Biomedical subjects

Yang Gao

Publications and source records attributed to Yang Gao.

At least 55 records · Page 3Linked to original sources

PubMed2004

Enantioselective synthesis of (S)-3-carboxy-4-((carboxy)difluoromethyl)phenylalanine in protected form and its incorporation into a PTP-1B-directed tripeptide.

Recent findings have shown that, when expressed in the tripeptide platform, 'Fmoc-Glu-Xxx-Leu-amide', the phosphotyrosyl mimetic (pTyr), Xxx=(S)-3-carboxy-4-(carboxymethyl)-Phe, provides higher PTP-1B affinity than that obtained with Xxx=(S)-difluorophosphonomethyl-Phe (F(2)Pmp). This was of note, since difluorophosphonomethyl-containing pTyr mimetics have typically exhibited higher PTP-inhibitory potencies than carboxy-based mimetics, indicating the potential value of 3-carboxy-4-(carboxymethyl)-Phe as a starting point for further analogue development. Therefore, relying on precedence that alpha-fluorination often enhances PTP-1B affinity, (S)-3-carboxy-4-((carboxy)difluoromethyl)-Phe was designed as a PTP-1B-directed pTyr mimetic. Reported herein is the synthesis of this new amino acid analogue through application of commercially available Williams chiral auxiliary. The target was prepared in an orthogonally protected form suitable for peptide synthesis according to Fmoc chemistries and utilization for the synthesis of a PTP-1B-directed tripeptide bearing the sequence indicated above. Biological evaluation with in vitro PTP-1B assays indicated nearly total loss of affinity for this peptide. Evidence is provided that the unexpected deleterious effect of fluorination is probably not related to pK(a) effects.

Binding Sites↗

PubMed2004

Laboratory diagnosis of four recent sporadic cases of community-acquired SARS, Guangdong Province, China.

Four cases of severe acute respiratory syndrome (SARS) that occurred from December 16, 2003, to January 8, 2004, in the city of Guangzhou, Guangdong Province, China, were investigated. Clinical specimens collected from these patients were tested by provincial and national laboratories in China as well as members of the World Health Organization SARS Reference and Verification Laboratory Network in a collaborative effort to identify and confirm SARS-associated coronavirus (SARS-CoV) infection. Although SARS-CoV was not isolated from any patient, specimens from three patients were positive for viral RNA by reverse transcription-polymerase chain reaction assay, and all patients had detectable rises in SARS-CoV-specific antibodies. This study shows the effectiveness of a collaborative, multilaboratory response to diagnose SARS.

Adult↗

PubMed2004

[An epidemiologic investigation on infection with severe acute respiratory syndrome coronavirus in wild animals traders in Guangzhou].

OBJECTIVE: To investigate status of infection with severe acute respiratory syndrome coronovirus (SARS-CoV) in traders of wild animals wholesale markets in Guangzhou. METHODS: Serum antibody against SARS-CoV IgG was determined cross-sectionally and symptoms of respiratory infection were investigated retrospectively for part of traders of three wholesale markets for wild animals in Guangzhou. RESULTS: Overall rate of infection with SARS-CoV in 635 traders was 16.69%, varying in three different markets. Infection rate in market A mainly engaging in wild animals ranked the highest of 25.61%, significantly higher than that in markets B and C engaging in domestic fowls and snakes. Infection rate in traders only engaging in civet cats was 58.54%, significantly higher than that in traders engaging in snakes only (9.46%). In market A, infection rate varied in different persons, 59.34%, 20.59%, 16.00%, 15.22%, 10.40% and 9.68% in traders engaging in wild animals, managers, children of the traders, traders engaging in domestic fowls, traders engaging in snakes, and traders engaging in frozen food, respectively, in a decreasing pattern as their contact opportunities. During the period of SARS epidemic, detection rate of SARS-CoV antibody in people with symptoms of acute respiratory infection was higher (30.70%) than that in those without such symptoms (20.08%). Prevalence of symptoms of acute upper respiratory infection in people with positive antibody against SARS-CoV was higher (49.28%) than that in those with negative antibody (30.35%). CONCLUSIONS: Infection with SARS-CoV in traders of animal markets possibly related to their direct exposure to wild animals, particularly to civet cats. During the period of SARS epidemic, some of the traders did infect with SARS-CoV, but they were neglected due to clinically inapparent manifestations.

