[Brain characteristics of transgender individuals and consequences of gender assignment treatment]. / Características cerebrales de las personas transexuales y consecuencias del tratamiento de asignación de género.

The differences between the male and female brain in cisgender individuals, those in whom there is no incongruence between the so-called biological sex and the perceived sex, are known. The genetic basis that underlies the differences observed in the brains of transgender individuals compared to cisgender individuals is also becoming known. In transgender individuals, there is a fundamental change in the connectivity of neurons in the body perception network, which may give rise to gender dysphoria. This knowledge allows for the characterization of the transgender condition and distinguishes it from transgender identities such as non-binary gender, gender fluidity, or genderqueer. Articles published assume, from the perspective of depathologization imposed by Gender Ideology, that these differences are due to a different sexual development. The societal acceptance of this perspective over the last two decades paved the way for medical interventions aimed at affirming the perceived gender, different from the genetic sex, through the continuous administration of cross-sex hormones and, in some cases, mutilating surgery. In adolescents and children, affirmation treatment of the perceived gender begins with puberty blockers, which have negative consequences for ossification and growth. The importance and irreversibility of these 'side effects' require the utmost rigor and complete information about them. Spanish law pushes the ideology to the maximum, infringing on the rights of transgender individuals. Medical ethics emphasize the necessity - the right - of a medical and psychological diagnosis, free from ideological approaches, before initiating what is being called treatment. This includes the right to information, prior to consent, about the positive and negative effects of hormonal administration. It also includes the right to the recognition of diversity among transgender individuals, especially the right to research that allows for treating the brain without altering the body. These rights must be recognized and demanded by the laws.

[Transsexualism: a Brain Disorder that Begins to Known]. / Transexualidad: Una Alteración Cerebral que Comienza a Conocerse.

Transsexualism describes the condition when a person's psychological gender differs from his or her biological sex. People with gender identity disorder suffer persistently from this incongruence and they search hormonal and surgical sex reassignment to the desired anatomical sex. This review, from an ethical perspective, intends to give an overview of structural and functional neurobiological correlations of transsexualism and their course under cross-sex hormonal administration. Several studies demonstrate an increased functional connectivity between cortex regions reaffirming psychosocial distress of psychologicalbiological sex incongruity. Such distress can be ascribed to a disharmonic body image due to changes in the functional connectivity of the key components of body representation network. These brain alterations seem to imply a strategic mechanism dissociating bodily emotions from bodily images. For a number of sexually dimorphic brain structures or processes, signs of feminization or masculinization are observable in transsexual individuals, who during hormonal administration seem to partly further adjust to characteristics of the desired sex. These changes allow a reduction of psychosocial distress. However, a model leading to a ″gender affirmation″ does not solve the problem, since brain disorders causing it are not corrected. This is a serious medical ethics issue. Prejudices should be left aside. To know what happens in the brain of transsexuals is a medical need, both to define what is and what is not, and so to choose an adequate treatment, and to decide and guide legal actions.

[Neuroethics: Ethical Endowments of Human Brain]. / Neuroética: La Dotación Ética del Cerebro Humano.

The neurobiological processes underlying moral judgement have been the focus of Neuroethics. Neurosciences demonstrate which cerebral areas are active and inactive whilst people decide how to act when facing a moral dilemma; in this way we know the correlation between determined cerebral areas and our human acts. We can explain how the ″ethical endowments″ of each person, common to all human beings, is ″embedded″ in the dynamic of cerebral flows. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion related areas of the brain contribute to moral judgement. The outcome of man's natural inclinations is on one hand linked to instinctive systems of animal survival and to basic emotions, and on the other, to the life of each individual human uninhibited by automatism of the biological laws, because he is governed by the laws of freedom. The capacity to formulate an ethical judgement is an innate asset of the human mind.

[Biology and ethics of bioethics: an urgent need of realism]. / Biología y ética de la bioética: la urgente necesidad de realismo.

