Objective Radionuclide-labeled low molecular weight polypeptide is reeently advocated for the diagnosis and treatment of malignant tumor. The purpose of this study was to evaluate the anti-tumor effect of 131Ⅰ-Tyr-octreotide in nude mice bearing human non-small cell lung cancer (NSCLC). Methods 131Ⅰ-Tyr-octreotide was prepared by Ch-T method. The radiochemical purity was measured and biodistribution was evaluated. The nude mice models bearing human NSCLC were studied and divided into four groups: group A injected 131Ⅰ-Tyr-octreotide through tail vein, group B injected normal saline, group C injected 131Ⅰ-Tyroctreotide through stroma and group D injected 131Ⅰ through stroma. The radioactivity ratio of tumor to normal tissue (T/NT) was calculated over region of interest (ROI). The tumor cell cycle and cell apoptosis were analyzed by flow cytometry (FCM), terminal deoxynucleotidyl transferase mediated dUTP-biotion nick end labeling (TUNEL) and histopathological analysis. Statistical analysis was performed with SPSS 11.0, and the comparison for difference between groups performed with one-way ANOVA analysis. Results The labeled radiochemical purity was (95.23±1.67)% and specific activity of 3.5×106Bq/ug. The biodistributiou showed high uptake in kidney, and low uptake in liver and spleen. The radioactive uptake in group C was higher than the other groups, and the retention time was longer. The T/NT was 52.74±0.13 after 24 h, which was much higher than that the other groups (group D: 8.90±0.23, group A: 6.42±0.02, q=628.81 and 664.33, all P<0.05). The resuits of tmnor cell cycle determined by FCM showed that the G1 phase was blocked mast remarkably in group C than the other groups [group C: (83.17±6.86)%, group A: (57.02±18.81)%, group D: (49.29±7.80)%, group B: (45.88±5.13)%, q=5.29, 6.86, 7.55, 1.56, 2.26, 0.69, all P<0.05]. Apeptotic cells were observed by TUNEL, and apoptotic body was detected by immuno-histochemical examination. Conclusions 131Ⅰ-Tyr-octreotide was easily labeled by Ch-T. 131Ⅰ-Tyr-octreotide could induce tumor cell apoptosis and inhibit the tumor cell of NSCLC. It might be a potential target-directed agent in NSCLC.

To identify whether a highly repeated GT sequence from DCA1 promoter from Dunaliella salina,which have been proved to be a salt-inducible promoter in our previous study,would be a salt-inducible regulation element,different primers were designed to amplify 6 different-length fragments of DCA1 promoter from D.salina by PCR.After these fragments were respectively inserted into the HindⅢ-BamH I sites of the vector pU?GUS,serial expression vectors containing the gus gene were generated.D.salina cells transformed with these recombinant plasmids by electroporation were grown in liquid media containing different concentrations of sodium chloride respectively.GUS enzyme activity was measured histochemically and fluorometrically.The results revealed that 3 fragments containing GT repeated sequence drove the external gus gene expression and the expression pattern of the gus gene was regulated by the concentrations of sodium chloride.Additionally,the 2 fragments without tandem GT sequence drove the gus gene expression,but the expression pattern of the gus gene wasn't regulated by the concentration of sodium chloride;Also,the upstream fragment of the tandem GT sequence wasn't able to drive the gus gene expression.In conclusion,the highly repeated GT sequence from the DCA1 promoter plays an important role in the salt-inducible regulation of DCA1 promoter from D.salina and might be a novel salt-inducible element.

5 mm and ≤8 mm in 4 cases.The mean value was 4.2 mm. Four patients noticed reduction in their vision and two had diplopia.Those patients were examined by CT or MR.Direct venography was performed in each patient.After the diagnosis of OVM was confirmed, intralesional injection of BLE was performed.The efficacy of the treatment and complications were observed during the following 8 to 42 months(mean 23 months).Results The BLE were successfully injected in all the patients.All patients had resolution of proptosis and diplopia.Three patients gained improvement of visual acuity.The periorbital swelling occurred in all patients after operation and resolved within 1 week without special treatment.Other complications,such as orbital hemorrhage and periorbital scar,were not observed during following-up.Conclusion Intralesional injection with BLE is convenient,safe and efficient for the treatment of OVM.