Animals↗

PubMed2004

[Analysis on the risk factors of severe acute respiratory syndromes coronavirus infection in workers from animal markets].

OBJECTIVE: To investigate the possible risk factors of severe acute respiratory syndromes coronavirus (SARS-CoV) infection in workers from animal markets. METHODS: Self-designed questionnaires were used and serum samples were tested. Logistic regression analysis was used to analyze the data. RESULTS: Results from simple factor logistic regression analysis showed that jobs which dealing with domestic livestock, wild livestock, wild animals, aquatics were related to risk factors of SARS-CoV infection. Results from multifactor logistic regression analysis showed that jobs that dealing with wild livestock and poultry were important risk factors with OR 12.28 and 0.41. CONCLUSION: Job that dealing with palm civets was the main risk factor of SARS-CoV infection in animal market workers.

Animal Husbandry↗

PubMed2004

[An improved animal model of autoimmune inner ear disease].

OBJECTIVE: To establish an experimental autoimmune inner ear disease model, which could exhibit high reproducibility and be adopted for detailed immunological analysis. METHODS: Extraction of guinea pig inner ear antigens (IEAg). The inbred mice were given a single subcutaneous injection of diluted solution of pertussis and an emulsion containing equal parts of CFA and IEAg. The ABR threshold shifts were evaluated. The antibody level to IEAg in serum was detected by ELISA. Inner ear specimen were examined by light microscopy with hematoxylin and eosin staining. The infiltrated cells within cochlea were clarified with immunohistochemical techniques. RESULTS: The ABR thresholds of IEAg-sensitized animals were elevated significantly. Histological changes in cochlea were significant. Inflammatory cell infiltration was clearly observed in the cochlea of the animals following sensitization with IEAg. Degeneration of the spiral ganglion cells, which characterizes a decrease in cell numbers, and formation of endolymphatic hydrops were often seen too. Serum anti-IEAg levels after inoculation were significantly increased in the IEAg sensitised groups. Most of the infiltrated lymphocytes in scala tympani were CD4+ T cells. CONCLUSIONS: The experimental autoimmune inner ear disease can be induced by a single inoculation of IEAg-CFA emulsion and pertussis in inbred C57BL/6 mice.

Animals↗

PubMed2004

Inhibition of angiogenesis by growth factor receptor bound protein 2-Src homology 2 domain bound antagonists.

Growth factor receptor bound protein 2 (Grb2) is an intracellular adaptor protein that participates in the signal transduction cascades of several angiogenic factors, including hepatocyte growth factor, basic fibroblast growth factor, and vascular endothelial growth factor. We described previously the potent blockade of hepatocyte growth factor-stimulated cell motility, matrix invasion, and epithelial tubulogenesis by synthetic Grb2-Src homology 2 (SH2) domain binding antagonists. Here, we show that these binding antagonists block basic morphogenetic events required for angiogenesis, including hepatocyte growth factor-, vascular endothelial growth factor-, and basic fibroblast growth factor-stimulated endothelial cell proliferation and migration, as well as phorbol 12-myristate 13-acetate-stimulated endothelial cell migration and matrix invasion. The Grb2-SH2 domain binding antagonists also impair angiogenesis in vitro, as shown by the inhibition of cord formation by macrovascular endothelial cells on Matrigel. We further show that a representative compound inhibits angiogenesis in vivo as measured using a chick chorioallantoic membrane assay. These results suggest that Grb2 is an important mediator of key proangiogenic events, with potential application to pathologic conditions where neovascularization contributes to disease progression. In particular, the well-characterized role of Grb2 in signaling cell cycle progression together with our present findings suggests that Grb2-SH2 domain binding antagonists have the potential to act as anticancer drugs that target both tumor and vascular cell compartments.

