Neurotrophins Role in Depression Neurobiology: A Review of Basic and Clinical Evidence

Depression is a neuropsychiatric disorder affecting a huge percentage of the active population especially in developed countries. Research has devoted much of its attention to this problematic and many drugs have been developed and are currently prescribed to treat this pathology. Yet, many patients are refractory to the available therapeutic drugs, which mainly act by increasing the levels of the monoamines serotonin and noradrenaline in the synaptic cleft. Even in the cases antidepressants are effective, it is usually observed a delay of a few weeks between the onset of treatment and remission of the clinical symptoms. Additionally, many of these patients who show remission with antidepressant therapy present a relapse of depression upon treatment cessation. Thus research has focused on other possible molecular targets, besides monoamines, underlying depression. Both basic and clinical evidence indicates that depression is associated with several structural and neurochemical changes where the levels of neurotrophins, particularly of brain-derived neurotrophic factor (BDNF), are altered. Antidepressants, as well as other therapeutic strategies, seem to restore these levels. Neuronal atrophy, mostly detected in limbic structures that regulate mood and cognition, like the hippocampus, is observed in depressed patients and in animal behavioural paradigms for depression. Moreover, chronic antidepressant treatment enhances adult hippocampal neurogenesis, supporting the notion that this event underlies antidepressants effects. Here we review some of the preclinical and clinical studies, aimed at disclosing the role of neurotrophins in the pathophysiological mechanisms of depression and the mode of action of antidepressants, which favour the neurotrophic/neurogenic hypothesis

Eye drop Self-medication: Comparative Questionnaire-based study of two Latin American cities.

A broad spectrum of ocular symptoms are treated by self-medication with commercial eye-drops.  This behavior threatens individuals' visual health. In Latin America, evidence is poor. Objective:  To  detect,  characterize  and  compare  patterns  of  ophthalmic  self-medication  between  Córdoba (Argentina) and Barranquilla (Colombia).Design:  Analytic, cross-sectional and comparative population-based study. Setting: Two private tertiary care ophthalmology centers from Córdoba, Argentina, and Barranquilla, Colombia.Participants:  Patients 18 years of age or older who consulted for the first time in this two institutions duringAugust-November 2009, were included. A number of 570 patients were enrrolled.Methods:  Data collected through a semi-structured questionnaire. Main outcome measure: To determine thefrequency of self-medication with eyedrops on a specific population of two cities in Latin America.Results:  Comparable  rates  of  ocular  self-medication  were  found  (25.6%  and  25.7%  for  Cordoba  and Barranquilla, respectively). The percentage of men and women who self-medicated was not significantly different between both samples. The major source of eye drops recommendation in the Argentineans patients was the pharmacist (31%); while the social source was predominant in Colombian individuals (53%). In Cordoba, the most frequently used product was a non-steroidal anti-inflammatory drop in combination with a vasoconstrictive agent (32%); while in Barranquilla, antibiotic eye drops were preferred (33%). Self-medication was higher between the ages of 31 and 50 years old in Argentinean citizens (28%) and between 18 to 31 years old in the Colombiancommunity (39%). This habit was found mostly in patients who completed university studies in Cordoba (33%); in Barranquilla, individuals with lower educational level practice more this behavior (36%).Conclusion:  In both populations, patients commonly treat ocular conditions by self-medicating. Currently, anincreasing number of eye drops are obtainable without prescription and a high percentage of self-medicated patients in both samples ignore the possible side effects of the used medication.Fil: Marquez, Gabriel. Fundación VER; ArgentinaFil: Hildegard Piñeros-Heilbron. Fundación Oftalmológica del Caribe; ColombiaFil: Sanchez, Victoria M.. Fundación VER; ArgentinaFil: Torres, Victor Eduardo Roque. Fundación VER; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad. Universidad Nacional de Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad; ArgentinaFil: Gramajo, Ana L.. Fundación VER; ArgentinaFil: Juarez, Claudio P.. Fundación VER; Argentina. Fundación Oftalmológica del Caribe; ColombiaFil: Peña, Fernando. Fundación Oftalmológica del Caribe; ColombiaFil: Luna, José D.. Fundación VER; Argentin

Synthesis of stabilized analogues of fragments of Neisseria meningitidis type A capsular polysaccharide

The resistance to Neisseria meningitidis (N. m.), a gram-negative bacterium causing meningitis, is mediated by the presence of antibodies directed against its capsular polysaccharides (CPS), which are associated with different serogroups. One of the most virulent is serotype A (Men A), whose CPS is constituted of (\uf0ae6)-N-acetylmannosamine \uf061-1-O-Phosphate as a repeating unit. The already existing vaccines against N.m. give a T-cell independent immune response, therefore inefficient in infants. The response can be improved by conjugation of the saccharidic portion to a protein carrier, which invokes T-cell involvement. In addition, anomeric phosphodiester bridges are chemically labile and therefore not appropriate for a vaccine. To overcome these problems, phosphonate 4 and its oligomers 5 and 7 have been synthesised as stable analogues of the repeating unit of Men A CPS. Key steps of the synthetic strategy are: a) Synthesis of building blocks 3 and 4, the latter bearing a spacer at the reducing end suitable for conjugation to a proper protein carrier; b) Coupling of 3 with 4 via Mitsunobu reaction providing 5, followed by 6'-O-deacetylation and a second Mitsunobu coupling to give trimer 7. After removal of the protecting groups, the synthesized compounds have been evaluated through a competitive ELISA assay (IC50 values) by use of Men A antiserum. Moreover, preliminary approaches towards the carba-analogue 8 of N-acetylmannosamine 1-O-phosphate, a key building block for the synthesis of a new type of Men A analogues, will be also discussed

