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Purpose The study objective was to test the utilization of a crosslinked, thiolated hyaluronic acid (CMHA-S) film for treating corneal chemical burns. Methods Burns 5.5 mm in diameter were created on 10 anesthetized, male New Zealand white rabbits by placing a 1N NaOH soaked circular filter paper onto the cornea for 30 s. Wounds were immediately rinsed with balanced salt solution (BSS). CMHA-S films were placed in the left inferior fornix of five injured and five uninjured animals. Five animals received no treatment. At 0 h, 48 h, 96 h, and on day 14 post chemical burn creation, eyes were evaluated by white light imaging, fluorescein staining, and optical coherence tomography (OCT). Corneal histology was performed using H&E and Masson's Trichrome stains. Results Image analysis indicated biocompatible CMHA-S treatment resulted in significant decreases in the areas of corneal opacity at 48 h, 96 h, and on day 14 postoperatively. A significant increase in re-epithelialization was seen 14 days post injury. CMHA-S treated corneas showed significantly less edema than untreated burns. No pathological differences were observed in corneal histological samples as a result of CMHA-S treatment. Conclusions CMHA-S films facilitate re-epithelialization and decrease the area of corneal opacity in our corneal alkali burn rabbit model.

The purpose of this study was to analyze the influence of professional self-concept and professional autonomy on clinical performance of clinical nurses. Participants were clinical nurses working at the university hospital in Seoul. Data were collected using questionnaires that contained items on individual characteristic, professional self-concept, professional autonomy, nursing performance. Data were analyzed using descriptive statistics, t-test, analysis of variance, Pearson correlation coefficients, and hierarchical multiple regression. The study results indicate that, flexibility, medium autonomy, and position are factors that affect nursing performance. In conclusion, the improvement of nurses’ professional self-concept and autonomy will improve their nursing performance of clinical nurses. Therefore, strategies that strengthen professional self-concept and autonomy should be developed in order to improve nursing performance of clinical nurses.

This was a report of a concept analysis of body image of people living with HIV/AIDS. Rodgerss evolutionary method of concept analysis was used. Data were collected from published literature related to body image of people living with HIV/AIDS. Body image of people living with HIV/AIDS was identified with two antecedents and one attribute, and two consequences. The antecedents of the body image of people living with HIV/AIDS were "HIV infection & AIDS diagnosis" and "previous body perception". The attribute of the body image of people living with HIV/AIDS was "HIV related stigma" whereas the consequences of the body image of people living with HIV/AIDS were "negative health outcomes" and, "lower quality of life". In conclusion, to identify the body image of people living with HIV/AIDS is important in the care of people living with HIV/AIDS.

This paper considers the problem of robust stability of uncertain neural networks with two additive time varying delay components. The activation functions are monotone nondecreasing with known lower and upper bounds. By constructing of a modified augmented Lyapunov function, some new stability criteria are established in terms of linear matrix inequalities, which is easily solved by various convex optimization techniques. Compared with the existing works, the obtained criteria are less conservative due to reciprocal convex technique and an improved inequality, which provides more accurate upper bound than Jensen inequality for dealing with the cross-term. Finally, two numerical examples are given to illustrate the effectiveness of the proposed method.

To control Bemisia tabaci on tomato, we applied five different combinations of chemicaltreatments as below: 1) treatment of combinations of cyantraniliprole on the root area and leaf with theexisting registered chemicals three times; 2) treatment of combinations of cyantraniliprole on the root areaand dinotefuran + emamectin benzoate on the leaf with the existing registered chemicals three times; 3)treatment of combinations of dinotefuran on the root area and cyantraniliprole on the leaf with the existingregistered chemicals three times; 4) treatment of combinations of dinotefuran on the root area and dinotefuran+ emamectin benzoate on the leaf with the existing registered chemicals three times; 5) untreated control plot(Table 1). Twenty days after treatment (17 th Aug.), the number of population of B. tabaci was zero on the 1,2, 3, 4 treatments of combinations, and only 2 individuals were found on the 5 treatment of combination pereach 20 plant. On 17 th Sep., in the last observation, the average number of population of B. tabaci was 10.3,10.3, 10.6 on the 1, 2, 3 treatments of combinations on the 20 plants per each combination, however, theaverage number of 23.3 and 37.6 were examined on the 4 and 5 treatments of combinations, respectively.TYLCV was not occurring on the 1 and 2 treatments of combinations, and presented only 3% and 17% onthe 3 and 4 treatments of combinations, respectively, which indicates that the treatments (1-4) should beeffective on TYLCV control as considering that 33% of TYLCV occurred on the untreated control plot.However, after the third flowering period, there is no difference among the five combinations. The amount ofproducts was 9,148g and 9,698g on the 1 and 2 treatments of combinations, respectively, which was the mostamong the 5 combinations. The number of fallen fruits and the average weight of fruits showed the similartendency.Key words Bemisia tabaci, control effect, cyantraniliprole, tomato, tomato yellow leaf curl virus*Corresponding authorTel: +82-42-821-5769, Fax: +82-42-823-8679E-mail: youngnam@cnu.ac.krORIGINAL ARTICLES / CONTROL