Tenets and recommendations of bioethics should be based on a profound knowledge of biological processes and at the same time deeply integrated with their human significance. Integration has been usually distorted by those implied in disciplines involved with human nature. Biology of fertilization and embryo development have been often fodder of science fiction, when considering that techniques can achieve any aim without acknowledging natural limits, and often handling data, and accepting without any critical attitude pseudoscientific dogma. In the middle of that pseudo-biology bioethics has suffered the onslaught of the ideology of man believing himself autonomous and claiming he is the only one who dictates the rules of reality of world and man, and leading development and progress with this technological power in his hands. The profoundly different response to this deep question of whether what is properly human and essential to each man emerges as a consequence of his own construction and development or, on the contrary, is inherent to the constitution of each man, has caused the splitting of bioethics into two really irreconcilable bioethics. And that because of their different reasoning and criteria. The Ethics of Bioethics requires a new thinking on this crucial point allowing it to grow as an unprejudiced Science. Serious consequences derive from taking one perspective or another. Adopting one or another perspective confront us with a serious problem. Is human life disposable? Or should it be elegantly preserved?

[Select embryos: preimplantation genetic diagnosis]. / Selección de Embriones Humanos. Diagnóstico Genético Preimplantación.

The ability to detect chromosomal or genetic defects in embryos in vitro, associated with assisted human reproduction techniques before his possible transfer to the uterus to complete its development was presented as an alternative to eugenic abortion. And an option for older women to procreate, to avoid pregnancy of embryos with chromosomal defects. Genetic diagnosis before implantation (PGD) and screening of embryos in vitro (by the acronym, PSC), offers the image of the disabled person as an individual excluded from society. It assumes a direct human experimentation without therapeutic purposes or to manipulate the embryo that is chosen or discarded according to diagnosis or for advancement in perinatal medicine. Because these techniques can have multiple embryos, eugenics has also generated a ″positive eugenics″ that seeks to select embryos according to a third party, having certain characteristics, sex, or lack of predisposition to disease. Several issues demand unavoidable ethical duty to report on this form of eugenics, in addition to be directly and intentionally directed to destroy human life in its early stages, and does not meet the minimum requirements of rigorous scientific research or biotechnology. There have been no previous animal tests to validate the techniques so that there are serious errors in diagnosis with false positives and false negatives. Recently it has been shown that some discarded embryos can eliminate their detected defects two days after the biopsy. Moreover, the study about what may or may not be diagnosed is retrospective and unrecoverable damage. And, of particular importance is the fact that it is not known with certainty the effects that an embryo biopsy may cause to those diagnosed.

[Delay the age of procreation, decline in fertility and increased use of assisted reproduction: risk of birth defects]. / Retraso de la Edad de la Procreación, Incremento de la Infertilidad Y Aumento del Recurso a la Reproducción Asistida. Consecuencias en la Salud de los Hijos.

In recent years there has been a progressive decline in fertility, originated mainly on women by the aging of ovules and on man through changes in genetic material of sperm due to cumulative environmental factors over time. Infertility treatments and techniques of assisted reproduction, IVF or insemination, consist of, or preceded by ovarian stimulation treatment aimed to obtain a large number of mature ovules in one cycle. This stimulation does not resolve the crucial issue of changing the pattern of chemical modification, parental imprinting, which occurs in the epigenetic process of oogenesis. Ovules induced to mature and / or forced to fertilization, do not to provide a fresh genome to be passed in each generation passes from parents to children. These changes affect the regulation of expression of a gene cluster (known as imprinted genes) during embryonic development of the child, give him a predisposition to rare diseases that originate precisely in the chaos of such genes. Some factors that cause infertility can be traced to early stages of development. Therefore, infertility is already a generational issue. It is therefore necessary to inform and alert to important factors, and ways of life, giving rise to emerging problems.

[Estrogens and feminine brain maturation during adolescence: emergency contraceptive pill]. / Estrógenos y Desarrollo del Cerebro Femenino en la Adolescencia: Anticoncepción de Emergencia.

