Abstract:
:The pivotal therapeutic role of myocardial metabolic modulation in ischemic heart disease (IHD) is increasingly recognized. Among the others, inhibitors of free fatty acids (FFA) oxidation have been consistently shown to play an important role in the therapeutic strategy of IHD patients. Additionally, abnormalities of glucose homeostasis are consistently present in patients with IHD, definitely contributing to the progression of the primary disease. If not adequately treated, in most patients glucose metabolism abnormalities will heavily contribute to the occurrence of complications, of whom severe left ventricular dysfunction is at present one of the most frequent and insidious. Apart from a meticulous metabolic control of frank diabetes, special attention should be also paid to insulin resistance, a condition that is generally underdiagnosed as a distinct clinical entity. An important metabolic alteration in diabetic patients is the increase in free fatty acid concentrations and the increased muscular and myocardial free fatty acid uptake and oxidation. The increased uptake and utilization of free fatty acid and the reduced utilization of glucose as source of energy during stress and ischemia are responsible for the increased susceptibility of the diabetic heart to myocardial ischemia and to a greater decrease of myocardial performance for a given amount of ischemia compared to non diabetic hearts. In order to shift cardiac metabolism from FFA to preferential glucose utilization, the use of FFA inhibitors has been advocated. Among FFA inhibitors etomoxir, perhexiline, oxfenicine and trimetazidine have been evaluated. Among them, trimetazidine, specifically a 3-ketoacyl coenzyme A thiolase inhibitor, has been shown to improve overall glucose metabolism in IHD patients with diabetes and left ventricular dysfunction. The observed combined beneficial effects of FFA inhibitors on myocardial ischemia, left ventricular function and glucose metabolism, represent an additional advantage of these drugs, especially when myocardial and glucose metabolism abnormalities coexist. In this paper, the recent literature on the beneficial therapeutic effects of FFA oxidation inhibitors on myocardial ischemia, left ventricular dysfunction and glucose metabolism in patients with ischemic heart disease and abnormalities of carbohydrate metabolism is reviewed and discussed.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Fragasso G,Salerno A,Spoladore R,Cera M,Montanaro C,Margonato Adoi
10.2174/138161209787582093subject
Has Abstractpub_date
2009-01-01 00:00:00pages
857-62issue
8eissn
1381-6128issn
1873-4286journal_volume
15pub_type
杂志文章,评审abstract::Neuroinflammation is a common characteristic of several mental health conditions such as major depression, bipolar disorder, post-traumatic stress disorder (PTSD) and schizophrenia (SCHZ). Inflammatory processes trigger and/or further deteriorate mental functions and are regarded as targets for therapeutic drug develo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161282210160304112511
更新日期:2016-01-01 00:00:00
abstract::Cardiovascular disease remains the number one killer in the United States and many other countries. Each year, there are enormous research efforts on its pathogenesis, prevention and treatment led by scientists worldwide. One of the most significant research areas is the impact and mechanisms of existing or new cardio...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113196660744
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abstract::Arrhythmias in left ventricular hypertrabeculation/noncompaction (LVHT) comprise sustained or non-sustained ventricular tachycardia (VT) (n=135), atrial fibrillation (AF) (n=96) AV block (n=55) and QT prolongation (n=47). The prevalence differs between children and adults. In children most frequent are WPW-syndrome (n...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210793176518
更新日期:2010-01-01 00:00:00
abstract::The organ shortage for kidney transplantation remains a challenging issue worldwide. Incompatibility between donor-recipient pairs, commonly occurring among transplant candidates who were sensitized from prior antigen exposure, serves as a significant barrier to kidney transplantation. In efforts to overcome this obst...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200521141749
更新日期:2020-01-01 00:00:00
abstract::Among pediatric patients, preterm neonates and newborns are the most vulnerable subpopulation. Rapid developmental changes of physiological factors affecting the pharmacokinetics of drug substances in newborns require extreme care in dose and dose regimen decisions. These decisions could be supported by in silico meth...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150901110533
更新日期:2015-01-01 00:00:00
abstract::Our clinical observations proved that the the duodenal ulcer in patients healed without any inhibition of gastric acid secretion (1965), and the healing rates of atropine vs cimetidine vs Carbenoxolone were equal and superior to that of placebo in randomized, prospective and multiclinical study of DU patients (1978). ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161211796197016
