The advantages of fentanyl for the treatment of pain: Studies of pharmacological profiles and fentanyl relatedside effects

The understanding of the pharmacological profiles of fentanyl and fentanyl-related side effects seems to be critical for the management for control of pain. Therefore, the present study was designed to investigate the advantages for treatment with fentanyl and the side effects such as emesis and gastrointestinal transit inhibition. The results demonstrated that fentanyl produced a profound antinociception in ferrets and mice than that induced by morphine. These findings are consistent with the experiences in the clinic. Morphine with lower doses than antinociceptive doses, produced a significant increase in gastrointestinal transit inhibition. However, fentanyl produced no gastrointestinal transit inhibition unlike morphine. These findings are consistent with the clinical experiences in the use of fentanyl. The clinical studies in patients chronic cancer pain showed that transdermal therapeutic delivery system for fentanyl (TTS-fentanyl) produces less side effects such as constipation, nausea and vomiting than that induced by oral morphine. Morphine with lower doses than that used for antinociceptive assay also produced either in the number of retching or vomiting. However, fentanyl failed to produce emetic response in ferrets. These findings indicate that fentanyl produces much less emesis than that induced by morphine. Finally, we conclude that fentanyl produced potent antinociception in ferrets and mice. In addition, fentanyl produced much less side effects including emesis and constipation. These findings may provide evidence for benefit and usefulness of fentanyl for clinical frame on the management of pain treatment.Key word: fentanyl; antinociception; emesis; ferret

Effect of a selective GABAB receptor agonist, baclofen, on the opioid-induced antinociception and rewarding effect

The management of excessive adverse effects is a major clinical problem. Multiple approaches have been described to address this problem. Successful pain management with opioids required the adequate analgesia without excessive side effects. The present study was designed to investigatethe effect of a selective GABAB receptor agonist baclofen on the opioid induced antinociception and rewarding effect. In the present study, we confirmed that either morphine or fentanyl produced a dose dependent antinociceptive effect in mice using tail-flick test. The results demonstratedthat co-administration of baclofen with morphine, fentanyl or oxycodone produced the synergistic effect on antinociception in mice. In the place preference study, we found that baclofen inhibited on morphine or fentanylinduced place preference in rats. These results suggest that coadministrationof baclofen with opioids produce synergistic antinociception with less effects of place preference We propose here that co-administration of baclofen with opioids may pave the way for the new strategy for the control of pain and recommended for the adjuvant drug.Key words : opioid, place preference, rewarding effects, baclofe

Reduced Adult Hippocampal Neurogenesis and Cognitive Impairments following Prenatal Treatment of the Antiepileptic Drug Valproic Acid

SummaryPrenatal exposure to valproic acid (VPA), an established antiepileptic drug, has been reported to impair postnatal cognitive function in children born to VPA-treated epileptic mothers. However, how these defects arise and how they can be overcome remain unknown. Using mice, we found that comparable postnatal cognitive functional impairment is very likely correlated to the untimely enhancement of embryonic neurogenesis, which led to depletion of the neural precursor cell pool and consequently a decreased level of adult neurogenesis in the hippocampus. Moreover, hippocampal neurons in the offspring of VPA-treated mice showed abnormal morphology and activity. Surprisingly, these impairments could be ameliorated by voluntary running. Our study suggests that although prenatal exposure to antiepileptic drugs such as VPA may have detrimental effects that persist until adulthood, these effects may be offset by a simple physical activity such as running

Cognitive dysfunction and amyloid β accumulation are ameliorated by the ingestion of green soybean extract in aged mice

AbstractThe effects of soybean extracts were investigated in senescence-accelerated (SAMP10) mice, a mouse model of brain senescence with cognitive dysfunction. Mature soybeans are usually yellow. However, the green soybean retains green color after being ripened. Cognitive functions were significantly better-preserved in aged mice fed green soybean than age-matched control mice with or without yellow soybean feeding. Molecular mechanisms of the beneficial effect of green soybean on brain functions were examined through transcriptome analysis of SAMP10 hippocampus. The high expression of Ptgds was significantly associated with green soybean diet, which encodes lipocalin-type prostaglandin D2 synthase, a putative endogenous amyloid β(Αβ)-chaperone. In consonance, Aplp1 expression was significantly reduced, a member of amyloid precursor proteins. Furthermore, the amount of Aβ 40 and 42 was reduced in the insoluble fraction of cerebral cortex. These results suggest that the intake of green soybean ameliorates cognitive dysfunction of aged mice through the reduction of Aβ accumulation

