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Research paper thumbnail of Exacerbation of intestinal permeability in rats after a two-hit injury: Burn and Enterococcus faecalis infection*

Critical Care Medicine, 2004

To determine alterations in intestinal epithelial permeability to solutes in burn injured rats wi... more To determine alterations in intestinal epithelial permeability to solutes in burn injured rats with and without Enterococcus faecalis infection and the role of neutrophils in the intestinal permeability changes. Prospective sham-controlled animal study. University research laboratory. Male Sprague-Dawley rats. Rats were subjected to 30% total body surface burn (B group), E. faecalis infection (EF group) induced via intra-abdominal implantation of bacterial pellet, or combination of burn injury and E. faecalis infection (B+EF group). In vivo measurements of intestinal permeability were carried out after intraluminal injection of H lactulose and C mannitol in the ileum of sham, B, EF, and B+EF groups of rats, 1 and 2 days after injury. Lactulose permeability was increased in the injured rat groups (B, EF, B+EF) on day 1 postinjury compared with sham. The combined injury group (B+EF) had the highest level of lactulose permeability. Although a significant change in lactulose permeability from day 1 to day 2 postinjury could not be demonstrated in the B and EF groups, lactulose permeability in the B+EF group on day 2 postinjury markedly decreased from day 1 but was still significantly higher than that in the sham group. Mannitol permeability was increased in all injured rat groups on day 1 postinjury; on day 2 it remained elevated post-B, decreased post-EF, and further increased after B+EF. Ex vivo measurements of lactulose movements across intestinal epithelial monolayers (IEC-18) were carried out in the presence of blood neutrophils from sham, B, EF, or B+EF rats. We also measured ex vivo transepithelial migration of neutrophils from sham, B, EF, or B+EF rat groups. Neither the transepithelial lactulose movement in the presence of neutrophils from, nor neutrophil migration in, the B or EF rats was significantly different from sham. However, a significant increase in transepithelial lactulose movement and neutrophil migration occurred in the B+EF group. Immunoblot analyses and in situ histochemical localizations of intestinal tight junction proteins, occludin and claudin-3, showed decreases in the distribution of occludin but not claudin-3 in the B, EF, and B+EF groups. Alterations in intestinal solute permeability and disruption of tight junction integrity after a two-hit injury with burn and E. faecalis infection, but not after individual injuries of burn or E. faecalis infection, are likely associated with heightened neutrophil flux across the intestinal epithelium.

Research paper thumbnail of Scurvy diagnosed in a pediatric liver transplant patient awaiting combined kidney and liver retransplantation

Pediatric Transplantation, 2008

Research paper thumbnail of Increased Intestinal Solute Permeability and Related Changes in Epithelial Tight Junction Proteins Occludin and CLAUDIN-3 in Burninjured Rats with Enterococcus Faecalis Infection

Critical Care Medicine, 2002

Research paper thumbnail of Tissue Factor Pathway Inhibitor and Thrombin Activatable Fibrinolytic Inhibitor Plasma Levels following Burnand Septic Injuries in Rats

Clinical and Applied Thrombosis/Hemostasis, 2004

Burn and septic injuries induce profound changes in coagulation status. This study examined the c... more Burn and septic injuries induce profound changes in coagulation status. This study examined the changes in plasma tissue factor pathway inhibitor (TFPI) and thrombin activatable fibrinolytic inhibitor (TAFI) levels in a rat model of burn and septic injuries. Rats underwent 30% TBSA cutaneous scald burn injury and septic insult was induced by caecal ligation and puncture (CLP). CLP was superimposed on burn injury to mimic the clinical model of sepsis complicating burn injury. Rats were pretreated with Cprofloxacin orally to colonize their gut with Enterococcus faecalis. TFPI and TAFI plasma levels were measured using functional activity assay kit with a chromogenic method at 24 and 72 hours following the injuries. TFPI levels decreased significantly at 24 hours in burn, CLP, and burn+CLP groups, followed by incomplete rebound recovery at 72 hours in all three groups. On the other hand, TAFI levels increased significantly at 24- and 72-hour time points in all three groups. These resul...

