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Objective To design a novel automatic dispensing and injecting system of positron radiopharmaceuticals,for precise dose dispensing,simplified operation,and reduction of occupational radiation exposure. Methods The automatic dispensing and injecting system was fabricated with tungsten alloy as the shielding material.The performance and radiation protection of the device were assessed. Results The total time of injection using the automatic dispensing and injecting system was about 60 s.The ratio of successful injection in stability test was 100%.The deviation of the dispensing dose with the system was ≤3%.With the tungsten alloy shield(40 mmPb of the cabinet,60 mmPb of the countertop,15 mmPb of the protective shield,and 50 mmPb of the inbuilt jar for radiopharmaceuticals),the average dose rate at 30 cm from the device was 1.44 μSv/h,and the radiation dose at the operator's extremity was reduced by 99%. Conclusions This automatic dispensing and injecting system of positron radiopharmaceuticals is easy to operate with precise dispensing dose.It is safe and meets the requirements of radiation protection.
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Elétrons , Exposição Ocupacional/análise , Doses de Radiação , Proteção Radiológica , Compostos RadiofarmacêuticosRESUMO
Malaria is an acute febrile illness caused by Plasmodium. In Africa where the burden of malaria is extremely high, febrile symptoms caused by respiratory tract infections may challenge the diagnosis of malaria, and patients with unclear diagnosis and administration of antimalarial drugs require more attention. Hereby, a peacekeeper with Plasmodium falciparum infection complicated with bronchopneumonia was reported.
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Objective • To study whether lysine crotonylation can be used as a candidate biomarker for prostate cancer diagnosis, and its correlation with clinical stages and pathologic grades. Methods • Seventy-three cases of tumor and 7 normal prostate tissues were included in the study. The global levels of lysine crotonylation and histone H4 acetylation were detected in each sample by immunohistochemistry. Statistical comparison and correlation analysis were performed. Results • Compared with normal prostate tissue, the global level of lysine crotonylation was significantly reduced in prostate cancer tissue (P=0.001), while histone H4 acetylation levels were close to each other in two groups (P=0.704). No statistical difference in the levels of lysine crotonylation or histone H4 acetylation were found in different clinical stages and pathologic grades (P>0.05). There was no correlation between histone H4 acetylation and clinical stages or pathologic grades of prostate cancer. There was a positive correlation between lysine crotonylation and the grading of prostate cancer (r=0.493, P=0.000). Conclusion • Compared to histone H4 acetylation, lysine crotonylation is a better candidate biomarker to diagnose prostate cancer.
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Objective To evaluate the safety and immunogenicity of split influenza vaccine (Anflu(R) ). Methods An open-labeled clinical trial was carried out in adults aged 18-60 years and elders aged over 60 years from August to September, 2010 in Shenyang, Liaoning province. One dose of split influenza vaccine was administered and adverse events were observed. Serum samples were obtained prior to vaccination and 21 days post vaccination. A/H1N1, A/H3N2 and B antibodies against influenza virus were measured using micro-hemagglutination inhibition (HI) assay. Results A total of 130 subjects were recruited and 120 paired serum samples were obtained. The overall rate of adverse events was 2.3% (3/130) and all of them with systemic reaction. No single serious adverse event was reported. 21 days after the vaccination, the sero-conversion rates of A/H1N1, A/H3N2 and B antibodies against influenza virus among adults were 82.5%, 93.7% and 92.1%, respectively. The Geometric Mean Titer (GMT) ratios were 20.2, 32.0 and 11.4, while the sero-protection rates were 92.1%, 98.4% and 98.4%, respectively. The sero-conversion rates of antibodies among elders were 89.5%, 91.2% and 87.7%, with the GMT ratios as 23.9, 39.8 and 15.1, respectively. The seroprotection rates were 93.0%, 94.7% and 96.5%,respectively. Conclusion All indexes ofA/H1N1,A/H3N2 and B antibodies exceeded the licensure criteria established by the EU Committee for Medicinal Products for Human Use,proving the trial vaccine Anflu(R) with good safety and immunogenicity.
