The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case-control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E-9) and Italian (OR, 1.84; P=6.0E-5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner.

Study of the immunologic response of marine-derived collagen and gelatin extracts for tissue engineering applications.

The host immunologic response to a specific material is a critical aspect when considering it for clinical implementation. Collagen and gelatin extracted from marine sources have been proposed as biomaterials for tissue engineering applications, but there is a lack of information in the literature about their immunogenicity. In this work, we evaluated the immune response to collagen and/or gelatin from blue shark and codfish, previously extracted and characterized. After endotoxin evaluation, bone marrow-derived macrophages were exposed to the materials and a panel of pro- and anti-inflammatory cytokines were evaluated both for protein quantification and gene expression. Then, the impact of those materials in the host was evaluated through peritoneal injection in C57BL/6 mice. The results suggested shark collagen as the less immunogenic material, inducing low expression of pro-inflammatory cytokines as well as inducible nitric oxide synthase (encoded by Nos2) and high expression of Arginase 1 (encoded by Arg1). Although shark gelatin appeared to be the material with higher pro-inflammatory expression, it also presents a high expression of IL-10 (anti-inflammatory cytokine) and Arginase (both markers for M2-like macrophages). When injected in the peritoneal cavity of mice, our materials demonstrated a transient recruitment of neutrophil, being almost non-existent after 24 hours of injection. Based on these findings, the studied collagenous materials can be considered interesting biomaterial candidates for regenerative medicine as they may induce an activation of the M2-like macrophage population, which is involved in suppressing the inflammatory processes promoting tissue remodeling. STATEMENT OF SIGNIFICANCE: Marine-origin biomaterials are emerging in the biomedical arena, namely the ones based in marine-derived collagen/gelatin proposed as cell templates for tissue regeneration. Nevertheless, although the major cause of implant rejection in clinical practice is the host's negative immune response, there is a lack of information in the literature about the immunological impact of these marine collagenous materials. This work aims to contribute with knowledge about the immunologic response to collagen/gelatin extracted from blue shark and codfish skins. The results demonstrated that despite some differences observed, all the materials can induce a macrophage phenotype related with anti-inflammation resolution and then act as immuno-modulators and anti-inflammatory inducible materials.

Optimization of silver-containing bioglass nanoparticles envisaging biomedical applications.

Bioglass nanoparticles (BGs) are of outmost importance in the biomedical field, because their unique characteristics, namely osteoconductivity and osteoinductivity, and also in certain conditions, angiogenic and bactericidal properties. In this work, novel bioglass nanoparticles containing silver (AgBGs) were synthesized by a sol-gel method, adopting different thermal treatments to obtain new nanoparticles with bioactive and antibacterial features. This is the first systematic study of the effect of the thermal treatment on the properties of AgBGs. The effect of the studied thermal treatments on the properties of synthesized nanoparticles was analyzed by several characterization techniques: FT-IR, XRD, S-TEM, SEM-EDS and Zeta potential. FT-IR allowed the identification of the characteristic peaks of the nanoparticles and XRD revealed the presence of the characteristic peaks of an apatite-like phase. By S-TEM analysis it was found that the produced nanoparticles are dense and have a diameter <200 nm. The SEM micrographs showed their surface morphology and Zeta potential measurements were performed to study their suspension stability. Additionally, in vitro bioactivity tests confirmed their bioactive potential and the microbiological tests evidenced their bactericidal effect. These promising AgBGs could be incorporated either in 2D or 3D structures for several biomedical applications, namely in the orthopedic and dental fields.

Antibacterial bioadhesive layer-by-layer coatings for orthopedic applications.

In this study, thin LbL films were produced by combining the adhesive properties of the hyaluronic acid-dopamine conjugate with the bioactivity and bactericidal properties of silver doped bioactive glass nanoparticles. The build-up of these films was investigated by quartz crystal microbalance with dissipation monitoring. LbL coatings were then constructed on a glass substrate for further characterization. We found that these antimicrobial bioinspired films display enhanced adhesive strength. In vitro bioactivity tests were performed by immersing them in simulated body fluid solution for 14 days where the constructed films promoted the formation of a bone-like apatite layer. From microbiological assays, it was found that coatings containing silver doped nanoparticles exhibited a remarkable antibacterial effect against Staphylococcus aureus and Escherichia coli cultures. Finally, in vitro cellular behavior tests showed enhanced cell adhesion, proliferation and viability for these antibacterial bioadhesive films. Therefore, the constructed thin films showed promising properties and evidenced great potential to be used as coatings for orthopedic implants.

Lymphotoxin beta receptor signaling limits mucosal damage through driving IL-23 production by epithelial cells.

