Fucoidan, a sulfated polyanionic polymer of L-fucose, is obtained from brown marine macroalgae. In the present study, neuroprotective effect of fucoidan against N-methyl- D-aspartate (NMDA)-induced excitotoxicity in the hippocampus was investigated. The patch clamp study revealed that fucoidan significantly inhibited NMDA receptor-activated ion current in the acutely dissociated hippocampal CA1 neurons. In an organotypic hippocampal slice culture, fucoidan inhibited NMDA-induced neuronal cell death in a dose-dependent manner. The present study showed that fucoidan possesses a neuroprotective effect against NMDA-induced excitotoxicity, and that the suppressive effect of fucoidan on the NMDA-induced ion current can be suggested as being the underlying neuroprotective mechanism of fucoidan.
Animals ; Cell Death ; D-Aspartic Acid ; Hippocampus ; N-Methylaspartate ; Neurons ; Neuroprotective Agents ; Polymers ; Polysaccharides ; Rats ; Seaweed

BACKGROUND: There is considerable controversy about the exact molecular mechanisms of excitatory amino acid receptors in epileptogenesis. METHODS: We used in situ hybridization to examine the hybridization density (HD) of n-methyl- D-aspartic acid receptor type 1 (NMDAR-1) and alpha-amino-3-hydroxy -5-methyl-4-isoxazole-propionate (AMPA) receptor type 2 (GluR-2) mRNA, in the hippocampus obtained from the kainic acid (KA)-induced status epilep-ticus (SE) model. Some Sprague-Dawley rats were injected with KA (10 mg/Kg; I.p.), and others with MK-801 (4 mg/kg) 20 minutes prior to KA. The rats were allowed to have 4-hour SE and were killed at 8 hours or 4 weeks after KA or MK-801/KA injection. HD of NMDAR-1 and GluR-2 mRNA in subfields of the hippocampus was measured by an image analysis system. RESULTS: A typical neuropathological finding of hippocampal sclerosis and spontaneous repetitive seizures (SRS) were observed in the KA injected rats, but not in the MK-801 pretreated rats, killed at 4 weeks. Compared with controls, the rats killed at 8 hours after KA showed increased CA1, CA2, and CA3 NMDAR-1 HD, and stratum granulosum (SG) GluR-2 HD. The increase of NMDAR-1, not GluR-2, HD was blocked effectively by MK-801. The increase of SG GluR-2 HD remained until 4 weeks after the KA injection. CONCLUSIONS: Not only the NMDAR-1activa-tionbut also the GluR-2 activation is an important factor in delaying hippocampal neuronal loss and epileptogenesis. (J Korean Neurol Assoc 19(1):36~44, 2001
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid ; Animals ; D-Aspartic Acid ; Dizocilpine Maleate ; Epilepsy, Temporal Lobe ; Gene Expression* ; Glutamic Acid* ; Hippocampus ; In Situ Hybridization ; Kainic Acid ; N-Methylaspartate ; Neurons ; Rats ; Rats, Sprague-Dawley ; Receptors, Glutamate* ; RNA, Messenger ; Sclerosis ; Seizures ; Temporal Lobe*

This study was performed to investigate the effect of dietary intakes and nutritional status for fatty liver male patients with fatty livers. General characteristics, nutritional knowledge, and dietary intakes were obtained from fatty liver male patients aged 20-60yr living in Seoul and Kyunggi province by individual interview and blood samples. The Results were as follows : the mean age of the subjects was 39yrs. Old and over half the subjects were overweight. Although nutritional knowledge, recognition, and accuracy scores were good, these did not affect the subject's health. The average alcohol intake of subjects was 79.8g/day and the drinking duration was 5-40yrs(averge : 17yrs). The subjects drank alcohol over 4tiles/week and preferred Soju. Most side dishes taken with alcohol drinking by the subjects were foods from animal sources. Half of the subjects also drank alcohol the next day for breakfast as a hangover-chaser. The reasons for drinking were due to social relationships and by habit. Vitamin D and folate were lower than the RDA for Koreans, and other nutrient amounts were higher than the RDA. The amounts of aspartate aminotransferase(AST), Alanine amino-transferase(ALT), gamma-glutamyl transpeptidase(gamma-GTP), Triglyceride(TG) for the subjects were higher. In conclusion, fatty liver patients drank excessively and frequently. It seems that heavy alcohol drinking is more prone to overweight or obese people and contributes to fatty livers. Therefore, the subjects need to be taken effectively educated about alcohol-induced liver damage and the importance of a balanced diet for on healthy liver.
Alanine ; Alcohol Drinking ; Animals ; Aspartic Acid ; Breakfast ; Diet ; Drinking ; Fatty Liver* ; Folic Acid ; Gyeonggi-do ; Humans ; Liver ; Male ; Nutritional Status* ; Overweight ; Seoul ; Vitamin D

