Influence of temperature on hatching success of skipjack tuna (Katsuwonus pelamis): Implications for spawning availability of warm habitats.

Exploring the effects of water temperature on egg development in skipjack tuna (Katsuwonus pelamis) has substantial implications for evaluations of wild spawning habitats. In the present study, we examined the hatching success and duration as a function of temperature from 21 to 33°C under captive environments. A high hatching rate of over 50% between 23 and 31°C was observed, with the shortest hatching duration at 31°C. Because the egg period is vulnerable to predators, a shortened hatching duration with warming water would be ecologically advantageous for K. pelamis, as its main spawning grounds are located in tropical areas.

Tocotrienols Prevent the Decline of Learning Ability in High-Fat, High-Sucrose Diet-Fed C57BL/6 Mice.

Obesity has been increasing worldwide and is well-known as a risk factor for cognitive decline. It has been reported that oxidative stress in the brain is deeply involved in cognitive dysfunction in rodent models. While there are many studies on oxidation in the liver and adipose tissue of obese mice, the relationship between obesity-induced cognitive dysfunction and brain oxidation has not been elucidated. Here, we show that obesity induced by a high-fat, high-sucrose diet (HFSD) alters cognitive function in C57BL/6 male mice, and it may involve the acceleration of brain oxidation. Tocotrienols (T3s), which are members of the vitamin E family, can prevent HFSD-induced cognitive changes. To elucidate these mechanisms, respiratory metabolism, locomotor activity, temperature around brown adipose tissue, and protein profiles in the cerebrum cortex were measured. Contrary to our expectation, respiratory metabolism was decreased, and temperature around brown adipose tissue was increased in the feeding of HFSD. The proteins that regulate redox balance did not significantly change, but 12 proteins, which were changed by HFSD feeding and not changed by T3s-treated HFSD compared to control mice, were identified. Our results indicated that HFSD-induced obesity decreases mouse learning ability and that T3s prevent its change. Additionally, feeding of HFSD significantly increased brain oxidation. However, further study is needed to elucidate the mechanisms of change in oxidative stress in the brain by obesity.

LOX-1 mediates inflammatory activation of microglial cells through the p38-MAPK/NF-κB pathways under hypoxic-ischemic conditions.

BACKGROUND: Microglial cells play an important role in the immune system in the brain. Activated microglial cells are not only injurious but also neuroprotective. We confirmed marked lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression in microglial cells in pathological lesions in the neonatal hypoxic-ischemic encephalopathy (nHIE) model brain. LOX-1 is known to be an activator of cytokines and chemokines through intracellular pathways. Here, we investigated a novel role of LOX-1 and the molecular mechanism of LOX-1 gene transcription microglial cells under hypoxic and ischemic conditions. METHODS: We isolated primary rat microglial cells from 3-day-old rat brains and confirmed that the isolated cells showed more than 98% Iba-1 positivity with immunocytochemistry. We treated primary rat microglial cells with oxygen glucose deprivation (OGD) as an in vitro model of nHIE. Then, we evaluated the expression levels of LOX-1, cytokines and chemokines in cells treated with or without siRNA and inhibitors compared with those of cells that did not receive OGD-treatment. To confirm transcription factor binding to the OLR-1 gene promoter under the OGD conditions, we performed a luciferase reporter assay and chromatin immunoprecipitation assay. In addition, we analyzed reactive oxygen species and cell viability. RESULTS: We found that defects in oxygen and nutrition induced LOX-1 expression and led to the production of inflammatory mediators, such as the cytokines IL-1ß, IL-6 and TNF-α; the chemokines CCL2, CCL5 and CCL3; and reactive oxygen/nitrogen species. Then, the LOX-1 signal transduction pathway was blocked by inhibitors, LOX-1 siRNA, the p38-MAPK inhibitor SB203580 and the NF-κB inhibitor BAY11-7082 suppressed the production of inflammatory mediators. We found that NF-κB and HIF-1α bind to the promoter region of the OLR-1 gene. Based on the results of the luciferase reporter assay, NF-κB has strong transcriptional activity. Moreover, we demonstrated that LOX-1 in microglial cells was autonomously overexpressed by positive feedback of the intracellular LOX-1 pathway. CONCLUSION: The hypoxic/ischemic conditions of microglial cells induced LOX-1 expression and activated the immune system. LOX-1 and its related molecules or chemicals may be major therapeutic candidates. Video abstract.

