A low conductance, non-selective cation channel from human placenta

Non-selective cation channels have been identified in the plasma membranes of many different cells. Previous research using fluorescent techniques has demonstrated the presence of cation conductances in membranes from human trophoblast. The purpose of this work was to explore, by electrophysiological methods, a non-selective cation channel in apical membranes from human placenta. Human placental apical membranes were purified by differential centrifugation and reconstituted in giant liposomes. These giant liposomes were then used for electrophysiological studies and were probed for the presence of cation channels by the patch-clamp method. The channel identified had a linear current-potential relationship with a conductance of around 16 pS in symmetrical Na(+) solution. Under asymmetrical conditions the reversal potential was close to the reversal potential for Na(+). The channel was equally permeable to sodium and potassium and the permeability sequence was NH+4>Cs(+) approximately Rb(+)>Na(+) approximately K(+)>Li(+). The channel also showed permeability to calcium and barium. The channel was insensitive to calcium but was blocked by millimolar concentration of Mg(2+). We have demonstrated the presence of a low conductance, non-selective cation channel in placental apical membranes. These channels share some properties with non-selective cation channels previously described in other different cells. The precise role of these channels in placental physiology has yet to be determined.     

Fetal and postnatal pulmonary circulation in the Alto Andino

Lowland mammals at high altitude constrict the pulmonary vessels, augmenting vascular resistance and developing pulmonary arterial hypertension. In contrast, highland mammals, like the llama, do not present pulmonary arterial hypertension. Using wire myography, we studied the sensitivity to norepinephrine (NE) and NO of small pulmonary arteries of fetal llamas and sheep at high altitudes. The sensitivity of the contractile responses to NE was decreased whereas the relaxation sensitivity to NO was augmented in the llama fetus compared to the sheep fetus. Altogether these data show that the fetal llama has a lower sensitivity to a vasoconstrictor (NE) and a higher sensitivity to a vasodilator (NO), than the fetal sheep, consistent with a lower pulmonary arterial pressure found in the neonatal llama in the Andean altiplano. Additionally, we investigated carbon monoxide (CO) in the pulmonary circulation in lowland and highland newborn sheep and llamas. Pulmonary arterial pressure was augmented in neonatal sheep but not in llamas. These sheep had reduced soluble guanylate cyclase and heme oxygenase expression and CO production than at lowland. In contrast, neonatal llamas increased markedly pulmonary CO production and HO expression at high altitude. Thus, enhanced pulmonary CO protects against pulmonary hypertension in the highland neonate. Further, we compared pulmonary vascular responses to acute hypoxia in the adult llama versus the adult sheep. The rise in pulmonary arterial pressure was more marked in the sheep than in the llama. The llama pulmonary dilator strategy may provide insights into new treatments for pulmonary arterial hypertension of the neonate and adult.     

Uso de las redes sociales por parte de los cirujanos generales. Resultados de la encuesta nacional de la Asociación Española de Cirujanos

Introduction

The use and utility of social media (SM) among Spanish general surgeons is unknown.

Could short thyroid hormone withdrawal be an effective strategy for radioiodine remnant ablation in differentiated thyroid cancer patients?

Purpose

Current guidelines recommend thyroid hormone withdrawal (THW) of 3–4 weeks before radioiodine remnant ablation (RRA) of differentiated thyroid carcinoma (DTC). We aimed to evaluate (1) the reliability of a shorter THW (i.e., 14 days) to achieve adequate TSH levels (i.e., 30 mU/l), (2) the association between length of THW and response to therapy, and (3) the potential association between pre-ablation TSH levels and patients’ outcome.

Methods

After thyroidectomy, all patients started LT4 therapy, which was subsequently discontinued in order to perform RRA. Patients were broken down into two groups according to the length of THW: group A, 2 weeks of THW, and group B, 3–4 weeks of THW. We used clinical, biochemical, and imaging data to evaluate patients’ outcome. By means of univariate and multivariate analysis, including main DTC prognostic factors, we assessed the impact of THW length and TSH levels on patients’ outcome.

Results

We evaluated 222 patients, 85 of whom were treated with RRA after a THW period of 2 weeks (group A). All other 137 patients underwent RRA after 3–4 weeks THW (group B). At the time of RRA all patients presented TSH levels ≥30 mU/l. After a median follow-up time of 3.4 years, we found 183 patients (82%) with excellent response to treatment and 39 patients (18%) showing incomplete response. Kaplan–Meier response to therapy curves showed that ablation-Tg, tumor size, and lymph node status were significantly associated with prognosis; no associations were found between THW length, TSH levels, and prognosis. Multivariate Cox model showed that only ablation-Tg was significantly associated with treatment response.

Conclusions

Prior to RRA, a short 2-week THW is an effective method to stimulate TSH levels. No difference in terms of incomplete response to treatment was observed between DTC patients prepared for RRA with a short THW and those with the long THW.

     

Optimization and application of electrophoretic mobility analysis of human red blood cells to study their in vitro stability, interaction with polycations and proteolytic enzymes

Electrophoretic light scattering method has been considered to determine both the mean and polydispersity of electrophoretic mobility of normal human red blood cells. The final goal of our study was to optimize an in vitro test allowing us to investigate the interaction of xenobiotics, in particular polyelectrolytes, with blood cells. The feasibility of our method has been evaluated based on the reproducibility of our technique to analyze the native electrophoretic mobility of human RBCs, as well as their evolution in the presence of polycationic compounds, i.e. a natural polyamine, spermine, and a synthetic polycation, a polyethylenimine (PEI). Additionally, the follow-up of the human RBCs electrophoretic mobility has been controlled after their incubation with neuraminidase.     

Production of the subdomains of the Plasmodium falciparum apical membrane antigen 1 ectodomain and analysis of the immune response

The apical membrane antigen 1 of Plasmodium falciparum is one of the leading candidate antigens being developed as a vaccine to prevent malaria. This merozoite transmembrane protein has an ectodomain that can be divided into three subdomains (D I, D II, and D III). We have previously expressed a major portion of this ectodomain and have shown that it can induce antibodies that prevent merozoite invasion into red blood cells in an in vitro growth and invasion assay. To analyze the antibody responses directed against the individual subdomains, we constructed six different genes that express each of the domains separately (D I, D II, or D III) or in combination with another domain (D I+II, D II+III, or D I+III). These proteins were purified and used to immunize rabbits to raise construct-specific antibodies. We demonstrated that D I+II induced a significant amount of the growth-inhibitory antibodies active in the growth and invasion assay.