• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.331-341
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• 2018

The aim of the present study was to examine the effects of preemptive analgesia on the development of trigeminal neuropathic pain. For this purpose, mechanical allodynia was evaluated in male Sprague-Dawley rats using chronic constriction injury of the infraorbital nerve (CCI-ION) and perineural application of 2% QX-314 to the infraorbital nerve. CCI-ION produced severe mechanical allodynia, which was maintained until postoperative day (POD) 30. An immediate single application of 2% QX-314 to the infraorbital nerve following CCI-ION significantly reduced neuropathic mechanical allodynia. Immediate double application of QX-314 produced a greater attenuation of mechanical allodynia than a single application of QX-314. Immediate double application of 2% QX-314 reduced the CCI-ION-induced upregulation of GFAP and p-p38 expression in the trigeminal ganglion. The upregulated p-p38 expression was co-localized with NeuN, a neuronal cell marker. We also investigated the role of voltage-gated sodium channels (Navs) in the antinociception produced by preemptive application of QX-314 through analysis of the changes in Nav expression in the trigeminal ganglion following CCI-ION. Preemptive application of QX-314 significantly reduced the upregulation of Nav1.3, 1.7, and 1.9 produced by CCI-ION. These results suggest that long-lasting blockade of the transmission of pain signaling inhibits the development of neuropathic pain through the regulation of Nav isoform expression in the trigeminal ganglion. Importantly, these results provide a potential preemptive therapeutic strategy for the treatment of neuropathic pain after nerve injury.

• Journal of The Korean Society of Clinical Toxicology
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• v.17 no.2
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• pp.66-78
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• 2019

Purpose: Thallium (TI+) autometallography is often used for the imaging of neuronal metabolic activity in the rodent brain under various pathophysiologic conditions. The purpose of this study was to apply a thallium autometallographic technique to observe changes in neuronal activity in the forebrain of rats following acute carbon monoxide (CO) intoxication. Methods: In order to induce acute CO intoxication, adult Sprague-Dawley rats were exposed to 1100 ppm of CO for 40 minutes, followed by 3000 ppm of CO for 20 minutes. Animals were sacrificed at 30 minutes and 5 days after induction of acute CO intoxication for thallium autometallography. Immunohistochemical staining and toluidine blue staining were performed to observe cellular damage in the forebrain following intoxication. Results: Acute CO intoxication resulted in significant reduction of TI+ uptake in major forebrain structures, including the cortex, hippocampus, thalamus, and striatum. In the cortex and hippocampal CA1 area, marked reduction of TI+ uptake was observed in the cell bodies and dendrites of pyramidal neurons at 30 minutes following acute CO intoxication. There was also strong uptake of TI+ in astrocytes in the hippocampal CA3 area following acute CO intoxication. However, there were no significant histological findings of cell death and no reduction of NeuN (+) neuronal populations in the cortex and hippocampus at 5 days after acute CO intoxication. Conclusion: The results of this study suggest that thallium autometallography can be a new and useful technique for imaging functional changes in neural activity of the forebrain structure following mild to moderate CO intoxication.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.255-264
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• 2023

Background: Red ginseng (RG) alleviates psychiatric disorders. Fermented red ginseng (fRG) alleviates stress-induced gut inflammation. Gut dysbiosis causes psychiatric disorders with gut inflammation. To understand the gut microbiota-mediated action mechanism of RG and fRG against anxiety/depression (AD), we investigated the effects of RG, fRG, ginsenoside Rd, and 20(S)-β-D-glucopyranosyl protopanaxadiol (CK) on gut microbiota dysbiosis-induced AD and colitis in mice. Methods: Mice with AD and colitis were prepared by exposing to immobilization stress (IS) or transplanting the feces of patients with ulcerative colitis and depression (UCDF). AD-like behaviors were measured in the elevated plus maze, light/dark transition, forced swimming, and tail suspension tests. Results: Oral gavage of UCDF increased AD-like behaviors and induced neuroinflammation, gastrointestinal inflammation, and gut microbiota fluctuation in mice. Oral administration of fRG or RG treatment reduced UCDF-induced AD-like behaviors, hippocampal and hypothalamic IL-6 expression, and blood corticosterone level, whereas UCDF-suppressed hippocampal BDNF⁺NeuN⁺ cell population and dopamine and hypothalamic serotonin levels increased. Furthermore, their treatments suppressed UCDF-induced colonic inflammation and partially restored UCDF-induced gut microbiota fluctuation. Oral administration of fRG, RG, Rd, or CK also decreased IS-induced AD-like behaviors, blood IL-6 and corticosterone and colonic IL-6 and TNF-α levels, and gut dysbiosis, while IS-suppressed hypothalamic dopamine and serotonin levels increased. Conclusion: Oral gavage of UCDF caused AD, neuroinflammation, and gastrointestinal inflammation in mice. fRG mitigated AD and colitis in UCDF-exposed mice by the regulation of the microbiota-gut-brain axis and IS-exposed mice by the regulation of the hypothalamic-pituitary-adrenal axis.

