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::Ablation has become an important treatment for many pediatric patients with common supraventricular tachycardias (SVTs). Many multicenter studies have documented that radiofrequency (RF) catheter ablation is a safe and effective procedure for treatment of a large variety of SVTs in children and adults with a high succ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784007680
更新日期:2008-01-01 00:00:00
abstract::Myocarditis is a disease whose pathogenesis is not completely understood and whose prevalence is likely underestimated. Individuals afflicted with this condition may be treated with agents that relieve symptoms arising from inflammation and concurrent cellular damage. One class of drugs commonly used in the treatment ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033455440
更新日期:2003-01-01 00:00:00
abstract::Systemic hypersensitivity (HS) to corticosteroids (CS) is paradoxical but does exist. Some patients with a previous contact allergy to topical CS may develop a systemic contact dermatitis (SCD) while receiving CS orally or intravenously. However, a previous contact sensitization is not mandatory for developing a syste...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161013092339
更新日期:2016-01-01 00:00:00
abstract::The receptor for urokinase plasminogen activator (uPAR) is required in hematopoietic stem/progenitor cells (HSC, HPC) mobilization in the mouse. Indeed, uPAR Ko mice are deficient both in retention and mobilization of HSC and HPC, because uPAR causes their retention in the BM through its interaction with the α4β1 inte...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161211796718206
更新日期:2011-01-01 00:00:00
abstract::The involvement of the central nervous system (CNS) is one of the major causes of morbidity and mortality in systemic lupus erythematosus (SLE) patients and the less understood aspect of the disease. Its recognition and treatment continue to represent a major diagnostic and therapeutic challenge. Due to the lack of co...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208799316401
更新日期:2008-01-01 00:00:00
abstract::Immunotoxins (ITs) are protein-based drugs combining a target-specific binding domain (usually derived from an antibody) and a cytotoxic domain to kill target cells. They are among the most promising new therapeutic tools to fight cancer, and several clinical trials have been completed with encouraging results. Althou...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788923930
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Sulfur mustard (SM)-induced airway injuries and chronic obstructive pulmonary disease (COPD) are characterized by chronic inflammation of the respiratory tract and share some similarities regarding the cellular and molecular mechanisms orchestrating airway destruction. Since available data regarding the immu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160307150818
更新日期:2016-01-01 00:00:00
abstract::Separating emotions from cognition seems impossible in everyday experiences of a human being. Emotional processes have an impact on the ability of planning and solving problems, or decision-making skills. They are a valuable source of information about ourselves, our partners in interactions and the surrounding world....
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151230110738
更新日期:2016-01-01 00:00:00
abstract::Hypertension is the most common medical disorder during pregnancy. Approximately 70 percent of women diagnosed with hypertension during pregnancy will have gestational hypertension-preeclampsia. The term gestational hypertension-preeclampsia is used to describe a wide spectrum of patients who may have only mild elevat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053381864
更新日期:2005-01-01 00:00:00
abstract::Cellular uptake of therapeutic oligonucleotides and subsequent intracellular trafficking to their target sites represents the major technical hurdle for the biological effectiveness of these potential drugs. Accordingly, laboratories worldwide focus on the development of suitable delivery systems. Among the different ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786898806
更新日期:2008-01-01 00:00:00
abstract::Human tryptase is a structurally unique and mast cell specific trypsin-like serine protease. Recent biological and immunological investigations have implicated tryptase as a mediator in the pathology of numerous allergic and inflammatory conditions including rhinitis, conjunctivitis, and most notably asthma. A growing...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:1998-10-01 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::In the mid seventies a drug design programme using the Amanita muscaria constituent muscimol (7) as a lead structure, led to the design of guvacine (23) and (R)-nipecotic acid (24) as specific GABA uptake inhibitors and the isomeric compounds isoguvacine (10) and isonipecotic acid (11) as specific GABAA receptor agoni...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003399608
更新日期:2000-08-01 00:00:00
abstract::The prevalence of hypertension (HTN) worldwide is high and is constantly rising. HTN is considered to be a silent killer since often there are no obvious symptoms but long-term, HTN significantly increases the risk of coronary heart disease and cerebrovascular diseases. Those with diagnosed HTN or at high risk of its ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170215144649
更新日期:2017-01-01 00:00:00
abstract::Cytokines are glycoproteins that serve as chemical messengers between cells. They assist in the regulation of cell growth and repair and also have immune modulating properties. Cytokines play a role in diverse clinical processes and phenomena such as fatigue, fever, sleep, pain, stress and aching. A review of the fibr...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2006-01-01 00:00:00
abstract::Psoriasis is an immune-mediated, chronic and recurrent inflammatory skin disease, prevalent worldwide, and represents an important burden in life quality of patients. The most common clinical variant is termed as psoriasis vulgaris or plaque psoriasis, which with an individualized and carefully monitored therapy can d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190618122024