An XMM-Newton and INTEGRAL view on the hard state of EXO 1745-248 during its 2015 outburst

CONTEXT - Transient low-mass X-ray binaries (LMXBs) often show outbursts lasting typically a few-weeks and characterized by a high X-ray luminosity ($L_{x} \approx 10^{36}-10^{38}$ erg/sec), while for most of the time they are found in X-ray quiescence ($L_X\approx10^{31} -10^{33}$ erg/sec). EXO 1745-248 is one of them. AIMS - The broad-band coverage, and the sensitivity of instrument on board of {\xmm} and {\igr}, offers the opportunity to characterize the hard X-ray spectrum during {\exo} outburst. METHODS - In this paper we report on quasi-simultaneous {\xmm} and {\igr} observations of the X-ray transient {\exo} located in the globular cluster Terzan 5, performed ten days after the beginning of the outburst (on 2015 March 16th) shown by the source between March and June 2015. The source was caught in a hard state, emitting a 0.8-100 keV luminosity of $\simeq10^{37}$~{\lumcgs}. RESULTS - The spectral continuum was dominated by thermal Comptonization of seed photons with temperature $kT_{in}\simeq1.3$ keV, by a cloud with moderate optical depth $\tau\simeq2$ and electron temperature $kT_e\simeq 40$ keV. A weaker soft thermal component at temperature $kT_{th}\simeq0.6$--0.7 keV and compatible with a fraction of the neutron star radius was also detected. A rich emission line spectrum was observed by the EPIC-pn on-board {\xmm}; features at energies compatible with K-$\alpha$ transitions of ionized sulfur, argon, calcium and iron were detected, with a broadness compatible with either thermal Compton broadening or Doppler broadening in the inner parts of an accretion disk truncated at $20\pm6$ gravitational radii from the neutron star. Strikingly, at least one narrow emission line ascribed to neutral or mildly ionized iron is needed to model the prominent emission complex detected between 5.5 and 7.5 keV. (Abridged)Comment: 14 pages, 6 figure, 2 tables. Accepted for publication on A&A (21/03/2017

Thermal and phase transformations analysis in a PREMOMET® steel

Thermal analysis in a PREMOMET® steel has been performed by differential scanning calorimetry (DSC) and highresolution dilatometry. The phase transformation temperatures (Ac1, Ac3, Ms and Mf) of this steel were obtained by the two methods at different heating rates showing good agreement between both techniques. The enthalpy of α-γ transformation for this steel was measured using the thermograms acquired by DSC and microstructure was analyzed by scanning electron microscope (SEM). The results showed that this steel retained a martensitic structure for all conditions

Diet-Induced Swine Model with Obesity/Leptin Resistance for the Study of Metabolic Syndrome and Type 2 Diabetes

The objective of the present study was to determine the suitability of a swine breed with leptin resistance and predisposition to obesity (the Iberian pig) as model for studies on metabolic syndrome and type 2 diabetes. Thus, six Iberian sows had ad libitum access to food enriched with saturated fat (SFAD group; food consumption was estimated to be 4.5 kg/animal/day) whilst four females acted as controls and were fed with 2 kg/animal/day of a commercial maintenance diet. After three months of differential feeding, SFAD animals developed central obesity, dyslipidemia, insulin resistance and impaired glucose tolerance, and elevated blood pressure; the five parameters associated with the metabolic syndrome. Thus, the current study characterizes the Iberian pig as a robust, amenable, and reliable translational model for studies on nutrition-associated diseases

Co2+ sorption capacity indicators of La Plata region´s soils. Insights and correlations with soil properties

Notwithstanding soil act as a pollutant sink, its Co sorption capacity presents still controversial results. Here, Co2+ sorption on soil samples from La Plata (Argentina) was analyzed. Four sorption indicators were used: Kdis (estimated from the entire sorption isotherm), KF1 (estimated from the lineal part of the sorption isotherm), Kdx, (solid-solution distribution coefficient) and Kr, a dimensionless parameter recently developed. Pearson correlation coefficients between the parameters and soil properties were calculated. Significant and negative correlations with silt were obtained, while significant and positive correlations were established with clay and smectite content. Soil clay fractions were isolated and Co2+ sorption was evaluated, observing relatively high removal. The correlations with kaolinite, magnetite and Mn and Fe oxides showed debatable results: Kdis could be more sensitive than Kr to magnetite variations while Kr seems to be more sensitive to Mn changes. KF1 presented similar behavior to Kr. The studied soils presented a high Co2+ sorption capacity, making them an effective barrier of this pollutant, avoiding its passage to groundwater and crops.Fil: Montes, María Luciana. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Fernandez M. A. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Tecnología de Recursos Minerales y Cerámica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Tecnología de Recursos Minerales y Cerámica; ArgentinaFil: Brendle, J. Université Haute-alsace. Institut de Science Des Matériaux de Mulhouse.; FranciaFil: Michelin, L.. Université Haute-alsace. Institut de Science Des Matériaux de Mulhouse.; FranciaFil: Taylor, Marcela Andrea. Universidad Nacional de La Plata. Facultad de Ingeniería; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Torres Sanchez, Rosa Maria. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Tecnología de Recursos Minerales y Cerámica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Tecnología de Recursos Minerales y Cerámica; Argentin