Topical microbicides to prevent HIV: clinical drug development challenges.

abstract：:A number of exciting findings have been made in astrocytes during the past 15 years that have led many researchers to redefine how the brain works. Astrocytes are now widely regarded as cells that propagate Ca(2+) over long distances in response to stimulation, and, similar to neurons, release transmitters (called gli...

journal_title：Annual review of pharmacology and toxicology

authors： Fiacco TA,Agulhon C,McCarthy KD

更新日期：2009-01-01 00:00:00

abstract：:The promise of drug repurposing is to accelerate the translation of knowledge to treatment of human disease, bypassing common challenges associated with drug development to be more time- and cost-efficient. Repurposing has an increased chance of success due to the previous validation of drug safety and allows for the ...

journal_title：Annual review of pharmacology and toxicology

authors： Pulley JM,Rhoads JP,Jerome RN,Challa AP,Erreger KB,Joly MM,Lavieri RR,Perry KE,Zaleski NM,Shirey-Rice JK,Aronoff DM

更新日期：2020-01-06 00:00:00

abstract：:The mammalian circadian system is organized in a hierarchical manner in that a central pacemaker in the suprachiasmatic nucleus (SCN) of the brain's hypothalamus synchronizes cellular circadian oscillators in most peripheral body cells. Fasting-feeding cycles accompanying rest-activity rhythms are the major timing cue...

journal_title：Annual review of pharmacology and toxicology

authors： Levi F,Schibler U

更新日期：2007-01-01 00:00:00

abstract：:Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme ...

journal_title：Annual review of pharmacology and toxicology

authors： Insel PA,Amara SG,Blaschke TF,Meyer UA

更新日期：2017-01-06 00:00:00

abstract：:The recognition that the wall tone of most arteries and veins can change in response to shear stress has several implications for our understanding of the effects of drugs on the circulation. By a primary action on the heart and vasculature, drugs can cause changes in cardiac output and blood pressure that lead to cha...

journal_title：Annual review of pharmacology and toxicology

authors： Bevan JA,Henrion D

更新日期：1994-01-01 00:00:00

abstract：:Arterial tone is coordinated among vessel segments to optimize nutrient transport and organ function. Coordinated vasomotor activity is remarkable to observe and depends on stimuli, sparsely generated in tissue, eliciting electrical responses that conduct lengthwise among electrically coupled vascular cells. The condu...

journal_title：Annual review of pharmacology and toxicology

authors： Welsh DG,Tran CHT,Hald BO,Sancho M

更新日期：2018-01-06 00:00:00

abstract：:The recent advances made in elucidating the processes of nociception have altered the way that chronic pain therapy and analgesic drug development are approached. Recent studies have highlighted new targets for drug discovery, including inhibition of inflammatory mediators (kinins, growth factors), newly expressed pro...

journal_title：Annual review of pharmacology and toxicology

authors： Dray A,Urban L

更新日期：1996-01-01 00:00:00

abstract：:Pluripotent stem cells (PSCs) are a potential replacement tissue source for degenerative diseases. Age-related macular degeneration (AMD) is a blinding disease triggered by degeneration of the retinal pigment epithelium (RPE), a monolayer tissue that functionally supports retinal photoreceptors. Recently published cli...

journal_title：Annual review of pharmacology and toxicology

authors： Sharma R,Bose D,Maminishkis A,Bharti K

更新日期：2020-01-06 00:00:00

abstract：:Transgenic rodent models for measuring mutations provide a tool for assessing tissue-specific mutations following in vivo treatment. These systems are based on the insertion into the rodent genome Escherichia coli lacI (lac repressor) or lacZ (beta-galactosidase) genes that serve as targets for mutations. Following in...

journal_title：Annual review of pharmacology and toxicology

authors： Mirsalis JC,Monforte JA,Winegar RA

更新日期：1995-01-01 00:00:00

abstract：:Mutant ras oncogenes and alterations in the mitogenic signaling pathways that they regulate are associated with a wide variety of solid tumors and leukemias for which existing chemotherapeutics have limited utility. Of the possible approaches to inhibit Ras function, much attention has focused on a posttranslational m...

journal_title：Annual review of pharmacology and toxicology

authors： Gibbs JB,Oliff A

更新日期：1997-01-01 00:00:00

abstract：:Conflicting views abound on the peripheral neurotransmitter and neuromodulator roles of purine compounds. Substantial organ- and species-related variations have become apparent. There is, however, a body of compelling evidence for such roles, if not so broad and ubiquitous as those envisioned (7) for the central nervo...

