Communication between the temporomandibular joint articular space and the extradural space in patients with temporal bone pneumatization: implications for temporomandibular joint surgery.

The pneumatization of the articular portion of the temporal bone is an anatomical variant that can modify the barrier between the articular space and the middle cranial fossa. Thus, this study aimed to identify the presence and degree of pneumatization, as well as the existence of pneumatic cell dehiscence towards the extradural or articular space determining whether it could lead to direct communication between the articular and extradural spaces. Hence, One-hundred skull computed tomography images were selected. The presence and extension of pneumatization were classified according to scores 0, 1, 2, and 3. Dehiscence towards extradural and articular spaces was recorded. In total, 200 TMJ from 100 patients were assessed and 40.5% of pneumatization cases were observed. The most prevalent score was 0 (restricted to the mastoid process), while the least prevalent score was 3 (extending beyond the crest of articular eminence). Dehiscence of the pneumatic cells towards the extradural space is more common than towards the articular space. One complete communication between the extradural and articular spaces was observed. Considering the results, it was concluded that to avoid neurological and ontological complications, awareness of the potential anatomical communications between articular and extradural spaces, particularly in patients with extensive pneumatisation, is necessary.

Relationships between management factors in dairy production systems and mental health of farm managers in Japan.

To facilitate sustainable dairy farming, it is essential to assess and support the mental health of dairy farm workers, which is affected more than that of workers in other industries, as indicated by the relatively few studies to date. In addition, the limited investigations on mental health in dairy workers minimize the opportunities to suggest practical approaches of improvement of their mental health. Therefore, further data acquisition and analysis is required. In the present study, we undertook quantitative surveys on 17 management factors and administered a mental health questionnaire to 81 dairy farm managers (80 male, 1 female) in Hokkaido, northern Japan. The management factors were categorized into 3 groups: production input, production output, and facility indicator; mental health was evaluated based on the Center for Epidemiologic Studies Depression Scale (CES-D). Principal component analysis assigned the factors into 2 groups: intensiveness factors of dairy production systems (PC1: livestock care cost, fat- and protein-corrected milk, stocking density, medical consultation fee per unit time per animal unit, nonfamily wages, fertilizer and pesticide expenses, and net agricultural income ratio) and basic dairy management factors (PC2: net agricultural income ratio, quantity of concentrate feed, and milk quality variable). The depression symptoms of dairy farm managers were not significantly associated with PC1 and milking methods; however, they were significantly negatively associated with PC2, which integrated 3 management factors, including factors related to finances, feeding, and milk quality. According to the findings of the present study, the efforts needed for stable economic farm management, adequate feed supply, and milk quality maintenance may increase the depression levels of dairy farm managers and negatively affect their mental health. These findings could be the basis for future studies on the relationship between the mental health of farm managers and sustainable dairy farm management and production.

Routine Referral by Urologists Increase Opportunities for Corneal Donation.

BACKGROUND: The levels of corneal donation are insufficient to meet the demand for corneal transplantation in Japan. To overcome this problem, we started to routinely mention the possibility of corneal donation to the families of patients who died in our hospital's Urology Department in February 2008. In this study, we evaluated the effectiveness of this approach. METHODS: We retrospectively reviewed the medical records of the patients who died in the Department of Urology, St. Marianna University School of Medicine Hospital, and analyzed the patients' characteristics and information about corneal donation. RESULTS: In total, 211 patients died in our department between February 2008 and March 2017, and 155 patients were medically suitable corneal donors. We mentioned the possibility of corneal donation to 129 (83.2%) families, and 29 (18.7%) families agreed. Three families subsequently withdrew their consent. Finally, 26 (16.8%) of the families that were approached about corneal donation by urologists agreed to donate their relatives' corneas. Another 2 families voluntarily offered to donate their relatives' corneas. Thus, 28 (18.1%) of 155 medically suitable donors donated their corneas for transplantation. Twenty-six (92.8%) donors were 60 years or older and all donors were affected with malignant genitourinary tumors. Fifty-four (96.4%) corneas were successfully transplanted into recipients. CONCLUSIONS: Even elderly patients who die of solid carcinoma can be an important source of corneal donors. In this study, we showed that routine referral by urologists increased corneal donation. If this approach were adopted by other departments, it might further increase the number of corneal donations.

