Analysis of Neurotoxic Amino Acids from Marine Waters, Microbial Mats, and Seafood Destined for Human Consumption in the Arabian Gulf.

Human health risks associated with exposure to algal and cyanobacterial toxins (phycotoxins) have been largely concerned with aquatic habitats. People inhabiting desert environments may be exposed to phycotoxins present in terrestrial environments, where cyanobacterial crusts dominate. Seafood comprises a significant portion of the human diet in desert environments proximal to an ocean or sea.

Dissolution of lipids from mucus: a possible mechanism for prompt disruption of gut barrier function by alcohol.

Acute and/or chronic alcohol ingestion has been shown to exacerbate the morbidity and mortality rate associated with acute mechanical and/or thermal trauma. While alcohol ingestion can affect many organs and systems, clinical and preclinical studies indicate that alcohol ingestion can cause a 'leaky gut' syndrome which in turn contributes to infection and systemic organ dysfunction. This study investigated the acute effect of alcohol on gut barrier function.

A sphingosine-1 phosphate agonist (FTY720) limits trauma/hemorrhagic shock-induced multiple organ dysfunction syndrome.

Background: Trauma/hemorrhagic shock (T/HS) is one of the major consequences of battlefield injury as well as civilian trauma. FTY720 (sphingosine-1-phosphate agonist) has the capability to decrease the activity of the innate and adaptive immune systems and, at the same time, maintain endothelial cell barrier function and vascular homeostasis during stress. For this reason, we hypothesize that FTY720, as part of resuscitation therapy, would limit T/HS-induced multiple organ dysfunction syndrome in a rodent T/HS model.

The intestinal mucus layer is a critical component of the gut barrier that is damaged during acute pancreatitis.

Gut barrier failure has been implicated in the progression from single-organ injury to multiple-organ failure. The unstirred mucus layer is a major component of the physiological gut barrier; its role in acute pancreatitis (AP) is not clearly defined. Rats underwent biliopancreatic duct ligation-induced AP; two controls were used: biliopancreatic duct ligation with drainage and sham duct ligation.

Intraluminal nonbacterial intestinal components control gut and lung injury after trauma hemorrhagic shock.

Objective: To test whether the mucus layer, luminal digestive enzymes, and intestinal mast cells are critical components in the pathogenesis of trauma shock-induced gut and lung injury.

Background: Gut origin sepsis studies have highlighted the importance of the systemic component (ischemia-reperfusion) of gut injury, whereas the intraluminal component is less well studied.

Methods: In rats subjected to trauma hemorrhagic shock (T/HS) or sham shock, the role of pancreatic enzymes in gut injury was tested by diversion of pancreatic enzymes via pancreatic duct exteriorization whereas the role of the mucus layer was tested via the enteral administration of a mucus surrogate.

Oral pretreatment with recombinant human lactoferrin limits trauma-hemorrhagic shock-induced gut injury and the biological activity of mesenteric lymph.

Background: Lactoferrin (LF) is a pleiotropic glycoprotein that is found in bodily secretions and is postulated to enhance the gastrointestinal barrier and promote mucosal immunity. Thus, the ability of talactoferrin, an oral recombinant form of human LF, to limit gut injury and the production of biologically active gut-derived products was tested using a rat model of trauma-hemorrhagic shock (T/HS).

Methods: Male rats were orally dosed with vehicle or talactoferrin (1000 mg/kg, every day) for 5 d before being subjected to T/HS or trauma-sham shock (T/SS).

Does recombinant factor XIII eliminate early manifestations of multiple-organ injury after experimental burn similarly to gut ischemia-reperfusion injury or trauma-hemorrhagic shock?

The authors have previously shown that recombinant factor XIII (rFXIII) eliminates early manifestations of multiple-organ injury caused by experimental superior mesenteric artery occlusion or trauma-hemorrhagic shock. The aim of the present study was to test the hypothesis that rFXIII provides similar protective effect in experimental burn injury. Rats were randomly divided into five groups (eight animals per group): group 1: burn + placebo treatment; group 2: burn + rFXIII pretreatment; group 3: burn + rFXIII treatment; group 4: sham burn + placebo treatment, and group 5: sham burn + rFXIII treatment.

IRAK1-dependent signaling mediates mortality in polymicrobial sepsis.

Interleukin-1 receptor-associated kinase (IRAK1) is a key regulatory protein in TLR/IL1R-mediated cell activation during inflammatory response. Studies indicated that pending on the nature of the used inflammatory model, downregulation of IRAK1 may be beneficial or detrimental. However, the role of IRAK1 in affecting outcome in polymicrobial sepsis is unknown.

