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11	Benzalkonio ir metenamino analogų antimikrobinio aktyvumo nustatymas in vitro ir jo priklausomybė nuo aerozolio dalelių krūvio / Establishment of benzalkonium and methenamine analoques antimicrobic activity in vitro and its dependency upon the electrical charge of the particles in the aerosol Grigonis, Aidas 14 February 2007 (has links) Antibacterial effectiveness in vitro of the original quaternary ammonium compounds that were synthesized in the Laboratory of Biologically active substances was determined and the dependence of this activity upon chemical structure of the compound was established. Also generalisations have been made concerning the regularity of this dependency, the effectiveness of the compounds was compared to benzalkonium chloride, their advantages and disadvantages were discussed. Acute toxicity of the most effective compound was established and compared to that of benzalkonium chloride. It was found that these compounds showed good antibacterial activity against Gr+ and Gr- bacteria and low toxicity, thus this original data was summarized in the patent Nr. 4712. For the first time it was found that upon disintegration of quaternary methenamonium compounds new quaternary ammonium compounds, aldehydes and ammonia are produced. The first two of the three show further antimicrobic activity. Using quaternary ammonium salts and cholrhexydine a biocide for disinfection was created. The created biocide was tested for effectiveness when used for disinfection of air in the premises, horizontal and vertical surfaces. The compound was used in the form of aerosols and electro-aerosols. The research data showed that strong concentrations of Dezinfektas IV are necessary (up to 30%), but small amount of the solution per volume is enough (20-30 ml/m3). Ten times higher concentration is needed for... [to full text] Veterinary Medicine U-77 Benzalkonium chloride Ketvirtiniai amonio junginiai Dezinfektas Quaternary ammonium compounds Benzalkonio chloridas
12	Metagenomic and metatranscriptomic investigation of microorganisms exposed to benzalkonium chloride disinfectants Oh, Seung Dae 12 January 2015 (has links) Benzalkonium chlorides (BACs) are widely used, broad-spectrum disinfectants and frequently detected in the environment, even at toxic levels for life. Since such disinfectants can induce broad resistance capabilities, BACs may fuel the emergence of antibiotic resistance in the environment. A substantial body of literature has reported that exposure to BACs causes antibiotic resistance; yet, other studies suggest that the resistance linkage is rare, unsystematic, and/or clinically insignificant. Accordingly, whether or not disinfectant exposure mediates antibiotic resistance and, if so, what molecular mechanisms underlie the resistance link remains to be clearly elucidated. Further, understanding how microbial communities degrade BACs is important not only for alleviating the possible occurrence of antibiotic resistance but also reducing the potential risks to environmental and public health. An integrated strategy that combines metagenomics, metatranscriptomics, genetics, and traditional culture-dependent approaches was employed to provide novel insights into these issues. The integrative approach showed that a microbial community exposed to BACs can acquire antibiotic resistance through two mechanisms: i) horizontal transfer of previously uncharacterized efflux pump genes conferring resistance to BACs and antibiotics, which were encoded on a conjugative plasmid and co-selected together upon BACs and ii) selective enrichment of intrinsically multi-drug resistant organisms. Further, a microbial community adapts to BAC exposure via a variety of mechanisms, including selective enrichment of BAC-degrading species and amino acid substitutions and horizontal transfer of genes related to BAC resistance and degradation. The metatranscriptomic data suggests that the BAC-adapted microbial community metabolized BACs by cooperative interactions among its members. More specifically, Pseudomonas nitroreducens cleaved (i.e., dealkylated) BACs, metabolized the alkyl chain (the dealkylated product of BACs), and released benzyldimethylamine (the other product of BACs), which was further metabolized by other community members (e.g., Pseudomonas putida). Collectively, this study demonstrates the role of BACs in promoting antibiotic resistance and advances current understanding of a microbial community degrading BACs. The results of this work have important implications for (appropriate) usage of disinfectants and for assessing, predicting, and optimizing biological engineering processes treating BAC-bearing waste streams. Benzalkonium chloride Quaternary ammonium compounds Disinfectants Antibiotic resistance Biodegradation Metagenomics Metatranscriptomics Horizontal gene transfer
