Na+/K+-ATPase: More than an Electrogenic Pump.

The sodium pump, or Na+/K+-ATPase (NKA), is an essential enzyme found in the plasma membrane of all animal cells. Its primary role is to transport sodium (Na+) and potassium (K+) ions across the cell membrane, using energy from ATP hydrolysis. This transport creates and maintains an electrochemical gradient, which is crucial for various cellular processes, including cell volume regulation, electrical excitability, and secondary active transport. Although the role of NKA as a pump was discovered and demonstrated several decades ago, it remains the subject of intense research. Current studies aim to delve deeper into several aspects of this molecular entity, such as describing its structure and mode of operation in atomic detail, understanding its molecular and functional diversity, and examining the consequences of its malfunction due to structural alterations. Additionally, researchers are investigating the effects of various substances that amplify or decrease its pumping activity. Beyond its role as a pump, growing evidence indicates that in various cell types, NKA also functions as a receptor for cardiac glycosides like ouabain. This receptor activity triggers the activation of various signaling pathways, producing significant morphological and physiological effects. In this report, we present the results of a comprehensive review of the most outstanding studies of the past five years. We highlight the progress made regarding this new concept of NKA and the various cardiac glycosides that influence it. Furthermore, we emphasize NKA's role in epithelial physiology, particularly its function as a receptor for cardiac glycosides that trigger intracellular signals regulating cell-cell contacts, proliferation, differentiation, and adhesion. We also analyze the role of NKA ß-subunits as cell adhesion molecules in glia and epithelial cells.

Expression of miR-34a and miR-15b during the progression of cervical cancer in a murine model expressing the HPV16 E7 oncoprotein.

The high-risk human papillomavirus (HR-HPV) E7 oncoprotein appears to be a major determinant for cell immortalization and transformation altering critical processes such as cell proliferation, apoptosis, and immune response. This oncoprotein plays an essential role in cervical carcinogenesis, but other cofactors such as long-term use of hormonal contraceptives are necessary to modulate the risk of cervical cancer (CC). The role of HR-HPVs in the alteration of microRNA (miRNA) levels in persistent viral infections currently remains unclear. The aim of this study was to evaluate the miR-34a and miR-15b expression levels in the murine HPV16K14E7 (K14E7) transgenic model after chronic estrogen (E2) treatment and their involvement in CC. Interestingly, results showed that, although miR-34a expression is elevated by the HPVE7 oncogene, this expression was downregulated in the presence of both the E7 oncoprotein and chronic E2 in cervical carcinoma. On the other hand, miR-15b expression was upregulated along cervical carcinogenesis mainly by the effect of E2. These different changes in the expression levels of miR-34a and miR-15b along cervical carcinogenesis conduced to low apoptosis levels, high cell proliferation and finally, to cancerous cervical tissue development. In this work, we also determined the relative mRNA expression of Cyclin E2 (Ccne2), Cyclin A2 (Ccna2), and B cell lymphoma 2 (Bcl-2) (target genes of miR-34a and miR-15b); Sirtuin 1 (Sirt1), Cmyc, and Bax (miR-34a target genes); and p21/WAF1 (mir15b target gene) and the H-ras oncogene. Given the modifications in the expression levels of miR-34a and miR-15b during the development of cervical cancer, it will be useful to carry out further investigation to confirm them as molecular biomarkers of cancer.

Prevalence of Cyclomodulin-Positive E. coli and Klebsiella spp. Strains in Mexican Patients with Colon Diseases and Antimicrobial Resistance.

Colon diseases, such as colorectal cancer (CRC), are multifactor diseases that affect more than one million people per year; recently, the microbiota has been associated with an etiologic factor, specifically bacterial cyclomodulin positivity (CM+). Unfortunately, there are no studies from Mexico that detail the presence of bacterial CM+ in patients with colon diseases. We therefore performed a comprehensive study to investigate the associations and prevalence of cyclomodulin-positive Diarrheagenic E. coli (DEC), non-DEC, and Klebsiella spp. strains isolated from Mexican subjects with colon diseases. In this work, we analyzed 43 biopsies, 87 different bacteria were isolated, and E. coli was the most frequently noted, followed by Klebsiella spp., and Enterococcus spp. E. coli, non-DEC, and EPEC belonging to phylogroup B2 were the most prevalent. More than 80% of E. coli and Klebsiella were CM+. pks, cdt, cnf, and cif were identified. cdt was associated with non-DEC, cif and its combinations with EPEC, as well as cdt and psk with Klebsiella. Lastly, all the CM+ bacteria were resistant to at least one antibiotic (34% were MDR, and 48% XDR). In conclusion, the high prevalence of bacterial CM+ in colon disease patients suggests that these bacteria play an important role in the genesis of these diseases.

Single oral dose of maraviroc does not prevent ex-vivo HIV infection of rectal mucosa in HIV-1 negative human volunteers.

