Interleukin-6 and tumor necrosis factor production in an enterocyte cell model (Caco-2) during exposure to Escherichia coli.

Data linking interactions between bacteria and the intestine with elevated serum cytokine levels has led to the concept of the gut as a cytokine-producing organ. An in vitro cell culture model was used to investigate the potential role of intestinal mucosa within this paradigm. Polarized monolayers of human enterocytes (Caco-2) were grown in a two compartment system where the apical and basal aspects of the membrane could be studied.

Academic surgeons' knowledge of Food and Drug Administration regulations for clinical trials.

Objectives: To identify knowledge levels of academic surgeons about Food and Drug Administration (FDA) and Institutional Review Board (IRB) regulations for clinical research and to determine whether being a member in an IRB, conducting or participating in clinical trials, or being a member in surgical societies affected knowledge levels.

Design: Survey of surgical department faculty members in 20 universities.

Results: Sixty-five responses were received from 14 sites.

The relationship between gut-derived bacteria and the development of the multiple organ dysfunction syndrome.

Abnormal colonisation, infections of gut origin and bacterial translocation are all signs of gut failure that have been hypothesised as being implicated in the pathogenesis of the multiple organ dysfunction syndrome (MODS). We have summarised published experimental and clinical studies that have tried to correlate the occurrence or prevention of these phenomena with the development of MODS. We conclude that in some patients loss of intestinal barrier function or the onset of infection precedes the development of MODS.

Effect of heat shock and endotoxin stress on enterocyte viability apoptosis and function varies based on whether the cells are exposed to heat shock or endotoxin first.

Background: Stress-gene responses, including the heat shock (HS) response and the acute phase response, are protective mechanisms for cells after exposure to stress. Both responses cannot occur simultaneously, and, in endothelial cells, the sequence of stress-gene expression seems to be a critical factor in whether cellular protection or injury occurs.

Objective: To determine if the sequence of stress-gene expression affects cellular protection or injury in epithelial cells.

Trauma, shock, and gut translocation.

This article reviews the scientific and clinical evidence that supports trauma and shock as potential etiologies for translocation of intestinal microorganisms and their by-products. The potential for loss of intestinal barrier function to cause the eventual septic deaths observed in such patients, as well as possible mechanisms for preventing and treating this entity is also discussed.

Role of the gut in multiple organ failure: bacterial translocation and permeability changes.

It is clear that increased gut permeability and bacterial translocation play a role in multiple organ failure (MOF). Failure of the gut barrier remains central to the hypothesis that toxins escaping from the gut lumen contribute to activation of the host's immune inflammatory defense mechanisms, subsequently leading to the autointoxication and tissue destruction seen in the septic response characteristic of MOF. However, the role of the gut is more than that of a sieve, which simply allows passage of bacteria and endotoxin from the gut lumen to the portal or systemic circulation.

Infection, the gut and the development of the multiple organ dysfunction syndrome.

It has been hypothesised that failure of the gut is an important pathophysiological phenomenon of the generalised inflammatory response that leads to the multiple organ dysfunction syndrome (MODS). Abnormal colonisation, infections of gut origin, bacterial translocation are all signs of gut failure that have been implicated in the pathogenesis of MODS. We have concluded after summarising published experimental and clinical studies that have tried to correlate the occurrence or prevention (by selective decontamination of the digestive tract) of these phenomena with the development of MODS, it seems that in some patients it is clear that loss of intestinal barrier function or the onset of infection precedes the development of MODS.

Alterations in intestinal bacterial flora modulate the systemic cytokine response to hemorrhagic shock.

To test the hypothesis that the resident gut flora plays an active role in modulating the cytokine response to hemorrhagic shock, plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were measured from the following three groups of rats before, immediately after, and 3, 8, or 24 h post-hemorrhagic shock (90 min at 30 mmHg)/sham shock: 1) rats with a normal gut flora (NF), 2) rats whose gut flora had been decontaminated with oral antibiotics (AD), and 3) rats with intestinal overgrowth with E. coli. In all three groups, portal and systemic TNF and IL-6 levels were 2- to 10-fold higher in the shock than the sham-shock rats (P < 0.

