Evaluating the Need for and Effect of Percutaneous Transluminal Angioplasty on Arteriovenous Fistulas by Using Total Recirculation Rate per Dialysis Session (“Clearance Gap”)

The functioning of an arteriovenous fistula (AVF) used for vascular access during hemodialysis has been assessed mainly by dilution methods. Although these techniques indicate the immediate recirculation rate, the results obtained may not correlate with Kt/V. In contrast, the clearance gap (CL-Gap) method provides the total recirculation rate per dialysis session and correlates well with Kt/V. We assessed the correlation between Kt/V and CL-Gap as well as the change in radial artery (RA) blood flow speed in the fistula before percutaneous transluminal angioplasty (PTA) in 45 patients undergoing continuous hemodialysis. The dialysis dose during the determination of CL-Gap was 1.2 to 1.4 Kt/V. Patients with a 10% elevation or more than a 10% relative increase in CL-Gap underwent PTA (n＝45), and the values obtained for Kt/V and CL-Gap before PTA were compared with those obtained immediately afterward. The mean RA blood flow speed improved significantly (from 52.9 to 97.5cm/sec) after PTA, as did Kt/V (1.07 to 1.30) and CL-Gap (14.1% to －0.2%). A significant correlation between these differences was apparent (r＝－0.436 and p＝0.003). These findings suggest that calculating CL-Gap may be useful for determining when PTA is required and for assessing the effectiveness of PTA, toward obtaining better dialysis

Calaxin is required for cilia-driven determination of vertebrate laterality

Sasaki, K., Shiba, K., Nakamura, A. et al. Calaxin is required for cilia-driven determination of vertebrate laterality. Commun Biol 2, 226 (2019). https://doi.org/10.1038/s42003-019-0462-

Glaucomatous Visual Field Defect Severity and the Prevalence of Motor Vehicle Collisions in Japanese: A Hospital/Clinic-Based Cross-Sectional Study

Purpose. This study examined the association between the severity of visual field defects and the prevalence of motor vehicle collisions (MVCs) in subjects with primary open-angle glaucoma (POAG). Methods. This is a cross-sectional study. Japanese patients who have had driver’s licence between 40 and 85 years of age were screened for eligibility. Participants answered a questionnaire about MVCs experienced during the previous 5 years. Subjects with POAG were classified as having mild, moderate, or severe visual field defect. We evaluated associations between the severity of POAG and the prevalence of MVCs by logistic regression models. Results. The prevalence of MVCs was significantly associated with the severity of POAG categorized by worse eye MD (control: 30/187 = 16.0%; mild POAG: 17/92 = 18.5%; moderate POAG: 14/60 = 23.3%; severe POAG: 14/47 = 29.8%; P=0.025, Cochran-Armitage trend test). Compared to the control group, the adjusted OR for MVC prevalence in subjects with mild, moderate, or severe POAG in the worse eye was 1.07 (95% CI: 0.55 to 2.10), 1.44 (95% CI: 0.68 to 3.08), and 2.28 (95% CI: 1.07 to 4.88). Conclusions. There is a significant association between the severity of glaucoma in the worse eye MD and the prevalence of MVCs

Calaxin establishes basal body orientation and coordinates movement of monocilia in sea urchin embryos

Through their coordinated alignment and beating, motile cilia generate directional fluid flow and organismal movement. While the mechanisms used by multiciliated epithelial tissues to achieve this coordination have been widely studied, much less is known about regulation of monociliated tissues such as those found in the vertebrate node and swimming planktonic larvae. Here, we show that a calcium sensor protein associated with outer arm dynein, calaxin, is a critical regulator for the coordinated movements of monocilia. Knockdown of calaxin gene in sea urchin embryos results in uncoordinated ciliary beating and defective directional movement of the embryos, but no apparent abnormality in axoneme ultrastructure. Examination of the beating cycle of individual calaxin-deficient cilia revealed a marked effect on the waveform and spatial range of ciliary bending. These findings indicate that calaxin-mediated regulation of ciliary beating is responsible for proper basal body orientation and ciliary alignment in fields of monociliated cells

Synthesis and evaluation of radioiodinated 1-(2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl)piperidin-4-amine derivatives for platelet-derived growth factor receptor β (PDGFRβ) imaging

