Crafting urban equality through grassroots critical pedagogies: weave, sentipensar, mobilize, reverberate, emancipate.

How do ordinary citizens, activists and urban practitioners learn to become agents of change for a socially just habitat? The paper explores this question through the experiences of eight grassroots schools of popular urbanism working under the umbrella of the Habitat International Coalition (HIC) in Latin America. Building on a process of self-documentation and collective pedagogic reflection driven by the protagonists of these schools, the analysis explores the core pedagogic practices identified across the schools to enact popular urbanism as a collective and intentional praxis: to weave, sentipensar, mobilize, reverberate and emancipate. We argue that, put in motion, these pedagogic practices transgress the rules and boundaries of the formal classroom, taking participants to and through other sites and modes of learning that host significant potential to stimulate collectivizing and alternative ways of seeking change towards urban equality.

G protein-coupled receptors as therapeutic target.

Receptors are proteins coded by DNA, some of which have already been crystalized, thus allowing the details of their structure at the atomic level and some aspects of their function to be known. This review focuses on the most diverse and abundant family of receptors, G protein-coupled receptors. This family of receptors recognizes and mediates the action of several endogenous ligands (hormones, neurotransmitters, growth factors and local hormones) and also intervenes in the pathogenesis of various diseases, which is why they are targeted by approximately 30 to 40% of medications that are used in daily clinical practice and of various illegal drugs as well. X-ray crystallography is one of the essential tools that has allowed to observe the structure of these receptors in the amino acids that participate in this interaction, which allows to know the binding site of the endogenous ligand and of synthetic molecules that act on them to modulate their action. Molecular modeling or "docking" is also a computational bioinformatics tool that supports research on receptor-ligand binding, which allows the design and development of increasingly specific drugs. These developments have brought along significant changes in fundamental pharmacodynamic concepts.

Los receptores son proteínas codificadas por el ADN, algunos de los cuales ya han sido cristalizados, lo que permite conocer los detalles de su estructura a nivel atómico y algunos aspectos de su función. Esta revisión se enfoca en los más diversos y abundantes, los receptores acoplados a la proteína G. Esta familia de receptores reconoce y media la acción de varios ligandos endógenos (hormonas, neurotransmisores, factores de crecimiento y hormonas locales) y también interviene en la patogenia de diversas enfermedades, por lo que son el blanco terapéutico de aproximadamente 30 a 40 % de los medicamentos que se emplean en la práctica clínica cotidiana y de diversas drogas ilegales. La cristalografía de rayos X es una de las herramientas clave que ha permitido observar la estructura de estos receptores en los aminoácidos que participan en esta interacción, lo que posibilita conocer el sitio de unión del ligando endógeno y de moléculas sintéticas que actúan sobre ellos para modular su acción. El modelado molecular es también una herramienta bioinformática computacional que apoya la investigación sobre la unión receptor-ligando, que hace posible el diseño y desarrollo de fármacos cada vez más específicos. A estos desarrollos se suman importantes cambios en los conceptos farmacodinámicos fundamentales.

Clinical profile of Plasmodium falciparum and Plasmodium vivax infections in low and unstable malaria transmission settings of Colombia.

BACKGROUND: Malaria transmission in Latin America is generally hypoendemic and unstable, with Plasmodium vivax as the most prevalent species. However, only a few studies have been carried out in areas with low and unstable transmission, whereas the clinical profile of malaria has been broadly described in hyperendemic areas. The pattern of clinical manifestations and laboratory findings in low to moderate endemic areas of Colombia is reported here. METHODS: A passive surveillance study was conducted between 2011 and 2013 involving 1,328 patients with Plasmodium falciparum, P. vivax or mixed malaria infections attending malaria points-of-care of four malaria endemic-areas with distinct transmission intensities and parasite distribution. Trained physicians recorded clinical symptoms and signs as well as socio-demographic characteristics of study participants. Haematological, biochemical and urine tests were performed at the time of diagnosis. RESULTS: Out of 1,328 cases, 673 (50.7%) were caused by P. vivax; 650 (48.9%) were due to P. falciparum; and five (0.4%) patients had mixed infections (P. falciparum/P. vivax). Most patients (92.5%) presented with uncomplicated malaria characterized by fever, chills, headache, sweating, myalgia/arthralgia and parasitaemia ≤ 20,000 parasites/µL. Fever, tachycardia, pallor and abdominal pain on palpation were more frequent in P. falciparum patients, whereas mild hepatomegaly and splenomegaly were mostly observed with P. vivax. Non-severe anaemia (Hb 7.0-10.9 g/dL) was observed in 20% of the subjects, whereas severe anaemia (Hb < 7.0 g/dL) was present in four patients. Half of the patients presented thrombocytopaenia regardless of parasite species. Leukopaenia, neutrophilia and monocytosis were frequently observed in patients infected with P. falciparum. Mild-to-moderate biochemical alterations were present in ~25% of the patients, particularly abnormal bilirubin in those with P. falciparum and abnormal transaminases in P. vivax malaria patients. Proteinuria was present in ~50% of the patients regardless of parasite species, whereas haemoglobinuria was more common in P. vivax infections. Only 7.5% of the cases were classified as clinically severe malaria, caused by both P. vivax and P. falciparum. CONCLUSIONS: The high prevalence of uncomplicated malaria associated with moderate parasitaemia suggests the importance of timely diagnosis and effective treatment and encourages new activities to further decrease complicated malaria cases and mortality.

