In Trauma Patients, the Occurrence of Early-Onset Nosocomial Infections is Associated With Increased Plasma Concentrations of Chromogranin A:

In previously healthy persons suffering from acute illnesses, nosocomial infections (NIs) are frequent. Their prevalence suggests the existence of as yet unknown conditions that may promote care-related infection. This study assessed whether the measurement of plasma chromogranin A, a stress-related protein involved in innate defense, is related to NI risk, and whether any chromogranin A-derived fragment included in vasostatin-I displays immunosuppressive activities related to AP-1 or NF-kappa B downregulation. At the clinical level, trauma patients and healthy controls were recruited to be eligible. Clinical histories were recorded, and standard biological tests (including plasma chromogranin A) were performed. For 9 randomly chosen patients and 16 controls, the time-dependent concentrations of chromogranin A (CGA) were assessed twice a day over 66 h. The data show that trauma patients present a higher value of CGA concentration during 66 h in comparison with healthy controls. In addition, patients maintaining this significant increase in CGA readily develop NIs. We therefore studied the effects of chromogranin A-derived peptides on monocytes, focusing on transcription factors that play a central role in inflammation. In vitro assay demonstrated that a chromogranin A-derived fragment (CGA47-70) displays a significant inhibition of NF-kappa B and AP-1 transcriptional activities in these cells. In conclusion, the occurrence of NI in trauma patients is associated with significantly increased plasma CGA concentrations. Downregulation of the two transcription factors by CGA47-70 might induce early acquired immune defect after a serious medical stress

Modification of macroporous titanium tracheal implants with biodegradable structures: tracking in vivo integration for determination of optimal in situ epithelialization conditions.

Previously, we showed that macroporous titanium implants, colonized in vivo together with an epithelial graft, are viable options for tracheal replacement in sheep. To decrease the number of operating steps, biomaterial-based replacements for epithelial graft and intramuscular implantation were developed in the present study. Hybrid microporous PLLA/titanium tracheal implants were designed to decrease initial stenosis and provide a surface for epithelialization. They have been implanted in New Zealand white rabbits as tracheal substitutes and compared to intramuscular implantation samples. Moreover, a basement membrane like coating of the implant surface was also designed by Layer-by-Layer (LbL) method with collagen and alginate. The results showed that the commencement of stenosis can be prevented by the microporous PLLA. For determination of the optimum time point of epithelialization after implantation, HPLC analysis of blood samples, C-reactive protein (CRP), and Chromogranin A (CGA) analyses and histology were carried out. Following 3 weeks the implant would be ready for epithelialization with respect to the amount of tissue integration. Calcein-AM labeled epithelial cell seeding showed that after 3 weeks implant surfaces were suitable for their attachment. CRP readings were steady after an initial rise in the first week. Cross-linked collagen/alginate structures show nanofibrillarity and they form uniform films over the implant surfaces without damaging the microporosity of the PLLA body. Human respiratory epithelial cells proliferated and migrated on these surfaces which provided a better alternative to PLLA film surface. In conclusion, collagen/alginate LbL coated hybrid PLLA/titanium implants are viable options for tracheal replacement, together with in situ epithelialization.journal articleresearch support, non-u.s. gov't2012 Aug2012 03 02importe