Rs11726196 Single-Nucleotide Polymorphism of the Transient Receptor Potential Canonical 3 (TRPC3) Gene Is Associated with Chronic Pain.

Chronic pain is reportedly associated with the transient receptor potential canonical 3 (TRPC3) gene. The present study examined the genetic associations between the single-nucleotide polymorphisms (SNPs) of the TRPC3 gene and chronic pain. The genomic samples from 194 patients underwent linkage disequilibrium (LD) analyses of 29 SNPs within and around the vicinity of the TRPC3 gene. We examined the associations between the SNPs and the susceptibility to chronic pain by comparing the genotype distribution of 194 patients with 282 control subjects. All SNP genotype data were extracted from our previous whole-genome genotyping results. Twenty-nine SNPs were extracted, and a total of four LD blocks with 15 tag SNPs were observed within and around the TRPC3 gene. We further analyzed the associations between these tag SNPs and chronic pain. The rs11726196 SNP genotype distribution of patients was significantly different from the control subjects even after multiple-testing correction with the number of SNPs. The TT + TG genotype of rs11726196 is often carried by chronic pain patients, suggesting a causal role for the T allele. These results contribute to our understanding of the genetic risk factors for chronic pain.

Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1-Related Microglial Activation in Neonatal Hypoxic-Ischemic Encephalopathy: Morphologic Consideration.

Neonatal hypoxic-ischemic encephalopathy (nHIE) is a major neonatal brain injury. Despite therapeutic hypothermia, mortality and sequelae remain severe. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is associated with the pathophysiology of nHIE. In this study, morphologic change and microglial activation under the nHIE condition and LOX-1 treatment were investigated. The microglial activity and proliferation were assessed with a novel morphologic method, immunostaining, and quantitative PCR in the rat brains of both nHIE model and anti-LOX-1 treatment. Circumference ratio, the long diameter ratio, the cell area ratio, and the roundness of microglia were calculated. The correlation of the morphologic metrics and microglial activation in nHIE model and anti-LOX-1 treated brains was evaluated. LOX-1 was expressed in activated ameboid and round microglia in the nHIE model rat brain. In the evaluation of microglial activation, the novel morphologic metrics correlated with all scales of the nHIE-damaged and treated brains. While the circumference and long diameter ratios had a positive correlation, the cell area ratio and roundness had a negative correlation. Anti-LOX-1 treatment attenuated morphologic microglial activation and proliferation, and suppressed the subsequent production of inflammatory mediators by microglia. In human nHIE, round microglia and endothelial cells expressed LOX-1. The results indicate that LOX-1 regulates microglial activation in nHIE and anti-LOX-1 treatment attenuates brain injury by suppressing microglial activation.

Straightforward upriver migration to spawning sites by chum salmon Oncorhynchus keta homing to coastal short rivers in the Sanriku region.