13	The Evaluation of the Effect of Anionic and Cationic Surfactants on the Hindered Settling of Light Calcium Carbonate Suspensions Chalamuri, Shanmuka Harish January 2014 (has links) No description available. Pharmaceuticals Pharmacy Sciences Hindered settling light calcium carbonate calcium carbonate sodium lauryl sulfate benzalkonium chloride
14	Incidence des pratiques d'entretien des toitures sur la qualité des eaux de ruissellement : cas des traitements par produits biocides Van De Voorde, Antoine, Van De Voorde, Antoine 06 June 2012 (has links) (PDF) Ce travail de thèse a dans un premier temps permis de mettre en évidence les différentes pratiques de traitement de toiture existantes en France. Après avoir sélectionné la pratique de traitement majoritaire (à savoir le traitement biocide), le protocole d'analyse de la molécule la plus répandue dans les différents produits : le benzalkonium (ou alkyldiméthylbenzylammonium) a été développé. Ce protocole a ensuite été appliqué pour évaluer les niveaux de concentration en biocide dans l'eau de ruissellement de toiture après un traitement. Une double approche a été mise en œuvre : "Suivi sur une durée d'un an des flux de benzalkonium dans les eaux de ruissellement de 12 bancs d'essais exposés en conditions naturelles", évaluation en condition de pluie simulée au laboratoire de différents paramètres (nature du matériau de couverture, dosage du produit et intensité de la pluie) sur les processus d'émission du benzalkonium. Enfin, l'ensemble des données acquises ont permis d'évaluer l'incidence sur la contamination des eaux de ruissellement de toiture après un traitement biocide, à une échelle locale et à l'échelle d'un petit bassin versant résidentiel. Le suivi de la contamination des eaux de ruissellement par bancs d'essais a permis de mettre en évidence une très forte contamination en benzalkonium dans les premiers millimètres de pluie (5 à 27 mg/L), très supérieures aux EC50 disponibles pour les organismes aquatiques (5,9 µg/L) et dépendante de la nature du matériau de toiture utilisé, les tuiles en terre cuite ayant émis moins de biocide que les tuiles en béton. La contamination diminue avec la succession des pluies, mais reste significative plusieurs mois après le traitement. Par ailleurs, l'étude au laboratoire a montré que l'état de surface des tuiles influence beaucoup le lessivage. Ainsi, les tuiles très imperméables en surface ont émis une quantité de benzalkonium proportionnelle à la masse épandue lors du traitement, alors que les tuiles sans traitement de surface ne sont pas sensibles au dosage du produit. A l'échelle locale, des précautions doivent être prise lors d'un traitement de toiture vis-à-vis de la collecte / utilisation des eaux de ruissellement. En effet, les très fortes concentrations en benzalkonium dans les premières pluies suivant le traitement peuvent avoir des impacts sur les végétaux arrosés, sur l'équilibre microbien de la cuve de récupération, voir des effets irritants sur l'homme. Une déconnexion minimale de 3 à 5 mois de la cuve permettrait de limiter les risques. Enfin, sur la base des résultats des bancs d'essais et d'un travail d'enquête sur l'étendue des pratiques de traitement, les concentrations et flux de benzalkonium susceptibles d'être émis dans les eaux pluviales d'un bassin versant résidentiel ont été modélisés. Les résultats mettent en évidence une contamination significative des eaux pluviales, liée essentiellement à la phase particulaire. La masse annuelle de benzalkonium exportée dans les eaux pluviales pourrait être de l'ordre de 0,85 kg / ha imperméabilisé / an Ruissellement de toiture Biocide Benzalkonium Contamination Récupération des eaux de pluie
15	Survival, regrowth and morphotype formation of Salmonella strains after exposure to high or low concentrations of first generation QAC in water Umutesi, Grace 09 December 2022 (has links) This study determines the differences in survival of eight Salmonella strains concentration of BAC in water, followed by regrowth in high and low nutrition conditions containing sublethal concentration of BAC. Our results show strain difference in survival, persistence of Salmonella in BAC at different concentrations. All eight strains of Salmonella were non-recoverable when exposed to 40 to 48 µg/ml BAC for 1h in water. When exposed to 24 µg/ml of BAC for 1 h in water, S. Typhimurium ATCC 14028 and S. Heidelberg ATCC 8326 cells were non-detectable from the initial 7 log CFU/ml. S. Blockley 7175, S. Virchow 7207, S. Poona 01A4242 and S. Poona 00A3208, were non-detectable after 1 h exposure at 24 µg/ml and continued to be non-detectable in 12 µg/ml BAC in both nutrient conditions after 24 h. 3/8 strains formed rugose morphotypes when exposed to BAC thus leading to understanding the role of strain differences. Salmonella benzalkonium chloride quaternary ammonium compounds sublethal and lethal concentrations tolerance and persistence Agriculture Animal Sciences Food Science Microbiology
