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Underwater disturbances are the largest error source in Global Navigation Satellite System - Acoustic ranging combination technique (GNSS-A) seafloor geodetic observation. In particular, the gradient of sound speed structure (SSS) directly affects the horizontal accuracy and needs to be examined. Previous studies have not investigated its temporal change component. In this paper, we verified the assumption that the underwater gradient structure does not change significantly during GNSS-A observation for several hours through applying a modified version of an analysis software called GARPOS to actual data of SGO-A (provided by Japan Coast Guard). Obtained results suggested that this assumption holds at many observation data, and the positioning accuracy becomes better. Some non-improved observation epochs were speculated to be accompanied by structure changes for which this assumption was not valid. It is suggested that the SSS change during observation will be an important research topic in GNSS-A. [ABSTRACT FROM AUTHOR]

Cores recovered during the International Continental Scientific Drilling Program project "Drilling into Seismogenic zones of M2.0 to M5.5 earthquakes in deep South African Gold Mines" include fault breccia from within the aftershock cloud of the 2014 Orkney earthquake (M5.5). The breccia and surrounding intrusive rocks, probably lamprophyres rich in talc, biotite, calcite, and amphibole, had high magnetic susceptibilities owing to the presence of magnetite. All of these characteristics can be attributed to fluid‐related alteration. Both the breccia and the lamprophyres had low friction coefficients and showed evidence of velocity strengthening, which is inconsistent with the occurrence of earthquakes. Variable amounts of talc, biotite, calcite, and amphibole within the lamprophyres might have produced complex frictional properties and spatial heterogeneity of fault stability. The altered lamprophyres may be the host rocks of the 2014 Orkney earthquake, but frictional complexity may have governed the magnitudes of the main‐ and aftershocks and their distributions. Plain Language Summary: Drilling into seismogenic zones is an important scientific endeavor, not only to advance our understanding of the mechanisms of earthquakes, but also to provide information that will improve the resilience of humankind to these deadly hazards. The International Continental Scientific Drilling Program supported deep drilling into the aftershock region of the 2014 Orkney earthquake (M5.5) and successfully recovered samples of faulted rock material from about 3.3 km depth by drilling from a depth of about 3 km in a South African gold mine. The samples were intensively sheared and rich in talc, which is a weak mineral with a very low friction coefficient. The fault zone probably developed within this talc‐rich rock, which would indicate that the earthquake was closely related to a pre‐existing weak geological structure. However, other minerals in the fault rocks might also have influenced the spatial heterogeneity of fault stability and earthquake generation. Key Points: Fault breccia was recovered from within the aftershock cloud of the 2014 Orkney earthquake (M5.5)The fault breccia and surrounding altered lamprophyres had high talc contents and low friction coefficientsVariable amounts of talc, biotite, calcite, and amphibole might have produced complex friction properties in the lamprophyres [ABSTRACT FROM AUTHOR]

The frequency of snowmelt‐induced soil slope instabilities is increasing in some seasonally cold regions because of climate change. Reliable hazard assessment and risk mitigation of snowmelt‐induced landslides require physically‐based prediction models. However, existing models either apply only at the slope scale or assume precipitation as the sole landslide trigger. In doing so, they neglect the complexity and coupled nature of the thermo‐hydro‐mechanical processes leading to slope instability in seasonally cold regions (such as snow accumulation and melting, infiltration and surface runoff, soil saturation, pore water pressure buildup and dissipation). Here, we present a spatially distributed and sequentially coupled numerical model to simulate snowmelt‐induced slope instabilities at the catchment scale. The model accounts for temperature‐dependent changes in the soil hydraulic behavior related to changes in water state by means of a routine implemented in a geographic information system. We verified the performance of the model using a case study of spring snowmelt‐induced soil slope failures that occurred after the 2004 Mid‐Niigata earthquake in Japan. Considering limitations and simplifications, the model was able to predict the triggering condition, magnitude, and spatial distribution of the snowmelt‐induced landslides with a satisfactory degree of accuracy. We believe that the robustness and simplicity of our numerical approach make it suitable for implementation in early warning systems. Plain Language Summary: Climate change is responsible for an increasing number of natural disasters in seasonally cold regions, where heavier snowfalls and sudden snowmelts can cause destructive landslides on hill slopes. These landslides are not easy to study because the mechanisms that trigger them are different from those of shallow landslides occurring in response to rainfall. Moreover, advanced models that incorporate the complex relations among rain, snow, temperature, soil freezing, melting, and slope stability at a detailed scale are still cumbersome and very demanding in terms of computational power. For these reasons, evaluating the risk to people and assets in seasonally cold regions is not straightforward, and existing models tend to underestimate it. In this paper, we propose a novel modeling strategy to study the stability of soil slopes under the influence of both snowmelt and rainfall at a regional scale. First, we explain the governing mechanisms of snowmelt‐induced landslides; then, we present our strategy along with detailed explanations of the equations we use. We test our model by predicting a known case study (the snowmelt‐induced landslides of 2005 in Niigata, Japan) and obtain a reasonably good result. This simple strategy could be applied in an early warning system for snowmelt‐induced landslides. Key Points: Developed a novel spatially distributed numerical model for snowmelt‐induced shallow landslidesSimplified account of below‐freezing temperature on hydro‐mechanical‐behavior for catchment‐scale slope stability assessmentModel performance evaluated on snowmelt‐induced post‐seismic landslides occurred in Niigata, Japan, in 2005 [ABSTRACT FROM AUTHOR]

Background: The metastatic involvement of regional lymph nodes is the most important prognostic factor for overall survival of skin cancer patients. The sonographic technique of freehand real‐time tissue elastography (RTE), which displays tissue rigidity as a colour overlay of the tissue image, was developed. Objective: Our purpose was to evaluate the benefit of RTE for detecting lymph node metastases of skin cancer non‐invasively before operation. Methods: We first selected lymph nodes of skin cancer patients which had already been diagnosed by biopsy as being reactive or metastatic, and then retrospectively collected images of RTE and B‐mode and colour Doppler ultrasound on those lymph nodes performed preoperatively. Twenty‐one lymph nodes from 12 patients with squamous cell carcinoma (SCC), 23 lymph nodes from 14 patients with malignant melanoma (MM) and 14 lymph nodes from six patients with extramammary Paget disease (Paget) were investigated. Elastographic images were assessed on a scale of one to four according to the percentage of high elasticity (hard) area (HEA) in the lymph node. Results: In all three skin cancers, lymph nodes evaluated as grade 3 or 4 by RTE were metastatic. All lymph nodes evaluated as grade 1 or 2 by RTE were reactive in SCC, whereas some lymph nodes evaluated as grade 1 or 2 were metastatic in MM and Paget. Conclusion: Real‐time tissue elastography may aid in distinguishing reactive lymph nodes from metastatic ones especially in SCC. [ABSTRACT FROM AUTHOR]

