Phenothiazinium derivatives for pathogen inactivation in blood products

Wainwright, Mark; Mohr, H.; Walker, Wolfram H.

doi:10.1016/j.jphotobiol.2006.07.005

Cited by 119 publications

(73 citation statements)

References 69 publications

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“…MB is a phenothiazine compound which intercalates into viral nucleic acid, and subsequent illumination generates singlet oxygen leading to guanosine oxidation and destruction of the viral nucleic acid preventing viral replication [46,47] (fig. 4).…”

Section: Pathogen Reduction Capacitymentioning

confidence: 99%

Main Properties of the THERAFLEX MB-Plasma System for Pathogen Reduction

Seghatchian¹,

Struff

Reichenberg

2011

Transfus Med Hemother

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Methylene blue (MB) treated plasma has been in clinical use for 18 years. The current THERAFLEX MB-Plasma has a number of improved features compared with the original Springe methodology. This overview embodies: the biochemical characteristics of MB, the mechanism of the technology, toxicology, pathogen reduction capacity, current position in clinical setting and status within Europe. The THERAFLEX MB (TMB) procedure is a robust, well standardised system lending itself to transfusion setting and meets the current guidelines. The pathogen kill power of the TMB system, like the other available technologies, is not limitless, probably in order of 6 log for most enveloped viruses and considerably less for non-enveloped ones. It does not induce either new antigen or grossly reducing the function and life span of active principle in fresh frozen plasma (FFP). The removal of the residual MB at the end of the process has the beneficial effect of reducing potential toxic impacts. Clinical haemovigilance data, so far, indicate that cell-free MB plasma is effective in all therapeutic setting requiring FFP, besides inconsistent thrombotic thrombocytopenia purpura data, without serious side-effects or toxicity. The current system is in continuous improvement e.g. regarding virus reduction range, illumination device, software used, and process integration in the blood bank setting.

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Section: Pathogen Reduction Capacitymentioning

confidence: 99%

Main Properties of the THERAFLEX MB-Plasma System for Pathogen Reduction

Seghatchian¹,

Struff

Reichenberg

2011

Transfus Med Hemother

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“…This inactivation deficiency, observed in plasma, cannot be attributed to the decrease in light intensity due to absorption or scattering, because the fresh human plasma used is clear and neither absorbs in the 661-nm excitation wavelength region nor scatters the LED light. Singlet oxygen is the dominant active species responsible for the photoinactivation of bacteria (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21), with MB being the primary photosensitizing agent used for the generation of singlet oxygen and the sterilization of plasma (22)(23)(24)(25)(26)(27). To that effect we investigated possible reactions between plasma and MB that may be responsible for decrease in singlet oxygen generation that would explain the low bacteria inactivation rate in plasma.…”

mentioning

confidence: 99%

Rationale and mechanism for the low photoinactivation rate of bacteria in plasma

Chen

Cesario

Rentzepis

2013

Proc. Natl. Acad. Sci. U.S.A.

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The rate of bacterial photoinactivation in plasma by methylene blue (MB), especially for Gram-negative bacteria, has been reported to be lower, by about an order of magnitude, than the rate of inactivation in PBS and water solutions. This low inactivation rate we attribute to the bleaching of the 660-nm absorption band of MB in plasma that results in low yields of MB triplet states and consequently low singlet oxygen generation. We have recorded the change of the MB 660-nm-band optical density in plasma, albumin, and cysteine solutions, as a function of time, after 661-nm excitation. The transient triplet spectra were recorded and the singlet oxygen generated in these solutions was determined by the rate of decrease in the intensity of the 399-nm absorption band of 9, 10-anthracene dipropionic acid. We attribute the bleaching of MB, low singlet oxygen yield, and consequently the low inactivation rate of bacteria in plasma to the attachment of a hydrogen atom, from the S-H group of cysteine, to the central nitrogen atom of MB and formation of cysteine dimer.ADPA | photoinactivation deficiency | Leuco methylene blue | electrophilic attack | transient spectroscopy E ven though infections from bacterially contaminated plasma are thought to be very few (1) and the frequency of patient sepsis caused by transfusion of blood contaminated by bacteria is as low or less than the transfusion-associated hepatitis C virus infection (2), the possibility of such infection cannot be entirely discounted in view of the fact that new or even more resistant strains of known bacteria are being encountered. To a large extent, pooled human plasma is sterilized by the solvent-detergent method (3-5), whereas single-donor human plasma is often decontaminated by methylene blue (MB) photoexcitation, which generates reactive oxygen species that safely inactivate many viruses (6, 7). However, several Gram-positive and especially Gram-negative bacteria are found to be very resistant to photoinactivating agents such as porphyrins and thiazine dyes, possibly because the outer walls of Gram-negative bacteria, such as Serratia marcescens (SM), are composed of negatively charged lipopolysaccharides, which are resistant to photoinactivation by these dyes (8).Gram-positive bacteria and several Gram-negative bacteria are relatively easily inactivated, especially in high-pH MB-PBS solutions, after irradiation with 661-nm light for a rather short period, i.e., 10 min (9). Gram-negative bacteria usually require longer exposure times for inactivation. Table 1 lists the time required for the inactivation of two representative bacteria, coagulasenegative Staphilcocci, CoNS (Gram-positive) and SM (Gramnegative). Inactivation of bacteria dispersed in PBS at pHs 7 and 9 occurs within 20 min or less; however, note that when the same concentration of bacteria, 10 7 /mL, was dispersed in a solution of human plasma containing 2 × 10 −5 M MB and irradiated with the same photon flux of 6.8-mW, 661-nm light-emitting diode (LED) light, the inactivation rate was found ...

