Cartilage chondroprotection and repair with pulsed electromagnetic fields: I-ONE therapy

Articular cartilage is a complex tissue characterised by chondrocytes that are embedded within an organised dense extracellular matrix of collagen and proteoglycan. Under physiologic condition, articular metabolism is slow, but under pathological condition turnover can increase and the matrix undergoes faster mechanical failure and deterioration, resulting in cartilage degeneration. Moreover, modest damage of the articular cartilage, resulting from trauma or less invasive surgical procedure, produces an inflammatory reaction of the joint cartilage, which can cause irreversible degeneration through the increase in catabolic cytokines synthesis and the decrease in anabolic activity of chondrocytes. Pro-inflammatory cytokines increase the synthesis of matrix-degrading enzymes and limit the production of proteoglycans. It is known that physical stimuli modulate cartilage metabolism. In particular, pulsed electromagnetic fields (I-ONE therapy, Igea, Carpi, Italy) allow to treat homogenously the whole cartilage surface and thickness and the underlying subchondral bone. In vitro I-ONE therapy increases the binding between adenosine and A_2A adenosine receptor on human neutrophils cell membrane, on bovine chondrocytes and on fibroblast-like synoviocytes. It has been shown that drugs with A_2A adenosine receptor agonist activity prevent articular cartilage degeneration in animals. We hypothesised that the adenosine agonist effect of I-ONE therapy can also prevent cartilage degeneration. In a recent study, De Mattei et al. demonstrated how I-ONE therapy can strongly inhibit the release of PGE₂ in bovine synovial fibroblasts exerting an anti-apoptotic effect on cells. Ex vitro, in bovine full thickness articular cartilage explants, I-ONE therapy induces the largest increase in proteoglycan synthesis and in IGF-1 synthesis, when cartilage is exposed to specific parameters of pulsed electromagnetic fields. These effective parameters were subsequently used in in vivo experiments. The effect of I-ONE therapy was investigated on Dunkin Hartley osteoarthritic knee by Mankin score and by histomorphometric and densitometric analysis; I-ONE therapy prevented cartilage degeneration and subchondral bone sclerosis. Osteochondral grafts were performed in the knees of sheep; I-ONE therapy favoured osteochondral grafts integration and prevented cyst-like resorption area formation, which can compromise the stability of graft and the success of the technique. To support the in vitro results, biochemical analyses of the synovial fluid were also performed in this animal model. The amount of inflammatory catabolic cytokines (IL-1β and TNF-α) in the synovial fluid of I-ONE treated animals was significantly lower than in control animals. On the contrary, TGF-β1 was significantly higher in stimulated animals than it was in controls. These results demonstrate not only the capability of I-ONE therapy to control the inflammatory reaction but also its capability to favour cartilage anabolic activity. These results provide the rational to design clinical studies to demonstrate the possibility to transfer the treatment to humans. Two randomised, prospective, double-blind clinical studies (Level I), one conducted to patients treated by arthroscopy with condroabrasion and/or perforations at the knee and the other after anterior cruciate ligament reconstruction, demonstrated that biophysical stimulation with I-ONE therapy leads to complete patient’s recovery in a significantly shorter time (P < 0.005). Moreover, a significant number of treated patients made lower use of anti-inflammatory drugs than the patients in the placebo group. We did not observe negative side effects, patient’s compliance was good and treatment was well accepted. I-ONE therapy significantly reduces patients’ recovery time, joint swelling and has a chondroprotective effect over articular cartilage. I-ONE treatment is a new therapy for the joint preservation.     

通过逻辑框架和项目周期管理来更加高效地执行和评估项目:国际发展项目实证

国际发展项目在国际援助领域的重要性正在提高。针对这些项目的特点,已经有一些具体的方法学来指导有效地开展社会影响评价和项目执行,如项目周期管理和逻辑框架法。但很少有人对这些方法的应用范围进行研究,特别是非政府组织对其的使用。通过对在意大利非政府组织就职的109名项目管理人员的调查,证实相比其他标准方法论(如项目管理知识体系和国际项目管理协会推荐的方法),项目周期管理和逻辑框架法在非政府组织中应用范围很广。但是,两种方法的使用也与项目使用者的知识面有关,这也说明了培训的重要性。最后,发现非政府组织的项目管理人员认为这些方法虽然不太容易使用,但能优化项目的社会影响,这与之前的研究结果是一致的。     

