OBJECTIVETo investigate the absolute bioavailability of caffeic acid in rats and its intestinal absorption properties.

METHODThe absolute bioavailability (Fabs) of caffeic acid was obtained after iv (2 mg x kg(-1)) or ig (10 mg x kg(-1)) administration to rats. The intestinal absorption of caffeic acid was explored by the recirculating vascularly perfused rat intestinal preparation. Caco-2 cell model was applied to measure the permeability of caffeic acid from apical to basolateral said (A-B) and from basolateral to apical said (B-A).

RESULTA two-compartment pharmacokinetic model was best to describe the pharmacokinetics of caffeic acid following iv or ig administration. The Fabs of caffeic acid was 14. 7% , and its intestinal absorption was 12.4%. The values of Papp A-->B and Papp B-->A of caffeic acid were retained stable while its concentration was changed. The efflux ratio values in this study surveyed were above 2.0, and suggesting caffeic acid was active transport.

CONCLUSIONCaffeic acid was shown to have poor permeability across the Caco-2 cells, low intestinal absorption and low oral bioavailability in rats.

Animals ; Biological Availability ; Caco-2 Cells ; Caffeic Acids ; metabolism ; pharmacokinetics ; Humans ; Intestinal Absorption ; Male ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Chinese traditional osteopathy is long in history, unique in manipulation and miraculous in therapeutic effect. But people understand it more m perception rather than in theory, more in application rather than in development. There is little research truly on the bioseience.OBJECTIVE: To probe into the macro-idea of Chinese traditional osteopathy, micro-mechanisms on characters and mathematics-physics models, aiming to provide new principles and approaches of treatment for the daily increased bone trauma, fracture and sport injury.SETTING: Physics and machine-electron college of a university, and its affiliated hospital.METHODS: Based on the natural concept of "integration between heaven and human being" and new concept of holistic medicine in Chinese traditional osteopathy, the macro-idea and characters of reduction and union of fracture are generalized from the characters of natural therapy and the biomechanical mechanisms and characters of reduction and union of fracture are summarized from the micro-reaction of bone repair and union so as to discover biomechanical mechanisms and characters of reduction and union of fracture and further to set up biomechanical models and mathematics-physics expressions during the treatment.RESULTS: Chinese traditional osteopathy envelopes macro-idea of "initiative reduction-functional union" in fracture and micro-mechanism on "stress adaptability-functional adaptability" of bone repair and union.CONCLUSION: Chinese traditional osteopathy compiles with the natural,green and non-traumatic therapy in bio-natural law of bone repair and union and supports the theme of "high thought and high skill".

OBJECTIVETo clone DNA sequence of the survivin promoter and study is transcriptional activities in human prostate cancer cells and normal Chang liver cells.

METHODSThe fragment of the survivin promoter was acquired by PCR amplification and inserted into pPRIME vectors to reconstruct a recombinant plasmid named pPRIME-S1pro and pPRIME-S2pro. Then the reconstructed plasmid was transiently transfected into human prostate cancer cells lines LNCaP and normal Chang liver cells. The transcriptional activities of the survivin promoter in various cells was determined by measuring the expression of green fluorescent protein (GFP).

RESULTSThe survivin promoter had transcriptional activities in LNCaP cells and the transcriptional activity of the S2pro was much higher that of the S1pro, reaching a level of 39% of the transcriptional activity of the CMV promoter.

CONCLUSIONThe survivin promoter cloned in the therapy for prostate cancer.

Cell Line, Tumor ; Humans ; Inhibitor of Apoptosis Proteins ; Male ; Microtubule-Associated Proteins ; biosynthesis ; genetics ; Neoplasm Proteins ; biosynthesis ; genetics ; Plasmids ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Prostatic Neoplasms ; genetics ; metabolism ; Transfection

OBJECTIVETo detect and compare the transcriptional activities of prostate-specific membrane antigen (PSMA) promoter and enhancer and survivin promoter in different human prostate cancer cell lines, and to search for some evidence for the targeting gene therapy of human prostate cancer.

METHODSThe fragments of the PSMA promoter and enhancer and survivin promoter were amplified by PCR and inserted into pGL3-Basic. The recombinant plasmids were transiently transfected into human prostate cancer cell lines and normal Chang liver cells, and, their transcriptional activities in various cells were determined by measuring the expression of luciferase.

RESULTSThe survivin promoter exhibited a higher transcriptional activity than PSMA promoter and enhancer in tumor cell lines, and the S2pro promoter showed the highest activity, reaching one third of that of the CMV promoter.

