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Biomedical subjects

R D Berg

Publications and source records attributed to R D Berg.

At least 37 records · Page 2Linked to original sources
PubMed1992

A study of the relationship among survival, gut-origin sepsis, and bacterial translocation in a model of systemic inflammation.

Several factors, including uncontrolled inflammation, gut barrier failure, and sepsis, have been implicated in the development of multiple organ failure. To investigate the relative importance and interrelationships among some of these factors, increasing doses of the inflammatory agent zymosan were used to induce a systemic inflammatory state in mice. At nonlethal doses (0.1 and 0.5 mg/g body weight), zymosan caused injury to the intestinal mucosa, increased intestinal xanthine oxidase activity, and promoted bacterial translocation in a dose-dependent fashion. Inhibition or inactivation of xanthine oxidase activity was effective in reducing mucosal injury and bacterial translocation when zymosan was injected at 0.1 mg/g but not at 0.5 mg/g body weight. At a dose of 1 mg/g, the lethal effects of zymosan appeared to be related to gut-origin sepsis, since cefoxitin (1 mg/g) reduced the seven-day mortality rate from 100% to 20% (p less than 0.01). However, at a zymosan dose of 2 mg/g, antibiotics did not improve survival. Zymosan thus induced gut barrier failure and systemic infection in a dose-dependent fashion. Additionally, the mechanism of zymosan-induced bacterial translocation and the relationship of gut-origin sepsis to survival appeared to be related to the magnitude of the inflammatory insult (the dose of zymosan).

Allopurinol↗
PubMed1991

Studies of the route, magnitude, and time course of bacterial translocation in a model of systemic inflammation.

Bacteria have been documented to translocate from the gut to systemic organs, yet the exact route by which they translocate remains unclear. To determine the route of bacterial translocation, different dosages of zymosan were used to activate complement and cause systemic inflammation. At a zymosan dose of 0.1 mg/g, bacteria translocated only to the mesenteric lymph node complex, whereas at a dose of 0.5 mg/g the bacteria translocated systematically. In rats receiving 0.5-mg/g doses of zymosan, the bacteria appeared to reach systemic organs via the portal blood rather than via the mesenteric lymph, as bacteria were present in 87% of portal blood samples but only 25% of lymph samples. The number of bacteria exiting the portal vein was 11,500 times greater than the number exiting via the lymph. Thus, both the route and extent of bacterial translocation varies based on the magnitude of the inflammatory insult, with the portal blood being the major route of bacterial translocation to systemic organs.

Animals↗
PubMed1991

Interleukin-2 enhances the translocation of Escherichia coli from the intestines to other organs.

To determine if interleukin-2 (IL-2) would inhibit gastrointestinal bacterial translocation, mice were gut-decontaminated and recolonized with Escherichia coli C25; some groups were pretreated with 200 mg/kg cyclophosphamide. IL-2 (1.68 mg/kg) or sterile diluent was injected twice daily for 3 or 5 days, and mice were sacrificed the next day. High cecal levels of E. coli C25 were present in all mice. The overall incidence of E. coli C25 translocation to mesenteric lymph nodes was not reduced by IL-2. The median numbers of translocated E. coli C25/g of mesenteric lymph node were significantly (P less than .005) higher after both 3 days (659 vs. 117) and 5 days (550 vs. 50) of treatment with IL-2 with cyclophosphamide and after 5 days (1784 vs. 225) of IL-2 without cyclophosphamide. IL-2 prevented neutropenia and exacerbated lymphopenia caused by cyclophosphamide. The in vitro growth of E. coli C25 was not affected by up to 10(5) units/ml IL-2. Ileal and cecal structures assessed by light and electron microscopy were not altered by IL-2. Thus, IL-2 unexpectedly enhanced the translocation of E. coli C25 from the gastrointestinal tracts of both cyclophosphamide-pretreated and normal mice.

Animals↗
PubMed1991

Endotoxin-induced bacterial translocation and mucosal permeability: role of xanthine oxidase, complement activation, and macrophage products.

