Pharmacokinetics of a Single Intake of a Self-Emulsifying Drug Delivery System Containing the Triglyceride Form of DHA: A Randomized, Double-Blinded, Crossover Study.

Background: The health benefits of n-3 (ω-3) PUFAs are well studied. A self-emulsifying drug delivery system (SEDDS) is expected to improve n-3 PUFA absorption. Objectives: The present study investigated how a single ingestion of a new SEDDS containing the triglyceride (TG) form of DHA (22:6n-3) (DHA/TG) would affect the plasma DHA concentration in healthy participants. Methods: Fifteen healthy participants (age: 20-65 y; BMI: 18.5-25 kg/m2) were enrolled in this randomized, double-blind, crossover study. Participants in a fasting state consumed a single dose of 920 mg DHA and 80 mg EPA (20:5n-3) in SEDDS soft capsules (SEDDS capsule) or non-emulsifying soft capsules (control capsule). Blood was sampled at 0, 1.5, 3, 5, 7, and 9 h after dosing. The primary outcome was the baseline-adjusted incremental AUC (iAUC) for plasma DHA concentrations (iAUC_DHA). Results: The iAUC_DHA was significantly higher for the SEDDS capsule (147.9 ± 15.8 µg·h/mL) than for the control capsule (106.4 ± 18.1 µg·h/mL) (P = 0.018; SEDDS/control ratio: 1.4:1). However, plasma EPA concentrations and iAUC values did not significantly differ between the SEDDS and control capsules. Cmax was significantly higher with the SEDDS capsule for both DHA (P = 0.019) and EPA (P = 0.012) than with the control capsule. Conclusions: These results suggest that a SEDDS improves the absorbability of DHA/TG in healthy participants. This indicates that SEDDS capsules would be beneficial for efficient ingestion of DHA.This trial was registered at https://www.umin.ac.jp/ctr/ as UMIN000044188.

Intake of 25-Hydroxyvitamin D3 May Reduce the Severity of Upper Respiratory Tract Infection: Post hoc Analysis of a Randomized, Double-Blind, Placebo-Controlled, Parallel Group Comparison Study.

To evaluate the effects of 25-hydroxyvitamin D3 (25OHD) on symptoms at the onset of the upper respiratory tract infection (URTI) in subjects with insufficient or deficient serum 25-hydroxyvitamin D levels, we conducted a post hoc analysis of data from a randomized, placebo-controlled study; the subjects received 10 µg of 25OHD per day or a placebo for 16 weeks. The Wisconsin Upper Respiratory Symptom Survey-21 was used to determine URTI. The study endpoints included WURSS-21 scores, number of URTI events, and proportion of medication (antibiotics, antipyretic analgesics) usage. We found that the physical symptom scores for "Runny nose," "Sneezing," and "Head congestion" were significantly lower in the 25OHD group than in the placebo group; for all items except "Breathe easily, "the quality of life" scores were significantly improved in the 25OHD group. There was no significant difference in the number of URTI events or the proportion of medication use between the groups. Collectively, the findings of this study indicate that a sufficient 25OHD intake can reduce physical symptoms at the onset of upper respiratory tract infection, particularly nasal symptoms, and may improve the quality of life at the time of onset.

Processing Ambiguous Morphemes in Chinese Compound Word Recognition: Behavioral and ERP Evidence.

This study examined the processing of ambiguous morphemes in Chinese word recognition with a masked priming lexical decision task. Both behavioral and event-related potential (ERP) were recorded. All targets were bimorphemic compound words that contained ambiguous morphemes as the first morphemes. The ambiguous morphemes either took the dominant or subordinate interpretation, depending on the second morphemes. The prime words contained the same ambiguous morphemes in the dominant interpretation, the subordinate interpretation, or were unrelated to the targets. Analyses on response times revealed significant facilitative priming whenever primes and targets shared morphemes, but the strength of facilitation was stronger when the morpheme meanings were consistent. A similar pattern was found in the analyses of N400 (300-500 ms after target onset) amplitudes. However, in the earlier N250 time window (200-300 ms after target onset), only the dominant targets, but not the subordinate ones, were primed by the morpheme-sharing primes. More importantly, the strength of facilitation was similar between the dominant and subordinate primes. These results have two implications to the processing of ambiguous morphemes during Chinese compound word recognition. First, the morpheme meanings could be activated rapidly. Second, the more frequently used dominant meanings could be activated more easily than the less frequently used subordinate meanings.

