• Title/Summary/Keyword: Anti-epilepsy

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The Indian Magical Herb 'Sanjeevni' (Selaginella bryopteris L.) - A Promising Anti-inflammatory Phytomedicine for the Treatment of Patients with Inflammatory Skin Diseases

  • Paswan, Shravan Kumar;Gautam, Arti;Verma, Pritt;Rao, Chandana Venkateswara;Sidhu, Om Prakash;Singh, Ajeet Pratap;Srivastava, Sajal
    • Journal of Pharmacopuncture
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    • v.20 no.2
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    • pp.93-99
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    • 2017
  • Objectives: Selaginella bryopteris L. (family: Selaginaceae), is often used in traditional Indian systems of medicine for the prevention and cure of several disorders and for the treatment of patient with spermatorrhoea, venereal disease, constipation, colitis, urinary tract infections, fever, epilepsy, leucorrhoea, beri-beri and cancer. It is also used as a strength tonic. This study aimed to evaluate the mechanisms underlying the anti-inflammatory effects of topically administered aqueous, polar and non-polar methanolic fractions ($10mg/20{\mu}L$) of Selaginella bryopteris. Methods: An acute oral toxicity study of Selaginella bryopteris at doses from 250 to 2,000 mg/kg body weight (bw) was performed. Aqueous, polar and non-polar methanolic extracts ($10mg/20{\mu}L$) applied topically for 5 days were evaluated for their anti-inflammatory effects against 12-tetra-O-decanoyl phorbol acetate (TPA)- induced inflammation by using the redness in the ear, the ear's weight (edema), oxidative stress parameters, such as lipid-peroxide (LPO) and nitric oxide (NO), and the pro-inflammatory cytokines involved in inflammation, such as tumour necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$ and IL-6. Indomethacine ($0.5mg/20{\mu}L$) was used for the positive control. Results: Selaginella bryopteris produced no mortalities when administered orally at doses from 250 to 2,000 mg/kg bw. Topical treatment with the non-polar methanolic fraction ($10mg/20{\mu}L$) significantly suppressed redness ($2.4{\pm}0.5$) and edema ($30.4{\pm}1$) and effectively reduced the LPO level ($32.3{\pm}3.3$). The NO level was ($8.07{\pm}0.55$), and the $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 levels were decreased to $69.6{\pm}15.5$, $7.7{\pm}4.8$ and $82.6{\pm}5.9$, respectively. Conclusion: This study demonstrated for the first time the mechanisms underlying the anti-inflammatory effect of medicinal plants like Selaginella bryopteris and quantified the pharmacological interactions between them. The present study showed this herbal product to be a promising anti-inflammatory phytomedicine for the treatment of patients with inflammatory skin diseases.

A Case of Tuberous Sclerosis with Pulmonary Involvement (폐를 침범한 결절성 경화증 1예)

  • Ahn, Jong-Ho;Suh, Gee-Young;Kim, Young-Whan;Shim, Young-Soo;Kim, Keun-Youl;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.39 no.5
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    • pp.433-437
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    • 1992
  • Tuberous sclerosis is a syndrome characterized by the facial skin lesion, epilepsy, and mental retardation. Pulmonary involvement is uncommon, but when the lung is involved by tuberous sclerosis it shows characteristic reticulonodular infiltration and cystic changes. We experienced a 34-year-old female patient of known tuberous sclerosis admitted due to pneumothorax. Chest PA showed diffuse fine reticulonodular infiltration and chest CT revealed diffuse cystic changes of the lung. Pleurodesis with tetracycline was done to prevent recurrence, but chylothorax occurred four months after the treatment. Pleurosis was tried again and anti estrogen treatment began.

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Determination of Novel Synthetic 5HT2C Agonist KOPC20010 by Gas-Chromatography/Mass Spectrometry and its Bioavailability in Sprague-Dawley Rats

