• 제목/요약/키워드: Ganglion.

검색결과 720건 처리시간 0.022초

Ginsenoside Rg5, a potent agonist of Nrf2, inhibits HSV-1 infection-induced neuroinflammation by inhibiting oxidative stress and NF-κB activation

  • Buyun Kim;Young Soo Kim;Wei Li;Eun-Bin Kwon;Hwan-Suck Chung;Younghoon Go;Jang-Gi Choi
    • Journal of Ginseng Research
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    • 제48권4호
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    • pp.384-394
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    • 2024
  • Background: Herpes simplex virus type 1 (HSV-1), known to latently infect the host's trigeminal ganglion, can lead to severe herpes encephalitis or asymptomatic infection, potentially contributing to neurodegenerative diseases like Alzheimer's. The virus generates reactive oxygen species (ROS) that significantly impact viral replication and induce chronic inflammation through NF-κB activation. Nuclear factor E2-related factor 2 (Nrf2), an oxidative stress regulator, can prevent and treat HSV-1 infection by activating the passive defense response in the early stages of infection. Methods and results: Our study investigated the antiviral effects of ginsenoside Rg5, an Nrf2 activator, on HSV-1 replication and several host cell signaling pathways. We found that HSV-1 infection inhibited Nrf2 activity in host cells, induced ROS/NF-κB signaling, and triggered inflammatory cytokines. However, treatment with ginsenoside Rg5 inhibited ROS/NF-κB signaling and reduced inflammatory cytokines through NRF2 induction. Interestingly, the Nrf2 inhibitor ML385 suppressed the expression of NAD(P)H quinone oxidoreductase 1(NQO1) and enhanced the expression of KEAP1 in HSV-1 infected cells. This led to the reversal of VP16 expression inhibition, a protein factor associated with HSV-1 infection, thereby promoting HSV-1 replication. Conclusion: These findings suggest for the first time that ginsenoside Rg5 may serve as an antiviral against HSV-1 infection and could be a novel therapeutic agent for HSV-1-induced neuroinflammation.

Analgesic and anti-inflammatory effects of galangin: a potential pathway to inhibit transient receptor potential vanilloid 1 receptor activation

  • Kaiwen Lin;Datian Fu;Zhongtao Wang;Xueer Zhang;Canyang Zhu
    • The Korean Journal of Pain
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    • 제37권2호
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    • pp.151-163
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    • 2024
  • Background: Galangin, commonly employed in traditional Chinese medicine for its diverse medicinal properties, exhibits potential in treating inflammatory pain. Nevertheless, its mechanism of action remains unclear. Methods: Mice were randomly divided into 4 groups for 7 days: a normal control group, a galangin-treated (25 and 50 mg/kg), and a positive control celecoxib (20 mg/kg). Analgesic and anti-inflammatory effects were evaluated using a hot plate test, acetic acid-induced writhing test, acetic acid-induced vascular permeability test, formalin-induced paw licking test, and carrageenan-induced paw swelling test. The interplay between galangin, transient receptor potential vanilloid 1 (TRPV1), NF-κB, COX-2, and TNF-α proteins was evaluated via molecular docking. COX-2, PGE2, IL-1β, IL-6, and TNF-α levels in serum were measured using ELISA after capsaicin administration (200 nmol/L). TRPV1 expression in the dorsal root ganglion was analyzed by Western blot. The quantities of substance P (SP) and calcitonin gene-related peptide (CGRP) were assessed using qPCR. Results: Galangin reduced hot plate-induced licking latency, acetic acid-induced contortions, carrageenan-triggered foot inflammation, and capillary permeability in mice. It exhibited favorable affinity towards TRPV1, NF-κB, COX-2, and TNF-α, resulting in decreased levels of COX-2, PGE2, IL-1β, IL-6, and TNF-α in serum following capsaicin stimulation. Galangin effectively suppressed the upregulation of TRPV1 protein and associated receptor neuropeptides CGRP and SP mRNA, while concurrently inhibiting the expression of NF-κB, TNF-α, COX-2, and PGE2 mRNA. Conclusions: Galangin exerts its anti-inflammatory pain effects by inhibiting TRPV1 activation and regulating COX-2, NF-κB/TNF-α expression, providing evidence for the use of galangin in the management of inflammatory pain.

