Frontiers in pharmacology
-
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.
-
Frontiers in pharmacology · Jan 2019
Efficacy and Safety of Sodium Tanshinone IIA Sulfonate Injection on Hypertensive Nephropathy: A Systematic Review and Meta-Analysis.
Background: Sodium tanshinone IIA sulfonate (STS) injection, the extractive of traditional Chinese medicine Danshen, is supposed to be a supplementary treatment in hypertensive nephropathy. Objectives: To evaluate the efficacy and safety of STS in treatment of hypertensive nephropathy. Methods: We systematically searched China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wan-fang database, Chinese Biomedicine Database (CBM), PubMed, Embase, Web of Science, and Cochrane Library from their inception to December 2018. ⋯ Conclusions: STS combined with ARBs had a stronger effect on improving renal function in patients with primary hypertensive nephropathy than ARB monotherapy. The combination therapy also provided auxiliary hypotensive effects. Further large-scale, multicenter, and rigorously designed randomized controlled trials (RCTs) should be conducted to confirm our findings.
-
Frontiers in pharmacology · Jan 2019
Impact of Vaptans on Clinical Outcomes in Cirrhosis Patients: A Meta-Analysis of Randomized Controlled Trials.
Background: Vaptans have been confirmed to mobilize ascites and improve hyponatremia in cirrhosis patients. However, the effects of vaptans on all-cause mortality, ascites-related complications, and adverse events in cirrhosis patients have not been fully determined. Objectives: To systematically evaluate the impact of vaptans on the clinical outcomes in patients with cirrhosis. ⋯ Vaptans did not affect the incidence of adverse events in cirrhosis patients. Discussion: Treatment with vaptans is not associated with improved survival in cirrhosis patients, although it may reduce the risk of hepatic encephalopathy and spontaneous bacterial peritonitis in these patients. The limitations of the current study include limited number of available studies, small sample sizes of the included studies, variations of baseline patient characteristics, and differences in the dose and duration of vaptans.
-
Frontiers in pharmacology · Jan 2019
Role of Neuromuscular Blocking Agents in Acute Respiratory Distress Syndrome: An Updated Meta-Analysis of Randomized Controlled Trials.
The therapeutic role of neuromuscular blocking agents (NMBA) in patients with acute respiratory distress syndrome (ARDS) remains controversial. ⋯ Infusion of NMBA could reduce ICU mortality and the incidence of barotrauma. The risk of ICU-acquired weakness was higher in moderate-to-severe ARDS patients treated with NMBA. The real effects of NMBA need to be further evaluated and confirmed by a study with a stricter design.
-
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.