Search

A method for the simultaneous quantification of 13 bioactive compounds (psoralen, isopsoralen, isobavachin, bakuchalcone, neobabaisoflavone, bavachin, corylin, psoralidin, isobavachalcone, bavachinin, corylifol A, bavachalcone, and bakuchiol) by ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry has been developed and validated in rat plasma. Osthol was used as an internal standard and plasma samples were pretreated with one-step liquid-liquid extraction. These analytes were separated using a gradient mobile phase system of water and acetonitrile at a flow rate of 0.2 mL/min on a reverse-phase C18 column and analyzed in the selected multiple reactions monitoring mode. All calibration curves were linear (r > 0.9952) over the tested ranges. The intra- and interday accuracy and precisions of these analytes at three different concentration levels were within the acceptable limits of

Previous research has revealed that the von-Hippel-Lindau tumor suppressor protein (pVHL) may downregulate never-in-mitosis A-related kinase 8 (NEK8) via hypoxia-inducible factor-α (HIF-α). The HIF-independent functions of pVHL also serve an important role in its tumor-suppressor action. In the present study, the association between pVHL and NEK8 was demonstrated in the human gastric cancer cell line, SGC-7901, indicating a direct interaction of pVHL with NEK8. Subsequently, it was reported that MG-132, a specific proteasome inhibitor, may attenuate pVHL overexpression-induced reductions in NEK8 protein expression levels. In addition, the present study revealed that pVHL may stimulate the rapid degradation of NEK8 protein and promote its ubiquitination. The association between the expression profile of NEK8 and the survival status of patients with gastric cancer was analyzed from an online database. Kaplan-Meier survival plots indicated that higher expression levels of NEK8 may lead to poor survival, as suggested by the transcriptomic data of 1,065 patients with gastric cancer. It was found that NEK8-knockdown mediated by RNA interference inhibited SGC-7901 and SNU-1 proliferation, colony formation and migration in vitro, and tumor growth in vivo. Collectively, the present study proposed that NEK8 may be a novel target of pVHL as a ubiquitin E3 ligase, and may serve a role as a potential oncoprotein in human gastric cancer.

The majority of molecular targets of anticancer agents are limited to a subset of patients, and therefore identification of more specific biomarkers that can be used to improve clinical outcomes is of increasing interest. The present study showed that von Hippel‑Lindau tumor suppressor (VHL) tumor‑suppressor activity may influence the therapeutic response to Aurora kinase A (AURKA) inhibitors in human renal cell carcinoma (RCC). VHL protein (pVHL) expression was evaluated by immunoblotting in the human RCC cell lines CAKI, ACHN, 786‑O, 769‑P and A498. The anti‑tumor activities of alisertib, an AURKA‑specific chemical inhibitor, were detected by Cell Counting Kit‑8 assay in vitro and mouse xenograft model in vivo. Additionally, the VHL‑mediated anti‑tumor activity was assessed in 769‑P and CAKI cells via the loss or gain of VHL. The results revealed that VHL‑deficient 786‑O, 769‑P and A498 cells were sensitive to alisertib. By contrast, alisertib‑resistant CAKI and ACHN cells expressed the wild type VHL gene. In addition, rescue or knockdown of VHL was observed to increase or decrease alisertib anti‑proliferation activity, respectively, in RCC cells. The inverse correlation between the VHL gene expression profile and alisertib sensitivity was further confirmed in human cancer xenografts models. Taken together, these results suggested that VHL loss could potentially serve as a biomarker for predicting the efficacy of AURKA inhibitors.