Ferroptosis inhibitor ferrostatin-1 attenuates morphine tolerance development in male rats by inhibiting dorsal root ganglion neuronal ferroptosis

  • Hasan Dirik;Ahmet Sevki Taskiran;Ziad Joha
    • The Korean Journal of Pain
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    • 제37권3호
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    • pp.233-246
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    • 2024
  • Background: Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats. Methods: This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG. Results: After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance (P < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS (P < 0.001), while simultaneously causing a decrease in TAS levels (P < 0.001). Conclusions: The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.

일출일몰 데이터를 이용한 인간 중심 조명 구현에 관한 연구 (A Study on Implementation of Human Centric Lighting Using Sunrise and Sunset Data)

  • 장두원;김충혁;조규원
    • 한국전기전자재료학회논문지
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    • 제37권5호
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    • pp.486-493
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    • 2024
  • Lighting has been used for a long time as a medium to convey brightness from darkness, and through incandescent lamps and fluorescent lamps, LED light sources have now become the standard in the lighting industry. Recently, the lighting equipment industry has been undergoing rapid digital transformation, starting with smart lighting, and is evolving into smart lighting customized for individuals and spaces through the development of IoT technology, cloud-based services, and data analysis. However, the blue light emitted from digital devices (computers, smartphones, tablets, etc.) or LED lights stimulates the melanopsin in the optic ganglion cells in the retina of the eye, which in turn stimulates the secretion of melatonin through the pineal gland, which regulates the secretion of melatonin. This can reduce sleep quality or disrupt biological rhythms. This interaction between blue light and melatonin has such a significant impact on human sleep patterns and overall health that it is essential to reduce exposure to blue light, especially in the evening. Human-centered lighting refers to lighting that takes into account the effects of light on the physical and mental areas, such as human activity and awakening, improvement of sleep quality, and health management. Many research institutes study the effects in the visible area and the non-visible area. By studying the impact, it is expected to improve the quality of human life. In this study, we plan to study ways to implement human-centered lighting by collecting sunrise and sunset data and linking commercialized LED packages and control devices with open-source hardware.

수장부 다한증에서 Clipping에 의한 흉부4번 교감신경절 상부 차단술과 흉부4번 교감신경절 완전 차단술에 대한 장기성적 비교 (Long Term Outcome of Endoscopically Clipping the Upper Part of R4 Sympathetic Block and R4 Sympathetic Block for the Treatment of Palmar Hyperhidrosis)

