Eriodictyon angustifolium extract, but not Eriodictyon californicum extract, reduces human hair greying.

OBJECTIVE: Yerba Santa (Eriodictyon angustifolium and Eriodictyon californicum) has been used for many years in traditional medicine. However, the effect of Yerba Santa on melanogenesis has not yet been investigated. We aimed to assess the biological effects of Yerba Santa on hair pigmentation. METHODS: Yerba Santa extracts were assessed for their cytological effects following X-ray irradiation treatment and then tested directly for the prevention of human hair greying. Ultra-performance liquid chromatography (UPLC) was utilized to identify the individual extract components. RESULTS: Eriodictyon angustifolium extract significantly increased melanin synthesis in the melanoma cell line through activation of the WNT/MITF/tyrosinase-signalling pathway. In contrast, E. californicum had no effect on melanin synthesis. E. angustifolium extract also demonstrated a protective effect against the damage induced by X-ray irradiation in human keratinocytes. Application of the extracts to subjects who had grey beards demonstrated a reduced number of grey beard hair per year specifically with the E. angustifolium extract. A significant decrease in grey head hair was also observed after application of E. angustifolium extract. Upregulation of gene expression related to melanin production and WNT signalling was observed after the application of E. angustifolium extract. Sterubin was the most abundant flavonoid detected by UPLC in E. angustifolium extract. In addition, sterubin showed the highest difference in terms of quantity, between E. angustifolium and E. californicum extract. CONCLUSION: Eriodictyon angustifolium extract, which is abundant in sterubin, may be suitable as a potential cosmetic and medical agent for the prevention and improvement of hair greying.

OBJECTIF: Yerba Santa (Eriodictyon angustifolium et Eriodictyon californicum) est utilisé depuis de nombreuses années en médecine traditionnelle. Cependant, l'effet de Yerba Santa sur la mélanogenèse n'a pas encore été étudié. Notre objectif était d'évaluer les effets biologiques de Yerba Santa sur la pigmentation des cheveux. MÉTHODES: Les extraits de Yerba Santa ont été évalués pour leurs effets cytologiques après un traitement d'irradiation aux rayons X, puis testés directement pour la prévention du grisonnement des cheveux humains. La chromatographie liquide ultra-performante (UPLC) a été utilisée pour identifier les composants d'extrait individuels. RÉSULTATS: L'extrait d'E. angustifolium a augmenté de manière significative la synthèse de mélanine dans la lignée cellulaire du mélanome par l'activation de la voie de signalisation WNT/MITF/tyrosinase. En revanche, E. californicum n'a eu aucun effet sur la synthèse de mélanine. L'extrait d'E. angustifolium a également démontré un effet protecteur contre les dommages induits par l'irradiation aux rayons X dans les kératinocytes humains. L'application des extraits à des sujets qui avaient une barbe grise a démontré un nombre réduit de poils gris par an spécifiquement avec l'extrait d'E. angustifolium. Une diminution significative des cheveux gris a également été observée après l'application d'extrait d'E. angustifolium. Une régulation à la hausse de l'expression des gènes liée à la production de mélanine et à la signalisation WNT a été observée après l'application d'extrait d'E. angustifolium. La stérubine était le flavonoïde le plus abondant détecté par UPLC dans l'extrait d'E. angustifolium. De plus, la stérubine a montré la plus grande différence en termes de quantité entre E. angustifolium et E. californicum. CONCLUSION: L'extrait d'E. angustifolium, qui est abondant en stérubine, peut convenir comme agent cosmétique et médical potentiel pour la prévention et l'amélioration du grisonnement des cheveux.

Dual-layer detector CT of chest, abdomen, and pelvis with a one-third iodine dose: image quality, radiation dose, and optimal monoenergetic settings.

