• Parasites, Hosts and Diseases
• /
• v.46 no.2
• /
• pp.95-99
• /
• 2008

Eosinophil degranulation plays a crucial role in tissue inflammatory reactions associated with helminth parasitic infections and allergic diseases. Paragonimus westermani, a lung fluke causing human paragonimiasis, secretes a large amount of cysteine proteases, which are involved in nutrient uptake, tissue invasion, and modulation of hos's immune responses. There is, however, limited information about the response of eosinophils to direct stimulation by cysteine proteases (CP) secreted by P. westermani. In the present study, we tested whether degranulation and superoxide production from human eosinophils can be induced by stimulation of the 2 CP (27 kDa and 28 kDa) purified from excretory-secretory products (ESP) of P. westermani newly excysted metacercariae (PwNEM). A large quantity of eosinophil-derived neurotoxin (EDN) was detected in the culture supernatant when human eosinophils isolated from the peripheral blood were incubated with the purified 27 kDa CP. Furthermore, the 27 kDa CP induced superoxide anion production by eosinophils in time- and dose-dependent manners. In contrast, the purified 28 kDa CP did not induce superoxide production and degranulation. These findings suggest that the 27 kDa CP secreted by PwNEM induces superoxide production and degranulation of human eosinophils, which may be involved in eosinophil-mediated tissue inflammatory responses during the larval migration in human paragonimiasis.

• YAKHAK HOEJI
• /
• v.49 no.4
• /
• pp.355-364
• /
• 2005

A neurotoxin, 6-hydroxydopamine (6-OHDA) has long been used to form a Parkinson's disease (PD) model by inducing the lesion in catecholaminergic pathways, particularly the nigrostriatal dopamine (DA) pathway. Whereas l-deprenyl, a selective inhibitor of monoamine oxidase (MAO) type B, is now widely used in the treatment of PD, the precise action mechanism of the drug remains elusive. In this study, we investigated whether l-deprenyl shows protective effect against the DA depletion induced by 6-OHDA in rat brain, and against 6-OHDA-induced neurotoxicity and oxidative stress in catecholaminergic neuroblastoma SH-SY5Y cells that are known to lack MAO-B activity. Pretreatment of l-deprenyl significantly enhanced the striatal DA, 3,4-dihydroxyphenylacetic acid, homovanilic acid, and 3-methoxytyramine levels compared to the untreated 6-OHDA-lesioned rat, indicating that l-deprenyl pretreatment prevents 6-OHDA-induced depletion of not only striatal dopamine but also its metabolites. Treatment of 6-OHDA for 24hrs decreased the cell viability and increase the generation of ROS in dose-dependent manners. We further investigated whether caspase activity is involved in the action of l-deprenyl. Treatment of l-deprenyl $(0.1\~100{\mu}M)$ did not produce any changes in 6-OHDA-induced cleavage of poly (ADP-ridose) polymerase in SH-SY5Y cells. Our results suggest that the neuroprotective effect of l-deprenyl against 6-OHDA is due to its increased scavenger activity, but independent of inhibition of MAO-B or caspase-3 activation.

• The Journal of Internal Korean Medicine
• /
• v.16 no.1
• /
• pp.1-16
• /
• 1995

This study was done in order to investigate the etiology and pathology of dementia in the variety literature. Dementia in elderly persons(above the age of 60) mainly classfied Alzheimer disease and Cerebral vascular dementia. The results were as follows: 1. Dementia patients have abnormal mental function, who have no mental weakness but defects of memory, verbal disturbance, behavior disturbance and loss of intellectual function. 2. Dementia regard as 'me-beng(?病)', 'jeon-gwang(癲狂)', and 'heo-ro(虛勞)' in oriental medicine and the symptom is a silence with no response, mixing, a crying or a laugh, a stranger behavior and a amnesia; disturbances of speech, emotion, behavior. 3. Dementia caused by Alzheimer disease, Multi infarct dementia, Parkinson's disease, sequelae of acute CO poisoning, head injury and alcoholism(occidental medically) and the 'Dam(痰) and Damhwa(痰火), weakness of heart and spleen(心脾虛) caused by pent up anger of seven emotions(七情鬱結), the weakness of liver and kidney(肝腎不足)(oriental medically). 4. The causes of Alzheimer disease are various; a heredity factor, a morphological factor of brain tissues, a psychological factor and a biochemical factor (occidental medically) ; the 'Dam(痰) and Damhwa(痰火) caused by weakness of the internal organs and disturbance of the emotions(oriental medically). 5. Cerebral vascular dementia caused by loss of the certain cerebral neurons and oriental medically caused by obstruction of 'dam(痰)' or 'eo heul(瘀血)'. It is recommended that further study of many sided investigations, specially against a weakness of spiritual functions and a certain neurotoxin in the future.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
• /
• v.24 no.2
• /
• pp.90-95
• /
• 2013

