LITAF mediation of increased TNF-α secretion from inflamed colonic lamina propria macrophages.

Dysregulation of TNF-α in lamina propria macrophages (LPM) is a feature of inflammatory bowel diseases (IBD). LPS-Induced-TNF-Alpha-Factor (LITAF) is a transcription factor that mediates TNF-α expression. To determine whether LITAF participates in the mediation of TNF-α expression in acutely inflamed colonic tissues, we first established the TNBS-induced colonic inflammation model in C57BL/6 mice.

N-acetyl-l-cysteine decreases intra-abdominal adhesion formation through the upregulation of peritoneal fibrinolytic activity and antioxidant defenses.

Background: Intraperitoneal adhesions occur in more than 94% of patients after abdominal surgery. Mechanisms that decrease oxidative stress and upregulate peritoneal fibrinolysis reduce adhesions. N-acetyl-l-cysteine (NAC) is a clinically relevant antioxidant whose effect on peritoneal fibrinolysis and ability to decrease adhesions has not been established.

The efficacy of a hyaluronate-carboxymethylcellulose bioresorbable membrane that reduces postoperative adhesions is increased by the intra-operative co-administration of a neurokinin 1 receptor antagonist in a rat model.

Background: Bioresorbable membranes composed of hyaluronic acid and carboxymethylcellulose (HA/CMC) are the most effective method to prevent intra-abdominal adhesions; however, their efficacy may be limited to the site of application. Previous studies in our laboratory have shown that the intraperitoneal administration of a neurokinin-1 receptor antagonist (NK-1RA) reduces adhesions; however, the co-administration of HA/CMC plus an NK-1RA has not been studied.

Methods: Adhesions were induced in rats by creating ischemic buttons on the peritoneum.

Stasis predisposes ileal pouch inflammation in a rat model of ileal pouch-anal anastomosis.

Background: While restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the definitive surgical treatment for patients suffering from chronic ulcerative colitis (CUC), pouchitis still remains a major late complication. Fecal stasis has been implicated in the etiology of ileal inflammation; however, the mechanism(s) remain unclear, in part due to the lack of an animal model. Our goal was to surgically mimic the IPAA procedure in a rat to investigate the hypothesis that stasis leads to biochemical changes that predispose the ileal pouch to inflammation.

Inhibitory effects of a neurokinin-1 receptor antagonist on postoperative peritoneal adhesion formation.

Intra-abdominal adhesions are a costly, long-term sequela of abdominal surgeries. They occur in up to 94% of patients following abdominal operation and cause significant postoperative morbidity including difficult reoperative surgeries, small bowel obstructions, and infertility. The pathophysiology of adhesion formation remains poorly defined, and a uniformly effective method of adhesion prevention does not exist.

Practical limitations of bioresorbable membranes in the prevention of intra-abdominal adhesions.

Introduction: Intra-abdominal adhesions are a significant source of postoperative morbidity. Bioresorbable barriers composed of hyaluronic acid and carboxymethylcellulose (HA/CMC) reduce adhesion formation by physically separating injured or healing peritoneal surfaces. To assess whether the efficacy of a physical barrier can extend beyond the site of application, we evaluated the effectiveness of an HA/CMC barrier in preventing adhesions distal to the site of placement.

Pharmacologic inhibition of adhesion formation and peritoneal tissue-type plasminogen activator activity.

Intraperitoneal adhesions remain a costly, long-term sequela of abdominal surgery. They cause significant postoperative morbidity and difficult reoperative surgery. Although adhesions have been recognized for more than 250 years, a uniformly effective method of adhesion prevention does not exist.

An FDA approved neurokinin-1 receptor antagonist is effective in reducing intraabdominal adhesions when administered intraperitoneally, but not orally.

Introduction: Postoperative adhesions pose a continued healthcare problem. We previously demonstrated that intraperitoneal (i.p.

