Effects of repeated oral intake of a quercetin-containing supplement on allergic reaction: a randomized, placebo-controlled, double-blind parallel-group study.

OBJECTIVE: The present study aimed to investigate the effects of a 4-week repeated oral intake of a quercetin-containing supplement on allergen-induced reactions and relative subjective symptoms in Japanese adults who complained of discomfort in the eyes and nose. SUBJECTS AND METHODS: A randomized, placebo-controlled, double-blind parallel-group study was conducted on 66 subjects (22-78 years old) with allergic symptoms of pollinosis. The subjects were given the test product (200 mg quercetin) or the control product (vehicle) daily for 4 weeks. The Japanese Rhino-conjunctivitis Quality of Life Questionnaire (JRQLQ) scores and other tests were examined in each subject before and after starting the product intake. A new food-grade bioavailable formulation of quercetin, Quercetin phytosome®, was used. RESULTS: At 1:4 weeks after the start of the supplement intake, several scores of JRQLQ, including allergic symptoms, such as eye itching, sneezing, nasal discharge, and sleep disorder, were significantly improved in the quercetin-containing supplement group compared with the placebo group. Furthermore, the quality of life of these subjects significantly improved based on the original questionnaire and visual analog scale. Minor notable adverse effects were noted throughout the study. CONCLUSIONS: The results indicated that oral intake of quercetin-containing supplements might effectively reduce some allergy symptoms derived from pollinosis.

Effects of 5-aminolevulinic acid supplementation on milk production, iron status, and immune response of dairy cows.

The objective of this study was to investigate the effect of 5-aminolevulinic acid (5-ALA) as a dietary supplement on milk yield and composition as well as iron status and immune response in lactating dairy cows. In this study 13 lactating Holstein cows were randomly assigned to either a control group or a treatment group supplemented with 10 mg of 5-ALA per kilogram of dry matter. During feeding, 5-ALA was mixed with a small amount of the total mixed ration and top-dressed. The experiments followed a crossover design with 2 periods. Each period consisted of an adaptation period of 12 d and a test period of 2 d. Dairy cows fed the diet supplemented with 5-ALA exhibited increased counts of white blood cells and granulocytes compared with the control group. The rate of phagocytosis and mitogen-induced proliferation of peripheral blood mononuclear cells in cows fed 5-ALA were higher than in cows fed a basal diet. However, 5-ALA did not affect iron status or plasma biochemical composition. Supplementation with 5-ALA improved milk protein and milk casein contents; however, it had no effect on milk production, milk fat, lactose, total solids, or solids-not-fat, compared with the control. We conclude that dietary supplementation of 5-ALA to lactating dairy cows may have a positive effect on milk protein synthesis and the immune response.

Stereoselective Aromatic Ring Hydrogenation over Supported Rhodium Catalysts in Supercritical Carbon Dioxide Solvent.

The combination of supported rhodium metal catalysts and supercritical carbon dioxide solvent was effective for the stereoselective ring hydrogenations of aromatic compounds at low temperature. Higher solubility of hydrogen in supercritical carbon dioxide provides higher concentration of hydrogen on the rhodium surface, but lower that of the intermediate on rhodium surface, which suppresses the flipping of surface intermediate, leading to higher catalyst activities and cis selectivities to the corresponding ring-hydrogenated products as compared with those in organic solvents.

Sexuality education in Japanese medical schools.

The present study aimed to investigate current sexuality education in Japanese medical schools and the impact of position title in the Japanese Society for Sexual Medicine (JSSM). Questionnaires were mailed to urology departments in all Japanese medical schools. The responses were evaluated according to four factors: the number of lecture components, curriculum hours, degree of satisfaction with the components and degree of satisfaction with the curriculum hours. We also investigated differences in these four factors among three groups: Directors, Council members and non-members of the JSSM. The medians of curriculum hours and the number of the lecture components were 90.0 min and 7.0, respectively. The curriculum hours of the Directors (140.0 min) were significantly longer than those of the non-members (90.0 min; P<0.05). The number of lecture components taught by Directors (9.5) was significantly higher than that of the Council (4.0; P<0.01) and non-members (7.0; P<0.05). More than half of the faculties were not satisfied with the lecture components and curriculum hours. This is the first study on sexuality education in Japanese medical schools. It showed the inadequacy of both curriculum hours and lecture components, and that the position title of department chair affects sexuality education in medical schools.