• Journal of Digestive Cancer Research
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• v.3 no.1
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• pp.30-34
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• 2015

We report a case of a 55-year-old man who diagnosed with advanced gastric cancer (AGC), with A review of the literature. A 55-year old man was transferred to our hospital for further evaluation and treatment after being diagnosed with adenocarcinoma through endoscopic biopsy during a regular health examination. An abdominal computed tomography (CT) showed AGC, stage IIA (T3N3M0), while an endoscopic examination showed AGC, Borrmann type 2. The patient is currently under observation after undergoing radical subtotal gastrectomy with gastroduodenostomy and subsequent administration of oral chemotherapeutic agents. As an abdominal CT response assessment performed after surgery revealed new metastasis to the liver, the patient received palliative chemotherapy as progressive disease was suspected. After receiving chemotherapy in the order of FOLFOX (5-fluorouracil (5-FU)) + Leucovorin + Oxaliplatin), FOLFIRI (5-FU + Leucovorin + Irinotecan), EAP-II (Etoposide + Doxorubicin + Cisplatin), ELF (Etoposide + Leucovorin + 5-FU), TS-1 (Tegafur + Gimeracil) + Cisplatin, an abdominal CT response assessment showed progressive disease for which the regimen was altered to PFL (Paclitaxel + 5-FU + Leucovorin). The patient has currently completed his second cycle of chemotherapy and after an abdominal CT response assessment, further course of therapy will be decided.

• Reproductive and Developmental Biology
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• v.28 no.4
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• pp.247-252
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• 2004

Human embryonic stem (ES) cells are derived from the inner cell mass of the preimplantation embryo. Human ES cells have the capacity to differentiate into various types of cells in the body. Human ES cells are indefinite source of cells for cell therapy in various degenerative disorders including neuronal disorders. Directed differentiation of human ES cells is a prerequisite for their clinical application. The objective of this study is to develop the culture condition for the derivation of neural precursor cells from human ES cells. Neural precursor cells were derived from human ES cells in a stepwise culture condition. Neural precursor cells in the form of neural rosette structures developed into neurospheres when cultured in suspension. Suspension culture of neurospheres has been maintained over 4 months. Expressions of nestin, soxl, sox2, pax3 and pax6 transcripts were upregulated during differentiation into neural precursor cells by RT-PCR analysis. In contrast, expression of oct4 was dramatically downregulated in neural precursor cells. Immunocytochemical analyses of neural precursor cells demonstrated expression of nestin and SOX1. When induced to differentiate on an adhesive substrate, neuro-spheres were able to differentiate into three lineages of neural systems, including neurons, astrocytes and oligo-dendrocytes. Transcripts of sox1 and pax6 were downregulated during differentiation of neural precursor cells into neurons. In contrast, expression of map2ab was elevated in the differentiated cells, relative to those in neural precursor cells. Neurons derived from neural precursor cells expressed NCAM, Tuj1, MAP2ab, NeuN and NF200 in immunocytochemical analyses. Presence of astrocytes was confirmed by expression of GFAP immuno-cytochemically. Oligodendrocytes were also observed by positive immuno-reactivities against oligodendrocyte marker O1. Results of this study demonstrate that a stepwise culture condition is developed for the derivation of neural precursor cells from human ES cells.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.6
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• pp.239-246
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• 2007

Expressions of endoplasmic reticulum stress response (ERSR) genes were examined during the neuronal differentiation of rat fetal cortical precursor cells (rCPC) and rat pheochromocytoma PC12 cells. When rCPC were differentiated into neuronal cells for 7 days, early stem cell marker, nest in, expression was decreased from day 4, and neuronal markers such as neurofilament-L, -M and Tuj1 were increased after day 4. In this condition, expressions of BIP, ATF6, and phosphorylated PERK as well as their down stream signaling molecules such as CHOP, ATF4, XBP1, GADD34, Nrf2 and $p58^{IPK}$ were significantly increased, suggesting the induction of ERSR during neuronal differentiation of rCPC. ERSR was also induced during the differentiation of PC12 cells for 9 days with NGF. Neurofilament-L transcript was time-dependently increased. Both mRNA and protein levels of Tuj1 were increased after the induction, and the significant increase in NeuN was observed at day 9. Similar to the expression patterns of neuronal markers, BIP/GRP78 and CHOP mRNAs were highly increased at day 9, and ATF4 mRNA was also increased from day 7. These results strongly suggest the induction and possible role of ERSR in neuronal differentiation process. Further study to identify targets responsible for neuronal induction will be necessary.

