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
The Bioequivalence of Emulsified Isoflurane With a New Formulation of Emulsion: A Single-Center, Single-Dose, Double-Blinded, Randomized, Two-Period Crossover Study.
Background: Emulsified isoflurane is a novel intravenous general anesthetic obtained by encapsulating isoflurane molecules into emulsion. The formulation of emulsion has been improved according to the latest regulations of the China Food and Drug Administration. This study was designed to compare the bioequivalence of the new and previous formulation emulsion of isoflurane. ⋯ The effectiveness of general anesthesia was similar between the two formulations. Conclusion: The CI90 of Cmax, AUC0-t, AUC0-∞, NFEI, and PFEI were within the range of 80%-125%, suggesting bioequivalence between NFEI and PFEI. The safety and anesthesia effectiveness were also similar.
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Frontiers in pharmacology · Jan 2021
ReviewClinical Efficacy and Safety of Shensong Yangxin Capsule-Amiodarone Combination on Heart Failure Complicated by Ventricular Arrhythmia: A Meta-Analysis of Randomized Controlled Trials.
Background: Shensong Yangxin capsule (SSYX) is a well-known traditional Chinese patent medicine for treating arrhythmia. Recently, a flurry of randomized controlled trials (RCTs) of SSYX combined with amiodarone (SSYX-amiodarone) was reported in the treatment of heart failure (HF) complicated by ventricular arrhythmia (VA) in China. However, these RCTs have not been systematically evaluated. ⋯ No significant difference of enhancing LVEF [MD = 4.32; 95%CI (-0.56, 9.20); p = 0.08] and reducing NT-proBNP [SMD = 0.17; 95%CI (-0.81, 1.14); p = 0.73] was observed between SSYX-amiodarone and amiodarone group. Conclusions: Despite the apparent positive findings reported, the evidence provided by this meta-analysis was still insufficient to support the routine use of SSYX-amiodarone for HF-VA due to the poor methodological quality of included studies. The overall effect should to be verified in further through more well-design clinical studies with reasonable sample and good methodological quality.
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Frontiers in pharmacology · Jan 2021
ReviewEffect of Angiotensin-Neprilysin Versus Renin-Angiotensin System Inhibition on Renal Outcomes: A Systematic Review and Meta-Analysis.
Aims: We aim to perform a systematic review and meta-analysis examining randomized controlled trials assessing the efficacy and safety of sacubitril/valsartan in patients on renal outcomes, in comparison with the renin-angiotensin-aldosterone system inhibitor (RAASi). Methods: Eligible studies were retrieved on MEDLINE, EMBASE, and Cochrane until September 2021. The primary outcome was the incidence of renal impairment, which was defined as the composite of increases in serum creatinine by >0.3 mg/dl and/or a reduction in eGFR ≥25%, development of ESRD, or renal death. ⋯ However, patients with heart failure appeared to have increased microalbuminuria, not patients without HF (p = 0.80 for interaction). Conclusion: Sacubitril/valsartan was associated with a lower incidence of composite renal impairment especially in patients with HFpEF, but higher microalbuminuria in patients with heart failure (both HFrEF and HFpEF) compared with RAASi. The lower incidence of severe hyperkalemia and drug discontinuation due to renal events in patients with sacubitril/valsartan treatment demonstrated its superior safety compared with RAASi.
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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.