The use of plasma-based resuscitation for trauma patients in hemorrhagic shock has been associated with a decrease mortality. Although some have proposed beneficial effect through replacement coagulation proteins, the putative mechanisms protection afforded by plasma are unknown. We previously shown cell culture model that decreases endothelial permeability comparison crystalloid. glycocalyx consists proteoglycans and glycoproteins attached to syndecan backbone, which together protect...

The early use of fresh frozen plasma as a resuscitative agent after hemorrhagic shock has been associated with improved survival, but the mechanism protection is unknown. Hemorrhagic causes endothelial cell dysfunction and we hypothesized that would restore integrity reduce syndecan-1 shedding shock. A prospective, observational study in severely injured patients demonstrated significantly elevated levels (554±93 ng/ml) injury, which decreased resuscitation (187±36 was compared to normal...

We have recently demonstrated that injured patients in hemorrhagic shock shed syndecan 1 and the early use of fresh frozen plasma (FFP) these is correlated with improved clinical outcomes. As lungs are frequently after trauma, we hypothesized shock–induced shedding exposes underlying pulmonary vascular endothelium to injury resulting inflammation hyperpermeability effects would be mitigated by FFP. In vitro, endothelial permeability, monolayer flux, transendothelial electrical resistance,...

Peroxisome proliferator–activated receptor-delta (PPAR-δ) is overexpressed in human colon cancer, but its contribution to colonic tumorigenesis controversial. We generated a mouse model which PPAR-δ was genetically disrupted epithelial cells by targeted deletion of exon 4. Elimination colon-specific expression confirmed real-time reverse transcription–polymerase chain reaction (real-time RT-PCR), immunoblotting, and activity assays. Mice with without genetic disruption (10–11 mice per group)...

BACKGROUND In retrospective and prospective observational studies, fresh frozen plasma (FFP) has been associated with a survival benefit in massively transfused trauma patients. A dry product, such as spray-dried (SDP), offers logistical advantages over FFP. Recent studies on FFP have demonstrated that modulates systemic vascular stability inflammation. The effect of SDP these measures not previously examined. This study compares using vitro assays endothelial function vivo lung injury mouse...

In severe trauma and hemorrhage the early empiric use of fresh frozen plasma (FFP) is associated with decreased morbidity mortality. However, utilization FFP comes significant burden shipping storage blood products. Dried or lyophilized (LP) can be stored at room temperature, transported easily, reconstituted rapidly ready availability in remote austere environments. We have previously demonstrated that mitigates endothelial injury ensues after hemorrhagic shock (HS). current study, we...

Intravenous tranexamic acid (TXA) is an effective adjunct after hemorrhagic shock (HS) because of its antifibrinolytic properties. TXA also a serine protease inhibitor, and recent laboratory data demonstrated that intraluminal into the small bowel inhibited digestive proteases protected gut. A Disintegrin And Metalloproteinase 17 (ADAM-17) tumor necrosis factor α (TNF-α) are sheddases intestinal syndecan-1, which when shed, exposes underlying epithelium to subsequent systemic insult. We...

Syndecan-1 (Sdc1) is considered a biomarker of injury to the endothelial glycocalyx following hemorrhagic shock, with shedding Sdc1 deleterious. Resuscitation fresh frozen plasma (FFP) has been correlated restitution pulmonary and reduction lung injury, but precise contribution FFPs protection in remains unclear. Human cells were used assess time dose-dependent effect FFP on expression silencing vitro cell permeability actin stress fiber formation. Wild-type mice subjected shock followed by...

Expression of 15-lipoxygenase-1 (15-LOX-1) is decreased in many human cancers; however, the mechanistic significance its expression has been difficult to determine because mouse homolog 12/15-LOX opposing functions. We generated a model which 15-LOX-1 transgene was targeted intestinal epithelium via villin promoter. Targeted confirmed by real-time reverse transcription–polymerase chain reaction and immunoblotting. When expressed colonic epithelial cells two independent lines (B6 FVB),...

Hemorrhagic shock is the leading cause of preventable deaths in civilian and military trauma. Use fresh frozen plasma (FFP) patients requiring massive transfusion associated with improved outcomes. FFP contains significant amounts adiponectin, which known to have vascular protective function. We hypothesize that improves barrier function largely via adiponectin. Plasma adiponectin levels were measured 19 severely injured hemorrhagic (HS). Compared normal individuals, decreased 49% HS before...

ABSTRACT Background: Endothelial dysfunction during hemorrhagic shock (HS) is associated with loss of cell-associated syndecan-1 (Sdc1) and hyperpermeability. Fresh frozen plasma (FFP) preserves Sdc1 reduces permeability following HS, although the key mediators remain unknown. Antithrombin III (ATIII) a protein potent anti-inflammatory endothelial protective activity. We hypothesized that effects FFP on are mediated, in part, through ATIII. Methods: ATIII were measured severely injured...

