Comparison between ketorolac- and fentanyl-based patient-controlled analgesia for acute kidney injury after robot-assisted radical prostatectomy: a retrospective propensity score-matched analysis.

PURPOSE: It is unclear whether ketorolac-based patient-controlled analgesia (PCA) leads to acute kidney injury (AKI) after robot-assisted radical prostatectomy (RARP) in patients susceptible to AKI. We compared the postoperative AKI incidence with ketorolac- and fentanyl-based PCA after RARP. METHODS: After medical record review, eligible patients were divided in ketorolac and fentanyl groups. We conducted propensity score matching of 3239 patients and assigned 641 matched patients to each group, and compared the AKI incidence. We investigated potential risk factors for postoperative AKI, defined according to the Kidney Disease Improving Global Outcomes criteria. We collected preoperative data (age, height, weight, body mass index, American Society of Anesthesiologists physical status, medical history, creatinine level, estimated glomerular filtration rate, and hemoglobin level) and intraoperative data (maintenance anesthetics, surgery duration, anesthesia duration, crystalloid amount, colloid use, total amount of fluid administered, estimated blood loss, norepinephrine use, phenylephrine use, and PCA type). RESULTS: The postoperative AKI incidence was significantly higher in the ketorolac than in the fentanyl group, both before (31.1% vs. 20.4%; p < 0.001) and after (31.5% vs. 22.6%; p < 0.001) matching. In the univariate analysis, ketorolac was significantly associated with postoperative AKI, both before (odds ratio [OR], 1.762; 95% confidence interval [CI], 1.475-2.105; p < 0.001) and after (OR, 1.574; 95% CI, 1.227-2.019; p < 0.001) matching. In the multivariate analysis, ketorolac-based PCA was independently associated with development of postoperative AKI in the matched groups (OR, 1.659; 95% CI, 1.283-2.147; p < 0.001). CONCLUSION: Ketorolac-based PCA may increase postoperative AKI incidence after RARP; thus, renal function should be monitored in these patients.

8-Methoxybutin inhibits α-MSH induced melanogenesis and proliferation of skin melanoma by suppression of the transactivation activity of microphthalmia-associated transcription factor.

Microphthalmia-associated transcription factor (MITF) is highly expressed in melanocytes and is the main regulator of melanogenesis and melanocyte cell fate. Although MITF is important for the differentiation and development of melanocytes, it is also considered an oncogene of skin melanoma. Based on these findings, MITF could be an attractive therapeutic target for skin cancer intervention. This study identified 8-methoxybutin as an inhibitor of MITF and investigated the underlying mechanism. 8-Methoxybutin inhibited α-MSH-induced melanogenesis in murine melanoma cells (B16F10) and skin melanoma proliferation by reducing melanogenic gene expression via blockade of the transactivation activity of MITF. In silico docking analysis and pull-down analysis suggested that 8-methoxybutin binds to the DNA-binding domain of MITF and further inhibits its binding to the E-box in the promoter of target genes, including tyrosinase. In addition, 8-methoxybutin suppressed growth of skin melanoma in a xenograft mouse model. These results indicate that 8-methoxybutin has potential as a therapeutic agent for hyperpigmentation disorder and skin cancer. SIGNIFICANCE STATEMENT: 8-Methoxybutin inhibits MITF transactivation activity resulting suppression of melanogenesis and skin melanoma growth.

Benzisothiazolinone upregulates the MUC5AC expression via ERK1/2, p38, and NF-κB pathways in airway epithelial cells.

Mucus plays an important role in protecting the respiratory tract from irritants. However, mucus hypersecretion is a major indicator of airway diseases. 1,2-Benzisothiazolin-3-one (BIT), as a microbicide, induces asthmatic inflammation. Therefore, we focused on the effects of BIT-related mucin secretion in airway epithelial cells. Our in vivo study showed increased mucus and MUC5AC expressions in the bronchioles of mice that inhaled BIT. For investigating the signaling pathways, we performed experiments in human airway epithelial cells. BIT induced the MUC5AC expression and significantly increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The specific inhibitors of ERK1/2, p38, and NF-κB blocked the BIT-induced MUC5AC expression. Therefore, these results suggest that BIT induces the MUC5AC expression via the ERK1/2, p38, and NF-κB pathways in human airway epithelial cells, which may be involved in mucus hypersecretion associated with airway inflammatory diseases.