Okayama University Medical SchoolActa Medica Okayama0386-300X7062016Isoflurane Induces Transient Impairment of Retention of Spatial Working Memory in Rats455460ENMasaakiTaninoDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMotomuKobayashiDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshihiroSasakiDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenTakataDepartment of Anesthesiology and Intensive Care Medicine, Kawasaki Medical SchoolYoshimasaTakedaDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiMizobuchiDivision of Anesthesiology, Department of Surgery Related, Kobe University Graduate School of MedicineKiyoshiMoritaOkayama UniversityTakuNagaiDepartment of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of MedicineHiroshiMorimatsuDepartment of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOriginal Article10.18926/AMO/54808Postoperative cognitive dysfunction (POCD) occurs in nearly one-third of patients after non-cardiac surgery. Many animal behavior studies have investigated the effect of general anesthesia on cognitive function. However, there have been no studies examining the effects on working memory specifically, with a focus on the retention of working memory. We demonstrate here that isoflurane anesthesia induces deficits in the retention of spatial working memory in rats, as revealed by an increase in isoflurane-induced across-phase errors in the delayed spatial win-shift (SWSh) task with a 30-min delay in an 8-arm radial arm maze on post-anesthesia days (PADs) 1,2,4, and 10. A post-hoc analysis revealed a significant increase in across-phase errors on PAD 1 and recovery on PAD 10 in the isoflurane group. In contrast, within-phase errors independent of the retention of working memory were unaffected by isoflurane. These results demonstrate that isoflurane anesthesia transiently impairs the retention of spatial working memory in rats.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6632012Antinociceptive Effects of Intrathecal Landiolol Injection in a Rat Formalin Pain Model285289ENSatoshiMizobuchiYoshikazuMatsuokaNorihikoObataRyujiKakuYoshitaroItanoNaotoTomotsukaArataTaniguchiHiroyukiNishieHirotakaKanzakiMamoruOuchidaKiyoshiMoritaOriginal Article10.18926/AMO/48569Perioperative beta-blocker administration has recently been recommended for patients undergoing cardiac or other surgery due to the beneficial cardiovascular effects of these agents. In addition, some studies have reported that perioperatively administered beta-blockers also have analgesic effects. In this study, to investigate the antinociceptive effects and the analgesic profile of landiolol, we examined the effects of intrathecal landiolol administration on nociceptive pain behavior and c-fos mRNA expression (a neural marker of pain) in the spinal cord using a rat formalin model. We found that pain-related behavior was inhibited by intrathecal landiolol administration. Moreover, the increase in c-fos mRNA expression on the formalin-injected side was less pronounced in rats administered landiolol
than in saline administered controls. Thus, intrathecal administration of landiolol exhibited antinociceptive
effects. Further investigation of the antinociceptive mechanism of landiolol is required.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6532011Expansion of CpG Methylation in the SFRP2 Promoter Region during Colorectal Tumorigenesis169177ENMasanoriTakedaTakeshiNagasakaSunDong-ShengHiroyukiNishieTetsuhiroOkaEijiYamadaYoshikoMoriKunitoshiShigeyasuTatsuyaMorikawaSatoshiMizobuchiToshiyoshiFujiwaraOriginal Article10.18926/AMO/46628Secreted frizzled-related protein 2, (SFRP2) is a Wnt inhibitor whose promoter CpGs were recently found to be methylated at high frequency in colorectal cancers (CRCs). We hypothesized that the pattern of SFRP2 methylation may differ throughout the promoter during progressive tumorigenesis. Using combined bisulfite restriction analysis (COBRA), two methylation-sensitive regions (Regions A and B) of the SFRP2 promoter were investigated in 569 specimens of colorectal tissue:222 CRCs, 103 adenomatous polyps (APs), 208 normal colonic mucosa from CRC patients (N-Cs), and 36 normal colonic mucosa from subjects with no evidence of colorectal neoplasia at colonoscopy (N-Ns). Extensive (including both Regions A and B) and partial (either Region A or B) SFRP2 methylation levels were found in 61.7% and 24.8% of CRCs, 8.7% and 37.9% of APs, 3.9% and 39.9% of N-Cs, and 0% and 30.6% of N-Ns, respectively. Extensive methylation of the SFRP2 promoter was present primarily in CRCs, while partial methylation was common in APs. Whereas APs with the KRAS mutant showed no correlation to any pattern of SFRP2 methylation, extensive methylation of the SFRP2 promoter was significantly associated with KRAS mutant CRCs (p＜.0001), suggesting that genetic alteration in the RAS-RAF pathway might precede the spread of CpG methylation through the SFRP2 promoter, which is observed in over 60% of advanced colorectal tumors.