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Best Practice & Research. Clinical... 2006The desire to rid the blood supply of pathogens of all types has led to the development of many technologies aimed at the same goal--eradication of the pathogen(s)... (Review)
Review
The desire to rid the blood supply of pathogens of all types has led to the development of many technologies aimed at the same goal--eradication of the pathogen(s) without harming the blood cells or generating toxic chemical agents. This is a very ambitious goal, and one that has yet to be achieved. One approach is to shun the 'one size fits all' concept and to target pathogen-reduction agents at the Individual component types. This permits the development of technologies that might be compatible with, for example, plasma products but that would be cytocidal and thus incompatible with platelet concentrates or red blood cell units. The technologies to be discussed include solvent detergent and methylene blue treatments--designed to inactivate plasma components and derivatives; psoralens (S-59--amotosalen) designed to pathogen-reduce units of platelets; and two products aimed at red blood cells, S-303 (a Frale--frangible anchor-linker effector compound) and Inactine (a binary ethyleneimine). A final pathogen-reduction material that might actually allow one material to inactivate all three blood components--riboflavin (vitamin B2)--is also under development. The sites of action of the amotosalen (S-59), the S-303 Frale, Inactine, and riboflavin are all localized in the nucleic acid part of the pathogen. Solvent detergent materials act by dissolving the plasma envelope, thus compromising the integrity of the pathogen membrane and rendering it non-infectious. By disrupting the pathogen's ability to replicate or survive, its infectivity is removed. The degree to which bacteria and viruses are affected by a particular pathogen-reducing technology relates to its Gram-positive or Gram-negative status, to the sporulation characteristics for bacteria, and the presence of lipid or protein envelopes for viruses. Concerns related to photoproducts and other breakdown products of these technologies remain, and the toxicology of pathogen-reduction treatments is a major ongoing area of investigation. Clearly, regulatory agencies have a major role to play in the evaluation of these new technologies. This chapter will cover the several types of pathogen-reduction systems, mechanisms of action, the inactivation efficacy for specific types of pathogens, toxicology of the various systems and the published research and clinical trial data supporting their potential usefulness. Due to the nature of the field, pathogen reduction is a work in progress and this review should be considered as a snapshot in time rather than a clear picture of what the future will bring.
Topics: Anti-Infective Agents; Blood; Blood-Borne Pathogens; Detergents; Graft vs Host Disease; Humans; Methylene Blue; Riboflavin; Transfusion Reaction
PubMed: 16377551
DOI: 10.1016/j.beha.2005.04.001 -
Skin Therapy Letter Mar 2003Skin cleansers may be an important adjunct to the regimen of those who use cosmetics, have sensitive or compromised skin, or utilize topical therapies. Cleansers... (Comparative Study)
Comparative Study Review
Skin cleansers may be an important adjunct to the regimen of those who use cosmetics, have sensitive or compromised skin, or utilize topical therapies. Cleansers emulsify dirt, oil and microorganisms on the skin surface so that they can be easily removed. During cleansing, there is a complex interaction between the cleanser, the moisture skin barrier, and skin pH. Cleansing, with water soap or a liquid cleanser, will affect the moisture skin barrier. Soap will bring about the greatest changes to the barrier and increase skin pH. Liquid facial cleansers are gentler, effecting less disruption of the barrier, with minimal change to skin pH, and can provide people with a cleanser that is a combination of surfactant classes, moisturizers and acidic pH in order to minimize disruption to the skin barrier.
Topics: Detergents; Humans; Skin Care
PubMed: 12858234
DOI: No ID Found -
Acta Biochimica Et Biophysica Sinica Aug 2022Structure determination of membrane proteins has been a long-standing challenge to understand the molecular basis of life processes. Detergents are widely used to study... (Review)
Review
Structure determination of membrane proteins has been a long-standing challenge to understand the molecular basis of life processes. Detergents are widely used to study the structure and function of membrane proteins by various experimental methods, and the application of membrane mimetics is also a prevalent trend in the field of cryo-EM analysis. This review focuses on the widely-used detergents and corresponding properties and structures, and also discusses the growing interests in membrane mimetic systems used in cryo-EM studies, providing insights into the role of detergent alternatives in structure determination.
Topics: Cryoelectron Microscopy; Detergents; Membrane Proteins
PubMed: 35866608
DOI: 10.3724/abbs.2022088 -
Molecules (Basel, Switzerland) Nov 2022Bicelles are disk-shaped models of cellular membranes used to study lipid-protein interactions, as well as for structural and functional studies on transmembrane...
