• 대한약침학회지
• /
• 제22권3호
• /
• pp.192-199
• /
• 2019

Objectives: KCHO-1(Mecasin), also called Gamijakyakgamchobuja-tang originally, is a combination of some traditional herbal medicines in East Asia. This medicine has been used mainly for alleviating neuropathic pains for centuries in Korean traditional medicine. KCHO-1 was developed to treat pain, joint contracture and muscular weakness in patients with amyotrophic lateral sclerosis. This study was carried out to investigate the chronic toxicity of KCHO-1 oral administration in rats for 26 weeks. Methods: Sprague-Dawely rats were divided into four groups and 10 rats were placed in the control group and the high-dose group, respectively. Group 1 was the control group and the remaining groups were the experimental groups. In the oral toxicity study, 500 mg/kg, 1,000 mg/kg, and 2,000 mg/kg of KCHO-1 were administered to the experimental group, and 10 ml/kg of sterile distilled water was administered to the control group. Survival rate, body weight, feed intake, clinical signs, and visual findings were examined. Urinalysis, ophthalmologic examination, necropsy, organ weight, hematologic examination, blood chemical examination and histopathologic examination were performed. Results: Mortality and toxicological lesions associated with the administration of test substance were not observed in all groups. Conclusion: NOAEL(No observed adverse effect level) of KCHO-1 is higher than 2000 mg/kg/day. And, the above findings suggest that treatment with KCHO-1 is relatively safe.

• 대한약침학회지
• /
• 제23권4호
• /
• pp.237-246
• /
• 2020

Objectives: Capsaicin-containing (CP) pharmacopuncture was developed to treat neuropathic pain. This study was conducted to assess the toxicity of CP extract for pharmacopuncture, using a micronucleus test. Methods: First, a dose range finding study was conducted. Then an in vivo micronucleus test was performed to determine the induction of micronuclei in mouse bone marrow cells after intramuscular administration of CP twice with a 24-hour interval to 8-week-old ICR mice. A high dose of 0.2 mL/animal was selected, and this was sequentially diluted by applying a geometric ratio of 2 to produce two lower dose levels (0.1 and 0.05 mL/animal). In addition, negative and positive control groups were set up, and an HPLC analysis was conducted to confirm the capsaicin content of CP. Results: The incidence of micro-nucleated polychromatic erythrocytes in polychromatic erythrocytes in the CP-treated group was similar to that in the negative-control group, while that in the positive-control group was significantly greater. In addition, the ratio of polychromatic erythrocytes to total erythrocytes in the CP treatment group and the positive control group was not significantly different from the negative control group. In the HPLC analysis, capsaicin in the CP was identified through a comparison with the retention time of the capsaicin standard of 27 min. Conclusion: CP did not show any indication of any potential to induce micronuclei formation in bone marrow cells of ICR mice under the conditions of this study. Further toxicity studies are necessary to ensure the safety of the use of CP in clinical practice.

• 대한한의학방제학회지
• /
• 제31권1호
• /
• pp.21-28
• /
• 2023

Objective : Scolopendra, a dried body of Scolopendra subspinipes mutilans, is one of Korean medicine. Several reports revealed that Scolopendra has therapeutic effects for arthritis, neuroinflammatory diseases and neuropathic pain. However, the fetal adaptive response or teratogenicity associated with administration of Scolopendra is unclear. Therefore, this study aimed to investigate the fetal toxicity effects that were induced following oral administration of Scolopendra water extract (SWE) in pregnant mice. Methods : The pregnant mice were administrated SWE at dosed of 0, 100, 500 and 1000 mg/kg/day during gestation day 0-18. The mortality, body weight and clinical signs of pregnant mice were observed throughout experimental period. Also, the mortality and malformations in foetus were examined. Results : No meaningful changes were observed in the mortality and clinical signs of pregnant mice between the normal control group and SWE administrated groups. Additionally, there are no significant changes in fetal mortalities, and malformations by SWE administration. conclusion : These results suggest that oral exposure to SWE during pregnancy at oral dosages up to 1000 mg/kg/day did not induce teratogenic toxicity in regard to fetal mortality and morphology.

