Oral Administration of Silybin Protects Against MPTP-Induced Neurotoxicity by Reducing Pro-inflammatory Cytokines and Preserving BDNF Levels in Mice.

Parkinson's disease (PD) is the second most frequent neurodegenerative disease associated with motor dysfunction secondary to the loss of dopaminergic neurons in the nigrostriatal axis. Actual therapy consists mainly of levodopa; however, its long-term use promotes secondary effects. Consequently, finding new therapeutic alternatives, such as neuroprotective molecules, is necessary. Among these alternatives is silybin (Sb), the major bioactive flavonolignan in silymarin. Both exert neuroprotective effects, preserving dopamine levels and dopaminergic neurons when administered in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse PD model, being probably Sb the potential therapeutic molecule behind this effect. To elucidate the role of Sb in the PD model, we determined the dose-dependent conservation of striatal dopamine content following Sb oral administration. Then, we evaluated motor deficit tests using the best dopamine conservative dose of Sb and determined a cytokine-dependent inflammatory profile status, malondialdehyde as an oxidative stress product, and neurotrophic factors content in the MPTP-induced mouse PD model. Our results show that oral Sb at 100 mg/kg dose conserved about 60% dopamine levels. Also, Sb improved motor deficits, preserved neurotrophic factors content and mitochondrial function, reduced lipid peroxidation, diminished proinflammatory cytokines to basal levels, enhanced fractalkine production in the striatum and substantia nigra, and increased IL-10 and IL-4 levels in the substantia nigra in the MPTP mice. Thus, oral Sb may be a potential pharmacological PD treatment alternative.

How pills undermine skills: Moralization of cognitive enhancement and causal selection.

Despite the promise to boost human potential and wellbeing, enhancement drugs face recurring ethical scrutiny. The present studies examined attitudes toward cognitive enhancement in order to learn more about these ethical concerns, who has them, and the circumstances in which they arise. Fairness-based concerns underlay opposition to competitive use-even though enhancement drugs were described as legal, accessible and affordable. Moral values also influenced how subsequent rewards were causally explained: Opposition to competitive use reduced the causal contribution of the enhanced winner's skill, particularly among fairness-minded individuals. In a follow-up study, we asked: Would the normalization of enhancement practices alleviate concerns about their unfairness? Indeed, proliferation of competitive cognitive enhancement eradicated fairness-based concerns, and boosted the perceived causal role of the winner's skill. In contrast, purity-based concerns emerged in both recreational and competitive contexts, and were not assuaged by normalization.

How do people use 'killing', 'letting die' and related bioethical concepts? Contrasting descriptive and normative hypotheses.

Bioethicists involved in end-of-life debates routinely distinguish between 'killing' and 'letting die'. Meanwhile, previous work in cognitive science has revealed that when people characterize behaviour as either actively 'doing' or passively 'allowing', they do so not purely on descriptive grounds, but also as a function of the behaviour's perceived morality. In the present report, we extend this line of research by examining how medical students and professionals (N = 184) and laypeople (N = 122) describe physicians' behaviour in end-of-life scenarios. We show that the distinction between 'ending' a patient's life and 'allowing' it to end arises from morally motivated causal selection. That is, when a patient wishes to die, her illness is treated as the cause of death and the doctor is seen as merely allowing her life to end. In contrast, when a patient does not wish to die, the doctor's behaviour is treated as the cause of death and, consequently, the doctor is described as ending the patient's life. This effect emerged regardless of whether the doctor's behaviour was omissive (as in withholding treatment) or commissive (as in applying a lethal injection). In other words, patient consent shapes causal selection in end-of-life situations, and in turn determines whether physicians are seen as 'killing' patients, or merely as 'enabling' their death.

