A randomised controlled trial evaluating the effect of a brief motivational intervention to promote breastfeeding in postpartum depression.

Postpartum depression (PPD) is the most frequent psychiatric complication during the postnatal period. According to existing evidence, an association exists between the development of PPD and the maintenance of breastfeeding. A brief motivational intervention (bMI), based on the motivational interview, seems effective in promoting breastfeeding. The objective of this study was to analyse the impact of a bMI aiming to promote breastfeeding on the development of PPD and explore the mediating/moderating roles of breastfeeding and breastfeeding self-efficacy in the effect of the intervention on developing PPD. Eighty-eight women who gave birth by vaginal delivery and started breastfeeding during the immediate postpartum period were randomly assigned to the intervention group (bMI) or control group (breastfeeding education). Randomisation by minimisation was carried out. The breastfeeding duration was longer in the intervention group (11.06 (± 2.94) weeks vs 9.02 (± 4.44), p = 0.013). The bMI was associated with a lower score on the Edinburgh Postnatal Depression Scale, with a regression ß coefficient of - 2.12 (95% CI - 3.82; - 0.41). A part of this effect was mediated by the effect of the intervention on the duration of breastfeeding (mediation/moderation index ß = - 0.57 (95% CI - 1.30; - 0.04)). These findings suggest that a bMI aiming to promote breastfeeding has a positive impact preventing PPD mainly due to its effectiveness in increasing the duration of breastfeeding.

Modelos cognitivos de reconstrucción de ensueños / Cognitive models of dreaming

En este trabajo se revisan los estudios más relevantes de la última década acerca de cómo se construyen los ensueños. Tras describir las características de éstos, se exponen los principales modelos de producción de ensueños (psicoanalíticos, neurobiológicos, psicofisiológicos y cognitivos). Se analizan en particular los modelos cognitivos, considerando el origen de los sueños, su composición, las diferencias de organización estructural entre los ensueños que se dan en sueño REM y los de sueño No REM, algunos de los factores que influyen en su recuerdo, las características de los ensueños del principio y del final de la noche y la evolución de éstos durante la infancia. Los datos existentes indican que la actividad mental existe a lo largo de todo el período de sueño, que sus características varían según la fase y el ciclo del sueño en que ocurran y su contenido depende del estilo cognitivo y el estado emocional del durmiente. En cuanto a cómo se construyen los ensueños, la mayoría de los investigadores opina que sólo hay un sistema de producción, responsable tanto de los ensueños de REM como de los de NREM, cuyas fuentes son la memoria episódica y la semántica y los estímulos previos al sueño. Su nivel de funcionamiento varía a lo largo del sueño así como la cantidad de recursos cognitivos disponibles para construir cada ensueño. Hay una continuidad temática en los ensueños sucesivos de distintas fases del sueño de una noche. Las diferencias cualitativas entre los ensueños de REM y los de NREM no parecen ser significativas. Estas podrían deberse ya sea a fallos en los procesos de codificación y recuperación de la información o a que el sistema de producción no dispone de la misma cantidad y tipo de recuerdos en REM que en NREM: los ensueños de REM se construyen principalmente con elementos de memoria semántica mientras que los de NREM se basan en la memoria autobiográfica (AU)

Ba(2+)-induced chromaffin cell death: cytoprotection by Ca(2+) channel antagonists.