Summary This work reveals how tobacco pistil and style may communicate with pollen tubes and regulate their growth during fertilization via the γ-aminobutyric acid–Ca2+-permeable channel–glutamate decarboxylase–calmodulin signalling pathway., γ-Aminobutyric acid (GABA) is implicated in pollen tube growth, but the molecular and cellular mechanisms that it mediates are largely unknown. Here, it is shown that exogenous GABA modulates putative Ca2+-permeable channels on the plasma membranes of tobacco pollen grains and pollen tubes. Whole-cell voltage-clamp experiments and non-invasive micromeasurement technology (NMT) revealed that the influx of Ca2+ increases in pollen tubes in response to exogenous GABA. It is also demonstrated that glutamate decarboxylase (GAD), the rate-limiting enzyme of GABA biosynthesis, is involved in feedback controls of Ca2+-permeable channels to fluctuate intracellular GABA levels and thus modulate pollen tube growth. The findings suggest that GAD activity linked with Ca2+-permeable channels relays an extracellular GABA signal and integrates multiple signal pathways to modulate tobacco pollen tube growth. Thus, the data explain how GABA mediates the communication between the style and the growing pollen tubes.

This article use the Sulphide Isobutene (T321), Five Sufides Dialkyl(RC2540) and Star of Phosphorus(P110) as the additives,Neopentyl Polyol Ester(NPE) and mineral oil N32 as base oil. Compound above additives and base oil for the four levels. A sample: adding 4% T321 additive in NPE. B sample: adding 4% T321 additive in N32. C sample: adding 4% RC2540 additive in NPE. D sample: adding RC2540, T321 and P110 additives in NPE (all is mass fraction). The oral acute toxicity test, eye mucous stimulation test, skin hypersensitive test, soaking tail toxicity tests were conducted in above samples. The test results show that. The mineral oil, it’s not only toxic then synthetic oil but also has a poor lubricating ability compare with the same percent additive in synthetic oil. In oral acute toxicity test, eye mucous stimulation test, skin hypersensitive test, soaking tail toxicity tests, Toxic reaction of mineral N32+4%wt Sulphide Isobutene (T321) obviously from other oil samples.

This study investigated the effects of acute and chronic administration of the non-competitive NMDA receptor antagonists MK-801 on c-Fos protein expression in different brain regions of mice with or without clozapine. MK-801 (0.6 mg/kg) acute administration produced a significant increase in the expression of c-Fos protein in the layers III-IV of posterior cingulate and retrosplenial (PC/RS) cortex, which was consistent with the previous reports. Moreover, we presented a new finding that MK-801 (0.6 mg/kg) chronic administration for 8 days produced a significant increase of c-Fos protein expression in the PC/RS cortex, prefrontal cortex (PFC) and hypothalamus of mice. Among that, c-Fos protein expression in the PC/RS cortex of mice was most significant. Compared to acute administration, we found that MK-801 chronic administration significantly increased the expression of c-Fos protein in the PC/RS cortex, PFC and hypothalamus. Furthermore, pretreatment of mice with clozapine significantly decreased the expression of c-Fos protein induced by MK-801 acute and chronic administration. These results suggest that c-Fos protein, the marker of neuronal activation, might play an important role in the chronic pathophysiological process of schizophrenic model induced by NMDA receptor antagonist.

SARS‐CoV spike (S) protein‐mediated cell fusion is important for the viral entry mechanism and identification of SARS‐CoV entry inhibitors. In order to avoid the high risks involved in handling SARS‐CoV and to facilitate the study of viral fusion mechanism, we established the cell lines: SR‐COS7 cells that stably express both SARS‐CoV S protein and red fluorescence protein, R‐COS7 cells that stably express red fluorescence protein, and AG‐COS7 cells that stably express both ACE2 and green fluorescence protein, respectively. When SR‐COS7 cells or R‐COS7 cells were cocultured with AG‐COS7 cells, syncytia with yellow fluorescence were conveniently observed after 12 h in SR‐COS7 cells plus AG‐COS7 cells, but not in R‐COS7 cells plus AG‐COS7 cells. The cell‐to‐cell fusion efficiency was simply determined for quantitative analysis based on the number of syncytium detected by flow cytometry. Such new cell‐to‐cell fusion model was further assessed by the potent HR2 peptide inhibitor, which led to the obvious decrease of the cell‐to‐cell fusion efficiency. The successful fusion and inhibition of cell‐based binding assay shows that it can be well used for the study of SARS‐CoV entry and inhibition. iubmb Life, 58: 480 ‐ 486, 2006