Polymer-derived SiC-polycrystalline fiber (Tyranno SA) shows excellent heat-resistance up to 2000oC, and relatively high strength. However, to extend the application field, increase in the fiber's strength is eagerly required. Up to now, through our research, the relationship between the strength and residual defects of the fiber, which were formed during the heat-treatment processes (degradation of raw fiber and sintering), has been clarified. In this paper, we addressed the relationship between the heat-treatment condition and the surface roughness of the obtained SiC-polycrystalline fiber, using three different raw fibers (Elementary ratio: Si1Al0.01C1.5O0.4~0.5) and three types of carbon vessel (Open system, Partially closed system, and Closed system). With increase in the oxygen content in the raw fiber, the degradation during the heat-treatment process easily proceeded. This led to nearly stoichiometric composition of SiC crystal. And, higher oxygen content in the raw fiber and the closed system led to relatively high partial-pressure of SiO at the initial stage of the degradation process. In this case, the degradation reactions (SiO+2C=SiC+CO and SiO2+3C=SiC+2CO) in the inside of each filament became faster, and then the CO partial pressure at the surface region of each filament was found to be increased. In consequence, according to Le Chatelier's principle, the surface degradation reaction and grain growth of formed SiC crystals would be considered to become slower. That is to say, using the raw fiber with higher oxygen content and closed system (highest CO content in the reactor), much smoother surface of the SiC-polycrystalline fiber could be achieved. [ABSTRACT FROM AUTHOR]

Background and Objectives: Previous reports suggest that several serum biomarkers play roles in the pathogenesis, inflammatory response, and oxidative stress in periodontitis caused by bacterial infections, linking chronic periodontitis to atherosclerotic vascular disease (ASVD). The aim of this preliminary study was to investigate, in a Japanese cross‐sectional community survey, potential serum biomarkers of periodontitis that are associated with ASVD and chronic periodontitis. Material and Methods: The study cohort included a total of 108 male subjects who underwent annual health examinations. Serum biomarkers (high‐sensitivity C‐reactive protein [hs‐CRP], proprotein convertase subtilisin/kexin type 9 [PCSK9], interleukin‐6, tumor necrosis factor‐α, soluble CD14, myeloperoxidase, matrix metalloproteinase‐3, adiponectin, total bilirubin [TBIL], and serum lipids) were analyzed to determine their association (if any) with periodontal parameters. Aortic stiffness was evaluated using the brachial‐ankle aortic pulse wave velocity (PWV) index and the cardio‐ankle vascular index (CAVI). Results: The concentrations of PCSK9 and hs‐CRP were increased (P = .001 and .042, respectively), and the concentration of TBIL was decreased (P = .046), in subjects with periodontal disease (determined as a probing depth of ≥4 mm in at least one site) compared with periodontally healthy subjects. The ratio of low‐density lipoprotein cholesterol (LDL‐C) to high‐density lipoprotein cholesterol and the concentrations of triglycerides, remnant‐like particles‐cholesterol, and oxidized LDL were elevated in subjects with periodontal disease compared with periodontally healthy subjects (P = .038, .007, .002, and .049, respectively). Multivariate regression analyses indicated that the number of sites with a pocket depth of ≥4 mm was associated with the concentration of PCSK9 and inversely associated with the concentration of TBIL independently (standardized β = .243, P = .040; standardized β = −.443, P = .0002; respectively). Analysis of receiver operating characteristic curves of PCSK9 indicated moderate accuracy for predicting the presence of disease sites (probing depth ≥ 4 mm) (area under the curve = 0.740). No significance in the values of PWV and CAVI was observed between subjects with periodontal disease and periodontally healthy subjects. Conclusion: In Japanese male subjects, the concentrations of serum PCSK9 and TBIL were correlated with periodontal parameters. Moreover, PCSK9 could be a candidate biomarker for diagnosing chronic periodontitis, and may also have potential to evaluate the risk for periodontitis to cause ASVD. Longitudinal studies of larger populations are necessary to confirm the exact association of periodontitis with increased serum PCSK9 and decreased TBIL. [ABSTRACT FROM AUTHOR]

SUMMARY: Extra‐high‐quality audio devices, which are reproducible sound of broadband, have appeared in recent years. Such audio devices of broadband can feel like a deeper sense of realism as an air field by feeling the vibration of the air with entire body. This technology is expected application as sense of presentation technology. Using this technology, development of the new stimulus medium that is the field generating device, such as wrapped up in air is enabled. The purpose of this study is to create a completely new sense with the airflow stimulus termed “air sensation” by using the air field. In this study, we measured the psychophysical quantities to clarify the cognitive characterization of air sensation as a basic examination. Specifically, we measured the absolute thresholds to detect the air‐flow stimulus and sensitivity characteristics with respect to the strength of the stimulus. Consequently, it was revealed that cognitive characterizations vary with the properties of signal waveform, stimulus presentation site, and stimulus presentation order. [ABSTRACT FROM AUTHOR]

Objectives We describe a novel scoring system, the facial Palsy Prognosis Prediction score ( PPP score), which we test for reliability in predicting pre-therapeutic prognosis of facial palsy. We aimed to use readily available patient data that all clinicians have access to before starting treatment. Design Multicenter case series with chart review. Setting Three tertiary care hospitals. Participants We obtained haematological and demographic data from 468 facial palsy patients who were treated between 2010 and 2014 in three tertiary care hospitals. Patients were categorised as having Bell's palsy or Ramsey Hunt's palsy. Main outcome measures We compared the data of recovered and unrecovered patients. PPP scores consisted of combinatorial threshold values of continuous patient data (eg platelet count) and categorical variables (eg gender) that best predicted recovery. We created separate PPP scores for Bell's palsy patients ( PPP-B) and for Ramsey Hunt's palsy patients ( PPP-H). Results The PPP-B score included age (≥65 years), gender (male) and neutrophil-to-lymphocyte ratio (≥2.9). The PPP-H score included age (≥50 years), monocyte rate (≥6.0%), mean corpuscular volume (≥95 fl) and platelet count (≤200 000 /μL). Patient recovery rate significantly decreased with increasing PPP scores (both PPP-B and PPP-H) in a step-wise manner. PPP scores (ie PPP-B score and PPP-H score) ≥2 were associated with worse than average prognosis. Conclusions Palsy Prognosis Prediction scores are useful for predicting prognosis of facial palsy before beginning treatment. [ABSTRACT FROM AUTHOR]

