Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2018
The Fibrin Cleavage Product Bβ15-42 Channels Endothelial and Tubular Regeneration in the Post-acute Course During Murine Renal Ischemia Reperfusion Injury.
Early and adequate restoration of endothelial and tubular renal function is a substantial step during regeneration after ischemia reperfusion (IR) injury, occurring, e.g., in kidney transplantation, renal surgery, and sepsis. While tubular epithelial cell injury has long been of central importance, recent perception includes the renal vascular endothelium. In this regard, the fibrin cleavage product fibrinopeptide Bβ15-42 mitigate IR injury by stabilizing interendothelial junctions through its affinity to VE-cadherin. ⋯ Similar dynamics were observed for the intermediate filament vimentin, the cytoprotective protein klotho, stathmin and the proliferation cellular nuclear antigen, which were significantly up-regulated at the same points in time. These results suggest a beneficial effect of anatomical contiguously located endothelial cells on tubular regeneration through stabilization of endothelial integrity. Therefore, it seems that Bβ15-42 represents a novel pharmacological approach in the targeted therapy of acute renal failure in everyday clinical practice.
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Frontiers in pharmacology · Jan 2018
Effects of Transcranial Direct Current Stimulation Block Remifentanil-Induced Hyperalgesia: A Randomized, Double-Blind Clinical Trial.
Background: Remifentanil-induced hyperalgesia (r-IH) involves an imbalance in the inhibitory and excitatory systems. As the transcranial Direct Current Stimulation (tDCS) modulates the thalamocortical synapses in a top-down manner, we hypothesized that the active (a)-t-DCS would be more effective than sham(s)-tDCS to prevent r-IH. We used an experimental paradigm to induce temporal summation of pain utilizing a repetitive cold test (rCOLDT) assessed by the Numerical Pain Score (NPS 0-10) and we evaluated the function of the descending pain modulatory system (DPMS) by the change on the NPS (0-10) during the conditioned pain modulation (CPM)-task (primary outcomes). ⋯ Thereby, tDCS could be considered as a new approach to contra-regulate paradoxical mechanisms involved in the r-IH. Clinical trials identification: NCT02432677. URL:https://clinicaltrials.gov/.
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Frontiers in pharmacology · Jan 2018
Case ReportsFirst Case in Italy of Fatal Intoxication Involving the New Opioid U-47700.
The drug commonly known as U-47700 is a strong μ-opioid agonist with an approximate potency 7.5 times higher than morphine. It has been available in Europe since 2014, where it is usually sold through the internet or black market as an abuse morphine-like substance. In the case reported here, a Caucasian man was found dead in his apartment. ⋯ Finally, U-47700 was identified as the main component of the powder and the liquids contained in the nasal spray bottles. The combined circumstantial elements and toxicological results of the case revealed the occurrence of an acute intoxication produced by U-47700 abuse. To the best of our knowledge, this is the first fatal intoxication case reported on the Italian territory involving the synthetic opioid U-47700.
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Frontiers in pharmacology · Jan 2018
Sulodexide for Secondary Prevention of Recurrent Venous Thromboembolism: A Systematic Review and Meta-Analysis.
Background: Patients with venous thromboembolism have high risk of recurrence after discontinuation of anticoagulant treatment. Extended anticoagulation, such as traditional anticoagulants, can reduce the risk of recurrence but is associated with increased risk of hemorrhage. Sulodexide is a natural glycosaminoglycan mixture which can prevent recurrent venous thromboembolism. ⋯ The safety of sulodexide was also reliable. The rate of bleeding was 0.28% in the sulodexide group and 1.60% in the control group, and design of study did not influence these results. Conclusions: Sulodexide could significantly reduce the recurrence of VTE after discontinuation of anticoagulation treatment as compared with placebo.
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Frontiers in pharmacology · Jan 2018
Selective Blockade of HCN1/HCN2 Channels as a Potential Pharmacological Strategy Against Pain.
A prominent role of hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels has been suggested based on their expression and (dys)function in dorsal root ganglion (DRG) neurons, being likely involved in peripheral nociception. Using HCN blockers as antinociceptive drugs is prevented by the widespread distribution of these channels. However, tissue-specific expression of HCN isoforms varies significantly, HCN1 and HCN2 being considered as major players in DRG excitability. ⋯ MEL55A was able to relieve chemotherapy-induced neuropathic pain. In conclusion, selective blockade of HCN1/HCN2 channels, over HCN4 isoform, was able to modulate electrophysiological properties of DRG neurons similarly to that reported for classical Ih blockers, ivabradine, resulting in a pain-relieving activity. The availability of small molecules with selectivity toward HCN channel isoforms involved in nociception might represent a safe and effective strategy against chronic pain.