Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2018
South-West of England's Experience of the Safety and Tolerability Pirfenidone and Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis (IPF).
Purpose: Pirfenidone and nintedanib are two novel antifibrotic agents licensed for the treatment IPF. Prior to being approved for use in England for patients with FVC >50% and <80%, these were made available for all IPF patients under the Mild Patient Program (MPP) and Patient In Need Scheme (PIN). Prescribing of these medications is restricted to specialist centers. ⋯ The TEAE profile of pirfenidone was higher than clinical trial data would suggest, although comparable to real-world datasets. Further work is required to explore the possible reasons underpinning this finding, including whether this is related to population co-morbidities or center threshold. No new safety concerns were identified.
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Frontiers in pharmacology · Jan 2018
ReviewMajor Bioactive Compounds in Essential Oils Extracted From the Rhizomes of Zingiber zerumbet (L) Smith: A Mini-Review on the Anti-allergic and Immunomodulatory Properties.
Zingiber zerumbet (L) Smith is part of the Zingiberaceae family, one of the largest families of the plant kingdom. Z. zerumbet is a perennial, aromatic and tuberose plant that grows in humid locations where its center of distribution is located in the South-East Asia region. This plant has been traditionally used in foods and beverages and for ornamental purposes. ⋯ The rhizome is among the part of Z. zerumbet that has been widely used for many studies due to its exceptional biomedical applications. Most of these studies have shown that the essential oil, which can be obtained through hydro-distillation of the rhizomes from Z. zerumbet, is enriched with various active metabolites. Therefore, this mini-review provides an overview of the main aspects related to the anti-allergic and immunomodulatory properties of the major bioactive compounds found in the essential oils extracted from the rhizomes of Z. zerumbet, with the aim of demonstrating the importance of essential oil extracted from the rhizomes of Z. zerumbet and its bioactive compounds in the treatment of allergy and allergy-related diseases, in addition to other widely reported and extensively studied biomedical applications.
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Frontiers in pharmacology · Jan 2018
Haplotypic and Genotypic Association of Catechol-O-Methyltransferase rs4680 and rs4818 Polymorphisms and Treatment Resistance in Schizophrenia.
Treatment-resistant schizophrenia (TRS) continues to be a challenge. It was related to different factors, including alterations in the activity of brain dopaminergic system, which could be influenced by the dopamine-degrading enzyme, catechol-O-methyltransferase (COMT). Variants of the COMT gene have been extensively studied as risk factors for schizophrenia; however, their association with TRS has been poorly investigated. ⋯ In women with TRS, the high activity G-G/G-G haplotype was rare, while carriers of other haplotypes were overrepresented (p = 0.009). Such associations of COMT rs4680 and rs4818 high-activity (G variants), as well as G-G/G-G haplotype, with the lower risk of TRS in females, but not in males, suggest significant, but sex-specific influence of COMT variants on the development of treatment-resistance in patients with schizophrenia. However, due to relatively low number of females, those findings require replication in a larger sample.
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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.