italic>α-Conotoxin ArIB[V11L,V16D] is currently the most optimal selective inhibitor of α7 nicotinic acetylcholine receptor (nAChR) known. In order to explore chemical modification methods and enrich its application in targeting nAChR, this study utilized the linker to covalently connect camptothecin and 7-amino-4-methylcoumarin to the [2,4] disulfide bond of ArIB[V11L,V16D]. Therefore, two peptide-drug conjugates (PDCs), ArIB[V11L,V16D]-5 and ArIB[V11L,V16D]-6, and one fluorescent-labeled peptide, ArIB[V11L,V16D]-7 were constructed. Cytotoxicity evaluation showed that the IC₅₀ values against non-small cell lung cancer cell line A549 of the two PDCs were respectively 1.3 and 4.1 times of camptothecin, indicating slight reduction in activity at the cellular level which was related to the linker structure. Fluorescence spectrum scanning revealed that the excitation and emission wavelength of the fluorescent-labeled peptide were 340 nm and 403 nm respectively, and the fluorescence features of 7-amino-4-methylcoumarin as a marker were retained without fluorescence quenching. This modification strategy laid a solid foundation for the further application of α-conotoxin ArIB[V11L,V16D] in PDCs and fluorescent probes.

New Chemical Entities (NCEs) development is a systematic long-term project that involves multiple disciplines. The translation research will help to build an advanced R&D system from the basic laboratory research, preclinical studies and clinical evaluation to clinical application of drug, for the purpose of shortening the R&D cycle and accelerate the launch of new drugs. In new drug R&D and its clinical application, drug disposition (absorption, distribution, metabolism, excretion, ADME) properties are important criteria for assessing drug-likeness of candidates. ADME evaluation of NCEs plays an important role in the translation research throughout innovative drug R&D process. Therefore, ADME evaluation at the early stage of drug design and development will be helpful to improve the success rate and reduce costs, and further access to safe, effective drugs.

Objective To determine the role of erythrocytes immunoadhering in the pathogenesis of the patients with mesangiopro-liferative glomerulonephntis (MsPGN). Methods The immunoadhering functions of erythroeytes and leukoeytcs were measured in 31 patients with no- IgAN,24 patients with IgAN and 30 normal children by rosette tests:RCR,RICR,TRR,TNR and TLR. Results 1. The immunoadhering functions of erythroeytes (RCR and TRR) of the patients with no- IgAN and IgAN were obviously decreased compared to those of control group,but RICR showed no significant difference;2. The immunoadhering functions of leukocytes (TNR and TLR ) of the patients with no- IgAN and IgAN were obviously decreased compared to those of control group;3 The degree of the decreased immunoadhering functions of erythroeytes was correlated respectively with that of the immunoadhering functions of leukoeytes. Conclusions The decrease of the function of erythroeyte and leukocyte immunoadhering plays an important role in the pathogenesis in patients with MsPGN. These rosette tests may be used in clinic.

Objective To study the expression of VEGF,Cox2 and mPGES in colon cancer.Methods VEGF,Cox2 and mPGES mRNA expression in 32 paired samples(tumor and adjacent normal tissue)were de- termined by using real time RT-PCR.Results VEGF was overexpressed in 19 of 32(59.3 %)tumor tissues compared with that in 6 of 32(18.7 %)adjacent normal tissue;COX2 was overexpressed in 20 of 32(62.5 %) tumor tissues compared with that in 5 of 32(15.6 %)adjacent normal tissue;mPGES was overexpressed in 24 of 32(75 %)tumor tissues compared with that in 9 of 32(28.12 %)adjacent normal tissue.Conclusion Our result suggested that VEGF165,mPGES and COX2 overexpressed in colon cancer.

OBJECTIVETo evaluate the correlation of neutral alpha-glucosidase in seminal plasma with the location of epididymal obstruction in azoospermia men.

METHODSWe detected neutral alpha-glucosidase activity in the seminal plasma of 59 men with obstructive azoospermia followed by determining the location of epididymal obstruction by scrotal exploratory surgery. Then we analyzed the correlation between neutral alpha-glucosidase and the location of epididymal obstructive azoospermia.

RESULTSAmong the total number of patients, there were 25 cases of bilateral cauda epididymal obstruction, 15 bilateral corpus, 12 bilateral caput, 4 unilateral caput-opposite cauda, and 3 unilateral corpus-opposite cauda. The neutral alpha-glucosidase levels in the seminal plasma of bilateral cauda, corpus and capus epididymal obstructions were (4.1 +/- 1.9), (13.8 +/- 4.4) and (46.8 +/- 19.3) mU per ejaculate, respectively, with statistically significant differences among the three groups (P < 0.05).

CONCLUSIONNeutral alpha-glucosidase activity is significantly correlated with the location of epididymal obstruction in azoospermia men, which helps to locate epididymal obstruction, evaluate surgical prognosis and reduce the time of scrotal exploratory surgery.

Adult ; Azoospermia ; enzymology ; pathology ; Epididymis ; pathology ; surgery ; Humans ; Male ; Semen ; enzymology ; alpha-Glucosidases ; metabolism

Objective To explore the nursing intervention Oil the rehabilitation of patients with coronary heart disease,help the patients build healthy daily habits.make their life better.Methods 118 patients who have the heart illness and were admitted to our hospital between July 2004 and December 2006 were selected and tlleir knowledge about the heart attack.their dailv life style and how they take the medicine were evaluated.Depend oil the result of the evaluatioil,the speeches about healthy life.scientific life style and how to take the medicine scientifically were given,and then the second evaluation Was conducted after having the speeches 6 months.1 year and 2years later.Results The patient'S knowledge about the decease was obviously increasing (average P

ry for different pregnant women or puerperal population, to enlarge the coverage rate of hepatitis B knowledge.

