3-Nitropropionic acid (3-NP) inhibits electron transport in mitochondria, leading to a metabolic failure. In order to elucidate the mechanism underlying this toxicity, we examined a few biochemical changes possibly involved in the process, such as metabolic inhibition, generation of reactive oxygen species (ROS), DNA strand breakage, and activation of Poly(ADP-ribose) polymerase (PARP). Exposure of SK-N-BE(2)C neuroblastoma cells to 3-NP for 48 h caused actual cell death, while inhibition of mitochondrial function was readily observed when exposed for 24 h to low concentrations (0.2${\sim}$2 mM) of 3-NP. The earliest biochemical change detected with low concentration of 3-NP was an accumulation of ROS (4 h after 3-NP exposure) followed by degradation of DNA. PARP activation by damaged DNA was also detectable, but at a later time. The accumulation of ROS and DNA strand breakage were suppressed by the addition of glutathione or N-acetyl-L-cysteine (NAC), which also partially restored mitochondrial function and cell viability. In addition, inhibition of PARP also reduced the 3-NP-induced DNA strand breakage and cytotoxicity. These results suggest that oxidative stress and activation of PARP are the major factors in 3-NP-induced cytotoxicity, and that the inhibition of these factors may be useful in protecting neuroblastoma cells from 3-NP-induced toxicity.
Han, Rafael Taeho;Kim, Han-Byul;Kim, Young-Beom;Choi, Kyungmin;Park, Gi Yeon;Lee, Pa Reum;Lee, JaeHee;Kim, Hye young;Park, Chul-Kyu;Kang, Youngnam;Oh, Seog Bae;Na, Heung Sik
The Korean Journal of Physiology and Pharmacology
/
v.22
no.2
/
pp.173-182
/
2018
Recent studies have provided several lines of evidence that peripheral administration of oxytocin induces analgesia in human and rodents. However, the exact underlying mechanism of analgesia still remains elusive. In the present study, we aimed to identify which receptor could mediate the analgesic effect of intraperitoneal injection of oxytocin and its cellular mechanisms in thermal pain behavior. We found that oxytocin-induced analgesia could be reversed by $d(CH_2)_5[Tyr(Me)^2,Dab^5]$ AVP, a vasopressin-1a (V1a) receptor antagonist, but not by $desGly-NH_2-d(CH_2)_5[D-Tyr^2,Thr^4]OVT$, an oxytocin receptor antagonist. Single cell RT-PCR analysis revealed that V1a receptor, compared to oxytocin, vasopressin-1b and vasopressin-2 receptors, was more profoundly expressed in dorsal root ganglion (DRG) neurons and the expression of V1a receptor was predominant in transient receptor potential vanilloid 1 (TRPV1)-expressing DRG neurons. Fura-2 based calcium imaging experiments showed that capsaicin-induced calcium transient was significantly inhibited by oxytocin and that such inhibition was reversed by V1a receptor antagonist. Additionally, whole cell patch clamp recording demonstrated that oxytocin significantly increased potassium conductance via V1a receptor in DRG neurons. Taken together, our findings suggest that analgesic effects produced by peripheral administration of oxytocin were attributable to the activation of V1a receptor, resulting in reduction of TRPV1 activity and enhancement of potassium conductance in DRG neurons.
Objective : Because the cause and etiology of chronic headache is not yet fully explained, the treatment of this symptom is not simple. This study compares the effects of aroma acupuncture and normal acupuncture applied on chronic headache patients, in order to establish a primary data for further studies of new treatments and developments of new practical acupunctures. Methods : 38 clinical experiment participants were gathered and through a questionnaire patients who experienced headache for more than 4 hours a day and more than 15 days per month were qualified as Chronic Headache patients. The qualified patients were classified in to two groups, aroma acupuncture group(Aroma AT group, n=23) and normal acupuncture group(AT group, n=15). Treatment was applied 2 times a weeks for 8 weeks. The acupoints, GV20, HN23, ST8, HN46, TE17, GB20, LI20, LI11, LI14, ST36, and LR3 were stimulated for 20 minutes in both the groups. The effects of both groups were analyzed using VAS scores and BPI (Brief Pain Inventory). Results : The VAS pain scores improved significantly in both groups. The decrease rate was larger in the Aroma AT group(p<0.05). The BPI scores for the both groups also decreased. The improvement in the Aroma AT group was larger(p<0.05). Conclusion : Aroma acupuncture applied on chronic headache patients showed effects of relieving pain, improving general activities, changing the mood, and improving sleeping behaviors. These effects were analyzed using VAS scores and BPI. The Aroma AT group showed significant changes of VAS and BPI compared to the AT group, suggesting that this new practical acupuncture is very effective when treating chronic headaches. Further researches are needed to evaluate the distinct functional mechanism of aroma acupuncture, but this study is meaningful in the sense that it will act as a fundamental study to build on.