BACKGROUND AND METHODS: Previously, we documented that nonlethal doses of endotoxin injure the intestinal mucosal barrier and promote bacterial translocation from the gut to systemic organs. The current study was performed to determine the role of cytokines and complement activation in the pathogenesis of endotoxin-induced mucosal injury and bacterial translocation, as well as to quantify the magnitude of endotoxin-induced intestinal mucosal permeability. RESULTS: The frequency of endotoxin-induced bacterial translocation was similar between normal outbred (88%), complement deficient (67%), and macrophage-hyporesponsive (55%) mice, indicating that neither complement nor macrophage activation is necessary for endotoxin-induced bacterial translocation to occur. As early as 2 hrs after endotoxin challenge, there was evidence of a greater than two-fold increase in ileal (p = .008) but not jejunal (p = .11) permeability as measured by the clearance of 51Cr EDTA. Both the increase in endotoxin-induced ileal permeability and the occurrence of bacterial translocation were largely prevented by pretreatment with allopurinol, a competitive inhibitor of xanthine oxidase. CONCLUSIONS: These results suggest that endotoxin-induced bacterial translocation, mucosal injury, and ileal permeability are mediated via activation of xanthine oxidase, and not through complement activation or the liberation of macrophage products.

Animals↗
PubMed1991

Oral-TPN-induced bacterial translocation and impaired immune defenses are reversed by refeeding.

Although certain defined diets have been shown to promote bacterial translocation (BT), the ability to reverse diet-induced BT has not previously been investigated. Furthermore, little is known about the effects of defined diets on host immune defenses. To address these questions, we measured BT and immune reactivity in rats fed a normal diet or enteral elemental (ORAL-TPN) diet. After 7 days on the elemental or normal diet, the rats were killed, and BT and mitogen responsiveness to concanavalin A and phytohemagglutinin were measured. In separate experiments, the effects of these diets on in vivo host defenses was measured with a Staphylococcus aureus abscess model. Additional experiments were performed to determine the time required to reverse ORAL-TPN-induced BT and impairment of host immune defenses by reinstituting normal feedings. Administration of the ORAL-TPN diet for 7 days was associated with BT to the mesenteric lymph node complex of all animals, decreased blastogenic response of blood and splenic lymphocytes to mitogens, and decreased ability to control an in vivo infectious challenge with S. aureus. Each of the derangements was reversed by the reinstitution of normal feedings. In summary, the enteral administration of an elemental diet for 7 days is associated with disruption of the gut microflora, BT, and the development of an immunocompromised state, all of which can be reversed by refeeding the animals a normal diet.

Analysis of Variance↗
PubMed1991

Bacterial translocation from the gut impairs systemic immunity.

The goal of this study was to determine the influence of bacterial translocation on systemic immunity, since bacteria and their products play a major role in the development and maintenance of the host's immune system. To test this hypothesis, we measured the blastogenic response of mononuclear cells harvested from the blood, spleen, Peyer's patches, and mesenteric lymph nodes of control and Escherichia coli C25 monoassociated mice to a battery of mitogens. The E. coli C25 monoassociation model was used because this bacterial translocation model is not associated with experimental manipulations that are likely to affect the systemic immune system. The mitogenic response of lymphocytes isolated from the E. coli C25 monoassociated mice was significantly depressed compared to the control groups (p less than 0.01). Since the biologic significance of depressed in vitro mitogen responsiveness is difficult to determine, we assessed the ability of the mice to control a bacterial challenge using an in vivo Staphylococcus aureus abscess model. It appears that the observed changes in mitogen responsiveness may be of biologic significance, since the ability of the E. coli C25 monoassociated mice to control the injected S. aureus was impaired (p less than 0.01). These results suggest that an association exists between bacterial translocation and decreased systemic immune responsiveness.

Animals↗
PubMed1990

Obstructed intestine as a reservoir for systemic infection.

