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Group-III nitride semiconductors have attracted much attention for application in optoelectronic devices such as light emitting diodes and laser diodes. In particular, highly efficient light emitting devices using self-assembled quantum dots have been pained much attention. For InN and InGaN grown on GaN(0001) substrate, it has been reported that three-dimensional (3D) islands are formed after two-dimensional (2D) wetting layers, resulting in Stranski-Krastanow (SK) growth mode [1,2]. Moreover it has been reported that the growth modes of InN on GaN(0001) substrate during molecular beam epitaxy depend on growth conditions such as V/III ratio and substrate temperature[3]: N-rich condition favors 3D growth, whereas In-rich condition leads to 2D growth. However, it is still unclear what is the crucial factor for determining the growth modes of InN and InGaN depending on the growth condition. In this study, the growth mode of InN and InGaN thin films on GaN(0001) substrate are investigated using the macroscopic theory using free energy formula [4] with the aid of empirical potential calculations [5] as well as ab initio calculations [6]. Effects of pyramids island with {1-103} facets and misfit dislocation (MD) formation are taken into account for the evaluation of free energies of InN and InGaN thin films on GaN(0001) substrate. The calculations of cohesive energy difference ΔE as a function of InN film thickness for 2D coherent growth (2D-coherent) and 2D growth with MD (2D-MD) using empirical interatomic potentials reveals that 2D-MD is more stable than 2D-coherent for InN films beyond 0.7 monolayers (ML). On the basis of these results, the MD formation energy Ed and the effective elastic constant M are estimated to be 1.31 eV/Å and 5.60×1011 N/m2. The calculated result of Ed reasonably agrees with previous calculations for dislocation core energy in bulk InN (1.51 eV/Å) [7]. Moreover, the analysis of free energies using the value of Ed and M and surface energies obtained by ab initio calculations (~ 0.074 eV/ Å2) demonstrate that the critical thickness between growth 2D-coherent and 2D-MD under In-rich conditions is 0.45 ML. The calculated results are qualitatively consistent with the experimental results [3]. The calculated phase diagram for growth mode as functions of surface energy of (0001) and surface energy difference between (0001) and (1-103) planes suggest that growth mode boundary between 2D-MD and 3D coherent growth with hexagonal pyramid island formation (3D-coherent) strongly depends on the surface energy difference between (0001) and (1-103) planes. 2D-MD is favorable when the surface energy of InN(1-103) is larger than that of InN(0001), whereas 3D-coherent is favorable when the surface energies of InN(1-103) is smaller than InN(0001). These results imply that the relative stability between (0001) and (1-103) planes depending on the growth condition is decisive for the growth modes of InN on GaN(0001) substrate. [1] S. Ploch et al., Phys. Status. Solidi C 6, 574 (2009). [2] C. Adelmann et al., Appl. Phys. Lett. 76, 1570 (2000). [3] Y. F. Ng et al., Appl. Phys. Lett. 81, 3960 (2002). [4] K. Shiraishi et al., J. Cryst. Growth 237, 206 (2002). [5] K. E. Khor, and S. Das Sarma, Phys. Rev. B 38, 3318 (1988). [6] T. Akiyama et al., Phys. Status Solidi B 255, 1700329 (2018). [7] T. Ito et al., J. Cryst. Growth 298, 186 (2007). Figure: Phase diagrams of growth modes boundary between 2D-MD and 3D-coherent of InN on GaN(0001) substrate as functions of surface energy of (0001) and surface energy difference between (0001) and (1-103) planes. Figure 1

Various lactobacilli have been suggested to exert beneficial effects in humans. In this study, we examined the effects of intraduodenal (ID) administration of heat-killed Lactobacillus delbrueckii LAB4 (LAB4) on activities of efferent sympathetic nerves innervating the liver and pancreas. Consequently, it was observed that ID administration of LAB4 significantly reduced either the efferent hepatic sympathetic nerve activity (hepatic-SNA) or pancreatic sympathetic nerve activity (pancreatic-SNA) in urethane-anaesthetised rats. Moreover, the effect of acute and chronic administration of LAB4 (1×109 cells/ml) on hyperglycaemia induced by intracranial injection of 2-deoxy-D-glucose (2DG) were examined in conscious rats. We found that LAB4 significantly inhibited 2DG-induced hyperglycaemia. These findings suggest that ID administration of heat-killed LAB4 might lower plasma glucose level via changes in the autonomic nervous system in rats.

