Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2019
ReviewAdapting Proteostasis and Autophagy for Controlling the Pathogenesis of Cystic Fibrosis Lung Disease.
Cystic fibrosis (CF), a fatal genetic disorder predominant in the Caucasian population, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (Cftr) gene. The most common mutation is the deletion of phenylalanine from the position-508 (F508del-CFTR), resulting in a misfolded-CFTR protein, which is unable to fold, traffic and retain its plasma membrane (PM) localization. The resulting CFTR dysfunction, dysregulates variety of key cellular mechanisms such as chloride ion transport, airway surface liquid (ASL) homeostasis, mucociliary-clearance, inflammatory-oxidative signaling, and proteostasis that includes ubiquitin-proteasome system (UPS) and autophagy. ⋯ There is emerging experimental and clinical evidence that supports the notion that impaired cellular proteostasis and autophagy plays a central role in regulating pathogenesis of chronic CF lung disease. Thus, correcting the underlying proteostasis and autophagy defect in controlling CF pulmonary disease, primarily via correcting the protein processing defect of F508del-CFTR protein has emerged as a novel intervention strategy. Hence, we discuss here both the rationale and significant therapeutic utility of emerging proteostasis and autophagy modulating drugs/compounds in controlling chronic CF lung disease, where targeted delivery is a critical factor-influencing efficacy.
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Frontiers in pharmacology · Jan 2019
ReviewNew Trends in Migraine Pharmacology: Targeting Calcitonin Gene-Related Peptide (CGRP) With Monoclonal Antibodies.
Migraine is a common neurologic disorder characterized by attacks consisting of unilateral, throbbing headache accompanied by photophobia, phonophobia, and nausea which remarkably reduces the patients' quality of life. Not migraine-specific non-steroidal anti-inflammatory drugs (NSAIDs) are effective in patients affected by mild episodic migraine whilst in moderate or severe episodic migraine and in chronic migraineurs triptans and preventative therapies are needed. Since these treatments are endowed with serious side effects and have limited effectiveness new pharmacological approaches have been investigated. ⋯ Currently, four mAbs, eptinezumab, fremanezumab, galcanezumab for CGRP and erenumab for CGRP canonical receptor, have been studied in clinical trials for episodic and chronic migraine. Apart from the proven effectiveness, these antibodies have resulted well tolerated and could improve the compliance of the patients due to their long half-lives allowing less frequent administrations. This study aims at investigating the still poorly clear pathogenesis of migraine and the potential role of anti-CGRP mAbs in the scenario of prophylaxis of migraine.
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Frontiers in pharmacology · Jan 2019
Respiratory Fluoroquinolones Monotherapy vs. β-Lactams With or Without Macrolides for Hospitalized Community-Acquired Pneumonia Patients: A Meta-Analysis.
Background: The choice of empirical antibiotic treatment for patients with community-acquired pneumonia (CAP) who are admitted to non-intensive care unit (ICU) hospital wards is complicated by the limited availability of evidence. We systematically reviewed the efficacy and safety of strategies of empirical treatment with respiratory fluoroquinolone monotherapy and β-lactam with or without macrolide for non-ICU hospitalized CAP patients. Methods: We searched databases including PubMed, the Cochrane Library (Issue11, 2018), EMbase, China National Knowledge Internet (CNKI), WanFang Data, VIP, and China Biology Medicine disc (CBMdisc) to identify randomized controlled trials (RCTs) involving the comparison of respiratory fluoroquinolone monotherapy and β-lactam with or without macrolide for the non-ICU hospitalized patients with CAP up to November 2018. ⋯ The advantage of respiratory fluoroquinolone was statistically significant on the drug-related adverse events (RR 0.87, 95% CI 0.77-0.97). Conclusions: Current evidence shows that fluoroquinolone monotherapy has similar efficacy and favorable safety compared with β-lactam with or without macrolide for non-ICU hospitalized CAP patients. Since the limitation of region, quantity and quality of included studies, more RCTs with large scale and high quality are needed to verify the above conclusion.
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Frontiers in pharmacology · Jan 2019
Synergistic and Hepatoprotective Effect of Total Glucosides of Paeony on Ankylosing Spondylitis: A Systematic Review and Meta-Analysis.
The objective of this systematic review was to conduct a meta-analysis of the efficacy and safety of total glucosides of paeony (TGP) for the treatment of ankylosing spondylitis (AS). TGP is commonly applied as a complementary medicine, especially in combination with disease-modifying antirheumatic drugs (DMARDs) and/or non-steroidal anti-inflammatory drugs (NSAIDs) to treat AS in China. Nevertheless, the efficacy and safety of TGP combination treatment still needs more validation. ⋯ Adverse events (AEs) were significantly decreased (95% CI 0.48-0.79) with the usage of TGP. It is worthwhile to apply TGP as an auxiliary medicine on AS for better efficacy and less side effects, especially when considering the impact of traditional treatment on the liver. Still, further clinical trials with larger sample and better methodological quality are warranted to ascertain the potential benefits of TGP on AS.
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Frontiers in pharmacology · Jan 2019
Comparative Efficacy and Safety of Neuroprotective Therapies for Neonates With Hypoxic Ischemic Encephalopathy: A Network Meta-Analysis.
Context: Several interventions are available for the management of hypoxic ischemic encephalopathy (HIE), but no studies have compared their relative efficacy in a single analysis. This study aims to compare and determine the effectiveness of available interventions for HIE using direct and indirect data. Methods: Large randomized trials were identified from PubMed, EMBASE, CINAHL Plus, AMED, and Cochrane Library of Clinical Trials database from inception until June 30, 2018. ⋯ Similarly, there were lower rates of seizures among neonates treated with erythropoietin (0.35; 0.13-0.94; 1 trial) and whole body hypothermia (0.64; 0.46-0.87, 7 trials). Conclusion: The findings support current guidelines using therapeutic hypothermia in neonates with HIE. However, more trials are needed to determine the role of adjuvant therapy to hypothermia in reducing the risk of mortality and/or neurodevelopmental delay.