Biological characteristics of staphylococcal enterotoxin Q and its potential risk for food poisoning.

AIMS: To elucidate the biological characteristics and stability of a newly identified staphylococcal enterotoxin Q (SEQ) against heating and digestive enzymes and to evaluate the risk of seq-harbouring Staphylococcus aureus in food poisoning. METHODS AND RESULTS: Purified SEQ was treated with heating, pepsin and trypsin which are related to food cooking, stomach and intestine conditions, respectively. Superantigenic activity of SEQ was assessed by determining the ability of IL-2 induction in mouse spleen cells. The emetic activity of SEQ was assessed using house musk shrew, a small emetic animal model. The results revealed that SEQ exhibits a remarkable resistance to heat treatment and pepsin digestion and has significant superantigenic and emetic activities. Furthermore, a sandwich ELISA for detection of SEQ production was developed, and the results showed that seq-harboring S. aureus isolates produce a large amount of SEQ. CONCLUSIONS: The newly identified SEQ had remarkable stability to heat treatment and digestive enzyme degradation and exhibited significant superantigenic and emetic activities. In addition, seq-harbouring S. aureus isolated from food poisoning outbreaks produced a large amount of SEQ, suggesting that seq-harbouring S. aureus could potentially be a hazard for food safety. SIGNIFICANCE AND IMPACT OF THE STUDY: This study found, for the first time, that SEQ, a nonclassical SE, had remarkable stability to heat treatment and enzyme degradation and exhibited significant emetic activity, indicating that SEQ is a high-risk toxin in food poisoning.

Sensitization of TRPV1 by protein kinase C in rats with mono-iodoacetate-induced joint pain.

OBJECTIVE: To assess the functional changes of Transient receptor potential vanilloid 1 (TRPV1) receptor and to clarify its mechanism in a rat mono-iodoacetate (MIA)-induced joint pain model (MIA rats), which has joint degeneration with cartilage loss similar to osteoarthritis. METHODS: Sensitization of TRPV1 in MIA rats was assessed by transient spontaneous pain behavior induced by capsaicin injection in knee joints and electrophysiological changes of dorsal root ganglion (DRG) neurons innervating knee joints in response to capsaicin. Mechanisms of TRPV1 sensitization were analyzed by a newly developed sandwich enzyme-linked immunosorbent assay that detects phosphorylated TRPV1, followed by functional and expression analyses of protein kinase C (PKC) in vivo and in vitro, which involves TRPV1 phosphorylation. RESULTS: Pain-related behavior induced by intra-articular injection of capsaicin was significantly increased in MIA rats compared with sham rats. In addition, capsaicin sensitivity, evaluated by capsaicin-induced inward currents, was significantly increased in DRG neurons of MIA rats. Protein levels of TRPV1 remained unchanged, but phosphorylated TRPV1 at Ser800 increased in DRG neurons of MIA rats. Phosphorylated-PKCɛ (p-PKCɛ) increased and co-localized with TRPV1 in DRG neurons of MIA rats. Capsaicin-induced pain-related behavior in MIA rats was inhibited by intra-articular pretreatment of the PKC inhibitor bisindolylmaleimide I. In addition, intra-articular injection of the PKC activator phorbol 12-myristate 13-acetate increased capsaicin-induced pain-related behavior in normal rats. CONCLUSION: TRPV1 was sensitized at the knee joint and at DRG neurons of MIA rats through PKC activation. Thus, TRPV1 sensitization might be involved in chronic pain caused by osteoarthritis.