The mechanisms by which Doxorubicin (Dox) causes acute and late cardiotoxicity are not completely understood. One understudied area is the innate immune response, in particular role of neutrophils Dox-induced cardiotoxicity. Here, using echocardiography, flow cytometry immunofluorescence staining, we demonstrated increased infiltration that correlated with decreased heart function, disruption vascular structures collagen deposition after Dox treatment. Depleting protected from changes...

We have shown in a rodent model of hemorrhagic shock (HS) that fresh frozen plasma (FFP) reduces lung inflammation and injury are correlated with restitution syndecan-1. As the gut is believed to contribute distant organ after shock, current study sought determine if protective effects would extend elucidate contribution syndecan-1 this effect. also examined potential role TNFα, disintegrin metalloproteinase (ADAM)-17, both intestinal sheddases Wild-type (WT) syndecan-1−/− (KO) mice were...

BackgroundThe role of extracellular signal-regulated protein kinase (ERK) in intestinal ischemia/reperfusion (I/R) injury has not been well investigated. The aim the current study was to examine effect inhibition ERK pathway an vitro and vivo model I/R injury. MethodsERK1/2 activity inhibited using specific inhibitor, U0126, epithelial cells under hypoxia/reoxygenation conditions mice subjected 1 hour ischemia followed by 6 hours reperfusion. In vitro, cell proliferation assessed MTT...

We have demonstrated that enteral glutamine provides protection to the postischemic gut, and peroxisome proliferator-activated receptor-γ (PPARγ) plays a role in this protection. Using Cre/lox technology generate an intestinal epithelial cell (IEC)-specific PPARγ null mouse model, we now investigated contribution of IEC glutamine's local distant organ-protective effects. These mice exhibited absence expression intestine but normal other tissues. After 1 h ischemia under isoflurane...

Syndecan 1 is the predominant heparan sulfate proteoglycan found on surface of epithelial cells and, like glutamine, essential in maintaining intestinal barrier. We therefore hypothesized that loss syndecan would abrogate gut-protective effects enteral glutamine. Both an vitro and vivo model gut ischemia-reperfusion (IR) was utilized. In vitro, underwent hypoxia-reoxygenation to mimic IR with 2 mM (physiologic) or 10 glutamine supplementation. Permeability, caspase activity, cell growth,...

Despite aggressive combination chemotherapy and surgery, outcomes for patients with osteosarcoma have remained stagnant more than 25 years, numerous clinical trials identified no new therapies. p53 deletion or mutation is found in 80% of tumors. In p53-deficient cancers structurally altered p63 p73, interfering tumor cell metabolism using Pramlintide (an FDA-approved drug type 2 diabetes) results regression. response mediated through upregulation islet amyloid polypeptide (IAPP). Here, we...

Clinical studies have demonstrated that the early and empiric use of plasma improves survival after hemorrhagic shock. We in rodent models shock resuscitation with is protective to lungs compared lactated Ringer's solution. As our long-term objective determine molecular mechanisms modulate plasma's effects injured bleeding patients, we used human a mouse model The goal current experiments if there are significant adverse on lung injury when using versus an established murine laparotomy.Mice...

To mimic Alzheimer's disease, transgenic mice overexpressing the amyloid precursor protein (APP) were used in this study. We hypothesize that neuroprotective effects of ETAS®50, a standardized extract Asparagus officinalis stem produced by Amino Up Co., Ltd. (Sapporo, Japan), are linked to inhibition apoptosis cascade through an enhancement stress-response proteins: heat shock proteins (HSPs). APP-overexpressing (double-transgenic APP and PS1 mouse strains with 129s6 background), ages 6-8...

Introduction: Endothelial damage and extravasation are deleterious consequences of hemorrhagic shock (HS), associated with inflammation, loss the endothelial glycocalyx barrier hyperpermeability. Fresh frozen plasma (FFP) has been shown to preserve mitigate dysfunction following HS, although mediators this phenomenon remain unknown. Antithrombin III (ATIII) is a protein potent anticoagulant anti-inflammatory activity. ATIII levels decreased trauma particularly in those suffering from HS....

It is now well established that the involvement of gastrointestinal tract great interest as a contributing factor to development and progression neurodegenerative diseases. The dysregulation Gut‐Brain‐Axis (GBA) may be associated with manifestations preceding disorders cognitive and/or memory learning process, supporting hypothesis pathological process spread from gut brain (Mayer et al. 2014). extensive in diseases such Parkinson's disease, even its early stages, has led evaluation enteric...

The Gut-Brain-Axis may be associated with gastrointestinal manifestations preceding disorders of cognitive and/or learning process, supporting the hypothesis that pathological process is spread from gut to brain. We showed exposure lipopolysaccharide (LPS) rats exhibits many features early neurodegeneration, including increases in cytokine production, synthesis neurotrophins, NOS isoforms, α-synuclein aggregates and immune cell infiltration olfactory bulb. also discovered LPS-induced...