• Title/Summary/Keyword: Nervous system disorders

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Concurrency of Guillain-Barre syndrome and acute transverse myelitis: a case report and review of literature

  • Tolunay, Orkun;Celik, Tamer;Celik, Umit;Komur, Mustafa;Tanyeli, Zeynep;Sonmezler, Abdurrahman
    • Clinical and Experimental Pediatrics
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    • v.59 no.sup1
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    • pp.161-164
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    • 2016
  • Guillain-$Barr{\acute{e}}$ syndrome and acute transverse myelitis manifest as demyelinating diseases of the peripheral and central nervous system. Concurrency of these two disorders is rarely documented in literature. A 4-year-old girl presenting with cough, fever, and an impaired walking ability was admitted to hospital. She had no previous complaints in her medical history. A physical examination revealed lack of muscle strength of the lower extremities and deep tendon reflexes. MRI could not be carried out due to technical problems; therefore, both Guillain-$Barr{\acute{e}}$ syndrome and acute transverse myelitis were considered for the diagnosis. Intravenous immunoglobulin treatment was started as first line therapy. Because this treatment did not relieve the patient's symptoms, spinal MRI was carried out on the fourth day of admission and demyelinating areas were identified. Based on the new findings, the patient was diagnosed with acute transverse myelitis, and high dose intravenous methylprednisolone therapy was started. Electromyography findings were consistent with acute polyneuropathy affecting both motor and sensory fibers. Therefore, the patient was diagnosed with concurrency of Guillain-$Barr{\acute{e}}$ syndrome and acute transverse myelitis. Interestingly, while concurrency of these 2 disorders is rare, this association has been demonstrated in various recent publications. Progress in diagnostic tests (magnetic resonance imaging and electrophysiological examination studies) has enabled clinicians to establish the right diagnosis. The possibility of concurrent Guillain-$Barr{\acute{e}}$ syndrome and acute transverse myelitis should be considered if recovery takes longer than anticipated.

Determination of 5-HT2C agonist KKHQ80114 and KKHQ80109 in Rat Plasma and Urine by Gas-Chromatography/Mass Spectrometry

  • Im, Hye-Yeon;Park, Hye-Sil;Choo, Hyun-Ah;Pae, Ae-Nim;Kwon, Oh-Seung
    • Journal of Pharmaceutical Investigation
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    • v.39 no.5
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    • pp.321-325
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    • 2009
  • 5-HT$_{2C}$ receptors have been considered as therapeutic targets for the treatment of various central nervous system disorders such as depression, anxiety, epilepsy, schizophrenia and sleep disorders. We chemically synthesized KKHQ80114 (K14) and KKHQ80109 (K09), selective 5-HT$_{2C}$ agonists, with the purpose of developing therapeutic agents for the treatment of obesity. The objective of this work is to investigate analytical methods of these compounds in the plasma and urine of rats by gas chromatography/mass spectrometry. In this experiment, K14 was determined in plasma and urine by using K09 as internal standard. Calibration curves give a good linearity in plasma (r$^2$=0.9993) and urine (r$^2$=0.9988). Among hexane, ethyl acetate and diethyl ether, the highest peak was observed in diethyl ether. However, ethyl acetate was used since more interfering peaks were observed with diethyl ether. Inter-day precision and accuracy were determined in the ranges of 50-500 ng/mL for plasma and 10-500 ng/ml for urine. Quantitation limits were 50 ng/mL plasma and 25 ng/ mL urine. These data may be applicable for further studies of these compounds including absorption and metabolism due to no pharmacokinetic or analytical data available.

Pharmacokinetics and Bioavailability of New Synthetic 5-HT2C Agonists, KKHQ80109 and KKHQ80114, in Sprague-Dawley Rats

  • Im, Hye-Yeon;Choo, Hyun-Ah;Pae, Ae-Nim;Kwon, Oh-Seung
    • Journal of Pharmaceutical Investigation
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    • v.39 no.5
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    • pp.327-331
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    • 2009
  • 5-HT$_{2C}$ receptors have been considered as therapeutic targets for the treatment of various central nervous system disorders such as depression, anxiety, epilepsy, schizophrenia and sleep disorders. We chemically synthesized KKHQ80109 (K09) and KKHQ80114 (K14), selective 5-HT$_{2C}$ agonists, with the purpose of developing therapeutic agents for the treatment of obesity. The objective of this work is to investigate pharmacokinetic parameters and bioavailability of K09 and K14 in rats given orally or intravenously. Oral administration of 20 mg/kg K09 results in 4.11 hr of the terminal half-life and 89.16 ng/mL of C$_{max}$ at 5.00 hr (T$_{max}$). The terminal half-life of K14 was 3.83 hr with 215.81 ng/mL of C$_{max}$ at 3.33 hr (T$_{max}$) after oral dosing of 20 mg/kg K14, indicating that K14 is more rapidly absorbed than K09. Bioavailability showed 0.17-0.21 for K09 and 0.19-0.23 for K14. Urinary excretion of parent K09 and K14 was less than 1%, indicating that K09 and K14 undergo very extensive hepatic metabolism.