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This study was aimed to explore the potential therapy of Gambogic acid (GA) combined with magnetic nanoparticle of Fe3O4 (Fe3O4-MNP) on leukemia. The proliferation of U937 cells and the cytotoxicity were evaluated by MTT assay. Cell apoptosis was observed and analyzed by microscopy and flow cytometry respectively. The expressions of gene and protein were detected by quantitative real-time polymerase chain reaction and Western blot respectively. The results showed that GA enhanced the cytotoxicity for U937 cells in dose- and time-dependent manners. The Fe3O4-MNP itself had not cytotoxicity, but could enhance the inhibitory effect of GA on proliferation of U937 cells. The apoptotic rate of U937 cells induced by combination of GA with Fe3O4-MNP was higher than that by GA alone. The typical apoptotic features of cells treated with GA and Fe3O4-MNP were observed. The expression levels of caspase-3 and bax after co-treatment of GA and Fe3O4-MNP were higher than that exposed to GA or Fe3O4-MNP alone, but the expressions of bcl-2, NF-kappaB and survivin were down-regulated. It is concluded that Fe3O4-MNP can promote GA-induced apoptosis in U937 cells, and the combination of GA with Fe3O4-MNP may be a safer and less toxic new therapy for leukemia.
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Humanos , Apoptose , Compostos de Ferro , Farmacologia , Magnetismo , Nanopartículas , Células U937 , Xantonas , FarmacologiaRESUMO
Objective: To detect and identify differentially expressed proteins in the seta of patients with HBV-related primary hepatic carcinoma and discuss their possible role in early diagnosis of primary hepatic carcinoma. Methods: The surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS) was used to screen for the differentially expressed serum proteins in patients with HBV-related primary hepatic carcinoma, liver cirrhosis, chronic hepatitis, and healthy adults. Then the most differential protein sample was isolated and purified by ionic exchange chromatography and was subjected to mass spectrometry analysis. The screening results were used to establish a diagnosis model for hepatic carcinoma and the accuracy and sensitivity of the model were assessed. Results: CM10(weak cation exchange)chip found 44 differentially expressed protein peaks (P<0.05) in hepatic carcinoma group compared with those in the healthy adult group, with 21 up-regulated and 23 down-regulated. Fifty-one differential peaks were identified in hepatic carcinoma group compared with those in the liver cirrhosis group (P<0.05), with 47 up-regulated and 4 down-regulated. The expression of protein with a mass-to-charge ratio (m/z) of 5 805 gradually increased in order in the healthy adult, chronic hepatitis, liver cirrhosis and hepatic carcinoma patients; and the expression in hepatic carcinoma group was significantly higher than that in the healthy adult group (P<0.01); peptide mass fingerprint (PMF) after enzyme hydrolysis showed that 2 of the peptides were partially identical to chondroitin sulfate synthase 2. A diagnosis model of hepatic carcinoma was successfully established based on the differentially expressed proteins, with an accuracy of 94.82% ([23+32]/58), a sensitivity of 88.46% (23/ 26), and a specificity of 100% (32/32). Conclusion: We have successfully screened out the differentially expressed proteins in the sera of patients with HBV-related primary hepatic carcinoma; the most differentially expressed protein (5 805) has 2 peptides partially identical to chondroitin sulfate synthase 2 in sequence. The established model may help to diagnose HBV-related primary hepatic carcinoma.
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Objective: To investigate the dynamic expression profile of KCNQ1 channel in rat developing pancreas and adult rat islets, so as to provide experimental basis for further analyzing the possible role of KCNQ1 channel in β-cell development and function. Methods: The gene expression patterns of embryonic day 12. 5 (E12. 5), E15. 5, E18. 5, new-born and adult rat pancreas were compared using the GeneChipRAE 230A. The expressions of KCNQ1 channel subunits in rat pancreas at the above five stages and adult rat islets were also detected and analzyed by RT-PCR. Results: The results of genechip showed that the expression of transcription factors related to endocrine cell differention and maturation peaked at E15. 5 and E18. 5, respectively. The expression of mature β-cell specific genes increased significantly at E18. 5, but KCNQ1 and KCNE1 only started to express at E18. 5. The results of RT-PCR showed expression of multiple KCNQ1 channel subunits in adult rat pancreas and islet. Conclusion: The expression of KCNQ1 channel appears in the later stage of pancreatic development when the endocrine cells undergo further maturation, and has a higher level in adult islets. The expression profile of KCNQ1 channel subunits indicates that KCNQ1 channel might be expressed in mature β-cell and involved in its endocrine function.