OBJECTIVETo assess the clinical efficacy and safety of surrounding needle, moxibustion and hot compress of TCM herbs for localized scleroderma.

METHODSForty-two cases of localized scleroderma were randomly divided into an acupuncture + herb group (23 cases, group A) and a heparin sodium group (19 cases, group B). Both the two groups were orally administrated with centella triterpenes tablets and vitamin E, group A was additionally treated with surrounding needle at local area, moxibustion at affected site and Hegu (LI 4), Zu sanli (ST 36) as well as hot external application of "hot compress herbs" at local location, while group B was treated with external application of heparin sodium cream. Both the two groups were treated for consecutive 6 months, and scores of skin sclerosis, joint pain and function were compared before and after the treatment. Also the efficacy and safety of TCM syndrome were assessed.

RESULTSCompared with that before the treatment, the scores of skin sclerosis, joint pain and joint function in the group A after treatment were significantly decreased (all P < 0.01), the score of skin sclerosis in the group B was improved (P < 0.05), and the three types of score in the group A was obviously lower than those in the group B (both P < 0.05). The total effective rate was 86.4% (19/22) in the group A, which was superior to 52.6% (10/19) in the group B (P < 0.05).

CONCLUSIONThe surrounding needle, moxibustion and external application of "hot compress herbs" could improve skin sclerosis in patients with localized scleroderma, which has obvious efficacy and relative safety.

Acupuncture Therapy ; Adolescent ; Adult ; Aged ; Combined Modality Therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Moxibustion ; Scleroderma, Systemic ; drug therapy ; therapy ; Young Adult

OBJECTIVETo optimize the preparation process of gemcitabine polybutylcyanoacrylate nanoparticles (GCTB- PBCA-NP).

METHODSAccording to the particle size, the entrapment efficiency and the loading quantity of GCTB-PBCA-NP, single factor analysis was carried out to optimize the component composition and preparation process based on an orthogonal design.

RESULTSThe mean particle size of the NP was (112-/+9) nm with an entrapment efficiency of (54.12-/+2.43)% and drug loading of (11.08-/+0.89)%.

CONCLUSIONAn optimized nanoparticular drug delivery system is obtained by emulsion polymerization.

Chemistry, Pharmaceutical ; Deoxycytidine ; analogs & derivatives ; chemical synthesis ; Drug Delivery Systems ; Enbucrilate ; chemical synthesis ; Nanoparticles ; chemistry

BACKGROUNDIn tumors the process of apoptosis occurs over an interval of time after chemotherapy. It is important to determine the best time for detecting apoptosis by in vivo imaging. In this study, we evaluated the dynamics and feasibility of imaging non-small cell lung cancer (NSCLC) apoptosis induced by paclitaxel treatment using a (99)Tc(m)-labeled Annexin V recombinant with ten consecutive histidines (His10-Annexin V) in a mouse model.

METHODS(99)Tc(m)-His10-Annexin V was prepared by one step direct labeling; radio-chemical purity (RCP) and radio-stability was tested. The binding of (99)Tc(m)-His10-Annexin V to apoptotic cells was validated in vitro using camptothecin-induced Jurkat cells. In vivo bio-distribution was determined in mice by dissection. The human H460 NSCLC tumor cell line (H460) tumor-bearing mice were treated with intravenous paclitaxel 24, 48 and 72 hours later. (99)Tc(m)-His10-Annexin V was injected intravenously, and planar images were acquired at 2, 4 and 6 hours post-injection on a dual-head gamma camera fitted with a pinhole collimator. Tumor-to-normal tissue ratios (T/NT) were calculated by ROI analysis and they reflected specific binding of (99)Tc(m)-His10-Annexin V. Mice were sacrificed after imaging. Caspase-3, as the apoptosis detector, was determined by flow cytometry, and DNA fragmentation was analyzed by the terminal deoxynucleotidytransferase mediated dUTP nick-end labeling (TUNEL) assay. Nonspecific accumulation of protein was estimated using bovine serum albumin (BSA). The imaging data were correlated with TUNEL-positive nuclei and caspase-3 activity.