A 36-year old nulligravid who initially presented with a one-week history of flu-like symptoms suddenly developed behavioral changes, agitation and irritability. Diagnostic tests were done and empiric treatment for viral encephalitis were initiated. Symptoms persisted with progressive unresponsiveness and episodes of seizure. Hypoventilation from dysautonomia required mechanical ventilation. Elevated levels of immunoglobulin on cerebrospinal fluid (CSF) and deterioration despite treatment raised suspicion for an autoimmune encephalitis. A referral to a gynecologist to rule out an ovarian focus was done. Ultrasound and biopsy established the presence of ovarian teratoma. The diagnosis of anti-N-methy-D-Aspartate receptor encephalitis was confirmed when the patient's serum and CSF tested positive for these antibodies. In addition, her CSF was also positive for anti-alpha-amino-3-hydroxy-5-methylisoxazole-4 propionic acid receptor (Anti-AMPar) antibodies. In the Philippines, this was the second documented case of Anti-NMDar encephalitis associated with ovarian teratoma and the first to have antibodies present causing encephalitis.

Human ; Female ; Adult ; Anti-n-methyl-d-aspartate Receptor Encephalitis ; Hashimoto's Encephalitis ; Aspartic Acid Receptor ; Teratoma, Ovarian ; Hashimoto Disease ; Ovarian Neoplasms ; Primary Dysautonomias

Cathepsin D (CatD, EC 3.4.23.5) is a member belonging to the subfamily of aspartic endopeptidases, which are classified into the MEROPS clan AA, family A1. Helminth parasites express a large set of different peptidases that play pivotal roles in parasite biology and pathophysiology. However, CatD is less well known than the other classes of peptidases in terms of biochemical properties and biological functions. In this study, we identified 2 novel CatDs (CsCatD1 and CsCatD2) of Clonorchis sinensis and partially characterized their properties. Both CsCatDs represent typical enzymes sharing amino acid residues and motifs that are tightly conserved in the CatD superfamily of proteins. Both CsCatDs showed similar patterns of expression in different developmental stages of C. sinensis, but CsCatD2 was also expressed in metacercariae. CsCatD2 was mainly expressed in the intestines and eggs of C. sinensis. Sera obtained from rats experimentally infected with C. sinensis reacted with recombinant CsCatD2 beginning 2 weeks after infection and the antibody titers were gradually increased by maturation of the parasite. Structural analysis of CsCatD2 revealed a bilobed enzyme structure consisting of 2 antiparallel β-sheet domains packed against each other forming a homodimeric structure. These results suggested a plausible biological role of CsCatD2 in the nutrition and reproduction of parasite and its potential utility as a serodiagnostic antigen in clonorchiasis.
Animals ; Aspartic Acid Endopeptidases ; Biology ; Cathepsin D ; Cathepsins ; Clonorchiasis ; Clonorchis sinensis ; Eggs ; Helminths ; Humans ; Intestines ; Metacercariae ; Ovum ; Parasites ; Peptide Hydrolases ; Rats ; Reproduction

BACKGROUND: The present investigation was undertaken to evaluate the neuroprotective effect of etomidate against N-methyl-D- aspartate (NMDA) induced neurotoxicity in rat cortical neurons by measuring lactate dehydrogenase (LDH). METHODS: The cerebral cortical neurons of fetal rat were grown for 12 days in dissociated cell culture. They were divided into four groups: first group acted as control with no drug administration and other groups treated with either NMDA 100microM or Etomidate (ET) 10microM + NMDA 100microM or ET 100microM + NMDA 100microM After 24 hrs, cell death was assessed by morphology under the light microscope and quantified by measuring the LDH in the culture media. RESULTS: In the light microscopic findings, the intact cortical neurons were increased in the ET groups. NMDA-induced LDH production also significantly suppressed in ET group (P<0.05). There were no significant difference between the ET 10microM and 100microM groups. CONCLUSIONS: These results suggest that the etomidate has protective effect on the cultured rat cortical neurons against NMDA-induced neurotoxicity.
Animals ; Aspartic Acid ; Cell Culture Techniques ; Cell Death ; Culture Media ; Etomidate* ; L-Lactate Dehydrogenase ; N-Methylaspartate* ; Neurons* ; Neuroprotective Agents ; Rats*

