Annals of medicine
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Review
CD163: a regulated hemoglobin scavenger receptor with a role in the anti-inflammatory response.
CD163 is a hemoglobin scavenger receptor exclusively expressed in the monocyte-macrophage system. A particularly high expression is seen in macrophages of the 'alternative activation' phenotype playing a major role in dampening the inflammatory response and in scavenging components of damaged cells. CD163-mediated endocytosis of haptoglobin-hemoglobin complexes formed upon red blood cell hemolysis leads to lysosomal degradation of the ligand protein and metabolism of heme by cytosolic heme oxygenase. ⋯ In addition to being present on the macrophage surface, continuous shedding of the extracellular domain of CD163 leads to substantial amounts of soluble receptor in plasma. An increased shedding is due to inflammatory stimuli, and a role for soluble CD163 in immune suppression has been proposed. Furthermore, recent data indicate that soluble CD163 may be a valuable diagnostic parameter for monitoring macrophage activation in inflammatory conditions.
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The pathophysiology of tobacco-related diseases is complex and multifactorial. Among the approximately 4,000 compounds in tobacco smoke are carcinogens such as nitrosamines, irritants such as a variety of phenolic compounds, volatiles such as carbon monoxide, and of course nicotine. ⋯ This review discusses the mechanisms by which nicotine contributes to tobacco-related disease, with a focus on the surprising new finding that nicotine is a potent angiogenic agent. Nicotine hijacks an endogenous nicotinic cholinergic pathway present in endothelial cells that is involved in physiological, as well as pathological angiogenesis.
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A variety of clinical conditions may cause systemic activation of coagulation, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation (DIC). DIC consists of a widespread systemic activation of coagulation, resulting in diffuse fibrin deposition in small and midsize vessels. There is compelling evidence from clinical and experimental studies that DIC is involved in the pathogenesis of microvascular dysfunction and contributes to organ failure. ⋯ Interestingly, an extensive cross-talk between activation of inflammation and coagulation exists, where inflammatory mediators (such as cytokines) not only activate the coagulation system, but vice versa activated coagulation proteases and protease inhibitors may modulate inflammation through specific cell receptors. Supportive strategies aimed at the inhibition of coagulation activation may theoretically be justified and have been found beneficial in experimental and initial clinical studies. These strategies comprise inhibition of tissue factor-mediated activation of coagulation or restoration of physiological anticoagulant pathways, for example by means of the administration of recombinant human activated protein C.
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Within the past decade it has been possible to identify susceptibility gene loci that predispose to migraine using genetic markers distributed across the human genome. Five new loci with significant linkage to common types of migraine--migraine with or without aura--have been identified on four different chromosomes using a genome-wide screen approach. So far, only the locus on 4q has been replicated but no specific, disease-causing mutations have been described in these common forms of migraine. ⋯ In 50%-70% of FHM families, mutations in the calcium channel gene CACNA1A in chromosome 19p13 have been identified. In some families, mutations in the ATP1A2 gene encoding the alpha2 subunit of the Na+, K+-ATPase are associated with FHM, linked to 1q23. Here we discuss the current knowledge of the heritability of migraine and rare migraine variants as models for understanding the pathophysiology of common migraine and animal models that might contribute to understanding common forms of migraine.
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We discuss in this review the role of the neuregulin (NRG1) gene in schizophrenia. NRG1 contributes to the genetics of schizophrenia in both Icelandic and Scottish schizophrenia patients. ⋯ NRG1 plays a central role in neural development and is most likely involved in regulating synaptic plasticity, or how the brain responds or adapts to the environment. The discovery that defects in NRG1 signaling may be involved in some cases of schizophrenia, not only implicates NRG1, but suggests that its biological pathway, active both at developing and mature synapses, is worth inspecting further in a search for other schizophrenia genes possibly in epistasis with NRG1.