We compared the background characteristics of patients with chronic hepatitis C who achieved eradication of hepatitis C virus ( HCV), that is sustained virologic response ( SVR), with interferon ( IFN)-based versus IFN-free antiviral therapy in Japan. In addition, we used a previously reported risk assessment model to compare the incidence of hepatocellular carcinoma ( HCC) after SVR by treatment type. Pretreatment characteristics of 1533 patients who achieved SVR with IFN-based therapy and 1086 patients with IFN-free therapy from five institutions across Japan were compared. The risk of HCC after SVR was assessed based on pretreatment characteristics, and the incidence of HCC after SVR was estimated in both groups. Age and serum alpha-fetoprotein levels were higher, platelet count was lower, and liver fibrosis was more advanced in patients who achieved SVR with IFN-free therapy compared with IFN-based therapy. The incidence of HCC after SVR in the IFN-free group was estimated to be more than twofold higher than in the IFN-based therapy group (7.29% vs. 3.09%, and 6.23% vs. 3.01% when excluding patients who have underwent curative treatment for HCC). There are large differences in pretreatment characteristics between patients who achieved SVR with IFN-based and IFN-free therapies in Japan, which are associated with differential risk of HCC after SVR. These differences can influence the incidence of HCC after SVR and should be taken into consideration when comparing IFN-based and IFN-free therapies in terms of hepatocarcinogenesis suppression with HCV eradication. [ABSTRACT FROM AUTHOR]

A persistent hepatitis B virus ( HBV) infection is characterized by a lack of or a weak immune response to HBV, which may be reflective of tolerance to HBV. Efficient induction of HBV-specific immune response leads to the clearance of HBV in patients with a chronic HBV infection. CpG oligodeoxynucleotides ( ODN) has a powerful adjuvant effect in HBV vaccination. A recent report demonstrated that the immunization by B/K CpG ODN (K3) wrapped by the nonagonistic Dectin-1 ligand, schizophyllan ( SPG), namely K3- SPG, was more effective in the induction of antigen-specific immune response than that by K3. In this study, we examined the efficacy of K3- SPG as a HBV vaccine adjuvant. Wild-type ( WT) mice and HBV transgenic ( HBV-Tg) mice were subcutaneously immunized with hepatitis B surface antigen ( HBsAg) alone, HBsAg and K3, or HBsAg and K3- SPG. The vaccination with HBsAg and K3- SPG significantly enhanced humoral and cellular immune response to HBV antigen compared to the other vaccinations in WT and HBV-Tg mice. K3- SPG induced the accumulation of dendritic cells ( DCs) into draining lymph node and the activation of DCs. The expression of cytokines and chemokines related to Th1 and Th2 responses was upregulated after the vaccination including with K3- SPG. In conclusion, these results indicated that the vaccination using K3- SPG may overcome tolerance even in patients with chronic HBV infection. [ABSTRACT FROM AUTHOR]

Direct metrology of coherent short-wavelength beamlines is important for obtaining operational beam characteristics at the experimental site. However, since beam-time limitation imposes fast metrology procedures, a multi-parametric metrology from as low as a single shot is desirable. Here a two-dimensional (2D) procedure based on high-resolution Fresnel diffraction analysis is discussed and applied, which allowed an efficient and detailed beamline characterization at the SACLA XFEL. So far, the potential of Fresnel diffraction for beamline metrology has not been fully exploited because its high-frequency fringes could be only partly resolved with ordinary pixel-limited detectors. Using the high-spatial-frequency imaging capability of an irradiated LiF crystal, 2D information of the coherence degree, beam divergence and beam quality factor M2 were retrieved from simple diffraction patterns. The developed beam metrology was validated with a laboratory reference laser, and then successfully applied at a beamline facility, in agreement with the source specifications. [ABSTRACT FROM AUTHOR]

The rusts of different kinds of weathering steels and mild steel formed by CCT and exposure to a coastal atmosphere were examined by the adsorption of nitrogen and water molecules. The specific surface area (S) of the rusts was determined from the adsorption isotherms. The rusts of the weathering steels showed higher S and smaller particle size than those of the mild steel, indicating that the weathering steels form more compact rust layers compared to the mild steel. The S of the rusts formed at different positions of a simulated girder located in the coast strongly depended on the setting position. [ABSTRACT FROM AUTHOR]

We recently reported the absence of the articular disc, which is a constant structure in mammals, in the temporomandibular joint of the adult Tasmanian devil. However, whether the articular disc disappears with growth of the animal was unknown. The aim of this study was to determine whether a pouch young of the Tasmanian devil has the articular disc. The temporomandibular joint of a fresh carcass of the pouch young, whose crown-rump length was 43 mm, was examined microscopically and by microcomputed tomography. The absence of the articular disc in the pouch young temporomandibular joint was histologically confirmed. It is suggested that the articular disc of the Tasmanian devil is naturally absent. [ABSTRACT FROM AUTHOR]

The articles present a case study of two female Miniature Schnauzer dogs, first a three year old intact with evaluation of right heart enlargement, and second an eight month old intact with same but cardiac murmur was also present which causes atrial septal defect (ASD). Topics related to diagnosis of partial anomalous pulmonary venous connection (PAPVC) discussed include echocardiography, computed tomography angiography (CTA), and multidetector-row computed tomography (MDCT) angiography.

