Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2020
Clinical TrialVolume Matters in Ultrasound-Guided Perineural Dextrose Injection for Carpal Tunnel Syndrome: A Randomized, Double-Blinded, Three-Arm Trial.
Ultrasound-guided perineural dextrose injection (PDI) has been reported effective for carpal tunnel syndrome (CTS). Higher volume of injectate may reduce adhesion of median nerve from other tissues, but volume-dependent effects of PDI in CTS remain unknown. We aimed to investigate whether PDI with different injectate volumes had different effects for CTS participants. ⋯ There was no significant difference between the three groups at the 24th-week post-injection follow-up. Clinical Trial Registration: www. ClinicalTrials.gov, identifier NCT03598322.
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Frontiers in pharmacology · Jan 2020
Evaluation of the Quality of Antibiotic Prescribing in Primary Care: A Multicenter Longitudinal Study From Shenzhen, China.
Background: Currently, there is no comprehensive evaluation of the quality of antibiotic prescribing in China's primary care facilities based on longitudinal data. Methods: We randomly selected 11 community health centers in Shenzhen, China, and collected all outpatient prescriptions of these centers from 2010 to 2015. To evaluate the quality of antibiotic prescribing, we used six quality indicators for analysis, including number of antibiotics per 100 consultations, ratio between broad-spectrum and narrow-spectrum antibiotics (B/N ratio), percentage of first-line antibiotics recommended by guidelines, percentage of oral antibiotics with a duration exceeding the guideline recommendation, and new pediatric-specific indicators such as percentage of antibiotics with amoxicillin (A index) and ratio between amoxicillin and broad-spectrum antibiotics (A/B ratio). ⋯ Conclusion: A review of antibiotic prescribing in Shenzhen, China, showed a substantial reduction in antibiotic use in primary care. However, problems such as widespread use of broad-spectrum antibiotics, insufficient use of first-line antibiotics and low use of amoxicillin were prevalent. Improving and optimizing the quality of antibiotic prescribing, particularly in children prescriptions, will be the focus of future antibiotic stewardship in China.
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Frontiers in pharmacology · Jan 2020
CFTR Modulator Therapy Enhances Peripheral Blood Monocyte Contributions to Immune Responses in People With Cystic Fibrosis.
CFTR modulators decrease some etiologies of CF airway inflammation; however, data indicate that non-resolving airway infection and inflammation persist in individuals with CF and chronic bacterial infections. Thus, identification of therapies that diminish airway inflammation without allowing unrestrained bacterial growth remains a critical research goal. Novel strategies for combatting deleterious airway inflammation in the CFTR modulator era require better understanding of cellular contributions to chronic CF airway disease, and how inflammatory cells change after initiation of CFTR modulator therapy. Peripheral blood monocytes, which traffic to the CF airway, can develop both pro-inflammatory and inflammation-resolving phenotypes, represent intriguing cellular targets for focused therapies. This therapeutic approach, however, requires a more detailed knowledge of CF monocyte cellular programming and phenotypes. ⋯ Our results demonstrate that ivacaftor causes acute changes in blood monocyte transcriptional profiles and plasma chemokines, and suggest that increased monocyte inflammatory signals and changes in myeloid cell trafficking may contribute to changes in airway inflammation in people taking CFTR modulators. To our knowledge, this is the first report investigating the transcriptomic response of circulating blood monocytes in CF subjects treated with a CFTR modulator.
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Frontiers in pharmacology · Jan 2020
Exogenous Hydrogen Sulfide Ameliorates Diabetic Myocardial Fibrosis by Inhibiting Cell Aging Through SIRT6/AMPK Autophagy.
Stress aging of myocardial cells participates in the mechanism of myocardial fibrosis (MF). Previous studies have shown that hydrogen sulfide (H2S) can improve MF, however the specific internal mechanism remains still unclear. Therefore, this study aims to explore whether H2S can improve myocardial cell aging induced by high glucose and myocardial fibrosis in diabetic rats by activating autophagy through SIRT6/AMPK. ⋯ The results showed that myocardial collagen fibers were significantly deposited, myocardial tissue senescent cells were significantly increased and the expression of CSE protein was down-regulated, while SIRT6/AMPK signaling pathway and cell autophagy were significantly inhibited. H2S-treated (NaHS; 56 μmol/kg) could significantly reverse the above phenomenon. In conclusion, these findings suggest that exogenous H2S can inhibit myocardial cell senescence and improve diabetic myocardial fibrosis by activating CSE and autophagy through SIRT6/AMPK signaling pathway.
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Frontiers in pharmacology · Jan 2020
Cellular and Molecular Pathways of COVID-19 and Potential Points of Therapeutic Intervention.
With the objective of linking early findings relating to the novel SARS-CoV-2 coronavirus with potentially informative findings from prior research literature and to promote investigation toward therapeutic response, a coherent cellular and molecular pathway is proposed for COVID-19. The pathway is consistent with a broad range of observed clinical features and biological markers and captures key mediators of pathophysiology. In this proposed pathway, membrane fusion and cytoplasmic entry of SARS-CoV-2 virus via ACE2 and TMPRSS2-expressing respiratory epithelial cells, including pulmonary type-II pneumocytes, provoke an initial immune response featuring inflammatory cytokine production coupled with a weak interferon response, particularly in IFN-λ-dependent epithelial defense. ⋯ Although certain elements are likely to be revised as new findings emerge, the proposed pathway suggests multiple points of investigation for potential therapeutic interventions. Initial candidate interventions include prophylaxis to augment epithelial defense (e.g., AT1 receptor blockade, type III and type I interferons, melatonin, calcitriol, camostat, and lopinavir) and to reduce viral load (e.g., remdesivir, ivermectin, emetine, Abelson kinase inhibitors, dopamine D2 antagonists, and selective estrogen receptor modulators). Additional interventions focus on tempering inflammatory signaling and injury (e.g., dexamethasone, doxycycline, Ang1-7, estradiol, alpha blockers, and DHA/EPA, pasireotide), as well as inhibitors targeted toward molecular mediators of the maladaptive COVID-19 immune response (e.g., IL-6, TNF-α, IL-17, JAK, and CDK9).