scholarly journals Inactivation of Prions by Low-Temperature Sterilization Technology Using Vaporized Gas Derived from a Hydrogen Peroxide–Peracetic Acid Mixture

Pathogens ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 24
Author(s):  
Akikazu Sakudo ◽  
Daiki Anraku ◽  
Tomomasa Itarashiki
Keyword(s):  
Hydrogen Peroxide ◽  
Medical Devices ◽  
Neurodegenerative Disorders ◽  
Peracetic Acid ◽  
Protein Misfolding ◽  
Prion Diseases ◽  
Proteinase K ◽  
Acid Mixture ◽  
Cover Glass ◽  
Standard Mode

Prion diseases are proteopathies that cause neurodegenerative disorders in humans and animals. Prion is highly resistant to both chemical and physical inactivation. Here, vaporized gas derived from a hydrogen peroxide–peracetic acid mixture (VHPPA) was evaluated for its ability to inactivate prion using a STERIACE 100 instrument (Saraya Co., Ltd.). Brain homogenates of scrapie (Chandler strain) prion-infected mice were placed on a cover glass, air-dried, sealed in a Tyvek package, and subjected to VHPPA treatment at 50–55 °C using 8% hydrogen peroxide and <10% peracetic acid for 47 min (standard mode, SD) or 30 min (quick mode, QC). Untreated control samples were prepared in the same way but without VHPPA. The resulting samples were treated with proteinase K (PK) to separate PK-resistant prion protein (PrPres), as a marker of the abnormal isoform (PrPSc). Immunoblotting showed that PrPres was reduced by both SD and QC VHPPA treatments. PrPres bands were detected after protein misfolding cyclic amplification of control but not VHPPA-treated samples. In mice injected with prion samples, VHPPA treatment of prion significantly prolonged survival relative to untreated samples, suggesting that it decreases prion infectivity. Taken together, the results show that VHPPA inactivates prions and might be applied to the sterilization of contaminated heat-sensitive medical devices.

scholarly journals Effect of Non-Concentrated and Concentrated Vaporized Hydrogen Peroxide on Scrapie Prions

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 947
Author(s):  
Akikazu Sakudo ◽  
Risa Yamashiro ◽  
Chihiro Harata
Keyword(s):  
Hydrogen Peroxide ◽  
Prion Protein ◽  
Protein Misfolding ◽  
Soft Mode ◽  
Brain Homogenate ◽  
Proteinase K ◽  
Mouse Bioassay ◽  
Half Cycle ◽  
Cover Glass ◽  
Standard Mode

To date, there have been no studies on the sterilization of prions by non-concentrated and concentrated vaporized hydrogen peroxide (VHP) applied by the same instrument. Here, the effect of the two types of VHP applied using an ES-700 sterilizer on prions was investigated. Brain homogenate from scrapie (Chandler) prion-infected mice was spotted on a cover glass and subjected to ES-700 treatment in soft (non-concentrated VHP from 59% hydrogen peroxide) or standard (concentrated VHP from 80% hydrogen peroxide) mode. Proteinase K-resistant prion protein (PrPres), an indicator of the abnormal isoform of prion protein (PrPSc), was reduced by ES-700 treatment under several conditions: SFT1/4 (soft mode, quarter cycle), SFT1/2 (soft mode, half cycle), SFT1 (soft mode, full cycle), and STD1/2 (standard mode, half cycle). PrPres was detected after the first and second rounds of protein misfolding cyclic amplification (PMCA) of untreated samples, but was undetectable in SFT1/4, SFT1/2, SFT1, and STD1/2 treated samples. In a mouse bioassay, SFT1/2 and STD1/2 treatment of prions significantly prolonged survival time, suggesting that prion infectivity is reduced after ES-700 treatment. In summary, both non-concentrated and concentrated VHP inactivate prions and may be useful for the low-temperature sterilization of prion-contaminated medical devices.

scholarly journals PrP-specific camel antibodies with the ability to immunodetect intracellular prion protein

2010 ◽  
Vol 91 (8) ◽  
pp. 2121-2131 ◽  
Author(s):  
Mourad Tayebi ◽  
William Alexander Taylor ◽  
Daryl Rhys Jones ◽  
Clive Bate ◽  
Monique David
Keyword(s):  
Protein Misfolding ◽  
Prion Diseases ◽  
Neuroblastoma Cells ◽  
Proteinase K ◽  
Target Antigen ◽  
Additional Advantage ◽  
Intracellular Compartments ◽  
High Concentrations ◽  
Misfolding Diseases ◽  
Late Stages