In chum salmon (Oncorhynchus keta) homed to the Sanriku region, Japan, most of the fish are matured in bays and spawn near river mouths in coastal short rivers; therefore, their upriver migration is extremely short, but their behavioural characteristics have remained unknown. Upriver migration in the Otsuchi River, a typical coastal river, was evaluated from behavioural and physiological aspects. Homing salmon tracked in Otsuchi Bay held in the inner bay for less than 1 day to more than 10 days before river entry. The varied holding duration was negatively correlated with plasma 17α, 20ß-dihydroxy-4-pregnen-3-one (DHP) concentration, an indicator of maturation. After river entry, however, most fish were captured in weirs near the river mouths within 2 days regardless of the DHP concentration. Of the 34 fish released in the river, on the contrary, eighteen and five fish were seen next day in the main spawning sites located at c. 1.5 km upstream and in the branch creek, respectively, and 85% of the fish held position there until their death. The mean survival time of released fish was 5.8 days. Plasma DHP level suggested that preparations for spawning were already completed at the timing of the release. Taken together, homing salmon completed spawning preparation in the bay, and then they moved to their spawning sites immediately after river entry and spawned there during their short remaining life. This upriver migration contrasts with those of other populations, such as early migrants and long river migrants, whose maturation is completed during upriver migration.

Tocotrienols Attenuate White Adipose Tissue Accumulation and Improve Serum Cholesterol Concentration in High-Fat Diet-Treated Mice.

Tocotrienols (T3s), which are vitamin E homologs, have not only antioxidant function but also inhibitory effects on body weight gain and hepatic lipid droplet accumulation. However, the mechanisms of the anti-obesity effects of T3s are not yet understood. In this study, C57BL/6 mice were fed a high-fat diet in the presence or absence of T3s. Treatment with T3s inhibited white adipose tissue accumulation and elevation of serum cholesterol concentrations. Additionally, to clarify the relationship between obesity-induced cognitive dysfunction and the neuroprotective effect of T3s, cognitive function, brain oxidation, and protein expression levels of brain-derived neurotrophic factor (BDNF), which is strongly involved in neuronal growth and differentiation, were measured. Although mice behaviors were improved by oral T3 intake, there were no significant differences in brain oxidation levels and BDNF expression. These results suggest that T3s attenuate obesity via inhibition of body fat and serum cholesterol increase.

Relationships between maturational status and migration behavior of homing chum salmon Oncorhynchus keta in inner bays of the Sanriku coast.

The correlations among gonad maturity and various homing behaviors of chum salmon, Oncorhynchus keta, were evaluated using acoustic tracking of tagged fish in Otsuchi Bay, Japan. There was a negative correlation between the time duration from release of tagged fish until river entry and the plasma 17α, 20ß-dihydroxy-4-pregnen-3-one (DHP) levels, an indicator of final maturation. Females with high DHP entered the rivers soon after the release, whereas females with low DHP (<10 ng/ml) took a few days to more than one week until river entry. Similar correlation was also found in males. A pattern of river entry correlated with maturational conditions was also observed in fish entering the rivers of neighboring bays. DHP concentrations of fish caught in the rivers were consistently higher. On the other hand, more than half of released salmon departed from the bay regardless of their plasma DHP level, suggesting that maturational status does not force homing adults to enter the most available nearest rivers. Fish entering the rivers experienced ambient temperatures less than 8 °C, which is approximately 5 °C lower than that of the bay. These results indicate that homing salmon hold their position in the bay until just before spawning, which may be attributable to low temperature avoidance. This characteristic type of river entry may be suitable to geographical features and thermal regimes of this region.

Short-term outcomes in infants with mild neonatal encephalopathy: a retrospective, observational study.