journal_title：Annual review of pharmacology and toxicology

authors： Su C

更新日期：1983-01-01 00:00:00

abstract：:Arsenic is a naturally occurring metalloid and one of the few metals that can be metabolized inside the human body. The pervasive presence of arsenic in nature and anthropogenic sources from agricultural and medical use have perpetuated human exposure to this toxic and carcinogenic element. Highly exposed individuals ...

journal_title：Annual review of pharmacology and toxicology

authors： Chen QY,Costa M

更新日期：2021-01-06 00:00:00

abstract：:Behavioral consequences of low-level lead (Pb) exposure include impairments in learning processes and in Fixed-Interval schedule-controlled operant behavior. Although the neurobiological bases of these effects remain undetermined, current evidence suggests that inhibitory effects of Pb on the NMDA receptor complex may...

journal_title：Annual review of pharmacology and toxicology

authors： Cory-Slechta DA

更新日期：1995-01-01 00:00:00

abstract：:The protein variously named ABCG2/BCRP/MXR/ABCP is a recently described ATP-binding cassette (ABC) transporter originally identified by its ability to confer drug resistance that is independent of Mrp1 (multidrug-resistance protein 1) and Pgp (P-glycoprotein). Unlike Mrp1 and Pgp, ABCG2 is a half-transporter that must...

journal_title：Annual review of pharmacology and toxicology

authors： Krishnamurthy P,Schuetz JD

更新日期：2006-01-01 00:00:00

abstract：:Numerous lines of evidence demonstrate that calpains, a family of 14 Ca(2+)-activated neutral cysteine proteases, are involved in oncotic cell death in a variety of models. At this time, the biochemistry of most calpains and the specific roles of different calpains in physiology and pathology remain to be determined. ...

journal_title：Annual review of pharmacology and toxicology

authors： Liu X,Van Vleet T,Schnellmann RG

更新日期：2004-01-01 00:00:00

abstract：:Electron cryo-microscopy (cryo-EM) has revolutionized structure determination of membrane proteins and holds great potential for structure-based drug discovery. Here we discuss the potential of cryo-EM in the rational design of therapeutics for membrane proteins compared to X-ray crystallography. We also detail recent...

journal_title：Annual review of pharmacology and toxicology

authors： García-Nafría J,Tate CG

更新日期：2020-01-06 00:00:00

abstract：:Either an excess or a deficiency of vitamin A and related compounds (retinoids) causes abnormal morphological development (teratogenesis). Potential retinoid sources come from dietary intake, nutritional supplements, and some therapeutic drugs. Therefore, understanding the mechanisms of retinoid teratogenesis is impor...

journal_title：Annual review of pharmacology and toxicology

authors： Collins MD,Mao GE

更新日期：1999-01-01 00:00:00

abstract：:Long-acting contraceptives are the most effective reversible contraceptive methods. Increasing patients' access to these contraceptives may translate into fewer unintended pregnancies and lead to substantial individual and public health benefits. However, development of long-acting products can be complex and challeng...

journal_title：Annual review of pharmacology and toxicology

authors： Li L,Tran D,Zhu H,Balimane P,Willett G,Zhao P,Gerrard SE,Vogelsong KM,Wang Y,Seo SK

更新日期：2021-01-06 00:00:00

abstract：:γ-Secretases are a group of widely expressed, intramembrane-cleaving proteases involved in many physiological processes. Their clinical relevance comes from their involvement in Alzheimer's disease, cancer, and other disorders. A clinical trial with the wide-spectrum γ-secretase inhibitor semagacestat has, however, de...

journal_title：Annual review of pharmacology and toxicology

authors： De Strooper B,Chávez Gutiérrez L

更新日期：2015-01-01 00:00:00

abstract：:Kv7 channels (Kv7.1-7.5) are voltage-gated K+ channels that can be modulated by five β-subunits (KCNE1-5). Kv7.1-KCNE1 channels produce the slow-delayed rectifying K+ current, IKs, which is important during the repolarization phase of the cardiac action potential. Kv7.2-7.5 are predominantly neuronally expressed and c...