Intestinal motility, absorption, and secretion are altered after intestinal obstruction, but at what point the normal bacterial barrier function of the viable gut fails after intestinal obstruction is unclear. Thus, we tested whether after simple intestinal obstruction bacteria would translocate across the viable intestinal wall to cause systemic infection. Within 6 hours of intestinal ligation 1 cm proximal or distal to the ileocecal valve, bacteria had translocated to the mesenteric lymph nodes, and by 24 hours after intestinal obstruction, bacteria had spread to the liver, spleen, and blood stream. Bacterial translocation rarely occurred in the animals undergoing laparotomy and sham intestinal ligation, indicating that bacterial translocation was not due to surgical stress. Based on the results of these studies, bacterial translocation induced by intestinal obstruction appears to be due to disruption of the ecology of the normal gut microflora, leading to intestinal overgrowth with certain enteric bacilli and mucosal damage. Although the exact mechanism(s) by which simple mechanical obstruction injures the intestine is not known, the fact that mucosal injury did not occur in germ-free mice suggests that bacteria may play a role in the pathogenesis of obstruction-induced intestinal injury.

Animals↗
PubMed1990

Protein malnutrition predisposes to inflammatory-induced gut-origin septic states.

The development of an uncontrolled inflammatory response has been implicated in the pathogenesis of adult respiratory distress syndrome and multiple-organ failure. Because zymosan activates complement and induces a systemic inflammatory response, the effect of zymosan on intestinal structure and barrier function was measured in normally nourished (NN) and protein malnourished (PM) mice. Normally nourished and protein malnourished (up to 21 days) mice challenged intraperitoneally with zymosan (0.1 mg/g body weight) were killed 24 hours after zymosan challenge and their organs cultured for translocating bacteria. Zymosan-induced bacterial translocation was limited to the mesenteric lymph nodes of the NN mice, whereas translocating bacteria spread from the gut to the liver, spleen, and blood stream (p less than 0.05) in the PM mice. Zymosan-induced bacterial translocation appeared to be related primarily to the combination of mucosal injury and a disruption of the gut flora ecology in the PM mice and to mucosal injury in the NN mice. The extent of mucosal injury was greater the longer the mice were protein malnourished before zymosan challenge. The effect of zymosan on survival was measured in separate groups of mice. At a dose of 0.1 mg/g body weight, no deaths occurred in NN mice or in 7-day PM mice. However 20% of the 14-day PM mice and 80% of the 21-day PM mice receiving zymosan died. Thus PM predisposes to mucosal damage and the development of potentially lethal gut origin septic state during periods of systemic inflammation.

Animals↗
PubMed1990

Splenectomy influences endotoxin-induced bacterial translocation.

To determine whether splenectomy affects the antibacterial defenses of the gut, experiments were performed using bacterial translocation (BT) as a marker of intestinal barrier failure. The incidence of BT was measured 8 days after splenectomy or sham-splenectomy in mice receiving or not receiving endotoxin (0.1 mg IP). Splenectomy does not appear to promote BT from the gut, since the incidence of bacterial translocation after splenectomy or sham-splenectomy (5%) were not different. A second experiment was performed to determine whether the resistance to endotoxin-induced BT was modified after splenectomy. The incidence of endotoxin-induced BT was 73% in the unoperated control group, 59% in the sham-splenectomy group, but 23% in the splenectomy group (p less than 0.002). Thus, splenectomy but not sham-splenectomy increased the resistance of otherwise healthy mice to endotoxin-induced BT.

Animals↗
PubMed1990

Food without fiber promotes bacterial translocation from the gut.

To determine whether the route and/or composition of nutritional support alters intestinal barrier function (measured as bacterial translocation), rats were divided into three groups: food (controls), intravenous total parenteral nutrition (IV-TPN) fed, and oral total parenteral nutrition (ORAL-TPN) fed. Bacterial translocation did not occur in the rats that were fed normally, but did occur in 60% of the rats fed the IV-TPN or the ORAL-TPN diets for 7 days (p less than 0.05). Since both the IV-TPN and ORAL-TPN diets induced bacterial translocation and the TPN solution (28% glucose and 4.5% amino acids) lacks fiber, two additional groups of rats were fed orally 2.5 gm cellulose powder/day plus TPN solution by either the intravenous or the oral route. The addition of cellulose powder decreased the incidence of bacterial translocation to 8% in the group fed the ORAL-TPN diet and to 0% in the group fed the IV-TPN diet. Cellulose improved intestinal barrier function, even though it did not prevent bacterial overgrowth or the loss of mucosal mass in the rats fed the IV-TPN or ORAL-TPN diets. Cellulose powder appears to have prevented bacterial translocation primarily by preventing IV-TPN- or ORAL-TPN-induced alterations in mucosal structure. Thus the oral administration of this fiber maintains intestinal barrier function and prevents bacterial translocation even in the absence of oral nutrients.

