Increase in circulating microparticles in inflammatory bowel disease patients induces vascular alterations

Alterations of vascular function participate to the development of the inflammatory bowel disease (IBD). We have previously reported the presence of inflammation-related vasoactive factors in small mesenteric arteries from Crohn’s disease patients (Tabernero et al., Circulation, 2003). Microparticles (MPs) are membrane vesicles released during cell activation and apoptosis whose circulating levels have been shown to be increased in patients with IBD, including MPs from platelets and activated platelets, endothelial, leukocyte and erythrocyte origins (Leonetti et al., Archives of Cardiovascular Diseases, Tome 102-Supplement 1-Mars 2009.).Here, we investigated whether MPs from IBD patients (IBD-MPs) play a role in the regulation of endothelial function and vascular reactivity in this disease. Male Swiss mice were injected intravenously with IBD-MPs or saline solution and sacrificed 24 h after. Endothelial function and vascular reactivity were studied on aortic rings by myography. The involvement of nitric oxide (NO), cyclooxygenase (COX) metabolites and superoxide anion (O2- ) was also assessed using the following inhibitors: NG-L-Nitro-arginine (NO synthase inhibitor, L-NA); indomethacin (non-selective COX inhibitor); SC-560 (selective COX-1 inhibitor), NS-398 (selective COX-2 inhibitor) and MnTMPyP (permeable superoxide dismutase mimetic). In aorta, IBD-MPs significantly reduced both endothelium-dependent induced by acetylcholine and the NO donor, sodium nitroprusside, respectively. IBD-MPs decreased the contraction to serotonin (5-HT) compared to saline that was completely prevented in the presence of L-NA. Moreover, aorta from mice treated with IBD-MPs displayed increase NO production. Interestingly, the ability of NS-398 to reduce 5-HT-induced contraction in control mice was abolished in vessels taken from mice treated with IBD-MPs. Although IBD-MPs decreased O2- production in the aorta, the O2- scavenger MnTMPyP reduced the contraction to 5-HT in an identical manner in aorta from both control and IBD-MPs treated mice. The present study provides evidence of the capacity of IBD-MPs to induce endothelial dysfunction and vascular hyporeactivity. These effects result from a subtle alteration of the balance between NO, reactive oxygen species and metabolites from COX-2. They underscore the participation of MPs in the course of vascular alterations in this disease. (Partially supported by Ferring France Laboratories)

Predictive value of PSA velocity over early clinical and pathological parameters in patients with localized prostate cancer who undergo radical retropubic prostatectomy

OBJECTIVES: To analyze the behavior of the prostate specific antigen velocity (PSAV) in localized prostate adenocarcinoma. MATERIALS AND METHODS: We conducted a retrospective study of 500 men who had localized prostate adenocarcinoma, who underwent radical retropubic prostatectomy between January 1986 and December 1999. The PSAV was calculated for each patient and subsequently, the values were correlated with 5 groups: age, initial PSA value, clinical stage, tumor volume and Gleason score. RESULTS: The behavior of PSAV presented statistic significance with an increment between 1.3 ng/mL and 9.6 ng/mL, ranging from 38.6% and 59.8% when compared with the initial PSA value (p < 0.0001), clinical stage (p = 0.0002), tumor volume (p < 0.0001) and Gleason score (p = 0.0009). CONCLUSION: PSAV up to 2.5 ng/mL/year is associated with factors of good prognosis, such as initial PSA below 10 mg/mL, clinical stage T1, tumor volume below 20% and Gleason score lower than 7.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Division of UrologyUNIFESP, EPM, Division of UrologySciEL

Application of Model-driven engineering to multi-agent systems: a language to model behaviors of reactive agents

Many users of multi-agent systems (MAS) are very commonly disinclined to model and simulate using current MAS platforms. More specifically, modeling the dynamics of a system (in particular the agents' behaviors) is very often a challenge to MAS users. This issue is more often observed in the domain of socio-ecological systems (SES), because SES domain experts are rarely programmers. Indeed, the majority of MAS platforms were not conceived taking into consideration domain-experts who are non-programmers. Most current MAS tools are not dedicated to SES, or nor do they possess an easily understandable formalism to represent the behaviors of agents. Moreover, because it is platform-dependent, a model realized in a given MAS platform cannot be properly used on another platform due to incompatibility between MAS platforms. To overcome these limitations, we propose a domain-specific language (DSL) to describe the behaviors of reactive agents, regardless of the MAS platform used for simulation. To achieve this result, we used model-driven engineering (MDE), an approach that provides tools to develop DSLs from a meta-model (abstract syntax), textual editors with syntax highlighting (for the concrete syntax) and code generation capabilities (for source-code generation of a model). As a result, we implemented a language and a textual editor that allow SES domain experts to describe behaviors in three different ways that are close to their natural expression: as equations when they are familiar with these, as a sequence of activities close to natural language or as an activity diagram to represent decisions and a sequence of behaviors using a graphic formalism. To demonstrate interoperability, we also developed code generators targeting two different MAS platforms (Cormas and Netlogo). We tested the code generators by implementing two SES models with the developed DSL. The generated code was targeted to both MAS platforms (Cormas and Netlogo), and successfully simulated in one of them. We conclude that the MDE approach provides adequate tools to develop DSL and code generators to facilitate MAS modeling and simulation by non-programmers. Concerning the DSL developed, although the behavioral aspect of MAS simulation is part of the complexity of modeling in MAS, there are still other essential aspects of model and simulation of MAS that are yet to be explored, such as model initialization and points of view on the model simulated worl

