Una lectura de la neurobiología actual desde la antropología trascendental de Leonardo Polo

La noción poüana de "potencia formal" permite teorizar los datos de las neurociencias. El cerebro constituye una unidad funcional con dinámica epigenética que armoniza múltiples y diversas funciones, en orden al conocimiento, en orden a lo tendencial, a lo motor, etc., porque existe una "función unitaria de conexión". La unidad no es fija sino que esta función armoniza las variaciones, interrupciones y comienzos. La regulación de la dinámica funcional, que indetermina y libera las estructuras psíquicas humanas del automatismo neurológico, supone el frenado intrínseco de los flujos de información cognitiva y emocional de los procesos neuronales. Se describe la integración de áreas cognitivas-afectivas de los circuitos que permiten evaluar la información sensorial, elaborar la respuesta en relación con los demás, o tomar decisiones. Tal función reguladora de la integración dinámica de las múltiples facultades cerebrales se ejerce en la cúspide de la jerarquía del sistema nervioso, la corteza cerebral, especialmente el lóbulo frontal

La investigación con células troncales y la creatividad científica

La descripción del itinerario investigador de la biología de las células troncales permite una reflexión sobre la racionalidad de la creatividad científica. En 1998 aparecieron las células troncales procedentes de embriones humanos. Inmediatamente llegaron, motivadas por razones ideológicas, políticas y económicas, las especulaciones sobre sus posibilidades terapéuticas. Pero las dificultades para su uso médico resultaron insuperables. En 2007 aparecieron las células troncales humanas de pluripotencialidad inducida (iPS). Esta trayectoria investigadora revela aspectos claves del pensamiento creativo en ciencia: a) La importancia de la motivación ética para encontrar un punto de partida no destructivo que marca la racionalidad del camino: los procesos fisiológicos ocurren en la unidad de un organismo vivo. b) La necesidad de un conocimiento profundo de la experiencia científica acumulada para escoger la vía más natural. c) La visión de futuro que agota las posibilidades que ofrecen las pruebas en animales, y que encuentra aplicaciones útiles a los conocimientos que se van obteniendo. d) La imprescindible responsabilidad sobre las consecuencias.Human Embryonic Stem Cells were discovered in 1998 and many speculations arose about their therapeutic possibilities, motivated by ideological, political and economic aspects. The difficulties were insurmountable. However, induced Pluripotent Stem Cells appeared in 2007 and this research trajectory showed key aspects of creative thinking. a) Motivation ethics to find a nondestructive starting point to mark the rationality of that way: the physiological processes occur within the unit of an organism. b) A thorough knowledge of the scientific experience to choose the most natural way. c) Future vision exhausting possibilities offered by animal testing and finding useful applications for the knowledge obtained. d) Responsibility for the consequences

Las células troncales pluripotenciales en la terapia celular

Las células con pluripotencialidad inducida (iPS) son un nuevo tipo de célula troncal derivada de células somáticas humanas, mediante reprogramación con factores de transcripción. Estas células iPS tienen características de las células troncales embrionarias, como la capacidad de convertirse en todos los tipos de células diferenciadas del organismo. A corto plazo, las células de pacientes reprogramadas están siendo útiles para crear modelos celulares de enfermedades, en las que estudiar los procesos patológicos y probar fármacos. A pesar de algunas críticas, se ha ido acumulando evidencia en los trabajos preclínicos, sobre la efectividad de la terapia celular con los clones de iPS apropiadamente seleccionados. La generación de células iPS ha propiciado el desarrollo de otras técnicas,como por ejemplo, la transdiferenciación por la que se convierte directamente in vivo fibroblastos cardiacos en miocitos. Este tipo celular pluripotencial es de un gran valor en la investigación biomedicina y abre nuevas posibilidades a la terapia celular.Induced pluripotent stem (iPS) cells are a novel stem cell population derived from human somatic cells through reprogramming using a set of transcription factors. These iPS cells were shown to share the characteristics of embryonic stem cells, including the ability to give rise to differentiated cells of every tissue type of the body. In the shorter term, iPS cells will be useful for creating patient-identical disease model cells in which the pathological process can be studied and drugs can be tested. Despite critical attitudes, accumulating preclinical evidence supports the effectiveness of iPSCbased cell therapy on the selection of appropriate iPSC clones. The production of iPS cells has also spurred the development of other techniques, for example, transdifferentiation by researchers can now convert heart fibroblasts directly in vivo into myocytes by similar methods. This pluripotent cells is indeed of great value in medical research and it is opening new possibilities in cell therapy