Small conductance Ca(2+)-activated potassium channels (SK channels) distributing in the nervous system play an important role in learning, memory and synaptic plasticity. Most pharmacological properties of them are determined by short-chain scorpion toxins. Different from most voltage-gated potassium channels and large-conductance Ca(2+)-activated potassium channels, SK channels are only inhibited by a small quantity of scorpion toxins. Recently, a novel peptide screener in the extracellular pore entryway of SK channels was considered as the structural basis of toxin selective recognition. In this review, we summarized the unique interactions between scorpion toxins and SK channels, which is crucial not only in deep-researching for physiological function of SK channels, but also in developing drugs for SK channel-related diseases.

The present study was designed to investigate the effects of acute and chronic administration of MK-801 (0.6 mg/kg), a noncompetitive NMDA-receptor antagonist on extracellular glutamate (Glu) and ascorbic acid (AA) release in the prefrontal cortex (PFC) of freely moving mice using in vivo microdialysis with open-field behavior. In line with earlier studies, acute administration of MK-801 induced an increase of Glu in the PFC. We also observed single MK-801 treatment increased AA release in the PFC. In addition, our results indicated that the basal AA levels in the PFC after MK-801 administration for 7 consecutive days were significantly decreased, and basal Glu levels also had a decreased tendency. After chronic administration (0.6 mg/kg, 7 days), MK-801 (0.6 mg/kg) challenge significantly decreased dialysate levels of AA and Glu. Our study also found that both acute and chronic administration of MK-801 induced hyperactivity in mice, but the intensity of acute administration was more than that of chronic administration. Furthermore, in all acute treatment mice, individual changes in Glu dialysate concentrations and the numbers of locomotion were positively correlated. In conclusion, this study may provide new evidence that a single MK-801 administration induces increases of dialysate AA and Glu concentrations in the PFC of freely moving mice, which are opposite to those induced by repeated MK-801 administration, with an unknown mechanism. Our results suggested that redox-response might play an important role in the model of schizophrenic symptoms induced by MK-801.

This study is to establish a simple and practical co-culture method of cortical neurons and astrocytes of rats. The cortex of the new-born SD rats was digested by 0.125% pancreatic enzyme, and the differential adherence was applied to obtain the mixed cell suspension of neurons and astrocytes. A low concentration of cytarabine was used to inhibit the astrocytes in a moderate way to get neuronal and astrocyte co-culture. The morphological characteristics of the cells in different times were observed under the inverted microscope. The cells began to adhere the wall 2 h after the inoculation. Neurons and astrocytes grew in a good condition under the inverted microscope 9 days after the inoculation. The results of the immunofluorescence staining and Rosenfeld's staining indicated that the co-culture of neurons and astrocytes was successful and the ratio of neurons and astrocytes was close to 1:1. A new neurons and astrocytes co-culture method, which is simple and convenient, was successfully established. It will be an efficient method for the related researches about neuronal and astrocyte co-culture in vitro.

Background The human ether-a-go-go-related gene potassium channel (hERG) has an unusual long turret, whose role in recognizing scorpion toxins remains controversial. Here, BmKKx2, the first specific blocker of hERG channel derived from scorpion Mesobuthus martensii, was identified and the turret role of hERG channel was re-investigated using BmKKx2 as a molecular probe. Results BmKKx2 was found to block hERG channel with an IC50 of 6.7 ± 1.7 nM and share similar functional surface with the known hERG channel inhibitor BeKm-1. The alanine-scanning mutagenesis data indicate that different residue substitutions on hERG channel by alanine decreased the affinities of toxin BmKKx2 by about 10-fold compared with that of wild-type hERG channel, which reveals that channel turrets play a secondary role in toxin binding. Different from channel turret, the pore region of hERG channel was found to exert the conserved and essential function for toxin binding because the mutant hERG-S631A channel remarkably decreased toxin BmKKx2 affinity by about 104-fold. Conclusions Our results not only revealed that channel turrets of hERG channel formed an open conformation in scorpion toxin binding, but also enriched the diversity of structure-function relationships among the different potassium channel turrets.

