Inducible nitric oxide synthase links NF-κB to PGE(2 )in polyunsaturated fatty acid altered fibroblast in-vitro wound healing

BACKGROUND: This study investigated mechanisms of altered fibroblast collagen production induced by polyunsaturated fatty acids. 3T3-Swiss fibroblasts were grown in medium containing either eicosapentaenoic or arachidonic acid. The effects of nuclear factor-kappaB activation by lipopolysaccharide on inducible nitric oxide synthase, nitric oxide, prostaglandin E(2), collagen production, and in-vitro wound healing were studied. RESULTS: Eicosapentaenoic acid treated cells produced less prostaglandin E(2 )but had increased inducible nitric oxide synthase expression, nitric oxide production, collagen formation, and recoverage area during in-vitro wound healing than cells treated with arachidonic acid. Activation of nuclear factor-kappaB with lipopolysaccharide increased inducible nitric oxide synthase expression, the production of nitric oxide, prostaglandin E(2), collagen, and the in-vitro wound recoverage area. The nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester, decreased lipopolysaccharide-induced nitric oxide, but the amount of nitric oxide was greater in eicosapentaenoic acid treated cells. N(G)-nitro-L-arginine methyl ester plus lipopolysaccharide treatment increased collagen production and cellular recoverage area while treatment with N(G)-nitro-L-arginine methyl ester alone decreased it in wounded fibroblasts. CONCLUSION: The activation of the NF-κB pathway and PGE(2 )can be linked by the cross-talk of iNOS and NO in the PUFA altered fibroblast collagen production and wound healing. Additional studies are needed to determine how polyunsaturated fatty acids can be used as adjuvants in combination with other treatments (i.e, drugs) to design therapies to either enhance healthy collagen production or inhibit production and reduce fibrosis

Escaping Poverty: How Cities can Address Structural Forces Keeping the Poor In Poverty

City and local governments can make the greatest positive impact on their low-income residents through the development and implementation of policies that can provide relief from the structural forces that keep many poor residents trapped in poverty. While there are numerous state and federal policies that address important policy areas like transportation, housing, and homelessness, city governments are often the ones that are left to enforce these policies. By taking a more active role in developing their own policies in these areas, city and local governments can better provide positive impacts to their most vulnerable residents and neighborhoods. Case studies of Austin, TX, San Antonio, TX, San Diego, CA and New York City, NY, show the differences between cities that are more engaged with policy and program creation and willing to implement evidence-based programs and those that are not. Reviewing city council ordinances and other city documents provides insight into what policies cities are prioritizing and if they are effective at reducing poverty. Analyzing data available from these cities and other sources also provides a clearer picture of how city policies and ordinances are impacting some of the structural forces that keep people in poverty, such as policies that attempt to address median housing value and median rent. Cities that engage more with residents, tenants and landlords have more success lifting barriers that poor residents face when attempting to access better services and access to equitable employment opportunities, public transportation, and affordable housing. Cities that rely more on the private market for housing and are not as proactive with policy interventions are inefficient at delivering services and benefits to low income residents, exacerbating the already significant barriers they face when attempting to lift themselves out of poverty. Additionally, a city’s willingness to implement innovative policies, such as Housing First, that are evidence-backed can be much more effective than continuing to conduct policy business as usual

Protection from reperfusion injury in the isolated rat heart by postischaemic deferoxamine and osypurinol administration

The Langendorff isolated rat heart preparation was used to determine the effect of oxypurinol, a xanthine oxidase inhibitor, and deferoxamine, an iron binding agent, on the extent of myocardial reperfusion injury after 60 minutes of ischaemia. Thirty rats were divided into three groups of 10. and an isolated heart preparation made from each rat. The isolated hearts were perfused for 15 minutes with a modified Krebs-Henseleit perfusate solution to permit stabilisation of the preparation. Each heart was then subjected to 60 minutes of total ischaemia at 37°C followed by 60 minutes of reperfusion with either saline treated perfusate, oxypurinol treated perfusate (1.3 mmol/litre), or deferoxamine treated perfusate (0.61 mmol/litre). Reperfusion injury was assessed by the total amount of creatine phosphokinase released into the perfusate, by changes in myocardial vascular resistance, and by morphological examination. The saline treated group released significantly more creatine phosphokinase into the perfusate than either the oxypurinol treated group (p\u3c0.05) or the deferoxamine treated group (p \u3c 0.05). The mean vascular resistance increased for all groups during the 60 minutes of reperfusion compared with that just before ischaemia but was significantly greater in the saline treated group than in the drug treated groups (p \u3c 0.01). Ultrastructural examination of a randomly selected heart from each group after 60 minutes of reperfusion showed pronounced attenuation of mitochondria1 and endoplasmic reticulum swelling, increased maintenance of membrane integrity, and diminished separation of myofilaments in the oxypurinol treated and deferoxamine treated hearts. The mean cross sectional area of mitochondria after 60 minutes of reperfusion was significantly greater in the saline treated group than in the drug treated groups. Thus both oxypurinol and deferoxamine, given after 60 minutes of ischaemia at the onset of reperfusion, can protect the isolated rat heart from reperfusion injury

