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https://www.readbyqxmd.com/read/27919590/rebuttal-to-the-manuscript-by-r-j-porter-epires-d-16-00150
#1
D G A Kasteleijn-Nolst Trenité
Development of new effective medicines for patients, who continue to have seizures or experience unwanted side-effects, is an important goal. The human "Photosensitivity Model", a POC study, helps to achieve this goal by providing accurate PharmacoKinetic / PharmcoDynamic (PK/PD) data in epilepsy patients at a very early stage and in a highly controlled, standardized and safe setting (in- hospital video-EEG photic stimulation tests and single-dose AED administration). All information referred to in this rebuttal is based on evidence and not on personal communication...
November 27, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27918547/optical-inactivation-of-synaptic-ampa-receptors-erases-fear-memory
#2
Kiwamu Takemoto, Hiroko Iwanari, Hirobumi Tada, Kumiko Suyama, Akane Sano, Takeharu Nagai, Takao Hamakubo, Takuya Takahashi
The synaptic delivery of neurotransmitter receptors, such as GluA1 AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors, mediates important processes in cognitive function, including memory acquisition and retention. Understanding the roles of these receptors has been hampered by the lack of a method to inactivate them in vivo with high spatiotemporal precision. We developed a technique to inactivate synaptic GluA1 AMPA receptors in vivo using chromophore-assisted light inactivation (CALI)...
December 5, 2016: Nature Biotechnology
https://www.readbyqxmd.com/read/27918473/motion-of-adsorbed-nano-particles-on-azobenzene-containing-polymer-films
#3
REVIEW
Sarah Loebner, Joachim Jelken, Nataraja Sekhar Yadavalli, Elena Sava, Nicolae Hurduc, Svetlana Santer
We demonstrate in situ recorded motion of nano-objects adsorbed on a photosensitive polymer film. The motion is induced by a mass transport of the underlying photoresponsive polymer material occurring during irradiation with interference pattern. The polymer film contains azobenzene molecules that undergo reversible photoisomerization reaction from trans- to cis-conformation. Through a multi-scale chain of physico-chemical processes, this finally results in the macro-deformations of the film due to the changing elastic properties of polymer...
December 3, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27915252/photoinactivation-of-bacteria-by-endogenous-photosensitizers-and-exposure-to-visible-light-of-different-wavelengths-a-review-on-existing-data
#4
M Hessling, B Spellerberg, K Hoenes
Visible light has strong disinfectant properties, a fact which is not well known in comparison to the antibacterial properties of UV light. This review compiles the published data on bacterial inactivation caused by visible light and endogenous photosensitizers. It evaluates more than 100 published studies containing information on about 40 different bacterial species irradiated within the spectral range from 380 to 780 nm. In the available data a high variability of the photoinactivation sensitivity is observed, which may be caused by undefined illumination conditions...
December 2, 2016: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/27915030/the-effect-of-anionic-dicephalic-surfactants-on-fabrication-of-varied-core-nanocarriers-for-sustained-release-of-porphyrin-photosensitizers
#5
Urszula Bazylińska, Renata Frąckowiak, Zbigniew Brzózka, Kazimiera A Wilk
Double-headed anionic surfactants could provide a profound group of efficient stabilizers of new template-mediated nanocarriers for effective encapsulation and sustained release of highly hydrophobic photosensitizers, and therefore their improved therapeutic activity in photodynamic therapy (PDT) protocols. We have thus encapsulated porphyrin-origin dyes, i.e., verteporfin (VP) and meso-tetraphenylporphyrin (TPP) in different types of sodium alkyliminobisacetates, Cn(COONa)2-stabilized nanosystems including biocompatible poly(l-glutamic acid)/poly(l-lysine) - PGA/PLL, multilayer nanocapsules (NCs)...
