Ética médica en la práctica clínica / Medical ethics in clinical practice

La actividad médica se puede ver en dos contextos diferentes, tanto en la práctica clínica como en la investigación científica. El concepto de práctica clínica es todo acto realizado sobre un paciente con el objetivo de diagnosticar o tratar enfermedades. Por otro lado, la investigación clínica cuestiona diferentes aspectos relacionados con la salud humana. Este estudio busca inicialmente esclarecer los aspectos y componentes que orientan la relación y comunicación médico-paciente, definiendo los valores éticos de esta práctica, donde el profesional médico modela su carácter, mediante una relación entre los principios abordados en el ámbito de la ética de los profesionales de la salud. La demostración de una adecuada y sana relación de los profesionales médicos con sus pacientes es necesaria y fundamental a través del respeto y principalmente a través del principio de autonomía, ya que todo ser humano debe ser reconocido como fin y dueño de sí mismo, donde las actividades médicas comprenden procesos que involucran vida, salud e integridad física. Así, el presente trabajo abordará los diversos aspectos de la ética médica, en relación con el contexto de la práctica clínica del médico.

The medical activity can be seen in different contexts, both in clinical practice and in scientific research. The concept of clinical practice is every act performed on a patient with the objective of diagnosing or treating illnesses. On the other hand, clinical research questions different aspects related to human health. This study initially seeks to clarify the aspects and components that guide the doctor-patient relationship and communication, defining the ethical values of this practice, from which the medical professional models its character, through a relationship between the principles addressed in the scope of their ethics. health professionals. The demonstration of an adequate and healthy relationship between medical professionals and their patients is necessary and fundamental through respect and mainly through the principle of autonomy, since every human being must be recognized as an end and duen of symbolism, hence medical activities include processes that involve life, health and physical integrity. Thus, this work will address the various aspects of medical ethics, in relation to the context of the clinical practice of the doctor.

Three-dimensional HepaRG model as an attractive tool for toxicity testing.

The culture of HepaRG cells as three dimensional (3D) structures in the spinner-bioreactor may represent added value as a hepatic system for toxicological purposes. The use of a cost-effective commercially available bioreactor, which is compatible with high-throughput cell analysis, constitutes an attractive approach for routine use in the drug testing industry. In order to assess specific aspects of the biotransformation capacity of the bioreactor-based HepaRG system, the induction of CYP450 enzymes (i.e., CYP1A2, 2B6, 2C9, and 3A4) and the activity of the phase II enzyme, uridine diphosphate glucuronoltransferase (UGT), were tested. The long-term functionality of the system was demonstrated by 7-week stable profiles of albumin secretion, CYP3A4 induction, and UGT activities. Immunofluorescence-based staining showed formation of tissue-like arrangements including bile canaliculi-like structures and polar distribution of transporters. The use of in silico models to analyze the in vitro data related to hepatotoxic activity of acetaminophen (APAP) demonstrated the advantage of the integration of kinetic and dynamic aspects for a better understanding of the in vitro cell behavior. The bioactivation of APAP and its related cytotoxicity was assessed in a system compatible to high-throughput screening. The approach also proved to be a good strategy to reduce the time necessary to obtain fully differentiated cell cultures. In conclusion, HepaRG cells cultured in 3D spinner-bioreactors are an attractive tool for toxicological studies, showing a liver-like performance and demonstrating a practical applicability for toxicodynamic approaches.

Potent neuroprotective effects of novel structural derivatives of valproic acid: potential roles of HDAC inhibition and HSP70 induction.

Emerging evidence suggests that the neuroprotective effects of valproic acid (VPA) occur via inhibition of histone deacetylases (HDACs) and activation of gene expression. This study assessed the ability of four VPA derivatives to cause histone hyperacetylation and protect against glutamate-induced excitotoxicity in cultured neurons. We found that (S)-2-pentyl-4-pentynoic acid (compound III) and (+/-)-2-hexyl-4-pentynoic acid (compound V) were far more potent and robust than VPA in inducing histone hyperacetylation and protecting against glutamate excitotoxicity. Thus, the increase in histone acetylation elicited by compounds III and V was significant at 5microM and reached a maximal increase of 600-700% at 50-100microM, compared with only a 200% increase by VPA at 100microM. The neuroprotective effects of compounds III and V were evident at 10-25microM and reached a complete protection at 50-100microM, while a significant partial protection by VPA was observed at 100microM. These two compounds were also more effective than VPA in increasing HSP70-1a and HSP70-1b mRNA levels. At 50microM, compound V was most robust in increasing HSP-1a mRNA levels, followed by compound III, and then by VPA. HSP-1b mRNA was only significantly upregulated by compounds V and III, but not by VPA or other VPA derivatives under these treatment conditions. Our results suggest that these two VPA derivatives may ultimately be developed into potent neuroprotective drugs in preclinical and clinical studies.

Metabolic activation capacity by primary hepatocytes expands the applicability of the embryonic stem cell test as alternative to experimental animal testing.

The murine embryonic stem cell test (EST) represents a validated alternative method for in vivo embryotoxicity testing. In the present study, primary hepatocytes were combined with the EST by a preincubation approach to improve its predictivity on bioactivation caused teratogenicity. As substances the well-known proteratogens cyclophosphamide (CPA) and valpromide (VPD) were used. The embryotoxic potential of CPA was detected by a strong decrease of the resulting ID(50)-concentration (50% inhibition of ES cell differentiation) after incubation with murine hepatocytes. Interspecies variation in metabolism was detected by testing VPD. After incubation of VPD with murine hepatocytes no inhibition of ES cell differentiation was observed, since hardly any teratogenic VPD metabolites were formed. In contrast, with human hepatocytes a significant conversion of VPD into the teratogen valproic acid (VPA) was observed. In summary we developed a co-culture approach for embryotoxicity testing, whereby the test compounds were incubated with hepatocytes and the supernatant was added to the ES cell culture to obtain a dose dependency of the preincubated test substances.