Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2019
Resveratrol Promotes Diabetic Wound Healing via SIRT1-FOXO1-c-Myc Signaling Pathway-Mediated Angiogenesis.
Background/Aims: Diabetic non-healing skin ulcers represent a serious challenge in clinical practice, in which the hyperglycemia-induced disturbance of angiogenesis, and endothelial dysfunction play a crucial role. Resveratrol (RES), a silent information regulator 1 (SIRT1) agonist, can improve endothelial function and has strong pro-angiogenic properties, and has thus become a research focus for the treatment of diabetic non-healing skin ulcers; however, the underlying mechanism by which RES regulates these processes remains unclear. Therefore, the present study was intended to determine if RES exerts its observed protective role in diabetic wound healing by alleviating hyperglycemia-induced endothelial dysfunction and the disturbance of angiogenesis. ⋯ Furthermore, examination of the overexpression of forkhead box O1 (FOXO1), a transcription factor substrate of SIRT1, in HUVECs and db/db mice revealed that RES activated SIRT1 to restore hyperglycemia-triggered endothelial dysfunction and disturbance of angiogenesis, followed by the promotion of diabetic wound healing in a c-Myc-dependent manner. Pretreatment with 10058-F4, a c-Myc inhibitor, repressed RES-mediated endothelial protection, angiogenesis, and diabetic wound healing. Conclusion: Our findings indicate that the positive role of RES in diabetic wound healing via its SIRT1-dependent endothelial protection and pro-angiogenic effects involves the inhibition of FOXO1 and the de-repression of c-Myc expression.
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Frontiers in pharmacology · Jan 2019
Optimal Dexmedetomidine Dose to Prevent Emergence Agitation Under Sevoflurane and Remifentanil Anesthesia During Pediatric Tonsillectomy and Adenoidectomy.
Background: Emergence agitation (EA) is a common pediatric complication after sevoflurane anesthesia that can be prevented with dexmedetomidine. However, an inappropriate dose of dexmedetomidine can cause prolonged sedation and cardiovascular complications. Thus, we evaluated the optimal dose (ED95) of dexmedetomidine for preventing EA with sevoflurane and remifentanil anesthesia after pediatric tonsillectomy and adenoidectomy. ⋯ If EA occurred, the next surgical procedure included increased dexmedetomidine by 0.1 μg/kg, and if not, the drug was reduced by 0.1 μg/kg. Results: The 50% effective dose (ED50) of dexmedetomidine for preventing EA after sevoflurane and remifentanil anesthesia for tonsillectomy and adenoidectomy was 0.13 μg/kg, and its 95% confidence interval is 0.09-0.19 μg/kg; ED95 was 0.30 μg/kg, and its 95% confidence interval is 0.21-1.00 μg/kg. Conclusion: Intravenous dexmedetomidine infusion at ED50 (0.13 μg/kg) or ED95 (0.30 μg/kg) during induction for 10 min can prevent half or almost all EA after sevoflurane and remifentanil anesthesia during pediatric tonsillectomy and adenoidectomy.
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Frontiers in pharmacology · Jan 2019
The Nimodipine-Sparing Effect of Perioperative Dexmedetomidine Infusion During Aneurysmal Subarachnoid Hemorrhage: A Prospective, Randomized, Controlled Trial.
Background: Nimodipine can block the influx of calcium into the vascular smooth muscle cell and prevent secondary ischemia in patients with aneurysmal subarachnoid hemorrhage. However, the reduction of blood pressure after long-term intravenous administration of nimodipine has been associated with neurological deterioration. Yet, no effective solutions have been suggested to address this phenomenon. ⋯ There were no significant differences among the three groups in consumption of propofol, cisatracurium, fentanyl, and vasoactive drugs during operation, recovery time at PACU, satisfaction of patients and neurosurgeon, and number of applied urapidil and GCS during the first 48 h after surgery. The incidence of symptomatic cerebral vasospasm during 7 days after surgery, GOS of 3 months, and cerebral infarction after 30 days were also comparable among the three groups. Conclusions: Dexmedetomidine (infusion at 0.5 µg·kg-1 for 10 min, then adjusted to 0.4 µg·kg-1·h-1 during the surgery) significantly reduced the total consumption of nimodipine during the first 48 h after surgery and promoted early rehabilitation of patients although the incidences of symptomatic cerebral vasospasm, GOS, and cerebral infarction were not reduced.
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Frontiers in pharmacology · Jan 2019
Edgeworthia gardneri (Wall.) Meisn. Water Extract Ameliorates Palmitate Induced Insulin Resistance by Regulating IRS1/GSK3β/FoxO1 Signaling Pathway in Human HepG2 Hepatocytes.
The flower of Edgeworthia gardneri (Wall.) Meisn is commonly used in beverage products in Tibet and has potential health benefits for diabetes. However, the mechanisms underlying anti-insulin resistance (IR) action of the flower of E. gardneri are not fully understood. This study aims to investigate the effects of the water extract of the flower of E. gardneri (WEE) on IR in palmitate (PA)-exposed HepG2 hepatocytes. ⋯ The GLUT2 and GLUT4 translocation were also promoted by WEE treatment in PA-treated HepG2 cells. Taken together, WEE has potential anti-IR effect in PA-exposed HepG2 cells; the underlying mechanism of this action may be associated with the regulation of IRS1/GSK3β/FoxO1 signaling pathway. This study provides a pharmacological basis for the application of WEE in the treatment of metabolic diseases such as type 2 diabetes mellitus.
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Frontiers in pharmacology · Jan 2019
ReviewNew Trends in Migraine Pharmacology: Targeting Calcitonin Gene-Related Peptide (CGRP) With Monoclonal Antibodies.
Migraine is a common neurologic disorder characterized by attacks consisting of unilateral, throbbing headache accompanied by photophobia, phonophobia, and nausea which remarkably reduces the patients' quality of life. Not migraine-specific non-steroidal anti-inflammatory drugs (NSAIDs) are effective in patients affected by mild episodic migraine whilst in moderate or severe episodic migraine and in chronic migraineurs triptans and preventative therapies are needed. Since these treatments are endowed with serious side effects and have limited effectiveness new pharmacological approaches have been investigated. ⋯ Currently, four mAbs, eptinezumab, fremanezumab, galcanezumab for CGRP and erenumab for CGRP canonical receptor, have been studied in clinical trials for episodic and chronic migraine. Apart from the proven effectiveness, these antibodies have resulted well tolerated and could improve the compliance of the patients due to their long half-lives allowing less frequent administrations. This study aims at investigating the still poorly clear pathogenesis of migraine and the potential role of anti-CGRP mAbs in the scenario of prophylaxis of migraine.