Recognition and Management of the Difficult Airway
John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie in Basic Sciences Endocrine Surgery Rhinology, 2018
Fibre-endoscopic skills appear in the core competencies for trainee anaesthetists and include visual inspection of the respiratory tract for diagnostic purposes and placement of double lumen tracheal tubes. The problems associated with the intubating fibrescope are that it is a skilled technique requiring training and practice, the devices are expensive and require careful handling, and disinfection requires chemical agents. There has been particular concern over the inability of cold sterilizing agents to destroy prions. The recommendation from the Department of Health is that a register should be maintained such that all patients treated with an individual fibrescope can be traced easily. Fibre-optic intubation may be part of a practitioners initial plan A strategy or part of a plan B, possibly an asleep fibre-optic intubation or in conjunction with an intubating laryngeal mask airway or supraglottic airway device–Aintree catheter technique.
Prions
Dongyou Liu in Laboratory Models for Foodborne Infections, 2017
Several diagnostic methods have been used for prion diseases. These include enzyme-linked immunosorbent assay (ELISA), western blotting, and immunohistochemistry (IHC) [4]. As an index of prion infection, representative changes in the brain are generally assayed. Prion protein (PrP) accumulates in the brain to form deposits. PrPres is biochemically detected after treatment with PK using western blotting (Figure 7.1) and ELISA (Figure 7.2). In the case of ELISA for BSE, a homogenate is usually prepared from the obex region of the brain, which is subsequently treated with PK. The PK-treated sample is then applied to a microtiter plate for absorption and reacted with an anti-PrP antibody. This method is commercially exploited in the Bio-Rad TeSE BSE kit (Bio-Rad, France), Enfer-TSE kit (Abbott Laboratories, USA), and FRELISA BSE Kit (Fujirebio Inc., Japan). Although the extensively employed ELISA is a sensitive and high-throughput method, the large number of false positives remains a significant problem. Therefore, if a result is positive, ELISA must be repeated to validate the finding. If a positive result is obtained again, western blotting and IHC are performed.
An Overview of Microbes Pathogenic for Humans
Nancy Khardori in Bench to Bedside, 2018
Prions are small infectious pathogens that cause rapidly fatal degenerative neurologic diseases. These pathogens are particularly noteworthy for their resistance to many standard procedures of decontamination and sterilization. Due to their lack of nucleic acid, sterilization techniques that normally cause nucleic acid destruction are not effective. Interestingly, prion diseases can undergo incubation periods up to several decades before exhibiting clinical symptoms. Once these clinical symptoms manifest, death usually follows within several months. There are five known prion diseases described in humans: Kuru, Creutzfeldt-Jakob Disease (CJD), variant Crutzfeldt-Jakob Disease (vCJD), Gerstmann-Strausslër-Scheinker Syndrome (GSS), and fatal familial insomnia. Bovine spongiform encephalopathy in humans, colloquially known as “mad-cow disease” is a prion disease that affects animals and its appearance has increased public attention to prion diseases as a whole. Prions exert their effects by causing host-encoded prion proteins to undergo conformational changes in their structure, forming aberrant proteins. These proteins accumulate over the course of decades and manifest as neurologic dysfunction with the subsequent development of dementia. Death usually ensues over the course of months. Kuru was endemic in remote tribal areas of New Zealand, believed to be due to cannibalistic practices. The disease is no longer endemic since the practice was stopped. Prion infections are transmitted to humans through ingestion of bovine meat products or through medical interventions involving infected tissues (e.g., corneal transplants).
Synthesis and anti-prion aggregation activity of acylthiosemicarbazide analogues
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Dong Hwan Kim, Jaehyeon Kim, Hakmin Lee, Dongyun Lee, So Myoung Im, Ye Eun Kim, Miryeong Yoo, Yong-Pil Cheon, Jason C. Bartz, Young-Jin Son, Eun-Kyoung Choi, Yong-Sun Kim, Jae-Ho Jeon, Hyo Shin Kim, Sungeun Lee, Chongsuk Ryou, Tae-gyu Nam
Prions are the infectious protein that cause prion diseases, including bovine spongiform encephalopathy, scrapie, and Creutzfeldt–Jakob disease (CJD)1,2. The clinical signs of prion diseases are related to impaired brain function, such as cognitive dysfunction, cerebral ataxia and motor dysfunction1,3. The neuropathological features of prion diseases include spongiform degeneration and gliosis in accociation with the accumulation of PrPsc in the brain4. Recent studies at the cellular and molecular levels report that spongiosis and neurodegeneration are caused by prion-induced chronic endoplasmic reticulum (ER) stress leading to the depletion of an intracellular lipid molecule and impaired lysosomal trafficking in brain cells5,6.
Recent advances in cellular models for discovering prion disease therapeutics
Published in Expert Opinion on Drug Discovery, 2022
Lea Nikolić, Chiara Ferracin, Giuseppe Legname
Following the discovery of PrP as the major prion disease-causing agent, other proteins, in diverse organisms, were identified as proteinaceous infectious particles (prions). Although these proteins have different primary sequences and functions, they share many similarities with the disease-causing prions. For instance, they are PK resistant, they can spread their misfolded conformation to the native isoform, they exist in multiple distinct variants, and they can spread from one cell to another and its progeny. In yeasts, at least ten prions have been identified so far. The most studied yeast prions are Saccharomyces Cerevisiae [URE3], the prion form of Ure2p (a protein involved in the regulation of nitrogen metabolism), and [PSI+], the prion form of Sup35 (a translation termination factor); but also other engineered yeast prions have been developed. An example is an engineered Sup35 protein fused to various regions of the mouse PrP protein [107,108].
Ultrasensitive techniques and protein misfolding amplification assays for biomarker-guided reconceptualization of Alzheimer’s and other neurodegenerative diseases
Published in Expert Review of Neurotherapeutics, 2021
Nicole Campese, Maria Francesca Beatino, Claudia Del Gamba, Elisabetta Belli, Linda Giampietri, Eleonora Del Prete, Alessandro Galgani, Andrea Vergallo, Gabriele Siciliano, Roberto Ceravolo, Harald Hampel, Filippo Baldacci
Prions are ‘small proteinaceous infectious particles, which are resistant to inactivation by most procedures that modify nucleic acids’ according to Stanley Prusiner’s definition [27]. First described in the late sixties by Alper and Griffith in their main biochemical and biological features and recognized as the pathogenic agents of scrapie [28–30], prions consist of PrPsc, pathological aggregates of the misfolded Cellular Prion Protein (PrPc) [31]. PrPc may undergo misfolding and aberrant aggregation processes, under still not completely clarified pathophysiological mechanisms, leading to the formation of β-sheet-rich oligomers. These may subsequently promote PrPc misfolding and aggregation into highly ordered protofibrils and fibrils [31]. Protofibrils and fibrils may decay into smaller fragments acting as nucleating agents, inducing further spreading of the aberrant proteins based on sequential nucleation–fragmentation cycles [31].
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