THE MONITORING SYSTEM OF THE ROCK SLOPE BY LAYING OPTICAL STRAIN SENSOR IN THE PRINT OF V

光ファイバをひずみセンサとして利用して、岩盤斜面のモニタリングに適用するために室内基礎実験を行なうとともに、実岩盤への適用性について検討した。The optics fiber is usually used to the basic main lines of informatics transmission. In recently，it has been attracted special interest that the optics fiber can be used to the strain sensor lines applicable on the some characterizations of this fiber. In this study the focus was on the strain measurement technology of optical fibers. It was conducted fundamental research for applying optical fibers to rock slope strain measurement. On the basis of theresult，the optical strain sensor was laid in the print of V in natural fracture rock slope. And the movement of a natural slope was measured by laid fibers on the slope.「第11回岩の力学国内シンポジウム」　日時：平成14年1月24～25日　場所：(財)海外職業訓練協会（千葉県幕張

Infectious virus shedding duration reflects secretory IgA antibody response latency after SARS-CoV-2 infection

新型コロナウイルス排出と粘膜抗体の関係を解明 --呼吸器ウイルスのヒト間伝播を制御・予防する第一歩--. 京都大学プレスリリース. 2023-12-25.Articles: Infectious virus shedding duration reflects secretory IgA antibody response latency after SARS-CoV-2 infection. 京都大学プレスリリース. 2023-12-25.Infectious virus shedding from individuals infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is used to estimate human-to-human transmission risk. Control of SARS-CoV-2 transmission requires identifying the immune correlates that protect infectious virus shedding. Mucosal immunity prevents infection by SARS-CoV-2, which replicates in the respiratory epithelium and spreads rapidly to other hosts. However, whether mucosal immunity prevents the shedding of the infectious virus in SARS-CoV-2-infected individuals is unknown. We examined the relationship between viral RNA shedding dynamics, duration of infectious virus shedding, and mucosal antibody responses during SARS-CoV-2 infection. Anti-spike secretory IgA antibodies (S-IgA) reduced viral RNA load and infectivity more than anti-spike IgG/IgA antibodies in infected nasopharyngeal samples. Compared with the IgG/IgA response, the anti-spike S-IgA post-infection responses affected the viral RNA shedding dynamics and predicted the duration of infectious virus shedding regardless of the immune history. These findings highlight the importance of anti-spike S-IgA responses in individuals infected with SARS-CoV-2 for preventing infectious virus shedding and SARS-CoV-2 transmission. Developing medical countermeasures to shorten S-IgA response time may help control human-to-human transmission of SARS-CoV-2 infection and prevent future respiratory virus pandemics

Tumour resistance in induced pluripotent stem cells derived from naked mole-rats

The naked mole-rat (NMR, Heterocephalus glaber), which is the longest-lived rodent species, exhibits extraordinary resistance to cancer. Here we report that NMR somatic cells exhibit a unique tumour-suppressor response to reprogramming induction. In this study, we generate NMR-induced pluripotent stem cells (NMR-iPSCs) and find that NMR-iPSCs do not exhibit teratoma-forming tumorigenicity due to the species-specific activation of tumour-suppressor alternative reading frame (ARF) and a disruption mutation of the oncogene ES cell-expressed Ras (ERAS). The forced expression of Arf in mouse iPSCs markedly reduces tumorigenicity. Furthermore, we identify an NMR-specific tumour-suppression phenotype—ARF suppression-induced senescence (ASIS)—that may protect iPSCs and somatic cells from ARF suppression and, as a consequence, tumorigenicity. Thus, NMR-specific ARF regulation and the disruption of ERAS regulate tumour resistance in NMR-iPSCs. Our findings obtained from studies of NMR-iPSCs provide new insight into the mechanisms of tumorigenicity in iPSCs and cancer resistance in the NMR

冷水強制水泳誘発抗侵害作用の発現における脳内β-endorphinならびにεオピオイド受容体の関与

The involvement of endogenous opioid peptides and opioid receptors in supraspinal site on the antinociception induced by cold water swimming was determined using the mouse tail-flick test. The mice forced to swim in cold water for 3 min, showed the marked antinociception. The antinociception induced by cold water swimming was significantly attenuated by intracerebroventricularly (i.c.v.) pretreatment with antiserum against β-endorphin, but not against dynorphin A or [Leu^5] enkephalin. On the other hand, the antinociception was not affected by i.c.v. pretreatment with μ-opioid receptor antagonists β-funaltrexamine and D-Phe-cyclo-(Cys-Tyr-D-Trp-Orn-Thr-Pen)-Thr-NH_2, δ-opioid receptor antagonists naltrindole, 7-benzylidene naltrexone and naltriben, or κ-opioid receptor antagonist nor-binaltorphimine. The present results suggest that the antinociception induced by cold water swimming may be mainly mediated through the release of β-endorphin in the supraspinal site, which act on β-endorphin-sensitive non-μ-, non-δ-, and non-κ-opioid receptor, so called putative ε-opioid receptor