Current medicinal chemistry
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Asthma is a heterogeneous disease with regard to the inflammatory pathways activated. In recent years, biologic drugs (monoclonal antibodies) directed towards specific components of type 2 inflammation have been approved for the treatment of severe asthma. ⋯ FeNO could be useful to assess treatment response or identify candidates for a specific drug that acts on type 2 inflammation mechanisms linked to Nitric Oxide (NO) production, such as the IL-4/IL-13 pathway or upstream processes. The value of FeNO as a biomarker predictive of responses to the biologics available for treating severe asthma is discussed based on the published studies at the moment of the review.
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Janus kinases (JAKs) are a family of non-receptor tyrosine kinases, composed by four members, JAK1, JAK2, JAK3 and TYK2. JAKs are involved in different inflammatory and autoimmune diseases, as well as in malignancies, through the activation of the JAK/STAT signalling pathway. Furthermore, the V617F mutation in JAK2 was identified in patients affected by myeloproliferative neoplasms. ⋯ In this review we will report many representative compounds that have been published in articles or patents in the last five years (period 2013-2017). The inhibitors will be classified on the basis of their chemical structure, focusing, when possible, on their structure activity relationships, selectivity and biological activity. For every class of derivatives, compounds disclosed before 2013 that have entered clinical trials will also be briefly reported, to underline the importance of a particular chemical scaffold in the search for new inhibitors.
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Anti-tumor necrosis factor (anti-TNF) monoclonal antibodies have revolutionized the treatment of inflammatory bowel diseases (IBD). However, because of their complexity, their production is expensive contributing to their high price. As the patent protection of these therapies has expired in several countries, biosimilars have been developed to reduce the healthcare costs. The aim of this article is to review the literature on the safety, efficacy and immunogenicity of biosimilars in IBD. ⋯ The infliximab biosimilar seems to be efficacious, safe and with a similar immunogenicity profile as the originator in IBD. Large prospective post-marketing studies are needed to assess the long-term safety profile of CT-P13. The use of infliximab biosimilars may lead to major healthcare cost savings.
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Review
Functional Neuroimaging Biomarkers in Migraine: Diagnostic, Prognostic and Therapeutic Implications.
In current migraine clinical practice, conventional neuroimaging examinations are often sought to exclude possible causes of secondary headaches or migraineassociated disorders. Contrariwise, although advanced Magnetic Resonance Imaging (MRI) has improved tremendously our understanding of human brain processes in migraine patients, to the state of the art they have not superseded the conventional neuroimaging techniques in the migraine clinical setting. ⋯ The identification of diagnostic, prognostic and therapeutic advanced neuroimaging biomarkers in the migraine clinical setting, in order to approach to patients in a more and more rational and "tailored" way, is extremely intriguing and futuristic. Unfortunately, reliable and robust neuroimaging biomarkers are still lacking for migraine, probably due to both not completely understood pathogenesis and clinical and neuroimaging heterogeneity. Although further longitudinal advanced neuroimaging studies, aimed to identify effective neuroimaging biomarkers, are needed, this review aims to collect the main and most recent works on this topic.
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Migraine is the most common neurological disorder and the second most disabling human condition, whose pathogenesis is favored by a combination of genetic, epigenetic, and environmental factors. In recent years, several efforts have been made to identify reliable biomarker(s) useful to monitor disease activity and/or ascertain the response to a specific treatment. ⋯ The characterization of migraine-specific biomarkers would be fundamental in a perspective of precision medicine, enabling risk assessment and tailored treatments. However, speculating on the clinical validity of migraine biomarkers may be premature and controlled clinical trials are presently needed to investigate both the diagnostic and therapeutic value of these biomarkers in migraine.