Flavonoids in hypertension: a brief review of the underlying mechanisms

Different pathways implicated in the effects of flavonoids on blood pressure regulation.

1. Download : Download high-res image (112KB)
2. Download : Download full-size image

     

海洛因成瘾者的情绪障碍及其可能的神经生物学机制

药物成瘾已经成为当前世界上最严重的公共卫生问题之一,其成瘾过程是由偶尔的用药过渡到强迫性用药的过程,一般表现为用药后的欣快状态、撤药后的戒断症状、对药物的强烈渴求以及不可控制的觅药行为[1].海洛因的成瘾性很强,脱毒后复吸率高[2].无论是用药后的欣快状态还是撤药后的戒断症状,海洛因成瘾者都普遍伴随着情绪异常问题,尤其是戒断后的负性情绪反应,对复吸有很大的影响.本文综述了海洛因成瘾者情绪状态和情绪加工的行为异常、脑功能和结构异常及与情绪相关的神经内分泌异常.     

Teratogenicity and underlying mechanisms of homocysteine in animal models: A review

BackgroundHyperhomocysteinemia in humans is a risk factor for adverse pregnancy outcome, especially congenital malformations. This review summarizes the studies directed on the teratogenicity of homocysteine carried out in animal studies, and elaborates on the underlying mechanisms.MethodsLiterature was searched in Pubmed (NCBI) through January 2010 and selected manually. Keywords comprised homocysteine, congenital abnormalities and animals.ResultsIncreased frequencies of a wide range of congenital malformations are reported especially in the chicken embryo after exposure to homocysteine (Hcy) in various dosages and forms. Reduced embryonic growth and abnormalities of the vascularization of the yolk sac are described in mouse studies. A study in rats revealed a reduced development of blastocysts. The congenital malformations observed in the chicken embryo model share the mutual involvement of Hcy sensitive neural crest cells. Derangements in the behavior of these cells by interactions between Hcy and pathways involved in vascularization, growth, metabolism, signaling, and DNA synthesis and methylation may explain the wide range of effects on embryonic organs, the yolk sac and placental tissues.ConclusionsThe associations between human hyperhomocysteinemia and congenital malformations are substantiated by chicken and rodent studies. Moreover, derangements of several pathways induced by Hcy are demonstrated with adverse effects on both reproduction and long term health. Because of the high prevalence of hyperhomocysteinemia in both the reproductive and general population, research on underlying epigenetic mechanisms is warranted.     

Energy intake and energy expenditure during the menstrual cycle in short-term smoking cessation

The effect of short-term smoking abstinence on energy intake and expenditure parameters was investigated for women in different phases of the menstrual cycle (follicular or late luteal) in a rigorous inpatient laboratory setting. Twenty-one participants were randomized to a continued smoking (n = 5) or a smoking abstinence (n = 16) group and admitted for 2 7-day inpatient periods during alternate cycle phases. The smoking abstinence group experienced 2 days of baseline smoking and 5 days of smoking abstinence. Measurements included caloric intake (kcal/24 hours), energy expenditure (by indirect calorimetry), and weight. Results of within-subject analyses indicated no smoking abstinence effect on mean daily total kilocalorie intake, sweet kilocalorie intake, or resting metabolic rate. However, a significant cycle phase effect was observed, with increased kilocalorie intake and expenditure-as well as minor weight gain-occurring during the late luteal phase when premenstrual symptoms are highest. In light of this phase effect, women smokers might benefit by attempting to quit smoking during the follicular phase of their cycle.     

The neurochemical mechanisms underlying possible recurrences of alcoholism]

Experiments on chronic alcoholized rats revealed the similar changes in brain dopamine receptors, in brain and blood catecholamines as well as in blood cyclic adenosine monophosphate during both short- and long-term alcohol deprivation. It is concluded that such changes may form material basis for alcoholism relapses.     