Although there is currently no effective treatment for prion diseases, significant advances have been made in suppressing its progress, using antibodies that block the conversion of PrPC into PrPSc. In order to be effective in treating individuals that have prion diseases, antibodies must be capable of arresting disease in its late stages. This requires the development of antibodies with higher affinity for PrPSc and systems for effective translocation of antibodies across the blood–brain barrier in order to achieve high concentrations of inhibitor at the site of protein replication. An additional advantage is the ability of these antibodies to access the cytosol of affected cells. To this end, we have generated PrP-specific antibodies (known as PrioV) by immunization of camels with murine scrapie material adsorbed to immunomagnetic beads. The PrioV antibodies display a range of specificities with some recognizing the PrP27–30 proteinase K-resistant fragment, others specific for PrPC and a number with dual binding specificity. Independent of their PrP conformation specificity, one of the PrioV antibodies (PrioV3) was shown to bind PrPC in the cytosol of neuroblastoma cells. In marked contrast, conventional anti-PrP antibodies produced in mouse against similar target antigen were unable to cross the neuronal plasma membrane and instead formed a ring around the cells. The PrioV anti-PrP antibodies could prove to be a valuable tool for the neutralization/clearance of PrPSc in intracellular compartments of affected neurons and could potentially have wider applicability for the treatment of so-called protein-misfolding diseases.

Validating the Efficacy of Peracetic Acid Mixture as an Antimicrobial in Poultry Chillers

2008 ◽  
Vol 71 (6) ◽  
pp. 1119-1122 ◽  
Author(s):  
LAURA J. BAUERMEISTER ◽  
JORDAN W. J. BOWERS ◽  
JULIE C. TOWNSEND ◽  
SHELLY R. McKEE
Keyword(s):  
Hydrogen Peroxide ◽  
Peracetic Acid ◽  
Acid Mixture ◽  
Campylobacter Species ◽  
Campylobacter Spp

Peracetic acid mixture (PAHP), which is a combination of peracetic acid and hydrogen peroxide, has been approved as an antimicrobial for use in poultry chillers. To validate its effectiveness, 85 ppm of PAHP was compared with the 30-ppm chlorine treatment in a commercial setting. In this trial, 100 carcasses were sampled for Salmonella and Campylobacter spp. prior to chilling and 100 carcasses were sampled after chilling. In all, 400 carcasses were sampled using 85 ppm of PAHP in the chiller and 400 carcasses were sampled using the chlorine treatment. PAHP at 85 ppm reduced Salmonella-positive carcasses by 92% exiting the chiller, whereas treatment with 30 ppm of chlorine reduced Salmonella by 57%. Additionally, PAHP reduced Campylobacter species–positive carcasses exiting the chiller by 43% while chlorine resulted in a 13% reduction. These results suggest that peracetic acid in combination with hydrogen peroxide may be an effective antimicrobial in poultry chiller applications.

scholarly journals Association of Bcl-2 with Misfolded Prion Protein Is Linked to the Toxic Potential of Cytosolic PrP

2006 ◽  
Vol 17 (8) ◽  
pp. 3356-3368 ◽  
Author(s):  
Angelika S. Rambold ◽  
Margit Miesbauer ◽  
Doron Rapaport ◽  
Till Bartke ◽  
Michael Baier ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Misfolding ◽  
Apoptotic Cell ◽  
Prion Diseases ◽  
Protective Role ◽  
Proteinase K ◽  
Apoptotic Protein ◽  
Induced Apoptosis ◽  
Toxic Potential ◽  
Cellular Compartments

Protein misfolding is linked to different neurodegenerative disorders like Alzheimer’s disease, polyglutamine, and prion diseases. We investigated the cytotoxic effects of aberrant conformers of the prion protein (PrP) and show that toxicity is specifically linked to misfolding of PrP in the cytosolic compartment and involves binding of PrP to the anti-apoptotic protein Bcl-2. PrP targeted to different cellular compartments, including the cytosol, nucleus, and mitochondria, adopted a misfolded and partially proteinase K–resistant conformation. However, only in the cytosol did the accumulation of misfolded PrP induce apoptosis. Apoptotic cell death was also induced by two pathogenic mutants of PrP, which are partially localized in the cytosol. A mechanistic analysis revealed that the toxic potential is linked to an internal domain of PrP (amino acids 115–156) and involves coaggregation of cytosolic PrP with Bcl-2. Increased expression of the chaperones Hsp70 and Hsp40 prevented the formation of PrP/Bcl-2 coaggregates and interfered with PrP-induced apoptosis. Our study reveals a compartment-specific toxicity of PrP misfolding that involves coaggregation of Bcl-2 and indicates a protective role of molecular chaperones.