  • 최봉춘;김용한;사영조;박재길;이선희;심성보
    • Journal of Chest Surgery
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    • 제40권11호
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    • pp.752-758
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    • 2007
  • 배경: 수장부다한증의 치료 후 손의 원활한 활동을 위해 적당한 보습성을 유지하고 보상성 다한증과 같은 합병증이 없는 경우에 보다 높은 만족도를 나타낼 것이다. 저자들은 수부다한증의 치료 후 보상성 다한증을 피하기 위한 노력의 일환으로 두부족으로 영향을 미치는 교감신경의 보존을 위해 제4번 흉부교감신경절 상부의 신경다발을 차단하는 시술을 시행하였다. 대상 및 방법: 흉부 제4번 교감신경절을 상하 완전 차단한 1군과 보다 간편하게 흉부 제4번 교감신경절 상부 차단술만 시행한 2군으로 분류하였고, 두 방법의 장기성적을 평가하기 위하여 수술 후 만족도 등에 대한 전화설문 조사를 실시하였다. 대상 환자는 71명(남자 45명, 여자 26명)이며, 1군은 31명(평균 연령 25.5세), 2군은 40명(평균 연령 25.9세)이었고 추적 조사기간은 1군이 수술 후 평균 24.9개월, 2군은 18.9개월이었다. 결과: 수술 후 수술부위에 땀이 나는 정도는 1군에서 전혀 나지 않는다(41.9%), 환경에 따라 약간 난다(48.4%)에 비해 2군은 각각 60.0%, 35.0%였다. 수술 후 땀이 나기 시작한 경우는 1군이 58.1%, 2군이 40.0%였고, 수술 후 손의 건조한 정도는 별다른 불편이 없다고 한 경우가 1군에서 높았고 손크림을 바를 정도라고 응답한 경우는 2군에서 높았다. 보상성 다한증의 발생은 없거나 생활에 불편하지 않은 경우가 각각 71.0% (1군), 62.5% (2군)로 응답하였고, 수술을 후회하는 경우는 1군이 1명, 2군이 2명 있었다. 보상성 다한증의 발생부위는 1군이 등, 허벅지, 가슴 순이었고 2군은 등, 가슴, 배 순이었다. 미각성 다한증은 1군에서 몹시 불편하거나(25.8%), 약간 생겼지만 불편하지는 않다(45.2%)고 한 반면, 2군은 몹시 불편한 경우는 12.5%, 미각성 다한증이 생기지 않은 경우가 45%였다. 수술 후 얼굴에 나는 땀의 정도는 양 군 대다수가 불편이 없다고 응답하였다. 수술 후 만족도는 1군과 2군 대부분이 치료에 만족하였다. 결론: 흉부 제4번 교감신경절 완전 차단술과 상부 차단술은 수장부 다한증의 치료에 효과적이며, 보상성 다한증의 발생을 줄이고 증세를 완화하는 효과가 있다. 특히 흉부 제4 번 교감신경절 상부 차단술은 수술이 쉽고 안전하며 미각성 다한증의 발생이 저하되고, 수술 후 환자의 만족도가 높았다.

흰쥐에서 WGA-HRP와 pseudorabies virus를 이용한 정관의 신경로에 대한 연구 (Neural pathway innervating ductus Deferens of rats by pseudorabies virus and WGA-HRP)

  • 이창현;정옥봉;고병문;이봉희;김수명;김인식;양홍현
    • 대한수의학회지
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    • 제43권1호
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    • pp.11-24
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    • 2003
  • This experimental studies was to investigate the location of PNS and CNS labeled neurons following injection of 2% WGA-HRP and pseudorabies virus (PRY), Bartha strain, into the ductus deferens of rats. After survival times 4-5 days following injection of 2% WGA-HRP and PRV, the rats were perfused, and their brain, spinal cord, sympathetic ganglia and spinal ganglia were frozen sectioned ($30{\mu}m$). These sections were stained by HRP histochemical and PRY inummohistochemical staining methods, and observed with light microscope. The results were as follows ; 1. The location of sympathetic ganglia projecting to the ductus deferens were observed in pelvic ganglion, inferior mesenteric ganglion and L1-6 lwnbar sympathetic ganglia. 2. The location of spinal ganglia projecting to the ductus deferens were observed in T13-L6 spinal ganglia. 3. The PRY labeled neurons projecting to the ductus deferens were observed in lateral spinal nucleus, lamina I, II and X of cervical segments. In thoracic segments, PRY labeled neurons were observed in dorsomedial part of lamina I, II and III, and dorsolateral part of lamina IV and V. Densely labeled neurons were observed in intermediolateral nucleus. In first lumbar segment, labeled neurons were observed in intermediolateral nucleus and dorsal commisural nucleus. In sixth lumbar segment and sacral segments, dense labeled neurons were observed in sacral parasympathetic nuc., lamina IX and X. 4. In the medulla oblongata, PRV labeled neurons projecting to the ductus deferens were observed in the trigeminal spinal nuc., A1 noradrenalin cells/C1 adrenalin cells/caudoventrolateral reticular nuc., rostroventrolateral reticular nuc., area postrema, nuc. tractus solitarius, raphe obscurus nuc., raphe pallidus nuc., raphe magnus nuc., parapyramidal nuc., lateral reticular nuc., gigantocellular reticular nuc.. 5. In the pons, PRV labeled neurons projecting to the ductus deferens were ohserved in parabrachial nuc., Kolliker-Fuse nuc., locus cooruleus, subcooruleus nuc. and AS noradrenalin cells. 6. In midbrain, PRV labeled neurons projecting to the ductus deferens were observed in periaqueductal gray substance, substantia nigra and dorsal raphe nuc.. 7. In the diencephalon, PRV labeled neurons projecting to the ductus deferens were observed in paraventricular hypahalamic nuc., lateral hypothalamic nuc., retrochiasmatic nuc. and ventromedial hypothalamic nuc.. 8. In cerebrum, PRV labeled neurons projecting to the ductus deferens were observed in area 1 of parietal cortex. These results suggest that WGA-HRP labeled neurons of the spinal cord projecting to the rat ductus deferens might be the first-order neurons related to the viscero-somatic sensory and sympathetic postganglionic neurons, and PRV labeled neurons of the brain and spinal cord may be the second and third-order neurons response to the movement of smooth muscles in ductus deferens. These PRV labeled neurons may be central autonomic center related to the integration and modulation of reflex control linked to the sensory and motor system monitaing the internal environment. These observations provide evidence for previously unknown projections from ductus deferens to spinal cord and brain which may be play an important neuroanatornical basic evidence in the regulation of ductus deferens function.