In the period between puberty and maturity takes place the process of brain maturation. Hormone levels induce changes in neurons and direct the architecture and structural functionality thus affecting patterns of development of different brain areas. The onset of puberty brings with it the invasion of the female brain by high levels of hormones, cyclic surges of estrogen and progesterone in addition to steroids produced in situ. Control centers of emotions (amygdala), memory and learning (hippocampus) and sexual activity (hypothalamus) are modified according to the cyclical concentrations of both hormones. Sex hormones stimulate multimodal actions, both short and longer terms, because neurons in various brain areas have different types of receptors, membrane, cytoplasmic and nuclear. The composition of emergency contraceptive pill (postcoital pill) with high hormonal content raises the urgency of a thorough knowledge about the possible effect that the lack of control of the menstrual cycle in a time of consolidation of brain maturation, can bring in structuring and development of brain circuitry. Changes in the availability of sex steroids during puberty and adolescence underlie psychiatric disorders whose prevalence is typically feminine, such as depression, anxiety disorders. It is a fundamental ethical duty to present scientific data about the influence of estrogen in young female brain maturation, both for full information to potential users, and also to induce the appropriate public health measures.

El cigoto de nuestra especie es cuerpo humano / The zygote of our species is the human body

Este artículo muestra cómo la palabra de la ciencia aporta un conocimiento directo e indiscutible acerca del comienzo de la vida de cada concebido de nuestra especie: dice cuándo estamos en presencia de un cuerpo humano en los procesos temporales de transmisión de la vida. Aporta también conocimiento directo acerca del carácter personal del embrión por la continuidad de su desarrollo, ya que lo decisivo no es que tenga lugar una continuidad desde el inicio, las etapas embrionarias y fetales, y el nacimiento, sino que esa continuidad suponga continuidad del cuerpo, que siempre es personal. Y un conocimiento indirecto del origen de cada ser humano, al mostrar qué es un cuerpo humano y cómo este tiene ese carácter peculiar exclusivo de los hombres, el carácter personal. En definitiva, la ciencia pone de manifiesto la presencia de una potencia real, distinta de la fuerza de la vida, involucrada en el origen de cada ser humano. El entrelazamiento en la vida única de cada hombre de la dimensión personal y la dimensión biológica es manifestación inequívoca de que existe un único sujeto personal con dos dinamismos. Un ser personal de naturaleza humana.

This article clearly shows science offers us direct and indisputable knowledge about the beginning of human life. It tells us when we are in the presence of a human body in the temporal processes involving the transmission of life. It also gives us direct information about the personal nature of the embryo through the continuity of its development. The decisive fact is not that there is an uninterrupted sequence from the start; that is, from the early embryonic and fetal stages and birth, but that this continuity assumes the continuity of a body, which is always personal. Science offers us indirect knowledge about the origin of each human being, showing it has a human body and every human body has a trait exclusive to man: that of being a person. Science definitely demonstrates the presence of a real power, one that is different from the living force and is involved in the origin of each human being. The intertwining of biological and personal dimensions in the life of every man is a clear sign that every human being exists as one subject with two dynamisms: a personal being that is human in nature.

Este artigo mostra como a palavra da ciência oferece um conhecimento direto e indiscutível sobre o início da vida de cada ser concebido de nossa espécie: dize quando esperamos na presença de um corpo humano nos processos temporais de transmissão da vida. Também fornece conhecimento direto sobre o caráter pessoal do embrião em seu desenvolvimento, já que o fator decisivo não é a continuidade desde o início, as etapas embrionárias e fetais e o nascimento, mas que a continuidade assumir a continuidade do corpo, que é sempre pessoal. Assim mesmo, o artigo provê conhecimento indireto da origem de todo ser humano, mostrando que é um corpo humano e como ele tem a natureza peculiar dos homens, o caráter pessoal. Em suma, a ciência revela a presença de uma potencia real, diferente da força da vida, envolvida na origem de todo ser humano. O entrelaçamento da dimensão pessoal e a dimensão biológica na vida de cada homem é a manifestação clara de que existe um único sujeito pessoal com duas dinâmicas. Um ser pessoal de natureza humana.

[Communication between mother and embryo or foetus]. / Comunicación materno-filial en el embarazo.

Molecular interactions and cellular exchanges between mother and foetus or embryo in pregnancy generate an intimate symbiosis of two different lives. Interpersonal communication is an established requirement in the life of each man to reach personal plenitude. Initially on a biological basis, each person is open to others and his surroundings. While the body of the child is developing in the womb of the mother, the mother prepares the "last finish", which will allow him to assimilate and adapt to his peculiar world. In parallel, the brain of the mother, stimulated by hormones and pregnancy factors, becomes ready for a rich and complex behaviour.