BACKGROUND: Neonatal encephalopathy due to acute perinatal asphyxia is a major cause of perinatal brain damage. Moderate to severe neonatal encephalopathy is associated with high mortality and morbidity rates. However, the neurodevelopmental outcomes in neonates with mild neonatal encephalopathy are unclear. The primary aim of this single-center observational study was to assess the short-term outcomes in term neonates with mild neonatal encephalopathy due to perinatal asphyxia. A secondary aim was to identify predictors of poor prognosis by identifying the characteristics of these infants according to their short-term outcomes. METHODS: We retrospectively investigated all infants with perinatal asphyxia at Tokyo Metropolitan Children's Medical Center from January 2014 to December 2019. An abnormal short-term outcome was defined as any one of the following: seizures or abnormal electroencephalography, abnormal brain magnetic resonance imaging obtained within the first 4 weeks of life, and abnormal neurological examination findings at discharge. RESULTS: In total, 110 term infants with perinatal asphyxia during the study period were screened and 61 were diagnosed with mild neonatal encephalopathy. Eleven (18 %) of these infants had an abnormal short-term outcome. The median Thompson score at admission was significantly higher in infants with abnormal short-term outcomes than in those with normal short-term outcomes (5 [interquartile range, 4-5.5] vs. 2 [interquartile range, 1-3], p < 0.01). Receiver operating characteristic curve analysis showed that a cutoff value of 4 had high sensitivity and specificity (90.9 and 83.0 %, respectively) for prediction of an abnormal short-term outcome. CONCLUSIONS: 18 % of infants with mild encephalopathy had an abnormal short-term outcome, such as abnormal brain magnetic resonance imaging findings. The Thompson score at admission may be a useful predictor of an abnormal short-term outcome in infants with mild neonatal encephalopathy.

Tocotrienols reach the brain and play roles in the attenuation of body weight gain and improvement of cognitive function in high-fat diet-treated mice.

Obesity induces severe disorders such as type 2 diabetes and cardiovascular events, and the number of people with obesity is increasing all over the world. Furthermore, it is possible that obesity increases the risk of cognitive dysfunction via the acceleration of oxidative damage. Tocotrienols, which are part of the vitamin E family, have antioxidant and anti-obesity effects. However, the effects of tocotrienols on high-fat diet-treated mice have not been completely elucidated. In this study, we assessed changes in body weight, spatial reference memory acquisition, liver lipid droplet size, blood brain barrier-related protein expressions and antioxidative defense systems in high-fat diet-treated mice in the presence or absence of tocotrienols. The results showed that tocotrienols significantly inhibited body weight gain and lipid droplet synthesis. Although the amount was very small, it was confirmed that tocotrienols surely reached the brain in the perfused brain. Treatment with tocotrienols was tended to improve cognitive function in the control mice. However, tocotrienols did not modulate blood brain barrier-related protein expressions or antioxidative defense systems. These results indicate that treatment with tocotrienols could be effective for the prevention of obesity and cognitive dysfunction. Further extended research is needed to elucidate the relationship between anti-obesity and antioxidant effects of tocotrienols, especially in the brain.

Hemoglobin phase of oxygenation and deoxygenation in early brain development measured using fNIRS.

A crucial issue in neonatal medicine is the impact of preterm birth on the developmental trajectory of the brain. Although a growing number of studies have shown alterations in the structure and function of the brain in preterm-born infants, we propose a method to detect subtle differences in neurovascular and metabolic functions in neonates and infants. Functional near-infrared spectroscopy (fNIRS) was used to obtain time-averaged phase differences between spontaneous low-frequency (less than 0.1 Hz) oscillatory changes in oxygenated hemoglobin (oxy-Hb) and those in deoxygenated hemoglobin (deoxy-Hb). This phase difference was referred to as hemoglobin phase of oxygenation and deoxygenation (hPod) in the cerebral tissue of sleeping neonates and infants. We examined hPod in term, late preterm, and early preterm infants with no evidence of clinical issues and found that all groups of infants showed developmental changes in the values of hPod from an in-phase to an antiphase pattern. Comparison of hPod among the groups revealed that developmental changes in hPod in early preterm infants precede those in late preterm and term infants at term equivalent age but then, progress at a slower pace. This study suggests that hPod measured using fNIRS is sensitive to the developmental stage of the integration of circular, neurovascular, and metabolic functions in the brains of neonates and infants.

Tocotrienols Influence Body Weight Gain and Brain Protein Expression in Long-Term High-Fat Diet-Treated Mice.

