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ABSTRACT: Consumption of fructose has been linked to the development of metabolic syndrome, whereas the cardiomyopathic changes and cardiac apoptosis of dietary high-fructose intake have not yet been clarified. The purpose of this study was to evaluate the effects of high-fructose on cardiac apoptotic and survival pathways. Thirty-two Wistar rats were randomly divided into a control group (CON), which received a standard chow diet, and a fructose-induced metabolic syndrome group (FIMS), which received a 50% fructose-content diet for 13 weeks. Histopathological analysis, TUNEL assays and Western blotting were performed on the excised hearts from both groups. The blood pressure, glucose, insulin, triglyceride and cholesterol levels were significantly increased in the FIMS group, compared with the CON group. The abnormal myocardial architecture, enlarged interstitial space and increased cardiac TUNEL-positive apoptotic cells were observed in the FIMS group. The TNF-α, TNF receptor 1, Fas ligand, Fas receptor, FADD, and activated caspase-3 and 8 protein levels (Fas pathway) and the Bax, Bak, Bax/Bcl-2, Bak/Bcl-xL, cytosolic cytochrome c, and activated caspase-3 and nine protein levels (mitochondria pathway) were increased in the FIMS group compared with those in the CON group. The IGFI, IGFI-R, p-PI3K, p-Akt, Bcl-2 and Bcl-xL protein levels (survival pathway) were all significantly decreased in the FIMS group compared with those in the CON group. High-fructose intake elevated blood pressure and glucose levels; moreover, high-fructose diet activated cardiac Fas-dependent and mitochondria-dependent apoptotic pathways and suppressed the survival pathway, which might provide one possible mechanism for developing heart failure in patients with metabolic syndrome. Copyright © 2013 John Wiley & Sons, Ltd.
Cell Biochemistry and Function 05/2013; · 1.77 Impact Factor
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ABSTRACT: Sleep-disordered breathing (SDB) and cardiometabolic risk factors are male prevalent.
This study investigated whether gender differences remained prominent after matching for the apnea hypopnea index (AHI) and postmenopause.
In a retrospective analysis of 350 eligible SDB patients, female patients were matched with male patients of the same age and body mass index (BMI) (age-BMI-matched [nAHImt]; n = 102 pairs) or were matched with male patients of the same age, BMI, and AHI (age-BMI-AHI-matched [AHImt]; n = 66 pairs). The nAHImt or AHImt patients were further separated into junior and senior subgroups.
In the nAHImt/junior group, women had shorter neck circumferences, better sleep architecture, and lower AHI, Epworth Sleepiness Scale (ESS) score, blood pressure (BP), total cholesterol (TC), triglyceride (TG), and uric acid (UA) than nAHImt/junior men. In the AHImt/junior group, women had shorter neck circumferences, lower waist/hip ratios, ESS, BP, TG, and UA than AHImt junior men. In the nAHImt/senior group, women had lower AHI, neck circumferences, waist/hip ratios, diastolic BP, and UA than men. In contrast, in the AHImt/senior group, most cardiometabolic parameters were similar between women and men. After further matching for the AHI, many elements of gender differences disappeared.
Compared with AHImt men, women had lower UA, TG, BP, and daytime sleepiness before menopause, but gender differences became indistinguishable postmenopause. We suggested that matching sleep quality or adjusting AHI would be noteworthy and required for studying gender differences.
Gender Medicine 02/2012; 9(1):9-20. · 2.10 Impact Factor
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ABSTRACT: The behaviors of children may be affected by sleep-disordered breathing (SDB). This study adopts a cross-sectional approach to investigate the relationship between the sleep apneas-hypopneas index during sleep and the behavioral and academic performance of schoolchildren in Taiwan.
A total of 138 children (85 boys and 53 girls), ages 6-11, were recruited from two elementary schools to participate in this study. Overnight polysomnographic examinations in hospital were performed to assess sleep quality, including total sleep time, arousal index, apneas-hypopneas index, desaturation index, and lowest oxygen saturation, as well as the percentage of total sleep time spent in rapid eye movement, stage 1, stage 2, stage 3, and stage 4. The children's parents and teachers were required to complete a Chinese version of the Child Behavior Checklist and Teacher's Report Form to assess child behavior and academic achievement.