It is difficult to clarify the characteristics of flood flows in a total river system because of insufficient data for the upper river basin. Numerical analysis is an effective tool for complementing flood observation data in space and time. The objective of this study is to develop an unsteady 2D numerical analysis method for a river with tributary inflows in the upper river basin. The inflow boundary conditions of sharp discharge hydrographs from tributaries were estimated using water level hydrographs obtained from observation stations in the main stream; these stations were installed far downstream from the confluence points. This paper demonstrates that the method could be used to investigate the propagation and transformation of the discharge hydrographs from the main and tributary streams by using the sparse water level hydrographs observed in the main stream. The installation method for the water level observation stations is also discussed. [ABSTRACT FROM AUTHOR]

The articular disc of the temporomandibular joint is a constant structure in mammals. According to Parsons' report in 1900, however, it is absent in four animals: the armadillo, two kinds of monotremes and the Tasmanian devil. Thereafter, no research was performed to confirm this observation. The aim of this study was to determine by anatomical and histological examination whether the Tasmanian devil has an articular disc in its temporomandibular joint. Six fresh frozen corpses and one dry skull of Tasmanian devils were obtained from the School of Zoology, University of Tasmania. The corpses were dissected and the morphology of the temporomandibular joint was carefully observed by gross anatomical and histological examination. The structure of the temporomandibular joint of the dry skull was examined macroscopically and by micro-computed tomography. In all cases, absence of the articular disc in the Tasmanian devil temporomandibular joint was morphologically confirmed. The surface layer of both the condyle and the glenoid fossa comprised a thick fibrous tissue. Micro-computed tomography revealed dense and fine trabecular bone in the condyle. The thick fibrous tissue covering the condyle and high-density trabecular bone in the condyle might play a role in absorption against powerful mastication and heavy loading of the Tasmanian devil temporomandibular joint. [ABSTRACT FROM AUTHOR]

Background The effects of carperitide on left atrial pressure ( LAP) in dogs with mitral valve disease (mitral regurgitation, MR) have not been documented. Objective The objective was to compare the short-term effects of carperitide versus furosemide on LAP and neurohumoral factors in MR dogs. Animals Six healthy Beagle dogs weighing 9.8-12.6 kg (2 males and 4 females; aged 3 years) were used. Methods Experimental, randomized, cross-over, and interventional study. Carperitide 0.1 μg/kg/min or furosemide 0.17 mg/kg/h (1 mg/kg/6 h) was administered to dogs with surgically induced MR for 6 hours, and after a 14 day wash-out period, the other drug was administered. LAP, plasma renin activity, plasma aldosterone, and echocardiographic variables were measured. Results Left atrial pressure was decreased similarly after the administration of carperitide 0.1 μg/kg/min and furosemide 0.17 mg/kg/h (1 mg/kg/6 h) compared with baseline in dogs with MR (Baseline 14.75 ± 3.74 mmHg, carperitide 10.24 ± 4.97 mmHg, P < .01, furosemide 10.77 ± 5.06 mmHg, P < .05). Plasma renin activity and plasma aldosterone were significantly lower after the administration of carperitide than after the administration of furosemide ( P < .05, respectively). Conclusions and Clinical Importance Carperitide significantly decreased LAP in dogs with acute MR caused by experimental chordal rupture. Carperitide can have additional benefits from the viewpoint of minimal activation of neurohumoral factors in the treatment of dogs with MR. Additional studies in dogs with spontaneous disease are warranted. [ABSTRACT FROM AUTHOR]

This white paper provides a critical analysis of methods for estimating transporter kinetics and recommendations on proper parameter calculation in various experimental systems. Rational interpretation of transporter-knockout animal findings and application of static and dynamic physiologically based modeling approaches for prediction of human transporter-mediated pharmacokinetics and drug-drug interactions (DDIs) are presented. The objective is to provide appropriate guidance for the use of in vitro, in vivo, and modeling tools in translational transporter science. [ABSTRACT FROM AUTHOR]

An increased risk of testicular cancer in men with infertility and poor semen quality has been reported. In view of the high cure rates for testicular germ cell tumours, increasing clinical importance is being placed on the protection of fertility. High-dose cytostatic therapy may be expected to cause long-term infertility. Thus, the standard procedure for fertility protection is the cryopreservation of ejaculated spermatozoa or testicular tissue before therapy. Four male patients with azoospermia and two patients with very severe oligozoospermia underwent onco-testicular sperm extraction ( TESE). We attempted onco- TESE in patients with azoospermia and very severe oligozoospermia after orchiectomy. Of the patients with testicular germ cell tumours, four had spermatozoa in their testicular tissues. Sertoli cell-only syndrome was found in one patient, and one patient showed maturation arrest without the detection of spermatozoa. Three of six showed seminomatous germ cell tumour, two of six had nonseminomatous germ cell tumour and one patient showed no malignancy. Two patients achieved clinical pregnancy. Fertility challenges in men with cancer are the most straightforward because of the relative ease of obtaining and cryopreserving sperm. Testicular sperm extraction is a useful technique for obtaining spermatozoa before cytotoxic therapy in azoospermic and very severely oligozoospermic cancer patients. [ABSTRACT FROM AUTHOR]

Introduction Indications for the application of hematopoietic stem cell transplantation ( HSCT) from alternative donors have remarkably broadened in scope; however, the incidence of infections that lead to failure of HSCT, such as human herpesvirus-6 ( HHV-6) encephalitis, has also increased. Methods We analyzed risk factors for symptomatic HHV-6 reactivation and the development of HHV-6 encephalitis in 140 consecutive adult patients who received allogeneic HSCT at our institution. Stem cell sources for the recipients were as follows: related-donor bone marrow in 40, related-donor peripheral blood in 5, unrelated bone marrow in 67, and unrelated cord blood in 28. Results Symptomatic HHV-6 reactivation occurred in 22 patients (16%), and 11 patients manifested encephalitis. Multivariate Cox proportional hazards regression analysis identified cord blood cell transplantation ( CBT) as an independent predictor of HHV-6 reactivation ( P = 0.008). Hyponatremia or hypernatremia at the time of HHV-6 reactivation was detected before the development of HHV-6 encephalitis in 2 or 4 patients, respectively. Two patients died of HHV-6 encephalitis and 6 patients died of relapse of underlying diseases. Survival analysis identified higher risk of the disease ( P = 0.021) and HHV-6 encephalitis ( P = 0.003) as independent risk factors for reduced overall survival. Conclusion In cases involving CBT or unrelated-donor transplantation, patients should be carefully monitored for the symptomatic reactivation of HHV-6. [ABSTRACT FROM AUTHOR]

A Si(111) winged crystal has been designed to minimize anticlastic bending and improve sagittal focusing efficiency. The crystal was thin with wide stiffening wings. The length-to-width ratio of the crystal was optimized by finite element analysis, and the optimal value was larger than the `golden value'. The analysis showed that the slope error owing to anticlastic bending is less than the Darwin width. The X-rays were focused two-dimensionally using the crystal and a tangentially bent mirror. The observed profiles of the focal spot agreed well with the results of a ray-tracing calculation in the energy range from 8 to 17.5 keV. X-ray diffraction measurements with a high signal-to-noise ratio using this focusing system were demonstrated for a small protein crystal. [ABSTRACT FROM AUTHOR]

