21 research outputs found

    Vitamin D Binding Protein-Macrophage Activating Factor Directly Inhibits Proliferation, Migration, and uPAR Expression of Prostate Cancer Cells

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    Background: Vitamin D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of tumor growth. Its activity, however, has been attributed to indirect mechanisms such as boosting the immune response by activating macrophages and inhibiting the blood vessel growth necessary for the growth of tumors. Methods and Findings: In this study we show for the first time that DBP-maf exhibits a direct and potent effect on prostate tumor cells in the absence of macrophages. DBP-maf demonstrated inhibitory activity in proliferation studies of both LNCaP and PC3 prostate cancer cell lines as well as metastatic clones of these cells. Flow cytometry studies with annexin V and propidium iodide showed that this inhibitory activity is not due to apoptosis or cell death. DBP-maf also had the ability to inhibit migration of prostate cancer cells in vitro. Finally, DBP-maf was shown to cause a reduction in urokinase plasminogen activator receptor (uPAR) expression in prostate tumor cells. There is evidence that activation of this receptor correlates with tumor metastasis. Conclusions: These studies show strong inhibitory activity of DBP-maf on prostate tumor cells independent of it

    Immobilization of Escherichia coli Cells by Use of the Antimicrobial Peptide Cecropin P1

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    An immobilization scheme for bacterial cells is described, in which the antimicrobial peptide cecropin P1 was used to trap Escherichia coli K-12 and O157:H7 cells on microtiter plate well surfaces. Cecropin P1 was covalently attached to the well surfaces, and E. coli cells were allowed to bind to the peptide-coated surface. The immobilized cells were detected colorimetrically with an anti-E. coli antibody-horseradish peroxidase conjugate. Binding curves were obtained in which the signal intensities were dependent upon the cell concentration and upon the amount of peptide attached to the well surface. After normalization for the amount of peptide coupled to the surface and the relative binding affinity of the antibody for each strain, the binding data were compared, which indicated that there was a strong preference for E. coli O157:H7 over E. coli K-12. The cells could be immobilized reproducibly at pH values ranging from 5 to 10 and at ionic strengths up to 0.50 M

    THE VIBRATIONAL FREQUENCIES OF HALOSIL YLENES HSiX (X = F, Cl, Br)

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    Author Institution: Department of Chemistry, The University of KentuckyThere are a number of ambiguities and curiosities found in the published Si-H stretching vibrational frequencies of the ground states, X~1A′\tilde{X}^{1}A^{\prime}, and first excited singlet states, A~1A\tilde{A}^{1}A, of the halosilylenes HSiF, HSiCl, and HSiBr. Here we have investigated these molecules using self-consistent field. SCF, configuration interaction including all single and double excitations, CISD, and triple excitations, CISDT, and complete active space, CAS-SCF, quantum mechanical methods. For the ground and first excited triplet states, all these methods give similar results, but for the excited singlet states, only the CASSCF results are believable

    Outcomes of inadequate empiric therapy and timing of newer antibacterial therapy in hospitalized adults with culture-positive Enterobacterales and Pseudomonas aeruginosa: a multicenter analysis

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    Abstract Background Infections caused by multi-drug resistant Gram-negative pathogens are associated with worse clinical outcomes in critically ill patients. We evaluated hospital outcomes based on adequacy of overall and newer antibacterial therapy for Enterobacterales (ENT) and Pseudomonas aeruginosa (PsA) in US patients. Methods Hospitalized adults ≥ 18 years old with facility-reported antibiotic susceptibility from 2018–2022 across 161 facilities in the BD Insights Research Database were identified as ENT- or PsA-positive. Generalized linear mixed models were used to evaluate the impact of inadequate empiric therapy (IET) and time to initiate newer antibacterials (ceftazidime-avibactam; ceftolozane-tazobactam; cefiderocol; meropenem-vaborbactam; eravacycline; and imipenem-cilcastatin-relebactam) on hospital mortality and post-culture length of stay (LOS). Results Among 229,320 ENT and 36,027 PsA susceptibility results, 1.7% and 16.8% were carbapenem non-susceptible (carb-NS), respectively. Median time to first susceptibility result was longer for carb-NS vs. carb susceptible in ENT (64 h vs. 48 h) and PsA (67 h vs. 60 h). For ENT, IET was associated with significantly higher mortality (odds ratio [OR],1.29 [95% CI, 1.16–1.43, P < 0.0001]) and longer hospital LOS (14.8 vs. 13.3, P < 0.0001). Delayed start to newer antibacterial therapy was associated with significantly greater hospital mortality for ENT (P = 0.0182) and PsA (P = 0.0249) and significantly longer post-culture LOS for ENT (P < 0.0001) and PsA (P < 0.0001). Conclusions Overall, IET and delayed use of newer antibacterials are associated with significantly worse hospital outcomes. More rapid identification of high-risk patients can facilitate adequate therapy and timely use of newer antibacterials developed for resistant Gram-negative pathogens