We previously showed that mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP) exhibit attenuated light-induced phase shift. To explore the underlying mechanisms, we performed gene expression analysis of laser capture microdissected suprachiasmatic nuclei (SCNs) and found that lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is involved in the impaired response to light stimulation in the late subjective night in PACAP-deficient mice. L-PGDS-deficient mice also showed impaired light-induced phase advance, but normal phase delay and nonvisual light responses. Then, we examined the receptors involved in the response and observed that mice deficient for type 2 PGD2 receptor DP2/CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cells) show impaired light-induced phase advance. Concordant results were observed using the selective DP2/CRTH2 antagonist CAY10471. These results indicate that L-PGDS is involved in a mechanism of light-induced phase advance via DP2/CRTH2 signaling., Kawaguchi et al. show that mice deficient in lipocalin-type prostaglandin (PG) D synthase (L-PGDS) exhibit impaired light-induced phase advance, but normal phase delay and nonvisual light responses. This study suggests the role of L-PGDS for the light-induced phase advance possibly via a chemoattractant receptor DP2/CRTH2.

The autonomic nervous system (ANS) is implicated in maintaining homeostasis of the internal environment in mammals. Therefore, changes occurring in the ANS can cause alterations of physiological phenomena. Ethyl hexanoate (EH) is known as the aroma component of apples. To study the action of ethyl hexanoate on physiological phenomena, we examined the effect of an intragastric (IG) injection of 1 mL/kg body weight of 0.1 ppm EH solution on sympathetic nerve activity innervating the brown adipose tissue (BAT) and white adipose tissue (WAT) in anesthetized rats. Consequently, IG administration of EH increased activity of the sympathetic nerves innervating both the BAT and WAT. In addition, the effects of the IG injection on body temperature above the interscapular BAT and plasma free fatty acid (FFA) concentration were also examined in conscious rats. In this attempt IG injection of EH elevated both the body temperature and plasma FFA levels. Furthermore, subdiaphragmatic vagotomy eliminated the effects of EH on sympathetic nerves innervating BAT and WAT. These findings suggest that EH causes excitations of sympathetic nerves innervating BAT and WAT, and enhances thermogenesis and lipolysis via the afferent vagus nerve. Thus, these present findings also suggest the possibility that EH might have anti-obesity effects.

Beneficial effects of sesame lignans, especially antioxidative effects, have been widely reported; however, its potential effects on autonomic nerves have not yet been investigated. Therefore, the current study aimed to investigate the effect of sesame lignans on the autonomic nervous system. The sympathetic nerve activity in rat skeletal muscle was measured using electrophysiological approaches, with blood flow determined using the laser Doppler method. Sesame lignans were administered intragastrically at 2 and 20 mg/kg, and after 60 min, the sympathetic nerve activity was observed to increase by 45.2 % and 66.1 %, respectively. A significant increase in blood flow (39.6 %) was also observed for the 20-mg/kg dose when measured at 55 min after administration. These sympathomimetic effects were completely prevented by subdiaphragmatic vagotomy, and the increase in blood flow was eliminated in the presence of the β2-adrenergic receptor inhibitor butoxamine. Thus, it is proposed that sesame lignans can increase the blood flow of skeletal muscle, possibly by exciting sympathetic nerve activity through the afferent vagal nerve.

Background Kinematically aligned total knee arthroplasty (KA-TKA), in which femoral component is placed 3–5° of internal rotation relative to mechanically aligned (MA)-TKA, may have a potential risk of patellofemoral malalignment. This study aimed to assess patellofemoral alignment and compare the data between KA-TKA and MA-TKA, and the relationship with patellofemoral radiographic parameters and patient reported outcomes. Methods Among patients who underwent TKA in 2015 and 2016 in our institute, 28 KA-TKAs with a metal-backed patellar component were retrospectively assessed for patellofemoral alignment, and 28 MA-TKAs with a metal-backed patellar component served as controls. A year postoperatively, patellar tilt and shift at 30°, 60°, and 90° knee flexion were measured on Merchant views and compared between the two TKAs. Implant positioning in each patient was assessed based on preoperative CT images and correlations of femoral component positioning with patellar tilt/shift were assessed. Results Patellar shift at 30° flexion was significantly greater in KA-TKA than in MA-TKA (p = 0.04), whereas patellar tilt angle was comparable between the two TKAs. No statistical correlation was evident between femoral component positioning and patellar shift/tilt, regardless of knee flexion angle in the two TKAs. Knee Society Score 2011 at 1 year follow-up was comparable in all subcategories between the two TKAs. Conclusion Radiographic analysis of KA-TKA revealed lateral shift of the patella at 30° knee flexion at 1 year postoperatively, however patients with patellar shift were asymptomatic. Further long-term observation is required to examine the impact of KA-TKA on the patellofemoral complication.