The extract of Siegesbeckia pubescens herb and its chemical constituents were tested for the ability to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglia. The methanol extract and the 90% MeOH fraction of S. pubescens effectively attenuated lipopolysaccharide-induced nitric oxide production. Several steps of chromatography yielded eight ent-kaurane diterpenes (1-8) and one ent-pimarane diterpene (9) from the 90% MeOH fraction. Among these compounds, compounds 2-9 showed significant inhibitory effect on lipopolysaccharide-induced nitric oxide production in BV2 microglia. Compounds 3 and 9 concentration-dependently decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), supported by quantitative real time polymerase chain reaction (PCR) and Western blot analysis. These results suggest that ent-kaurane and ent-pimarane diterpenes isolated from S. pubescens are expected to be potential candidates against neuroinflammation-related disease.

Botrytis 선택배지(BSM)를 이용하여 토마토 포장에서 꽃잎의 감염시기를 착과 직후, 착과 25일 후, 착과 45일 후로 나누어 조사하였던 바 착과 직후의 꽃잎에서는 65%의 감염률을 보였으나 착과 25일 후의 꽃잎에서는 87%, 45일 후의 꽃잎에서는 100%의 감염률을 보였다. 착과 후 시간이 지날수록 잿빛곰팡이병균의 꽃잎 감염율은 증가하였다. 한편, 토마토 품종별 꽃잎의 감염시기를 개화 전, 개화 후, 착과 후로 구분하여 조사하였던 바 전체적으로 개화 전에 비하여 개화 후 시간이 지날수록 감염율이 급격히 증가하였으며, 일반토마토 3품종의 감염율이 방울토마토에 비하여 현저히 높았다. 즉 일반토마토의 착과 후 꽃잎 감염율이 70~80%인데 비하여 방울토마토의 꽃잎 감염율은 20~45%였다. 일반토마토 및 방울토마토 포장에서 잿빛곰팡이병균의 포자 비산량을 BSTM을 이용하여 조사한 결과 토마토 생육기간이 길어질수록 비산 포자량은 증가하였으며 특히 일반 토마토품종에서 잿빛곰팡이병의 발생 이후에 급격하게 증가하였다. 그러나 포장 내의 병원균 포자비산량의 증가에도 불구하고 방울토마토는 잿빛곰팡이병의 발병이 매우 적었다. BSM 및 BSTM을 이용한 잿빛곰팡이병 약제저항성균 간이검정법의 포장 적용시험을 통하여 바 이들의 활용가능성을 확인하였으며, 부여 및 익산지역 12농가에서 8개 약제를 공시하여 실증시험을 실시하였던 바 fluazinam 및 diethofencarb+carbendazim 혼합제가 주로 방제에 적합한 약제로 판정되었다. BSM을 이용한 kit는 잿빛곰팡이병이 발생하기 이전에 조기에 약제 저항성 병원균 판별이 가능하나 8개의 약제배지에 접종할 경우 2시간 정도의 시간이 필요하다. BSTM을 활용한 kit는 배지를 설치 후 24시간이 지난 후 수거하기 때문에 사용은 간편하나 잿빛곰팡이병이 발생하기 이전에 설치하면 낙하 포자량이 적어 약제저항성균 판별에 어려움이 있을 것이라 생각된다. 【Grey mold infection rate in tomato was investigated with the inoculation of dead flowers on Botrytis selective media. The grey mold infection rate of flower after fruiting were higher in the order of after 45 days, after 25 days, and fruiting day with 100%, 87% and 65%, respectively. The number of infected flowers were increased with time increase after the flowering before fruiting. BSM (Botrytis selective medium) was used to check grey mold infection rate depending on the flowering stage and cultivar. Grey mold infection rate depending on the flowering stage was similar in all the beef-tomato cultivar as 1.5~5% at preflowering, 1.5~45% at flowering and 75~90% at fruiting. On the other hand, cherry tomato cultivar "KoKo" had lower infection rates of 0~3.5% at pre-flowering, 10~30% at flowering and 20~50% at fruiting. These resulted from the fact that beaf-tomato cultivar have much bigger flowers and larger amount of pollens compared to those of cherry tomato cultivar. The amounts of falling pollens of Botrytis spp. were checked for beaf-tomato cultivar and cherry tomato cultivar using BSTM. The amounts of falling pollens were increased as growth period was extended, and the amount of spores increased rapidly during the outbreak of grey mold. Twelve field trials in Buyeo and Iksan areas showed that Fluazinam, and Diethofencarb+Carbendazim were effective fungicides to control tomato grey mold, and these results were similar to those of field trials with BSTM. This is the first report of Fluazinam as a effective fungicide for the control of grey mold of tomato even though it has not been registered yet for the control of gray mold in tomato.】