OBJECTIVE: Maraviroc (MVC) is a potential candidate for 'on demand' preexposure prophylaxis. In the present study, we evaluated the efficacy of a single oral dose of MVC to prevent ex-vivo HIV-1 infection of rectal tissue in humans. DESIGN AND METHODS: Eight HIV-1-negative healthy volunteers received a single oral dose of MVC (300 or 600 mg), and two additional volunteers received tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, 300/200 mg) for 10 days. Rectal biopsies were performed prior to the ex-vivo challenge (day 0), at day 7 (4 h after MVC) or after 10 days with TDF/FTC. Rectal biopsies were infected ex-vivo, and viral inhibition and CCR5 occupancy was analyzed. MVC concentration in plasma and rectal tissue was measured just after biopsy and after viral incubation. RESULTS: Ex-vivo rectal tissue protection with MVC was incomplete in all but two participants, whereas TDF/FTC avoided ex-vivo infection in the two controls. Median dose-normalized concentration of MVC was significantly higher in rectal tissue than in plasma (561.1 and 155.1 ng/ml, respectively). A significant loss of MVC during the virus incubation (about 60%) and a low CCR5 occupancy (approximately 45%) were detected in rectal cells. CONCLUSIONS: An ex-vivo challenge with a single oral dose of MVC does not prevent ex-vivo infection of human rectal mucosa. The lack of prophylactic efficacy observed suggests that 'on demand' MVC preexposure prophylaxis would not prevent rectal HIV-1 transmission.

Aportación española a la farmacia cubana decimonónica / Spain's contribution to pharmacy in 19th century Cuba

La llegada de los españoles a Cuba supuso una organización que fue un reflejo de la establecida en la metrópoli. En materia farmacéutica, se intentó regularizar el ejercicio de la misma y formar profesionales. Con este objetivo, entre otros, se constituyó en 1711 el Real Tribunal del Protomedicato de La Habana, sustituido en 1833 por las Reales Juntas Superiores Gubernativas de Medicina y Cirugía y de Farmacia hasta 1842, cuando quedaron en manos de la Universidad de La Habana sus competencias en lo relativo a la enseñanza. Durante este tiempo, la Facultad de Farmacia en Cuba permaneció unida a la de medicina, hasta 1863. No podemos dejar sin mencionar la Real Academia de Ciencias Médicas, Físicas y Naturales de La Habana y las publicaciones científicas sobre farmacia de mediados de siglo.

With the arrival of the Spanish in Cuba, society was organized along the lines of what already existed in the metropolis. In the area of pharmacy, this meant standardizing the practice of pharmacy and training professionals. It was with this and other purposes in mind that the Real Tribunal del Protomedicato de La Haban was established in 1711. In 1833 it was replaced by the Reales Juntas Superiores Gubernativas de Medicina y Cirugía y de Farmacia until 1842, when educational responsibilities were transferred to the Universidad de La Habana. Throughout this period, the Facultad de Farmacia in Cuba kept its links with the Facultad de Medicina, until 1863. Another contribution are the Real Academia de Ciencias Médicas, Físicas y Naturales de La Habana and the scientific publications on pharmacy in the midle the century.

Lower circulating insulin-like growth factor I and 1,25-dihydroxyvitamin D levels in preeclampsia

Objetivo. Evaluar si las concentraciones e la somatomedina C )IGF-I) en el suero de mujeres preeclámticas son menores que las encontradas en mujeres embarazadas normotensasm y si las concentraciones en el suero del IGF-I se correlacionan con las de la 1,25-dihidroxivitamina D (1,25-(OH)2D). Diseño del estudio. El estudio fue transversal y se realizó entre las semanas 26.7 y 39.7 del embarazo. Los resultados obtenidos en mujeres preeclámpticas se compararon con los obtenidos en mujeres embarazadas normotensas de la misma edad gestacional (grupo testigo). Lugar. Todas las voluntarias eran pacientes del Hospital General de México, México, D.F., y todos los análisis de laboratorio se realizaron en el Instituto Nacional de la Nutrición Salvador Zubirán, México, D.F. Sujetos. En el estudio participaron 26 mujeres preeclámpticas y 26 mujeres embarazadas normotensas. Todas participaron informada y libremente. Procedimiento. Se realizaron las siguientes medicaciones: concentraciones en el suero del IGF-I, de la 1,25-(OH)2D, de la hormona paratiroidea intacta (PTH), del fósforo inorgánico, de la creatinina y del calcio y magnesio totales y iónicos. Además, se midieron la excreción urinaria del calcio y la depuración renal de la creatinina y se obtuvieron datos antropométricos y sobre la dieta habitual. Todos los análisis de laboratorio se realizaron en forma ciega. La comparación entre grupos se realizó mediante la prueba U de Mann-Whitney y las asociaciones entre variables se analizaron mediante las pruebas de correlación de rangos de Sperman y regresión por pasos. Resultados. Las concentraciones del IGF-I en el suero fueron 26.1 ñ 10.2 nmol/L (promedio ñ DE) en el grupo de mujeres preeclámticas y 49.9 ñ 14.3 nmol/L en el grupo testigo (p= 0.0003). Las concentraciones de la 1,25-(OH)2d en el suero fueron 43.6 ñ 8.2 pg/mL en el grupo de mujeres preeclámpticas y 52.1 ñ 10.2 pg/mL en el grupo testigo (p= 0.005). Las concentraciones de PTH intacta en el suero fueron similares en el grupo de mujeres preeclámpticas y en el grupo testigo. Las concentraciones en el suero del IGF-I, de la 1,25-(OH)2D y de la PTH intacta se correlacionaron significativamente entre sí en el grupo testigo. En las mujeres preeclámpticas sólo se correlacionaron los valores del IGF-I y de la 1,25-(OH)2D. Conclusiones. Del presente estudio se derivan dos observaciones originales: primero, que las concentraciones del IGF-I en el suero de las mujeres preeclámpticas fueron significativamente menores que las observadas en las embarazadas testigo; y segundo, la existencia de una correlación significativa entre las concentraciones séricas de IGF-I y de 1,25-(OH)2D tanto en el grupo testigo como en las mujeres preclámpticas