a-novel-approach-for-administration-medications-fluids-emergency

A Novel Approach for the Administration of Medications and Fluids in Emergency Scenarios and Settings

The available routes of administration commonly used for medications and fluids in the acute care setting are generally limited to oral, intravenous, or ...

Advocate Christ Medical Center

Macrophages are often associated to pathophysiological processes and were found at hypoxic areas. However, cell adaption greatly depends on hypoxia-inducible factors (HIF). Activation of these transcription factors is induced by heterodimerization of an α-(HIF-1α, -2α, -3α) and HIF-1β subunit. The main regulatory pathway is represented by α-subunit stability. Beside, little is known about the exact mechanisms of fine-tuning in Hif-regulation. The present study characterizes the hypoxia-induced regulation of HIF-1α and -2α in human macrophages. The hypoxic increase of both subunits is initially mediated by protein stabilization. Sustained hypoxia caused a distinct regulation of HIF-1α and -2α. The striking increase of HIF-2α protein expression was contrasted by a dramatic decrease of HIF-1α. The long-term downregulation of HIF-1α is due to downregulation of its mRNA. This decrease was accompanied by increased expression of ahif, a natural cis-antisense transcript of HIF-1α. The ahif-transcript was strongly inducible by hypoxia and rapidly degraded under reoxygenation. Using an adenoviral overexpression and siRNA silencing approach revealed that the targeted regulation of ahif is mediated by the HIF-system itself. Furthermore it could be shown that ahif indeed is able to modulate the hypoxic expression of HIF-1α and influences the expression of the HIF-target gene Enolase-2. Taken together, this study characterizes a new regulation process of the HIF-transcription factor-system in human macrophages under hypoxia. For the first time evidence is provided that ahif is regulated by the HIF-system and influences HIF-1α expression in primary human macrophages.

Regulation of the HIF-system in human macrophages--differential regulation of HIF-α subunits under sustained hypoxia.

Hypoxia plays a pivotal role in development and progression of restenosis after vascular injury. Under hypoxic conditions the hypoxia-inducible factors (HIFs) are the most important transcription factors for the adaption to reduced oxygen supply. Therefore the aim of the study was to investigate the effect of a local HIF-inhibition and overexpression on atherosclerotic plaque development in a murine vascular injury model.

Local inhibition of hypoxia-inducible factor reduces neointima formation after arterial injury in ApoE-/- mice.

Objective The objective of this study was to evaluate whether trimester-specific D-dimer levels or the modified Wells score (MWS) is a useful risk stratification tool to exclude pregnant women at low risk of pulmonary embolism (PE) from diagnostic imaging. Study Design This is a prospective and retrospective cohort study. Pregnant women who underwent diagnostic imaging for suspected PE were prospectively enrolled. D-dimer serum levels were drawn, and a MWS was assigned. Pregnant women diagnosed with a PE before study launch who underwent diagnostic imaging and had a D-dimer level drawn were also evaluated. Results In this study, 17 patients were diagnosed with a PE and 42 patients had no PE on diagnostic imaging. Sixteen out of 17 patients with a PE versus 11 out of 42 without PE had an abnormal D-dimer level (p = 0.001). Four patients with a PE versus zero without a PE had an abnormal MWS (p = 0.005). The combination of a trimester-specific D-dimer level along with the MWS was abnormal in all 17 patients with a documented PE versus 11/42 (26.2%) patients without a documented PE (p = 0.001). Conclusion A combination of trimester-specific D-dimer levels along with a MWS can be used in pregnancy to triage women into a low-risk category for PE and thereby avoid radiation exposure in a majority of pregnant patients.

Article	Year
Regulation of the HIF-system in human macrophages--differential regulation of HIF-α subunits under sustained hypoxia. Molecular immunology\| PubMed ID: 24176785	2014
Local inhibition of hypoxia-inducible factor reduces neointima formation after arterial injury in ApoE-/- mice. Atherosclerosis\| PubMed ID: 24561491	2014
Diagnosing Pulmonary Embolism in Pregnancy: Are Biomarkers and Clinical Predictive Models Useful? AJP reports\| PubMed ID: 27119048	2016

Kathleen Hesse

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