Immunomodulation induced by synthetic peptides derived from Staphylococcus aureus protein A

Peptides from 10 to 22 amino acids containing sequences encompassed by Staphylococcus aureus protein A were synthesized. Some of these peptides, when present in cultures of lymphomononuclear cells from healthy donors or from cancer patients (melanoma, breast carcinoma, non-Hodgkin lymphoma and renal cell carcinoma) promoted: (i) changes in the phenotype of the lymphomononuclear population, (ii) stimulation of monocytes (release of IL-1 and TNF-alpha), and (iii) an increase in cytotoxicity against K562, Daudi and HT-29 cells. Isolated monocytes responded also to those peptides with a release of IL-1 and TNF alpha and an increase of cytotoxicity against HT-29 cells. It was found that the active peptides had the following structural pattern: a length of at least 15 amino-acid residues with a proline at position 6, valine, leucine, isoleucine, glycine, alanine or lysine at position 2, and glutamic or aspartic acid at position 11. Replacement of Pro at position 6 with any other residue turned the peptide inactive. Replacement of residues at positions 2 and 11 with amino-acid residues other than those required for activity resulted in compounds with a marked decrease in the immunomodulating properties described, or lacking these properties altogether

Inducible nitric oxide synthase in human lymphomononuclear cells activated by synthetic peptides derived from extracellular matrix proteins.

Synthetic peptides with sequences present in extracellular matrix proteins are capable of causing the expression of the inducible form of nitric oxide synthase (iNOS), detected by immunocytochemistry, and the release of NO by human lymphomononuclear cells incubated in their presence. Active peptides are 15-mers containing a characteristic 2-6-11 motif in which the amino acid residue at position 2 is Leu, Ile, Val, Gly, Ala or Lys; the residue at position 6 is always Pro; and residue 11 is Glu or Asp. The induction of iNOS in human monocytes and macrophages could be involved in the cytotoxicity against tumor cell lines also elicited by these peptides

Cutaneous Biology: In vivo blockade of pemphigus vulgaris acantholysis by inhibition of intracellular signal transduction cascades

Pemphigus vulgaris (PV) is an autoimmune disease characterized by mucocutaneous intraepithelial blisters and pathogenic autoantibodies against desmoglein 3. The mechanism of blister formation in pemphigus has not been defined; however, in vitro data suggest a role for activation of intracellular signalling cascades. OBJECTIVES: To investigate the contribution of these signalling pathways to the mechanism of PV IgG-induced acantholysis in vivo. METHODS: We used the passive transfer mouse model. Mice were injected with IgG fractions of sera from a patient with PV, with or without pretreatment with inhibitors of proteins that mediate intracellular signalling cascades. RESULTS: Inhibitors of tyrosine kinases, phospholipase C, calmodulin and the serine/threonine kinase protein kinase C prevented PV IgG-induced acantholysis in vivo. CONCLUSIONS: These observations strongly support the role of intracellular signalling cascades in the molecular mechanism of PV IgG-induced acantholysi

Effect of bicarbonate on chloride-dependent transmural potential and ATPase activity in the rectal wall of Schistocerca gregaria

An activating effect of bicarbonate on the active transport of Cl- across the rectal wall of Schistocerca gregario has been found, as revealed by an increase of the transmural potential and short-circuit current. Acetazolamide, an inhibitor of both parameters, does not show this inhibitory effect, even at much higher concentrations, when added in the presence of bicarbonate. A Cl- or S O , anion dependent ATPase, different from the Na+, K+ ATPase, has also been Cound, which can be further stimulated by bicarbonate