Oligoclonal antibody targeting ghrelin increases energy expenditure and reduces food intake in fasted mice

Ghrelin, an enteric peptide hormone linked to the pathophysiology of obesity has been a therapeutic target of great interest over the past decade. Many research efforts have focused on the antagonism of ghrelin's endogenous receptor GHSR1a, which is found along ascending vagal afferent fibers, as well as in the arcuate nucleus of the hypothalamus. Additionally, peptidic inhibitors of ghrelin O-acyltransferase, the enzyme responsible for the paracrine activation of ghrelin, have recently been studied. Our research has taken an alternative immunological approach, studying both active and passive vaccination as a means to sequester ghrelin in the periphery, with the original discovery in rat of decreased feed efficiency and adiposity, as well as increased metabolic activity. Using our previous hapten designs as a stepping-stone, three monoclonal antibodies (JG2, JG3, and JG4) were procured against ghrelin and tested in vivo. While mAb JG4 had the highest affinity for ghrelin, it failed to attenuate the orexigenic effects of food deprivation on energy metabolism or food intake in mice. However, animals that were administered a combination of JG3:JG4 (termed a doublet) or JG2:JG3:JG4 (termed a triplet) demonstrated higher heat dispersion and rate of respiration (higher CO(2) emission and O(2) consumption) during a 24 h fast refeed. Mice administered the triplet cocktail of JG2:JG3:JG4 also demonstrated decreased food intake upon refeeding as compared to control animals. Recently, Lu and colleagues reported that a passive approach using a single, high affinity N-terminally directed monoclonal antibody did not abrogate the effects of endogenous ghrelin. Our current report corroborates this finding, yet, refutes that a monoclonal antibody approach cannot be efficacious. Rather, we find that a multiple monoclonal antibody (oligoclonal) approach can reproduce the underlying logic to previously reported efficacies using active vaccinations.     

Animal models to explore the effects of CNS drugs on food intake and energy expenditure

Obesity has reached epidemic proportions globally with an increasing incidence not just in Western cultures but also Mexico, Brazil, China and parts of Africa. In terms of pharmacological intervention, the track record of drug treatments for obesity is poor, especially in the case of centrally acting medicines, and there remains an unmet need for the development of safer compounds delivering superior efficacy. Animal models are of importance not only in detecting changes in food intake, energy expenditure and body weight but also providing confidence that these changes are behaviourally specific and not a result of drug-induced side effects. We review animal models of feeding behaviour that are used to aid our understanding of the control of body weight and energy regulation with special reference to CNS-acting drugs. The use of such models in the discovery of new drugs for the treatment of obesity is given particular emphasis. This article is part of a Special Issue entitled 'Central Control of Food Intake'.     

Exercise in a pill: feasibility of energy expenditure targets

The possibility of developing a pill to increase energy expenditure is explored by examining the metabolic processes involved. Such a pill should be targeted at organ systems involved in facultative thermogenesis. In rodents, these are brown adipose tissue (BAT) and skeletal muscle. Since BAT-mediated thermogenesis is not available in adult humans, emphasis here is on skeletal muscle. A hypothesis is presented based on three known facts: (1) plasticity of skeletal muscle, with interconversion of fiber types that differ in their fuel efficiency; (2) presence of thyroxine 5'-deiodinase type 2 (TD2) in human skeletal muscle; (3) gradual increase in thermogenesis that occurs during rehabilitation after starvation, probably in muscle. A low capacity thermogenic system, muscle efficiency thermogenesis (MET), is proposed to occur as adipose stores refill during the transition from famine to feasting to obesity. This system involves increased activity of TD2 and a T3-induced increase in proportion of type II fibers, less efficient at rest and during activity. The protective effect of this system is probably overwhelmed by long-term eating in excess of energy needs. Better understanding of the complex remodeling of differentiated muscle fibers in the conversions proposed and of the regulation of TD2 activity in human skeletal muscle may reveal targets for increasing energy expenditure in humans. In addition, the possibility of exploiting the plasticity of the adipose organ, with conversion of white adipocytes in white adipose tissue to atypical brown adipocytes and increasing thermogenesis in them is considered as another potential target for increasing energy expenditure in humans.     

