Role of polyunsaturated fatty acids in Japanese patients with coronary spastic angina.

BACKGROUND: n-3 polyunsaturated fatty acids (PUFAs) reduce the risk of ischemic heart disease. However, there are few reports of a relationship between n-3 PUFAs and coronary spastic angina (CSA). This study aimed to assess the age-dependent role of serum levels of fatty acid in patients with CSA. METHODS AND RESULTS: We enrolled 406 patients who underwent ergonovine tolerance test (ETT) during coronary angiography for evaluation of CSA. All ETT-positive subjects were diagnosed as having CSA. We categorized the patients by age and results of ETT as follows: (1) young (age ≤ 65 years) CSA-positive (n = 32), (2) young CSA-negative (n = 134), (3) elderly (age > 66 years) CSA-positive (n = 36), and (4) elderly CSA-negative (n = 204) groups. We evaluated the serum levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid, and dihomo-gamma-linolenic acid. In the young groups, the serum levels of EPA (64.3 ±â€¯37.7 µg/mL vs. 49.4 ±â€¯28.8 µg/mL, p = 0.015) and DHA (135.7 ±â€¯47.6 µg/mL vs. 117.4 ±â€¯37.6 µg/mL, p = 0.020) were significantly higher in the CSA-positive group than in the CSA-negative group, respectively. However, this was not the case with elderly groups. In the multivariate analysis in young groups, the serum levels of EPA (p = 0.028) and DHA (p = 0.049) were independently associated with the presence of CSA, respectively. CONCLUSION: Our results suggested that the higher serum levels of EPA and/or DHA might be involved in the pathophysiology of CSA in the young population but not in the elderly population.

Effects of the timing of acute mulberry leaf extract intake on postprandial glucose metabolism in healthy adults: a randomised, placebo-controlled, double-blind study.

BACKGROUND/OBJECTIVES: Glucose tolerance is controlled by the internal clock and is worse in the evening. From a chrononutrition perspective, diabetes prevention requires evaluating the antidiabetic effects of the timing of functional ingredients and nutrient intake. The purpose of this study was to investigate the timing effects of acute mulberry leaf extract (MLE) intake on postprandial glucose levels in young adults. SUBJECTS/METHODS: Twelve young adults underwent four trials. Blood samples were collected in a fasting state and at 30, 60, 120, and 180 min after eating a mixed meal. The study had a randomised, placebo-controlled, double-blind trial design involving: (1) morning placebo trial (08:00 h; MP trial), (2) evening placebo trial (18:00 h; EP trial), (3) morning MLE trial (08:00 h; MM trial), and (4) evening MLE trial (18:00 h; EM trial). RESULTS: The incremental area under the blood glucose curve (iAUC) in the EM trials was significantly lower than that in the EP trials (P = 0.010). The postprandial glucose concentrations 120 min after the meal were significantly lower in the EM trials than those in the EP trials (P = 0.006). The postprandial insulin concentrations at 120 min were significantly lower in the MM trials than those in the MP trials (P = 0.034). Moreover, the postprandial insulin concentrations 180 min after the meal were significantly lower in the EM trials than those in the EP trials (P = 0.034). CONCLUSIONS: MLE intake in the evening, but not in the morning, was effective in improving glucose tolerance. TRIAL REGISTRATION: Clinical trial reference: UMIN 000045301; website of trial registry: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000051340 .

Transcutaneous Electrical Nerve Stimulation Improves Stair Climbing Capacity in People with Knee Osteoarthritis.

This study aimed to examine the effect of transcutaneous electrical nerve stimulation (TENS) on stair climbing capacity in individuals with pre-radiographic to mild knee osteoarthritis (OA). This is a secondary analysis of data from a single, participant-blinded, randomized controlled trial with a pre-post design. Participants with pre-radiographic to mild knee OA (mean age, 59.1 years; 72.9% women) were randomly assigned into two groups, a TENS (n = 30) and a sham-TENS groups (n = 29). TENS or sham-TENS treatments were applied to all participants by using the prototype TENS device with pre-specified parameters. The primary outcome measures included valid and reliable functional measures for stair climbing (stair-climb test [SCT]), visual analog scale for knee pain during the SCT, and quadriceps muscle strength. TENS improved SCT time by 0.41 s (95% confidence interval [CI]: 0.07, 0.75). The time reduction in the transition phase explains the TENS therapeutic effect. Post-hoc correlation analyses revealed a non-significant but positive relationship between the pain relief effect and improved 11-step SCT time in the TENS group but not in the sham-TENS group. These results indicate that the TENS intervention may be an option for reducing the burden of early-stage knee OA.