Obesity induces serious diseases such as diabetes and cardiovascular disease. It has been reported that obesity increases the risk of cognitive dysfunction. Cognitive dysfunction is a characteristic symptom of Alzheimer's and Parkinson's diseases. However, the detailed mechanisms of obesity-induced cognitive dysfunction have not yet been elucidated. The onset and progression of obesity-induced severe secondary diseases such as diabetes, cardiovascular events, and hypertension are deeply connected to oxidative stress. We hypothesized that obesity induces cognitive dysfunction via acceleration of reactive oxygen species (ROS) production. Vitamin E, which is a lipophilic vitamin, has strong antioxidative effects and consists of two groups: tocopherols and tocotrienols. Recently, it has been demonstrated that tocotrienols have strong neuroprotective and anti-obesity effects. In this study, we fed mice a high-fat diet (HFD) from 9 to 14 months of age and assessed the effect of tocotrienols treatment on body weight, brain oxidation levels, and cognitive function. The results revealed that treatment with tocotrienols inhibited body weight gain; further, tocotrienols reached the brain and attenuated oxidation in HFD-treated mice. These results indicate that tocotrienols have anti-obesity effects and inhibit obesity-induced brain oxidation.

A Pilot Study of Soluble Form of LOX-1 as a Novel Biomarker for Neonatal Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: To evaluate the soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) as a biomarker of severity staging and prognosis in neonatal hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We performed an observational study enrolling 27 infants with HIE and 45 control infants of gestational age ≥36 weeks and birth weight ≥1800 g. The HIE criteria were pH ≤7.0 or a base deficit ≥16 mmol/L within 60 minutes after birth, and a 10-minute Apgar score ≤5 or resuscitation time ≥10 minutes. HIE severity was evaluated using modified Sarnat staging. We measured plasma sLOX-1 level and assessed general and neurologic signs at discharge, and classified infants with no neurosensory impairments as intact survival. RESULTS: sLOX-1 level within 6 hours after birth was correlated with the severity of HIE. sLOX-1 differentiated moderate-severe HIE (median, 1017 pg/mL; IQR, 553-1890 pg/mL) from mild HIE (median, 339 pg/mL; IQR, 288-595 pg/mL; P = .007). The sensitivity and specificity of the differentiation with a cutoff value of ≥550 pg/mL were 80.0% and 83.3%, respectively. In 19 infants with therapeutic hypothermia, a sLOX-1 cutoff value of <1000 pg/mL differentiated intact survival (median, 761 pg/mL; IQR, 533-1610 pg/mL) from death or neurosensory impairment (median, 1947 pg/mL; IQR, 1325-2506 pg/mL; P = .019) with 100% specificity and a positive predictive value. CONCLUSION: sLOX-1 may be a useful biomarker of neonatal HIE for severity staging and outcome prediction. Further investigations will facilitate its clinical use.

Spreading of River Water Guides Migratory Behavior of Homing Chum Salmon Oncorhynchus keta in Otsuchi Bay, a Narrow Inlet with Multiple River Flows.

The Sanriku-ria coast of Japan, a homing area for chum salmon, Oncorhynchus keta, is characterized by a large number of small closed bays into which one or multiple short rivers flow. The present behavioral investigation of chum salmon in this region was designed to gain deeper insight into the migration of chum salmon to their natal rivers. Eighty-three fish caught at the middle part of Otsuchi Bay were tracked using an acoustic transmitter in the narrow inlet into which flow three rivers: the Otsuchi, Koduchi, and Unosumai. The majority of 18 fish that entered the Unosumai River, which flows into the southwest side of the bay, directly approached the river along the southern coast. More than half of fish that entered the Otsuchi and Koduchi Rivers, which flow into the northwest side, also migrated into the inner bay via the southerly route, and then entered these rivers frequently after passing the mouth of the Unosumai River. In the inner bay, the salinity of sea surface water suggested that water from the three rivers circulates in a counterclockwise direction at a depth of less than 1.0 m, flowing eastwardly along the southern coast. The observed migratory paths of homing salmon in Otsuchi Bay thus correspond well with the counterflow of surface river water in the bay. The present results suggest that homing migration of salmon in the Sanriku narrow inlet is guided by natal river flows.