The Literature Review of FibroMyalgia Syndrome (섬유근통 증후군에 대한 문헌고찰)

  • Kim Myung-Chul;Kim Jin-Sang
    • The Journal of Korean Physical Therapy
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    • v.16 no.4
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    • pp.23-37
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    • 2004
  • Fibromyalgia syndrome(FMS) is a chronic pain disorder of unknown etiology characterized by widespread musculoskeletal aches and pains, stiffness, and general fatigue, disturbed sleep and sleepiness. Frequently misdiagnosed, FMS is often confused with myofascial pain syndrome, polymyalgia rheumatica, polymyositis, hypothyroidism, metastatic carcinoma, rheumatoid arthritis (RA), juvenile rheumatoid arthritis, chronic fatigue syndrome, or systemic lupus erythematosus, any of which may occur concomitantly with FMS. The management of FMS often begins with a thorough examination and a diagnosis from a physician who is formally trained in tender-point/trigger-point recognition. An initial diagnosis provides reassurance to the patient and often reduces the anxiety and depression patterns associated with FMS. The most common goals in the management of FMS are (1) to break the pain cycle, (2) to restore sleep patterns, and (3) to increase functional activity levels. Because FMS is a multifactorial syndrome, it is likely that the best treatment will encompass multiple strategies. Medication with analgesics and antidepressants and also physiotherapy, are often prescribed and give some relief. The other most effective intervention for long-term management of FS to date is physical exercise. Physical therapists can instruct patients in the use of heat at home (moist hot packs, heating pads, whirlpools, warm showers or baths, and hot pads) to increase local blood flow and to decrease muscle spasm and tension. Also instruct patients in the proper use of cold modalities (ice packs, ice massage, and cool baths) to anesthetize localized areas of pain (tender points) and break the pain cycle. Massage and tender-point massage also may promote muscle relaxation. To date, the two most important interventions for the long-term management of FS are patient education and physical exercise. Lately, is handling FMS and Chronic Fatigue syndrome(CFS) together, becuase FMS and CFS are poorly understood disorders that share similar demographic and clinical characteristics. Because of the clinical similarities between both disorders it was suggested that they share a common pathophysiological mechanism, namely, central nervous system dysfunction.

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Korean Red Ginseng mitigates spinal demyelination in a model of acute multiple sclerosis by downregulating p38 mitogen-activated protein kinase and nuclear factor-κB signaling pathways

  • Lee, Min Jung;Chang, Byung Joon;Oh, Seikwan;Nah, Seung-Yeol;Cho, Ik-Hyun
    • Journal of Ginseng Research
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    • v.42 no.4
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    • pp.436-446
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    • 2018
  • Background: The potential therapeutic values of Korean Red Ginseng extract (KRGE) in autoimmune disorders of nervous system have not been fully investigated. Methods: We used an acute experimental autoimmune encephalomyelitis animal model of multiple sclerosis and determined the effects and mechanism of KRGE on spinal myelination. Results: Pretreatment with KRGE (100 mg/kg, orally) for 10 days before immunization with myelin basic protein $(MBP)_{68-82}$ peptide exerted a protective effect against demyelination in the spinal cord, with inhibited recruitment and activation of immune cells including microglia, decreased mRNA expression of detrimental inflammatory mediators (interleukin-6, interferon-${\gamma}$, and cyclooxygenase-2), but increased mRNA expression of protective inflammatory mediators (insulin-like growth factor ${\beta}1$, transforming growth factor ${\beta}$, and vascular endothelial growth factor-1). These results were associated with significant downregulation of p38 mitogen-activated protein kinase and nuclear factor-${\kappa}B$ signaling pathways in microglia/macrophages, T cells, and astrocytes. Conclusion: Our findings suggest that KRGE alleviates spinal demyelination in acute experimental autoimmune encephalomyelitis through inhibiting the activation of the p38 mitogen-activated protein kinase/nuclear factor-${\kappa}B$ signaling pathway. Therefore, KRGE might be used as a new therapeutic for autoimmune disorders such as multiple sclerosis, although further investigation is needed.

