AIMTo search for potential anti-atherosclerosis drugs with vascular relaxation activity, a series of agonists of endothelial targets were designed and synthesized.

METHODSCoupling N-methyl-1,2, 3,6-tetrahydrapyridine ring system with 3,4-dibenzenesulfonyl-1,2,5-oxadiazole-2-oxide through esterification or amidation, a series of arecoline derivatives containing NO donors were designed and synthesised.

RESULTSA novel series of compounds structurally related to arecoline have been prepared, the proposed structures of eighteen new compounds were established by IR, 1H NMR, MS spectroscopy and elemental analysis. The effects of the target compounds on the vasodilation activity were tested in the isolated preparation of mice thoratic aorta.

CONCLUSIONThis preliminary pharmacological tests showed that the candidates have good vasodilation activities and were worthy to be intensively studied.

Animals ; Aorta, Thoracic ; drug effects ; Arecoline ; analogs & derivatives ; chemical synthesis ; pharmacology ; In Vitro Techniques ; Nitric Oxide Donors ; chemistry ; pharmacology ; Rats ; Vasodilation ; drug effects ; Vasodilator Agents ; chemical synthesis ; pharmacology

OBJECTIVE: To evaluate the influence of fewer courses and prolonged intervals of chemotherapy on survival rate of advanced non small cell lung cancer (NSCLC) patients treated by sequential chemo-radiation therapy combined with traditional Chinese medicine (TCM). METHODS: From Jan. 2000 to Dec. 2001, 54 untreated advanced NSCLC patients (2 stage IIIa, 18 stage IIIb, 34 stage IV) were treated by sequential chemo-radiation therapy combined with TCM. The courses of chemotherapy were reduced and the intervals of chemotherapy were longer than that of the standard regimen. The efficacy and survival rate were documented and the prognostic factors were analyzed. RESULTS: Complete remission (CR) was observed in 1 case and partial remission (PR) in 20 cases. The overall objective response rate was 40.4%. Median survival was 15.3 months, 1-, 2- and 3-year survival rate were 53.7%, 28.9% and 9.6% respectively. The median survival of stage III and IV were 21.8 months and 12.5 months respectively. The 1-, 2-, and 3-year survival rates of stage III were 65.0%, 49.5%, 24.7% and that of stage IV were 47.0%, 23.3%, 0%, respectively. The quality of life was improved in most of the patients. Cox's proportional hazards regression showed that improved quality of life and treatment of TCM were the significant prognostic factors of overall survival. CONCLUSION: Chemotherapy and radiotherapy combined with TCM is beneficial to extending the interval of chemotherapy, improving the quality of life, and increasing the survival rate of advanced NSCLC patients.

The aim of this paper is to apply Raman spectroscopy technique to develop rapid quantitative models for five kinds of Traditional Chinese Medicine containing CaCO3. In the experiment, Raman spectras of 67 batch of sample including Otolithum Sciaenae, Galaxeae Os, Ophicalcitum, Calcite, Stalactite and their mixture which had different content of CaCO3 were collected, and the quantitative models were established by using an improved siPLS to optimize the characteristic spectral bands and using the CaCO3 contents which were measured by EDTA titration method as references. Compared with the results by EDTA titration, the established quantitative model for CaCO, content showed a prediction result that the average relative deviation of the prediction results is 2. 71% and the average recovery rate was 100.46%, when the content is between 0.465 4-0.999 7, and when the characteristic spectral bands of 1 290-1 280, 730-714, 700-690, 660-650, 465-460, 455-445, 405-385 cm(-1) had been optimized. The result also showed that the model using Raman spectroscopy and based on an improved siPLS can get a rapid determination for contents of 5 kinds of Traditional Chinese Medicine containing CaCO3.
Calcium Carbonate ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Least-Squares Analysis ; Models, Statistical ; Plants, Medicinal ; chemistry ; Spectrum Analysis, Raman ; methods

