Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2018
The Selective Antagonism of Adenosine A2B Receptors Reduces the Synaptic Failure and Neuronal Death Induced by Oxygen and Glucose Deprivation in Rat CA1 Hippocampus in Vitro.
Ischemia is a multifactorial pathology characterized by different events evolving in time. Immediately after the ischemic insult, primary brain damage is due to the massive increase of extracellular glutamate. Adenosine in the brain increases dramatically during ischemia in concentrations able to stimulate all its receptors, A1, A2A, A2B, and A3. ⋯ A2Breceptor antagonism significantly prevented astrocyte modifications. Both A2B receptor antagonists did not protect CA1 neurons from the neurodegeneration induced by glutamate application, indicating that the antagonistic effect is upstream of glutamate release. The selective antagonists of the adenosine A2B receptor subtype may thus represent a new class of neuroprotective drugs in ischemia.
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Frontiers in pharmacology · Jan 2018
ReviewThe Protectin Family of Specialized Pro-resolving Mediators: Potent Immunoresolvents Enabling Innovative Approaches to Target Obesity and Diabetes.
A western type diet and lifestyle play an important role in the development of chronic diseases, yet little insight into the precise cellular and biomolecular mechanisms has emerged. It is known that an unbalanced diet may result in obesity and diabetes. Sufficient amounts and proper balance of omega-6 and omega-3 polyunsaturated fatty acids is key for maintenance of health. ⋯ This review covers the bioactions, G-coupled protein receptors pharmacology, biosynthesis, and medicinal chemistry of the PD family of specialized pro-resolving mediators with an emphasis on obesity and anti-diabetic effects. In order to enable drug development and medicinal chemistry efforts against these diseases, stereoselective total organic synthesis of each of these mediators is required for confirmation of structure, stereochemical biosynthesis, and their functions. We provide an overview of our ongoing efforts and the current knowledge.
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Frontiers in pharmacology · Jan 2018
Lack of Effects of Extended Sessions of Transcranial Direct Current Stimulation (tDCS) Over Dorsolateral Prefrontal Cortex on Craving and Relapses in Crack-Cocaine Users.
Background: Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) has been investigated as additional therapeutic tool for drug use disorder. In a previous study, we showed that five sessions of tDCS applied bilaterally over the dorsolateral prefrontal cortex (dlPFC) reduced craving to the use of crack-cocaine in inpatients from a specialized clinic. In the present study, we examine if an extended number of sessions of the same intervention would reduce craving even further and affect also relapses to crack-cocaine use. ⋯ Relapse rates were high and quite similar between groups in the 30- and 60-days follow-up after discharge from the hospital. Conclusion: Extended repetitive bilateral tDCS over the dlPFC had no add-on effects over regular treatment when considering craving and relapses to the crack-cocaine use in a sample of crack-cocaine patients with severe use disorder. Different tDCS montages targeting other cortical regions and perhaps additional extension of sessions need to be investigated to reach more efficiency in managing craving and relapses to crack-cocaine use.
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Frontiers in pharmacology · Jan 2018
Estimating Adherence Based on Prescription or Dispensation Information: Impact on Thresholds and Outcomes. A Real-World Study With Atrial Fibrillation Patients Treated With Oral Anticoagulants in Spain.
Objective: To estimate drug exposure, Proportion of Days Covered (PDC) and percentage of patients with PDC ≥ 80% from a cohort of atrial fibrillation patients initiating oral anticoagulant (OAC) treatment. We employed three different approaches to estimate PDC, using either data from prescription and dispensing (PD cohort) or two common designs based on dispensing information only, requiring at least one (D1) or at least two (D2) refills for inclusion in the cohorts. Finally, we assessed the impact of adherence on health outcomes according to each method. ⋯ Physician-initiated discontinuation is a major contributor to reduced OAC exposure. When using the PDC80 threshold, very different groups of patients may be classified as adherent or non-adherent depending on the method used for the calculation of days' supply measures. High adherence and high exposure to OAC treatment in NVAF patients is associated with better health outcomes.
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Frontiers in pharmacology · Jan 2018
Hydrogen Sulfide Ameliorates Blood-Spinal Cord Barrier Disruption and Improves Functional Recovery by Inhibiting Endoplasmic Reticulum Stress-Dependent Autophagy.
Spinal cord injury (SCI) induces the disruption of blood-spinal cord barrier (BSCB), which elicits neurological deficits by triggering secondary injuries. Hydrogen sulfide (H2S) is a gaseous mediator that has been reported to have neuroprotective effect in the central nervous system. However, the relationship between H2S and BSCB disruption during SCI remains unknown. ⋯ But the autophagy inhibitor (3-Methyladenine, 3-MA) only inhibited autophagy without obvious effects on ER stress. Finally, we had revealed that NaHS significantly alleviated BSCB permeability and improved functional recovery after SCI, and these effects were markedly reversed by TM and Rapa. In conclusion, our present study has demonstrated that NaHS treatment is beneficial for SCI recovery, indicating that H2S treatment is a potential therapeutic strategy for promoting SCI recovery.