Anomalous Hopping Exponents of Ultrathin Films of Metals

The temperature dependence of the resistance R(T) of ultrathin quench-condensed films of Ag, Bi, Pb and Pd has been investigated. In the most resistive films, R(T)=Roexp(To/T)^x, where x=0.75. Surprisingly, the exponent x was found to be constant for a wide range of Ro and To in all four materials, possibly implying a consistent underlying conduction mechanism. The results are discussed in terms of several different models of hopping conduction.Comment: 6 pages, 5 figure

Pressure field study of the Tevatron cold compressors

The Fermilab Tevatron cryogenic system utilizes high-speed centrifugal cold compressors, manufactured by Ishikawajima-Harima Heavy Industries Co. Ltd. (IHI), for high-energy operations [1]. The compressor is designed to pump 60 g/sec of 3.6 K saturated helium vapor at a pressure ratio of 2.8, with an off-design range of 40 to 70 g/sec. Operating speeds are between 40 and 95 krpm, with a speed of 80 krpm at the design point. Different heat loads and magnet quench performance of each of the twenty-four satellite refrigerators dictates different process pressure and flow rates of the cold compressors. Reducing the process flow rate can cause the centrifugal cold compressor to stop pumping and subsequently surge. Tests have been conducted at the Cryogenic Test Facility at Fermilab to map the pressure field and appropriate efficiency of the IHI hydrodynamic cold compressor. The information allows tuning of each of the twenty-four Tevatron satellite refrigerators to avoid cold compressor operation near the surge and choke lines. A new impeller has also been tested. The Tevatron cold compressor pressure field and efficiency data with the new impeller are presented in this paper

Electrical transport studies of quench condensed Bi films at the initial stage of film growth: Structural transition and the possible formation of electron droplets

The electrical transport properties of amorphous Bi films prepared by sequential quench deposition have been studied in situ. A superconductor-insulator (S-I) transition was observed as the film was made increasingly thicker, consistent with previous studies. Unexpected behavior was found at the initial stage of film growth, a regime not explored in detail prior to the present work. As the temperature was lowered, a positive temperature coefficient of resistance (dR/dT > 0) emerged, with the resistance reaching a minimum before the dR/dT became negative again. This behavior was accompanied by a non-linear and asymmetric I-V characteristic. As the film became thicker, conventional variable-range hopping (VRH) was recovered. We attribute the observed crossover in the electrical transport properties to an amorphous to granular structural transition. The positive dR/dT found in the amorphous phase of Bi formed at the initial stage of film growth was qualitatively explained by the formation of metallic droplets within the electron glass.Comment: 7 pages, 6 figure

Natural inhibitors of pancreatic lipase as new players in obesity treatment.

Obesity is a multifactorial disease characterized by an excessive weight for height due to an enlarged fat deposition such as adipose tissue, which is attributed to a higher calorie intake than the energy expenditure. The key strategy to combat obesity is to prevent chronic positive impairments in the energy equation. However, it is often difficult to maintain energy balance, because many available foods are high-energy yielding, which is usually accompanied by low levels of physical activity. The pharmaceutical industry has invested many efforts in producing antiobesity drugs; but only a lipid digestion inhibitor obtained from an actinobacterium is currently approved and authorized in Europe for obesity treatment. This compound inhibits the activity of pancreatic lipase, which is one of the enzymes involved in fat digestion. In a similar way, hundreds of extracts are currently being isolated from plants, fungi, algae, or bacteria and screened for their potential inhibition of pancreatic lipase activity. Among them, extracts isolated from common foodstuffs such as tea, soybean, ginseng, yerba mate, peanut, apple, or grapevine have been reported. Some of them are polyphenols and saponins with an inhibitory effect on pancreatic lipase activity, which could be applied in the management of the obesity epidemic

Antidiabetic effects of natural plant extracts via inhibition of carbohydrate hydrolysis enzymes with emphasis on pancreatic alpha amylase

Introduction: The increasing prevalence of type 2 diabetes mellitus and the negative clinical outcomes observed with the commercially available anti-diabetic drugs have led to the investigation of new therapeutic approaches focused on controlling postprandrial glucose levels. The use of carbohydrate digestive enzyme inhibitors from natural resources could be a possible strategy to block dietary carbohydrate absorption with less adverse effects than synthetic drugs. Areas covered: This review covers the latest evidence regarding in vitro and in vivo studies in relation to pancreatic alpha-amylase inhibitors of plant origin, and presents bioactive compounds of phenolic nature that exhibit anti-amylase activity. Expert opinion: Pancreatic alpha-amylase inhibitors from traditional plant extracts are a promising tool for diabetes treatment. Many studies have confirmed the alpha-amylase inhibitory activity of plants and their bioactive compounds in vitro, but few studies corroborate these findings in rodents and very few in humans. Thus, despite some encouraging results, more research is required for developing a valuable anti-diabetic therapy using pancreatic alpha-amylase inhibitors of plant origin