November 19, 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/27914257/photosensitized-degradation-of-acetaminophen-in-natural-organic-matter-solutions-the-role-of-triplet-states-and-oxygen
#6
Yanyun Li, Yanheng Pan, Lushi Lian, Shuwen Yan, Weihua Song, Xin Yang
The photolysis of acetaminophen, a widely used pharmaceutical, in simulated natural organic matter solutions was investigated. The triplet states of natural organic matter ((3)NOM*) were found to play the dominant role in its photodegradation, while the contributions from hydroxyl radicals and singlet oxygen were negligible. Dissolved oxygen (DO) plays a dual role. From anaerobic to microaerobic (0.5 mg/L DO) conditions, the degradation rate of acetaminophen increased by 4-fold. That suggests the involvement of DO in reactions with the degradation intermediates...
November 22, 2016: Water Research
https://www.readbyqxmd.com/read/27913075/the-photosensitivity-model-is-not-a-model-for-partial-focal-seizures-rebuttal
#7
Roger J Porter
New, more effective and less toxic medications are desperately needed for patients with partial (focal) epilepsy. Many hurdles prevent the appropriate study of promising compounds. One of these hurdles is the gap between Phase I and Phase II-the expensive proof of concept to suggest that human trials in partial seizure patients will be successful. A short-cut, the photoparoxysmal response (PPR) model has recently been used to increase confidence in moving a compound into Phase II and III. This shortcut has substantial limitations...
November 22, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27912171/the-topographical-distribution-of-epileptic-spikes-in-juvenile-myoclonic-epilepsy-with-and-without-photosensitivity
#8
P R Bauer, K Gorgels, W Spetgens, N E C van Klink, F S S Leijten, J W Sander, G H Visser, M Zijlmans
OBJECTIVE: Up to 30% of people with juvenile myoclonic epilepsy (JME) have photoparoxysmal responses (PPR). Recent studies report on structural and pathophysiological differences between people with JME with (JME+PPR) and without PPR (JME-PPR). We investigated whether electrophysiological features outside photic stimulation differ between these subtypes. METHODS: We analysed EEG recordings of people with JME at a tertiary epilepsy centre and an academic hospital...
November 14, 2016: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/27911705/disease-mechanisms-of-x-linked-retinitis-pigmentosa-due-to-rp2-and-rpgr-mutations
#9
REVIEW
Rodanthi Lyraki, Roly Megaw, Toby Hurd
Photoreceptor degeneration is the prominent characteristic of retinitis pigmentosa (RP), a heterogeneous group of inherited retinal dystrophies resulting in blindness. Although abnormalities in many pathways can cause photoreceptor degeneration, one of the most important causes is defective protein transport through the connecting cilium, the structure that connects the biosynthetic inner segment with the photosensitive outer segment of the photoreceptors. The majority of patients with X-linked RP have mutations in the retinitis pigmentosa GTPase regulator (RPGR) or RP2 genes, the protein products of which are both components of the connecting cilium and associated with distinct mechanisms of protein delivery to the outer segment...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911037/decoding-the-molecular-basis-for-the-population-mechanism-of-the-triplet-phototoxic-precursors-in-uva-light-activated-pyrimidine-anticancer-drugs
#10
Lara Martínez-Fernández, Giovanni Granucci, Marvin Pollum, Carlos Crespo-Hernández, Maurizio Persico, Ines Corral Perez
Photosensitization of DNA by thionucleosides is a promising photo-chemotherapeutic treatment option for a variety of malignancies. DNA metabolization of thiated prodrugs can lead to cell death upon exposure to a low dose of UVA light. The exact mechanisms of thionucleoside phototoxicity are still not fully understood. In this work, we have combined femtosecond broadband transient absorption experiments with state-of-the-art molecular simulations to provide mechanistic insights for the ultrafast and efficient population of the triplet-state in the UVA-activated pyrimidine anticancer drug: 4-thiothymine...
