Aplicaciones clínicas de células madres derivadas de tejido adiposo y aspectos relacionados con buenas prácticas de manufactura

En la actualidad la terapia celular, a través de las aplicaciones clínicas de las células madres (stem cell, SC), ha adquirido importancia como tratamiento frente a enfermedades que involucran la reparación de tejidos u órganos, frente a las cuales el organismo no es capaz de responder adecuadamente. Un campo de reciente interés se centra en el uso de células madres derivadas de adipocitos (adipose-derived stem cells, ASCs), que presentan ventajas en comparación a las células madres mesenquimales derivadas de médula ósea (mesenchymal stem cells derived from bone marrow, MSC-BM), las que han sido ampliamente investigadas. Los múltiples estudios enfocados en las aplicaciones clínicas de este tipo celular han sido muy prometedores y satisfactorios, lo que ha permitido que recientemente hayan sido aprobadas por la Agencia Europea del Medicamento (EMA) para el tratamiento de fístulas complejas en enfermedad de Crohn. Como consecuencia de lo anterior, al igual que cualquier medicamento de uso humano, requieren de un sistema de normas que regule su producción, como son las Buenas Prácticas de Manufactura (BPM), cuyo objetivo es asegurar la eficacia y seguridad para los pacientes. En esta revisión se abordan aspectos relevantes en relación a las ventajas, aplicaciones clínicas y normas que rigen la producción de ASCs

PTHrP on MCF-7 breast cancer cells: a growth factor or an antimitogenic peptide?

Letter to the Edito

Historia, presente y proyecciones de la Farmacopea

El término “farmacopea” parece tener su origen en Grecia en el siglo II o III A.C y deriva de ϕαρμακον que significa hechizo, veneno o droga y πουεîν que significa hacer. Nace de la necesidad de disponer de un texto que estableciera normas y materiales de referencia para satisfacer los requerimientos de calidad, seguridad y eficacia de los productos farmacéuticos. En el transcurso de más de 500 años desde la aparición de las primeras farmacopeas, se generó trabajo en conjunto entre médicos y farmacéuticos, con predominio posterior del farmacéutico, armonización de los contenidos entre los diferentes textos, tanto nacionales como regionales para cubrir el mercado global. También se ha efectuado una actualización continua y modernización de los contenidos, transitando desde lo natural a lo químico y en la actualidad a lo químico-natural-biológico, en conjunto hoy en día con la incorporación de nuevas y sofisticadas metodologías que generan monografías, más modernas y completas.El término “farmacopea” parece tener su origen en Grecia en el siglo II o III A.C y deriva de ϕαρμακον que significa hechizo, veneno o droga y πουεîν que significa hacer. Nace de la necesidad de disponer de un texto que estableciera normas y materiales de referencia para satisfacer los requerimientos de calidad, seguridad y eficacia de los productos farmacéuticos. En el transcurso de más de 500 años desde la aparición de las primeras farmacopeas reconocidas, se  generó trabajo en conjunto entre médicos y farmacéuticos, con predominio posterior del farmacéutico, armonización de los contenidos entre los diferentes textos, tanto nacionales como regionales para cubrir el mercado global. También se ha efectuado una actualización continua y modernización de los contenidos, transitando desde lo natural a lo químico y en la actualidad a lo químico-natural-biológico, en conjunto hoy en día con la incorporación de nuevas y sofisticadas metodologías que generan monografías, más modernas y completas

Stationary Black Holes: Uniqueness and Beyond

The spectrum of known black-hole solutions to the stationary Einstein equations has been steadily increasing, sometimes in unexpected ways. In particular, it has turned out that not all black-hole-equilibrium configurations are characterized by their mass, angular momentum and global charges. Moreover, the high degree of symmetry displayed by vacuum and electro-vacuum black-hole spacetimes ceases to exist in self-gravitating non-linear field theories. This text aims to review some developments in the subject and to discuss them in light of the uniqueness theorem for the Einstein-Maxwell system.Comment: Major update of the original version by Markus Heusler from 1998. Piotr T. Chru\'sciel and Jo\~ao Lopes Costa succeeded to this review's authorship. Significantly restructured and updated all sections; changes are too numerous to be usefully described here. The number of references increased from 186 to 32

Settling for second best: when should doctors agree to parental demands for suboptimal medical treatment?