In the present study, we investigated the effects of acute and chronic systemic administration of MCI-225 (4-(2-fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno[2,3-d]pyrimidine monohydrate hydrochloride), a newly-developed selective noradrenaline (NA) reuptake inhibitor with 5-HT3-receptor-blocking action, on extracellular NA levels in the hypothalamus of stressed and non-stressed rats by utilizing intracerebral microdialysis. Acute administration of MCI-225 (3 and 10 mg/kg, p.o.) significantly and dose-dependently increased extracellular NA levels in the hypothalamus in non-stressed rats. Footshock for 20 min also significantly increased NA levels in the hypothalamus of both groups of rats pretreated with vehicle and MCI-225. Although chronic administration of MCI-225 (3 or 10 mg/kg, p.o. for 14 days) did not alter the basal extracellular NA levels in the hypothalamus, the stress-induced increases in extracellular NA levels were significantly lower in rats chronically treated with MCI-225 (10 mg/kg) than those of rats pretreated with vehicle for the same period. The increase in extracellular NA levels induced by MCI-225 challenge (3 or 10 mg/kg, p.o.) were not different between rats chronically treated with MCI-225 or vehicle. These results suggest that MCI-225 enhances extracellular NA levels in the hypothalamus in both non-stressed and stressed rats by inhibiting NA uptake and that chronic systemic administration of MCI-225 did not alter basal extracellular NA levels, but reduced the increase in NA release caused by footshock stress. These data suggest the possibility that MCI-225 might possess anxiolytic and/or antidepressant properties.

Quantitative evaluation of service quality is very important in modern service industry, so there has important theoretical and practical significance of studying comprehensive evaluation method of customer satisfaction. This paper discusses customer satisfaction concept and constructs evaluation index system for customer satisfaction oriented information service, then describes the theories and procedures of TOPSIS evaluation method and entropy weighted method. Finally, this paper takes university library-a typical kind of information service industry for example, using TOPSIS method to evaluate the library's reader satisfaction, discusses the evaluation results and gives suggestions for improving its information service quality and level based on the results.

This paper systematically analyzed specialized market's demands and business models of E-Commerce, made a research on the construction of E-Commerce platform for specialized market, and presented the general system structure. On this basis, a modular and integrate function structure was proposed by structural system design. Finally we used a specific case to provide a feasible solution for the development of E-Commerce platform for specialized market.

To investigate the intrinsic mechanisms underlying spike programming at pyramidal neurons and interneurons in layer II/III of sensorimotor cortex.Electrical signals at the cortical neurons were recorded in current clamp model with multi-clamp700B Amplifiers. Signals were inputted into pClamp and Origin for data acquisition and analyses.Compared to pyramidal neurons, interneurons express the higher capacity of spikes and the more stability of spike programming, which are mechanistically caused by lower threshold potentials and shorter refractory periods.The refractory periods and threshold potentials directly influence the programming of sequential spikes.

This paper carried on an analysis to the knowledge management requirements of learning organizations. Based on the requirements and the knowledge management methods, a new knowledge management solution on the learning organizations has been proposed, and the functions of the new solution have been pointed out concretely.

To evaluate exactly the performance of knowledge management (KM) is an important part of the construction of enterprise knowledge management systems. Based on enterprise capital, a performance evaluation index system has designed by using intellectual capital, organization capital and market capital as subjects in this paper. In order to realize quantitative calculation for qualitative index, a fuzzy calculation method, that is triangular fuzzy number (TFN) evaluation method is proposed. Then the method’s theory and steps are discussed. Finally, the empirical study has been done on three IT enterprises, use TFN method to evaluate their KM performance, and some improvement suggestions are given based on evaluation results.

