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15-Lipoxygenases (15-LOs) catalyse the peroxidation reaction of arachidonic acid (AA) in mammals with remarkable regioand stereospecificity. This positional-specific peroxidation is of paramount importance because it determines the nature and biological functions of the final metabolites generated by each LO as a result of the oxidative metabolism of AA. Although several hypotheses have been formulated concerning the regio- and stereospecificity of LOs, the molecular basis of such behaviour is still unclear. Herein, we combined quantum mechanics/molecular mechanics calculations with molecular dynamics simulations of the complete rabbit 15-LO/AA solvated model to examine the most accepted hypotheses for the regio- and stereospecificity of LOs. We have found that the clue to explain this specificity is the oxygen-targeting hypothesis through steric shielding of specific residues (mainly Leu597, Gln548 and Phe175, as well as the AA tail itself). Our deductions are based primarily on the analysis of the energy barrier heights from the oxygen addition reaction profiles, Spanish Ministerio de Econom a y Competitividad, Generalitat de Catalunya, Alianza 4U, Depto. de Química Física, Fac. de Ciencias Químicas, TRUE, pub

So far, the possibility of synthesizing hydrogels based on multiple biopolymers has been investigated, and among them lignin has proven to be one of the potentials for this purpose due to the multiple advantages it offers. However, because of its high molecular weight, steric hindrance and few reactive sites on its structure, it is sometimes necessary to improve its reactivity though chemical modifications. On the basis of previous results, two chemical modifications were selected in order to enhance almond, walnut and commercial alkaline and organosolv lignins' reactivity: a peroxidation reaction for alkaline ones and a hydroxymethylation for organosolv ones. Both reactions were confirmed by multiple techniques (i.e. FTIR, GPC and TGA). Hydrogels were syn-thesized from these lignins according to previous works. The high lignin waste of the synthesized hydrogels suggested that despite the modification of the lignins, just the highest molecular weight fractions reacted with the matrix polymer. Moreover, the swelling capacity of modified alkaline lignin-based hydrogels was negatively affected, whereas the one for organosolv lignin-based samples improved. The SEM micrographs explained the aforementioned, and the results from the DSC and compression tests were in accordance with them. Self -extracted quercetin loading and release studies suggested that these samples could be used for controlled drug delivery.

In the present study, UV-induced membrane destabilization by TiO2 (anatase) nanoparticles was investigated by neutron reflectometry (NR), small-angle X-ray scattering (SAXS), quartz crystal microbalance with dissipation (QCM-D), dynamic light scattering (DLS), and zeta-potential measurements for phospholipid bilayers formed by zwitterionic palmitoyloleoylphos-phatidylcholine (POPC) containing biologically relevant poly unsaturations. TiO2 nanoparticles displayed pH-dependent bind ing to such bilayers. Nanoparticle binding alone, however, has virtually no destabilizing effects on the lipid bilayers. In contrast, UV illumination in the presence of TiO2 nanoparticles activates membrane destabilization as a result of lipid oxidation caused by the generation of reactive oxygen species (ROS), primarily (OH)-O-center dot radicals. Despite the short diffusion length characterizing these, the direct bilayer attachment of TiO2 nanoparticles was demonstrated to not be a sufficient criterion for an efficient UV-induced oxidation of bilayer lipids, the latter also depending on ROS generation in bulk solution. From SAXS and NR, minor structural changes were seen when TiO2 was added in the absence of UV exposure, or on UV exposure in the absence of TiO2 nanoparticles. In contrast, UV exposure in the presence of TiO2 nanoparticles caused large-scale structural transformations, especially at high ionic strength, including gradual bilayer thinning, lateral phase separation, increases in hydration, lipid removal, and potential solubilization into aggregates. Taken together, the results demonstrate that nanoparticle-membrane interactions ROS generation at different solution conditions act in concert to induce lipid membrane destabilization on UV exposure and that both of these need to be considered for understanding the performance of UV-triggered TiO2 nanoparticles in nanomedicine.

BACKGROUND:Oxidized derivatives of polyunsaturated fatty acids, collectively known as oxylipins, are labile bioactive mediators with diverse roles in human physiology and pathology. Oxylipins are increasingly being measured in plasma collected in clinical studies to investigate biological mechanisms and as pharmacodynamic biomarkers for nutrient-based and drug-based interventions. Whole blood is generally stored either on ice or at room temperature prior to processing. However, the potential impacts of delays in processing, and of temperature prior to processing, on oxylipin concentrations are incompletely understood. OBJECTIVE:To evaluate the effects of delayed processing of blood samples in a timeframe that is typical of a clinical laboratory setting, using typical storage temperatures, on concentrations of representative unesterified oxylipins measured by liquid chromatography-tandem mass spectrometry. DESIGN:Whole blood (drawn on three separate occasions from a single person) was collected into 5 mL purple-top potassium-EDTA tubes and stored for 0, 10, 20, 30, 60 or 120 min at room temperature or on wet ice, followed by centrifugation at 4 °C for 10 min with plasma collection. Each sample was run in duplicate, therefore there were six tubes and up to six data points at each time point for each oxylipin at each condition (ice/room temperature). Representative oxylipins derived from arachidonic acid, docosahexaenoic acid, and linoleic acid were quantified by liquid chromatography tandem mass spectrometry. Longitudinal models were used to estimate differences between temperature groups 2 h after blood draw. RESULTS:We found that most oxylipins measured in human plasma in traditional potassium-EDTA tubes are reasonably stable when stored on ice for up to 2 h prior to processing, with little evidence of auto-oxidation in either condition. By contrast, in whole blood stored at room temperature, substantial time-dependent increases in the 12-lipoxygenase-derived (12-HE

The behaviour of slightly oxidized virgin and refined soybean oils during in vitro digestion was studied by H-1 nuclear magnetic resonance (H-1 NMR) and solid phase microextraction-gas chromatography/mass spectrometry. The main objectives were to analyze lipolysis extent and oxidation during digestion, and to assess the impact of two different proportions of ovalbumin on both processes. At the same time gamma-tocopherol fate was monitored, when possible, by H-1 NMR. The results reveal that the initial oxidation degree of the oils negatively influences the lipolysis extent, reducing the bioaccessibility of the major oil components, which include some essential fatty acids. Although the low ovalbumin proportion tested does not significantly affect lipolysis, this is greatly enhanced when ovalbumin is added at a high level, improving lipid bioaccessibility. It has also been shown that oxidation does not seem to have occurred to a great enough extent during digestion for it to be detected from polyunsaturated acyl group degradation. Moreover, the changes observed in the oxidation product profile of the starting oils after digestion can be considered to be due mainly to the transformation of the initially present hydroperoxides, whose concentration diminishes in the digested samples to give hydroxy-dienes, epoxides and aldehydes. In presence of a high ovalbumin proportion, hydroperoxide reduction to hydroxy-dienes is favoured and lower levels of aldehydes and epoxides are observed. This latter could be due to a diminution in their generation and/or to their reaction with ovalbumin. A high proportion of this protein in the system also increases gamma-tocopherol bioaccessibility.