Type-1 polarised dendritic cells are a potent immunogen against Mycobacterium tuberculosis.

OBJECTIVE: Application of immunotherapy using dendritic cells (DCs) is considered an effective treatment strategy against persistent Mycobacterium tuberculosis infection. With the goal of developing improved therapeutic vaccination strategies for patients with tuberculosis (TB), we tested the ability of ex vivo-generated DCs to induce an effective TB antigen-specific type-1 immune response. METHODS: Monocyte-derived DCs from TB patients were induced to mature using a 'standard' cytokine cocktail (interleukin [IL] 1ß, tumour necrosis factor alpha [TNF-α], IL-6 and prostaglandin E2) or a type 1-polarised DC (DC1) cocktail (IL-1ß, TNF-α, interferon [IFN] α, IFN-γ and polyinosinic:polycytidylic acid), and were loaded with the established TB antigen 6-kDa early secretory antigenic target protein (ESAT-6). RESULTS: Although DC1s from TB patients expressed the same levels of multiple co-stimulatory molecules (CD83, CD86, CD80 and CD40) as the standard DCs (sDCs), DC1s secreted substantially higher levels of IL-12p70. Furthermore, when DCs pulsed with or without ESAT-6 were cultured with lymphocytes from the same patients, DC1s induced much higher numbers of ESAT-6-specific IFN-γ-producing T-cells than sDCs, as manifested by their superior induction of natural killer cell activation and antigen-independent suppression of regulatory T-cells. CONCLUSION: TB antigen-loaded DC1s are potent inducers of antigen-specific T-cells, which could be used to develop improved immunotherapies of TB.

Overexpression of bone morphogenetic protein-3b (BMP-3b) in adipose tissues protects against high-fat diet-induced obesity.

BACKGROUND: Bone morphogenetic protein-3b (BMP-3b) is a member of the transforming growth factor-ß superfamily and has several activities that differ from those of other BMPs. We previously found that BMP-3b is highly expressed in adipocytes, its level is increased during obesity, and it inhibits adipogenesis by suppressing peroxisome proliferator-activated receptor γ (PPARγ) in vitro. However, the function of BMP-3b in adipose tissues in vivo remains unknown. METHODS: To determine the role of BMP-3b overexpression in adipose tissues in vivo, we generated transgenic mice (BMP-3b Tg) by using a conditional overexpression approach in fatty acid-binding protein 4-expressing adipocytes. We examined BMP-3b Tg mice fed a high-fat diet to elucidate the effects of BMP-3b on obesity. Adipocyte function was evaluated as expression of adipogenic and lipogenic markers in adipose tissue. We also performed glucose and insulin tolerance tests (GTT and ITT, respectively), and biochemical analysis of serum and measured energy expenditure by indirect calorimetry. RESULTS: BMP-3b Tg mice fed a high-fat diet showed decreases in weight gain, fat-pad mass and adipocyte area, compared with wild-type mice. The adipose tissues of BMP-3b Tg mice showed downregulated expression of PPARγ and its target gene encoding fatty acid translocase/CD36. In addition, BMP-3b Tg mice had decreased blood glucose levels on GTT and ITT, and their serum leptin levels were decreased and adiponectin concentrations were increased. These changes in BMP-3b Tg mice were accompanied by increased energy expenditure, indicated as increased locomotor activity and oxygen consumption. CONCLUSIONS: These results provide in vivo evidence that BMP-3b regulates adipocyte function to cause an anti-obesity effect.