scholarly journals Cerebrospinal Fluid and Plasma Small Extracellular Vesicles and miRNAs as Biomarkers for Prion Diseases

2021 ◽  
Vol 22 (13) ◽  
pp. 6822
Author(s):  
Óscar López-Pérez ◽  
David Sanz-Rubio ◽  
Adelaida Hernaiz ◽  
Marina Betancor ◽  
Alicia Otero ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Protein Misfolding ◽  
Prion Diseases ◽  
Clinical Stage ◽  
Proteinase K ◽  
Transmissible Spongiform Encephalopathies ◽  
Alternative Source ◽  
Spongiform Encephalopathies ◽  
In Vivo Diagnosis

Diagnosis of transmissible spongiform encephalopathies (TSEs), or prion diseases, is based on the detection of proteinase K (PK)-resistant PrPSc in post-mortem tissues as indication of infection and disease. Since PrPSc detection is not considered a reliable method for in vivo diagnosis in most TSEs, it is of crucial importance to identify an alternative source of biomarkers to provide useful alternatives for current diagnostic methodology. Ovine scrapie is the prototype of TSEs and has been known for a long time. Using this natural model of TSE, we investigated the presence of PrPSc in exosomes derived from plasma and cerebrospinal fluid (CSF) by protein misfolding cyclic amplification (PMCA) and the levels of candidate microRNAs (miRNAs) by quantitative PCR (qPCR). Significant scrapie-associated increase was found for miR-21-5p in plasma-derived but not in CSF-derived exosomes. However, miR-342-3p, miR-146a-5p, miR-128-3p and miR-21-5p displayed higher levels in total CSF from scrapie-infected sheep. The analysis of overexpressed miRNAs in this biofluid, together with plasma exosomal miR-21-5p, could help in scrapie diagnosis once the presence of the disease is suspected. In addition, we found the presence of PrPSc in most CSF-derived exosomes from clinically affected sheep, which may facilitate in vivo diagnosis of prion diseases, at least during the clinical stage.

Molecular Chaperones in Neurodegeneration

2020 ◽  
pp. 354-379 ◽  
Author(s):  
Mukesh Pandey ◽  
Jahangir Nabi ◽  
Nahida Tabassum ◽  
Faheem Hyder Pottoo ◽  
Renuka Khatik ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Protein Quality ◽  
Prion Diseases ◽  
Experimental Models ◽  
Genetic Mutations ◽  
Control Network ◽  
Molecular Crowding ◽  
Age Related ◽  
Lateral Sclerosis

Cellular chaperones are essential players to this protein quality control network that functions to prevent protein misfolding, refold misfolded proteins, or degrade them, thereby maintaining neuronal proteostasis. Moreover, overexpression of cellular chaperones is considered to inhibit protein aggregation and apoptosis in various experimental models of neurodegeneration. Alterations or downregulation of chaperone machinery by age-related decline, molecular crowding, or genetic mutations are regarded as key pathological hallmarks of neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and Prion diseases. Therefore, chaperones may serve as potential therapeutic targets in these diseases. This chapter presents a generalized view of misfolding and aggregation of proteins in neurodegeneration and then critically analyses some of the known cellular chaperones and their role in several neurodegenerative disorders.

scholarly journals Proteasome inhibitors promote the sequestration of PrPSc into aggresomes within the cytosol of prion-infected CAD neuronal cells

2009 ◽  
Vol 90 (8) ◽  
pp. 2050-2060 ◽  
Author(s):  
Michel Dron ◽  
Françoise Dandoy-Dron ◽  
Muhammad Khalid Farooq Salamat ◽  
Hubert Laude
Keyword(s):  
Endoplasmic Reticulum ◽  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Neuronal Cells ◽  
Proteasome Inhibitors ◽  
Proteasome Inhibition ◽  
Cell System ◽  
Proteinase K ◽  
Wild Type ◽  
Infected Cells

Dysfunction of the endoplasmic reticulum associated protein degradation/proteasome system is believed to contribute to the initiation or aggravation of neurodegenerative disorders associated with protein misfolding, and there is some evidence to suggest that proteasome dysfunctions might be implicated in prion disease. This study investigated the effect of proteasome inhibitors on the biogenesis of both the cellular (PrPC) and abnormal (PrPSc) forms of prion protein in CAD neuronal cells, a newly introduced prion cell system. In uninfected cells, proteasome impairment altered the intracellular distribution of PrPC, leading to a strong accumulation in the Golgi apparatus. Moreover, a detergent-insoluble and weakly protease-resistant PrP species of 26 kDa, termed PrP26K, accumulated in the cells, whether they were prion-infected or not. However, no evidence was found that, in infected cells, this PrP26K species converts into the highly proteinase K-resistant PrPSc. In the infected cultures, proteasome inhibition caused an increased intracellular aggregation of PrPSc that was deposited into large aggresomes. These findings strengthen the view that, in neuronal cells expressing wild-type PrPC from the natural promoter, proteasomal impairment may affect both the process of PrPC biosynthesis and the subcellular sites of PrPSc accumulation, despite the fact that these two effects could essentially be disconnected.