Botulinum toxin, a neurotoxin, is known to be an inhibitor of cholinergic neuromuscular transmission. Recently, it was reported that the administration of botulinum toxin is effective for the treatment of focal neurological motor disorders such as cervical dystonia, blepharospasm, hemifacial spasm, spasmodic dysphonia, and writer's cramp. Several case studies reported that the botulinum toxin was administered for the treatment of motor tic or vocal tic. It was found that this toxin reduces the frequency and severity of the tic as well as the premonitory urge and symptoms. In our case study, a noticeable decrease of motor tic symptom was observed after an intramuscular injection of 300mg of botulinum toxin in an 18-year-old patient with Tourette's disorder who showed only a little improvement of motor tic and vocal tic symptoms after treatment with antipsychotic drugs for several years. This case is reported in our study and literature survey was undertaken for reviewing similar cases. In our study, an 18-year-old boy diagnosed with Tourette's disorder based on Diagnostic and Statistical Manual of Mental Disorders, fourth edition presented with the following scores : the Clinical Global Impression scale, Yale Global Tic Severity Scale (motor/vocal/severity), Premonitory Urge Score, Korean Attention-Deficit Hyperactivity Disorder Rating scale, and Kovac Depression scale which were performed prior to the treatment were 5, 21/5/50, 100, 17, and 18 points, respectively. Two weeks after the injection of botulinum toxin, the scores were 4, 17/5/40, 50, 16, and 19 points, respectively. Eight weeks after the injection of botulinum toxin, they had become 3, 15/5/30, 25, 16, and 20 points, respectively, which clearly indicates a noticeable decrease of motor tic symptom.

• Korean Journal of Veterinary Research
• /
• v.51 no.3
• /
• pp.185-191
• /
• 2011

Trimethyltin chloride (TMT) has been used as a neurotoxin for inducing brain dysfunction and neuronal death. Neuronal death in the hippocampus by TMT may generate excessive nitric oxide, but there are few studies about nitric oxide synthase enzyme involved in the synthesis of nitric oxide. The purpose of present study is to analyze the TMT toxicity in each region of rat hippocampus. To evaluate the involvement of nitric oxide, we analyzed the effects of aminoguanidine known as a selective inhibitor for inducible nitric oxide synthase on behavioral changes and the hippocampus of rat by TMT toxicity. 6-week-old male Sprague-Dawley rats were administered with a single dose of TMT (8 mg/kg b.w., i.p.) and the control group was similarly administered with distilled water. TMT + aminoguanidine-treated groups were administered with aminoguanidine (10 mg/kg or 100 mg/kg b.w., i.p.) for 3 days prior to TMT injection. The rats were sacrificed 2 days after TMT administration. In the TMT-treated group, a number of cell losses were seen in CA1, CA3 and the dentate gyrus. In the TMT + aminoguanidine-treated group, neuronal death was seen in CA1 and CA3, but reduced in the dentate gyrus compared to the TMT-treated group. Western blot analysis showed that cleaved caspase-3 expression was increased in the TMT-treated group compared to the control group. However, the expression significantly declined in the TMT + aminoguanidine-treated group. The present findings suggest that inducible nitric oxide synthase is involved in neuronal death induced by TMT.