AIM: To compare the image quality and radiation dose of reduced iodine dose dual-layer detector (DL) computed tomography (CT) with those of a conventional 120 kVp protocol for chest-abdomen-pelvis CT (CAP-CT). MATERIALS AND METHODS: Forty patients with renal dysfunction (estimated glomerular filtrating ratio <45 ml/min/1.73 m2) underwent reduced iodine dose CAP-CT (120 kVp, 200 mg iodine/kg) on DLCT. Virtual monochromatic images (VMI) at 40-70 keV (5 keV interval) were reconstructed retrospectively. Forty matched patients who underwent conventional CAP-CT (120 kVp, 600 mg iodine/kg, iterative reconstruction) were included as controls. The size-specific dose estimate (SSDE), image noise, CT attenuation, and contrast-to-noise ratio (CNR) were compared between the protocols. Two radiologists rated image contrast, image noise, streak artefact, and diagnostic confidence on a five-point scale. RESULTS: The SSDE of the DLCT group was approximately 20% lower than that of the 120 kVp group (15.4±1.9 versus 19.4±2.3 mGy, p<0.01). DLCT-VMI provided almost constant image noise throughout the range of energies (differences of ≤13%), with the noise being equivalent or lower than 120 kVp in the abdomen. CT attenuation and CNR gradually increased as the energy decreased, with values comparable to 120 kVp being attained at around 45-50 keV. Although streak artefact was accentuated at 40-50 keV (p<0.01), the highest scores for diagnostic confidence were assigned at 40 and 45 keV, both of which were equivalent to 120 kVp (p=1.0). CONCLUSION: For CAP-CT with a one-third iodine dose, DLCT-VMI at 40-45 keV allows for a 20% reduction in radiation dose, while preserving image quality comparable to that of conventional 120 kVp protocol.

Study of factors related to the reflection abilities of dental trainees.

INTRODUCTION: This study analysed the internal and external factors related to the reflection abilities of dental trainees. PARTICIPANTS AND METHODS: We created transcripts from oral presentations by the dental trainees of Hiroshima University Hospital (n = 35, 2012-2013) at a significant event analysis conference. The reflection depths were compared between the trainees of the university hospital and external clinical combination groups. We determined and statistically analysed the reflection depths. RESULTS: At the end of training, a Mann-Whitney U-test revealed a significant difference in the median reflection depths of the groups (U = 66, W = 342 and P = 0.007). The results of multiple regression analysis indicated a significant relation between the reflection depth and external training completion (P = 0.024). There were no relations with other factors, including gender and academic background. CONCLUSION: Experiences in external clinics create a close connection between the staff and trainees because communities of practice can cause deeper reflections. We need to create small groups in large-scale organisations such as university hospitals. This construct can be adapted not only for Japanese dental trainees but also for global dental and other medical trainees.

Effectiveness of a simulated patient training programme based on trainee response accuracy and appropriateness of feedback.

INTRODUCTION: Simulated patients (SPs) need education and training in required skills to be effective resources in education. This study was conducted to examine the effectiveness of an SP training programme based on the accuracy of trainee responses and the appropriateness of their feedback. METHODS: Thirty-two applicants to the training programme and 35 experienced SPs were included in this study. The experienced SPs served as a reference group. The rate of accurate responses and the rate of appropriate feedback were assessed with pre- and post-training tests, and these two outcome measures were compared with those of the experienced SPs. RESULTS: No significant differences were found in trainee response accuracy or appropriateness of feedback between pre- and post-training tests. The response accuracy rate of the trainees on the pre-training test was significantly lower than that of SPs with 1-2 years of experience, whilst there was no significant difference between these SPs and the trainees on the post-training test. CONCLUSIONS: Although our study suggests that more training is needed to improve the skills of SPs, the training programme may contribute to helping trainees reach a novice level in the skill of providing accurate responses. SP training should be encouraged to contribute to the effectiveness of such teaching and to establish the validity of the assessment.

OSCEs in Japanese postgraduate clinical training Hiroshima experience 2000-2009.