Altered Expression of Astrocyte-Related Receptors and Channels Correlates With Epileptogenesis in Hippocampal Sclerosis.

BACKGROUND: Hippocampal sclerosis (HS) is one of the major causes of intractable epilepsy. Astrogliosis in epileptic brain is a peculiar condition showing epileptogenesis and is thought to be different from the other pathological conditions. The aim of this study is to investigate the altered expression of astrocytic receptors, which contribute to neurotransmission in the synapse, and channels in HS lesions. METHODS: We performed immunohistochemical and immunoblotting analyses of the P2RY1, P2RY2, P2RY4, Kir4.1, Kv4.2, mGluR1, and mGluR5 receptors and channels with the brain samples of 20 HS patients and 4 controls and evaluated the ratio of immunopositive cells and those expression levels. RESULTS: The ratio of each immunopositive cell per glial fibrillary acidic protein-positive astrocytes and the expression levels of all 7 astrocytic receptors and channels in HS lesions were significantly increased. We previously described unique astrogliosis in epileptic lesions similar to what was observed in this study. CONCLUSION: This phenomenon is considered to trigger activation of the related signaling pathways and then contribute to epileptogenesis. Thus, astrocytes in epileptic lesion may show self-hyperexcitability and contribute to epileptogenesis through the endogenous astrocytic receptors and channels. These findings may suggest novel astrocytic receptor-related targets for the pharmacological treatment of epilepsy.

δ-Tocopherol promotes thermogenic gene expression via PGC-1α upregulation in 3T3-L1 cells.

Activation of thermogenic adipocytes (brown and beige) has been considered an attractive target for weight loss and treatment of metabolic disease. Peroxisome proliferator-activated receptor γ co-activator-1 α (PGC1-α) is a master regulator of thermogenic gene expression in thermogenic adipocytes. We previously reported that α-tocopherol upregulated PGC-1α gene expression and promoted thermogenic adipocyte differentiation in mammalian adipocytes. In this study, we investigated the effects of the vitamin E analogs (α-, γ- and δ-tocopherol) on PGC-1α and uncoupling protein 1 (UCP1) gene expression in 3T3-L1 cells. The expression of PGC-1α and UCP1 increased significantly with the addition of δ-tocopherol. In δ-tocopherol-treated cells, nuclear translocation of PGC-1α increased, as did p38 mitogen-activated protein kinase (MAPK) expression and phosphorylation. Our results suggest that p38 MAPK activation by δ-tocopherol contributes to PGC-1α activation and UCP1 induction.

Excessive Vitamin E Intake Does Not Cause Bone Loss in Male or Ovariectomized Female Mice Fed Normal or High-Fat Diets.

Background: Animal studies on the effects of vitamin E on bone health have yielded conflicting and inconclusive results, and to our knowledge, no studies have addressed the effect of vitamin E on bone in animals consuming a high-fat diet (HFD).Objective: This study aimed to evaluate the effect of excessive vitamin E on bone metabolism in normal male mice and ovariectomized female mice fed a normal diet (ND) or HFD.Methods: In the first 2 experiments, 7-wk-old male mice were fed an ND (16% energy from fat) containing 75 (control), 0 (vitamin E-free), or 1000 (high vitamin E) mg vitamin E/kg (experiment 1) or an HFD (46% energy from fat) containing 0, 200, 500, or 1000 mg vitamin E/kg (experiment 2) for 18 wk. In the third experiment, 7-wk-old sham-operated or ovariectomized female mice were fed the ND (75 mg vitamin E/kg) or HFD containing 0 or 1000 mg vitamin E/kg for 8 wk. At the end of the feeding period, blood and femurs were collected to measure bone turnover markers and analyze histology and microcomputed tomography.Results: In experiments 1 and 2, vitamin E intake had no effect on plasma alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) activity, or bone formation, resorption, or volume in femurs in mice fed the ND or HFDs. In experiment 3, bone volume was significantly reduced (85%) in ovariectomized mice compared with that in sham-operated mice (P < 0.05), but it did not differ among mice fed the 3 diets. Plasma ALP and TRAP activities and bone formation and resorption in femur were similar among ovariectomized mice fed the HFD containing 0 or 1000 mg vitamin E/kg.Conclusions: The results suggest that excess vitamin E intake does not cause bone loss in normal male mice or in ovariectomized or sham-operated female mice, regardless of dietary fat content.