Effects of Timing of Acute and Consecutive Catechin Ingestion on Postprandial Glucose Metabolism in Mice and Humans.

We examined the effects of the timing of acute and consecutive epigallocatechin gallate (EGCG) and catechin-rich green tea ingestion on postprandial glucose in mice and human adults. In mouse experiments, we compared the effects of EGCG administration early (morning) and late (evening) in the active period on postprandial glucose. In human experiments, participants were randomly assigned to the morning-placebo (MP, n = 10), morning-green tea (MGT, n = 10), evening-placebo (EP, n = 9), and evening-green tea (EGT, n = 9) groups, and consumed either catechin-rich green tea or a placebo beverage for 1 week. At baseline and after 1 week, participants consumed their designated beverages with breakfast (MP and MGT) or supper (EP and EGT). Venous blood samples were collected in the fasted state and 30, 60, 120, and 180 min after each meal. Consecutive administration of EGCG in the evening, but not in the morning, reduced postprandial glucose at 30 (p = 0.006) and 60 (p = 0.037) min in the evening trials in mice. In humans, ingestion of catechin-rich green tea in the evening decreased postprandial glucose (three-factor analysis of variance, p < 0.05). Thus, catechin intake in the evening more effectively suppressed elevation of postprandial glucose.

Effects of timing of acute catechin-rich green tea ingestion on postprandial glucose metabolism in healthy men.

Green tea polyphenols, particularly catechins, decrease fasting and postprandial glucose. However, no studies have compared the timing of green tea ingestion on glucose metabolism and changes in catechin concentrations. Here, we examined the effects of timing of acute catechin-rich green tea ingestion on postprandial glucose metabolism in young men. Seventeen healthy young men completed four trials involving blood collection in a fasting state and at 30, 60, 120, and 180 min after meal consumption in a random order: 1) morning placebo trial (09:00 h; MP trial), 2) evening placebo trial (17:00 h; EP trial), 3) morning catechin-rich green tea trial (09:00 h; MGT trial), and 4) evening catechin-rich green tea trial (17:00 h; EGT trial). The concentrations of glucose at 120 min (P=.031) and 180 min (P=.013) after meal intake were significantly higher in the MGT trials than in the MP trials. Additionally, the concentration of glucose was significantly lower in EGT trials than in the EP trials at 60 min (P=.014). Moreover, the concentrations of glucose-dependent insulinotropic polypeptide were significantly lower in the green tea trials than in the placebo trials at 30 min (morning: P=.010, evening: P=.006) and 60 min (morning: P=.001, evening: P=.006) after meal intake in both the morning and evening trials. Our study demonstrated that acute ingestion of catechin-rich green tea in the evening reduced postprandial plasma glucose concentrations.

Additional distal femoral osteotomy for insufficient correction after high tibial osteotomy.

A 70-year-old man who was treated with a closed-wedge high tibial osteotomy (HTO) had recurrent right medial knee pain 12 years after the initial osteotomy. We planned a recorrection osteotomy because the patient led an active lifestyle, had well-preserved range of motion and the lateral compartment was still intact. According to preoperative deformity analysis, which indicated a tibia in slight valgus and a femur in moderate varus, recorrection of the distal femur was chosen. Seven degrees of biplanar distal femoral osteotomy (DFO) was performed using a contralateral version of the TomoFix Medial Distal Femur. At 1 year follow-up, the femorotibial angle had improved from 178° to 170°, and the Japanese Orthopaedic Association score had improved from 75 to 95 points. Additional DFO could be a viable alternative for total knee arthroplasty or recorrection HTO when the centre of the deformity is located at the distal femur.

Comparison of the effects of kilohertz- and low-frequency electric stimulations: A systematic review with meta-analysis.

