• Journal of Dairy Science and Biotechnology
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• v.24 no.2
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• pp.21-24
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• 2006

The ubiquitous presence of lactoferrin(LF) receptor in human as reported by the research group of Prof. Bo Lonnerdal, Univ. California (Suzuki, Y. A.,2001) encouraged us to search for the unknown physiological roles of Lf. Under the collaboration with Prof. Etsumori Harada, Tottori Univ., and his research group, we have found two novel biological activities of LF as the control of the lipid metabolism and the effect on the central nervous system. Relating to the lipid metabolism, LF could, in animal experiments, reduce triglyceride and total cholesterol both in blood and liver (Takeuchi, T et αl., 2003). LF increased plasms HDL-C and lowered LDL-C. In the central nervous system, LF showed anti-nociceptive activity mediated by ${\mu}$-opioid receptor in the rat spinal cord (Hayashida, K. et al., 2003). LF enhanced analgesic action of morphine synergistically via nitric oxide synthesis (Hayashida, K., et al., 2003) LF showed opioid-mediated suppressive effect on distress induced by maternal separation in rat pups (Takeuchi, T., et al., 2003).

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.62-62
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• 1993

Morphine은 강력한 진통작용으로 약효를 나타내고 있고 이와 같은 진통작용은 대체로 크게 대별하여 두 가지 기전으로 설명이 된다. 그 첫째는 수의 opioid수용체에 작용하여 척수에서 상행으로 전달되는 통각정보를 차단하는 것이며 또 다른 하나는 뇌에 존재하는 opioid수용체에 작용하여 진통작용을 발현한다고 알려져 있다. 실지로 임상에서 morphine을 실내에 주입하여 강한 진통작용을 가진바가 많이 보고되었다. 그러나, 아직 마약성 진통제가 뇌를 통하여 진통작용을 가지는 그 기전에 대해선 잘 밝혀지지 않았다. 많은 연구가 마약성 진통제가 뇌에 주입되면 뇌에 존재하는 opioid수용체에 작용하고 이 수용체를 가진 신경세포가 하향성 억제를 함으로써 척수에서 통각정보를 차단하여 진통작용을 나타냄을 시사한다. 그러나 아직도 이의 정확한 기전이 명쾌히 밝혀지지 않고 있다. 즉, 뇌실내에 morphine을 주입하면 이것이 과연 척수세포를 억제할 것인가에 대한 답이 없기 때문이다. 그와는 반대로 뇌실내 morphine주입은 척수세포에 아무런 영향을 미치지 못한다는 보고가 있다. 이에 본 실험은 뇌실에 주입된 morphine이 척수세포를 어떤 영향을 미치는가를 확인하고자 하였다.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.130.2-130.2
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• 2003

The present study was undertaken to examine the hypothesis that $\mu$-opioid receptors play a crucial role in behavioral sensitization to nicotine using $\mu$-opioid receptor knockout mice. All mice were treated acutely or repeatedly with nicotine 0.05 mg/kg twice daily for 7 consecutive days. The mice were challenged with nicotine on day 11. And locomotor activity was measured for 30min. (omitted)

• Journal of Hospice and Palliative Care
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• v.27 no.2
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• pp.77-81
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• 2024

This case report explores the challenges and complexities associated with opioid management of cancer pain, emphasizing the importance of early involvement of a hospice consultation team and the adoption of a multidisciplinary approach to care. A 56-year-old man with advanced pancreatic cancer experienced escalating pain and inappropriate opioid prescriptions, highlighting the shortcomings of traditional pain management approaches. Despite procedural intervention by the attending physician and increased opioid dosages, the patient's condition deteriorated. Subsequently, the involvement of a hospice consultation team, in conjunction with collaborative psychiatric care, led to an overall improvement. The case underscores the necessity of early hospice engagement, psychosocial assessments, and collaborative approaches in the optimization of patient-centered palliative care.