Adaptor Proteins, Signal Transducing↗

PubMed2004

[The influence of CGE on expression of IL-1beta and c-fos protein in the hippocampus region in rats following cerebral ischemia-reperfusion].

OBJECTIVE: To observe inhibiting effect of CGE (compound ginseng extract) on increased expression of IL-1beta and c-fos protein following cerebral ischemia-reperfusion. METHOD: The vascular dementia model was made by middle cerebral artery occlusion for 2 hours. Expression of IL-1beta and c-fos were determined by immunohistochemistry in the hippocampus regions in brain tissue at the 0.5 h-7 d after reperfusion. CGE was diluted by CMC and poured into the stomach by 0.7 mL x (100 g)(-1) with a high dosage (19.34 x 10(3) g x L(-1) row herbs), a middle dosage (9.67 x 10(3) g x L(-1)), a low dosage (4.83 x 10(3) g x L(-1)). There were an IL-1ra (rhIL-1ra 20 microg injected into the left cerebral ventricle), a sham operation (NaCl 20 microL injected into the left cerebral ventricle) and a model as control. RESULT: Compared with control group, three dose groups (low, middle and high) in CGE showed significant inhibiting effects on the expression of c-fos protein at 2, 3, 4, 12 hours and 3 day following cerebral ischaemic-reperfusion. The level of the inhibiting effects in small and middle groups were lower at all time points than that in IL-1ra group (P < 0.05 to P < 0.01). CGE inhibited the expression of hippocampus IL-1beta protein, taking effect from the 2 h after reperfusion. Both HD group (531 +/- 151.1) and MD group (589.3 +/- 78.6) showed more obvious effect which lasted until the 72 h compared with the model group (687.6 +/- 116.7) (P < 0.01 and 0.05). Large dose group (81.3 +/- 16.1) showed the same level of the inhibiting effect on expression of c-fos protein as IL-1ra group (67.2 +/- 25.7) from 4 hour on following cerebral ischaemic reperfusion (P > 0.05). CONCLUSION: CGE with function of Yiqi Bushen, Huoxue Huatan has effect of inhibiting up-regulated expression of IL-1beta and c-fos protein following cerebral ischemia-reperfusion. However, this effect of CGE starts relatively later than that of IL-1ra. The effect of CGE is associated with its dosage, i.e. a larger dosage has a better effect on expression of c-fos protein in post-stroke dementia.

Animals↗

PubMed2004

[Analysis on the characteristics of blood serum Ab-IgG detective result of severe acute respiratory syndrome patients in Guangzhou, China].

OBJECTIVE: To probe blood serum Ab-IgG characteristics of severe acute respiratory syndrome (SARS) patients in Guangzhou and investigate the related factors. METHODS: The serum of such population diagnosed as SARS convalescent patients, non-SARS patients, family consanguineous contraction persons, wild animal and vegetable salesman and community common people was collected. The lab detective method of ELISA was adopted for these serum samples. And the epidemic investigations for the SARS patients were also carried out. RESULTS: Of these populations, the detective rate of Ab-IgG for the clinic diagnosed SARS patients, which was 53.7%; That for the wild animal salesman and community common people were 16.7% and 0.9%, respectively. Among the clinic diagnosed SARS patients, the positive antibody detective rate was 90.4% for those which had specific contact history or infectivity, which was higher than that for other population. Among the specific contact history or infectivity cases, the antibody positive rate for the young and the old was lower than that for the adult. Meanwhile the difference did not exist among other cases. The antibody positive rate was identical between the male and the female. And the antibody detective rate was decreased by the month. CONCLUSION: As a whole SARS-CoV Ab-IgG detective rate for the clinic diagnosed SARS patients was 53.7% only. The reasons for that mainly lie in the wrong clinic diagnosis besides these factors such as age, hormone use and reagent and so on. The combination of lab detection results and epidemic investigation was propitious to the diagnosis veracity. It was impossible for the sub-clinic infection of SARS-CoV virus. The importance in the virus transmitting course need to be further studied.