We present systematic theoretical investigations for the adsorption behavior of Al and N adatoms on vicinal AlN(0001) surface under metal–organic vapor phase epitaxy (MOVPE) growth condition by means of ab initio electronic structure calculations. Prior to the investigation adatoms, we reveal the growth condition dependence of stable structure for bilayer step edges during the MOVPE. The vicinal surface with hydrogen terminated N atom and NH2 (N-H + Al-NH2) is found to be the most stable under N-rich limit whereas the surface with hydrogen terminated N atom (N-H + Al-H) with NH2 at the step edge is favorable over the wide range of Al chemical potential. This suggests that N-H + Al-NH2 and N-H + Al-H with NH2 at the step edge appear at high and low temperatures, respectively. For both surface models, we also elucidate that the adsorption energy of Al adatoms at the step edge is much lower than that in the terrace region, indicating that Al adatoms are easily incorporated into the step edge. The estimated values of Ehrlich-Schwobel barrier (ESB) of Al adatoms for N-H + Al-NH2 and N-H + Al-H with NH2 at the step edge are −1.4 and −1.9 eV, respectively. The relationship between the adsorption behavior and surface morphology during the MOVPE is discussed on the basis of calculated ESB as well as adsorption energies and migration barriers.

Knee adduction moment (KAM) has been recognized as a good clinical surrogate for medial tibiofemoral joint loading and is associated with implant durability after total knee arthroplasty (TKA). This study aimed to examine the effects of joint line obliquity in kinematically aligned TKA (KA-TKA) on KAM during gait. The study enrolled 21 knees from 18 patients who underwent cylindrical axis reference KA-TKA and a matched group of 21 knees from 18 patients who underwent mechanically aligned (MA)-TKA as controls. Gait analyses were performed the day before TKA and at an overall mean of 2.6 years postoperatively. First peak KAM and variables associated with frontal knee kinetics were determined and compared between groups. In KA-TKA, the proximal tibia was resected with 3.4° ± 1.5° of varus in relation to the mechanical axis, and the final femorotibial shaft axis was 176.7° ± 3.8° with KA-TKA and 174.4° ± 3.0° with MA-TKA. KAM was significantly smaller with KA-TKA than with MA-TKA (p

Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable non-selective cation channel, which is activated by various noxious or irritant substances in nature. TRPA1 activators have been generally recognized as noxious, however, foods and beverages containing TRPA1 activators are preferably consumed; the reasons for this discrepancy are not well understood. We demonstrate that TRPA1 is involved in the stimulatory appetite control mechanism. β-Eudesmol is an oxygenated sesquiterpene contained in medicinal or edible plants which activates TRPA1. Oral administration of β-eudesmol brought significant increments in food intake in rats and elevated plasma ghrelin levels. Gastric vagal nerve activity (GVNA) has been reported to affect feeding behavior. In vivo electrophysiological measurement of GVNA revealed that oral-ingestion of β-eudesmol significantly increased GVNA. This GVNA elevation was eliminated by TRPA1 inhibitor (HC-030031) treatment prior to β-eudesmol administration. The physiological effects of β-eudesmol, for example, incremental increase in food intake, ghrelin elevation and activation of GVNA, were significantly reduced in TRPA1 knockout rats. Our results indicated that β-eudesmol stimulates an increase in appetite through TRPA1, and suggests why TRPA1 activator containing foods and beverages are preferably consumed.

Background: Systolic blood pressure (SBP) of rats decreases significantly following exposure to the odor generated from the Maillard reaction of protein digests with xylose. This study identified active odorants that affect blood pressure and demonstrated the mechanism of action.; Results: Among the four potent odorants that contribute most to the odor of the Maillard reaction sample, 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) and 5-methyl-2-pyrazinemethanol (MPM) decreased SBP significantly. The earliest decrease in blood pressure was observed 5 min after exposure to DMHF. Application of zinc sulfate to the nasal cavity eliminated the effect. Furthermore, gastric vagal (parasympathetic) nerve activity was elevated and renal sympathetic nerve activity was lowered after exposure to DMHF.; Conclusion: It is indicated that DMHF affects blood pressure through the olfactory system, and the mechanism for the effect of DMHF on blood pressure involves the autonomic nervous system. © 2017 Society of Chemical Industry.; © 2017 Society of Chemical Industry.

The autonomic nervous system innervates various peripheral tissue functions. Various external stimuli affect autonomic nerve activity, however, there is little information about the involvement of sensory receptors in the responses. The TRPA1 is a calcium-permeable non-selective cation channel which plays a crucial role in the susceptibility to various stimuli. β-Eudesmol, an oxygenated sesquiterpene found in hop essential oil and beer, activates the TRPA1. Intragastric administration of β-eudesmol decreased efferent adrenal sympathetic nerve activity (ASNA) in rats, whereas subcutaneous administration did not. ASNA suppression by β-eudesmol was not observed in TRPA1 knockout rats. The β-eudesmol derived ASNA suppression was partially, but significantly, eliminated by subdiaphragmatic vagotomy in rats, suggesting the afferent vagal nerve from the gastrointestinal tract to the brain is involved in the effect of β-eudesmol on ASNA. Our results indicate that β-eudesmol suppresses ASNA, partly through TRPA1 and the afferent vagus nerve. These findings introduce the physiological significance of the TRPA1 in the control of ASNA.

