Objective To forward the concept of solution space of pharmacokinetics for studying radiophannaceutical distributions in animal models. Methods On the basis of special solutions of differential equations of pharmacokinetics, the solution space was established using the characteristics of linearly independent particular solutions and used to express the pharmacokinetics of pharmaceuticals in vivo. 0. 2 ml (7.4 MBq) 2β-carbomethoxy-3β- (4-corophenyl)-8-(2-18F-fluoroethyl) nortropane (18F-FECNT) was injected through tail vein into normal mice. The mice were sacrificed by decapitation at 5, 15, 30, 60, 120 and 180 min post-injection. Brain tissues were removed and weighed, and radioactivity was counted with the γ-counter. The solution space theory was used to study pharmacokinetics of 18F-FECNT in brain tissues of mice. Results The result showed that all solutions of pharmacokinetics models, based on differential equations, were included in the solution space. The solution of any organ or tissue could be linearly expressed by bases of the solution space. When the dimension number of the solution space was no more than 3, the solution could be directly expressed with coordinate picture. By this rule in our theory, the quantity of 18F-FECNT in brain tissues of mice changed with time, which was accorded with the experiment. The coordinates of striatum, frontal cortex, temporal cortex, occipital cortex, parietal cortex, hippocampus and cerebellum in the solution space were ( 10.13, 1.49), (4.27, 0. 84), (4.48, 0.81 ), (2.89, 0.98), (3.65, 0. 83),(3.55, 0. 98) and (2.03, 1.25 ), respectively. Conclusion The theory of solution space could be used to study pharmacokinetics of 18 F-FECNT in mice brain.

Objective To investigate the prognostic factors regarding overall survival in locally advanced stage of esophageal squamous cell carcinoma (ESCC) patients after receiving concurrent chemoradiotherapy (CRT).Methods Each of 80 patients with locally advanced ESCC was treated by doxtel 135-175 mg/m2 d1 and cisplatin 40 mg/m2 d2,3 combined with radiotherapy 60 Gy.ECOG (0-1),tumor locations,tumor sizes,TNM classifications as well as the levels of CA199,SCC-Ag were detected before concurrent treatments and 4 weeks after treatment.The relationship wasanalyzed between the prognosis of disease and CA199,SCC-Ag levels.Each index was studied by Cox statistical regression analysis and P value was determined.Results All patients had completed 4 cycles' treatments successfully.The major adverse effects included neutrophilic granuloaytopenia,calvities,nausea,emesis and diarrhea.The severe effect was Ⅲ degree neutrophilic granuloaytopenia for 2 cases (2.5 ％),all the side-affect had recovered after symptomatic treatments.The median survival time were 50 months and 72.5 months in the patients who were greater than 60 year-old and less than or equal to 60 year-old,respectively (P =0.004).Regarding to 5-year overall survival,the figures were 73.3 ％,69.4 ％,41.7 ％ and 0 in the patients with cT1-2N1M0,cT3N1M0,cT4NoM0 and cT4N1M0 classification,respectively (P =0.024),they were 42.9 ％,70.0 ％,and 60.9 ％ in the patients with upper thoracic esophagus,middle thoracic esophagus,and lower thoracic esophagus,respectively (P =0.971),they were 100 ％ in the patients with ECOG 0 and 54.1％ in the patients with ECOG 1 (P =0.044),they were 86.7 ％ in the patients with CA199≤37 kU/L,and 52.0 ％ in the patients with CA199 more than 37 kU/L (P =0.008),they were 95.5 ％ in the patients with SCC-Ag≤ 1.9 μg/L,and 53.4 ％ with ＞1.9 μg/L (P =0.012).Conclusion For ESCC patients treated with CRT,the age,TNM stage,ECOG,CA199 and SCC-Ag levels are independent forecasting factors regarding their overall survival.

OBJECTIVETo observe the expressions of Wnt/beta-catenin and the effects of tanshinone IIA (TII A) on Wnt/beta-catenin signaling pathway in high glucose induced renal tubular epithelial cell transdifferentiation.

METHODSHuman kidney proximal tubular epithelial cells (HK-2) were divided into three groups, i. e., the normal glucose group, the high glucose group, and the high glucose plus tanshinone IIA group. The expression of beta-catenin was observed using immunocytochemical staining. The protein expression of beta-catenin, E-cadherin, and alpha-smooth muscle actin (alpha-SMA) were detected by Western blot. The mRNA levels of beta-catenin and E-cadherin were detected by RT-PCR.