BACKGROUND: Hiroshima University Hospital used the Objective Structured Clinical Examination (OSCE) as a formative and summative assessment tool to evaluate trainees' competence. AIM: To reflect on Hiroshima University Hospital experience of OSCEs in postgraduate training in terms of OSCE structure and trainees' perception of the OSCE they attended. METHODS: A total 27 OSCEs implemented in Hiroshima University Hospital from 2000 to 2009 were examined. The OSCE in postgraduate training, Hiroshima University Hospital, was influenced by many factors from organisational and pedagogical perspectives, and changed to meet social and curriculum needs. At each OSCE, all examinees were required to answer an anonymous questionnaire, which consisted of ten checklists, just after their experience of OSCE. RESULTS: Five hundred and forty trainees who attended each OSCE were required to answer a questionnaire and 510 were returned (94.4%). In the comparison between formative and summative OSCEs, the number of trainees who answered "the OSCE is meaningful" in formative OSCE was significantly higher than that in summative OSCE (P < 0.001). In the comparison between before and after the 2006/2007 academic year, trainees who indicated that OSCEs were meaningful increased after 2006/2007 (P < 0.05), and trainees who felt they were evaluated appropriately by these OSCEs increased after 2006/2007 (P < 0.01). CONCLUSION: Trainees viewed OSCEs positively and appreciated their effectiveness from a pedagogical perspective, and OSCE positively affected the trainees' approach to learning. A ten-year process of OSCE change has helped with educational reforms because of its adaptability. Flexible attitudes to change are necessary for stakeholders to achieve the desired reforms.

Nociceptin/orphanin FQ: role in nociceptive information processing.

Recently, opioid receptor like1 (ORL1) receptor was identified. The ORL1 receptor is a G protein coupled receptor and the sequence of the ORL1 receptor is closely related to that of the opioid receptors. Nociceptin/orphanin FQ has been identified as a potent endogenous agonist of the ORL1 receptor and the sequence of nociceptin/orphanin FQ is closely related to that of dynorphin A. Nociceptin/orphanin FQis not active at the classical opioid receptors, such as mu, kappa and delta receptors. The distribution of prepronociceptin mRNA is distinct from that of the opioid peptide precursor. Mice lacking the ORL1 receptor showed no significant differences in nociceptive threshold compared with wild mice. The role of nociceptin/orphanin FQ on nociceptive transmission is unclear. Intracerebroventricular (i.c.v.) injection of nociceptin/orphanin FQ produced hyperalgesia and allodynia and antagonized morphine analgesia. On the other hand, intrathecal injection of low dose nociceptin/orphanin FQ produces allodynia, but high dose of nociceptin/orphanin FQ produces an analgesic effect. Although we do not fully understand the mechanisms that produce the difference between the effect of i.c.v. injection of nociceptin/orphanin FQ and that of intrathecal injection of nociceptin/orphanin FQ, we believe that spinal ORL1 receptor may be the next receptor which should be targeted by drugs designed for the treatment of pain.

Mechanism of glucose-induced biphasic insulin release: physiological role of adenosine triphosphate-sensitive K+ channel-independent glucose action.

The mechanism of glucose-induced biphasic insulin release by the B cell was investigated using isolated rat pancreatic islets. In perifusion experiments, 16.7 mM glucose in combination with 25 mM K+ transformed the high K(+)-induced monophasic insulin release into a biphasic one in the presence of diazoxide (Dz), an ATP-sensitive K+ channel opener. Inclusion of Dz during the initial 6 min of glucose stimulation abolished the first phase, but was without effect on the second phase. In batch incubation experiments, fuels, including 16.7 mM glucose, 6 mM D-glyceraldehyde, and 10 mM 2-ketoisocaproate, but not sulfonylurea, caused time-dependent potentiation of the B cell so that the response to 25 mM K+, applied later, was increased in the fuel-primed islets. Inclusion of Dz or lowering extracellular Ca2+ (to micromolar range) during the priming, which eliminates the initiation of insulin release, did not eradicate the potentiation. We conclude that high glucose closes ATP-sensitive K+ channels, leading to membrane depolarization, Ca2+ influx, and initiation of insulin release (first phase), and subsequently self-augments insulin release in an ATP-sensitive K+ channel-independent manner (second phase), acting at steps distal to cytosolic Ca2+ elevation. The biphasic insulin release is thus generated by an interaction of ATP-sensitive K+ channel-dependent and -independent glucose actions.