  • Im, Hye-Yeon;Pae, Ae-Nim;Yang, Ha-Yun;Park, Woo-Kyu;Seo, Ji-Eun;Haque, Md. Mamunul;Kwon, Oh-Seung
    • Journal of Pharmaceutical Investigation
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    • v.41 no.1
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    • pp.31-36
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    • 2011
  • $5HT_{2C}$ receptor among fourteen 5-HT subtypes plays important roles in several disorders such as depression, anxiety, epilepsy, schizophrenia and sleep disorders. The purpose of the study is to investigate pharmacokinetic parameters and bioavailability of a newly synthesized selective agonist of $5-HT_{2C}$ receptor, KOPC-20010 (KP10) in rats after intravenous and oral administration for the development of therapeutic anti-obesity agents. KP10 was administered orally (40 mg/kg) or intravenously (20 mg/kg), blood was collected via a catheter, and analyzed by GC/MSD. The calibration curve of KP10 in plasma and urine showed high linearity ($r^2$ >0.999). The retention times of KP10 in plasma and urine were 8.7 and 9.7 min, respectively. After oral administration of 40 mg/kg, pharmacokinetic parameters were calculated as follows; $C_{max}$ value was $1242.9{\pm}1195.5$ ng/mL at $1.1{\pm}0.6$ hr ($T_{max}$). $AUC_{0->24hr}$ and $AUC_{0>{\infty}}$ were $8034.2{\pm}960.7$ and $10464.1{\pm}681.5\;ng{\cdot}hr/mL$, respectively. The terminal half-life was $21.9{\pm}7.6$ hr. $AUC_{0->24hr}$ and $AUC_{0>{\infty}}$ were $4292.4{\pm}523.0$ and $6111.2{\pm}756.2\;ng{\cdot}hr/mL$, respectively, after 20 mg/kg of intravenous administration. The terminal half-life after intravenous administration was $25.1{\pm}9.4$ hr. Bioavailability of KP10 was determined to 86%. The excretion amount into the urine within 48 hr was approximately 4.7 to 6.7% of the dose administered. These data may be beneficial to the anti-obesity drug development of KP10.

The Effects of Gabapentin on Facial Formalin Test (백서에서 Gabapentin 전신투여가 Facial Formalin Test에 미치는 영향)

  • Kim, Chul-Hong;Baik, Seong-Wan;Kim, Hae-Kyu;Kwon, Jae-Young;Kim, Kyoung-Hun;Choi, Sung-Hwan
    • Journal of The Korean Dental Society of Anesthesiology
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    • v.3 no.2 s.5
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    • pp.92-97
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    • 2003
  • Background: Gabapentin is a novel anti-epileptic drug, which is used in clinical practice to treat epilepsy. This drug is also used as an analgesic in pain patients. The antinociceptive effect of this drug was assessed using the formalin test in the rat. Methods: In order to investigate the effects of gabapentin on the trigeminal nerve territory, we injected 0.5% formalin into the upper lip. Adult, male, Sprague-Dawley rats received a $50{\mu}l$ subcutaneous injection of 5% formalin into one vibrissal pad and the consequent, facial grooming behavior was monitored. Consistent with previous investigations using tile formalin model, animals exhibited biphasic nocifensive grooming (phase 1, 0-12 min; phase 2, 12-60 min). Results: The intraperitoneal administration gabapentin 5 minutes prior to the formalin injection led to a significant, dose-dependent reduction in grooming time during phase 2. In high doses, gabapentin also reduced the time of grooming during phase 1. Conclusions: The Intraperitoneal injection of gabapentin has an analgesic effect in the facial formalin rat model and this analgesic effect increases dose-dependently.

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Proteomic Changes by Acupuncture Stimulation at HT7 in the Hippocampus of Rat Pups (신문혈 자침이 어린 백서 해마의 단백질 발현에 미치는 영향)

  • Bae, Chang-Hwan;Kim, Dong-Soo;Kim, Seung-Tae
    • Korean Journal of Acupuncture
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    • v.29 no.2
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    • pp.260-270
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    • 2012
  • Objectives : Hippocampus, a region of temporal lobe, plays an important role in the pathogenic mechanisms of brain diseases such as Alzheimer's disease, depression and temporal lobe epilepsy. This research is designed to investigate hippocampal changes after acupuncture stimulation at Shinmun(HT7) using 2-dimensional gel electrophoresis(2-DE). Methods : On postnatal-day 15, rat pups were randomly devided into Normal(NOR) or HT7 group. All of Pups kept with their mothers for 7 days, but pups in HT7 group received acupuncture stimulation at HT7 daily. On postnatal-day 21, hippocampus of each rat pup was dissceted 30 minutes after last acupuncture stimulation and the protein expressions were investigated using 2-DE. Results : After acupuncture stimulation at HT7, expression of 20 proteins were significantly increased. Succinate semialdehyde dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase-like, transketolase, aconitate hydratase and phosphoglucomutase-1 were related to glucose methabolism. Eukaryotic initiation factor(eIF) 4A-II, eIF 4A-III, mitochondrial Tu translation elongation factor and chain A of crystal structure of the 70-Kda heat shock cognate protein involve in the protein synthesis in ribosome. Tubulin ${\beta}$-4 chain, tubulin T ${\beta}$-15 and tubulin ${\alpha}$-1B chain comprise cytoskeleton. Glutathione S-transferase(GST) ${\omega}$-1, GST P and GST Yb-3 can reduce oxidative stress. ${\beta}$-soluble N-ethylmaleimide-sensitive fusion protein attachment protein is required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus, glycerol-3-phosphate dehydrogenase plays a major role in lipid biosynthesis, creatine kinase U-type catalyses the conversion of creatine and consumes adenosine triphosphate to create phosphocreatine and adenosine diphosphate. Platelet-activating factor acetylhydrolase IB subunit alpha and voltage depedent anion-selective channel protein 2 were also increased. Conclusions : The results suggest that acupuncture stimulation at HT7 may enhance glucose and lipid metabolism, protein synthesis, cytoskeletal substance and anti-oxidative stress in hippocampus.