Sympathetic hyper-excitation in obesity and pulmonary hypertension: physiological relevance to the 'obesity paradox'.

BACKGROUND: Within the lung, sympathetic nerve activity (SNA) has an important role in facilitating pulmonary vasodilation. As SNA is elevated in obesity, we aimed to assess the impact of sympathetic hyper-excitation on pulmonary vascular homeostasis in obesity, and its potential role in ameliorating the severity of pulmonary hypertension (PH); the well-documented 'obesity paradox' phenomenon. METHODS: Zucker obese and lean rats were exposed to normoxia or chronic hypoxia (CH-10% O2) for 2 weeks. Subsequently, pulmonary SNA (pSNA) was recorded (electrophysiology), or the pulmonary microcirculation was visualized using Synchrotron microangiography. Acute hypoxic pulmonary vasoconstriction (HPV) was assessed before and after blockade of ß1-adrenergic receptors (ARs) (atenolol, 3 mg kg(-1)) and ß1+ß2-adrenergic (propranolol, 2 mg kg(-1)). RESULTS: pSNA of normoxic obese rats was higher than lean counterparts (2.4 and 0.5 µV s, respectively). SNA was enhanced following the development of PH in lean rats, but more so in obese rats (1.7 and 6.8 µV s, respectively). The magnitude of HPV was similar for all groups (for example, ~20% constriction of the 200-300 µm vessels). Although ß-blockade did not modify HPV in lean rats, it significantly augmented the HPV in normoxic obese rats (ß1 and ß2 blockade), and more so in obese rats with PH (ß2-blockade alone). Western blots showed, while the expression of pulmonary ß1-ARs was similar for all rats, the expression of ß2-ARs was downregulated in obesity and PH. CONCLUSIONS: This study suggests that sympathetic hyper-excitation in obesity may have an important role in constraining the severity of PH and, thus, contribute in part to the 'obesity paradox' in PH.

Large anisotropic deformation of skyrmions in strained crystal.

Mechanical control of magnetism is an important and promising approach in spintronics. To date, strain control has mostly been demonstrated in ferromagnetic structures by exploiting a change in magnetocrystalline anisotropy. It would be desirable to achieve large strain effects on magnetic nanostructures. Here, using in situ Lorentz transmission electron microscopy, we demonstrate that anisotropic strain as small as 0.3% in a chiral magnet of FeGe induces very large deformations in magnetic skyrmions, as well as distortions of the skyrmion crystal lattice on the order of 20%. Skyrmions are stabilized by the Dzyaloshinskii-Moriya interaction, originating from a chiral crystal structure. Our results show that the change in the modulation of the strength of this interaction is amplified by two orders of magnitude with respect to changes in the crystal lattice due to an applied strain. Our findings may provide a mechanism to achieve strain control of topological magnetic structures based on the Dzyaloshinskii-Moriya interaction.

Emerging applications of single-cell diagnostics.

The performance of DNA sequencers (next generation sequencing) is rapidly enhanced these days, being used for genetic diagnostics. Although many phenomena could be elucidated with such massive genome data, it is still a big challenge to obtain comprehensive understanding of diseases and the relevant biology at the cellular level. In general terms, the data obtained to date are averages of ensembles of cells, but it is not certain whether the same features are the same inside an individual cell. Accordingly, important information may be masked by the averaging process. As the technologies for analyzing bio-molecular components in single cells are being developed, single cell analysis seems promising to address the current limitations due to averaging problems. Although the technologies for single cell analysis are still at the infant stage, the single cell approach has the potential to improve the accuracy of diagnosis based on knowledge of intra- and inter-cellular networks. In this review several technologies and applications (especially medical applications) of genome and transcriptome analysis or single cells are described.

Contribution of calpain to myoglobin efflux from cardiomyocytes during ischaemia and after reperfusion in anaesthetized rats.