Background Platelet concentrates ( PC) are prepared by centrifugation of platelet-rich plasma ( PRP) that is prepared by centrifugation of whole blood. The resuspension of the platelet pellet during PC preparation from dogs is difficult because of platelet activation induced by centrifugation. Objectives To investigate the efficacy of adding prostaglandin E1 ( PGE1) to prevent platelet activation during PC preparation from dogs. Animals Fifteen healthy Beagle dogs. Methods Prospective, experimental trial: PGE1 was added to PRP before the high-speed centrifugation during PC preparation. To estimate the effect of this addition, we assessed the platelet aggregability before transfusion, the survival of the platelets after transfusion, and the platelet reactivity after transfusion, which is estimated by the P-selectin expression of the platelets when stimulated by thrombin. Results The difficulty associated with platelet resuspension was resolved by PGE1. PGE1 strongly inhibited platelet aggregation induced by collagen and ADP; however, it recovered after the platelets were resuspended in plasma without PGE1 (mean aggregation ratio; collagen: 10.00-80.80%, ADP: 8.20-53.60%). Survival of the platelets after transfusion was not affected by PGE1 (mean 8.04 and 7.56 days, without and with PGE1), and thrombin-induced P-selectin expression after transfusion in PGE1-treated PC was also well maintained (mean positive ratio 53.7 and 47.9%, before and 24 hours after transfusion). Conclusions and Clinical Importance The addition of PGE1 in PRP before the centrifugation of PRP can improve the preparation efficiency of PC from dogs, while maintaining the therapeutic efficacy of the platelets. [ABSTRACT FROM AUTHOR]

Background The effects of pimobendan on left atrial pressure ( LAP) in dogs with mitral valve disease ( MR) have not been documented in a quantitative manner. Objective The objective was to document and study the short-term effects of pimobendan on LAP and echocardiographic parameters in MR dogs. Animals Eight healthy Beagle dogs weighing 10.0-14.7 kg (3 males and 5 females; aged 2 years) were used. Methods Experimental, cross-over, and interventional study. Dogs with surgically induced MR received pimobendan at either 0.25 mg/kg or 0.50 mg/kg PO q12h for 7 days and then, after a 7-day wash-out period, the other dosage. LAP was measured for 30 minutes at baseline and again on days 1, 2, 4, and 7 of pimobendan administration. Results Mean LAP was significantly decreased after the administration of 0.25 mg/kg (15.81 ± 5.44 mmHg to 12.67 ± 5.71 mmHg, P < .001) and 0.50 mg/kg (15.76 ± 5.45 mmHg to 10.77 ± 5.23 mmHg, P < .001). Also, the 0.50 mg/kg group led to a significantly lower LAP ( P < .01) compared with the 0.25 mg/kg group. Significant reduction was seen for the first time 4 days after the administration of 0.25 mg/kg and a day after the administration of 0.50 mg/kg. Conclusions and Clinical Importance Pimobendan decreased LAP in a dose-dependent manner in dogs with acute MR caused by experimental chordal rupture. This study did not evaluate adverse effects of high-dose pimobendan, and additional studies in clinical patients are warranted. [ABSTRACT FROM AUTHOR]

The article focuses on the molecular aspect of SmartAmp method and its clinical application to detect single-nucleotide polymorphism (SNP) in relation to personalized medicine. SmartAmp involves isothermal DNA amplification reaction with five primers and mismatch binding protein. It mentions that several studies examined different drug transporter genes such as Thiopurine S-methyltransferase (TPMT) and ATP-binding cassette, sub-family C, member 4 (ABCC4) in the Japanese blood samples.

With 5 figures and 2 tables Use of resistance genes would be the most effective way to address Fusarium wilt caused by Fusarium oxysporum f.sp. melonis in melon. In this study, based on the BAC 31O16 sequence which contains the cluster of melon resistance gene homologue, we developed four new DNA markers linked to Fom‐1, a dominant resistance gene against F. oxysporum f.sp. melonis races 0 and 2. Linkage analysis using 125 F2 plants derived from the cross between P11 (fom‐1fom‐1) and MR‐1 (Fom‐1Fom‐1) indicated that Fom‐1 was located between CAPS markers C‐MRGH12 and 62‐CAPS at a distance of 0.4 and 1.2 cM, respectively. Map position of Fom‐1 was confirmed using another mapping population consisting of 104 recombinant inbred lines derived from the cross P11 × MR‐1. The analysis of 43 fixed lines and 27 commercial F1 hybrids showed that the developed DNA markers linked to Fom‐1 correctly predicted the genotype in relation to the variety, suggesting that the region around the Fom‐1 locus is very polymorphic or there is no linkage disequilibrium between the locus and the marker loci. [ABSTRACT FROM AUTHOR]

The effects of furosemide on left atrial pressure (LAP) in dogs with mitral regurgitation (MR) have not been documented in a quantitative manner and between different routes of administration. To document LAP and echocardiographic parameters in MR dogs administered furosemide IV or PO, in order to document changes in LAP after furosemide treatment. Five healthy Beagle dogs (3 males and 2 females; aged 2 years) were used. Experimental, cross-over, and interventional study. LAP was measured before the administration of furosemide, and 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours after administration. Furosemide 1, 2, or 4 mg/kg IV, PO or placebo was administered. LAP was significantly decreased with all administrations of furosemide but not after placebo ( P < .05, respectively). The max reduction was observed 1 hour (1 mg/kg IV, 15.04 ± 7.02 mmHg), 3 hours (2, 4 mg/kg IV, 13.28 ± 8.01, 9.23 ± 4.92 mmHg), 4 hours (1 mg/kg PO, 14.68 ± 11.51 mmHg), and 5 hours (2, 4 mg/kg PO, 13.19 ± 10.52, 10.70 ± 7.69 mmHg). E wave and E/Ea were significantly decreased corresponding to the reduction of LAP after administration of 2 and 4 mg/kg ( P < .05, respectively). LAP was decreased in proportion to the dosage of furosemide, which did not significantly differ between IV and PO of the same dosages. E wave and E/Ea might be useful for the treatment evaluation of furosemide. [ABSTRACT FROM AUTHOR]