The respiratory system is continuously exposed to variety of biological and chemical irritants that contain reactive oxygen species, and these are well known to cause oxidative stress responses in lung epithelial cells. There is a clinical need to identify biomarkers of oxidative stress which could potentially support early indicators of disease and health management. To identify volatile biomarkers of oxidative stress, we analyzed the headspace above human bronchial epithelial cell cultures (HBE1) before and after hydrogen peroxide (H2O2) and cigarette smoke extract (CSE) exposure. Using stir bar and headspace sorptive extraction-gas chromatography-mass spectrometry, we searched for volatile organic compounds (VOC) of these oxidative measures. In the H2O2 cell peroxidation experiments, four different H2O2 concentrations (0.1, 0.5, 10, 50 mM) were applied to the HBE1 cells, and VOCs were collected every 12 h over the time course of 48 h. In the CSE cell peroxidation experiments, four different smoke extract concentrations (0%, 10%, 30%, 60%) were applied to the cells, and VOCs were collected every 12 h over the time course of 48 h. We used partial-least squares (PLS) analysis to identify putative compounds from the mass spectrometry results that highly correlated with the known applied oxidative stress. We observed chemical emissions from the cells that related to both the intensity of the oxidative stress and followed distinct time courses. Additionally, some of these chemicals are aldehydes, which are thought to be non-invasive indicators of oxidative stress in exhaled human breath. Together, these results illustrate a powerful in situ cell culture model of oxidative stress that can be used to explore the putative biological genesis of exhaled breath biomarkers that are often observed in human clinical studies.

BACKGROUND: Oxidized derivatives of polyunsaturated fatty acids, collectively known as oxylipins, are labile bioactive mediators with diverse roles in human physiology and pathology. Oxylipins are increasingly being measured in plasma collected in clinical studies to investigate biological mechanisms and as pharmacodynamic biomarkers for nutrient-based and drug-based interventions. Whole blood is generally stored either on ice or at room temperature prior to processing. However, the potential impacts of delays in processing, and of temperature prior to processing, on oxylipin concentrations are incompletely understood. OBJECTIVE: To evaluate the effects of delayed processing of blood samples in a timeframe that is typical of a clinical laboratory setting, using typical storage temperatures, on concentrations of representative unesterified oxylipins measured by liquid chromatography-tandem mass spectrometry. DESIGN: Whole blood (drawn on three separate occasions from a single person) was collected into 5 mL purple-top potassium-EDTA tubes and stored for 0, 10, 20, 30, 60 or 120 min at room temperature or on wet ice, followed by centrifugation at 4 °C for 10 min with plasma collection. Each sample was run in duplicate, therefore there were six tubes and up to six data points at each time point for each oxylipin at each condition (ice/room temperature). Representative oxylipins derived from arachidonic acid, docosahexaenoic acid, and linoleic acid were quantified by liquid chromatography tandem mass spectrometry. Longitudinal models were used to estimate differences between temperature groups 2 h after blood draw. RESULTS: We found that most oxylipins measured in human plasma in traditional potassium-EDTA tubes are reasonably stable when stored on ice for up to 2 h prior to processing, with little evidence of auto-oxidation in either condition. By contrast, in whole blood stored at room temperature, substantial time-dependent increases in the 12-lip

BackgroundLinoleic acid (LA) is abundant in modern industrialized diets. Oxidized LA metabolites (OXLAMs) and reactive aldehydes, such as 4-hydroxy-2-nonenal (4-HNE), are present in heated vegetable oils and can be endogenously synthesized following consumption of dietary LA. OXLAMs have been implicated in cerebellar degeneration in chicks; 4-HNE is linked to neurodegenerative conditions in mammals. It unknown whether increasing dietary LA or OXLAMs alters the levels of oxidized fatty acids (oxylipins), precursor fatty acids, or 4-HNE in mammalian brain.ObjectivesTo determine the effects of increases in dietary OXLAMs and dietary LA, on levels of fatty acids, oxylipins, and 4-HNE in mouse brain tissues.MethodsMice (n = 8 per group) were fed one of three controlled diets for 8 weeks: (1) a low LA diet, (2) a high LA diet, or (3) the low LA diet with added OXLAMs. Brain fatty acids, oxylipins, and 4-HNE were quantified in mouse cerebellum and cerebral cortex by gas chromatography-flame ionization detection, liquid chromatography-tandem mass spectrometry, and immunoblot, respectively.ResultsIncreasing dietary LA significantly increased omega-6 fatty acids, decreased omega-3 fatty acids, and increased OXLAMs in brain. Dietary OXLAMs had minimal effect on oxidized lipids but did decrease both omega-6 and omega-3 fatty acids. Neither dietary LA nor OXLAMs altered 4-HNE levels.ConclusionBrain fatty acids are modulated by both dietary LA and OXLAMs, while brain OXLAMs are regulated by endogenous synthesis from LA, rather than incorporation of preformed OXLAMs.

We previously showed that an alkyl-ether analog of lysophosphatidic acid, AGP (alkyl-glycerophosphate), accumulates in human atherosclerotic plaques and is a potent agonist of peroxisome proliferator-activated receptor-gamma (PPAR gamma). On the other hand, cyclic phosphatidic acid (cPA), similar in structure to AGP, can negatively regulate PPAR gamma. However, in this study, cPA had no effect on the expression and secretion of C-C motif chemokine 2 (CCL-2), a chemokine that is also linked to inflammatory responses and atherosclerosis. We showed that AGP enhances CCL-2 mRNA expression and secretion in a dose-dependent manner. Furthermore, oxidative stress plays a major role in the pathology of cardiovascular diseases; we showed that AGP triggers ROS generation and lipid peroxidation and that ROS and 8-isoprostane generation can be suppressed by a PPAR gamma antagonist. These results suggest that an imbalance of the PPAR gamma agonist-antagonist equilibrium is involved in changes in cellular functions, including ROS generation and lipid peroxidation., Article, BIOMEDICINE & PHARMACOTHERAPY. 106:686-691 (2018)

Thirty male merino lambs were fed with a pelleted total mixed ration (TMR) alone or supplemented with hop(Humulus lupulus L.) cones at two different doses (1.5 and 3.0 g hop cones/kg pelleted TMR, respectively), tostudy the effects of this dietary source of antioxidants on animal performance, ruminal parameters and meatquality attributes. The results showed that dietary supplementation with hop cones decreased lambs' growth rate(P < 0.05) due to a shift in ruminal fermentation, towards a more acetic and less propionic acid production(P < 0.05). These changes in animal growth rate might have promoted microstructural modifications in thequantity and size of muscle fibres, thereby inducing the differences observed in meat chemical composition,colour and texture (P < 0.05), regardless of the lack of differences in meat antioxidant status (P > 0.10)

The article presents results of the comparative analysis of peroxidation process activity of caspase-3 and caspase-8 in patients with thyroid adenoma (TA) and nodular goiter with autoimmune thyroiditis (NGAIT). Studying peroxidation processes in the tissue of the thyroid gland abnormal tissue was detected to be characterized by increase in of protein oxidative modification (POM) indices at the same time, the antioxidant enzymes activity (AEA) was significantly reduced and was more likely in patients with NGAIT. Significant increase in activity of both caspase 3 and 8 was shown in patients with NGAIT compared to macroscopically unchanged tissue and thyroid adenoma. Possible mechanisms of the detected disorders were discussed.

