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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Bleomycin was discovered in 1966 by the Japanese scientist Hamao Umezawa who was screening culture filtrates of Streptomyces verticillus. Due to its complexity, the structure was not elucidated and reported until 1972, with a correction published in 1978. Despite its size (individual molecular weights are in the region of 1,300) and the complexity of the various bleomycin variants, particularly with regard to the number of chiral centers, the first total synthesis of bleomycin A2 was reported in 1982. It was first launched in Japan by Nippon Kayaku in 1969, and gained FDA approval in the US in 1973 under the brand name BlenoxaneTM marketed by Bristol Laboratories, the commercial precursor of Bristol-Myers Squibb (BMS). In the UK, it is now distributed as Bleo-KyowaTM, a 15,000 unit powder for reconstitution for IV injection manufactured by Kyowa Kirin Ltd.
Electron Spin Resonance Spectroscopy
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
George C. Yang, Adorjan Aszalos
Bleomycin was originally isolated as a Cu(II) complex from the fermentation broth of Streptomyces verticillus [15]. Darbowiak et al. [16] detected an ESR spectrum of the 1:1 Cu(II)-bleomycin A2 complex with g∥ = 2.203, g⊥ = 2.058, and A∥ (Cu) = 0.0186 cm-1. The ESR data support the previously’ prepared square planar structure, with Cu(II) ligated by four nitrogens or three nitrogens and one oxygen atom [16]. Similar to the BLM-Fe(II)O2 system, BLM-Cu(I)-O2 also produces a reactive oxygen radical that has been spin-trapped using BPN (1.0 mM 1:1 BLM-Cu(I) complex and 0.08M BPN) [17], with g = 1.0057 and AN = 15.3G, typical of the ·OH spin adduct of BPN.
Ethanol sclerotherapy: Is it gold standard for venous malformation management as well?
Published in Byung-Boong Lee, Peter Gloviczki, Francine Blei, Jovan N. Markovic, Vascular Malformations, 2019
Bleomycin is a cytotoxic antibiotic isolated from the gram-positive bacteria Streptomyces verticillus. Bleomycin inhibits DNA synthesis and is used as a chemotherapy agent. When used as a sclerosing agent, it induces an inflammatory reaction that subsequently causes fibrosis. It is very well tolerated with minimal swelling and pain after sclerotherapy.4 In a systemic review and meta-analysis, the outcomes of intralesional bleomycin injection for VMs were studied in 12 articles including 690 patients. Good to excellent size reduction was reported in 87% of VMs without nerve injury.13 Pulmonary fibrosis was not reported. Nausea, vomiting, and chills may occur soon after sclerotherapy. Treatment with bleomycin alone usually requires more procedures than other sclerosing agents.4, 13 A combination of bleomycin and other sclerosing agents (ethanol or foam sclerosing agents) shows better results with less complication rates. Because of concern for pulmonary fibrosis, the bleomycin dose is limited to 0.5 units/kg or 15 units per procedure, with a lifetime limit of 400 units.
Combined therapy of plantar warts with topical bleomycin and microneedling: a comparative controlled study
Published in Journal of Dermatological Treatment, 2020
Hend D. Gamil, Mohamed M. Nasr, Fathia M. Khattab, Amira M. Ibrahim
Bleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. It acts by inhibiting the deoxyribonucleic acid (DNA) synthesis in cells and viruses; it induces strand cleavage of the DNA molecule (5). Microneedling is a minimally invasive procedure; dermapen designed in a special form to control depth penetration of the skin (6). The microneedles penetrate through the epidermis but do not remove it; so, the epidermis is only punctured and rapidly heals based on the controlled mechanical stimulation of the wound-healing process by the needle (6,7). It has also been shown to augment transdermal drug delivery. By creating micropores through the stratum corneum and into the underlying epidermis, microneedling bypasses the barrier function of the stratum corneum to rapidly deliver topical medications into the dermal microcirculation without penetrating deep enough to stimulate nerves within the dermis. Choice of dermapen becomes important, as bleeding induced by longer needles has been hypothesized to inhibit drug absorption (8). The aim of this study was to assess the efficacy of combination between microneedling with dermapen and topical bleomycin in the treatment of plantar warts in comparison with intralesional bleomycin and intralesional saline.
A comparative study of intratracheal and aerosolization instillations of bleomycin inducing experimental lung fibrosis in rat
Published in Toxicology Mechanisms and Methods, 2019
Anouar Abidi, Sana Bahri, Saloua Ben Khamsa, Alexandre Legrand
To investigate the presence of biomarkers associated with different stages of pulmonary fibrosis (PF), groups were checked once installed (day 1), at the beginning of the inflammatory phase (days 3 and 7) and during the fibrosis phase (days 14 and 21). A control group (G1) treated with saline (intratracheally 2 mg/kg/day) was also followed for 21 days. Concerning intratracheal aerosolization, the oropharynx was first anesthetized using a local administration of lidocaine. A micro sprayer (Model IA-1C, Penn-Century, US) connected to a high-pressure syringe (Model FMJ-250, Penn-Century, US) was then inserted transorally into the tracheal lumen. BLM solution (2 mg/kg in 200 μl saline; bleomycin sulfate which represents a mixture of thirteen antibiotics having the same basic structure. It was isolated from Streptomyces verticillus, the used BLM was purchased from Sanofi, Gentilly, France) was then aerosolized according to manufacturer’s instructions, at a rate of about 15 µl/second (particle size: 16–22 µm; operating pressure: 3000 psi). This procedure was realized under fiberoptic laryngoscope to visualize epiglottis and ensure a good positioning of the microsprayer (Robbe et al. 2015; Abidi et al. 2017a).
Use of percutaneous bleomycin sclerotherapy for orbital lymphatic malformations
Published in Orbit, 2019
Adam M. Hanif, Justin A. Saunders, C. Matthew Hawkins, Ted H. Wojno, Hee Joon Kim
Recently, use of intralesional sclerosing agents has been reported. To date, the use of OK-432, sodium tetradecyl sulfate, alcohol, and sodium morrhuate has been reported for orbital lymphatic malformations with some success.4,8,10–13 Bleomycin, an anti-neoplastic antibiotic isolated from Streptomyces verticillus, is another sclerosing agent that has shown promising results in the literature.14–17 Through mechanisms that have yet to be fully elucidated, it inhibits nucleic acid synthesis and causes a nonspecific inflammatory reaction within endothelial cells lining the cysts, leading to fibrosis and involution of the lesion.13 In treatment of lymphatic malformations, it is injected directly into cysts after aspiration of the cyst contents with fluoroscopic and sonographic guidance. Though such off-label use is still investigational, its use in lymphatic malformations of the head and neck region is well documented. However, documentation in the literature regarding its use specifically in the orbit is comparably lacking. In this study, we therefore sought to summarize the clinical manifestations and outcome of the use of percutaneous bleomycin sclerotherapy for orbital lymphatic malformations by way of an institutional review board-approved retrospective chart review.