OBJECTIVE: This study aimed to determine whether kilohertz-frequency alternating current (KFAC) is superior to low-frequency pulsed current (PC) in increasing muscle-evoked torque and lessening discomfort. DATA SOURCES: The electronic databases PubMed, PEDro, CINAHL, and CENTRAL were searched for related articles, published before August 2017. Furthermore, citation search was performed on the original record using Web of Science. REVIEW METHODS: Randomized controlled trials, quasi-experimental studies, and within-subject repeated studies evaluating and comparing KFAC and PC treatments were included. The pooled standardized mean differences (SMDs) of KFAC and PC treatments, with 95% confidence intervals (CIs), were calculated using the random effects model. RESULTS: In total, 1148 potentially relevant articles were selected, of which 14 articles with within-subject repeated designs (271 participants, mean age: 26.4 years) met the inclusion criteria. KFAC did not significantly increase muscle-evoked torque, compared to PC (pooled SMD: -0.25; 95% CI: -0.53, 0.06; P = 0.120). KFAC had comparable discomfort compared to that experienced using PC (pooled SMD: -0.06; 95% CI: -0.50, 0.38; P = 0.800). These estimates of the effects had a high risk of bias, as assessed using the Downs and Black scale, and were highly heterogeneous studies. CONCLUSIONS: This meta-analysis does not establish that KFAC is superior to PC in increasing muscle-evoked torque and lessening discomfort level. However, no strong conclusion could be drawn because of a high risk of bias and a large amount of heterogeneity. High quality studies comparing the efficacy between PC and KFAC treatments with consideration of potential confounders is warranted to facilitate the development of effective treatment.

The acute effects of green tea and carbohydrate coingestion on systemic inflammation and oxidative stress during sprint cycling.

Green tea (Camellia sinensis) has anti-oxidative and anti-inflammatory effects, which may be beneficial to athletes performing high-intensity exercise. This study investigated the effects of carbohydrate and green tea coingestion on sprint cycling performance and associated oxidative stress and immunoendocrine responses to exercise. In a crossover design, 9 well-trained male cyclists completed 3 sets of 8 repetitions of 100-m uphill sprint cycling while ingesting green tea and carbohydrate (TEA) (22 mg/kg body mass catechins, 6 mg/kg body mass caffeine, 230 mg/kg glucose, and 110 mg/kg fructose) or carbohydrate only (CHO) (230 mg/kg body mass glucose and 110 mg/kg body mass fructose) during each 10-min recovery period between sets. Blood samples were collected before exercise, 10 min after exercise, and 14 h after exercise. There was no effect of acute TEA ingestion on cycling sprint performance (p = 0.29), although TEA maintained postexercise testosterone and lymphocyte concentrations, which decreased significantly in the CHO group (p < 0.001). While there was a trend for lower postexercise neutrophil count with TEA (p = 0.05), there were no significant differences between TEA and CHO for circulating cytokines (p > 0.20), markers of oxidative stress and antioxidant capacity (p > 0.17), adiponectin concentration (p = 0.60), or muscle damage markers (p > 0.64). While acute green tea ingestion prevents the postexercise decrease in testosterone and lymphocytes, it does not appear to benefit cycling sprint performance or reduce markers of oxidation and inflammation when compared with carbohydrate alone.

Acute ingestion of catechin-rich green tea improves postprandial glucose status and increases serum thioredoxin concentrations in postmenopausal women.

Elevated postprandial hyperglycaemia and oxidative stress increase the risks of type 2 diabetes and CVD. Green tea catechin possesses antidiabetic properties and antioxidant capacity. In the present study, we examined the acute and continuous effects of ingestion of catechin-rich green tea on postprandial hyperglycaemia and oxidative stress in healthy postmenopausal women. Participants were randomly assigned into the placebo (P, n 11) or green tea (GT, n 11) group. The GT group consumed a catechin-rich green tea (catechins 615 mg/350 ml) beverage per d for 4 weeks. The P group consumed a placebo (catechins 92 mg/350 ml) beverage per d for 4 weeks. At baseline and after 4 weeks, participants of each group consumed their designated beverages with breakfast and consumed lunch 3 h after breakfast. Venous blood samples were collected in the fasted state (0 h) and at 2, 4 and 6 h after breakfast. Postprandial glucose concentrations were 3 % lower in the GT group than in the P group (three-factor ANOVA, group × time interaction, P< 0·05). Serum concentrations of the derivatives of reactive oxygen metabolites increased after meals (P< 0·05), but no effect of catechin-rich green tea intake was observed. Conversely, serum postprandial thioredoxin concentrations were 5 % higher in the GT group than in the P group (three-factor ANOVA, group × time interaction, P< 0·05). These findings indicate that an acute ingestion of catechin-rich green tea has beneficial effects on postprandial glucose and redox homeostasis in postmenopausal women.