Practical applications of the fenton reaction to the removal of chlorinated aromatic pollutants

BACKGROUND: Chlorophenols (CPs) constitute a group of organic pollutants that are introduced into the environment as a result of several man-made activities, such as uncontrolled use of pesticides and herbicides, and as byproducts in the paper pulp bleaching. Promising removal technologies of chlorinated aromatics consist in the application of advanced oxidation processes (AOPs) that can provide an almost total degradation of a variety of contaminants. Among these, wide application find Fenton systems based on generation of reactive species having a high oxidizing power, such as hydroxyl radical HO*. Our objective was that of determining the overall degradation efficiency of the model compound 2,4-dichlorophenol (DCP) by thermal Fenton-type oxidation systems with a view toward defining in more details relevant process parameters, the effect of reaction temperature and of co-catalyst Cu2+. METHODS: Reaction conditions were similar to those generally adopted as optimal in many practical applications, i.e. pollutant/Fe2+ (as FeSO4) ratio ca. 20, Fe2+/Cu2+ (co-catalyst) 2:1, pH adjusted and controlled at pH 3, and H2O2 in excess (up to four-fold over the stoichiometric amount required for complete mineralization). RESULTS AND DISCUSSION: The results demonstrate that it is advantageous to carry out the reaction at a temperature markedly higher (70 degrees C) than ambient. The stepwise addition of H2O2 in aliquots yields an efficient transformation, while allowing a convenient control of the reaction exothermicity. Under these conditions, the essentially complete removal of the initial DCP is accomplished using just one equiv of H2O2 during 15 min; excess H2O2 (5 equivalents) yields extensive substrate mineralization. Also relevant, at 70 degrees C dechlorination of the initial DCP (and of derived reaction intermediates) is remarkably extensive (3-5% residual TOX), already with the addition of 1 equiv of H2O2. At the end of the reaction, IC and IC-MS analyses of the solution reveal that only low-molecular weight carboxylic acid (acetic, formic, oxalic, malonic, tartaric, etc.) contribute to the residual TOC. CONCLUSIONS: The whole of the results herein point to the advantage of performing the process at temperatures substantially higher than ambient (70 degrees C). Under the conditions adopted, almost complete degradation of the initial toxic compound can be achieved using hydrogen peroxide in fair excess (e.g., 3.5 equiv H2O2). RECOMMENDATIONS AND OUTLOOK: In applying practical Fenton-type degradation systems to heavily polluted wastes, either for the pre-treatment of waters with a high COD value prior to biodegradation or for complete mineralization of pollutants, the set up of appropriate reaction conditions appears to be a key factor. Also, it is desirable to keep the concentration of iron salts within the lower limits in order to minimize the production and disposal of iron oxide sludges.     

Environmental toxicity assessment in the Paraná river delta (Argentina): simultaneous evaluation of selected pollutants and mortality rates of Corbicula fluminea (Bivalvia) early juveniles

Water and sediment samples were collected in the lower Paraná delta at four sites with different levels of exposure to pollution to evaluate the anthropogenic impact through chemical analyses and mortality bioassays. Individual polychlorinated biphenyls, chlorinated pesticides, aliphatic hydrocarbons, polycyclic aromatic hydrocarbons, and heavy metals were measured in waters, porewaters and sediments. The same three phases were also subjected to toxicity assays with straight-hinged juveniles of Corbicula fluminea. Concentrations of several pollutants were above levels recommended for the protection of aquatic life: in waters, Zn, Cu and Cr were 1.6-4.9 times higher, whereas in the sediments Cr was 1.8-3.6, and benzo(a)pyrene was 2.8-5.6 times higher. Pollutant concentrations followed a clear geographic pattern with highest values in the densely populated area of the Reconquista and Luján rivers, lower levels in the San Antonio, and lowest loadings in the remote Paraná de las Palmas. This gradient was adequately matched by the pattern of mortality rates of C. fluminea early juveniles, which were highest in the Reconquista-Luján (40-93%) and lowest (and not significantly different from the control) in the Paraná (3.3-23%). Mortality rates also increased from surface waters (3.3-53%), to porewaters (12-73%), to sediments (23-93%). Although toxicity was probably mainly due to dissolved contaminants, agreement between chemical and biological evidence of pollution was best for the sediment compartment, whereas porewater and surface water showed a higher degree of variability.