Dehydroascorbate Reductases and Glutathione Set a Threshold for High-Light-Induced Ascorbate Accumulation.

Plants require a high concentration of ascorbate as a redox buffer for survival under stress conditions, such as high light. Dehydroascorbate reductases (DHARs) are enzymes that catalyze the reduction of DHA to ascorbate using reduced glutathione (GSH) as an electron donor, allowing rapid ascorbate recycling. However, a recent study using an Arabidopsis (Arabidopsis thaliana) triple mutant lacking all three DHAR genes (herein called ∆dhar) did not find evidence for their role in ascorbate recycling under oxidative stress. To further study the function of DHARs, we generated ∆dhar Arabidopsis plants as well as a quadruple mutant line combining ∆dhar with an additional vtc2 mutation that causes ascorbate deficiency. Measurements of ascorbate in these mutants under low- or high-light conditions indicated that DHARs have a nonnegligible impact on full ascorbate accumulation under high light, but that they are dispensable when ascorbate concentrations are low to moderate. Because GSH itself can reduce DHA nonenzymatically, we used the pad2 mutant that contains ∼30% of the wild-type GSH level. The pad2 mutant accumulated ascorbate at a wild-type level under high light; however, when the pad2 mutation was combined with ∆dhar, there was near-complete inhibition of high-light-dependent ascorbate accumulation. The lack of ascorbate accumulation was consistent with a marked increase in the ascorbate degradation product threonate. These findings indicate that ascorbate recycling capacity is limited in ∆dhar pad2 plants, and that both DHAR activity and GSH content set a threshold for high-light-induced ascorbate accumulation.

Differential Impact of the Renal Resistive Index on Future Cardiovascular Events in Hospitalized Atherosclerotic Cardiovascular Patients According to Left Ventricular Ejection Fraction　- The Jichi Vascular Hemodynamics in Hospitalized Cardiovascular Patients (J-VAS) Study.

BACKGROUND: Determinants of poor outcome in atherosclerotic cardiovascular disease (ASCVD) according to left ventricular ejection fraction (LVEF) are unclear. The renal resistive index (RRI) correlates well with atherosclerotic vascular damage, which, in turn, is correlated with cardiovascular outcomes. This study investigated whether high RRI is associated with poor cardiovascular outcomes in ASCVD patients classified by LVEF.Methods and Results:Records of 1,598 acute coronary syndromes (ACS) and acute decompensated heart failure (ADHF) patients, categorized into preserved (p), mid-range (mr), and reduced (r) ejection fraction (EF) groups (EF ≥50% [n=1,130], 40-50% [n=223], and <40% [n=245], respectively), were analyzed retrospectively. The primary endpoint was any cardiovascular-related event: fatal and non-fatal ACS, ADHF, stroke, and sudden cardiac death. Over 1.9-years follow-up (3,030 person-years), 233 events occurred: 122, 37, and 74 in the pEF, mrEF, and rEF groups, respectively. Adjusted Cox regression analysis revealed RRI ≥0.8 was associated with the primary endpoint in the pEF group (hazard ratio [HR] 1.67; 95% confidence interval [CI] 1.09-2.56), but not in the mrEF or rEF groups. The primary endpoint risk of pEF patients with an RRI ≥0.8 was comparable to that of mrEF patients using the pEF+RRI <0.8 group as the reference (HR 1.89 [95% CI 1.26-2.83] and 1.77 [95% CI 1.19-2.63], respectively). CONCLUSIONS: RRI was associated with the risk of cardiovascular events in ASCVD patients with pEF.

Relationship between underreporting of energy intake and blood ketone levels in Japanese women with obesity: A retrospective study.

Underreporting is a problem in dietary surveys, and data on Japanese individuals with obesity are lacking. In addition, in dietary surveys of individuals with obesity, underreporting and extreme energy restrictive practices for short periods of time have been reported, and blood total ketone levels (ketone bodies) may be able to distinguish between these factors. The present study aimed to examine the relationship between underreporting [energy intake (EI)/basal metabolic rate estimate (BMR)] and ketone bodies in obese Japanese women. The participants included 91 women with obesity aged 47±9 years with a body mass index (BMI) of 29.8±3.9 kg/m² who met the exclusion criteria out of 164 individuals who participated in an institutional cohort study baseline survey between September 2006 and September 2015. The current study defined the relationship between EI/BMR, BMI and the participants' ketone body levels. EI/BMR <1.35 and ketone body level <1.0 mmol/l was defined as underreporters, while EI/BMR <1.35 and ketone body level ≥1.0 mmol/l was defined as energy-restricted reporters based on previous research. The EI/BMR of the participants was 1.44±0.32, and 25.3% had an abnormally high level of ketone bodies. Multiple regression analysis indicated that ketone bodies were explanatory variables for EI/BMR. Analysis using EI/BMR and ketone bodies estimated that 26.4% were underreporters and 12.1% were energy-restricted reporters. There were no significant differences in reported energy intake, carbohydrate intake (g/day), and percentage carbohydrate (%) between the underreporters and energy-restricted reporters. In conclusion, low EI/BMR was associated with high ketone body levels in Japanese women with obesity. The combination of EI/BMR and ketone bodies may distinguish between or screen for underreporters and energy-restricted reporters during a dietary survey.

Class effect of xanthine oxidase inhibitors on flow-mediated dilatation in hypertensive patients: A randomized controlled trial.