Compared with children without SDB (apneas-hypopneas index ≤1), those with severe SDB (apneas-hypopneas index >15) exhibited more irregular behavioral performance in somatic complaints (odds ratio (OR) = 9.43; 95% confidence interval (CI) = 1.04-85.71) and attention (OR = 9.95; 95% CI = 1.02-97.00). However, different severities of SDB groups did not show significant associations in academic performance.
Our study suggests that children with severe SDB may predispose to somatic complaints and attention problems so that sleep examination or medical intervention might be provided at an early age in these children.
Sleep And Breathing 01/2011; 15(1):91-8. · 1.84 Impact Factor
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ABSTRACT: The aim of the current study was to investigate whether changes in post- to pre-overnight sleep systolic blood pressure (SSBP) are associated with sleep respiratory disturbance, pro-inflammatory state, and metabolic situation in patients with sleep-disordered breathing (SDB).
Anthropometry, sleep polysomnography, biochemical markers, and pre- and post-overnight sleep BP were measured from 263 SDB patients. All SDB patients were further subgrouped into MORNING SURGE (% changes from post- to pre-overnight SSBP >+1SD of this cohort), MORNING DROP (% changes <-1SD), CONSTANT HIGH (% changes within+/-1SD, averaged SSBP>130mmHg) and CONSTANT LOW (% changes within+/-1SD, averaged SSBP<130mmHg).
BMI, neck circumference, waistline circumference, respiratory disturbance index, arousal index, lowest oxygen saturation, duration of SaO(2)<90%, blood glucose, hs-CRP, and metabolic syndrome score in MORNING SURGE and CONSTANT HIGH were significantly greater than those in CONSTANT LOW. Except metabolic syndrome score, all other parameters in MORNING DROP were similar to those in CONSTANT LOW.
Patients with SDB whose post- to pre-overnight SSBPs were elevated or maintained a constant high have more sleep respiratory disturbance, more pro-inflammatory state, and higher metabolic syndrome indices than the rest. Without subdividing into CONSTANT LOW, MORNING DROP, CONSTANT HIGH, and MORNING SURGE, the important pathophysiologic points of SDB patients will possibly be missed.
Sleep Medicine 10/2008; 10(7):720-5. · 3.40 Impact Factor
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ABSTRACT: The aim of this study was to investigate whether GABA(A) and/or GABA(B) receptor-mediated mechanisms contribute to the impaired ventilatory response and reduced maximal aerobic exercise capacity in obese Zucker rats. Ten lean and 10 obese Zucker rats were studied at 12 wk of age. Minute ventilation (Ve), tidal volume (Vt), and breathing frequency (f) during room air breathing and in response to 10 min of hypercapnia (8% CO(2)) and 30 min of hypoxia (10% O(2)) were measured by the barometric method, and peak oxygen consumption (Vo(2 peak)) was measured by an enclosed metabolic treadmill following the randomized blinded subcutaneous administration of equal volumes of DMSO (vehicle), bicuculline (selective GABA(A) receptor antagonist, 1 mg/kg), and phaclofen (selective GABA(B) receptor antagonist, 1 mg/kg). Administration of bicuculline and phaclofen to lean animals had no effect on Ve and Vo(2 peak). Similarly, phaclofen failed to alter Ve and Vo(2 peak) in obese rats, although it did significantly increase f after 5-20 min of hypoxia. In contrast, bicuculline increased Ve and Vt relative to DMSO during room air breathing and after 10-30 min of hypoxic exposure in obese rats, but it did not increase Ve at 5 min of hypoxemia. Bicuculline increased Vo(2 peak) relative to DMSO in obese Zucker rats. We conclude that endogenous GABA acting on GABA(A) receptors can modulate Ve and Vo(2 peak) in obese but not in lean Zucker rats, whereas endogenous GABA acting on GABA(B) receptors modulates f during hypoxia (5-20 min) in obese rats in a very different manner from that when acting on GABA(A) receptors.
