In thrombin stimulated human platelets Citalopram, Promethazine, Risperidone, and Ziprasidone, but not Diazepam, may exert their pharmacological effects also through intercalation in membrane phospholipids in a receptor-independent manner

Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processes according to the drugs’ intercalation capability. We investigated effects of Promethazine, Citalopram, Ziprasidone, Risperidone, and Diazepam on phospholipase A2 (PLA2) and polyphosphoinositide (PPI) metabolism in thrombin-stimulated human platelets. We also examined effects of the drugs on monolayers of glycerophospholipids using the Langmuir technique. Diazepam did not influence PLA2 activity, had no effects on PPI cycle, and caused no change in mean molecular area of phospholipid monolayers. The remaining psychotropic drugs affected these parameters in different ways and levels of potency suggesting that they act by being intercalated between the molecules of adjacent membrane phospholipids, thus causing changes in substrate availability for phospholipid-hydrolyzing enzymes (PLA2 and Phospholipase C). We show that several psychotropic drugs can also have other cellular effects than receptor antagonism. These effects may be implicated in the psychotropic effects of the drugs and/or their side effects

The application of neural network based on the parameters of EEG-signal spectrum characteristics for classification of movement, intention of movement and personal affiliation of the signal

Badanie zmian zachodzących w sygnale elektroencefalograficznym (EEG) pod wpływem zadanego bodźca wymaga założenia, że ta reakcja ma własną i powtarzalną charakterystykę, w przeciwieństwie do ciągłej, spontanicznej aktywności mózgu, która w tym kontekście może być traktowana jako addytywny szum. Na podstawie powyższego założenia podzielono otrzymane w eksperymencie próbki sygnału EEG na grupy danych, związanych z odpowiedzią mózgu na zadane bodźce. Artykuł przedstawia wyniki otrzymane po zastosowaniu prostej sieci neuronowej LVQ (learning vector quantization) do rozróżnienia otrzymanych w eksperymencie danych. Porównano dane związane z ruchem palca i z wyobrażeniem ruchu palcem oraz przeprowadzono rozróżnienie danych otrzymanych od różnych osób. Zastosowanie sieci neuronowej samoorganizującej LVQ, opartej na parametrach charakterystyki widma EEG, pozwoliło na rozróżnienie przynależności personalnej sygnału EEG pomiędzy dwiema osobami ze średnią skutecznością 87,31% oraz pomiędzy czterema osobami ze średnią skutecznością 77,39%.The evaluation of changes within electroencephalography signal (EEG) occurred in response to stimuli, requires the assumption that this reaction has its own, repeatable characteristics compare to the continuous spontaneous brain activity, which can be treated in this context as the additive noise. Therefore, the recorded EEG signal samples, were divided into data groups connected with brain response to the stimuli. The simple neural network LVQ (learning vector quantization) was applied to evaluate recorded data. Movement of finger and voluntary intention of movement were examined. The application of simple neural network LVQ based on parameters of EEG-signal spectrum characteristics allowed for differentiation of EEG signal between two persons with the average efficiency of 87.31% and between four persons with the 77.39% accuracy

Spectroscopic properties and reactivity of free radical forms of A2E

A pyridinium bisretinoid (A2E) is the only identified blue-absorbing chromophore of retinal lipofuscin that has been linked to its aerobic photoreactivity and phototoxicity. Pulse radiolysis has been used to study both the one-electron oxidation and the one-electron reduction of A2E in aqueous micellar solutions. The reduction to the semireduced A2E (lambda(max) broad and between 500 and 540 nm) was achieved with formate radicals and the subsequent decay of A2E* was slow (over hundreds of milliseconds) via complex kinetics. The long lifetime of the A2E* should facilitate its reactions with other biomolecules. For example, with oxygen, the A2E* produced the superoxide radical anion with a rate constant of 3 x 10(8) M(-1) s(-1). The A2E was also reduced by the NAD radical, the corresponding rate constant being 2.3 x 10(8) M(-1) s(-1). Other experiments showed that the one-electron reduction potential of A2E lies in the range -640 to -940 mV. The semioxidized form of A2E (lambda(max) 590 nm) was formed via oxidation with the Br2*- radical and had a much shorter lifetime than the semireduced form. With strongly oxidizing peroxyl radicals (CCl3O2*) our kinetic data suggest the formation of a radical adduct followed by dissociation to the semioxidized A2E. With milder oxidizing peroxyl radicals such as that from methanol, our results were inconclusive. In benzene we observed an efficient oxidation of zeaxanthin to its radical cation by the A2E radical cation; this may be relevant to a detrimental effect of A2E in vision