Caco-2 and IEC-18 intestinal epithelial cells exert bactericidal activity through an oxidant-dependent pathway.

Intestinal epithelial cells have receptors that recognize bacterial antigens and in some circumstances are actively involved in bacterial internalization. To test the hypothesis that intestinal epithelial cells possess bactericidal capabilities, the bactericidal activity of two intestinal cell lines (IEC-18 and Caco-2) was measured using Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli as test organisms. The relative bactericidal efficacy of these two intestinal cell lines to kill these bacteria was compared against neutrophils (PMN) using a standard in vitro bactericidal assay.

Adoptive transfer of T lymphocytes to T-cell-depleted mice inhibits Escherichia coli translocation from the gastrointestinal tract.

Bacterial translocation is defined as the passage of viable bacteria from the gastrointestinal (GI) tract to extraintestinal sites, such as the mesenteric lymph node (MLN), spleen, liver, kidneys, and blood. Previously, we reported that depletion of CD4+ and/or CD8+ T cells promotes bacterial translocation from the GI tract to the MLN. In the present study, CD4+ and/or CD8+ T cells, harvested from donor mice, were adoptively transferred to mice previously depleted of T cells by thymectomy plus intraperitoneal injection of rat anti-mouse T-cell monoclonal antibodies.

The gut: a cytokine-generating organ in systemic inflammation?

The aim of this study was to test the hypothesis that the gut is capable of becoming a cytokine-generating organ following either a lethal or nonlethal inflammatory insult. Adult male rats were given an intraperitoneal challenge with saline, or with a nonlethal (.1 mg/g) or LD50 (.

Induction of heat shock gene expression in colonic epithelial cells after incubation with Escherichia coli or endotoxin.

Objective: The universal cellular response to stress is the expression of a family of genes known as heat shock or stress proteins. We investigated whether bacteria or bacterial products (endotoxin) can induce heat shock protein expression in human enterocytes.

Design: Controlled, in vitro study.

Nutritional support of the burn patient.

Nutritional support of the burn patient is essential to optimize host immune defenses and to promote prompt wound healing. The interdependent relationship between metabolism, nutrition, and infection is discussed, followed by an extensive description of the various means of determining the appropriate type, form, and amount of nutritional support to provide to patients of various ages and with differing burn sizes. A concise discussion of the role of various growth factors and micronutrients completes this article.

Presence of the stress-inducible form of hsp-70 (hsp-72) in normal rat colon.

The expression of heat shock proteins (hsp) is probably one of the most primitive mechanisms of cellular protection from stress. Pathogens such as viruses and bacteria have recently been found to induce the heat shock gene expression. In the present study hsp-72, the stress-inducible form of hsp-70, was detected by Western blotting in samples from rat distal colon (DC), proximal colon (PC), and terminal ileum (TI), but was not found in proximal small bowel (PSB) or other organs (liver, kidney, spleen, heart, and brain) of unstressed animals.

Comparison of plasma cytokine levels in rats subjected to superior mesenteric artery occlusion or hemorrhagic shock.

The overall goal of this study was to compare the effects of systemic hypotension (hemorrhagic shock) versus local gut ischemia (superior mesenteric artery (SMA) occlusion) on cytokine production and bacteria/endotoxin translocation. Sham or actual SMA occlusion led to an increase in tumor necrosis factor (TNF), which was greatest at the end of the occlusion period, while the IL-6 response peaked 3 h post-SMA occlusion. The TNF and IL-6 response after hemorrhagic shock differed from that observed after SMA occlusion in that the peak response occurred later and was of lower magnitude (p < .

Sepsis and multiple organ dysfunction syndrome: a clinical-mechanistic overview.

Multiple organ dysfunction syndrome (MODS) is the primary cause of death in patients admitted to ICUs. Despite the development of better resuscitation, more powerful antibiotics, and more sophisticated methods for organ support, our ability to rescue patients from established MODS has not improved significantly since the syndrome was first described two decades ago. Rapid advancements in molecular biology have begun to unravel some of the potential mechanisms behind the development of this syndrome, and have suggested many potential therapeutic approaches.