Background Doctors sometimes encounter parents who object to prescribed treatment for their children, and request suboptimal substitutes be administered instead (suboptimal being defined as less effective and/or more expensive). Previous studies have focused on parental refusal of treatment and when this should be permitted, but the ethics of requests for suboptimal treatment has not been explored. Methods The paper consists of two parts: an empirical analysis and an ethical analysis. We performed an online survey with a sample of the general public to assess respondents’ thresholds for acceptable harm and expense resulting from parental choice, and the role that religion played in their judgement. We also identified and applied existing ethical frameworks to the case described in the survey to compare theoretical and empirical results. Results Two hundred and forty-two Mechanical Turk workers took our survey and there were 178 valid responses (73.6%). Respondents’ agreement to provide treatment decreased as the risk or cost of the requested substitute increased (p<0.001). More than 50% of participants were prepared to provide treatment that would involve a small absolute increased risk of death for the child (<5%) and a cost increase of US$<500, respectively. Religiously motivated requests were significantly more likely to be allowed (p<0.001). Existing ethical frameworks largely yielded ambiguous results for the case. There were clear inconsistencies between the theoretical and empirical results. Conclusion Drawing on both survey results and ethical analysis, we propose a potential model and thresholds for deciding about the permissibility of suboptimal treatment requests

The Felix-trial. Double-blind randomization of interspinous implant or bony decompression for treatment of spinal stenosis related intermittent neurogenic claudication

Abstract. Background. Decompressive laminotomy is the standard surgical procedure in the treatment of patients with canal stenosis related intermittent neurogenic claudication. New techniques, such as interspinous process implants, claim a shorter hospital stay, less post-operative pain and equal long-term functional outcome. A comparative (cost-) effectiveness study has not been performed yet. This protocol describes the design of a randomized controlled trial (RCT) on (cost-) effectiveness of the use of interspinous process implants versus conventi

A phase I, open-label, randomized crossover study to assess the effect of dosing of the MEK 1/2 inhibitor Selumetinib (AZD6244; ARRY-142866) in the presence and absence of food in patients with advanced solid tumors

&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; This Phase I study assessed whether food influences the rate and extent of selumetinib absorption in patients with advanced solid malignancies and determined the safety, tolerability, and pharmacokinetic (PK) profile of selumetinib and its active metabolite N-desmethyl-selumetinib in fed and fasted states.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; A single dose of 75 mg selumetinib was to be taken with food on Day 1 followed by a single dose of 75 mg after fasting for at least 10 h on Day 8, or vice versa, followed by twice daily dosing of 75 mg selumetinib from Day 10. Plasma concentrations and PK parameters were determined on Days 1 and 8. Patients could continue to receive selumetinib for as long as they benefitted from treatment.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; In total, 31 patients were randomized to receive selumetinib; 15 to fed/fasted sequence and 16 to fasted/fed sequence. Comprehensive PK sampling was performed on 11 and 10 patients, respectively. The geometric least-squares means of C&lt;sub&gt;max&lt;/sub&gt; and AUC for selumetinib were reduced by 62% (ratio 0.38 90% CI 0.29, 0.50) and 19% (ratio 0.81 90% CI 0.74, 0.88), respectively, under fed compared with fasting conditions. The rate of absorption (t&lt;sub&gt;max&lt;/sub&gt;) of selumetinib (fed) was delayed by approximately 2.5 h (median). The food effect was also observed for the active metabolite N-desmethyl-selumetinib. Selumetinib was well tolerated.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; The presence of food decreased the extent of absorption of selumetinib. It is recommended that for further clinical studies, selumetinib be taken on an empty stomach. Selumetinib demonstrated an acceptable safety profile in the advanced cancer population.&lt;/p&gt