Protective effect of sesamin administration on exercise-induced lipid peroxidation

To investigate the mechanism of antioxidative effects of sesamin in vivo, 32 male ddY mice were administered with 10 mg/kg or 100 mg/kg of sesamin (S10, S100), 100 mg/kg of vitamin E (VE100) or control sample (C). They were subjected to 30 min of swimming exercise 2 h after the sample administration by using a new forced-swimming apparatus, i. e. an adjustable-current swimming pool. Exercise resulted in a significant increase in plasma lipid peroxides (LPO) in C and VE100 (p < 0.01), but not in S10 and S100. S100 showed significantly higher total glutathione peroxidase activity and glutathione S-transferase activity in liver compared to C (p < 0.05). In conclusion, sesamin may enhance LPO degradation in the liver resulting in the strong protective effects against exercise-induced plasma lipid peroxidation.     

Uncoupling protein 1 gene −3826 A/G polymorphism is associated with weight loss on a short-term, controlled-energy diet in young women

Uncoupling protein 1 (UCP1) plays an important role in thermogenesis in brown adipose tissue. Previously, we reported an association between −3826 A/G single-nucleotide polymorphism (SNP) in the promoter of UCP1 gene and lower thermogenesis in young women, suggesting this SNP has an adverse effect on the regulation of energy balance. Based on the hypothesis that this SNP (G allele) may have resistance against diet-induced weight loss, we examined its effects on anthropometric and metabolic responses to short-term, controlled-energy diet in young women. Seventeen lean women (20.9 ± 0.2 years; body mass index, 22.1 ± 0.5 kg/m²) were fed a controlled-energy diet (5.0 MJ/d, 62% carbohydrate, 19% protein, and 19% fat) administered by dietitians for 2 weeks. Clinical measurements were determined at baseline and after the dietary intervention. The subjects' physical activity was obtained using pedometers and self-reporting. The thermoregulatory sympathetic nervous system was evaluated using heart rate variability power spectral analysis. Upon the completion of the intervention, subjects were genotyped using an allele-specific DNA primer assay and results compared with their clinical measurements focusing on with or without the G allele. After dietary intervention, G allele subjects (A/G + G/G, n = 10) showed significantly smaller changes in body weight, body mass index, and waist circumference compared with A/A genotype subjects (n = 7). Similar changes were observed in parameters regarding glucose or lipid metabolism in both groups. These results suggest that the UCP1 gene −3826 G allele may result in smaller weight loss after a short-term, controlled-energy diet in young, lean women.     

Alterations of autonomic nervous activity and energy metabolism by capsaicin ingestion during aerobic exercise in healthy men

We investigated whether capsaicin ingestion (150 mg) enhances substrate oxidation associated with thermogenic sympathetic activity as an energy metabolic modulator without causing prolongation of the cardiac OT interval during aerobic exercise in humans. Ten healthy males [24.4 (4.3) y] volunteered for this study. The cardiac autonomic nervous activities evaluated by means of heart rate variability of power spectral analysis, energy metabolism, and ECG QT interval were continuously measured during 5-min rest and 30-min exercise at 50% of maximal ventilatory threshold (50% VT(max)) on a stationary ergometer with placebo or capsaicin oral administration chosen at random. The results indicated that there were no significant differences in heart rate during rest or exercise between the two trials. Autonomic nervous activity increased in the capsaicin tablet trial during exercise, but the difference did not reach statistical significance. Capsaicin, however, significantly induced a lower respiratory gas exchange ratio [0.92 (0.02) vs. 0.94 (0.02), means (SE), p < 0.05] and higher fat oxidation [0.17 (0.04) vs. 0.12 (0.04) g/min, means (SE), p < 0.05] during exercise. On the other hand, the data on the cardiac OT interval showed no significant difference, indicating that oral administration of capsaicin did not cause any adverse effect on cardiac depolarization-repolarization. In conclusion, it may be considered that capsaicin consumption 1 h before low intensity exercise (50% VT(max)) is a valuable supplement for the treatment of individuals with hyperlipidemia and/or obesity because it improves lipolysis without any adverse effects on the cardiac depolarization and repolarization process.     

