Nephroprotective Effect of the Virgin Olive Oil Polyphenol Hydroxytyrosol in Type 1-like Experimental Diabetes Mellitus: Relationships with Its Antioxidant Effect

The aim of this study was to determine whether hydroxytyrosol administration prevented kidney damage in an experimental model of type 1 diabetes mellitus in rats. Hydroxytyrosol was administered to streptozotocin-diabetic rats: 1 and 5 mg/kg/day p.o. for two months. After hydroxytyrosol administration, proteinuria was significantly reduced (67–73%), calculated creatinine clearance was significantly increased (26–38%), and the glomerular volume and glomerulosclerosis index were decreased (20–30%). Hydroxytyrosol reduced oxidative and nitrosative stress variables and thromboxane metabolite production. Statistical correlations were found between biochemical and kidney function variables. Oral administration of 1 and 5 mg/kg/day of hydroxytyrosol produced an antioxidant and nephroprotective effect in an experimental model of type 1-like diabetes mellitus. The nephroprotective effect was significantly associated with the systemic and renal antioxidant action of hydroxytyrosol, which also influenced eicosanoid production

Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

Big science and big data in nephrology

There have been tremendous advances during the last decade in methods for large-scale, high-throughput data generation and in novel computational approaches to analyze these datasets. These advances have had a profound impact on biomedical research and clinical medicine. The field of genomics is rapidly developing toward single-cell analysis, and major advances in proteomics and metabolomics have been made in recent years. The developments on wearables and electronic health records are poised to change clinical trial design. This rise of ‘big data’ holds the promise to transform not only research progress, but also clinical decision making towards precision medicine. To have a true impact, it requires integrative and multi-disciplinary approaches that blend experimental, clinical and computational expertise across multiple institutions. Cancer research has been at the forefront of the progress in such large-scale initiatives, so-called ‘big science,’ with an emphasis on precision medicine, and various other areas are quickly catching up. Nephrology is arguably lagging behind, and hence these are exciting times to start (or redirect) a research career to leverage these developments in nephrology. In this review, we summarize advances in big data generation, computational analysis, and big science initiatives, with a special focus on applications to nephrology

Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents : an in vitro study

Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB) to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K+, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS) inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state

Quantum Non-Demolition Detection of Strongly Correlated Systems

Preparation, manipulation, and detection of strongly correlated states of quantum many body systems are among the most important goals and challenges of modern physics. Ultracold atoms offer an unprecedented playground for realization of these goals. Here we show how strongly correlated states of ultracold atoms can be detected in a quantum non-demolition scheme, that is, in the fundamentally least destructive way permitted by quantum mechanics. In our method, spatially resolved components of atomic spins couple to quantum polarization degrees of freedom of light. In this way quantum correlations of matter are faithfully mapped on those of light; the latter can then be efficiently measured using homodyne detection. We illustrate the power of such spatially resolved quantum noise limited polarization measurement by applying it to detect various standard and "exotic" types of antiferromagnetic order in lattice systems and by indicating the feasibility of detection of superfluid order in Fermi liquids.Comment: Published versio

The significance of macrophage phenotype in cancer and biomaterials

Macrophages have long been known to exhibit heterogeneous and plastic phenotypes. They show functional diversity with roles in homeostasis, tissue repair, immunity and disease. There exists a spectrum of macrophage phenotypes with varied effector functions, molecular determinants, cytokine and chemokine profiles, as well as receptor expression. In tumor microenvironments, the subset of macrophages known as tumor-associated macrophages generates byproducts that enhance tumor growth and angiogenesis, making them attractive targets for anti-cancer therapeutics. With respect to wound healing and the foreign body response, there is a necessity for balance between pro-inflammatory, wound healing, and regulatory macrophages in order to achieve successful implantation of a scaffold for tissue engineering. In this review, we discuss the multitude of ways macrophages are known to be important in cancer therapies and implanted biomaterials