Imaging mass spectrometry detects dynamic changes of phosphatidylcholine in rat hippocampal CA1 after transient global ischemia.

BACKGROUND AND PURPOSE: The initial steps in the cascade leading to cell death are still unknown because of the limitations of the existing methodology, strategy, and modalities used. METHODS: Imaging mass spectrometry (IMS) was used to measure dynamic molecular changes of phosphatidylcholine (PC) species in the rat hippocampus after transient global ischemia (TGI) for 6min. Fresh frozen sections were obtained after euthanizing the rats on Days 1, 2, 4, 7, 10, 14, and 21. Histopathology and IMS of adjacent sections compared morphological and molecular changes, respectively. RESULTS: Histopathological changes were absent immediately after TGI (at Day 1, superacute phase). At Days 2-21 after TGI (from subacute to chronic phases), histopathology revealed neuronal death associated with gliosis, inflammation, and accumulation of activated microglia in CA1. IMS detected significant molecular changes after TGI in the same CA1 domain: increase of PC (diacyl-16:0/22:6) in the superacute phase and increase of PC (diacyl-16:0/18:1) in the subacute to chronic phases. CONCLUSIONS: Histopathology and IMS can provide comprehensive and complementary information on cell death mechanisms in the hippocampal CA1 after global ischemia. IMS provided novel data on molecular changes in phospholipids immediately after TGI. Increased level of PC (diacyl-16:0/22:6) in the pyramidal cell layer of hippocampal CA1 prior to the histopathological change may represent an early step in delayed neuronal death mechanisms.

Evaluation of the Glasgow Prognostic Score in patients receiving chemoradiotherapy for stage III and IV esophageal cancer.

High Glasgow Prognostic scores (GPSs) have been associated with poor outcomes in various tumors, but the values of GPS and modified GPS (mGPS) in patients with advanced esophageal cancer receiving chemoradiotherapy (CRT) has not yet been reported. We have evaluated these with respect to predicting responsiveness to CRT and long-term survival. Between January 2002 and December 2011, tumor responses in 142 esophageal cancer patients (131 men and 11 women) with stage III (A, B and C) and IV receiving CRT were assessed. We assessed the value of the GPS as a predictor of a response to definitive CRT and also as a prognostic indicator in patients with esophageal cancer receiving CRT. We found that independent predictors of CRT responsiveness were Eastern Cooperative Oncology Group (ECOG) performance status, GPS and cTNM stage. Independent prognostic factors were ECOG performance status and GPS for progression-free survival and ECOG performance status, GPS and cTNM stage IV for disease-specific survival. GPS may be a novel predictor of CRT responsiveness and a prognostic indicator for progression-free and disease-specific survival in patients with advanced esophageal cancer. However, a multicenter study as same regime with large number of patients will be needed to confirm these outcomes.

Goblet cells are involved in translocation of staphylococcal enterotoxin A in the intestinal tissue of house musk shrew (Suncus murinus).

AIMS: To elucidate an entry site of staphylococcal enterotoxin A (SEA), which is a major toxin for staphylococcal foodborne poisoning, into gastrointestinal tissue using a house musk shrew model. METHODS AND RESULTS: House musk shrews were per orally administered with recombinant SEA and localization of SEA in gastrointestinal tissues was investigated by immunohistochemistry and immunoelectron microscopy 30 min after administration. SEA was detected in a subset of intestinal epithelial cells and lamina propria in the villi of jejunum and ileum. This observation was also found in gastrointestinal loops. Morphological characteristics of the SEA-immunopositive cells indicated that goblet cells are an entry site of SEA.SEA entered mucus-expelling goblet cells and the induction of mucus secretion by alyll isothiocyanate resulted in an intensive SEA signal. These results suggest that mucus secretion by goblet cells is important for the translocation of SEA. CONCLUSIONS: SEA can translocate across intestinal epithelia via mucus-expelling goblet cells. SIGNIFICANCE AND IMPACTS OF THE STUDY: An entry site of SEA during translocation across the gastrointestinal mucosal barrier was investigated. This study was the first to demonstrate the significance of goblet cells as an entry site of this bacterial toxin.

