Application of 18 F-FDG microPET/CT in the screening of cerebral ischemia reperfusion models / 中华核医学与分子影像杂志

Objective To investigate the feasibility of 18F-fluorodeoxyglucose (FDG) microPET/CT in the screening of cerebral ischemia reperfusion ( CIR) models. Methods The suture-occluded method was used to establish CIR rat models with reversible middle cerebral artery embolism. After that only awake rats whose Zea-Longa scores were 1-4 were selected for the following experiments, and 18 male SD rats were selected. Garcia scale with 18 points was used to evaluate the neurological function of rats at 2 and 24 h post-operation. At the same time points, 18 F-FDG was injected into caudal vein after anesthesia and micro-PET/CT scan was conducted at 40 min post-injection. Visual and semi-quantitative analyses were adopted to analyze the images. The autopsy and HE staining were performed on accidentally dead rats. The other alive rats were sacrificed after microPET/CT scan at 24 h post-operation, and their brain tissues were taken out quickly to detect the infarction by triphenyl tetrazolium chloride ( TTC) staining. The pathological results were taken as the gold criteria. Fisher exact test was used to compare the difference of accuracy for diagno-sing CIR models between neurological function score ( NFS) and microPET/CT. Results According to the pathology, there were 11 CIR models, 4 with subarachnoid hemorrhage ( SAH) , 3 with SAH and cerebral hemorrhage. Between 8-12 h post-operation, 4 rats died accidentally. At 2 h post-operation, the diagnostic accuracies of NFS and microPET/CT were 11/18 and 15/18 (P<0.05). At 24 h post-operation, the diag-nostic accuracies of NFS and microPET/CT were 11/14 and 14/14, respectively, no statistical difference was observed( P>0.05) . Conclusion 18 F-FDG microPET/CT is better than NFS in screening CIR models in early stage.

The inhibitory effect of Withaferin A on the growth of orthotopic xenograft tumor of hepatocellular carcinoma in nude mice and the mechanism / 中国医师杂志

Objective To investigate the inhibitory effect of Withaferin A ( WFA) on the growth of orthotopic xenograft tumor of hepatocellular carcinoma in nude mice and the mechanism of its antitumoral effect. Methods For in vivo model, anti-tumor efficacy of Withaferin A was evaluated in nude mice mod-els of human liver cancer orthotopic xenograft. The nude mice were randomly divided into model group, Sunitinib group,and Withaferin A groups [6, 3 mg/(kg·d)]. All mice were given intraperitoneal injec-tion for 14 days. Tumor volume and tumor weight were observed. Antiangiogenic effects were assessed in vi-vo by the tumor inhibition rate and microvessel density. Quantitative polymerase chain reaction ( QPCR) as-say was used to detect the mRNA expression of vascular endothelial growth factor ( VEGF) , basic fibroblast growth factor (bFGF), angiopoietin-2 (Ang-2), vascular endothelial growth factor receptor 2 (VEGFR2) from tumor tissues. For in vitro experiments, the cell count kit 8 ( CCK8 ) assay was used to detect the effect of Withaferin A on HepG2 cells proliferation. QPCR assay and enzyme-linked immunosorbent assay ( ELISA) were used to detect the mRNA expression of VEGF. Results Compared to the model group, the high-dose Withaferin A group and the Sunitinib group had a significantly lower tumor weight (P<0. 05). The tumor inhibition rate was 42. 69％ in the high-dose Withaferin A group, 20. 22％ in the low-dose With-aferin A group, and 49. 43％ in the Sunitinib group. The growth of HepG2 cells was significantly inhibited by different concentrations of Withaferin A,and the 50％ concentration of inhibition ( IC50 ) of Withaferin A were (2. 64 ± 0. 18)μmol/L at 24 h. Withaferin A (6,3 μmol/L) could inhibit the protein and mRNA ex-pression of VEGF ( P<0. 05 ) . Conclusions Withaferin A significantly reduces the growth of orthotopic xenograft tumor of hepatocellular carcinoma in nude mice via antiangiogenic effect. Downregulation of the protein and mRNA expression of VEGF by WFA may be one mechanism of its anti-liver cancer effect.