Journal of Applied Physiology 02/2007; 102(1):350-7. · 3.75 Impact Factor
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ABSTRACT: Secreted factors present in the medium following growth of the periodontal pathogen Porphyromonas gingivalis cause increased cardiomyocyte hypertrophy and apoptosis, whereas secreted factors from Actinobacillus actinomycetemcomitans and Prevotella intermedia have no such effects. The purpose of this study was to clarify the role of mitogen-activated protein kinase (MAPK)/extracellular-regulated protein kinase (ERK) pathways in P. gingivalis medium-induced H9c2 myocardial cell hypertrophy and apoptosis. Cellular morphology, DNA fragmentation, nuclear condensation, total mitogen-activated protein kinase/extracellular-regulated protein kinase-1 (ERK-1), total ERK-1 protein, and phosphorylated ERK-1 protein products in cultured H9c2 myocardial cells were measured by actin immunofluorescence, agarose gel electrophoresis, nuclear condensation, and western blotting following stimulation with P. gingivalis spent growth medium or pre-administration of U0126, a potent MEK-1/2 inhibitor. Components of P. gingivalis spent culture medium not only resulted in increased total MEK-1 and ERK-1 protein products, but also caused increased cellular size, DNA fragmentation, and nuclear condensation in H9c2 cells. These three parameters, and the phosphorylated ERK-1 protein products of H9c2 cells treated with P. gingivalis medium, were all significantly reduced after pre-administration of U0126. The results suggest that P. gingivalis-secreted factors may initiate MEK/ERK signal pathways and lead to myocardial cell hypertrophy and apoptosis.
European Journal Of Oral Sciences 05/2006; 114(2):154-9. · 1.88 Impact Factor
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ABSTRACT: The effects of electroacupuncture (Ea) on circulatory dynamics were investigated in anesthetized rats. The arterial blood pressure (BP) and the heart rate (HR) in response to Ea stimulations at the Tsusanli point (St-36) and the Hoku point (Li-4) were tested by a low frequency Ea (2 Hz; LFEa) and a high frequency Ea (20 Hz; HFEa) with stimulation intensities 20 times the motor threshold. Neither the HR nor the BP was affected when the Tsusanli point was stimulated. Whereas, Ea stimulations at the Hoku point elicit chronotropic and pressor effects. The patterns of pressor responses caused by the LFEa were different from that of an HFEa, i.e., the LFEa elicited a tonic effect, while an HFEa had a phasic one. The HFEa-induced pressor and chronotropic effects were attenuated, while the LFEa induced effects were completely blocked by an intravenous infusion of an alpha-adrenergic blocker (moxisylyte 0.2 mg/min/kg, i.v., for 20 min). A co-infusion with alpha-and beta-adrenergic blockers (propanolol 0.2 mg/min/kg, i.v., for 20 min) completely blocked the HFEa-induced pressor and chronotropic effects. We concluded that Ea stimulations, at the Hoku acupoint, with appropriate stimulation parameters can increase and maintain BP. Furthermore, the LFEa stimulation activates sympathetic vasomotor tone, whereas the HFEa stimulation causes an additional potentiation on the sympathetic drive to the heart.
Autonomic Neuroscience 02/2006; 124(1-2):18-25. · 1.86 Impact Factor
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ABSTRACT: The static/dynamic changes of gas exchange, heart rate (HR) and blood pressure in terms of work rate (WR) and WR changes in ramp exercise were investigated by cardio-pulmonary exercise tests (CPETs) in hyperhidrosis patients before (W0), one week (W1) and four weeks (W4) after bilateral T2-sympathectomy. Accompanied by constant oxygen consumption and WR at peak exercise and similar oxygen debt in recovery, the HR significantly (p<0.05) decreased statically in all stages of CPET, but was not altered dynamically, i.e., similar slope but significantly diminished intercept in HR changes versus WR changes (70+/-6.0 vs. 82+/-19 beats/min, p<0.01), in W1 (n=11), compared to W0 (n=13). However, this surgical effect on static HR changes seemed to have disappeared in W4 (n=8), albeit at that time the static blood pressure decreased significantly during exercise. These findings suggest that bilateral T2-sympathectomy will reduce static HR without causing cardiovascular insufficiency in one week, and would then recover by one month in hyperhidrosis patients.