Research on Modified Rubbers. Part IV. The Oxidation of Rubber with Aqueous Hydrogen Peroxide-Acetic Acid Mixtures

1934 ◽  
Vol 7 (3) ◽  
pp. 454-461
Author(s):  
G. F. Bloomfield ◽  
E. H. Farmer
Keyword(s):  
Hydrogen Peroxide ◽  
Acetic Acid ◽  
Peracetic Acid ◽  
Glacial Acetic Acid ◽  
Chloroform Solution ◽  
Effective Control ◽  
Acid Mixture ◽  
Hydroxyl Groups ◽  
Derivatives Of ◽  
Degree Of Degradation

Abstract Mair and Todd (J. Chem. Soc., 1932,, 386), in extending the earlier work of Robertson and Mair (J. Soc. Chem. Ind., 46, 41T (1927)), studied the interaction of a chloroform solution of purified rubber with concentrated hydrogen peroxide (100 vols.) dissolved in glacial acetic acid; by this means they obtained a non-acidic substance of the empirical formula C50H92O16, which was unsaturated toward bromine and permanganate, and was considered to have all its oxygen present in the form of hydroxyl groups. Other workers have reported that when peracetic acid dissolved in glacial acetic acid is used in place of the hydrogen peroxide—acetic acid mixture, the products of reaction are acetylated derivatives of rubber (British Patent 369,716). These acetylated derivatives are stated to be obtainable either from solid rubber or from solutions of rubber, but no evidence as to their constitution has been advanced. Now the oxidative degradation of rubber is of considerable interest from two points of view: first, with regard to the light which it may throw on the size, structure, homogeneity, and normality of chemical behavior of the molecules of rubber; and, second, with regard to its efficacy as a means of transforming rubber into derivatives of similar or smaller molecular weight, capable of useful application in industry. The very careful work of Mair and Todd has gone far to show that hydrogen peroxide under the conditions of their experiments attacks the unsaturated centers of the rubber molecule and effects more or less complete hydroxylation of the carbon chain; at the same time it brings about a considerable degree of degradation of the molecule. The product of Mair and Todd, however, is produced under rather restricted conditions of reaction and the reagents employed are costly; consequently the extent to which the character of the product can be modified (i. e., by controlling the degree of degradation, hydroxylation, and acetylation) is left undetermined, and the possibility of producing useful materials at a reasonably low cost by modifying the conditions of reaction and the form of reactants is left unexplored. On the other hand, the employment of peracetic acid as an oxidizing agent, though offering a theoretically elegant way of effecting hydroxylation or acetoxylation at the unsaturated centers of the rubber molecule, is not without drawbacks: the preparation of the reagent is expensive and on a large scale dangerous; moreover, in spite of the fact that it is claimed to be employable either with solutions of rubber or with solid rubber, its reaction with rubber is so vigorous that the prospect of exercising any effective control over the extent of degradation or degree of hydroxylation (acetoxylation) is greatly diminished.

scholarly journals Mechanisms of prion-induced neurodegeneration

2016 ◽  
Vol 18 ◽  
Author(s):  
Paula Saá ◽  
David A. Harris ◽  
Larisa Cervenakova
Keyword(s):  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Prion Diseases ◽  
Neuronal Loss ◽  
Cellular Prion Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Therapeutic Approaches ◽  
Spongiform Encephalopathies ◽  
Membrane Bound ◽  
The Brain

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders characterised by long incubation period, short clinical duration, and transmissibility to susceptible species. Neuronal loss, spongiform changes, gliosis and the accumulation in the brain of the misfolded version of a membrane-bound cellular prion protein (PrPC), termed PrPTSE, are diagnostic markers of these diseases. Compelling evidence links protein misfolding and its accumulation with neurodegenerative changes. Accordingly, several mechanisms of prion-mediated neurotoxicity have been proposed. In this paper, we provide an overview of the recent knowledge on the mechanisms of neuropathogenesis, the neurotoxic PrP species and the possible therapeutic approaches to treat these devastating disorders.

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