Histone deacetylases (HDACs) as therapeutic target for depressive disorders

Major depressive disorder (MDD) represents approximately 40% of the disability caused by mental illnesses globally. The poorly understood pathophysiology and limited efficiency of pharmacological treatment (based primarily on the principles of the monoaminergic hypothesis) make depression a serious medical, public and socio-economical problem. An increasing number of studies suggest that epigenetic modifications (alterations in gene expression that are not due to changes in DNA sequence) in certain brain regions and neural circuits represent a key mechanism through which environmental factors interact with individual's genetic constitution to affect risk of mental disorders. Accordingly, chromatin-based epigenetic regulation seems to be a promising direction for the development of new, more effective antidepressant drugs. Recently, several inhibitors of histone deacetylases (HDAC) have been extensively studied in the context of antidepressant action. So far, none of them has been used to treat depression in humans due to the low selectivity for specific HDAC isoforms, and consequently, a risk of serious adverse events. In this review, we focus on the HDAC inhibitors (HDACi) with the greatest antidepressant efficacy and their activity in the preclinical studies. Moreover, we discuss their potential therapeutic usefulness in depression and the main limitations.     

How to measure heart rate?

Objective Heart rate has been shown to predict cardiovascular morbidity and mortality in a very reliable and easily accessible manner. The exact definition of the conditions under which heart rate is measured appears to be as crucial as the determinations of blood pressure or plasma catecholamines. It was investigated how accurately heart rate measurements were performed, and conditions were described in 56 studies identified from prominent journals within the Medline database: (a) search phrases were heart rate and rest or resting; (b) publication date was from 1996 to 2001; and (c) publication type was clinical trial.Methods Five conditions were considered as most influential: (a) resting period before measurement; (b) posture of the patient; (c) environmental conditions such as temperature or visual and acoustic stimuli; (d) method used to record heart rate; and (e) data analysis, i.e., derivation from raw data. An average of only 1.7 of those 5 criteria for the determination of heart rate were met in the studies included. Information on conditions of, for example, resting period, or environmental conditions is almost completely lacking.Results and conclusion The data show that a very important risk predictor and treatment target—heart rate—is not reported in a scientifically sufficient manner, even in large trials. Valuable information is lost despite the fact that the investment of adequately defining, controlling, and performing this determination is modest in comparison to the potential gain. It is recommended to standardize heart rate measurements in analogy to that of blood pressure determinations.The experiments comply with the current laws of the country in which they were performed, inclusive of ethics approval.     

Taxodione and Extracts from Salvia austriaca Roots as Human Cholinesterase Inhibitors

Taxodione, an abietane diterpenoid, was isolated from Salvia austriaca transformed roots grown in in vitro conditions. The compound is known to have antibacterial, cytotoxic and anti‐tumour properties. This study evaluates the ability of pure taxodione and extracts obtained from the S. austriaca hairy roots and roots from field‐grown plants to inhibit human acetylcholinesterase and butyrylcholinesterase. Both extracts were found to have similar actions against acetylcholinesterase. The IC₅₀ for extracts from transformed and untransformed roots were 142.5 and 139.5 µg ml^?1, respectively. The highest activity towards human acetylcholinesterase was demonstrated by taxodione (IC₅₀ = 54.84 µg ml^?1). With respect to BChE inhibition, the root extracts demonstrated stronger activity (IC₅₀ = 23.6 µg ml^?1: field‐grown plants and 41.6 µg ml^?1: transformed roots) than taxodione (IC₅₀ = 195.9 µg ml^?1). Taxodione showed significant cytotoxicity against A549 cell line (IC₅₀ = 9.1 µg ml^?1), whereas the activities for the extracts from S. austriaca roots of field‐grown plants (IC₅₀ = 75.7 µg ml^?1) and hairy roots (IC₅₀ = 86.2 µg ml^?1) were lower. Computer modelling suggests that taxodione should not demonstrate cardiotoxic or genotoxic activity. It also indicates that taxodione should demonstrate very rapid transport from the body with very good blood–brain barrier penetration, but with no cumulative effect on the human body. The obtained results indicate that taxodione is a safe compound and may be used for further investigations in pharmacological activities. Copyright © 2015 John Wiley & Sons, Ltd.     

