Reduction Of Oxidative Damage And Inflammatory Response In The Diaphragm Muscle Of Mdx Mice Using Iron Chelator Deferoxamine.

Oxidative stress and inflammatory processes strongly contribute to pathogenesis in Duchenne muscular dystrophy (DMD). Based on evidence that excess iron may increase oxidative stress and contribute to the inflammatory response, we investigated whether deferoxamine (DFX), a potent iron chelating agent, reduces oxidative stress and inflammation in the diaphragm (DIA) muscle of mdx mice (an experimental model of DMD). Fourteen-day-old mdx mice received daily intraperitoneal injections of DFX at a dose of 150 mg/kg body weight, diluted in saline, for 14 days. C57BL/10 and control mdx mice received daily intraperitoneal injections of saline only, for 14 days. Grip strength was evaluated as a functional measure, and blood samples were collected for biochemical assessment of muscle fiber degeneration. In addition, the DIA muscle was removed and processed for histopathology and Western blotting analysis. In mdx mice, DFX reduced muscle damage and loss of muscle strength. DFX treatment also resulted in a significant reduction of dystrophic inflammatory processes, as indicated by decreases in the inflammatory area and in NF-κB levels. DFX significantly decreased oxidative damage, as shown by lower levels of 4-hydroxynonenal and a reduction in dihydroethidium staining in the DIA muscle of mdx mice. The results of the present study suggest that DFX may be useful in therapeutic strategies to ameliorate dystrophic muscle pathology, possibly via mechanisms involving oxidative and inflammatory pathways.

Broad-temperature range spectroscopy of the two-centre modular redox metalloprotein Desulfovibrio desulfuricans desulfoferrodoxin

Dalton Trans., 2003, 3328-3338

Magnetic and in vitro heating properties of implants formed in situ from injectable formulations and containing superparamagnetic iron oxide nanoparticles (SPIONs) embedded in silica microparticles for magnetically induced local hyperthermia

The biological and therapeutic responses to hyperthermia, when it is envisaged as an anti-tumor treatment modality, are complex and variable. Heat delivery plays a critical role and is counteracted by more or less efficient body cooling, which is largely mediated by blood flow. In the case of magnetically mediated modality, the delivery of the magnetic particles, most often superparamagnetic iron oxide nanoparticles (SPIONs), is also critically involved. We focus here on the magnetic characterization of two injectable formulations able to gel in situ and entrap silica microparticles embedding SPIONs. These formulations have previously shown suitable syringeability and intratumoral distribution in vivo. The first formulation is based on alginate, and the second on a poly(ethylene-co-vinyl alcohol) (EVAL). Here we investigated the magnetic properties and heating capacities in an alternating magnetic field (141 kHz, 12 mT) for implants with increasing concentrations of magnetic microparticles. We found that the magnetic properties of the magnetic microparticles were preserved using the formulation and in the wet implant at 37 degrees C, as in vivo. Using two orthogonal methods, a common SLP (20 Wg(-1)) was found after weighting by magnetic microparticle fraction, suggesting that both formulations are able to properly carry the magnetic microparticles in situ while preserving their magnetic properties and heating capacities. (C) 2010 Elsevier B.V. All rights reserved.

Tuotantofilosofiat

Työssä esitellään käytetyimpiä tuotantofilosofioita. Tuotantofilosofia on hyvin laaja käsite ja sen vuoksi myös jotkin esiteltävistä menetelmistä ovat hyvin kaukana toisistaan. Työ koostuu teoriaosiosta, jossa on esitelty kukin tuotantofilosofia ja lopuksi johtopäätöksiä-osiossa käsitellään sitä, kuinka menetelmät liittyvät toisiinsa. Työssä esitellään JIT/JOT-tuotanto, Lean-tuotanto, Monozukuri, Modulointi, Standardointi, Strategiatyö, Six Sigma, TQM, TPM, QFD, MFD, Simulointi, Digitaalinen valmistus, DFX ja ns. uudet tuotantofilosofiat. Eri menetelmistä löytyvää lähdemateriaalia on tarjolla monipuolisesti, josta johtuen menetelmistä on voitu esitellä vain pääpiirteet. Tuotantofilosofioiden avulla voidaan saavuttaa monia eri asioita. Osa menetelmistä on luotu tuotannon tehostamiseksi ja yksinkertaistamiseksi, osa puolestaan lisää tuotannon tai koko yrityksen laatutasoa ja osa puolestaan helpottaa tuotteiden suunnittelu-työtä. Moni esiteltävistä filosofioista ei istu yksinomaan yhteen edellä mainituista kategorioista vaan kattaa laajempia alueita pitäen sisällään jopa kaikkia kolmea mainittua tulosta. Näiden lisäksi työssä on esitelty lyhyesti uusia tuotantofilosofioita, jotka ovat hieman irrallisia kokonaisuuksia verrattuna muihin työssä esiteltäviin filosofioihin. Työn tarkoituksena on auttaa hahmottamaan suurta kokonaisuutta jonka tuotantofilosofiat tuottavat. On tärkeää osata hahmottaa filosofioiden riippuvuus toisistaan ja se, että otettaessa käyttöön jotain tuotantofilosofiaa, tarkoittaa se myös mahdollisesti monen muunkin asian huomioonottamista. Tätä näkökantaa selvennetään johtopäätöksissä.