We herein report clinical assessments of efficacy and side effects of T replacement therapy (TRT) in men with late-onset hypogonadism (LOH). The study included 56 patients who were diagnosed with LOH and treated with TRT for at least 6 months at our institution. Age, ageing male symptom (AMS) scale, and androgen decline in the ageing male (ADAM) questionnaires were examined. Fasting blood samples were analysed for sex hormones, total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), red blood cell count (RBC), haemoglobin (Hb), haematocrit (Ht), and prostate-specific antigen (PSA). Total and psychological symptoms scores were measured by the AMS scale and the ADAM questionnaire score, demonstrating that the sum of positive responses to the questions were significantly improved after TRT ( P < 0.05). TC, HDL, and LDL cholesterol, TG, AST, ALT, γ-GTP, RBC, Hb, Ht, and PSA were not significantly different between before and after TRT. Although TRT for men with LOH may cause favorable changes in psychological conditions, it may not have effects on lipid metabolism, liver function, RBC, and PSA level. [ABSTRACT FROM AUTHOR]

Background: Despite many epidemiological reports concerning the efficacy of angiotensin-converting enzyme (ACE) inhibitors in dogs with mitral regurgitation (MR), the hemodynamic effects of ACE inhibitor administration have not been fully evaluated. Objectives: To document left atrial pressure (LAP) in dogs with MR administered ACE inhibitors, in order to obtain interesting information about daily LAP changes with administration of ACE inhibitors. Animals: Five healthy Beagle dogs weighing 9.8 to 14.2 kg (2 males and 3 females; aged 2 years). Methods: Experimental, crossover, and interventional study. Chordae tendineae rupture was induced, and a radiotelemetry transmitter catheter was inserted into the left atrium. LAP was recorded for 72 consecutive hours during which each of 3 ACE inhibitors—enalapril (0.5 mg/kg/d), temocapril (0.1 mg/kg/d), and alacepril (3.0 mg/kg/d)—were administered in a crossover study. Results: Averaged diurnal LAP was significantly, but slightly reduced by alacepril ( P= .03, 19.03 ± 3.01–18.24 ± 3.07 mmHg). The nightly drops in LAP caused by alacepril and enalapril were significantly higher than the daily drops ( P= .03, −0.98 ± 0.19 to −0.07 ± 0.25 mmHg, and P= .03, −0.54 ± 0.21–0.02 ± 0.17 mmHg, respectively), despite the fact that the oral administrations were given in the morning. Systolic blood pressure (122.7 ± 14.4–117.4 ± 13.1 mmHg, P= .04) and systemic vascular resistance (5800 ± 2685–5144 ± 2077 dyne × s/cm5, P= .03) were decreased by ACE inhibitors. Conclusions and Clinical Importance: ACE inhibitors decrease LAP minimally, despite reductions in left ventricular afterload. ACE inhibitors should not be used to decrease LAP. [ABSTRACT FROM AUTHOR]

Background: Intravenous administration of human immunoglobulin G (hIVIgG) has been suggested to potentiate thromboembolism in dogs, but supportive scientific reports are lacking. Objectives: To determine if hIVIgG therapy promotes hypercoagulability and inflammation in dogs. Animals: Twelve healthy Beagle dogs. Methods: Prospective, experimental trial. An hIVIgG/saline solution was infused IV at 1 g/kg BW over 8 hours to 6 dogs, and physiological saline was infused to the other 6 dogs. Blood samples were drawn before, during, and after infusion for serial measurement of indicators of coagulation and inflammation. Data were analyzed by 2-way repeated measures analysis of variance. Results: Dogs administered hIVIgG developed mildly decreased blood platelet concentrations without thrombocytopenia (median, 200 × 103/μL; range, 150–302 × 103/μL; P < .01), leukopenia (median, 3.5 × 103/μL; range, 20–62 × 103/μL; P < .001), and mildly increased plasma total protein concentrations (median, 6.3 g/dL; range, 5.6–6.7 g/dL; P < .001). Administration of hIVIgG was also associated with increases in fibrin/fibrinogen degradation products in all dogs (either 5 μg/mL or 10 μg/dL), thrombin-antithrombin III complexes (median, 7.2 ng/mL; range, 4.9–14.2 ng/mL; P < .001), and C-reactive protein concentrations (median, 2.5 mg/dL; range, 0.5–4.3 mg/dL; P < .01). Conclusion and Clinical Importance: Administration of hIVIgG to dogs promotes hypercoagulability and an inflammatory state. This should be further evaluated and considered when using hIVIgG in dogs with IMHA or other prothrombotic conditions. [ABSTRACT FROM AUTHOR]

Testicular torsion causes ischaemia-reperfusion (I-R) injury of testis and might lead to male infertility. Its injury initiates a pathophysiological cascade, including an activation of inflammatory cytokines and generation of nitric oxide and other reactive oxygen species. Vascular endothelial growth factor (VEGF) mediates angiogenesis and promotes endothelial cell survival. The aim of our study was to investigate the time course expression of VEGF, VEGF-receptor (R)1, VEGF-R2, nitric oxide synthases (NOS) in experimental I-R injury of rat testis. In torsion side testis, the expression of VEGF protein and mRNA significantly increased in a time-dependent manner ( P < 0.001 and P < 0.001, respectively). Although the expression of VEGF-R1 mRNA was increased in a similar way ( P < 0.001), VEGF-R2 mRNA expression was not detected. In immunohistochemistry, the increase in VEGF protein staining was observed in testicular vascular endothelial cells and germ cells at 24 h after reperfusion. Significant activation of inducible NOS and endothelial NOS was investigated at 12 and 24 h after reperfusion ( P < 0.01 and P < 0.001, respectively). This is the first report to show the time course expression of VEGF in experimental I-R rat testis. [ABSTRACT FROM AUTHOR]