A neurokinin-1 receptor antagonist that reduces intraabdominal adhesion formation increases peritoneal matrix metalloproteinase activity.

Adhesions remain a significant complication of abdominal surgery. There is a growing body of evidence suggesting that remodeling of peritoneal extracellular matrix by matrix metalloproteinases (MMPs) is involved in adhesion formation. We have shown that administration of a specific neurokinin-1 receptor (NK-1R) antagonist (CJ-12,255, Pfizer) to rats within 5 hours of surgery reduces intraabdominal adhesion formation.

Intraperitoneal administration of methylene blue attenuates oxidative stress, increases peritoneal fibrinolysis, and inhibits intraabdominal adhesion formation.

Background: Mounting evidence indicates that postoperative oxidative stress may be linked to decreased fibrinolytic activity and, subsequently, the development of intraabdominal adhesions. The goal of this study was to determine if methylene blue, a highly redox active dye that has been shown to inhibit adhesion formation (1) acts as an antioxidant in the postoperative peritoneum, and (2) subsequently affects fibrinolytic activity.

Materials And Methods: Intraabdominal adhesions were surgically induced in rats receiving methylene blue (30 mg/kg) or vehicle (sterile water) intraperitoneally at surgery.

A neurokinin-1 receptor antagonist that reduces intra-abdominal adhesion formation decreases oxidative stress in the peritoneum.

Oxidative stress has been implicated in intra-abdominal adhesion formation. Substance P, a neurokinin-1 receptor (NK-1R) ligand, facilitates leukocyte recruitment and reactive oxygen species (ROS) generation. We have shown in a rat model of adhesion formation that intraperitoneal administration of a NK-1R antagonist at the time of abdominal operation reduces postoperative adhesion formation.

Carcinoembryonic antigen-stimulated THP-1 macrophages activate endothelial cells and increase cell-cell adhesion of colorectal cancer cells.

The liver is the most common site for metastasis by colorectal cancer, and numerous studies have shown a relationship between serum carcinoembryonic antigen (CEA) levels and metastasis to this site. CEA activates hepatic macrophages or Kupffer cells via binding to the CEA receptor (CEA-R), which results in the production of cytokines and the up-regulation of endothelial adhesion molecules, both of which are implicated in hepatic metastasis. Since tissue macrophages implicated in the metastatic process can often be difficult to isolate, the aim of this study was to develop an in vitro model system to study the complex mechanisms of CEA-induced macrophage activation and metastasis.

The effectiveness of a single intraperitoneal infusion of a neurokinin-1 receptor antagonist in reducing postoperative adhesion formation is time dependent.

Background: Current methods to prevent intraabdominal adhesions are not uniformly effective. We recently showed in rats that a neurokinin-1 receptor (NK-1R) antagonist is capable of reducing adhesion formation. To determine the clinical feasibility of using an NK-1R antagonist to reduce adhesions, this study examined the time dependence for the effectiveness of NK-1R antagonist administration and its effects on wound healing.

Statins (HMG-CoA reductase inhibitors) decrease postoperative adhesions by increasing peritoneal fibrinolytic activity.

Objectives: The aims of this study were to determine if statins reduce adhesion formation in vivo and to identify the mechanism of action in vitro.

Background: : Intraperitoneal adhesions develop in up to 95% of patients following laparotomy. Adhesions are reduced by mechanisms that up-regulate fibrinolysis within the peritoneum.

NF-kappaB activation precedes increases in mRNA encoding neurokinin-1 receptor, proinflammatory cytokines, and adhesion molecules in dextran sulfate sodium-induced colitis in rats.

Nuclear factor kappa B (NF-kappa B) plays a key role in initiating inflammation associated with colitis. A systematic study was conducted in the rat DSS colitis model to determine the temporal relationship between NF-kappa B activation and expression of substance P (SP), neurokinin-1 receptor (NK-1R), proinflammatory cytokines, and adhesion molecules. Rats were given 5% DSS in their water and sacrificed daily for 6 days.