Administration, Oral↗
PubMed1989

Genetic susceptibility to mucosal damage leads to bacterial translocation in a murine burn model.

Since genetic factors may be important in host resistance to infections after thermal injury, we screened the susceptibility of three mouse strains (CD-1, Balb/c, and C57/bl) to thermally induced bacterial translocation from the GI tract. Bacteria translocated to the MLNs of Balb/c but not the CD-1 or C57/bl mice receiving 25% body burns. The increased incidence of bacterial translocation in the burned Balb/c mice appeared to be due to a burn-induced gut mucosal injury, since the intestinal mucosa of the Balb/c but not the CD-1 or C57/bl mice was damaged 24 hr after the thermal injury. The mucosal injury appears to be mediated, at least in part, by xanthine oxidase-generated oxygen-free radicals, since inhibition of xanthine oxidase activity with allopurinol, or inactivation of xanthine oxidase activity by a molybdenum-free tungsten diet, prevented the mucosal injury and reduced the extent of bacterial translocation.

Animals↗
PubMed1989

Lethal burn-induced bacterial translocation: role of genetic resistance.

Since genetic factors may influence outcome after trauma or during infection, the current experiments were performed to examine the resistance of three genetically different mouse strains to burn-induced bacterial translocation. Outbred ICR, inbred Balb/c, and inbred C57/B1 mice, with a normal or disrupted (monoassociated with Escherichia coli C25) GI tract microflora, were subjected to sham or actual 25% body burns. In Balb/c, but not ICR mice, replacing the normal intestinal microflora with E. coli C25 converted the thermal injury from a nonlethal (0% mortality) to a lethal (68% mortality) injury. The increased mortality of the burned Balb/c mice monoassociated with E. coli C25 was associated with a higher incidence (p less than 0.05) and magnitude (p less than 0.05) of E. coli C25 translocation from the GI tract. The C57/B1 mice were intermediate between the Balb/c and ICR strains, in that C57/B1 mice monoassociated with E. coli C25 had a higher mortality and greater E. coli C25 translocation than mice with a normal microflora after thermal injury. Thus the composition of the intestinal microflora as well as the genetic background of the host influence the susceptibility of the host to burn-induced bacterial translocation and survival.

Animals↗
PubMed1989

Inhibition of endotoxin-induced bacterial translocation in mice.

The primary functions of the gut are to absorb nutrients and exclude bacteria and their products. However, under certain circumstances the gut may lose its barrier function and serve as a reservoir for systemic microbial infections. These experiments were performed to determine the mechanisms whereby endotoxin causes bacteria to escape (translocate) from the gut. Bacteria translocated from the gut to the mesenteric lymph nodes of mice challenged with nonlethal doses of Escherichia coli 026:B6 or E. coli 0111:B4 endotoxin. Physical disruption of the gut mucosal barrier appears to be the primary mechanism whereby endotoxin promotes bacterial translocation. Mucosal injury and endotoxin-induced bacterial translocation were reduced by inhibition (allopurinol) or inactivation (tung-sten diet) of xanthine oxidase activity (P less than 0.01), but were not affected by the platelet-activation factor antagonists, SRI 63-441 or BN 52021. Because the inhibition or inactivation of xanthine oxidase activity reduced both the extent of mucosal injury and endotoxin-induced bacterial translocation, the effect of endotoxin on the gut appears to be mediated, at least to some degree, by xanthine oxidase-generated, oxygen-free radicals.

Allopurinol↗
PubMed1988

Immunosuppression and intestinal bacterial overgrowth synergistically promote bacterial translocation.

