Abstract:
:Human immunodeficiency virus type 1 resistance to nucleoside reverse transcriptase inhibitors such as 3'-azido-2', 3'-dideoxythymidine (AZT) can arise through mutations in the coding region of reverse transcriptase (RT) that enhance the enzyme's ability to remove the drug after it has been incorporated. This excision activity of HIV-1 RT has been well characterized in a number of in vitro systems. However, the in vitro findings do not provide a complete picture of the in vivo significance of this resistance mechanism. This review will attempt to bridge the gap between the in vitro observations and the in vivo environment by summarizing the fragmentary information that is available about the intracellular conditions that may influence drug excision in cell subpopulations that are infected by HIV-1. Topics that will be discussed include (a) intracellular compounds HIV-1 RT may use to remove chain terminators; (b) how dNTPs can affect excision activity and how these effects differ in different immune cell subpopulations; (c) the influence of HIV infection on excision activity--e.g., through immune activation of infected cells or through changes indirectly induced in cells that subsequently become infected; (d) intracellular conditions that favor selection for mutations that increase the excision-based resistance mechanism; (e) the importance of macrophages in the selection of resistance mutations. Understanding factors that control excision in the intracellular environment will greatly enhance our understanding of the process of selection for this class of drug resistance mutations and may open doors for the development of novel targets for antiviral therapy.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Smith AJ,Scott WAdoi
10.2174/138161206776873572subject
Has Abstractpub_date
2006-01-01 00:00:00pages
1827-41issue
15eissn
1381-6128issn
1873-4286journal_volume
12pub_type
杂志文章,评审abstract::A large body of evidence has accumulated indicating involvement of oxidative stress (OS) in the mode of action of various bioactive substances, including those of the immune system. The data for anticancer drugs (main and miscellaneous) are summarized herein. Although diverse origins pertain, reactive oxygen species (...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003401046
更新日期:2000-02-01 00:00:00
abstract::Surgery for epilepsy dates back to 1886 and has undergone significant developments. Today it is considered a key treatment modality in patients who are resistant to pharmacological intervention. It improves seizure control, cognition and quality of life. New technologies, advances in surgical technique and progress in...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666171031101839
更新日期:2017-01-01 00:00:00
abstract::The heart is a sophisticated endocrine gland synthesizing a family of peptide hormones by three different genes. These cardiac hormones are stored as 3 prohormones, i.e. atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) prohormones. Within the ANP prohormones are 4 ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210790963887
更新日期:2010-01-01 00:00:00
abstract::The current gold standard for imaging infection is radiolabeled white blood cells. For reasons of safety, simplicity and cost, it would be desirable to have a receptor-specific ligand that could be used for imaging infection and that would allow a differential diagnosis between sterile and septic inflammatory processe...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786549416
更新日期:2008-01-01 00:00:00
abstract::There is extensive evidence that changes in immune system activation accompany the pathological changes of Alzheimer's disease (AD), but a mechanistic understanding of how the immune system actually participates in disease pathogenesis is still largely lacking. Because of the complexity of the immunological response, ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161205774370843
更新日期:2005-01-01 00:00:00
abstract::Treatment of chronic lymphocytic leukemia (CLL) has recently undergone revolutionary changes. Two large randomized trials demonstrated superiority of chemoimmunotherapy combining fludarabine and cyclophosphamide with monoclonal anti-CD20 antibody rituximab (FCR) over fludarabine and cyclophosphamide (FC) alone in firs...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212801227096
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Intracerebral hemorrhage (ICH) is the most lethal subtype of stroke, a leading cause of death and disability in developed countries. Therapeutic options are notably limited. There is no specific pharmacological treatment, and early surgery has few indications that represent only a small clinically relevant s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161221153937
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Cell-cell adhesion is essential in maintaining the structure and function of an organ. Several adhesion molecules have recently been identified as associated with heroin dependence in both genetic and peripheral plasma studies. METHODS AND RESULTS:We reviewed literature concerning studies on adhesion molecu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200116144147
更新日期:2020-01-01 00:00:00
abstract::CHD is one of the most common serious chronic conditions in postmenopausal women and leads to extremely high risk for recurrent myocardial infarction and death. On the basis of the currently available randomized clinical-trial results the role of conventional HRT for treatment and prevention of CHD is rapidly evolving...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161205774913237
更新日期:2005-01-01 00:00:00
abstract::We carried out a systematic review of HPV vaccine pre- and post-licensure trials to assess the evidence of their effectiveness and safety. We find that HPV vaccine clinical trials design, and data interpretation of both efficacy and safety outcomes, were largely inadequate. Additionally, we note evidence of selective ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::Phytoestrogens are plant-derived compounds with estrogen-like activities. Certain foods such as soy-derived products are known to have high levels of phytoestrogens, and about 25% of commercial infant formulas used in the United States are soy-based. One of the most important phytoestrogens is the isoflavone genistein...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043383683
更新日期:2004-01-01 00:00:00
abstract::Drug-drug interactions may occur when to combine two or more drugs and may cause some adverse events such as Cardiotoxicity, Central neurotoxicity, Hepatotoxicity, etc. Although a large number of researchers who are proficient in pharmacokinetics and pharmacodynamics have been engaged in drug assays and trying to find...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612827666210127122312
更新日期:2021-01-27 00:00:00
