AIM Action of adenosine triphosphate(ATP)on longitudinal muscle strips of the rat distal colon has been reported, however, that of the rat proximal colon remains to be clarified. In this study we investigated the effects of ATP on longitudinal muscle strips isolated from the rat proximal colon and the receptors involved in the effects. METHODSIsometric relaxant and contractile responses to ATP (0.1 μmol · L- 1 - 1 mmol· L- 1 ) and adenosine (1 - 100 μmol· L-1) in longitudinal muscle strips of the rat proximal colon were observed. RESULTS ATP (0.1 μmol· L- 1 - 1 mmol· L- 1 ) produced a complicated response including an inhibition of rhythmic contraction and a weakly transient decrease in basic tone (0.05-0.08 g) followed by a concentration-dependent contraction (0.04- 0.44 g) in longitudinal muscle strips of the rat proximal colon at resting tension. Tetrodotoxin (0.1 μmol·L-1) did not influence the responses to ATP.Adenosine (1 - 100 μmol· L-1) did not produce an obvious contractile response in the preparation at resting tension. Concentration-dependent relaxant responses to ATP ( 1 μmol· L- 1 - 1 mmol· L- 1 ) in the preparation precon tracted with 5-hydroxytryptamine or with acetylcholine were 23.2％ - 94.6％ or 24.8 ％ - 92.4％, however the relaxant responses to adenosine were much weaker than those to ATP. CONCLUSION ATP produces contractileresponsesmainly via purine and pyrimidine (P) 2receptors and relaxant responses partially via P1 receptors in longitudinal muscle strips of the rat proximal colon.

Aim To investigate the effect of racemic-doxazosin(rac-DOX),S-doxazosin(S-DOX) and R-doxazosin(R-DOX) on the proliferation of vascular smooth muscle cells(VSMCs) of the rat aorta.Methods VSMCs of the rat aorta were cultured,MTT assay was used to determine the cell proliferation and the morphological changes in VSMCs were analyzed using Giemsa's staining.Results The treatment with rac-DOX,S-DOX or R-DOX at 3~30 ?mol?L-1 for 96 h inhibited the proliferation of VSMCs significantly.However,the inhibitory effect of S-DOX on cell proliferation was more potent than that of R-DOX at the same concentration(P

Extracellular adenosine triphosphate (ATP) and adenosine are important signaling molecules in both intracellular and extracellular microenviroments of cells. They exert cytoxic and apoptotic effects in some tissues such as tumor. The proapoptotic mechanisms of adenosine and its receptors are involved in Adenylyl cyclase(AC), cAMP, Ca 2+ , etc. Apoptosis induced by ATP is as sociated with several purinergic receptors including P2X_1, P2X_2, P2X_7, P2Y_1, P2Y_2, et al, it is also involved in FasL/FasR, T cell receptor(TCR), and gene regulations of bcl-2 and bax.

Objective To discuss pathogenic effects of low high-density lipoprotein cholesterol(HDL-C)on atherosclerosis and thromboembolism,the influences of HDL-C on platelet cytosolic free calcium concentration([Ca2+]i),platelet release reaction products beta-thromboglobulin(?-TG)and platelet factor 4(PF4)were observed in dyslipoproteinemia patients with low HDL-C.Methods i,?-TG and PF4 were measured by fluorescent probe Fura 2-AM and ELISA skills respectively,in 42 patients with low HDLC(LHDL-C)and 25 healthy controls(CONT).Results Compared with those in CONT group,the platelet[Ca2+]i,?-TG and PF4 were all higher in LHDL-C group(all P

AIM To study the growth inhibition of adenosine triphosphate (ATP) and adenosine (ADO) on cultured tumor cells in vitro. METHODS MTT assays were used to determine the inhibition of proliferation of ATP and ADO on several tumor cell lines, including human squamous esophageal carcinoma cells TE-13, human stomach carcinoma cells HGC-27 and human erythroleukemia cells K562. The morphological changes of ATP and ADO on the cell lines were observed under light microscope. RESULTS ATP and ADO produced a certain inhibition effect on TE-13, HGC-27, K562 cells at different concentration between 0.01～1.0 mmol?L -1. The maxium inhibition fraction of TE-13, HGC-27, K562 cells exposed to ATP for 72 h was 80.52%, 58.67% and 45.07%, respectively; and to ADO for 72 h, was 74.03%, 52% and 30.99%, respectively. Under light microscope, the tumor cells exposed to higher concentration(1 mmol?L -1) of ATP and ADO displayed morphological changes of apoptosis. CONCLUSION These results suggested that ATP has a certain cytotoxic effect on several tumor cell lines, it might partly be related to ADO. Its mechanism might involve apoptosis.