• The Korean Society of Law and Medicine
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• v.13 no.1
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• pp.331-357
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• 2012

Obwohl die Preisbekanntmachung der individuellen Gesundheitsleistung(PiG), die im Jahr 2010 im Arztrecht neu eingef$\ddot{u}$hrt wird, zum Management der Gesundheitskosten sehr n$\ddot{u}$tzig werden soll, muss eine verfassungsrechtliche Rechtfertigungspr$\ddot{u}$fung von PiG zun$\ddot{a}$chst durchgef$\ddot{u}$hrt werden. Angesichts der staatlichen Regulierung und Lenkung auf die Wirtschaft des Art. 119 Abs. 2 KV besitzt die PiG zun$\ddot{a}$chst eine Verfassungsrechtfertigung. Nach der st$\ddot{a}$ndigen Rechtsprechung des koreanischen Verfassungsgerichts folgt das Selbstbestimmungsrecht der Verbraucher aus der Menschenw$\ddot{u}$rde von Art. 10 Abs. 1 Koreanische Verfassung(KV) und dem Recht auf Gl$\ddot{u}$ck von Art. 10 Abs. 2 KV. Demnach k$\ddot{o}$nnen Konsumenten den Einkauf der G$\ddot{u}$ter und Service, die Partei des Vertrags, Gesch$\ddot{a}$ftsbedingungen, usw. frei entscheiden. Indem der Preis der individuellen Gesundheitsleistung mithin bekanntgemacht wird, werden das Selbstbestimmungsrecht der Verbraucher sowie das Recht der Konsumenten sicherlich gew$\ddot{a}$hrleistet. Dar$\ddot{u}$ber hinaus steht die PiG im Einklang mit dem Recht auf Information, aber auch z$\ddot{a}$hlt sie nicht zu den Informationen der Nichtbekanntmachung vom Gesetz $\ddot{u}$ber die Bekanntmachung der Information(GBI). Nach der staatlichen Gesundheitspflicht des Art. 36 Abs. 3 KV kann die PiG eine Verfassungslegitim$\ddot{a}$t besitzen. Im Hinblick auf die Berufsfreiheit kann die PiG einen Eingriff in den Gesch$\ddot{a}$ftsaktivit$\ddot{a}$ten der Unternehmen bedeuten. Trotzdem ist die PiG als eine verfassungsrechtliche Legitimit$\ddot{a}$t zu qualifizieren. In der Konsequenz kann die PiG, die auf dem Selbstbestimmungsrecht, dem Recht auf Information, dem Gesundheitsrecht, der Regulierung und Lenkung auf die Wirtschaft von Art. 119 Abs. 2 KV, und dem Recht der Verbraucher beruht, als eine verfassungm${\ddot{a}}{\ss}$ige Politik gesch$\ddot{a}$tzt werden.

• Journal of Legislation Research
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• no.44
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• pp.315-342
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• 2013

Die Rechtsschutzversicherung ist als eine echte Schadenversicherung eine neue Versicherung, die $Spezialit{\ddot{a}}t$ des versichertes Risikos hat. Das bedeutet, dass der Rechtschutzversicherer nur bestimmte vertraglich vereinbarte Risiken $tr{\ddot{a}}gt$. Diese Risiken sind in den Allgemeinen Bedingungen $f{\ddot{u}}r$ die Rechtsschutzversicheurng (ARB) im Zusammenhang mit Versicherungsvertragsgesetz (VVG) ${\S}$ 125 exact beschrieben. VVG ${\S}$ 125 spricht allegemein von Leistung des Versicherers im vereinbarten versicherten Umfang. Entscheidend ist also die Vereinbarung in den ARB, welche in ${\S}$ 1 die Kostentragung $f{\ddot{u}}r$ den Versicherten als Hauptleistung des Versicherers beschrieben ist. Also in den VVG ${\S}{\S}$ 125 bis 129 gibt es keine Definition ${\ddot{u}}ber$ die Sparte der Rechtsschutzversicherung, jedoch mindestens es $w{\ddot{a}}re$ $m{\ddot{o}}glich$, diese Sparte zu definieren. Um die $k{\ddot{u}}nftige$ Produktentwicklung nicht zu hindern, $enth{\ddot{a}}lt$ die Vorschrift keine gesetzliche Definition der Rechtsschutzversicherung nach Angabe der amtlichen $Begr{\ddot{u}}ndung$. Weil in Korea die Rechtsschutzversicherung relativ neu in Versicherungsmarket ist, sind daher VVG ${\S}{\S}$ 125 ein gutes gesetzgeberisches Vorbild, um pragmatisch und auch dazu rechtswissenschaftlich zu diskutieren und diese fsetzustellen. Im Schritt von Ausdehnungen der juristischen Dienstleistung $w{\ddot{a}}re$ es $n{\ddot{o}}tig$, zu betrachten, wie Leistungsumfang des Versicherers in der Rechtsschutzversicherung erweitert werden kann. And noch dazu ist die Informationspflicht des Versicherers in Hinsicht auf Versicherungsunfall und Leistungsumfang noch weitert zu ${\ddot{u}}berlegen$, weil diese Sparte der Rechtsschutzversicherung noch professioneller als die anderen Versicherungsbereiche ist.