The development of industry informationization and electronic commerce (e-commerce) promote the emergence of electronic market (e-market). One called electronic exchange (e-exchange) is a typical business model. It requires a higher security level for the business operating system. This paper systematically studies the e-exchange security problems from the view of e-commerce security, analyzes the security requirements of e-exchange and discusses the security mechanism and service. Basing on these, the paper proposes a security solution of the e-exchange. Finally the paper elaborates the realization and application of this solution combined with the case of Guangdong Plastics Exchange (GDPE.com).

Knowledge management (KM) is a new problem for e- commerce and enterprise application integration (EAI) , and it has become one of the research front and hotspots in management science and engineering. In this paper, the requirements and key problems of e-commerce application oriented enterprise KM are discussed, a enterprise information portal(EIP) based KM solution is presented, the key techniques for implementation are pointed. At last, a case of Midea is studied, in addition, the developing trends and foreground of KM are discussed also.

As an important part of knowledge management (KM), the KM performance evaluation tries to find out the key factors restraining the enhancement of the enterprises' performance. In this paper, some primary factors of the performance of enterprises KM are analyzed and an index system of KM performance is established by considering some aspects, such as marketing capability, information management, maturity degree of the learning organizations, and knowledge stocks. A principal component analysis and the arithmetic steps for principal component analysis are presented to evaluate the KM performance. The case analysis shows that the principal component analysis method is efficient and practical for the KM performance evaluation.

To investigate the apoptosis-inducing effects of NNAMB, a novel polyamine conjugate, in erythroleukemia K562 cells and its molecular mechanism.Cell viability was assessed by MTT assay and trypan blue dye exclusion method. The cell morphology was observed by fluorescence microscopy. The cell cycle distribution, apoptosis and mitochondrial membrane potential were measured by flow cytometry. The expression of caspase-3, -8, -9, cytochrome c in the K562 cells was detected by Western blot.NNAMB inhibited the proliferation of K562 cells. The cells treated with NNAMB showed a typical apoptotic morphology, Sub-G1 peak and loss of mitochondrial membrane potential. Western blot assay showed that NNAMB increased the expression of caspase-3, -9, cytochrome c but not caspase-8 in a dose-and time-dependent manner.NNAMB induces apoptosis via mitochondrial pathway in K562 cells.

Chronic organophosphate-induced neuropsychiatric disorder is a less well-characterized syndrome, which is usually delay-occurred, persists long and is similar to the symptom of cholinergic deficit, its mechanism is unclear. The characteristics of chronic organophosphate-induced neuropsychiatric disorder are somewhat opposite to the direct action of OP pesticide, since withdrawal effect is usually opposite to the original effect of a drug, hypothesis that chronic organophosphate-induced neuropsychiatric disorder is a kind of withdrawal syndrome is suggested.

Dispute about conception and research area of knowledge management exists always. In order to distinguish and evaluate about the influence factor of the success or failure of knowledge management project, it is necessary to understand it in the point of system thought and to design an integrated entirely knowledge management framework model that is accepted at large. Firstly, this article starts with the research on the present knowledge management and the analysis of different views, discussing the system framework, connotation and extension of knowledge management with systemic viewpoint. Then the paper will develop a knowledge management framework model and propose a system framework of knowledge management system and its practical application.

As the reform development of telecom industry and the entrance of WTO, the competition among the telecom enterprises is becoming tougher. Nowadays, "customer-oriented" is the new principle of telecom market competition. As the enterprises in telecom industry have much more customers and customer data than those in other industries, the application of customer relationship management (CRM) in telecom industry becomes one of the hottest topics on enterprise informationlization. The thesis discusses the discovery of telecom customer knowledge based on data-mining. In this paper, a customer analysis model is founded by the method of data mining, including customer segmentation analysis, customer churn analysis, customer owing and fraud analysis. In the end, the thesis introduces a real case of a customer segmentation project in a mobile communication company and illustrates the application detail of customer intelligence in this company. In this case, the author uses SPSS Clementine to conduct data-mining. Meanwhile, diverse marketing strategy is also proposed based on the customer segmentation knowledge.

