Abstract Pituitary adenomas (PA) can impair sexual function (SF). The study (cross-sectional and comparative) assessed the SF of patients with functional and nonfunctional PA and determined its relationship with biopsychosocial variables. 66 patients completed a semi- structured interview and self-administered questionnaires. The total SF mean score overcame the cut-off and 26 % of women and 38 % of men presented impaired SF. Hypogonadism, the perception of sexual discomfort, and anxiety in women, whereas the age in men, had a decreasing effect on the total SF score (p˂0.05). The studied patients with PA showed a moderate overall SF performance and sex-related vulnerabilities expressed in specific sexual domains.

Resumen Los adenomas hipofisarios (AH) pueden afectar la función sexual (FS). El estudio (transversal y comparativo) evaluó la FS de pacientes con AH funcionantes y no funcionantes y determinó su relación con variables biopsicosociales. 66 pacientes completaron una entrevista semiestructurada y cuestionarios autoadministrados. La puntuación media de la FS superó el punto de corte y el 26 % de mujeres y 38 % de varones presentaron deterioro de la FS. El hipogonadismo, la percepción de dificultades sexuales y la ansiedad en las mujeres, y la edad en los hombres, se asociaron a disminución del puntaje total de FS (p˂0.05). Los pacientes con AH tuvieron un desempeño sexual moderado y vulnerabilidades en dominios sexuales específicos en mujeres y varones.

Background: Patients with a cardiovascular (CV) history may be at greater risk of becoming ill and die due to SARS-CoV-2. Aim: To assess the incidence of CV complications in COVID-19 patients, the type of complication, and their association with CV history. Material and Methods: The clinical course of 1,314 patients with COVID-19 admitted consecutively to critical care units of 10 Chilean hospitals was registered between April and August of 2020. Results: The median age of patients was 59 years and 66% were men. One hundred-four (8%) had a CV history, namely heart failure (HF) in 53 (4.1%), coronary heart disease in 50 (3.8 %), and atrial fibrillation in 36 (2.7 %). There were CV complications in 359 patients (27.3%). The most common were venous thrombosis in 10.7% and arrhythmias in 10.5%, HF in 7.2%, type 2 acute myocardial infarction in 4.2%, arterial thrombosis in 2.0% and acute coronary syndrome (ACS) in 1.6%. When adjusted by age, sex and risk factors, only HF (Odds ratio (OR) = 7.16; 95% confidence intervals (CI), 3.96-12.92) and ACS (OR = 5.44; 95% CI, 1.50-19.82) were significantly associated with CV history. There was no association with arrhythmias, type 2 acute myocardial infarction, arterial or venous thrombosis. Conclusions: Patients with a history of CV disease are at greater risk of suffering HF and ACS when hospitalized due to COVID-19. Arrhythmias, type 2 AMI, and arterial or venous thrombosis occur with the same frequency in patients with or without CV history, suggesting that these complications depend on inflammatory phenomena related to the infection.

Abstract Background: Levonorgestrel (LNG) is a progesterone receptor agonist used in both regular and emergency hormonal contraception; however, its effects on the endometrium as a contraceptive remain widely unknown and under public debate. Objective: To analyze the effects of LNG or mifepristone (MFP), a progesterone receptor antagonist and also known as RU-486, administered at the time of follicle rupture (FR) on endometrial transcriptome during the receptive period of the menstrual cycle. Methods: Ten volunteers ovulatory women were studied during two menstrual cycles, a control cycle and a consecutively treated cycle; in this last case, women were randomly allocated to two groups of 5 women each, receiving one dose of LNG (1.5 mg) or MFP (50 mg) the day of the FR by ultrasound. Endometrial biopsies were taken 6 days after drug administration and prepared for microarray analysis. Results: Genomic functional analysis in the LNG-treated group showed as activated the bio-functions embryo implantation and decidualization, while these bio-functions in the T-MFP group were predicted as inhibited. Conclusions: The administration of LNG as a hormonal emergency contraceptive resulted in an endometrial gene expression profile associated with receptivity. These results agree on the concept that LNG does not affect endometrial receptivity and/or embryo implantation when used as an emergency contraceptive.