Objectives: This study aimed to compare the gait patterns of cerebellar infarction patients with those of corticospinal tract stroke patients through a follow-up of patients with ataxic gait due to cerebellar infarction and corticospinal tract stroke. Methods: We investigated two cases of patients with cerebellar infarction and two cases each of acute or chronic corticospinal tract stroke who were hospitalized at Wonkwang University Gawangju Medical Center from September 1, 2017 to February 15, 2020 based on medical records and gait analyses. The spatiotemporal gait parameters of each patient were measured three times at 2-week intervals except those of the chronic corticospinal tract stroke patients, which were measured twice at a 1-month interval. Results: Spatiotemporal gait parameters, which include velocity, cadence, step length, stride length, and single support, were consistently increased in the cerebellar infarction patients in comparison to the corticospinal tract stroke patients. The stance phase was decreased in all the patients. Conclusions: The cerebellar infarction patients' gait spatiotemporal parameters were found to consistently improve. Moreover, gait analysis can be used to effectively measure improvement of ataxic gait.
Kim Yo Han;Sung Kang Keyng;Lee Kwang Ro;Lee Sang Kwan;Cheong Sang Su;Kang Sei Young;Lee So Young
Journal of Physiology & Pathology in Korean Medicine
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v.17
no.3
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pp.829-836
/
2003
Seogakjihwang-tang (SJT) was widely used to treat patients suffering from cerebral infarction. But scientific investigation has been carried out very little. The aim of the present study is to investigate the effect of SJT on the production of various cytokines in the patients with cerebral infarction (CI). We investigated interleukin (IL)-4, IL-10 and transforming growth factor (TGF)-1 in the sera of 27 patients with cerebral infarction under consciousness disorders and 10 normal controls using an originally devised sensitive sandwich enzyme-linked immunosorbent assay (ELISA). We found that plasma levels of IL-4 were slightly elevated in patients with cerebral infarction, whereas plasma levels of IL-10 (P<0.001) and TGF-1 were reduced. Peripheral blood mononuclear cells (PBMC) obtained from the patient with CI were cultured for 24 h in the presence or absence of lipopolysaccharide (LPS) or phytohaemagglutinin (PHA). The amount of IL-4, IL-10 and TGF-1, in culture supernatant, was significantly increased in the LPS or PHA treated cells compared to unstimulated cells (P<0.05), We also show that increased cytokines IL-4, and IL-10 level was significantly inhibited by SJT in a dose-dependent manner. Maximal inhibition rate of IL-4 and IL-10 production by SJT was 45.63.3% and 614.7% for LPS-stimulated cell and 27.31.2% and 83.62% for PHA-stimulated cells, respectively (P<0.05). On the other hand, SJT significantly increased the LPS or PHA-induced TGF-1 production (P<0.05). These data suggest that SJT has a regulatory effect on the cytokines production, which might explain its beneficial effect in the treatment of CI.
Botanas, Chrislean Jun;Yoon, Seong Shoon;de la Pena, June Bryan;dela Pena, Irene Joy;Kim, Mikyung;Woo, Taeseon;Seo, Joung-Wook;Jang, Choon-Gon;Park, Kyung-Tae;Lee, Young Hun;Lee, Yong Sup;Kim, Hee Jin;Cheong, Jae Hoon
Biomolecules & Therapeutics
/
v.25
no.2
/
pp.122-129
/
2017
A diversity of synthetic cathinones has flooded the recreational drug marketplace worldwide. This variety is often a response to legal control actions for one specific compound (e.g. methcathinone) which has resulted in the emergence of closely related replacement. Based on recent trends, the nitrogen atom is one of the sites in the cathinone molecule being explored by designer type modifications. In this study, we designed and synthesized two new synthetic cathinones, (1) ${\alpha}-piperidinopropiophenone$ (PIPP) and (2) ${\alpha}-piperidinopentiothiophenone$ (PIVT), which have piperidine ring substituent on their nitrogen atom. Thereafter, we evaluated whether these two compounds have an abuse potential through the conditioned place preference (CPP) in mice and self-administration (SA) in rats. We also investigated whether the substances can induce locomotor sensitization in mice following 7 days daily injection and challenge. qRT-PCR analyses were conducted to determine their effects on dopamine-related genes in the striatum. PIPP (10 and 30 mg/kg) induced CPP in mice, but not PIVT. However, both synthetic cathinones were not self-administered by the rats and did not induce locomotor sensitization in mice. qRT-PCR analyses showed that PIPP, but not PIVT, reduced dopamine transporter gene expression in the striatum. These data indicate that PIPP, but not PIVT, has rewarding effects, which may be attributed to its ability to affect dopamine transporter gene expression. Altogether, this study suggests that PIPP may have abuse potential. Careful monitoring of this type of cathinone and related drugs are advocated.