Bicelles are disk-shaped models of cellular membranes used to study lipid-protein interactions, as well as for structural and functional studies on transmembrane proteins. One challenge for the incorporation of transmembrane proteins in bicelles is the limited range of detergent and lipid combinations available for the successful reconstitution of proteins in model membranes. This is important, as the function and stability of transmembrane proteins are very closely linked to the detergents used for their purification and to the lipids that the proteins are embedded in. Here, we expand the toolkit of lipid and detergent combinations that allow the formation of stable bicelles. We use a combination of dynamic light scattering, small-angle X-ray scattering and cryogenic electron microscopy to perform a systematic sample characterization, thus providing a set of conditions under which bicelles can be successfully formed.
Topics: Lipid Bilayers; Surface-Active Agents; Detergents; Magnetic Resonance Spectroscopy; Micelles; Membrane Proteins; Pulmonary Surfactants
PubMed: 36364455
DOI: 10.3390/molecules27217628 -
Current Protocols in Protein Science Aug 2014Well-characterized membrane protein detergent complexes (PDC) that are pure, homogenous, and stable, with minimized excess detergent micelles, are essential for... (Review)
Review
Well-characterized membrane protein detergent complexes (PDC) that are pure, homogenous, and stable, with minimized excess detergent micelles, are essential for functional assays and crystallization studies. Procedural steps to measure the mass, size, shape, homogeneity, and molecular composition of PDCs and their host detergent micelles using size-exclusion chromatography (SEC) with a Viscotek Tetra Detector Array (TDA; absorbance, refractive index, light scattering, and viscosity detectors) are presented in this unit. The value of starting with a quality PDC sample, the precision and accuracy of the results, and the use of a digital benchtop refractometer are emphasized. An alternate and simplified purification and characterization approach using SEC with dual absorbance and refractive index detectors to optimize detergent and lipid concentration while measuring the PDC homogeneity is also described. Applications relative to purification and characterization goals are illustrated as well.
Topics: Chromatography, Gel; Detergents; Membrane Proteins; Micelles; Refractometry
PubMed: 25081744
DOI: 10.1002/0471140864.ps2910s77 -
Methods in Molecular Biology (Clifton,... 2021Lipid rafts are microdomains on plasma membrane that contain high levels of cholesterol and sphingolipids. Because of the detergent-resistant property of lipid rafts,...
Lipid rafts are microdomains on plasma membrane that contain high levels of cholesterol and sphingolipids. Because of the detergent-resistant property of lipid rafts, lipid rafts isolated by methods that use detergents frequently yield different results. Artifacts can also be introduced through the use of detergents. These limitations could be overcome with a detergent-free method which eliminates possible artificial influences. Importantly, lipid rafts prepared with a detergent-free method is more compatible to mass spectrometric analysis since the ion suppression effect is largely reduced.This chapter describes a detergent-free two-step method for preparation of lipid rafts. Firstly, a purified plasma membrane fraction is prepared from cells by sedimentation of the postnuclear supernatant (PNS) in a Percoll gradient. Secondly, the as-prepared plasma membranes are sonicated to release lipid rafts which are further isolated by flotation in a continuous gradient of Optiprep solution. Then, we introduce a typical shotgun lipidomics workflow that can be used as a cost-effective and relatively high throughput method to determine the lipidomes of lipid rafts.The method also makes an easy start for lipidomics studies.
Topics: Cell Fractionation; Cholesterol; Detergents; Lipidomics; Mass Spectrometry; Membrane Microdomains; Sphingolipids
PubMed: 32770499
DOI: 10.1007/978-1-0716-0814-2_2 -
Chemistry and Physics of Lipids Apr 2013Because detergents are commonly used to solvate membrane proteins for structural evaluation, much attention has been devoted to assessing the conformational bias... (Review)
Review
Because detergents are commonly used to solvate membrane proteins for structural evaluation, much attention has been devoted to assessing the conformational bias imparted by detergent micelles in comparison to the native environment of the lipid bilayer. Here, we conduct six 500-ns simulations of a system with >600,000 atoms to investigate the spontaneous self assembly of dodecylphosphocholine detergent around multiple molecules of the integral membrane protein PagP. This detergent formed equatorial micelles in which acyl chains surround the protein's hydrophobic belt, confirming existing models of the detergent solvation of membrane proteins. In addition, unexpectedly, the extracellular and periplasmic apical surfaces of PagP interacted with the headgroups of detergents in other micelles 85 and 60% of the time, respectively, forming complexes that were stable for hundreds of nanoseconds. In some cases, an apical surface of one molecule of PagP interacted with an equatorial micelle surrounding another molecule of PagP. In other cases, the apical surfaces of two molecules of PagP simultaneously bound a neat detergent micelle. In these ways, detergents mediated the non-specific aggregation of folded PagP. These simulation results are consistent with dynamic light scattering experiments, which show that, at detergent concentrations ≥600 mM, PagP induces the formation of large scattering species that are likely to contain many copies of the PagP protein. Together, these simulation and experimental results point to a potentially generic mechanism of detergent-mediated protein aggregation.