journal_title：Annual review of pharmacology and toxicology

authors： Thompson E,Eldstrom J,Fedida D

更新日期：2021-01-06 00:00:00

abstract：:The Risk Assessment Committee of the European Chemicals Agency issued an opinion on classifying titanium dioxide (TiO2) as a suspected human carcinogen upon inhalation. Recent animal studies indicate that TiO2 may be carcinogenic through the oral route. There is considerable uncertainty on the carcinogenicity of TiO2,...

journal_title：Annual review of pharmacology and toxicology

authors： Braakhuis HM,Gosens I,Heringa MB,Oomen AG,Vandebriel RJ,Groenewold M,Cassee FR

更新日期：2021-01-06 00:00:00

abstract：:Research spanning (genetically engineered) animal models, healthy volunteers, and sleep-disordered patients has identified the neurotransmitters and neuromodulators dopamine, serotonin, norepinephrine, histamine, hypocretin, melatonin, glutamate, acetylcholine, γ-amino-butyric acid, and adenosine as important players ...

journal_title：Annual review of pharmacology and toxicology

authors： Holst SC,Valomon A,Landolt HP

更新日期：2016-01-01 00:00:00

abstract：:Recent discoveries of novel and potentially important biological activity have spurred interest in the chemistry and biochemistry of nitroxyl (HNO). It has become clear that, among all the nitrogen oxides, HNO is unique in its chemistry and biology. Currently, the intimate chemical details of the biological actions of...

journal_title：Annual review of pharmacology and toxicology

authors： Fukuto JM,Switzer CH,Miranda KM,Wink DA

更新日期：2005-01-01 00:00:00

abstract：:Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) are two Ca(2+) messengers derived from NAD and NADP, respectively. Although NAADP is a linear molecule, structurally distinct from the cyclic cADPR, it is synthesized by similar enzymes, ADP-ribosyl cyclase and its homolog, CD38. The c...

journal_title：Annual review of pharmacology and toxicology

authors： Lee HC

更新日期：2001-01-01 00:00:00

abstract：:Oligonucleotides (ONs) can interfere with biomolecules representing the entire extended central dogma. Antisense gapmer, steric block, splice-switching ONs, and short interfering RNA drugs have been successfully developed. Moreover, antagomirs (antimicroRNAs), microRNA mimics, aptamers, DNA decoys, DNAzymes, synthetic...

journal_title：Annual review of pharmacology and toxicology

authors： Smith CIE,Zain R

更新日期：2019-01-06 00:00:00

abstract：:The cost of drugs is a major and rapidly rising component of health-care expenditures. We survey recent literature on the ethics and economics of skyrocketing pharmaceutical prices and find that advances in economic research have increased the sharpness and focus of the ethically based calls to increase access by modi...

journal_title：Annual review of pharmacology and toxicology

authors： Parker-Lue S,Santoro M,Koski G

更新日期：2015-01-01 00:00:00

abstract：:Both pharmacologic and genetic methods are now available to manipulate intracellular levels of the protein thiol metallothionein. These approaches have begun to reveal the protective roles metallothioneins (MTs) have against oxygen, nitrogen, and carbon-centered free radicals, as well as the contributory role of MT to...

journal_title：Annual review of pharmacology and toxicology

authors： Lazo JS,Pitt BR

更新日期：1995-01-01 00:00:00

abstract：:Parkinson's disease (PD) is a chronic, progressive, disabling neurodegenerative disorder that begins in mid to late life and is characterized by motor impairment, autonomic dysfunction, and, in many, psychological and cognitive changes. Recent advances have helped delineate pathogenetic mechanisms, yet the cause of PD...

journal_title：Annual review of pharmacology and toxicology

authors： Goldman SM

更新日期：2014-01-01 00:00:00

abstract：:Though opioid receptors are more difficult to purify and characterize than other cell surface receptors, significant progress has been made in the past several years. At least a dozen groups have now reported purification of opioid-binding proteins, either in a form that retains ligand-binding properties, or in a cova...

journal_title：Annual review of pharmacology and toxicology

authors： Loh HH,Smith AP

更新日期：1990-01-01 00:00:00

abstract：:The developing central nervous system (CNS) is more vulnerable to injury than the adult one. Although a great deal of research has been devoted to subtle effects of developmental exposure, such as neurobehavioral changes, this review instead focuses on a number of chemicals that have been shown, in several experimenta...

journal_title：Annual review of pharmacology and toxicology

authors： Costa LG,Aschner M,Vitalone A,Syversen T,Soldin OP

更新日期：2004-01-01 00:00:00