Poly-N-acetyl glucosamine nanofibers: a new bioactive material to enhance diabetic wound healing by cell migration and angiogenesis.

Introduction: In several fields of surgery, the treatment of complicated tissue defects is an unsolved clinical problem. In particular, the use of tissue scaffolds has been limited by poor revascularization and integration. In this study, we developed a polymer, poly-N-acetyl-glucosamine (sNAG), with bioactive properties that may be useful to overcome these limitations.

Effects of poly-N-acetyl glucosamine (pGlcNAc) patch on wound healing in db/db mouse.

Background: Poly-N-acetyl glucosamine (pGlcNAc) nanofiber-based materials, produced by a marine microalga, have been characterized as effective hemostatic agents. In this study, we hypothesized that a pGlcNAc fiber patch may enhance wound healing in the db/db mouse.

Methods: pGlcNAc patches were applied on 1-cm, full-thickness, skin wounds in the db/db mouse model.

Effect of recombinant platelet-derived growth factor (Regranex) on wound closure in genetically diabetic mice.

Burns, especially those involving large surface areas, represent a complex wound healing problem. Platelet-derived growth factor (PDGF) is released by activated platelets to recruit inflammatory cells toward the wound bed. It has effects on promoting angiogenesis and granulation tissue formation.

Expired liquid preserved platelet releasates retain proliferative activity.

Background: Donated platelets for clinical use currently have a shelf life of 5 days as the result of possible bacterial contamination and loss of hemostatic function. Platelet releasates contain multiple growth factors that have been shown to accelerate wound healing. We sought to demonstrate that although expired platelets can no longer sustain hemostasis, they serve a longer term role as a reservoir of growth factors that could be harnessed in wound healing applications.

Reperfusion injury to skeletal muscle affects primarily type II muscle fibers.

Introduction: The injury caused by reperfusion of ischemic skeletal muscle is mediated by the membrane attack complex of complement (C) . This C activation results from local classical pathway activation after deposition of IgM in injured muscle, an event analogous to C deposition in the mucosa of the gut during reperfusion . Our past analysis has indicated that the injury is not uniform even within a single microscopic section.

IgM binding to injured tissue precedes complement activation during skeletal muscle ischemia-reperfusion.

Background: Skeletal muscle reperfusion injury is mediated by IgM natural antibodies and by complement activation, as shown by the attenuation of reperfusion injury seen in mice with no natural IgM [] and in mice deficient in complement C3 and C4 []. We postulate that tissue, when ischemic, expresses neoantigens to which preformed natural IgM antibodies bind, in turn producing harmful complement activation and reperfusion injury.

Materials And Methods: C57Bl/6 mice were subjected to 2 h of tourniquet-induced hind limb ischemia followed by variable periods of reperfusion.

Murine hindlimb reperfusion injury can be initiated by a self-reactive monoclonal IgM.

Background: Murine hindlimb reperfusion injury (I/R), is initiated by activation of the classical pathway of complement. Complement receptor-2 knockout mice (Cr2-/-) are protected from I/R injury due to defective B-1 cells with a resulting deficient natural immunoglobulin M (IgM) repertoire. Cr2-/- and wild type (WT) mice were studied to isolate the antibody or antibodies responsible for initiation of I/R.

Hemostasis in the absence of clotting factors.

Background: This study tests whether the hemostatic action of poly-N-acetyl glucosamine (p-GlcNAc) fiber material involves vasoconstrictor release leading to closure of an aortic laceration.

Methods: A 22-gauge cannula was inserted into an infrarenal aortic segment of a rat. Surrounding ligatures were tied, and the aorta was flushed with 60 mL of saline from a reservoir held at 80 cm.

Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury.

Reperfusion injury of ischemic tissue represents an acute inflammatory response that can cause significant morbidity and mortality. The mechanism of injury is not fully elucidated, but recent studies indicate an important role for natural antibody and the classical pathway of complement. To test the hypothesis that injury is initiated by specific IgM, we have screened a panel of IgM-producing hybridomas prepared from peritoneal cells enriched in B-1 cells.

Ischaemia-reperfusion is an event triggered by immune complexes and complement.

Background: Reperfusion injury is a common clinical problem that lacks effective therapy. Two decades of research implicating oxygen free radicals and neutrophils has not led to a single successful clinical trial.

Methods: The aim was to review new clinical and preclinical data pertaining to the alleviation of reperfusion injury.

The role of complement and natural antibody in intestinal ischemia-reperfusion injury.

Activation of the complement cascade is central to many types of injury. Ischemia-reperfusion is an important example of such an event. Using intestinal ischemia-reperfusion as a model, we have further elucidated the importance and mechanism of this activation.

Functional activity of natural antibody is altered in Cr2-deficient mice.

The major source of natural IgM Abs are B-1 cells, which differ from conventional B cells in their anatomic location, cell surface phenotype, restricted usage of particular V(H) genes and limited use of N-region addition during V-D-J rearrangement. The origin of B-1 cells is unclear. However, they are capable of self-renewal and their development is sensitive to signaling via the B cell receptor, as genetic defects that impair the strength of the signal often result in limited development.

Comparison of the effects of a 50% exchange-transfusion with albumin, hetastarch, and modified hemoglobin solutions.