We previously obtained evidence suggesting that physical exercise increases the release of L-carnosine (CAR) from muscles and that CAR affects autonomic neurotransmission and physiological phenomena in rats. It has also been reported that exercise elicits an increase in activity of the sympathetic nerve innervating the skeletal muscle. Therefore, in this study, we investigated the effect of CAR application, onto the surface of the right femoral muscle, on activity of the sympathetic nerve innervating the left femoral muscle, in urethane-anesthetized rats. Topical application of 10 pg (44.2 fmol) of CAR increased either skeletal muscle sympathetic nerve activity (skeletal muscle-SNA) or skeletal muscle blood flow (skeletal muscle-BF) of the contralateral skeletal muscle. Furthermore, thioperamide, a histamine H3-antagonist, inhibited the increase in skeletal muscle-SNA, and butoxamine, a β2-antagonist, abolished the increase in skeletal muscle-BF caused by topical application of CAR. The present results suggest that CAR released from muscles during physical exercise might affect skeletal muscle-SNA and skeletal muscle-BF on the opposite side of the body via a CAR evoked effect in muscles.

Background Restoration of the natural joint line is a cornerstone for kinematically aligned total knee arthroplasty (TKA). The purpose of this study was to investigate the relative orientation of the tibial growth plate (GP) with respect to the tibial plateau (TP) for possible application in predicting natural joint line for knees with highly advanced osteoarthritis patient at the time of kinematically aligned TKA. Methods Images from computed tomography (CT) of 27 normal knees (9 males, 18 females; mean age, 31.6 years) were studied. Geometry of the GP was extracted from CT images, and its moment-of-inertia axes were calculated for the whole GP and the medial and lateral halves. Angular orientations of each GP axis with respect to the TP plane were measured in anatomical coordinates. Results The TP and GP planes were oriented in 2.3 ± 1.8° of varus and 1.1 ± 1.9° of valgus relative to the tibial mechanical axis, respectively. With respect to the TP plane, the whole GP plane was inclined in 3.4 ± 1.5° of valgus. Orientation of the GP plane differed drastically between medial and lateral halves. The medial GP was in 4.9 ± 2.9° of varus and 1.8 ± 2.5° of anterior inclination, and the lateral half was in 10.4 ± 2.4° of valgus and 18.6 ± 4.0° of anterior inclination relative to the TP. Conclusions Angular orientation of the original TP plane can be predicted in reference to the GP plane and may provide reasonable guidance for the target bone resection angle of the tibia in kinematically aligned TKA.

Lactobacilli exhibit several health benefits in mammals, including humans. Our previous reports established that heat-killed Lactobacillus brevis SBC8803 (SBC8803) increased both efferent gastric vagal nerve activity and afferent intestinal vagal nerve activity in rats. We speculated that this strain could be useful for the treatment of gastrointestinal (GI) disorders. In this study, we examined the effects of SBC8803 on peristalsis and the activity of the efferent celiac vagal nerve innervating the intestine in rats. First, we examined the effects of intraduodenal (ID) administration of SBC8803 on efferent celiac vagal nerve activity (efferent CVNA) in urethane-anesthetised rats using electrophysiological studies. The effects of intravenous injection of the serotonin 5-HT3 receptor antagonist granisetron on changes in efferent CVNA due to ID administration of SBC8803 were also investigated. Finally, the effects of oral gavage of SBC8803 on GI transit were analysed using the charcoal propulsion method in conscious rats treated with or without granisetron. ID administration of SBC8803 increased efferent CVNA. Pretreatment with granisetron eliminated SBC8803-dependent changes in efferent CVNA. Furthermore, oral gavage of SBC8803 significantly accelerated GI transit, while pretreatment with granisetron inhibited GI transit. Our findings suggested that SBC8803 increased efferent CVNA and GI transit of charcoal meal via 5-HT3 receptors. Moreover, SBC8803 enhanced the activity of efferent vagal nerve innervating the intestine and promoted peristalsis via 5-HT3 receptors.

The biological production of 1,3-propanediol from glycerol, which is a by-product in a bio-diesel production process, is of great interest. However, major difficulties still exist in downstream processing because 1,3-propanediol has a high boiling point. In this study, reactive extraction with aldehydes in the presence of a hydrophobic acidic ionic liquid as an acidic catalyst was used to extract 1,3-propanediol from an aqueous solution. Hydrophobic acidic ionic liquids have successfully played the role of acidic catalysts for acetalization as well as hydrochloric acid. Aromatic compounds as diluents were preferable for this acetalization. Conversion of 60 g/dm 3 of 1,3 propanediol reached 96% at a concentration of 4.0 mol/dm 3 of 1-butanal in toluene.

