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Current Opinion in Pharmacology

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https://www.readbyqxmd.com/read/29334676/statins-in-the-treatment-of-copd-and-asthma-where-do-we-stand
#1
REVIEW
Jennifer Y So, Santosh Dhungana, Joanna J Beros, Gerard J Criner
Asthma and chronic obstructive pulmonary disease (COPD) are the two most prevalent obstructive lung diseases that account for tremendous morbidity and mortality throughout the world. These diseases have strong inflammatory components, with multiple prior studies showing elevated levels of various inflammatory markers and cells in those with COPD and asthma. Therefore, efforts to target inflammation in management of these diseases are of great interest. Statins, which define a class of drugs that are HMG-CoA inhibitors, are used to decrease cholesterol levels and have also been described to have many pleotropic effects that include anti-inflammatory and anti-oxidative properties...
January 12, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29331768/the-cholinergic-anti-inflammatory-pathway-an-innovative-treatment-strategy-for-respiratory-diseases-and-their-comorbidities
#2
REVIEW
Mitsuhiro Yamada, Masakazu Ichinose
Over the past few decades, it has been clarified that the nervous system and immune system have overlapping distributions and their interactions are critical in the regulation of immunological and inflammatory responses. The cholinergic anti-inflammatory pathway, including the parasympathetic nerve systems and humoral factors orchestrate the immune responses to protect the body during infection and tissue injury. Recent investigations have attempted to clarify how the parasympathetic nerve systems attenuate the systemic inflammatory responses and identified the α7 nicotinic acetylcholine receptor (α7nAChR) as a crucial target for attenuating the release of inflammatory cytokines from inflammatory cells including macrophages and dendritic cells...
January 11, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29288933/targeting-the-renin-angiotensin-system-as-novel-therapeutic-strategy-for-pulmonary-diseases
#3
REVIEW
Wan Shun Daniel Tan, Wupeng Liao, Shuo Zhou, Dan Mei, Wai-Shiu Fred Wong
The renin-angiotensin system (RAS) plays a major role in regulating electrolyte balance and blood pressure. RAS has also been implicated in the regulation of inflammation, proliferation and fibrosis in pulmonary diseases such as asthma, acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Current therapeutics suffer from some drawbacks like steroid resistance, limited efficacies and side effects. Novel intervention is definitely needed to offer optimal therapeutic strategy and clinical outcome...
December 27, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29278824/metabotropic-glutamate-receptors-the-potential-for-therapeutic-applications-in-alzheimer-s-disease
#4
REVIEW
Filippo Caraci, Ferdinando Nicoletti, Agata Copani
A dysfunction of glutamate signaling is implicated at several levels in the pathogenesis of Alzheimer's disease. Currently, metabotropic glutamate receptors, which have a wide distribution in the central nervous system and activate a multitude of cell signaling pathways, are pursued as targets for therapeutic intervention in Alzheimer's disease. Research is still limited, but results underscore the relevance of ongoing studies. Here we discuss the latest updates regarding metabotropic glutamate receptors and their role in Alzheimer's disease, as well as promising metabotropic glutamate receptor ligands that have been investigated in preclinical models of Alzheimer's disease...
December 23, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29223018/targeting-oxidant-dependent-mechanisms-for-the-treatment-of-respiratory-diseases-and-their-comorbidities
#5
REVIEW
Neil C Thomson
Oxidative stress is implicated in the pathogenesis of respiratory diseases, such as COPD and its comorbidities, asthma, idiopathic pulmonary fibrosis and radiation pneumonitis. Antioxidants drugs, such as small molecule thiols, nuclear erythroid-2 related factor 2 activators and catalytic enzyme mimetics have been developed to target oxidant-dependent mechanisms. The therapeutic effects of antioxidants have been generally disappointing. A small number of antioxidants are approved for clinical use, such as the small molecule thiol N-acetyl-l-cysteine for chronic obstructive pulmonary disease, and in the United States, the superoxide dismutase mimetic AEOL 10150 for severe radiation pneumonitis...
December 6, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29202375/coronary-versus-carotid-artery-plaques-similarities-and-differences-regarding-biomarkers-morphology-and-prognosis
#6
REVIEW
Fragiska Sigala, Evangelos Oikonomou, Alexis S Antonopoulos, George Galyfos, Dimitris Tousoulis
Carotid and coronary artery disease are two major atherosclerotic conditions that have shown an increased prevalence in the last three decades that is associated with high morbidity and mortality. Recent data have revealed that the development of the atherosclerotic plaque-the basic entity in both diseases-may share similar characteristics and mechanisms irrespective of the location site. Even though the biology of atherosclerotic process is similar, there are differences in plaque morphology and characteristics...
