Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2021
Optogenetic Manipulations of Amygdala Neurons Modulate Spinal Nociceptive Processing and Behavior Under Normal Conditions and in an Arthritis Pain Model.
The amygdala is an important neural substrate for the emotional-affective dimension of pain and modulation of pain. The central nucleus (CeA) serves major amygdala output functions and receives nociceptive and affected-related information from the spino-parabrachial and lateral-basolateral amygdala (LA-BLA) networks. The CeA is a major site of extra-hypothalamic expression of corticotropin releasing factor (CRF, also known as corticotropin releasing hormone, CRH), and amygdala CRF neurons form widespread projections to target regions involved in behavioral and descending pain modulation. ⋯ Optical activation of CeA-CRF neurons or of BLA axon terminals in the CeA increased the evoked responses of spinal WDR neurons and induced pain-like behaviors (hypersensitivity and vocalizations) under normal condition. Conversely, optical silencing of CeA-CRF neurons or of BLA axon terminals in the CeA decreased the evoked responses of spinal WDR neurons and vocalizations, but not hypersensitivity, in the arthritis pain model. These findings suggest that the amygdala can drive the activity of spinal cord neurons and pain-like behaviors under normal conditions and in a pain model.
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Frontiers in pharmacology · Jan 2021
Cardiotoxicity Induced by Immune Checkpoint Inhibitors: A Pharmacovigilance Study From 2014 to 2019 Based on FAERS.
This study was to scientifically and systematically explore the association between cardiotoxicity and immune checkpoint inhibitors (ICIs) and also to characterize the spectrum of ICI-related cardiac complications. From the first quarter of 2014 to the fourth quarter of 2019, data from the FDA Adverse Event Reporting System database were selected to conduct the disproportionality analysis. Reporting odds ratios and information components were used to evaluate the signal after statistical shrinkage transformation. ⋯ Among them, myocarditis was the only one caused by all ICIs with strong signal value and high risk, warranting further attention. Overall, this investigation mainly showed the profile of cardiotoxicities caused by ICIs, which varied between different ICI therapies, but also shared some similarities in specific symptoms such as myocarditis. Therefore, it is vital and urgent to recognize and manage ICI-related cardiotoxicities, known to frequently occur in clinical practice, at the earliest point.
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Frontiers in pharmacology · Jan 2021
ReviewThe Optimal Adjuvant Strategy of Aidi Injection With Gemcitabine and Cisplatin in Advanced Non-small Cell Lung Cancer: A Meta-analysis of 70 Randomized Controlled Trials.
Introduction: Aidi injection (Aidi) is composed of cantharidin, astragaloside, ginsenoside, and elentheroside E. As an important adjuvant therapy, Aidi in combination with gemcitabine and cisplatin (GP) is often used in the treatment of non-small cell lung cancer (NSCLC). Objectives: We performed a new evaluation to demonstrate the clinical efficacy and safety of the Aidi and GP combination and further explored an optimal strategy for achieving an ideal response and safety level in advanced NSCLC. ⋯ Conclusion: Current evidence indicates that Aidi's value in adjuvant chemotherapy may be broad-spectrum, not just for some regimens. The Aidi and GP combination may show a good short-term response, antitumor immunity, and safety level in patients with NSCLC. Aidi (50 ml/day, 7-14 days/cycle for one and two cycles) with GEM (1000 mg/m2) and DDP (20-30 mg/m2 or 40-50 mg/m2) may be an optimal regimen for realizing an ideal goal in patients who are first-treatment, elderly, or have a KPS score ≥ 60 or AST≥3 months.
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Frontiers in pharmacology · Jan 2021
ReviewImmune Axonal Neuropathies Associated With Systemic Autoimmune Rheumatic Diseases.
Immune axonal neuropathies are a particular group of immune-mediated neuropathies that occasionally accompany systemic autoimmune rheumatic diseases such as connective tissue dissorders and primary systemic vasculitides. Apart from vasculitis of vasa nervorum, various other mechanisms are involved in their pathogenesis, with possible therapeutic implications. Immune axonal neuropathies have highly heterogeneous clinical presentation and course, ranging from mild chronic distal sensorimotor polyneuropathy to severe subacute mononeuritis multiplex with rapid progression and constitutional symptoms such as fever, malaise, weight loss and night sweats, underpinning a vasculitic process. ⋯ Diagnosis and initiation of treatment are often delayed, leading to accumulating disability. Considering the lack of validated diagnostic criteria and evidence-based treatment protocols for immune axonal neuropathies, this review offers a comprehensive perspective on etiopathogenesis, clinical and paraclinical findings as well as therapy guidance for assisting the clinician in approaching these patients. High quality clinical research is required in order to provide indications and follow up rules for treatment in immune axonal neuropathies related to systemic autoimmune rheumatic diseases.
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Frontiers in pharmacology · Jan 2021
ReviewEvaluation of the Efficacy and Safety of Chinese Herbal Injection Combined With Trimetazidine for Viral Myocarditis: A Network Meta-Analysis.
Background: Viral myocarditis (VMC) is a common emergency of cardiovascular disease. Current treatment for VMC includes the prohibition of exercise plus supportive and symptomatic treatment, given the lack of specific antiviral therapeutic options and insufficient evidence for the use of novel immunosuppressive therapies. Trimetazidine, a drug used to improve myocardial energy metabolism, is frequently used for the treatment of viral myocarditis. ⋯ However, a lack of safety monitoring in some selected studies meant that the safety of some interventions could not be fully evaluated. Conclusion: CHIs combined with trimetazidine may have therapeutic value in the treatment of viral myocarditis, and Shenmai injection, Astragalus injection, and Salviae miltiorrhizae and ligustrazine hydrochloride injection may represent the most effective CHIs. Further clinical investigation is required to confirm these results.