Досліджено вплив УВЧ-опромінення потужністю 40 та 80 Вт на показники кількості формених елементів крові, активність амінотрансфераз, вмісту малонового діальдегіду та відновленого глутатіону. Виявлено, що потужність 40 Вт при одноразовій та дворазовій дії не призводить до змін досліджуваних показників. Опромінення потужністю 80 Вт викликає активацію процесів перекисного окислення ліпідів та обміну метаболітів. Довготривала (впродовж 40 хв) дія проявляється вже через дві години, а менш тривала (впродовж 20 хв) – через добу., Introduction. A person is not able to physically feel the electromagnetic field that surrounds them but some frequencies can influence health and working ability, and cause changes of the adaptive reserves.Purpose. The aim of the research was to determine the hematological and biochemical parameters in rats under UHF irradiation with power of 40 and 80 Watts.Results. The influence of UHF irradiation with power of 40 and 80 Watts on parameters of the number of erythrocytes, leukocytes, platelets, transaminases, the content of malondialdehyde and reduced glutathione was studied. It was found that power of 40 Watts in single and double action did not lead to changes in parameters 2, 4, 24 and 26 hours after exposure. Irradiation of 80 Watts caused activation of lipid peroxidation and the exchange of metabolites. Long-term (for 40 minutes) exposure was manifested after two hours, and less long-term exposure (for 20 minutes) was manifested after a day.The study showed that dose of 40 Watts is safe, activates antioxidant protection of cells, reduces the level of MDA and can be used for the further study of the impact of ultrahigh radiation on the body., Проблема. Человек не в состоянии физически чувствовать электромагнитное поле, которое окружает его, но некоторые частоты могут влиять на здоровье и работоспособность, вызывать изменения адаптивных резервов.Целью исследования было определение гематологических и биохимических показателей у крыс при УВЧ-облучении мощностью 40 и 80 Вт.Результаты. Исследовано влияние УВЧ-облучения мощностью 40 и 80 Вт на показатели количества форменных элементов крови, активность аминотрансфераз, содержания малонового диальдегида и восстановленного глутатиона. Выявлено, что мощность 40 Вт при одноразовом и двухразовом действии не приводит к изменениям показателей через 2, 4, 24 и 26 часов после воздействия. Излучение мощностью 80 Вт вызывает активацию процессов перекисного окисления липидов и обмена метаболитов. Длительное (в течение 40 мин) действие проявляется уже через два часа, а менее длительное воздействие (в течение 20 мин) проявляется через сутки.Заключение. В ходе исследования показано, что доза 40 Вт является безопасной, активирует антиоксидантную защиту клеток, уменьшает уровень МДА и может быть использована для дальнейшего изучения влияния на организм ультравысокочастотного облучения.

Effect of low dose irradiation was investigated in human neuronal progenitor cells. As a result, over 1 Gy X-ray irradiation caused apoptosis and lipid peroxidation. DNA array assay was tested using a smaller dose (0.5 Gy) than that of 1 Gy, and it was found that it still caused apoptosis related gene expressions.

En este trabajo reportamos la oxidación de una serie de compuestos organoazufrados volátiles (COV) catalizada por la enzima cloroperoxidasa obtenida del hongo Caldariomyces fumago. Los COV se consideran contaminantes atmosféricos debido a su olor desagradable y a su bajo umbral de detección. El sulfuro de etilo, disulfuro de dimetilo, propanotiol, butanotiol y hexanotiol fueron transformados por la enzima en un medio de reacción acuoso a pH 6 y en presencia de peróxido de hidrógeno. El análisis de los productos demostró que los sulfuros fueron oxidados a sus respectivos sulfóxidos, mientras que los tioles fueron oxidados a sus correspondientes disulfuros. Los productos identificados tienen una presión de vapor significativamente menor que los compuestos originales, por lo que son mucho menos volátiles y por tanto no se consideran contaminantes atmosféricos. Se ensambló un reactor de dos fases de 70 mL de volumen con el fin de determinar la eficiencia del tratamiento enzimático. La fase líquida, compuesta por 85% de amortiguador y 15% de solvente orgánico, se puso en contacto con la fase gaseosa, compuesta por aire enriquecido con el sustrato. Usando disulfuro de metilo como sustrato modelo, encontramos únicamente reacción enzimática en este sistema; al controlar la concentración de enzima y de peróxido en la fase líquida se logró transferir el sustrato a la fase acuosa en donde 1 mol de enzima convirtió aproximadamente 12,400 moles de sustrato, resaltando el potencial de los tratamientos enzimáticos para las corrientes gaseosas con mal olor por COV., In this work we report the oxidation of volatile organosulfur compounds (VOC) catalyzed by the enzyme chloroperoxidase from Caldariomyces fumago. VOC are regarded as atmospheric pollutants due to their unpleasant odor and low detection threshold. Diethyl sulfide, dimethyl disulfide, propanethiol, butanethiol and hexanethiol were found to be substrates for the enzyme in a liquid medium reaction at pH 6, under peroxidatic conditions. Product analysis showed that sulfides were oxidized to their respective sulfoxides whereas thiols were oxidized to the corresponding disulfides. The identified products showed significantly lower vapor pressure than the parental compounds; thus, the products are not considered atmospheric pollutants. A 70-mL two-phase reactor was assembled in order to determine the efficiency of the enzymatic treatment. The liquid phase, consisting of 15% organic solvent and 85% buffer, was contacted with the gaseous phase, consisting of a substrate-enriched air stream. Using dimethyl disulfide as model substrate, we found that only enzymatic oxidation occurred in this system; by controlling the enzyme and peroxide concentration, we found that the substrate is transferred to the aqueous phase where 1 mol of enzyme converted approximately 12,400 mol of substrate, thus highlighting the potential of enzymatic treatment of malodorous gaseous streams.

The deterioration of lipids by oxygen, termed peroxidation, is a constitutive process in living systems. Enzymatic peroxidation is required for some forms of cell signalling, but the non-enzymatic peroxidation of polyunsaturated fatty acids (PUFA) produces numerous toxic and mutagenic products associated with pathology and aging. Phospholipids containing PUFA are common in mammalian membranes, but an inverse relationship has been found between membrane susceptibility to peroxidation and maximal lifespan (MLS). Past studies of peroxidation have focused on the PUFA content of phospholipids, but other elements of phospholipid composition including class and saturated fatty acid (SFA) or monounsaturated fatty acid (MUFA) content may also influence peroxidation. This thesis presents three studies investigating the relationship between phospholipid composition and peroxidation.