Wilt damage on tomato plants caused by Ralstonia solanacearum has been increased as the areas of tomato cultivation increased during the warm seasons. Also, the tomato rootstocks used to prevent the disease occurrence are not effective in the highly prevailing regions. Therefore, bacterial wilt resistant eggplant rootstock EG203, collected from AVRDC, was tested for its effect to deter the Ralstonia solanacearum wilt disease in the greenhouses at Buyeo Tomato Experiment Station from 2003 to 2005, and at Gumi, Kyungpook province from 2009-2011. Planting of eggplant rootstock EG203 should be done three weeks before the planting of tomato scions so that they can have similar stem diameter (2.5-3.0 mm) and can be easily grafted. Both insertion and inarching grafting showed 93-96% success rates. In the greenhouse tests at Buyeo Tomato Experiment Station from 2003 to 2005, eggplant rootstock EG203-grafted tomatoes showed the disease occurrence of 4.3%. On the other hand, non-grafted or other commercial rootstock-grafted tomatoes showed disease occurrence of 58.0% and 25.0-36.7%, respectively. In the greenhouse tests at Gumi, Kyungpook province in 2009, the disease occurrence on the EG203-grafted and non-grafted tomatoes was 2-5% and 20-80%, respectively. In 2010, at Gumi, Kyungpook province, when the wilt disease occurred slightly, the tomatoes grafted with tomato rootstocks B-blocking and Chung-gang, and eggplant rootstock EG203 showed similar disease severities, but EG203-grafted tomatoes formed lately cluster, resulting in the reduction of yield compared to tomato-grafted tomatoes. In 2011, at Gumi, Kyungpook province, when the wilt disease occurred severely, the tomato rootstocks `B-blocking` and Chung-gang and eggplant rootstock EG203-grafted tomatoes showed disease occurrences of 60-85% and 0-1%, respectively. Therefore, it was concluded that tomato rootstocks `B-blocking` and `Chung-gang` are more useful in the areas contaminated with low levels of pathogen and eggplant rootstock EG203 is more useful in the areas contaminated with high levels of pathogen.

Ethnopharmacological relevance The fruits of Schisandra chinensis (Trucz.) Baill. (Schisandraceae) which have been used as a tonic especially for kidney yin deficiency in Chinese traditional medicine are recently receiving attention for its preventive activity on age-related neurodegenerative diseases. A variety of studies demonstrated the cognitive-enhancing effects of Schisandra chinensis through animal tests and also in clinical trials. Aim of study In this study, we attempted to investigate the effects of the lignan-riched extract of Schisandra chinensis fruits (ESP-806) on neurotoxicity and memory impairment induced by Aβ 1–42 injection in mice. Materials and methods The fruits of Schisandra chinensis were extracted with the mixture of n -hexane:ethanol (9:1), which is riched with bioactive dibenzocyclooctadiene lignans, schizandrin, gomisin N, wuweigisu C. After oral treatment of ESP-806 (100 mg/kg body weight) followed by injection of Aβ 1–42 (2 μg/mouse, i.c.v. ), novel object recognition and passive avoidance tests were evaluated. To verify the cognition enhancing effects of ESP-806, we examined the effects of ESP-806 on the activities of β -secretase and acetylcholinesterase, and the contents of Aβ and the reduced glutathione within the cortex and hippocampus of Aβ-injected mice. Results Oral treatment of ESP-806 (100 mg/kg body weight) significantly attenuated Aβ 1–42 -induced memory impairment evaluated by behavioral tests. Furthermore, the treatment of ESP-806 attenuated the elevation of β -secretase activity accompanying the reduced level of Aβ 1–42 in the cortex and hippocampus of the brain. ESP-806 also significantly inhibited the acetylcholinesterase activity in the hippocampus and increased the content of the reduced glutathione in the cortex and hippocampus of mouse brain. Conclusions These data suggested that the extract of Schisandra chinensis fruits riched with dibenzocyclooctadiene lignans may be useful in the prevention and treatment of Alzheimer's disease.

