O2 modulates large-conductance Ca2+-dependent K+ channels of rat chemoreceptor cells by a membrane-restricted and CO-sensitive mechanism

Producción CientíficaHypoxic inhibition of large-conductance Ca2+-dependent K+ channels (maxiK) of rat carotid body type I cells is a well-established fact. However, the molecular mechanisms of such inhibition and the role of these channels in the process of hypoxic transduction remain unclear. We have examined the mechanisms of interaction of O2 with maxiK channels exploring the effect of hypoxia on maxiK currents recorded with the whole-cell and the inside-out configuration of the patch-clamp technique. Hypoxia inhibits channel activity both in whole-cell and in excised membrane patches. This effect is strongly voltage- and Ca2+-dependent, being maximal at low [Ca2+] and low membrane potential. The analysis of single-channel kinetics reveals a gating scheme comprising three open and five closed states. Hypoxia inhibits channel activity increasing the time the channel spends in the longest closed states, an effect that could be explained by a decrease in the Ca2+ sensitivity of those closed states. Reducing maxiK channels with dithiothreitol (DTT) increases channel open probability, whereas oxidizing the channels with 2,2′-dithiopyridine (DTDP) has the opposite effect. These results suggest that hypoxic inhibition is not related with a reduction of channel thiol groups. However, CO, a competitive inhibitor of O2 binding to hemoproteins, fully reverts hypoxic inhibition, both at the whole-cell and the single-channel level. We conclude that O2 interaction with maxiK channels does not require cytoplasmic mediators. Such interaction could be mediated by a membrane hemoprotein that, as an O2 sensor, would modulate channel activity.Dirección General de Investigación Científica y Técnica (grant PB97/0400

Fragmentation of carbohydrate anomeric alkoxy radicals: a new synthesis of chiral 1-halo-1-iodo alditols

10 pages, 3 tables, 2 schemes.-- PMID: 14673851 [PubMed].-- Supporting information (52-page PDF file) available at: http://www.wiley-vch.de/contents/jc_2111/2003/f5294_s.pdfTreatment of 1,2-fluorohydrins, 1,2-chlorohydrins, 1,2-bromohydrins, and 1,2-iodohydrins of the D-gluco, D-galacto, D-lacto, L-rhamno, D-allo, L-arabino, 3-deoxy-D-gluco, and 3,4-dideoxy-D-gluco families of carbohydrates with the (diacetoxyiodo)benzene/iodine system afforded 1-fluoro-1-iodo, 1-chloro-1-iodo, 1-bromo-1-iodo, and 1,1-diiodo alditols, respectively, in excellent yields. The reaction was achieved by radical fragmentation of the C1bond;C2 bond, triggered by the initially formed anomeric alkoxy radical, and subsequent trapping of the C2-radical by iodine atoms. This methodology is compatible with the stability of the protective groups most frequently used in carbohydrate chemistry. The potential utility of these 1-halo-1-iodo alditols as chiral synthons was evaluated by their transformation into alk-1-enyl iodides and in the Takai E-olefination reaction.This work was supported by the Investigation Programs nos. PPQ2000-0728, BQU2000-0650, and BQU2001-1665 of the Dirección General de Investigación Científica y Técnica, Spain. C.R.-F. thanks the Dirección General de Universidades e Investigación del Gobierno de Canarias for a fellowship

Viral gene transfer of dominant-negative Kv4 construct suppresses an O2-sensitive K+ current in chemoreceptor cells

Producción CientíficaHypoxia initiates the neurosecretory response of the carotid body (CB) by inhibiting one or more potassium channels in the chemoreceptor cells. Oxygen-sensitive K+ channels were first described in rabbit CB chemoreceptor cells, in which a transient outward K+ current was reported to be reversibly inhibited by hypoxia. Although progress has been made to characterize this current with electrophysiological and pharmacological tools, no attempts have been made to identify which Kv channel proteins are expressed in rabbit CB chemoreceptor cells and to determine + with adenoviruses that enabled ecdysone-inducible expression of the dominant-negative constructs and reporter genes in poly- cistronic vectors. In voltage-clamp experiments, we found that, whereas adenoviral infections of chemoreceptor cells with Kv1.xDN did not modify the O -sensitive K+ current, infections with Kv4.xDN suppressed the transient outward current in a time-dependent manner, significantly depolarized the cells, and abolished the depolarization induced by hypoxia. Our work dem- onstrate that genes of the Shal K+ channels underlie the tran- + their contribution to the native O2-sensitive K current. To probe sient outward, O2-sensitive, K current of rabbit CB chemore- the molecular identity of this current, we have used dominant- negative constructs to block the expression of functional Kv channels of the Shaker (Kv1.xDN) or the Shal (Kv4.xDN) subfam- ceptor cells and that this current contributes to the cell depolarization in response to low pO2. + ilies, because members of these two subfamilies contribute to Key words: O2-sensitive K current; viral gene transfer; the transient outward K+ currents in other preparations. Delivery of the constructs into chemoreceptor cells has been achieved2018-03-2

Influence of Pregnancy on Sexual Desire in Pregnant Women and Their Partners: Systematic Review

Objectives: Pregnancy is a stage in which different physical and psychological changes take place that can affect the sexuality of the couple. The aim of the study is to identify how the physical and psychological changes derived from pregnancy affect the sexual desire of women and men.Methods: A systematic review of the literature was carried out in five databases, from which a total of 16,126 documents were obtained. After applying the PRISMA selection criteria, a total of 19 documents were selected.Results: Levels of sexual desire fluctuate during pregnancy, being the second trimester of gestation the period in which desire is at its highest and in which physical limitations and emotional changes decrease. Women have lower levels of sexual desire in the first trimester, while men have the lowest levels of desire in the third trimester.Conclusion: Pregnancy is a stage marked by physiological and psychological changes that modify several areas, including sexuality. Healthcare professionals should promote a healthy sexuality, avoiding the appearance of fears or sexual dysfunctions caused by the changes that occur during pregnancy

ADHD symptomatology in eating disorders : a secondary psychopathological measure of severity?