The aim of this paper is to clarify the mineral origin of traditional Chinese medicine (TCM) Yangqishi and Yinqishi and guide identification of the both, by X-ray diffraction (XRD) Fourier patterns. Morphological identification and conventional physical and chemical analysis wee used to identify 22 batches of Yangqishi and Yinqishi. It used XRD Fourier patterns which has been collected from sample powders to analyze phase composition. It has been found experimentally that the mineral origin of Yinqishi is Talc schist and the mineral origin of Yangqishi is tremolite and actinolite. The results also showed that the method using XRD can get not only an accurate but also rapid identification of Yangqishi and Yinqishi. There are many differences in medicinal properties, efficacy, indications and composition of Yangqishi and Yinqishi, so be careful not to mix them up.
Asbestos, Amphibole ; chemistry ; Drugs, Chinese Herbal ; chemistry ; X-Ray Diffraction

OBJECTIVETo observe the effect of Guizhi plus Gegen Decoction (GGD) on ultrastructural changes of intervertebral disc annulus fibrosus cells.

METHODSRats' intervertebral disc annulus fibrosus cells were isolated and cultured using adherence wall screening method. After annulus fibrosus cells were intervened by GGD, the microstructure and ultrastructural features of untreated annulus fibrosus cells and annulus fibrosus cells treated by GGD containing serum at different concentrations were observed under optical microscope and electron microscope.

RESULTSUnder optical microscope, most annulus fibrosus cells showed irregular polygons and few in star shape with rich superficial ecphyma. The nuclei were oval, large and complete. Under electron microscope, most cells in the blank group were oval after intervened by GGD containing serum at different concentrations. The nucleus was large, deviated, and irregular, the heterochromatin scattered diffusely, partial mitochondria vacuolized, and rough endoplasmic reticulum dilated. In the low dose GGD group, increased mitochondria and condensed density could be seen. The rough endoplasmic reticulum were expanded, lipid drops or glycogen could be occasionally seen. In the middle dose GGD group, increased endoplasmic reticulum expansion and condensed density could be seen. More medium density protein sediment could be seen. Increased mitochondria with condensed density could be seen, showing irregular cystic form with various sizes nucleus. In the high dose GGD group, increased rough endoplasmic reticulum with obvious expansion could be seen. More high density protein sediment could be seen. The nuclei were deviated. More mitochondria could be seen with secretory granules in them.

CONCLUSIONSAfter intervened by GGD containing serum at different concentrations, the ultrastructure of annulus fibrosus cells were manifested as follows: (1) The endoplasmic reticulum increased more in the middle and high dose GGD groups than in the blank group and the low dose GGD group. Greater density protein sediment occurred, especially in the high dose GGD group. (2) GGD played an important role in preventing ultrastructural changes induced by the degeneration of annulus fibrosus cells.

Animals ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Intervertebral Disc ; cytology ; drug effects ; ultrastructure ; Rats ; Serum

Objective To observe the expression of pannexin1(PX1) in the dorsal horn of spinal cord in model ratwith neu-ropathipain afteselective ligation of sciatinerve branche.Method50 male SD ratwere randomly divided into 3 group,inclu-ding the control group(Wgroup ,n= 10) ,sham operation group(sham group ,n= 10) and sciatinerve branch selective injury group(SNI group ,n=30) .30 ratwere killed on postoperative 3 ,5 ,7 ,14 d and the lumbasegmenof the spinal cord wataken fodetecting the expression of PX1 by using Western blo.Othe20 ratwere killed on 7 d afteSNI and the expression of glial fibril-lary acidiprotein(GFAP) in the spinal cord wadetected with immunohistology .Among them ,10 ratin the SNI group were trea-ted with intrathecal intubation before operation and administrated with saline 20 μL ocarbenoxolone(CBX) 20 μL by intrathecal injection on postoperative 7 d fodetermining the expression of GFAP by the immunohistology .ResultThe expression of PX1 in the SNI group waincreased and enhanced with time ,which wasignificantly highethan thain the Wgroup and the sham group (P＜0 .05);the GFAP expression on 7 d in the SNI group waobviously increased compared with the Wgroup and the sham group(P＜0 .05);afteintrathecal injection of CBX ,the expression of GFAP wasignificantly decreased compared with thain the normal saline group(P＜0 .05) .No statistically significandifferencein the expression of PX1 and GFAP were found in the Wgroup and the sham group .Conclusion PX1 may be involved in the activation of astrocyte,prompting thaPX1 playan importanrole in the neuropathipain caused by the peripheral nervel injury .