흰쥐 삼차신경감각핵에서 $P2X_3$와 TRPV1의 공존에 관한 연구 (Coexpression of $P2X_3$ with TRPV1 in the Rat Trigeminal Sensory Nuclei)

  • 문용석;류창현;조이슬;김홍태;박매자;백상규;문제일;김윤숙;배용철
    • Applied Microscopy
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    • 제38권3호
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    • pp.151-157
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    • 2008
  • 삼차신경계에서 $P2X_3$와 TRPV1 면역양성 일차들신경섬유는 통각정보의 전달에 중요한 역할을 한다. 본 연구에서는 삼차신경절 및 삼차신경꼬리핵에서 $P2X_3$와 TRPV1 면역양성 신경세포의 형태학적 특성 및 투사양식을 이해하기 위하여, 흰쥐 삼차신경절 및 삼차신경꼬리핵에서 $P2X_3$와 TRPV1에 대한 항체를 사용하여 형광면역염색법 및 형태계측학적인 기법을 시행하여 다음과 같은 결과를 얻었다. $P2X_3$ 면역양성 신경세포중 77.4%의 신경세포에서 (1,401/1,810) TRPV1이 동시에 발현되었으며, TRPV1 면역양성 신경세포중 51.9% (1,401/2,698)의 신경세포에서 $P2X_3$와 공존을 보였다. $P2X_3$와 TRPV1에 동시에 면역양성반응을 보이는 신경세포는 중간크기의 신경세포에서 주로 관찰되었으며, $P2X_3$ 혹은 TRPV1 면역양성 신경세포중 아주 작거나 큰 신경세포에서는 공존하지 않았다. 삼차신경꼬리핵에서 $P2X_3$ 면역양성 신경섬유 및 신경종말들은 제1층과 제2층에 분포하는데 주로 제2층의 안쪽부위에서 밀도가 높게 관찰되었으며, TRPV1 면역양성 신경섬유 및 신경종말들은 제1층과 제2층의 바깥쪽에서 밀도가 높게 관찰되었다. $P2X_3$와 TRPV1이 공존하는 신경섬유 및 신경종말들은 제2층의 안쪽과 바깥쪽의 경계부위에서 관찰되었다. 이러한 연구결과는 $P2X_3$와 TRPV1을 동시에 발현하는 신경세포는 구강안면영역에서 통각정보의 처리에 독특한 역할을 수행할 것이라는 것을 시사한다.