We compared the hemodynamic effects of replacing 50% of the blood volume of anesthetized rats with an equal volume of five solutions: human serum albumin (HSA), hetastarch, unmodified hemoglobin, diaspirin-crosslinked hemoglobin, and o-raffinose-crosslinked hemgolobin. Control rats were exchange-transfused with their own blood. HSA and hetastarch caused a severe reduction in systemic vascular resistance (SVR), hypotension, and acute renal failure immediately after the exchange-transfusion.

Survival and function of baboon RBCs released from clotted blood and washed before autologous transfusion.

Background: One alternative to an allogeneic transfusion is the salvaging of the patient's own shed blood. In this study, baboon blood was allowed to clot and the RBCs that were released from the clotted blood lysed with and without urokinase were washed before autologous transfusion.

Study Design And Methods: Forty-four studies were done in 13 baboons (Papio cynocephalus or Papio anubis) over a 3-year period.

Survival, function, and hemolysis of shed red blood cells processed as nonwashed blood and washed red blood cells.

Background: Shed nonwashed blood and shed washed red blood cells (RBC) are being used as alternatives to allogeneic liquid-preserved RBC for patients during thoracic and cardiovascular surgical procedures.

Methods: Mongrel dogs were bled a volume of blood into the abdominal cavity and the shed blood was reinfused as nonwashed blood or washed RBC. The 51Cr RBC volumes were measured before, immediately after, and 24 hours after the exchange transfusion to assess the recovery of the shed RBC and the 24-hour posttransfusion survival.

Sialyl Lewis(x) hybridized complement receptor type 1 moderates acid aspiration injury.

The potentially enhanced anti-inflammatory effects of the sialyl Lewis(x) (sLe(x))-decorated version of soluble complement receptor type 1 (sCR1) in moderating acid aspiration injury are examined. HCl was instilled in tracheostomy tubes placed in mice, and extravasation of (125)I-labeled albumin in bronchoalveolar lavage (BAL) fluid was used to calculate the vascular permeability index (PI). Neutrophil counts in BAL fluid and immunohistochemistry were performed.

Inflammation-induced subcellular redistribution of VE-cadherin, actin, and gamma-catenin in cultured human lung microvessel endothelial cells.

The inflammation-induced subcellular redistribution of key cytoskeletal and junctional proteins in cultured human lung microvessel endothelial cells is investigated as part of a study on the posttranslational regulation of paracellular permeability. Inflammatory agonist-stimulated cells are detergent fractionated into three subcellular compartments followed by quantitative immunoblot analysis. Actin, gamma-catenin, and VE-cadherin increasingly associate with the cytoskeletal fraction upon thrombin stimulation.

Mast cell mediation of muscle and pulmonary injury following hindlimb ischemia-reperfusion.

We have observed extensive mast cell degranulation in the reperfused hindlimb muscle of the mouse, accompanied by pathological changes within the muscle. As quantitated by the tissue:blood (125)I permeability ratio, both the hindlimbs and lungs exhibited a significant increment in permeability during hindlimb reperfusion. In lungs of the same mice, mast cell-derived chymase mMCP-1 coats alveolar macrophages, an event noted by us in acid-induced direct lung injury.

Mast cells mediate complement activation after acid aspiration.

A significant role for the alternative complement pathway in acid aspiration has been demonstrated by the observation that C3 but not C4 genetic knockout mice are protected from permeability edema. Using mast cell-deficient mice (W/Wv), we tested the hypothesis that mast cells mediate complement activation after acid aspiration. Tracheostomy tubes were placed in anesthetized mice and 2 mL/kg 0.

Recombinant soluble P-selectin glycoprotein ligand 1 moderates local and remote injuries following experimental lower-torso ischaemia.

Background: A central role for the polymorphonuclear leucocyte (PMN) in skeletal muscle ischaemia-reperfusion has been demonstrated by the observation that PMN depletion reduced local and remote pulmonary vascular permeability. This study investigated the role of recombinant soluble P-selectin glycoprotein ligand-immunoglobulin fusion protein (rPSGL-Ig), a P- and E-selectin antagonist, in moderating injury.

Methods: Mice underwent 2 h of hindlimb ischaemia and 3 h of reperfusion.

Moderation of skeletal muscle reperfusion injury by a sLe(x)-glycosylated complement inhibitory protein.

The role of the sialyl Lewis(x) (sLe(x))-decorated version of soluble complement receptor type 1 (sCR1) in moderating skeletal muscle reperfusion injury, by antagonizing neutrophil endothelial selectin interaction and complement activation, is examined. Mice underwent 2 h of hindlimb ischemia and 3 h of reperfusion. Permeability index (PI) was assessed by extravasation of 125I-labeled albumin.

The presence of v-abl-transformed V3 mast cells in the lungs augments pulmonary vascular permeability to acid aspiration.

Acid aspiration causes pulmonary vascular permeability and PMN sequestration. By increasing pulmonary mast cells through adoptive transfer of v-abl-transformed mast cells (V3MCs) into BALB/c mice, we now show that the greater mast cell number in the lung is associated with increased pulmonary injury.

Neutrophils, not complement, mediate the mortality of experimental hemorrhagic pancreatitis.

Chemoactivation of the neutrophil (PMN) via the complement system has been observed in many inflammatory conditions and is thought to play a pathogenic role in acute pancreatitis. This study examined the effects of PMN depletion in experimental hemorrhagic pancreatitis and tested the role played by complement. Severe pancreatitis was induced by a choline-deficient, 0.