Background: Mitral valve regurgitation (MR) causes increased left atrial pressure (LAP) and is associated with occurrence of clinical signs. It will be useful to understand diurnal variations of LAP for the management of MR. Hypothesis: Circulatory parameters and diurnal rhythm are linked to clinical signs in cardiac diseases. LAP also exhibits a diurnal rhythm in dogs with MR. Animals: Five healthy Beagle dogs weighing 9.8–12.8 kg (3 males and 2 females; aged 2 years) were used. Methods: A radiotelemetry system for continuous measurement of LAP was used in this study. Rupture of the chordae tendineae was experimentally induced via left atriotomy, and a transmitter catheter was inserted into the left atrium. The body of the transmitter was implanted SC. After clinical condition was stabilized, the severity of MR was evaluated by echocardiography, and LAP was recorded for 72 consecutive hours for the analysis of diurnal variation. Results: Abrupt increases in LAP, which averaged 16.7 mmHg, were observed at feeding periods. In contrast, strong diurnal LAP variations were found, with a significant but slight increase in daytime LAP compared with nighttime LAP. Conclusions and Clinical Importance: Diurnal LAP is characterized by a slight but significant nocturnal decrease and abrupt increases in response to excitation. The latter seemed to be more important considering the relationship with clinical manifestations. The clinical relevance of exercise restriction in the management of MR was acknowledged. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate predictors of the improvement of semen characteristics after low ligation for patients with varicoceles. The records of 97 oligozoospermic patients who underwent microsurgical left or bilateral inguinal varicocele repair were retrospectively evaluated. We assessed factors that could be predictors of the improvement of semen characteristics using logistic regression analysis. We evaluated age, testicular volume, varicocele grade, serum follicle-stimulating hormone (FSH), luteinising hormone, testosterone, sperm concentration and motility before low ligation. Among the 97 patients, sperm concentration improved from 6.4 ± 5.8 to 24.2 ± 35.1 million ml−1 and sperm motility increased from 32.8 ± 24.9% to 41.0 ± 14.6% in 55 patients (57%). In logistic regression analysis, pre-operative serum FSH and testosterone concentration were predictors of sperm concentration improvement. Varicocele repair improved sperm concentration and motility. Low serum FSH and high testosterone are significant factors predicting the improvement of semen characteristics before low ligation. [ABSTRACT FROM AUTHOR]

Similarly, whilst most pancreatic cancer, including metastatic lesion has hypovascular pattern, metastatic tumours from Paget's disease has an isovascular pattern, suggesting that sweat gland adenocarcinoma may have a different contrast pattern from that of gastrointestinal adenocarcinoma. Endoscopic ultrasonography (EUS) showed hypoechoic masses in the head (Fig 1c) and body of the pancreas with irregular borders, unclear tumor boundaries, and relatively homogeneous internal echoes. Gastrointestinal: Pancreatic metastasis from extramammary Paget's disease diagnosed by endoscopic ultrasound-guided fine-needle biopsy. [Extracted from the article]

Immunoglobulin A (IgA) is considered to play a major role in protection of the mucosal surface. However, its immunological and biological properties have not been extensively studied because the production of IgA class monoclonal antibodies (mAbs) is difficult. We compared the properties of IgA and IgG mAbs against Shiga toxin B subunits (Stx1B). These mAbs were secreted from hybridomas that had been produced from mice after intranasal immunization with recombinant Stx1B and cholera toxin. The dose response curves for the binding of the IgA (clone G2G7) and IgG (clone D11C6) mAbs to immobilized Stx1B were similar, as revealed on ELISA. The majority of the IgA mAb formed dimers while the IgG mAb was monomeric, as judged by immunoblot analysis. The IgG mAb completely inhibited the binding of Stx1B to Burkitt’s lymphoma cell line Ramos, while the inhibition by the IgA mAb was only partial. The IgG mAb was able to neutralize the cytotoxicity of Stx1 holotoxin towards Vero cells, whereas the IgA mAb was not. The binding affinity of each binding site was compared by means of surface plasmon resonance analysis involving a capture method, with which the binding of soluble Stx1B to immobilized mAb was detected. The association rate was similar but the dissociation rate was twofold faster in the case of the IgA mAb, resulting in twofold higher affinity of the IgG mAb. These results suggest that one can obtain high affinity IgA mAb but toxin neutralization is another challenge as to therapeutic antibodies of the IgA class. [ABSTRACT FROM AUTHOR]

It has been postulated that immune modulation and activation play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM), but evidence for this has not yet been well documented. We explored the changes in peripheral immunocompetent cells in relationship to the severity of T2DM in 142 patients, and 34 healthy individuals in Japan. A severity index with 0-12 grades was derived based on the HbA1c level and the number of complications. By multiple regression analysis, the severity index was positively associated with neutrophil counts and negatively associated with platelet and CD19+ lymphocyte counts. However, we did not observe any significant changes in other lymphocyte subsets such as CD4+, CD8+, and CD56+. These results suggest that poor diabetic control may be marked by changes in some blood cell types. [ABSTRACT FROM AUTHOR]

Background Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollens is a major problem in Japan. Omalizumab, a humanized monoclonal anti-IgE antibody, improves symptoms associated with SAR, but a comparative study with an anti-allergy drug has not yet been conducted. Objective To compare the efficacy and safety of omalizumab with suplatast tosilate, a selective T-helper type 2 (Th2) cytokine inhibitor, in patients with Japanese cedar pollen-induced SAR. Methods A randomized, double-blind, double-dummy study was conducted in 308 Japanese patients with a history of moderate-to-severe SAR who showed a CAP-RAST value (⩾2+) specifically to Japanese cedar pollens. Patients were treated for 12 weeks with omalizumab plus placebo of suplatast tosilate or suplatast tosilate plus placebo of omalizumab. Results The mean daily nasal symptom medication scores (sum of the daily nasal symptom severity score and daily nasal rescue medication score) were significantly lower in the omalizumab group than in the suplatast tosilate group during three evaluation periods ( P<0.001). The omalizumab group also had significantly lower mean daily nasal severity scores, each of the mean daily nasal and ocular symptom severity scores (sneezing, runny nose, stuffy nose, itchy nose, itchy eyes, watery eyes, and red eyes). Omalizumab reduced rescue medication requirements, and the proportion of days with any rescue medication use in the omalizumab group was significantly lower. Serum-free IgE levels markedly decreased in the omalizumab group and it was associated with clinical efficacy. The adverse reaction profiles were similar between the two groups. The overall incidence of injection site reactions was higher in the omalizumab group than in the suplatast tosilate group, but all these events were of mild degree. No anti-omalizumab antibodies were detected. Conclusion Omalizumab showed significantly greater improvements than suplatast tosilate in the treatment of SAR induced by Japanese cedar pollens. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the short-term impact of an occlusal highspot on the occurrence of orofacial symptoms by collecting self-evaluation and using electromyography (EMG) evaluation. A rigid unilateral intercuspal occlusal highspot (A cast onlay of 0·5 mm) was placed on the right lower first molar of six adult volunteers (three males, three females), and remained for 6 days. Continuously all the induced orofacial symptoms were collected and the subjects scored the orofacial pain on a 10-cm visual analogue scale (VAS) during the placement of onlay. The surface EMG was recorded before the placement of onlay, during (on the 3rd and 6th day) and after the onlay was removed. Then the contractile symmetry of bilateral masseter (MAL, MAR) and anterior temporalis (TAL, TAR) was measured by using an asymmetry index. On the 3rd day of the placement of the occlusal highspot, all subjects complained of headache in right temporal region (meanVAS ± s.d. = 3·7 ± 0·5); the activity of TAR at rest position of mandible increased significantly ( P = 0·027). In addition, on the 3rd and 6th day with the highspot the EMG activity of the tested muscles during maximal voluntary contraction (MVC) was significantly reduced; the asymmetry index of bilateral anterior temporalis during MVC was increased significantly ( P3rd = 0·028; P6th = 0·046). A unilateral occlusal highspot may make the ipsilateral anterior temporalis become tenser at rest position. Furthermore, the activity of bilateral anterior temporalis becomes more unsymmetrical during MVC although there are inter-individual differences between subjects. The changes in muscular activity may have some relationship with the occurrence of tension-type headache in temporal region. [ABSTRACT FROM AUTHOR]