Receptor mechanisms underlying the actions of substance P and related neuropeptides]

The excitability of peripheral and central neurons is regulated by two types of ion channels, voltage- and ligand-operated ones. Recent studies have revealed that the activities of these ion channels are under the control of a variety of classical neurotransmitters and neuropeptides. In particular, certain ion channels such as voltage-dependent Ca and K channels are reciprocally regulated by excitatory and inhibitory neurotransmitters, leading to the excitation and inhibition of nerve cells: for example, 1) the activation of voltage-dependent K channel is facilitated by somatostatin and inhibited by substance P, and 2) the opening of voltage-gated Ca channel is augmented by substance P and suppressed by somatostatin and certain opioid peptides. The ligand-gated ion channel, nicotinic acetylcholine receptor is also controlled by the actions of neuropeptides, substance P and calcitonin gene related peptide (CGRP). The regulation of ion channels with neuropeptides may contribute not only to the control of neuronal excitability but also to the plasticity of the nervous system.     

Psychiatric disorders in Ecstasy (MDMA) users: a literature review focusing on personal predisposition and drug history

3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) has been implicated in the onset of a number of psychological disorders and associated with a number of psychiatric symptoms that have persisted after cessation of the drug. This paper is a review of the published psychiatric case studies from the last 10 years involving MDMA. Only 24% of patients had a previous psychiatric history and 34% had a psychiatric illness amongst first degree relatives. The percentage of patients not having had a personal or family history of psychiatric illness and the temporal relationship between MDMA ingestion and the experience of recurring symptoms strongly suggest a causal relationship between the drug and neuropsychiatric manifestations. Further supporting evidence comes from several studies using non-clinical samples. Ecstasy users that don't present themselves in healthcare settings as having clinical symptoms have significantly higher scores on certain subscales of the SCL-90 compared with Ecstasy-naive controls, with higher pathology scores in heavier Ecstasy users. The full-blown psychiatric cases may represent the broad end of this problematic spectrum. Copyright 2001 John Wiley & Sons, Ltd.     

纳米材料诱导细胞自噬的机制和生物学效应

自噬是一种复杂的代谢途径,通过溶酶体降解细胞内过剩的或多余的细胞质组分.另外,自噬是细胞自身调节维持稳态平衡的重要过程,也是细胞的一种防御和应激调控机制.越来越多的研究表明,纳米材料作为机体的外源物质,被生物体摄取后,作为机体对外来物质或有毒物质的一种防御保护反应,会诱导细胞发生自噬.纳米材料引起的自噬具有两面性,一方面可增强机体的自噬清除能力,另一方面也可能引起细胞程序性死亡.这篇综述介绍了机体自然发生的和工程纳米材料诱导自噬发生的机制,全面分析了纳米材料对溶酶体-自噬系统的影响及其生物学效应.     

Obesity,cardiovascular disease,and role of vitamin C on inflammation: a review of facts and underlying mechanisms

Obesity means the accumulation of excessive fat that may interfere with the maintenance of optimal state of health. Obesity causes cardiac and vascular disease through well-known mediators such as hypertension, type-2 diabetes mellitus, and dyslipidemia, but there are evidences for other mediators such as chronic inflammation, oxidative stress, and thrombosis. The decreased levels of antioxidants factors and nitric oxide predispose to further cardiovascular adverse events. To reduce the risks, antioxidants can help by neutralizing the free radicals and protecting from damage by donating electrons. Having the capacity, vitamin C protects from oxidative stress, prevention of non-enzymatic glycosylation of proteins, and enhances arterial dilation through its effect on nitric oxide release. It also decreases lipid peroxidation, and alleviates inflammation. The anti-inflammatory property of vitamin C could be attributed to ability to modulate the NF-_kB DNA binding activity and down-regulation in the hepatic mRNA expression for the interleukins and tumor factors.     