We combined quantum mechanics/molecular mechanics calculations with molecular dynamics simulations to study the addition of O2 to the pentadienyl radical of arachidonic acid (AA) catalyzed by the Leu597Val and Leu597Ala mutants of rabbit 15-lipoxygenase (15-rLO). In the Leu597Val mutant, the addition of O2 to C15 of AA is the predominant path, although it reduces the C15/C11 product ratio by almost ten times with respect to the wildtype enzyme. The S stereochemistry is kept. Mutation to Ala causes just the opposite effect: regiospecificity favoring addition to C15 is somewhat sharper than that in the wildtype, but the stereochemistry is R. This is because the extra space created by the mutation to Ala is big enough for AA to move so that it can adopt an alternative binding mode, and this opens new feasible paths for the attack of O2 . So, we showed that the Leu597Ala mutant of 15r-LO works as an aspirin-acetylated cyclooxygenase-2, which makes 15-(R)- hydroperoxyeicosatetraenoic acid, Ministerio de Economia y ́Competitividad, Generalitat de Catalunya, Depto. de Química Física, Fac. de Ciencias Químicas, TRUE, pub

The results of biomedical research on the impact of additive «Maltovin » with antioxidant properties on the state of the antioxidant system of animals by biochemical parameters are given in the paper. The main objective of the research was to determine the toxicological safety of using chopped meat products with complex additive «Maltovin» for biological objects and solve the problem of improving the quality of meat products by increasing their resistance to oxidation processes. Subchronic administration of the additive “Maltovin” in chopped meat products, which have passed the preliminary heat treatment, to the diet of laboratory rats did not result in any statistically significant changes in indicators of morphometry, metabolism and overall functional state of experimental animals compared with the control group. There was no lag in the weight gain, structure indicators and ratio of blood cells, hemoglobin content in experimental animals, behind that of control animals. The activity of key enzymes of carbohydrate and protein metabolism changed insignificantly that proves the lack of the negative impact of additive and foods with it on the hepatorenal system. Safety of using the additive is also confirmed by indicators, characterizing preserving the balance between pro- and antioxidant systems (by indicators of MDA, DP, GR, G-6, FDG) of animals. Analysis of the obtained results showed that “Maltovin” can be used as an effective antioxidant additive, which promotes preserving the quality of meat products with significant fat content and does not affect the state of the main physiological systems., В статье представлены результаты медико-биологических исследований по изучению воздействия добавки «Мальтовин» с антиокислительными свойствами на состояние антиоксидантных систем лабораторных животных по биохимическим показателям – активности ферментов антиоксидантной защиты и уровню перекисного окисления липидов. Установлено, что длительное употребление полуфабрикатов с пищевой добавкой не оказывает негативного воздействия на метаболизм и состояние основных физиологических систем организма., В статті представлені результати медико-біологічних досліджень щодо впливу добавки з антиокислювальними властивостями «Мальтовин» на стан антиоксидантної системи тварин за біохімічними показниками – активністю ферментів антиоксидантного захисту і рівню перекисного окиснення ліпідів у лабораторних тварин. Встановлено, що тривале споживання напівфабрикатів з харчовою добавкою не викликає негативних функціональних зрушень у метаболізмі та стані основних фізіологічних систем організму.

In this study, non-oxidative and oxidative thermogravimetric analysis was applied as a method for determining the thermal stability of the total lipids extracted from Zlatibor bacon in different phases of production (raw samples, 10th and 30th day of smoking and 30th day of storage). The activation energies of the thermal degradation and oxidation of the total lipids extracted from examined samples were determined. A moderate increase of the activation energy, as well as the other information gained from TG analyses, indicated that there were no significant oxidative changes in Zlatibor bacon lipids during the production and storing.

The increase in polyunsaturated fatty acid (PUFA) consumption has prompted research into alternative resources other than fish oil. In this study, a new approach based on focal-plane-array Fourier transform infrared (FPA-FTIR) microspectroscopy and multivariate data analysis was developed for the characterisation of some marine microorganisms. Cell and lipid compositions in lipid-rich marine yeasts collected from the Australian coast were characterised in comparison to a commercially available PUFA-producing marine fungoid protist, thraustochytrid. Multivariate classification methods provided good discriminative accuracy evidenced from (i) separation of the yeasts from thraustochytrids and distinct spectral clusters among the yeasts that conformed well to their biological identities, and (ii) correct classification of yeasts from a totally independent set using cross-validation testing. The findings further indicated additional capability of the developed FPA-FTIR methodology, when combined with partial least squares regression (PLSR) analysis, for rapid monitoring of lipid production in one of the yeasts during the growth period, which was achieved at a high accuracy compared to the results obtained from the traditional lipid analysis based on gas chromatography. The developed FTIR-based approach when coupled to programmable withdrawal devices and a cytocentrifugation module would have strong potential as a novel online monitoring technology suited for bioprocessing applications and large-scale production.

Background: Pulmonary surfactants are important parts of host defence against respiratory infections. Bacterial pneumonia in late preterm or term newborn infants often causes surfactant inactivation or peroxidation, leading to surfactant deficiency or dysfunction. Studies of animal models of pneumonia and case reports suggest that exogenous surfactant may be beneficial for infants with bacterial pneumonia. Method(s): We used standard Cochrane Collaboration methodology to conduct our search of databases including MEDLINE (accessed via PubMed), EMBASE and the Cochrane Central Register of Controlled Trials in June 2011. We limited our search to randomised and quasi-randomised trials of surfactant replacement therapy in infants >35 weeks gestation with bacterial pneumonia in the first 28 days of life. The primary outcome measures were death, time to resolution of pneumonia, incidence of chronic lung disease, pneumothoraces and pulmonary haemorrhage. All studies were assessed with predefined criteria as to whether they were eligible for inclusion. We used the standard Cochrane Collaboration methodology for data collection and analysis, on assessment of risk of bias in any studies, heterogeneity, treatment effect, missing data and reporting bias where appropriate. Data were abstracted where appropriate into RevMan 5. Result(s): Although 2 publications were identified from the search that dealt with surfactant replacement in neonatal pneumonia, no studies met our inclusion criteria, Conclusion(s): There is no evidence from randomised controlled trials to support or refute the efficacy of surfactant in near term and term infants with proven or suspected bacterial pneumonia. Randomised controlled trials are still required to answer this question.

Phospholipids where both fatty acids are polyunsaturated are very rare. Most organisms prefer to couple their polyunsaturated fatty acids (PUFA) with either a saturated (SAT) or a monounsaturated (MUFA) fatty acid. This study examined if these natural couplings are there to protect PUFA from themselves. Specifically, does the coupling of PUFA to SAT or MUFA reduce the potential for increased rates of peroxidation by shrouding these highly peroxidisable fatty acids with less peroxidisable fatty acids? The influence of head group was examined by using the two most common phospholipids found in vertebrate membranes i.e. phosphatidylcholine and phosphatidylethanolamine species. Fatty acid pairings included 16:0/18:2 versus 18:2/18:2 and 16:0/22:6 versus 22:6/22:6. All phospholipids were incorporated into liposomes that were matched for their total PUFA content i.e. 25% PUFA/PUFA or 50% SAT/PUFA with phosphatidylcholine 16:0/16:0 used as the background phospholipid. An iron initiator (Fe2+/H2O2) was used to induce peroxidation and lipid hydroperoxide production was used to measure peroxidation. The results show that coupling of PUFA together on the same molecule does not increase peroxidation rates and therefore does not support the proposed hypothesis. The lower than expected levels of peroxidation measured for some phospholipid species (e.g. PtdEtn 22:6/22:6) is possibly due to the partitioning of these molecular species into the inner leaflet of the bilayer.