3种含酚羟基化合物对蘑菇酪氨酸酶活性影响及动力学研究

选取3种具有酚羟基的芳香类化合物,测定其对酪氨酸酶的活性影响。结果表明,1,5-二羟基萘在120~600 μmol·L-1范围内对酪氨酸酶的激活活性＞450%,最高为537%;2,2′-联苯酚的激活活性最大为284%;2,2′-联吡啶-3,3′二醇无激活活性。动力学研究表明,1,5-二羟基萘表现为非竞争性激活;2,2′-联苯酚为混合性激活作用,在酶促反应体系中,既影响底物与酶的结合,又改变酶的空间构型,综合提高反应速度。     

The components of self-rated health among adults in Ouagadougou,Burkina Faso

Background

Although the relationship between self-rated health (SRH) and physical and mental health is well documented in developed countries, very few studies have analyzed this association in the developing world, particularly in Africa. In this study, we examine the associations of SRH with measures of physical and mental health (chronic diseases, functional limitations, and depression) among adults in Ouagadougou, Burkina Faso, and how these associations vary by sex, age, and education level.

Methods

This study was based on 2195 individuals aged 15 years or older who participated in a cross-sectional interviewer-administered health survey conducted in 2010 in areas of the Ouagadougou Health and Demographic Surveillance System. Logistic regression models were used to analyze the associations of poor SRH with chronic diseases, functional limitations, and depression, first in the whole sample and then stratified by sex, age, and education level.

Results

Poor SRH was strongly correlated with chronic diseases and functional limitations, but not with depression, suggesting that in this context, physical health probably makes up most of people’s perceptions of their health status. The effect of functional limitations on poor SRH increased with age, probably because the ability to circumvent or compensate for a disability diminishes with age. The effect of functional limitations was also stronger among the least educated, probably because physical integrity is more important for people who depend on it for their livelihood. In contrast, the effect of chronic diseases appeared to decrease with age. No variation by sex was observed in the associations of SRH with chronic diseases, functional limitations, or depression.

Conclusions

Our findings suggest that different subpopulations delineated by age and education level weight the components of health differently in their self-rated health in Ouagadougou, Burkina Faso. In-depth studies are needed to understand why and how these groups do so.

     

Zinc as a marker of affective disorders

Depression is considered as a chronic and recurring illness with functional impairment, significant disability, morbidity and mortality. Despite the extensive research carried out on depression, its pathophysiology is still poorly understood. An important problem concerning research into depressive disorder is the lack of biological markers which could improve diagnosis or indicate a risk of developing depression or risk of relapse. Several reports indicated decreased zinc concentrations and even its deficit in clinical depression, so the measurement of the concentration of this element in the blood of patients was suggested as a useful and specific clinical marker of depression. The reported results indicated that the serum zinc level might be a marker of depression as a state (state marker) in treatment responsive patients. However, in drug-resistant depression a decreased concentration of zinc may be a marker of traits (trait marker). It seems, however, that the measurement of the concentrations of zinc might be in the future a component of the battery of tests; of markers of immune activation and oxidative stress rather than itself alone.     

Trusting patients, trusting nurses

Abstract  The general expectation that patients should be willing to trust nurses is rarely explored or challenged despite claims of diminishing public trust in social and professional institutions. Everyday meanings of trust take account of circumstance and suggest that our understanding of what it means to trust is contextually bound. However, in the context of health care, to trust implies a particular understanding which becomes apparent when abuses of this trust are reported and acknowledged as scandals. The predominant assumption in the literature that trust is something that occurs between equally competent adults cannot explain trust in nursing precisely because of the unequal power relationships between patients on the one hand and healthcare professionals on the other. Moreover, the tendency to conflate terms such as trust, reliance, confidence and so on suggests that confusion permeates discussions of trust in nursing. In this paper, I argue in support of Annette Baier's requirement of good will (or lack of ill will) as the essential feature of trust, and outline how this account (i) enables us to make the necessary distinctions between trust on the one hand and 'trust pretenders' on the other; and (ii) lays the foundations for understanding trust in relationships, such as those between patients and nurses, where power differentials exist.     

