abstract：:L-carnitine (LC) deficiency is commonly observed in chronic hemodialysis (HD) patients. As a result of this and other causes of secondary LC deficiencies, LC has been described as a "conditionally essential nutrient" or "conditional vitamin". Although a large number of clinical trials regarding the beneficial effects ...

journal_title：Pharmacology & therapeutics

authors： Arduini A,Bonomini M,Savica V,Amato A,Zammit V

更新日期：2008-11-01 00:00:00

abstract：:There is substantial molecular evidence for the involvement of beta1 integrin in tissue organisation and remodelling, which confers a key role in cell growth, differentiation, migration, and survival. This role has been, in part, highlighted using the transgenic approach which does little to define the more subtle fun...

journal_title：Pharmacology & therapeutics

authors： Al-Jamal R,Harrison DJ

更新日期：2008-11-01 00:00:00

abstract：:The "late sodium current" (I(NaL)) is a sustained component of the fast Na+ current of cardiac myocytes and neurons. As recently appreciated, common neurological and cardiac conditions are associated with abnormal I(NaL) enhancement, which may contribute to the pathogenesis of both electrical and contractile dysfuncti...

journal_title：Pharmacology & therapeutics

authors： Zaza A,Belardinelli L,Shryock JC

更新日期：2008-09-01 00:00:00

abstract：:In the heart, Ca(2+) released from the intracellular Ca(2+) storage site, the sarcoplasmic reticulum (SR), is the principal determinant of cardiac contractility. SR Ca(2+) release is controlled by dedicated molecular machinery, composed of the cardiac ryanodine receptor (RyR2) and a number of accessory proteins, inclu...

journal_title：Pharmacology & therapeutics

authors： Györke S,Carnes C

更新日期：2008-09-01 00:00:00

abstract：:Drug-induced arrhythmias or QT interval prolongation is one of the two most common reasons for drugs to be denied regulatory approval or to have warnings imposed on their clinical labelling. The assessment of torsades de pointes (TdP) risk during clinical development of a new pharmaceutical compound has been an issue ...

journal_title：Pharmacology & therapeutics

authors： Vik T,Pollard C,Sager P

更新日期：2008-08-01 00:00:00

abstract：:Proarrhythmic susceptibility to drug-induced Torsades de Pointes is restricted to individuals with a predisposed phenotype characterized by a reduced repolarization reserve. Additional factors are often involved in a further impairment of repolarization, possibly culminating with dangerous ventricular polymorphic tach...

journal_title：Pharmacology & therapeutics

authors： Oros A,Beekman JD,Vos MA

更新日期：2008-08-01 00:00:00

abstract：:For decades, intensive studies have attempted to identify the mechanisms underlying malignant tumor growth. Despite significant progress, most therapeutic approaches fail to eliminate all tumor cells. The remaining tumor cells often result in recurrence and metastasis. Recently, the idea of a cancer stem cell was prop...

journal_title：Pharmacology & therapeutics

authors： Zhao RC,Zhu YS,Shi Y

更新日期：2008-07-01 00:00:00

abstract：:The small heat shock proteins (HSPs) HSP20, HSP27 and alphaB-crystallin are chaperone proteins that are abundantly expressed in smooth muscles are important modulators of muscle contraction, cell migration and cell survival. This review focuses on factors regulating expression of small HSPs in smooth muscle, signaling...

journal_title：Pharmacology & therapeutics

authors： Salinthone S,Tyagi M,Gerthoffer WT

更新日期：2008-07-01 00:00:00

abstract：:Brain-derived neurotrophic factor (BDNF) has emerged as a regulator of development, plasticity and, recently, addiction. Decreased neurotrophic activity may be involved in ethanol-induced neurodegeneration in the adult brain and in the etiology of alcohol-related neurodevelopmental disorders. This can occur through de...

journal_title：Pharmacology & therapeutics

authors： Davis MI

更新日期：2008-04-01 00:00:00

abstract：:AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor trafficking is a fundamental mechanism for regulating synaptic strength, and hence may underlie cellular processes involved in learning and memory. PICK1 (protein interacting with C-kinase) is a PDZ and BAR domain-containing protein that has rece...