Cómo ser prudentes con la biología sintética. Biología sintética y principio de precaución / No disponible

La Biología Sintética es una novedosa disciplina que presenta una doble vertiente: por un lado ofrece la promesa de rendir beneficios que pueden aliviar algunos de los males que asolan a la humanidad; por otro lado, como todas las tecnologías, encierra riesgos. Ante estos, los más críticos, y preocupados por los riesgos, invocan la aplicación del Principio de Precaución, habitual en los casos en los que una actividad o tecnología nuevas genera riesgos para el medio ambiente y/o la salud humana, pero que lejos de ser universalmente aceptado resulta ser uno de los Principios más controvertidos en la actualidad. En este trabajo se analiza la cuestión de los riesgos y beneficios de la Biología Sintética, así como la pertinencia de la aplicación del Principio de Precaución. Para ello se procede del modo siguiente. En la primera parte se centra en la Biología sintética. En un primer momento, se caracteriza esta disciplina, con especial atención a aquello que tiene de novedoso frente a la conocida como "ingeniería genética". En un segundo momento se analizan tanto los beneficios como los riesgos asociados a ella. La primera parte concluye con un repaso a los esfuerzos que en la actualidad se realizan para controlar o minimizar los riesgos. La segunda parte tiene como objeto el análisis del Principio de precaución y su posible pertinencia para el caso de la Biología Sintética. En un primer momento, se repasan las distintas versiones e interpretaciones del principio y las diversas críticas de las que ha sido objeto. Para finalizar, y tras desechar el Principio de Precaución como una herramienta útil, se contempla como más adecuadas algunas propuestas recientes para tratar tecnologías que tienen en cuenta no solo los riesgos, sino también los beneficios (AU)

Synthetic biology is a new discipline that is twofold: firstly it offers the promise to pay benefits that can alleviate some of the ills that plague mankind; On the other hand, like all technologies, holds risks. Given these, the most critical and concerned about the risks, invoke the application of the precautionary principIe, common in cases where an activity or new technology creates risks to the environment and I or human health, but far from universally accepted happens to be currently one of the most controversial principles. In this paper the question of the risks and benefits of synthetic biology and the relevance of applying the precautionary principle are analyzed. To do this we proceed as follows. The first part focuses on synthetic biology. At first, this discipline is characterized, with special attention to what is novel compared to the known as "genetic engineering". In the second stage both the benefits and the risks associated with it are discussed. The first part concludes with a review of the efforts currently being made to control or minimize the risks. The second part aims to analyze the precautionary principIe and its possible relevance to the case of Synthetic Biology. At first, the different versions and interpretations of the principle and the various criticisms of which has been the subject are reviewed. Finally, after discarding the Precautionary Principle as an useful tool, it is seen as more appropriate some recent proposals to treat technologies that take into account not only risks but also their benefits (AU)

[How to be prudent with synthetic biology. Synthetic Biology and the precautionary principle]. / Cómo ser prudentes con la biología sintética. Biología sintética y principio de precaución.

Synthetic biology is a new discipline that is twofold: firstly it offers the promise to pay benefits that can alleviate some of the ills that plague mankind; On the other hand, like all technologies, holds risks. Given these, the most critical and concerned about the risks, invoke the application of the precautionary principle, common in cases where an activity or new technology creates risks to the environment and/or human health, but far from universally accepted happens to be currently one of the most controversial principles. In this paper the question of the risks and benefits of synthetic biology and the relevance of applying the precautionary principle are analyzed. To do this we proceed as follows. The first part focuses on synthetic biology. At first, this discipline is characterized, with special attention to what is novel compared to the known as "genetic engineering". In the second stage both the benefits and the risks associated with it are discussed. The first part concludes with a review of the efforts currently being made to control or minimize the risks. The second part aims to analyze the precautionary principle and its possible relevance to the case of Synthetic Biology. At first, the different versions and interpretations of the principle and the various criticisms of which has been the subject are reviewed. Finally, after discarding the Precautionary Principle as an useful tool, it is seen as more appropriate some recent proposals to treat technologies that take into account not only risks but also their benefits.