Adult↗

PubMed2003

Acylsulfonamide-containing PTP1B inhibitors designed to mimic an enzyme-bound water of hydration.

Previously, it had been reported that 6-(phosphonodifluoromethyl)-2-naphthoic acid binds to the protein-tyrosine phosphatase PTP1B with its 2-carboxyl group interacting only indirectly through a bridging water molecule. Reported herein is a family of new analogues that utilize acylsulfonamido functionality both to mimic this water of hydration and to provide an additional new site for elaboration not found in the parent carboxyl-containing analogue. Target acylsulfonamides were prepared in two steps from commercially available primary sulfonamides, which were selected based on in silico screening for their potential ability to interact with one of three binding surfaces proximal to the PTP1B catalytic site. In general, modest potency enhancements were observed. Arylacylsulfonamides represent a structure-based extension of inhibitor design that may have broader utility in the development of PTP1B inhibitors.

Amino Acids, Acidic↗

PubMed2003

1H-Pyrazolo-[3,4-c]cyclophepta[1,2-c]thiophenes: a unique structural class of dopamine D4 selective ligands.

A series of novel 1H-pyrazolo-[3,4-c]cyclophepta[1,2-c]thiophenes was prepared and screened at selected dopamine receptor subtypes. Compound 4 (NGB 4420) displayed high affinity and selectivity (>100-fold) for the D(4) over D(2) and other CNS receptors. This compound was identified as a D(4) antagonist via its attenuation of dopamine agonist-induced GTPgamma(35)S binding at D(4) receptor.

Dopamine Antagonists↗

PubMed2003

[Influence of beta-endorphin on function of immune system of patients with cerebral hemorrhage].

OBJECTIVE: To study the influence of beta-endorphin (beta end) on the function of immune system of patients with cerebral hemorrhage at different stages. METHODS: Radioimmunal analysis was applied to detect the serum beta-endorphin concentration in the peripheral blood of 28 patients with cerebral hemorrhage, aged 65.5 +/- 13, 28 age-matched patients with cerebral thrombosis, and 28 sex and age-matched normal controls. Mononuclear cells from peripheral blood of these 3 kinds of subjects were cultured and then beta end 10(-8) g/L, beta end 10(-11) g/L, beta end 10(-14) g/L, or beta end 10(-11) g/L + naloxone 10(-5) g/L were added into the media respectively and the MNCs were cultured for more 24 hours (beta end 10(-8) g/L group, beta end 10(-11) g/L group, beta end 10(-14) g/L group, and beta end 10(-11) g/L + Nal group). Another MNCs were cultured without addition of beta end (beta end 0 g/L group). Then the MNCs were collected. RT-PCR was used to detect the expressions of interleukin (IL)-1beta, IL-2, IL-8 and iNOS mRNA in the MNCs. RESULTS: The serum beta-end level of the patients with cerebral hemorrhage at the acute stage was 129 +/- 82 ng/L, significantly lower than that of the normal controls (321 +/- 62 ng/L, P<0.01) and that of the patients with cerebral thrombosis (264 +/- 163 ng/L, P<0.05), but not significantly different from that of the patients with cerebral hemorrhage in the convalescent stage (160 +/- 72 ng/L, P>0.05). The expression of IL-1beta and the expression of IL-2 of the patients with cerebral hemorrhage at the acute stage were significantly lower than those of the patients with cerebral thrombosis and the controls (all P<0.01). The expression of IL-1beta of the patients with cerebral hemorrhage at the convalescent stage were higher than that in the acute stage, however, the difference was not significant (P>0.05). The expression of IL-2 of the patients with cerebral hemorrhage at the convalescent stage was higher than that at the acute stage (P<0.01). The expression of IL-8 and the expression of iNOS of the patients with cerebral hemorrhage at the acute stage were significantly higher than those of the patients of cerebral thrombosis and the controls (both P<0.01). The expression of IL-8 and the expression of iNOS of the patients with cerebral hemorrhage at the convalescent stage were significantly lower than those in the acute stage (both P<0.01). The expressions of IL-1beta, IL-2, IL-8, and iNOS mRNA in the peripheral blood MNCs in vitro in the beta end 10(-8) g/L group and beta end 10(-11) g/L group were significantly higher than those of the beta end 0 g/L group, beta end 10(-11) g/L group, and beta-end 10(-11) g/L + Nal 10(-5)g/L group. The expressions of IL-1beta, IL-2, IL-8, and iNOS mRNA in the peripheral blood MNCs in the beta-end 10(-11) g/L +Nal 10(-5) g/L group were higher than those of the beta end 0 g/L group, however, not significantly. CONCLUSIONS: The endogenous beta-endorphin level of cerebral hemorrhage patients is low. The immune system function is up-regulated at the acute stage and then down-regulated. Thereafter the immune system function is invariably low. Exogenous beta-endorphin enhances the IL-1 beta, IL-2, IL-8 and iNOS mRNA expression of peripheral blood MNCS. beta-endorphin receptor antagonist naloxone blocks the positive immunoregulation by beta-endorphin.