December 2, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27909098/reversible-disruption-of-neuronal-mitochondria-by-ischemic-and-traumatic-injury-revealed-by-quantitative-two-photon-imaging-in-the-neocortex-of-anesthetized-mice
#11
Mikhail Kislin, Jeremy Sword, Ioulia V Fomitcheva, Deborah Croom, Evgeny Pryazhnikov, Eero Lihavainen, Dmytro Toptunov, Heikki Rauvala, Andre S Ribeiro, Leonard Khiroug, Sergei A Kirov
: Mitochondria play a variety of functional roles in cortical neurons, from metabolic support and neuroprotection to the release of cytokines that trigger apoptosis. In dendrites, mitochondrial structure is closely linked to their function, and fragmentation (fission) of the normally elongated mitochondria indicates loss of their function under such pathological conditions as stroke and brain trauma. Using in vivo two-photon microscopy in mouse brain, we quantified mitochondrial fragmentation in a full spectrum of cortical injuries ranging from severe to mild...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27908525/the-photosensitivity-model-is-not-a-model-for-partial-focal-seizures
#12
Roger J Porter
New, more effective and less toxic medications are desperately needed for patients with partial (focal) epilepsy. Many hurdles prevent the appropriate study of promising compounds. One of these hurdles is the difficult gap between Phase I and Phase II-the expensive proof of concept to suggest that human trials in partial seizure patients will be successful. A short-cut, the photoparoxysmal response (PPR) model has recently been used to increase confidence in moving a compound into Phase II and III (K-N Trenite et al...
November 22, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27903969/targeting-tissue-factor-as-a-novel-therapeutic-oncotarget-for-eradication-of-cancer-stem-cells-isolated-from-tumor-cell-lines-tumor-xenografts-and-patients-of-breast-lung-and-ovarian-cancer
#13
Zhiwei Hu, Jie Xu, Jijun Cheng, Elizabeth McMichael, Lianbo Yu, William E Carson Iii
Targeting cancer stem cell (CSC) represents a promising therapeutic approach as it can potentially fight cancer at its root. The challenge is to identify a surface therapeutic oncotarget on CSC. Tissue factor (TF) is known as a common yet specific surface target for cancer cells and tumor neovasculature in several solid cancers. However, it is unknown if TF is expressed by CSCs. Here we demonstrate that TF is constitutively expressed on CD133 positive (CD133+) or CD24-CD44+ CSCs isolated from human cancer cell lines, tumor xenografts from mice and breast tumor tissues from patients...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27896346/visible-light-driven-mesoporous-ag-embedded-zno-nanocomposites-reactive-oxygen-species-enhanced-photocatalysis-bacterial-inhibition-and-photodynamic-therapy
#14
Jagriti Gupta, Jeotikanta Mohapatra, D Bahadur
We present here the multitasking capabilities of Ag-embedded ZnO nanocomposites (Ag-ZnO NCs), which include the photocatalytic degradation of organic dyes, bacterial inhibition, and cancer therapeutics. Ag-embedded ZnO nanocomposites (Ag-ZnO NCs) of mesoporous spherical morphology (size ∼ 150 ± 50 nm) are successfully synthesized by a facile and single step soft-chemical approach. To understand the effect of Ag loading on multitasking properties, Ag-ZnO NCs are synthesized with different wt% of Ag. It was found that Ag5-ZnO NCs (5 wt% of Ag) showed excellent solar light-induced photocatalytic degradation properties against both cationic as well as anionic dyes...
November 29, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/27893096/chemogenetic-activation-of-iprgcs-drives-changes-in-dark-adapted-scotopic-electroretinogram
#15
Nina Milosavljevic, Annette E Allen, Jasmina Cehajic-Kapetanovic, Robert J Lucas
Purpose: The purpose of this study was to investigate the impact of activating melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) on dark-adapted (scotopic) electroretinograms (ERG). Methods: We used mice (Opn4Cre/+) expressing cre recombinase in melanopsin-expressing cells for a targeted gene delivery of a chemogenetic Gq-coupled receptor, hM3Dq, to ipRGCs. Intraperitoneal injection of clozapine N-oxide (CNO) at 5 mg/kg was used for acute activation of hM3Dq and thus excitation of ipRGCs in darkness...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27892715/incorporation-of-chemotherapeutic-agent-and-photosensitizer-in-a-low-temperature-sensitive-liposome-for-effective-chemo-hyperthermic-anticancer-activity
#16
Hanh Thuy Nguyen, Tuan Hiep Tran, Raj Kumar Thapa, Tung Thanh Pham, Jee-Heon Jeong, Yu Seok Youn, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
OBJECTIVES: In this study, we combined chemo- and hyperthermia therapy in a low temperature-sensitive liposome (LTSL) for potential cancer treatment. METHODS: Docetaxel (DOC) and indocyanine green (ICG) as a therapeutic agent and photosensitizer, respectively, were incorporated in a low temperature-sensitive liposome (LTSL/DI). Nanoparticles were evaluated for the physicochemical characterizations, in vitro uptake and cytotoxicity, and furthermore in vivo anticancer activity...