• Journal of Legislation Research
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• no.44
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• pp.465-485
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• 2013

Mit dem Patientenrechtegesetz, das im $Fr{\ddot{u}}jahr$ 2013 in Kraft treten soll, $f{\ddot{u}}rt$ der Gesetzgeber eine jahrzehntelange Diskussion um die Rechte von Patientinnen und Patienten zu einem guten Ende. Demnach geht es darum, Transparenz ${\ddot{u}}ber$ die bereits heute bestehenden, umfangreichen Rechte der Patientinnen und Patienten herzustellen, die $tats{\ddot{a}}chliche$ Durchsetzung dieser Rechte zu verbessern, zugleich Patientinnen und Patienten im Sinne einer verbesserten Gesundheitsversorgung zu $sch{\ddot{u}}tzen$ und insbesondere im Fall eines Behandlungsfehlers $st{\ddot{a}}rker$ zu $unterst{\ddot{u}}tzen$. In Verfolgung dieser Zwecke $schl{\ddot{a}}gt$ die Bundesregierung ein Artikelgesetz vor, dessen wesentliche Teile das BGB und das Recht der sozialen Krankenversicherung betreffen. In das BGB soll ein neuer Abschnitt ${\ddot{u}}ber$ den "Behandlungsvertrag" $eingef{\ddot{u}}gt$ werden. Als Standort ist der ${\ddot{U}}bergang$ vom Dienstin das Werkvertragsrecht vorgesehen, der um die neu zu schaffenden Vorschriften der ${\S}{\S}$ 630 a bis 630 h BGB erweitert wird. Die acht Paragrafen enthalten im Kern eine Kodifikation der von der Rechtsprechung entwickelten $Grunds{\ddot{a}}tze$ zur Arzthaftung. Der Beitrag stellt die bisherige politische Diskussion des Patientenrechtegesetzes vor (II). Im Anschluss daran wird die einzige wesentliche Neuerung des Gesetzes $n{\ddot{a}}her$ untersucht und werden Regelungsziel und Grundkonzept der Kodifikation einer $Pr{\ddot{u}}fung$ unterzogen (III). $Schlie{\ss}lich$ werden einen politischen Ausblick auf die neuen Herausforderungen und die Bewertung der $gegenw{\ddot{a}}rtigen$ Lage und der erwarteten Entwicklung gezogen (IV).

• Journal of Ginseng Research
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• v.45 no.2
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• pp.325-333
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• 2021

Background: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. Enhancing hippocampal neurogenesis by promoting proliferation and differentiation of neural stem cells (NSCs) is a promising therapeutic strategy for AD. 20(S)-protopanaxadiol (PPD) and oleanolic acid (OA) are small, bioactive compounds found in ginseng that can promote NSC proliferation and neural differentiation in vitro. However, it is currently unknown whether PPD or OA can attenuate cognitive deficits by enhancing hippocampal neurogenesis in vivo in a transgenic APP/PS1 AD mouse model. Here, we administered PPD or OA to APP/PS1 mice and monitored the effects on cognition and hippocampal neurogenesis. Methods: We used the Morris water maze, Y maze, and open field tests to compare the cognitive capacities of treated and untreated APP/PS1 mice. We investigated hippocampal neurogenesis using Nissl staining and BrdU/NeuN double labeling. NSC proliferation was quantified by Sox2 labeling of the hippocampal dentate gyrus. We used western blotting to determine the effects of PPD and OA on Wnt/GSK3β/β-catenin pathway activation in the hippocampus. Results: Both PPD and OA significantly ameliorated the cognitive impairments observed in untreated APP/PS1 mice. Furthermore, PPD and OA significantly promoted hippocampal neurogenesis and NSC proliferation. At the mechanistic level, PPD and OA treatments resulted in Wnt/GSK-3β/β-catenin pathway activation in the hippocampus. Conclusion: PPD and OA ameliorate cognitive deficits in APP/PS1 mice by enhancing hippocampal neurogenesis, achieved by stimulating the Wnt/GSK-3β/β-catenin pathway. As such, PPD and OA are promising novel therapeutic agents for the treatment of AD and other neurodegenerative diseases.