Elemental diet and IV-TPN-induced bacterial translocation is associated with loss of intestinal mucosal barrier function against bacteria.

Objective: The goal of the current study was to directly assess the role of loss of mucosal barrier function in nutritionally induced bacterial translocation.

Background: Parenteral and certain elemental enteral diets have been shown to promote bacterial translocation. The mechanisms underlying this observation, especially the question of whether nutritionally induced bacterial translocation is primarily related to loss of intestinal barrier function, versus an impaired immune system, remain to be fully elucidated.

Multiple organ failure: a common problem in surgical intensive care unit patients.

The management of the surgical patient with multiple system organ failure remains a formidable problem. Despite advances in critical care, the mortality of multiple organ failure remains unchanged since the syndrome was characterized almost two decades ago. At the present time there are no modalities that can actively reverse established organ failure, hence the treatment of these patients consists of metabolic and haemodynamic support until the process reverses itself or death occurs.

Calcium and phospholipase A2 appear to be involved in the pathogenesis of hemorrhagic shock-induced mucosal injury and bacterial translocation.

Objective: The mechanism by which hemorrhagic shock injures the gut and leads to the translocation of bacteria remains incompletely determined. Since increased free cellular calcium levels and phospholipase A2 activity can lead to cellular injury and both have been documented in certain shock states, the hypothesis that calcium or phospholipase A2 may play a role in hemorrhagic shock-induced gut mucosal injury and bacterial translocation was tested.

Design: Prospective animal study with concurrent controls.

Secretory immunoglobulin A, intestinal mucin, and mucosal permeability in nutritionally induced bacterial translocation in rats.

Objective: The authors investigated the role of mucin and secretory immunoglobulin A (slgA) in a model of nutritionally induced bacterial translocation.

Background: Parenteral and certain elemental diets have been shown to impair intestinal barrier function, whereas fiber has been shown to protect against nutritionally induced bacterial translocation. However, the factors responsible for these phenomenon have not been fully determined.

Role of mucin, mannose, and beta-1 integrin receptors in Escherichia coli translocation across Caco-2 cell monolayers.

Our previous work suggests that Caco-2 cells play an active role in bacterial translocation (BT). Since bacterial enterocyte interactions may be receptor-mediated, the current study was performed to investigate the role of beta 1 integrin and mannose receptors as well as the general protective effect of the mucous layer in this process. Caco-2 cells grown to confluence on semipermeable membranes contained in the upper compartment of a two compartment system were utilized.

T lymphocytes in host defense against bacterial translocation from the gastrointestinal tract.

Flow cytofluorometric analyses of lymphocytes harvested from the mesenteric lymph node (MLN), mucosal epithelium, and lamina propria of C57BL/6 mice demonstrate that expression of alpha/beta or gamma/delta T-cell receptors (TCR) and CD4 or CD8 molecules by T lymphocytes in the intestinal immune system varies depending upon their anatomic location. The MLN contained equivalent numbers of CD4+ and CD8+ T cells, the vast majority of which were alpha/beta TCR positive (alpha/beta TCR+). The lamina propria T cells were predominantly CD4+ and alpha/beta TCR+, while the intestinal intraepithelial lymphocytes consisted of equivalent numbers of alpha/beta and gamma/delta T cells, the majority of which were CD8+.

Nutrition and infection.

It is now apparent that nutritional status has a profound impact on immune function and that the immune system may be modulated by the use of specific modes of nutritional support. In selected malnourished or severely injured patients, early nutritional support has been shown to improve outcome and decrease the incidence of infectious complications following major surgery or trauma. Enteral feedings appear to support the immune system better than parenteral feedings.

Diabetic foot infections. Pathophysiology and treatment.

Foot infections are among the most common reasons for hospital admission of the diabetic patient. A diabetic foot infection represents a failure by the patient and his management team to understand and correct the multifactorial conditions that predisposed the patient to the infection. Efforts directed toward prevention of the foot infection are much more likely to meet with success than is therapy of the established foot infection.