Knowledge management (KM) system includes KM strategic planning, technique, culture foundation, knowledge resource, process of knowledge transformation and exterior circumstance. Whether the definitude of KM stratagem or the early requirement design of KM implement, it must to evaluate the KM performance, to audit the KM requirement and program and to fulfill the KM process positive and feedback closed loop system. Organizations can set down KM strategy and programming and implement effectively no other than understanding its own knowledge stock, processes and requirement; can optimize KM no other than timely evaluating and auditing KM. This article introduce the concept of knowledge capital which root in intellectual capital as the object of the knowledge audit, thus the research fruit of intellectual capital could be used to study knowledge audit. Based on that, this article put forwards the integrity conception of KM audit, constitutes a conception model of knowledge audit and presents the workflow and currently methods of implementing knowledge audit.

With the development of information system, there is an urgent need for enterprises to change from information management to knowledge management. In the network-computing environment, enterprises need to apply the complex, dynamic and integrated, object-oriented knowledge management system. First, this paper analyzed the essence of knowledge and knowledge management, discussed the concept and characteristics of enterprise knowledge portal. On this basis, the article proposed a management object oriented solution of knowledge management system, focusing on the framework of the system, mode of operation and the value of application with a case study. Such a solution can help enterprises to establish open, dynamic and integrated information and knowledge management systems.

Human immunodeficiency virus (HIV) is a retrovirus, belongs to Lentiviridae family. As long as viral genetic material entering into host cytoplasm, double-strand DNAs synthesis occurs which is catalyzed by reverse transcriptase (RT) with viral plus-strand RNA as template. This reverse transcription is a key link of HIV-1 life cycle and an important target for anti-HIV drug development. The process of reverse transcription can be divided into several steps: formation of minus-strand strong-stop DNA; the first translocation; initiation of plus-strand DNA synthesis; and, the second translocation and the completion of both strands. These steps can be detected individually by using polymerase chain reaction (PCR) according to the amplified products on the region of R/U5, U3, U5/PBS and the sequence between LTR and Gag. In this review, we summarize the principle for detecting stages of HIV-1 reverse transcription by using PCR.

Recent advances in Internet and e-commerce have led industry to reengineer their organizational structures and value chains. One of the most prominent trends in this change is to conduct work and operation in the distributed or virtual environments. A new kind of business model, termed as value-net, is emerging. In this paper, the business and system mode from the value-net system is studied and proposed. The feature of this business model suitable for Mobile Commerce (M-Commerce) is analyzed on the basis of value-net. The ecosystems (ecology system) model based on value-net is presented for the M-Commerce with systematic structure, collaborate mode and working mechanism. A modified value-net based ecosystem for M-Commerce operators is proposed in this paper with practical case analysis.

LmKTx8, the first toxic gene isolated from the venom of scorpion Lychas mucronatus by constructing cDNA library method, was expressed and characterized physiologically. The mature peptide has 40 residues including six conserved cysteines, and is classified as one of α-KTx11 subfamily. Using patch-clamp recording, the recombinant LmKTx8 (rLmKTx8) was used to test the effect on voltage-gated K+ channels (Kv1.3) stably expressed in COS7 cells and large conductance-Ca2+-activated K+ (BK) channels expressed in HEK293. The results of electrophysiological experiments showed that the rLmKTx8 was a potent inhibitor of Kv1.3 channels with an IC50 = 26.40 ± 1.62 nM, but 100 nM rLmKTx8 did not block the BK currents. LmKTx8 or its analogs might serve as a potential candidate for the development of new drugs for autoimmune diseases.