The bioactive peptides Ile-Pro-Pro (IPP) and Val-Pro-Pro (VPP) are believed to improve blood pressure and arterial function. To gain a better understanding of the mechanisms underlying the action of these peptides, we investigated their effects upon autonomic neurotransmission and blood pressure in spontaneously hypertensive rats (SHR). Both IPP and VPP caused a significant reduction in cutaneous arterial sympathetic nerve activity (CASNA) and reduced mean arterial pressure (MAP); however, both of these effects were eliminated following sub-diaphragmatic vagotomy. On the other hand, captopril, an angiotensin-converting enzyme inhibitor, reduced MAP without changing CASNA, and maintained this hypotensive effect following vagotomy. Moreover, the effects of IPP and VPP upon CASNA were observed following gastric administration but not by duodenal administration. These results suggest that IPP and VPP reduce CASNA via the stomach and afferent vagus nerve, thus causing reductions in MAP in SHR.

Systolic blood pressure (SBP) of rats decreases significantly following exposure to the odor generated from the Maillard reaction of protein digests with xylose. This study identified active odorants that affect blood pressure and demonstrated the mechanism of action.Among the four potent odorants that contribute most to the odor of the Maillard reaction sample, 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) and 5-methyl-2-pyrazinemethanol (MPM) decreased SBP significantly. The earliest decrease in blood pressure was observed 5 min after exposure to DMHF. Application of zinc sulfate to the nasal cavity eliminated the effect. Furthermore, gastric vagal (parasympathetic) nerve activity was elevated and renal sympathetic nerve activity was lowered after exposure to DMHF.It is indicated that DMHF affects blood pressure through the olfactory system, and the mechanism for the effect of DMHF on blood pressure involves the autonomic nervous system. © 2017 Society of Chemical Industry.

Splenic sympathetic nerve activity (SNA) modulates cellular immune functions such as splenic natural killer cell activity. Lactobacillus pentosus strain S-PT84 enhances splenic natural killer cell activity. Here, we examined whether S-PT84 affects splenic natural killer activity through splenic SNA in BALB/c mice. Splenic SNA was significantly decreased following the administration of S-PT84. This phenomenon was inhibited by pretreatment with thioperamide (histamine H3 receptor antagonist), suggesting that S-PT84 directly affected splenic SNA. Thioperamide also inhibited the increase in splenic natural killer activity by S-PT84. Thus, the change in splenic natural killer activity by S-PT84 may be partially modulated through SNA.

When mammals are exposed to an odor, that odor is expected to elicit a physiological response in the autonomic nervous system. An unpleasant aversive odor causes non-invasive stress, while a pleasant odor promotes healing and relaxation in mammals. We hypothesized that pleasant odors might reduce a stress response previously induced by an aversive predator odor. Rats were thus exposed to pleasant and unpleasant odors in different orders to determine whether the order of odor exposure had an effect on the physiological response in the autonomic nervous system. The first trial examined autonomic nerve activity via sympathetic and parasympathetic nerve response while the second trial examined body temperature response. Initial exposure to a pleasant odor elicited a positive response and secondary exposure to an unpleasant odor elicited a negative response, as expected. However, we found that while initial exposure to an unpleasant odor elicited a negative stress response, subsequent secondary exposure to a pleasant odor not only did not alleviate that negative response, but actually amplified it. These findings were consistent for both the autonomic nerve activity response trial and the body temperature response trial. The trial results suggest that exposure to specific odors does not necessarily result in the expected physiological response and that the specific order of exposure plays an important role. Our study should provide new insights into our understanding of the physiological response in the autonomic nervous system related to odor memory and discrimination and point to areas that require further research.

The effects of neuropeptide Y (NPY) injected into the hypothalamic suprachiasmatic nucleus (SCN) or the lateral cerebral ventricle (LCV) at four different time points of the day on the subsequent 2h food intake from three macronutrient rich diets were examined. Adult Wistar male rats on 12-12 h light-dark cycles received either saline or NPY (lOOpmol) through chronically implanted guide cannulas into the SCN or the LCV. The results show that NPY was effective at stimulating energy intake from the dextrin/sucrose diet when injected in the SCN after lights-on, and total energy intake when injected in the LCV before and after lights-on. This suggests that NPY is effective at altering nychthemeral variations in total energy and energy from dextrin/sucrose diets, but this modulation is specific to the site of administration.