Analgesic effect of intrathecally administered nociceptin, an opioid receptor-like1 receptor agonist, in the rat formalin test.

Nociceptin (a heptadecapeptide also known as orphanin FQ) is a potent endogenous agonist of the opioid receptor-like1 receptor and has a sequence similar to dynorphin A. It has been reported that intracerebroventricularly injected nociceptin produced hyperalgesia in mice and that intrathecal injection of nociceptin inhibits the spinal sensitization. In the present study, we investigated the effect of intrathecally administered nociceptin in the rat formalin test (a model of inflammatory pain) and the rat hot plate test. In the formalin test, drugs were administered 10 min before (pre-treatment study) or 7 min after (post-treatment study) the formalin injection. The paw formalin injection induces a biphasic flinching (phase 1, 0-7 min; phase 2, 10-60 min) of the injected paw. In the pre-treatment study, intrathecally administered nociceptin depressed both the phase 1 and phase 2 flinching behaviour in a dose-dependent manner, and, in the post-treatment study, intrathecal injection of nociceptin depressed the phase 2 flinching behaviour. In the pre-treatment study, the potency of nociceptin in depressing the phase 1 response was the same as that in depressing the phase 2 response. These effects of nociceptin were not antagonized by the co-administration of naloxone. Intrathecal injection of nociceptin had no effect on the hot plate test. These data suggest that nociceptin plays an important role in spinal nociceptive transmission through the activation of a naloxone-insensitive receptor, and spinally administered nociceptin produces an analgesic effect during the rat formalin test, but not the hot plate test.

Inhibition of spinal N-acetylated-alpha-linked acidic dipeptidase produces an antinociceptive effect in the rat formalin test.

N-acetyl-aspartyl-glutamate is a putative neurotransmitter and acts as a weak agonist at the N-methyl-D-aspartate receptor. N-acetyl-aspartyl-glutamate also acts as an agonist at the metabotropic glutamate receptor 3. N-acetyl-aspartyl-glutamate is hydrolyzed by N-acetylated-alpha-linked acidic dipeptidase to liberate N-acetyl-aspartate and glutamate. Recently, a specific inhibitor of N-acetylated-alpha-linked acidic dipeptidase, 2-(phosphonomethyl)pentanedioic acid, has been reported. In the present study, we examined the effect of i.t. administered 2-(phosphonomethyl)pentanedioic acid in the rat formalin test (a model of inflammatory pain) and the rat hot plate test. In the formalin test, drugs were administered 10min before (pre-treatment study) or 7min after (post-treatment study) the formalin injection. The paw formalin injection induces biphasic flinching (phase 1: 0-2min; phase 2: 10-60min) of the injected paw. In the pre-treatment study, i.t. administered 2-(phosphonomethyl)pentanedioic acid depressed both phases 1 and 2 flinching behavior in a dose-dependent manner but 2-(phosphonomethyl)pentanedioic acid had no effect on the flinching behavior in the post-treatment study. In the pre-treatment study, the potency of 2-(phosphonomethyl)pentanedioic acid in depressing the phase 2 response is greater than that in depressing the phase 1 response. Intrathecal injection of 2-(phosphonomethyl)pentanedioic acid had no effect in the hot plate test. We suggest that N-acetylated-alpha-linked acidic dipeptidase plays an important role in spinal nociceptive transmission and that inhibition of spinal N-acetylated-alpha-linked acidic dipeptidase produces an antinociceptive effect during the rat formalin test but not during the hot plate test.

Differential metabolic requirement for initiation and augmentation of insulin release by glucose: a study with rat pancreatic islets.

