Molecularly imprinted polymers (MIPs) were applied as molecular recognition elements to an electrochemical sensor for phenylephrine. A MIPs membrane was created on a glassy carbon electrode. SEM revealed a gradual change on the morphology of modified electrodes as the ratios of function monomer and cross-linking varied. When the ratio was 4:40, the surface morphology between the imprinted electrode (M-electrode) and the control electrode (N-electrode) became unambiguously different. This artificial receptor exhibited high selectivity for the template compared to closely related analogue. The response of the sensor varied in different concentration range might due to the heterogeneity of the MIPs membrane. This sensor was also used to determine phenylephrine in tablet samples.
Acute myeloid leukemia (AML) remains a therapeutic challenge. Long-term survival rates, in particular for older AML patients, remain poor, highlighting the need for improved and well-tolerated treatment options. AML patients who are unfit for high dose chemotherapy in the US are often prescribed hypomethylating agents (azacitidine or decitabine) although the efficacy of these agents in this population was modest (Estey, Leukemia 2013). SGN-CD33A is a CD33-directed antibody drug conjugate (ADC) that is comprised of a cysteine-engineered anti-CD33 antibody, a cleavable dipeptide linker that is highly stable in circulation, and a PBD dimer that binds DNA with high intrinsic affinity. The ADC is active as a single agent in preclinical models of AML that are characteristically resistant to chemotherapy (multi-drug-resistant, MDR-positive) (Sutherland et al. Blood 2013). In the present study, we tested the activity of SGN-CD33A in combination with hypomethylating agents (HMA), azacitidine or decitabine. We hypothesized that the combination of SGN-CD33A with an HMA will have greater impact on the DNA repair pathway in leukemic cells, furthering the processes of apoptosis and cell death. MDR-positive AML cells were treated for 96 hours with SGN-CD33A and each of the HMAs alone and in combination, evaluating both simultaneous as well as sequential administration. Enhanced tumor cell killing was observed when AML cells were treated concomitantly with the combination of SGN-CD33A and an HMA or pre-treated with HMAs prior to the addition of SGN-CD33A. Superior anti-leukemic activity of subtherapeutic doses of SGN-CD33A in combination with HMAs was observed in mouse xenograft models generated with MDR-positive AML cell lines. In the difficult to treat HEL9217 model, decitabine or a single dose of 200 mcg/kg SGN-CD33A delayed tumor growth, while significant reductions in tumor growth were observed for the combination treatment (p=0.0001). Improved antitumor activity in this model was also observed for SGN-CD33A in combination with azacitidine. SGN-CD33A in combination with decitabine significantly reduced tumor burden compared to either agent alone in the TF1-α AML model (p=0.0002). Similarly, sequenced dosing of azacitidine followed by a subtherapeutic dose of 30 mcg/kg SGN-CD33A in mice bearing KG-1 xenografts delivered greater antitumor activity compared to the individual agents (p=0.0001). To investigate the mechanism underlying the enhancement in antileukemic activity, we looked at the impact of HMAs alone and in combination with SGN-CD33A on myeloid marker expression, PBD drug release, and impact on the DNA damage and apoptotic pathways. In AML cell lines that did not show improved cytotoxic activity with the combination of SGN-CD33A and HMA, HMA treatment appeared to have no positive effect on the cell surface levels of CD33. However in responsive cell lines such as TF1-α, HMA treatment resulted in time- and dose-dependent increases in the levels of CD33. Significant increases in expression were observed between 2 and 4 days with decitabine and after 4 days with azacitidine. In addition, more PBD dimer drug from SGN-CD33A was incorporated into DNA in HMA treated cells. Concomitant, the treatment of AML cells with the combination of SGN-CD33A and HMA resulted in greater DNA damage and apoptosis as shown by the increased levels of the early DNA damage marker, γH2AX, and the formation of cleaved PARP, an apoptosis marker, compared to either agent alone. Studies are in progress to investigate the effects on other components of the DNA repair and cell cycle pathways. These findings demonstrate that SGN-CD33A can be successfully combined with hypomethylating agents to deliver marked antitumor activity in preclinical drug-resistant models of AML. Disclosures Sutherland: Seattle Genetics, Inc.: Employment. Yu:Seattle Genetics, Inc.: Employment. O'Day:Seattle Genetics,Inc: Employment. Alley:Seattle Genetics,Inc.: Employment. Anderson:Seattle Genetics, Inc.: Employment. Emmerton:Seattle Genetics, Inc.: Employment. Zeng:Seattle Genetics, Inc.: Employment. O'Meara:Seattle Genetics, Inc: Employment, Equity Ownership. Feldman:Seattle Genetics,Inc: Employment. Kennedy:Seattle Genetics,Inc: Employment, Equity Ownership, Honoraria, Speakers Bureau. Ryan:Seattle Genetics, Inc.: Employment. Benjamin:Seattle Genetics, Inc: Employment.
Background: Development dysplasia of the hip (DDH) is a common childhood orthopedic disease in clinic. The cause of DDH is not yet clear. If DDH is not treated promptly or correctly, it will seriously affect the life quality of the child. At present, surgery is the main means of treating older DDH, but it is easy to appear development dysplasia of the hip after surgery, and the joint movement is limited after surgery. For modern medicine, it has not many treatments to solve this problem. As one of the commonly used treatment methods, but the effect of routine functional exercise is not ideal. Traditional Chinese medicine fumigation and washing belongs to the category of Chinese medicine external treatment, which can directly act on the focus. It has the functions of relaxing muscles and tendons and removing obstruction from meridians, activating blood to eliminate stagnation. It has achieved good effects in relieving joint disorders, but it is lack of the high-quality evidence support, so there is controversy about the clinical application of traditional Chinese medicine fumigation and washing. This study will conduct a systematic review to compare the application effect and safety of traditional Chinese medicine fumigation and washing as a complementary and alternative therapy and traditional rehabilitation training in the treatment of postoperative joint function recovery after development dysplasia of the hip in children. The research results will provide evidence-based medical evidence to support the choice of treatment for the disease. Methods: Using computer to retrieve PubMed, ScienceDirect, Web of Science, EMBase, Cochrane Library, WANFANG Database, CNKI, and VIP Database, CBM, and using the method of combining mesh words with item words to retrieve the Chinese and English databases, to retrieve the randomized controlled study on the application of traditional Chinese medicine fumigation and washing on the recovery of joint function after development dysplasia of the hip in children. The retrieval time is from January 1990 to January 2021. Two researchers screen and evaluate the quality of the retrieved literatures according to the inclusion and exclusion criteria. In the event of a disagreement, a third researcher will join the discussion to resolve the disagreement. Using Revman 5.3 software to conduct meta-analysis. Results: This study will compare the application effect and safety of traditional Chinese medicine fumigation and washing as a complementary and alternative therapy and traditional rehabilitation training in the treatment of postoperative joint function recovery after development dysplasia of the hip in children. Conclusion: The results of this study will be published in an internationally influential academic journal to provide evidence-based medical evidence for the selection of supplement and alternative therapies on the recovery of joint function after development dysplasia of the hip in children. Ethics and dissemination: This study does not involve specific patients, and all research data comes from publicly available professional literature, so an ethics committee is not required to conduct an ethical review and approval of this study. OSF Registration: DOI 10.17605/OSF.IO/RUHK5.
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