Research paper thumbnail of Enterococcus faecalis Exacerbates Burn Injury-Induced Host Responses in Rats

Shock, 2002

Pathophysiology of burn injury with complications of gram-positive infections is not well charact... more Pathophysiology of burn injury with complications of gram-positive infections is not well characterized. We have developed an in vivo rat model to study the effects of burn injury along with intra-abdominal inoculation of Enterococcus faecalis. We hypothesized that although burn injury or E. faecalis inoculation by itself may not induce significant pathophysiological responses, the combination of the two can lead to adverse pathophysiological consequences. Sprague-Dawley rats were divided into 4 groups: group 1(C), controls; group 2(B), burn injury on 30% total body surface area; group 3(EF), intra-abdominal implantation of bacterial pellet impregnated with E. faecalis; group 4(B+EF), burn injury plus bacterial pellet implantation. The mortality was 25% and 60% on day 1 and 2 in Group 4(B+EF), respectively; no significant mortality was observed in other groups. In group 4(B+EF), metabolic acidosis, respiratory alkalosis, and a hyperdynamic state developed on day 1, and metabolic and respiratory acidosis and a hypodynamic state on day 2. There were no significant alterations in metabolic or hemodynamic measurements in other groups. Intestinal microvascular permeability to albumin on day 1 and 2 was increased in group 4(B+EF). In group 2(B), microvascular permeability was not increased significantly. Although the permeability was increased on day 1 in group 3(EF), it declined on day 2. The metabolic and hemodynamic alterations were correlated with increased intestinal microvascular permeability to albumin. E. faecalis appeared to be involved in initiating a vicious cycle of burn injury-mediated disruption of intestinal integrity along with metabolic and hemodynamic derangements.

Research paper thumbnail of Burn Injury Exacerbates Hemodynamic and Metabolic Responses in Rats with Polymicrobial Sepsis

Journal of Burn Care & Research, 2006

The most common and life-threatening complication of severe burn injury is infection, which often... more The most common and life-threatening complication of severe burn injury is infection, which often results in multiple organ failure (MOF). However, the mechanism of development of MOF after burn injury associated with infection is not fully understood. Our previous studies showed that when polymorphonuclear neutrophils (PMNs) are depleted, burn injury-induced increase in microvascular permeability to albumin is markedly attenuated. Thus, we hypothesized that the combination of burn injury and polymicrobial infection exacerbates PMN activation, increases intestinal microvascular permeability to albumin, and alters hemodynamics and metabolism more than burn injury or infection alone. Sprague–Dawley rats (250–275 g) were divided into four groups. In the burn group, rats were subjected to a 30% TBSA burn injury. In the cecal–ligation puncture (CLP) group, CLP was performed using a 22-gauge needle with one puncture. In burn + CLP group, rats were subjected to CLP immediately after burn p...

Research paper thumbnail of Exacerbation of intestinal permeability in rats after a two-hit injury: Burn and Enterococcus faecalis infection*

Critical Care Medicine, 2004

To determine alterations in intestinal epithelial permeability to solutes in burn injured rats wi... more To determine alterations in intestinal epithelial permeability to solutes in burn injured rats with and without Enterococcus faecalis infection and the role of neutrophils in the intestinal permeability changes. Prospective sham-controlled animal study. University research laboratory. Male Sprague-Dawley rats. Rats were subjected to 30% total body surface burn (B group), E. faecalis infection (EF group) induced via intra-abdominal implantation of bacterial pellet, or combination of burn injury and E. faecalis infection (B+EF group). In vivo measurements of intestinal permeability were carried out after intraluminal injection of H lactulose and C mannitol in the ileum of sham, B, EF, and B+EF groups of rats, 1 and 2 days after injury. Lactulose permeability was increased in the injured rat groups (B, EF, B+EF) on day 1 postinjury compared with sham. The combined injury group (B+EF) had the highest level of lactulose permeability. Although a significant change in lactulose permeability from day 1 to day 2 postinjury could not be demonstrated in the B and EF groups, lactulose permeability in the B+EF group on day 2 postinjury markedly decreased from day 1 but was still significantly higher than that in the sham group. Mannitol permeability was increased in all injured rat groups on day 1 postinjury; on day 2 it remained elevated post-B, decreased post-EF, and further increased after B+EF. Ex vivo measurements of lactulose movements across intestinal epithelial monolayers (IEC-18) were carried out in the presence of blood neutrophils from sham, B, EF, or B+EF rats. We also measured ex vivo transepithelial migration of neutrophils from sham, B, EF, or B+EF rat groups. Neither the transepithelial lactulose movement in the presence of neutrophils from, nor neutrophil migration in, the B or EF rats was significantly different from sham. However, a significant increase in transepithelial lactulose movement and neutrophil migration occurred in the B+EF group. Immunoblot analyses and in situ histochemical localizations of intestinal tight junction proteins, occludin and claudin-3, showed decreases in the distribution of occludin but not claudin-3 in the B, EF, and B+EF groups. Alterations in intestinal solute permeability and disruption of tight junction integrity after a two-hit injury with burn and E. faecalis infection, but not after individual injuries of burn or E. faecalis infection, are likely associated with heightened neutrophil flux across the intestinal epithelium.