Insulin release, glucose utilization (3H2O formation from [5-3H]glucose), and glucose oxidation (14CO2 formation from [14C(U)]glucose) were determined in pancreatic islets from 96-h fasted rats at 37 degrees C and those from fed rats at 22 degrees C, using the islets from fed rats incubated at 37 degrees C as controls. In the islets from 96-h fasted rats and those from fed rats incubated at 22 degrees C, we could not demonstrate significant insulin release in response to high glucose concentrations of up to 16.7 mmol/l. However, 16.7 mmol/l glucose clearly augmented insulin release caused by a depolarizing concentration (50 mmol/l) of K+ in these islets: i.e. 16.7 mmol/l glucose plus 50 mmol/l K+ produced significantly greater insulin release than 50 mmol/l K+ alone. Glucose utilization and oxidation by the islet cells were suppressed by 96-h fasting of the rats or by lowering the incubation temperature to 22 degrees C, and depolarization with K+ at 50 mmol/l did not at all augment glucose utilization and oxidation by the islets. Thus we conclude that reduction of glucose metabolism in islets from fasted rats and in those incubated at low temperature eliminated initiation, but not augmentation, of insulin release by 16.7 mmol/l glucose. The data indicate that the metabolic threshold for the initiation of insulin release is significantly higher than it is for the augmentation of release by glucose.

Dynamic viscoelastic properties and the age changes of long-term soft denture liners.

The dynamic viscoelastic properties of long-term soft denture liners were measured over a wide range of frequencies using a dynamic viscoelastometer based on a non-resonance-forced vibration principle. Changes in properties over a 3 yr period have also been monitored. One acrylic material, one fluoroelastomer, one heat cured silicone and one self-curing addition silicone were used. Complex dynamic tensile modulus (E*), tensile storage modulus (E'), tensile loss modulus (E") and loss tangent (tan delta) were determined over the frequency range from 0.01 to 100 Hz on administration of a 0.27% strain at 37 degrees C. The dynamic viscoelasticity of the acrylic and fluoroelastomer products was more sensitive to changes in frequency than that of silicone products. The acrylic material and fluoroelastomer exhibited viscoelastic behaviour whilst silicones exhibited elastic behaviour. The silicone products remained unchanged after soaking for 3 yr whilst the acrylic and fluoroelastomer products underwent significant change.

The thermic effect is greater for structured medium- and long-chain triacylglycerols versus long-chain triacylglycerols in healthy young women.

The purpose of this study was to investigate the hypothesis that a single dose of structured medium- and long-chain triacylglycerols (SMLCTs) composed of medium-chain (20%) and long-chain (80%) fatty acids would increase the metabolic rate more than a dose of long-chain triacylglycerols (LCTs) in 15 healthy young women aged 18 to 28 years. The effects on postingestive energy expenditure were compared for SMLCTs versus LCTs. On the experimental days, the subjects fasted overnight and then ingested 1,680 kJ SMLCTs or LCTs each day. Energy expenditure and the respiratory quotient (RQ) were measured before and after SMLCT and LCT ingestion by indirect calorimetry. Blood samples were collected before and after ingestion to obtain plasma and serum. Postingestive total energy expenditure (PTEE) was significantly higher after SMLCT ingestion versus LCT ingestion (26.9 +/- 1.0 v 25.5 +/- 1.1 kJ/kg/6 h, P < .05). The thermic effects of the test oil were also significantly greater after SMLCT ingestion compared with LCT ingestion (3.02 +/- 0.49 v 1.47 +/- 0.82 kJ/kg/6 h, P < .01). Plasma glucose and serum triacylglycerol concentrations were not significantly different. Serum free fatty acid and 3-hydroxybutyric acid concentrations were higher after SMLCT ingestion versus LCT ingestion. These results suggest that long-term substitution of SMLCTs for LCTs will produce body fat loss if energy intake remains constant.

Role of spinal cyclooxygenase (COX)-2 on thermal hyperalgesia evoked by carageenan injection in the rat.

Prostaglandins, which are known to play an important role in the nociceptive transmission in the spinal cord, are produced by cyclooxygenase (COX). Two forms of COX have been identified, COX-1 (constitutive form) and COX-2 (a form highly inducible in response to inflammatory stimuli). COX-2 mRNA was reported to be expressed in the brain in normal rats in the absence of inflammation. We investigated the role of spinal COX-2 in the maintenance of thermal hyperalgesia induced by paw carageenan injection in the rat using NS-398, a selective COX-2 inhibitor. Intrathecally administered NS-398 attenuated the level of thermal hyperalgesia in a dose-dependent manner. This suggested that spinal COX-2 plays an important role in the maintenance of thermal hyperalgesia induced by paw carageenan injection.