Topics: Detergents; Hydrophobic and Hydrophilic Interactions; Membrane Proteins; Molecular Dynamics Simulation; Protein Denaturation; Protein Multimerization; Protein Stability; Protein Structure, Quaternary; Protein Structure, Secondary; Water
PubMed: 23466535
DOI: 10.1016/j.chemphyslip.2013.02.005 -
Acta Crystallographica. Section F,... Dec 2014At the time when the first membrane-protein crystal structure was determined, crystallization of these molecules was widely perceived as extremely arduous. Today, that... (Review)
Review
At the time when the first membrane-protein crystal structure was determined, crystallization of these molecules was widely perceived as extremely arduous. Today, that perception has changed drastically, and the process is regarded as routine (or nearly so). On the occasion of the International Year of Crystallography 2014, this review presents a snapshot of the current state of the art, with an emphasis on the role of detergents in this process. A survey of membrane-protein crystal structures published since 2012 reveals that the direct crystallization of protein-detergent complexes remains the dominant methodology; in addition, lipidic mesophases have proven immensely useful, particularly in specific niches, and bicelles, while perhaps undervalued, have provided important contributions as well. Evolving trends include the addition of lipids to protein-detergent complexes and the gradual incorporation of new detergents into the standard repertoire. Stability has emerged as a critical parameter controlling how a membrane protein behaves in the presence of detergent, and efforts to enhance stability are discussed. Finally, although discovery-based screening approaches continue to dwarf mechanistic efforts to unravel crystallization, recent technical advances offer hope that future experiments might incorporate the rational manipulation of crystallization behaviors.
Topics: Crystallization; Crystallography; Detergents; Membrane Proteins; Protein Stability
PubMed: 25484203
DOI: 10.1107/S2053230X14025035 -
Current Opinion in Structural Biology Oct 1997Five new membrane protein structures have been determined since 1995 using X-ray crystallography: bacterial light-harvesting complex; bacterial and mitochondrial... (Review)
Review
Five new membrane protein structures have been determined since 1995 using X-ray crystallography: bacterial light-harvesting complex; bacterial and mitochondrial cytochrome c oxidases; mitochondrial bc1 complex; and alpha-hemolysin. These successes are partly based on advances in the crystallization procedures for integral membrane proteins. Variation of the size of the detergent micelle and/or increasing the size of the polar surface of the membrane protein is the most important route to well-ordered membrane protein crystals. The use of bicontinuous lipidic cubic phases also appears to be promising.
Topics: Bacterial Proteins; Crystallization; Crystallography, X-Ray; Detergents; Lipids; Membrane Proteins; Models, Molecular; Protein Structure, Secondary
PubMed: 9345629
DOI: 10.1016/s0959-440x(97)80080-2 -
Science China. Life Sciences Jan 2015Membrane proteins are involved in various critical biological processes, and studying membrane proteins represents a major challenge in protein biochemistry. As shown by... (Review)
Review
Membrane proteins are involved in various critical biological processes, and studying membrane proteins represents a major challenge in protein biochemistry. As shown by both structural and functional studies, the membrane environment plays an essential role for membrane proteins. In vitro studies are reliant on the successful reconstitution of membrane proteins. This review describes the interaction between detergents and lipids that aids the understanding of the reconstitution processes. Then the techniques of detergent removal and a few useful techniques to refine the formed proteoliposomes are reviewed. Finally the applications of reconstitution techniques to study membrane proteins involved in Ca(2+) signaling are summarized.
Topics: Detergents; In Vitro Techniques; Membrane Proteins; Microscopy, Electron; Structure-Activity Relationship
PubMed: 25576454
DOI: 10.1007/s11427-014-4769-0