• Asian-Australasian Journal of Animal Sciences
• /
• v.17 no.1
• /
• pp.127-130
• /
• 2004

Lathyrus sativus, locally known as Khesari, is a leguminous pulse crop grown in many parts of the world for food (used by poor people) and animal feed/fodder. Its seeds are rich in protein and energy but contains anti-nutritional factors prominent among which is ${\beta}$-N-Oxalylamino-L-Alanine (BOAA), a neurotoxin causing lathyrism in humans due to prolong consumption. Keeping in view the chemical characteristics of this toxin and literary facts on L. sativus feeding in terrestrial animals, it was hypothesized that aquatic species may better utilise this ingredient in mixed extruded diets. Diets were prepared with varying levels (0, 10, 18, 26 and 34%) of L. sativus seeds and fed for 60 days to study growth, body composition and digestibility of nutrients. Final body weight, specific growth rate and feed and protein conversion ratio did not differ (p>0.05) between treatments. Crude protein digestibility was reduced (p<0.01) beyond 26% inclusion level of L. sativus. Final carcass composition with regard to protein, lipid and ash did not differ (p>0.05) among the treatments. Comparable craniosomatic, viscerosomatic, renosomatic and hepatic indices and no mortality implies no apparent adverse effect on the vital organs and fish health. It was concluded that L. sativus can be a promising feed ingredient that can be used up to 34% or possibly higher level in fingerlings diet. To our knowledge, it appears to be the first report of its kind under laboratory conditions.

• Nutritional Sciences
• /
• v.9 no.2
• /
• pp.61-67
• /
• 2006

Green tea has attracted attention with respect to its potential for preventing and treating neurodegenerative disease. The neurotoxin, 6-hydroxydopamine (6-OHDA), was used to produce experimental Parkinson's disease (PD) model. The purpose of this study was to investigate the effects of green tea diet on behavioral changes, striatal dopamine content, and hepatic antioxidant parameters of PD model rats. In this study, we used male Sprague-Dawley rats weighing $200\sim220g$ and injected 6-OHDA into the right substantia nigra and medial forebrain bundle of the brain. The supply of green tea diet was started at 2 weeks before 6-OHDA lesion and continually supplied during 0, 2, and 4 weeks after 6-OHDA lesion (GT-0, GT-2, GT-4). Behavioral disturbance was measured by the stepping and d-amphetamine drug-induced rotation tests. Then, we assayed the striatal dopamine content and the hepatic malondialdehyde (MDA), hydrogen peroxide $(H_2O_2)$, and superoxide dismutase (SOD) activity. The percentage of lesioned forepaw to non-lesioned forepaw step scores was the highest in GT-4 group among all groups at both 3 and 4 weeks after 6-OHDA lesion. At 4 weeks after 6-OHDA lesion, the rotation score was the lowest in GT-2 group (p<0.05). However, increasing rate of the rotation score from 2 to 4 weeks after 6-OHDA lesion was the lowest in GT-4 group. The striatal dopamine content was not significantly different among four groups by green tea diet. The hepatic MDA level was the lowest in GT-4 group among four groups. The hepatic SOD activity was increased with the prolongation of green tea diet period These results suggest that green tea diet affects behavioral changes in rats of PD model. It seems that continuous green tea supplementation has an influence on the reduction of behavioral disturbance and the hepatic MDA level. Accordingly, continuous green tea supplementation was recommended for the prevention and treatment of PD. However, further studies are needed to investigate the mechanisms and efficacy of green tea in PD.

• Journal of environmental and Sanitary engineering
• /
• v.23 no.4
• /
• pp.37-44
• /
• 2008

In this study we developed the analytical methods for the determination of three neurotoxin; anatoxin-a, saxitoxin and neosaxitoxin using HPLC/FLD system and this analytical methods were applied to real sample; algae culture and algae extracts. For the HPLC/FLD analysis of anatoxin-a samples were concentrated on WCX(Weak Cation Exchanger) SPE and then anatoxin-a in concentrate was derivatized with NBD-F solution. Supernatant was injected on HPLC system. For the HPLC/FLD analysis of saxitoxin and neosaxitoxin samples were separated on the column and then derivatizied by post column reactor for fluorescen detection. For post column reaction of saxitoxin we feed two kinds of reaction solution; Oxidizing Reagent of which composition was periodic acid(7mM) in 50mM potassium phosphate buffer, pH 9 and acidifying reagent of which Composition was 0.5M acetic acid. The LOD value for anatoxin-a, saxitoxin and neosaxitoxin in HPLC/FLD method was 24.3 ng. $35{\mu}g/L$, $27{\mu}g/L$ respectively. We determined the anatoxin-a content of lyophilized anabaena flos-aquae and $20{\mu}g/g$ d.w. of anatoxin-a was detected. We analyzed saxitoxin and neosaxitoxin in algae culture media and extracts of lypopyllized algal cell cultured and that of Deachung reservior. Saxitoxin and neosaxitoxin in real sample were below the limit of detection. Although there are various water treatment processes for removing neurotoxins were suggested no process give simultaneous and complete removal of neurotoxins. It was cocluded that nanofiltration which reject material by size can be a process for removal of neurotoxins.