November 28, 2016: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/27892657/effective-delivery-of-porphyrazine-photosensitizers-to-cancer-cells-by-polymer-brush-nanocontainers
#17
Natalia Y Shilyagina, Nina N Peskova, Svetlana A Lermontova, Anna A Brilkina, Vladimir A Vodeneev, Alexander V Yakimasky, Larisa G Klapshina, Irina V Balalaeva
Efficient drug delivery can be assigned to tasks that attract the most acute attention of researchers in the field of anticancer drug design. We have reported the first case of using amphiphilic polymer brushes as nanocontainers for photosensitizer delivery to cancer cells. Regular graft-copolymers of hydrophobic polyimides with hydrophilic polymethacrylic acid side chains were loaded with photosensitive dye tetra(4-fluorophenyl)tetracyanoporphyrazine (Pz) providing a sufficiently stable homogeneous fraction of fluorescent Pz-loaded nanoparticles with a size of 100-150 nm...
November 28, 2016: Journal of Biophotonics
https://www.readbyqxmd.com/read/27892573/thermodynamics-of-dna-sensitizer-recognition-characterizing-binding-motifs-with-all-atom-simulations
#18
Hugo Gattuso, Elise Dumont, Christophe Chipot, Antonio Monari, François Dehez
We report the investigation of the thermochemical properties of benzophenone interacting with B-DNA studied by all-atom molecular dynamic simulations. In particular, we determine the binding free energy for two competitive binding modes, minor groove binding and double insertion. Our results allow us to quantitatively resolve for the first time the mode of binding of this paradigmatic photosensitizer, indicating a marked preference for minor groove binding. Furthermore, we have settled a protocol allowing for the determination of binding energies in the case of non-covalent interaction with DNA, in particular, tackling the non-trivial problem of the strong reorganization of the DNA imposing extended statistical sampling...
November 28, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27890773/primary-photosensitization-caused-by-ingestion-of-froelichia-humboldtiana-by-dairy-goats
#19
Danielle S Santos, Caio C B Silva, Valber O Araújo, Maria de Fátima Souza, Patrícia B Lacerda-Lucena, Sara V D Simões, Franklin Riet-Correa, Ricardo B Lucena
This study aimed to describe the first report of an outbreak of primary photosensitization in dairy goats caused by Froelichia humboldtiana. The disease occurred from March to May 2014, in a mixed flock of 15 Saanen, Alpine, and crossbred lactating goats. The entire flock was affected; however, the Saanen and cross-bred goats developed more severe lesions, and their milk production decreased by as much as 75%. Lesions were progressive and consisted of skin hyperemia, edema, and necrosis, especially in depigmented areas...
November 24, 2016: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/27890593/evaluation-of-the-crystal-structure-of-a-fimbrillin-fima-from-porphyromonas-gingivalis-as-a-therapeutic-target-for-photo-activated-disinfection-with-toluidine-blue-o
#20
Maryam Pourhajibagher, Abbas Bahador
BACKGROUND: Porphyromonas gingivalis is one of the etiological agents in the initiation of combined periodontal-endodontic (perio-endo) lesions. Successful treatment of perio-endo lesions with photo-activated disinfection (PAD) as a novel therapeutic approach depends on the selection of an appropriate target site, specific photosensitizer (PS), and wavelength of light. Since the fimbrillin (FimA) is the most important pathogenic agent in P. gingivalis it was evaluated as a target site against PAD with toluidine blue O (TBO) as a PS...
November 23, 2016: Photodiagnosis and Photodynamic Therapy
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