Aged↗

PubMed2003

Tripeptide inhibitors of Yersinia protein-tyrosine phosphatase.

The protein-tyrosine phosphatase (PTP) 'YopH' is a virulence factor of Yersinia pestis, the causative agent of plague. Potential use of Yersinia as a bioterrorism agent renders YopH inhibitors of therapeutic importance. Previously, we had examined the inhibitory potencies of a variety of phosphotyrosyl (pTyr) mimetics against the human PTP1B enzyme by displaying them in the EGFR-derived hexapeptide sequence, 'Ac-Asp-Ala-Asp-Glu-Xxx-Leu-amide', where Xxx=pTyr mimetic. The poor inhibitory potencies of certain of these pTyr mimetics were attributed to restricted orientation within the PTP1B catalytic pocket incurred by extensive peripheral interaction of the hexapeptide platform. Utilizing the smaller tripeptide platform, 'Fmoc-Glu-Xxx-Leu-amide' we demonstrate herein that several of the low affinity hexapeptide-expressed pTyr mimetics exhibit high PTP1B affinity within the context of the tripeptide platform. Of particular note, the mono-anionic 4-(carboxydifluoromethyl)Phe residue exhibits affinity equivalent to the di-anionic F(2)Pmp residue, which had previously been among the most potent PTP-binding motifs. Against YopH, it was found that all tripeptides having Glu residues with an unprotected side chain carboxyl were inactive. Alternatively, in their Glu-OBn ester forms, several of the tripeptides exhibited good YopH affinity with the mono-anionic peptide, Fmoc-Glu(OBn)-Xxx-Leu-amide, where Xxx=4-(carboxymethyloxy)Phe providing an IC(50) value of 2.8 microM. One concern with such inhibitors is that they may potentially function by non-specific mechanisms. Studies with representative inhibitors, while failing to provide evidence of a non-specific promiscuous mode of inhibition, did indicate that non-classical inhibition may be involved.

Algorithms↗

PubMed2003

[The cross-sectional study of awareness and practice of SARS epidemic in community residents in Beijing].

OBJECTIVE: To investigate the awareness and practice of SARS in community residents in Beijing. METHODS: A cross-sectional study was conducted in different-level communities of SARS epidemic strength in Beijing. Typical samples were selected and 480 residents were surveyed. RESULTS: 92% of the residents focused on SARS epidemic in Beijing and 72.5% didn't worry that they would be attacked by SARS. The sources of stress included fatal outcomes, lack of efficient treatment, rapid spreading and high risk of medical workers. 86.8% felt the media often over-reported. 50% were afraid of going to the clinics. 86% thought that measures taken by the government were active and efficient. Meanwhile, 60% could follow the government recommendation to prevent SARS. CONCLUSION: Most of the residents believe SARS have influenced on regular life, stability of society, development of economy and international communication.

