Abstract:
:The antimicrobial agents used in the treatment of mycobacterial infections have remained largely unchanged for several decades. Primary treatment of tuberculosis relies on four drugs, isoniazid, a rifamycin, pyrazinamide, and ethambutol (or streptomycin), and generally results in >95% cure in uncomplicated tuberculosis infection. Drug resistance greatly complicates treatment of this disease. Treatment of tuberculosis caused by multiply drug-resistant strains with "second-line" drugs remains complex, and is generally tailored to the individual patient and strain. Several of the fluoroquinolones have shown promise as second line drugs for treatment of active disease and, in combination with clarithromycin or azithromycin, ethambutol, and other agents, for treatment of Mycobacterium avium complex infection. While large clinical trials are not possible with second line drugs, clinical treatment data are available and suggest that the quinolones have various degrees of promise in treatment of these infections. Bacterial type II DNA topoisomerases, DNA gyrase and topoisomerase IV, are the targets of quinolones, and provide the genetic basis for quinolone activity in mycobacteria. Mutations in these enzymes results in resistance, and characterization of resistant mutants allows correlation of genotype with susceptibility phenotype. Structure-activity relationship studies have provided further insight into optimal use of quinolones in mycobacterial infections. Care should be taken in treating pneumonia with fluoroquinolones if there is a degree of suspicion of tuberculosis, since quinolone monotherapy may rapidly select for quinolone resistance, thereby removing that class of antibiotic from the small range of treatment options.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Jacobs MRdoi
10.2174/1381612043383296subject
Has Abstractpub_date
2004-01-01 00:00:00pages
3213-20issue
26eissn
1381-6128issn
1873-4286journal_volume
10pub_type
杂志文章,评审abstract::Macrolides have broad antibacterial spectrum and proven efficacy in the management of respiratory tract infections. Over the past decade there has been progressive interest in these agents for their potential role as tissue modifying, anti-inflammatory agents. Increasingly, the effect of macrolides on numerous cell ty...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043383304
更新日期:2004-01-01 00:00:00
abstract::Free energy perturbation (FEP) theory coupled to molecular dynamics (MD) or Monte Carlo (MC) statistical mechanics offers a theoretically precise method for determining the free energy differences of related biological inhibitors. Traditionally requiring extensive computational resources and expertise, it is only rece...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212799436421
更新日期:2012-01-01 00:00:00
abstract::Despite the significant progresses made in antiretroviral therapy, current drugs still cannot cure or prevent HIV infection. And all drugs continue to select for drug-resistant HIV strains. Consequently, new antiretroviral drugs are constantly being developed. To ensure safety, these drugs are usually designed to inhi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043382422
更新日期:2004-01-01 00:00:00
abstract:: ...
journal_title:Current pharmaceutical design
pub_type: 社论
doi:10.2174/1381612825999190515120510
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:According to the World Health Organization (WHO), diabetes mellitus is considered the 7th leading cause of death as of 2016, while almost half of all deaths related to high blood glucose occur before the age of 70. According to the 2019 American Diabetes Association's (ADA) guidelines, metformin is the first...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200408095310
更新日期:2020-01-01 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::Osteoblasts pass through a sequence of events controlled by hormones and transcriptional factors ensuring proper development of phenotype and functional properties until the osteoblast enter the osteocyte phenotype and/or undergo apoptosis. During its life cycle, the osteoblasts proliferate, deposit matrix proteins an...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013398167
更新日期:2001-03-01 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::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::Dengue is one of the most important arboviral infections worldwide, infecting up to 390 million people and causing 25,000 deaths annually. Although a licensed dengue vaccine is available, it is not efficacious against dengue serotypes that infect people living in South East Asia, where dengue is an endemic disease. He...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170913163904
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Central serous chorioretinopathy (CSC) is the fourth most frequent retinal disorder in terms of prevalence. It typically occurs in young subjects and affects men more often than women. CSC is characterized by serous retinal detachment (SRD) involving mainly the macular area. The clinical course is usually se...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190123165914
更新日期:2018-01-01 00:00:00
abstract::The snake is the symbol of medicine due to its association with Asclepius, the Greek God of medicine, and so with good reasons. More than 725 species of venomous snakes have toxins specifically evolved to exert potent bioactivity in prey or victims, and snakebites constitute a public health hazard of high impact in As...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160623073438
更新日期:2016-01-01 00:00:00
abstract::Methicillin-resistant Staphylococcus aureus (MRSA) remains the single biggest challenge in infectious disease in the civilized world. Moreover, vancomycin resistance is also spreading, leading to fears of untreatable infections as were common in ancient times. Molecular microbiology and bioinformatics have revealed ma...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150310101851
更新日期:2015-01-01 00:00:00
abstract::Inhibition of the renin-angiotensin system (RAS) has been shown to have beneficial effects in cardiovascular disease prognosis and therapy.Discovery of (pro)renin receptor [(P)RR] revealed that (P)RR upon binding to both renin or prorenin in their proenzyme inactive form made them enzymatically active, thus aiding the...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990472
更新日期:2014-01-01 00:00:00