journal_title：Pharmacology & therapeutics

authors： Hanley JG

更新日期：2008-04-01 00:00:00

abstract：:Thromboxane A(2) (TXA(2)), an unstable arachidonic acid metabolite, elicits diverse physiological/pathophysiological actions, including platelet aggregation and smooth muscle contraction. TXA(2) has been shown to be involved in allergies, modulation of acquired immunity, atherogenesis, neovascularization, and metastas...

journal_title：Pharmacology & therapeutics

authors： Nakahata N

更新日期：2008-04-01 00:00:00

abstract：:Islet function is regulated by a number of different signals. A main signal is generated by glucose, which stimulates insulin secretion and inhibits glucagon secretion. The glucose effects are modulated by many factors, including hormones, neurotransmitters and nutrients. Several of these factors signal through guanin...

journal_title：Pharmacology & therapeutics

authors： Winzell MS,Ahrén B

更新日期：2007-12-01 00:00:00

abstract：:Mammals dispose of cholesterol mainly through 7alpha-hydroxylated bile acids, and the enzyme catalyzing the 7alpha-hydroxylation, cholesterol 7alpha-hydroxylase (CYP7A1), has a deep impact on cholesterol homeostasis. In this review, we present the study of regulation of CYP7A1 as a good exemplification of the extraord...

journal_title：Pharmacology & therapeutics

authors： Gilardi F,Mitro N,Godio C,Scotti E,Caruso D,Crestani M,De Fabiani E

更新日期：2007-12-01 00:00:00

abstract：:During the last 20 years, an expanding body of research has elucidated the central role of amyloid precursor protein (APP) processing and amyloid beta peptide (Abeta) production in the risk, onset, and progression of the neurodegenerative disorder Alzheimer's disease (AD), the most common form of dementia. Ongoing res...

journal_title：Pharmacology & therapeutics

authors： Findeis MA

更新日期：2007-11-01 00:00:00

abstract：:This review concerns the development of small molecule therapeutics for the inherited neurodegenerative disease Friedreich ataxia (FRDA). FRDA is caused by transcriptional repression of the nuclear FXN gene, encoding the essential mitochondrial protein frataxin and accompanying loss of frataxin protein. Frataxin insuf...

journal_title：Pharmacology & therapeutics

authors： Gottesfeld JM

更新日期：2007-11-01 00:00:00

abstract：:beta(2)-adrenoceptor agonists are the mainstay for the acute symptomatic treatment of asthma and provide effective bronchoprotection to a wide range of bronchoconstrictor agents. However, over the past 4 decades there has been a continuing debate concerning whether regular chronic treatment with these drugs may be doi...

journal_title：Pharmacology & therapeutics

authors： Bond RA,Spina D,Parra S,Page CP

更新日期：2007-09-01 00:00:00

abstract：:Although the existence of halogenated lipids in lower organisms has been known for many years, it is only since the 1990s that interest in their occurrence in mammalian systems has developed. Chlorinated (and other halogenated) lipids can arise from oxidation by hypohalous acids, such as HOCl, which are products of th...

journal_title：Pharmacology & therapeutics

authors： Spickett CM

更新日期：2007-09-01 00:00:00

abstract：:Nerve growth factor (NGF) and other members of the neurotrophin family are critical for the survival and differentiation of neurons and have been implicated in the pathophysiology of numerous disease states. Although the therapeutic potential of neurotrophins has generated much excitement over the past decade, inconve...

journal_title：Pharmacology & therapeutics

authors： Price RD,Milne SA,Sharkey J,Matsuoka N

更新日期：2007-08-01 00:00:00

abstract：:Unless it is carefully controlled, bias often distorts the results of clinical trials, usually exaggerating the magnitude of true efficacy. For that reason, procedures to limit bias have been mandated by the FDA when assessing efficacy in clinical trials. The present review shows that the effects of bias in preclinica...

journal_title：Pharmacology & therapeutics

authors： Lindner MD

更新日期：2007-07-01 00:00:00

abstract：:Pulmonary hypertension (PH) in newborns and infants can present in its idiopathic form or complicate a long list of other diseases. Most of these conditions are either pulmonary or cardiovascular in origin. In the present review our current knowledge regarding pathophysiology, structural changes, diagnosis, and availa...

journal_title：Pharmacology & therapeutics

authors： Hoehn T

更新日期：2007-06-01 00:00:00

abstract：:Proteolytic degradation of unwanted proteins by the ubiquitin-proteasome system (UPS) is critical for normal maintenance of various cellular functions. Parkinson's disease (PD), one of the most prevalent neurodegenerative disorders, is characterized by prominent and irreversible nigral dopaminergic neuronal loss and i...