The synthesis of 3-pyridinols carrying alkyltelluro, alkylseleno, and alkylthio groups is described together with a detailed kinetic, thermodynamic, and mechanistic Study of their antioxidant activity. When assayed for their capacity to inhibit azo-initiated peroxidation of linoleic acid in a water/chlorobenzene two-phase system, tellurium-containing 3-pyridinols were readily regenerable by N-acetylcysteine contained in the aqueous phase. The best inhibitors quenched peroxyl radicals more efficiently than alpha-tocopherol, and the duration of inhibition was limited only by the availability of the thiol reducing agent. fn homogeneous phase, inhibition of styrene autoxidation absolute rate constants k(inh) for quenching of peroxyl radical were as large as 1 x 10(7) M-1 s(-1), thus Outperforming the best phenolic antioxidants including alpha-tocopherol. Tellurium-containing 3-pyridinols could be quantitatively regenerated in homogeneous phase by N-tert-butoxycarbonyl cysteine methyl ester, a lipid-soluble analogue of N-acetylcysteine. In the presence of an excess of the thiol, a catalytic mode of action was observed, similar to the one in the two-phase system. Overall, compounds bearing the alkyltelluro moiety ortho to the OH group were much more effective antioxidants than the corresponding para isomers. The origin of the high reactivity of these compounds was explored using pulse-radiolysis thermodynamic measurements, and a mechanism for their unusual antioxidant activity was proposed. The tellurium-containing 3-pyridinols were also found to catalyze reduction of hydrogen peroxide in the presence of thiol reducing agents, thereby acting as multifunctional (preventive and chain-breaking) catalytic antioxidants., QC 20100902

1. The oxidative stress theory of ageing predicts that animals living longer will have less cumulative oxidative damage together with structural characteristics that make them more resistant to oxidative damage itself. 2. Although a general relationship between body size, metabolism and longevity does not exist in marine invertebrates, they are generally characterized by low rates of metabolism and reactive oxygen species (ROS) formation associated with lower antioxidant enzyme activities compared to vertebrates. 3. Birds and mammals have very similar size-affected metabolic rates and their metabolic intensity explains only some of the variation in maximum lifespan potential (MLSP).Within each class, smaller animals have higher rates of metabolism and ROS production and membranes that are more susceptible to oxidative damage and autocatalytic propagation of free radicals than larger ones. 4. Although the high variation in life-history strategies is accompanied by substantial variation in MLSP, there is a consistent positive correlation between rates of ROS formation and antioxidant levels among most animals examined so far for these traits. The consensus of these studies is that ROS and antioxidant levels are inversely related to MLSP. 5. The lack of a clear stoichiometric relation between variables contributing to oxidative stress limits our capacity to infer longevity consequences from measures of pro-oxidant or antioxidant status among or within species

Plant-pathogen interactions are associated with plant defense mechanism known as hypersensitive response (HR), which is a form of programmed cell death (PCD). In the present work we have tested the potency of chemicals, proven as PCD inhibitors in other systems, to prevent the spread of cell death in detached tobacco leaves challenged with ß- xylanase from Aspergillus awamori K1. Xylanase induced cell death that was accompanied by electrolyte leakage and increased levels of the stress metabolites hydrogen peroxide and malondialdehyde. Lesion development, ion leakage and the production of stress metabolites were suppressed if the infiltration site was pre-infiltrated with broad range caspase inhibitor benzyoxycarbonyl-Asp-2,6-dichlorobenzoyloxymethylketone (Z-Asp-CH2-DCB), cysteine protease inhibitor iodoacetamide (IA), serine protease inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF), the antioxidant l-galactone-¿-lactone (L-gal) and the ethylene blocker (S)-trans-2-Amino-4-(2-aminoethoxy)-3-butenoic acid hydrochloride (AVG). Massive ROS accumulation, as determined by staining with 3-3¿-diaminobenzidine and 2¿,7¿-dichlorofluorescein diacetate, occurred in xylanase-infiltrated lesions and was substantially reduced by the inhibitors. To the best of our knowledge, this is the first report showing that ß- xylanase produced by Aspergillus awamori K1 induces cell death response in tobacco and proteolysis, ROS and ethylene are involved in the mediation of the signaling.

When assayed for their capacity to inhibit azo-initiated peroxidation of linoleic acid in a water/chlorobenzene two-phase system, tellurium-containing 3-pyridinols were readily regenerable by N-acetylcysteine contained in the aqueous phase. The best inhibitors quenched peroxyl radicals more efficiently than alpha-tocopherol, and the duration of inhibition was limited only by the availability of the thiol reducing agent. The compounds were also found to catalyze reduction of hydrogen peroxide in the presence of thiol reducing agent., QC 20100902

The membrane pacemaker hypothesis predicts that long-living species will have more peroxidation- resistant membrane lipids than shorter living species. We tested this hypothesis by comparing the fatty acid composition of heart phospholipids from long-living Procellariiformes (petrels and albatrosses) to those of shorter living Galliformes (fowl). The seabirds were obtained from by-catch of commercial fishing operations and the fowl values from published data. The 3.8-fold greater predicted longevity of the seabirds was associated with elevated content of peroxidation-resistant monounsaturates and reduced content of peroxidation-prone polyunsaturates and, consequently, a significantly reduced peroxidation index in heart membrane lipids, compared with fowl. Peroxidation-resistant membrane composition may be an important physiological trait for longevous species.

Developing atherosclerotic lesions in hypercholesterolemic rabbits are depleted in zinc, while iron accumulates. This study examined the influence of zinc supplementation on the development of atherosclerosis and used isotope dilution gas chromatography-mass spectrometry techniques to measure biomarkers of oxidative lipid damage in atherosclerotic rabbit aorta. Our previous method for F2-isoprostane measurement was adapted to include the quantitation of cholesterol oxidation products in the same sample. Two groups of New Zealand white rabbits were fed a high cholesterol (1% w/w) diet and one group was also supplemented with zinc (1 g/kg) for 8 weeks. Controls were fed a normal diet. Zinc supplementation did not significantly alter the increase in total plasma cholesterol levels observed in animals fed high cholesterol. However, in cholesterol-fed animals zinc supplementation significantly reduced the accumulation of total cholesterol levels in aorta which was accompanied by a significant reduction in average aortic lesion cross-sectional areas of the animals. Elevated levels of cholesterol oxidation products (5,6-α and β cholesterol epoxides, 7β-hydroxycholesterol, 7-ketocholesterol) in aorta and total F2-isoprostanes in plasma and aorta of rabbits fed a cholesterol diet were significantly decreased by zinc supplementation. Our data indicate that zinc has an antiatherogenic effect, possibly due to a reduction in iron-catalyzed free radical reactions. © 2006 Elsevier Inc. All rights reserved.