Adolescent↗

PubMed2003

Macrocyclization in the design of Grb2 SH2 domain-binding ligands exhibiting high potency in whole-cell systems.

While most SH2 domains bind phosphotyrosyl (pTyr) containing peptides in extended fashion, the growth factor receptor-bound protein 2 (Grb2) SH2 domain preferentially binds ligands in bend conformations. Accordingly, incorporation of bend-inducing functionality into synthetic ligands could potentially enhance their affinity for this SH2 domain. A macrocyclic tripeptide mimetic that contains a simplified pTyr surrogate lacking an alpha-nitrogen has recently been shown to exhibit high Grb2 SH2 domain-binding affinity in extracellular ELISA-based assays. However, the same compound is largely ineffective in whole-cell assays. It is known that acidic functionality originating from the alpha-nitrogen of pTyr residues or from the alpha-position of P0 pTyr mimetics not only increases binding affinity of peptides to Grb2 SH2 domains in extracellular assays but also enhances potency in cell-based systems. Such functionality is absent from the previously reported macrocycle. Therefore, the current study was undertaken to examine the effects of introducing carboxylic functionality at the pTyr mimetic alpha-position of macrocyclic ligands. It was found that such a modification not only enhanced Grb2 SH2 domain binding in extracellular assays but also conferred high efficacy in whole-cell systems. The most potent compound of the current study exhibited an IC(50) value of 0.002 microM in an extracellular ELISA-based assay, and in MDA-MB-453 cells, it both inhibited the association of Grb2 with p185(erbB-2) and exhibited antimitogenic effects with submicromolar IC50 values.

Adaptor Proteins, Signal Transducing↗

PubMed2003

[Changes in GAT-3 and GABA-T mRNA expression of C6 glioma cells in response to a 2-week treatment with sodium valproate and withdrawal].

OBJECTIVE: To examine the effects of sodium valproate(VPA) treatment and withdrawal on the expression of GABA transporter-3 (GAT-3) and GABA transaminase (GABA-T) mRNA in C6 glioma cells, and to explore the role of GAT-3 and GABA-T in the rebound mechanism of VPA withdrawal. METHODS: C6 glioma cells were maintained for 2 weeks in DMEM medium containing VPA (50 mg/L) to establish the cell model of chronic exposure to VPA. Semi-quantitative RT-PCR was used to examine the changes of GAT-3 and GABA-T mRNA expression in response to VPA treatment and withdrawal. RESULTS: Chronic exposure to VPA down-regulated GAT-3 mRNA expression to 39.1% +/-0.5% from 46% +/-1.3% in the control group; After VPA withdrawal, GAT-3 mRNA expression level kept decreasing, reaching the minimum (11.7% +/-1.6%) 24 h after the withdrawal and with an increase to the level of 33.5%+/-1.1% after another 24 hr. GABA-T mRNA expression was up-regulated to 71.31% +/-8.39% from 34.77% +/-2.36% of the control level after VPA treatment, the withdrawal of which resulted in decreased GABA-T mRNA expression. Till 12 h after the withdrawal, the GABA-T mRNA expression level decreased to the minimum, 25.36% +/-7.68%. CONCLUSIONS: Chronic treatment with VPA can down-regulate GAT-3 mRNA expression and up-regulate GABA-T mRNA expression in C6 glioma cells, and this undulation may involve VPA withdrawal rebound.

4-Aminobutyrate Transaminase↗

PubMed2003

[Rapid construction and identification of full-length cDNA library of human glioma tissues].