16	Architecture des biofilms et résistance à la désinfection : apport de l'imagerie de fluorescence multimodale Bridier, Arnaud 09 June 2011 (has links) (PDF) Dans les environnements naturels, industriels ou médicaux, les microorganismes sont majoritairement présents en étant associés aux surfaces dans des communautés hautement organisées appelées biofilms. Ces édifices biologiques constituent une stratégie de survie étonnement efficace témoignant d'une grande capacité de résistance à différent stress environnementaux tels que les traitements de nettoyage et de désinfection. L'impact des biofilms d'un point de vue sanitaire est donc considérable du fait qu'ils permettent la persistance et la transmission de germes pathogènes dans l'environnement. Dans ce contexte, ce travail de thèse avait pour objectif une meilleure compréhension des phénomènes limitant l'efficacité de désinfectants au sein des biofilms en s'appuyant notamment sur des techniques innovantes d'imagerie de fluorescence non-invasive. Le but final étant d'apporter des éléments utiles à l'optimisation des traitements de désinfection. Dans une première partie, une méthode d'investigation structurale à haut-débit par microscopie confocale a été développée et utilisée pour étudier la diversité architecturale des biofilms bactériens formés par un large panel de souches. Cette étude nous a permis d'identifier des souches d'intérêt en termes de structures de biofilms formés pour la suite du travail. Nous avons notamment pu mettre en évidence la capacité de B. subtilis à former des structures importantes et avec une architecture spécifique dans un système immergé. Dans une deuxième partie, les dynamiques d'action spatiotemporelles de désinfectants ont été visualisées dans les biofilms de souches de P. aeruginosa ou B. subtilis par des approches de microscopie confocale de fluorescence en temps réel. L'utilisation de cette technique nous a permis de mettre en évidence les difficultés de pénétration du chlorure de benzalkonium au sein des structures formées par différentes souches de P. aeruginosa. La corrélation des paramètres cinétiques d'inactivation et des données obtenues par la caractérisation biochimique de la matrice suggère un rôle majeur des substances extracellulaires dans la limitation de pénétraton du désinfectant. Nous avons également pu montrer une résistance marquée du biofilm formé par une souche de B. subtilis isolée d'un dispositif médical à l'acide péracétique, à la concentration et au temps d'utilisation du biocide dans le milieu médical. De plus, les structures tridimensionnelles formées par cette souche étaient capables de protéger le pathogène Staphylococcus aureus dans un biofilm mixte vis-à-vis du même traitement soulignant l'importance des interactions multi-espèces dans la résistance des bactéries aux désinfectants et la persistance de pathogènes dans nos environnements. Biofilm désinfection fluorescence pseudomonas aeruginosa bacillus subtilis microscopie confocale chlorure de benzalkonium acide peracétique
17	In vitro anti-bacterial activity of titanium oxide nano-composites containing benzalkonium chloride and chlorhexidine gluconate Atbayga, Abdalla Mohammed Ali January 2013 (has links) Thesis submitted in fulfilment of the requirements for the degree Master of Technology: Biomedical Technology In the Faculty of Health and Wellness Sciences At Cape Peninsula University of Technology 2013 / Newly developed and commercial dental resins which are commonly used nowadays have to be tested for their antimicrobial susceptibility. The purpose of this in vitro study was to investigate the antimicrobial activity of a titanium oxide (TiO2) nano-composite which was prepared with different antibacterial substances and used as restoratives in dentistry to combat certain selected bacteria that are considered the principle causes of some tooth diseases, for example, tooth decay and to prevent unsuccessful dental restoration. The TiO2 nano-composite was prepared and divided into four groups: The first group was an untreated TiO2 nano-composite. The second group was silane-treated TiO2 nano-composite. The third group was treated TiO2 nano-composite which was combined with chlorhexidine gluconate (CHxG). The fourth group was treated TiO2 nano-composite which was combined with benzalkonium chloride (BzCl). Five of the selected bacteria were grown overnight in Petri dishes. Four of them, namely, Escherichia coli (E. coli) ATCC 11775, Staphylococcus aureus (S. aureus) ATCC 