277 research outputs found
Spectroscopic Study of the Anti-Inflammatory Action of Propofol and its Oxidant Derivatives - Inhibition of the Myeloperoxidase Activity and of the Superoxide Anions Production by Neutrophils
Synoviocytes, not chondrocytes, release free radicals after cycles of anoxia/re-oxygenation
peer reviewedBy oxymetry and electron paramagnetic resonance (EPR), we investigated the effects of repeated anoxia/re-oxygenation (A/R) periods on the respiration and production of free radicals by synoviocytes (rabbit HIG-82 cell line and primary equine synoviocytes) and equine articular chondrocytes. Three periods of 20 min anoxia followed by re-oxygenation were applied to 10(7)cells; O(2) consumption was measured before anoxia and after each re-oxygenation. After the last A/R, cellular free radical formation was investigated by EPR spectroscopy with spin trapping technique (n=3 for each cell line). Both types of synoviocytes showed a high O(2) consumption, which was slowered after anoxia. By EPR with the spin trap POBN, we proved a free radical formation. Results were similar for equine and rabbit synoviocytes. For chondrocytes, we observed a low O(2) consumption, unchanged by anoxia, and no free radical production. These observations suggest an oxidant activity of synoviocytes, potentially important for the onset of osteoarthritis
C-60-containing nanostructured polymeric materials with potential biomedical applications
Star-shaped polymers with a fullerene (C-60) Core and an unexpanded structure were successfully prepared by reaction Of C60 with amino end-capped polyesters HxC60(NHPCLn)(x) and polyethers HxC60(NHPEG(n))(x), respectively. Upon irradiation of these C-60-derivatives, a large amount of singlet oxygen was released. Compared to previously synthesized star-shaped azafulleroids with an expanded structure, the photosensitivity of HxC60(NHPCLn)(x) is higher as assessed by a higher production of singlet oxygen. The cytotoxicity of the photoactive water-soluble HxC60(NHPEG(n))(x) derivatives was tested against THP-1 cells and expressed in terms of cell viability. Moreover, they were processed as micro-/nanosized fibers by electrospinning, which however required the addition of poly(F-caprolactone) (PCL). The diameter distribution of the fibers was trimodal, where the fraction with the 270 nm average diameter was the major population. Because of their photoactivity, the herein reported star-shaped C-60-derivatives are promising candidates for photodynamic cancer therapy and treatment of multidrug resistant pathogens. (c) 2007 Elsevier Ltd. All rights reserved
Effects of sphingosine and sphingosine analogues on the free radical production by stimulated neutrophils: ESR and chemiluminescence studies
Sphingolipids inhibit the activation of the neutrophil (PMN) NADPH oxidase by protein kinase C pathway. By electron spin resonance spectroscopy (ESR) and chemiluminescence (CL), we studied the effects of sphingosine (SPN) and ceramide analogues on phorbol 12-myristate 13-acetate (PMA, 5 Ă— 10-7M) stimulated PMN (6 Ă— 106 cells). By ESR with spin trapping (100 mM DMPO: 5,5-dimethyl-1-pyrroline-Noxide), we showed that SPN (5 to 8 Ă— 10-6M), C2-ceramide (N-acetyl SPN) and C6-ceramide (N-hexanoyl SPN) at the final concentration of 2 Ă— 10-5 and 2 Ă— 10-4M inhibit the production of free radicals by stimulated PMN. The ESR spectrum of stimulated PMN was that of DMPO-superoxide anion spin adduct. Inhibition by 5 Ă— 10-6M SPN was equivalent to that of 30 U/ml SOD. SPN (5 to 8 Ă— 10-6M) has no effect
on in vitro systems generating superoxide anion (xanthine 50 mM/xanthine oxidase 110 mU/ml) or hydroxyl radical (Fenton reaction: 88 mM H2O2, 0.01 mM Fe2+ and 0.01 mM EDTA). SPN and N-acetyl SPN also inhibited the CL of PMA stimulated PMN in a dose dependent manner (from 2 Ă— 10-6 to 10-5M), but N-hexanoyl SPN was less active (from 2 Ă— 10-5 to 2 Ă— 10-4M). These effects were compared with those of known PMN inhibitors, superoxide dismutase, catalase and azide. SPN was a better inhibitor compared with these agents. The complete inhibition by SPN of ESR signal and CL of stimulated PMN confirms that this compound or one of its metabolites act at the level of NADPH-oxidase, the key enzyme responsible for production of oxygen-derived free radicals
Production of Free Radicals and Oxygen Consumption by Primary Equine Endothelial Cells During Anoxia-Reoxygenation
The endothelium plays an active role in ischemia/reperfusion injuries. Herein, we report the effect of a single or successive cycles of anoxia/reoxygenation (A/R) on the mitochondrial respiratory function of equine endothelial cells (cultured from carotids) monitored by high resolution oxymetry, and on their production of reactive oxygen species (ROS). ROS were measured by electron paramagnetic resonance (ESR) using POBN and DMPO spin traps, and by gas chromatography (GC) of ethylene released by ROS-induced α-keto-γ-(methylthio)butyric acid (KMB) oxidation. The oxygen consumption significantly decreased with the number of A/R cycles, and POBN-ESR spectra were specific of adducts formed in the cells from superoxide anion. After a one-hour A/R cycle, high intensity DMPO-ESR spectra were observed and assigned to superoxide anion trapping; the GC results confirmed an important production of ROS compared to normoxic cells. These results show that A/R induces mitochondrial alterations in endothelial cells, and strongly stimulates their oxidative activity as demonstrated by ESR and GC methods
Targeting Myeloperoxidase Activity and Neutrophil ROS Production to Modulate Redox Process: Effect of Ellagic Acid and Analogues.