CONCLUSIONThe survivin promoter is highly activated in prostate cancer cell lines and may serve as a new tool for the transcriptional targeting gene therapy of prostate cancer.

Antigens, Surface ; genetics ; Cell Line, Tumor ; Glutamate Carboxypeptidase II ; genetics ; Humans ; Inhibitor of Apoptosis Proteins ; genetics ; Male ; Plasmids ; Promoter Regions, Genetic ; Prostatic Neoplasms ; genetics ; therapy ; Transcription Initiation Site ; Transcriptional Activation ; Transfection

Objective:To evaluate the cumulative dose of the target volume and organs at risk (OARs) in intensity-modulated radiation therapy (IMRT) for large volume non-small cell lung cancer (NSCLC) based on rigid and deformation registration methods. The dosimetric changes between the initial and second treatment plans were compared.Methods:Thirty patients treated with IMRT for large volume NSCLC with twice 4DCT scans acquired before radiotherapy and after 20 fractions of radiotherapy were recruited. The initial treatment plan (Plan 1) based on the average density projection CT (CT 1-avg) of the first 4DCT images and the second treatment plan (Plan 2) based on the average density projection CT (CT 2-avg) of the second 4DCT images were calculated. Then, the dose distributions of Plan 1 and Plan 2 were accumulated based on rigid and deformation registration methods to obtain Planrig and Plandef, respectively. Finally, the volume changes of gross tumor volume (GTV) and OARs between two CT scans were compared. The dose-volume parameters between Plan 1 and other plans (including Plan 2, Planrig and Plandef) were also statistically compared. Results:Compared with the initial CT scan, the mean volume of GTV and heart on the second CT was decreased by 44.2% and 5.5%, respectively, while the mean volume of ipsilateral lung, contralateral lung and total lung was increased by 5.2%, 6.2% and 5.8%, respectively (all P<0.05). Compared with Plan 1, the D 95%, D 98% and V 100% of target volume IGTV (GTV fusion of 10 4DCT phases) and PTV in Plan 2 did not significantly change (all P>0.05), and those in Planrig and Plandef were decreased (all P<0.05). The dose-volume parameters of spinal-cord, heart, ipsilateral lung and total lung in Plan 2, Planrig and Plandef were significantly lower than those in Plan 1(all P<0.05). Among them, the V 30Gy and D mean of heart were decreased by 27.3%, 16.5%, 15.3% and 15.2%, 6.6%, 5.6%, respectively. The V 20Gy and D mean of total lung were decreased by 15.6%, 4.5%, 3.7% and 15.7%, 6.2%, 5.1%, respectively. Some dose-volume parameters (including D 95% and D 98% of target volume, V 40Gy of heart, V 20Gy and D mean of the ipsilateral lung and the total lung) of Plandef were higher than those in Planrig (all P<0.05). The Dice similarity coefficients (DSCs) of OARs after deformation registration were significantly higher than those after rigid registration ( P<0.05). Conclusions:The dose-volume parameters of OARs significantly differ between Plan 1 and Plan 2. Hence, all these parameters have a large degree of deviation in predicting radiation-induced injury of OARs. Nevertheless, the dose-volume parameters obtained by deformation registration can enhance the prediction accuracy.

Hashimoto's encephalopathy(steroid-responsive encephalopathy associated with autoimmune thyroiditis,SREAT)is a rare disorder,accompanied by seizures,tremor,myoclonus,ataxia,psychosis,and stroke-like episodes,breaking out with an acute or subacute onset and having a relapsing/remitting or progressive course which is not correlated to thyroid hormone levels.Patients with Hashimoto's encephalopathy are usually euthyroid or dysthyroid with positive antithyroid antibodies,have a moderately raised cerebrospinal fluid protein content,and have a global slowing of the electroencephalogram and a normal or near normal imaging except in rare cases.The pathogenesis of Hashimoto's encephalopathy is still obscure.This paper reports a case diagnosed as"Hashimoto's encephalopathy".It is suggested that the diagnosis of Hashimoto's encephalopathy should be considered in cases with unexplained encephalopathy associated with high levels of antithyroid antibodies despite normal thyroid function.

OBJECTIVEThis study aimed at exploring the feasibility of using dried blood spots (DBS) to detect HIV drug resistance genotyping in China by comparing the results of drug resistance from DBS, plasma and whole blood samples.