Cytokine Profiles in Pericardial Effusion in a Down Syndrome Infant with Transient Abnormal Myelopoiesis.

Infants with Down Syndrome (DS) are at risk of developing a transient abnormal myelopoiesis (TAM). TAM is characterised by increased circulating blast cells but usually self-limiting. DS patients with TAM sometimes show fetal hydrops and effusion in body cavities, but the mechanism remains unclear. We report here a case of infant with DS who had pericardial effusion, TAM, and eosinophilia. In her pericardial effusion, white blood cell count was 6.0 × 103/µL, 41% of which were eosinophils. After administration of prednisolone, pericardial effusion gradually decreased, and TAM and eosinophilia improved. In order to elucidate the immunological mechanism, we measured the levels of 17 cytokines in her pericardial effusion fluid and serum. In her pericardial fluid, there were high levels of 12 cytokines, and they were higher than those in her serum. In particular, IL-6 (44,573 pg/mL), IL-8 (4,865 pg/mL), and IL-13 (579.41 pg/mL) were at extremely high levels in her pericardial fluid. After administration of prednisolone, the levels of 8 of the 12 elevated cytokines in her pericardial fluid decreased and all of the elevated cytokines decreased in her serum. Corticosteroids can be effective to reduce cytokine levels and the amount of effusion in patients with DS. It is presumed that effusion seen in DS with TAM could be related to an abnormal production of cytokines at the effusion site.

Oleuropein improves insulin resistance in skeletal muscle by promoting the translocation of GLUT4.

As the beneficial effects of the Mediterranean diet on human health are well established, the phenolic compounds in olive oil have been gaining interest. Oleuropein, a major phenolic compound in olives, is known to reduce the blood glucose levels in alloxan-induced diabetic rats and rabbits, however, its effect on type 2 diabetes caused by obesity is not clear. The purpose of this study is clarifying the effect of oleuropein on the glucose tolerance in skeletal muscle under the condition of lipotoxicity caused by type 2 diabetes. Oleuropein enhanced glucose uptake in C2C12 cells without insulin. Translocation of glucose transporter 4 (GLUT4) into the cell membrane was promoted by activation of adenosine monophosphate-activated protein kinase (AMPK) but not protein kinase B (Akt). Physiological concentration of oleuropein (10 µM) was sufficient to express beneficial effects on C2C12 cells. Oleuropein prevented palmitic acid-induced myocellular insulin resistance. Furthermore, in gastrocnemius muscles of mice fed a high fat diet, oleuropein also induced the GLUT4 localization into cell membrane. These results suggest the possibility of oleuropein to be effective for type 2 diabetes by reducing insulin resistance in skeletal muscles.

Association between the rs1465040 single-nucleotide polymorphism close to the transient receptor potential subfamily C member 3 (TRPC3) gene and postoperative analgesic requirements.

An association between postoperative analgesic requirements in subjects who underwent orthognathic surgery and the rs1465040 single-nucleotide polymorphism close to the transient receptor potential subfamily C member 3 (TRPC3) gene was suggested by our previous genome-wide association study. To verify this association, we analyzed the association between the rs1465040 SNP and analgesic requirements, including opioid requirements, after open abdominal surgery. The association between the rs1465040 SNP and postoperative analgesic requirements was confirmed in the open abdominal surgery group (P = 0.036), suggesting that the TRPC3 SNP may contribute to predicting postoperative analgesic requirements.