Role of autophagy in doxorubicin-induced cardiotoxicity:review / 中国药理学与毒理学杂志

Doxorubicin (Dox) is an effective wide-spectrum antitumor drug. However, its clinical application may be hampered by dose-dependent cardiotoxicity. The mechanisms of cardiotoxicity have not been clearly elucidated, but are known to involve oxidative stress, mitochondrial dysfunction and apoptosis. Autophagy is a lysosome-dependent protein degradation pathway. More recently, many studies have suggested that autophagy plays an important role in Dox-induced cardiotoxicity. This paper gives a systematic review of the role of autophagy in Dox-induced cardiotoxicity.

Simultaneous determination and pharmacokinetics of eight ginsenosides by LC-MS/MS after intravenously infusion of 'SHENMAI' injection in dogs

SHENMAI injection, a prescription comprised of Panax ginseng and Ophiopogon japonicas, is being extensively applied in the field of cardio-protection and immune-modulation in China. Ginsenosides are the main active components in SHENMAI injection. In order to capture and analyze the pharmacokinetic profile of major ginsenosides of SHENMAI injection in Beagle dogs, liquid chromatography equipped with electro-spray ionization and tandem mass spectrometry method was applied in simultaneous determination for protopanaxatriol type ginsenoside [Re, Rf, Rg1], protopanaxadiol type ginsenoside [Rb2, Rb1, Rd, Rc] and oleanolic acid type ginsenoside [Ro]. A C18 column [150 × 2.1mm, 5micro m] and a linear gradient program were used to achieve chromatographic separation, with 0.02% acetic acid solution and acetonitrile. I.S. and ginsenosides were detected by LC-MS/MS in selective reaction mode. Good linearity spanning 5- 1500ng/mL was achieved with the R[2] values higher than 0.99 for all analytes. Limit of quantification of all analytes were 3ng/mL. Intra- and inter-day precisions ranges from 0.47 to15.68 % and accuracies were within the range of 85.27-117.57%. Validated analyzing method was then used in the pharmacokinetic experiment for SMI in dogs. The results showed that the pharmacokinetic profile of protopanaxadiol, protopanaxatriol and oleanolic acid type ginsenoside were significant difference in dogs. Protopanaxadiol type ginsenosides exhibited an extremely higher level of exposure and a much slower elimination process. Whereas protopanaxatriol type ginsenosides were quickly eliminated. We concluded that 20 [S] - protopanaxadiol type ginseno sides could be a potential pharmacokinetic marker of SHENMAI injection

Synthesis of 6-18F-Py-AMD3465 and the microPET/CT imaging of this agent in mice bearing A549 tumor / 中华核医学与分子影像杂志

Objective To synthesize 628F-Py-AMD3465,to investigate its biodistribution in mice and to perform the microPET/CT imaging on mice bearing human lung cancer cell (A549).Methods AMD3465 quaternary ammonium salt precursor was directly labeled with 18F,then 628F-Py-AMD3465 was synthesized through nucleophilic reaction,hydrolysis,neutralization and the product was purified using HPLC.The labeling yield and radiochemical purity were analyzed by HPLC.Fifteen Kunming mice were injected with 5.55 MBq of 628F-Py-AMD3465 and sacrificed at 5,20,40,60 and 120 min postinjection.The selected tissues were harvested and weighed,and the radioactivity in the tissues was measured by an automated γ-spectrometer.The ％ID/g was calculated.MicroPET/CT studies were performed on A549-bearing mice after injecting 6-18F-Py-AMD3465 through vena caudal.Paired t test was used.Results 6-18F-Py-AMD3465 was successfully synthesized with the labeling yield of (9.0±2.0)％,the total synthesis time was about 60 min,and the radiochemical purity was more than 98％.Biodistribution studies showed that the radiouptake was higher in the kidneys and bladder of normal mice,which demonstrated that 6-18 F-Py-AMD3465 was mainly excreted through the kidneys.Biodistribution in A549-bearing mice was similar to that in normal mice.The tumor/muscle ratio at 40 min was 5.0,but the radiouptake of the tumor was still lower than that of the normal lung:(8.05±0.35) ％ID/g vs (9.33±0.66) ％ID/g;t=5.26,P＜0.05.MicroPET/CT imaging showed that the high-uptake location of 6-18F-Py-AMD3465 in tumor-bearing mice was similar to the normal mice,and the tumor uptake reached the maximum level at 45 min post-injection (SUV 0.67).Conclusions 6-18F-Py-AMD3465 can be synthesized by a simple method.A lower uptake could be shown in the tumor compared to that in the lung and the tracer has limited diagnostic value for lung cancer.