AIM: Calpain activation has a putative role in ischaemia-reperfusion injury of cardiomyocytes. This study clarified the in vivo contribution of calpain to disruption of cardiomyocyte sarcolemma during ischaemia and after reperfusion in anaesthetized rats. METHODS: Using a microdialysis technique in the hearts of anaesthetized rats, we investigated the effects of the calpain inhibitors on myocardial interstitial myoglobin level in the ischaemic region during coronary occlusion and after reperfusion. The calpain inhibitors were administered locally via a dialysis probe. Two durations of coronary occlusion were tested. RESULTS: Thirty-minute coronary occlusion: dialysate myoglobin concentration increased markedly from 385 ± 46 ng mL(-1) at baseline to 3701 ± 527 ng mL(-1) at 20-30 min of occlusion. After reperfusion, dialysate myoglobin concentration further increased, reaching a peak (12 296 ± 1564 ng mL(-1) ) at 10-20 min post-reperfusion and then declined gradually. The calpain inhibitors, MDL-28170 and SNJ-1945 did not change dialysate myoglobin concentration during occlusion but attenuated the increase after reperfusion to 6826 ± 1227 and 8130 ± 938 ng mL(-1) at 10-20 min post-reperfusion (P < 0.05), respectively. Ninety-minute coronary occlusion: dialysate myoglobin concentration increased from 516 ± 33 ng mL(-1) at baseline to 5463 ± 387 ng mL(-1) at 80-90 min after occlusion. After reperfusion, there was no significant increase in dialysate myoglobin concentration. MDL-28170 did not affect dialysate myoglobin concentration during occlusion or after reperfusion. CONCLUSION: Calpain contributes to sarcolemmal disruption immediately after reperfusion following 30-min coronary occlusion, but has little effects during ischaemia and after reperfusion in 90-min coronary occlusion.

Sympathetic afferent stimulation inhibits central vagal activation induced by intravenous medetomidine in rats.

AIM: To examine whether sympathetic afferent stimulation (SAS) inhibits central vagal activation induced by α2 -adrenergic stimulation. METHODS: In anaesthetized Wistar-Kyoto rats, a cardiac microdialysis technique was applied to the left ventricle, and the effect of α2 -adrenergic stimulation by medetomidine on myocardial interstitial acetylcholine (ACh) levels was examined in the absence (n = 6) or the presence (n = 6) of SAS delivered from the left stellate ganglion. The effect of electrical vagal efferent stimulation on myocardial interstitial ACh release was also examined in the absence or the presence of SAS (n = 6). RESULTS: Intravenous medetomidine (0.1 mg kg(-1) ) significantly increased myocardial interstitial ACh levels in the absence of SAS (from 1.95 ± 0.79 to 3.36 ± 1.61 nM, P < 0.05), but not in the presence of SAS (from 1.67 ± 0.67 to 2.01 ± 0.78 nM). In contrast, electrical vagal nerve stimulation increased myocardial interstitial ACh level to the same degree regardless of SAS (from 1.66 ± 0.16 to 3.93 ± 0.72 nM without SAS vs. 4.05 ± 0.89 nM with SAS). CONCLUSION: Sympathetic afferent stimulation inhibited medetomidine-induced ACh release, but not electrical stimulation-induced ACh release, suggesting that SAS inhibited medetomidine-induced vagal activation via central mechanisms. While central vagal activation by α2 -adrenergic agonists could be an alternative to electrical vagal activation, blocking sympathetic afferent input may be important to increase the efficacy of α2 -adrenergic agonists in enhancing vagal nerve activity.

Mixture design applied for the study of the tartaric acid effect on starch/polyester films.