[From the totipotence of the zygote to mature stem cells and reserve cells]. / De la totipotencia del cigoto a las células troncales maduras y de reserva.

In the process of life-transmission, when could we say that we are in the presence of a developing human body? A new human being starts with conception, after the specific gametes of father and mother recognize and fuse with each other; inherited genetic information is fed back reciprocally between the two "pronuclei", during a number of hours, and the resulting egg cell is more than the sum resulting from the fusion of the gametes. It is a living being in its totipotent unicellular stage, a body indeed, with corporal axes assigned, and ready to develop following a "continuum", a marked-out sequence. Divisions initiated in the totipotent fertilized egg give rise to diverse stem cells: pluripotent, multipotent and germinating cells; these latter cells maturing in special niches. Space-cellular organization of each organ and tissue has a precise site in the early, developing organism following a process with precise starting and finishing times and always preserving the individual as a unit. At precisely linked stages the individual temporarily activates potentialities proper of his biological identity. The fact, being tracked through human biology, that each human body is a manifestation of its owner, offers a clear response to the debated question of the connection between the temporal beginning of each man as a zygote or fertilized egg and the origin of his specifically human capacities.

[Lack of biological exchange in assisted reproductive techniques]. / Carencias de la comunicación biológica en las técnicas de reproducción asistida.

There is a clear dividing line in the group of actions aimed at solving sterility, and the techniques aimed at generating embryos to be transferred to a womb. The dividing line is now clearly established by science. The growing alarm among paediatricians raised by the higher risk of malformations and diseases in children when generated in vitro, with respect to those normally engendered, is leading to the need to clearly establish the consequences of in vitro technologies and informing society in an honest way. Two types of lack of exchange of information, cellular and molecular, cause the detected defects. In the fi rst place it is clear that both gametes should recognize each other when adequately mature and in the appropriate natural environment. In vitro technologies force these conditions and either one or both gametes might be impaired and consequently negative effects for the child might be caused. In the second place both embryo and maternal womb are deprived of that early mother-child communication facilitating implantation.

[Does 2009 mark a revival of embryonic stem cells?]. / ¿Resucitan al inicio del 2009 las células troncales procedentes de embriones?

The legal possibility of using federal funds to work with embryonic cells and destroy embryos started on March 2009 in the USA. It has nothing to do with regenerative therapies. It is directed to create banks with human cells, banks directed by a few scientists involved in biotechnology enterprises connected with centers of in vitro reproduction. They pursue the use of ad hoc human embryos for biomedical research. The idea of using cell lines derived from embryos is quite spread, and even the idea of obtaining new lines of this type to validate reprogrammed somatic pluripotential cells, the so called iPS cell (induced pluripotent stem), without destroying embryos or using ovules. This type of cells is indeed of great value in medical research and it is opening new possibilities in Cell Therapy. Recent data are analyzed and considerations are advanced encouraging rational alternatives to eliminate embryonic cells in the evaluation of iPS cells.

Specific protein nitration in nitric oxide-induced apoptosis of human monocytes.

The sustained overproduction of nitric oxide (NO) observed in inflammatory conditions can contribute to cell demise by affecting apoptosis. Nitration of tyrosine residues occurs in a range of diseases involving macrophage activation. Since NO induces apoptosis in monocytes/macrophages, we tested the hypothesis that nitration of specific proteins could result in apoptotic cell death. The peroxynitrite generator SIN-1 promoted apoptosis in monocytes based on oligonucleosomal DNA fragmentation, caspase-3 and -9 activation, Bcl-2 depletion and accumulation of Bax and p53 proteins. We also found that the signaling pathway triggered by SIN-1 was initiated through tyrosine kinase and Rac activation and resulted in increased JNK and p38 activities. Among the tyrosine-nitrated proteins, Rac and Lyn were identified. Using specific inhibitors for different signaling and effector molecules involved in the apoptotic process we demonstrate that NO, via protein-nitration, could play an important role in controlling the inflammatory response by regulation of monocyte homeostasis.

[Ethical principles in research related to regenerative therapy]. / Etica de la Investigación en Terapia Regenerativa.

