BackgroundKetamine can act as a multifunctional neuroprotective agent by inhibiting oxidative stress, cellular dysfunction, and apoptosis. Although it has been proven to be effective in various neurologic disorders, the mechanism of the treatment of traumatic brain injury (TBI) is not fully understood. The aim of this study was to investigate the neuroprotective function of ketamine in models of TBI and the potential role of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in this putative protective effect.Materials and methodsWild-type male mice were randomly assigned to five groups: Sham group, Sham + ketamine group, TBI group, TBI + vehicle group, and TBI + ketamine group. Marmarou’s weight drop model in mice was used to induce TBI, after which either ketamine or vehicle was administered via intraperitoneal injection. After 24 h, the brain samples were collected for analysis.ResultsKetamine significantly ameliorated secondary brain injury induced by TBI, including neurological deficits, brain water content, and neuronal apoptosis. In addition, the levels of malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were restored by the ketamine treatment. Western blotting and immunohistochemistry showed that ketamine significantly increased the level of Nrf2. Furthermore, administration of ketamine also induced the expression of Nrf2 pathway-related downstream factors, including hemeoxygenase-1 and quinine oxidoreductase-1, at the pre- and post-transcriptional levels.ConclusionKetamine exhibits neuroprotective effects by attenuating oxidative stress and apoptosis after TBI. Therefore, ketamine could be an effective therapeutic agent for the treatment of TBI.
Background Tigecycline has broad-spectrum anti-bacterial activity and often used for critically ill patients with complicated infections. Only a few clinical studies have reported the coagulation disorder induced by tigecycline. The aim of this study was to investigate the association between tigecycline and coagulation dysfunction using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Method Data from January 2005 to December 2020 in FAERS were retrieved. We investigated the clinical characteristics of the coagulation dysfunction events and conducted disproportionality analysis by using reporting odds ratios (ROR) to compare tigecycline with the full database and other antibiotics. Results The total number of reports of coagulation dysfunction related to tigecycline as the primary suspect drug was 223. The median time to event of the coagulation dysfunction events was 10 (interquartile range [IQR] 6.75–13) days. 80.72% coagulation-related adverse events appeared within the first 14 days since the initiation of tigecycline administration. The overall ROR (95% CI) for coagulation-related adverse events was 3.55 (3.08, 4.09). The RORs (95% CI) for thrombocytopenia, hypofibrinogenaemia, coagulopathy, activated partial thromboplastin time prolonged, international normalized ratio increased, prothrombin time prolonged were 8.21 (6.34, 10.62), 705.41 (526.81, 944.54), 30.67 (21.92, 42.92), 42.98 (24.85, 74.31), 4.67 (2.51, 8.71), and 27.99 (15.01, 52.19), respectively. In analyses stratified on comparing tigecycline to vancomycin and daptomycin, significant coagulation dysfunction signals were found with the RORs (95% CI) 2.74 (2.34, 3.22) and 3.08 (2.57, 3.70). Conclusions We found a strong signal of high frequency of reporting coagulation dysfunction in tigecycline. Health professionals should be aware of the potential coagulation disorders risk and monitor coagulation parameters during anti-bacterial therapy with tigecycline, particularly the need to monitor fibrinogen levels.
Bacterial contamination of medical devices not only constitutes a serious threat to the health of patients, but also promotes the evolution of bacterial drug-resistance. Here, a new strategy to fabricate...
Background: This study aimed to assess the severity of acute lung injury after mild or severe hemorrhagic shock and resuscitation, and to examine the therapeutic effects of suberoylanilide hydroxamic acid (SAHA) on lung injury. Methods: Mild and severe hemorrhagic shock were induced by total blood volume loss of 20% or 40%, respectively, which was maintained for 60 min. Then, resuscitation was performed by autologous blood and SAHA or a vehicle solution accordingly. Mean arterial pressure, heart rate, and arterial blood gas were measured during the experiment. Histological assays, wet/dry weight ratio, inflammatory cytokines, and the extent of histone acetylation were evaluated at 3 h post-resuscitation. Results: There were no significant differences of the most indicators measured between the mild hemorrhagic shock and Sham groups. Although in severe hemorrhagic shock group, mean arterial pressure was markedly reduced, lactic acid was significantly increased after hemorrhage. Moreover, the lung injury score was increased, the wet/dry weight ratio was elevated, inflammatory factor expression levels were upregulated, the expression of phosphorylated NF-κB/p65 was enhanced, and the extent of histone acetylation was decreased at 3 h post-resuscitation. Remarkably, adjuvant treatment with SAHA decreased the lactic acid, the pathological injury score, the wet/dry weight ratio, the content of inflammatory factor, as well as the level of activated NF-κB/p65, but promoted the expression of acetylated H4. Conclusions: Total blood volume loss of 40% results in acute lung injury, whereas loss of 20% does not. Treatment with SAHA alleviates lung injury induced by severe hemorrhagic shock and resuscitation and the underlying mechanism involves a reversal of decreased histone acetylation and inhibition of the NF-κB pathway.
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