견관절부 외상후 발생된 Shoulder-Hand Syndrome (A Case of the Shoulder-Hand Syndrome Caused by a Crush Injury of the Shoulder)

  • 전재수;이성근;송후빈;김선종;박욱;김성열
    • The Korean Journal of Pain
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    • 제2권2호
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    • pp.155-166
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    • 1989
  • Bonica defined, that reflex sympathetic dystrophy (RSD) may develop pain, vasomotor abnoramalities, delayed functional recovery, and dystrophic changes on an affected area without major neurologic injury following trauma, surgery or one of several diseased states. This 45 year old male patient had been crushed on his left shoulder by a heavily laden rear car, during his job street cleaning about 10 years ago (1978). At first the pain was localizea only to the site of injury, but with time, it spreaded from the shoulder to the elbow and hand, with swelling. X-ray studies in the local clinic, showed no bone abnormalities of the affected site. During about 10 years following the injury, the had recieved several types of treatments such as nonsteroidal analgesics, steroid injections into the glenoidal cavity (10 times), physical therapy, some oriental herb medicines, and acupuncture over a period of 1~3 months annually. His shoulder pain and it's joint dysfunction persisted with recurrent paroxysmal aggrevation because of being mismanaged or neglected for a sufficiently long period these fore permiting progression of the sympathetic imbalance. On July 14 1988 when he visited our clinic. He complained of burning, aching and had a hyperpathic response or hyperesthesia in touch from the shoulder girdle to the elbow and the hand. Also the skin of the affected area was pale, cold, and there was much sweating of the axilla and palm, but no edema. The shoulder girdle was unable to move due to joint pain with marked weakness. We confirmed skin temperatures $5^{\circ}C$ lower than those of the unaffected axilla, elbow and palm of his hand, and his nails were slightly ridged with lateral arching and some were brittle. On X-ray findings of both the shoulder AP & lateral view, the left humerus and joint area showed diffuse post-traumatic osteoporosis and fibrous ankylozing with an osteoarthritis-like appearance. For evaluating the RSD and it's relief of pain, the left cervical sympathetic ganglion was blocked by injecting 0.5% bupivacaine 5 ml with normal saline 5 ml (=SGB). After 15 minutes following the SGB, the clinical efficacy of the block by the patients subjective score of pain intensity (=PSSPI), showed a 50% reduction of his shoulder and arm pain, which was burning in quality, and a hyperpathic response against palpation by the examiner. The skin temperatures of the axilla and palm rose to $4{\sim}5^{\circ}C$ more than those before the SGB. He felt that his left face and upper extremity became warmer than before the SGB, and that he had reduced sweating on his axilla and his palm. Horner's sign was also observed on his face and eyes. But his deep shoulder joint pain was not improved. For the control of the remaining shoulder joint pain, after 45 minutes following the SGB, a somatic sensory block was performed by injecting 0.5% bupivacaine 6 ml mixed with salmon calcitonin, $Tridol^{(R)}$, $Polydyn^{(R)}$ and triamcinolone into the fossa of the acromioclavicular joint region. The clinical effect of the somatic block showed an 80% releif of the deep joint pain by the PSSPI of the joint motion. Both blocks, as the above mentioned, were repeated a total of 28 times respectively, during 6 months, except the steroid was used just 3 times from the start. For maintaining the relieved pain level whilst using both blocks, we prescribed a low dose of clonazepam, prazocin, $Etravil^{(R)}$, codeine, etodolac micronized and antacids over 6 months. The result of the treatments were as follows; 1) The burning, aching and hyperpathic condition which accompanied with vaosmotor and pseudomotor dysfunction, disappeared gradually to almost nothing, within 3 weeks from the starting of the blocks every other day. 2) The joint disability of the affected area was improved little by little within 6 months. 3) The post-traumatic osteoporosis, fibrous ankylosis and marginal sclerosis with a narrowed joint, showed not much improvement on the X-ray findings (on April 25, 1989) 10 months later in the follow-up. 4) Now he has returned to his job as a street cleaner.

