Chemical Constituents of Euphorbia ebracteolata

Aim To study the chemical constituents of Euphorb/a ebracteolata Hayata. Methods Column chromatography was used in the isolation procedure, while the structures of isolated compounds were elucidated by spectral data. Results Six compounds were isolated and their structures were identified as baccatin (1), 3-acetyl-β-amyrin (2), 3,3‘-diacetyl-4,4‘-dim-ethoxy- 2,2‘, 6,6‘-tetrah ydroxy diphenylmethane (3), 2,4- dihydroxy-6-methoxy-3-methyl acetophenone (4), β-sitosterol（5), and daucosterol (6). Conclusion Baccatin was obtained from Euphorbia ebracteolata for the first time.     

Chemical Constituents of Stellera chamaejasme

从瑞香狼毒（ＳｔｅｌｅｒａｃｈａｍａｅｊａｓｍｅＬ）的根中得到１２个化合物。经理化鉴别和光谱分析推定晶（８）为７甲氧基西瑞香素（７ｍｅｔｈｏｘｙｄａｐｈｎｏｒｅｔｉｎ）是新化合物，命名为异西瑞香素（ｉｓｏｄａｐｈｎｏｒｅｔｉｎ），晶（７）为西瑞香素（ｄａｐｈｎｏｒｅｔｉｎ），晶（２）为伞形花内酯（ｕｍｂｅｌｉｆｅｒｏｎｅ），晶（５）为胡萝卜甙，晶（３）为β谷甾醇，晶２，５和８是首次从该植物中分得。     

Lifibrol: first member of a new class of lipid-lowering drugs?

Management of dyslipoproteinaemia is one of the key strategies in the prevention of cardiovascular disease. The major target of hypolipidaemic drugs is the reduction of low density lipoprotein (LDL) cholesterol. Lifibrol, a novel lipid-lowering agent, is highly potent in reducing total cholesterol, LDL cholesterol, and apolipoprotein B. Its efficacy in lowering serum triglycerides, lipoprotein(a) and fibrinogen implies additional benefit in the prophylaxis and treatment of coronary heart disease. Thus, lifibrol appears to be a multivalent anti-atherosclerotic agent. The hypolipidaemic properties of lifibrol have been examined in several clinical trials and in various animal models. The mode of action of lifibrol involves at least three mechanisms: lifibrol enhances LDL catabolism by sterol-independent stimulation of LDL receptor activity, reduces cholesterol absorption from the intestine, and slightly decreases hepatic cholesterol biosynthesis. Lifibrol's lipid-lowering profile and putative mode of action clearly distinguish it from other classes of hypolipidaemic drugs, such as HMG-CoA reductase inhibitors or fibric acid derivatives. Thus, lifibrol may represent a new class of agents affecting lipid metabolism.     

Kynurenic acid: a new effector of valproate action?

We investigated the changes in hippocampal kynurenic acid (KYNA) concentrations and the amino acids involved in neuronal activity regulation following valproate (VPA) administration (400 mg/kg ip) in pentylenetetrazole-kindled rats (in vivo). We found a remarkably long-lasting increase in KYNA levels following VPA administration, and this effect correlated with a rise in GABA levels. No changes in the concentration of other analyzed amino acids were present. It is likely that the antiepileptic and neuroprotective properties of VPA may also be a consequence of an increase in the hippocampal KYNA concentration.     

The palmitoylethanolamide family: a new class of anti-inflammatory agents?

The discovery of anandamide as an endogenous ligand for the cannabinoid receptors has led to a resurgence of interest in the fatty acid amides. However, N-palmitoylethanolamine (PEA), a shorter and fully saturated analogue of anandamide, has been known since the fifties. This endogenous compound is a member of the N-acylethanolamines, found in most mammalian tissues. PEA is accumulated during inflammation and has been demonstrated to have a number of anti-inflammatory effects, including beneficial effects in clinically relevant animal models of inflammatory pain. It is now engaged in phase II clinical development, and two studies regarding the treatment of chronic lumbosciatalgia and multiple sclerosis are in progress. However, its precise mechanism of action remains debated. In the present review, the biochemical and pharmacological properties of PEA are discussed, in particular with respect to its analgesic and anti-inflammatory properties.     

Darusentan: a new perspective for treatment of resistant hypertension?

Despite multi-drug therapy, hypertension remains uncontrolled in a significant amount of patients, especially those with multiple cardiovascular risk factors. Endothelin-1 is a long lasting and very potent vasoconstrictor and plays a key role in cardiovascular hemostasis. Endothelin mediates its biological activity in humans through the endothelin A and B receptors. The selective endothelin--A receptor antagonist darusentan may be a new treatment option in patients with resistant hypertension. The objectives were that the clinical experience and the evidence for therapy with darusentan in resistant systemic hypertension were reviewed. The methods by the authors were that the leading journals which publish basic science and clinical research in the area of cardiovascular diseases and PubMed were scanned. In conclusion, early clinical results from Phase II studies suggest that darusentan may find a place in the treatment of resistant hypertension.     