A series of 2,3-dihydrobenzo[b]selenophene-5-ol antioxidants was prepared by subjecting suitably substituted allyl 4-methoxyphenyl selenides to microwave-induced seleno-Claisen rearrangement/intramolecular Markovnikov hydroselenation followed by boron tribromide-induced O-demethylation. The novel antioxidants were assayed for their capacity to inhibit azo-initiated peroxidation of linoleic acid in a water/chlorobenzene two-phase system containing N-acetylcysteine as a thiol reducing agent in the aqueous phase. Antioxidant efficiency as determined by the inhibited rate of peroxidation, Rinh, increased with increasing methyl substitution (Rinh = 46−26 μM/h), but none of the compounds could match α-tocopherol (Rinh = 22 μM/h). Regenerability as determined by the inhibition time, Tinh, in the presence of the thiol regenerating agent decreased with increasing methyl substitution. Thus, under conditions where the unsubstituted compound 5a inhibited peroxidation for more than 320 min, α-tocopherol worked for 90 min and the trimethylated antioxidant 5g for 60 min only. Sampling of the aqueous phase at intervals during peroxidation using antioxidant 5a showed that N-acetylcysteine was continuously oxidized with time to the corresponding disulfide. In the absence of the regenerating agent, compounds 5 inhibited peroxidation for 50−60 min only. A (RO)B3LYP/LANL2DZdp//B3LYP/LANL2DZ model was used for the calculation of homolytic O−H bond dissociation enthalpies (BDE) and adiabatic ionization potentials (IP) of phenolic antioxidants 5. Both BDE (80.6−76.3 kcal/mol) and IP (163.2−156.0 kcal/mol) decrease with increasing methyl substitution. The phenoxyl radical corresponding to phenol 5g gave an intense ESR signal centered at g = 2.0099. The H−O bond dissociation enthalpy of the phenol was determined by a radical equilibration method using BHA as an equilibration partner. The observed BDE (77.6 ± 0.5 kcal/mol) is in reasonable agreement with calculations (76.3 kcal/mol). As judge

Het was al bekend dat UV-licht uitstekend geschikt is voor desinfectie van water. Sinds kort is het ook bekend dat UV-licht en waterstofperoxide een prima barrière vormen voor ongewenste organische stoffen. Naast middendruk UV-lampen blijken ook lagedruk UV-lampen daarvoor geschikt te zijn

A solar photocatalytic cascade reactor was constructed to study the photocatalytic oxidation of benzoic acid in water under various experimental and weather conditions at HKUST. Nine stainless steel plates coated with TiO2 catalyst were arranged in a cascade configuration in the reactor. Photolytic degradation and adsorption were confirmed to be insignificant total organic carbon (TOC) removal mechanisms. A turbulent flow pattern and, hence, improved mixing in the liquid film were achieved due to the unique cascade design of the reactor. The photoinduced consumption of oxygen during reactions was demonstrated in a sample experiment. The proposed rate equations provided good fits to 90 data points from 17 experiments. The regression results showed that the TOC removal rates averaged over 30 min intervals did not illustrate significant dependence on TOC0 and that I-mean was more important in affecting the photocatalytic process within the ranges of the data examined. The percentage removal of TOC in 71 of 100 mg/l (or 100 ppm) benzoic acid solutions increased from 30\% to 83\% by adding 10ml of hydrogen peroxide solution (30wt\%). Hydrogen peroxide was also shown to enhance the efficiency of the degradation process at elevated temperatures. Ortho-, meta-and para-hydroxybenzoic acids were identified by HPLC analysis as the intermediates of benzoic acid during reactions without She addition of hydrogen peroxide solutions. (C) 2002 Elsevier Science Ltd. All rights reserved.

Lipoxygenasen sind nichthämeisenhaltige Dioxygenasen, die die Bildung von Hydroperoxiden aus molekularem Sauerstoff und mehrfach ungesättigten Fettsäuren katalysieren. Im Rahmen dieser Arbeit wurden verschiedene Lipoxygenase-Ligand-Wechselwirkungen untersucht: a) Durch gezielte Substratveränderungen und ortsgerichtete Mutagenese konnte gezeigt werden, dass Fettsäuren normalerweise mit dem Methylende in der Bindungstasche tierischer Lipoxygenasen gebunden werden. Unterschiedliche Positionsspezifitäten basieren demzufolge auf dem Volumen der Substratbindungstasche (Volumenhypothese). Darüber hinaus konnte bei der 15-Lipoxygenase eine inverse Substratbindung (Carboxylgruppe im aktiven Zentrum) durch Modifikation beider Enden der Fettsäure erzwungen werden, wodurch ausschließlich 5-Lipoxygenierung katalysiert wurde. b) Untersuchungen mit dem Hemmstoff Ebselen ergaben unterschiedliche Hemmmechanismen für verschiedene Enzymzustände. Die Hemmung der Lipoxygenase im Grundzustand (Fe[II]) erfolgt durch kovalente Bindung und Veränderung der Eisenligandensphäre irreversibel nach einem nicht-kompetitiven Mechanismus. Dagegen wird die aktive Lipoxygenase (Fe[III]) nur noch kompetitiv durch Ebselen gehemmt. c) Die Membranbindung der tierischen 15-Lipoxygenase erfolgt über hydrophobe Wechselwirkungen, vermittelt durch oberflächenexponierte, hydrophobe Aminosäuren aus beiden Enzymdomänen. Die Expression einer enzymatisch aktiven Trunkationsmutante, der die N-terminale Domäne fehlt, zeigte, dass diese nicht essentiell ist für die Membranbindung., Lipoxygenases are nonheme iron-containig dioxygenases that catalyze the oxygenation of polyunsaturated fatty acids to hydroperoxy derivatives. Here, the interaction of lipoxygenases with various ligands was investigated: a) From substrate modifications and site directed mutagenesis it was concluded that fatty acids are bound with their methyl end in the substrate binding pocket of mammalian lipoxygenases. The positional specificity is therefore related to different volumes of this binding pocket (space-based hypothesis). For the 15-lipoxygenase an inverse substrate binding (carboxy terminus in the pocket) could be forced by simultaneous modification of both ends of the fatty acid. This lead to an exclusive 5-lipoxygenation by the 15-lipoxygenase. b) The mechanism of lipoxygenase inhibition by ebselen depends on the enzyme's state. The groundstate lipoxygenase (containing Fe[II]) is irreversibly inhibited in a non-competetive manner due to covalent modification and alteration of the iron ligand sphere. The active enzyme (containing Fe[III]) on the other hand is only competetively inhibited. c) The membrane binding of the mammalian 15-lipoxygenase is based on hydrophobic interactions mediated by solvent exposed, hydrophobic amino acid residues of both enzyme domains. The expression of an enzymatically active truncation mutant, which lacks the entire N-terminal domain, showed that this domain is not essential for membrane binding.

Glucose at pathophysiological concentrations was able to accelerate copper-induced oxidation of isolated low-density lipoprotein (LDL) and whole serum. The efficiency of glucose was favored under the following circumstances: (a) when LDL oxidation was induced by low copper concentration, (b) when LDL was partly oxidized, i.e. enriched with lipid peroxides. The glucose derivative methyl-alpha-D-glucoside was ineffective on Cu2+-induced LDL oxidation, pointing out the essential role of the reactivity of the aldehydic carbon for the pro-oxidative effect. When LDL oxidation was induced by a peroxyl radical generator, as a model of transition metal independent oxidation, glucose was ineffective. Glucose was found to stimulate oxidation of LDL induced by ceruloplasmin, the major copper-containing protein of human plasma. Thus, glucose accelerated oxidation of LDL induced by both free and protein bound copper. Considering the requirement for catalytically active copper and for the aldehydic carbon, the pro-oxidative effect of glucose is likely to depend on the increased availability of Cu+; this is more efficient in decomposing lipid peroxide than Cu2+, accounting for acceleration of LDL oxidation. The possible biological relevance of our work is supported by the finding that glucose was able to accelerate oxidation of whole serum, which was assessed by monitoring low-level chemiluminescence associated with lipid peroxidation.

