Hipotermia como alternativa terapéutica

La hipotermia terapéuticaconsiste en mantener una temperatura corporal específica por un período determinado y está dirigida a reducir las secuelas de laisquemiaen el sistema nervioso. En este trabajo se exponen los mecanismos del daño celular inducido por la isquemia y se describenlos procesos bioquímicos en los que incide el efecto de la hipotermia. Se revisaron 43 artículos indexados en PubMed. Los objetivos de este trabajo se dirigen adescribir los efectos beneficiosos de la hipotermia terapéutica en el contexto de la respiración celular afectada por el evento isquémico, y a describir, desde un punto de vista molecular, el efecto neuroprotector de la hipotermia. La comprensión de los elementos asociados al beneficio de la hipotermia terapéutica permite integrar conocimientos de las ciencias básicas con situaciones clínicas y contribuye a incentivar el aprendizaje significativo en estudiantes de medicina

Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial

ObjectiveThis study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality.MethodsA multi-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18–80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 μg rEGF + 3.5 mg GHRP6 i.v., n=10), II (75 μg rEGF + 5 mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6 months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index and modified Rankin scale (mRS)] outcomes.ResultsThe study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8–11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06–1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03–1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by their moderate to strong effect size. At 6 months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis including merged treated groups and utility-weighted mRS also showed a benefit of this combined therapy.ConclusionEGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study.Clinical Trial RegistrationRPCEC00000214 of the Cuban Public Registry of Clinical Trials, Unique identifier: IG/CIGB-845I/IC/1601

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Effect of the 2-phenyl-4,4-bis-hydroxymethyl-2-oxazoline in the dentate gyrus response to stimulation of entorhinal cortex and spontaneous electrical activity of the Mongolian gerbil

La epilepsia constituye un desorden neurológico de gran incidencia en la población, con un marcado impacto familiar y social. El gerbil de Mongolia es un modelo de epilepsia de gran utilidad, pues este animal desarrolla crisis espontáneas fenomenológicamente similares a las epilepsias refractarias. En el presente trabajo se estudió el efecto de la 2-fenil-4,4-bis-(hidroximetil)-2-oxazolina (OX) en la respuesta del giro dentado a la estimulación eléctrica de la corteza endorrinal y en la actividad eléctrica espontánea en el gerbil de Mongolia. Se detectó un efecto inhibitorio de OX en esta sinapsis, con una reducción en la amplitud de la espiga de población. El registro de la actividad eléctrica espontánea permitió detectar una disminución de la actividad paroxística del EEG dependiente de la dosis.Epilepsy constitutes a neurological disorder that has great incidence and an enormous familiar and social impact. Mongolian gerbil is a useful epilepsy model because these animals develop spontaneous crisis seemed to the refracted epilepsies. In this paper we studied the effect of the 2-phenyl-4,4-bis-hydroximethyl-2-oxazoline (OX) in the response of the dentate gyrus, during electrical stimulation of entorhinal cortex and the spontaneous electrical activity in the Mongolian Gerbil. It was found an inhibitory effect of OX in that synapsis, with a reduction in the population spikes amplitude. The record of the electric spontaneous activity allowed the detection of a doses-dependent decrease in the paroxistical activity.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Effect of the 2-phenyl-4,4-bis-hydroxymethyl-2-oxazoline in the dentate gyrus response to stimulation of entorhinal cortex and spontaneous electrical activity of the Mongolian gerbil