Expressions of MK2, HuR, and ICAM-1 in the pulmonary microvascular endothelial cells of the mouse with acute respiratory distress syndrome / 医学研究生学报

Objective Intercellular adhesion molecule-1 (ICAM-1) plays an important role in mediating pulmonary infiltration of neutrophils .The aim of the study was to observe the expression of ICAM-1 and its potential regulators MK 2/HuR in pulmonary micro-vascular endothelial cells ( PMVEC ) in mice with acute respiratory distress syndrome ( ARDS) induced by lipopolysaccharide ( LPS) . Methods Ten 6-8 weeks old healthy C57BL/6 mice were randomly divided into an LPS and a control group of equal number , the former injected intraperitoneally with LPS diluted in 100 μL PBS while the latter with PBS only , both at 5 mg per kg of the body weight .At 24 hours after injection , all the mice were sacrificed .Real-time PCR was used to determine the mRNA expressions of HuR and ICAM-1 in the PMVECs, Western bolt employed to detect the protein expressions of MK2, HuR and ICAM-1, and flow cytometry adopted to measure the ICAM-1 expression on the surface of the PMVECs and pulmonary infiltration of neutrophils . Results The W/D ratio in the lung tissue of the mice was significantly lower in the LPS than in the control group (3.61 ±0.28 vs 6.16 ±0.40, P<0.05), while the rate of neutrophil infiltration markedly higher in the former than in the latter ([13.92 ±3.23]%vs [3.24 ±1.24]%, P<0.05).The mRNA and protein expressions of ICAM-1 in the PMVECs were significantly elevated in the LPS group as compared with that in the control (P<0.05), and so was the mRNA expression of HuR (P<0.05).No remarkable changes were observed in the expressions of total MK 2 and HuR proteins, but phosphorylated MK2 (p-MK2) and cytoplasmic HuR were increased in the LPS-stimulated mice. Conclusion Specific blockage or reduction of the HuR expression in PMVECs may lower the expression of ICAM-1, reduce neutrophil infiltration , and lessen pathophysiological changes in mice with ARDS .

Changes of glucose metabolism in mouse models of intracerebral hemorrhage：18 F-FDG microPET/CT study / 中华核医学与分子影像杂志

Objective To investigate the brain glucose metabolism with 18 F?FDG microPET/CT in mouse models of intracerebral hemorrhage (ICH). Methods A total of 12 healthy adult male mice were randomly divided into sham operation group (group A, n=6) and ICH model group (group B, n=6) by simple random sampling method. The animal models were established by injecting collagenase Ⅳ into the caudate nucleus of mice. Thereafter (5.5±0.3) MBq of 18F?FDG was injected into caudal vein at 6 h, 24 h, 48 h and 3 d, 5 d, 8 d, 14 d, respectively, following anesthesia. 18 F?FDG microPET/CT scans were ac?quired 30 min after the trace injection. SUV in the perihematomal brain tissue of ICH was measured and an?alyzed. Two?sample t test was used to compare SUV between groups. Results ( 1) Some mice had mild neurologic deficit after the sham operation in group A, while all mice had a marked neurologic deficit in group B, especially at 24 h after 18 F?FDG injection. ( 2) After 6 h, FDG uptake in perihematomal brain tis?sue decreased(SUV=0.80±0.04), which significantly lower than that in the opposite side(SUV=1.10± 0?04;t=2.69, P<0.05) and decreased to the minimum at 24 h(SUV=0.50±0.05). 18F?FDG uptake in perihematomal brain tissue began to increase at 3 d(SUV=1.20±0.05) and kept increasing during the 14 d observation. Compared with the group A, glucose metabolism in group B was significantly lower at each time point(t=37.67-86.60, all P<0.05). Conclusions 18 F?FDG microPET/CT may dynamically reflect the changes of brain glucose metabolism in ICH mouse models. The FDG uptake in the center of ICH may disap?pear and the volume of hematoma with decreased uptake may shrink during the observation period.

