European journal of pharmacology
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This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief and the authors as panels from Figure 3D appear similar to panels from Figure 3C of article published by Zhi Wang, Hong Zhang, Liling Dai, Tongguo Song, Ping Li, Yali Liu and Luning Wang in Cell Biochemistry and Biophysics 73 (2015) 213–219 https://doi.org/10.1007/s12013-015-0660-2. Also, bands from Figure 6B appear similar (after a horizontal flip) to bands from Figure 5B and Figure 1C of the articles published by the corresponding authors et al in Acta Pharmacologica Sinica 37 (2016) 264–275 https://doi.org/10.1038/aps.2015.115 and the American Journal of Cancer Research 6(2) (2016) 425–439 http://www.ajcr.us/files/ajcr0022099.pdf. Quadrants showing flowcytometry patterns appear similar within Figure 6C although purportedly illustrating different experimental conditions. Although this article was published earlier than most of the other articles, the Editor decided to retract this article given the concerns on the reliability of the data. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.
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An interesting research and therapeutic problem is the reduced beneficial efficacy of opioids in the treatment of neuropathic pain. The present study sought to investigate the potential role of IL-1 family members in this phenomenon. We studied the time course of changes in IL-1alpha, IL-1beta, IL-1 receptor type I and IL-1 receptor antagonist mRNA and protein levels experienced by rats after chronic constriction injury (CCI) of the sciatic nerve using qRT-PCR and Western blot analysis. ⋯ Interestingly, we observed that IL-1beta mRNA and protein levels were strongly elevated in the ipsilateral part of the dorsal spinal cord on the 7th and 14th days following CCI. Moreover, in rats exposed to a single intrathecal administration of an IL-1 receptor antagonist (100 ng i.t.) on the 7th and 14th day following CCI, symptoms of neuropathic pain were attenuated, and the analgesic effects of morphine (2.5 µg i.t.) and buprenorphine (2.5 µg i.t.) were enhanced. In summary, restoration of the analgesic activity of morphine and buprenorphine by blockade of IL-1 signaling suggests that increased IL-1beta responses may account for the decreased analgesic efficacy of opioids observed in the treatment of neuropathy.
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Metabolic syndrome (MetS) is a cluster ofassociated metabolic traits that collectively confer unsurpassed risk for development of cardiovascular disease (CVD) and type 2 diabetes compared to any single CVD risk factor. Truncal obesity plays an exceptionally critical role among all metabolic traits of the MetS. Consequently, the prevalence of the MetS has steadily increased with the growing epidemic of obesity. ⋯ New classes of anti-diabetic drugs, including glucagon-like peptide 1 receptor (GLP-1R) agonists and Dipeptidyl-peptidase IV (DPP-IV) inhibitors, are currently being evaluated for their effects on obesity and metabolic traits. The genetic studies of obesity and metabolic syndrome have identified novel molecules acting on the hunger and satiety peptidergic signaling of the gut-hypothalamus axis or the melanocortin system of the brain and are promising targets for future drug development. The goal is to develop drugs that not only treat obesity, but also favorably impact its associated traits.
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Opioid receptors are important drug targets for pain management, addiction, and mood disorders. Although substantial research on these important subtypes of G protein-coupled receptors has been conducted over the past two decades to discover ligands with higher specificity and diminished side effects, currently used opioid therapeutics remain suboptimal. Luckily, recent advances in structural biology of opioid receptors provide unprecedented insights into opioid receptor pharmacology and signaling. We review here a few recent studies that have used the crystal structures of opioid receptors as a basis for revealing mechanistic details of signal transduction mediated by these receptors, and for the purpose of drug discovery.
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Review
Obstructive sleep apnea syndrome, continuous positive airway pressure and treatment of hypertension.
Obstructive sleep apnea (OSA), present in ~15% of the general population, increases the risks of stroke, heart failure, and premature death. Importantly, individuals with cardiovascular disease have a higher prevalence yet they often have few symptoms to alert clinicians to its presence. OSA with an apnea-hypopnea index (AHI) ≥15 events/hour is present in ≥30% of patients with primary hypertension and in up to 80% of those with drug resistant hypertension, suggesting that the neural, hormonal, inflammatory and vascular cascades triggered by OSA may elevate blood pressure chronically. ⋯ The prevailing view that the effect of treatment on blood pressure is modest arises from the inability of most contemporary technology to measure accurately the true impact of CPAP on OSA-entrained surges in nocturnal blood pressure. Moreover the exclusive focus on blood pressure, as if this is the principal determinant of cardiovascular event rates in this population, is naïve. The capacity to reduce cardiovascular risk by treating OSA with CPAP likely transcends a simple blood pressure effect; formal testing of this hypothesis will require adequately powered randomized clinical trials.