RESULTSCompared with the normal glucose group, both the protein and the mRNA expressions of beta-catenin were significantly enhanced (P < 0.01), the expression of E-cadherin significantly decreased (P < 0.01), the expression of beta-catenin increased in the cytoplasm and nucleus in the high glucose group. TIIA at the final concentration of 100 micromol/L significantly reduced the ectopic expression of beta-catenin. At that concentration, the protein and mRNA expressions of beta-catenin in the nucleus significantly decreased, while the protein and mRNA expressions of E-cadherin were up-regulated. Meanwhile, the expression of alpha-SMA obviously decreased.

CONCLUSIONSWnt/beta-catenin signaling pathway participated in the high glucose induced renal tubular epithelial cell transdifferentiation. TIIA inhibited the transdifferentiation process possibly through down-regulating the activities of Wnt/beta-catenin signaling pathway, thus further playing a role in renal protection.

Cadherins ; metabolism ; Cell Line ; Cell Transdifferentiation ; drug effects ; Diterpenes, Abietane ; pharmacology ; Epithelial Cells ; cytology ; drug effects ; metabolism ; Glucose ; adverse effects ; Humans ; Kidney Tubules, Proximal ; cytology ; drug effects ; metabolism ; Wnt Signaling Pathway ; drug effects ; beta Catenin ; metabolism

Objective To evaluate the quality of the portal images acquired by computed radiography(CR)system and conventional screen-film system,respectively.Methods imaging plates (IP)and X-ray films of a home-devised lead phantom with a leakage of 6.45% were acquired,and modulation transfer function(MTF)curves of the both images were measured using edge method.Portal images of 40 nasopharyngeal cancer patients were acquired by IP and screen-film system respectively.Two doctors with similar experience evaluated the damage degree of petrosa] bone,the receiver operating characteristic(ROC)curve of CR images and general images were drawn according to two doctors evaluation results.Results The identification frequency of CR system and screen-film system were 1.159 and 0.806 Lp/mm respectively.For doctor one,the area under ROC curve of CR images and general images were 0.802 and 0.742 respectively.For doctor two,the area under ROC curve of CR images and general images were 0.751 and 0.600 respectively.The MTF curve and ROC curve of CR are both better than those of screen-film system.Conclusion The image quality of CR portal imaging is much better than that of screen-film system.The utility of CR in linear accelerator for portal imaging is promising in clinic.

Aviation ; Humans ; Physical Fitness ; Resistance Training ; Schools ; Students

【Objective】 To establish a simple, economical and rapid method for the determination of methylene blue (MB) release in virus inactivation bag. 【Methods】 Based on the fluorescence energy transfer between MB and BSA-stabilized gold nanoclusters (BSA-AuNCs), the standard curve of MB determination was established by measuring the fluorescence quenching degree of MB to BSA-AuNCs in different concentrations to conduct the determination of MB release in virus inactivation bag. 【Results】 There was a good linear relationship between the MB concentration (cMB) and the fluorescence quenching degree of BSA-AuNCs[ (I0-I)/I0=0.018cMB+ 0.021(r=0.996)] when the fluorescence emission wavelength was about 620 nm and the cMB was in the range of (0.9-36) μmoL/L. The recovery of MB was 98.00% -101.95 % when applied to determine MB at high, medium, and low concentrations, the obtained intra-day variation coefficients were 0.73%, 0.81% and 0.77% respectively, and the obtained inter-day variation coefficients were 3.92%, 3.81%, and 4.73% respectively. There was no significant difference between the results measured by this method and those measured by combination of solid-phase extraction and spectrophotometry(P>0.05). 【Conclusion】 The fluorescence energy transfer method could achieve simple and rapid determination of MB release in virus inactivation bag with accurate and reliable results.

OBJECTIVETo explore the molecular mechanism of dutasteride inhibiting fertility by studying its effects on the expressions of the epididymal epithelial junction proteins Claudin1 and β-catenin in rats.