BackgroundThe effects of extremely low frequency electromagnetic fields (ELF-EMFs) on public health have attracted wide attentions.The association of the thermal effect of ELF-EMFs with cancer and ocular tissue damage has been of concern.However,the pathological changes of scleral tissue after exposure to ELF-EMFs as well as the relationship between these changes and myopia are still poorly understood.ObjectiveThe present study was to investigate the molecular pathological changes of human fetal scleral fibroblasts (HFSFs) after exposure to ELF-EMFs in vitro and to explore the possible mechanism in the occurrence and development of myopia.MethodsHFSFs were cultured and passaged and then exposed to 50 Hz electromagnetic fields,and HFSFs that did not receive the irradiation of ELF-EMFs were used as the control group.The expression of collagen type Ⅰ (COL1A1 ) mRNA and matrix metalloproteinase-2 (MMP-2) mRNA in cultured HFSFs were detected by real-time qualitative polymerase chain reaction (real-time PCR) under different magnetic field intensites (0,0.1,0.2,0.5,1.0 mT) and different exposure time (0,6,12,24,36,48 hours).Cell proliferation assay of HFSFs was detected by the cell counting kit 8 ( CCK8 ) assay.The expression levels of COL1 A1 and MMP-2 proteins in HFSFs were further confirmed by immunofluorescence staining.Results The expression of COL1A1 mRNA was significantly down-regulated under the exposure of 0.2 mT ELF-EMFs for 6 hours,in comparison with the control group;moreover,it decreased in parallel with the increased of flux density (0.099±0.008 vs.0.050±0.004) (P =0.009 ).The expression of MMP-2mRNA was up-regulated conspicuously after exposure to 0.1 mT ELF-EMFs for 24 hours,and it increased with exposure time in comparison with the control group ( 0.009 ±0.001 vs.0.018±0.003 ) ( P =0.038 ).Proliferation of HFSFs (A450) was inhibited following the exposure to 0.2 mT ELF-EMFs for 24 hours in comparison with the control group (P =0.009 ).The expression of COL1 A1 in the experimental group was decreased,compared with the control group,but the expression of MMP-2 was increased.ConclusionsELF-EMFs inhibit the proliferation of HFSFs and expression of COL1 A1 in HFSFs,which might be one of the reasons for the development of myopia.

Objective To explore the pathological changes by CT scan on localized thermochemotherapy dur- ing and after the operation of human gliomas.Methods Retrospective analysis was given to the CT scan of 37 pa- tients receiving thermochemotherapy during and after the operation,and the relation of the tumorous cells and mi- crovessels and CT density by EM were analyzed.Changes of tumorous cells and microvessels after localized ther- mochemotherapy on C_6 gliomas in rat were analyzed.Results When the tumor was low dense on CT pattern,less cellular number with increasing the amount of fluid between the cells was demonstrated pathologically.On EM,a lower cellular electron density was observed.The amount of fluid in cytoplasm was increased,the cytoplasm was porous,swelling denaturation was chiefly seen in organelle.If the tumor had mixed density on CT,cellular number was more,the amount of fluid was less.On EM,cellular electron density increased correspondingly,the fluid in cyto- plasm decreased,organdie was aggregated.After thermochemotherapy,the tumor reduced,liquefied,and vanished by CT scan.It could be observed that the tumorous cell become smaller,concentrated and cataclased,finally formed apoprotic bodies and separated from the cell in C_6 gliomas in EM.The tumorous vessels was less,smaller and thinker. Some vessels only could see the base membrane and no endothelioid cells.Conclusion The remaining tumors is van- ished by CT scan.The mechanisms of tumors disappearance proposes to explain that thermochemotherapy can dam- age C_6 glioma cells and microvessels,decrease microvessels density and induce tumor ceils apoptosis.That inhibits tu- morous angiogenesis and proliferation.