La epilepsia constituye un desorden neurológico de gran incidencia en la población, con un marcado impacto familiar y social. El gerbil de Mongolia es un modelo de epilepsia de gran utilidad, pues este animal desarrolla crisis espontáneas fenomenológicamente similares a las epilepsias refractarias. En el presente trabajo se estudió el efecto de la 2-fenil-4,4-bis-(hidroximetil)-2-oxazolina (OX) en la respuesta del giro dentado a la estimulación eléctrica de la corteza endorrinal y en la actividad eléctrica espontánea en el gerbil de Mongolia. Se detectó un efecto inhibitorio de OX en esta sinapsis, con una reducción en la amplitud de la espiga de población. El registro de la actividad eléctrica espontánea permitió detectar una disminución de la actividad paroxística del EEG dependiente de la dosis.Epilepsy constitutes a neurological disorder that has great incidence and an enormous familiar and social impact. Mongolian gerbil is a useful epilepsy model because these animals develop spontaneous crisis seemed to the refracted epilepsies. In this paper we studied the effect of the 2-phenyl-4,4-bis-hydroximethyl-2-oxazoline (OX) in the response of the dentate gyrus, during electrical stimulation of entorhinal cortex and the spontaneous electrical activity in the Mongolian Gerbil. It was found an inhibitory effect of OX in that synapsis, with a reduction in the population spikes amplitude. The record of the electric spontaneous activity allowed the detection of a doses-dependent decrease in the paroxistical activity.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Efecto de la administración previa de ozono-médico sobre mortalidad aguda inducida por de la digoxina en ratones

Varios reportes de estudios básicos y clínicos han sugerido un efecto beneficioso de la administración de ozono en la contractibilidad cardíaca, a partir de experimentos en corazón aislado y en investigaciones clínicas. Sin embargo, no existen estudios sobre la interacción del ozono médico con otros agentes farmacológicos empleados crónicamente en el tratamiento de dicha condición clínica. El objetivo del presente trabajo fue estudiar la interacción del ozono médico con la digoxina, a través de la acción cardiotóxica de esta última. En los experimentos se emplearon ratones C-57 machos de 20 g a 24 g de peso corporal. Se conformaron 4 grupos divididos a su vez en 6 subgrupos de 6 animales cada uno. Dos de los grupos recibieron oxígeno (control) u ozono-oxígeno (1,2 mg/kg), respectivamente, por vía rectal, en volúmenes de 0,5 mL, 30 min antes de la administración de digoxina por vía intraperitoneal, en dosis de 2,0; 2,5; 3,0; 3,5; 4,0 y 4,5 mg/kg correspondientes a los diferentes subgrupos. Los otros dos grupos recibieron oxígeno u ozono-oxígeno durante 6 días consecutivos y digoxina 24 h después, empleando la vía y dosis referidas. Se empleó el método de Lichtfield y Wilcoxon para el cálculo de las DL10, DL50 y DL90, así como para el análisis del paralelismo y desplazamiento de las curvas dosis-respuesta. Los resultados mostraron un incremento en la toxicidad de la digoxina en los animales tratados con ozono cuando se compararon con el grupo que recibió oxígeno

Diabetic Foot Ulcers and Epidermal Growth Factor: Revisiting the Local Delivery Route for a Successful Outcome

Soon after epidermal growth factor (EGF) discovery, some in vivo models appeared demonstrating its property to enhance cutaneous wound healing. EGF was the first growth factor (GF) introduced in the clinical arena as a healing enhancer, exerting its mitogenic effects on epithelial, fibroblastoid, and endothelial cells via a tyrosine kinase membrane receptor. Compelling evidences from the 90s documented that, for EGF, locally prolonged bioavailability and hourly interaction with the receptor were necessary for a successful tissue response. Eventually, the enthusiasm on the clinical use of EGF to steer the healing process was wiped out as the topical route to deliver proteins started to be questioned. The simultaneous in vivo experiments, emphasizing the impact of the parenterally administered EGF on epithelial and nonepithelial organs in terms of mitogenesis and cytoprotection, rendered the theoretical fundamentals for the injectable use of EGF and shaped the hypothesis that locally infiltrating the diabetic ulcers would lead to an effective healing. Although the diabetic chronic wounds microenvironment is hostile for local GFs bioavailability, EGF local infiltration circumvented the limitations of its topical application, thus expanding its therapeutic prospect. Our clinical pharmacovigilance and basic studies attest the significance of the GF local infiltration for chronic wounds healing