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Anatomical Considerations to Improve Aesthetic Treatments Using Neuromodulators
Published in Yates Yen-Yu Chao, Optimizing Aesthetic Toxin Results, 2022
Nicholas Moellhoff, Sebastian Cotofana
Apart from the treatment of facial rhytids, neuromodulators can be utilized for several different indications, including body sculpting procedures. The aim is to cause muscular atrophy, rather than relaxation, as is the case when treating the face. Similar to the treatment of muscle spasticity, high doses of neurotoxin are injected deep into the muscular tissue, causing slimming and definition of the treated area. Common examples include injections into the trapezius, biceps, triceps, deltoid, or gastrocnemius muscles (Yi et al. 2020; Cheng et al. 2020).
The Neuromuscular Junction
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
The drug hemicholinium-3 inhibits the reuptake of choline at the presynaptic terminal, which depresses ACh synthesis because most of the choline needed for ACh synthesis is provided through reuptake of the choline resulting from hydrolysis of ACh in the synaptic cleft, and only a relatively small amount of choline is transported from the cell body. α-latrotoxin is an extremely potent neurotoxin, that is a poison of the nervous system, contained in the venom of the black widow spider. It causes massive exocytosis of ACh from presynaptic terminals either by forming open pores in the presynaptic membrane that allow the influx of Ca2+ and Na+ or by binding to special receptors, thereby initiating processes that lead to exocytosis. The depletion of ACh eventually leads to muscle paralysis. Botulinum toxin, produced by a bacterium found in poisoned foods, is one of the most toxic substances known. Only 2 ng of a form of this toxin, when injected intravenously, can kill a human adult by preventing ACh vesicles from fusing with the presynaptic membrane and releasing ACh into the synaptic cleft. Extremely small doses of other forms of this toxin, commercially known as Botox, are injected into the skin to relax muscles causing wrinkles. Botox is also used in the treatment of disorders caused by overactive muscle movement or conditions arising from hyperactivity of some nerves.
Chemical and Biological Threats to Public Safety
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
Supportive care and maintenance of vital functions, especially respiration, is of the utmost importance in treatment. Specific antitoxin is available for some of the neurotoxin types (A, B, and E). With good supportive care and antitoxin administration, the mortality rate is reduced to 25%. Prolonged or permanent muscle paralysis may persist indefinitely.
In vitro discovery of a human monoclonal antibody that neutralizes lethality of cobra snake venom
Published in mAbs, 2022
Line Ledsgaard, Andreas H. Laustsen, Urska Pus, Jack Wade, Pedro Villar, Kim Boddum, Peter Slavny, Edward W. Masters, Ana S. Arias, Saioa Oscoz, Daniel T. Griffiths, Alice M. Luther, Majken Lindholm, Rachael A. Leah, Marie Sofie Møller, Hanif Ali, John McCafferty, Bruno Lomonte, José M. Gutiérrez, Aneesh Karatt-Vellatt
Snakebite envenoming is a neglected tropical disease, which each year claims hundreds of thousands of victims, who are either left permanently disfigured or meet an untimely death.1 It is estimated that every year 1.8–2.7 million envenomings occur, which result in 81,000–138,000 deaths and more than 400,000 people left with permanent physical and psychological sequelae.1 Asia is the continent where most envenomings and deaths occur, estimated to 1.2–2 million cases and 57,000–100,000 fatalities.1 In Southern and Southeast Asia, the monocled cobra (Naja kaouthia) is responsible for a large number of the recorded severe snakebite cases,2,3 which is exemplified by the fact that 34% of snakebite-related deaths in Bangladesh from 1988 to 1989 were attributed to bites from either N. kaouthia or the closely related species, N. naja.4 Life-threatening clinical manifestations of N. kaouthia envenomation include flaccid paralysis due to the actions of abundant long-chain α-neurotoxins, which block neuromuscular transmission by binding to the nicotinic acetylcholine receptor (nAChR) with high affinity, causing a curare-mimetic effect.5,6 These long-chain α-neurotoxins belong to the three-finger toxin superfamily, which dominate the venom in terms of abundance and toxicity, as judged by their high toxicity scores,6–8 and are thus the main toxin targets to be neutralized for successful intervention in human snakebite cases.
Emerging trends in microneedle-based drug delivery strategies for the treatment of rheumatoid arthritis
Published in Expert Opinion on Drug Delivery, 2022
Srividya Gorantla, Unnati Batra, Samshritha RN , Eswara Rao Puppala, Tejashree Waghule, V. G. M. Naidu, Gautam Singhvi
Yao et al. prepared flexible and safe biocomfortable flexible two-layered dissolving microneedles to deliver neurotoxin for treating RA. Neurotoxin is a vital peptide component of Naja naja atra venom, which has shown anti-inflammatory effects [12]. The microneedle was prepared using PVP and chondroitin sulfate, and in the needle, neurotoxin was encapsulated. The mechanical strength of the dissolving microneedles was 0.20 ± 0.01 axial fracture force and 1.47 ± 0.09 N transverse failure force, which showed that DMN neurotoxin has enough mechanical strength to penetrate the stratum corneum. The in vitro penetration test in Wistar rats showed skin insertion of 70 μm depth and 50 μm size of micropore, depicting it has penetrated stratum corneum smoothly. Results showed a reduction in TNF-α and IL-1β in serum, with no adverse reactions observed after 15 days of administration [12]. From this study, it was concluded that the morphology, mechanical strength, skin permeability, and stability of DMN-loaded neurotoxin were good, indicating that it has potential clinical application. Due to good therapeutic potential and painless treatment, it could be used in treating RA.
An overview on cyanobacterial blooms and toxins production: their occurrence and influencing factors
Published in Toxin Reviews, 2022
Isaac Yaw Massey, Muwaffak Al osman, Fei Yang
Anatoxin-a is a small alkaloid and potent neurotoxin promoter. It is a bicylic secondary amine, smallest cyanotoxin, and has a molecular weight of 165 Da. Osswald et al. (2007) indicated that Anabaena sp., Aphanizomenon sp., Microcystis sp., Oscillatoria sp., Arthrospira sp., Raphidiopsis sp., Planktothrix sp., Phormidium sp., Nostoc sp. and Cylindrospermum sp. are capable to produce this toxin. The amine pKa value of 9.4 renders the cationic form of anatoxin-a the most prevalent form in natural waters and its oxidation may be pH-dependent. Homoanatoxin-a with an additional methylene unit on its side chain has been identified as a variant of anatoxin-a (Skulberg et al.1992). Anatoxin-a is a potent nicotinic agonist capable of producing neuromuscular blockade leading to paralysis and eventually death owing to respiratory arrest (Fawell et al.1999, Osswald et al.2007). Although anatoxin-a is not considered widespread as the cyclic peptide hepatotoxins, it is documented to have caused animal poisonings in some parts of the world identified (Fawell et al.1993, Sivonen and Jones 1999, Svircev et al.2019). Due to the toxic consequences, Fawell et al. (1999) recommended 1 µg/L anatoxin-a concentration to provide significant water safety since no official drinking water guideline is established.