The immune mechanisms regulating epithelial cell repair after injury remain poorly defined. We demonstrate here that lymphotoxin beta receptor (LTßR) signaling in intestinal epithelial cells promotes self-repair after mucosal damage. Using a conditional gene-targeted approach, we demonstrate that LTßR signaling in intestinal epithelial cells is essential for epithelial interleukin-23 (IL-23) production and protection against epithelial injury. We further show that epithelial-derived IL-23 promotes mucosal wound healing by inducing the IL-22-mediated proliferation and survival of epithelial cells and mucus production. Additionally, we identified CD4(-)CCR6(+)T-bet(-) RAR-related orphan receptor gamma t (RORγt)(+) lymphoid tissue inducer cells as the main producers of protective IL-22 after epithelial damage. Thus, our results reveal a novel role for LTßR signaling in epithelial cells in the regulation of intestinal epithelial cell homeostasis to limit mucosal damage.

Light-induced absorption spectra of the D1-D2-cytochrome b 559 complex of Photosystem II: Effect of methyl viologen concentration.

The light-induced difference absorption spectra associated to the photo-accumulation of reduced pheophytin a were studied in the isolated D1-D2-Cyt b559 complex in the presence of variable methyl viologen concentrations and different illumination conditions under anaerobiosis. Depending on the methyl viologen/reaction centre ratio, the relative intensities of the spectral bands at 681.5+/-0.5, 667.0+/-0.5 and 542.5+/-0.5 nm were modified. The reduced pheophytin a located at the D1-branch of the complex absorbs at 681.7+/-0.5 nm, and at least two additional pigment species contribute to the Q(y) band of the difference absorption spectra with maxima at 667.0+/-0.5 and 680.5+/-0.5 nm. We propose the additional species correspond to a peripheral chlorophyll a and the pheophytin a located at the D2-branch of the complex, respectively. The blue absorbing chlorophyll at 667 nm is susceptible to chemical redox changes with a midpoint reduction potential of +470 mV. The Q(x) absorption bands of both pheophytins localised at the D2- and D1-branch of the D1-D2-Cyt b559 complex were at 540.7+/-0.5 and 542.9+/-0.5, respectively. The results indicated that the two pheophytin molecules can be photoreduced in the D1-D2-Cyt b559 complex in certain experimental conditions.

Prediction on admission of in-hospital mortality in patients older than 70 years with acute myocardial infarction.

STUDY OBJECTIVE: To identify the differential characteristics regarding risk factors, presentation, and clinical status on hospital admission in patients aged 70 years or older with acute myocardial infarction (MI) of less than 24 h of evolution, compared with patients younger than 70 years, and to analyze possible factors that could affect mortality on admission in the group of patients older than 70 years. STUDY DESIGN: Of 1,289 patients admitted in the coronary care unit with acute MI during the period 1988 to 1991, with a delay from onset of symptoms of less than 24 h, we defined two groups according to age: younger than 70 years (group 1) and 70 years or older (group 2) in order to analyze the possible predictive factors for mortality on hospital admission in patients older than 70 years (n = 322). By means of univariate analysis, we studied clinical variables that were present on admission; age; sex; medical history of diabetes, cerebrovascular accident, stable angina, previous MI, cardiac failure, right bundle branch block, and atrial fibrillation; previous treatment with digoxin, calcium antagonists, angiotensin-converting enzyme inhibitors (ACEI), antiaggregants or beta-blockers; location and extension of the acute MI, and thrombolysis. The association between mortality, as the dependent variable, and all other variables, as independent variables, was evaluated using a stepwise logistical regression procedure. RESULTS: In patients older than 70 years of age, the model included the following as independent predictors of mortality: female sex (odds ratio [OR], 2.59); complete right bundle branch block (CRBBB) (OR, 4.88); Q-wave MI (OR, 0.35 for non-Q-wave MI); and Forrester grade 2 to 3 (OR, 6.36) and 4 (OR, 80.14). CONCLUSIONS: In patients with acute MI and older than 70 years at the time of admission to the coronary care unit, together with the variables indicating the degree of hemodynamic involvement and the extension of the acute MI, factors such as female sex and CRBBB stand out as independent predictors of mortality.

[The female sex and mortality after acute myocardial infarct]. / Sexo femenino y mortalidad tras infarto agudo de miocardio.