The Infundibular Recess Passes through the Entire Pituitary Stalk.

BACKGROUND AND PURPOSE: The infundibular recess (IR), commonly illustrated as a V-shaped hollow in the sagittal view, is recognized as a small extension of the third ventricle into the pituitary stalk. The precise morphology of the human IR is unknown. The present study sought to delineate the morphology of the IR using magnetic resonance imaging. MATERIALS AND METHODS: Subjects included 100 patients without acute cerebral infarcts, intracranial hemorrhage, intrasellar or suprasellar cysts, hydrocephalus, inflammatory disease, or brain tumors. Patients with symptoms of increased intracranial pressure, intracranial hypotension, or pituitary dysfunction were excluded. Thin-sliced, seamless T2-weighted sequences involving the optic chiasm, entire pituitary stalk, and pituitary gland were performed in axial and sagittal planes for each patient. The numbers of slices delineating the pituitary stalk and IR were recorded from the axial images and quantified as ratios. RESULTS: The pituitary stalk consistently appeared as a styloid- or cone-shaped structure with variable inclinations toward the third ventricle floor. The IR was delineated as a smoothly tapering, tubular extension of the third ventricle located in the central portion of the pituitary stalk. In 81 % of patients, the IR passed through the entire length of the pituitary stalk and reached the upper surface of the pituitary gland, which was identified in 40 % of the midsagittal images. CONCLUSIONS: The IR is a cerebrospinal fluid-filled canal passing through the center of the pituitary stalk and connects the third ventricle to the pituitary gland. It may function in conjunction with the pituitary gland.

Proton pump inhibitor after endoscopic resection for esophageal squamous cell cancer: multicenter prospective randomized controlled trial.

BACKGROUND: Whether proton pump inhibitors (PPIs) relieve heartburn or precordial pain after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to investigate the efficacy of PPI therapy for these symptoms after ER for ESCC. METHODS: We conducted a multicenter prospective randomized controlled trial among 15 hospitals in Japan. In total, 229 patients with cT1a ESCC were randomly assigned to receive PPI therapy for 5 weeks after ER (the PPI group, n = 115) or follow-up without PPI therapy (the non-PPI group, n = 114). The primary end point was the incidence of gastroesophageal reflux disease (GERD)-like symptoms after ER from a self-reported questionnaire (Frequency Scale for Symptoms of GERD). Secondary end points were ulcer healing rate at 5 weeks, incidence of pain, improvement rate of symptoms in those who started PPI therapy because of GERD-like symptoms in the non-PPI group, and adverse events. RESULTS: No significant difference was observed in the incidence of GERD-like symptoms after ER between the non-PPI and PPI groups (30 % vs 34 %, respectively). No significant differences were observed in the ulcer healing rate at 5 weeks (84 % vs 85 %) and incidence of pain within 1 week (36 % vs 45 %). In nine of ten patients (90 %) who started PPI therapy because of GERD-like symptoms in the non-PPI group, PPI administration relieved GERD-like symptoms. No adverse events related to PPI administration were observed. CONCLUSION: PPI therapy is not efficacious in reducing symptoms and did not promote healing of ulcers in patients undergoing ER for ESCC.

The Impact of c-Fos/Activator Protein-1 Inhibition on Allogeneic Pancreatic Islet Transplantation.