Cloning and characterization of a functional type II gonadotropin-releasing hormone receptor with a lengthy carboxy-terminal tail from an ancestral vertebrate, the sea lamprey.

A full-length transcript encoding a functional type II GnRH receptor was cloned from the pituitary of the sea lamprey, Petromyzon marinus. The current study is the first to identify a pituitary GnRH receptor transcript in an agnathan, which is the oldest vertebrate lineage. The cloned receptor retains the conserved structural features and amino acid motifs of other known GnRH receptors and notably includes a C-terminal intracellular tail of approximately 120 amino acids, the longest C-terminal tail of any vertebrate GnRH receptor identified to date.

A neurokinin 1 receptor antagonist decreases postoperative peritoneal adhesion formation and increases peritoneal fibrinolytic activity.

Fibrous adhesions remain a major sequela of abdominal surgery. The proinflammatory peptide substance P (SP), known to participate in inflammatory events, may play a key role in adhesion formation. This hypothesis was tested by using an antagonist, CJ-12,255 (Pfizer), that blocks the binding of SP to the neurokinin 1 receptor (NK-1R).

Osteocyte-based image analysis for quantitation of histologically apparent femoral head osteonecrosis: application to an emu model.

Femoral head osteonecrosis is often characterized histologically by the presence of empty lacunae in the affected bony regions. The shape, size and location of a necrotic lesion influences prognosis, and can, in principle, be quantified by mapping the distribution of empty lacunae within a femoral head. An algorithm is here described that automatically identifies the locations of osteocyte-filled vs.

A neurokinin 1 receptor antagonist reduces an ongoing ileal pouch inflammation and the response to a subsequent inflammatory stimulus.

Ileal pouch-anal anastomosis (IPAA) is an excellent surgical option for patients with chronic ulcerative colitis (CUC) requiring colectomy; however, persistent episodes of ileal pouch inflammation, or pouchitis, may result in debilitating postoperative complications. Because considerable evidence implicates substance P (SP) as an inflammatory mediator of CUC, we investigated whether SP participates in the pathophysiology of pouchitis. With the use of a rat model of IPAA that we developed, we showed that ileal pouch MPO levels and neurokinin 1 receptor (NK-1R) protein expression by Western blot analysis were significantly elevated 28 days after IPAA surgery.

Focal cryogen insults for inducing segmental osteonecrosis: computational and experimental assessments of thermal fields.

Orthopaedic management of femoral head osteonecrosis is a common clinical problem for which there presently is no good solution. Current animal models are inappropriate to study potential new solutions, since it has been difficult to replicate the natural history of structural collapse seen in the human disorder. Recently, progression to collapse was obtained for cryogenically induced osteonecrosis in emus, although the lesions involved were imprecisely controlled in terms of size or location.

Neurokinin-1 receptor and substance P messenger RNA levels increase during intraabdominal adhesion formation.

Background: Intraabdominal peritoneal adhesions are a significant cause of postoperative morbidity and remain one of the major long-term complications associated with abdominal surgery. Adhesion formation at the molecular level involves a complex interaction of cytokines, growth factors, cell adhesion molecules, and neuropeptides, as well as many other factors secreted by cells proximate to the traumatized area. Limited studies exist which investigate the molecular processes involved in adhesion formation.

The spatial relationship of gamma-aminobutyric acid (GABA) neurons and gonadotropin-releasing hormone (GnRH) neurons in larval and adult sea lamprey, Petromyzon marinus.

In this study we examined the spatial relationship of GABA-containing and GnRH-containing neurons by immunocytochemistry and in situ hybridization in larval and adult brains of sea lamprey, Petromyzon marinus. In immunocytochemical studies, GABA-containing neurons were detected early in lamprey development, by day 20 post-fertilization. At this time point, one population of GABA-containing neurons was visualized in the hypothalamus and preoptic area, and another population was located in the olfactory bulb of the telencephalon.