The viva: the non-operative clinical practice of neurosurgery
Vivian A. Elwell, Ramez Kirollos, Syed Al-Haddad in Neurosurgery, 2014
Mode of action. Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs that has anti-inflammatory and immunosuppressant effects. It is 25 times more potent than cortisol in its glucocorticoid effect, while having minimal mineralocorticoid effect. Glucocorticoids enter cells through passive diffusion and form a complex with a receptor protein. This complex then undergoes an irreversible activation and enters the cell nucleus, where it binds to DNA, leading to biological effects induced by these hormones, including increased hepatic gluconeogenesis, increased lipolysis, muscle catabolism, and inhibition of peripheral glucose uptake in muscle and adipose tissue. In addition, dexamethasone increases angiopoietin-1 and decreases vascular endothelial growth factor (VEGF) in the endothelial cell.
Bacterial Meningitis
Thomas T. Yoshikawa, Shobita Rajagopalan in Antibiotic Therapy for Geriatric Patients, 2005
There is an important multicenter trial from Europe utilizing dexamethasone as part of the initial therapy to reduce the effects of inflammatory cytokines with demonstrated improved outcomes, but the routine use of this agent may further complicate treatment decisions. High-dose dexamethasone (10 mg intravenously every 6hr for 4 days) was beneficial in S. pneumoniae meningitis as shown by decreases in mortality and in other adverse complications such as seizures, impairment of consciousness, and cardiorespiratory failure. In this study, however, none of the patients had penicillin- or cephalosporin-resistant S. pneumoniae. Thus, the authors did not need to address the particularly problematic penetration of vancomycin into the CSF with the reduction of inflammation caused by the use of the steroid medication (32).
Antiemetics and Cancer Chemotherapy
John Kucharczyk, David J. Stewart, Alan D. Miller in Nausea and Vomiting: Recent Research and Clinical Advances, 2017
Markman et al.62 conducted a randomized double-blind crossover study comparing the antiemetic efficacy of dexamethasone to prochlorperazine in patients receiving various chemotherapeutic regimens for a variety of tumors. Only 5% of patients received cisplatin and 24% received previous chemotherapy. Dexamethasone was given 20 mg i.v. 30 min prechemotherapy followed by 10 mg p.o. every 6 h for 24 h. Prochlorperazine was given 10 mg i.v. 30 min prechemotherapy followed by 10 mg p.o. every 6 h for the next 24 h. Of 42 patients, 60% experienced no nausea with dexamethasone compared to 33% of patients taking prochlorperazine. Similarly, 69% of patients receiving dexamethasone did not vomit compared to 43% receiving prochlorperazine. Somnolence was the most frequent side effect occuring in 50% of patients receiving prochlorperazine vs. 12% of those receiving dexamethasone. Each of these differences was statistically significant. Interference with normal activity was reported more frequently with prochlorperazine than with dexamethasone. Other side effects seen with dexamethasone included insomnia (31%), anxiety (24%), and euphoria (17%). Of those treated, 50% preferred dexamethasone vs. 12% who preferred prochlorperazine.
Anti-inflammatory activities of a new VEGF blocker, Conbercept
Published in Immunopharmacology and Immunotoxicology, 2021
In addition to the test the effect of Conbercept on collagen-induced arthritis in rats, we also tested whether Conbercept could inhibit acute inflammation. The method of xylene-induced ear edema is a simple and useful method to evaluate anti-inflammatory agents. Xylene induces an acute inflammatory response associated with certain inflammatory mediators such as histamine, kinin, and fibrinolysin [31]. Dexamethasone is used to treat inflammatory-related diseases such as allergies, arthritis, and breathing disorders. It significantly inhibited xylene-inducible ear edema in our study. Conbercept also significantly inhibited the xylene-induced ear edema. This indicated that inhibition of VEGF-dependent angiogenesis may reduce the release of inflammatory mediators such as histamine, kinin, and fibrinolysin. But the highest concentration of Conbercept (50 mg/kg) did not achieve the same effect as Dexamethasone. This indicated that anti-VEGF treatment showed its limitation to inhibit acute inflammation.
In vivo assessment of respiratory burst inhibition by xenobiotic exposure using larval zebrafish
Published in Journal of Immunotoxicology, 2020
Drake W. Phelps, Ashley A. Fletcher, Ivan Rodriguez-Nunez, Michele R. Balik-Meisner, Debra A. Tokarz, David M. Reif, Dori R. Germolec, Jeffrey A. Yoder
Dexamethasone (DEX) is a glucocorticoid pharmaceutical used as an anti-inflammatory and anti-cancer therapeutic (Löwenberg et al. 2007; Burwick and Sharma 2019). Though DEX has been shown to have immunosuppressive properties in larval zebrafish – as determined by impaired wound healing and increased rates of infections (Sharif et al. 2015; Voelz et al. 2015), the current study did not observe a suppression of the respiratory burst. This outcome is in line with data in human neutrophils wherein DEX inhibited bactericidal activity and neutrophil extracellular trap (NET) formation, but did not inhibit ROS production (Wan et al. 2017). DEX has been shown to have direct action on T-cells, leading to immunosuppression (Löwenberg et al. 2007), which may indicate that T-cell signaling is required for DEX-induced immunosuppression in innate immune populations. A pharmacodynamic study of DEX in adult humans supports this hypothesis, i.e. DEX treatment resulted in reduced ROS production by neutrophils and mononuclear cells (Dandona et al. 1999). Given that larval zebrafish do not possess functional T-cells, testing this hypothesis was beyond the scope of this study. In contrast, it was reported that DEX exposure increased ROS levels in a human osteoblast cell line (Liu et al. 2018), as well as in human M2 macrophages; the latter finding was unusual in that M2 macrophages are generally regarded as an anti-inflammatory (Kraaij et al. 2011).
Extract of Pinus densiflora needles suppresses acute inflammation by regulating inflammatory mediators in RAW264.7 macrophages and mice
Published in Pharmaceutical Biology, 2022
Seul-Yong Jeong, Won Seok Choi, Oh Seong Kwon, Jong Seok Lee, Su Young Son, Choong Hwan Lee, Sarah Lee, Jin Yong Song, Yeon Jin Lee, Ji-Yun Lee
We applied 0.1, 0.3 and 1 mg of PINE to mouse ears and the concentration of the test agent was based on previous research of the topical application of 0.1, 0.3 and 1 mg extracts/ear in mouse studies (Ascari et al. 2019; Formagio-Neto et al. 2019). Dexamethasone, a synthetic glucocorticoid, induces anti-inflammatory effects through inhibition of the NF-κΒ signalling pathway (Chen et al. 2021). Dexamethasone has been commonly used as a positive control in inflammation-related studies (Huang et al. 2018). We used 0.1 mg/ear of dexamethasone for topical application based on the findings of a previous study (de Brum et al. 2016). We measured the anti-inflammatory activity of PINE in inflamed ICR mouse ears by using arachidonic acid to induce oedema in ear tissues. All tested concentrations of PINE significantly suppressed ear oedema and MPO activity. Elevated MPO levels are associated with inflammation and increased oxidative stress (Ndrepepa 2019). This study showed that MDA levels, which are a marker of oxidative stress (Gaweł et al. 2004), decreased after PINE treatment. Thus, the results suggest that PINE exerts anti-inflammatory activity not only in vitro but also under in vivo conditions.
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