Gram-negative, enteric bacilli of the indigenous gastrointestinal tract microflora translocated primarily to the mesenteric lymph nodes in mice given either oral penicillin G sodium or clindamycin hydrochloride. These bacteria also translocated to the mesenteric lymph nodes in mice injected with cyclophosphamide or prednisone. However, in mice treated with the combination of an oral antibiotic plus an immunosuppressive drug, the translocating bacteria spread systemically to the peritoneal cavity. When the treatment with clindamycin and prednisone was extended to 12 days, the mice died of lethal sepsis beginning eight days after treatment. Thus, the combination of intestinal bacterial overgrowth and host immunosuppression synergistically promoted bacterial translocation from the gastrointestinal tract that resulted in lethal sepsis.

Animals↗
PubMed1988

Comparison of translocation rates of various indigenous bacteria from the gastrointestinal tract to the mesenteric lymph node.

Bacterial translocation is defined as the passage of indigenous bacteria from the gastrointestinal (GI) tract through the lamina propria to the mesenteric lymph nodes (MLN) and other organs. We compared the relative abilities of various aerobic, facultatively anaerobic, and obligately anaerobic bacteria to translocate from the GI tract to the MLN in gnotobiotic mice colonized with single strains of bacteria. Indigenous gram-negative enteric bacilli translocated in large numbers to the MLN, whereas gram-positive bacteria translocated at intermediate levels and obligately anaerobic bacteria at only very low levels. Our results suggest that enteric bacilli such as Escherichia coli, Proteus, and Enterobacter are associated with a higher incidence of bacteremia in debilitated patients, because these bacteria translocate more efficiently from the GI tract than do other bacteria, especially obligate anaerobes.

Animals↗
PubMed1988

Hemorrhagic shock induces bacterial translocation from the gut.

Sepsis and multiple organ failure are common after hemorrhagic shock. The goal of the current experiments was to determine whether hemorrhagic shock would promote the translocation of bacteria from the gut to visceral organs. Twenty-four hours after being subjected to sham shock, or 30, 60, or 90 minutes of shock (30 mm Hg), rats were sacrificed and their organs quantitatively cultured for translocating bacteria. There was a direct relationship between the duration of hemorrhagic shock and the 24-hour mortality rate (p = 0.02). Bacteria did not translocate from the gut in the sham-shock rats, but did translocate to the mesenteric lymph nodes, livers, and spleens of the rats subjected to hemorrhagic shock (p less than 0.01). Rats subjected to 90 minutes of shock shock exhibited a greater degree of bacterial translocation than rats receiving 30 or 60 minutes of shock (p less than 0.05). The most common translocating bacteria were Escherichia coli and Enterococcus. Hemorrhagic shock injured the gut mucosa and caused subepithelial edema and focal areas of necrosis. Thus hemorrhagic shock followed by reinfusion of shed blood disrupts the gut barrier and allows indigenous bacteria normally contained within the gut to cause systemic infections.

Animals↗
PubMed1987

Endotoxin but not malnutrition promotes bacterial translocation of the gut flora in burned mice.

Previously we have shown that under certain conditions, bacteria can pass through the intact epithelial mucosa to the mesenteric lymph nodes (MLN), liver, spleen, and bloodstream to cause infection, a process termed bacterial translocation. To extend these studies, we determined the influence of protein malnutrition and endotoxemia on bacterial translocation in burned (25% TBSA) and unburned mice. The results of these experiments documented that protein malnutrition did not promote bacterial translocation from the gut in either burned or unburned animals, although it did disrupt the normal indigenous gut flora. In contrast, a nonlethal dose of endotoxin (IP) promoted bacterial translocation to the mesenteric lymph nodes in burned and unburned mice, but only in burned mice did the bacteria translocate from the gut to other systemic organs (p less than 0.01). Furthermore, the mortality rate of mice receiving only endotoxin or burn was less than 10%, while the combination of endotoxin plus a thermal injury increased the mortality rate to 100% (p less than 0.01). These studies support the concept that bacteria may translocate from the gut to other organs and be a potential source of lethal infections after thermal injury.

Animals↗