The flexion-extension axis (FEA) of the femur is substantially changed after mechanically aligned total knee arthroplasty (TKA) due to a discrepancy in bone cut thickness between the posterior and distal femoral regions. This study assessed the bony gap changes and FEA displacement caused by this problem in osteoarthritis patients.The study enrolled 60 knees from 60 patients for whom primary TKA was planned due to medial knee osteoarthritis. All patients underwent computed tomography, and 3-dimensional (3D) bone models were reconstructed on 3D-planning software. Bone cuts of the distal femur and proximal tibia were simulated to be perpendicular to each mechanical axis. Bony gap change was computed as the difference in bone cut thickness between medial and lateral compartments. Each femoral condyle was assessed for potential FEA displacement, as the difference in bone cut thickness between posterior and distal femoral regions.The mean magnitude of bony gap discrepancy necessary for mediolateral balancing was 1.6 ± 3.3 mm (range -7 to 8.2 mm) at 0° extension and -0.2 ± 2.6 mm (range -6.4 to 4.3 mm) at 90° flexion. At least 2 mm of bony gap discrepancy at 0° extension and 90° flexion was found in 40 patients (67%) and 26 patients (43%), respectively. In terms of femoral bone cut, posterior bone cut thickness was significantly larger than distal bone cut thickness in the medial compartment (p 0.001). Bony gap discrepancy between distal and posterior regions of the femoral condyle was ≥2 mm in 28 patients (47%).This study focused on two flaws of mechanically aligned TKA in OA patients. Substantial numbers of patients inevitably required2 mm of medial collateral ligament release at 0° extension and showed a bone cut discrepancy between distal and posterior regions, carrying a risk of FEA displacement and subsequent unnatural knee motions during knee extension and flexion. Level of evidence IV.

Reproducing a functional flexion–extension axis (FEA) of the femur is key to achieving successful collateral ligament balance and joint line in total knee arthroplasty (TKA). This study compared the feasibility of cylindrical axis (CA)-reference bone cut and articular surface-reference bone cuts in reproducing the FEA for Japanese osteoarthritis patients. The study enrolled 122 knees from 86 patients who underwent primary TKA due to grade III or IV osteoarthritis. Data from pre-operative CT were reconstructed into three-dimensional (3D) models using 3D-planning software. Cylindrical radii of the condyles were measured, and femoral bone cut angles relative to anatomical landmarks were determined in the coronal and axial reference planes based on CA-reference and articular surface-reference methods. Mean cylindrical radii for medial and lateral femoral condyles were 17.4 ± 1.6 and 17.3 ± 1.4 mm, respectively. Of the 122 knees, 46 exhibited >1 mm of difference between condyles. Fifty-three and 22 knees exhibited >2° of angular difference between CA-reference and articular surface-reference bone cuts in the coronal and axial planes. Mean angle of the CA and surgical epicondylar axis in 3D space was 4.6 ± 2.1°. As practical parameters for TKA, the angle between CA and IM rod was significantly larger than that between the distal articular surface line and IM rod in the coronal plane (p

Background/purpose: We observed that olfactory stimulation with scent of grapefruit oil elevated the activities of sympathetic nerves, and increased the plasma glycerol concentration and blood pressure. In contrast, olfactory stimulation with scent of lavender oil had opposite effects in rats. These suggest that changes in autonomic activities cause physiological functions via histaminergic H1 and H3 receptor. Moreover, it has been reported that somatic sensory stimulation affected autonomic neurotransmission. To examine effects of skin application of urea-containing cream on cutaneous arterial sympathetic nerve activity (CASNA), blood flow, and transepidermal water loss (TEWL). Method: The activity of CASNA was determined by electrophysiological method, and cutaneous blood flow was determined using laser flowmeter in urethane-anesthetized rats, TEWL was measured using VapoMeter in the back skin of HWY hairless rats. Results: CASNA was markedly and significantly inhibited by skin application of 10% urea-containing cream, whereas cutaneous blood flow was significantly elevated via histaminergic H3-receptor. In conscious hairless rats, TEWL was significantly decreased 24 h after application of 10% urea-containing cream to the back skin. Conclusion: These findings suggest that skin application of 10% urea-containing cream increases the cutaneous blood flow and water retaining ability, and that histaminergic H3-receptors may mediate these effects.

Autonomic nerves, consisting of both sympathetic and parasympathetic nerves, regulate various bodily functions such as blood pressure, body temperature, glucose metabolism, energy metabolism, and digestion. Our studies in rats and mice have demonstrated that food, flavor, and music affect physiological phenomena via changes in autonomic neurotransmissions. Intestinal injection of Lactobacillus johnsonii La1 (NCC533) suppressed sympathetic nerves that innervate the adrenal gland and kidney of urethane-anesthetized rats, lowering blood glucose and blood pressure levels, and excited the gastric parasympathetic nerve, elevating appetite and body weight. In contrast, intestinal injection of Lactobacillus paracasei ST11 (NCC2461) excited sympathetic nerves that innervate white and brown fat and the adrenal gland, increasing lipolysis and body temperature, and suppressed the gastric parasympathetic nerve, reducing appetite and body weight. Interestingly, we found that the hypothalamic suprachiasmatic nucleus (SCN), a master circadian clock, and histamine receptors in histaminergic neurons play important roles in peripheral autonomic control. To investigate the possible role of SCN and histamine receptors in lactobacilli-mediated pathology, we created an SCN-lesion model and experimented with histaminergic blocker injections. SCN lesion or injection of thioperamide, a histamine H3-receptor antagonist, eliminated the suppression of renal sympathetic nerve activity by NCC533, preventing blood pressure decline, and inhibited the enhancement of the gastric parasympathetic nerve induced by NCC533. In addition, diphenhydramine, a histamine H1-receptor antagonist, abolished the increases in renal sympathetic nerve activity and blood pressure caused by NCC2461. Infradiaphragmatic vagotomy eliminated the suppression of renal sympathetic nerve activity by NCC533, but did not affect the excitation of the renal sympathetic nerve by NCC2461. Collectively, these findings strongly suggest that SCN and histamine neurons are involved in the lactobacilli-mediated pathology of autonomic nerves and related physiological changes through abdominal afferent vagal pathway input to the central nervous system.