METHODSBlood samples were collected from 39 AIDS patients from Anhui (10), Yunnan (13), Hunan (6) and Xinjiang (10) provinces and autonomous regions. The HIV strains that infected these patients covered all the major HIV-1 subtypes prevailing in China (B, CRF01_AE, CRF07_BC). HIV drug resistance genotyping assay was performed on DBS as well as on the whole blood and plasma samples from the same patients simultaneously by using an in-house nest RT-PCR method. Drug resistance levels were determined based on Stanford University HIV drug resistance database, and the results from these three types of samples were compared.

RESULTSThe percentages of successful amplification of protease and reverse transcriptase regions in the pol gene were 95% (37/39) from DBS, 92% (36/39) from whole blood and 100% (39/39) from plasma samples. The sequences from the three types of samples showed more than 99% identity.86% (31/36) of the DBS samples had the same set of drug resistance mutations as those which were detected from plasma samples. The differences probably resulted from mixed bases.

CONCLUSIONSThere was no major difference in detecting HIV drug resistance genotyping among DBS, plasma and whole blood samples. Therefore, DBS is useful for detection of HIV drug resistance genotyping and is particularly valuable in developing countries like China, especially in remote rural regions.

Dried Blood Spot Testing ; Drug Resistance, Viral ; genetics ; Feasibility Studies ; Genotype ; HIV Infections ; blood ; genetics ; virology ; HIV Seropositivity ; blood ; genetics ; virology ; HIV-1 ; drug effects ; genetics ; Humans ; Reverse Transcriptase Polymerase Chain Reaction ; Viral Load

BACKGROUNDAtherosclerotic plaque rupture is the primary mechanism of thrombosis which plays a key role in the onset of acute coronary syndromes. Detection of these plaques prone to rupture (vulnerable plaque) could be clinically significant for prevention of cardiac events. It has been shown that high metabolism cells have a high uptake of fluorine-18 fluorodeoxyglucose ((18)F-FDG). The objective of this study was to investigate the correlation of FDG uptake and the immuno-histochemistry parameters of plaques, and the effect of atorvastatin on vulnerable atherosclerotic plaque in a rabbit model.

METHODSTen male New Zealand White rabbits were divided into three groups as follows: (1) normal control group (n = 2, C group): the animals were fed a standard diet at 120 g/d and were given water ad labium; (2) atherosclerosis group (n = 4, As group): animals were fed with high fat diet for 5 months after aortic endothelia damage; (3) treatment group (atherosclerosis + atorvastatin, n = 4, Statin group): animals were fed with high fat diet for 5 months and then changed into normal chow plus atorvastatin (2.5 mg·d(-1)·kg(-1)) treatment for another 4 months. Then these four rabbits were imaged with fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and sacrificed for pathohistologic studies. FDG uptake by the aorta was expressed as target-to-background ratio (TBR). Maximal standardized uptake value (SUV) was measured over the thoracic and abdominal aortas. The aortic smooth muscle cell (SMC) number, CD-14 antibody positive cell (macrophage) number and the ratio of the thickness of fibrous cap to the thickness of lipid core (cap-to-core ratio) in atherosclerotic plaques were analyzed.

RESULTSAs group showed significantly higher uptake of FDG than C group (SUVs: 0.746 ± 0.172 vs. 0.286 ± 0.073, P < 0.001). After 4 months of atorvastatin treatment and the modification of diet, SUVs decreased significantly (Statin group: 0.550 ± 0.134, compared to As group, P < 0.001). However, no marked difference was found in TBR, the number of macrophages, the number of SMC and the cap-to-core ratio in the aortic segments between Statin group and As group. The correlation of aortic FDG uptake with SMC assessed by histopathology was negatively significant (r = -0.57, P < 0.001). When aortic FDG uptake was expressed as TBR, it correlated significantly (r = 0.69, P < 0.001) with the macrophage number, and also correlated significantly (r = -0.78, P < 0.001) with the cap-to-core ratio.

CONCLUSION(18)F-FDG PET/CT might serve as a useful non-invasive imaging technique for detection of atherosclerotic plaque and potentially permit monitoring of relative changes in inflammation within the atherosclerotic lesion.

Animals ; Aorta ; diagnostic imaging ; pathology ; Atherosclerosis ; diagnostic imaging ; Fluorodeoxyglucose F18 ; Male ; Plaque, Atherosclerotic ; diagnostic imaging ; Positron-Emission Tomography ; methods ; Rabbits

OBJECTIVETo construct eukaryotic expression vectors by using the pSilencer3. 1-H1 neo vector for inhibiting human survivin gene by RNA interference, and to detect the effect of the silenced survivin gene on PC-3 cells.

