Current drug targets
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Current drug targets · Jan 2014
ReviewIron deficiency: the hidden miscreant in inflammatory bowel disease.
Iron deficiency (ID) and anemia of chronic diseases (ACD) are the most common causes of anemia in inflammatory bowel disease (IBD), and frequently coexist. In these circumstances, detection of ID may be difficult as inflammation influences the parameters of iron metabolism. The prevalence of iron deficiency anemia (IDA) ranges between 36% and 76% in this population of patients. ⋯ Iron carboxymaltose has been shown to be safe and effective in IBD patients with IDA. Furthermore, it allows for rapid administration of high single doses, saving time and costs. If proven to be efficacious and well tolerated, it may become the standard therapy in the near future.
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Current drug targets · Nov 2013
ReviewJanus kinase inhibition with tofacitinib: changing the face of inflammatory bowel disease treatment.
The advent of anti-Tumor Necrosis Factor (TNF) therapy has changed the way of treating inflammatory bowel disease (IBD). However, primary and secondary failure are relatively frequent with all anti-TNF agents, which are available only as parenteral agents. ⋯ First data in IBD are promising, especially in ulcerative colitis. Ongoing clinical trials in both UC and Crohn's disease (CD) are needed to further explore its efficacy in CD and to better assess its safety profile.
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Astrocytes, classically considered as supportive cells for neurons without a direct role in brain information processing, are emerging as relevant elements in brain physiology through their ability to regulate neuronal activity and synaptic transmission and plasticity. In relation to the key role of astrocyte-neuron interactions in synaptic physiology, accumulating evidence suggests that dysfunctions of neuron-astrocyte signaling may be linked to the pathology of various neurological and neurodegenerative diseases. In this article, we summarize the evidence supporting the importance of astrocyte-neuron communication in synaptic physiology, which have led to reveal astrocytes as integral elements of synaptic function. We also discuss how this novel view of astrocytic functions on brain physiology is prompting us to reconsider the possible astrocytic roles in brain diseases, and specifically in depression.
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Age-related diseases pose as an enormous problem on aging populations of the world. Despite the fact that many advances have been made on understanding of the neurodegeneration, there is still no cure available for the age-related brain disorders. Sirtuins are NAD-dependent protein deacetylases that were shown to have beneficial effects against age-related diseases. ⋯ Despite the enormous amount of research that has been conducted so far, there is still no cure or treatment for almost all of the neurodegenerative disorders. In addition, the mechanisms underlying brain aging and also the link between aging and neurodegeneration are not understood. This review focuses on the role of sirtuins as possible drug targets for neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's Diseases.
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The current generation of antidepressant drugs acts predominantly by targeting the serotonin transporter (SERT). The original trend to do this selectively (e.g., with SSRIs or selective serotonin reuptake inhibitors) has given way to combining various additional pharmacologic mechanisms with SERT inhibition, including dual actions by single drugs (e.g., SNRIs or serotonin norepinephrine reuptake inhibitors), or by augmenting SSRIs with a second drug of a different mechanism (e.g., bupropion with dopamine and norepinephrine reuptake inhibition; trazodone with 5HT2A antagonism; mirtazapine with 5HT2A/5HT2C/5HT3/alpha2 antagonism; buspirone or some atypical antipsychotics with 5HT1A partial agonism; other atypical antipsychotics with 5HT2C/5HT7 antagonism and other mechanisms). Novel drugs in development include those that combine multiple simultaneous pharmacologic mechanisms in addition to SERT inhibition within the same molecule, such as vilazodone (combining 5HT1A partial agonism with SERT inhibition), triple reuptake inhibitors (combining norepinephrine and dopamine reuptake inhibition with SERT inhibition), and vortioxetine, a multimodal antidepressant combining actions at the G protein receptor mode (5HT1A and 5HT1B partial agonism and 5HT7 antagonism), at the ion channel mode (5HT3 antagonism) as well as the neurotransmitter transporter mode (SERT inhibition). These various strategies that build upon SERT inhibition provide promise for novel therapeutic approaches to depression, including the possibility of targeting residual symptoms not well treated by SERT inhibition alone, and reducing side effects, such as sexual dysfunction.