Exposure of bovine adrenal medullary chromaffin cells to Ba(2+) ions (in the absence of Ca(2+) ions) caused their death, measured as lactate dehydrogenase (LDH) release. The concentration of Ba(2+) required to damage the cells by about 65% ranged between 1 and 10 mM (no Ca(2+) added); the required exposure time was rather brief (15 min-4 h). The simultaneous presence of Ca(2+), Mg(2+) or Zn(2+) together with Ba(2+) (2 mM, 4 h) afforded cyprotection (60-80%). Individual selective blockers of Ca(2+) channel subtypes afforded no protection. However, combined nifedipine (3 microM) plus omega-conotoxin MVIIC (3 microM) offered full protection. Substantial protection was also seen with the "wide-spectrum" Ca(2+) channel blockers penfluridol (0.3 microM), lubeluzole (3 microM), dotarizine (3 microM), flunarizine (3 microM), and mibefradil (3 microM). This protection was due to blockade of Ba(2+) entry through Ca(2+) channels because dotarizine (10 microM) inhibited the increase in cytosolic [Ba(2+)] seen in fura-2-loaded chromaffin cells. Once Ba(2+) accumulated in the cytosol, it was not extruded by the Na(+)/Ca(2+) exchanger, as shown by the prolonged and sustained elevation of the fura-2 signal. This contrasts with the fast dissipation of the fura-2 signal generated by [Ca(2+)](i) elevation. Thus, Ba(2+) overload can cause cell death by mechanisms similar to those reported for Ca(2+) overload and might be used as a novel and convenient tool to search for new cytoprotective compounds.

Absence of an interaction between ibuprofen and zaleplon.

The potential interaction between zaleplon and ibuprofen was studied. Healthy adult volunteers were given a dose of zaleplon 10 mg alone, a dose of ibuprofen 600 mg alone, or a dose of zaleplon 10 mg and a dose of ibuprofen 600 mg concomitantly in an open-label, randomized, three-period crossover study. There was a seven-day washout period between treatments. Venous blood samples were collected for pharmacokinetic analysis at various intervals up to 14 hours after drug administration. A total of 17 subjects (11 men and 6 women) completed the study. There were no significant differences between zaleplon monotherapy and combination therapy in mean +/- SD, of zaleplon clearance (CL) (2.80 +/- 0.72 versus 2.72 +/- 0.89 L/hr/kg, respectively), maximum plasma concentration (Cmax) (37.1 +/- 17.9 versus 39.8 +/- 20.0 ng/mL), or area under the concentration-versus-time curve (AUC) (56.7 +/- 22.8 versus 59.2 +/- 22.0 ng.hr/mL). There were no significant differences between ibuprofen monotherapy and combination therapy in ibuprofen CL (71.6 +/- 17.0 versus 71.7 +/- 14.9 L/hr/kg), Cmax (40.8 +/- 10.2 versus 40.4 +/- 10.0 micrograms/mL), or AUC (127.6 +/- 29.6 versus 126.4 +/- 29.7 micrograms.hr/mL). Three subjects had one or more adverse effects with zaleplon alone, one subject had one or more with ibuprofen alone, and one subject had one or more with combination therapy. The adverse effects were mild and resolved without intervention. There was no evidence of a significant interaction between zaleplon and ibuprofen.

Effect of zaleplon on digoxin pharmacokinetics and pharmacodynamics.

The pharmacokinetics and pharmacodynamics of digoxin alone and digoxin plus zaleplon were studied. Healthy, nonsmoking men between 18 and 45 years of age were given a single oral dose of digoxin 0.375 mg daily on days 1 through 9. On days 10 through 14, the subjects received digoxin 0.375 mg plus oral zaleplon 10 mg daily. Blood samples were obtained on days 3, 5, 8, 9, and 14, and serum digoxin concentration data were analyzed by model-independent pharmacokinetic methods. Blood pressure, heart rate, PR interval, and QTc interval were recorded to determine the effect of zaleplon on digoxin pharmacodynamics. A total of 20 men completed the study. Maximum serum digoxin concentration and area under the serum digoxin concentration-versus-time curve from 0 to 24 hours met bioequivalence test criteria. There were no significant differences in QTc or PR interval between days 9 (digoxin alone) and 14 (digoxin plus zaleplon), and there were no clinically important changes from baseline to the study's end in vital signs, physical examination findings, or ECG results for individual subjects. Eighteen percent of the subjects who received digoxin alone and 35% of those who received digoxin plus zaleplon reported one or more adverse effects; all were mild and resolved quickly. Zaleplon had no significant effects on selected pharmacokinetic and pharmacodynamic properties of digoxin.