• 대한암한의학회지
• /
• 제28권1호
• /
• pp.33-44
• /
• 2023

목적: 항암유발말초신경병증은 암 환자가 겪는 흔한 항암 부작용이나 현재까지 효과적으로 알려진 치료법은 없다. 본 연구의 목적은 항암유발말초신경병증에 대한 침 치료와 가바펜틴의 병용 요법의 효과와 안전성을 평가하는 것이다. 방법: 항암유발말초신경병증을 겪고 있는 24명의 암 환자를 침 치료 단독군 (AG, acupuncture group)과 침과 가바펜틴의 병용요법군 (CG, combined acupuncture and gabapentin group)으로 무작위 배정하였다. 두 그룹 모두 침 치료는 주 3회, 4주간 수행하였다. 병용 요법군은 침 치료와 더불어 1일 900mg의 가바펜틴을 복용하도록 하였다. 치료 효과는 Neuropathic Pain Symptom Inventory (NPSI), visual analogue scale (VAS), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 items (EORTC-CIPN20)를 이용하여 측정하였다. 치료로 인한 부작용은 대상자가 방문할 때마다 조사하였다. 결과: 총 23명의 대상자(AG, n=12; CG, n=11)의 평가지표를 분석한 결과, 치료 4 주 후 침 치료 단독군은 NPSI 점수가 44.33±25.04에서 30.58±21.55으로 감소하였고, 병용 요법군은 30.55±25.59에서 18.64±19.42로 감소하였으며, 두 군 모두 통계적으로 유의미하게 감소하였다(p<0.001). VAS점수는 침 치료 단독군에서는 4.79±2.17 에서 3.42±2.49으로 감소하였고, 병용 요법군에서는 3.55±2.07에서 2.73±2.49 로 감소하였다(p<0.05). 치료 효과는 치료 완료 2주후까지 지속되었으며, 두 군간의 유의미한 차이는 없었다. EORTC-CIPN20은 침 치료 단독군은 30.27±18.87에서 20.84±16.35으로 감소하여(p<0.01), 두 군 모두에서 삶의 질이 향상되었다. 결론: 본 연구로 침 치료와 가바펜틴의 병용 요법이 항암유발말초신경병증 환자의 증상 및 삶의 질 개선에 효과적이며 안전한 치료법임을 확인하였다. 그러나 침 치료와 가바펜틴의 시너지 효과에 대해서는 확인 할 수 없었으며, 이를 확인하기 위해 추가적인 연구가 필요할 것으로 사료된다.

• Journal of Yeungnam Medical Science
• /
• 제41권3호
• /
• pp.220-227
• /
• 2024

Background: Electrodiagnostic testing (EDX) is important in the diagnosis and follow-up of neuropathic and myopathic diseases. This study aimed to demonstrate the compatibility between clinical prediagnosis and electrophysiological findings. Methods: EDX results from 2004 to 2020 at the physical medicine and rehabilitation (PM&R) clinic were screened. Tests with missing data, reevaluation studies, and cases of peripheral facial paralysis were excluded. The clinical prediagnosis and EDX results were recorded, and their compatibility was evaluated. Results: A total of 2,153 tests were included in this study. The mean age was 49.0±13.9 years and 1,533 of them (71.2%) were female. The most frequently referred clinic was the PM&R clinic (90.0%). Numbness (73.6%) was the most common complaint, followed by pain (15.3%) and weakness (13.9%). The most common prediagnosis was entrapment neuropathy (55.3%), radiculopathy (16.1%), and polyneuropathy (15.7%). Carpal tunnel syndrome was the most frequently identified type of entrapment neuropathy (78.3%). Six hundred and seventy EDX results (31.1%) were within normal limits. While the EDX results were consistent with the prediagnosis in 1,328 patients (61.7%), a pathology different from the prediagnosis was detected in 155 patients (7.2%). In the discrepancy group, the most common pathologies were entrapment neuropathy (51.7%), polyneuropathy (17.3%), and radiculopathy (15.1%). The most common neuropathy type was carpal tunnel syndrome (79.3%). Conclusion: After adequate anamnesis and physical and neurological examinations, requesting further appropriate tests will increase the prediagnosis accuracy and prevent unnecessary expenditure of time and labor.

• Applied Microscopy
• /
• 제39권3호
• /
• pp.261-266
• /
• 2009

본 연구는 잘 알려진 통증모델을 대상으로 척수신경절세포의 변성과정을 경시적으로 관찰하고자 하였다. 10주령된 Sprague-Dawley 계통의 랫드를 실험동물로 사용하였고, pentobarbital (50mg/kg)로 마취상태에서 다섯째 허리신경(L5)의 앞가지를 결찰한 후 1일, 3일, 7일 실험군으로 구분하였다. 실험 1일과 3일군에서 작은 신경절세포에서 퇴행성변화가 먼저 관찰되었고, 중간 및 큰 신경절세포에서는 그 변화가 미약했다. 7일 실험군에서는 작은 신경절세포의 수가 크게 감소하였던 반면, 중간 및 큰 신경절세포에서는 큰 변화가 없었다. 전자현미경 소견으로는 작은 신경절세포의 경우 초기 1일 및 3일군에서 미토콘드리아의 능선의 변형과 부종이 관찰되었으며, 세포질은 검게 변성되었다. 반면 큰 신경절세포의 경우 모든 실험군에서 변형된 세포가 관찰되지 않았으며, 소기관들도 잘 보존되었다. 이상의 결과를 요약하면, 척수신경 결찰에 의한 통증자극으로 랫드 척수신경절 내 작은 신경절세포는 다른 신경절세포에 비해 퇴행성변화가 빠르게 나타났으며, 미토콘드리아 등 세포질소기관의 부종을 동반한 암적화변성(dark degeneration)을 통해 사멸되었다.