Tartaric acid (TA), a dicarboxylic acid, can act as a compatibiliser in starch/polyester blends. A mixture design was proposed to evaluate the effect of TA on the properties of starch/poly (butylene adipate co-terephthalate) (PBAT) blown films plasticised with glycerol. The interaction between the starch/PBAT and the TA has a positive effect on the tensile strength and puncture force. Additionally, greater proportions of TA increased Young's modulus. The starch+PBAT/TA and Gly/TA interactions contributed to a reduction in the water vapour permeability of the films. The inclusion of TA did not change the crystallinity of the samples. Formulations with intermediate proportions of TA (0.8 g/100 g) were shown to produce the best compatibilising effect. This was observed by DMA analysis as a consequence of the perfect equilibrium between the contributions of TA as a compatibiliser and in the acidolysis of starch, resulting in films with a tensile strength of 5.93 MPa, a possible alternative to non-biodegradable packaging.

Development of biodegradable flexible films of starch and poly(lactic acid) plasticized with adipate or citrate esters.

Biodegradable films were produced from blends contained a high amount of thermoplastic starch (TPS) and poly(lactic acid) (PLA) plasticized with different adipate or citrate esters. It was not possible to obtain pellets for the production of films using only glycerol as a plasticizer. The plasticization of the PLA with the esters and mixture stages added through extrusion was critical to achieve a blend capable of producing films by blow extrusion. Adipate esters were the most effective plasticizers because they interacted best with the PLA and yielded films with appropriate mechanical properties.

Contribution of serotonin uptake and degradation to myocardial interstitial serotonin levels during ischaemia-reperfusion in rabbits.

AIM: Although deleterious effects of serotonin (5-HT) have been demonstrated during myocardial ischaemia-reperfusion, little information is available on myocardial interstitial 5-HT kinetics. This study evaluated the contribution of 5-HT reuptake and degradation to myocardial interstitial 5-HT levels during ischaemia-reperfusion. METHODS: Using microdialysis technique in anaesthetized rabbits, we monitored myocardial interstitial 5-HT levels in the ischaemic region during ischaemia (30 min) followed by reperfusion (60 min) and investigated the effects of local infusion of fluoxetine, a 5-HT uptake inhibitor, and/or pargyline, a monoamine oxidase inhibitor. RESULTS: In vehicle control, dialysate 5-HT concentration increased gradually from 16 ± 3 at baseline to 85 ± 18 nM during 20-30 min of ischaemia. Dialysate 5-HT concentration further increased to 236 ± 47 nM at 0-10 min of reperfusion and then began to decline. Averaged 5-HT concentration was 61 ± 11 during ischaemia and 113 ± 13 nM during reperfusion. Fluoxetine elevated dialysate 5-HT level at baseline and at 10-30 min of reperfusion; it increased averaged dialysate 5-HT concentration by approx. 304% during reperfusion compared to control. Pargyline elevated averaged dialysate 5-HT concentration during ischaemia by approx. 243% and that during reperfusion by approx. 250% compared to control. The changes in dialysate 5-HT concentration by fluoxetine + pargyline were similar to those of fluoxetine alone. CONCLUSION: The 5-HT reuptake function plays an important role in the clearance of myocardial interstitial 5-HT during reperfusion. When 5-HT reuptake function is intact, degradation of 5-HT by monoamine oxidase contributes to reduce myocardial interstitial 5-HT level throughout ischaemia-reperfusion.

Assessment of serum KL-6 as a prognostic marker in pulmonary tuberculosis patients.

Although serum Krebs von den Lungen-6 (KL-6) levels are reported to increase in pulmonary tuberculosis (PTB) patients according to disease activity, the relationship between serum KL-6 levels and prognosis remains unclear. In this study, we prospectively examined serum KL-6 levels in 188 PTB patients and assessed 60-day mortality. Univariate and multivariate logistic regression analysis demonstrated that serum KL-6 levels were not significantly associated with prognosis. For receiver operating characteristic analysis, the area under the curve had low accuracy for predicting mortality. These findings indicate that serum KL-6 levels do not perform adequately for use as a prognostic marker in patients with PTB.

Drug lymphocyte stimulation test is not useful for side effects of anti-tuberculosis drugs despite its timing.