Effects of dotarizine and flunarizine on chromaffin cell viability and cytosolic Ca2+.

Dotarizine (a novel piperazine derivative with antimigraine properties) and flunarizine (a Ca2+ channel antagonist) were compared concerning: first, their ability to cause chromaffin cell damage in vitro; second, the possible correlation of their octanol/water partition coefficients and those of another 28 compounds (i.e., Ca2+ channel antagonists, blockers of histamine H1 receptors, antimycotics, beta-adrenoceptor antagonists, neuroleptics), with their ability to cause cell damage; third, their capacity to protect the cells against the damaging effects of veratridine; and fourth, their capabilities to enhance the basal cytosolic Ca2+ concentration in fura-2-loaded single chromaffin cells, or to modify the pattern of [Ca2+]i oscillations elicited by veratridine. After 24-h exposure to 1-30 microM dotarizine, the viability of bovine adrenal chromaffin cells (measured under phase contrast or as lactate dehydrogenase, released into the medium) was similar to that of control, untreated cells; at 100 microM, 80% lactate dehydrogenase release was produced. At 1-3 microM flunarizine caused no cell damage; however 10 microM caused 20% lactate dehydrogenase release and 30 and 100 microM over 90% lactate dehydrogenase release. The time course of cell damage was considerably faster for flunarizine, in comparison to dotarizine. Out of 30 molecules tested (at 10 microM), having different octanol/water partition coefficients (log P), dotarizine was among the molecules causing no cell damage; flunarizine caused 20% cell loss, lidoflazine and verapamil over 50% cell loss, and penfluridol, draflazine, astemizole or nifedipine over 80% cell loss. No correlation was found between log P and cytotoxicity. Both dotarizine (10-30 microM) and flunarizine (3-10 microM) provided protection against veratridine-induced cell death; however, at 30 microM dotarizine afforded a pronounced protection while flunarizine enhanced the cytotoxic effects of veratridine. Dotarizine (30 microM) (but not flunarizine) caused a prompt transient elevation of the basal [Ca2+]i. Both compounds abolished the K+-induced increases of [Ca2+]i as well as the oscillations of [Ca2+]i induced by veratridine. The blocking effects of dotarizine were readily reversed after washout, while those of flunarizine were long-lasting. These differences might be relevant to the clinical use of dotarizine as an antimigraine drug.

[Catecholaminergic secretions and monovalent cations in adrenal medulla]. / Secreción catecolaminérgica y cationes monovalentes en la médula adrenal.

Taken together the results of this work indicate that 1st) The countertransport systems, [Na+]i-[Ca2+]o or [Li+]i-[Ca2+]o are implicated on the catecholamine secretory response evoked by ouabaine and lithium in the cat adrenal medulla. 2nd) Both procedures (ouabain, or lithium) induce an increment of cytosolic [Ca2+]i, secundary to the accumulation of monavalents cations (Na+ or Li+) in the cytosol, which is finally responsible for the catecholamine secretory response and 3rd) In addition to [Na+]i-[Ca2+]o or [Li+]i-[Ca2+]o counter transport systems, either Na+ or Li+ could depolarize the cell and therefore activate voltage-dependent Ca2+, and possibly Na+ channels leading to further increments of [Ca2+]i.

Effects of the neuroprotectant lubeluzole on the cytotoxic actions of veratridine, barium, ouabain and 6-hydroxydopamine in chromaffin cells.

