Role of the Shiga toxin in the Hemolytic Uremic Syndrome

En los últimos años, las infecciones por Escherichia coli productor de toxina Shiga (STEC) y el desarrollo del Síndrome Urémico Hemolítico (SUH) han cobrado tal relevancia desde el punto de vista clínico y como problema de salud pública, que se considera uno de los patógenos emergentes más importantes de infecciones transmitidas por alimentos. Las infecciones por STEC pueden manifestarse dentro de un amplio espectro clínico, tales como infecciones asintomáticas intestinales, diarrea acuosa, diarrea sanguinolenta (colitis hemorrágica) y complicaciones sistémicas conocidas con el nombre de SUH. En Argentina, el SUH es la principal causa pediátrica de insuficiencia renal aguda y la segunda de insuficiencia renal crónica. Hasta el presente no existe un tratamiento específico para tratar las infecciones por STEC y disminuir la progresión del SUH. Los mecanismos por los cuales la toxina Shiga (Stx) induce SUH pueden ayudar a encontrar nuevas estrategias para impedir o mejorar el pronóstico del SUH. En este artículo se describen recientes progresos que contribuyen a entender el papel de Stx en la patogénesis del SUH y nuevas estrategias usadas para prevenir el pasaje de la toxina a la circulación sistémica durante la fase diarreica o luego del establecimiento del SUH.In the last years, infection associated with Shiga toxin-producing Escherichia coli (STEC) and subsequent Hemolitic-Uremic Syndrome (HUS) became relevant as a public health since it was considered as one of the most important emergent patogen present in the food contaminated by cattle feces. STEC infection may be asymptomatic or begins with a watery diarrhea that may or may not progress to bloody diarrhea (hemorrhagic colitis) and HUS. In Argentina, HUS is the most common pediatric cause of acute renal insufficiency and the second cause of chronic renal failure. Up to now, STEC infection lacks of known effective treatment strategies that diminish risk of progression to HUS. The mechanisms by which Shiga toxin (Stx) induce HUS may help to find strategies to prevent or ameliorate HUS. In this article, recent progress that has contributed to understanding the disease pathogenesis of STEC is reviewed. New strategies to prevent further uptake of Shiga from the gut, either during the diarrheal phase or once HUS has developed are discussed.Fil: Pistone Creydt, Virginia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Nuñez, Pablo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; ArgentinaFil: Boccoli, Javier. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; ArgentinaFil: Silberstein, Claudia Marcela. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; ArgentinaFil: Zotta, Elsa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; ArgentinaFil: Goldstein, Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; ArgentinaFil: Ibarra, Cristina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Fisiopatogenia; Argentin

Tethering of Gly-Arg-Gly-Asp-Ser-Pro-Lys Peptides on Mg-Doped Hydroxyapatite

Stem cell homing, namely the recruitment of mesenchymal stem cells (MSCs) to injured tissues, is highly effective for bone regeneration in vivo. In order to explore whether the incorporation of mimetic peptide sequences on magnesium-doped (Mg-doped) hydroxyapatite (HA) may regulate the homing of MSCs, and thus induce cell migration to a specific site, we covalently functionalized MgHA disks with two chemotactic/haptotactic factors: either the fibronectin fragment III1-C human (FF III1-C), or the peptide sequence Gly-Arg-Gly-Asp-Ser-Pro-Lys, a fibronectin analog that is able to bind to integrin transmembrane receptors. Preliminary biological evaluation of MSC viability, analyzed by 3-(4,5-dimethyl­thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, suggested that stem cells migrate to the MgHA disks in response to the grafted haptotaxis stimuli

Effect of Ethyl Ester L-Lysine Triisocyanate addition to produce reactive PLA/PCL bio-polyester blends for biomedical applications

We report in this paper the effects of Ethyl Ester L-Lysine Triisocyanate (LTI) on the physical-mechanical properties of Poly(lactide)/Poly(ε-caprolactone) (PLA/PCL) polyesters blends. The PLA/PCL ratios considered were 20/80, 50/50 and 80/20 (wt/wt %) and LTI was added in amounts of 0.0-0.5-1.0 phr. PLA and PCL reacted with LTI during processing in a Brabender twin screw internal mixer to produce block copolymers in-situ. The resulting blends have been characterized by torque measurements, uniaxial tensile tests, Differential Scanning Calorimeter, contact angle measurements with a Phosphate Buffered Saline (PBS) solution, ATR analysis and morphological SEM observations. Experimental results highlighted how LTI enhanced interaction and dispersion of the two components, resulting into a synergic effect in mechanical properties. Mechanical and physical properties can be tailored by changing the blend composition. The most noticeable trend was an increase in ductility of the mixed polymers. Besides, LTI decreased blend’s wet ability in PBS and lowered the starting of crystalline phase formation for both polymers, confirming an interaction among them. These reactive blends could find use as biomedical materials, e.g. absorbable suture threads or scaffolds for cellular growth

Observation of J/ψpJ/\psi p resonances consistent with pentaquark states in Λb0→J/ψK−p{\Lambda_b^0\to J/\psi K^-p} decays