Conceptual Product Development in Small Corporations

The main objective of the thesis “Conceptual Product Development in Small Corporations” is by the use of a case study test the MFD™-method (Erixon G. , 1998) combined with PMM in a product development project. (Henceforth called MFD™/PMM-method). The MFD™/PMM-method used for documenting and controlling a product development project has since it was introduced been used in several industries and projects. The method has been proved to be a good way of working with the early stages of product development, however, there are almost only projects carried out on large industries which means that there are very few references to how the MFD™/PMM-method works in a small corporation. Therefore, was the case study in the thesis “Conceptual Product Development in Small Corporations” carried out in a small corporation to find out whether the MFD™/PMM-method also can be applied and used in such a corporation.The PMM was proposed in a paper presented at Delft University of Technology in Holland 1998 by the author and Gunnar Erixon. (See appended paper C: The chart of modular function deployment.) The title “The chart of modular function deployment” was later renamed as PMM, Product Management Map. (Sweden PreCAD AB, 2000). The PMM consists of a QFD-matrix linked to MIM (Module Indication Matrix) via a coupling matrix which makes it possible to make an unbroken chain from the customer domain to the designed product/modules. The PMM makes it easy to correct omissions made in creating new products and modules.In the thesis “Conceptual Product Development in Small Corporations” the universal MFD™/PMM-method has been adapted by the author to three models of product development; original-, evolutionary- and incremental development.The evolutionary adapted MFD™/PMM-method was tested as a case study at Atlings AB in the community Ockelbo. Atlings AB is a small corporation with a total number of 50 employees and an annual turnover of 9 million €. The product studied at the corporation was a steady rest for supporting long shafts in turning. The project team consisted of management director, a sales promoter, a production engineer, a design engineer and a workshop technician, the author as team leader and a colleague from Dalarna University as discussion partner. The project team has had six meetings.The project team managed to use MFD™ and to make a complete PMM of the studied product. There were no real problems occurring in the project work, on the contrary the team members worked very well in the group, having ideas how to improve the product. Instead, the challenge for a small company is how to work with the MFD™/PMM-method in the long run! If the MFD™/PMM-method is to be a useful tool for the company it needs to be used continuously and that requires financial and personnel resources. One way for the company to overcome the probable lack of recourses regarding capital and personnel is to establish a good cooperation with a regional university or a development centre.

Oxidative stress and antioxidant capacity in sickle cell anaemia patients receiving different treatments and medications for different periods of time

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Multiple pathways of neuroprotection against oxidative stress and excitotoxic injury in immature primary hippocampal neurons

In the immature brain hydrogen peroxide accumulates after excitotoxic hypoxia-ischemia and is neurotoxic. Immature hippocampal neurons were exposed to N-methyl-D-aspartate (NMDA), a glutamate agonist, and hydrogen peroxide (H(2)O(2)) and the effects of free radical scavenging and transition metal chelation on neurotoxicity were studied. alpha-Phenyl-N-tert.-butylnitrone (PBN), a known superoxide scavenger, attenuated both H(2)O(2) and NMDA mediated toxicity. Treatment with desferrioxamine (DFX), an iron chelator, at the time of exposure to H(2)O(2) was ineffective, but pretreatment was protective. DFX also protected against NMDA toxicity. TPEN, a metal chelator with higher affinities for a broad spectrum of transition metal ions, also protected against H(2)O(2) toxicity but was ineffective against NMDA induced toxicity. These data suggest that during exposure to free radical and glutamate agonists, the presence of iron and other free metal ions contribute to neuronal cell death. In the immature nervous system this neuronal injury can be attenuated by free radical scavengers and metal chelators.

Evaluating the impact of design decisions on the financial performance of manufacturing companies

Product design decisions can have a significant impact on the financial and operation performance of manufacturing companies. Therefore good analysis of the financial impact of design decisions is required if the profitability of the business is to be maximised. The product design process can be viewed as a chain of decisions which links decisions about the concept to decisions about the detail. The idea of decision chains can be extended to include the design and operation of the 'downstream' business processes which manufacture and support the product. These chains of decisions are not independent but are interrelated in a complex manner. To deal with the interdependencies requires a modelling approach which represents all the chains of decisions, to a level of detail not normally considered in the analysis of product design. The operational, control and financial elements of a manufacturing business constitute a dynamic system. These elements interact with each other and with external elements (i.e. customers and suppliers). Analysing the chain of decisions for such an environment requires the application of simulation techniques, not just to any one area of interest, but to the whole business i.e. an enterprise simulation. To investigate the capability and viability of enterprise simulation an experimental 'Whole Business Simulation' system has been developed. This system combines specialist simulation elements and standard operational applications software packages, to create a model that incorporates all the key elements of a manufacturing business, including its customers and suppliers. By means of a series of experiments, the performance of this system was compared with a range of existing analysis tools (i.e. DFX, capacity calculation, shop floor simulator, and business planner driven by a shop floor simulator).