Autonomic Neuroscience 09/2005; 121(1-2):74-80. · 1.86 Impact Factor
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ABSTRACT: To clarify the effect of electroacupuncture (Ea) on the activity of the cardiovascular system in normal individuals, hemodynamic parameters including arterial blood pressure (BP), finger blood flow (FBF) and heart rate (HR) as well as paravertebral temperature (PVT) were non-invasively recorded under Ea stimulation. Surface stimulation electrode was placed on the Hoku point (Li-4). Square wave pulses (0.05 ms) were applied from a stimulator with a stimulation frequency of 2 Hz (3 min). The stimulation intensity was five times of sensory threshold. BP and FBF were decreased (68.5+/-6.0%, P<0.01 and 96.8+/-1.1%, P<0.01 of control, respectively, n=7) while HR and PVT were increased significantly (115.0+/-5.1 of control, P<0.05 and 0.054+/-0.004 degree C, P<0.01, respectively, n=7) during Ea treatment. The results suggested an inhibition in sympathetic outflow, which induced vasodilatation of systemic arteriole and decrease in BP and FBF were elicited by Ea stimulation.
Autonomic Neuroscience 08/2003; 107(1):60-4. · 1.86 Impact Factor
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ABSTRACT: The kinetics of the decrease in venous O(2) content in response to constant work rate exercise below the lactic acidosis threshold (LAT) is very rapid, reaching a constant value by approximately 1 min. However, for work rates above the LAT, a slow further decrease in venous O(2) content takes place that is attributable to the Bohr effect rather than further decrease in end capillary PO. We hypothesized that similar differences, with respect to the LAT, will be observed in muscle deoxygenation kinetics when studied with near-infrared spectroscopy (NIRS).
Twelve normal subjects performed three constant work rate tests from unloaded cycling at 60% of LAT, 80% LAT, each with four repetitions, and above LAT (LAT + 35% between LAT and VO(2max) three times, on a cycle ergometer for 6 min. We measured tissue deoxygenation with NIRS, with the probe over the vastus lateralis muscle, time-averaging the repetitions. Gas exchange and heart rate (HR) were measured breath-by-breath and beat-by-beat.
Tissue deoxygenation kinetics were significantly faster than VO(2) and HR at 60%- and 80%-LAT work rates. By 1 min of exercise, deoxygenation was constant for the work rate below the LAT. At 30 s, tissue deoxygenation was 70-95% complete, whereas VO(2) and HR were only 30-60% complete. For the work rate above the LAT, a steady state for muscle deoxygenation was not reached during the 6 min of exercise. After 1 min of above-LAT exercise, either one of two patterns of slow change in tissue oxygenation developed, deoxygenation or reoxygenation. It is postulated that these different responses might be due to effects of the exercise lactic acidosis. H accompanying lactate increase might cause further deoxygenation due to the Bohr effect, and acidosis-induced vasodilatation might cause reoxygenation after the initial deoxygenation.
1) The kinetics of tissue deoxygenation are significantly more rapid than VO(2) and HR kinetics at all work rates studied, and 2) steady-state in tissue deoxygenation is seen by 1 min of constant work rate exercise below the LAT, but this is much delayed for work rates above the LAT.