METHODSThree target gene segments were synthesized and cloned into the pSilencer3. 1-H1 neo vector respectively to construct three recombinant eukaryotic expression vectors: pSilencer3. 1-SVV1, pSilencer3. 1-SVV2 and pSilencer3. 1-SVV3, which were identified by enzyme digestion analysis and DNA sequencing. Then the PC-3 cells were transfected with the recombinant vectors and the interference effect detected by RT-PCR, Western blot and immunohistochemical staining. The apoptosis index of the PC-3 cells was detected by flow cytometry and their proliferation detected by MTT method.

RESULTSEnzyme digestion analysis and DNA sequencing showed that three target segments were cloned into pSilencer3. 1-H1-neo vectors. The results of RT-PCR, Western blot and immunohistochemical staining indicated that pSilencer3. 1-SVV2 and pSilencer3. 1-SVV3 vectors could knock down the transcription and expression of survivin gene. After transfected with pSilencer3. 1-SVV2 and pSilencer3. 1-SVV3 vectors, the apoptosis index of the PC-3 cells was increased by 10% - 15% and their growth obviously slowly down.

CONCLUSIONThe transcription and expression of survivin gene were inhibited effectively by the recombinant eukaryotic expression vectors (pSilencer3. 1-SVV2 and pSilencer3. 1-SVV3) in the prostate cancer cell line PC-3. After transfected with pSilencer3. 1-SVV2 and pSilencer3. 1-SVV3 vectors, the apoptosis index of the PC-3 cells was increased and their growth inhibited.

Apoptosis ; Cell Line, Tumor ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; drug effects ; Genetic Vectors ; Humans ; Inhibitor of Apoptosis Proteins ; Male ; Microtubule-Associated Proteins ; biosynthesis ; genetics ; Neoplasm Proteins ; biosynthesis ; genetics ; Prostatic Neoplasms ; metabolism ; pathology ; RNA Interference ; RNA, Small Interfering ; pharmacology ; Transfection

OBJECTIVETo investigate the expressions of E-cadherin (E-cd) and alpha-catenin (alpha-cat) proteins in benign and malignant prostate tumors, and determine whether they could be used as molecular markers for the prognosis of prostate cancer (PCa).

METHODSWe detected the expressions of E-cd and alpha-cat in the prostatic tissues from 45 cases of PCa and 10 cases of benign prostatic hyperplasia (BPH) by immunohistochemical Elivision staining, and analyzed the relationships of E-cd and alpha-cat expressions with the PCa stage, PCa grade, preoperative PSA, results of endocrine therapy and prognosis.

RESULTSThe E-cd protein was abnormally expressed in 86.7% of the PCa and 10.0% of the PSA patients, and the E-cd expression was significantly lower in the former than in the latter (P < 0.05). The abnormal expressions of E-cd in the PCa patients with metastasis, non-metastasis, Gleason score < or = 7 and > 7 were 85.0, 87.5, 100.0 and 86.7%, respectively, with no significant between-group differences (P > 0.05), those in the PCa patients with PSA < or = 10 and > 10 microg/L were 40.0 and 97.1%, respectively, significantly higher in the former than in the latter (P < 0.05), and those in the PCa patients with and without response to endocrine therapy were 93.8 and 72.7%, respectively, with no significant differences between the two groups (P > 0.05). The alpha-cat protein was abnormally expressed in 93.3% of the PCa and 30.0% of the BPH patients, respectively, and the alpha-cat expression was significantly lower in the former than in the latter (P < 0.05). The abnormal alpha-cat expressions in the PCa patients with metastasis, non-metastasis, Gleason score > 7 and < or = 7 were 90.0, 100.0, 90.0 and 100.0%, respectively, with no significant between-group differences (P > 0.05), those in the PCa patients with PSA < or = 10 and > 10 microg/L were 40.0 and 94.3%, respectively, significantly higher in the former than in the latter (P < 0.05), and those in the PCa patients with and without response to endocrine therapy were 100.0 and 81.8%, respectively, with no significant differences between the two groups (P > 0.05).

CONCLUSIONThe expressions of E-cd and alpha-cat are significantly lower in PCa than in BPH, and they are not associated with cancerous metastasis, but negatively correlated with the PSA level in PCa patients.

Aged ; Aged, 80 and over ; Cadherins ; metabolism ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Prognosis ; Prostate ; metabolism ; pathology ; Prostatic Hyperplasia ; metabolism ; pathology ; Prostatic Neoplasms ; metabolism ; pathology ; alpha Catenin ; metabolism