High-dose I-metaiodobenzylguanidine therapy in patients with high-risk neuroblastoma in Japan.

Objective: The aim of the study was to investigate the outcomes and prognostic factors of high-dose I-metaiodobenzylguanidine (I-MIBG) therapy in patients with refractory or relapsed neuroblastoma (NBL) in Japan.

Methods: We retrospectively analyzed 20 patients with refractory or relapsed high-risk NBL who underwent I-MIBG therapy with an administration dose ranging from 444 to 666 MBq/kg at Kanazawa University Hospital, Japan, between September 2008 and September 2013. We focused on measurements regarding their initial responses, prognostic factors, survivals, and toxicities following I-MIBG therapy using our hospital data and questionnaires from the hospitals that these patients were initially referred from.

CSAHi study: Detection of drug-induced ion channel/receptor responses, QT prolongation, and arrhythmia using multi-electrode arrays in combination with human induced pluripotent stem cell-derived cardiomyocytes.

Introduction: The use of multi-electrode arrays (MEA) in combination with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provides a promising method to predict comprehensive cardiotoxicity, including drug-induced QT prolongation and arrhythmia. We previously demonstrated that MEA in combination with hiPSC-CMs could provide a generalizable platform by using 7 reference drugs at 10 testing facilities. Using this approach, we evaluated responses to reference drugs that modulate a range of cardiac ion currents and have a range of arrhythmogenic effects.

CSAHi study: Evaluation of multi-electrode array in combination with human iPS cell-derived cardiomyocytes to predict drug-induced QT prolongation and arrhythmia--effects of 7 reference compounds at 10 facilities.

Introduction: Drug-induced QT prolongation is a major safety issue during drug development because it may lead to lethal ventricular arrhythmias. In this study, we evaluated the utility of multi-electrode arrays (MEA) with human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to predict drug-induced QT prolongation and arrhythmia.

Methods: Ten facilities evaluated the effects of 7 reference drugs (E-4031, moxifloxacin, flecainide, terfenadine, chromanol 293B, verapamil, and aspirin) using a MED64 MEA system with commercially available hiPS-CMs.

Extremity Radioactive Iodine Uptake on Post-therapeutic Whole Body Scan in Patients with Differentiated Thyroid Cancer.

Objectives: We investigated a frequency of lower extremity uptake on the radioactive iodine (RAI) whole body scan (WBS) after RAI treatment in patients with differentiated thyroid cancer, in order to retrospectively examine whether or not the frequency was pathological.

Methods: This retrospective study included 170 patients with thyroid cancer, undergoing RAI treatment. Overall, 99(58%) and 71(42%) patients received single and multiple RAI treatments, respectively.

Effects and safety of ¹³¹I-metaiodobenzylguanidine (MIBG) radiotherapy in malignant neuroendocrine tumors: results from a multicenter observational registry.

Effective treatments for malignant neuroendocrine tumors are under development. While iodine-131 metaiodobenzylguanidine (¹³¹I-MIBG) radiotherapy has been used in the treatment of malignant neuroendocrine tumors, there are few studies evaluating its therapeutic effects and safety in a multicenter cohort. In the current study, we sought to evaluate the effects and safety of ¹³¹I-MIBG therapy for conditions including malignant pheochromocytoma and paraganglioma within a multicenter cohort.

[Classification of Japanese elderly in an urban area at risk of becoming homebound: knowledge for improving prevention strategies].

Objectives: This study aimed to assess the living situation and health of elderly people in an urban area of Japan at risk of becoming homebound, so as to tailor measures to prevent or delay this occurring. We identified the prevalence rate of people currently homebound and those at risk, classifying using predictors reported in previous studies. An assessment of physical and cognitive factors affecting each classified group was included.

[Homebound status and life space among Japanese community-dwelling elderly in an urban area].

Objectives: To examine the relationship between homebound status and physical, mental, social and life space factors among community-dwelling elderly in an urban area.

Methods: A cross-sectional survey was conducted using a mail-in self-administered questionnaire between July and September 2009. The target population comprised 149,991 community residents, aged 65 years and over, living in Setagaya Ward, Tokyo, as of April 2009.

Effects of bradykinin on prostaglandin I(2) synthesis in human vascular endothelial cells.