Clinical effect of hyperbaric oxygen therapy on groupment acute carbon monoxide poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To summarize the clinical experience of hyperbaric oxygen therapy in the patients with groupment acute carbon monoxide poisoning.</p><p><b>METHOD</b>172 patients with acute carbon monoxide poisoning were received hyperbaric oxygen therapy besides some other regular therapies from january 2007 to december 2011. The clinical effect were analyzed retrospectively.</p><p><b>RESULTS</b>160 patients were cured (93%), 12 cases improved (7%), the total effective rate was 100%. The cure rate of the patients with hyperbaric oxygen therapy within 6 hours after the poisoning for 100% (115/115), It was significantly higher than that of patients treated for more than 6 hours [The cure rate was 78.9% (45/57)], The difference was statistically significant (P < 0.05).</p><p><b>CONCLUSION</b>Treated by hyperbaric oxygen therapy early enough in the patients with acute carbon monoxide poisoning, can prevent or reduce the occurrence of delayed encephalopathy, decreasing disability and mortality.</p>

Diagnostic value of serum CEACAM1 in patients with pancreatic cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the diagnostic value of serum CEACAM1 in patients with pancreatic cancer.</p><p><b>METHODS</b>Fifty patients with pancreatic cancer and 50 with chronic pancreatitis were examine for serum levels of CEACAM1 by enzyme-linked immunosorbent assay (ELISA). The cut-off values and area under curve (AUC) of CEACAM1 was obtained by receiver operating characteristic (ROC) curve. The diagnostic efficiency of the tumor markers for pancreatic cancer was assessed by the fourfold table.</p><p><b>RESULTS</b>The serum level and positivity rate of CEACAM1 in pancreatic cancer patients were higher than those in chronic pancreatitis patients (P<0.05). Based on the ROC curve, the cut-off values and AUC of CEACAM1 were 13.835 ng/ml and 0.780, respectively (P<0.05). In pancreatic cancer patients, the diagnostic sensitivities of the tumor markers decreased in the order of CEACAM1 < CA242 < CA19-9 (P<0.05), and the specificity in the order of CA242 < CA19-9 < CEACAM1 (P<0.05).</p><p><b>CONCLUSION</b>CEACAM1 shows a higher diagnostic sensitivity than CA19-9 and CA242 for pancreatic cancer, but due to its low specificity this marker alone is not sufficient for diagnostic purposes.</p>

Effect of anti-arrhythmia drugs on mouse arrhythmia induced by Bufonis Venenum / 药学学报