Mutation of putative phosphorylation sites in the free fatty acid receptor 1: Effects on signaling, receptor phosphorylation, and internalization.

Free fatty acid receptor 1 phosphorylation sites were studied using mutants, including a) a mutant with T215V in the third intracellular loop (3IL), b) another with changes in the carboxyl terminus (C-term): T287V, T293V, S298A, and c) a mutant with all of these changes (3IL/C-term). Agonist-induced increases in intracellular calcium were similar between cells expressing wild-type or mutant receptors. In contrast, agonist-induced FFA1 receptor phosphorylation was reduced in mutants compared to wild type. Phorbol ester-induced FFA1 receptor phosphorylation was rapid and robust in cells expressing the wild-type receptor and essentially abolished in the mutants. Agonist-induced ERK 1/2 phosphorylation and receptor internalization were decreased in cells expressing the mutant receptors compared to those expressing the wild-type receptor. Our data suggest that the identified sites might participate in receptor phosphorylation, signaling, and internalization.

Los receptores acoplados a proteínas G como blanco terapéutico / G protein-coupled receptors as therapeutic target

Resumen Los receptores son proteínas codificadas por el ADN, algunos de los cuales ya han sido cristalizados, lo que permite conocer los detalles de su estructura a nivel atómico y algunos aspectos de su función. Esta revisión se enfoca en los más diversos y abundantes, los receptores acoplados a la proteína G. Esta familia de receptores reconoce y media la acción de varios ligandos endógenos (hormonas, neurotransmisores, factores de crecimiento y hormonas locales) y también interviene en la patogenia de diversas enfermedades, por lo que son el blanco terapéutico de aproximadamente 30 a 40 % de los medicamentos que se emplean en la práctica clínica cotidiana y de diversas drogas ilegales. La cristalografía de rayos X es una de las herramientas clave que ha permitido observar la estructura de estos receptores en los aminoácidos que participan en esta interacción, lo que posibilita conocer el sitio de unión del ligando endógeno y de moléculas sintéticas que actúan sobre ellos para modular su acción. El modelado molecular es también una herramienta bioinformática computacional que apoya la investigación sobre la unión receptor-ligando, que hace posible el diseño y desarrollo de fármacos cada vez más específicos. A estos desarrollos se suman importantes cambios en los conceptos farmacodinámicos fundamentales.

Abstract Receptors are proteins coded by DNA, some of which have already been crystalized, thus allowing the details of their structure at the atomic level and some aspects of their function to be known. This review focuses on the most diverse and abundant family of receptors, G protein-coupled receptors. This family of receptors recognizes and mediates the action of several endogenous ligands (hormones, neurotransmitters, growth factors and local hormones) and also intervenes in the pathogenesis of various diseases, which is why they are targeted by approximately 30 to 40% of medications that are used in daily clinical practice and of various illegal drugs as well. X-ray crystallography is one of the essential tools that has allowed to observe the structure of these receptors in the amino acids that participate in this interaction, which allows to know the binding site of the endogenous ligand and of synthetic molecules that act on them to modulate their action. Molecular modeling or "docking" is also a computational bioinformatics tool that supports research on receptor-ligand binding, which allows the design and development of increasingly specific drugs. These developments have brought along significant changes in fundamental pharmacodynamic concepts.

Peroxovanadate induces alpha 1B-adrenoceptor phosphorylation and association with protein kinase C.

Peroxovanadate induced a marked increase in the phosphorylation state of alpha(1B)-adrenoceptors. The effect was dose-dependent (EC(50) approximately 2 microM) and rapid, reaching its maximum in 5 min and remaining at this level for 30 min. Hydrogen peroxide also increased alpha(1B)-adrenoceptor phosphorylation but to a lesser extent, in an ephemeral fashion, and only at high (millimolar) concentrations. The effect of peroxovanadate was blocked by inhibitors of protein kinase C such as staurosporine and rottlerin and only partially reduced by genistein and inhibitors of phosphoinositide 3-kinase. Protein kinase C alpha, delta and epsilon are associated with the alpha(1B)-adrenoceptor under basal conditions, as reflected by coimmunoprecipitation. Such association was increased by peroxovanadate for all isoforms. In contrast, hydrogen peroxide increased only the association of the epsilon isoform to the adrenoceptor. Peroxovanadate decreased the ability of noradrenaline to increase intracellular calcium, indicating that the receptor phosphorylation induced has functional consequences.

Insulin induces alpha1B-adrenergic receptor phosphorylation and desensitization.