Oxidation-Induced Increase In Photoreactivity of Bovine Retinal Lipid Extract

Open access original paper Source : 10th EPR Workshop on Applications of EPR in Biology and Medicine, 2016 in Krakow, POLAND.International audienceThe mammalian retina contains a high level of polyunsaturated fatty acids, including docosahexaenoic acid (22:6) (DHA), which are highly susceptible to oxidation. It has been shown that one of the products of DHA oxidation-carboxyethylpyrrole (CEP), generated in situ, causes modifications of retinal proteins and induces inflammation response in the outer retina. These contributing factors may play a role in the development of age-related macular degeneration (AMD). It is also possible that some of the lipid oxidation products are photoreactive, and upon irradiation with blue light may generate reactive oxygen species. Therefore, in this work we analysed oxidation-induced changes in photoreactivity of lipids extracted from bovine neural retinas. Lipid composition of bovine neural retinas closely resembles that of human retinas making the bovine tissue a convenient model for studying the photoreactivity and potential phototoxicity of oxidized human retinal lipids. Lipid composition of bovine neural retinas Folch' extracts (BRex) was determined by gas chromatography (GC) and liquid chromatography coupled to an electrospray ionization source-mass spectrometer (LC-ESI-MS) analysis. Liposomes prepared from BRex, equilibrated with air, were oxidized in the dark at 37 A degrees C for up to 400 h. The photoreactivity of BRex at different stages of oxidation was studied by EPR-oximetry and EPR-spin trapping. Photogeneration of singlet oxygen (O-1(2), (1)Delta(g)) by BRex was measured using time-resolved detection of the characteristic phosphorescence at 1270 nm. To establish contribution of lipid components to the analysed photoreactivity of Folch' extract of bovine retinas, a mixture of selected synthetic lipids in percent by weight (w/w %) ratio resembling that of the BRex has been also studied. Folch's extraction of bovine neural retinas was very susceptible to oxidation despite the presence of powerful endogenous antioxidants such as alpha-tocopherol and zeaxanthin. Non-oxidized and oxidized BRex photogenerated singlet oxygen with moderate quantum yield. Blue-light induced generation of superoxide anion by Folch' extract of bovine neural retinas strongly depended on the oxidation time. The observed photoreactivity of the studied extract gradually increased during its in vitro oxidation

Relationship of intraoperative perfusion parameters to the need for immediate extracorporeal support following heart transplantation.

PURPOSE: We sought to assess the relationship of intraoperative perfusion parameters while on cardiopulmonary bypass, including oxygen delivery (DO METHODS: We included all adult (\u3e18 years old) OHTs performed at our institution since implementation of an electronic perfusion record (March 2019-February 2020). Multi-organ transplants were excluded. The primary outcome was the need for immediate venoarterial ECMO in the OR following OHT. Univariable statistics were computed across demographic, clinical, operative, and perfusion variables, including oxygen delivery (DO RESULTS: Fifty-three OHT were included with a median age of 54 years (interquartile range, 45-61). The primary outcome occurred in eight patients (15.1%). A significantly greater proportion of patients requiring ECMO had ischemic cardiomyopathy (50.0% (4/8) vs. 15.6% (7/45), p = 0.02) and had preoperative ventricular assist devices (37.5% (3/8) vs. 8.9% (4/45), p = 0.03). Median bypass times were longer in the ECMO group (217 vs. 147 minutes, p = 0.001). Phenylephrine doses were nonsignificantly higher in ECMO patients (4.1 vs. 1.9 mg, p = 0.10). No significant differences were observed in single-point median DO CONCLUSION: This is the first study to examine the relationship of perfusion parameters, including oxygen delivery, to outcomes following heart transplantation. We note that D

The role of plasmalogens in the photoreactivity of human retinal lipid extracts of different age groups

Purpose: Plasmalogens (PLs) constitute a specific subclass of phospholipids characterized by a vinyl-ether bond in SN-1 position of the glycerol backbone and account for 10% of total phospholipids in the retina, where are considered as sacrificial antioxidants. PLs above 50% of other phospholipids present in the retina contain polyunsaturated fatty acid (PUFA) chain in SN-2 position. In this work we analyzed the influence of PLs on of phospholipids naturally occurring in the human retina (SRL) in a model system and in retinal pigment epithelium cells in vitro. Methods: Lipid composition of human retinal extracts (RLE) has been determined by GC and LC/MS analysis. RLE and SRL with and without PLS were oxidized in the dark in liposomes equilibrated with air at 37°C. Blue-light induced photoreactivity of the oxidized lipid samples was measured in model systems and in ARPE-19 cells in vitro using time-resolved singlet oxygen phosphorescence at 1270nm, electron paramagnetic resonance (EPR) -oximetry, EPR-spin trapping and electrochemical detection of cholesterol hydroperoxides.Results: Human RLE are very sensitive to oxidation despite the presence of endogenous hydrophobic antioxidants. Both oxidised RLE and SRL generate singlet oxygen and superoxide anion upon irradiation with blue light. The observed photoreactivity of lipids extracted from human retinas increases with age of the donor. It also becomes more pronounced with autooxidation in case of both RLE and SRL.Conclusions: Our results indicate that plasmalogens mediate photoreactivity of retinal lipids in a complex way. It is detected by an increase in the photouptake of oxygen and decreased yields of singlet oxygen photogeneration by oxidized phospholipids