金沢大学新学術創成研究機構Platelet-derived growth factor receptor β (PDGFRβ) is a transmembrane tyrosine kinase receptor and it is upregulated in various malignant tumors. Radiolabeled PDGFRβ inhibitors can be a convenient tool for the imaging of tumors overexpressing PDGFRβ. In this study, [125I]-1-(5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinoline-8-yl)piperidin-4-amine ([125I]IIQP) and [125I]-N-3-iodobenzoyl-1-(2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl)-piperidin-4-amine ([125I]IB-IQP) were designed and synthesized, and their potential as PDGFRβ imaging agents was evaluated. In cellular uptake experiments, [125I]IIQP and [125I]IB-IQP showed higher uptake by PDGFRβ-positive cells than by PDGFRβ-negative cells, and the uptake in PDGFRβ-positive cells was inhibited by co-culture with PDGFRβ ligands. The biodistribution of both radiotracers in normal mice exhibited hepatobiliary excretion as the main route. In mice inoculated with BxPC3-luc (PDGFRβ-positive), the tumor uptake of radioactivity at 1h after the injection of [125I]IIQP was significantly higher than that after the injection of [125I]IB-IQP. These results indicated that [125I]IIQP can be a suitable PDGFRβ imaging agent. However, further modification of its structure will be required to obtain a more appropriate PDGFRβ-targeted imaging agent with a higher signal/noise ratio. © 2017.Embargo Period 12 month

Radiobrominated benzimidazole-quinoline derivatives as Platelet-derived growth factor receptor beta (PDGFRβ) imaging probes

金沢大学疾患モデル総合研究センターPlatelet-derived growth factor receptor beta (PDGFRβ) affects in numerous human cancers and has been recognized as a promising molecular target for cancer therapies. The overexpression of PDGFRβ could be a biomarker for cancer diagnosis. Radiolabeled ligands having high affinity for the molecular target could be useful tools for the imaging of overexpressed receptors in tumors. In this study, we aimed to develop radiobrominated PDGFRβ ligands and evaluate their effectiveness as PDGFRβ imaging probes. The radiolabeled ligands were designed by modification of 1-{2-[5-(2-methoxyethoxy)-1H- benzo[d]imidazol-1-yl]quinolin-8-yl}piperidin-4-amine (1), which shows selective inhibition profile toward PDGFRβ. The bromine atom was introduced directly into C-5 of the quinoline group of 1, or indirectly by the conjugation of 1 with the 3-bromo benzoyl group. [77Br]1-{5-Bromo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinoline-8-yl}piperidin-4-amine ([77Br]2) and [77Br]-N-3-bromobenzoyl-1-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}-piperidin-4-amine ([77Br]3) were prepared using a bromodestannylation reaction. In a cellular uptake study, [77Br]2 and [77Br]3 more highly accumulatd in BxPC3-luc cells (PDGFRβ-positive) than in MCF7 cells (PDGFRβ-negative), and their accumulation was significantly reduced by pretreatment with inhibitors. In biodistribution experiments, [77Br]2 accumulation was higher than [77Br]3 accumulation at 1 h postinjection. These findings suggest that [76Br]2 is more promising for positron emission tomography (PET) imaging of PDGFRβ than [76Br]3. © 2018 The Author(s).CC-BY 4.

In vivo differences between two optical isomers of radioiodinated o-iodo-transdecalinvesamicol for Use as a radioligand for the vesicular acetylcholine transporter

金沢大学疾患モデル総合研究センターPurposeTo develop a superior VAChT imaging probe for SPECT, radiolabeled (-)-OIDV and (+)-OIDV were isolated and investigated for differences in their binding affinity and selectivity to VAChT, as well as their in vivo activities.ProceduresRadioiodinated o-iodo-trans-decalinvesamicol ([125I]OIDV) has a high binding affinity for vesicular acetylcholine transporter (VAChT) both in vitro and in vivo. Racemic [125I]OIDV was separated into its two optical isomers (-)-[125I]OIDV and (+)-[125I]OIDV by HPLC. To investigate VAChT binding affinity (Ki) of two OIDV isomers, in vitro binding assays were performed. In vivo biodistribution study of each [125I]OIDV isomer in blood, brain regions and major organs of rats was performed at 2,30 and 60 min post-injection. In vivo blocking study were performed to reveal the binding selectivity of two [125I]OIDV isomers to VAChT in vivo. Ex vivo autoradiography were performed to reveal the regional brain distribution of two [125I]OIDV isomers and (-)-[123I]OIDV for SPECT at 60 min postinjection.ResultsVAChT binding affinity (Ki) of (-)-[125I]OIDV and (+)-[125I]OIDV was 22.1 nM and 79.0 nM, respectively. At 2 min post-injection, accumulation of (-)-[125I]OIDV was the same as that of (+)-[125I]OIDV. However, (+)-[125I]OIDV clearance from the brain was faster than (-)-[125I]OIDV. At 30 min post-injection, accumulation of (-)-[125I]OIDV (0.62 ± 0.10%ID/g) was higher than (+)-[125I]OIDV (0.46 ± 0.07%ID/g) in the cortex. Inhibition of OIDV binding showed that (-)-[125I]OIDV was selectively accumulated in regions known to express VAChT in the rat brain, and ex vivo autoradiography further confirmed these results showing similar accumulation of (-)-[125I]OIDV in these regions. Furthermore, (-)-[123I]OIDV for SPECT showed the same regional brain distribution as (-)-[125I]OIDV.ConclusionThese results suggest that radioiodinated (-)-OIDV may be a potentially useful tool for studying presynaptic cholinergic neurons in the brain.CC-BY 4.