Unpreventable allograft rejection is one of the main problems in pancreatic islet transplantation (PIT). Therefore, it is imperative to develop a more effective immunosuppressive strategy. The blockade of transcription factors has been a central part of T cell-depleting immunosuppressive therapies, as typified by the use of calcineurin inhibitors. The inhibition of activator protein-1 (AP-1) offers a novel strategy for immunosuppression in PIT, although to date, no reports on the effects of AP-1 inhibition are available. In this study, we investigated the immunosuppressive effects of T-5224, a c-Fos/AP-1-selective inhibitor, on murine T cells activated by αCD3+αCD28 mAbs. T-5224 inhibited proliferation, CD25 up-regulation, and the production of IL-2 and interferon-γ. In addition, T-5224 blocked the nuclear translocation of c-Fos/AP-1 in activated murine T cells. In BALB/c (H-2(d) )-to-C57BL/6J (H-2(b) ) mouse PIT, the 2-week administration of T-5224 prolonged survival of 600 islet allografts in a dose-dependent manner. When combined with a 2-week low-dose tacrolimus, the T-5224 treatment markedly prolonged allograft survival to over 300 days, while the efficacy was indeterminate when transplanted islet allograft mass was reduced to 300. We conclude that the c-Fos/AP-1 inhibition by T-5224 is a potentially attractive strategy for allogeneic PIT.

Identification and characterization of novel Staphylococcus aureus pathogenicity islands encoding staphylococcal enterotoxins originating from staphylococcal food poisoning isolates.

AIMS: Horizontal transfer of Staphylococcus aureus pathogenicity islands (SaPIs) plays an important role in acquiring pathogenicity. This study aimed to identify novel SaPIs encoding staphylococcal enterotoxins (SEs) and to characterize their SE productivity and replication process. METHODS AND RESULTS: Four novel SaPIs (SaPITokyo12413, SaPITokyo11212, SaPITokyo12571 and SaPITokyo12381) were determined using the SaPI scanning method. These SaPIs were composed of mosaic structures containing reported sequences. Four strains harbouring novel SaPIs produced significant amounts of SEs to cause staphylococcal food poisoning (SFP). With focus on the interaction between the replication initiator protein (Rep) and the replication origin (ori sites) that are proposed to be important for the replication of SaPIs, each Rep was prepared and their two functions were confirmed: binding activity to ori sites and helicase activity. These activities were present in the Reps of SaPITokyo11212, SaPITokyo12571 and SaPITokyo12381, but were both absent in the Rep of SaPITokyo12413. CONCLUSIONS: All four novel SaPIs could give sufficient toxicity to Staph. aureus to cause SFP. However, SaPITokyo12413 may be restricted in its replication capacity, suggesting that it lacks transfer ability unlike the other SaPIs. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report to identify four novel SE-encoding SaPIs and to examine their toxicity and replication capacity. Because SaPIs deeply participate in SE acquisition, it is important to elucidate their characteristics for understanding Staph. aureus virulence and speculating regarding its evolution as a pathogen.

The clinical analgesic efficacy of buprenorphine.

WHAT IS KNOWN AND OBJECTIVE: Based on in vitro assays and select animal models, buprenorphine is commonly called a 'partial agonist'. An implication is that it should produce less analgesic effect in humans than so-called 'full agonists' such as morphine or fentanyl. However, buprenorphine has a multimechanistic pharmacology, and thus partial agonism at a specific receptor is not particularly relevant to its overall analgesic action. We review published clinical trials that directly compared the magnitude of buprenorphine's analgesic effect to analgesics commonly considered full agonists. COMMENT: Due to different signal transduction pathways, a drug can be a full agonist on one endpoint and a partial agonist on another. Therefore, we limited the present review to buprenorphine's analgesic effect. WHAT IS NEW AND CONCLUSION: Twenty-four controlled clinical trials were identified, plus a case report and dose-response curve. Based on complete or comparable pain relief, in buprenorphine had full clinical analgesic efficacy in 25 of the 26 studies.

Circular muscle contraction in the mice rectum plays a key role in morphine-induced constipation.

