Serial Changes in Plasma Levels of Cytokines in Patients with Coronary Artery Disease

Roberto H Heinisch1, Carlos R Zanetti1, Fabiano Comin1, Juliano L Fernandes2, José A Ramires2, Carlos V Serrano Jr21Federal University of Santa Catarina, Florianópolis, Brazil; 2Heart Institute (InCor), University of São Paulo Medical School, São Paulo, BrazilObjectives: Inflammation is known to be a major determinant of the progression of coronary artery disease (CAD). In the present study we have evaluated the plasma levels of cytokines – tumor necrosis factor-α (TNF), interleukin-1α (IL-1), interleukin-6 (IL-6), interferon-γ (IFN), and interleukin-10 (IL-10) – to examine the association between these cytokines and C-reactive protein (CRP) in patients with CAD.Methods: Patients with acute coronary syndromes (ACS; n = 20) were compared with patients with stable angina (SA; n = 20) and with control volunteers (C; n = 20). Blood samples were collected at the time of admission from all patients and 15 and 30 days thereafter.Results: CRP levels (20.8 ± 8.8 mg/L) (mean ± SEM) were higher at baseline in ACS than SA patients (4.1 ± 0.8 mg/L) or the control subjects (5.1 ± 1.8 mg/L) (p < 0.05). At admission, IL-6 was detected in 50% of the ACS patients and 5% of the SA patients or control subjects, while TNF was detected in 35% of the ACS and SA patients but only in 5% of control subjects. Subsequently, IL-6 levels declined and were no longer detectable, while TNF levels increased among ACS patients at all time periods tested when compared with other patients. The presence of IL-1 and IL-10 were not detectable in the blood samples examined, and IFN could only be detected in the ACS group. A significant correlation was observed between IL-6 and CRP levels (r = 0.4; p < 0.01) in all groups. There were no correlations among any of the other cytokines and CRP levels.Conclusions: Our study demonstrates raised levels of TNF, IL6, IFN, and CRP in patients with ACS and a positive correlation between IL6 and CRP but not with the other cytokines. Keywords: cytokines, tumor necrosis factor-α, interleukin-6, C-reactive protein, coronary artery diseas

Novel approach to plasma facing materials in nuclear fusion reactors

A novel material design in nuclear fusion reactors is proposed based on W-nDiamond nanostructured composites. Generally, a microstructure refined to the nanometer scale improves the mechanical strength due to modification of plasticity mechanisms. Moreover, highly specific grainboundary area raises the number of sites for annihilation of radiation induced defects. However, the low thermal stability of fine-grained and nanostructured materials demands the presence of particles at the grain boundaries that can delay coarsening by a pinning effect. As a result, the concept of a composite is promising in the field of nanostructured materials. The hardness of diamond renders nanodiamond dispersions excellent reinforcing and stabilization candidates and, in addition, diamond has extremely high thermal conductivity. Consequently, W-nDiamond nanocomposites are promising candidates for thermally stable first-wall materials. The proposed design involves the production of WAV-nDiamondAV-Cu/Cu layered castellations. The W, W-nDiamond and W-Cu layers are produced by mechanical alloying followed by a consolidation route that combines hot rolling with spark plasma sintering (SPS). Layer welding is achieved by spark plasma sintering. The present work describes the mechanical alloying processsing and consolidation route used to produce W-nDiamond composites, as well as microstructural features and mechanical properties of the material produced Long term plasma exposure experiments are planned at ISTTOK and at FTU (Frascati)

Staphylococcus aureus in Some Brazilian Dairy Industries: Changes of Contamination and Diversity

Staphylococcus aureus, a major food-poisoning pathogen, is a common contaminant in dairy industries worldwide, including in Brazil. We determined the occurrence of S. aureus in five dairies in Brazil over 8 months. Of 421 samples, 31 (7.4%) were positive for S. aureus and prevalence varied from 0 to 63.3% between dairies. Sixty-six isolates from the 31 samples were typed by Multi-Locus Sequence Typing to determine if these isolates were persistent or continuously reintroduced. Seven known sequence types (STs), ST1, ST5, ST30, ST97, ST126, ST188 and ST398, and four new ST were identified, ST3531, ST3540, ST3562 and ST3534. Clonal complex (CC) 1 (including the four new ST), known as an epidemic clone, was the dominant CC. However, there were no indications of persistence of particular ST. The resistance toward 11 antibiotic compounds was assessed. Twelve profiles were generated with 75.8% of strains being sensitive to all antibiotic classes and no Methicillin-resistant S. aureus (MRSA) strains were found. The enterotoxin-encoding genes involved in food-poisoning, e.g., sea, sed, see, and seg were targeted by PCR. The two toxin-encoding genes, sed and see, were not detected. Only three strains (4.5%) harbored seg and two of these also harbored sea. Despite the isolates being Methicillin-sensitive S. aureus (MSSA), the presence of CC1 clones in the processing environment, including some harboring enterotoxin encoding genes, is of concern and hygiene must have high priority to reduce contamination

Non-peptidic Cruzain Inhibitors with Trypanocidal Activity Discovered by Virtual Screening and in Vitro Assay

A multi-step cascade strategy using integrated ligand-and target-based virtual screening methods was developed to select a small number of compounds from the ZINC database to be evaluated for trypanocidal activity. Winnowing the database to 23 selected compounds, 12 non-covalent binding cruzain inhibitors with affinity values (K-i) in the low micromolar range (3-60 mu M) acting through a competitive inhibition mechanism were identified. This mechanism has been confirmed by determining the binding mode of the cruzain inhibitor Nequimed176 through X-ray crystallographic studies. Cruzain, a validated therapeutic target for new chemotherapy for Chagas disease, also shares high similarity with the mammalian homolog cathepsin L. Because increased activity of cathepsin L is related to invasive properties and has been linked to metastatic cancer cells, cruzain inhibitors from the same library were assayed against it. Affinity values were in a similar range (4-80 mu M), yielding poor selectivity towards cruzain but raising the possibility of investigating such inhibitors for their effect on cell proliferation. in order to select the most promising enzyme inhibitors retaining trypanocidal activity for structure-activity relationship (SAR) studies, the most potent cruzain inhibitors were assayed against T. cruzi-infected cells. Two compounds were found to have trypanocidal activity. Using compound Nequimed42 as precursor, an SAR was established in which the 2-acetamidothiophene-3-carboxamide group was identified as essential for enzyme and parasite inhibition activities. the IC50 value for compound Nequimed42 acting against the trypomastigote form of the Tulahuen lacZ strain was found to be 10.6 +/- 0.1 mu M, tenfold lower than that obtained for benznidazole, which was taken as positive control. in addition, by employing the strategy of molecular simplification, a smaller compound derived from Nequimed42 with a ligand efficiency (LE) of 0.33 kcal mol(-1) atom(-1) (compound Nequimed176) is highlighted as a novel non-peptidic, non-covalent cruzain inhibitor as a trypanocidal agent candidate for optimization.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Sao Carlos, Dept Quim, BR-13560 Sao Carlos, SP, BrazilUniv São Paulo, Inst Quim Sao Carlos, Grp Quim Med IQSC USP, Sao Carlos, SP, BrazilUniv Calif San Francisco, Dept Pathol, Ctr Discovery & Innovat Parasit Dis, San Francisco, CA 94140 USAUniv São Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, BR-14049 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, São Paulo, BrazilFAPESP: 2011/01893-3,CNPq: 301614/2010-5CAPES: 5985/11-0Web of Scienc