Previous studies have demonstrated the virtual lack of analgesia in mu opioid receptor knockout mice after systemic administration of morphine. Thus, it has been suggested that analgesic actions of ...morphine are produced via the mu opioid receptor, despite its ability to bind to kappa and delta receptors in vitro. However, it is not clear whether the results of these studies reflect the effect of morphine in the spinal cord. In the present study, we report study of the analgesic actions of spinally-administered morphine and other opioid receptor agonists in mu opioid receptor knockout and wild type mice. Morphine produced a dose-dependent antinociceptive effect in the tail flick test in the knockout mice, although higher doses were needed to produce antinociception than in wild type mice. The antinociceptive effect of morphine was completely blocked by naloxone (a non-selective opioid antagonist) and nor-binaltorphimine (nor-BNI, a selective kappa-opioid receptor antagonist), but not by naltrindole (a selective delta-opioid receptor antagonist). U-50,488H (a selective kappa-opioid receptor agonist) also produced a dose-dependent antinociceptive effect in knockout mice but presented lower analgesic potency in knockout mice than in wild type mice. Analgesic effects of
d-Pen2,
d-Pen5enkephalin (DPDPE, a selective delta-opioid receptor agonist) were observed in wild type mice but abolished in knockout mice. SNC80 (a selective delta-opioid receptor agonist) was not antinociceptive even in wild type mice. The present study demonstrated that morphine can produce thermal antinociception via the kappa opioid receptor in the spinal cord in the absence of the mu opioid receptor. Lower potency of U50,488H in mu opioid receptor knockout mice suggests interaction between kappa and mu opioid receptors at the spinal level.
We report here a case of a primitive neuroectodermal tumor involving the frontal skull base in a 5-month-old male infant. He presented with rapidly progressing exophthalmos on the left side. ...Preoperative magnetic resonance imaging revealed a well-demarcated, enhanced mass of 6 cm in diameter in the intradural extra-axial frontal region. The tumor was totally removed by surgery. Pathological findings were consistent with a primitive neuroectodermal tumor (PNET). Intradural extra-axial PNET is very rare, and its prognosis is poor.
Serum uric acid (UA) levels reflect circulating xanthine oxidase activity and oxidative stress production. Hyperuricemia has been identified in patients who have congestive heart failure and is a ...marker of poor prognosis in such patients. We investigated the relation between serum UA levels and Killip’s classification suggestive of the severity of heart failure and whether hyperuricemia influences mortality of patients who have acute myocardial infarction (AMI). Using the Japanese Acute Coronary Syndrome Study database, we evaluated 1,124 consecutive patients who were hospitalized within 48 hours of onset of symptoms of AMI from January to December 2002. There was a close relation between serum UA concentration and Killip’s classification. Patients who developed short-term adverse events had high UA concentrations. Serum UA levels, Killip’s class, age, and peak creatine phosphokinase level were significant predictors of long-term mortality. The hazard ratio for patients in the highest quartile of UA was 3.7 compared with those in the lowest quartile for death after AMI after adjustment for independent factors that were related to mortality. The combination of the best UA cutoff (447 μmol/L) for predicting survival based on receiver-operating characteristics analysis and Killip’s class significantly predicted the prognosis of acute and long-term AMI-related complications. In conclusion, our results suggest that hyperuricemia after AMI is associated with the development of heart failure. Serum UA level is a suitable marker for predicting AMI-related future adverse events, and the combination of Killip’s class and serum UA level after AMI is a good predictor of mortality in patients who have AMI.
This study evaluated the role of nitric oxide (NO) in spinal cord nociceptive transmission during peripheral inflammation evoked by formalin injection into the rat paw, using Nω-nitro-L-arginine ...(N-Arg), an NO syn-thase inhibitor. Male rats were prepared with intrathecal (IT) catheters. To quantify the formalin response, the instances of “flinching behavior” were counted at 5-min intervals for 60 min. IT N-Arg depressed the flinching behavior in a dose-dependent manner when N-Arg was administered 10 min before the formalin injection. This N-Arg effect was reversed with L-arginine but not D-arginine. We conclude that NO plays an important role in nociceptive transmission in the spinal cord during the formalin test.
Background
Neuropathic pain is regarded as one of the main causes of cancer pain refractory to standard opioid therapy in palliative care. The use of adjuvant analgesics for neuropathic cancer pain ...is largely empirical and the true efficacy of these adjuvant analgesics has been unknown. Gabapentin is one of the new promising anticonvulsant drugs as an adjuvant analgesic for neuropathic cancer pain.
Methods
The clinical usefulness of gabapentin in combination with opioids for Japanese patients with neuropathic cancer pain was assessed in an open-label, single-center, prospective study. Gabapentin was initiated in addition to the drugs currently being administered. The dose of gabapentin was titrated from 200 mg to a maximum dose of 2400 mg per day over 15 days, based on discussion with each patient. The primary endpoint variable was the numerical rating scale (NRS) of 0–10 measured using the brief pain inventory.
Results
From February 2007 to December 2007, gabapentin was administered to 24 patients that were already receiving an opioid without sufficient analgesia. Administration of gabapentin statistically reduced the worst-NRS, the least-NRS, and the average-NRS (7.3 → 5.8, 3.6 → 3.0, 5.8 → 4.5, respectively). Four patients (16.7%) were withdrawn from the study because of adverse events (headache, myoclonus, heartburn, bronchial asthma).