BACKGROUND: The substantia nigra pars reticulata is a critical site for the control of epileptic seizures. The potentiation of the inhibitory gamma-amino butyric acid (GABA) ergic input from the striatum to the substantia nigra pars reticulata suppresses primary or secondary generalized seizures in rats. Recent data suggests that the projection from the subthala-mus to the substantia nigra pars reticulata plays a critical role in the control of some forms of epileptic seizures. METHODS: We examined the possible involvement of the excitatory glutamatergic input from the subthalamic nucleus (STN) to the substantia nigra in pilocarpine-induced seizures by the direct injection of GABA receptor agonist (muscimol) and n-methyl- D-aspartate (NMDA) receptor antagonist (MK-801) into the substantia nigra pars reticularis (SNr) and the subthalamic nucleus respectively. Sprague-Dawley rats were classified into four groups depending on the pretreatment; the injection of saline (STN sham) or muscimol (STN) into the subthalamic nucleus, and the injection of saline (SNr sham) or MK-801 (SNr) into the substantia nigra. Seizure was induced by the intraperitoneal injection of pilocarpine (400 mg/kg). RESULTS: Mean seizure stages in the STN group (1.5 +/-0.5) and SNr group (1.3 +/-0.5) were significantly lower than STN sham group (4.8 +/-0.4) and SNr sham group (4.8 +/-0.4) (P <0.05). Electroencephlograms showed typical status epilepticus patterns in the sham operation group but only discrete ictal discharges with slowing and intermittent ictal spikes were shown in both STN and SNr group. Viable cell numbers in the CA1 and CA3 in STN and SNr groups were significantly higher than those of the sham group (P <0.05). CONCLUSIONS: These results provide evidence for the role of subthalamo-nigral projections in the modulation of pilocarpine-induced seizures.
Animals ; Butyric Acid ; Cell Count ; D-Aspartic Acid ; Dizocilpine Maleate ; Epilepsy ; GABA Agonists ; Injections, Intraperitoneal ; Muscimol ; Pilocarpine* ; Rats* ; Rats, Sprague-Dawley ; Seizures* ; Status Epilepticus ; Substantia Nigra ; Subthalamic Nucleus ; Subthalamus

Anti-N-methyl D-aspartate receptor (anti-NMDAR) encephalitis, recently recognized as a form of paraneoplastic encephalitis, is characterized by a prodromal phase of unspecific illness with fever that resembles a viral disease. The prodromal phase is followed by seizures, disturbed consciousness, psychiatric features, prominent abnormal movements, and autonomic imbalance. Here, we report a case of anti-NMDAR encephalitis with initial symptoms of epilepsia partialis continua in the absence of tumor. Briefly, a 3-year-old girl was admitted to the hospital due to right-sided, complex partial seizures without preceding febrile illness. The seizures evolved into epilepsia partialis continua and were accompanied by epileptiform discharges from the left frontal area. Three weeks after admission, the patient's seizures were reduced with antiepileptic drugs; however, she developed sleep disturbances, cognitive decline, noticeable oro-lingual-facial dyskinesia, and choreoathetoid movements. Anti-NMDAR encephalitis was confirmed by positive detection of NMDAR antibodies in the patient's serum and cerebrospinal fluid, and her condition slowly improved with immunoglobulin, methylprednisolone, and rituximab. At present, the patient is no longer taking multiple antiepileptic or antihypertensive drugs. Moreover, the patient showed gradual improvement of motor and cognitive function. This case serves as an example that a diagnosis of anti-NMDAR encephalitis should be considered when children with uncontrolled seizures develop dyskinesias without evidence of malignant tumor. In these cases, aggressive immunotherapies are needed to improve the outcome of anti-NMDAR encephalitis.
Anti-N-Methyl-D-Aspartate Receptor Encephalitis* ; Antibodies ; Anticonvulsants ; Antihypertensive Agents ; Cerebrospinal Fluid ; Child* ; Child, Preschool ; Cognition ; Consciousness ; D-Aspartic Acid ; Diagnosis ; Dyskinesias ; Encephalitis ; Epilepsia Partialis Continua* ; Female ; Fever ; Humans ; Immunoglobulins ; Immunotherapy ; Korea* ; Methylprednisolone ; Rituximab ; Seizures ; Virus Diseases