更新日期:2011-01-01 00:00:00
abstract::Vascular smooth muscle cells (VSMC) respond to arterial wall injury by intimal proliferation and play a key role in atherogenesis by proliferating and migrating excessively in response to repeated injury, such as hypertension and atherosclerosis. In contrast, fully differentiated, quiescent VSMC allow arterial vasodil...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161210794454987
更新日期:2010-01-01 00:00:00
abstract::The development of targeted therapy drugs acting on tumor growth and progression is greatly expanding these last years. Among them kinase inhibitors have a prominent position and have demonstrated efficacy and clinical benefits in solid and hematologic malignancies. Compared to conventional systemic cytotoxic chemothe...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160226132630
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Casein kinase II (CK2) is a pro-oncogenic protein, which is emerging as a promising therapeutic target in cancer. Recent studies have revealed an important role for CK2 in tumorigenesis. High levels of CK2 are noted in many malignancies including leukemia. Use of CK2 inhibitors in various malignancies includ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161006154311
更新日期:2017-01-01 00:00:00
abstract::ADAM (a disintegrin and metalloproteinase) proteins have a predominant role in the protein ectodomain shedding of membrane-bound molecules. ADAMs have emerged as critical regulators of cell-cell signaling during development and homeostasis, and are believed to contribute to pathologies, such as cancer, where their reg...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788682415
更新日期:2009-01-01 00:00:00
abstract::α-Synuclein aggregation is centrally implicated in Parkinson's disease (PD). It involves multi-step nucleated polymerization process via the formation of dimers, soluble toxic oligomers and insoluble fibrils. In the present study, we synthesized a novel compound viz., Curcumin-glucoside (Curc-gluc), a modified form of...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212798919093
更新日期:2012-01-01 00:00:00
abstract::The influence of mitochondrial dysfunction on pathological states involving inflammatory and/or oxidative stress in tissues that do not show frank cellular apoptosis or necrosis has been rather difficult to unravel, and the literature is replete with contradictory information. Although such discrepancies have many pot...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140306095717
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Polyphenols are a family of natural antioxidants that in recent years have been studied and tested for their potential benefits towards cardiovascular diseases. OBJECTIVE:The aim of this review is to focus the attention on the presumed lipid-lowering and atheroprotective effects of polyphenols, administered...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666171128110408
更新日期:2018-01-01 00:00:00
abstract::Retinoids (vitamin A and its analogs) exert profound effects on a wide variety of life processes, including morphogenesis and embryonic development. Several retinoids are also effective drugs for therapy of skin diseases and some types of cancer. However, the applicability of this class of compounds is limited by thei...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013397708
更新日期:2001-06-01 00:00:00
abstract::The large conduit arteries of the thorax and abdomen are elastic while those in the arms and legs are muscular. Alterations in wall properties of elastic arteries occur over time and are usually permanent in nature; acute changes can, however, occur is response to a change in transmural pressure. Chronic alterations i...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787354258
更新日期:2009-01-01 00:00:00
abstract::Oral epithelium is a stratified squamous epithelium that functions as the barrier between the outside environment and the host. In the oral cavity, epithelial tissues are constantly exposed to a variety of bacteria, but most individuals maintain healthy homeostasis. Epithelial cells contribute to the innate host respo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207782110435
更新日期:2007-01-01 00:00:00
abstract::Monocytes are leading component of the mononuclear phagocytic system that play a key role in phagocytosis and removal of several kinds of microbes from the body. Monocytes are bone marrow precursor cells that stay in the blood for a few days and migrate towards tissues where they differentiate into macrophages. Monocy...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190102104642
更新日期:2018-01-01 00:00:00
abstract::Active pharmaceutical ingredients (APIs) can exist in different polymorphic forms as well as in amorphous state. Polymorphic and amorphous forms of APIs can differ in physicochemical properties which in turn can significantly influence their therapeutic safety and effectiveness of the treatment. This review focuses on...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160804100036
