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Introduction: The 2,2-dihydroxymethyl-1-[ 18 F]fluoropropane group, also called 18 F-labelled neopentyl glycol side-chain, is a novel 18 F-labelling group for positron emission tomography (PET) imaging agents. The aim of using this group is to develop simple purification with solid-phase extraction without high-performance liquid chromatography. However, the effects of the neopentyl 18 F-labelling group on the characteristics of brain imaging agents are unknown. Here, we added this side-chain to compounds with an aminostilbene structure to evaluate their effects on the biological properties of aminostilbene as an amyloid-β (Aβ) radioligand., Methods: Biodistributions of four novel 18 F-labelled stilbene compounds with different lengths of polyethylene glycol (PEG) linkers, called [ 18 F]Cpd-0, -1, -2, and -4, (PEG = 0, 1, 2, and 4), and [ 18 F]AV-1 in normal mice were evaluated. Metabolite analysis of [ 18 F]Cpd-0 and -1 was performed with mouse plasma and brain. A competitive binding assay of [ 18 F]AV-1 binding to Aβ 1 - 42 fibrils was performed to determine the binding properties of the compounds., Results: [ 18 F]Cpd-0, -1, and -2 demonstrated moderate initial brain uptake in mice (3.1-4.2% injected dose/g at 2 min post-injection) followed by fast clearance, and in vivo defluorination of these compounds was negligible. [ 18 F]Cpd-4 exhibited low brain uptake and high bone uptake. Compared with [ 18 F]Cpd-1, the percentage of [ 18 F]Cpd-0 in mouse brain was high at 10 min post-injection. A competitive binding assay revealed partial interference effects by the neopentyl glycol side-chain on binding of stilbene compounds to Aβ 1 - 42 fibrils., Conclusions: Aminostilbene compounds with two or fewer PEG linkers containing an 18 F-labelled neopentyl glycol side-chain demonstrated preferable pharmacokinetic properties as a brain imaging radioligand in normal mice. These side-chains can be used as an alternative labelling group for imaging agents targeting the brain., Competing Interests: Declaration of competing interest KH is an employee of NMP Business Support. KI was an employee of NMP Business Support., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Mitochondrial pH is a key determinant of mitochondrial energy metabolism. We have developed a new fluorescence-based ratiometric pH biosensor using a chloride-insensitive and hydrogen-sensitive probe for direct, quantitative and bleaching-free measurement in a living cell. Fusing this biosensor with a mitochondrial localization signal (MTpHGV) allowed us to determine mitochondrial pH. This new system was applied to measure mitochondrial pH in pancreatic β-cells, in which mitochondrial function plays a pivotal role in insulin secretion. Rat INS1 cells and mouse MIN6 cells are transfected with MTpHGV stably to monitor mitochondrial pH. While carbonyl cyanide 3-chlorophenylhydrazone (CCCP) treatment rapidly decreased mitochondrial pH in cultured rat MTpHGV-INS-1 cells, MTpHGV-MIN6 cells showed a rapid increase. These data suggest that MTpHGV probe exist in matrix side in INS-1 cells, but on the outer side of mitochondrial inner membrane in MIN6 cells. Moreover, while MTpHGV-INS-1 cells showed a rapid increase of pH by glucose stimulation, mitochondrial pH decreased quickly by glucose stimulation in all MTpHGV-MIN6 cells examined and recovered smoothly. Perfusion study of glucose load in MTpHGV-MIN6 cells under aminooxyacetate (AOA) or 100μM diazoxide showed that this mitochondrial pH acidification was dependent on nicotinamide adenine dinucleotide (NADH) shuttle, but independent from KATP channel. This new system for measuring mitochondrial pH is sensitive across the range of physiologic conditions and may be a useful tool for evaluating mitochondrial function in living cells., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: It is usually suggested that life expectancy of top athletes especially in endurance sports is longer than that of sedentary people. On the other hand, heart rate recovery (HRR) after exercise is an independent risk factor for cardiovascular disease and mortality, but differences in HRR between various top athletes are unclear. We examined HRR in various top athletes to clarify a role of HRR that may affect their life expectancy., Methods: HRR was defined as the difference between the heart rate at peak exercise and that at 2 min after the finish of exercise using symptom-limited maximal graded bicycle ergometer exercise testing. The relationships between HRR with the grade of static and dynamic component of classification of sports, age, and body mass index (BMI) were estimated., Subjects: The subjects were 720 male athletes participating in the National Sports Festival Japan in 2005-2008 and age-matched 28 sedentary controls., Results: HRR was significantly correlated (p<0.0001) with the higher grade of dynamic component of sports, younger age, and lower BMI in both univariate and multivariate analysis., Conclusions: HRR of top athletes is predicted by increased dynamic component of sports, younger age, and lower BMI., (Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objective: Heart rate recovery (HRR) after exercise is an independent risk factor for cardiovascular disease and mortality, and it is well known to be modifiable by weight loss. We investigated whether HRR was mainly improved by better cardiopulmonary function or by alteration of the metabolic profile., Methods: The weight loss program included 2h of group exercise per week and individual dietary instruction by a qualified dietician every week. Clinical assessment (including HRR) was done before and after the 3-month program., Patients: The subjects were 125 obese persons without a past history of stroke, cardiovascular events, or use of medications who participated in and completed our exercise plus weight loss program., Results: HRR (35.61+/-12.83 to 45.34+/-13.6 beats/min, p<0.0001) was significantly faster after the program. The change in HRR was significantly correlated (p<0.05) with the changes in body weight, body mass index, percent body fat, waist circumference, hip circumference, resting heart rate, peak exercise heart rate, exercise time, maximal work load, physical working capacity divided by body weight (PWC75%HRmax/weight), subcutaneous fat area, visceral fat area, low-density lipoprotein cholesterol, and leptin. Multivariate analysis showed that the change in HRR was significantly correlated (p<0.05) with the changes in resting heart rate, peak exercise heart rate, and PWC75%HRmax/weight., Conclusions: Our data demonstrated that HRR can be improved in obese subjects by a 3-month exercise and weight loss program. Improvement in cardiopulmonary function by exercise seems to be the main contributor to the increment of HRR., (Copyright 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)