• Journal of Hospice and Palliative Care
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• v.18 no.2
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• pp.105-111
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• 2015

Purpose: Fatigue, energy loss, feeling of helplessness, poor appetite, pain besides general weakness are major symptoms presented to terminally ill cancer patients. These symptoms are similar to those that appeared with adrenal insufficiency. Also, for terminally ill cancer patients who are hospitalized for palliative care, opioid agents are prescribed to control moderate to severe pain. We studied the relationship of opioid agents and adrenal insufficiency. Methods: From November 2013 through June 2014, we monitored the serum level of cortisol and dehydroepiandrosterone sulfate (DHEAS, serum) in 55 cancer patients who were over 18 years old and were treated at a hospice center. We also checked the treatment period and dosage of opioid agents. Results: The DHEAS level, treatment period and dosage of opioid agents did not have significant correlation. Correlation between the serum cortisol level and the opioid agent treatment period was not significant either, but the serum cortisol level was positively correlated with the dosage of opioid agents (P value 0.0322). Conclusion: This study did not identify a novel link between treatment period, dosage of opioid agents and adrenal insufficiency. But, the DHEAS level was mostly below the normal level in patients who were treated with opioid agents.

• Journal of Hospice and Palliative Care
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• v.17 no.3
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• pp.113-121
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• 2014

The major symptoms of terminally ill cancer patients are fatigue, loss of energy, feeling of helplessness, poor appetite and pain as well as general weakness, which are very similar to symptoms of adrenal insufficiency. Adrenal insufficiency-induced symptoms widely vary from mild symptoms to life-threatening conditions and may be resulted from variable medical causes. For terminally ill cancer patients who are hospitalized for palliative care, opioid agents are prescribed to control moderate to severe pain. The use of acute or chronic opioid agents is believed to negatively affect adrenal gland function. In most studies of opioid effects (preclinical/clinical with animal subjects or and patients suffering non-malignant pain, adrenal insufficiency and hormonal abnormalities were observed as side effects. However, opioid-induced adrenal insufficiency has been rarely reported in studies with patients with malignant cancer pain. Relationship between the type, treatment period, dosage of opioid agents and hormonal abnormalities can be examined by measuring the functional level of the adrenal glands. We hope to improve patient's quality of life by indicating hormone substitution to treat symptoms of adrenal insufficiency.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.193-201
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• 1999

This study was designed to evaluate the effects of opioid receptor agonists on the spontaneous alternation behaviour in an animal model of obsessivecompulsive disorder in rats. According to the theory that dopamine is related to the biological etiology of obsessive-compulsive disorder, the effect of the nalbuphine(opioid kappa agonist) and the tramadol(opioid mu agonist), which act as manipulating agents on the inhibition or stimulation of dopamine release, in the spontaneous alternation behaviour were evaluated. 24 hours prior to the experiment, rats were food-deprived. These rats were put into the T-maze, in which white and black goal boxes were baited with small amounts of chocolate milk. Each rat was given 2 set of 7 trials during which it was placed in the start box and allowed to choose the one of the goal boxes for each time. After identifying the stable baseline of spontaneous alternation behaviour, nonselective 5-HT agonist 5-MeODMT(1.25mg/kg/IP) disrupted spontaneous alternation. Rats were stratified into fluoxetine(10mg/kg/IP), nalbuphine(10mg/kg/IP), tramadol(46.4mg/kg/IP), and saline(0.5cc/IP) injection group with experimental drug treatment for 21 days. The effects on the 5-MeODMT(1.25mg/kg/IP) induced disruption of spontaneous alternation behaviour were checked at the next day of discontinuation of drug treatment. The results were as follows ; 1) At the day after 21 days of the drug treatment, the nalbuphine treated group and the fluoxetine treated group showed significant difference from the tramadol treated group and the saline treated group in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. 2) Within each drug treatment group, the fluoxetine treated group showed significant difference between before and after the treatment of fluoxetine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. And also, the nalbuphine treated group showed significant difference between before and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. There was no difference between the baseline and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. We indentified that the opioid kappa agonist that act as dopamine release inhibitor affect the spontaneous alternation behaviour which is an animal model of obsessive-compulsive disorder in rat.