(Mg, Al)-layered double hydroxides (LDHs) with different Mg/Al ratios in the octahedral layer were prepared via the coprecipitation method and were exchanged with varying amounts of molybdate. The composition of the LDH supports and the state of the molybdate in these materials were studied with X-ray diffractometry, X-ray photoelectron spectroscopy and Raman. As was proven by NIR luminescence, aqueous H2O2 is converted at the surface of these catalysts into excited, singlet molecular dioxygen (1O2). The singlet dioxygen diffuses away from the 1O2 generating centers and can perform selective oxygenations, such as endoperoxidations of dienes, or hydroperoxidations of olefins. Catalyst composition and reaction conditions (temperature, solvent) have major effects on the catalyzed 1O2 generation and the subsequent substrate oxygenation. In order to maximize the efficiency of the H2O2 use and to limit the epoxidation side reaction, it is advisable to limit the amount of exchanged molybdate to 0.2 mmol per g and to use an LDH with Mg0.9Al0.1 composition in the octahedral layer. The latter material provides the optimum basicity for the catalytic activity of the exchanged molybdate., SCOPUS: ar.j, info:eu-repo/semantics/published

A reliable test method is needed for predicting the long term storage stabilities of military aviation turbine fuel reserves as well as for evaluating the effectiveness of antioxidants approved for these fuels. This report addresses this need. It describes a reliable and practical accelerated test method for predicting the peroxidation potential of aviation turbine fuels that are stored for long term periods. A test methodology is also proposed for evaluating antioxidants for future qualification in the military specification, MIL-T-5624. This paper is based on the collective results of extensive rigorous studies performed by the four participating laboratories: Southwest Research Institute (SwRI), San Antonio, Texas; Naval Research Laboratory (NRL) Washington, D.C.; Naval Air Warfare Center (NAWC), Trenton, New Jersey; and the National Institute of Petroleum and Energy Research (NIPER), Bartlesville, Oklahoma.

ObjectiveTo determine whether cultured human peritoneal macrophages have functional scavenger receptor(s) and whether activation of macrophages in endometriosis may involve an increase in scavenger receptor activity.DesignA controlled clinical study comparing peritoneal fluid (PF) macrophages of women with endometriosis and controls without endometriosis.SettingWomen undergoing laparoscopic evaluation and treatment in a tertiary medical center.Patient(s)Twenty-one women undergoing evaluation for pelvic pain or infertility and 10 women undergoing elective laparoscopic tubal ligation.Intervention(s)None.Main outcome measure(s)Evidence for functional macrophage scavenger receptor and evidence of ligands for the scavenger receptor in PF.Result(s)Peritoneal macrophages of women with endometriosis degrade significantly more endothelial cell-low density lipoprotein (EC-LDL) and copper-oxidized LDL (Cu-LDL) than native LDL. Macrophages of women with endometriosis also incorporate more labeled oleic acid into cholesteryl ester in the presence of oxidized LDL (Ox-LDL) than in the presence of native LDL. Western blot analysis demonstrates the presence of adducts between lipid peroxidation products and proteins in PF of patients with and without endometriosis. The PF of women with endometriosis competes with labeled Ox-LDL for uptake by mouse peritoneal macrophages in a dose-dependent manner.Conclusion(s)We demonstrate for the first time that human macrophages have functional scavenger receptor(s) and that activation of macrophages in endometriosis involves an increase in scavenger receptor activity. Two lines of evidence indicate the presence of ligands for the scavenger receptor in PF.

Reactive Oxygen Species (ROS) may be involved in the damage occurring in the course of chronic HCV infection. Individuals with chronic hepatitis C present increased hepatic levels of malondialdehyde (MDA) and reduced levels of glutathione. To determine whether these observations are associated with serological evidence for ROS injury, MDA and protein carbonyl content (PCC) of serum was determined in 20 HCV positive patients (14 chronic active hepatitis-CAH and 6 cirrhosis) and 20 controls. Compared to controls, HCV positive subjects had increased levels of MDA (13.33 ± 0.21 SE ng/ml vs. 9.90 ± 0.65, P < .05) and PCC (4.74 ± 0.21 nmol/mg vs. 3.68 ± 0.21, p < .02). Patients with CAH had higher levels than did cirrhotics. Both MDA and PCC correlated with serum ALT levels (r = .792 and r = .818 respectively, p < .001). A common origin for MDA and PCC found in patients with chronic hepatitis C was suggested by the correlation between the two measures (r = .741, p < .001). No correlation were found between MDA or PCC and the hepatic iron content. These data demonstrate that: (1) lipid and protein oxidation occur in chronic hepatitis C, (2) oxidative damage can be demonstrated as increased serum levels of MDA and PCC, and (3) both MDA and PCC levels correlate with disease activity.

Haloperidol administration for 2 weeks results in significant reduction in the concentration of GSH in the CSF. Concomitantly, the levels of lipid peroxidation products increased as evidenced by increased malondialdehyde levels. The malondialdehyde levels in the CSF prior to haloparidol administration were not significantly higher than that seen in CSF from normal controls (data not shown) suggesting that increased oxidative stress did not exist in these patients prior to haloperidol administration. All the patients included in the present study were drug naive and hence the changes observed in the glutathione and malon6ialdehyde levels in the CSF were indeed mediated by haloperidol administration. The only other medication that was administered namely, anticholinergic drug, trihexyphenidyl is not known to cause any oxidative stress. The present study thus demonsuates that haloperidol administration results in significant oxidative stress. The generation of the oxidative stress is probably due to the increased turnover of dopemine caused by typical neuroleptics. Increased dopamine turnover is also observed in Parkinson's disease and the combination therapy consisting of antioxidant vitamin E and monoamine oxidase inhibitor, deprenyl has been shown to offer limited protection against the progression of the disease (Parkinson Disease Study Group 1989). In the present study, all the 15 patients exhibited extrapyramidal symptoms although the time of onset, the duration and the severity of the side effects differed between patients. On the presumption that the oxidative stress generated by haloperidel may cause extrapyramidal symptoms, the present study in humans taken together with the evidence provided in our earlier studies on rats (Shivakumar and Ravindranath 1992,1993) may justify experimental coadministration of antioxidanls (e.g., vitamin E) with typical neuroleptics like haloperidol to prevent the acute side effects.

Although well known for skin vesicating properties, pulmonary damage and associated infections account for most of the mortality associated with sulfur mustard (HD). We have employed an in vivo HD vapor exposure model, bronchoalveolar lavage and histopathology in conjunction with electron paramagnetic resonance (EPR) techniques to provide evidence for HD-induced (free radical/lipid peroxidation associated) lung injury. Anesthetized rats were intratracheally intubated and exposed to 0.35 mg HD vapor over 50 min. Immediately, 1 hr or 24 hr after exposure, lungs were lavaged with the spin trap, alpha-phenyl-t-butyl nitrone (PBN; 0.35 mg/ml). Recovered lavage fluid was assayed by EPR spectroscopy for radical spin adducts. Airway lipid extracts were assayed for thiobarbituric acid reactive products (TBARs); while separate groups of rats were used to evaluate histopathology. EPR results show the presence of an ascorbyl radical at 1 and 24 hr, and a carbon centered PBN spin adduct at 24 hr, both indicative of lipid peroxidation. TBAR (A532nm) formation was also detected at 24 hr. Histopathology revealed multifocal separation of the bronchial epithelium from the submucosa with little or no alveolar involvement at 24 hrs. These studies provide evidence that HD may affect lungs by a free radical mechanism which produces membrane and other tissue damage., This article is from 'Proceedings of the Medical Defense Bioscience Review (1993) Held in Baltimore, Maryland on 10-13 May 1993. Volume 1', AD-A275 667, p113-121.