AIMIn search of more potent, less toxic and selective potassium channel openers.

METHODSAccording to the structure-activity relationships of benzopyran compounds and the features of structures of aprikalim, dofetilide and nifekalant, twenty benzopyran-4-one hydrazone derivatives have been designed and synthesized from 4-cyanophenos through acetylation, Fries rearrangment, cyclization, hydrazone, substitution reaction and so on. The compounds were tested for their vasorelaxant activity in low (30 mmol.L-1) and high (80 mmol.L-1) KCl-induced contraction of rat aorta to identify potential potassium channel openers in vitro.

RESULTSThree series of twenty benzopyran-4-one hydrazone derivatives, nominated N-aminoacetyl-(6-cyano-3,4-dihydrospiro [2H-1-benzopyran-2,1'-cyclohexane]-4)-one hydrazone (I), 2-(6-cyano-3, 4-dihydro-2H-1-benzopyran-4-ylene) hydrazinethiocarboxamide derivatives (II) and N-(2-arylethyl) aminoacetyl-(6-cyano-3,4-dihydro-2H-1-benzopyran)-4-one hydrazone (III), have been synthesized. They (I1-9, II1-4 and III1-7) are new compounds. Their chemical structures were determined by IR, 1HNMR, MS and elemental analysis. The vasorelaxant effects of those novel compounds indicated that some of the compounds have vasorelaxant activities at 1 x 10(-6) mol.L-1.

CONCLUSIONThe vasorelaxant activities of compounds I9, III2 and III5 in inhibiting low KCl-induced vasocontraction at 1 x 10(-6) mol.L-1 are less potent than the reference compound emakalim. However they are more potent than emakalim to inhibition high concentration KCl-induced vasocontraction at 1 x 10(-5) mol.L-1. It is worthy of further study.

Animals ; Aorta ; drug effects ; Benzopyrans ; chemical synthesis ; pharmacology ; Molecular Structure ; Potassium Channels ; agonists ; Rats ; Vasodilation ; drug effects ; Vasodilator Agents ; chemical synthesis ; pharmacology

OBJECTIVETo analyze the differential protein expression of left-sided colon cancer and right-sided colon cancer.

METHODSTissue samples of left-sided colon cancer (n=7) and right-sided colon cancer (n=7) were collected. Tissue protein was abstracted and two-dimensional gel electrophoresis (2-DE) was used to examine the gel images. Peptide mass fingerprintings (PMF) was acquired by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and the proteins were identified by data searching with bioinformatics. Immunohistochemical SP method was used for the detection of glucose regulated protein 78 kD (GRP78) and heat shock protein 20 (HSP20) in left-sided colon cancer (n=50) and right-sided colon cancer (n=50) tissues.

RESULTSSixteen differentiating protein spots were identified. Compared with right-sided colon cancer, 10 proteins including GRP78 up-regulated and 6 proteins including HSP20 down-regulated in left-sided colon cancer. Immunohistochemical detection showed that in left and right sided colon cancer, the positive expression rate of GRP78 was 78% (39/50) and 56% (28/50) and the positive expression rate of HSP20 was 34% (17/50) and 72% (36/50), respectively, and the differences were statistically significant (both P<0.05). The positive rate of GRP78 was associated with tumor differentiation, infiltration layer, TNM staging, lymph node metastasis, and liver metastasis, while the positive rate of HSP20 was associated with tumor gross morphology, TNM staging, and lymph node metastasis (P<0.05).

CONCLUSIONSThere are differentially expressed proteins between left-sided colon cancer and right-sided colon cancer, especially for GRP78 and HSP20, which may be the cause leading to the biological differences between left-sided and right-sided colon cancer.

Adult ; Aged ; Colonic Neoplasms ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; HSP20 Heat-Shock Proteins ; metabolism ; Heat-Shock Proteins ; metabolism ; Humans ; Male ; Middle Aged