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

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

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

Fluoxetine: a case history of its discovery and preclinical development

Introduction: Depression is a multifactorial mood disorder with a high prevalence worldwide. Until now, treatments for depression have focused on the inhibition of monoaminergic reuptake sites, which augment the bioavailability of monoamines in the CNS. Advances in drug discovery have widened the therapeutic options with the synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. Areas covered: The aim of this case history is to describe and discuss the pharmacokinetic and pharmacodynamic profiles of fluoxetine, including its acute effects and the adaptive changes induced after long-term treatment. Furthermore, the authors review the effect of fluoxetine on neuroplasticity and adult neurogenesis. In addition, the article summarises the preclinical behavioural data available on fluoxetine’s effects on depressive-like behaviour, anxiety and cognition as well as its effects on other diseases. Finally, the article describes the seminal studies validating the antidepressant effects of fluoxetine. Expert opinion: Fluoxetine is the first selective SSRI that has a recognised clinical efficacy and safety profile. Since its discovery, other molecules that mimic its mechanism of action have been developed, commencing a new age in the treatment of depression. Fluoxetine has also demonstrated utility in the treatment of other disorders for which its prescription has now been approved

A lean six sigma framework for continuous and incremental improvement in the oil and gas sector

This article aims to explore synergies between Lean Production (LP) and Six Sigma principles in order to propose a Lean Six Sigma (LSS) framework for continuous and incremental improvement in the oil and gas sector. The Three-Dimensional LSS Framework seeks to provide various combinations about the integration between LP principles, DMAIC cycle and PDCA cycle to support operations management needs. Design/methodology/approach - The research method is composed of two main steps: (i) diagnostic of current problems and proposition of a conceptual framework that qualitatively integrates synergistic aspects of LP and Six Sigma; and (ii) analysis of the application of the construct through semi-structured interviews with leaders from oil and gas companies to assess and validate the proposed framework. Findings - As a result, a conceptual framework of LSS is developed contemplating the integration of LP and Six Sigma and providing a systemic and holistic approach to problemsolving through continuous and incremental improvement in the oil and gas sector. Originality/value - This research is different from previous studies because it integrates LP principles, DMAIC and PDCA cycles into a unique framework that fulfils a specific need of oil and gas sector. It presents a customized LSS framework that guides wastes and costs reduction, while enhances quality and reduces process variability to elevate efficiency in operations management of this sector. The paper type is an original research that present new and original scientific findings.N/