Hydrocarbon stapling is an effective strategy to stabilize the helical conformation of bioactive peptides. Here we describe application of stapling to anticonvulsant neuropeptides, galanin (GAL) and neuropeptide Y (NPY), that are implicated in modulating seizures in the brain. Dicarba bridges were rationally introduced into minimized analogs of GAL and NPY resulting in increased α-helical content, in vitro metabolic stability and n -octanol/water partitioning coefficient (log D ). The stapled analogs retained agonist activities towards their respective receptors and suppressed seizures in a mouse model of epilepsy.

The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague–Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800–1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production.

The glycosylation of neuroactive peptides is a promising strategy to treat neurological and psychiatric disorders. Herein we investigated the effects of site-specific glycosylation of neurotensin (NT). The glycosylated analogues have low-nanomolar affinities and agonist activities toward NTS1, and suppress seizures with sub-picomolar potency. Our work points to a new research direction of exploring BBB-permeable NT analogues as potential first-in-class antiepileptic drugs. Neurotensin (NT) is an endogenous neuropeptide involved in a variety of central and peripheral neuromodulatory effects. Herein we show the effects of site-specific glycosylation on the in vitro and in vivo pharmacological properties of this neuropeptide. NT analogues containing O-linked disaccharides (β-melibiose and α-TF antigen) or β-lactose units linked by a PEG3 spacer were designed and chemically synthesized using Fmoc chemistry. For the latter analogue, Fmoc-Glu-(β-Lac-PEG3-amide) was prepared. Our results indicate that the addition of the disaccharides does not negatively affect the sub-nanomolar affinity or the low-nanomolar agonist potency for the neurotensin receptor subtype 1 (NTS1). Interestingly, three glycosylated analogues exhibited sub-picomolar potency in the 6 Hz limbic seizure mouse model of pharmacoresistant epilepsy following intracerebroventricular administration. Our results suggest for the first time that chemically modified NT analogues may lead to novel antiepileptic therapies.

Conjugated polyamines are potential carriers for biotherapeutics targeting the central nervous system. We describe an efficient synthesis of a polyamine-based amino acid, Lysine-trimethylene(diNosyl)-spermine(triBoc) with Dde or Fmoc orthogonal protecting groups. This nonnatural amino acid was incorporated into a neurotensin analogue using standard Fmoc-based protocols. The analogue maintained high affinity and agonist potency for neurotensin receptors and exhibited dramatically improved analgesia in mice. Our work provides a basis for use of polyamine amino acids in polypeptides.

In the present study, we performed a concept analysis of the "body image of HIV/AIDS Patients". The antecedents of the body image of HIV/AIDS patients were "HIV infection & AIDS diagnosis" and "previous body perception". The attribute of the body image of HIV/AIDS patients was "HIV related stigma" whereas the consequences of the body image of HIV/AIDS patients were "negative health outcomes" and, "lower quality of life". In conclusion, the body image of HIV/AIDS patients is a key concept in the care of HIV/AIDS patients.

This was a descriptive study about the effect of professional self-concept and autonomy on nursing performance. The study results indicate that, flexibility, medium autonomy, and position are factors that affect nursing performance. In conclusion, the improvement of nurses' professional self-concept and autonomy will improve their nursing performance. Therefore, strategies that strengthen professional self-concept and autonomy should be developed in order to improve nursing performance.