Improvement of Functional Recovery by Cell Transplantation after Spinal Cord Injury (척수손상 후 세포이식에 의한 운동기능의 회복증진)

  • 이배환;이경희;성제경;황세진;김계성
    • Science of Emotion and Sensibility
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    • v.7 no.2
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    • pp.179-186
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    • 2004
  • Acute spinal cord injury can produce neurologic injury with many physical, psychological and social ramifications. It has been shown that two separate components combine to produce neurologic damage in acute spinal cord injury : the primary and secondary injuries. The primary mediators of spinal cord injury include the actual mechanical tissue disruption which is a passive process that occurs immediately following the trauma. A secondary injury cascade follows which appears mediated by cellular and molecular processes working through complex mechanisms. Both the primary and secondary injury cascades produce cell death both in neuronal and supporting cell tissues. Recovery from central nervous system(CNS) disorders is hindered by the limited ability of the vertebrate CNS to regenerate injured cells, replace damaged myelin sheath, and re-establish functional neuronal connections. Of many CNS disorders including multiple sclerosis, stroke, and other trauma, spinal cord injury is one of the important diseases because of the direct association with the functional loss of the body. Previous studies suggest that substantial recovery of function might be achieved through regeneration of lost neuronal cells and remyelination of intact axon in spinal cord injury which is occurred frequently. As a therapeutic approach in spinal cord injury, recently, cell transplantation provides a potential solution for the treatment of spinal cord injury. This review describes the characteristics of spinal cord injury and presents some evidence supporting functional recovery after cell transplantation following spinal cord injury.

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Cardiac Autonomic Control and Neural Arousal as Indexes of Fatigue in Professional Bus Drivers

  • Lecca, Luigi I.;Fadda, Paolo;Fancello, Gianfranco;Medda, Andrea;Meloni, Michele
    • Safety and Health at Work
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    • v.13 no.2
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    • pp.148-154
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    • 2022
  • Background: Bus driving is a mentally demanding activity that requires prolonged attention to ensure safety. The aim of the study was to assess mental fatigue caused by driving a public bus and to find a profile of workers at higher risk. Methods: We evaluated changes of critical flicker fusion (CFF) (index of central arousal) and heart rate variability (HRV) (index of autonomic balance) in a 6-hour driving shift on a real route, in 31 professional bus drivers, and we tested the influence of personal factors such as sleep quality, BMI, and age. Paired t-test was used to test differences of CFF and HRV between both initial and final phase of driving, while multiple linear regression tested the influence of personal variables on the indexes of mental fatigue. Results: Results showed that CFF significantly decreased after 6 hours of bus driving (41.91 Hz, sd 3.31 vs. 41.15 Hz, sd 3.15; p = 0.041), and heart rate significantly decreased in the final phase of driving, with respect to the initial phase (85 vs. 78 bpm, p = 0.027). Increasing age (beta = -0.729, p = 0.022), risk of obstructive sleep apnea syndrome (beta = -0.530, p = 0.04), and diurnal sleepiness (beta = -0.406, p = 0.017) showed a significant effect on influencing mental fatigue. Conclusion: Elderly drivers at higher risk of sleep disorders are more prone to mental fatigue, when exposed to driving activity. Monitoring indexes of central arousal and autonomic balance, coupled with the use of structured questionnaires can represent a useful strategy to detect profile of workers at higher risk of mental fatigue in such duty.

SKF96365 impedes spinal glutamatergic transmission-mediated neuropathic allodynia