The ability of insulin to induce alpha1B-adrenoceptor phosphorylation and desensitization was tested in two model systems: rat-1 cells that stably express alpha1B-adrenoceptors, through transfection, and endogenously express insulin receptors and DDT1 MF2 cells that endogenously express both receptors. Insulin induced concentration-dependent increases in the phosphorylation state of the adrenergic receptors in the two models with similar EC50 values (0.5-2 nM). The effect was rapid in the two systems but it was sustained in rat-1 cells and transient in DDT1 MF2 cells. In both cell lines, the insulin-mediated phosphorylation of alpha1B-adrenoceptors was blocked by wortmannin and LY 294002, and by staurosporine and bisindolylmaleimide I, indicating that the effect involved phosphoinositide 3-kinase and protein kinase C activities. The adrenoceptor phosphorylation induced by insulin was associated to desensitization as evidences by a diminished elevation of intracellular calcium in response to noradrenaline. Inhibitors of phosphoinositide 3-kinase and protein kinase C blocked the functional desensitization induced by insulin.

Dissecting how receptor tyrosine kinases modulate G protein-coupled receptor function.

Receptor tyrosine kinases and G protein-coupled receptors modulate physiological processes and are also involved in the pathogenesis of some diseases. These receptors have intense bidirectional crosstalks leading to interactions in their signaling pathways and also modulation of the receptors themselves. In some cases, the receptor tyrosine kinases phosphorylate G protein-coupled receptors whereas in others phosphoinositide 3-kinase, protein kinase B and protein kinase C are key elements in these crosstalks. Two paracrine/ autocrine processes also participate, i.e., epidermal growth factor transactivation and sphingosine 1-phosphate generation and signaling. G proteins seem to mediate actions of receptor tyrosine kinases, but how this takes place is far from completely understood; some models are presented. Recent data indicate that the mitogen activated protein kinase cascade also mediate crosstalks. In the present perspective these processes are outlined using information from receptors that have been intensively studied, and important gaps in our knowledge are indicated.

α(1D)-Adrenergic receptors constitutive activity and reduced expression at the plasma membrane.

Adrenergic receptors are a heterogeneous family of the G protein-coupled receptors that mediate the actions of adrenaline and noradrenaline. Adrenergic receptors comprise three subfamilies (α(1), α(2), and ß, with three members each) and the α(1D)-adrenergic receptor is one of the members of the α(1) subfamily with some interesting traits. The α(1D)-adrenergic receptor is difficult to express, seems predominantly located intracellularly, and exhibits constitutive activity. In this chapter, we will describe in detail the conditions and procedures used to determine changes in intracellular free calcium concentration which has been instrumental to define the constitutive activity of these receptors. Taking advantage of the fact that truncation of the first 79 amino acids of α(1D)-adrenergic receptors markedly increased their membrane expression, we were able to show that constitutive activity is present in receptors truncated at the amino and carboxyl termini, which indicates that such domains are dispensable for this action. Constitutive activity could be observed in cells expressing either the rat or human α(1D)-adrenergic receptor orthologs. Such constitutive activity has been observed in native rat arteries and we will discuss the possible functional implications that it might have in the regulation of blood pressure.

Algunos factores que influyen en la relación humana enfermera-paciente, servicios de medicina-hospital: Goyeneche, Arequipa 1995

El presente estudio que fue realizado en los servicios de Medicina Mujeres y Varones del Hospital Goyeneche, en los meses de Octubre y Noviembre del presente año, donde se analizó los factores que influyen en la relación humana Enfermera-Paciente; utilizando el método descriptivo con un diseño de correlación. Para el estudio se tomó a las 11 enfermeras que laboraran indistintamente en los Servicios de Medicina Mujeres y Varones y, una población muestral de 82 pacientes (41 mujeres y 41 varones). Se aplicó una guía de observación a la Enfermera que consta de 11 items, los cuales fueron observados en los Servicios de Medicina Mujeres y Varones, en los turnos de mañana, tarde y guardia diurna, cada items tiene un valor de 6 puntos, haciendo un puntaje total de 66 puntos; orientada a observar como la enfermera propicia las relaciones humanas con el paciente; y una encuesta para obtener datos generales de la misma, con un total de 8 items. Se aplicó una encuesta a los pacientes para determinar los factores propios que influyen en la percepción de la Relacion Humana enfermera-paciente, consta de 3 items generales y de 7 items referente a la relación humana enfermera-paciente, con un puntaje total de 8 puntos. Aplicados los instrumentos, se procedió a la tabulación de los datos obtenidos y el análisis se realizó con la prueba estadística Ji cuadrado para determinar si las variables independientes influyen significativamente en la relación humana enfermera-paciente. Se determinó que la relación enfermera-paciente, no difiere significativamente. Según lo observado del 100 por ciento de enfermeras, el 18 por ciento propician relaciones humanas regulares con el paciente y el 81,82 por ciento relaciones humanas malas. Del 100 por ciento de lo manifestado por el paciente se concluye que la relación humana enfermera-paciente son buena en un 5,10 por ciento, regulares en un 31,71 por ciento y m,alas en un 62,20 por ciento.