更新日期:2019-01-01 00:00:00
abstract::In the stomach, pre-absorptive perception of food constituents is of particular importance in maintaining secretion and motility that matches the quantity and quality of nutrients. Products of food protein hydrolysis, free amino acids and short peptides, are the most potent chemical stimulants of the gastric phase of ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990581
更新日期:2014-01-01 00:00:00
abstract::Tissue-engineered oral mucosal equivalents have been developed for in vitro studies for a few years now. However, the usefulness of currently available models is still limited by many factors, mainly the lack of a physiological extracellular matrix (ECM) and the use of cell populations that do not reflect the properly...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212803307482
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:New Oral Anticoagulants (NOACs) are effective and widely used to prevent and treat thromboembolic diseases, but the response to NOACs differs according to ABCB1 genotypes. OBJECTIVE:We investigated the effects of ABCB1 genotypes on the pharmacokinetics and clinical outcomes of NOACs. METHODS:We searched Pu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,meta分析,评审
doi:10.2174/1381612824666181018153641
更新日期:2018-01-01 00:00:00
abstract::The triggering receptor expressed on myeloid cells (TREM)-1 is a member of the Ig-like immunoregulatory receptor family and a major amplifier of innate immune responses. TREM- 1 has been implicated in the development and perpetuation of a number of inflammatory disorders, and soluble TREM-1 levels are a clinically val...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160826110539
更新日期:2016-01-01 00:00:00
abstract::Drug design based on the structure of specific enzymes playing a role in carcinogenesis, e.g. tyrosine kinases, has been successful at identifying novel effective anticancer drugs. In contrast, no success has been achieved in drug design attempts, in which transcription factors or DNA-transcription factor complexes in...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207781757097
更新日期:2007-01-01 00:00:00
abstract::By updating John Littleton's work published 15 years ago this review summarizes recent work on pharmacodynamic aspects of acamprosate and the perspective for future developments. In addition to insights into the role of glutamatergic receptor systems, craving and relapse inspired by acamprosate, clinical research poin...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210791516341
更新日期:2010-01-01 00:00:00
abstract::The impact of depression on physical disability is undisputed. There is convincing evidence that depression increases the subsequent risk for physical disability and, in turn, physical disability results in increased depressive symptoms. Moreover, depression affects also the earlier stages of the disablement process (...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113196660060
更新日期:2014-01-01 00:00:00
abstract::In recent years, combination of different types of therapies using nanoparticles has emerged as an advanced strategy for cancer treatment. Most of all, combination of chemotherapeutic drug and siRNA in nanoformulation has shown a great potential, because siRNA-mediated specific gene silencing can compensate for the in...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150531165059
更新日期:2015-01-01 00:00:00
abstract::Both high arterial blood pressure (BP) and elevated levels of fine particulate matter (PM2.5) air pollution have been associated with an increased risk for several cardiovascular (CV) diseases, including stroke, heart failure, and myocardial infarction. Given that PM2.5 and high BP are each independently leading risk ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151109111712
更新日期:2016-01-01 00:00:00
abstract::Plasma concentrations of phytosterols and non-cholesterol sterol precursors of cholesterol synthesis have been used as markers of intestinal cholesterol absorption and synthesis in inherited and secondary dyslipidemias and in population-based investigations to evaluate the risk for cardiovascular disease, respectively...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200730220230
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Type 2 diabetes mellitus (DM) is associated with a considerable risk of cardiovascular and renal disease, including heart failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated unprecedented cardiorenal protective effects in large scale clinical trials of patients with or without diabet...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201103122813
更新日期:2020-11-03 00:00:00
abstract::Nanoparticles have gained ground in several fields. However, it is important to consider their potentially hazardous effects on humans, flora, and fauna. Human exposure to nanomaterials can occur unintentionally in daily life or in industrial settings, and the continuous exposure of the biological components (cells, r...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190926161209
更新日期:2019-01-01 00:00:00
abstract::Packaging small-molecule drugs into nanoparticles improves their bio-availability, bio-compatibility and safety profiles. Multifunctional particles carrying large drug payloads for targeted transport, immune evasion and favourable drug release kinetics at the target site, require a certain minimum size usually 30-300 ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787002870
更新日期:2009-01-01 00:00:00
abstract::The analysis of enantiorecognition processes involves the detection of enantiomeric species as well as the study of chiral discrimination mechanisms. In both fields Nuclear Magnetic Resonance (NMR) spectroscopy plays a fundamental role, providing several tools, based on the use of suitable chiral auxiliaries, for obse...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778743628
更新日期:2006-01-01 00:00:00