BACKGROUND: Although opioids induce intestinal muscle contraction and provoke constipation, the intestinal region(s) that contribute to the constipation have remained unclear. We report here a region-specific response of intestinal muscle contraction to morphine and its correlation with in vivo constipation. METHODS: Regions of mice small and large intestines were dissected histologically and circular muscle contractile responses were measured using isometric transducers. Bead expulsion assays were performed to assess in vivo constipation. KEY RESULTS: The strongest contraction in response to morphine was detected in the rectum. The distal and transverse colon also showed strong contractions, whereas weak responses were detected in the proximal colon, jejunum, and ileum. Regarding the sustainability of muscle contractions during morphine exposure, prolonged waves were detected only in the rectum, while the waves diminished gradually in other regions. To identify the mechanism(s) underlying this difference, we focused on nitric oxide synthase (NOS). In the distal colon, decreased contraction during morphine exposure was recovered by application of a NOS inhibitor (L-NAME), while a NOS substrate (L-arginine) enhanced contractile degradation. In contrast L-NAME and L-arginine modestly affected the sustained contraction in the rectum. To confirm the correlation with constipation, beads were inserted into the transverse colon, distal colon, or rectum after morphine administration and expulsion times were examined. Beads tended to stop at the rectum even when inserted in the deeper colonic regions. CONCLUSIONS & INFERENCES: The rectum showed the greatest response to morphine in both in vitro and in vivo analyses, therefore it may play a key role for opioid-induced constipation.

Global methylation levels in peripheral blood leukocyte DNA by LUMA and breast cancer: a case-control study in Japanese women.

BACKGROUND: Global hypomethylation has been suggested to cause genomic instability and lead to an increased risk of cancer. We examined the association between the global methylation level of peripheral blood leukocyte DNA and breast cancer among Japanese women. METHODS: We conducted a hospital-based case-control study of 384 patients aged 20-74 years with newly diagnosed, histologically confirmed invasive breast cancer, and 384 matched controls from medical checkup examinees in Nagano, Japan. Global methylation levels in leukocyte DNA were measured by LUminometric Methylation Assay. Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between global hypomethylation and breast cancer were estimated using a logistic regression model. RESULTS: Compared with women in the highest tertile of global methylation level, ORs for the second and lowest tertiles were 1.87 (95% CI=1.20-2.91) and 2.86 (95% CI=1.85-4.44), respectively. Global methylation levels were significantly lower in cases than controls, regardless of the hormone receptor status of the cancer (all P values for trend <0.05). INTERPRETATION: These findings suggest that the global methylation level of peripheral blood leukocyte DNA is low in patients with breast cancer and may be a potential biomarker for breast cancer risk.

Development and external validation of a nomogram for overall survival after curative resection in serosa-negative, locally advanced gastric cancer.

BACKGROUND: Few nomograms can predict overall survival (OS) after curative resection of advanced gastric cancer (AGC), and these nomograms were developed using data from only a few large centers over a long time period. The aim of this study was to develop and externally validate an elaborative nomogram that predicts 5-year OS after curative resection for serosa-negative, locally AGC using a large amount of data from multiple centers in Japan over a short time period (2001-2003). PATIENTS AND METHODS: Of 39 859 patients who underwent surgery for gastric cancer between 2001 and 2003 at multiple centers in Japan, we retrospectively analyzed 5196 patients with serosa-negative AGC who underwent Resection A according to the 13th Japanese Classification of Gastric Carcinoma. The data of 3085 patients who underwent surgery from 2001 to 2002 were used as a training set for the construction of a nomogram and Web software. The data of 2111 patients who underwent surgery in 2003 were used as an external validation set. RESULTS: Age at operation, gender, tumor size and location, macroscopic type, histological type, depth of invasion, number of positive and examined lymph nodes, and lymphovascular invasion, but not the extent of lymphadenectomy, were associated with OS. Discrimination of the developed nomogram was superior to that of the TNM classification (concordance indices of 0.68 versus 0.61; P < 0.001). Moreover, calibration was accurate. CONCLUSIONS: We have developed and externally validated an elaborative nomogram that predicts the 5-year OS of postoperative serosa-negative AGC. This nomogram would be helpful in the assessment of individual risks and in the consideration of additional therapy in clinical practice, and we have created freely available Web software to more easily and quickly predict OS and to draw a survival curve for these purposes.