12600, Enterococcus faecalis (E. faecalis) ATCC 29212, and Pseudomonas aeruginosa (P. aeruginosa) ATCC 10145, were grown on Müller-Hinton Agar (MHA). Streptococcus mutans (S. mutans) ATCC 25175 was grown on Brain Heart Infusion (BHI) agar. All these bacteria were tested against the TiO2 nano-composite, and incubated for 24 hours at 37°C, except S. mutans, which was incubated separately and exposed to CO2. It was placed into a CO2 water-jacketed incubator in an atmosphere of 5% CO2 for 24 hours at 37°C. The obtained results showed that neither of the groups of TiO2 nano-composites, (untreated TiO2 nano-composite and treated TiO2 nano-composite) exhibited antimicrobial activity against the pathogens. Only preparations of TiO2 nano-composites at a concentration of 3 %m/m of both CHxG and BzCl showed antimicrobial activity against S. aureus. Antimicrobial activity against S. mutans, E. coli, P. aeruginosa, E. faecalis and S. aureus, were only realized at a concentration of 10 %m/m for both CHxG and BzCl.. Dental resins Dental materials Composite materials Nanostructured materials Nanocomposites (Material) Carbon dioxide Titanium oxide Camphorquinone Urethane dimethacrylate Silane Dental restoratvie materials Antimicrobial activity Benzalkonium chloride Chlorhexidine gluconate
18	Investigation of drug ionic liquid salts for topical delivery systems Bansiwal, Mukesh January 2017 (has links) Pharmaceutical companies and FDA (Federal Drug Administration) rules rely heavily on crystalline active pharmaceutical ingredients delivered as tablets and powders in the form of neutral compounds, salts and solvates of neutral compounds and salts. About half of all drugs sold in the market are in the form of salts which are held together by ionic bonds along with some other forces. Recently, Ionic liquids (ILs) an interesting class of chemical compounds have offered potential opportunity for exploration as novel drug ionic liquid salts, particularly in the field of transdermal/topical drug delivery. Due to the multifunctional nature of these salts they could allow generation of new pathway to manipulate the transport and deposition behaviour of the drug molecule. It is this modular approach of IL that forms the basis of the research presented here, in which pharmaceutically acceptable compounds are combined with selected drugs with known problems. IL salts were generated by combining at least one drug molecule with FDA approved compounds and were assessed for physicochemical properties, skin deposition and permeation studies. Skin deposition data suggested that these systems exhibit high skin retention, which was found to correlate with the molecular weight. On the other hand, permeation data displayed an inverse relationship between flux values and molecular weight of the permeant. Similar work was extended with ILs with mixed anions containing two drugs. The benzalkonium-sulfacetamide ILs were investigated for synergism and the biological studies data display no synergistic effect. It was also illustrated that in-situ IL based ibuprofen hydrogels systems could be manipulated via IL approach for topical application. These findings suggest the potential applicability of IL based formulations for topical delivery of drugs. Ionic liquids (ILs) Poorly water soluble drugs Topical drug delivery Partitioning Ion-pairing Carbomer Oligomer Benzalkonium ILs Ionic liquids with mixed anions Hydrogel NSAIDs Sulfacetamide Pharmaceutical performance
19	Development of Sensitive In Vitro Assays to Assess the Ocular Toxicity Potential of Chemicals and Ophthalmic Products McCanna, David January 2009 (has links) The utilization of in vitro tests with a tiered testing strategy for detection of mild ocular irritants can reduce the use of animals for testing, provide mechanistic data on toxic effects, and reduce the uncertainty associated with dose selection for clinical trials. The first section of this thesis describes how in vitro methods can be used to improve the prediction of the toxicity of chemicals and ophthalmic products. The proper utilization of in vitro methods can accurately predict toxic threshold levels and reduce animal use in product development. Sections two, three and four describe the development of new sensitive in vitro methods for predicting ocular toxicity. Maintaining the barrier function of the cornea is critical for the prevention of the penetration of infections microorganisms and irritating chemicals into the eye. Chapter 2 describes the development of a method for assessing the effects of chemicals on tight junctions using a human corneal epithelial and canine kidney epithelial cell line. In Chapter 3 a method that uses a primary organ culture for assessing single instillation and multiple instillation toxic effects is described. The