the lateral tooth movement

ジョウガク シソウ キテイ キュウフクケイ ト チョウリョク トノ カンケイ

Objective: It has been reported that maxillary constriction could cause an aberration of normal breathing and affect the middle ear, resulting in hearing loss. The purpose of this study was to evaluate the correlation of the basal arch width of the maxilla and the hearing level. We hypothesized that a strong correlation would be observed. Methods: A total of 103 subjects (52 boys and 51 girls, aged between 7 to 13 years) without an obvious hearing loss were used for this study. An audiometer was used to determine the hearing level, and the basal arch width of the maxilla was measured from study casts. In addition, nasal resistance was examined by the cloudiness of a mirror. Results: There was no correlation between the basal arch width of the maxilla and the hearing level in any subjects (r=-0.0073); however, in the nasal resistance group (n=25), a weak but no significant correlation was observed (r=-0.280). Conclusions: Contrary to our hypothesis, there was no correlation between the basal arch width of the maxilla and the hearing level in subjects without obvious hearing loss; however, the result in nasal resistance subjects indicated an interaction with maxillary constriction, nasal stenosis, and hearing loss

Correlation between inflammation state and successful medical cardioversion using bepridil for refractory atrial fibrillation

AbstractBackgroundIt has been reported that inflammation is associated with long-term maintenance of sinus rhythm after electrical cardioversion for non-valvular atrial fibrillation (AF). However, the relation between high-sensitive C-reactive protein (hs-CRP) and the recurrence of AF after medical cardioversion is unknown. On the other hand, bepridil is very effective in restoring sinus rhythm for patients with refractory AF.Methods and resultsIn 119 patients with non-valvular AF lasting >6 months who failed to maintain sinus rhythm after medical cardioversion without bepridil or electrical cardioversion, we prescribed bepridil. We divided our patients into success group who maintained sinus rhythm for at least 6 months using bepridil and failure group, and compared the following parameters, which were measured just before prescription of bepridil, between the two groups: hs-CRP as a marker of inflammation, left ventricular end-diastolic dimension, ejection fraction, and left atrial dimension as echocardiographic markers, and the incidence of dyslipidemia, hypertension, and diabetes mellitus. After the treatment with bepridil, 57 patients converted to sinus rhythm; however, 12 patients among these 57 patients could not maintain sinus rhythm. Therefore, the success group consisted of 45 patients (38%). Univariate analysis revealed that left atrial dimension and the value of hs-CRP were significantly lower and ejection fraction was significantly higher in the success group than the failure group. Multivariate analysis showed that hs-CRP and left atrial dimension were independent factors for AF recurrence.ConclusionsBepridil is effective in restoring sinus rhythm for refractory AF patients. Inflammation, in addition to left atrial dimension, may be associated with successful cardioversion using bepridil

Near-Infrared Imaging Polarimetry of the Serpens Cloud Core: Magnetic Field Structure, Outflows, and Inflows in A Cluster Forming Clump

We made deep NIR imaging polarimetry toward the Serpens cloud core. The polarization vector maps enable us to newly detect 24 small IR reflection nebulae with YSOs. Polarization measurements of NIR point sources indicate an hourglass-shaped magnetic field, of which symmetry axis is nearly perpendicular to the elongation of the C18O (J=1-0) or submillimeter continuum emission. The bright part of C18O (J=1-0), submillimeter continuum cores as well as many class 0/I objects are located just toward the constriction region of the hourglass-shaped magnetic field. Applying the CF method, the magnetic field strength was estimated to be ~100 muG, suggesting that the ambient region of the Serpens cloud core is moderately magnetically supercritical. These suggest that the Serpens cloud core first contracted along the magnetic field to be an elongated cloud, which is perpendicular to the magnetic field, and that then the central part contracted cross the magnetic field due to the high density in the central region of the cloud core, where star formation is actively continuing. Comparison of this magnetic field with the previous observations of molecular gas and large-scale outflows suggests a possibility that the cloud dynamics is controlled by the magnetic field, protostellar outflows and gravitational inflows. This appears to be in good agreement with the outflow-driven turbulence model and implies the importance of the magnetic field to continuous star formation in the center region of the cluster forming region.Comment: 36 pages, 11 figures, 2 tables, accepted for publication in the Astrophysical Journa

Disassembly of the apical junctional complex during the transmigration of Leptospira interrogans across polarized renal proximal tubule epithelial cells

Bacterial pathogens have evolved multiple strategies to disassemble epithelial cell apical junctional complexes (AJCs) and infect epithelial cells. Leptospirosis is a widespread zoonotic infection, mainly caused by Leptospira interrogans, and its dissemination across host cell barriers is essential for its pathogenesis. However, the mechanism of bacterial dissemination across epithelial cell barriers remains poorly characterised. In this study, we analysed the interaction of L. interrogans with renal proximal tubule epithelial cells (RPTECs) and found that at 24 hr post-infection, L. interrogans remain in close contact with the plasma membrane of the RPTEC by extracellularly adhering or crawling. Leptospira interrogans cleaved E-cadherin and induced its endocytosis with release of the soluble N-terminal fragment into the extracellular medium. Concomitantly, a gradual decrease in transepithelial electrical resistance (TEER), mislocalisation of AJC proteins (occludin, claudin-10, ZO-1, and cingulin) and cytoskeletal rearrangement were observed. Inhibition of clathrin-mediated E-cadherin endocytosis prevented the decrease in TEER. We showed that disassembly of AJCs in epithelial cells and transmigration of bacteria through the paracellular route are important for the dissemination of L. interrogans in the host