N-Methylmesoporphyrin IX Fluorescence As A Reporter Of Strand Orientation In Guanine Quadruplexes

Guanine quadruplexes (GQ) are four-stranded DNA structures formed by guanine-rich DNA sequences. The formation of GQs inhibits cancer cell growth, although the detection of GQs invivo has proven difficult, in part because of their structural diversity. The development of GQ-selective fluorescent reporters would enhance our ability to quantify the number and location of GQs, ultimately advancing biological studies of quadruplex relevance and function. N-methylmesoporphyrin IX (NMM) interacts selectively with parallel-stranded GQs; in addition, its fluorescence is sensitive to the presence of DNA, making this ligand a possible candidate for a quadruplex probe. In the present study, we investigated the effect of DNA secondary structure on NMM fluorescence. We found that NMM fluorescence increases by about 60-fold in the presence of parallel-stranded GQs and by about 40-fold in the presence of hybrid GQs. Antiparallel GQs lead to lower than 10-fold increases in NMM fluorescence. Single-stranded DNA, duplex, or i-motif, induce no change in NMM fluorescence. We conclude that NMM shows promise as a turn-on\u27 fluorescent probe for detecting quadruplex structures, as well as for differentiating them on the basis of strand orientation

Evidence That Free Fatty Acid-Iron Complexes Directly Initiate Lipid Peroxidation in Vitro and in Vivo: A New Mechanism of Oxidative Stress

Through a series of biochemical and histochemical experiments we explored the novel hypothesis that iron and free fatty acids, liberated after tissue injury, combine to form liposoluble complexes that directly initiate lipid peroxidation. The addition of 100 M ferric iron to 30 mM linoleate suspensions at pH 7.4 produced time dependent lipid peroxidation, measured as conjugated diene formation. Complexes of 100 M ferric iron and 600 M pentanoate also initiated formation of conjugated dienes in linoleate suspensions and formation of malondialdehyde-like materials in rat liver slices. A histochemical stain for free fatty acids revealed positive reactions within cell membranes in traumatized regions of rat liver tissue that underwent compression injury followed by thirty minutes of blood perfusion, but not in nontraumatized control regions. The diaminobenzidine-H2O2 histochemical reaction for iron, revealed increased levels of redox cyclable iron in the membranes and the cytoplasm of traumatized hepatocytes. We propose that traumatic injury initiates cascades leading to liberation of iron from storage proteins and free fatty acids from membranes, which combine, distribute to the lipid domains of cell membranes, and directly initiate lipid peroxidation

Progressive content-based retrieval of image and video with adaptive and iterative refinement

A method and apparatus for minimizing the time required to obtain results for a content based query in a data base. More specifically, with this invention, the data base is partitioned into a plurality of groups. Then, a schedule or sequence of groups is assigned to each of the operations of the query, where the schedule represents the order in which an operation of the query will be applied to the groups in the schedule. Each schedule is arranged so that each application of the operation operates on the group which will yield intermediate results that are closest to final results

Models and measures to evaluate the effectiveness of funds utilization for scientific research and development of advanced technologies

The purpose of this report was to construct some alternative methods to estimate the effectiveness of investments in scientific research and development of advanced technologies, especially their long-term effects. The Study Group decided to focus on the sub-problem of finding the relation between the spending on science and the quality of science itself. As a result, we have developed two independent methodologies. The most promising one is based on the theory of time-delay systems, which allows capturing effects of the time-lag between the use of funds and the results related to scientific work. Moreover, the methodology gives an opportunity to seek the optimal spending scenario that would fulfill some prescribed constraints (e.g. it would minimize costs and at the same time remain above a desired level of quality of science). The second methodology is premised on Stochastic Frontier Analysis and it can be applied to determine the form of relation between the amount of financing and the results of scientific work. It offers considerable advantages for analyses of several forms of relation at once (production functions) and for a suitable choice of the best one. Both methods are promising, however, additional work is necessary to apply them successfully to some real-life problems