Squalene epoxidase (SE) catalyzes the conversion of squalene to (3S)-2,3-oxidosqualene. Photolabeling and site-directed mutagenesis were performed on recombinant rat SE (rrSE) in order to identify the location of the substrate-binding site and the roles of key residues in catalysis. Truncated 50-kDa rrSE was purified and photoaffinity labeled by competitive SE inhibitor (Ki=18.4 microM), [(3)H]TNSA-Dza. An 8-kDa CNBr/BNPS-skatole peptide was purified and the first 24 amino acids were sequenced by Edman degradation. The sequence PASFLPPSSVNKRGVLLLGDAYNL corresponded to residues 388-411 of the full-length rat SE. Three nucleophilic residues (Lys-399, Arg-400, and Asp-407) were labeled by [(3)H]TNSA-Dza. Triple mutants were prepared in which bulky groups were used to replace the labeled charged residues. Purified mutant enzymes showed lower enzymatic activity and reduced photoaffinity labeling by [(3)H]TNSA-Dza. This constitutes the first evidence as to the identity of the substrate-binding site of SE.

Neurotensin receptors have been studied as molecular targets for the treatment of pain, schizophrenia, addiction, or cancer. Neurotensin (NT) and Contulakin-G, a glycopeptide isolated from a predatory cone snail Conus geographus, share a sequence similarity at the C-terminus, which is critical for activation of neurotensin receptors. Both peptides are potent analgesics, although affinity and agonist potency of Contulakin-G toward neurotensin receptors are significantly lower, as compared to those for NT. In this work, we show that the weaker agonist properties of Contulakin-G result in inducing significantly less desensitization of neurotensin receptors and preserving their cell-surface density. Structure-activity relationship (SAR) studies suggested that both glycosylation and charged amino acid residues in Contulakin-G or NT played important roles in desensitizing neurotensin receptors. Computational modeling studies of human neurotensin receptor NTS1 and Contulakin-G confirmed the role of glycosylation in weakening interactions with the receptors. Based on available SAR data, we designed, synthesized, and characterized an analog of Contulakin-G in which the glycosylated amino acid residue, Gal-GalNAc-Thr10, was replaced by memantine-Glu10 residue. This analog exhibited comparable agonist potency and weaker desensitization properties as compared to that of Contulakin-G, while producing analgesia in the animal model of acute pain following systemic administration. We discuss our study in the context of feasibility and safety of developing NT therapeutic agents with improved penetration across the blood-brain barrier. Our work supports engineering peptide-based agonists with diverse abilities to desensitize G-protein coupled receptors and further emphasizes opportunities for conotoxins as novel pharmacological tools and drug candidates.

Alzheimer’s disease (AD) is a neurodegenerative disease induced by cholinergic neuron damage or amyloid-beta aggregation in the basal forebrain region and resulting in cognitive disorder. We previously reported on the neuroprotective effects of Betula platyphylla bark (BPB) in an amyloid-beta-induced amnesic mouse model. In this study, we obtained a cognitive-enhancing compound by assessing results using a scopolamine-induced amnesic mouse model. Our results show that oral treatment of mice with BPB and betulin significantly ameliorated scopolamine-induced memory deficits in both passive avoidance and Y-maze tests. In the Morris water maze test, administration of BPB and betulin significantly improved memory and cognitive function indicating the formation of working and reference memories in treated mice. Moreover, betulin significantly increased glutathione content in mouse hippocampus, and the increase was greater than that from betulinic acid treatment. We conclude that BPB and its active component betulin have potential as therapeutic, cognitive enhancer in AD. Betulin and BPB Significantly Ameliorated Scopolamine-Induced Memory Deficits in Mice in the Passive Avoidance, Y-maze, and Water Maze Tests.

Alzheimer's disease (AD) is closely associated with amyloid β (Aβ)-induced neurotoxicity and oxidative stress in the brain. Betula platyphylla, which has been used to treat various oxidative-stressed related diseases, has recently received attention for its preventive activity on age-related neurodegenerative diseases. In this study, we attempted to investigate the effects of B. platyphylla bark (BPB-316) on Aβ(1-42)-induced neurotoxicity and memory impairment. Oral treatment using BPB-316 significantly attenuated Aβ-induced memory impairment which was evaluated by behavioral tests including the passive avoidance, Y-maze and Morris water maze test. BPB-316 also inhibited the elevation of β-secretase activity accompanying the reduced Aβ(1-42) levels in the hippocampus of the brain. Furthermore, BPB-316 significantly decreased the acetylcholinesterase activity and increased the glutathione content in the hippocampus. In addition, we confirmed that the expression of both cAMP responsive element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the hippocampus of Aβ(1-42)-injected mice were markedly upregulated by the treatment of BPB-316. Our data suggest that the extracts of B. platyphylla bark might be a potential therapeutic agent against AD.