Molecular Taxonomy of a Soil Actinomycete Isolate, KCCM10454 Showing Neuroprotective Activity by 16S rRNA and rpoB Gene Analysis

  • Lee Bong Hee;Kim Hong;Kim Hyun Ju;Lim Yoon Kyu;Byun Kyung Hee;Hutchinson Brian;Kim Chang Jin;Ko Young Hwan;Lee Keun Hwa;Cha Chang Yong;Kook Yoon Hoh;Kim Bum Joon
    • Journal of Microbiology
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    • v.43 no.2
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    • pp.213-218
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    • 2005
  • Epilepsy constitutes a significant public health problem, and even the newest drugs and neurosurgical techniques have proven unable to cure the disease. In order to select a group of isolates which could generate an active compound with neuroprotective or antiepileptic properties, we isolated 517 actinomycete strains from soil samples taken from Jeju Island, in South Korea. We then screened these strains for possible anti-apoptotic effects against serum deprivation-induced hippocampal cell death, using the 3-(4, 5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) assay as an in vitro test. The excitotoxic glutamate analog, kainic acid (KA), was used to induce seizures in experimental mice in our in vivo tests. As a result of this testing, we located one strain which exhibited profound neuroprotective activity. This strain was identified as a Streptomyces species, and exhibited the rifampinresistant genotype, Asn$(AAC)^$442, according to the results of 16S rRNA and rpoB gene analyses

The literatural study of the drug dependence (약물의존(藥物依存)에 대한 문헌적(文獻的) 고찰(考察))

  • Lee, Jun Young;Lee, Sang Ryong
    • Journal of Haehwa Medicine
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    • v.9 no.1
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    • pp.711-724
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    • 2000
  • I reached following conclusion through a bibliographic study about the drug dependence. 1. The drug dependence is the case that taking drugs continually in order to get around discomfort and get mental drug efficacy. that is also the state of poisoning that shows compulsions that using all means to get drugs. the drug dependence is coincident with alcolism in Oriental Medicine. 2 Medicinal matters that causes the drug dependence consist of two field. one is licit drugs, including a tranquilizer, a sleeping pill, anti-anxiety drug, alcohol, caffeine, tobacco, etc. the other is illict drugs, including opium products, psychostimulant, a hallucinogen, aromatic agent(adhesives, LSD, etc.) 3. Drugs that causes dependences has the habit which causing mental dependences and the medicinal poisining which causing physical dependences. 4. A syndrome of abstain from the drug which rides on all kinds of drugs is analogous to depressive psychosis, epilepsy, insanity, depressive syndromes, disorder of internal organs, histery, dizziness, etc. 5. The drug dependence causes visceral dysfunction, that is chiefly inflammatory lesion of brain, heart lung etc. (inflammatory lesions os mainly due to infect.) and injuries liver which removes toxic agents and kidney which is an excretory organ. 6. The treatment of the drug dependence, which needs at first check the medical record and the syndrome, is consist of the expectant treatment and isolating treatment as a rule and sometimes mental therapeutics is going on at the same time. 7. The oriental medical cure of the drug dependence needs more concrete study.

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Therapeutic effects of stiripentol against ischemia-reperfusion injury in gerbils focusing on cognitive deficit, neuronal death, astrocyte damage and blood brain barrier leakage in the hippocampus

  • Shin, Myoung Cheol;Lee, Tae-Kyeong;Lee, Jae-Chul;Kim, Hyung Il;Park, Chan Woo;Cho, Jun Hwi;Kim, Dae Won;Ahn, Ji Hyeon;Won, Moo-Ho;Lee, Choong-Hyun
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.1
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    • pp.47-57
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    • 2022
  • Stiripentol is an anti-epileptic drug for the treating of refractory status epilepticus. It has been reported that stiripentol can attenuate seizure severity and reduce seizure-induced neuronal damage in animal models of epilepsy. The objective of the present study was to investigate effects of post-treatment with stiripentol on cognitive deficit and neuronal damage in the cornu ammonis 1 (CA1) region of the hippocampus proper following transient ischemia in the forebrain of gerbils. To evaluate ischemia-induced cognitive impairments, passive avoidance test and 8-arm radial maze test were performed. It was found that post-treatment with stiripentol at 20 mg/kg, but not 10 or 15 mg/kg, reduced ischemia-induced memory impairment. Transient ischemia-induced neuronal death in the CA1 region was also significantly attenuated only by 20 mg/kg stiripentol treatment after transient ischemia. In addition, 20 mg/kg stiripentol treatment significantly decreased ischemia-induced astrocyte damage and immunoglobulin G leakage. In brief, stiripentol treatment after transient ischemia ameliorated transient ischemia-induced cognitive impairment in gerbils, showing that pyramidal neurons were protected and astrocyte damage and blood brain barrier leakage were significantly attenuated in the hippocampus. Results of this study suggest stiripentol can be developed as a candidate of therapeutic drug for ischemic stroke.

