Matrix Metalloproteinase-3 is Key Effector of TNF-α-Induced Collagen Degradation in Skin.

Inflammatory processes in the skin augment collagen degradation due to the up-regulation of matrix metalloproteinases (MMPs). The aim of the present project was to study the specific impact of MMP-3 on collagen loss in skin and its interplay with the collagenase MMP-13 under inflammatory conditions mimicked by the addition of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Skin explants from MMP-3 knock-out (KO) mice or from transgenic (TG) mice overexpressing MMP-3 in the skin and their respective wild-type counterparts (WT and WTT) were incubated ex vivo for eight days. The rate of collagen degradation, measured by released hydroxyproline, was reduced (p < 0.001) in KO skin explants compared to WT control skin but did not differ (p = 0.47) between TG and WTT skin. Treatment with the MMP inhibitor GM6001 reduced hydroxyproline media levels from WT, WTT and TG but not from KO skin explants. TNF-α increased collagen degradation in the WT group (p = 0.0001) only. More of the active form of MMP-13 was observed in the three MMP-3 expressing groups (co-incubation with receptor-associated protein stabilized MMP-13 subforms and enhanced detection in the media). In summary, the innate level of MMP-3 seems responsible for the accelerated loss of cutaneous collagen under inflammatory conditions, possibly via MMP-13 in mice.

Degradable polyester scaffolds with controlled surface chemistry combining minimal protein adsorption with specific bioactivation.

Advanced biomaterials and scaffolds for tissue engineering place high demands on materials and exceed the passive biocompatibility requirements previously considered acceptable for biomedical implants. Together with degradability, the activation of specific cell­material interactions and a three-dimensional environment that mimics the extracellular matrix are core challenges and prerequisites for the organization of living cells to functional tissue. Moreover, although bioactive signalling combined with minimization of non-specific protein adsorption is an advanced modification technique for flat surfaces, it is usually not accomplished for three-dimensional fibrous scaffolds used in tissue engineering. Here, we present a one-step preparation of fully synthetic, bioactive and degradable extracellular matrix-mimetic scaffolds by electrospinning, using poly(D,L-lactide-co-glycolide) as the matrix polymer. Addition of a functional, amphiphilic macromolecule based on star-shaped poly(ethylene oxide) transforms current biomedically used degradable polyesters into hydrophilic fibres, which causes the suppression of non-specific protein adsorption on the fibres' surface. The subsequent covalent attachment of cell-adhesion-mediating peptides to the hydrophilic fibres promotes specific bioactivation and enables adhesion of cells through exclusive recognition of the immobilized binding motifs. This approach permits synthetic materials to directly control cell behaviour, for example, resembling the binding of cells to fibronectin immobilized on collagen fibres in the extracellular matrix of connective tissue.

Intrathoracic versus cervical anastomosis after resection of esophageal cancer: a matched pair analysis of 72 patients in a single center study.

BACKGROUND: The aim of this study was to analyze the early postoperative outcome of esophageal cancer treated by subtotal esophageal resection, gastric interposition and either intrathoracic or cervical anastomosis in a single center study. METHODS: 72 patients who received either a cervical or intrathoracic anastomosis after esophageal resection for esophageal cancer were matched by age and tumor stage. Collected data from these patients were analyzed retrospectively regarding morbidity and mortality rates. RESULTS: Anastomotic leakage rate was significantly lower in the intrathoracic anastomosis group than in the cervical anastomosis group (4 of 36 patients (11%) vs. 11 of 36 patients (31%); p = 0.040). The hospital stay was significantly shorter in the intrathoracic anastomosis group compared to the cervical anastomosis group (14 (range 10-110) vs. 26 days (range 12 - 105); p = 0.012). Wound infection and temporary paresis of the recurrent laryngeal nerve occurred significantly more often in the cervical anastomosis group compared to the intrathoracic anastomosis group (28% vs. 0%; p = 0.002 and 11% vs. 0%; p = 0.046). The overall In-hospital mortality rate was 6% (4 of 72 patients) without any differences between the study groups. CONCLUSIONS: The present data support the assumption that the transthoracic approach with an intrathoracic anastomosis compared to a cervical esophagogastrostomy is the safer and more beneficial procedure in patients with carcinoma of the lower and middle third of the esophagus due to a significant reduction of anastomotic leakage, wound infection, paresis of the recurrent laryngeal nerve and shorter hospital stay.

Abdominal compartment syndrome in childhood: diagnostics, therapy and survival rate.

PURPOSE: The abdominal compartment syndrome (ACS) in childhood is a rare but dire disease if diagnosed delayed and treated improperly. The mortality amounts up to 60% (Beck et al. in Pediatr Crit Care Med 2:51-56, 2001). ACS is defined by a sustained rise of the intraabdominal pressure (IAP) together with newly developed organ dysfunction. The present study reports on 28 children with ACS to evaluate its potential role in the diagnosis, treatment and outcome of ACS. METHODS: Retrospectively, medical reports and outcome of 28 children were evaluated who underwent surgical treatment for ACS. The diagnosis of ACS was established by clinical signs, intravesical pressure-measurements and concurrent organ dysfunction. RESULTS: Primary ACS was found in 25 children (89.3%) predominantly resulting from polytrauma and peritonitis. Three children presented secondary ACS with sepsis (2 cases) and combustion (1 case) being the underlying causative diseases. Therapy of choice was the decompression of the abdominal cavity with implantation of an absorbable Vicryl(®) mesh. In 18 cases the abdominal cavity could be closed later, while in the other ten cases granulation of the mesh was allowed. The overall survival rate was 78.6% (22 of 28 children). The cause of death in the remaining six cases (21.4%) was sepsis with multiorgan failure. CONCLUSION: Our results suggest that early establishment of the specific diagnosis of ACS followed by swift therapy with reduction of intraabdominal hypertension is essential in order to further reduce the high mortality rate associated with this condition.