Suppression of hyperexcitability of trigeminal nociceptive neurons associated with inflammatory hyperalgesia following systemic administration of lutein via inhibition of cyclooxygenase-2 cascade signaling.

INTRODUCTION: Lutein is a dietary constituent known to inhibit inflammation; however, its effect on nociceptive neuron-associated hyperalgesia remains to be determined. The present study therefore investigated under in vivo conditions whether administration of lutein attenuates the inflammation-induced hyperexcitability of trigeminal spinal nucleus caudalis (SpVc) neurons that is associated with mechanical hyperalgesia. RESULTS: Complete Freund's adjuvant (CFA) was injected into the whisker pads of rats to induce inflammation, and then mechanical stimulation was applied to the orofacial area to assess the threshold of escape. The mechanical threshold was significantly lower in inflamed rats compared to uninjected naïve rats, and this lowered threshold was returned to control levels by 3 days after administration of lutein (10 mg/Kg, i.p.) Also the lutein administration, inflammation-induced thickness of edema was returned to control levels. The mean increased number of cyclooxygenase-2 (Cox-2)-immunoreactive cells in the whisker pads of inflamed rats was also returned to control levels by administration with lutein. The mean discharge frequency of SpVc wide-dynamic range (WDR) neurons to both nonnoxious and noxious mechanical stimuli in inflamed rats was significantly decreased after lutein administration. In addition, the increased mean spontaneous discharge of SpVc WDR in inflamed rats was significantly decreased after lutein administration. Similarly, lutein significantly diminished noxious pinch-evoked mean after discharge frequency and occurrence in inflamed rats. Finally, lutein restored the expanded mean size of the receptive field in inflamed rats to control levels. CONCLUSION: These results together suggest that administration of lutein attenuates inflammatory hyperalgesia associated with hyperexcitability of nociceptive SpVc WDR neurons via inhibition of the peripheral Cox-2 signaling cascade. These findings support the proposed potential of lutein as a therapeutic agent in complementary alternative medicine strategies for preventing inflammatory mechanical hyperalgesia.

The dietary constituent resveratrol suppresses nociceptive neurotransmission via the NMDA receptor.

Background Although we have previously reported that intravenous resveratrol administration inhibits the nociceptive neuronal activity of spinal trigeminal nucleus caudalis neurons, the site of the central effect remains unclear. The aim of the present study was to examine whether acute intravenous resveratrol administration in the rat attenuates central glutamatergic transmission of spinal trigeminal nucleus caudalis neurons responding to nociceptive mechanical stimulation in vivo, using extracellular single-unit recordings and microiontophoretic techniques. Results Extracellular single-unit recordings using multibarrel electrodes were made from the spinal trigeminal nucleus caudalis wide dynamic range neurons responding to orofacial mechanical stimulation in pentobarbital anesthetized rats. These neurons also responded to iontophoretic application of glutamate, and the evoked neuronal discharge frequency was significantly increased in a current-dependent and reversible manner. The mean firing frequency evoked by the iontophoretic application of glutamate (30, 50, and 70 nA) was mimicked by the application of 10 g, 60 g, and noxious pinch mechanical stimulation, respectively. The mean firing frequency of spinal trigeminal nucleus caudalis wide dynamic range neurons responding to iontophoretic application of glutamate and N-methyl-D-aspartate were also significantly inhibited by intravenous administration of resveratrol (2 mg/kg) and the maximal inhibition of discharge frequency was observed within 10 min. These inhibitory effects lasted approximately 20 min. The relative magnitude of inhibition by resveratrol of the glutamate-evoked spinal trigeminal nucleus caudalis wide dynamic range neuronal discharge frequency was similar to that for N-methyl-D-aspartate iontophoretic application. Conclusion These results suggest that resveratrol suppresses glutamatergic neurotransmission of the spinal trigeminal nucleus caudalis neurons responding to nociceptive mechanical stimulation via the N-methyl-D-aspartate receptor in vivo, and resveratrol may be useful as a complementary or alternative therapeutic agent for the treatment of trigeminal nociceptive pain.

Acute intravenous administration of dietary constituent theanine suppresses noxious neuronal transmission of trigeminal spinal nucleus caudalis in rats.