Early trauma-hemorrhage-induced splenic and thymic apoptosis is gut-mediated and toll-like receptor 4-dependent.

Immune depression after trauma-hemorrhage has been implicated as an important factor in the pathogenesis of sepsis and septic-organ failure. Although recent studies have implicated immune-cell apoptosis as an important factor in the evolution of this posttrauma immune-suppressed state, neither the initial triggers that induce this response nor the cellular pathways through which these triggering pathways act have been fully defined. Thus, the current study tests the hypothesis that acute splenic and thymic immune-cell apoptosis developing after trauma-hemorrhagic shock (T/HS) is due to gut-derived factors carried in intestinal lymph and that this T/HS lymph-induced immune depressed state is mediated through Toll-like receptor 4 (TLR4).

Cellular basis of burn-induced cardiac dysfunction and prevention by mesenteric lymph duct ligation.

Background: Myocardial contractile depression develops 4 to 24 h after major burn injury. We have reported previously that in a rat burn injury model (≈40% of total body surface area burn), mesenteric lymph duct ligation (LDL) prior to burn prevented myocardial dysfunction. However, the underlying cellular and molecular mechanisms are not well understood.

Preexisting mental illness and risk for developing a new disorder after hurricane Katrina.

To investigate predisaster mental illness as a risk factor of poor postdisaster mental health outcomes, veterans with (n = 249) and without (n = 250) preexisting mental illness residing in the Gulf Coast during Hurricane Katrina were surveyed after Katrina and screened for posttraumatic stress disorder (PTSD), depression, generalized anxiety disorder, and panic. Logistic regression examined the association between preexisting mental disorders and positive screens after the hurricane, adjusting for demographics and exposure to hurricane-related stressors. The odds of screening positive for any new mental disorder were 6.

Parasympathetic stimulation via the vagus nerve prevents systemic organ dysfunction by abrogating gut injury and lymph toxicity in trauma and hemorrhagic shock.

We tested if vagus nerve stimulation (VNS) would prevent gut injury, mesenteric lymph toxicity, and systemic multiple organ dysfunction syndrome following trauma-hemorrhagic shock (T/HS). Four groups of experiments were performed. The first tested whether VNS (5 V for 10 min) would protect against T/HS-induced increases in gut and lung permeability as well as neutrophil priming.

Oxidative modification of the intestinal mucus layer is a critical but unrecognized component of trauma hemorrhagic shock-induced gut barrier failure.

Recent studies demonstrate that mechanisms underlying gut barrier failure include systemic processes and less studied luminal processes. We thus tested the hypothesis that mucus layer oxidation is a component of trauma/hemorrhagic shock-induced gut injury and dysfunction. Male Sprague-Dawley rats underwent trauma/hemorrhagic shock.

Role of lipase-generated free fatty acids in converting mesenteric lymph from a noncytotoxic to a cytotoxic fluid.

Recent studies have shown that mesenteric lymph plays a very important role in the development of multiple-organ dysfunction syndrome under critical conditions. Great efforts have been made to identify the biologically active molecules in the lymph. We used a trauma-hemorrhagic shock (T/HS) model and the superior mesenteric artery occlusion (SMAO) model, representing a global and a localized intestinal ischemia-reperfusion insult, respectively, to investigate the role of free fatty acids (FFAs) in the cytotoxicity of mesenteric lymph in rats.

Vagal nerve stimulation modulates gut injury and lung permeability in trauma-hemorrhagic shock.

Background: Hemorrhagic shock is known to disrupt the gut barrier leading to end-organ dysfunction. The vagus nerve can inhibit detrimental immune responses that contribute to organ damage in hemorrhagic shock. Therefore, we explored whether stimulation of the vagus nerve can protect the gut and recover lung permeability in trauma-hemorrhagic shock (THS).

Systemic inflammatory response does not correlate with acute lung injury associated with mechanical ventilation strategies in normal lungs.

Background: Mechanical ventilation (MV) can lead to ventilator-induced lung injury secondary to trauma and associated increases in pulmonary inflammatory cytokines. There is controversy regarding the associated systemic inflammatory response. In this report, we demonstrate the effects of MV on systemic inflammation.

Activation of toll-like receptor 4 is necessary for trauma hemorrhagic shock-induced gut injury and polymorphonuclear neutrophil priming.