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The aim of this study was to investigate the potential benefit of combination therapy with magnetic nanoparticle of Fe(3)O(4) and 5-Bromotetrandrine (5-BrTet) on chronic leukemia. The apoptosis was detected by flow cytometry (FCM), Wright staining and light microscope; the expressions of BAX and BCL-2 were measured by Western blot. The results showed that combination of daunorubicin (DNR) with either MNP (Fe(3)O(4)) or 5-BrTet exerted a potent cytotoxic effect on K562/A02 cells, while MNP (Fe(3)O(4)) and 5-BrTet co-treatment could synergistically enhance DNR-induced apoptosis. After treated with this regimen, the typical apoptotic morphological features were found in K562/A02 cells; the expression level of BCL-2 decreased and BAX increased markedly. It is concluded that MNP (Fe(3)O(4)) or 5-BrTet with DNR can induce apoptosis in K562/A02 cells, and they show distinct synergism when used together. The down-regulation of BCL-2 and the up-regulation of BAX may play important roles.
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Humanos , Apoptose , Benzilisoquinolinas , Farmacologia , Daunorrubicina , Farmacologia , Regulação para Baixo , Compostos Férricos , Regulação Leucêmica da Expressão Gênica , Células K562 , Nanopartículas , Proteínas Proto-Oncogênicas c-bcl-2 , Metabolismo , Regulação para Cima , Proteína X Associada a bcl-2 , MetabolismoRESUMO
This study was aimed to investigate the reversal effect of 5-bromotetrandrine (5-BrTet) and magnetic nanoparticle of Fe(3)O(4) (Fe(3)O(4)-MNPs) combined with DNR in vivo. The xenograft leukemia model with stable multiple drug resistance in nude mice was established. The two sub-clones of K562 and K562/A02 cells were respectively inoculated subcutaneously into back of athymic nude mice (1 x 10(7) cells/each) to establish the leukemia xenograft models. Drug resistant and the sensitive tumor-bearing nude mice were both assigned randomly into 5 groups: group A was treated with NS; group B was treated with DNR; group C was treated with nanoparticle of Fe(3)O(4) combined with DNR; group D was treated with 5-BrTet combined with DNR; group E was treated with 5-bromotetrandrine and magnetic nanoparticle of Fe(3)O(4) combined with DNR. The incidence of tumor formation, growth characteristics, weight and volume of tumor were observed. The histopathologic examination of tumors and organs were carried out. The protein levels of BCL-2, BAX, and Caspase-3 in resistant tumors were detected by Western blot. The results indicated that 5-BrTet and magnetic nanoparticle of Fe(3)O(4) combined with DNR significantly suppressed growth of K562/A02 cell xenograft tumor, histopathologic examination of tumors showed the tumors necrosis obviously. Application of 5-BrTet and magnetic nanoparticle of Fe(3)O(4) inhibited the expression of BCL-2 protein and up-regulated the expression of BAX, and Caspase-3 protein in K562/A02 cell xenograft tumor. It is concluded that 5-bromotetrandrine and magnetic nanoparticle of Fe(3)O(4) combined with DNR have significant tumor-suppressing effect on MDR leukemia cell xenograft model.