Clinical study on the combined effect of capsaicin, green tea extract and essence of chicken on body fat content in human subjects

This study was conducted to assess the body fat content of free-living healthy human subjects taking a health supplement containing 0.4 mg capsaicin, 625 mg green tea extract (125 mg catechins and 50 mg caffeine) and 800 mg essence of chicken (CGTE). Subjects were advised to maintain their regular dietary habits and routine physical activity throughout study duration. Their body fat content was measured before and throughout the trial duration using a hand-grip body fat monitor. After 2 wk of supplementation with CGTE, the mean body fat percentage of males and female subjects was significantly less than the initial value (p < 0.05; t-test). 70.6%, of volunteers showed a trend for decreasing body fat content with 4 subjects showing a significant decrease in body fat content over time. The findings suggested that the effects were more prominent in subjects with higher initial body fat content. It was also demonstrated that the resting energy expenditure (REE) of the subjects taking the test samples were significantly increased in groups supplemented with CGTE, compared to placebo group. Thus, the combined thermogenic effect of capsaicin, green tea extract and essence of chicken could translate to a positive clinical effect by reducing approximately 460 g of body fat, following 2 wk of supplementation and the application of this natural health supplement for excess fat regulation, should be considered.     

Biological properties of a specific Galpha q/11 inhibitor, YM-254890, on platelet functions and thrombus formation under high-shear stress

1 The effects of YM-254890, a specific Galpha(q/11) inhibitor, on platelet functions, thrombus formation under high-shear rate condition and femoral artery thrombosis in cynomolgus monkeys were investigated. 2 YM-254890 concentration dependently inhibited ADP-induced intracellular Ca(2+) elevation, with an IC(50) value of 0.92+/-0.28 microM. 3 P-selectin expression induced by ADP or thrombin receptor agonist peptide (TRAP) was strongly inhibited by YM-254890, with IC(50) values of 0.51+/-0.02 and 0.16+/-0.08 microM, respectively. 4 YM-254890 had no effect on the binding of fibrinogen to purified GPIIb/IIIa, but strongly inhibited binding to TRAP-stimulated washed platelets. 5 YM-254890 completely inhibited platelet shape change induced by ADP, but not that induced by collagen, TRAP, arachidonic acid, U46619 or A23187. 6 YM-254890 attenuated ADP-, collagen-, TRAP-, arachidonic acid- and U46619-induced platelet aggregation with IC(50) values of <1 microM, whereas it had no effect on phorbol 12-myristate 13-acetate-, ristocetin-, thapsigargin- or A23187-induced platelet aggregation. 7 High-shear stress-induced platelet aggregation and platelet-rich thrombus formation on a collagen surface under high-shear flow conditions were concentration dependently inhibited by YM-254890. 8 The antithrombotic effect of YM-254890 was evaluated in a model of cyclic flow reductions in the femoral artery of cynomolgus monkeys. The intravenous bolus injection of YM-254890 dose dependently inhibited recurrent thrombosis without affecting systemic blood pressure or prolonging template bleeding time. 9 YM-254890 is a useful tool for investigating Galpha(q/11)-coupled receptor signaling and the physiological roles of Galpha(q/11).     

Electrical activity and soreness in muscles after exercise

Electrical activity and soreness in the quadriceps muscles were examined during a 48-h period after eccentric (EC) and concentric contraction (CC) to study the amplitude and frequency characteristics of the electrical signal after exercise and to study the relationship between the electrical signal and muscle soreness. The exercise protocol included a step test performed for 15 min using a 46-cm step in which one quadriceps contracted eccentrically and one contracted concentrically. Electrical activity was quantified by computing both root mean square electromyograph (rmsEMG) and mean power frequency of the myoelectrical signal during low-level contractions of the muscles. Recordings of muscle activity were made before exercise, immediately after exercise, 1, 12, 24 and 48 h after exercise in 12 volunteer subjects (mean age 28.5 yr). Recordings were made with the subject seated, holding the leg being tested slightly off the ground. Subjects were given a subjective pain rating scale. The before exercise values for rmsEMG (EC = 13.3 microV; CC = 13 microV) and mean power frequency (EC = 55.3 Hz; CC = 54.4 Hz) were within the range that would be expected for surface electrodes. The mean rating of soreness for the eccentrically exercised muscles ranged from slightly uncomfortable at 12 h after exercise to sore during the period 24-48 h after exercise. Subjects reported the concentrically exercised muscles as normal to slightly uncomfortable during the whole recording period. Analysis of variance revealed a significant (P less than 0.05) difference between EC and CC rmsEMG value at 1 h after exercise (EC = 17.2 +/- 7.6; CC = 12.3 +/- 5.5) and at 12 h after exercise (EC = 15.0 +/- 5.0; CC = 12.3 +/- 4.2). The results suggest that an increase in the electrical activity of muscles is needed to produce the same pre-exercise contraction after performing eccentric exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transport of monocarboxylic acids at the blood-brain barrier: studies with monolayers of primary cultured bovine brain capillary endothelial cells