The objects of research on the resources chemistry of Chinese medicinal materials (RCCMM) are promotion of efficient production, rational utilization and improving quality of CMM and natural products. The development of TCM cause depends on the efficient utilization and sustainable development of CMM, hinges on the technologies and methods for using and discovering medicinal biological resources, stand or fall on the extension of industy chains, detailed utilizaion of resource chemical components by multi-way, multi-level. All of these may help to the recycling utilization and sound development of RCMM. In this article, five respects were discussed to the RCCMM researches and resources recycling utilization ways and goals and tasks. First, based on the principle of resource scarcity, discovering or replacing CMM resources, protecting the rare or endangered species or resources. Second, based on the multifunctionality of CMM, realizing the value-added and value compensation, and promoting the utilization efficiency through systermatic and detailed exploitation and utilization. Third, based on the resource conservation and environment-friendly, reducing raw material consumption, lowering cost, promoting recycling utilization and elevating utilization efficiency. Fourth, based on the stratege of turning harm into good, using the invasive alien biological resources by multi-ways and enriching the medicial resources. Fifth, based on the method of structure modification of chemical components, exploring and enhancing the utility value of resouces chemical substances. These data should provide references and attention for improving the utilization efficiency, promoting the development of recycling economy, and changing the mode of economic growth of agriculture and industry of CMM fundamentally.
Agriculture ; economics ; trends ; China ; Conservation of Natural Resources ; economics ; trends ; Drugs, Chinese Herbal ; chemistry ; economics ; Materia Medica ; chemistry ; economics ; Medicine, Chinese Traditional ; economics ; trends ; Plants, Medicinal ; chemistry ; growth & development

Objective To compare the genetic barriers to development of primary mutations related to drug resistance to protease inhibitors (PI), nucleioside reverse transcriptase inhibitors ( NRTI ), and non-nucleioside reverse transcriptase inhibitors ( NNRTI ) among human immunodeficiency virus (HIV)-1 CRF01_AE, CRF07_BC, and CRF08_BC strains, and to understand the difference of varying patterns of drug resistance related mutations within these subtypes. Methods One hundred and ninety naive HIV-positive subjects from Nanning City and Liuzhou City, Guangxi Zhuang Autonomous Region, were recruited. Peripheral blood samples were collected from all participants. HIV-1 RNAs were extracted from plasma, and the pol regions were amplified and sequenced. Sequences were subjected to phylogenetic analysis to determine the subtypes of HIV-1 isolates. Nucleotide transitions and transversions were counted for each primary mutation in these sequences. According to the phenomena that transitions occur on average 2. 5 times frequently than transversions, each transition was scored as 1, and each transversion scored as 2. 5. The sum of the scores for a particular substitution was calculated, and this value was taken as the genetic barrier to development of this mutation. Then, the differences of genetic barriers among the subtypes were assessed by Kruskal-Wallis test and Nemenyi test. Results A total of 123 sequences of CRF01_AE,CRF07_BC and CRF08_BC strains were selected. CRF08_BC had a lower genetic barrier for T/S69Dsubstitution than CRF01_AE and CRF07_BC (χ2 =107. 501, P＜0.01), while CRF01_AE and CRF07_BC had lower genetic barriers for V118I and L210W substitution than CRF08_BC. In addition,CRF07_BC had a decreased genetic barrier for V106M compared with CRF01_AE and CRF08_BC.Conclusions In the presence of the same selective pressure, subtypes CRF01_AE and CRF07_BC may be more likely to develop V118I and L210W substitution than CRF08_BC. However, CRF08_BC may be more likely to develop T/S69D substitution than CRF01_AE and CRF07_BC. Meanwhile, CRF07_BC may be easier to develop V106M substitution than CRF01_AE and CRF08_BC.

AIMTo determine scutellarin in dog plasma and study the pharmacokinetics of scutellarin in the dog.

METHODSScutellarin in plasma of six dogs at different sampling time was determined after single dose of 120 mg i.v. by RP-HPLC. The mean plasma concentration-time curve was protracted and pharmacokinetic parameters were calculated.

RESULTSThe concentration-time curve of scutellarin can be fitted to a three-compartment model with the main pharmacokinetic parameters as follows: T1/2 gamma, T1/2 alpha and T1/2 beta were (1.1 +/- 0.8) min, (7.0 +/- 2.8) min and (52 +/- 29) min, respectively, Vc was (880 +/- 508) mL, CL was (190 +/- 54) mL.min-1, AUC0-90 and AUC0-infinity were (574 +/- 134) mg.min.L-1 and (559 +/- 132) mg.min.L-1 respectively.

CONCLUSIONThe concentration of scutellarin in plasma declined rapidly after single dose of 120 mg i.v. in dogs, and this suggested that the T1/2 of scutellarin should be taken into account in preparation exploitation and drug administration.

Animals ; Apigenin ; Area Under Curve ; Asteraceae ; chemistry ; Chromatography, High Pressure Liquid ; Dogs ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacokinetics ; Female ; Flavonoids ; blood ; isolation & purification ; pharmacokinetics ; Glucuronates ; blood ; isolation & purification ; pharmacokinetics ; Injections, Intravenous ; Male ; Plants, Medicinal ; chemistry ; Vasodilator Agents ; administration & dosage ; pharmacokinetics