The odor of 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a synthetic compound isolated from fox feces, induces various emotional behavioral and stress responses. Here we examined the effect of TMT on behavioral responses and adrenal sympathetic nerve activity (ASNA) in rats. TMT increased freezing behavior, defensive-burying and defensive-attack, and decreased exploration, grooming and approach behaviors. On the other hand, butyric acid (BA), a pungent but non-predatory odor, increased defensive-burying only. TMT increased ASNA strongly, whereas the effects of BA increased ASNA extremely weakly. Furthermore, pre-treatment with the histaminergic H1-receptor antagonist diphenhydramine eliminated the effects of TMT on ASNA. These findings suggest that TMT odor affects autonomic neurotransmission via histaminergic neurons. Exposure to TMT odor likely regulates the controlling autonomic function and output to a motor system simultaneously, evoking behavioral stress responses.

Eucommia ulmoides Oliver leaf extracts (ELE) have been shown to exert a hypolipidemic effect in hamsters. Therefore, it was hypothesized that ELE might affect lipid metabolism via changes in autonomic nerve activities and causes changes in thermogenesis and body weight. We examined this hypothesis, and found that intraduodenal (ID) injection of ELE elevated epididymal white adipose tissue sympathetic nerve activity (WAT-SNA) and interscapular brown adipose tissue sympathetic nerve activity (BAT-SNA) in urethane-anesthetized rats and elevated the plasma concentration of free fatty acids (FFA) (a marker of lipolysis) and body temperature (BT) (a marker of thermogenesis) in conscious rats. Furthermore, it was observed that ID administration of ELE decreased gastric vagal nerve activity (GVNA) in urethane-anesthetized rats, and that ELE given as food reduced food intake, body and abdominal adipose tissue weights and decreased plasma triglyceride level. These findings suggest that ELE stimulates lipolysis and thermogenesis through elevations in WAT-SNA and BAT-SNA, respectively, suppresses appetite by inhibiting the activities of the parasympathetic nerves innervating the gastrointestinal tract, including GVNA, and decreases the amount of abdominal fat and body weight via these changes.

Nutrient information from the gastrointestinal tract to the brain plays a critical role in the regulation of appetite and energy homeostasis. The autonomic nervous system controls the functions of several tissues to regulate the energy homeostasis of the whole body. Autonomic nerve activity is influenced by environmental or exogenous changes in even a single tissue. In the present study, we investigated the effect of an intraduodenal injection of fat on the activities of the autonomic nerves innervating the adrenal gland and stomach in urethane-anesthetized rats. An intraduodenal injection of corn oil suppressed adrenal efferent sympathetic nerve activity (ASNA) and stimulated gastric efferent vagal nerve activity (GVNA). A lipase inhibitor, ɛ-polylysine, coinjected with corn oil completely suppressed the corn oil-induced changes in ASNA and GVNA. Further, an intraduodenal injection of fatty acid (linoleic acid) moderately suppressed ASNA and significantly stimulated GVNA; these results indicate that fat may affect autonomic nerve activity partly through the chemoreception of free fatty acids (FFAs), which are produced during the hydrolysis of fat (corn oil) by a pancreatic lipase, in the intestinal lumen. Furthermore, an intraduodenal injection of an intravenous fat emulsion with the same pH and osmotic pressure as the body fluid affected ASNA and GVNA in a similar manner as corn oil. These results suggest that intraduodenal fat suppresses ASNA and stimulates GVNA partly via the chemoreception of FFAs—the degradation products of fats—in the intestinal lumen.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a peptidergic neurotransmitter that is expressed in high levels in nervous systems. Here, we investigated the roles of PACAP in autonomic system regulation by evaluating the changes caused in the autonomic nerve activities after injecting PACAP into the central nervous system (CNS) and examining stress-induced blood glucose changes in PACAP-deficient (PACAP−/−) mice. Renal sympathetic nerve activity (RSNA), blood pressure, and heart rate were elevated after injecting PACAP into the third cerebral ventricle (3CV). Similarly, other sympathetic nerve activities, including adrenal sympathetic nerve activity (ASNA), celiac sympathetic nerve activity (CSNA), and brown adipose tissue sympathetic nerve activity (BAT-SNA), were accelerated by PACAP injection. In contrast, injecting PACAP into 3CV significantly suppressed parasympathetic nerve activities, including gastric vagal nerve activity (GVNA) and celiac vagal nerve activity (CVNA). In addition, blood glucose elevations induced by stress, such as immobilization or ether exposure, were disrupted in PACAP−/− mice, although basal glucose levels in mutants were comparable to that in wild-type mice. These results suggest that CNS PACAP regulates autonomic function by maintaining a sympathetic–parasympathetic balance and contributes to peripheral homeostatic maintenance, especially under conditions of stress.