RESULTS(99)Tc(m)-His10-Annexin V had a RCP > 98% and high stability 2 hours after radio-labeling, and it could bind to apoptotic cells with high affinity. Bio-distribution of (99)Tc(m)-His10-Annexin V showed predominant uptake in kidney, relatively low uptake in myocardium, liver and gastrointestinal tract, and rapid clearance from blood and kidney was observed. The T/NT was significantly increased after paclitaxel treatment, whereas it was low in untreated tumors (T/NT = 1.43 ± 0.18). The %ID/g activity in Group 2 (24 hours), Group 3 (48 hours) and Group 4 (72 hours) after treatment was 2.55 ± 0.73, 3.35 ± 1.10, and 3.4 ± 0.96, respectively. Whereas in the non-treated group, Group 1, %ID/g was 1.10 ± 0.18. The radiotracer uptake was positively correlated to the apoptotic index (r = 0.852, P < 0.01), as well as caspase-3 activity (r = 0.816, P < 0.01).

CONCLUSIONThis study addresses the dynamics and feasibility of imaging non-small cell lung tumor apoptosis using (99)Tc(m)- His10-Annexin V.

Animals ; Annexin A5 ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Apoptosis ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cell Line, Tumor ; Disease Models, Animal ; Histidine ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Mice ; Organotechnetium Compounds ; Paclitaxel ; therapeutic use ; Radiopharmaceuticals

OBJECTIVE: To establish a simple, sensitive in vitro method to evaluate oxygen/glucose deprivation (OGD)-induced injury of brain hippocampal slices in rats. METHODS: Rat hippocampal slices were incubated in 2% 2, 3, 5-triphenyltetrazolium chloride (TTC) solution after oxygen/glucose deprivation. They were then soaked in a measured volume of ethanol and dimethylsulfoxide (50:50) to extract the TTC formazan Product which was then measured by spectrophotometry. OGD induced LDH release was simultaneously measured. RESULTS: Progressive prolongation of OGD induced hippocampal injury resulted in decreased formazan coloration as determined by spectrophotometry. There was a parallel increase in LDH release, thus a negative correlation in these two products was noted. (r=-0.933,P <0.01). The injury was attenuated in the brain slices pre-treated with nimodipine, dexamethasone, and ketamine, but not ONO-1078. CONCLUSION: Solvent extraction and spectrophotometric quantification of formazan represents an objective measurement of OGD-induced injury of rat hippocampal slices.

OBJECTIVETo explore the functional brain localization with magnetic resonance imaging (MRI) after acupuncturing the Yuan-Source and He-Sea acupoints of Stomach Meridian of Foot-Yangming (ST).

METHODSThe study was performed in 30 healthy volunteers who underwent acupuncture at Yuan-Source acupoint (Chongyang, ST42) and He-Sea acupoint (Zusanli, ST36) (ST group). Ten of these were also underwent acupuncture at the non-acupoints as the control group. Blood oxygenation level dependent functional MRI was performed.

RESULTSIn the ST group, signal increasing areas were demonstrated in bilateral superior temporal gyri (Broadmann 22), bilateral supramarginal gyri (Broadmann 40), bilateral cerebellar hemispheres, bilateral cingulate gyri and isthmus of cingulate gyri (Broadmann 32, 30), bilateral superior parietal lobules (Broadmann 7); signal decreasing areas were shown in bilateral orbital gyri (Broadmann 11), bilateral temporal pole (Broadmann 38), right inferior frontal gyrus (Broadmann 47) and right medial occipitotemporal gyrus (Broadmann 36). In the control group, signal increases areas were demonstrated in superior temporal gyri, precentral gyri, cingulate gyri, thalamus, insula and cerebellum. The size, signal intensity and number of increasing areas in control group are less than in ST group.