Chemical Constituents of Illicium difengpi Bark

从中药地枫皮（ＩｌｉｃｉｕｍｄｉｆｅｎｇｐｉＫＩＢｅｔＫＩＭ）中分离出３个化合物，经理化常数和波谱数据解析，分别鉴定为地枫皮素（１），厚朴酚（２）和β谷甾醇（３）。化合物１为一新化合物，其化学结构为４ａｌｙｌ２，６ｄｉｍｅｔｈｏｘｙｐｈｅｎｏｌｃｉｎｎａｍａｔｅ，命名为地枫皮素（ｄｉｆｅｎｇｐｉｎ）。     

Duration of treatment of deep vein thrombosis: time for a new approach?

The American College of Chest Physicians Consensus Conference on Antithrombotic Therapy recommends that patients with initial idiopathic deep vein thrombosis (DVT) receive treatment for at least 6-12 months. However, controversy exists as to what treatment duration and intensity are optimal. Some investigators have suggested that it may be feasible to identify patients who are at low risk and those who are at high risk of recurrent venous thromboembolism. If patients can be stratified according to risk, then it might be safe and effective to withdraw oral anticoagulation therapy in those at low risk of recurrence and continue the therapy in those at high risk. Parameters that have been used to attempt to stratify patients with idiopathic DVT according to risk are D-dimer levels, resolution of thrombosis on ultrasound, and sex.     

Chemical Constituents of the Roots of Oplopanax elatus Nakai

Nine compounds were isolated from the extract of the roots of Oplopanax elatus Nakai(Echinopanax elatus Nakai),family Araliaceae.The chemical structures of six compounds wereestablished by measuring chemical and physical constants,spectral data(IR,EI-MS,FD-MS,~1HNMR and ~(13)CNMR)and chemical methods,as 1-heptacosanol,β-sitosterol,daucosterol,     

Beyond a ‘post-cure’ world: Sketches for a new futurology of hepatitis C

Australia's recent investment in, and optimism about, direct-acting antivirals to treat hepatitis C brings with it the promise of new drug futures, including the possibility of a post-hepatitis C world and a revolution in the lives of people affected by the disease. But is the situation more complicated than we might assume? What expectations are being produced about post-cure lives? And what is being overlooked along the way? We argue that hepatitis C policy, practice and research can instantiate a problematic orientation towards medicine and ‘the future’ and explore ways of moving beyond these orientations. The essay then proceeds into two main stages. First, combining critiques from existing research with preliminary insights from a new study on hepatitis C ‘post-cure’ lives, we outline some of the key logics regarding cure and post-cure, and explain why such logics are problematic. We argue against the assumption that the availability of a medical cure will alone reverse the entrenched social, political and structural dynamics that drive infections and limit service access. To do so, we note, is to overlook the net of meanings and power relations that co-constitute hepatitis C and injecting drug use and render those associated with them marginalised and disenfranchised. Such optimism erases the legacy of laws and policies devised in a pre-cure world, and their role in generating and limiting new ways of being. Second, we introduce new ideas to the field and articulate a vision for what we call a ‘futurology’ of hepatitis C, designed to counter these assumptions and take us beyond problematic temporal logics. Our futurology is inspired by the work of Cuevas-Hewitt (2011) on the ‘futurology of the present’. Cuevas-Hewitt's approach discards linear temporalities, expectations of revolution and reform, and instead pays attention to multiplicities of becoming in the perpetual present. Taking up ideas from Cuevas-Hewitt, we introduce our own sketches for a ‘futurology of hepatitis C’. This is a set of practices for thinking, researching, writing about and otherwise engaging with hepatitis C, characterised by attention not to what an imagined, singular future might look like, or to assumptions about treatment as revolutionary, but to what Cuevas-Hewitt (2011) calls the multiple ‘perpetual presents’ already with us, and aims to foment hope for change.     

Nitric oxide-releasing non-steroidal anti-inflammatory drugs: a new generation of antithrombotics?