Kim, Seong-Rim;Lee, Kyung Jin;Cho, Jeong Gi;Rha, Hyung Kyun;Park, Hae Kwan;Kang, Joon Ki;Choi, Chang Rak
Journal of Korean Neurosurgical Society
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v.30
no.sup1
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pp.85-90
/
2001
Objective : DREZotomy is effective for the treatment of deafferentation pain as a consequence of root avulsion, postparaplegic pain, posttraumatic syrinx, postherpetic neuralgia, spinal cord injury, and peripheral nerve injury. We performed microsurgical DREZotomy to the patients with deafferentation pain and relieved pain without any serious complication. The purpose of this study is to evaluate the usefulness of the microsurgical DREZotomy for deafferentation pain. Methods : We evaluated 4 patients with deafferntation pain who were intractable to medical therapy. Two of them were brachial plexus injury with root avulsion owing to trauma, one was axillary metastasis of the squamous cell carcinoma of the left forearm, and the last was anesthesia dolorosa after surgical treatment(MVD and rhizotomy) of trigeminal neuralgia. Preoperative evaluation was based on the neurologic examination, radiologic imaging, and electrophysiological study. In the case of anesthesia dolorosa, we produced two parallel lesions in cephalocaudal direction, 2mm in distance, from the C2 dorsal rootlet to the 5mm superior to the obex including nucleus caudalis, after suboccipital craniectomy and C1-2 laminectomy, with use of microelectrode. In the others, we confirmed lesion site with identification of the nerve root after hemilaminectomy. We performed arachnoid dissection along the posterolateral sulcus and made lesion with microsurgical knife and microelectrocoagulation, 2mm in depth, 2mm in distance, to the direction of 30-45 degrees in the medial portion of the Lissauer's tract and the most dorsal layers of the posterior horn at the one root level above and below the lesion. Results : Compared with preoperative state, microsurgical DREZotomy significantly diminished dosage of the drugs and relieved pain meaningfully. One patient showed tansient ipsilateral ataxia, but recovered soon. There was not any serious complication. Conclusion : It may be concluded that microsurgical DREZotomy is very useful and safe therapeutic modality for deafferentation pain, especially segmentally distributed intermittent or evoke pain. Complete preoperative evaluation and proper selection of the patients and lesion making device are needed to improve the result.
Park, Kee-eon;Lee, Insung;Oh, Jaegun;Lee, Ilsuk;Choi, Sanho;Lee, Sangkwan;Sung, Kang-keyng
The Journal of the Society of Stroke on Korean Medicine
/
v.14
no.1
/
pp.71-79
/
2013
■ Objectives The goal of this pilot study is to observe the change of stroke gait by auditory cue training. ■ Methods An intracranial hemorrhage patient was trained for 4 weeks. For the 1st consecutive 6days(the 1st week), the patient was trained to walk with auditory cue, what was called auditory cue gait training condition. For the 2nd consecutive 6days(the 2nd week), the patient was trained to walk naturally without auditory cue, what was called free gait training condition. For the 3rd consecutive 6days(the 3rd week), the patient was trained to walk under auditory cue gait training condition. For the 4th consecutive 6days(the 4th week), the patient was trained to walk under free gait training condition. We analyzed the gait using a treadmill gait analysis system 3 hours after the 6th gait training. ■ Results Auditory cue gait training showed effects on gait parameters, which were increasing walking velocity, step length, stride length, decreasing cadence, step time and stride time. ■ Conclusion Auditory cue gait training improved gait parameters of a stroke patient.
Writer's cramp is a type of idiopathic focal hand dystonia characterized by muscle cramps that accompany execution of the writing task specifically. There has been renewed interest in neurosurgical procedures for the treatment of dystonia over the past several years. In particular, deep brain stimulation (DBS) has received increasing attention as a therapeutic option for patients with dystonia. However, to date, limited reporters made investigations into DBS in relation to the Writer's cramp. In this case, unilateral Ventro-oralis complex (Vo) DBS resulted in a major improvement in patient's focal dystonic movement disorders. Her post-operative Burke-Fahn-Marsden Dystonia Rating (BFMDR) scale demonstrated 1 compared with pre-operative BFMDR scale 4. We conclude that thalamic Vo complex DBS maybe an important neurosurgical therapeutic option for Writer's cramp.
Cho, Han Byul;Kim, Young Hoon;Yeom, Arim;Yoon, Sujung
Korean Journal of Biological Psychiatry
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v.22
no.3
/
pp.113-117
/
2015
Psychiatry has progressed with neurobiological basis, providing individually tailored treatment, preventing mental illness, and managing public mental health. Foundational knowledge that may contribute to the development of psychiatry and neuroscience has been attained through continual national and international investment in research. However, this knowledge obtained from neurobiological research is not being applied to clinical practice proactively. This may be due to a lack of support for translational research connecting neuroscience with clinical practice, and a lack of development and availability of educational programs for clinical psychiatrists. To solve these problems, it is essential to support translational research conducted by clinicians and to establish an appropriate reward system. Considering the direction of progress in psychiatry and the demand from clinicians, appropriate investment in research and education programs that provide neurobiological knowledge applicable to clinical practice is required. Researchers and educators must also communicate and collaborate to deliver neurobiological findings effectively.
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