Squalene epoxidase (SE) (EC 1.14.99.7) is a flavin-requiring, non-cytochrome P-450 oxidase that catalyzes the conversion of squalene to (3 S )-2,3-oxidosqualene. Photolabeling and site-directed mutagenesis were performed on recombinant rat SE (rrSE) to elucidate the location and roles of active-site residues important for catalysis. Two new benzophenone-containing analogs of NB-598, a nanomolar inhibitor of vertebrate SE, were synthesized in tritium-labeled form. These photoaffinity analogs (PDA-I and PDA-II) became covalently attached to SE when irradiated at 360 nm. Lys-C digestion and HPLC purification of [ 3 H]PDA-I-labeled rrSE resulted in isolation of a single major peptide. MALDI-TOF mass spectrometry of this peptide indicated a covalent adduct between PDA-I and a tripeptide, Asp-Ile-Lys, beginning at Asp-426 of rat SE. Based on the labeling results, three mutant constructs were made. First, the D426A and K428A constructs showed a 5- to 8-fold reduction in SE activity compared with wild-type enzyme, while little change was observed in the I427A mutant. Second, a set of five mutant constructs was prepared for the conserved region based on the structure of the flavoprotein p -hydroxybenzoate hydroxylase (PHBH). Compared with wild-type, D284A and D407A showed less than 25% SE activity. This reduction also appeared to correlate with reduced affinity of the mutant proteins for FAD. Finally, each of the seven Cys residues of rrSE were individually mutated to Ala. Three Cys substitutions had no effect on SE activity, and substitutions at Cys-500 and Cys-533 showed a 50% lower SE activity. Mutations at Cys-490 and Cys-557 produced proteins with negligible SE activity, implicating these residues as being either structurally or catalytically essential. Chemical modification of wild-type and Cys mutants with a thiol-modifying reagent support the existence of a disulfide bond between Cys-490 and Cys-557.

The extract of Siegesbeckia pubescens herb and its chemical constituents were tested for the ability to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglia. The methanol extract and the 90% MeOH fraction of S. pubescens effectively attenuated lipopolysaccharide-induced nitric oxide production. Several steps of chromatography yielded eight ent-kaurane diterpenes (1-8) and one ent-pimarane diterpene (9) from the 90% MeOH fraction. Among these compounds, compounds 2-9 showed significant inhibitory effect on lipopolysaccharide-induced nitric oxide production in BV2 microglia. Compounds 3 and 9 concentration-dependently decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), supported by quantitative real time polymerase chain reaction (PCR) and Western blot analysis. These results suggest that ent-kaurane and ent-pimarane diterpenes isolated from S. pubescens are expected to be potential candidates against neuroinflammation-related disease.

Delivery of neuropeptides into the central and/or peripheral nervous systems supports development of novel neurotherapeutics for the treatment of pain, epilepsy and other neurological diseases. Our previous work showed that the combination of lipidization and cationization applied to anticonvulsant neuropeptides galanin (GAL) and neuropeptide Y (NPY) improved their penetration across the blood-brain barrier yielding potent antiepileptic lead compounds, such as Gal-B2 (NAX 5055) or NPY-B2. To dissect peripheral and central actions of anticonvulsant neuropeptides, we rationally designed, synthesized and characterized GAL and NPY analogues containing monodisperse (discrete) oligoethyleneglycol-lysine (dPEG-Lys). The dPEGylated analogues Gal-B2-dPEG(24), Gal-R2-dPEG(24) and NPY-dPEG(24) displayed analgesic activities following systemic administration, while avoiding penetration into the brain. Gal-B2-dPEG(24) was synthesized by a stepwise deprotection of orthogonal 4-methoxytrityl and allyloxycarbonyl groups, and subsequent on-resin conjugations of dPEG(24) and palmitic acids, respectively. All the dPEGylated analogues exhibited substantially decreased hydrophobicity (expressed as logD values), increased in vitro serum stabilities and pronounced analgesia in the formalin and carrageenan inflammatory pain assays following systemic administration, while lacking apparent antiseizure activities. These results suggest that discrete PEGylation of neuropeptides offers an attractive strategy for developing neurotherapeutics with restricted penetration into the central nervous system.