Changes in the activity of the autonomic nervous system are good indicators of alterations in physiological phenomena such as the body temperature, blood glucose, blood pressure. Hesperidin, a flavanone known as vitamin P, has been shown to reduce the levels of serum lipids, cholesterol, and blood pressure. However, hesperidin is not water-soluble and is not well absorbed from the intestine. G-hesperidin (4G-alpha-glucopyranosyl hesperidin) is more water-soluble and more rapidly absorbed than hesperidin. In order to clarify the functions of G-hesperidin, we examined the effects of oral administration of G-hesperidin on interscapular brown adipose tissue-sympathetic nerve activity (BAT-SNA) and cutaneous sympathetic nerve activity (CASNA) in rats weighing about 300 g. In this study, we found that oral administration of 60 mg of G-hesperidin increased the BAT-SNA but decreased the CASNA in urethane-anesthetized rats. Since an elevation in BAT-SNA increases heat production (i.e. body temperature (BT)) and a decrease in CASNA increases cutaneous perfusion, we examined whether oral administration of G-hesperidin had an effect on the peripheral BT in rats. Consequently, we observed that the subcutaneous BT at the caudal end of the back after oral administration of 60 mg of G-hesperidin was significantly higher than the subcutaneous BT after oral administration of water in conscious rats. These findings suggest that G-hesperidin enhances the BAT-SNA and suppresses the CASNA resulting in an increase in the peripheral BT, probably by an increase in the thermogenesis in the BAT and an elevation in the cutaneous blood flow.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with pleiotropic functions. We report here that PACAP-deficient (PACAP-/-) mice showed increased immobility in a forced swimming test, which was reduced by the antidepressant desipramine, to a similar extent as in wild-type mice. The atypical antipsychotic risperidone and the selective serotonin (5-HT)(2) antagonist ritanserin normalized the depression-like behavior in PACAP-/- mice. The 5-HT(2) agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine-induced 5-HT syndrome was exaggerated in PACAP-/- mice, which suggests a 5-HT(2)-receptor-dependent mechanism in the depression-like behavior. The circadian rhythm of plasma corticosterone and body core temperature was significantly flattened in the mutants. mRNA expression of glucocorticoid receptor was reduced in the mutant hippocampus. The present results suggest that alterations in PACAP signaling might contribute to the pathogenesis of certain depressive conditions amenable to atypical antipsychotic drugs.

Oral supplementations of L-arginine and L-lysine show tumor inhibition abilities. The splenic sympathetic nerve is involved in central modulation of cellular immunity and suppresses splenic natural killer cell activity in rats. An intravenous administration of a mixture of 10 mM L-arginine and L-lysine decreased splenic sympathetic nerve activity (splenic-SNA). We examined the effect of L-arginine and L-lysine mixtures on splenic-SNA in urethane-anesthetized rats by administration of 1 ml mixtures of 2 mM, 10 mM, and 50 mM L-arginine and L-lysine. We also studied the effect of the above mixtures on human colon cancer cell proliferation in athymic nude mice. An increase in splenic-SNA and tumor volume (2 mM), no effect (10 mM), and a decrease in both values (50 mM) were seen. Bivariate correlation analysis revealed a positive correlation between changes in splenic-SNA and tumor volume, indicating the tumor suppressing ability of weakened splenic-SNA.

The spleen is an important organ for tumor immunity, and the splenic sympathetic nerve has a suppressive effect on splenic natural killer (NK) cytotoxicity. On the basis of this and reports that Lentinus edodes (Shiitake mushroom) has tumor-inhibitory effects, the authors hypothesized that an extract of a mycelial culture of L. edodes grown in a solid medium of sugar-cane bagasse and defatted rice bran–L·E·M–might affect the sympathetic splenic sympathetic nerve activity (Splenic-SNA) and thus inhibit tumor proliferation. Thus, the effect of L·E·M on Splenic-SNA and human cancer cell proliferation was examined. Splenic-SNA was found to be suppressed by an intraduodenal L·E·M injection in urethane-anesthetized rats, which significantly inhibited increases in the tumor volume of human colon and breast cancer cells implanted in athymic nude mice. These findings suggest that L·E·M has an inhibitory effect on tumor proliferation possibly via a reduction in NK cytotoxicity through the suppression of Splenic-SNA.