December 1, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29169069/anti-inflammatory-agents-in-peripheral-arterial-disease
#7
REVIEW
Alexios S Antonopoulos, Evi Papanikolaou, Georgia Vogiatzi, Evangelos Oikonomou, Dimitris Tousoulis
Inflammation is pivotally involved in coronary and peripheral atherosclerotic disease. This established concept is based on both experimental animal models of vascular inflammation and Mendelian randomization studies demonstrating a causal relationship between pro-inflammatory cytokines (e.g. interleukin-6) and cardiovascular disease risk. More recently, the reduction of cardiovascular events by use of an interleukin-1β inhibitor (canakinumab) has revived interest in the use of anti-inflammatory agents for the treatment of atherosclerotic disease, including peripheral arterial disease...
November 20, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29156443/ensuring-quality-pharmacokinetic-analyses-in-antimicrobial-drug-development-programs
#8
REVIEW
Elizabeth A Lakota, Justin C Bader, Christopher M Rubino
Pharmacokinetic studies and analyses can be expensive, time consuming, and labor intensive. However, it is crucial to understand that much of what happens in antimicrobial drug development, such as dose-selection and clinical study design, can be optimized with a strong understanding of the underlying pharmacokinetics of an agent. In this way, pharmacokinetics forms the bedrock of a pharmacometric approach to antimicrobial development. Thus, pharmacokinetic analyses must be considered an integral part of a drug's development strategy and studies must be planned and designed accordingly...
November 17, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29154194/micrornas-in-intestinal-barrier-function-inflammatory-bowel-disease-and-related-cancers-their-effects-and-therapeutic-potentials
#9
REVIEW
Esmerina Tili, Jean-Jacques Michaille, Victoria Piurowski, Brooke Rigot, Carlo M Croce
The initiation and development or inflammatory bowel disease (IBD) and associated colorectal cancers, have been linked to inflammation. MicroRNAs are non-coding regulators of gene expression that have gained great attention due to their capability to regulate the expression of a number of target transcripts. It is now generally admitted that microRNAs are instrumental in gut pathologies, in particular through their targeting of transcripts encoding proteins of the intestinal barrier (IB) and their regulators...
November 15, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29149731/purinergic-drug-targets-for-gastrointestinal-disorders
#10
REVIEW
Geoffrey Burnstock, Kenneth A Jacobson, Fievos L Christofi
Purinergic receptors are implicated in the pathogenesis of gastrointestinal disorders and are being explored as potential therapeutic targets. Gut inflammation releases ATP that acts on neuronal, glial, epithelial and immune cells. Purinergic signalling in glia and neurons is implicated in enteric neuropathies. Inflammation activates glia to increase ATP release and alter purinergic signalling. ATP release causes neuron death and gut motor dysfunction in colitis via a P2X7-dependent neural-glial pathway and a glial purinergic-connexin-43 pathway...
November 14, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29145012/the-gut-brain-interaction-in-opioid-tolerance
#11
REVIEW
Hamid I Akbarali, William L Dewey
The prevailing opioid crisis has necessitated the need to understand mechanisms leading to addiction and tolerance, the major contributors to overdose and death and to develop strategies for developing drugs for pain treatment that lack abuse liability and side-effects. Opioids are commonly used for treatment of pain and symptoms of inflammatory bowel disease. The significant effect of opioids in the gut, both acute and chronic, includes persistent constipation and paradoxically may also worsen pain symptoms...
November 13, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29136587/management-of-eosinophilic-esophagitis-and-celiac-disease
#12
REVIEW
Rok Seon Choung, Jeffrey A Alexander, David A Katzka, Joseph A Murray
Eosinophilic esophagitis (EoE) and celiac disease (CeD) are chronic immune mediated gastrointestinal disorders characterized by mucosal inflammation, both of which are related to food antigens, but with differences in clinical and histopathological features. When untreated, both diseases lead to destruction of the epithelium. While a strict gluten-free diet is the only effective therapy for CeD, several therapeutic options, such as proton pump inhibitors, topical steroids and diet elimination therapy are available for EoE...
November 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29136540/the-application-of-in-vitro-surveillance-data-for-antibacterial-dose-selection
#13
REVIEW
Robert K Flamm, Helio S Sader, Mariana Castanheira, Ronald N Jones
In vitro surveillance data, which provide key information to interpret the results of pharmacokinetic/pharmacodynamics (PK-PD) target attainment studies, are used to support dose selection decisions and recommendations for in vitro susceptibility testing criteria for antibacterial agents during drug development. Considerations for designing the in vitro surveillance database to support the development of antibacterial agents include the choice of pathogens to study, the sample size of isolate collections needed, and target patient populations from which clinical isolates should be collected...
