Nebulized glycyrrhizin/enoxolone drug modulates IL-17A in COVID-19 patients: a randomized clinical trial.

Introduction: Glycyrrhizin (GA) and its derivative Enoxolone (18ß), isolated from the Glycyrrhiza glabra plant, are two potential molecules for treating viral diseases. Both demonstrate to regulate immune system with antiviral and anti-inflammatory activities, with the latter mainly due to modulation of inflammatory cytokines. The aim of this clinical trial was to evaluate the safety and efficacy of a nebulized GA/18ß drug for treating COVID-19 patients. Methods: An open label, randomized, placebo-controlled clinical trial was conducted in Mexico City from January-August 2022 (Registration No. PROTAP-CLI-00). Clinical and biochemical parameters were recorded. Blood samples from patients were regularly collected to evaluate interleukins IL-4, IL-2, IL-1b, TNF-α, IL-17A, IL-6, IL-10,IFN-γ, IL-12, IL-8 and TGF-ß1, as well as IgM and IgG against SARS-CoV-2. Two doses of the drug were used - 30/2 mg (dose A) and 90/4 mg (dose B). Results and discussion: Both GA/18ß doses modulated inflammatory response by reducing mainly IL-17A expression, which in turn kept IL-1ß, IL-6, IL-8 and TNF-α interleukins unchanged, indicating significant modulation of key interleukin levels to prevent exacerbation of the immune response in COVID-19 patients. Early on, dose A increased IgM, while dose B induced expression of the antiviral IFN-γ. No severe side effects were seen with either dose, indicating nebulized GA/18ß is a safe treatment that could be used for COVID-19 and potentially other viral infections involving inflammatory response.

Metamizol acts as an ATP sensitive potassium channel opener to inhibit the contracting response induced by angiotensin II but not to norepinephrine in rat thoracic aorta smooth muscle.

Clinically metamizol (MZ) has been related to alteration on haemodynamic parameters and modifications on blood pressure in humans when administered intravenously. These effects have been observed at MZ therapeutic doses. Experimentally, MZ is able to induce relaxation on several types of vascular smooth muscles and modulates the contraction induced by phenylephrine. However, the mechanism underlying the MZ effects on vascular reactivity is not clear. Potassium channels (K) present on vascular smooth muscle cells closely regulate the vascular reactivity and membrane potential. There are four described types of K in vascular tissue: K voltage sensitive (K(V)), K calcium sensitive (K(Ca)2+), K ATP sensitive (K(ATP) and K inward rectification (K(IR), voltage sensitive). The aim of this work was to investigate MZ effects on angiotensin II (AT II) and noradrenaline (NA) induced contraction and to evaluate the K participation on MZ modulating effect on vascular smooth muscle contraction, using isometric and patch clamp techniques. MZ induces relaxation in a concentration dependent manner. Furthermore, MZ strongly inhibits in a concentration dependent fashion the contraction induced by AT II. However, MZ inhibition on NA induced contraction was moderated compared with that observed on AT II. MZ effects on AT II induced contraction was blocked by glybenclamide (a specific K(ATP) blocker, 3 microM, *p < 0.01). In patch clamp experiments, MZ (3 mM) induces an increase on potassium current (K+) mediated by K(ATP) in similar way as diazoxide (a specific K(ATP) opener, 3 microM). Our results suggest that MZ induces relaxation and inhibits contraction induced by AT II acting as a K(ATP) opener.

Evaluating knowledge retention of third-year medical students taught with an innovative pharmacology program.

PURPOSE: To explore the degree of retention of pharmacologic knowledge of third-year medical students taught in a new pharmacology teaching program. METHOD: In 1997, the authors administered a retention test consisting of 100 multiple-choice questions, each with only one correct answer, to 457 third-year medical students at the National University of Mexico. Students were not told in advance about this diagnostic evaluation, which was given eight months after they completed the second-year pharmacology course. As a comparison, the authors also analyzed the results obtained by the same students in the three partial examinations taken during the second-year pharmacology course. The Kolmogorov-Smirnov procedure and Wilcoxon and chi-square tests were used to analyze data. RESULTS: The distribution of scores obtained in the partial exams well approximated a symmetrical bell-shaped curve, and the mean score was 59.9%. In contrast, in the retention test the distribution was negatively skewed, the mean score (69.8%) was significantly higher (p <.001), and the curve was clearly displaced to the right of that corresponding to the partial exams. The percentage of students obtaining at least a passing score (60%) was considerably higher for the retention test (82.5 versus 51.9). CONCLUSION: These findings, indicating that medical students taught in a new pharmacology program developed adequate basic pharmacologic knowledge, should encourage other medical schools to formally evaluate their teaching programs and continue efforts to improve pharmacologic education of medical students.