AIM The effects of calcium antagonist diltiazem on plasma insulin levels were investigated in rats. METHODS Plasma insulin was measured with radioimmunoassay method. RESULTS In the fasting rat, plasma insulin levels were significantly increased after ig diltiazem 10 mg?kg -1 and 100 mg?kg -1 , and the level of plasma insulin was increased by 131% 30 min after administration of diltiazem 100 mg?kg -1 in comparison with that of control group. Diltiazem increased the plasma insulin level markedly in glucose tolerance test of the rat. In the hyperglycemia rat induced by adrenaline, diltiazem 100 mg?kg -1 weakly increased the plasma insulin level only at 1 h after administration. CONCLUSION Diltiazem increases the plasma insulin levels in the fasting rat and glucose loaded rat. The increase of plasma insulin level induced by diltiazem is due to the hyperglycemic action of diltiazem and other effect, probably a direct or an indirect insulin release action on pancreas of the rat.

P-glycoprotein (P-gp) is an ATP-dependent multidrug efflux pump that acts as a major obstacle for oral drug delivery and cancer therapy. Recent reports have provided evidence that excipients often used in pharmaceutical formulations, such as Pluronic and TPGS, also have inhibitory effects on P-glycoprotein. Because inhibition of efflux transporters by polymeric inhibitors may dramatically increase the bioavailability of P-gp substrates with negligible side effects, identification of the mechanism and their structure activity relationship is therefore of significant importance for pharmaceutical development. Other than competitive inhibition for traditional inhibitors, polymeric inhibitors may modify P-gp function through alterations on membrane fluidity, inhibition of P-gp ATPase, depletion of intracellular ATP and down-regulating of P-gp expression. In the present review, the inhibition mechanism of potential polymeric inhibitors and their structure activity relationship will be discussed along with a brief introduction to the established methodologies.

BACKGROUND:Humeral supracondylar fracture is a common fracture occurred in children. The selection of internal fixation for humeral supracondylar fracture remains controversial. OBJECTIVE:To compare the biocompatibility between internal fixation with Kirschner wire and bioabsorbable implants for humeral supracondylar fractures. METHODS: From January 2007 to January 2013, 246 cases of humeral supracondylar fractures, from Affiliated Hospital of Luzhou Medical Colege, were treated by internal fixation with Kirschner wire. Meanwhile, the studies on internal fixation for treating supracondylar fracture of humerus in children were searched. Efficacy was evaluated by preoperative and postoperative elbow range of motion and the incidence of cubitus varus, and the results were statisticaly analyzed, and compared with other therapeutic methods. RESULTS AND CONCLUSION:Al cases were folowed up for 6-36 months, averagely 18 months. According to Mayo elbow performance score, function of the elbow joint was excelent in 194 cases, and good in 48 cases, with good and excelent rate being 98.4%. Four cases suffered < 5° cubitus varus, with incidence rate of 1.63%. The internal fixation with Kirschner wire provided functional recovery of elbow joint, but the second stage operation was needed to pick out the wires. And it might be perplexed by Kirschner wire loosening or needle withdrawal, resulting in instable fixation. Bioabsorbable implants were effective in the treatment of supracondylar fracture of humerus. Bioabsorbable sticks would break down over time, without harming to human body or influencing imaging examination. Elbow function development of the epiphysis would not be affected. However, due to lack of large-sample observation, long-term effects of bioabsorbable implants for treating supracondylar fracture of humerus in children deserve further studies.

