BackgroundHypoxia inducible factor (HIF)-1 is the key transcriptional factor involved in the adaptation process of cells and organisms to hypoxia. Recent findings suggest that HIF-1 plays also a crucial role in inflammatory and infectious diseases.Methodology/Principal FindingsUsing patient skin biopsies, cell culture and murine infection models, HIF-1 activation was determined by immunohistochemistry, immunoblotting and reporter gene assays and was linked to cellular oxygen consumption. The course of a S. aureus peritonitis was determined upon pharmacological HIF-1 inhibition. Activation of HIF-1 was detectable (i) in all ex vivo in biopsies of patients suffering from skin infections, (ii) in vitro using cell culture infection models and (iii) in vivo using murine intravenous and peritoneal S. aureus infection models. HIF-1 activation by human pathogens was induced by oxygen-dependent mechanisms. Small colony variants (SCVs) of S. aureus known to cause chronic infections did not result in cellular hypoxia nor in HIF-1 activation. Pharmaceutical inhibition of HIF-1 activation resulted in increased survival rates of mice suffering from a S. aureus peritonitis.Conclusions/SignificanceActivation of HIF-1 is a general phenomenon in infections with human pathogenic bacteria, viruses, fungi and protozoa. HIF-1-regulated pathways might be an attractive target to modulate the course of life-threatening infections.

Background: Despite advances in the monitoring of free flaps, there is still a demand for new technology to detect ischemic complications at an early stage. The aim of the present study was to evaluate the reliability of the O2C-device in terms of detecting flap failure in commonly used perforator flaps for breast reconstruction. Methods: A total of 34 patients undergoing breast reconstruction were involved in this study. The perfusion dynamics of 23 deep inferior epigastric perforator flaps and 11 superior gluteal arterial perforator flaps were assessed using the O2C-device, which combines a laser light, to determine blood flow (flow), velocity, and white light to determine hemoglobin oxygenation (SO 2 ) and relative amount of hemoglobin (rHB). Measurements were carried out intra-operatively after clamping and declamping the perforator vessels. In the post-operative period measurements were carried out every hour for the first 48 hours and from 3rd to 7th for every 2 hours. These dates were compared to findings of clinical assessment. Results: Several intra-operative measurements, during the clamping and declamping the different perforator vessels, revealed a high correlation for all parameters: Flow (r 5 0.89, P < 0. 05), Velo (r 5 0.92, P < 0. 05), SO 2 (r 50.84, P <0. 05), and rHB (r 50.83 P < 0.05). Vessel occlusion was detected in five cases, of which three were due to arterial thrombosis and two further cases were due to venous occlusion. Of the five cases, one flap loss caused by venous occlusion was noted. Conclusion: The O2C-device seems to be a reliable, objective, and non-invasive device for the monitoring of free flaps. Thus, it may improve flap survival rates by detecting vascular compromise at an early stage. V V C 2013 Wiley Periodicals, Inc. Microsurgery 33: 350-357, 2013.

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