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6532011The Excitement of Multiple Noradrenergic Cell Groups in the Rat Brain Related to Hyperbaric Oxygen Seizure163168ENMinakoAraiKenTakataYoshimasaTakedaSatoshiMizobuchiKiyoshiMoritaOriginal Article10.18926/AMO/46627The mechanism of oxygen toxicity for central nervous system and hyperbaric oxygen (HBO) seizure has not been clarified. Noradrenergic cells in the brain may contribute to HBO seizure. In this study, we defined the activation of noradrenergic cells during HBO exposure by c-fos immunohistochemistry. Electroencephalogram electrodes were pre-implanted in all animals under general anesthesia. In HBO seizure animals, HBO was induced with 5 atm of 100% oxygen until manifestation of general tonic convulsion. HBO non-seizure animals were exposed to 25 min of HBO. Control animals were put in the chamber for 120 min without pressurization. All animals were processed for c-fos immunohistochemical staining. All animals in the HBO seizure group showed electrical discharge on EEG. In the immunohistochemistry, c-fos was increased in the A1, A2 and A6 cells of the HBO seizure group, and in the A2 and A6 cells of the HBO non-seizure group, yet was extremely low in all three cell types in the control group. These results suggest the participation of noradrenaline in HBO seizure, which can be explained by the early excitement of A1 cells due to their higher sensitivity to high blood pressure, hyperoxia, or by the post-seizure activation of all noradrenergic cells.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-15581069-101994無機フッ素による家兎腎障害に関する実験的研究10531061ENSatoshiMizobuchiSome of the halogenated inhalation anesthetics are metabolized partly in the liver to produce inorganic fluoride, and serum inorganic fluoride in continuous high concentration may cause renal dysfunction. In this study, the influence of elevated serum inorganic fluoride concentration and the duration of its action on renal function were studied by continuous infusion of sodium fluoride in rabbits for 24hours. The rabbits were divided into Control (group C), Low dose (group L) and High dose (group H) groups with mean serum inoganic fluoride levels of 1.9 μ M, 62.4 μ M and 237.7μ M, respectively. Twinty-four hour total urine volume increased in group H compared to group C. Urinary excretion of β2-microgloblin (β(2)MG), leucine aminopeptidase (LAP) and N-acetyl-β-D-glucosaminidase (NAG), collected every 6 hours, increased significantly in group H within 0～6 hours, whereas LAP increased within 18～24 hours and NAG within 12～18 hours in group L, compared to group C. The area under the curve of serum inorganic fluoride concentration, when the increase of NAG (the earliest among β(2)MG, LAP and NAG) excretion was detected (6 hours in group H, 18 hours in group L), were similar (group H ; 1272±165 μ M・hours, group L ; 1197±189 μ M・hours). Free water clearance over 24 hours increased significantly in group H only. Morphological examination showed the absence of the brush border and that cellular damage had occurred in the renal tubules in both group L and group H. These findings were more apparent in group H. In conclusion, it was revealed that not only the elevated serum inorganic fluoride concentration but also its duration were the factors inducing renal dysfunction, beginning with proximal tubuar damage and subsequently developing to decreased water reabsorption.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030155811912007末梢血行障害による虚血性疼痛に対するモルヒネ内服の効果5760ENHiroyukiNishieSatoshiMizobuchiTakashiMatsusakiAsakoMiyakeRyujiKakuShinichiIshikawaKenjiSatoMasakiMatsumiMoritaKiyoshiPeripheral arterial disease often causes ischemic ulcers due to impaired blood flow and consequentially induces intractable pain. For these patients, we have recently begun to administer morphine orally. In this study, we retrospectively examined the effects of oral morphine for the relief of pain caused by peripheral arterial disease.
Oral morphine was administered to 17 cases of peripheral arterial disease between January, 2004 and February, 2006. The initial dosage was 5 mg or 10 mg, started on an as-needed basis. After the daily dosage of morphine became constant, we divided the dosage into four or six times a day and administered it regularly. With the exception of one case, a small amount of oral morphine, from 20 mg to 70 mg a day, could alleviate patient's pain. Eight cases had side effects such as nausea, constipation or drowsiness.
Oral morphine is effective for pain relief of peripheral arterial disease patients. However, now in Japan, oral morphine, which we can prescribe for those patients with insurance, has a shorter duration of action, so we need to administer slow-release morphine. Oral morphine must be administered carefully because many peripheral arterial disease patients have cardiac disease or renal dysfunction as complications.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama1994無機フッ素による家兎腎障害に関する実験的研究ENSatoshiMizobuchiNo potential conflict of interest relevant to this article was reported.