Objective To explore the imaging appearances of periprosthetic osteolysis after total hip arthroplasty(THA).Methods Imaging appearances of periprosthetic osteoleysis after THA in 24 cases confirmed by surgery and pathological examination were retrospectively analyzed.Twenty-four patients underwent X-ray examinations,and 17 of them underwent CT scanning additionally.Results (1) Location and type:Of the 24 cases with periprosthetic osteoleysis,23 femurs were involved (95.8％,expansile type in 15 cases and liner type in 8 cases).Lesions were located in Gruen 1-2 and 6-7 region (34.8％) in 8 cases,in Gruen 1 and 7 region in 8 cases (34.8％),in Gruen 1-7 region in 6 cases (26.0％),in Gruen 2-3 and 6 region in one case (4.3％).A total of 21 actabulums were involved (87.5％,expansile type in 14 cases and liner type in 7 cases included),with lesions located in Delee Ⅰ-Ⅲ in 14 cases (66.7％),in Delee Ⅰ and Ⅲ in 4 cases (19.0％),in Delee Ⅱ-Ⅲ in 2 cases (9.5％) and in Delee Ⅰ-Ⅱ in 1 case (4.8％).(2) Features of lesions:Adjacent cortex of the lucency lesion appeared irregular thin in 24 cases (100％),focally discontinuous in 18 cases (75.0％),disrupted in 16 cases (66.7％),and accompanied by a few tiny bony fragments in 10 cases (41.7％).Cortical thickening were seen near the lucency lesion in 3 cases(12.5％).Twenty-one cases (87.5％) presented with sclerotic margins,18 cases (75.0％) with crateriform interface.Of the 17 cases which underwent the CT scanning,16 cases (94.1％)had soft tissue mass.(3) Change of the prosthesis:Twenty-one cases (87.5％) presented with linear wear,11 cases (45.8％) with bony defect near the screw.The screw penetration was seen in 3 cases (12.5％),fractured screws were seen in 2 cases (8.3％),and screw invagination was seen in 1 case (4.2％),metal debris was seen in 12 cases (50.0％).(4) Complications:Nineteen cases (79.2％) presented with femur periprosthetic loosening,16 cases (66.7％) with actabulum periprosthetic loosening.Eleven cases (45.8％) presented with femur periprosthetic fractures,5 cases (20.8％) with actabulum periprosthetic fractures.Two cases (8.3％) had periprosthetic dislocation.Conclusions Linear or expansile lucent lesion of the bones around the prosthesis after THA,together with soft tissue mass and the imaging of linear wear can be diagnosed as the periprosthetic osteolysis.

Aim To study the mechanisms of inotropic responses to doxazosin enantiomers in the isolated rat atrium.Methods We analyzed the positive inotropic response to (-)doxazosin and the negative inotropic response to (+)doxazosin in the left atrium of rat u-sing receptor-pharmacological technique.Results In the preparation treated with verapamil,the positive in-otropic responses to 3 μmol·L-1 (-)doxazosin were significantly inhibited from the control level (245.7 1 ± 44.29)mg to (172.50 ±43.34)mg,(P<0.05).In the preparation treated with methylene blue,the posi-tive inotropic responses to 3 μmol·L-1 (-)doxazosin were significantly potentiated from the control level (245.7 1 ±44.29 )mg to (303.33 ±45 .90 )mg,(P<0.05 ).In the preparation treated with H-89 ,the positive inotropic responses to 3,10 and 30 μmol · L-1 (-)doxazosin were (338.57 ±96.86 ) mg, (471.43 ±107.61)mg and (520.00 ±103.44)mg, which were significantly (P<0.05 ~0.01)larger than the control levels of (245.71 ±44.29)mg,(314.29 ±90.34)mg and (357.14 ±68.49 )mg.Treatment with phenoxybenzamine,atropine,propranolol or indo-methacin did not significantly affect the responses to doxazosin enantiomers.Conclusion The positive ino-tropic responses to (-)doxazosin in the isolated left a-trium of rat are partially involved in L-type Ca2+chan-nels and intracellular cGMP level.However,α-adre-noceptors,muscarinic receptors,β-adrenoceptors and cyclooxygenases are not related to the responses to doxazosin enantiomers.