We have developed a HPLC method for the simultaneous determination of four lipid peroxidation products, namely, formaldehyde, malondialdehyde, acetaldehyde and acetone. This procedure has wide-spread applicability to exposure to environmental pollutants as well as the study of various disease states. Initial studies have clearly demonstrated that the in vitro exposure of peritoneal macrophages, mitochondria and microsomes to selected PCH results in the production of reactive oxygen species as well as a decrease in membrane fluidity. Furthermore, the administration of a variety of polyhalogented cyclic hydrocarbons to rats results in an induction of DNA damage as assessed by the formation of DNA single strand breaks. The results support our basic hypothesis concerning the ability of polyhalogenated cyclic hydrocarbons to induce production of reactive oxygen species which may lead to membrane damage and the subsequent manifestation of toxic symptoms following exposures.

Breathing oxygen-enriched atmosphere is a usual and customary emergency procedure for patients suffering from an acute ischemic injury to the brain. Clinicians show little concern that the resulting arterial Po2 is elevated. Instead, concern is focused on whether hypoxia is occurring as a consequence of respiratory complications. Exposure of Mongolian gerbils to a 100% oxygen atmosphere after 15 minutes of global brain ischemia resulted in a marked increase in the production of pentane, an in vivo product of lipid peroxidation. Much less pentane production occurred in animals subjected to global brain ischemia then exposed to an air atmosphere and in animals exposed to a 100% oxygen atmosphere without ischemia. Gerbils placed in 100% oxygen for 3-6 hours after 15 minutes of ischemia also had a threefold increase in 14-day mortality compared with gerbils subjected to ischemia and then placed in an air atmosphere. These findings raise a serious question about the use of oxygen- enriched atmospheres during reperfusion following ischemia. Keywords: Oxygen consumption, Therapy, Reprints., Pub. in Stroke, v18 n2 p426-430 Mar-Apr 1987.

The overall purpose of this study was the elucidation of interactions between proteins and peroxidizing lipids in foods and related systems, including: The nature of reactions leading to production of protein-centered free radicals upon exposure to peroxidizing lipids; The amino acids residues most susceptible to react under those conditions and the nature of changes occurring in them; Effects of environmental factors, especially water activity; and Mechanisms of antioxidant action in above systems.

This work was begun with the recognition that the current practice of resuscitation from cardiac arrest due to either medical or traumatic causes results in major neurologic injury in 50-80% of resuscitated patients. Only in the last 25 years has there begun to be a systematic examination of the pathophysiology and molecular biology attendant to brain ischemia and reperfusion. The present work continues to examine the sequence of critical events in brain ischemia and reperfusion and tests therapies which may be applied during the reperfusion phase to inhibit the development of biochemical and functional markers of irreversible brain injury. The major products of this work are significant advances in the understanding of the pathophysiology of brain ischemia and reperfusion. During this period, flunarizine (calcium antagonist) and choloropromazine (effects in myocardium include inhibition of both phospholipase and of lipid peroxidation) for protective effects across the injury parameters were examined. Neither flunarizine nor chloropromazine have so far exhibited marked protective effects. Keywords: Dogs; Laboratory animals.

This work has been undertaken to systematically characterize the contribution and time course of membrane damage by lipid peroxidation in the brain during cardiac arrest, resuscitation, and in the post-resuscitation care phase, and to develop effective interventions during resuscitation and post-resuscitation care to prevent biochemical, structural, and functional neurologic injury. It is now generally recognized that lipid peroxidation will not occur without catalysis by a transitional metal such as iron. We have used a 15 minute cardiac arrest model in the dog with resuscitation by internal cardiac massage and defibrillation for our biochemical studies. Intervention in the post-resuscitation phase with the potent iron chelator deferoxamine in a dose of 50 mg/kg IV returns tissue concentrations of lipid peroxidation products to pre-ischemic levels after 2 hours of reperfusion. We have also studied the effect of different artificial perfusion techniques on iron delocalization during a 30 minute resuscitation period following a 15 minute cardiac arrest. We also carried out a preliminary prospective and blind outcome trial in which treatment with both deferoxamine and lidoflazine (a calcium antagonist) during the post resuscitation care phase were compared to standard intensive care without specific drug intervention.

From the pattern of inheritance of normal ageing, this process inevitably results from either abnormal aggregation of subunits of enzymes, abnormal feedback inhibition of enzymes, receptor mutations, membrane defects, or deposition of abnormal fibrillar proteins (Vogel and Motulsky, 1986). The process of ageing should, due to the principle of universality, occur at a site common to all cells : general metabolism, chromatin structure and function ( eg. DNA replication and gene expression) or the physiology of the membrane. The cell type to be studied should be fully functional as to these three sites, and the theories potentially able to explain the ageing process should all encompass changes at any of these aspects . of cellular function. The system to be used throughout this thesis is the cultured human skin fibroblast, which still expresses genes, replicates DNA, has a general metabolism and has functional membranes. This cell type alos undergoes a loss of proliferative potential both in vivo and in culture (Martin et al.,1970). Furthermore, any kind of a phenotype expressed in fibroblast-like cells can theoretically be used for prenatal diagnosis of human genotypes (eg. Werner's syndrome and Spielmeyer-Vogt syndrome). The following postulates can be derived now. First, free radicals should cause the accumulation of lipid peroxides or decay products, which should further yield to the accumulation of autofluorescence. Second, free radicals, or the reactive products resulting from them should impair cellular proliferation to the extent as to cause an irreversible growth arrest of initially dividing cells. Third, crosslinking of proteins by reactive breakdown products of lipid peroxides should occur. Fourth, the capacity of the systems implied in the detoxification of free radicals, or the reactive products thereof, should decrease in capacity during ageing of cultured cells.

The rate of oxidation of dothistromin by hydrogen peroxide, and by hydrogen peroxide - peroxidase complex has been examined. Peroxidase, derived from horseradish, catalyses the oxidation of red dothistromin solutions to colourless products. This oxidation reaction is first order with respect to dothistromin concentration. Dothistromin can be oxidised by hydrogen peroxide alone, but the initial rate is extremely slow when compared with that of the enzyme-catalysed reaction. The rate of the uncatalysed oxidation increases with time, and it is suggested that this is due either to an induction period (for the actual oxidising species to be produced), or due to the formation of a peracid (derived from the initial products of dothistromin oxidation), which oxidises dothistromin faster than does hydrogen peroxide. The possible role of peroxidase isoenzymes of foliage of mature Pinus radiata in limiting lesion formation by Dothistroma pini is also briefly discussed.