    Hospital mortality and length of stay associated with Enterobacterales positive blood cultures: a multicenter analysis

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    ABSTRACT Delayed time to antimicrobial susceptibility results can impact patients’ outcomes. Our study evaluated the impact of susceptibility turnaround time (TAT) and inadequate empiric antibacterial therapy (IET) in patients with bloodstream infections (BSI) caused by Enterobacterales (ENT) species on in-hospital mortality and length of stay (LOS). This retrospective, multicenter investigation which included 29,570 blood ENT-positive admissions across 161 US healthcare facilities evaluated the association between antimicrobial susceptibility testing (AST) TAT, carbapenem susceptibility, and empiric therapy on post-BSI in-hospital mortality and LOS following an ENT BSI event in adult patients. After adjusting for outcomes covariates, post-BSI in-hospital mortality was significantly higher for patients in the IET vs adequate empiric therapy (AET) group [odds ratio (OR): 1.61 (95% CI: 1.32, 1.98); P 63 h [OR:1.48 (95% CI: 1.16, 1.90); P = 0.0017]. Patients with carbapenem non-susceptible (carb-NS) ENT BSI had significantly higher LOS (16.6 days, 95% CI: 15.6, 17.8) compared to carbapenem susceptible (carb-S, 12.2 days, 95% CI: 11.8, 12.6), (P 65 h (P = 0.005 and P< 0.0001, respectively) compared to TAT ≤42 h (reference). Inadequate empiric therapy (IET), carb-NS, and delayed AST TAT are significantly associated with adverse hospital outcomes in ENT BSI. Workflows that accelerate AST TAT for ENT BSIs and facilitate timely and adequate therapy may reduce post-BSI in-hospital mortality rate and LOS.IMPORTANCEFor patients diagnosed with bloodstream infections (BSI) caused by Enterobacterales (ENT), delayed time to antimicrobial susceptibility (AST) results can significantly impact in-hospital mortality and hospital length of stay. However, this relationship between time elapsed from blood culture collection to AST results has only been assessed, to date, in a limited number of publications. Our study focuses on this important gap using retrospective data from 29,570 blood ENT-positive admissions across 161 healthcare facilities in the US as we believe that a thorough understanding of the dynamic between AST turnaround time, adequacy of empiric therapy, post-BSI event mortality, and hospital length of stay will help guide effective clinical management and optimize outcomes of patients with ENT infections

    A plain language summary of how lefamulin alone can be used to treat pneumonia caught outside of the hospital due to common bacterial causes, including drug-resistant bacteria

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    What is this summary about?Bacterial pneumonia is an infection of the lung caused by bacteria that is potentially deadly, costly, and affects millions of people worldwide every year. Treatment is becoming more challenging-many current treatments no longer work well because some strains of bacteria that cause pneumonia have become resistant to current antibiotics. Many of the antibiotics that do still work have undesirable side effects. Therefore, new antibiotics that work differently are needed to treat bacterial pneumonia. Lefamulin (brand name, Xenleta®) is an antibiotic that was approved to treat bacterial pneumonia caught outside a hospital (also called community-acquired bacterial pneumonia, or CABP) based on results of two clinical studies. In both studies, participants started treatment with lefamulin before the type of bacteria causing the infection was known. Lefamulin was well tolerated and worked well in 5 to 7&nbsp;days to kill the bacteria causing the infection and to improve symptoms in almost all participants with CABP.What were the results?After the studies were completed, the researchers looked back at what kinds of bacteria were identified from the study participants. Lefamulin worked well to kill bacteria and to improve CABP symptoms for most kinds of infecting bacteria, including bacteria resistant to many current antibiotics.What do the results mean?These results suggest that lefamulin, by itself, provides a much-needed treatment option for CABP that covers most of the key bacteria causing this infection

    DBP-maf inhibits tumor cell migration.

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    <p>LNCaP (<b>A</b>), LNCaPLN3 (<b>B</b>), PC3M (<b>C</b>) or PC3MLN4 (<b>D</b>) cells were added (150,000/well) to the top chamber of a modified Boyden chamber (+/− DBP-maf) with 10% FBS in the bottom chamber. After 6 hours cells were removed that had not migrated and remaining cells were quantitated using an acid phosphatase assay. Results were normalized to control. Experiments were performed a minimum of three times and error is shown as +/− SD. Compared to cell growth without DBP-maf, adding DBP-maf had a statistically significant overall reduction of cell migration at 30% (P = 0.0003) for the combined four tumor cell types. Individual significant reduction rates were found with each of these tumor cell types. Compared to control, significant reduction was seen with DBP-maf at (<b>A</b>) 20% P = 0.0022 (<b>B</b>) 20% P = 0.0029 (<b>C</b>) 10% P = .0045 (<b>D</b>) 30% P = .0094. n = 3.</p
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