Cloning of cDNA encoding a Bombyx mori homolog of human oxidation resistance 1 (OXR1) protein from diapause eggs, and analyses of its expression and function.

To better understand the molecular mechanisms of diapause initiation, we used the sensitive cDNA subtraction (selective amplification via biotin- and restriction-mediated enrichment) method and isolated a novel gene expressed abundantly in diapause eggs of the silkworm, Bombyx mori, which encodes a homolog of the human oxidation resistance 1 (OXR1) protein. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses confirmed that BmOXR1 mRNA and its 140-kDa protein were differentially expressed in diapause eggs compared to non-diapause eggs. OXR1 double-stranded RNA (dsRNA) was injected into diapause-destined eggs before the cellular blastoderm stage, and 4days later, when untreated eggs reached the diapause stage, the OXR1 protein disappeared; however, these eggs remained in diapause, suggesting that BmOXR1 is not essential for diapause initiation and/or maintenance. To further investigate the in vivo function of BmOXR1 apart from its role in diapause, we overexpressed BmOXR1 in Drosophila melanogaster. The fruit fly male adult life-span was significantly extended in the 50%-survival time when adults were reared on diets both with and without H2O2 solution under 25°C incubation. These results suggest that BmOXR1 functions in D. melanogaster via a possible antioxidant effect. As BmOXR1 was expressed mainly in the nuclei of D. melanogaster cells, the mechanism underlying its antioxidation effect appears to be different from that in humans where it is expressed mainly in the mitochondria. Taken together, these results suggest that BmOXR1 might serve as an antioxidant regulator during the early diapause stage.

Synthetic approach toward alpha-aminomethyl-gamma-butyrolactones from beta-lactam synthons elaborated by SmI2-mediated reductive coupling reactions.

A simple and straightforward synthetic approach was developed to access a biologically important class of alpha-aminomethyl-gamma-butyrolactones via a beta-lactam synthon strategy involving successive ring-opening and lactonization processes from alpha-hydroxyethyl-substituted beta-lactams that were elaborated by SmI2-mediated reductive coupling reaction.

Evolution of the total syntheses of batzellasides, the first marine piperidine iminosugar.

Batzellasides A-C are C-alkylated piperidine iminosugars isolated from a sponge, Batzella sp. The first total synthesis of (+)-batzellaside B was achieved by employing a chiral pool approach starting from L-arabinose for the construction of a piperidine ring system. Subsequently, a practical second-generation synthesis was developed by utilizing a Sharpless asymmetric dihydroxylation for the preparation of the common piperidine intermediate elaborated in the first-generation synthesis. The overall yield of batzellaside B was improved to 3.3% by introducing the exocyclic C8 stereocenter via facial selective hydride addition to a linear ketone. These syntheses allowed for the determination of the absolute stereochemistry of this natural product as well as for providing precious samples, which would pave the way for further biological studies.

Effects of low-volume walking programme and vitamin E supplementation on oxidative damage and health-related variables in healthy older adults.