p-wave Holographic Superconductors and five-dimensional gauged Supergravity

We explore five-dimensional ${\cal N}=4$ $SU(2)\times U(1)$ and ${\cal N}=8$ SO(6) gauged supergravities as frameworks for condensed matter applications. These theories contain charged (dilatonic) black holes and 2-forms which have non-trivial quantum numbers with respect to U(1) subgroups of SO(6). A question of interest is whether they also contain black holes with two-form hair with the required asymptotic to give rise to holographic superconductivity. We first consider the ${\cal N}=4$ case, which contains a complex two-form potential $A_{\mu\nu}$ which has U(1) charge $\pm 1$. We find that a slight generalization, where the two-form potential has an arbitrary charge $q$, leads to a five-dimensional model that exhibits second-order superconducting transitions of p-wave type where the role of order parameter is played by $A_{\mu\nu}$, provided $q \gtrsim 5.6$. We identify the operator that condenses in the dual CFT, which is closely related to ${\cal N}=4$ Super Yang-Mills theory with chemical potentials. Similar phase transitions between R-charged black holes and black holes with 2-form hair are found in a generalized version of the ${\cal N}=8$ gauged supergravity Lagrangian where the two-forms have charge $q\gtrsim 1.8$.Comment: 35 pages, 14 figure

P07-05. HIV and STI prevalence among men who have sex with men (MSM) recruited through respondent driven sampling (RDS) in Buenos Aires, Argentina

Fil: Pando, María A. Centro Nacional de Referencia para el SIDA; Argentina.Fil: Marone, Rubén. Nexo Asociación Civil; Argentina.Fil: Balán, Iván C. Columbia University. HIV Center for Clinical and Behavioral Studies; Estados Unidos.Fil: Dolezal, Curtis. Columbia University. HIV Center for Clinical and Behavioral Studies; Estados Unidos.Fil: Squiquera, Luis. Nexo Asociación Civil; Argentina. Fil: Balan, Iván C. Columbia University. HIV Center for Clinical and Behavioral Studies; Estados Unidos.Fil: Picconi, María Alejandra. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Servicio Virus Oncogénicos; Argentina.Fil: Gonzales, J. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Servicio Virus Oncogénicos; Argentina.Fil: Rey, Jorge. Hospital de Clínicas José de San Martín; Argentina.Fil: Fernandez Toscano, M. Hospital de Clínicas José de San Martín; Argentina.Fil: Rodriguez Fermepín, Marcelo. UBA. Laboratorio de Inmunología Clínica; Argentina.Fil: Gallo Vaulet, Lucia. UBA. Laboratorio de Inmunología Clínica; Argentina.Fil: Carballo Dieguez, Alex. Columbia University. HIV Center for Clinical and Behavioral Studies; Estados Unidos.Fil: Avila, María M. Centro Nacional de Referencia para el SIDA; Argentina.Background MSM constitute one of the populations most affected by HIV and other STIs in Argentina. Previous prevalence studies were based on convenience samples. RDS, a methodology designed to access hidden populations, is being used for the first time in Argentina to recruit MSM. Methods RDS recruitment started in November 2007 with 16 first generation participants (seeds) who were selected for their potential to tap in MSM networks. Recruitment is ongoing. Men must be 18 years of age or older, be residents of Buenos Aires, self-report having sex with men at least 10 times in their lives and at least once in the past six months. They must have a coupon indicating they have been referred by a study participant. Specimens are being collected for HIV and STI diagnosis. All data are weighted using the RDS Analysis Tool (RDSAT). Results To date, 333 MSM were recruited through RDS showing a prevalence of 11.3, 16.6, 7.9, 17.6, 4.0 and 88.3% for HIV, HBV, HCV, T. pallidum, Chlamydia and HPV, respectively. Chlamydia and HPV diagnoses were only performed in 73 and 79 participants, respectively. Among HPV positive individuals, 47.8% had almost one of these high risk types (16, 58, 33, 45, 18 and 31) and 32% had multiple infections with 2 or more types. Conclusion Compared with previous studies, these results show similar HIV, HBV and T. pallidum prevalences but higher HCV prevalence. For the first time, an elevated prevalence of HPV was detected on MSM, with high frequency of types associated with ano-genital cancer. Preliminary analyses of socio demographic data show that RDS helps recruit a diversity of MSM, particularly of lower socio-economic level usually missed with other recruitment methods. The high prevalence of coinfections in this population should be taken into account if MSM are part of vaccine trials given that STI may increase HIV sexual transmission

Protein versus DNA as a marker for peripheral blood mononuclear cell counting

Quantitative analysis of intracellular analytes requires an accurate and precise assay not only for the quantitation of the analytes, but also for the quantitation of the number of cells in which they were determined. In this technical note we compare protein and DNA as markers for the number of peripheral blood mononuclear cells (PBMCs) isolated from whole blood. The protein content of samples was highly influenced by red blood cell contamination and was, therefore, a less suitable marker. The DNA-based method was unaffected by red blood cell contamination and was finally validated over a range from 10 × 106 to 300 × 106 PBMCs/mL