Expression of sonic hedgehog (Shh), a morphogen for the gastric fundic glands, is reduced in the atrophic mucosa that develops in association with Helicobacter pylori infection, resulting in impaired differentiation of the fundic gland cells, increased expression of trefoil factor family 2 (TFF2) and the formation of spasmolytic polypeptide (SP)-expressing metaplasia (SPEM), a preneoplastic lesion. However, it is still unresolved whether H. pylori-induced inflammation and the resultant reduction in parietal cell number or reduced parietal cell function per se reduces Shh expression. The present study was designed to clarify the expression of Shh and TFF2 in the context of parietal cell dysfunction in the absence of inflammation, using histamine H2 receptor-knockout (H2R-null) mice and an acid exposure model. Age-matched H2R-null mice and wild-type (WT) mice were used. The expression of Shh and TFF2 mRNA was quantified by quantitative RT-PCR. Immunohistochemistry was also performed to detect the expression of Shh, TFF2 and cell markers. To study the effects of acid exposure, HCl solution was administered to the animals. The H2R-null mice exhibited higher gastric pH, increased TFF2 expression and reduced Shh expression. Impaired mucous neck-to-zymogenic cell differentiation was observed in the H2R-null mice. Furthermore, Shh expression increased in the presence of gastric acid and showed a significant correlation with gastric surface pH. In conclusion, our results suggest that persistent parietal cell dysfunction alone (suppressed gastric acid secretion), in the absence of inflammation or parietal cell loss caused by H. pylori infection, may be sufficient to down-regulate Shh expression in TFF2-overexpressing preneoplastic lesions of the gastric fundus. Since exposure to acid restored fundic Shh expression, appropriate gastric acid secretion may play an important role in the morphogen dynamics involved in the maintenance of gastric fundic gland homeostasis. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background and Purpose: The reduction of skin blood flow induced by local cooling results from a reflex increase in sympathetic output and an enhanced vasoconstrictor activity of cutaneous vessels. The present study investigated the latter local response in vivo in tetrodotoxin-treated mice, in which the sympathetic nerve tone was abolished.Experimental Approach: Male ddY mice, anaesthetized with pentobarbitone, were treated with tetrodotoxin and artificially ventilated. The plantar skin blood flow (PSBF) was measured by laser Doppler flowmetry.Key Results: Cooling the air temperature around the left foot from 25 to 10 degrees C decreased the PSBF of the left foot. Bunazosin, an alpha (1)-adrenoceptor antagonist, RS79948, an alpha (2)-adrenoceptor antagonist, and MK-912, an alpha (2C)-adrenoceptor antagonist, all significantly inhibited the cooling-induced reduction of PSBF; the inhibition by bunazosin was relatively small compared with that by RS79948 and MK-912. The response was not affected by guanethidine or bretylium, but was diminished in adrenalectomized mice. An intra-arterial injection of clonidine, an alpha (2)-adrenoceptor agonist, to the left iliac artery of adrenalectomized mice caused a transient decrease in PSBF, which was significantly augmented at 10 degrees C. MK-912 suppressed only the augmented portion at 10 degrees C. Y-27632, H-1152 and fasudil, Rho kinase inhibitors, also inhibited the cooling-induced reduction of PSBF. RS79948 caused no further reduction of the cooling-induced response after the inhibition by Y-27632.Conclusions and Implications: Local cooling-induced reduction of skin blood flow in mice primarily results from increased reactivity of alpha (2C)-adrenoceptors to circulating catecholamines, in which the Rho/Rho kinase pathway is involved. [ABSTRACT FROM AUTHOR]

Background and purpose:The reduction of skin blood flow induced by local cooling results from a reflex increase in sympathetic output and an enhanced vasoconstrictor activity of cutaneous vessels. The present study investigated the latter local response in vivo in tetrodotoxin-treated mice, in which the sympathetic nerve tone was abolished.Experimental approach:Male ddY mice, anaesthetized with pentobarbitone, were treated with tetrodotoxin and artificially ventilated. The plantar skin blood flow (PSBF) was measured by laser Doppler flowmetry.Key results:Cooling the air temperature around the left foot from 25 to 10°C decreased the PSBF of the left foot. Bunazosin, an α1-adrenoceptor antagonist, RS79948, an α2-adrenoceptor antagonist, and MK-912, an α2C-adrenoceptor antagonist, all significantly inhibited the cooling-induced reduction of PSBF; the inhibition by bunazosin was relatively small compared with that by RS79948 and MK-912. The response was not affected by guanethidine or bretylium, but was diminished in adrenalectomized mice. An intra-arterial injection of clonidine, an α2-adrenoceptor agonist, to the left iliac artery of adrenalectomized mice caused a transient decrease in PSBF, which was significantly augmented at 10°C. MK-912 suppressed only the augmented portion at 10°C. Y-27632, H-1152 and fasudil, Rho kinase inhibitors, also inhibited the cooling-induced reduction of PSBF. RS79948 caused no further reduction of the cooling-induced response after the inhibition by Y-27632.Conclusions and implications:Local cooling-induced reduction of skin blood flow in mice primarily results from increased reactivity of α2C-adrenoceptors to circulating catecholamines, in which the Rho/Rho kinase pathway is involved.British Journal of Pharmacology (2007) 152, 91–100; doi:10.1038/sj.bjp.0707380; published online 9 July 2007 [ABSTRACT FROM AUTHOR]