journal_title：Pharmacology & therapeutics

authors： Sun F,Kanthasamy A,Anantharam V,Kanthasamy AG

更新日期：2007-06-01 00:00:00

abstract：:Heme, a complex of iron and protoporphyrin IX (PPIX), senses and utilizes oxygen in nearly all living cells. It is an essential component of various hemoproteins, including those involved in oxygen transport and storage (hemoglobin, myoglobin), electron transfer, drug and steroid metabolism (cytochromes), and signal t...

journal_title：Pharmacology & therapeutics

authors： Krishnamurthy P,Xie T,Schuetz JD

更新日期：2007-06-01 00:00:00

abstract：:The developing lung is highly susceptible to damage from exposure to environmental toxicants particularly due to the protracted maturation of the respiratory system, extending from the embryonic phase of development in utero through to adolescence. The functional organization of the lungs requires a coordinated ontoge...

journal_title：Pharmacology & therapeutics

authors： Kajekar R

更新日期：2007-05-01 00:00:00

abstract：:Tumor progression and metastasis are complex processes involving intricate interplay among multiple gene products. Astrocyte elevated gene (AEG)-1 was cloned as an human immunodeficiency virus (HIV)-1-inducible and tumor necrosis factor-alpha (TNF-alpha)-inducible transcript in primary human fetal astrocytes (PHFA) by...

journal_title：Pharmacology & therapeutics

authors： Emdad L,Sarkar D,Su ZZ,Lee SG,Kang DC,Bruce JN,Volsky DJ,Fisher PB

更新日期：2007-05-01 00:00:00

abstract：:Nongenomic estrogen signaling pathways involve extranuclear estrogen receptors or function independently from estrogen receptors. These pathways participate in neuroprotection elicited by the hormone. Additional nongenomic neuroprotective effects are attributable to antioxidant and antiinflammatory actions of estrogen...

journal_title：Pharmacology & therapeutics

authors： Prokai L,Simpkins JW

更新日期：2007-04-01 00:00:00

abstract：:Conditional gene knockout represents an extremely powerful approach to study the function of single genes in the nervous system. The Cre-LoxP system is the most advanced technology for spatial and temporal control of genetic inactivation, and there is rapid progress using this methodology in neuroscience research. In ...

journal_title：Pharmacology & therapeutics

authors： Gavériaux-Ruff C,Kieffer BL

更新日期：2007-03-01 00:00:00

abstract：:Clinical evidence indicates that female sex steroids may contribute to the high prevalence of migraine in women, as well as changes in the frequency or severity of migraine attacks that are in tandem with various reproductive milestones in women's life. While female sex steroids do not seem to be involved in the patho...

journal_title：Pharmacology & therapeutics

authors： Gupta S,Mehrotra S,Villalón CM,Perusquía M,Saxena PR,MaassenVanDenBrink A

更新日期：2007-02-01 00:00:00

abstract：:5-Lipoxygenase (5-LO) catalyzes the conversion of arachidonic acid (AA) into leukotriene (LT) A(4) and 5-hydroperoxyeicosatetraenoic acid. LTA(4) can then be converted into LTB(4) by LTA(4) hydrolase or into LTC(4) by LTC(4) synthase and the LTC(4) synthase isoenzymes MGST2 and MGST3. LTB(4) is a potent chemoattractan...

journal_title：Pharmacology & therapeutics

authors： Werz O,Steinhilber D

更新日期：2006-12-01 00:00:00

abstract：:A number of neuronal functions, including synaptic plasticity, depend on proper regulation of synaptic proteins, many of which can be rapidly regulated by phosphorylation. Neuronal activity controls the function of these synaptic proteins by exquisitely regulating the balance of various protein kinase and protein phos...

journal_title：Pharmacology & therapeutics

authors： Lee HK

更新日期：2006-12-01 00:00:00

abstract：:Cyclooxygenase (COX) enzymes, or prostaglandin-endoperoxide synthases (PTGS), are heme-containing bis-oxygenases that catalyze the first committed reaction in metabolism of arachidonic acid (AA) to the potent lipid mediators, prostanoids and thromboxanes. Two isozymes of COX enzymes (COX-1 and COX-2) have been identif...