ScanTox system was shown to be an ideal system to monitor the toxic effects over time as multiple readings can be taken of treated bovine lenses using the nondestructive method of assessing for the lens optical quality. Confirmations of toxic effects were made with the utilization of the viability dye alamarBlue. Chapter 4 describes the development of sensitive in vitro assays for detecting ocular toxicity by measuring the effects of chemicals on the mitochondrial integrity of bovine cornea, bovine lens epithelium and corneal epithelial cells, using fluorescent dyes. The goal of this research was to develop an in vitro test battery that can be used to accurately predict the ocular toxicity of new chemicals and ophthalmic formulations. By comparing the toxicity seen in vivo animals and humans with the toxicity response in these new in vitro methods, it was demonstrated that these in vitro methods can be utilized in a tiered testing strategy in the development of new chemicals and ophthalmic formulations. in vitro Alternative Methods alamarBlue rhodamine tight junctions bovine lens viability toxicity mitochondria mitochondria integrity benzalkonium chloride sodium dodecyl sulphate sodium lauryl sulfate scanning electron microscopy Draize Draize maximal average scores zonula occludens cosmetic directive PETA humane society animal league ICCVAM ECVAM JaCVAM BCOP bovine cornea ocular irritants ocular irritation ocular toxicity human corneal epithelial cells vitro confocal confocal microscopy metabolic activity optical quality reactive oxygen species contact lens contact lens care solutions barrier function microbial keratitis mulitipurpose solutions tight junction cell damage claudin ZO-1 occludin MDCK Madin Madin-Darby canine kidney cells cornea human cornea human corneal epithelium epithelial cell line human corneal epithelial cell line sodium fluorescein sodium fluorescein permeability fluorescein permeability ocular surface cell monolayer Araki-Sasaki cell physiology risk assessment safety assessment ScanTox scanning laser lens epithelium corneal cells in vitro model ophthalmic formulations multiple instillation back vertex animal testing rabbit testing alternatives to animal testing cultured bovine lens toxicity of chemicals irritation irritants laser scanner organ culture delayed toxicity toxins hydrogen peroxide cornea toxicity cornea toxicity models prediction of human toxicity no observable adverse effect level lowest observable adverse effect level NOAEL LOAEL toxicity thresholds safety factors cornea uncertainty factors preservatives disinfectants ophthalmic products preclinical preclinical testing epithelial barrier drug penetration clinical confocal microscopy animal rights rabbit cornea human cornea human clinical effects toxic animal rights activist sensitive measures toxic effect toxicity threshold agar overlay agar diffusion agar overlay method agar diffusion method cytochrome cytochrome c apoptosis necrotic apoptotic necrosis caspase rhodamine 123 resazuran resorufin cell death cell viability metabolic dye microsomal microsomal enzymes cytotoxicity cytotoxic cytotoxic effect MTT XTT WST-1 plasma membrane mitochondrial mitochondrial morphology ocular toxicity potential ocular toxicity human corneal epithelial cell line confocal analysis corneal epithelium cell fluorescence alamarBlue assay rhodamine dye animal welfare toxic injury degraded mitochondria epithelial monolayer disinfectants membrane integrity eye toxicity eye viability dye toxicity in humans human toxicity effects on the mitochondria mitochondrial toxicity in vitro battery in vitro test battery ophthalmic eye drop direct contact product safety cytotoxicity potential molecular molecular biology refine reduce replace sensitivity and relevance sensitivity relevance rabbit ocular irritation test product development cytotoxicity models cytotoxicity alternative methods replacements for animal testing three r's beagle tiered testing tiered testing strategy replacements animal testing mechanistic toxicity cornea mitochondria dose response threshold Vision Science and Biology