Central interleukin-10 attenuates lipopolysaccharide-induced changes in food intake,energy expenditure and hypothalamic Fos expression

Lipopolysaccharide (LPS) is often used to mimic acute infection and induces hypophagia, the selective partitioning of fat for energy, and fever. Interleukin-10 (IL-10) is an anti-inflammatory cytokine expressed in the brain which attenuates LPS-induced hypophagia; however the potential sites of interaction within the brain have not been investigated. Hypothalamic orexin (ORX) and melanin-concentrating hormone (MCH) regulate energy expenditure and food intake although the regulation of these neuropeptides through the interactions between central IL-10 and the inflammatory consequences of peripheral LPS have not been investigated. The present study in the rat investigated during the dark phase of the light–dark cycle the ability of central IL-10 (250 ng, i.c.v.) to attenuate the changes in food intake, energy substrate partitioning, and central Fos expression within the hypothalamus to peripheral LPS (100 μg/kg, i.p.); Fos expression changes specifically within ORX and MCH neurons were also investigated. Central IL-10 attenuated the peripheral LPS-induced hypophagia, reduction in motor activity, fever and reduction in respiratory exchange ratio. Central IL-10 also attenuated peripheral LPS-induced increases in Fos expression within ORX neurons and decreases in Fos expression within unidentified cells of the caudal arcuate nucleus. In contrast, both IL-10 and LPS injection independently decreased Fos expression within MCH neurons. The present study provides further insight into the interactions within the brain between the anti-inflammatory cytokine IL-10, the inflammatory consequences of LPS, and neuropeptides known to regulate energy expenditure and food intake.     

Treating obesity: pharmacology of energy expenditure

The pharmacological treatment options for obesity are currently very limited but the prevalence of the disease is increasing rapidly. Obesity has many serious sequelae, the most common of which is type-2-diabetes. The benefits of weight loss on health are established but the major impediment to weight loss treatments is maintenance of weight lost over the long term. The reduced- or post-obese individual undergoes physiological changes that are geared towards energy storage and weight regain. One of the physiological changes is a reduced capacity to oxidise fatty acids pushing them through pathways of triacylglycerol synthesis. In this review, some of the past drug treatments aimed at increasing energy expenditure, such as dinitrophenol and ephedrine. are discussed. Current, or nearly current therapies such as sibutramine and rimonabant are also discussed in the context of increased energy expenditure. The main part of the review focuses on future prospects with discussion around a selection of targets with potential in energy expenditure that lie in pathways with AMP-kinase at their centre and ending at the mitochondrion.     

The effect and underlying mechanisms of titanium dioxide nanoparticles on glucose homeostasis: A literature review

Titanium dioxide (TiO₂) is used extensively as a white pigment in the food industry, personal care, and a variety of products of everyday use. Although TiO₂ has been categorized as a bioinert material, recent evidence has demonstrated different toxicity profiles of TiO₂ nanoparticles (NPs) and a potential health risk to humans. Studies indicated that titanium dioxide enters the systemic circulation and accumulates in the lungs, liver, kidneys, spleen, heart, and central nervous system and may cause oxidative stress and tissue damage in these vital organs. Recently, some studies have raised concerns about the possible detrimental effects of TiO₂ NPs on glucose homeostasis. However, the findings should be interpreted with caution due to the methodological issues. This article aims to evaluate current evidence regarding the effects of TiO₂ NPs on glucose homeostasis, including possible underlying mechanisms. Furthermore, the limitations of current studies are discussed, which may provide a comprehensive understanding and new perspectives for future studies in this field.     

Distinct neural mechanisms underlying acute and repeated administration of antipsychotic drugs in rat avoidance conditioning

Rationale  

Acute antipsychotic treatment disrupts conditioned avoidance responding, and repeated treatment induces a sensitization- or tolerance-like effect. However, the neurochemical mechanisms underlying both acute and repeated antipsychotic effects remain to be determined.