Abstract Background Expression and activity of the potassium channel ether-à-go-go-1 (EAG1) are strongly related to carcinogenesis and tumor progression, which can be exploited for therapeutic purposes. EAG1 activity may be reduced by preventing its phosphorylation with epidermal growth factor receptor (EGFR) kinase inhibitors and by astemizole, which blocks the channel pore and downregulates its gene expression. Objective We aimed to study the potential cooperative antiproliferative effect of the EGFR inhibitor gefitinib and the EAG1-blocker astemizole, in breast cancer cells. Materials and Methods The cells were characterized by immunocytochemistry. Inhibitory concentrations were determined by non-linear regression analysis using dose-response curves. The nature of the pharmacological effect was evaluated by the combination index equation while cell cycle analysis was studied by flow cytometry. Results Astemizole and gefitinib inhibited cell proliferation in a concentration-dependent manner, with inhibitory concentrations (IC 50) values of 1.72 µM and 0.51 µM, respectively. All combinations resulted in a synergistic antiproliferative effect. The combination of astemizole and gefitinib diminished the percentage of cells in G2/M and S phases, while increased accumulation in G0/G1 of the cell cycle. Conclusions Astemizole and gefitinib synergistically inhibited proliferation in breast cancer cells expressing both EGFR and EAG1. Our results suggest that the combined treatment increased cell death by targeting the oncogenic activity of EAG1.

Available medical therapy is unable to completely prevent or revert the pathological cardiac remodeling secondary to ischemia or other injuries, which is responsible for the development of heart failure. Regenerative medicine through stem cells had an explosive development in the cardiovascular area during the past decade. Stem cells possess the capacity to regenerate, repair or substitute damaged tissue, allowing the reestablishment of its function. Stem cells can also modulate apoptosis, angiogenesis, fibrosis and inflammation, favoring the endogenous regenerative process initiated by the damaged tissue. These capacities have been corroborated in several animal models of cardiovascular diseases with positive results. In humans, therapies with bone marrow mononuclear stem cells, mesenchymal stem cells and cardiac stem cells are safe. Most randomized clinical trials in patients with myocardial infarction or cardiomyopathies of different etiologies have reported benefits on ventricular function, quality of life and even over mortality of treated patients. This article reviews the state of art of stem cell therapy in cardiovascular diseases, focusing on the most common cellular types used in patients with acute myocardial infarction and chronic cardiomyopathies of different etiologies.

The biosynthesis of steroid hormones is necessary to maintain reproductive functions and body homeostasis. This process, which is carried out in acutely and chronically regulated steroidogenic tissues, depends on the activation of signaling pathways particularly mediated by the cyclic adenosine monophosphate dependent protein kinase (PKA). Data obtained by our and other groups in human placenta and other tissues, have clearly showed that dynamic phosphorylation catalyzed by PKA is related to steroidogenesis, including its hormonal regulation. it is known, however, that this process also involves the participation of other PKA independent signaling cascades, which are activated by trophic hormones, cytokines or growth factors and others such as calcium, chloride ions and arachidonic acid metabolites. The understanding of the stimulating factors, as well as the mechanisms that regulate the synthesis of steroid hormones, will allow us the identification of potential intervention sites that may contribute to maintain body homeostasis and different functions depending on them.

La biosíntesis de las hormonas esteroides es necesaria para mantener la función reproductiva y la homeostasis en general. Este proceso que se lleva a cabo en tejidos esteroidogénicos regulados en forma aguda o crónica, activa vías de señalización mediadas particularmente por cinasas de proteínas dependientes del adenosín monofosfato cíclico/AMPc (PKA). Datos obtenidos en placenta humana por nuestro grupo de trabajo y en otros tejidos informados en la literatura, muestran que la fosforilación dinámica de proteínas catalizada por PKA, está asociada a la esteroidogénesis, incluyendo su regulación hormonal. sin embargo, se conoce la participación de otras cascadas de transducción de señales independientes de PKA y que son activadas por hormonas tróficas, citocinas o factores de crecimiento, así como por iones de cloruro y calcio e inclusive por metabolitos del ácido araquidónico. El estudio y comprensión de los factores estimulantes, así como de los mecanismos que regulan la síntesis de las hormonas esteroides, permitirá identificar los sitios potenciales de intervención y de esta manera coadyuvar al mantenimiento de la homeostasis y de las diferentes funciones dependientes de los mismos.

There is still controversy regarding the mechanism of action of levonorgestrel (LNG) for emergency contraception (EC). For those who state that pregnancy starts prior to implantation, any compound able to interfere with post-fertilization and pre-implantation stages, should be considered as abortifacient. Previous research suggests that EC in humans acts predominantly after fertilization. Current evidence with LNG-only EC supports a pre-fertilization mechanisms to explain its action. There are many potential mechanisms of action, which could vary pending on the day during the fertilization window of the ovarian cycle at which the contraceptive is given. This paper reviews the evidence for each potential mechanism of action. According to the most recently statements, it is concluded that the primary and possible the only mechanism of action of LNG-only EC is preventing or delaying ovulation.

