Frontiers in pharmacology
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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
Funding and Service Organization to Achieve Universal Health Coverage for Medicines: An Economic Evaluation of the Best Investment and Service Organization for the Brazilian Scenario.
There are many health benefits since 31 years after the foundation of the National Health Service (NHS) in Brazil, especially the increase in life expectancy. However, family-income inequalities, insufficient funding, and suboptimal private sector-public sector collaboration are still areas for improvement. The efforts of Brazil to achieve universal health coverage (UHC) for medicines have resulted in increased public financing of medicines and their availability, reducing avoidable hospitalization and mortality. However, lack of access to medicines still remains. Due to historical reasons, pharmaceutical service organization in developing countries may have important differences from high-income countries. In some cases, developing countries finance and promote medicine access by using the public infrastructure of health care/medical units as dispensing sites and cover all costs of medicines dispensed. In contrast, many high-income countries use private community pharmacies and cover the costs of medicines dispensed plus a fee, which includes all logistic costs. In this study, we will undertake an economic evaluation to understand the funding needs of the Brazilian NHS to reduce inequalities in access to medicines through adopting a pharmaceutical service organization similar to that seen in many high-income countries with hiring/accrediting private pharmacies. ⋯ The results of the economic evaluation demonstrate potential savings for the NHS and society. Achieving UHC for medicines reduces household expenses with health costs, health litigation, outpatient care, hospitalization, and mortality. An optimal private sector-public sector collaboration model with private community pharmacy accreditation is economically dominant with a feasible medicine price negotiation. The results show the potential to improve access to medicines by 25% for all income classes. This is most beneficial to the poorest families, whose medicines account for 76% of their total health expenses, with potential savings of lives and public resources.
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Frontiers in pharmacology · Jan 2020
Immune Checkpoint Inhibitor-Related Cytokine Release Syndrome: Analysis of WHO Global Pharmacovigilance Database.
Immune checkpoint inhibitors (ICIs) have proven effective in the treatment of numerous cancers; however, they have been associated with immune-related adverse events (irAEs), among which cytokine release syndrome (CRS) has been reported in a few case reports. To describe the burden of ICI-related CRS and raise awareness of CRS as irAE, we queried VigiBase, the World Health Organization global database of spontaneously reported suspected adverse drug reactions (ADRs), and retrieved safety reports of suspected CRS associated with ICIs, gathered in the database through January 12th 2020. We assessed ICI-related CRS safety reports in terms of geographical and temporal patterns of reporting, patient demographics and clinical features, treatment characteristics, CRS clinical presentation, timing, seriousness, and outcome. ⋯ Besides two fatal cases, CRS recovered/was recovering at the time of reporting in 35 (60%) cases. We observed differences in the geographical pattern of ICI-related CRS reporting, with a high proportion of ICI-related CRS cases in Australia and North America (0.14 and 0.10% respectively). Due to ICI expanding indications, clinicians should be aware that ICIs could contribute to CRS onset in cancer patients as pharmacological triggers.
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Frontiers in pharmacology · Jan 2020
Identifying Antibiotic Prescribing Patterns Through Multi-Level Latent Profile Analyses: A Cross-Sectional Survey of Primary Care Physicians.
Background: Overuse of antibiotics significantly fuels the development of Antimicrobial resistance, which threating the global population health. Great variations existed in antibiotic prescribing practices among physicians, indicating improvement potential for rational use of antibiotics. This study aims to identify antibiotic prescribing patterns of primary care physicians and potential determinants. ⋯ Higher use of antibiotics was associated with insufficient knowledge, indifference to changes, complacency with satisfied patients, low household income and rural location of the prescribers. Conclusion: Great variation in antibiotic prescribing patterns exists among primary care physicians in Hubei of China. High use of antibiotics is not only associated with knowledge shortfalls but also low socioeconomic status of prescribers.
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Frontiers in pharmacology · Jan 2020
Suppression of NLRP3 Inflammasome by Erythropoietin via the EPOR/JAK2/STAT3 Pathway Contributes to Attenuation of Acute Lung Injury in Mice.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common and devastating clinical disorders with high mortality and no specific therapy. An excessive inflammatory response results in the progression of ALI/ARDS, and the NLRP3 inflammasome is a key participant in inflammation. Erythropoietin (EPO), which is clinically used for anemia, reportedly exerts pleiotropic effects in ALI. ⋯ Meanwhile, EPO evidently decreased interleukin-1β (IL-1β) and interleukin-18 (IL-18) secretion, the expression of NLRP3 inflammasome components including pro-IL-1β, NLRP3, and cleaved caspase-1 as well as phosphorylation of nuclear factor-κB (NF-κB) p65, which may be associated with activation of EPO receptor (EPOR), phosphorylation of Janus-tyrosine kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). However, all the beneficial effects of EPO on ALI and modulation NLRP3 inflammasome were remarkably abrogated by the inhibition of EPOR/JAK2/STAT3 pathway and knockout (KO) of NLRP3 gene. Taken together, this study indicates that EPO can effectively attenuate LPS-induced lung injury in mice by suppressing the NLRP3 inflammasome, which is dependent upon activation of EPOR/JAK2/STAT3 signaling and inhibition of the NF-κB pathway.