A methanolic extract of ALNUS FIRMA barks (Betulaceae) significantly attenuated nitric oxide production in lipopolysaccharide-stimulated BV2 microglia. Two new compounds, characterized as 4-hydroxy-2,6-dimethoxyphenyl 6'- O-syringoyl- beta- D-glucopyranoside (1) and 4-hydroxy-2,6-dimethoxyphenyl 6'- O-vanilloyl- beta- D-glucopyranoside (2), were isolated from the barks of A. FIRMA using bioactivity-guided fractionation, together with two known phenolic glycosides (3, 4) and 11 known diarylheptanoids (5- 15). Among these compounds, 1- 4 and 6- 11 showed significant inhibitory effect on lipopolysaccharide-induced nitric oxide production in BV2 microglial cells at concentrations ranging from 10 microM to 100 microM.

Prosthesis of non-critical parts of a polypeptide backbone is an at- tractive strategy to simplify bioactive peptides. This approach was applied to an opi- oid neuropeptide, Met-enkephalin, in which two adjacent Gly2-Gly3 residues were replaced with a series of non-peptidic backbone spacers varying in length and/or physicochemical properties. The backbone spacers did not affect the overall struc- tural properties of the analogues, but they did dramatically reduce their affinities and agonist activities toward - and -opioid receptors. Molecular modeling sug- gested that the decrease of the affinity of Met-enkephalin to -opioid receptor could be accounted for by the loss of a single hydrogen bond. Remarkably, the ana- logues containing the most isostere spacers retained potent antinociceptive and anticonvulsant properties that were comparable to that of the endogenous pep- tide. This unexpected high in vivo potency could not be accounted for by an increase in metabolic stability. Moreover, the antiepileptic activity could not be reversed by opioid receptor antagonists. In summary, the results obtained with the analogues containing backbone spacers suggest a novel mechanism for seizure control in the brain that involves alternative non-opioid signaling.

Galanin is an endogenous neuropeptide that modulates seizures in the brain. Because this neuropeptide does not penetrate the blood-brain barrier, we designed truncated galanin analogues in which nonessential amino acid residues were replaced by cationic and/or lipoamino acid residues. The analogues prevented seizures in the 6 Hz mouse model of epilepsy following intraperitoneal administration. The most active analogue, Gal-B2 (NAX 5055), contained the -Lys-Lys-Lys(palmitoyl)-Lys-NH(2) motif and exhibited high affinity for galanin receptors (K(i) = 3.5 nM and 51.5 nM for GalR1 and GalR2, respectively), logD = 1.24, minimal helical conformation and improved metabolic stability. Structure-activity-relationship analysis suggested that cationization combined with position-specific lipidization was critical for improving the systemic activity of the analogues. Because the anticonvulsant activity of galanin is mediated by the receptors located in hippocampus and other limbic brain structures, our data suggest that these analogues penetrate into the brain. Gal-B2 may lead to development of first-in-class antiepileptic drugs.

This study was made to investigate the effect of adenoidectomy on dentofacial skeleton in naso-respiratory dysfunction children. The clinical material compromised the 24 children in a previous study who had naso-respiratory dysfunction and 24 children who were the nasal breathing with normal occlusion. The cephalograms were taken at the initial examination and 1 year later for the control group and experimental group the paired sample statistical analysis was performed. The result were as follows. 1. In cranial base variable, difference between two groups were not statistically significant. 2. In craniofacial variable, experimental group showed brachyfacial pattern but control groups didn't show significant growth pattern. 3. In maxillary variables, experimental group showed flattening the palptal plane. 4. In mandibular variables, experimental group showed the decrease of mandibular plane angle and gonial angle. 5. In facial height variables, experimental group showed horizontal growth rotation.

This study was made to investigate the influence of mouth breathing to tongue, mandible and hyoid bone position. It has been clinically suggested that the mouth breathing is induced by the respiratory dysfunction of nasopharyngeal airway causing by the Adenoids. The author used the 50 children, who were the nasal breathes with normal occlusion as the control group, and 50 children, who were mouth breathers with Adenoid as the experimental group. Results were as following: 1. In experimental group, the tongue was positioned more anterior and lower than that of the normal children. 2. In experimental group, the mandible was positioned more lower than that of the normal children. 3. In experimental group, the hyoid bone was positioned more anterior and lower than that of the normal children.