1. Incubation of bovine adrenal chromaffin cells with veratridine (10-100 microM) during 24 h, caused a concentration-dependent release of the cytosolic lactate dehydrogenase (LDH) into the bathing medium, an indicator of cell death. Lubeluzole or its R(-) enantiomer, R91154, did not enhance LDH release. Both lubeluzole and R91154 (0.3-10 microM) decreased the veratridine-induced LDH release. 2. Penfluridol did not increase LDH release at concentrations 0.003-1 microM; 3-10 microM increased LDH release to 50-60%, after 24 h exposure. Penfluridol (0.03-0.3 microM) did not protect against the cytotoxic effects of veratridine; at 1 microM, 15% protection was produced. Higher concentrations (3-10 microM) enhanced the cytotoxic effects of veratridine. 3. Ba2+ ions caused a concentration-dependent increase of LDH release. This cytotoxic effect was partially prevented by 3 microM lubeluzole and fully counteracted by 1 microM penfluridol. R91154 was less potent than lubeluzole and only protected against the lesion induced by 0.5 mM Ba2+. 4. Ouabain (10 microM during 24 h) increased LDH release to about 30%. Both lubeluzole (0.3-10 microM) and the lower concentrations of penfluridol (0.003-0.3 microM) prevented the ouabain cytotoxic effects. At higher concentrations (3 microM), penfluridol increased drastically the ouabain cytotoxic effects. 5. 6-Hydroxydopamine (6-OHDA) caused significant cytotoxic effects at 30 and 100 microM. Lubeluzole (3-10 microM) or penfluridol (0.03-0.3 microM) had no cytoprotective effects against 6-OHDA. 6. Lubeluzole (3 microM), R91154 (3 microM) and penfluridol (1 microM) blocked the current through Na+ channels in voltage-clamped chromaffin cells (I(Na)) by around 20-30%. Ca2+ current through Ca2+ channels (I(Ca)) was inhibited 57% by lubeluzole and R91154 and 50% by penfluridol. The effects of penfluridol were not washed out, but those of lubeluzole and R91154 were readily reversible. 7. Lubeluzole (3 microM) induced reversible blockade of the oscillations of the cytosolic Ca2+, [Ca2+]i, in fura-2-loaded cells exposed to 30 or 100 microM veratridine. Penfluridol (1 microM) inhibited those oscillations in an irreversible manner. 8. The results suggest that lubeluzole and its R-isomer caused cytoprotection against veratridine cell damage, by blocking the veratridine stimulated Na+ and Ca2+ entry, as well as the [Ca2+]i oscillations. The Ba2+ and ouabain cytotoxic effects were prevented more efficiently by penfluridol, likely by blocking the plasmalemmal Na+/Ca2+ exchanger. It remains dubious whether these findings are relevant to the reported neuroprotective action of lubeluzole in stroke; the doubt rests in the stereoselective protecting effects of lubeluzole in in vivo stroke models, as opposed to its lack of stereoselectivity in the in vitro model reported here.

Pharmacokinetic study of ebrotidine administered in multiple doses to healthy volunteers for 4 days.

The safety of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4- thiazolyl]methyl]thio]ethyl]amino] methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542), a new H2-receptor antagonist with gastroprotective activity, was assessed and its main pharmacokinetic parameters were determined in order to establish the dose linearity after the repeated administration of three different dose levels. The study was carried out in a group of 8 healthy volunteers of either sex, aged between 20 to 29 years. Oral doses of ebrotidine were administered in a randomized, single-blind design. Volunteers remained in the Unit for two days at each of the three study phases with washout intervals of 2 weeks and received seven doses of ebrotidine (150, 300 and 500 mg b.i.d). Pharmacological evaluation included vital signs, laboratory tests, adverse events and blood and urine samplings for pharmacokinetic analysis. Ebrotidine was determined by high performance liquid chromatography (HPLC) with UV detection. The results showed a good tolerability of ebrotidine after the administration of seven doses for 4 days, with no changes in the vital signs or laboratory parameters. No clinically significant dose-related adverse events were reported during the study. The absorption of ebrotidine was relatively rapid (tmax approximately 2 h) and linear within the dose range from 150 to 500 mg. Drug biotransformation was linear with doses tested, and no metabolic saturation occurred. The terminal elimination half-life of ebrotidine was between 7 and 11 h or even longer. There was no accumulation of ebrotidine and the steady state was reached, regardless of the dose administered, within the first 24-48 h.

The actions of ouabain and lithium chloride on cytosolic Ca2+ in single chromaffin cells.