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“…12 A técnica oferece vantagens como um amplo espectro de ação, sendo eficiente inclusive sobre microrganismos resistentes a antibióticos e apresentando menores efeitos colaterais nocivos quando comparada a outros tratamentos. 8,12,13 Além disso, uma vez que a inativação se dá por meio da produção de espécies altamente reativas com ataque a múltiplos alvos celulares, não se considera possível o desenvolvimento de resistência microbiana. Por essas vantagens, a utilização da TFDA tem se mostrado relevante, por exemplo, na esterilização de bolsas de sangue, na periodontia e no tratamento e conservação de alimentos.…”

Section: 4unclassified

Atividade Fotodinâmica E Conceitos: Um Experimento Demonstrativo

Silva¹,

Freitas²,

Tessaro³

et al. 2018

Quim. Nova

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PHOTODYNAMIC ACTIVITY AND CONCEPTS: A DEMONSTRATIVE EXPERIMENT. A simple and low cost experiment is proposed to chemistry students associating the Photodynamic Activity involving Chemical and Biochemical concepts. The inclusion of this experiment in undergraduate courses in Chemistry promotes interdisciplinarity and contextualization, combining current and relevant topics to the teaching of program content. The experiment used the Methylene Blue and Erythrosine B as dyes to demonstrate the photodynamic action of these photosensitizers in the inhibition of microbial growth. Both dyes presented satisfactory results against environmental microorganisms. The growth inhibition was caused exclusively by the photochemical processes undergone by the dye/light/oxygen, with LED light exposure.Keywords: photodynamic therapy; methylene blue; erythrosine B, LED, inactivation of microorganism. INTRODUÇÃOAo longo dos séculos a luz vem sendo empregada na medicina, tendo registros datados há mais de 4000 anos no Egito, na Grécia e na Índia, nos quais a luz solar era empregada na cura de vários distúrbios. Pensava-se que somente a luz solar era responsável pela cura de doenças como vitiligo, psoríase, raquitismo e até psicose. Com o avanço científico notou-se que geralmente o efeito era obtido após a ingestão de plantas, seguida pela exposição solar.1 Ressalta-se que naquele momento, não se conhecia a existência de raios ultravioleta (UV), que foram descobertos após 1801. 2Anos mais tarde pesquisadores perceberam que o efeito terapêu-tico estava relacionado à combinação da luz solar com os pigmentos presentes nas plantas ingeridas, ou seja, aos corantes. A idéia de usar um corante como agente terapêutico surgiu de uma observação realizada por Oscar Raab, na época aluno do professor von Tappeiner no Instituto Farmacológico do Ludwig Maximilian, na Universidade de Munique (1897-1898). Raab realizava um estudo sobre a letalidade do vermelho de acridina sobre o protozoário causador da malária (Paramecium caudatum). Ele identificou letalidade reduzida em um dia chuvoso, entretanto, em um dia ensolarado, o efeito foi pronunciado. A partir desta observação, ele concluiu que a luz ativava o corante, induzindo o microrganismo à morte. Em 1903, é reportada a primeira utilização fotodinâmica de corantes no tratamento de tumores por von Tappeiner e Jesionek, utilizando o corante eosina. 3A partir de então, inúmeros estudos foram realizados com intuito de compreender os efeitos fotodinâmicos acarretados pela combinação da luz com os corantes. Descobriu-se que a atividade só era efetiva se a luz empregada tivesse emissão em comprimentos de onda condizente com o espectro de absorção dos corantes, processo fotoquímico primário, e se houvesse a presença de oxigênio molecular ( 3 O 2 ). Assim surgiu a base da chamada Terapia Fotodinâmica (TFD), envolvendo a ativação de um composto fotossensibilizador (FS, corante) por luz de comprimento de onda adequado na presença de oxigênio. Dessa interação resulta a geração de oxigênio singleto ( 1 O 2 ) e esp...

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Phenothiazinium derivatives for pathogen inactivation in blood products

Cited by 119 publications

References 69 publications

Main Properties of the THERAFLEX MB-Plasma System for Pathogen Reduction

Main Properties of the THERAFLEX MB-Plasma System for Pathogen Reduction

Rationale and mechanism for the low photoinactivation rate of bacteria in plasma

Atividade Fotodinâmica E Conceitos: Um Experimento Demonstrativo

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