CONCLUSIONCombined acupuncture of Yuan-Source and He-Sea acupoints of ST can activate and decrease the multiple brain regions of "splanchnic brain" and thus reach a new functional balance to relieve pain.

Acupuncture Points ; Adult ; Brain ; physiology ; Electroacupuncture ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Meridians ; Young Adult

BACKGROUND: Brain injury can promote fracture healing is becoming an issue of concern, but the underlying mechanism remains unknown.OBJECTIVE: To establish a model of cerebral injury combined with right tibial fracture, and to investigate the cerebrospinal fluid and serum levels of calcitonin gene-related peptide, nerve growth factor and insulin-like growth factor-1.METHODS: New Zealand white rabbits were randomly divided into four groups: group A: blank control group;group B: simple brain injury group; group C: simple tibial fracture group; group D: tibial fracture combined with brain injury. The cerebrospinal fluid and serum levels of calcitonin gene-related peptide, nerve growth factor and insulin-like growth factor-1 were detected at different time points. The rabbits in the groups C and D were sacrificed at 1, 4 and 8 weeks after modeling to remove the whole tibia, and scanned by X-ray. The callus volume was calculated, and the pathological changes were analyzed.RESULTS AND CONCLUSION: The fracture healing was faster in the group D than the group C. The callus volume,trabecular width, trabecular area ratio, and the number of newly born vessels in the group D were significantly higher than those in the group C at 4 weeks after modeling (P < 0.05). The cerebrospinal fluid and serum levels of calcitonin gene-related peptide, nerve growth factor and insulin-like growth factor-1 in the group D were significantly higher than those in the group C (P < 0.05), and the cerebrospinal fluid levels reached the maximum values earlier than did the serum levels. Furthermore, in the group D, the calcitonin gene-related peptide level was increased earlier than the other two factors. To conclude, calcitonin gene-related peptide, nerve growth factor and insulin-like growth factor-1 are essential factors involved in promoting fracture healing after traumatic brain injury, and moreover calcitonin gene-related peptide shows a stronger ability than the other factors.

OBJECTIVETo study the effect of hyperbaric oxygenation (HBO) on the differentiation of the implanted human neural stem cells (hNSCs) into neurons in neonatal rats following hypoxic-ischemic brain damage (HIBD).

METHODSHIBD model was prepared by ligation of the left common carotid artery, followed by 8% hypoxia exposure in 7-day-old Sprague-Dawley rat pups. Three days later, the rats received implantation of hNSCs into the left cerebral ventricles. Then the survived rats were randomly divided into two groups: transplantation alone and transplantation+HBO (n=8 each). HBO treatment was administered (1.8 ATA, 1 hr once daily for 10 days) in the transplantation+HBO group 1 hr after hNSCs transplantation. Brains were removed 10 days after transplantation. Frozen coronal sections were prepared for immunofluorescence analysis to detect the neural differentiation of the transplanted cells in the cerebral cortex and hippocampus.

RESULTSDifferentiated neurons of implanted cells distributed mainly in the cortex and the hippocampus of the injured side. There was no difference in the number of neurons in the cortex between the two groups, while the number of neurons in the hippocampus significantly increased in the transplantation+HBO group compared with that in the transplantation alone group (231.4+15.1 vs 162.6+5.6; P<0.05).

CONCLUSIONSHBO treatment may promote the differentiation of implanted hNSCs into neurons in the hippocampus of neonatal rats following HIBD.

Animals ; Animals, Newborn ; Cell Differentiation ; Female ; Humans ; Hyperbaric Oxygenation ; Hypoxia-Ischemia, Brain ; therapy ; Male ; Neurons ; cytology ; Rats ; Rats, Sprague-Dawley ; Stem Cell Transplantation