The effects of ouabain, Li+ and veratridine on the concentration of cytosolic free Ca2+ ([Ca2+]i) were studied in single fura-2-loaded bovine adrenal chromaffin cells. Superfusion of cells with ouabain (10 microM for 60 min) caused only a delayed mild increase of the Ca2+]i, from around 0.1 microM to 0.2-0.3 microM; this increase was Nao(+)-dependent. Replacement of all NaCl of the Krebs-Hepes solution by LiCl (144 mM) produced a gradual increase of [Ca2+]i, which remained elevated at a stable plateau of 0.4-0.5 microM for 40-50 min. When ouabain (in the presence of normal Nao+) or Li+ (in the absence of Nao+) was given in Krebs-Hepes solution containing no Ca2+, the reintroduction of 2.5 mM Ca2+ produced a fast elevation of the [Ca2+]i. In the case of ouabain-treated cells, the [Ca2+]i curve exhibited an initial phasic component which inactivated to a tonic component. omega-Conotoxin MVIIC (3 microM) and R56865 (10 microM) inhibited the phasic but not the tonic component. Veratridine (30 microM) induced large [Ca2+]i oscillations. Both ouabain or Li+ abolished such oscillations. These results are compatible with ouabain causing elevation of [Ca2+]i in bovine chromaffin cells through a dual mechanism, i.e. cell depolarisation and slowing down of the Na(+)-Ca2+ exchanger of their plasmalemma. Through its binding to the Na+ site on the Na(+)-Ca2+ exchanger, Li+ ions generate powerful Cai2+ signals that might be relevant to its known effects on neurosecretory mechanisms.

Contribution of SK and BK channels in the control of catecholamine release by electrical stimulation of the cat adrenal gland.

1. Transmural electrical stimulation (10 Hz, 1 ms, 40 V for 10 s) of cat adrenal glands perfused at room temperature with Krebs-Hepes solution produced catecholamine secretory responses which were reproducible when stimulations were applied at 5 min intervals. Such responses were inhibited about 20% by atropine (1 microM) and 80% by hexamethonium (30 microM). Apamin (100 nM) increased the secretory response 2.5-fold in the presence of atropine and 8-fold in the presence of hexamethonium. 2. Potentiation by apamin of secretory responses evoked by 100-pulse trains was similar at 5, 10 and 20 Hz (about 2-fold). When glands were continuously stimulated at 3 Hz, apamin increased 4-fold the initial secretion plateau. Continuous stimulation at a higher frequency (20 Hz) produced a sharp secretory peak followed by a small, sustained plateau; apamin did not alter this plateau. Apamin also enhanced the secretory responses obtained with sustained stimulation with acetylcholine (10 or 200 microM). 3. Secretion peaks induced by brief acetylcholine pulses (10 microM for 10 s) applied to isolated and superfused cat adrenal chromaffin cells were enhanced more than 3-fold by 100 nM apamin. Charybdotoxin (10 nM) did not enhance these secretory peaks. 4. In perfused cat adrenal glands, charybdotoxin (10 nM) affected neither the secretion evoked by trains of electrical stimulation applied at different frequencies nor the secretion evoked by acetylcholine pulses. 5. In 0.5 mM [Ca2+]o, apamin enhanced 3-fold the secretion evoked by electrical stimulation trains of 100 pulses (10 Hz, 10 s) and almost 6-fold the acetylcholine (10 microM for 10 s)-induced secretion. In 5 mM Ca2+, apamin enhanced the secretory responses to electrical stimulation and acetylcholine 2- and 10-fold, respectively. Charybdotoxin enhanced 2.5-fold the secretory response to electrical stimulation in 0.5 mM Ca2+, although this effect was not statistically significant. A synergistic interaction between the two toxins on catecholamine release induced by electrical stimulation was observed at low but not at high [Ca2+]o. 6. Simultaneous release of acetylcholine and catecholamines upon electrical stimulation was achieved in glands in which the endogenous acetylcholine stores in the splanchnic nerve terminals had been prelabelled by perfusion with [3H]choline. While apamin enhanced more than 2-fold the postsynaptic release of catecholamines, the presynaptic release of acetylcholine remained unaffected. 7. The results are compatible with the hypothesis that, under physiological conditions, Ca(2+)-activated SK channels present in chromaffin cells control the firing patterns of action potentials induced by the acetylcholine released from splanchnic nerves during stress.(ABSTRACT TRUNCATED AT 400 WORDS)

Pharmacological protection against the cytotoxicity induced by 6-hydroxydopamine and H2O2 in chromaffin cells.