BACKGROUND: Both exercise and vitamin E supplementation have been shown to reduce oxidative stress and cardiovascular disease risk in older adults, and when combined there is evidence suggesting that they act synergistically. The currently recommended amount of exercise for older adults is 150 min/week of moderate-intensity exercise; however, the minimum amount of exercise necessary to achieve health benefits is not known. The purpose of this study was to investigate the effects of 12 weeks of participation in a low-volume walking exercise programme (i.e. 90 min/week) combined with daily vitamin E supplementation on thiobarbituric acid reactive substances (TBARS) and oxidised low-density lipoprotein (LDL) concentrations in older adults. METHODS: The participants were recruited from the following four groups separately: 1) control (CG, n = 14), 2) vitamin E supplementation (SG, n = 10), 3) walking (WG, n = 7), or 4) walking + supplementation (WSG, n = 7). In the CG, participants were advised to maintain their normal lifestyle during the study. Participants in both the SG and WSG received 450 IU (300 mg) /day of α-tocopherol for 12 weeks. The exercise programme for the WG and WSG consisted of two 30-60 minute sessions weekly for 12 weeks (average walking time was 44.5 ± 1.6 min/session). Blood samples were collected at baseline and at 12 weeks. RESULTS: Delta plasma oxidised LDL concentrations did not differ among four groups (One-factor ANOVA, P = 0.116). However, negative delta plasma TBARS, a marker of oxidative damage, concentrations were observed in the WG, WSG and SG relative to the CG at the end of the study period (One-factor ANOVA, P = 0.001; post hoc tests; CG compared with WG, WSG and SG, P = 0.005; P = 0.021; P = 0.024, respectively). CONCLUSION: These findings suggest that a low-volume of physical activity and/or vitamin E supplementation may be an effective intervention strategy for reducing TBARS concentrations of older adults. TRIAL REGISTRATION: UMIN000008304.

Additional reduction in serum phosphorus levels by pulverized lanthanum carbonate chewable in hemodialysis patients.

Lanthanum carbonate (LC) is one of the relatively new phosphate binders. The general LC dosage form is a chewable pharmaceutical preparation. This investigation was targeted to subjects who do not chew LC chewable preparations adequately, for the purpose of studying the clinical efficacy of changing to pulverized prescriptions, such as changes in serum phosphorus levels (P levels). The study took place at Minamisenju Hospital in October 2011, with 41 subjects on maintenance hemodialysis. We pulverized all of the LC chewable medicines of the LC insufficient mastication group (non-chewing: NC group, n = 18) using a crusher, and changed them to pulverized prescriptions. The testing period was set at 10 weeks. In the NC group, there was a significant lowering of P levels from 5.86 ± 1.31 mg/dL before pulverization of the LC chewable preparation (week 0) to 5.38 ± 1.26 mg/dL after 2 weeks of administration of the pulverized medication (P = 0.0310), 5.20 ± 1.25 mg/dL after 4 weeks (P = 0.0077), and 5.12 ± 1.34 mg/dL after 6 weeks (P = 0.0167). P levels in other patients than NC group showed no significant change. In this study, the P levels in the NC group was lowered significantly by changing the LC chewable to the pulverized prescription, and the residual LC images on the abdominal X-rays disappeared to the point where they could barely be confirmed.

Low-volume exercise training and vitamin E supplementation attenuates oxidative stress in postmenopausal women.

The purpose of this study was to investigate the effects of low-volume exercise training (90 min/wk) and vitamin E supplementation on oxidative stress markers in postmenopausal women. The participants were non-randomly assigned the following four groups: control (C, n=8), vitamin E (S, n=8), exercise (Ex, n=6), or vitamin E and exercise (S+Ex, n=7). The S and S+Ex groups were instructed to take vitamin E (α-tocopherol, 300 mg/d) capsules for 12 wk. The exercise program of Ex and S+Ex groups consisted of walking for a 30-60 min/session 2 d per week for 12 wk. The serum derivatives of reactive oxygen metabolites concentrations were significantly decreased in the Ex, and S+Ex groups after 12 wk compared with the baseline values (three-factor ANOVA, an interaction between exercise and time, p<0.05). Conversely, serum biological antioxidant potential concentrations in the S and Ex groups were significantly higher at 12 wk than at the baseline, but not in the S+Ex group (three-factor ANOVA, an interaction between supplementation, exercise and time, p<0.05). Plasma thioredoxin concentrations in the S, Ex, and S+Ex groups were significantly higher at 12 wk than at the baseline values (three-factor ANOVA, interactions between exercise and time, and between supplementation, exercise and time, p<0.05). Our findings suggest that low-volume physical activity may improve resting oxidative stress status in postmenopausal women.

Cranberry juice suppressed the diclofenac metabolism by human liver microsomes, but not in healthy human subjects.