Long-term use of aspirin as an antithrombotic agent is limited by its toxicity in the gastrointestinal tract. Even very low doses of aspirin can markedly increase the risk of gastrointestinal bleeding and ulceration. Addition of a nitric oxide (NO)-releasing moiety to non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to greatly reduce their ulcerogenic properties as well as their renal toxicity. We proposed that similar derivatisation of aspirin may yield a potent, gastrointestinal-sparing antithrombotic drug. Two prototype compounds (NCX-4215 and NCX-4016; Nicox SA) have been evaluated thus far. Each shows comparable or better anti-aggregatory activity to aspirin while not inducing detectable gastric damage. Current studies are aimed at determining what the optimal balance is between nitric oxide release and inhibition of thromboxane synthesis to achieve good antithrombotic activity with low toxicity. NO-aspirin derivatives appear to offer great potential as gastrointestinal-sparing antithrombotic drugs.     

Psychoneurendocrinology: a science of the past or a new pathway for the future?

Psychoneuroendocrinology is a branch of neuroscience that developed in the beginning of the last century, which investigates the possibility of a cause-effect link between endocrinopathies and mental disorders - with these studies ending in negative results. Psychoneuroendocrinology was then used as a methodological approach for the investigation of neurotransmitter function, on the basis of the observation that neurotransmitters regulate neurohormone and peripheral hormone secretions. Data were obtained for hypothalamic noradrenergic, serotoninergic, dopaminergic, gabaergic and acetylcholinergic functions, which could not be automatically extended to higher brain centers whose impairments might be etiopathogenetically involved in the development of mental disorders. Future studies should focus on new methodological approaches to brain biochemistry, on investigation of genetic, molecular biology, brain imaging, psychoneuroimmunoendocrinology, neuropeptide and neurosteroid secretion in relation to brain endocrine function in mental diseases.     

Protein Z: a new regulator of coagulation in arterial vessels?

Protein Z (PZ) is a vitamin K dependent factor identified in human plasma in 1984 whose physiological function was poorly understood. It was recently shown that protein Z is implicated in the down-regulation of coagulation by forming a complex with a plasma proteinase inhibitor called protein Z-dependent protease inhibitor (ZPI) which inhibits activated factor Xa on phospholipid surfaces. In the absence of an additional challenge, the disruption of PZ gene in mice is asymptomatic, but the association with the factor VLeiden mutation leads to a near complete mortality during the neonatal period with microvascular thrombosis. Unexpectedly, in humans, a relationship between protein Z deficiency and ischemic strokes, was firstly evidenced, but not confirmed by all the epidemiological study. Additional studies suggest that protein Z deficiency could be also a risk factor for acute coronary syndromes, early fetal losses, and increased the arterial risk in antiphospholipid syndrome. This review analyzes the different studies so far published and discusses the different results obtained in order to understand whether or not protein Z deficiency could be considered as an arterial ischemic risk factor.     

Role of serotonin in Alzheimer's disease: a new therapeutic target?

Mounting evidence accumulated over the past few years indicates that the neurotransmitter serotonin plays a significant role in cognition. As a drug target, serotonin receptors have received notable attention due in particular to the role of several serotonin-receptor subclasses in cognition and memory. The intimate anatomical and neurochemical association of the serotonergic system with brain areas that regulate memory and learning has directed current drug discovery programmes to focus on this system as a major therapeutic drug target. Thus far, none of these programmes has yielded unambiguous data that suggest that any of the new drug entities possesses disease-modifying properties, and significantly more research in this promising area of investigation is required. Compounds are currently being investigated for activity against serotonin 5-HT(1), 5-HT(4) and 5-HT(6) receptors. This review concludes that most work done in the development of selective serotonin receptor ligands is in the pre-clinical or early clinical phase. Also, while many of these compounds will likely find application as adjuvant therapy in the symptomatic treatment of Alzheimer's disease, there are currently only a few drug entities with activity against serotonin receptors that may offer the potential to alter the progression of the disease.     

GPR55: a new member of the cannabinoid receptor clan?

In this issue of the British Journal of Pharmacology, Ryberg et al. present convincing in vitro evidence that the orphan GPCR, GPR55, is a cannabinoid receptor. GPR55 was activated by a range of plant, synthetic and endogenous cannabinoids and blocked by the non-psychoactive phytocannabinoid, cannabidiol. Their experiments have revealed several differences between the pharmacology of GPR55 and the established cannabinoid CB1 and CB2 receptors. For example, the CB1 receptor antagonist, AM251, activated GPR55 and the main psychoactive constituent of cannabis, Delta9-tetrahydrocannabinol, displayed greater efficacy at GPR55 than at CB1 or CB2 receptors. They also compared the distribution of GPR55 and CB1 mRNA in mouse and report that GPR55 couples to Galpha13, that it is activated by virodhamine, palmitoylethanolamide and oleoylethanolamide, and that virodhamine displays relatively high efficacy as a GPR55 agonist. Still to be identified are the main roles played by GPR55 in health and disease and any potential therapeutic benefits of activating or blocking this receptor.