Protective effects of plasma products on the endothelial-glycocalyx barrier following trauma-hemorrhagic shock: Is sphingosine-1 phosphate responsible?

Background: Plasma is an important component of resuscitation after trauma and hemorrhagic shock (T/HS). The specific plasma proteins and the impact of storage conditions are uncertain. Utilizing a microfluidic device system, we studied the effect of various types of plasma on the endothelial barrier function following T/HS.

Acute hyperglycemia exacerbates trauma-induced endothelial and glycocalyx injury: An in vitro model.

Background: Early hyperglycemia is associated with higher mortality in trauma and predicts multiple organ failure. Endothelial cell (EC) injury and glycocalyx (GC) degradation occur following traumatic shock and are key factors in the development of trauma-induced coagulopathy and result in impaired microvascular perfusion and accompanying organ failure. Acute hyperglycemia has been shown to result in the loss of the GC layer, EC inflammation, and activation of coagulation in vivo.

The temporal response and mechanism of action of tranexamic acid in endothelial glycocalyx degradation.

Background: The endothelial glycocalyx (GCX) plays an important role in vascular barrier function. Damage to the GCX occurs due to a variety of causes including hypoxia, ischemia-reperfusion, stress-related sympathoadrenal activation, and inflammation. Tranexamic acid (TXA) may prevent GCX degradation.

Tranexamic acid and the gut barrier: Protection by inhibition of trypsin uptake and activation of downstream intestinal proteases.

Objective: Intraluminal pancreatic trypsin and other digestive enzymes injure the gut barrier following trauma-hemorrhagic shock (T/HS). Intestinal proteases (sheddases) exert important effects on normal gut function but may cause barrier disruption due to exaggerated production following T/HS. We hypothesized that the protective mechanism of TXA on the gut barrier following T/HS includes inhibition of these "downstream" proteases.

Gender dimorphism in adipose tissue response to stress conditions: A plausible mechanism to explain the conflicting data regarding trauma and obesity.

Introduction: Obesity is a chronic low-grade inflammatory condition associated with the elaboration of proinflammatory cytokines and adipokines from adipose tissue. Gender dimorphism (in part due to sex hormones) has been identified after injury and hemorrhagic shock. We hypothesized that the sex hormones estrogen (E2) and testosterone (DHT) have disparate effects on inflammatory mediator production from adipose tissue under stress conditions.

Early tranexamic acid administration: A protective effect on gut barrier function following ischemia/reperfusion injury.

Background: The mucus barrier is a critical component of the gut barrier and may be disrupted by pancreatic enzymes following trauma/hemorrhagic shock (T/HS). Luminal strategies against pancreatic enzyme activation or contact with the intestine are protective of the mucus layer and gut barrier integrity following T/HS. There is increasing evidence the use of tranexamic acid (TA) attenuates inflammatory responses in cardiac surgery and is readily absorbed from the gut.

Estrogen modulates intestinal mucus physiochemical properties and protects against oxidant injury.

Background: The intestinal epithelial barrier and the intestinal mucus layer may be protective against trauma/hemorrhage shock-induced injury in females. This effect is related to estradiol (E₂) concentrations and varies with the menstrual cycle. We examined the ability of E₂ to impact the physiochemical properties of intestinal mucus and to protect against oxidant-related injury to the mucus and underlying intestinal epithelial barrier in an in vitro model.

Gender dimorphism in the gut: mucosal protection by estrogen stimulation of IgA transcytosis.

Background: Laboratory studies demonstrate gender dimorphism following trauma/hemorrhagic shock (T/HS). These differences have been attributed to estrogen (E2) levels. Maintenance of gut barrier function by E2 following T/HS has been recently described.

CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts.

Recent evidence suggests that breast cancer and other solid tumors possess a rare population of cells capable of extensive self-renewal that contribute to metastasis and treatment resistance. We report here the development of a strategy to target these breast cancer stem cells (CSCs) through blockade of the IL-8 receptor CXCR1. CXCR1 blockade using either a CXCR1-specific blocking antibody or repertaxin, a small-molecule CXCR1 inhibitor, selectively depleted the CSC population in 2 human breast cancer cell lines in vitro.

Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature.

Tumors may be initiated and maintained by a cellular subcomponent that displays stem cell properties. We have used the expression of aldehyde dehydrogenase as assessed by the ALDEFLUOR assay to isolate and characterize cancer stem cell (CSC) populations in 33 cell lines derived from normal and malignant mammary tissue. Twenty-three of the 33 cell lines contained an ALDEFLUOR-positive population that displayed stem cell properties in vitro and in NOD/SCID xenografts.