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Animais , Feminino , Humanos , Camundongos , Antineoplásicos , Farmacologia , Benzilisoquinolinas , Farmacologia , Daunorrubicina , Farmacologia , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Compostos Férricos , Células K562 , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Multidrug resistance (MDR) plays a major role in the failure of cancer chemotherapy. Since Fe(3)O(4)-magnetic nanoparticle loaded with daunorubicin (DNR) can overcome multidrug-resistance of K562 cells in vitro, the effect of Fe(3)O(4)-magnetic nanoparticle loaded with DNR on multidrug-resistant K562 cells was studied in vivo, the K562-n and its MDR counterpart K562-n/VCR cells were inoculated subcutaneously into both sides of the back of nude mice to establish a human leukemia xenograft model. The mice were randomly divided into group A receiving normal saline, group B receiving DNR, group C receiving Fe(3)O(4)-magnetic nanoparticle, group D receiving Fe(3)O(4)-magnetic nanoparticle loaded with DNR and group E receiving Fe(3)O(4)-magnetic nanoparticle containing DNR with a magnetic field built on the surface of the tumor tissue. The tumor volume was measured on the day 1, 5, 9, 13, 17 and 21 after the first treatment. Tumor tissues were isolated for examination of the expression of mdr-1 by reverse transcription polymerase chain reaction and Western blotting. The results showed that for K562-n/VCR tumor, the tumor volume was markedly lower in groups D and E than that in groups A, B and C. Pathological observation revealed that the tumor cells of group A and B grew well, some disseminated necrosis and some cells with karyorrhexis and karyopyknosis existed in group C. However, significant fracture, necrosis of cell and subsequently fibrosis were seen in group D and E. The transcription of mdr-1 gene in groups D and E was significantly lower than that in groups A, B and C (group D and E vs group A, B or C, p < 0.05). However, there were no differences about the protein expression of P-gp between these groups. The tumor volume of K562-n in groups C, D and E was markedly lower than that in groups A and B (group C, D and E vs group A or B, p < 0.05). Pathological observation showed that the tumor cell of group A and B grew well, and no obvious necrosis was observed. Significant fracture, necrosis of cell and subsequently fibrosis were seen in group C, D and E. It is concluded that DNR-loaded Fe(3)O(4) magnetic nanoparticles can suppress the growth of the MDR K562-n/VCR tumor in vivo, but can not further enhance its efficacy on the sensitive K562-n tumor as compared to DNR alone. The additional external magnetic field failed to further improve the antitumor effect in vivo.
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Animais , Feminino , Humanos , Camundongos , Daunorrubicina , Farmacologia , Usos Terapêuticos , Portadores de Fármacos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Células K562 , Leucemia , Tratamento Farmacológico , Magnetismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas , Resultado do Tratamento , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The present study was aimed to evaluate the MDR reversal activity of bromotetrandrine (BrTet) in vitro and in vivo. The inhibitory effects of adriamycin (ADM) used alone or in combination with BrTet or Tet on the proliferation of K562 and K562/A02 cells were evaluated by MTT assay. The ADM accumulation and the protein levels of P-glycoprotein (P-gp) were detected by flow cytometry. The mRNA levels of P-gp were determined by RT-PCR. The in vivo effect of BrTet and Tet was investigated by using nude mice grafted with sensitive human leukemia cell line K562 and MDR cell line K562/A02. The results showed that BrTet at 0.25, 0.5 and 1 micromol/L reversed the resistance to ADM in MDR K562/A02 cells in a dose-dependent manner. Flow cytometry suggested that BrTet significantly increased the intracellular accumulation of ADM in K562/A02 cells in a dose-dependent manner. BrTet also inhibited the overexpression of P-gp in K562/A02 cells, and down-regulated mdr1 expression. In nude mice bearing K562 xenografts on the left flank and K562/A02 xenografts on the right flank, intraperitoneal injection of 10 mg/kg BrTet significantly enhanced the antitumor activity of ADM against K562/A02 xenografts with inhibitory rates of 26.1%, while ADM alone inhibited the growth of K562/A02 xenografts only by 5.8%. No enhancement effect by BrTet was seen in K562 xenografts. It is concluded that BrTet shows significant MDR reversal activity in vitro and in vivo. Its activity may be related to the inhibition of P-gp overexpression and the increase intracellular accumulation of anticancer drugs. BrTet may be a promising-MDR modulator for eventual assessment in the clinic.