peer reviewedMalaria is an infectious disease caused by a Plasmodium genus parasite that remains the most widespread parasitosis. The spread of Plasmodium clones that are increasingly resistant to antimalarial molecules is a serious public health problem for underdeveloped countries. Therefore, the search for new therapeutic approaches is necessary. For example, one strategy could consist of studying the redox process involved in the development of the parasite. Regarding potential drug candidates, ellagic acid is widely studied due to its antioxidant and parasite-inhibiting properties. However, its low oral bioavailability remains a concern and has led to pharmacomodulation and the synthesis of new polyphenolic compounds to improve antimalarial activity. This work aimed at investigating the modulatory effect of ellagic acid and its analogues on the redox activity of neutrophils and myeloperoxidase involved in malaria. Overall, the compounds show an inhibitory effect on free radicals as well as on the enzyme horseradish peroxidase- and myeloperoxidase (HRP/MPO)-catalyzed oxidation of substrates (L-012 and Amplex Red). Similar results are obtained with reactive oxygen species (ROS) produced by phorbol 12-mystate acetate (PMA)-activated neutrophils. The efficiency of ellagic acid analogues will be discussed in terms of structure-activity relationships
Oxygen consumption of equine articular chondrocytes: Influence of applied oxygen tension and glucose concentration during culture.
We investigated the oxygen (O2) uptake of equine articular chondrocytes to assess their reactions to anoxia/re-oxygenation. They were cultured under 5% or 21% gas phase O2 and at glucose concentrations of 0, 1.0 or 4.5 g/L in the culture medium (n = 3). Afterwards, the O2 consumption rate of the chondrocytes was monitored (oxymetry) before and after an anoxia period of 25 min. The glucose consumption and lactate release were measured at the end of the re-oxygenation period. The chondrocytes showed a minimal O2 consumption rate, which was hardly changed by anoxia. Independently from the O2 tension, glucose uptake by the cells was about 30% of the available culture medium glucose, thus higher for cells at 4.5 g/L glucose (n = 3). Lactate release was also independent from O2 tension, but lower for cells at 4.5 g/L glucose (n = 3). Our observations indicated that O2 consumption by equine chondrocytes was very low despite a functional mitochondrial respiratory chain, and nearly insensitive to anoxia/re-oxygenation. But the chondrocytes metabolism was modified by an excess of O2 and glucose
Cardiomiopatia hipertrĂłfica felina
A Cardiomiopatia HipertrĂłfica (CMH) Ă© uma doença Ă© a doença cardĂaca primária mais comum em gatos causada por uma mutação genĂ©tica autossĂłmica de dominância incompleta com apresentações clĂnicas variadas que apresenta uma grande dispersĂŁo mundial e racial.