A ten-year experience and follow-up of three hundred patients fitted with the Biomet/Lorenz Microfixation TMJ replacement system.

The purpose of this paper is to present the postoperative results obtained after full temporomandibular joint (TMJ) reconstruction employing the Biomet/Lorenz Microfixation TMJ replacement system (Jacksonville, FL, USA) in 300 patients (201 unilateral, 99 bilateral). Objective data (maximum inter-incisal opening; MIO) and subjective data (function and speech, diet, and pain) were collected preoperatively and at postoperative evaluations performed over a 10-year period (mean 3.5, standard deviation 2.1 years). The MIO measures were obtained using a calliper rule. Subjective data were evaluated using a visual analogue scale with scores ranging from 0 to 5 for each variable. The results were analyzed with the paired t-test (two-sided, α=5%). Each patient showed significant improvements for all of the variables at evaluation on postoperative day 7. The results for MIO, function and speech, and diet, showed improvements at each postoperative evaluation over a maximum of 3 years, with stabilization of the results from the fourth year. Complaints of pain decreased considerably up to the 1-month postoperative evaluation, and no patient reported severe pain at 6 months after surgery. The results presented show that the reconstruction of the TMJ through the installation of the Biomet/Lorenz system prosthesis is a safe and effective option for proper reestablishment of the joint and stomatognathic system function; significant long-term improvements in mandibular range of motion are promoted and pain levels decrease.

Identification of the sensory nerve fiber responsible for lysophosphatidic acid-induced allodynia in mice.

Lysophosphatidic acid (LPA) has been considered one of the molecular culprits for neuropathic pain. Understanding how LPA changes the function of primary afferent fibers might be an essential step for clarifying the pathogenesis of neuropathic pain. The present study was designed to identify the primary afferent fibers (Aß, Aδ, or C) participating in LPA-induced allodynia in ddY mice. Mechanical allodynia and thermal hyperalgesia were evaluated by the von Frey filament test and thermal paw withdrawal test, respectively. Sensory nerve fiber responsiveness was measured using a Neurometer. Daily repeated intrathecal treatment with LPA led to a decrease in the mechanical, but not thermal nociceptive threshold, and a reduction in the threshold for paw withdrawal induced by 2000-Hz (Aß fiber) and 250-Hz (Aδ fiber), but not 5-Hz (C fiber) sine-wave electrical stimulation. When the transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor agonist resiniferatoxin (RTX) was administered subcutaneously before the start of LPA treatment, LPA-induced mechanical allodynia and Aß and Aδ fiber hypersensitivity demonstrated by neurometry were not affected, indicating that TRPV1-expressing nerve fibers (possibly C fibers) might not be essential for LPA-induced allodynia. LPA-induced allodynia was reversed by treatment with RTX at 7 days after the start of LPA treatment. Expression of TRPV1 on myelinated nerve fibers after repeated intrathecal LPA treatment was observed in the dorsal root ganglion. These results suggest that sensitization of Aß and Aδ fibers, but not C fibers, contributes to the development of intrathecally administered LPA-induced mechanical allodynia. Moreover, increased or newly expressed TRPV1 receptors in Aß and Aδ fibers are considered to be involved in the maintenance of LPA-induced allodynia.

Magnetic phase diagram of clathrate compound Ce3Pd20Si6 with quadrupolar ordering.

We present results of specific heat measurements on a Ce3Pd20Si6 single crystal and construct the magnetic phase diagram for the three cubic principal directions [100], [110] and [111]. The highly anisotropic phase diagram is discussed and can be qualitatively explained by the Zeeman splitting at the 8c-site. For B â€– [100], the present study found two different quadrupolar ordered phases, which meet the paramagnetic phase at a tri-critical point and establish the new phase boundaries.