20	Development of Sensitive In Vitro Assays to Assess the Ocular Toxicity Potential of Chemicals and Ophthalmic Products McCanna, David January 2009 (has links) The utilization of in vitro tests with a tiered testing strategy for detection of mild ocular irritants can reduce the use of animals for testing, provide mechanistic data on toxic effects, and reduce the uncertainty associated with dose selection for clinical trials. The first section of this thesis describes how in vitro methods can be used to improve the prediction of the toxicity of chemicals and ophthalmic products. The proper utilization of in vitro methods can accurately predict toxic threshold levels and reduce animal use in product development. Sections two, three and four describe the development of new sensitive in vitro methods for predicting ocular toxicity. Maintaining the barrier function of the cornea is critical for the prevention of the penetration of infections microorganisms and irritating chemicals into the eye. Chapter 2 describes the development of a method for assessing the effects of chemicals on tight junctions using a human corneal epithelial and canine kidney epithelial cell line. In Chapter 3 a method that uses a primary organ culture for assessing single instillation and multiple instillation toxic effects is described. The ScanTox system was shown to be an ideal system to monitor the toxic effects over time as multiple readings can be taken of treated bovine lenses using the nondestructive method of assessing for the lens optical quality. Confirmations of toxic effects were made with the utilization of the viability dye alamarBlue. Chapter 4 describes the development of sensitive in vitro assays for detecting ocular toxicity by measuring the effects of chemicals on the mitochondrial integrity of bovine cornea, bovine lens epithelium and corneal epithelial cells, using fluorescent dyes. The goal of this research was to develop an in vitro test battery that can be used to accurately predict the ocular toxicity of new chemicals and ophthalmic formulations. By comparing the toxicity seen in vivo animals and humans with the toxicity response in these new in vitro methods, it was demonstrated that these in vitro methods can be utilized in a tiered testing strategy in the development of new chemicals and ophthalmic formulations. in vitro Alternative Methods alamarBlue rhodamine tight junctions bovine lens viability toxicity mitochondria mitochondria integrity benzalkonium chloride sodium dodecyl sulphate sodium lauryl sulfate scanning electron microscopy Draize Draize maximal average scores zonula occludens cosmetic directive PETA humane society animal league ICCVAM ECVAM JaCVAM BCOP bovine cornea ocular irritants ocular irritation ocular toxicity human corneal epithelial cells vitro confocal confocal microscopy metabolic activity optical quality reactive oxygen species contact lens contact lens care solutions barrier function microbial keratitis mulitipurpose solutions tight junction cell damage claudin ZO-1 occludin MDCK Madin Madin-Darby canine kidney cells cornea human cornea human corneal epithelium epithelial cell line human corneal epithelial cell line sodium fluorescein sodium fluorescein permeability fluorescein permeability ocular surface cell monolayer Araki-Sasaki cell physiology risk assessment safety assessment ScanTox scanning laser lens epithelium corneal cells in vitro model ophthalmic formulations multiple instillation back vertex animal testing rabbit testing alternatives to animal testing cultured bovine lens toxicity of chemicals irritation irritants laser scanner organ culture delayed toxicity toxins hydrogen peroxide cornea toxicity cornea toxicity models prediction of human toxicity no observable adverse effect level lowest observable adverse effect level NOAEL LOAEL toxicity thresholds safety factors cornea uncertainty factors preservatives disinfectants ophthalmic products preclinical preclinical testing epithelial barrier drug penetration clinical confocal microscopy animal rights rabbit cornea human cornea human clinical effects toxic animal rights activist sensitive measures toxic effect toxicity threshold agar overlay agar diffusion agar overlay method agar diffusion method cytochrome cytochrome c apoptosis necrotic apoptotic necrosis caspase rhodamine 123 resazuran resorufin cell death cell viability metabolic dye microsomal microsomal enzymes cytotoxicity cytotoxic cytotoxic effect MTT XTT WST-1 plasma membrane mitochondrial mitochondrial morphology ocular toxicity potential ocular toxicity human corneal epithelial cell line confocal analysis corneal epithelium cell fluorescence alamarBlue assay rhodamine dye animal welfare toxic injury degraded mitochondria epithelial monolayer disinfectants membrane integrity eye toxicity eye viability dye toxicity in humans human toxicity effects on the mitochondria mitochondrial toxicity in vitro battery in vitro test battery ophthalmic eye drop direct contact product safety cytotoxicity potential molecular molecular biology refine reduce replace sensitivity and relevance sensitivity relevance rabbit ocular irritation test product development cytotoxicity models cytotoxicity alternative methods replacements for animal testing three r's beagle tiered testing tiered testing strategy replacements animal testing mechanistic toxicity cornea mitochondria dose response threshold Vision Science and Biology

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