Regional differences in the coupling of 5-hydroxytryptamine-1A receptors to G proteins in the rat brain

Numerous data showed that 5-hydroxytryptamine-1A (5-HT1A) receptors couple to Galpha(o)/alpha(i) proteins for signal transduction. However, the alpha subunit isoforms really involved in 5-HT1A receptor coupling in brain remain to be identified. Moreover, regional differences in the functional characteristics of brain 5-HT1A receptors have been evidenced repeatedly. Because such differences could be due to variations in G proteins interacting with the same receptor, relevant approaches were used for identifying alpha subunits physically coupled to 5-HT1A receptors in different regions of the rat brain. Using immunoaffinity chromatography coupled to Western blot detection, 5-HT1A receptors were found to interact equally with Galpha(o) and Galpha(i3) in the cerebral cortex, mainly with Galpha(o) and weakly with Galpha(i3) in the hippocampus and exclusively with Galpha(i3) in the anterior raphe area. In the hypothalamus, 5-HT(1A) receptors seemed to be coupled to the latter two G proteins plus Galpha(i1) and Galpha(z). Complementary experiments based on an antibody capture technique coupled to both classic radioactivity and scintillation proximity assay detections showed that hippocampal 5-HT1A receptor stimulation induced 5'-O-(3-[35S]thio)triphosphate binding to immunoprecipitates with Galpha(i3) and Galpha(o) antisera. In the anterior raphe, such 5-HT1A receptor-mediated effect was obtained with Galpha(i3) antiserum only. These results demonstrated the existence of regional differences in the coupling of 5-HT1A receptors to G proteins in the rat brain. In the anterior raphe, 5-HT1A receptors seem to interact specifically with Galpha(i3), whereas in the hippocampus, they are mainly coupled to Galpha(o) proteins. Such a disparity in G-protein coupling might explain regional differences in adaptive regulations of brain 5-HT1A receptors.     

Contraceptive methods used by young women in the township of Lomé (Togo)

Despite intensive development of reproductive health services among Togolese youth over the past ten years, contraceptive prevalence remains low, particularly among young women. To help understand the reasons for the low rate of use of reproductive health services by young women (adolescents and young adults) and to assess prevalence of their contraceptive use in Lomé. In a cross-sectional study in the five precincts of Lomé township from March 08, 1999, to April 17, 1999, approximately 500 adolescent girls and young women (aged 10-24 years) were interviewed according to a semi-structured questionnaire. The variables studied were: social and demographic characteristics; knowledge about family planning, including whether they had discussed sexual issues with their parents; conditions of contraceptive use (method used by the interviewee or her sexual partner, who made the decision, geographical and financial accessibility of the method); suggestions to improve contraceptive prevalence. Data were analysed with Epi-Info 6.3 and comparisons tested with the chi-square test (significance set at 5%). 63.6% (318 of 500) of the young women and female teenagers lived with a partner; 43.4% discussed some aspects of reproductive health with their parents, especially menstruation and STDs, including AIDS. Although 93.4% of the interviewees knew about condoms and 68.2% about the calendar (rhythm) method, few of them used these (respectively 33.6% and 31.8%). The interviewees decided about contraceptive use with their partners (37%) or alone (28%), and rarely asked their parents (1%). Contraceptives were obtained at a health facility by 3.8% of the subjects, and at the drugstore or market by 20.6%. The main reason for the low rates of use of health facilities (10.4%) and of medical contraceptive methods (11.2% of all contraceptive methods used) were: lack of means, information, and interest (in such facilities and methods), and finally, lack of sexual activity. The condom was essentially the only modern contraceptive method used. The main reason for the low rate of use of reproductive health services may be that apart from the condom, women and female teenagers rarely use modern contraceptive methods. Improving information about reproductive health, creating more "young friendly clinics", and developing peer educators might improve the contraceptive prevalence rate among young women in Togo.     

青海省1996～1999年脊髓灰质炎病毒学监测

目的：掌握消灭脊灰工作进展情况和不同人群中脊灰野病毒和消亡状态，为制定有效免疫策略提供依据。方法：在1996－1999年所有AFP病例和AFP病例密切接触，重点地区5岁以下健康儿童中，采集粪便标本776份检测脊灰病毒，应用2种以上敏感传代细胞培养，用基因序列分析方法判断病毒型别。结果：共检测脊灰病毒24株，非脊灰肠道病毒81株，分离率分别为3．09％与13．53％，经国家脊灰实验室和美国CDC最终鉴定：脊灰野病毒Ⅰ型2株，与印度1998年Ⅰ型野病毒符合率＞98％，判定由印度传入野病毒，其它脊灰病毒均为疫苗病毒。结论：1994年以来全省无本土脊灰野病毒流行，各项监测指标达到和接近国家要求，主实我省已阻断本土脊灰野病毒传播，达到无脊灰标准。传入野病毒的及时发现，反映出AFP病例监测系统敏感性和及时性较高，但该病例的发生提示局部地区存在着脊灰疫苗免疫空白或低接种率水平。