November 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29128743/the-suppression-of-premature-termination-codons-and-the-repair-of-splicing-mutations-in-cftr
#14
REVIEW
Yifat S Oren, Iwona M Pranke, Batsheva Kerem, Isabelle Sermet-Gaudelus
Premature termination codons (PTC) originate from nucleotide substitution introducing an in-frame PTC. They induce truncated, usually non-functional, proteins, degradation of the PTC containing transcripts by the nonsense-mediated decay (NMD) pathway and abnormal exon skipping. Readthrough compounds facilitate near cognate amino-acyl-tRNA incorporation, leading potentially to restoration of a functional full-length protein. Splicing mutations can lead to aberrantly spliced transcripts by creating a cryptic splice site or destroying a normal site...
November 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29128853/use-of-monte-carlo-simulation-and-considerations-for-pk-pd-targets-to-support-antibacterial-dose-selection
#15
REVIEW
Michael Trang, Michael N Dudley, Sujata M Bhavnani
Monte Carlo simulation is used to generate data for pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses to assess antibacterial dosing regimens in early and late stage drug development. Careful consideration of the quality of data for pharmacokinetics, non-clinical PK-PD targets for efficacy, the choice of the bacterial reduction endpoint upon which the PK-PD target is based, variability in the PK-PD target, and effect site exposures ensures optimal dose selection. Relationships between drug exposure and efficacy and/or safety endpoints based on clinical data can also be applied to simulated data to support dose selection...
November 9, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29080476/corrector-combination-therapies-for-f508del-cftr
#16
REVIEW
John W Hanrahan, Elizabeth Matthes, Graeme Carlile, David Y Thomas
These are exciting times in the development of therapeutics for cystic fibrosis (CF). New correctors and potentiators of the cystic fibrosis transmembrane conductance regulator (CFTR) are being developed in academic laboratories and pharmaceutical companies, and the field is just beginning to understand their mechanisms of action. Studies of CFTR modulators are also yielding insight into the general principles and strategies that can be used when developing pharmacological chaperones, a new class of drugs. Combining two or even three correctors with a potentiator is an especially promising approach which should lead to further improvements in efficacy and clinical benefit for patients...
November 5, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29073476/cftr-potentiators-from-bench-to-bedside
#17
REVIEW
Kang-Yang Jih, Wen-Ying Lin, Yoshiro Sohma, Tzyh-Chang Hwang
One major breakthrough in cystic fibrosis research in the past decade is the development of drugs that target the root cause of the disease-dysfunctional CFTR protein. One of the compounds, Ivacaftor or Kalydeco, which has been approved for clinical use since 2012, acts by promoting the gating function of CFTR. Our recent studies have led to a gating model that features energetic coupling between nucleotide-binding domain (NBD) dimerization and gate opening/closing in CFTR's transmembrane domains (TMDs). Based on this model, we showed that ATP analogs can enhance CFTR gating by facilitating NBD dimerization, whereas Ivacaftor works by stabilizing the open channel conformation of the TMDs...
November 5, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29102744/modulating-bile-acid-pathways-and-tgr5-receptors-for-treating-liver-and-gi-diseases
#18
REVIEW
Harmeet Malhi, Michael Camilleri
Bile acids are central signals in enterohepatic communication and also integrate microbiota-derived signals into this signaling axis. Discovery of the tissue distribution and signaling pathways activated by the natural receptors for bile acids, farnesoid X receptor and G protein-coupled bile acid receptor 1 (GPBAR1) also known as TGR5, and bile acid transporters has led to the development of therapeutic agents that target these molecules. Obeticholic acid, a selective FXR agonist, and NGM282, a non-mitogenic FGF-19 analog, are two of the agents in this pipeline...
November 2, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29096172/%C3%AE-lactamase-inhibitors-what-you-really-need-to-know
#19
REVIEW
Paul G Ambrose, Olga Lomovskaya, David C Griffith, Michael N Dudley, Brian VanScoy
The world is awash in antibiotic-resistant bacteria. The usefulness of nearly every antibacterial agent available in our hospital pharmacies has been compromised. About half of the recently approved antimicrobial agents for gram-negative pathogens, those pending approval, and those entering clinical development are β-lactam-β-lactamase inhibitor combinations. Thus, we are betting heavily on the efficacy and durability of these agents. However, one needs to be cognizant that poor dose regimen design can result in suboptimal efficacy, on-therapy resistance development, and resistance selection that may harm the activity of all β-lactam-β-lactamase inhibitor combinations...
October 27, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29224800/editorial-overview-endocrine-and-metabolic-diseases-busting-bmi-new-strategies-for-the-treatment-of-obesity-and-metabolic-disease
#20
EDITORIAL
Gavin A Bewick
No abstract text is available yet for this article.
December 2017: Current Opinion in Pharmacology
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