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Beyond the Usual Suspects: Physiological Roles of the Arabidopsis Amidase Signature (AS) Superfamily Members in Plant Growth Processes and Stress Responses.
Moya-Cuevas, J, Pérez-Alonso, MM, Ortiz-García, P, Pollmann, S
Biomolecules. 2021;(8)
Abstract
The diversification of land plants largely relies on their ability to cope with constant environmental fluctuations, which negatively impact their reproductive fitness and trigger adaptive responses to biotic and abiotic stresses. In this limiting landscape, cumulative research attention has centred on deepening the roles of major phytohormones, mostly auxins, together with brassinosteroids, jasmonates, and abscisic acid, despite the signaling networks orchestrating the crosstalk among them are so far only poorly understood. Accordingly, this review focuses on the Arabidopsis Amidase Signature (AS) superfamily members, with the aim of highlighting the hitherto relatively underappreciated functions of AMIDASE1 (AMI1) and FATTY ACID AMIDE HYDROLASE (FAAH), as comparable coordinators of the growth-defense trade-off, by balancing auxin and ABA homeostasis through the conversion of their likely bioactive substrates, indole-3-acetamide and N-acylethanolamine.
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Oral treprostinil diethanolamine for pulmonary arterial hypertension.
Feldman, J, Im, Y, Gill, K
Expert review of clinical pharmacology. 2015;(1):55-60
Abstract
The approval of oral treprostinil is a landmark event in the treatment of pulmonary arterial hypertension. Nineteen years after epoprostenol was approved we now have an oral prostanoid available in the USA. Although the current data in prostanoid naïve patients are unimpressive, emerging data suggest that in carefully selected patients oral treprostinil may be able to replace continuously infused treprostinil; however, many hurdles exist for this new medication including overcoming a complex side effect profile, astronomical cost and perhaps other entrants into the oral prostanoid space.
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Structure, phase behaviour and membrane interactions of N-acylethanolamines and N-acylphosphatidylethanolamines.
Swamy, MJ, Tarafdar, PK, Kamlekar, RK
Chemistry and physics of lipids. 2010;(3):266-79
Abstract
N-Acylethanolamines (NAEs) and N-acylphosphatidylethanolamines (NAPEs) are naturally occurring membrane lipids, whose content increases dramatically in a variety of organisms when subjected to stress, suggesting that they may play a role in the stress-combating mechanisms of organisms. In the light of this, it is of great interest to characterize the structure, physical properties, phase transitions and membrane interactions of these two classes of lipids. This review will present the current status of our understanding of the structure and phase behaviour of NAEs and NAPEs and their interaction with major membrane lipids, namely phosphatidylcholine, phosphatidylethanolamine and cholesterol. The relevance of such interactions to the putative stress-combating and membrane stabilizing properties of these lipids will also be discussed.
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Formoterol versus short-acting beta-agonists as relief medication for adults and children with asthma.
Welsh, EJ, Cates, CJ
The Cochrane database of systematic reviews. 2010;(9):CD008418
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Abstract
BACKGROUND Formoterol is a long-acting beta(2)-agonist but because it has a fast onset of action it can also be used as a relief medication. OBJECTIVES To asses the efficacy and safety of formoterol as reliever therapy in comparison to short-acting beta(2)-agonists in adults and children with asthma. SEARCH STRATEGY We searched the Cochrane Airways Group Specialised Register and websites of clinical trial registers (for unpublished trial data), and we checked the Food and Drug Administration (FDA) submissions in relation to formoterol. The date of the most recent search was February 2010. SELECTION CRITERIA Randomised, parallel-arm trials of at least 12 weeks duration in patients of any age and severity of asthma. Studies randomised patients to any dose of as-needed formoterol versus short-acting beta(2)-agonist. Concomitant use of inhaled corticosteroids or other maintenance medication was allowed, as long as this was not part of the randomised treatment regimen. DATA COLLECTION AND ANALYSIS Two authors independently selected trials for inclusion in the review. Outcome data were extracted by one author and checked by the second author. We sought unpublished data on primary outcomes. MAIN RESULTS This review includes eight studies conducted in 22,604 participants (mostly adults). Six studies compared formoterol as-needed to terbutaline whilst two studies compared formoterol with salbutamol as-needed. Background maintenance therapy varied across the trials. Asthma exacerbations and serious adverse events showed a direction of treatment effect favouring formoterol, of which one outcome reached statistical significance (exacerbations requiring a course of oral corticosteroids). In patients on short-acting beta(2)-agonists, 117 people out of 1000 had exacerbations requiring oral corticosteroids over 30 weeks, compared to 101 (95% CI 93 to 108) out of 1000 for patients on formoterol as-needed. In patients on maintenance inhaled corticosteroids there were also significantly fewer exacerbations requiring a course of oral corticosteroids on formoterol as-needed (Peto OR 0.75; 95% CI 0.62 to 0.91). There was one death per 1000 people on formoterol or on short-acting beta(2)-agonists. AUTHORS' CONCLUSIONS In adults, formoterol was similar to short-acting beta(2)-agonists when used as a reliever, and showed a reduction in the number of exacerbations requiring a course of oral corticosteroids. Clinicians should weigh the relatively modest benefits of formoterol as-needed against the benefits of single inhaler therapy and the potential danger of long-term use of long-acting beta(2)-agonists in some patients. We did not find evidence to recommend changes to guidelines that suggest that long-acting beta(2)-agonists should be given only to patients already taking inhaled corticosteroids.There was insufficient information reported from children in the included trials to come to any conclusion on the safety or efficacy of formoterol as relief medication for children with asthma.