INTRODUCTION: To study the possible influence of gender on in-hospital mortality in patients suffering acute myocardial infarction. PATIENTS AND METHODS: We analyzed 1,951 consecutive patients admitted to our Coronary Unit between January 1986 and December 1991 with this diagnosis and with a delay of no more than 24 hours prior to admission. RESULTS: In-hospital mortality was 12.8% in the 1,603 males and 25.6% in the 348 females (p < 0.001). Age, previous history of: not smoking, diabetes, heart failure, stable angina, myocardial infarction, stroke, right branch block, atrial fibrillation, and treatment with digoxin were variables significantly associated with greater mortality (p < 0.05) as well as the localization of the infarction, the Forrester grade and/or presence of atrioventricular block on admission and not treatment with intravenous fibrinolytics and beta-blockers. Multivariate analysis of variables associated with mortality (selection criterion for variable entry p < 0.20) shows that age, gender, previous angina, situation and extension of the infarction determined by ECG and Forrester on admission are independent predictors of in-hospital mortality. CONCLUSIONS: Gender is an independent predictor of in-hospital mortality in acute myocardial infarction (female/male odds ratio = 1.63).

Fabrication of imaging and surgical guides for dental implants.

Research and experience have suggested that the success of dental implants depends on a well-developed and careful treatment plan approach. Historically, implant size and angulation were determined with the use of panoramic radiographs and clinical judgment during surgery. This occasionally resulted in mechanical and esthetic compromise. This article describes the step-by-step fabrication process for 4 different imaging and surgical guides. Set-up disks, which enhance the design and fabrication of guides, also are introduced. These guides are used in conjunction with cross-sectional tomography during the preimplant assessment of surgical sites.

Unusual tolerance to high temperatures in a new herbicide-resistant D1 mutant from Glycine max (L.) Merr. cell cultures deficient in fatty acid desaturation.

The unusual tolerance to heat stress of STR7, an atrazine-resistant mutant isolated from photosynthetic cell-suspension cultures of soybean (Glycine max L. Merr. cv. Corsoy) and characterized previously [M. Alfonso et al. (1996) Plant Physiol 112:1499-1508] has been studied. The STR7 mutant maintained normal growth and fluorescence parameters at higher temperatures than the wild type (WT). The temperature for 50% inactivation of the oxygen-evolving activity of STR7 thylakoids was 13 degrees C higher than in the WT. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analysis with specific antibodies revealed that the integrity of photosystem II in the STR7 mutant was maintained at higher temperatures than in the WT. This unusual intrinsic tolerance to high temperatures contrasted with the higher sensitivity to heat stress reported as a feature linked to the triazine-resistance trait. The chloroplast membrane of STR7 accumulated an unusually high content of saturated C16:0 and reduced levels of C16:1 and C18:3 unsaturated fatty acids compared with the WT. Among all the lipid classes, chloroplastic lipids synthesized via the prokaryotic pathway (mono-galactosyl-diacyl-glycerol, phosphatidylglycerol and di-galactosyl-diacyl-glycerol), which represented more than 75% of the total lipid classes, showed the most substantial differences in C16:0 and C18:3 levels. In addition, changes in the physicochemical properties of the thylakoid membrane and chloroplast ultrastructure were also detected.

Successful thrombolysis on a mechanical tricuspid prosthesis.

Recombinant tissue-type plasminogen activator (rt-PA) is presently used for the treatment of different clinical entities, mostly myocardial infarction. Its use for treatment of thrombotic dysfunction of prosthetic cardiac valves is more recent and has been only rarely reported. A 33-year-old woman with a St Jude Medical prosthesis in the tricuspid position, had suffered from thrombotic dysfunction of her prosthesis for more than 2 months. She was treated with rt-PA, and after infusion of 70 mg, the prosthesis functioned normally. She showed a moderate systemic fibrinolytic state associated with mild bleeding complications.

Chronic septal panniculitis caused by phaeohyphomycosis.

Panniculitis is caused by a heterogeneous group of clinical entities that tend to manifest themselves as erythematous-violaceous subcutaneous nodules on the legs. In addition to associations with rheumatic diseases including vasculitis, its causes may include various infections. The microorganisms most commonly involved are bacteria and fungi. Among the latter, Candida Sp,, Nocardia Sp., Sporotrichosis, cryptococcosis, histoplasmosis, cromomycosis, and inter alia, have been described. We present an immu-nocompetent patient with a persistent, neutrophilic, chronic septal panniculitis caused by Aureobasidium Pullulans, an infection-generating fungus belonging to the phaeohyphornycosis group. The patient was treated with amphotericin B 0.5 mg/kg/day, itraconazole 400 mg/day p.o., and 5 fluo-rocytosine 150 mg/kg/day for 4 weeks with excellent response.This is the first report in the literature on panniculitis caused by A. Pullulans's phaeohyphomycosis. We suggest that, whenever we observe patients with symptomatic panniculitis, especially if they are resistant to regular treatment, are of chronic course, and have neutrophilic infiltrates in their biopsies, panniculitis caused by uncommon organisms such as phaeohyphomycosis should be considered in the differential diagnosis.