abstract::Severe acute respiratory syndrome-coronavirus (SARS-CoV-2, or COVID-19 virus) is a worldwide pandemic pathogen infecting 210 territories. It belongs to the family coronaviriadae and the order Nidovirales. The SARS-CoV-2 virus is a positive-sense single-stranded RNA enveloped virus that includes spike proteins projecti...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201222162509
更新日期:2020-12-22 00:00:00
abstract::Cancer and tumor have been major reasons for numerous deaths in this century across the world. Many strategies have been designed to treat, diagnose, or prevent cancer. The success of chemotherapy largely depends on drug targeting. The advent of nanotechnology has vastly improved drug delivery for targeting and diagno...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200720235752
更新日期:2020-01-01 00:00:00
abstract::Elevated levels of Low Density Lipoprotein cholesterol (LDL-C) are directly associated with increased risk for atherosclerotic cardiovascular and cerebrovascular events. Statins have been used to control serum LDLC and this has translated into reduction in cardiovascular and cerebrovascular events. However, despite hi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180111105201
更新日期:2018-01-01 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::The OB-receptor or leptin receptor (LR) is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream. Under normal circumstances, circulating leptin levels are proportionate to the fat body mass. Sensing of elevated leptin levels ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113196660743
更新日期:2014-01-01 00:00:00
abstract::Pro-rich antimicrobial peptides are a group of linear peptides of innate immunity isolated from mammals and invertebrates, and characterised by a high content of proline residues (up to 50%). Members of this group are predominantly active against Gram-negative bacterial species which they kill by a non-lytic mechanism...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023395394
更新日期:2002-01-01 00:00:00
abstract::Diabetic retinopathy remains the most common microvascular complication suffered by diabetic patients and is the leading cause of registerable blindness in the working population of developed countries. The clinicopathological lesions of diabetic retinopathy have been well characterised and although a multitude of pat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043383124
更新日期:2004-01-01 00:00:00
abstract::Phosphodiesterase 2 (PDE2) is a ubiquitous enzyme whose major role is to hydrolyze the important second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). In the central nervous system, pharmacological inhibition of PDE2 results in boosted cAMP and/or cGMP signaling, which is r...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140826115245
更新日期:2015-01-01 00:00:00
abstract::The present review discusses the mechanism of late stent thrombosis and its distinction from restenosis and summarizes the advisory note issued by FDA on the proper usage of different treatments available for atherosclerosis. In light of the latest developments, a plethora of new stents have been and continue to be de...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208785294573
更新日期:2008-01-01 00:00:00
abstract::During the last two decades since the identification and characterization of T cell potassium channels great advances have been made in the understanding of the role of these channels in T cell functions, especially in antigen-induced activation. Their limited tissue distribution and the recent discovery that differen...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777585120
更新日期:2006-01-01 00:00:00
abstract::Since the discovery of human immunodeficiency virus (HIV) as a causative agent of acquired immune deficiency syndrome (AIDS) various strategies were employed to counter its devastating actions. One such concept relies on the prevention of HIV entry into host's "competent" cells by means of compounds known as entry inh...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319100003
更新日期:2013-01-01 00:00:00
abstract::The brain is a complex, regulated organ with a highly controlled access mechanism: The Blood-Brain Barrier (BBB). The selectivity of this barrier is a double-edged sword, being both its greatest strength and weakness. This weakness is evident when trying to target therapeutics against diseases within the brain. Diseas...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612824666171201115126
更新日期:2018-01-01 00:00:00
abstract::An integrative synthesis of concepts and an explosion of experimental and epidemiological findings allow new insights as to how the interactions of genetic, environmental, dietary, cultural (social, psychological, economic) factors can influence the aging and diseases of aging processes. Although the net effect of the...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786264106
更新日期:2008-01-01 00:00:00
abstract::Innate and adaptive immunity has been shown to be critically involved in the pathogenesis of atherosclerosis. In particular, immune suppression mediated by regulatory T cells (Tregs) or tolerogenic dendritic cells (DCs) serves as a vital mechanism for regulating pathogenic chronic inflammation in atherogensis, suggest...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666141013142518
更新日期:2015-01-01 00:00:00
abstract::Several diseases of the heart have been linked to an insufficient ability to generate enough energy (ATP) to sustain proper heart function. Hyperpolarized magnetic resonance (MR) is a novel technique that can visualize and quantify myocardial energy metabolism. Hyperpolarization enhances the MR signal from a biologica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140417113720
更新日期:2014-01-01 00:00:00
abstract::Estrogens are known as important modulators of development, growth and maintenance of primary sexual physiology. The medical field has also grown increasingly appreciative of the effects of estrogens on non-traditional target tissues such as bone, cardiovascular tissue and the CNS. Postmenopausal women have been the b...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023393404
更新日期:2002-01-01 00:00:00
abstract::Alzheimer's disease (AD) is a progressive age-related neurodegenerative disorder with distinct neuropathological features. Extracellular plaques, consisting of aggregated amyloid peptides of 39-43 amino acids are one of the most prominent pathological hallmarks of this disease. Although the exact neurochemical effecto...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206775474297
更新日期:2006-01-01 00:00:00
abstract::Carvedilol is a nonselective β-blocker with α1-adrenergic blocking and antioxidant properties. A number of preclinical experiments and clinical trials have demonstrated that carvedilol provides prominent benefit in heart failure. However, less research has been done in the area of animal models of viral myocarditis. T...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212799958530
更新日期:2012-01-01 00:00:00