Differential expression of potassium channels in placentas from normal and pathological pregnancies: targeting of the K(ir) 2.1 channel to lipid rafts.

Potassium channels play important physiological roles in human syncytiotrophoblasts (hSTBs) from placenta, an epithelium responsible for maternal-fetal exchange. Basal and apical plasma membranes differ in their lipid and protein composition, and the latter contains cholesterol-enriched microdomains. In placental tissue, the specific localization of potassium channels is unknown. Previously, we described two isolated subdomains from the apical membrane (MVM and LMVM) and their respective microdomains (lipid rafts). Here, we report on the distribution of K(ir)2.1, K(v)2.1, TASK-1, and TREK-1 in hSTB membranes and the lipid rafts that segregate them. Immunoblotting experiments showed that these channels are present mainly in the apical membrane from healthy hSTBs. Apical expression versus basal membrane was 84 and 16% for K(ir)2.1 and K(v)2.1, 60 and 30% for TREK-1, and 74 and 26% for TASK-1. Interestingly, K(v)2.1 showed differences between apical membrane subdomains: 26 ± 8% was located in the LMVM and 59 ± 9% in MVM. In pathological placentas, the expression distribution changed in the basal membrane: preeclampsia shifted to 50% and intrauterine growth restriction to 42% for TASK-1 and both pathologies increased to 25% for K(ir)2.1 and K(v)2.1, K(ir)2.1 appeared to be associated with rafts that were sensitive to cholesterol depletion in healthy, but not in pathological, placentas. K(v)2.1 and TREK-1 emerged in the nonraft fractions. The precise membrane localization of ion channels in hSTB membranes is necessary to understand the physiological events.

Lipid rafts and cytoskeletal proteins in placental microvilli membranes from preeclamptic and IUGR pregnancies.

Intrauterine growth restriction (IUGR) and preeclampsia (PE) are leading causes of perinatal and maternal morbidity and mortality. Previously we reported the expression of lipid rafts in classical microvillous membrane (MVM) and light microvillous membrane (LMVM), two subdomains in apical membrane from the human placental syncytiotrophoblast (hSTB), which constitute the epithelium responsible for maternal-fetal transport. Here the aim was to study the raft and cytoskeletal proteins from PE and IUGR. Microdomains from MVM and LMVM were tested with raft markers (placental alkaline phosphatase, lipid ganglioside, and annexin 2) and a nonraft marker (hTf-R). No changes were detected with those markers in whole purified apical membranes in normal, PE, and IUGR pregnancies; however, their patterns of distribution in lipid rafts were different in PE and IUGR. Cholesterol depletion modified their segregation, confirming their presence in lipid rafts, although unlike normal placenta, in these pathologies there is only one type of microdomain. Additionally, the cytoskeleton proteins actin, ezrin, and cytokeratin-7 showed clear differences between normal and pathological membranes. Cytokeratin-7 expression decreased to 50% in PE, and the distribution between LMVM and MVM (~43 and 57%, respectively) changed in both PE and IUGR, in contrast with the asymmetrical enrichment obtained in normal LMVM (~62%). In conclusion, lipid rafts from IUGR and PE have different features compared to rafts from normal placentae, and this is associated with alterations in the expression and distribution of cytoskeletal proteins.

[Non-pharmacological interventions for the treatment of erectile dysfunction in adult men: systematic review]. / Intervenciones no farmacológicas para el tratamiento de la disfunción eréctil en varones adultos: revisión sistemática.

OBJECTIVE: To review current evidence on the non-pharmacological (non-invasive) treatment of erectile dysfunction (ED). METHOD: We performed a systematic review of research articles that included adult men diagnosed with ED who had undergone some type of non-pharmacological and non-surgical intervention for this disorder. Free-access, complete texts with an available summary published between 2000 and 2006 were sought. Studies not published in English were excluded. RESULTS: A total for 124 articles were found, and after critical analysis only 8 matched the inclusion criteria (of the 8 articles, 2 were classified as showing quality criterion 1-B and none met the criterion for 1-A). Four types of non-pharmacological, non-surgical therapy were found, which could reverse or improve ED in patients with organic, psychological or mixed impairment and could be applied by nurses. Among these therapies were lifestyle changes (losing weight, pelvic musculature strengthening, psychotherapy and/or psychoeducation and the use of Internet and/or other multimedia devices. CONCLUSIONS: Alternative therapies are available for men with ED. These therapies help to improve or reverse ED and guarantee satisfactory and lasting Results. Nevertheless, we stress that our aim is not to compete with invasive and non-invasive therapies but rather to provide a greater number of treatment alternatives. The low quality of studies could be attributed to the lack of economic resources and the fact that ED is still an emerging subject in current medicine.