abstract::The pharmacophore concept is central to the rational drug design and discovery process. Traditionally, a pharmacophore is defined as a specific three-dimensional (3D) arrangement of chemical functional groups found in active molecules, which are characteristic of a certain pharmacological class of compounds. Herein, b...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013397834
更新日期:2001-05-01 00:00:00
abstract::Crohn's disease and ulcerative colitis are the two principal forms of inflammatory bowel disease (IBD). The root causes of these chronic and acute immunological disorders are unclear, but intestinal microorganisms are known to play a key role in the initiation and maintenance of disease. However, at present, there is ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788168146
更新日期:2009-01-01 00:00:00
abstract::The state-of-the-art in the investigation of drugs release from Silica-based ordered Mesoporous Materials (SMMs) is reviewed. First, the SMM systems used like host matrixes are described. Then, the model drugs studied until now, including their pharmacological action, structure and the mesoporous matrix employed for e...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151106121419
更新日期:2015-01-01 00:00:00
abstract::Neuregulin1 proteins (NRG1s) are epidermal growth factor (EGF) family members which are ligands for the ErbB receptor tyrosine kinases (RTKs). A decade of research has revealed that the NRG1-ErbB signaling is essential for the cardiac development and pivotal for maintaining the physiological function of the adult hear...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211796391010
更新日期:2011-01-01 00:00:00
abstract::In the last two decades a tremendous development has been noticed in our understanding of the purinergic system, consisting of heterogeneously expressed purinoceptor subtypes and its classical agonists: e.g., adenosine triphosphate, uridine triphosphate or complex dinucleoside polyphosphates. These agonists exert mult...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803582504
更新日期:2012-01-01 00:00:00
abstract::Cardiac ischemia, followed by reperfusion, often results in the development of cardiac contractile dysfunction that limits the recovery prognosis of patients. The current goal of pharmacological therapy in the course of ischemic heart disease is to improve the oxygen supply/demand ratio for the heart. Cardiac contract...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990556
更新日期:2014-01-01 00:00:00
abstract::The drug discovery process in general is a very resource intensive undertaking that has existed for a very long time. In the last two decades, performing molecular simulations that determine the level of interaction between a protein and ligand have been refined to the point where they are now an essential part of the...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160414142530
更新日期:2016-01-01 00:00:00
abstract::In the last two decades quantitative electroencephalogram (EEG) analysis has been widely used to investigate the neurophysiological characteristics of insomnia. These studies provided evidence in support of the hypothesis that primary insomnia is associated with hyperarousal of central nervous system and altered sleep...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786549326
更新日期:2008-01-01 00:00:00
abstract::Alzheimer's disease (AD) is the most common form of dementia in the elderly. Research focused on identifying compounds that restore cognition and memory in AD patients is a very active investigational pursuit, but unfortunately, it has been only successful in terms of developing symptomatic treatments. Aβ deposition a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150914121149
更新日期:2015-01-01 00:00:00
abstract::The tumor cell growth inhibitory activities (log 1/GI(50)) of 166 anticancer agents studied at the National Cancer Institute (NCI) in vitro anticancer screening program have allowed us to analyze the relative importance of physicochemical parameters in influencing the inhibitory activities. Increased molecular weight,...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612043384925
更新日期:2004-01-01 00:00:00
abstract::More and more evidences are still accumulating rapidly on the G-protein-coupled-receptors (GPCRs) dimerization/oligomerization. Such common feature of GPCRs has called extensive attention to both pharmacologists and medicinal chemists for illustration of the pharmacological functions and therapeutic utilities of such ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787315639
更新日期:2009-01-01 00:00:00
abstract::Drug hypersensitivity reactions (DHRs) represent a major burden on the healthcare system since their diagnostic and management are complex. As they can be influenced by individual genetic background, it is conceivable that the identification of variants in genes potentially involved could be used in genetic testing fo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666191105122414
更新日期:2019-01-01 00:00:00
abstract::Uveitis is a sight threatening intraocular inflammation accounting for approximately 10% of blindness worldwide. On the basis of aetiology, disease can be classified as infectious or non-infectious; and by anatomical localization of inflammation as anterior, posterior and panuveitis. Non-infectious uveitis is believed...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150316122928
更新日期:2015-01-01 00:00:00
abstract::The signal transducer and activator of transcription 3 (STAT3) transduces stress signals from the plasma membrane to the nucleus but has recently also been identified in mitochondria. Inhibition of cardiomyocyte mitochondrial STAT3 with the STAT3-specific inhibitor Stattic decreases ADP-stimulated respiration and enha...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161281939131127115940
更新日期:2013-01-01 00:00:00
abstract::Multidrug resistance (MDR) is a phenomenon through which tumor cells develop resistance against the cytotoxic effects of various structurally and mechanistically unrelated chemotherapeutic agents. The most consistent feature in MDR is overexpression and/or overactivity of ATP-dependent drug efflux transporters. Other ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151124234417
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Endothelial dysfunction is commonly present in estrogen-deficient states, e.g., after menopause. In the search for alternatives to hormone replacement therapy (HRT), treatments based on phytoestrogens or in non-hormonal mechanisms have been under evaluation. OBJECTIVE:Here we aim to present an overview of i...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200331084338
更新日期:2020-01-01 00:00:00