• Biomolecules & Therapeutics
• /
• 제22권6호
• /
• pp.532-539
• /
• 2014

Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC ($50{\mu}mol/L$), gp120 (500 pmol/L) plus ddC ($50{\mu}mol/L$), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC ($50{\mu}mol/L$) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC ($50{\mu}mol/L$) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (> $25{\mu}m$), whereas ddC mainly affected small diameter DRG neurons (${\leq}25{\mu}m$). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

• 약학회지
• /
• 제52권4호
• /
• pp.299-305
• /
• 2008

Gabapentin, 1-(aminomethyl) cyclohexaneacetic acid, is a amino acid derivative, and is clinically effective in the treatment of neuropathic pain and partial seizures of epilepsy as a complementary therapy. The purpose of the present study was to evaluate the bioequivalence of two gabapentin tablets, $Neurontin^{R}$ tablet 800 mg (Pfizer Pharmaceuticals Co., Ltd.) and Gabapenin tablet 800 mg (Hanmi Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of gabapentin from the two gabapentin formulations in vitro was tested using KP VIII Apparatus II method with 0.06 M HCI dissolution media. Twenty six healthy male subjects, $23.85{\pm}2.24$ years in age and $69.40{\pm}11.11$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ crossover study was employed. After a single tablet containing 800 mg as gabapentin was orally administered, blood samples were taken at predetermined time intervals and the concentrations of gabapentin in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in the tested dissolution media. The pharmacokinetic parameters such as $AUC_{t}$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_{t}$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Neurontin^{R}$, were 1.28%, 0.63% and 0.62% for $AUC_{t}$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., $log0.9097{\sim}log1.1598$ and $log0.8919{\sim}log1.1262$ for $AUC_{t}$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Gabapenin tablet 800 mg was bioequivalent to $Neurontin^{R}$ tablet 800 mg.

• Clinical and Experimental Pediatrics
• /
• 제51권11호
• /
• pp.1232-1235
• /
• 2008

삼환계 항우울제의 하나인 이미프라민은 우울장애와 야뇨증, 불안장애, 신경성 통증에 쓰인다. 그러나 이미프라민을 포함한 삼환계 항우울제는 많은 부작용이 관찰되는 데, 항콜린성 작용으로 초기에 입이 마르고 동공산대, 소변 정체, 동성빈맥을 보인다. 또한 중추신경계에 작용하여 섬망, 불안, 초조, 환각, 경련, 혼수를 야기할 수 있다. 그러나 앞에서 말한 부작용 보다도 치명적인 것인 삼환계 항우울제에 의해 소디움 채널 차단으로 인한 부정맥이다. QRS파의 연장과 QTc 연장, 넓은 QRS파 빈맥, Brugada 심전도 양상이 나타나며 이런 현상은 중탄산 나트륨을 통해 나트륨을 대량으로 공급하여 회복시킬 수 있다. 이미프라민을 포함한 삼환계 항우울제에는 아직도 널리 쓰이고 있지만 지금까지 소아에서 부정맥이 부작용으로 나타난 증례에 대한 보고가 없었다. 따라서 저자들은 이미프라민 과량복용 후 경련, 넓은 QRS파를 보이는 빈맥, Brugada 심전도 양상, 무뇨를 보인 환아를 경험, 치료하여 이를 보고한다.

• 대한치과마취과학회지
• /
• 제8권1호
• /
• pp.29-34
• /
• 2008

배경: 신경병증성 통증은 스테로이드, 아편유사제 등의 진통제에 잘 반응하지 않는다. 하지만 염증성 매개물질들이 신경병증성 통증의 발생에 관여한다는 보고가 있다. 특히 선택적 COX2 억제제인 celecoxib의 신경병증성 통증에 대한 효과에 관해서 상반된 연구결과가 존재한다. 본 연구는 신경병증성 통증 모델인 척추신경 결찰모델을 이용 기계적, 냉각 이질통 및 온도감각 과민현상의 발현에 celecoxib이 미치는 영향을 관찰하여 celecoxib의 항통각효과를 확인하고자 하였다. 방법: 30마리의 쥐를 이용 척추신경을 결찰하여 신경병증성 통증을 유도하였다 celecoxib (1, 10, 100, and 300 mg/kg)을 경구 투여하였고 총 30마리 중 12마리의 쥐에서 열, 기계적자극에 대해서 통각과민, 냉각자극에 의해 이질통이 발생하였다. 약물 투여 후 30, 60, 120, 180분 후 von Frey, 냉각자극검사, Hargreaves검사를 시행하여 쥐의 행동변화를 관찰하였다. 결과: 신경결찰 후 5일 후에 celecoxib의 용량에 관계없이 열, 기계적 자극에 의한 통각과민, 냉각 자극에 대한 이질통을 감소시키지 않았다(P > 0.05). 또한 celecoxib투여에 의한 장기간의 항 통각효과는 관찰되지 않았다(P > 0.05). 결론: celecoxib을 경구로 투여하였을 때 장기간 유지된 신경병증성 통증 흰쥐에서 약의 투여용량, 투여기간에 따른 항 통각작용은 관찰되지 않았다. 따라서 조직 손상후 발생된 장기간의 신경병증성 통증에 있어서 celecoxib은 효과가 없는 것으로 사료된다.