Neuronal injury in AIDS dementia: Potential treatment with NMDA open-channel blockers and nitric oxide-related species

  • Lipton, Stuart A.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.19-29
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    • 1996
  • The neurological manifestations of AIDS include dementia, encountered even in the absence of opportunistic superinfection or malignancy. The AIDS Dementia Complex appears to be associated with several neuropathological abnormalities, including astrogliosis and neuronal injury or loss. How can HIV-1 result in neuronal damage if neurons themselves are only rarely, if ever, infected by the vitus\ulcorner In vitro experiments from several different laboratiories have lent support to the existence of HIV- and immune-related toxins. In one recently defined pathway to neuronal injury, HIV-infected macrophages/microglia as well as macrophages activated by HIV-1 envelope protein gp120 appear to secrete excitants/neurotoxins. These substances may include arachidonic acid, platelet-activating factor, free radicals (NO - and O$_2$), glutamate, quinolinate, cysteine, cytokines (TNF-${\alpha}$, IL1-B, IL-6), and as yet unidentified factors emanating from stimulated macrophages and possibly reactive astrocytes. A final common pathway for newonal suscepubility appears to be operative, similar to that observed in stroke, trauma, epilepsy, and several neurodegenerative diseases, including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves excessive activation of N-methyl-D-aspartate (NMDA) receptor-operated channels, with resultant excessive influx of Ca$\^$2+/ leading to neuronal damage, and thus offers hope for future pharmacological intervention. This chapter reviews two clinically-tolerated NMDA antagonists, memantine and nitroglycerin; (ⅰ) Memantine is an open-channel blocker of the NMDA-associated ion channel and a close congener of the anti-viral and anti-parkinsonian drug amantadine. Memantine blocks the effects of escalating levels of excitotoxins to a greater degree than lower (piysiological) levels of these excitatory amino acids, thus sparing to some extent normal neuronal function. (ⅱ) Niuoglycerin acts at a redox modulatory site of the NMDA receptor/complex to downregulate its activity. The neuroprotective action of nitroglycerin at this site is mediated by n chemical species related to nitric oxide, but in a higher oxidation state, resulting in transfer of an NO group to a critical cysteine on the NMDA receptor. Because of the clinical safety of these drugs, they have the potential for trials in humans. As the structural basis for redox modulation is further elucidated, it may become possible to design even better redox reactive reagents of chinical value. To this end, redox modulatory sites of NMDA receptors have begun to be characterized at a molecular level using site-directed mutagenesis of recombinant subunits (NMDAR1, NMDAR2A-D). Two types of redox modulation can be distinguished. The first type gives rise to a persistent change in the functional activity of the receptor, and we have identified two cysteine residues on the NMDARI subunit (#744 and #798) that are responsible for this action. A second site, presumably also a cysteine(s) because <1 mM N-ethylmaleimide can block its effect in native neurons, underlies the other, more transient redox action. It appears to be at this, as yet unidentified, site on the NMDA receptor that the NO group acts, at least in recombinant receptors.

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A Case of Klinefelter Syndrome with Refractory Seizure in Infant (난치성 경련이 동반된 클라인펠터 증후군 영아)

  • Kim, Sun;Kim, Jong Seok;Kim, Dong Hyun;Lee, Ji Eun;Kwon, Young Se
    • Journal of the Korean Child Neurology Society
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    • v.26 no.4
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    • pp.276-279
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    • 2018
  • Klinefelter syndrome a genetic disorder with various clinical manifestations. Neurological symptoms, such as seizures, are rarely reported with Klinefelter syndrome, and it response well to anti-epileptic drugs. A 5-month-old boy visited the Inha university hospital due to jerking movements and hiccups. The patient had been diagnosed with Klinefelter syndrome at birth and had a medical history of admission to the neonatal intensive care unit due to opisthotonus and ocular deviation at 26 days of age. The patient's serum testosterone level was decreased and his anti-$M{\ddot{u}}llerian$ hormone level was increased. The brain image examination was normal and the electoencephalography and other blood test results showed no specific findings. However, after admission, the patient recurred generalized tonic-clonic-seizures recurred intermittently even after the administration of antiepileptic drugs. This paper reports a case of non-febrile seizures in a child with Klinefelter syndrome who presented with a refractory course.