Interactions of toll-like receptors (TLRs) with nonmicrobial factors play a major role in the pathogenesis of early trauma-hemorrhagic shock (T/HS)-induced organ injury and inflammation. Thus, we tested the hypothesis that TLR4 mutant (TLR4 mut) mice would be more resistant to T/HS-induced gut injury and polymorphonuclear neutrophil (PMN) priming than their wild-type littermates and found that both were significantly reduced in the TLR4 mut mice. In addition, the in vivo and ex vivo PMN priming effect of T/HS intestinal lymph observed in the wild-type mice was abrogated in TLR4 mut mice as well the TRIF mut-deficient mice and partially attenuated in Myd88 mice, suggesting that TRIF activation played a more predominant role than MyD88 in T/HS lymph-induced PMN priming.

Gut-origin sepsis: evolution of a concept.

The concept of bacterial translocation and gut-origin sepsis as a cause of systemic infectious complications and the multiple organ dysfunction syndrome (MODS) in surgical and ICU patients has emerged over the last several decades, although the exact clinical relevance of these phenomena continues to be debated. Thus, the goal of this review is to trace the evolution of gut-origin sepsis and gut-induced MODS and put these disorders and observations into clinical perspective. Additionally, the mechanisms leading to gut-derived complications are explored as well as therapeutic options to limit or prevent these complications.

Testosterone depletion or blockade in male rats protects against trauma hemorrhagic shock-induced distant organ injury by limiting gut injury and subsequent production of biologically active mesenteric lymph.

Background: We tested the hypothesis that testosterone depletion or blockade in male rats protects against trauma hemorrhagic shock-induced distant organ injury by limiting gut injury and subsequent production of biologically active mesenteric lymph.

Methods: Male, castrated male, or flutamide-treated rats (25 mg/kg subcutaneously after resuscitation) were subjected to a laparotomy (trauma), mesenteric lymph duct cannulation, and 90 minutes of shock (35 mm Hg) or trauma sham-shock. Mesenteric lymph was collected preshock, during shock, and postshock.

Effects of pre- and post-Katrina nonviolent and violent experiences on male veterans' psychological functioning.

Background: Identifying individuals at risk for mental health problems after a disaster often involves assessing potentially traumatic exposures inherent to the disaster. Survivors of disasters also may have been exposed, both before and during the event, to trauma not directly related to the disaster. A substantial literature suggests exposure to interpersonal violence may have more severe negative outcomes than exposure to non-violent events; however, it is unclear whether violent vs nonviolent exposures before and during a disaster have differential effects on postdisaster psychological functioning.

Ecto-5'-nucleotidase (CD73) decreases mortality and organ injury in sepsis.

The extracellular concentrations of adenosine are increased during sepsis, and adenosine receptors regulate the host's response to sepsis. In this study, we investigated the role of the adenosine-generating ectoenzyme, ecto-5'-nucleotidase (CD73), in regulating immune and organ function during sepsis. Polymicrobial sepsis was induced by subjecting CD73 knockout (KO) and wild type (WT) mice to cecal ligation and puncture.

β2-Adrenoreceptors of regulatory lymphocytes are essential for vagal neuromodulation of the innate immune system.

The nervous system is classically organized into sympathetic and parasympathetic systems acting in opposition to maintain physiological homeostasis. Here, we report that both systems converge in the activation of β2-adrenoceptors of splenic regulatory lymphocytes to control systemic inflammation. Vagus nerve stimulation fails to control serum TNF levels in either β2-knockout or lymphocyte-deficient nude mice.

Trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice.

Background: Injurious non-microbial factors released from the stressed gut during shocked states contribute to the development of acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS). Since Toll-like receptors (TLR) act as sensors of tissue injury as well as microbial invasion and TLR4 signaling occurs in both sepsis and noninfectious models of ischemia/reperfusion (I/R) injury, we hypothesized that factors in the intestinal mesenteric lymph after trauma hemorrhagic shock (T/HS) mediate gut-induced lung injury via TLR4 activation.

Methods/principal Findings: The concept that factors in T/HS lymph exiting the gut recreates ALI is evidenced by our findings that the infusion of porcine lymph, collected from animals subjected to global T/HS injury, into naïve wildtype (WT) mice induced lung injury.

Mesenteric lymph from rats with trauma-hemorrhagic shock causes abnormal cardiac myocyte function and induces myocardial contractile dysfunction.

Myocardial contractile dysfunction develops following trauma-hemorrhagic shock (T/HS). We have previously shown that, in a rat fixed pressure model of T/HS (mean arterial pressure of 30-35 mmHg for 90 min), mesenteric lymph duct ligation before T/HS prevented T/HS-induced myocardial contractile depression. To determine whether T/HS lymph directly alters myocardial contractility, we examined the functional effects of physiologically relevant concentrations of mesenteric lymph collected from rats undergoing trauma-sham shock (T/SS) or T/HS on both isolated cardiac myocytes and Langendorff-perfused whole hearts.