Background: Attention-deficit/hyperactivity disorder (ADHD) has commonly been described in psychiatric disorders. Although several studies have found positive associations between abnormal eating patterns during childhood and ADHD, there is a lack of studies on ADHD and Eating Disorders (ED). The aims of this exploratory study were 1) to assess the ADHD symptoms level in ED and to ascertain whether there are differences among ED subtypes; 2) to analyze whether the presence of ADHD symptoms is associated with more severe eating disorder symptoms and greater general psychopathology; and 3) to assess whether the ADHD symptoms level is associated with specific temperament and character traits. Methods: 191 female ED patients were included. Assessment was carried out with the EDI-2, ASRS-v1.1, the SCL-90-R and the TCI-R. Results: The ADHD symptoms level was similar in bulimia, eating disorder not otherwise specified and binge eating subtypes, and lower in anorexic patients. Obsessiveness and Hostility were significantly positively associated with ADHD symptoms. A path model showed that ADHD was associated with high Novelty Seeking and low Self-Directedness, whereas ED severity was influenced by ADHD severity and low Self-Directedness. Conclusions: Bingeing/purging ED subtypes have a high ADHD symptoms level, also related with more severe eating, general and personality psychopathology

Explicit and implicit emotional expression in bulimia nervosa in the acute state and after recovery

Expression of emotional state is considered to be a core facet of an individual's emotional competence. Emotional processing in BN has not been often studied and has not been considered from a broad perspective. This study aimed at examining the implicit and explicit emotional expression in BN patients, in the acute state and after recovery. Sixty-three female participants were included: 22 BN, 22 recovered BN (R-BN), and 19 healthy controls (HC). The clinical cases were drawn from consecutive admissions and diagnosed according to DSM-IV-TR diagnostic criteria. Self reported (explicit) emotional expression was measured with State-Trait Anger Expression Inventory-2, State-Trait Anxiety Inventory, and Symptom Check List-90 items-Revised. Emotional facial expression (implicit) was recorded by means of an integrated camera (by detecting Facial Feature Tracking), during a 20 minutes therapeutic video game. In the acute illness explicit emotional expression [anxiety (p<0.001) and anger (p<0.05)] was increased. In the recovered group this was decreased to an intermediate level between the acute illness and healthy controls [anxiety (p<0.001) and anger (p<0.05)]. In the implicit measurement of emotional expression patients with acute BN expressed more joy (p<0.001) and less anger (p<0.001) than both healthy controls and those in the recovered group. These findings suggest that there are differences in the implicit and explicit emotional processing in BN, which is significantly reduced after recovery, suggesting an improvement in emotional regulation

Share prices under Tory and Labour governments in the UK since 1945

Given the recent political landscape of the UK with the Labour Party forming a government for the first time since 1979, it is hardly surprising that the performance of the stock market under Tory and Labour governments is a topic of media and general interest. The primary purpose of this paper is to analyse the movement of the UK stock market over the post-war period against the background of different political parties being in power. The evidence presented concerning short-term share price movements indicates that the stock market responds both to the findings of opinion polls in the run up to elections and to elections themselves. Furthermore, the results from elections (inclusive of 'surprise' elections) indicate that there is a clear preference for a Tory government. In terms of share price movements across the period of a government's office, however, there is no statistically significant evidence (at commonly accepted confidence levels) to suggest that the stock market has performed better in either nominal or real terms under Tory government. In addition, via a simple comparison of share prices for the first and second halves of political terms of office, there is no evidence that either party is able to manipulate the economy and/or the market for election purposes. Given that longer-term share price movements do not support the short-term share price movements around elections, a number of key economic variables are examined. These indicate that Tory governments are not associated with superior performance in either real increases in GDP or company profits but that they have seen statistically significant lower levels of average inflation and higher average levels of real interest rates. As for share prices the paper considers whether the economic variables differ between the first and second halves of political terms of office; the results do not provide support for the management of economic variables for election purposes. Such a conclusion is supported by a more detailed analysis of GDP across political terms of office.

Fragmentation of carbohydrate anomeric alkoxy radicals: A new synthesis of chiral 1-halo-1-iodo compounds

The reaction of 1,2-halohydrins derived from easily available carbohydrates with (diacetoxyiodo)benzene (DIB) in the presence of bromine is a mild procedure for the synthesis of 1-deoxy-1-halo-1-bromo-alditols with one carbon less than the original carbohydrate. The reaction goes through β-fragmentation of the intermediate anomeric alkoxyl radicals. These 1-halo-1-bromo polyhydroxy compounds may be valuable synthetic intermediates in organic synthesis