Conclusion
Although gabapentin might be regarded as a promising new adjuvant analgesic for neuropathic cancer pain, our results indicated that the decrease in pain score was of minimal clinical benefit. Controlled trials with other adjuvant analgesics are needed.
The spinal mechanisms underlying the hyperesthetic state during inflammation are little understood. To gain a better understanding of these mechanisms, this study evaluated the effects of intrathecal ...morphine; MK-801, an N-methyl-D aspartic (NMDA) antagonist; and CP-96,345, an NK1 antagonist, on the hyperesthesia observed after carageenan injection of the rat paw.
In rats injected with 2 mg carageenan, the paw withdrawal latency (PWL) for the injected paw was typically 5-6 s less than that for the untreated paw, at 2 h after the carageenan injection. Drugs were administered 2 h after the carageenan injection. The magnitude of hyperesthesia was evaluated with the difference score (DS), which was calculated by subtracting the PWL of the untreated paw from the PWL of the injected paw.
Intrathecal morphine increased PWLs of both the injected and the untreated paws equally in a dose-dependent manner, but intrathecal morphine did not affect the level of DS. Intrathecal MK-801 increased PWLs of the injected paw to the level of the untreated paw in a dose-dependent manner and increased the DS levels. Intrathecal CP-96,345 had no effect on PWLs of either the injected or the untreated paw. Coadministration of MK-801 with morphine reduced the DS for each dose of morphine.
These data indicate that (1) an NMDA receptor, but not an NK1 receptor, plays an important role in maintaining the hyperesthesia after carageenan injection; and (2) NMDA antagonism has a simple additive interaction with morphine in the carageenan model of inflammatory hyperesthesia.
Diodes with GaAsNSb/GaAs multiple quantum wells (MQWs) were grown on p-GaAs(0
0
1) substrates by metalorganic molecular-beam epitaxy. Negative differential resistance (NDR) characteristics were ...clearly observed at room temperature. The peak-to-valley current ratio was as high as 6 and the peak current density was
∼1.7
A/
cm
2
. The NDR characteristics were also observed for a GaAsNSe/GaAs MQW diode and a GaAsNSe-based tunnel junction diode. The mechanism of the observed NDR is discussed considering the band offsets in the nitrogen-related GaAsNSb/GaAs and GaAsNSe/GaAs MQWs.
Endothelin (ET)-A and ET-B receptors have been reported to exist in the spinal cord but the roles of ET-A and ET-B receptors in the spinal cord are poorly understood. To gain a better understanding ...of the roles of ET-A and ET-B receptors in nociceptive information transmission in the spinal cord, this study evaluated the effects of ET-1, ET-3, Sarafotoxin S6c (an ET-B receptor-selective agonist) and (R)2-(R)-2-(S)-2-1- (hexahydro-1H-azepinyl)carbonylamino-4-methyl-pentanoylamino-3- 3-(1-methyl-1H-indolyl)propionylamino-3-(2-pyridyl)propionic acid (FR139317, an ET-A receptor-selective antagonist) on the agitation behavior evoked by formaldehyde solution injection and on the thermal nociceptive test. The s.c. injection of formaldehyde solution into the hind paw evoked a biphasic flinching (phase 1, 0-9 min; phase 2, 10-60 min) of the injected paw. For the purpose of data analysis, phase 2 was further divided into two phases (phase 2a, 10-34 min; phase 2b, 35-60 min). Intrathecal injection of ET-1 depressed the phase 1 and 2 flinching behavior in a dose-dependent manner and this ET-1 effect was antagonized by FR139317. Intrathecal injection of either ET-3 or Sarafotoxin S6c enhanced the phase 2a flinching behavior in a dose-dependent manner. Intrathecal injection of the highest doses of ET-1, ET-3 and Sarafotoxin S6c had no effect on the thermal nociceptive test. These data indicate that ET-A and ET-B receptors have a powerful effect on spinal nociceptive processing evoked by formaldehyde solution injection but not that evoked by thermal stimulation.
This paper describes techniques for an impedance-sensing circuit integrated into a capacitive fingerprint sensor to prevent spoofing with a fake finger. We have reported a sensor chip with an ...embedded impedance-sensing function. We proposed an impedance-sensing circuit that features current-to-voltage con- version using a unity gain buffer. Here, the design of the sensing circuit is discussed. The detectable impedance range and the sensitivity are analyzed within the impedance range for various human fingers. A test chip with the proposed circuit was fabricated using 0.5-μm CMOS/sensor processes. The results confirm that the difference in impedance between a real finger and a fake finger is detected without any degradation of the original characteristics of the fingerprint sensor chip.
Generally, a highly crystallized polymer has a significantly better thermal-conductive property than amorphous polymers. This is due to the more effective thermal-energy transmission of the ordered ...structure in the crystals. Therefore, it is reasonable to expect that the system in which the aligned network structure was introduced has a higher thermal-conductivity property. In this study, to obtain a highly ordered network structure, the liquid-crystalline epoxy resin was cured under a magnetic field. We then investigated the thermal-conductivity property of the cured epoxy resin, which has an ordered network structure. Moreover, we discuss the relationship between the thermal-conductivity property and the anisotropy of cured epoxy resin.