• Journal of Veterinary Clinics
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• v.32 no.2
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• pp.148-153
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• 2015

This study was performed to compare two opioid drugs with isoflurane and to determine the difference between isoflurane/remifentanil anesthesia and isoflurane/fentanyl anesthesia in terms of the anesthetic effects in beagle dogs. Isoflurane was maintained at 0.5 MAC, and the opioid drug was administered as a constant rate infusion. The anesthesia was maintained for 2 hours, and isoflurane and opioid drugs were discontinued 2 hours later. After discontinuing the anesthetics, the extremity movement time, eye global positioning time, gag reflex time, head up time, sternal recumbency time, standing time, walking time and complete recovery times were recorded for each dog. Both of the studied anesthetic protocols were suitable in beagle dogs because the anesthetic status was well maintained until the end of the procedure, and rapid recovery times were demonstrated in this experiment. And this study shows that the isoflurane/remifentanil group was more reliable than the isoflurane/fentanyl group because the recovery time CV was lower. Therefore, isoflurane/remifentanil combination anesthesia could be a better choice than isoflurane/fentanyl anesthesia if the patient is severely ill and stable recovery time is needed.

• Journal of Ginseng Research
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• v.23 no.4
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• pp.239-246
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• 1999

The analgesic effect of ginsenosides or morphine was determined following intrathecal (i.t.) administration in rat tail-flick test. The effects of intrathecal co-administration of ginsenosides with morphine on the development of opioid tolerance and dependence were also examined using rat tail-flick test and naloxone-pre-cipitated withdrawal, respectively. Administration of ginsenosides (i.t.) produced a weak antinociception in a dose-dependent manner. Administration of morphine (i.t.) also produced antinociception in a dose-dependent manner. The $ED_50$ was $1.20\;{\mu}g\;(1.14\~1.29\;{\mu}g)$. However, the acute co-administration of $200{\mu}g$ ginsenosides with 0.1-1.0${\mu}g$ morphine did not show additive effect on morphine induced analgesia in rat tail-flick test. I.t. co-administration of 200 ${\mu}g$ ginsenosides with 10 ${\mu}g$ morphine for 7 days inhibited development of tolerance induced by 10 ${\mu}g$ morphine in rat tail-flick test, although i.t. co-administration of 50 or 100 ${\mu}g$ ginsenosides with morphine was without effect. I.t. co-administration of 200 ${\mu}g$ ginsenosides for 7 days also partially attenuated the development of morphine dependence as assessed by naloxone-precipitated withdrawal. In conclusion, these results suggest that i.t. administered ginsenosides produce a weak antinociception in rat tail-flick test and also prevent opioid tolerance and attenuate opioid dependence in chronic treatment with morphine at the spinal sites.

• Journal of Acupuncture Research
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• v.23 no.5
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• pp.23-29
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• 2006

Objectives : The present study was conducted to evaluate the effects of automatically controlled rotating acupuncture (ACRA) on thermal allodynia in neuropathic pain rats, and to examine whether the endogenous opioid system mediates the effects of ACRA. Methods : For the neuropathic surgery, the right superior caudal trunk was resected at the level between S1 and S2 spinal nerves innervating the tail. Two weeks after the nerve injury, ACRA stimulation with 4 different stimulation conditions (i.e., angle and frequency of rotation: 90o+1Hz, 90o+1/4Hz, 360o+/1Hz, and 360o+1/4Hz) was delivered to the Zusanli (ST36) acupoint for 15 min. The behavioral signs of thermal allodynia were evaluated by the tail immersion test (i.e., immersing the tail in cold $(4^{\circ}C)$ or warm $(4^{\circ}C)$ water and measuring the latency to an abrupt tail movement) before and after the stimulation. In an additional set of experiments, we examined the effects of naloxone (opioid Results : ACRA stimulations under all of the conditions above significantly relieved thermal antagonist, 2mg/kg, i.p.) on the action of ACRA stimulation. allodynia. There is no difference in the anti-allodynic effects among the 4 stimulation conditions. In addition, the effect of ACRA on thermal allodynia was reversed by naloxone pretreatment. Conclusion : These results indicate that ACRA stimulations have relieving effects on thermal allodynia in neuropathic pain rats, irrespective of stimulation parameters, and that this is mediated by the endogenous opioid system.