Medicine & Science in Sports & Exercise 11/2002; 34(10):1614-23. · 4.43 Impact Factor
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ABSTRACT: The neural mechanism underlying the effect of electroacupuncture (Ea) on arterial blood pressure (BP) and renal nerve activity (RNA) in the intact state and during acute hemorrhage was investigated in anesthetized rats. Two acupoints, Hoku (Li-4, at the junction of the first and the second metacarpal bone) and Tsusanli (St-36, at the lateral upper tibia bone), were tested using Ea of two different frequencies (2 and 20 Hz). In the intact state, Ea at Hoku elicited an elevation of BP in parallel with RNA, while Ea found no response with identical parameters at Tsusanli. The pattern of the pressor response caused by a low frequency Ea (2 Hz) at Hoku was different than a high frequency one (20 Hz), i.e. a tonic effect was elicited with 2 Hz, while a phasic one was induced with 20 Hz. In mild hemorrhage conditions (10% of BP decrease), similar pressor effects, as in intact rats, were also elicited by Ea. However, in severe hemorrhage conditions (20 and 30% BP decrease), Ea induced a pressor effect on RNA and an attenuated effect on BP. BP and RNA showed a significant correlation in intact and mild hemorrhage conditions, but not in severe hemorrhage conditions. All the results suggested that Ea at Hoku with appropriate stimulation parameters can increase and maintain BP in normal and hemorrhage conditions, and such a therapeutic technique has potential in clinical practice.
Neuroscience Letters 08/2002; 327(1):5-8. · 2.11 Impact Factor
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ABSTRACT: To address the effect of electroacupuncture (Ea) on the autonomic nerve activity, responses of arteriole blood pressure (BP), intragastric pressure (IGP) and parasympathetic vagal nerve activity (VNA) to Ea were investigated in alpha-chloralose anesthetized rats. The acupoint: Hoku (Li-4) was tested with two different stimulation frequencies (2 and 20 Hz). Decrease in VNA and basal IGP associated with elevation of BP were elicited during Ea at Hoku with stimulation intensity of 20 times of motor threshold. The pattern of response induced by the low frequency Ea (LFEa) was different from that by the high frequency Ea (HFEa), i.e. a tonic effect was elicited by the LFEa, while a phasic one was induced by the HFEa. All the results in this study implicated that: (1) Ea at Hoku may activate the sympathetic and simultaneously inhibit the gastric parasympathetic nerve; (2) Ea at Hoku with different stimulation frequencies may elicit distinct mechanism to induce therapeutic effect; (3) Ea at Hoku may ameliorate the hyperactive stomach in clinical therapy.
Neuroscience Research 02/2002; 42(1):15-20. · 2.25 Impact Factor
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ABSTRACT: The prevalence of insomnia is very high in our society. Although pharmacological treatment of insomnia is available, most hypnotics have been shown to alter sleep architecture and have many adverse effects. Gabapentin was originally designed for antiepileptic therapy; however, some studies reported that its use increases slow-wave sleep in healthy volunteers or patients. Our goal was to evaluate the benefits of gabapentin in the treatment of primary insomnia in patients.
Eighteen patients with primary insomnia participated in the study. They received gabapentin treatment for at least 4 weeks. All patients received polysomnography, a biochemical blood test, and neuropsychological tests before and after the treatment period. All measures were analyzed with Student t test to examine the treatment effects of gabapentin, except that the measures of heart rate variability were analyzed with analysis of variance.
Polysomnographic study revealed increased sleep efficiency and slow-wave sleep, decreased wake after sleep onset, and spontaneous arousal index after gabapentin treatment. The biochemical blood test revealed decreased prolactin levels in the morning after treatment. Electroencephalographic power spectral analysis showed increased delta-2 and theta power in sleep stage 1 and decreased sigma activity power in sleep stages N2 and N3 after gabapentin treatment. Heart rate variability analyses also showed a significant increase in normalized high frequency percentage in sleep stages N2 and N3 and low frequency-high frequency ratio in sleep stage N2 after treatment. In addition, neuropsychological tests revealed the elevation of visual motor processing speed after gabapentin treatment.
Gabapentin enhances slow-wave sleep in patients with primary insomnia. It also improves sleep quality by elevating sleep efficiency and decreasing spontaneous arousal. The results suggest that gabapentin may be beneficial in the treatment of primary insomnia.
Clinical neuropharmacology 33(2):84-90. · 2.35 Impact Factor