A direct comparison of the effects of febuxostat and allopurinol on flow-mediated dilatation (FMD) will help to clarify which agent provides a better reduction of cardiovascular risk in hypertensive patients. Hypertensive patients with hyperuricemia were randomized into a febuxostat (10-40 mg, n = 33) or allopurinol (100-200 mg, n = 31) group and followed up for 6 months. Both the febuxostat (7.9 ± 1.3 mg/dL vs 5.6 ± 1.0 mg/dL, P < .001) and allopurinol (8.2 ± 1.3 mg/dL vs 6.1 ± 1.0 mg/dL, P < .001) groups exhibited significant reductions in uric acid after treatment. There was no significant difference in the change in FMD between the two treatment groups (0.6 ± 2.6% vs 0.2 ± 2.3%, P = .504). However, stratified analysis showed that febuxostat achieved a significantly greater change in FMD compared to allopurinol in the elderly group (1.3 ± 2.9% vs -0.7%±1.8%, P = .047). There was no difference in the improvement of FMD between febuxostat and allopurinol, but febuxostat may provide an improvement of FMD in elderly people.

Food intake and dietary patterns that affect urinary sodium excretion in young women.

We aimed to clarify food intake and dietary patterns that affect urinary sodium excretion (urinary salt excretion) among young women. We used 2012 to 2018 data from the health and nutrition testing on admission, which is a part of ongoing epidemiological studies, for students enrolling in the Faculty of Nutrition Science, Nakamura Gakuen University. Fasting urine samples were collected from the participants, and their estimated daily salt excretion was calculated using the Tanaka equation. The dietary assessment used was the semi-quantitative food frequency questionnaire, and we confirmed its validity. The participants included 2218 women aged 18 to 20 years who were classified into four groups according to urinary salt excretion (g/d) from their spot urine: Q1 , <5.56; Q2 , 5.56≤, <6.79; Q3 , 6.79≤, <8.12; and Q4 , 8.12<. The high urinary salt group had a significantly higher consumption of oil and fat, fish, meat, eggs, soybean, green and yellow vegetables, white vegetables, seaweeds, and pickled vegetables compared with the low urinary salt groups. When we compared the differences of the quartiles for urinary sodium excretion and the factor loadings for three dietary patterns by factor analysis with varimax rotation, the high urinary salt group showed a higher tendency for Japanese dietary patterns of factor 1 compared with the low urinary salt group. In conclusion, the various foods, including foods containing proteins and vegetables and Japanese dietary pattern centering on fish, vegetables, soybeans, and seaweed, affected the urinary sodium excretion in young women.

Lower Systolic Blood Pressure and Cardiovascular Event Risk Stratified by Renal Resistive Index in Hospitalized Cardiovascular Patients: J-VAS Study.

BACKGROUND: The threshold of blood pressure (BP) reduction in cardiovascular patients is debatable due to the J-shaped curve phenomenon, which is particularly observed in patients with increased arterial stiffness. The renal resistive index (RRI) correlates well with systemic arterial stiffness; therefore, we aimed to demonstrate the role of RRI in guiding the choice of optimal BP. METHODS: A retrospective analysis of prospectively collected data of the hospitalized cardiovascular patients at Jichi Medical University Hospital. All patients had the RRI measurement performed and were assigned to a higher (RRI ≥ 0.8) or lower RRI group. Each group was subdivided by quartiles of the BP at discharge. The primary endpoints were fatal and nonfatal cardiovascular events, including heart failure, acute coronary syndrome, acute aortic disease, acute arterial occlusion, and stroke. RESULTS: The mean follow-up period was 1.9 years (3,365 person-years), n = 1,777 (mean age 64.7 years). There were 252 cardiovascular events occurred, 24.0% and 12.2% in the higher and lower RRI populations, P < 0.001. In the higher RRI group, the lowest systolic BP (SBP) quartile (<105 mm Hg) was a risk factor for cardiovascular events when compared with the highest SBP quartile (≥130 mm Hg; adjusted hazard ratio, 2.42; 95% confidence interval, 1.17-5.03; P = 0.017). A 1 SD decrease of SBP (17.5 mm Hg) was associated with a 25% increase in the risk of cardiovascular events. In the lower RRI group, these associations were not observed. CONCLUSIONS: Lower SBP at discharge was associated with a risk of cardiovascular events in the hospitalized cardiovascular patients with RRI ≥ 0.8.

Interannual study of spot urine-evaluated sodium excretion in young Japanese women.

The authors investigated interannual differences in the sodium excretion levels of young healthy Japanese women as estimated from spot urine analysis at Nakamura Gakuen University from 1995 to 2015. Participants included 4931 women aged 18 to 20 years who were classified into three time periods according to year of health check: first (1995-2001), second (2002-2007), and third (2008-2015). Estimated daily urinary sodium and potassium excretion levels and the sodium to potassium ratio were 120.6±31.9 mmol, 35.2±8.1 mmol, and 3.5±0.9, respectively. Adjusted for body weight, sodium excretion, and potassium excretion significantly decreased in the second and third period compared with the first period (P<.001). Systolic blood pressure also decreased in the same way between time periods (P<.001). Estimated urinary excretion levels of sodium and potassium in young Japanese women have decreased over the past 20 years independently of body weight.

[Two cases of pulmonary hypertension crisis in patients with primary pulmonary hypertension].

Primary pulmonary hypertension (PPH) is an uncommon disease. We describe two cases of pulmonary hypertension crisis in patients with PPH during general anesthesia. Any factor that worsens primary pulmonary hypertension (strain, hypoxia, pain, hypercapnia, intubation, or hyperinflation) should be avoided.