METHODSSixteen 3-month-old SD male rats were equally divided into an experimental and a negative control group to be treated intragastrically with dutasteride at 40 mg/kg per day and the same dose of solvent, respectively, for 14 consecutive days. Then, the sperm motility and morphology of the rats were detected by computer-assisted sperm analysis, the serum levels of testosterone (T) and dihydrotestosterone (DHT) measured by ELISA, changes in the tight junction of epididymal cells observed under the transmission electron microscope, the protein and gene expressions of Claudin1 and β-catenin determined by RT-PCR and immunohistochemistry, and the conception rate of the mated female rats calculated.

RESULTSDutasteride significantly suppressed the serum DHT level, sperm motility, and fertility of the rats (P <0.05). Interspaces between epididymal epithelial cell tight junctions were observed, the volume of epididymal fluid obviously increased, and the expressions of Claudin1 and β-catenin gene and protein remarkably downregulated in the experimental rats (P <0.05).

CONCLUSIONDutasteride can significantly inhibit the fertility of male rats by reducing the serum DHT level, suppressing Claudin1 and β-catenin expressions, and damaging epididymal epithelial cell junctions.

Animals ; Azasteroids ; pharmacology ; Claudin-1 ; metabolism ; Dihydrotestosterone ; blood ; Dutasteride ; Epididymis ; drug effects ; metabolism ; Female ; Fertility ; drug effects ; Humans ; Intercellular Junctions ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Sperm Motility ; drug effects ; Testosterone ; blood ; Urological Agents ; pharmacology ; beta Catenin ; metabolism

Objective To explore the effect of dendritic cells (DC) modified with transforming growth factor β1 (TGF-β1) gene on the expressions of CD28/CTLA-4:B7 costimulatory molecules in peripheral blood mononuclear cells (PBMC) in the Lewis rats with experimental autoimmune myasthenia gravis (EAMG). Methods Thirty inbreeding line, healthy, female Lewis rats were divided randomly into 6 groups: normal group, EAMG group, DC treatment group, pcDNA3-TGF-β1-DCtreatment group, pcDNA3-DC control group and normal saline group. The rats were immunized with the AChR protein extracted from electric organ of Narcine timilei and CFA in the groups except normal group. 2×106 pcDNA3-TGF-β1-DCs/rat were injected subcutaneously into the backs of the rats which had been immunized 5 d earlier with AChR+CFA. The rats in DC treatment group, pcDNA3-DC control group and normal saline group were injected in parallel with untreated DC, pcDNA3-DC and normal saline, respectively. Seven weeks after the first immunization, the expressions of CD28 mRNA and CTLA-4 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR), and the levels of B7-1 and B7-2 on the surface of PBMC were examined using flow cytometry. Results (1)The low expression of CD28 mRNA and rare expression of CTLA-4 mRNA were found in the normal rats, and both expressions increased markedly in EAMG rats (P＜0.001). Compared to those in EAMG group, the expression of CD28 mRNA decreased and CTLA-4 mRNA was upregulated after the treatment with pcDNA3-TGF-β1-DC (P＜0.05). There was no significant difference in the expressions of CD28 mRNA and CTLA-4 mRNA among the EAMG group, DC treatment group, pcDNA3-DC control group and normal saline group (P＞0.05). (2) The expressions of CD28, CTLA-4, B7-1 and B7-2 on the surface of PBMC were rare in normal rats, which increased significantly in EAMG rats (P＜0.001). The levels of CD28, B7-1 and B7-2 in pcDNA3-TGF-β1-DC group were lower than those in EAMG group (P＜0.01), but the level of CTLA-4 was higher than that in EAMG group (P＜0.05). They showed no statistically difference among the EAMG group, DC treatment group, pcDNA3-DC control group and normal saline group (P＞0.05). Conclusions The expressions of CD28/CTLA-4:B7 costimulatory molecules are abnormal in the rats with EAMG. The regulation of CD28/CTLA-4:B7 costimulatory pathways may play a critical role in the mechanism of the treatment with DC transfected with pcDNA3-TGF-β1 in the incipient EAMG rats.

OBJECTIVECytokine mediated cell immunity is the main mode of anti-tumor immunity in organism, and the disequilibrium of cytokine network is the main cause of tumor cells escaping immunologic surveillance. High mobility group box 1 (HMGB1), a nuclear protein, has recently been identified as an important mediator of local and systemic inflammatory diseases when released into the extracellular milieu. In the present study, the investigators explored the clinical significance of alteration in the serum levels of HMGB1 in childhood acute lymphocytic leukemia (ALL) and the mechanism of HMGB1-induced tumor necrosis factor (TNF)-alpha secretion in leukemic cells.