Research paper thumbnail of Scurvy diagnosed in a pediatric liver transplant patient awaiting combined kidney and liver retransplantation

Pediatric Transplantation, 2008

Research paper thumbnail of Increased Intestinal Solute Permeability and Related Changes in Epithelial Tight Junction Proteins Occludin and CLAUDIN-3 in Burninjured Rats with Enterococcus Faecalis Infection

Critical Care Medicine, 2002

Research paper thumbnail of Tissue Factor Pathway Inhibitor and Thrombin Activatable Fibrinolytic Inhibitor Plasma Levels following Burnand Septic Injuries in Rats

Clinical and Applied Thrombosis/Hemostasis, 2004

Burn and septic injuries induce profound changes in coagulation status. This study examined the c... more Burn and septic injuries induce profound changes in coagulation status. This study examined the changes in plasma tissue factor pathway inhibitor (TFPI) and thrombin activatable fibrinolytic inhibitor (TAFI) levels in a rat model of burn and septic injuries. Rats underwent 30% TBSA cutaneous scald burn injury and septic insult was induced by caecal ligation and puncture (CLP). CLP was superimposed on burn injury to mimic the clinical model of sepsis complicating burn injury. Rats were pretreated with Cprofloxacin orally to colonize their gut with Enterococcus faecalis. TFPI and TAFI plasma levels were measured using functional activity assay kit with a chromogenic method at 24 and 72 hours following the injuries. TFPI levels decreased significantly at 24 hours in burn, CLP, and burn+CLP groups, followed by incomplete rebound recovery at 72 hours in all three groups. On the other hand, TAFI levels increased significantly at 24- and 72-hour time points in all three groups. These resul...

Research paper thumbnail of Enterococcus faecalis Exacerbates Burn Injury-Induced Host Responses in Rats

Shock, 2002

Pathophysiology of burn injury with complications of gram-positive infections is not well charact... more Pathophysiology of burn injury with complications of gram-positive infections is not well characterized. We have developed an in vivo rat model to study the effects of burn injury along with intra-abdominal inoculation of Enterococcus faecalis. We hypothesized that although burn injury or E. faecalis inoculation by itself may not induce significant pathophysiological responses, the combination of the two can lead to adverse pathophysiological consequences. Sprague-Dawley rats were divided into 4 groups: group 1(C), controls; group 2(B), burn injury on 30% total body surface area; group 3(EF), intra-abdominal implantation of bacterial pellet impregnated with E. faecalis; group 4(B+EF), burn injury plus bacterial pellet implantation. The mortality was 25% and 60% on day 1 and 2 in Group 4(B+EF), respectively; no significant mortality was observed in other groups. In group 4(B+EF), metabolic acidosis, respiratory alkalosis, and a hyperdynamic state developed on day 1, and metabolic and respiratory acidosis and a hypodynamic state on day 2. There were no significant alterations in metabolic or hemodynamic measurements in other groups. Intestinal microvascular permeability to albumin on day 1 and 2 was increased in group 4(B+EF). In group 2(B), microvascular permeability was not increased significantly. Although the permeability was increased on day 1 in group 3(EF), it declined on day 2. The metabolic and hemodynamic alterations were correlated with increased intestinal microvascular permeability to albumin. E. faecalis appeared to be involved in initiating a vicious cycle of burn injury-mediated disruption of intestinal integrity along with metabolic and hemodynamic derangements.

Research paper thumbnail of Burn Injury Exacerbates Hemodynamic and Metabolic Responses in Rats with Polymicrobial Sepsis

Journal of Burn Care & Research, 2006

The most common and life-threatening complication of severe burn injury is infection, which often... more The most common and life-threatening complication of severe burn injury is infection, which often results in multiple organ failure (MOF). However, the mechanism of development of MOF after burn injury associated with infection is not fully understood. Our previous studies showed that when polymorphonuclear neutrophils (PMNs) are depleted, burn injury-induced increase in microvascular permeability to albumin is markedly attenuated. Thus, we hypothesized that the combination of burn injury and polymicrobial infection exacerbates PMN activation, increases intestinal microvascular permeability to albumin, and alters hemodynamics and metabolism more than burn injury or infection alone. Sprague–Dawley rats (250–275 g) were divided into four groups. In the burn group, rats were subjected to a 30% TBSA burn injury. In the cecal–ligation puncture (CLP) group, CLP was performed using a 22-gauge needle with one puncture. In burn + CLP group, rats were subjected to CLP immediately after burn p...