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중심부 시야결손을 보이는 초기 녹내장 환자의 진단에서 자동시야계 C10-2의 유용성 (The Effectiveness of Visual Field C10-2 in the Early Detection of Glaucoma with Parafoveal Scotoma)

  • 황보인;박혜영;박찬기
    • 대한안과학회지
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    • 제58권3호
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    • pp.321-326
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    • 2017
  • 목적: 중심부 시야결손을 보이는 초기녹내장 환자를 진단하는 데 가장 효과적인 시야검사에 대한 방향성을 제시하고자 한다. 대상과 방법: 중심부 시야결손을 가진 초기 녹내장 환자의 총 57안을 대상으로 Humphrey 자동시야계 C24-2, C10-2, 주파수배가시야검사(frequency doubling technology perimetry, FDT) C24-2를 시행하여 이를 황반부의 신경절세포내망상층(the ganglion cell-inner plexiform layer, GC-IPL)의 평균두께와 구조기능적으로 비교분석하였다. 결과: Central sensitivity는 자동시야계 C24-2, 자동시야계 C10-2, FDT C24-2 순으로 각각 $27.51{\pm}5.43dB$, $27.39{\pm}5.05dB$, $22.09{\pm}5.08dB$ 순이었으며, 평균 GC-IPL thickness는 $70.2{\pm}8.5{\mu}m$였다. 각각의 시야검사의 central sensitivity와 optical coherence tomography에서의 평균 GC-IPL의 두께를 평가한 회귀분석에서는 자동시야계 C10-2만이 유의한 p-value를 보였으며 (p<0.05), logarithmic scale에서는 $logR^2$ 값이 0.498, antilogarithmic scale에서는 linear $R^2$ 값이 0.486을 보이며, FDT C24-2와 자동 시야계 C24-2에 비해 높은 값을 보였다. 초기 녹내장에서 이러한 관계가 더욱 뚜렷하였다. 결론: 중심부 시야결손을 보이는 초기 녹내장 환자에서 GC-IPL thickness와 중심부 시야 감도 사이의 구조-기능 관계는 Humphrey C10-2 자동시야계가 다른 시야 검사법에 비해 더 잘 반영하였다.

흰쥐에서 편측 반회후두신경 재지배 후 neuronal Nitric Oxide Synthase(nNOS)의 발현과 후두기능회복과의 관계 (The Expression of neuronal Nitric Oxide Synthase in Reinnervated Recurrent Laryngeal Nerve)

  • 정성민;김성숙;조윤희;구태완;박수경;신유리
    • 대한후두음성언어의학회지
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    • 제12권1호
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    • pp.46-54
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    • 2001
  • Background and Objectives : Nitric oxide(NO) is a short-lived molecule with messenger and cytotoxic functions in nervous, cardiovascular, and immune systems. Among the three distinct NOS isoforms, the neuronal isoform is expressed in small, discrete neuronal populations of CNS and PNS. Axonal injury in adult animals results in a dramatic NOS up-regulation in many types of central and peripheral neurons which normally lack the enzyme or express it only at very low levels. In previous study, we confirmed the efficacy of PEMS on the early functional recovery in rats with surgically transected and reanastomosed recurrent laryngeal nerve. Therefore, after we obtained functionally recovered rats using PEMS in this study, we studied to evaluate the expression of nNOS through the analysis of the difference between functional recovery group and non-recovery group in the recurrent laryngeal nerve. Materials and Method : Using 84 healthy male Sprague-Dawley rats, transections and primary anastomosis were performed on their left recurrent laryngeal nerves. Rats were then randomly assigned to 2 groups. The rats in group A(n=42) received PEMS by placing them in custom cages equipped with Helm-holz coils(3 hr/day, 5 days/wk, for 12 wk). The rats in group B(n=42) were handled the same way as the group A, except that they did not receive PEMS. Laryngovideoendoscopy was performed before and after surgery and followed up weekly. Laryngeal EMG was obtained in both PCA and TA muscles. Immunohistochemisty staining using monoclonal anti-neuronal nitric oxide synthase(nNOS) antibody was performed to detect nNOS in recurrent laryngeal nerve and nodose ganglion. Results : 20 rats(63%) in group A and 5 rats(17%) in the group B showed recovery of vocal fo1d motion. The number of NOS-positive cells was increased in functionally-recovered rats. NOS-staining intensity was reduced 12 weeks after nerve injury. The difference between PEMS group and non-stimulated group was not found. Conclusion : This study shows that nNOS may exert a beneficial effect on nerve regeneration and functional repair.

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