The effects of bradykinin on the regulatory mechanisms of prostacyclin synthesis in endothelial cells were investigated in association with intracellular Ca(2+) kinetics, cytosolic phospholipase A(2) (cPLA(2)) activity, and mRNA expression of cPLA(2) and prostaglandin H synthase (PGHS) isoforms. Bradykinin enhanced prostacyclin release from endothelial cells time-dependently, but pretreatment with EGTA H-7 or HOE 140 inhibited bradykinin-induced prostacyclin release. Bradykinin increased both the influx of extracellular Ca(2+) and Ca(2+) release from the intracellular Ca(2+) storage sites.

Effect of probucol on intracellular pH and proliferation of human vascular endothelial cells.

We investigated the effect of probucol on the intracellular pH ([pH]i) and proliferation of human umbilical vein endothelial cells (HUVEC), as well as their production of prostacyclin (PGI2). The addition of probucol produced a biphasic shift in [pH]i, with a brief initial acidification followed by a rapid alkaline shift. After pretreatment with EGTA, the initial decrease in [pH]i was abolished, and the subsequent increase was inhibited.

A role of protein kinase C in the regulation of cytosolic phospholipase A(2) in bradykinin-induced PGI(2) synthesis by human vascular endothelial cells.

The purpose of this study was to elucidate the mechanism by which bradykinin (BK) enhances prostacyclin (PGI(2)) production in human umbilical vein endothelial cells (HUVEC). BK-induced enhancement of PGI(2) synthesis was observed in a dose- and time-dependent manner, and it also increased [Ca(2+)](i) followed by enhancement of cytosolic phospholipase A(2) (cPLA(2)) activity. The PKC inhibitors GF109203X and H7 attenuated the BK-induced increase in [Ca(2+)](i) and inhibited the BK-induced PGI(2) synthesis.

Interleukin-1alpha stimulated prostacyclin release by increasing gene transcription of prostaglandin H synthase and phospholipase A2 in human vascular endothelial cells.

This study was conducted to evaluate the effects of interleukin-1alpha (IL-1alpha) on prostacyclin (PGI2) production in cultured human vascular endothelial cells in association with intracellular Ca2+, inositol 1,4,5-trisphosphate (IP3), and with prostaglandin H synthase (PGHS) and phospholipase A2 (PLA2) gene expression by using the competitive polymerase chain reaction (PCR) method. IL-1alpha did not increase PGI2 production for 15 min, but induced an increase of about three-fold relative to that in controls at 60 and 180 min. IL- 1alpha had no effect on intracellular Ca2+ levels throughout the experimental period.

Effects of high-density lipoproteins on intracellular pH and proliferation of human vascular endothelial cells.

We investigated the effects of high-density lipoprotein (HDL) on the intracellular pH ([pH]i), and on the proliferation of human vascular endothelial cells (HUVEC), as well as on their production of prostacyclin (PGI2). The [pH]i was slightly acidified when extracellular Ca2+ was chelated with EGTA. Pretreatment of HUVEC with amiloride, the Na+/H+ exchange inhibitor, caused the [pH]i to become strongly acidic.

[Relationship between sleep stage and blood pressure variability during apnea in patients with sleep apnea syndrome].

A marked transient increase in blood pressure can occur at the end of each apneic period in patients with sleep apnea syndrome (SAS) and SAS may be a risk factor for cerebrovascular disease. To estimate blood pressure variability during apnea arterial blood pressure was directly and continuously recorded, and the transient increase in blood pressure in each sleep stage was assessed. Polysomnography was done in 5 men with SAS: arterial blood pressure, oxygen saturation, and respiratory curves were recorded.

[Neoplastic angioendotheliosis presenting Tolosa-Hunt syndrome, intraspinal invasion and intraorbital tumor].

A 76-year-old woman with painful erythema on legs and right oculomotor disturbance was diagnosed as neoplastic angioendotheliosis (NAE, B cell type) by skin biopsy. Remission was obtained by 2 courses of VEPA regimen. But 3 months later, she relapsed with right oculomotor, optic, trochlear and trigeminal nerve disturbance which suggested that she had Tolosa-Hunt syndrome.