Theanine is a non-dietary amino acid linked to the modulation of synaptic transmission in the central nervous system, although the acute effects of theanine in vivo, particularly on nociceptive transmission in the trigeminal system, remain to be determined. The present study investigated whether acute intravenous theanine administration to rats attenuates the excitability of wide dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. Extracellular single unit recordings were made from 15 SpVc neurons in response to orofacial mechanical stimulation of pentobarbital-anesthetized rats, and responses to non-noxious and noxious mechanical stimuli were analyzed. The mean firing frequency of SpVc WDR neurons in response to all mechanical stimuli was dose-dependently inhibited by theanine (10, 50, and 100mM, i.v.) with the maximum inhibition of discharge frequency reached within 5min. These inhibitory effects were reversed after approximately 10min. The relative magnitude of theanine's inhibition of SpVc WDR neuronal discharge frequency was significantly greater for noxious than non-noxious stimulation. Iontophoretic application of l-glutamate induced the mean firing frequency of SpVc WDR neuron responding to noxious mechanical stimulation was also inhibited by intravenous administration of 100mM theanine. These results suggest that acute intravenous theanine administration suppresses glutaminergic noxious synaptic transmission in the SpVc, implicating theanine as a potential complementary and alternative therapeutic agent for the treatment of trigeminal nociceptive pain.

Rice Bran Extract Reduces the Risk of Atherosclerosis in Post-Menopausal Vietnamese Women.

We investigated whether pre-germinated brown rice bran extract containing acylated steryl glucosides (PSG) reduces the risk of atherosclerosis in post-menopausal Vietnamese women. A total of 60 post-menopausal Vietnamese women (45-65 y old) with high LDL cholesterol levels (over 140 mg/dL) were randomly divided into PSG (n=30) and placebo (n=30) groups. The subjects in the PSG group were assigned a daily intake of 6 capsules containing 50 mg PSG, and the subjects in the placebo group were assigned a daily intake of 6 capsules containing corn oil for 6 mo. Before baseline and after month 2, month 4, and month 6 of the intervention, we conducted anthropometric measurements, blood biochemical examinations, a nutrition survey, and physical activity, flow-mediated dilation (FMD), and cardio-ankle vascular index (CAVI) measurements. Serum LDL cholesterol concentrations were significantly reduced from 163.6±25.3 (mg/dL) to 135.9±26.8 (mg/dL) compared to the placebo group (p<0.001). FMD values of the placebo group were significantly reduced from 6.6±5.1 (%) to 4.7±2.6 (%) compared to the PSG group (p<0.05). Tumor necrosis factor (TNF)-α concentrations in the PSG group were significantly reduced from 19.8±11 (pg/mL) to 10.6±5.5 (pg/mL) compared to the placebo group (p<0.05). The findings suggest that PSG may improve LDL cholesterol, TNF-α levels, and FMD values. PSG might be considered in reducing the risk of atherosclerosis in post-menopausal Vietnamese women with high LDL cholesterol.

Systemic administration of resveratrol suppress the nociceptive neuronal activity of spinal trigeminal nucleus caudalis in rats.

Although a modulatory role has been reported for the red wine polyphenol resveratrol on several types of ion channels and excitatory synaptic transmission in the nervous system, the acute effects of resveratrol in vivo, particularly on nociceptive transmission of the trigeminal system, remain to be determined. The aim of the present study was to investigate whether acute intravenous resveratrol administration to rats attenuates the excitability of wide dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. Extracellular single unit recordings were made from 18 SpVc neurons in response to orofacial mechanical stimulation of pentobarbital-anesthetized rats. Responses to both non-noxious and noxious mechanical stimuli were analyzed in the present study. The mean firing frequency of SpVc WDR neurons in response to both non-noxious and noxious mechanical stimuli was inhibited by resveratrol (0.5-2 mg/kg, i.v.) and maximum inhibition of the discharge frequency of both non-noxious and noxious mechanical stimuli was seen within 10 min. These inhibitory effects were reversed after approximately 20 min. The relative magnitude of inhibition by resveratrol of SpVc WDR neuronal discharge frequency was significantly greater for noxious than non-noxious stimulation. These results suggest that, in the absence of inflammatory or neuropathic pain, acute intravenous resveratrol administration suppresses trigeminal sensory transmission, including nociception, and so resveratrol may be used as a complementary and alternative medicine therapeutic agent for the treatment of trigeminal nociceptive pain, including hyperalgesia.