We present in this report the characteristics of the damage induced by 6-hydroxydopamine and H2O2 on bovine chromaffin cells in primary culture. Cytotoxicity was quantified using catecholamine cell contents, lactate dehydrogenase (LDH) release, trypan blue exclusion and morphological appearance. An excellent correlation between these four parameters was found. The cytotoxic effects of 6-hydroxydopamine were Ca(2+)-independent. In spite of this, the Ca2+ channel antagonists R56865 (N-[1-(4-(fluorophenoxy)butyl)]-4-piperidinyl-N-methyl-2-benzo-thiazo lamine) lidoflazine exhibited marked cytoprotective effects against both 6-hydroxydopamine and H2O2. The selective dopamine uptake blocker, bupropion, increased the viability of 6-hydroxydopamine and H2O2-treated cells from 20% to around 80%. Catalase drastically protected against the cytotoxic effects of 6-hydroxydopamine and H2O2. In contrast, desferrioxamine gave better protection against H2O2 cytotoxicity; glutathione and N-acetylcysteine only afforded substantial protection against 6-hydroxydopamine. Three main conclusions emerge from this study. (1st) 6-Hydroxydopamine causes chromaffin cell damage via a mechanism probably related to the production of free radicals, but unrelated to Ca2+ ions. Cytoprotection afforded by R56865 and lidoflazine must be unrelated to their Ca2+ antagonist properties. This suggests a novel component in the cytoprotective mechanism of action of these drugs. (2nd) The strong cytoprotective effects of bupropion seem to be unrelated to its ability to block the plasmalemmal dopamine carrier. (3rd) Bovine adrenal chromaffin cells in primary cultures are a suitable model for adult neurons to study the basic mechanism of cell damage, and to screen new drugs with putative neuroprotective properties.

Endothelium-independent relaxation by 17-alpha-estradiol of pig coronary arteries.

We have studied the effects of 17-alpha-estradiol, a non-estrogenic steroid, on pig coronary arteries contracted by K+, Ca2+ or serotonin. Experiments were performed on helicoidal strips and rings of left circumflex coronary arteries from freshly slaughtered white pigs and on helicoidal strips of rat thoracic aorta. The strips and rings were suspended inside a water-jacketed muscle chamber in an oxygenated Krebs solution at 37 degrees C. From the initial K(+)-evoked contraction, 17-alpha-estradiol caused a relaxation with an IC50 (15 microM) which was in the range of the IC50s obtained for nitroglycerin (1.3 microM) and nicorandil (50 microM). Contractions evoked by Ca2+ were inhibited by 17-alpha-estradiol, but full blockade could not be achieved. Serotonin-evoked contractions were also blocked by 17-alpha-estradiol with an IC50 of 2.1 microM; 17-beta-estradiol also inhibited the serotonin-evoked contractions. In the presence of 100 microM of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester, the relaxing properties of 17-alpha-estradiol in pig coronary arteries and rat thoracic aorta were unaffected, suggesting that endothelial NO release was unrelated to these effects. 17-alpha-Estradiol also relaxed denuded pig coronary artery strips, suggesting that other endothelial-derived relaxing factors were not involved in its vascular effects. The results are compatible with the idea that 17-alpha-estradiol causes relaxation of coronary vessels by acting directly on the cell membrane of smooth muscle cells; these effects seem to be unrelated to the genomic physiological effects of estrogens.(ABSTRACT TRUNCATED AT 250 WORDS)