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《Journal of microbiology, immunology, and infection》2020,53(6):1030-1034
X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease. We reported two 7-month-old identical male twins with Pseudomonas aeruginosa sepsis who initially manifested as oral ecthyma gangrenosum and were finally diagnosed to have XLA. In both cases, we confirmed the c.862C > T BTK missense mutation in exon 10 at the SH2 domain. 相似文献
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Beta-adrenergic agonist protects retinal pigment epithelium against hydroxycholoroquine toxicity via c AMP-PKA signal pathway 下载免费PDF全文
AIM: To test our hypothesis that activation of protein kinase A(PKA) signal pathway by β-adrenergic agonist plays an important role in the protecting of cultured retinal pigment epithelial(RPE) cells against the hydroxychloroquine(HCQ) toxicity. METHODS: Cultured human RPE cells were treated with 1) HCQ, 2) HCQ with salbutamol(a β2-adrenergic receptor agonist), and 3) HCQ with salbutamol and a PKA inhibitor, and compared these to 4) untreated cells(controls). After treated for 24 h, cell vacuolation, cells viability, PKA and PKA kinase activity levels were determined by the measurement of the size of vacuoles using Image J software, the cell counting with a dye-exclusion testing, Western blot and PKA kinase detection, respectively. RESULTS: Cell vacuolation and cell death of cultured RPE cells were significantly increased by the treatment of HCQ. Salbutamol significantly elevated PKA and PKA activity levels and this was associated with the inhibition of the vacuolation and cell death. The PKA inhibitor significantly decreased the PKA levels and eliminated the protective effects of salbutamol on HCQ-treated RPE cells. CONCLUSION: The PKA pathway plays an important role in the protective effects of β2-adrenergic agonist on the RPE cells against HCQ toxicity. These findings reveal a novel potential strategy against HCQ retinopathy by treatment with PKA activating medications. 相似文献
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《Journal of infection and chemotherapy》2020,26(2):230-235
We investigated achievement of a target 24-h area under the concentration-time curve to minimum inhibitory concentration ratio (AUC/MIC) ≥666 and the factors influencing this ratio in patients who received daptomycin (DAP) for infectious disease treatment in a clinical setting. The target AUC/MIC was obtained in 6 patients (35.3%) at a 4–6 mg/kg dose (Group_4–6 mg/kg) and in 4 (18.2%) at a >6 mg/kg dose (Group_>6 mg/kg). There was a significant difference in clearance of DAP (CL_DAP) between these groups, but no other difference in characteristics. Multiple linear regression analysis was performed for prediction of AUC ≥666 based on patient factors and the presence or absence of sepsis. In a stepwise analysis, serum creatinine (SCr) was a significant predictor of AUC, but this parameter explained only 13% of the variance in achievement of the target AUC. These results show that the target AUC/MIC may or may not be achieved at the doses used in Group_4–6 mg/kg and Group_>6 mg/kg. Receiver operating characteristic analysis suggested that a CL_DAP >0.450 L/hr may lead to failure to reach the target AUC/MIC. Therefore, regardless of dose, the efficacy of DAP should be monitored closely to prevent failure of infectious disease treatment, particularly because therapeutic drug monitoring of DAP is limited by difficulty measuring the DAP serum concentration at many medical facilities. Our findings are preliminary, and a further study is required to identify factors that increase CL_DAP and to enable dose adjustment of DAP. 相似文献
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Alicia M. Blessing MD PhD Janice M. Santiago-O'Farrill MD PhD Weiqun Mao BS MD Lan Pang BS MD Jing Ning MD PhD Daewoo Pak MD PhD Lakshmi Reddy Bollu MD PhD Philip Rask BS MD LaKesla Iles BS MD Hailing Yang PhD MD Samantha Tran BS MD Ezzeddine Elmir BS MD Geoffrey Bartholomeusz MD PhD Robert Langley MD PhD Zhen Lu MD Robert C. Bast Jr MD 《Cancer》2020,126(15):3579-3592