This study is to investigate the effects of phenytoin sodium, lidocaine (sodium channel blockers), propranolol (beta-adrenergic receptor antagonist), amiodarone (drugs prolonging the action potential duration) and verapamil (calcium channel blockers) on arrhythmia of mice induced by Bufonis Venenum (Chansu) and isolated mouse hearts lethal dose of Chansu. Arrhythmia of mice were induced by Chansu and then electrocardiograms (ECGs) were recorded. The changes of P-R interval, QRS complex, Q-T interval, T wave amplitude, heart rate (HR) were observed. Moreover, arrhythmia rate, survival rate and arrhythmia score were counted. Isolated mouse hearts were prefused, and the lethal dose of Chansu was recorded. Compared with control group, after pretreatment with phenytoin sodium, broadening of QRS complex and HR were inhibited, and the incidence of ventricular arrhythmia was reduced dramatically, while survival rate was improved; the isolated mouse hearts lethal dose of Chansu was increased significantly. After pretreatment with lidocaine, the prolongation of P-R interval and broadening of QRS complex were inhibited, and the incidences of ventricular arrhythmia were reduced dramatically, while survival rate was improved; the isolated mouse hearts lethal dose of Chansu was increased significantly. After pretreatment with propranolol, prolongation of P-R interval, broadening of QRS complex, prolongation of Q-T interval and HR were inhibited, and the incidences of both supraventricular and ventricular arrhythmias were reduced dramatically, while survival rate was improved. After pretreatment with amiodarone, HR was inhibited, the incidences of ventricular tachycardia were reduced dramatically. Lastly, after pretreatment with verapamil, the prolongation of P-R interval and Q-T interval were inhibited and the incidences of both supraventricular and ventricular arrhythmias were reduced dramatically; the isolated mouse hearts lethal dose of Chansu was reduced significantly. In in vivo experiments, phenytoin sodium was most effective against the mice arrhythmias induced by Chansu while cautious use of verapamil for Chansu inducing arrhythmia should be noted. It is also concluded that mice ventricular arrhythmias induced by Chansu might be most closely related to sodium channel, supraventricular arrhythmias might be related to beta-adrenergic receptor, and calcium channel plays an important role in conduction block. In in vitro experiments, phenytoin sodium was most effective, followed by lidocaine and propranolol, and amiodarone had no obvious effect and verapamil reduced the lethal dose of Chansu.

Brain metastasis treated with Cyberknife / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cyberknife can greatly raise the fractional dose of stereotactic radiosurgery, thus improving its clinical efficacy. We retrospectively analyzed clinical outcomes of brain metastasis treated with Cyberknife.</p><p><b>METHODS</b>We analyzed 40 cases of brain metastases treated with Cyberknife in the Tianjin Cancer Hospital from August 1, 2006 to August 1, 2007, for a total of 68 lesions with maximal diameter of 0.4 - 7.5 cm (average 1.88 cm). Total hypofractional radiated dosage was 18 - 36 Gy (5 - 25 Gy/F, 1 - 5 F) by Cyberknife. We evaluated the remission rate of clinical symptoms, correlation factors to new foci, 3-month local control rates, and 3-month and 1-year survival rates. All patients were followed up for more than 14 months.</p><p><b>RESULTS</b>After 1 week, clinical remission was 90.0% (36/40). After 3 months, the local control rate and therapeutic effective rate were 77.9% (53/68) and 94.1% (64/68), respectively, as observed by cranium augmentation CT or MRI. The three-month, six-month and 1-year survival rates were 97.5% (39/40), 82.5% (33/40) and 67.5% (27/40), respectively. Fourteen patients had neopathy outside the original lesion after 3 months. Neopathy was not correlated with age, whole-brain radiotherapy, number of original lesions, maximum diameter of the original lesion, therapeutic dose per fraction, therapeutic frequency or total therapeutic dose.</p><p><b>CONCLUSIONS</b>Cyberknife got perfect clinical outcomes by higher dosage per fraction. It is an appropriate and valid treatment shortcut for brain metastasis.</p>

Cloning of HLA-A~*0201 and its transient expression on COS-7 cells / 中国免疫学杂志

Objective:To clone HLA A *0201 cDNA and express it transiently on COS 7 cells.Methods:HLA A cDNA isolated from the HLA A *0201 positive lymphocytes by using RT PCR was cloned into pBluescript II SK vector directionally.After the sequence was confirmed,the cDNA was inserted into mammalian expression vector pcDNA3.The recombinant vector was transfected into COS 7 cells by cation liposome.The transient expression on the cells was measured by flow cyteometer.Results:The cDNA was identical with HLA A *0201 cDNA published on Genebank.Determined by flow cytemeter,the expressing rate was recorded for 57%.Conclusion:We have cloned HLA A *0201 successfully and expressed it transiently on COS 7 cell,which would be potentially useful in research on killing tumor restricted by HLA A2.