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Arterial stiffness, hypertension, and rational use of nebivolol.
Agabiti-Rosei, E, Porteri, E, Rizzoni, D
Vascular health and risk management. 2009;(1):353-60
Abstract
Arterial stiffness plays a key role in the pathophysiology of the cardiovascular system. Some indices of arterial stiffness (pulse wave velocity, augmentation index, characteristics of central blood pressure waveform) may be presently calculated and evaluated in the clinical setting. Age and blood pressure are the two major clinical determinants of increased arterial stiffness, while molecular determinants of arterial stiffness are related to fibrotic components of the extracellular matrix, mainly elastin, collagen and fibronectin. Increased arterial stiffness has been consistently observed in conditions such as hypertension, dyslipidemia and diabetes. Arterial stiffness evaluated by means of carotid-femoral pulse wave velocity yielded prognostic significance beyond and above traditional risk factors. A more favorable effect of calcium channel blockers, diuretics and ACE inhibitors compared with beta-blockers on indices of arterial stiffness was observed in several studies. It is conceivable that newer beta-blockers with additional vasodilating properties, such as nebivolol, which has favorable effects on carbohydrate and lipid metabolism, as well as on endothelial function and on oxidative stress, may have favorable effects on arterial stiffness, compared with atenolol. In fact, in recent studies, nebivolol was demonstrated to improve artery stiffness to a greater extent than older beta-blockers. Because endothelial dysfunction and increased arterial stiffness play an important role in the early atherosclerotic processes and are associated with poor outcomes and increased mortality, independently of blood pressure, the ability of nebivolol to enhance release of endothelium-derived nitric oxide, and consequently improve endothelial function and arterial stiffness, may have significant clinical implications for the use of this agent in the treatment of hypertension and cardiovascular diseases.
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Endocannabinoids and related N-acylethanolamines in the control of appetite and energy metabolism: emergence of new molecular players.
Lambert, DM, Muccioli, GG
Current opinion in clinical nutrition and metabolic care. 2007;(6):735-44
Abstract
PURPOSE OF REVIEW Endocannabinoids (anandamide and 2-arachidonoylgycerol) and related N-acylethanolamines (N-oleoylethanolamine) exhibit opposite effects in the control of appetite. The purpose of this review is to highlight the similarities and differences of three major lipid-signaling molecules by focusing on their mode of action and the proteins involved in the control of food intake and energy metabolism. RECENT FINDINGS Anandamide and 2-arachidonoylglycerol promote food intake and are the main endogenous ligands of the cannabinoid receptors. One of them, the cannabinoid receptor 1, is responsible for the control of food intake and energy expenditure both at a central and a peripheral level, affecting numerous anorexigenic and orexigenic mediators (leptin, neuropeptide Y, ghrelin, orexin, endogenous opioids, corticotropin-releasing hormone, alpha-melanocyte stimulating hormone, cocaine and amphetamine-related transcript). In the gut, N-oleoylethanolamine plays an opposite role in food regulation, by interacting with two molecular targets different from the cannabinoid receptors: the nuclear receptor peroxisome proliferator-activated receptor alpha and a G-protein coupled receptor GPR119. SUMMARY Recent findings on the molecular mechanisms underlying the promotion of food intake or, in contrast, the suppression of food intake by anandamide and N-oleoylethanolamine, are summarized. Potential strategies for treating overweight, metabolic syndrome, and type II diabetes are briefly outlined.
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Vascular effects of newer cardiovascular drugs: focus on nebivolol and ACE-inhibitors.
Lüscher, TF, Spieker, LE, Noll, G, Cosentino, F
Journal of cardiovascular pharmacology. 2001;:S3-11
Abstract
Alterations in the function and structure of the blood vessel wall account for most clinical events in the coronary and cerebrovascular circulation such as myocardial infarction and stroke. Cardiovascular drugs may exert beneficial effects on the vascular wall both at the level of the endothelium and vascular smooth muscle cells. Therefore, endothelial mediators, in particular nitric oxide (NO) and endothelin (ET), are of special interest. Drugs can modulate the expression and actions of NO, a vasodilator with antiproliferative and antithrombotic properties, and of ET, a potent vasoconstrictor and proliferative mitogenic agent. The most successful drugs in this context are statins and angiotensin-converting enzyme (ACE)-inhibitors. While statins increase the expression of NO synthase. ACE-inhibitors increase the release of NO via bradykinin-mediated mechanisms. Antioxidant properties of drugs are also important, as oxidative stress is crucial in atherosclerotic vascular disease. These properties may explain part of the effects of calcium antagonists and ACE-inhibitors. Indeed, angiotensin II stimulates NAD(P)H oxidases responsible for the formation of superoxide, which inactivates NO. ACE-Inhibitors thus increase the bioavailability of NO. Newer cardiovascular drugs such as nebivolol are able to directly stimulate NO release from the endothelium both in isolated arteries and in the human forearm circulation. ET receptor antagonists may exert beneficial effects in the vessel wall by preventing the effects of ET at its receptors and by reducing ET production. In summary, cardiovascular drugs have important effects on the vessel wall, which may be clinically relevant for the prevention and treatment of cardiovascular disease.