journal_title：Pharmacology & therapeutics

authors： Hewett SJ,Bell SC,Hewett JA

更新日期：2006-11-01 00:00:00

abstract：:Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis, pneumonia, mechanical ventilation, and respiratory failure in infants in the US. No effective post-infection treatments are widely available, and currently there is no vaccine. RSV disease is the result of virus-induced airway damage and complex ...

journal_title：Pharmacology & therapeutics

authors： Moore ML,Peebles RS Jr

更新日期：2006-11-01 00:00:00

abstract：:The cardiovascular system is highly organised in time; blood pressure (BP), heart rate (HR), peripheral resistance, pressure and the release/activity of vasodilating hormones all display pronounced circadian variations. Pathophysiological events within the cardiovascular system are also not random, as shown for instan...

journal_title：Pharmacology & therapeutics

authors： Lemmer B

更新日期：2006-09-01 00:00:00

abstract：:Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptors family. PPARs are a family of 3 ligand-activated transcription factors: PPARalpha (NR1C1), PPARbeta/delta (NUC1; NR1C2), and PPARgamma (NR1C3). PPARalpha, -beta/delta, and -gamma are encoded by different genes but show sub...

journal_title：Pharmacology & therapeutics

authors： Moraes LA,Piqueras L,Bishop-Bailey D

更新日期：2006-06-01 00:00:00

abstract：:Major depression is a debilitating and recurrent disorder with a substantial lifetime risk and a high social cost. Depressed patients generally display co-morbid symptoms, and depression frequently accompanies other serious disorders. Currently available drugs display limited efficacy and a pronounced delay to onset o...

journal_title：Pharmacology & therapeutics

authors： Millan MJ

更新日期：2006-05-01 00:00:00

abstract：:A variety of drug transporters expressed in the body control the fate of drugs by affecting absorption, distribution, and elimination processes. In the small intestine, transporters mediate the influx and efflux of endogenous or exogenous substances. In clinical pharmacotherapy, ATP-dependent efflux transporters (ATP-...

journal_title：Pharmacology & therapeutics

authors： Takano M,Yumoto R,Murakami T

更新日期：2006-01-01 00:00:00

abstract：:Arterial obstructive syndromes result in heart disease, stroke and limb loss, disability, and mortality. Currently available therapeutics for patients with these conditions are inadequate or fail in a significant number of patients. The development of novel therapies for severe coronary arterial disease (CAD), periphe...

journal_title：Pharmacology & therapeutics

authors： Staudacher DL,Preis M,Lewis BS,Grossman PM,Flugelman MY

更新日期：2006-01-01 00:00:00

abstract：:The pulmonary endothelium plays a crucial role in lung development and function during the perinatal period. Its 2 most important functions at this time are to help reduce pulmonary vascular resistance (PVR) in order to permit the entire cardiac output to pass through the lungs for the first time and to facilitate the...

journal_title：Pharmacology & therapeutics

authors： Wojciak-Stothard B,Haworth SG

更新日期：2006-01-01 00:00:00

abstract：:Several amphetamine analogs are potent psychostimulants and major drugs of abuse. In animal models, the psychomotor and reinforcing effects of amphetamine, methamphetamine (METH), 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy), and methylphenidate (MPD; Ritalin) are thought to be dependent on increased extracellula...

journal_title：Pharmacology & therapeutics

authors： Itzhak Y,Ali SF

更新日期：2006-01-01 00:00:00

abstract：:Recent evidence indicates that ethanol modulates the function of specific intracellular signaling cascades, including those that contain cyclic adenosine 3', 5'-monophosphate (cAMP)-dependent protein kinase A (PKA), protein kinase C (PKC), the tyrosine kinase Fyn, and phospholipase D (PLD). In some cases, the specific...

journal_title：Pharmacology & therapeutics

authors： Newton PM,Messing RO

更新日期：2006-01-01 00:00:00

abstract：:Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), tissue remodeling, and airflow obstruction. The pathogenesis of asthma is only partly understood, and there is an urgent need for improved therapeutic strategies for this disease. Microarray technology has considerable promise ...

journal_title：Pharmacology & therapeutics

authors： Rolph MS,Sisavanh M,Liu SM,Mackay CR

更新日期：2006-01-01 00:00:00