AIM: To investigate a potential interaction between cranberry juice and diclofenac, a substrate of CYP2C9. METHODS: The inhibitory effect of cranberry juice on diclofenac metabolism was determined using human liver microsome assay. Subsequently, we performed a clinical trial in healthy human subjects to determine whether the repeated consumption of cranberry juice changed the diclofenac pharmacokinetics. RESULTS: Cranberry juice significantly suppressed diclofenac metabolism by human liver microsomes. On the other hand, repeated consumption of cranberry juice did not influence the diclofenac pharmacokinetics in human subjects. CONCLUSIONS: Cranberry juice inhibited diclofenac metabolism by human liver microsomes, but not in human subjects. Based on the present and previous findings, we think that although cranberry juice inhibits CYP2C9 activity in vitro, it does not change the pharmacokinetics of medications metabolized by CYP2C9 in clinical situations.

Cardiorenal protective effects of year-long antihypertensive therapy with an angiotensin-converting enzyme inhibitor or a calcium channel blocker in spontaneously hypertensive rats.

BACKGROUND: The objective of this study was to evaluate the effect of year-long antihypertensive therapy with a calcium channel blocker and an angiotensin-converting enzyme (ACE) inhibitor on cardiac and renal injury. METHODS: Male 15-week-old spontaneously hypertensive rats (SHR) were given either a normal diet and normal drinking water (n = 10), a diet containing 0.05% nitrendipine (n = 10), or drinking water containing 50 mg/L of quinapril (n = 10). After 12 months of antihypertensive treatment, cardiovascular organ injuries were evaluated. RESULTS: Tail-cuff blood pressure (BP) at 12 months was significantly lower in animals receiving nitrendipine or quinapril than in control animals (control, 231 +/- 2 mm Hg; nitrendipine, 194 +/- 3 mm Hg; quinapril, 191 +/- 3 mm Hg; P < .001). Furthermore, aortic thickness was reduced by nitrendipine (-19%, P < .001) or quinapril (-21%, P < .001), and cardiac ventricular weight was significantly reduced by quinapril (-18%, P < .001) but not by nitrendipine (-5%, P = not significant [NS]). Echocardiography at 12 months revealed that midwall fractional shortening was higher in the quinapril group than in the control or the nitrendipine groups (control, 9.3% +/- 0.5%; nitrendipine, 9.8% +/- 0.5%; quinapril, 10.6% +/- 0.6%; P < .05). Left ventricular hydroxyproline levels were lower in the nitrendipine group (-21%, P < .01) and the quinapril group (-36%, P < .001) than in the control animals. In control SHR, creatinine clearance began to decrease and proteinuria began to increase at 6 to 9 months. Quinapril but not nitrendipine attenuated these markers of renal impairment (creatinine clearance at 12 months: control, 4.7 +/- 0.4 mL/min/kg; nitrendipine, 5.0 +/- 0.4 mL/min/kg; quinapril, 6.1 +/- 0.4 mL/min/kg; P < .05). Histologically, the glomerular injury score was lower in the quinapril group than in the control or nitrendipine groups (control, 19 [range, 8 to 30]; nitrendipine, 18 [range, 9 to 32]; quinapril, 7 [range, 3 to 12]; P < .01). CONCLUSIONS: It is suggested that year-long antihypertensive therapy with an angiotensin-converting enzyme (ACE) inhibitor is superior to a calcium channel blocker in terms of cardiorenal protection in SHR.

[A case of pseudo-Bartter's syndrome induced by long-term ingestion of furosemide delivered orally through health tea].

A 32-year-old woman with a three-year history of muscle weakness and hypokalemia, was admitted to our hospital because of hypokalemic periodic paralysis. Clinical and laboratory findings were consistent with Bartter's syndrome. Although she denied any ingestion of diuretics substantial quantities of furosemide were detected in her urine. She had been drinking health tea which contained about 90 mg of furosemide per teabag daily for five years. Four years after discontinuation of drinking the tea, the hypokalemia was completely ameliorated, but poor renal concentration ability is still present. We conclude that is a case of pseudo-Bartter's syndrome that was caused by long-term ingestion of the health tea supplemented illegally with furosemide, and suspect that such cases may be observed more frequently than currently thought.