Articles: human.
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Biotechnology advances · Dec 2013
ReviewAn overview of the diverse roles of G-protein coupled receptors (GPCRs) in the pathophysiology of various human diseases.
G-protein coupled receptors (GPCRs) modulate diverse cellular responses to the majority of neurotransmitters and hormones within the human body. They exhibit much structural and functional diversity, and are responsive to a plethora of endogenous (biogenic amines, cations, lipids, peptides, and glycoproteins) and exogenous (therapeutic drugs, photons, tastants, and odorants) ligands and stimuli. ⋯ The pace of discovery of new GPCR-based drugs has recently accelerated due to rapid advancements in high-resolution structure determination, high-throughput screening technology and in silico computational modeling of GPCR binding interaction with potential drug molecules. This review aims to provide an overview of the diverse roles of GPCRs in the pathophysiology of various diseases that are the major focus of biopharmaceutical research as potential drug targets.
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The aim of this article is to describe the current and potential clinical translation of pharmacological inhibitors of poly(ADP-ribose) polymerase (PARP) for the therapy of various diseases. The first section of the present review summarizes the available preclinical and clinical data with PARP inhibitors in various forms of cancer. In this context, the role of PARP in single-strand DNA break repair is relevant, leading to replication-associated lesions that cannot be repaired if homologous recombination repair (HRR) is defective, and the synthetic lethality of PARP inhibitors in HRR-defective cancer. ⋯ In these disease indications, PARP overactivation due to oxidative and nitrative stress drives cell necrosis and pro-inflammatory gene expression, which contributes to disease pathology. Accordingly, multiple lines of preclinical data indicate the efficacy of PARP inhibitors to preserve viable tissue and to down-regulate inflammatory responses. As the clinical trials with PARP inhibitors in various forms of cancer progress, it is hoped that a second line of clinical investigations, aimed at testing of PARP inhibitors for various non-oncologic indications, will be initiated, as well.
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Neurobiology of aging · Dec 2013
Assessment of TREM2 rs75932628 association with Alzheimer's disease in a population-based sample: the Cache County Study.
Recent studies have identified the rs75932628 (R47H) variant in TREM2 as an Alzheimer's disease risk factor with estimated odds ratio ranging from 2.9 to 5.1. The Cache County Memory Study is a large, population-based sample designed for the study of memory and aging. ⋯ The minor allele frequency and population attributable fraction for R47H were 0.0029 and 0.004, respectively. This study replicates the association between R47H and Alzheimer's disease risk in a large, population-based sample, and estimates the population frequency and attributable risk of this rare variant.
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Sleep and headache have both generated curiosity within the human mind for centuries. The relationship between headache and sleep disorders is very complex. While Lieving in 1873 first observed that headaches were linked to sleep, Dexter and Weitzman in 1970 described the relationship between headache and sleep stages. ⋯ Patient education and lifestyle modification play a significant role in overall success of the treatment. Chronic tension-type headache and chronic migraine have high prevalence of insomnia and comorbid psychiatric disorders, which require behavioral insomnia treatment and medication if needed along with psychiatric evaluation. Apart from the abortive treatment tailored to the headache types, - such as triptans and DHE 45 for migraine and nonsteroidal anti-inflammatory medication for chronic tension-type headache, preventive treatment with different class of medications including antiepileptics (Topamax and Depakote), calcium channel blockers (verapamil), beta blockers (propranolol), antidepressants (amitriptyline), and Botox may be used depending upon the comorbid conditions.
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Despite the significant interest in the assessment of human cerebral perfusion, investigations into human spinal cord perfusion (SCP) are scarce. Current intraoperative monitoring of spinal cord relies on the assessment of neural conduction as a surrogate for SCP. However, there are various inherent limitations associated with the use of these techniques. Near infrared spectroscopy (NIRS) has been successfully used for monitoring and assessment of human cerebral perfusion and has shown promising results in intraoperative assessment of SCP in animal models. ⋯ Intraoperative NIRS with ICG tracer technique can identify an increase in the SCP in response to hypercapnia. It is possible to use this technique for monitoring SCP over the dura and the lamina. This technique could potentially be used to provide insight in to the pathophysiology and autoregulation of commonly acquired spinal cord conditions. Further research assessing the use of NIRS for monitoring of SCP is required.