METHODSThe serum levels of HMGB1 in healthy children and childhood ALL were assayed by Western blotting. K562 leukemic cells were stimulated with recombinant HMGB1 protein in vitro, and the secretion of TNF-alpha was determined by using ELISA. The effects of HMGB1 on activation of p38, c-Jun amino-terminal kinase (JNK), and extracellular-signal regulated protein kinase (ERK) and mitogen-activated protein kinase (MAPK) in K562 cells were assayed by using Western blotting. The effects of inhibitors specific for the MAPK on HMGB1-induced TNF-alpha secretion were assayed by using ELISA.

RESULTSThe serum levels of HMGB1 were significantly higher in ALL initial treatment group (n = 15, 43.78 +/- 4.62 microg/ml) than those in healthy control group (n = 15, 0.60 +/- 0.48 microg/ml, P < 0.01) and ALL complete remission group (n = 15, 0.89 +/- 0.62 microg/ml, P < 0.01). No significant difference was found between the healthy control group and ALL complete remission group in HMGB1 levels (P > 0.05). TNF-alpha started to become detectable at 2 h and was still increasing at 16 h after HMGB1 (1 microg/ml) treatment in K562 cell culture. TNF-alpha was also secreted from K562 cells in a dose-dependent manner after HMGB1 (1 ng/ml-1 microg/ml) exposure. HMGB1 induced the phosphorylation of p38, JNK and ERK in k562 cells. Inhibitors specific for the JNK (SP600125), MEK (PD98059), and p38 MAPK (SB203580), abrogated HMGB1-induced TNF-alpha secretion.

CONCLUSIONSThe measurement of serum HMGB1 is helpful to evaluate the prognosis of the childhood ALL. HMGB1 stimulates leukemic cells to secrete TNF-alpha through a MAPK-dependent mechanism.

Cell Line, Tumor ; Child ; Cytokines ; metabolism ; HMGB1 Protein ; metabolism ; Humans ; Imidazoles ; pharmacology ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Mitogen-Activated Protein Kinase Kinases ; metabolism ; Mitogen-Activated Protein Kinases ; metabolism ; Phosphorylation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; enzymology ; metabolism ; Protein Kinase Inhibitors ; pharmacology ; Pyridines ; pharmacology ; Signal Transduction ; drug effects ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the effects of glucocorticoid receptor antagonist-M8046 on the behavior and the cyclooxygenase-2/prostaglandin E2( COX-2/PGE2) expression in spinal cord dorsal horn and dorsal root ganglia (DRG) in chronic constrictive injury (CCI) rats.

METHODSOne hundred and forty-four male SD rats were randomly divided into 4 groups, 36 rats in each group: Sham operation group (Sham), chronic constrictive group (CCI), M8046 treated group (M8046) and solvent controlled group (Sc). M8046 3 mg/(kg x d) intraperitoneal injection was given after operation in group M8046. Paw thennal withdrawal (PTWL) and paw mechanical withdrawal threshold (PMWT) of rats were measured on 2 pre-operative and 1, 3, 7, 10, 14 post-operative days. The spinal cord and L15 DRG of the operated side was removed at 3, 7, 14 days after surgery. The change of COX-2 and PGE2 expression was determined by immunohistochemical staining and ELISA separately.

RESULTSPTWL and PMWT in CCI group were significantly lower than those in Sham group on every post-operative day (P < 0.05). PTWL and PMWT in M8046 group were significantly higher than those in CCI group on 7, 10, 14 post-operative day (P < 0.05). In spinal dorsal horn, the level of COX-2 and PGE2 expression in CCI group was significantly higher than that in Sham group (P < 0.05). M8046 could significantly attenuate the activation of COX-2 and PGE2 induced by CCI (P < 0.05). The expression of COX-2 and PGE2 in DRG was similar to that in spinal dorsal horn.

CONCLUSIONThe effects of M8046 ameliorate the CCI-induced neuropathic pain may be related to attenuate the expression of COX-2 and PGE2 in spinal cord and DRG.

Animals ; Cyclooxygenase 2 ; metabolism ; Dinoprostone ; metabolism ; Ganglia, Spinal ; drug effects ; metabolism ; Male ; Neuralgia ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid ; antagonists & inhibitors ; Spinal Cord ; drug effects ; metabolism