Recently published data on the function and properties of stem cells are examined and analyzed. This knowledge enhances our understanding of human development: stem cells follow a precise hierarchical pattern both in time and space, and they are part of the symbiosis of fetus and mother. The data do not support the idea of the existence of an early stage of the embryo development lacking a personal character. It has been suggested that an early embryo lacks an entity of sufficient ontological autonomy, which would be acquired with organogenesis at later stages. It is an ethical commitment of the scientific community to provide serious and precise information about the advances, problems and solutions involved an regenerative therapy. The use of autologous or heterologous human cells in this field demands of rules which determine their use and commercial potential. The induced reprogramming of adult cells to an embryonic stage (iPS) opens up new important perspectives both in basic research and for clinical treatments. The ethical commitment of Yamanaka, developer of this technology, with regard to its use in clinical treatments, is an example of the researcher's responsibility of the researcher, and, at the same time, an illustration of how that science may render a service to mankind only through ethical principles.

Maternal antigen presenting cells are a source of plasmatic HLA-G during pregnancy: longitudinal study during pregnancy.

The aim of this work was to investigate the longitudinal evolution of plasmatic soluble HLA-G (sHLA-G: shed HLA-G1 plus HLA-G5) during pregnancy, and if peripheral maternal antigen presenting cells (APC) can be a source of sHLA-G. Blood samples were obtained from 45 volunteers during normal pregnancy, 8 of them monthly; from 8 pregnant volunteers in the first weeks of pregnancy who had later a miscarriage, and from 14 healthy nonpregnant control women. Monocytes obtained during pregnancy showed a moderately HLA-G cell surface expression and stimulation with interferon (IFN)-gamma increased this expression. Monocytes-derived dendritic cells obtained from pregnant women during the first and third trimester of pregnancy secreted more sHLA-G than those obtained from nonpregnant women. Plasmatic sHLA-G concentration in pregnant women was significatively higher than in nonpregnant women, with a peak in the third month. We can conclude that maternal APC are a source of sHLA-G. Women who experienced miscarriage had previously very low or undetectable plasmatic sHLA-G levels in the second month of pregnancy. Data suggest that undetectable sHLA-G could be a risk of complications.

Liberar la verdad científica / To release the scientific truth

Al lenguaje de la ciencia positiva no le basta la gramática propia de las descripciones de los hechos, precisamente porque loshechos no son neutros, sino significativos, naturalmente con sentido. Un significado que está escrito en el lenguaje propio yuniversal de ese mundo, que es un lenguaje simbólico. Lo que aparece en primer plano, las apariencias, asequible al modohumano de conocer los hechos, es, a su vez, signo de la realidad profundamente misteriosa. La biología humana, al mostrarque cada ser humano no está sumergido en los procesos naturales de la fisiología, deja el conocimiento abierto al misterio.No existe una “propiedad biológica” que explique la apertura libre, intelectual y amorosa de los seres humanos hacia otrosseres. Pero la biología describe espléndidamente los presupuestos biológicos del don de la libertad personal. En efecto, hayexperiencias prototípicamente humanas y, por lo tanto, universales, que siendo hechos comprobables empíricamente dan lacerteza de que el mundo, la vida y cada uno de los seres humanos tienen sentido. La luminosidad de la naturaleza, por la quese hace accesible a nuestro conocimiento, es una revelación natural de su Hacedor, que fue además contada con la revelaciónprimitiva a todos y para todos los hombres, añadiéndose así a la racionalidad humana un apoyo en la confianza de quien relatalo que hizo. Y que sólo tomará una forma de expresión nítida en la revelación judeocristiana. Por ello, el conocimiento científicoforma parte de una racionalidad humana más amplia. Y abriéndose a las otras formas de conocimiento, puede ir haciaesos puntos de confluencia del pensamiento humano de todas las épocas, que permiten mirar limpiamente la realidad

Flavonoids induce apoptosis in human leukemia U937 cells through caspase- and caspase-calpain-dependent pathways.

