OBJECTIVE: Con¯icting results have emerged over the nature of autonomic nervous system abnormalities in human obesity. This present study was designed to investigate the sympatho-vagal activities and their responsiveness to acute cold exposure in age-and height-matched obese and non-obese young women. SUBJECTS: Twenty-four age-and height-matched obese (Weight: 68.1 AE 2.64 kg, BMI: 26.3 AE 0.74 kgam 2 , %Fat: 39.9 AE 1.23%) and non-obese young women (Weight: 46.9 AE 0.77 kg, BMI: 18.5 AE 0.18 kgam 2 , %Fat: 22.9 AE 0.8%). MEASUREMENTS: Plasma leptin, insulin, glucose and lipid concentrations were measured at rest. The sympathetic (SNS) and parasympathetic (PNS) nervous system activities were assessed by means of power spectral analysis of heart rate variability (HRV) for 15 min under control (25 C) or acute cold exposure (10 C) conditions. The very low (VLO) frequency component, and SNS (lowahigh power), and PNS (highatotal power) indexes were used to evaluate thermoregulatory sympathetic function, and cardiac sympathetic and parasympathetic nervous activities, respectively. RESULTS: Plasma leptin concentration was signi®cantly greater in the obese than in the control group (47.3 AE 7.00 vs 12.1 AE 1.22 ng Á ml 71 , P`0.001). There was a highly positive correlation between plasma leptin concentration and percent of body fat (r 0.863, P`0.001). During the resting condition, there was no signi®cant difference in any of the parameters of the HRV between the obese and control groups. Upon acute cold exposure, the VLO frequency component associated with thermoregulation (309 AE 49.9 vs 578 AE 142.2 ms 2 , P`0.05) as well as its responsiveness (25 ± 10 C delta changes: 17 AE 82.9 vs 326 AE 138.2 ms 2 , P`0.05) were signi®cantly lower in the obese than in the control group. CONCLUSION: Our data indicate that a reduced autonomic, especially sympathetic responsiveness associated with thermoregulation and possibly leptin resistance might be aetiological factors of obesity in young women.

Leptin is an adipocyte-derived blood-borne satiety factor that acts on its cognate leptin receptor (Ob-R) in the hypothalamus, thereby regulating food intake and energy expenditure. To explore whether mutations in the Ob-R gene cause obesity in humans, we have searched for mutations in the gene for Ob-Rb, a biologically active receptor isoform, in obese Japanese subjects. We have also examined associations between such mutants and obesity in the Japanese. Genomic DNAs were used as templates in polymerase chain reaction (PCR) with primers selected to amplify exons 2 to 20 of the human Ob-Rb gene. Direct sequence analysis of the PCR products revealed 7 nucleotide sequence variants (Lys109Arg, Gln223Arg, Ser343Ser, Ser492Thr, Lys656Asn, Ala976Asp, and Pro1019Pro) in the Ob-Rb coding region from 17 obese Japanese subjects with a family history of obesity (BMI 39.3 +/- 8.4 kg/m2). No missense and nonsense mutations were found such as those in Zucker fatty (fa/fa) rats and Koletsky (fa[k]/ fa[k]) rats. Nucleotide substitutions occurred at relatively high frequencies at codons 109, 223, 976, and 1019 (79, 91, 100, and 85%, respectively). Allele frequency of each variant determined by PCR-RFLP and PCR-single strand conformation polymorphism analyses showed no significant differences between 47 obese (BMI 35.1 +/- 6.5 kg/m2) and 68 non-obese (BMI 21.6 +/- 2.2 kg/m2) subjects. The present study represents the first report of sequence variants of the Ob-Rb gene in the Japanese and provides evidence against either obesity-causing mutations or association of sequence variants with obesity in obese Japanese subjects.

Summary Sesamin, one of the lignans contained in sesame, has been considered to have medicinal effects. It has been reported that sesamin suppressed the development of hypertension in rats. In this study, using a double-blind, cross-over, placebo-controlled trial, we investigated the effect of 4-wk administration of sesamin on blood pressure (BP) in mildly hypertensive humans. Twenty-five middle-aged subjects with mild hypertension were divided into two groups, matched by age and body mass index. Twelve subjects were allocated to 4-wk intake of capsules with 60 mg sesamin per day and 13 subjects to 4-wk intake of a placebo (period 1). After a 4-wk washout period, the subjects received the alternative administration for 4 wk (period 2). BP decreased with statistical significance with the administration of sesamin (systolic: 137.6 Ϯ 2.2 to 134.1 Ϯ 1.7 mmHg, p ϭ 0.044, diastolic: 87.7 Ϯ 1.3 to 85.8 Ϯ 1.0 mmHg, p ϭ 0.045), but little changed with the placebo (systolic: 135.0 Ϯ 1.8 to 135.1 Ϯ 1.7 mmHg, diastolic: 85.9 Ϯ 1.2 to 86.6 Ϯ 1.2 mmHg). In conclusion, 4-wk administration of 60 mg sesamin significantly decreased BP by an average of 3.5 mmHg systolic BP and 1.9 mmHg diastolic BP. These results suggest that sesamin has an antihypertensive effect in humans. Epidemiological studies suggested that a 2-3 mmHg decrease in BP reduces the rate of cardiovascular diseases; therefore, it is considered that BP reduction achieved by sesamin may be meaningful to prevent cardiovascular diseases. Key Words sesamin, hypertension, double-blind, cross-over study, antihypertensive effects Sesame seeds have been commonly used as a traditional health food since ancient times in Asian regions. Sesamin seeds contain not only oil and protein but also characteristic lignans, such as sesamin (0.01-1.0%) and sesamolin. Sesamin is epimerized during acid-clay bleaching in the oil refining process to form episesamin ( Fig. 1) ( 1 ).It seems that sesamin was absorbed via the portal vein in the native form and metabolized to the mono-or di-catechol compound by enzymes in hepatocytes. Both metabolites had antioxidant activity in the liver and were finally conjugated with glucuronic acid by glucuronidase for excretion into bile ( 2 ).Several studies have shown the biological activities of sesamin: anti-oxidative activity ( 2 , 3 ); cholesterol and lipid-lowering ( 4 -8 ); protection against liver damage ( 8 -10 ); synergy with ␣ -tocopherol ( 6 , 11 ) and improvement in the bioavailability of ␥ -tocopherol ( 12 -14 ); anticarcinogenic activities ( 15 , 16 ); and precursors of mammalian lignans ( 17 , 18 ). It has been also reported that sesamin suppressed the development of hypertension in rats ( 2 , 19 -26 ).There are also clinical studies about the effects of sesamin in humans. Hirata et al. ( 5 ) showed that, in males with hypercholesterolemia, oral administration of 9 capsules (each capsule contained 3.6 mg sesamin and 18 mg vitamin E) per day for 4 wk, followed by 18 capsules per day for 4 wk significantly reduced serum total and LDL chole...