BACKGROUND: Some patients have adverse reactions to anti-tuberculosis drugs. We have reported that drug lymphocyte stimulation testing (DLST), which we performed at Week 1 of adverse reactions, provides little useful information (14.9% sensitivity). However, it remains unclear whether the time of performance of the DLST contributed to these results. METHODS: Patients with adverse reactions to anti-tuberculosis drugs, including rash, hepatitis and fever, underwent DLST in the first week of the adverse reaction and were then randomly assigned to Group A (among whom a second DLST was performed 2 months after the reaction) or Group B (among whom a second DLST was performed >12 months after the reaction). We compared Group A with Group B to determine the optimal timing for the performance of DLST. The causative drug was identified by an oral drug provocation test. RESULTS: Consistent with the previous study, the sensitivity of DLST performed in the first week was low (14.3%). For DLST performed later, the sensitivity in Group A and Group B was respectively 5.0% and 6.7%. CONCLUSIONS: DLST is not useful for determining the causative drug in patients with rash, hepatitis or fever reactions to anti-tuberculosis drugs, regardless of when it is performed.

Central vagal activation by alpha(2) -adrenergic stimulation is impaired in spontaneously hypertensive rats.

AIM: To elucidate the abnormality of vagal control in spontaneously hypertensive rats (SHR) by measuring left ventricular myocardial interstitial acetylcholine (ACh) release in response to α(2) -adrenergic stimulation as an index of in vivo vagal nerve activity. METHODS: A cardiac microdialysis technique was applied to the rat left ventricle in vivo, and the effect of α(2) -adrenergic stimulation by medetomidine or electrical vagal nerve stimulation on myocardial interstitial ACh levels was examined in normotensive Wistar-Kyoto rats (WKY) and SHR under anaesthetized conditions. RESULTS: Intravenous medetomidine (0.1 mg kg(-1) ) significantly increased the ACh levels in WKY (from 2.4 ± 0.6 to 4.2 ± 1.3 nmol L(-1) , P < 0.05, n = 7) but not in SHR (from 2.5 ± 0.7 to 2.7 ± 0.7 nmol L(-1) , n = 7). In contrast, electrical vagal nerve stimulation increased the ACh levels in both WKY (from 1.0 ± 0.4 to 2.9 ± 0.9 nmol L(-1) , P < 0.001, n = 6) and SHR (from 0.9 ± 0.2 to 2.2 ± 0.4 nmol L(-1) , P < 0.001, n = 6). Intravenous administration of medetomidine (0.1 mg kg(-1) ) did not affect the vagal nerve stimulation-induced ACh release in either WKY or SHR. CONCLUSION: Medetomidine-induced central vagal activation was impaired in SHR, whereas peripheral vagal control of ACh release was preserved. In addition to abnormal sympathetic control, vagal control by the central nervous system may be impaired in SHR.

Extraordinary carrier multiplication gated by a picosecond electric field pulse.

The study of carrier multiplication has become an essential part of many-body physics and materials science as this multiplication directly affects nonlinear transport phenomena, and has a key role in designing efficient solar cells and electroluminescent emitters and highly sensitive photon detectors. Here we show that a 1-MVcm(-1) electric field of a terahertz pulse, unlike a DC bias, can generate a substantial number of electron-hole pairs, forming excitons that emit near-infrared luminescence. The bright luminescence associated with carrier multiplication suggests that carriers coherently driven by a strong electric field can efficiently gain enough kinetic energy to induce a series of impact ionizations that can increase the number of carriers by about three orders of magnitude on the picosecond time scale.

Examination of gas desorption by B4C resin for use in neutron scattering experiment.

Gas desorption rates for several types of B(4)C resins were investigated using a throughput method. The investigation was particularly focused on determining the out gas composition, effects of dry air, grain size (density) effects on the gas desorption rates. It is found that water is the main component of out gas and that dry air can effectively reduce gas desorption.