• Toxicological Research
• /
• v.34 no.3
• /
• pp.267-279
• /
• 2018

Neurolathyrism is a neurodegenerative disorder characterized by spastic paraplegia resulting from the excessive consumption of Lathyrus sativus (Grass pea). ${\beta}$-N-Oxalyl-L-${\alpha},{\beta}$-diaminopropionic acid (L-ODAP) is the primary neurotoxic component in this pea. The present study attempted to evaluate the proteome-wide alterations in chick brain 2 hr and 4 hr post L-ODAP treatment. Proteomic analysis of chick brain homogenates revealed several proteins involved in cytoskeletal structure, signaling, cellular metabolism, free radical scavenging, oxidative stress and neurodegenerative disorders were initially up-regulated at 2 hr and later recovered to normal levels by 4 hr. Since L-ODAP mediated neurotoxicity is mainly by excitotoxicity and oxidative stress related dysfunctions, this study further evaluated the role of L-ODAP in apoptosis in vitro using human neuroblastoma cell line, IMR-32. The in vitro studies carried out at $200{\mu}M$ L-ODAP for 4 hr indicate minimal intracellular ROS generation and alteration of mitochondrial membrane potential though not leading to apoptotic cell death. L-ODAP at low concentrations can be explored as a stimulator of various reactive oxygen species (ROS) mediated cell signaling pathways not detrimental to cells. Insights from our study may provide a platform to explore the beneficial side of L-ODAP at lower concentrations. This study is of significance especially in view of the Government of India lifting the ban on cultivation of low toxin Lathyrus varieties and consumption of this lentil.

• Journal of Ginseng Research
• /
• v.33 no.4
• /
• pp.294-304
• /
• 2009

Ginsenosides are among the most well-known traditional herbal medicines frequently used for the treatment of various symptoms in South Korea. The neuroprotective effects of ginsenoside $Rg_3$ (G-$Rg_3$) on cholesterol-oxide-(CO)-induced neurotoxicity were investigated through the analyses of rat brains. The recently accumulated reports show that ginseng saponins (GTS), the major active ingredients of Panax ginseng, have protective effects against neurotoxin insults. In the present study, the neuroprotective effects of G-$Rg_3$ on CO-induced hippocampal excitotoxicity were examined in vivo. The in-vitro studies using rat cultured hippocampal neurons revealed that G-$Rg_3$ treatment significantly inhibited CO-induced hippocampal cell death. G-$Rg_3$ treatment not only significantly reduced CO-induced DNA damage but also attenuated CO-induced apoptosis. The in-vivo studies that were conducted revealed that the intracerebroventricular (i.c.v.) pre-administration of G-$Rg_3$ significantly reduced i.c.v. CO-induced hippocampal damage in rats. To examine the mechanisms underlying the in-vitro and in-vivo neuroprotective effects of G-$Rg_3$ against CO-induced hippocampal excitotoxicity, the effect of G-$Rg_3$ on the CO-induced elevations of the apoptotic cells in cultured hippocampal cells was examined, and it was found that G-$Rg_3$ treatment inhibited CO-induced apoptosis. The histopathological evaluation demonstrated that G-$Rg_3$ significantly diminished the apoptosis in the hippocampus and also spared the hippocampal CA1, CA3, and dentate gyrus neurons. G-$Rg_3$ also significantly improved the CO-caused behavioral impairment. G-$Rg_3$ itself had no effect, however, on the CO-induced inhibition of succinate dehydrogenase activity (data not shown). These results collectively indicate the G-$Rg_3$-induced neuroprotection against CO in rat hippocampus. With regard to the wide use of G-$Rg_3$, this agent is potentially beneficial in treating CO-induced brain injury.