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Sediment and marine biota comprising several species of tidal flat and coastal organisms were analyzed for polychlorinated biphenyls (PCBs) including non- and mono-ortho coplanar congeners and polycyclic aromatic hydrocarbons (PAHs) to examine bioaccumulation profiles and toxic potencies of these contaminants. Concentrations of PCBs in tidal flat organisms ranged from 3.6 ng/g (wet wt) in clams to 68 ng/g (wet wt) in omnivore tidal flatfishes, a discernible trend reflecting concentrations and trophic levels. In contrast, PAHs concentrations were the highest in lower trophic organisms, such as crabs and lugworms from tidal flat, whereas those in coastal fishes, squid, and finless porpoises were less than detection limit. Greater bioaccumulation of PAHs was found in lugworms and crabs, which might be due to their direct ingestion of sediment particulates absorbed with PAHs. TCDD toxic equivalents (TEQs) were calculated for PCBs and PAHs in sediments and biota. PCBs accounted for a greater proportion of total TEQs (sum(TEQs): sum of TEQ(PCB) and TEQ(PAH)) in coastal and tidal flatfishes (>95%), while PAHs occupied a considerable portion of sum(TEQs) in sediment (>97%). Interestingly, TEQ(PAH) accounted for 37% and 81% of the sum(TEQs) in crabs and clams, respectively. Benzo[b]fluoranthene was the dominant contributor to TEQ(PAH) in both the species. Considering these observations, the environmental risks of PAHs may not be ignored in benthic tidal flat organisms due to their greater bioaccumulation through sediments.

The role of (+/-)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)-kainate and N-methyl-D-aspartate (NMDA) receptors in the rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM) on the central respiratory drive (CRD)-related activity of splanchnic sympathetic nerve activity (SNA) was examined in rats. SNA increased during inspiration (I peak) and postinspiration (PI peak). Bilateral microinjections of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; AMPA-kainate antagonist) or DL-2-amino-5-phosphonovaleric acid (APV; NMDA antagonist) into RVLM abolished the PI, but not the I, peak. Blockade of all excitatory amino acid receptors in RVLM with kynurenate, or mixtures of APV and CNQX, also failed to eliminate the I peak. Somatosympathetic responses were abolished by CNQX injection into RVLM, but were unaffected by APV. CNQX, but not APV, injection into CVLM increased the PI peak of SNA. Our findings suggest the following. 1) Both NMDA and AMPA-kainate receptors in RVLM are involved in the coupling between the sympathetic nervous system and CRD, which generates the PI peak seen in SNA. 2) The I peak of SNA is independent of excitatory amino acid transmission within RVLM. 3) There are different relative amounts of NMDA and AMPA-kainate receptors at synapses where respiratory and somatic inputs converge onto RVLM neurons. 4) Glutamatergic inputs to CVLM neurons modulate the coupling between SNA and CRD in RVLM.

Barosensitive neurons in the rostral ventrolateral medulla (RVLM) often have a respiratory-related modulation of their activity. However, the extent of the interaction between baroreceptor and respiratory inputs is controversial. The main aim of the present study was to determine the effect of central respiratory drive (CRD) on the barosensitivity of RVLM neurons. Extracellular recordings were obtained from 68 barosensitive neurons in the RVLM of anesthetized, paralyzed, and bilaterally vagotomized Sprague-Dawley rats. Examination of phrenic-triggered histograms revealed five activity patterns among barosensitive neurons: inspiratory depression (type I, n = 20), early inspiratory activation (type II, n = 14), postinspiratory activation (type III, n = 18), expiratory depression (type IV, n = 5) and no modulation (type V, n = 11). In most neurons (types I and III and 56% of type II) inhibition produced by aortic nerve stimulation was greater in inspiration than in expiration. Cardiac-related modulation, as an index of natural phasic baroreceptor activation, was also greater in inspiration than expiration in type III neurons. The results demonstrate that CRD modulates the baroreflex at the level of the RVLM.

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