Principios de farmacología en el embarazo / Pharmacological principles in pregnancy

El consumo materno de medicamentos es una práctica común que puede representar un riesgo en el bienestar embrio-fetal, debido a una alteración permanente en la forma y/o en la función. Las fisiologías materna y fetal pueden ejercer una influencia conpleja sobre la biodisponibilidad de un fármaco. Los cambios farmacocinéticos durante el embarazo deben considerarse en el contexto de una unidad integrada de múltiples compartimentos: madre-placenta-membranas extraamnióticas-líquido amniótico-feto. Cada uno tiene funciones propias, con características genéticas o celulares y controles diferentes. Por su importancia, el consumo de fármacos en el embarazo representa un problema que debe tratarse desde diferentes perspectivas, que incluyen estudios epidemiológicos y farmacológicos durante el embarazo, así como de toxicología genética y del desarrollo. De los que partirán estrategias de regulación sanitaria, actualización médica, asesoría farmacológica y educación para la salud en beneficio de las mujeres embarazadas y de sus hijos

Las matemáticas y el corazón / Mathematics and the heart

El modelado matemático en las ciencias biomédicas es especialmente difícil, debido a la gran cantidad de variables que el proceso biológico implica, a la dificultad de observación y experimentación y a la escasez de herramientas matemáticas capaces de incorporar a todas estas variables. A pesar de estas dificultades, hay modelos matemáticos de algunos fenómenos biológicos. Los que existen son modelos reduccionistas, modelos estructurales y modelos de intregración. Los modelos teóricos en biología se diseñan con propósitos claramente definidos y pueden abarcar los distintos niveles del fenómeno biológicos, desde el molecular hasta el organismo intacto. Definir claramente las variables que conforman los niveles y las relaciones entre ellas, permite estructurar un modelo útil. El corazón, tanto sano como enfermo, es un órgano susceptible a ser modelado matemáticamente por sus aspectos observables y medibles, como son la periodicidad, los patrones de activación, las relaciones entre variables conocidas y la estructura. Se mencionan algunos ejemplos. El modelado matemático del corazón puede servir para orientar a la investigación hacia elementos faltantes, para integrar los conocimientos existentes y como apoyo de la terapéutica

Efectos de la adenosina sobre el automatismo y las oscilaciones post-potencial en fibras de Purkinje de mamífero / The effects of adenosine on automacity and after potential oscillations on canine cardiac Purkinje fibers

Se estudiaron los efectos de la adenosina (ADO) sobre el automatismo y las oscilaciones post-potencial de fibras de Purkinje de corazones de perro. Se emplearon concentraciones de ADO desde 10-8 hasta 10-5 M. Se obtuvieron registros de la actividad eléctrica celular mediante microelectrodos. La ADO en concentraciones mayores de 10-8 M produce durante los dos primeros minutos un incremento súbito de la longitud del ciclo básico (LCB), de alrededor del 50 por ciento de su valor control, lo que después progresa hacia un estado estable. La curva dosis-respuesta en la fase estable es sigmoidal típica y semeja a las curvas de ocupación de receptores. Las pendientes del potencial de marcadores tienden a disminuir junto con la depresión de la LCB. Las oscilaciones post-potencial inducidas por tener de estimulación muestran que la pendiente de despolarización de la oscilación post-potencial disminuye con ADO 10-8 M pero no con concentraciones mayores. Los resultados encontrados sugieren que la ADO provoca un incremento en la corriente de potasio tiempo independiente. Este efecto parece depender de la estimulación de receptores específicos. El que la adenosina tenga un curso temporal bifásico sugiere la existencia de receptores purinérgicos con afinidades y constantes de disociación distinta pero con efectos similares y que podrían ser subtipos de receptores A1