PURPOSE: Glutamate and aspartate are the excitatory amino acid neurotransmitters and NMDA (N-methyl-D-aspartate) is one of their major receptors. NMDA agonist may sti mulate serotonergic nervous system that inhibit the penile erection as well as induce the penile erection. We investigate the effects of NMDA agonist on serotonin release from hippocampus. MATERIALS AND METHODS: The slices of hippocampus were incubated in a buffer con taining 0.1mM [(3)H]5-hydroxytryptamine (5-HT) for uptake in the male rat. The release of 5-HT into the buffer during each 10 minutes period was measured and the radio activities in each buffer and the tissue were counted. After 50 min from the initiation, NMDA agonist were administered at 6th and 7th 10 min period respectively. The changes of 5-HT release were expressed as percent values compared to the 5th 10 min period. Tetrodotoxin was used to determine the possible involvement of interneuron on the action of these neurotransmitters. RESULTS: A steady release of 5-HT was observed up to 100 minutes after the rapid release during the first 40 minutes. Treatment of tetrodotoxin (10(-6)M) did not change the spontaneous release of 5-HT. The 5-HT released during 10 and 20 minutes of NMDA agonist (10(-4M)) treatment significantly higher than those of control group. The increase of 5-HT release by NMDA agonist was blocked by pretreatment with tetro dotoxin. The release of 5-HT was increased by NMDA agonist and this response was blocked by tetrodotoxin. CONCLUSIONS: NMDA agonist increases the release of 5-HT through the activation of the interneurons and these results suggest that NMDA agonist may stimulate the serotonergic nervous system that inhibit the penile erection as well as inducing the penile erection.
Animals ; Aspartic Acid ; Excitatory Amino Acids ; Glutamic Acid ; Hippocampus* ; Humans ; Interneurons ; Male ; N-Methylaspartate* ; Nervous System ; Neurotransmitter Agents ; Penile Erection ; Rats* ; Serotonin* ; Tetrodotoxin

The sigma-1 receptor has recently been implicated in a myriad of cellular functions and biological processes. Previous studies have demonstrated that the spinal sigma-1 receptor plays a pro-nociceptive role in acute pain and that the direct activation of sigma-1 receptor enhances the nociceptive response to peripheral stimuli, which is closely associated with calcium-dependent second messenger cascades including protein kinase C (PKC). In addition, the activation of sigma-1 receptor increases PKC- and protein kinase alpha (PKA)-dependent phosphorylation of the N-Methyl- D-aspartate (NMDA) receptor in the spinal cord, which results in the potentiation of intrathecal NMDA-evoked spontaneous pain behavior. Moreover, the blockade of spinal sigma-1 receptor suppresses the development of neuropathic pain and blocks the increase of phosphorylation of extracellular signal-regulated kinase (ERK) as well as pNR1 in the spinal cord. Recently, it was also reported that spinal neurosteroids such as pregnenolone and dehydroepiandrosterone sulfate, which are recognized as endogenous ligands for sigma-1 receptor, could produce mechanical hypersensitivity via sigma-1 receptor-mediated increase of pNR1. Collectively, these findings demonstrate that the activation of spinal sigma-1 receptor or the increase of neurosteroids is closely associated with the acute pain sensation or the development of chronic pain, and imply that sigma-1 receptor can be a new potential target for the development of analgesics.
Acute Pain ; Analgesics ; Biological Processes ; Central Nervous System Sensitization ; Chronic Pain ; D-Aspartic Acid ; Dehydroepiandrosterone Sulfate ; Hypersensitivity ; Ligands ; Neuralgia ; Neurotransmitter Agents ; Phosphorylation ; Phosphotransferases ; Pregnenolone ; Protein Kinase C ; Protein Kinases ; Receptors, sigma ; Second Messenger Systems ; Sensation ; Spinal Cord