OBJECTIVE: To explore a method for rapid construction of a full-length cDNA library of human glioma tissues using switching mechanism at 5' end of RNA transcript (SMART). METHODS: The total RNA was extracted from several samples of human glioma tissues and the mRNA was subsequently separated. Multiple mRNA samples were mixed to be used as the template for the first-strand cDNA synthesis. The CDS /3' PCR primer (containing Sfi IB site) was used in the first-strand reaction, and the SMART IV Oligo(dT) (containing Sfi A site) served as the short, extended template at the 5' end of the mRNA. With the above two primers, the primer-extension step generated full-length double-strand cDNA, which was digested by Sfi I restriction enzyme and ligated to the Sfi I A & B -digested lambdaTriplEx2 vector. The ligated vector was then packaged by lambda packaging extract for the final construction of the cDNA library. RESULTS: The unamplified human glioma cDNA library consisted of 2.4x10(6) independent clones with a recombination rate of 100%. The titer of the amplified cDNA library was 4.5x10(9) pfu/ml, and the average exogenous inserts of the recombinants was 1.2 kb in length. CONCLUSION: A high-quality full-length cDNA library of human gliomas was constructed successfully, which may facilitate further study of the screening and cloning of new tumor suppressor genes and tissue-specific genes of human glioma.

DNA, Complementary↗

PubMed2003

[Bactericidal peptide targeted against penicillin/methicillin-resistant Staphylococcus aureus--an engineered multidomain protein machine].

OBJECTIVE: To construct a targeting bactericidal peptide machine by fusing two minidomains with different bioactivities and different protein origins. METHODS: Such fusion peptide was constructed by linking the gene of Staphylococcal AgrD pheromone with the gene of C-terminal (I626) of colicin Ia pore-forming region (K544-I626) with site-directed mutation. Mutated plasmid was transformed into E. coli TG1 cells to produce fusion peptide, peptides were purified by CM sepharose ion-exchange column. In vitro bactericidal assays were made to identify the bioactivity of fusion peptide. RESULTS: Fusion peptide presented a specific bactericidal activity which was over one hundred times as effective as that of penicillin/oxacillin against tested Staphylococcus aureus strains. CONCLUSION: Fusion peptide behaved with a targeting bactericidal activity against Staphylococcus aureus which was lacking at two precursors, Staphylococcal pheromone and colicin Ia pore-forming region. These results suggest that an engineered multidomain protein machine with specific bactericidal activity has been constructed in the present study.

Anti-Bacterial Agents↗

PubMed2003

[Effects of chronic valproic acid sodium treatment and withdrawal on glutamate and glutamine release of C6 glioma cells].

OBJECTIVE: To determine the effects of chronic valproic acid sodium (VPA) treatment and subsequent withdrawal on the release of glutamate (Glu) and glutamine (Gln) by C6 glioma cells, so as to understand the role of Glu and Gln released by astrocytes in the antiepileptic mechanism of VPA and the rebound mechanism of VPA withdrawal. METHODS: C6 glioma cells were maintained for 2 weeks in DMEM medium containing 50 mg/L VPA to establish the cell model of chronic VPA treatment. High-performance liquid chromatography (HPLC) was performed to detect the levels of Glu and Gln released by C6 glioma cells after chronic VPA treatment and subsequent withdrawal. RESULTS: Chronic VPA treatment increased Glu release of C6 glioma cells, and subsequent VPA withdrawal resulted in sustained decrease in the Glu level, reaching the lowest level 12 h after VPA withdrawal, which was obviously lower than the control level. Gradual but significant increase of Glu level was then observed to approach the control level till 48 h after VPA withdrawal. For Gln release, chronic VPA treatment resulted in its decrease while after VPA withdrawal, gradual increase occurred to recover the control level. CONCLUSIONS: Chronic VPA treatment can increase Glu and decrease Gln release by C6 glioma cells. Glu level undergoes a rebound in response to VPA withdrawal, while the relatively even changes of Gln level in the same setting may not involve VPA withdrawal rebound mechanism.

Anticonvulsants↗