Antagonism of ORLI receptor produces an algesic effect in the rat formalin test.

The authors investigated the role of endogenously released nociceptin (also known as orphanin FQ) spinal and supraspinal nociceptive transmission during the rat formalin test by examining the effect of intrathecal and intracerebroventricular injection of J-113397, a non-peptidyl ORL1 receptor selective antagonist. When J-113397 was injected intrathecally or intracerebroventricularly 10 min before the formalin injection, it enhanced the agitation behavior induced by paw formalin injection. This suggested that paw formalin injection induced nociceptin release in the spinal cord and the supraspinal brain sites, that this endogenously released nociceptin produced an analgesic effect and that J-113397 antagonized this analgesic effect of nociceptin and produced an algesic effect in the rat formalin test.

Zinc protoporphyrin IX, an inhibitor of the enzyme that produces carbon monoxide, blocks spinal nociceptive transmission evoked by formalin injection in the rat.

Carbon monoxide (CO) is now thought to act as a neural messenger, but the role of CO is poorly understood. In the present study, we investigated the role of CO in both the spinal thermal nociceptive transmission and spinal nociceptive transmission during peripheral inflammation using zinc protoporphyrin-IX (Zn-P), a potent inhibitor of hemoxygenase inhibitor (HO). Peripheral inflammation was induced by the paw formalin injection (formalin test). It is thought that CO acts as a second messenger for metabotropic glutamate receptor. We also investigated the effect of metabotropic glutamate receptor antagonists, L-2-amino-3-phosphonopropionic acid (L(+)AP3) and (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), on the formalin test. Drugs were administered intrathecally 5 min before (pre-treatment) or 7 min after (post-treatment) the formalin injection. In both the pre-treatment and the post-treatment study, Zn-P inhibited the formalin induced flinching behavior in a dose-dependent manner. Both L(+)AP3 and MCPG had no effect on the formalin induced flinching behavior in the pre-treatment study. Zn-P had no effect on the thermal nociceptive test. These data suggest that CO plays an important role in spinal nociceptive transmission during the formalin test, but not during the thermal nociceptive test, and that, during the formalin test, CO may not act as a second messenger for metabotropic glutamate receptor in the spinal cord.

Analysis of the effects of cyclooxygenase (COX)-1 and COX-2 in spinal nociceptive transmission using indomethacin, a non-selective COX inhibitor, and NS-398, a COX-2 selective inhibitor.

Prostaglandins are now thought to play an important role in nociceptive information transmission in the spinal cord. Prostaglandins are known to be produced by cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid. Two forms of COX have been identified: COX-1, which is constitutively expressed in most tissues and organs, and COX-2, which is an inducible enzyme and is localized primarily in inflammatory cells and tissues. COX-2 mRNA has been reported to be expressed in the brain in normal rats. We investigated the role of COX-1 and COX-2 in the spinal nociceptive transmission during the rat formalin test and the hot plate test using indomethacin, a non-selective COX-1 and COX-2 inhibitor, and NS398, a selective COX-2 inhibitor. In the formalin test, drugs were administered intrathecally or intraperitoneally 10 min before (pre-treatment study) or 7 min after (post-treatment study) the formalin injection. Both intrathecally administered indomethacin and NS398 inhibited the formalin induced flinching behavior in a dose-dependent manner in the pre-treatment study, but not in the post-treatment study. Both indomethacin and NS398 had no effect on the hot plate test at a dose which depressed the formalin induced flinching behavior. These data suggested that COX-2 is expressed in the central nervous system, including the spinal cord, and that COX-2 plays an important role in the spinal nociceptive transmission during the formalin test, but not during the hot plate test.

Spinal N-acetyl-alpha-linked acidic dipeptidase (NAALADase) inhibition attenuates mechanical allodynia induced by paw carrageenan injection in the rat.

