RESUMEN

Spironolactone, a potassium-sparing diuretic, is used to treat hypertension, heart failure, and certain hyperandrogenic disorders. Its use during pregnancy is not recommended due to the risk of feminizing male fetuses, primarily because of its antiandrogenic activity. However, human data remain scarce and largely inconclusive. Here, we present the first case of a 25-year-old pregnant woman, at 16 weeks of gestation, who was inadvertently exposed to spironolactone (240 mg/day) for 1 week due to a pharmacy dispensing error. The patient subsequently delivered a healthy male infant with normal genitalia at 38 weeks of gestation following vaginal delivery. Current follow-up shows that the infant is healthy and developing normally. This article summarizes the potential causes of spironolactone-induced anomalous genital development and explores the safety of new-generation mineralocorticoid receptor antagonists (MRAs) during pregnancy. The mechanisms behind spironolactone-induced anomalous genital development in male fetuses have not been fully elucidated. Spironolactone competes with dihydrotestosterone for binding to androgen receptors and inhibits enzymes involved in androgen biosynthesis, which may partly explain its antiandrogenic effects. Recent advancements in MRAs have led to the development of compounds with higher selectivity for the mineralocorticoid receptor, thereby reducing the incidence of antiandrogen side effects. These new-generation MRAs may be effective alternatives during pregnancy, but more data are needed to establish their safety in pregnant women. This case contributes to the limited but growing body of literature on the safety profile of spironolactone in pregnancy, providing insights into its effects during a critical period of fetal development.

RESUMEN

This study aims to explore the molecular mechanism of Ganoderma against gastric cancer based on network pharmacology, molecular docking, and cell experiment. The active components and targets of Ganoderma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and gastric cancer-related targets from GeneCards and Online Mendelian Inheritance in Man(OMIM). The protein-protein interaction(PPI) network of the common targets was constructed with STRING, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the common genes based on Bioconductor and R language. The medicinal-disease-component-target network and medicinal-disease-component-target-pathway network were established by Cytoscape. Molecular docking was performed between ß-sitosterol(the key component in Ganoderma) and the top 15 targets in the PPI network. Cell experiment was performed to verify the findings. A total of 14 active components and 28 targets of Ganoderma were retrieved, and the medicinal and the disease shared 25 targets, including caspase-3(CASP3), caspase-8(CASP8), caspase-9(CASP9), and B-cell lymphoma-2(BCL2). The common targets involved 72 signaling pathways and apoptosis and p53 signaling pathway may play a crucial role in the effect of Ganoderma against gastric cancer. ß-sitosterol had strong binding activity to the top 15 targets in the PPI network. The in vitro cell experiment demonstrated that ß-sitosterol inhibited gastric cancer AGS cell proliferation by inducing cell apoptosis and cell cycle arrest in the S phase, which might be related to the regulation of the p53 pathway. This study shows the multi-component, multi-target, and multi-pathway characteristics of Ganoderma against gastric cancer, which lays a scientific basis for further research on the molecular mechanism.

Asunto(s)

Ganoderma , Medicina Tradicional China , Neoplasias Gástricas , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética

RESUMEN

BACKGROUND: Vancomycin is frequently used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA). OBJECTIVES: To determine MRSA infection status and the use of vancomycin in its treatment at a teaching hospital in China. METHODS: We retrospectively reviewed 140 cases of MRSA infection that were treated from January 2013 to October 2014. We analyzed the etiology of MRSA infection and the use of vancomycin in these cases. RESULTS: MRSA infection mainly occurred in elderly patients concomitant with a variety of diseases, which incidence was more in men than women. More cases of MRSA infection were encountered in the ICU than in other departments. The positive culture results for MRSA were obtained in the sputum (38.57%), pharyngeal swab (19.29%), blood (5.71%), and wound secretion (11.43%) samples. The MRSA patients were sensitive to vancomycin, with the minimum inhibitory concentration (MIC) being 1 µg/mL in 53.80% of the cases and 2 µg/mL in 44.10% of the cases, respectively. Among the 35 (25%) cases treated with vancomycin, 23 were cured, while 3 died and 7 (20%) were considered as an unreasonable application. CONCLUSIONS: MRSA infection mainly appeared in patients admitted to the ICU. The MIC of vancomycin had a tendency to increase gradually.