The present study was designed to assess the synergistic antitumor effects of anthracenylmethyl homospermidine (ANTMHspd), a novel polyamine conjugate, with alpha-difluoromethylornithine (DFMO) and to elucidate the mechanism of these effects on human leukemia HL60 cells. Cell proliferation was assessed by the MTT assay. Cell cycle, apoptosis and mitochondria membrane potential (MMP) were evaluated by flow cytometry. Caspases and cytochrome c were detected by Western Blot analysis. The combination treatment strongly inhibited cell proliferation, induced cell apoptosis and caused an accumulation in the G1 phase with an accompaniment decrease in S phase. Moreover, reduction of MMP, release of cytochrome c and activation of caspase-3 and caspase-9 but not caspase-8 were observed during the combination-mediated apoptosis. All these findings demonstrated that the combination treatment with DFMO and ANTMHspd resulted in synergistic antitumor effects on HL60 cells.

This study investigated the effect of MK-801 and ketamine, N-methyl-D-aspartate (NMDA) receptor antagonists which can induce schizophrenic symptoms and have neurotoxicity in human and animals, on hydroxyl radical (*OH) generation in the posterior cingulate and retrosplenial (PC/RS) cortex of free-moving mice using the salicylic acid trapping technique. MK-801 (0.6 mg/kg) or ketamine (50 mg/kg) acute administration significantly increased *OH levels in mouse PC/RS cortex. The basal *OH levels after MK-801 and ketamine administrations for 7 consecutive days were significantly increased compared with the naive basal levels. MK-801 (0.6 mg/kg) or ketamine (50 mg/kg) challenge after chronic administration further significantly increased dialysate levels of *OH. Our study also found that the release of *OH was secondary to stereotyped behavior, and the intensity of stereotyped behavior induced by MK-801 was more than that induced by ketamine. The results suggested that NMDA receptor antagonists participate in the generation of *OH in the PC/RS cortex of mouse, and oxidative stress, derived from the formation of free radicals, might play an important role in the pathophysiology of these two models of schizophrenia.

The neuroprotective effects of Polygonum multiflorum extract (PME) and its two fractions, ethanol-soluble PME (PME-I) and -insoluble PME (PME-II), on the degeneration of nigrostriatal dopaminergic neurons induced by a combination of paraquat and maneb (PQMB) were investigated in male C57BL/6 mice. The mice were treated twice a week for 6 weeks with intraperitoneal injections of PQMB. This combination caused a reduction of spontaneous locomotor activity, motor incoordination, and declines of dopamine level in the striatum and tyrosine hydroxylase-positive neurons in the substantia nigra. Administration of PME and PME-I once daily for 47 days during 6 weeks of PQMB treatment and last 8 days after PQMB significantly attenuated the impairment of behavioral performance and the decrease in striatal dopamine level and substantia nigral tyrosine hydroxylase-positive neurons in the PQMB-treated animals, whereas the administration of PME-II had no effect on these behavioral, neurochemical and histological indices. The present findings suggest that PME has a beneficial influence on parkinsonism induced by PQMB and that the effects of PME are attributable to some substance(s) included in the ethanol-soluble fraction of PME (PME-I).

In order to compare psychological stress-induced dopamine (DA) release in two subterritories (e.g. shell and core) of the nucleus accumbens of the same animal, a novel dual-needle microdialysis probe has been developed. The two needles were placed in the ipsilateral shell and core subterritories of the nucleus accumbens under pentobarbital anesthesia and 24 h later the microdialysis was started. Basal DA output was not significantly different between the shell and the core. Psychological stress for 20 min significantly increased extracellular DA levels in the shell of the nucleus accumbens, however, the levels of dopamine remained almost unaltered in the core. This finding suggests that DA transmission in the shell of the nucleus accumbens was selectively activated during psychological stress, and that the shell plays an important role in emotional responses. The results further show that microdialysis using the novel dual-needle probe could be very useful to differentiate neurochemical changes occurring in neighboring areas in the brain.