Observations of exotic structures in the $J/\psi p$ channel, that we refer to as pentaquark-charmonium states, in $\Lambda_b^0\to J/\psi K^- p$ decays are presented. The data sample corresponds to an integrated luminosity of 3/fb acquired with the LHCb detector from 7 and 8 TeV pp collisions. An amplitude analysis is performed on the three-body final-state that reproduces the two-body mass and angular distributions. To obtain a satisfactory fit of the structures seen in the $J/\psi p$ mass spectrum, it is necessary to include two Breit-Wigner amplitudes that each describe a resonant state. The significance of each of these resonances is more than 9 standard deviations. One has a mass of $4380\pm 8\pm 29$ MeV and a width of $205\pm 18\pm 86$ MeV, while the second is narrower, with a mass of $4449.8\pm 1.7\pm 2.5$ MeV and a width of $39\pm 5\pm 19$ MeV. The preferred $J^P$ assignments are of opposite parity, with one state having spin 3/2 and the other 5/2.Comment: 48 pages, 18 figures including the supplementary material, v2 after referee's comments, now 19 figure

Quantum numbers of the X(3872)X(3872) state and orbital angular momentum in its ρ0Jψ\rho^0 J\psi decay

Angular correlations in $B^+\to X(3872) K^+$ decays, with $X(3872)\to \rho^0 J/\psi$, $\rho^0\to\pi^+\pi^-$ and $J/\psi \to\mu^+\mu^-$, are used to measure orbital angular momentum contributions and to determine the $J^{PC}$ value of the $X(3872)$ meson. The data correspond to an integrated luminosity of 3.0 fb$^{-1}$ of proton-proton collisions collected with the LHCb detector. This determination, for the first time performed without assuming a value for the orbital angular momentum, confirms the quantum numbers to be $J^{PC}=1^{++}$. The $X(3872)$ is found to decay predominantly through S wave and an upper limit of $4\%$ at $95\%$ C.L. is set on the fraction of D wave.Comment: 16 pages, 4 figure

Precise measurements of the properties of the B-1(5721)(0,+) and B-2*(5747)(0,+) states and observation of B-+,B-0 pi(-,+) mass structures

Invariant mass distributions of B+π− and B0π+ combinations are investigated in order to study excited B mesons. The analysis is based on a data sample corresponding to 3.0 fb−1 of pp collision data, recorded by the LHCb detector at centre-of-mass energies of 7 and 8 TeV. Precise measurements of the masses and widths of the B1(5721)0,+ and B2(5747)0,+ states are reported. Clear enhancements, particularly prominent at high pion transverse momentum, are seen over background in the mass range 5850-6000 MeV in both B+π− and B0π+ combinations. The structures are consistent with the presence of four excited B mesons, labelled BJ (5840)0,+ and BJ (5960)0,+, whose masses and widths are obtained under different hypotheses for their quantum numbers

Effect of Ethyl Ester L-Lysine Triisocyanate addition to produce reactive PLA/PCL bio-polyester blends for biomedical applications

This paper was accepted for publication in the journal Journal of the Mechanical Behavior of Biomedical Materials and the definitive published version is available at http://dx.doi.org/10.1016/j.jmbbm.2017.02.018We report in this paper the effects of Ethyl Ester L-Lysine Triisocyanate (LTI) on the physical-mechanical properties of Poly(lactide)/Poly(ε-caprolactone) (PLA/PCL) polyesters blends. The PLA/PCL ratios considered were 20/80, 50/50 and 80/20 (wt/wt %) and LTI was added in amounts of 0.0-0.5-1.0 phr. PLA and PCL reacted with LTI during processing in a Brabender twin screw internal mixer to produce block copolymers in-situ. The resulting blends have been characterized by torque measurements, uniaxial tensile tests, Differential Scanning Calorimeter, contact angle measurements with a Phosphate Buffered Saline (PBS) solution, ATR analysis and morphological SEM observations. Experimental results highlighted how LTI enhanced interaction and dispersion of the two components, resulting into a synergic effect in mechanical properties. Mechanical and physical properties can be tailored by changing the blend composition. The most noticeable trend was an increase in ductility of the mixed polymers. Besides, LTI decreased blend’s wet ability in PBS and lowered the starting of crystalline phase formation for both polymers, confirming an interaction among them. These reactive blends could find use as biomedical materials, e.g. absorbable suture threads or scaffolds for cellular growth

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care

Measurement of the forward Z boson production cross-section in pp collisions at √s = 13 TeV

A measurement of the production cross-section of Z bosons in pp collisions at √s=13 TeV is presented using dimuon and dielectron final states in LHCb data. The cross-section is measured for leptons with pseudorapidities in the range 2.0 20 GeV and dilepton invariant mass in the range 60 < m(ℓℓ) < 120 GeV. The integrated cross-section from averaging the two final states is σZℓℓ = 194.3 ± 0.9 ± 3.3 ± 7.6 pb, where the first uncertainty is statistical, the second is due to systematic effects, and the third is due to the luminosity determination. In addition, differential cross-sections are measured as functions of the Z boson rapidity, transverse momentum and the angular variable ϕη*