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Bufexamac
Published in Anton C. de Groot, Monographs in Contact Allergy, 2021
Bufexamac is a nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic properties. It is typically administered topically for the treatment of subacute and chronic eczema of the skin, including atopic eczema and other inflammatory dermatoses, as well as sunburn and other minor burns, and itching. Bufexamac has also been used in suppositories in combination with local anesthetics indicated for hemorrhoids. Due to undetermined clinical efficacy and a high prevalence of contact sensitization, in April 2010, the drug was withdrawn by the European Medicines Agency (EMA) (20). One month later, Japanese pharmaceutical companies voluntarily recalled bufexamac-containing medicines (19), soon thereafter followed by some Australian producers (53). However, it was still registered there in 2019 for other-the-counter use (55). Currently (2020) it is not available in New Zealand, Japan, the European Union, the United States of America and Canada (55).
HDAC inhibitor, MS-275, increases vascular permeability by suppressing Robo4 expression in endothelial cells
Published in Tissue Barriers, 2021
Taito Kashio, Keisuke Shirakura, Mayumi Kinoshita, Maaya Morita, Ryosuke Ishiba, Kosuke Muraoka, Tomoaki Kanbara, Masato Tanaka, Risa Funatsu, Nobumasa Hino, Shohei Koyama, Ryo Suzuki, Yasuo Yoshioka, Taiki Aoshi, Takefumi Doi, Yoshiaki Okada
To investigate whether HDACs regulate Robo4 expression in endothelial cells, HUVECs were treated with HDAC inhibitors targeting the different HDAC subtypes. Following this, Robo4 expression was analyzed at both the mRNA and protein levels (Figure 1a,b). TSA, TC-H 106, and MS-275, which inhibit HDAC1, HDAC2, and HDAC3, respectively, strongly suppressed Robo4 expression; conversely, MC 1568 and Bufexamac, which target other HDACs, resulted in moderate or no effect on Robo4 expression at the mRNA and protein levels. Moreover, MS-275-induced suppression of Robo4 was determined to be dose-dependent (Figure 1c). These results indicated that Robo4 expression is regulated by HDAC1, HDAC2, or HDAC3. To identify the HDAC that primarily regulates Robo4 expression, HUVECs were transfected with siRNAs against HDAC1, HDAC2, and HDAC3. The knockdown of HDAC3, but not of HDAC1 and HDAC2, suppressed Robo4 expression (Figure 2). This indicated that MS-275 suppresses Robo4 expression by inhibiting HDAC3.
Insights into endotoxin-mediated lung inflammation and future treatment strategies
Published in Expert Review of Respiratory Medicine, 2018
Amlan Chakraborty, Jennifer C. Boer, Cordelia Selomulya, Magdalena Plebanski, Simon G. Royce
Neutrophils are the first immune cells to reach the site of inflammation in the lung post an insult with LPS. Transmigrated neutrophils then secrete proteolytic enzymes and reactive oxygen species (ROS) which damages the lung endothelium and epithelium. The harm does not end in edema. The ROS leads to promutagenic alterations in DNA and causes a carcinogenic response post-chronic inflammation. Transcriptome analysis by Güngör and colleagues showed 218 genes which are differentially expressed with LPS induction in the presence of neutrophils [45]. Many pathways were found altered. Importantly complement pathways, CCR3 signaling, IL-10 signaling, and antigen presentation by MHCI were altered between LPS with and without neutrophils. CCR3 is responsible for eosinophil activation pointing toward a chronic inflammatory state. Whereas, IL-10 a pleiotropic anti-inflammatory cytokine represses the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β secreted by Mφs. Pharmacotherapeutic studies using proteins such as B7H3 and bufexamac have showed potential in attenuating LPS-induced injury [46,47]. This opens the possibility of utilizing these molecules in ameliorating the clinical condition of pulmonary inflammation. Vascular compartments, pulmonary tissue, and the underlying endothelial cells are also affected by LPS. Since LPS affects vascular compartments and pulmonary tissue, therefore, the factors which alter them need to be studied.
Cutaneous irritancy of an ibuprofen medicated plaster in healthy volunteers
Published in Postgraduate Medicine, 2018
Manisha Maganji, Mark P. Connolly, Aomesh Bhatt
The low contact sensitivity observed with the ibuprofen-medicated plaster is also consistent with a prior study that evaluated delayed contact hypersensitivity of several NSAIDs [17]. Gniazdowaska et al. (1999) administered plaster tests to 371 consecutive subjects with a series of NSAIDs, including acetylsalicylic acid, bufexamac, diclofenac, etofenamate, felbinac, flufenamic acid, ibuprofen, indomethacin, and piroxicam [17]. They found 17 subjects (4.6%) exhibited delayed hypersensitivity to one of the NSAID preparations: 12 subjects (3.2%) had plaster test reactions to bufexamac, 2 (0.5%) to etofenamate, 2 (0.5%) to indomethacin, and 1 subject (0.3%) to flufenamic acid. No subjects showed delayed hypersensitivity to ibuprofen. Allergic contact dermatitis has also been found to be relatively rare for transdermal NSAID therapies [23].