O carácter hereditário desta doença cardĂaca resulta de uma mutação genĂ©tica autossĂłmica dominante com penetração incompleta, sendo mais exuberante em situações de homozigotia. A mutação mais comum ocorre em genes que codificam para a ProteĂna C3 de Ligação Ă Miosina, com alterações estruturais do mesmo e consequente hipertrofia concĂŞntrica parcial ou total do ventrĂculo esquerdo. Com o aumento do septo interventricular, dos mĂşsculos papilares e/ou da parede do ventrĂculo esquerdo, ocorre comprometimento tanto do enchimento ventricular como do seu relaxamento, o que por sua vez contribui para a progressĂŁo da hipertrofia. A diminuição da câmara cardĂaca, a diminuição do dĂ©bito cardĂaco, o aumento compensatĂłrio do ritmo, o aumento da pressĂŁo de enchimento diastĂłlico e o aumento do átrio esquerdo predispõem para uma insuficiĂŞncia cardĂaca congestiva, formação trombos e atĂ© morte sĂşbita.
A avaliação clĂnica de um gato com suspeita de Cardiomiopatia HipertrĂłfica deve ser exaustiva, mesmo que o diagnĂłstico definitivo apenas possa ser confirmado atravĂ©s de ecocardiografia e de mĂ©todos de biologia molecular no sentido de identificar a mutação genĂ©tica. A ecocardiografia pode ainda ser Ăştil para direcionar a terapĂŞutica em função do grau de hipertrofia estabelecer prognĂłstico. Atualmente, em medicina humana, existem outras formas de terapĂŞutica, como o novo MYK 461, que se revelam bastante promissores.The Hypertrophic Cardiomyopathy is the heart disease more common in cats caused by a genetic autossomic mutation with imcomplete penetrance, having several clinic findings worldwide and inbreed.
This disease assumes an hereditary character associated with a genetic mutation autossomic dominant with incomplete penetrance, being more exuberant in homozigotic. It’s a common mutation in genes that codify for the Myosin Binding Protein C (MYBPC3), with structural alteration of itself and leading to the partial or total concentric hypertrophy os left ventricule. With the increase of the interventricular septum and/or papillary muscles and/or left ventricle hall there is a compromise of the ventricular filling and it’s relaxation, which in other hand contributes to the progression of the hypertrophy. The decrease of the cardiac chamber, the decrease of cardiac output, the compensatory increase of rhythm, the increase of pressure in diastolic filling and the increase of the left atrium predispose to congestive heart failure and even sudden death.
Cats clinical evaluation under the suspect of Hypertrophic Cardiomyopathy should be exhaustive, even if the definite diagnostic can only be confirmed throght Ultrasound and bio molecular methods looking for identification of genetic mutations. Ultrasound can also be useful to direct the therapeutics accordingly to the level of Hypertrophy, and better prognostics. Nowadays, there are other new therapeutic drugs, like MYK 461, that are showing promissing results
Antioxidant and Antiradical Activities of Manihot esculenta Crantz (Euphorbiaceae) Leaves and Other Selected Tropical Green Vegetables Investigated on Lipoperoxidation and Phorbol-12-myristate-13-acetate (PMA) Activated Monocytes
Abelmoschus esculentus (Malvaceae), Hibiscus acetosella (Malvaceae), Manihot esculenta Crantz (Euphorbiaceae) and Pteridium aquilinum (Dennstaedtiaceae) leaves are currently consumed as vegetables by migrants from sub-Saharan Africa living in Western Europe and by the people in the origin countries, where these plants are also used in the folk medicine. Manihot leaves are also eaten in Latin America and some Asian countries. This work investigated the capacity of aqueous extracts prepared from those vegetables to inhibit the peroxidation of a linoleic acid emulsion. Short chain, volatile C-compounds as markers of advanced lipid peroxidation were measured by gas chromatography by following the ethylene production. The generation of lipid hydroperoxides, was monitored by spectroscopy using N-N′-dimethyl-p-phenylene-diamine (DMPD). The formation of intermediate peroxyl, and other free radicals, at the initiation of the lipid peroxidation was investigated by electron spin resonance, using α-(4-pyridyl-1-oxide)-N-tert-butylnitrone as spin trap agent. The ability of the extracts to decrease the cellular production of reactive oxygen species (ROS) in “inflammation like” conditions was studied by fluorescence technique using 2′,7′-dichlorofluorescine-diacetate as fluorogenic probe, in a cell model of human monocytes (HL-60 cells) activated with phorbol ester. Overall the extracts displayed efficient concentration-dependent inhibitory effects. Their total polyphenol and flavonoid content was determined by classic colorimetric methods. An HPLC-UV/DAD analysis has clearly identified the presence of some polyphenolic compounds, which explains at least partially the inhibitions observed in our models. The role of these plants in the folk medicine by sub-Saharan peoples as well as in the prevention of oxidative stress and ROS related diseases requires further consideration
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