N-Acetylated-alpha-linked acidic dipeptidase (NAALADase) hydrolyzes N-acetyl-aspartyl-glutamate (NAAG) to liberate N-acetyl-aspartate and glutamate. NAAG is a putative neurotransmitter and acts as a mixed agonist/antagonist on N-methyl-D-aspartate (NMDA) receptors and acts as an agonist on the metabotropic glutamate receptor 3 (mGluR3). In the present study, we examined the role of spinal NAALADase in the maintenance of mechanical allodynia induced by carrageenan injection, skin incision and mild thermal injury using 2-(phosphonomethyl)pentanedioic acid (2-PMPA), a specific NAALADase inhibitor, in rats. Mechanical allodynia was induced by injection of 2 mg carrageenan into the paw (carrageenan model), by creating a 1-cm longitudinal skin incision of the plantar aspect of the foot (post-operative model), or by application of thermal stimulation (52.5 degrees C) for 45 s to the hind paw (mild thermal injury model). 2-PMPA was administered intrathecally at the time when the maximum mechanical allodynia occurred. Mechanical allodynia was assessed by the measurement of mechanical threshold using von Frey filaments. The mechanical threshold was measured 5, 15, 30, 60 and 90 min after the drug administration. In the carrageenan model, 100 microg of 2-PMPA attenuated the level of mechanical allodynia. 2-PMPA had no effect on the level of mechanical allodynia in both the post-operative pain model and the mild thermal injury model. These data suggested that the inhibition of spinal NAALADase alleviated mechanical allodynia induced by paw carrageenan injection.

Effects of intrathecally administered nociceptin, an opioid receptor-like1 (ORL1) receptor agonist, on the thermal hyperalgesia induced by carageenan injection into the rat paw.

Nociceptin is a 17 amino acid peptide and acts as a potent endogenous agonist of the opioid receptor-like1 (ORL1) receptor. Nociceptin is reported to depress glutamatergic transmission and to block the spinal facilitation which is thought to be mediated by the activation of N-methyl-D-aspartate (NMDA) receptor. Paw carageenan injection induces thermal hyperalgesia which has been reported to be maintained by the NMDA receptor dependent spinal facilitation. In the present study, we investigated the effect of intrathecally administered nociceptin on the level of thermal hyperalgesia induced by carageenan injection in the rat. Nociceptin depresses the level of thermal hyperalgesia in a dose-dependent manner. These data suggest that spinal ORL1 receptor activation depresses the spinal facilitation state induced by paw carageenan injection.

Usefulness of the evidence-based medicine-supported cancer pain management guideline.

The Japanese guidelines for the clinical practice of cancer pain management supported by evidence-based medicine were established by the Japanese Society for Palliative Medicine in 1999 [as their Evidence-based Medicine-supported Cancer Pain Management Guideline ]. To evaluate usefulness of the Guideline for the management of cancer pain, the same questionnaires were addressed to nurses and physicians of enrolled institutions twice. The first survey was conducted before the distribution of the Guideline in July, 1999 and the second was done after the distribution in January, 2000. Usefulness of the Guideline was examined by comparing the results of two surveys. Cancer patients were divided into two groups depending on their stages (conservative or terminal). (1) Morbidity of pain in cancer patients at each stage having some analgesics did not change at each survey period. (2) At the first survey the rate of pain relief in each stage of cancer patients was essentially unchanged from a previous result obtained in 1998. (3) The rate of pain relief shown in the second survey tended to be higher than that shown in the first in both groups of patients. (4) The rate of pain relief with per os morphine was shown to be significantly higher in the second survey than in the first for each group of patients at conservative or terminal stage. (5) The rate of pain relief of patients staying in the ward where the guidance for dosing of morphine had been carried out was 37.5% at the first survey versus 47.9% at the second. (6) The answers from physicians to questions about treatment of cancer pain remained unchanged between the first and the second survey. The usefulness of the Guideline for cancer pain management is partly confirmed by these results. The significance of the Guideline will be totally discussed by comparing its effects on nurses, pharmacists and physicians.