El mecanismo de acción del levonorgestrel (LNG) como anticonceptivo de emergencia (AE) es aún controvertido. Para quienes consideran que el embarazo inicia antes de la implantación, todo compuesto capaz de interferir con etapas posteriores a la fecundación y anteriores a la implantación se considera abortivo. Investigaciones previas sugieren que en seres humanos este método actúa también después de la fecundación. Sin embargo, en la actualidad existe sólida evidencia que demuestra que los efectos anteriores a la fecundación son en realidad los que explican la acción anticonceptiva del LNG. En este artículo se revisa la evidencia acumulada sobre los mecanismos de acción propuestos. Los consensos derivados de la información disponible establecen que los mecanismos prefecundación (inhibición o retardo de la ovulación) son los que explican la efectividad anticonceptiva de los AE de progestina sola.

There is still controversy regarding the mechanism of action of levonorgestrel (LNG) for emergency contraception (EC). For those who state that pregnancy starts prior to implantation, any compound able to interfere with post-fertilization and pre-implantation stages, should be considered as abortifacient. Previous research suggests that EC in humans acts predominantly after fertilization. Current evidence with LNG-only EC supports a pre-fertilization mechanisms to explain its action. There are many potential mechanisms of action, which could vary pending on the day during the fertilization window of the ovarian cycle at which the contraceptive is given. This paper reviews the evidence for each potential mechanism of action. According to the most recently statements, it is concluded that the primary and possible the only mechanism of action of LNG-only EC is preventing or delaying ovulation.

El mecanismo de acción del levonorgestrel (LNG) como anticonceptivo de emergencia (AE) es aún controvertido. Para quienes consideran que el embarazo inicia antes de la implantación, todo compuesto capaz de interferir con etapas posteriores a la fecundación y anteriores a la implantación se considera abortivo. Investigaciones previas sugieren que en seres humanos este método actúa también después de la fecundación. Sin embargo, en la actualidad existe sólida evidencia que demuestra que los efectos anteriores a la fecundación son en realidad los que explican la acción anticonceptiva del LNG. En este artículo se revisa la evidencia acumulada sobre los mecanismos de acción propuestos. Los consensos derivados de la información disponible establecen que los mecanismos prefecundación (inhibición o retardo de la ovulación) son los que explican la efectividad anticonceptiva de los AE de progestina sola.

We studied the sites of prolactin inhibition upon FSH induced ovarian steroidogenesis and the ability of prolactin (Prl) to inhibit the synthesis of estradiol and cAMP accumulation under the stimulation of FSH or cAMP dependent activators. The participation of other signal pathways such as PKC and Gi proteins on the inhibitory actions of Prl was also investigated using calfostine C andpertusis toxin as inhibitors. Results showed a dose dependent prolactin decrease in FSH-induced estradiol and cAMP production prior and after the generation of the cyclic nucleotide by a mechanism involving the catalytic subunit of adenyl cyclase and/or through activation of PKC or by the interaction with pertusin toxin sensitive G proteins. Our results suggest a mechanism by which G protein coupled receptors are linked with those coupled with tyrosine kinase through the involvement of a Gi protein mediated mechanism.

En este estudio se investigaron los sitios probables de la acción inhibitoria de prolactina (Prl) sobre la esteroidogénesis ovárica inducida por la hormona folículo estimulante (FSH). Para esta finalidad se estudió la capacidad de cultivos primarios de células de la granulosa de la rata de sintetizar estradiol y AMPc bajo la estimulación con FSH o de activadores de la vía dependiente de AMPc en presencia de Prl humana. La participación de otros sistemas de transducción de señal como los dependientes de PKC y proteínas Gi en los mecanismos de acción inhibitoria de la Prl fue también investigada utilizando inhibidores de estos sistemas como la calfostina C y la toxina pertusis. Los resultados demostraron la habilidad de la Prl de alterar la esteroidogénesis previa y posterior a la generación de AMPc, muy probablemente por mecanismos que involucran la activación de la subunidad catalítica de la adenilato ciclasa, así como a través de interactuar con sistemas de transducción de señal dependientes de PKC y proteínas sensibles a la toxina pertusis. Nuestros resultados sugieren un mecanismo de interacción entre receptores acoplados a proteínas G con aquéllos acoplados a cinasas de tirosinas mediado muy probablemente por vías de señalización dependientes de proteínas Gi.