The kinetics and mechanism of the transport of monocarboxylic acids (MCAs) were studied by using primary cultured bovine brain capillary endothelial cells. Concentration-dependent uptake of acetic acid was observed, and the kinetic parameters were estimated as follows: the Michaelis constant, Kt, was 3.41 +/- 1.87 mM, the maximum uptake rate, Jmax, was 144.7 +/- 55.7 nmol/mg of protein/min and the nonsaturable first-order rate constant, Kd, was 6.66 +/- 1.98 microliters/mg of protein/min. At medium pH below 7.0, the uptake rate of [3H]acetic acid increased markedly with decreasing medium pH, whereas pH-independent uptake was observed in the presence of 10 mM acetic acid. An energy requirement for [3H]acetic acid uptake was also demonstrated, because metabolic inhibitors (2,4-dinitrophenol and rotenone) reduced significantly the uptake rate (P less than .05). Carbonylcyanide-p-trifluoro-methoxyphenylhydrazone, a protonophore, inhibited significantly the uptake of [3H]acetic acid at medium pH of 5.0 and 6.0, whereas 4,4'-diisothiocyanostilben-2,2'-disulfonic acid did not. Several MCAs inhibited significantly the uptake rate of [3H]acetic acid, whereas di- and tricarboxylic acids did not. The uptake of [3H]acetic acid was competitively inhibited by salicylic acid, with an inhibition constant, Ki, of 3.60 mM, suggesting a common transport system between acetic acid and salicylic acid. Moreover, at the medium pH of 7.4, salicylic acid and valproic acid inhibited significantly the uptake of [3H]acetic acid, demonstrating that the transport of MCA drugs could also be ascribed to the MCA transport system at the physiologic pH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Structure-activity relationship of flavonoids for inhibition of epidermal growth factor-induced transformation of JB6 Cl 41 cells

We found that quercetin, myricetin, quercetagetin, fisetin, (-)-epigallocatechin gallate (EGCG), and theaflavins, among 24 flavonoids examined, markedly inhibited epidermal growth factor (EGF)-induced cell transformation of mouse epidermal JB6 Cl 41 cells. The six flavonoids suppressed the EGF-induced activation of activator protein 1 (AP-1). In addition, myricetin, quercetagetin, EGCG, and theaflavins directly inhibited EGF-induced phosphatidylinositol 3-kinase (PI3K) activation. The important structural features of flavonoids for cell transformation-inhibitory activity are 3'- and 4'-OH on the B-ring, 3-OH on the C-ring, C2=C3 double bond in the C-ring, and the phenylchromone (C6-C5-C6) skeleton in the flavonols, and the galloyl group in EGCG and theaflavins. Our results provide new insight into possible mechanisms of the anti-carcinogenic effects of flavonoids, and could help to provide a basis for the design of novel cancer chemopreventive agents.     

Enzyme histochemistry is useful to assess viability of tumor tissue after microwave coagulation therapy (MCT): metastatic adenocarcinoma treated by lateral segmentectomy after MCT

We report on a case of metastatic adenocarcinoma of liver that was removed and examined histochemically after microwave coagulation therapy (MCT). The patient was a 65-year-old woman who had a metastatic tumor in the liver (S3) after high anterior resection due to a rectal adenocarcinoma and received MCT against the tumor. One month after MCT, multiple metastatic tumors were detected by abdominal computed tomography (CT) scan. As it was difficult to control them by MCT alone, we performed lateral segmentectomy. To assess the effects of microwave ablation on cellular viability of metastatic tumor, we used enzyme histochemistry for acid phosphatase (AcP), which is positive in macrophages infiltrating in the tumor. In a part of the ablated area of resected liver, there was remaining neoplastic tissue of which the morphology was maintained in H&E staining. This was found to be microwave-fixed non-viable tissue because no enzyme activity of AcP was detected in the infiltrating macrophages. This case report suggests that enzyme histochemistry was useful to assess the effect of MCT, enabling us to distinguish fixed cells from viable cells.