更新日期:2016-01-01 00:00:00
abstract::Naturally occurring abietane diterpenoids have been studied over the years and have shown to display a wide range of biological activities. This review covers three main aspects of the abietane-type diterpenoids with hydroxy-p-quinone C ring, designated as royleanones. An overview of 1) the naturally occurrence, 2) ch...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151211094521
更新日期:2016-01-01 00:00:00
abstract::Two morphological features may be seen as a main result of the cardiovascular cell damage caused by cigarette smoking: myocardial cell necrosis and smoke cardiomyopathy that, however, can lead to cell necrosis in case of chronic prolonged exposure to tobacco smoke. Both these pathological patterns recognise hypoxia as...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784746699
更新日期:2008-01-01 00:00:00
abstract::Neuropathic pain is characterized by complicated combination of positive (e.g., hyperalgesia and allodynia) and negative (e.g., hypoesthesia and hypoalgesia) symptoms, and is often refractory to conventional pharmacological agents, including morphine. Although the molecular mechanisms for positive symptoms are extensi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666141027113923
更新日期:2015-01-01 00:00:00
abstract::The development of radioligands to image beta-amyloid (A beta) plaques and neurofibrillary tangles (NFTs) in vivo in the aging human brain is an important and active area of radiopharmaceutical design. When used in combination with positron emission tomography (Pet) or single photon emission computed tomography (spect...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384772
更新日期:2004-01-01 00:00:00
abstract::Integrins alpha(1)beta(1) and alpha(2)beta(1) are highly expressed on the microvascular endothelial cells, and blocking of their adhesive properties significantly reduced the VEGF-driven neovascularization ratio and tumor growth in animal models. Hence, inhibitors of the alpha(1)beta(1) and alpha(2) beta(1) integrins,...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207782023766
更新日期:2007-01-01 00:00:00
abstract::Parkinson's disease (PD) is a movement disorder caused by degeneration of the nigrostriatal dopamine (DA) neurons in the substantia nigra pars compacta and the resultant deficiency in the neurotransmitter DA at the nerve terminals in the striatum. We and other investigators found increased levels of pro-inflammatory c...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053381620
更新日期:2005-01-01 00:00:00
abstract::Development of effective drug delivery systems is important for medicine and healthcare. Polymer particulates (micro- and nanoparticles) have opened new opportunities in the field of drug delivery by overcoming various limitations of conventional delivery methods. The properties of polymeric particles can be readily t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160217125734
更新日期:2016-01-01 00:00:00
abstract::Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and RNA polymerase II transcription. Several pharmacological CDK inhibitors (PCIs) are currently in clinical trials as potential cancer therapeutics since CDK hyperactivation is detected in the majority of neoplasias. Within the last few years, the a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777442083
更新日期:2006-01-01 00:00:00
abstract::The mechanisms underlying neurodegeneration in amyotrophic lateral sclerosis (ALS) are multifactorial and include genetic and environmental factors. Nowadays, it is well accepted that neuronal loss is driven by non-cell autonomous toxicity. Non-neuronal cells, such as astrocytes, have been described to significantly c...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170615110856
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The 3' repair exonuclease 1 (TREX1) gene is the major DNA-specific 3'-5 'exonuclease of mammalian cells which reduces single- and double-stranded DNA (ssDNA and dsDNA) to prevent undue immune activation mediated by the nucleic acid. TREX1 is also a crucial suppressor of selfrecognition that pr...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190902113218
更新日期:2019-01-01 00:00:00
abstract::Clopidogrel, in combination wih aspirin, is currently the drug of choice to prevent thrombosis after coronary stent implantation. Currently, clopidogrel is administered to the vast majority of patients without any assessment of platelet inhibition. Response variability and resistance, however, definitely occur to clop...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206776361345
更新日期:2006-01-01 00:00:00
abstract::Nitric oxide is a ubiquitous molecule involved in a variety of biological processes. The specific action of NO depends on its enzymatic sources namely neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS) and all three isoforms have been localized in the gastrointestinal tract. Constit...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013398491
更新日期:2001-01-01 00:00:00