Flavonoids are polyphenolic phytochemicals that are ubiquitous in plants and present in the common human diet. They may exert diverse beneficial effects, including antioxidant and anticarcinogenic activities. In this study we tested the apoptotic activity of 22 flavonoids and related compounds in leukemic U937 cells. Several flavones but none of the isoflavones or flavanones tested induced apoptotic cell death under these conditions, as determined by reduction in cell viability, flow cytometry, and oligonucleosomal DNA fragmentation. Structure-activity relationship showed that at least two hydroxylations in positions 3, 5, and 7 of the A ring were needed to induce apoptosis, whereas hydroxylation in 3' and/or 4' of the B ring enhanced proapoptotic activity. At lower concentrations, these compounds were also able to sensitize these cells to apoptosis induced by tumor necrosis factor-alpha. Regarding the mechanisms, galangin, luteolin, chrysin, and quercetin induced apoptosis in a way that required the activation of caspases 3 and 8, but not caspase 9. In contrast, an active role of calpains in addition to caspases was demonstrated in apoptosis induced by fisetin, apigenin, and 3,7-dihydroxyflavone. Our data show evidence of the proapoptotic properties of some flavonoids that could support their rational use as chemopreventive and therapeutic agents against carcinogenic disease.

Effect of nitric oxide in the differentiation of human monocytes to dendritic cells.

The aim of this work was to study the influence of nitric oxide (NO) in the differentiation of human monocytes to dendritic cells. Human monocytes from healthy donors were differentiated to immature dendritic cells in presence of GM-CSF and IL-4. Maturation of dendritic cells was achieved with GM-CSF and TNF-alpha. Nitric oxide donors (SIN-1, DEA-NO or DETA-NO) were added during differentiation of monocytes to dendritic cells and also during dendritic cells maturation. Immature dendritic cells showed a characteristic phenotype CD80+ CD1a+ HLA-DR+ CD86+ CD40+ CD14(low/-), different from adherent monocytes CD80- CD1a- HLA-DR+ CD86+ CD40- CD14++. The addition of SIN-1 the first day of monocyte differentiation reduced cell viability and increased the percentage of apoptotic immature dendritic cells. Peroxynitrite donor, SIN-1, produced more toxic effects than DEA-NO or DETA-NO. An increase in the subpopulation CD1a+ CD80+ HLADR+ of immature dendritic cells was observed when SIN-1 or DEA-NO, but not DETA-NO, was added at the beginning of monocyte culture. There was a significant reduction in the expression of TNF-alpha receptor of mature dendritic cells when SIN-1 and DEA-NO were added together GM-CSF and TNF-alpha at the beginning of maturation. The presence of SIN-1, DEA-NO or DETA-NO in maturation induced an increase of CD83+ cells. These results suggest that nitric oxide affects differentiation and maturation of dendritic cells and this effect depends on the nitric oxide donor used.

Regulation of NF-kappaB activation by protein phosphatase 2B and NO, via protein kinase A activity, in human monocytes.

It has been reported previously that a short synthetic immunomodulating peptide (Pa) and the neuropeptide beta-endorphin modulate the immune system. We have found now that NF-kappaB participates in the stimulation of monocytes by both peptides and we investigated the molecular mechanism by which these stimuli activate NF-kappaB. Pa and beta-endorphin induce accumulation of cyclic 3('),5(')-adenosine monophosphate (cAMP) in a calcium/calmodulin-dependent fashion since it was completely inhibited by the calmodulin antagonist W-7. The effect of these complexes seems to be mediated, at least in part, by nitric oxide (NO) synthesized by constitutive NO synthase since the NO synthase inhibitor N-methyl-L-arginine (NMLA) reduced the elevation of cAMP. Furthermore, the NO donor SIN-1 provoked nitration of G(S)alpha, leading to the cAMP elevation that was suppressed by the G(S)alpha-selective antagonist NF-449. Interestingly, the rapid degradation of NF-kappaB inhibitor IkappaBalpha induced by Pa- and beta-endorphin was reversed by a pretreatment with H-89 and cyclosporin A, inhibitors of protein kinase A (PKA) and protein phosphatase 2B (PP2B), respectively. These observations are consistent with the inhibition caused by W-7, NMLA, H-89, and cyclosporin A on NF-kappaB induction by these agonists, indicating the involvement of PKA and PP2B in the regulation of NF-kappaB in human monocytes.