  • Qiru Wang;Yang Zhang;Qiong Du;Xinjie Zhao;Wei Wang;Qing Zhai;Ming Xiang
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.1
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    • pp.39-48
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    • 2023
  • Spinal nerve injury causes mechanical allodynia and structural imbalance of neurotransmission, which were typically associated with calcium overload. Storeoperated calcium entry (SOCE) is considered crucial elements-mediating intracellular calcium homeostasis, ion channel activity, and synaptic plasticity. However, the underlying mechanism of SOCE in mediating neuronal transmitter release and synaptic transmission remains ambiguous in neuropathic pain. Neuropathic rats were operated by spinal nerve ligations. Neurotransmissions were assessed by whole-cell recording in substantia gelatinosa. Immunofluorescence staining of STIM1 with neuronal and glial biomarkers in the spinal dorsal horn. The endoplasmic reticulum stress level was estimated from qRT-PCR. Intrathecal injection of SOCE antagonist SKF96365 dose-dependently alleviated mechanical allodynia in ipsilateral hind paws of neuropathic rats with ED50 of 18 ㎍. Immunofluorescence staining demonstrated that STIM1 was specifically and significantly expressed in neurons but not astrocytes and microglia in the spinal dorsal horn. Bath application of SKF96365 inhibited enhanced miniature excitatory postsynaptic currents in a dosage-dependent manner without affecting miniature inhibitory postsynaptic currents. Mal-adaption of SOCE was commonly related to endoplasmic reticulum (ER) stress in the central nervous system. SKF96365 markedly suppressed ER stress levels by alleviating mRNA expression of C/ EBP homologous protein and heat shock protein 70 in neuropathic rats. Our findings suggested that nerve injury might promote SOCE-mediated calcium levels, resulting in long-term imbalance of spinal synaptic transmission and behavioral sensitization, SKF96365 produces antinociception by alleviating glutamatergic transmission and ER stress. This work demonstrated the involvement of SOCE in neuropathic pain, implying that SOCE might be a potential target for pain management.

Investigating the Status of WHO VigiAccess Adverse Drug Event Reporting and Exploring its Potential for Application Using Anti-Obesity Agents as Examples (VigiAccess를 통한 WHO의 약물 이상사례 보고 현황 검색과 그 활용 가능성 탐색 : 비만 치료제를 중심으로)

  • Mikyung Kim
    • The Journal of Internal Korean Medicine
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    • v.45 no.1
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    • pp.55-74
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    • 2024
  • Objectives: This study reviewed the status of adverse event (AE) reporting in VigiAccess using anti-obesity agents as examples and explored the possibility of its use and future challenges. Methods: AE reports related to some representative drugs among herbal medicines (HMs), complex HM prescriptions, ingredients of supplements, and over-the-counter and prescription medicines were investigated using VigiAccess on February 1, 2024. Results: AE reports on prescription drugs were overwhelmingly higher than those on HMs or supplements. Although most reports were submitted from North America, reports on Ephedra sinica and green tea extract (GTE) were more from Asia and Europe, respectively. The female population reported more, and the difference in the sex ratio was the smallest for Ephedra spp. The age group was concentrated on young adults, but many older patients reported GLP-1 receptor agonist-related AEs. Symptoms related to the gastrointestinal and nervous systems were most commonly reported, but mental and cardiac disorders were common in Ephedra-type HMs. Hepatobiliary disorders are also commonly found in GTE-related reports. Conclusions: VigiAccess was useful for easily checking the global status of AE reporting for prescription drugs. However, several limitations were observed in using VigiAccess for HMs because of the few reports. Thus, it is necessary to increase the number of reports by education and to promote AE reporting among HM prescribers and users. The full range of HMs should be included in the pharmacovigilance system, and the coding and classification of HMs should be revised.

Atypical Antidepressant Activity of 3,4-Bis(3,4-Dimethoxyphenyl) Furan-2,5-Dione Isolated from Heart Wood of Cedrus deodara, in Rodents

  • Kumar, Nitesh;Dhayabaran, Daniel;Nampoothiri, Madhavan;Nandakumar, Krishnadas;Puratchikody, A.;Lalani, Natasha;Dawood, Karima;Ghosh, Aanesha
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.5
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    • pp.365-369
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    • 2014
  • Cedrus deodara (Pinaceae) has been used traditionally in Ayurveda for the treatment of central nervous system disorders. 3,4-bis(3,4-dimethoxyphenyl)furan-2,5-dione (BDFD) was isolated from heart wood of Cedrus deodara and was shown to have antiepileptic and anxiolytic activity. Thus, the present study was aimed to explore its anti-depressant effect and to correlate the effect with serotonin and nor adrenaline levels of brain. Albino mice were used as experimental animal. Animals were divided in to three groups; vehicle control, imipramine (30 mg/kg i.p.), BDFD (100 mg/kg i.p.). Tail suspension test (TST) and forced swim test (FST) was performed to evaluate antidepressant effect of BDFD. BDFD (100 mg/kg, i.p.) showed a significant decrease in immobility time when subjected to FST whereas immobility time was not significantly altered in TST. BDFD treatment increased serotonin and noradrenaline levels in the brain which is indicative of BDFD having possible atypical antidepressant action.