ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

&NA;SIRS (the Systemic Inflammatory Response Syndrome) and MODS (the Multiple Organ Dysfunction Syndrome) are not diseases or syndromes, but concepts. Common to both is the notion that the morbidity of critical illness arises indirectly, from the response of the host to an acute, life‐threatening challenge to systemic homeostasis. The biology of that response is complex and variable, yet implicit in our evolving understanding of systemic inflammation is the possibility that shared biologic mechanisms may permit the development of effective therapy for a wide variety of disorders that appear superficially heterogeneous. The challenge lies in characterizing common pathologic processes or diseases. The four criteria that define SIRS are non‐specific measures of physiologic severity, rather than distinctive manifestations of a disease process. Perhaps the use of the systemic correlates of the cardinal manifestations of inflammation developed by Galen and Celsus would provide a more satisfactory clinical characterization of the clinical disorder. However, the complexity of the biologic processes involved suggest that a clinical syndrome of systemic inflammation is of no more use to the clinician than a clinical syndrome of cancer. As thefunctio laesaof systemic inflammation, organ dysfunction is more appropriately viewed as an undesireable outcome of systemic inflammation, a complication to be prevented, rather than a disease to be treated. As concepts, SIRS and MODS provide a useful intellectual framework for investigation, but the clinician must treat diseases, no acronyms. The challenge will be to characterize these disease.

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

&NA;SIRS, MODS, and MOF are not diseases or even syndromes. They are simply clinical descriptors of people that are sick. They are symptoms and signs of various stages of illness progressing to death in the modern organ supporting ICU. They are catchy, popular acronyms but they cannot be treated specifically, and then only by support of organ functions. To help our patients and improve morbidity and mortality we must focus on specific diseases. Although ventilator associated pneumonia and pancreatitis may both produce an inflammatory response, cytokine‐mediator activation and SIRS, they must each be treated in a different way. I believe that SIRS has led us astray.

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

&NA;Previous reports have shown beneficial effects of pentoxifylline (PTX) and hypertonic saline (HS) in the treatment of hemorrhagic shock. We compared the effects of these solutions to those of conventional lactated Ringer's (LR) treatment on bacterial translocation (BT), lung injury and total and differential cell count in the bronchoalveolar lavage fluid (BAL) after hemorrhagic shock. Rats (280‐330 g) were bled to a MAP of 35 mmHg for 1 h and then randomized into 4 groups: LR (3× shed blood); HS (7,5% NaCI, 4mL/kg); LR+PTX (25mg/kg) and SHAM (no shock, no treatment). Additionally, total shed blood was reinfused. At 24 h lung injury was analyzed by a pathologist blinded to the groups, and a score was calculated. BT was determined by microbiological cultures of mesenteric lymph node complex. BAL was performed on a separate set of animals that received the same treatments. Lung score was significantly higher in LR group (11.5 ± 1.4) as compared to HS (6.8 ± 0.9), and PTX treated animals (7.2 ± 0.9). The percentage of neutrophils in the BAL of LR animals (15.8%) was also significantly higher as compared with HS (5.25%) and PTX groups (9.72%). BT was noted in 50% of rats for LR group, 30% for PTX, 10% for HS and 0% for sham group. HS and PTX reduced BT and lung injury after hemorrhage. Attenuation of lung injury could be the result of less neutrophil infiltration into the lungs of HS and PTX treated animals. LR resuscitation caused pronounced lung injury and BT.

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

&NA;Gram‐negative sepsis is a serious complication for patients with obstructive jaundice. The present study was conducted to elucidate the response of hepatic microcirculation to endotoxin 2 weeks after bile duct ligation (BDL) or sham‐operation in rats. Two hours after lipopolysaccharide (LPS) injection (1,10, or 100 μg/kg, iv.), the hepatic microvasculature was examined usingin vivomicroscopy. BDL elicited increases in leukocytes adhering to the sinusoidal wall, swelling of sinusoidal endothelial cells as well as phagocytic activity of hepatic macrophages and a decrease in the numbers of perfused sinusoids. LPS (1, 10, 100 μg/kg) further increased leukocyte adhesion and reduced the numbers of perfused sinusoids in a dose‐dependent manner. Leukocyte adhesion in response to LPS (1, 10, 100 μg/kg) in BDL rats was increased 6.1‐fold, 5.9‐fold, and 3.3‐fold, respectively when compared with sham‐operated rats. The numbers of perfused sinusoids in response to LPS (1, 10, 100 μg/kg) in BDL rats were decreased by 42%, 36%, and 45%. While 1 and 10 μg/kg LPS also elicited an increase in phagocytic activity in BDL rats when compared with sham‐operated rats, the response to 100 μg/kg LPS was suppressed. LPS did not affect the numbers of swollen endothelial cell in BDL rats. The present study demonstrated that chronic biliary obstruction enhanced the hepatic microvascular response to low doses of endotoxin. This observation suggests that exaggerated hepatic microcirculatory dysfunction during sepsis contributes to the development of liver injury and a high incidence of morbidity and mortality in biliary obstruction.

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

&NA;Resolving inflammation is a vital step in preventing the persistence of inflammatory disorders. Neutrophils play a major role in tissue damage associated with an inflammatory response. Their death by apoptosis is central to the final resolution of this response. Thiol depletion with diethylmaleate (DEM) or diamide represent important triggers for neutrophil apoptosis. The mechanism by which this process occurs remains unknown. The apoptotic cascade is associated with a number of cellular changes, including caspase activation and mitochondrial permeability. The aims of this study were to determine the role of mitochondrial permeability and the caspase cascade in thiol depletion‐induced neutrophil apoptosis. Total cellular glutathione was reduced by DEM and diamide. This reduction was associated with neutrophil apoptosis and an increase in caspase 3 activity. The effects of DEM were blocked by the caspase 3 inhibitor, Z‐DEVD‐FMK. Mitochondrial permeability that occurred was also increased during this induction of apoptosis. Bongkrekic acid, a mitochondrial membrane stabilizer, inhibited DEM‐induced apoptosis. The inhibitors' effects of LPS or GM‐CSF on spontaneous neutrophil apoptosis was reversed by DEM, which was mediated by an increase in caspase 3 activity and independent of mitochondrial disruption. Caspase activation is an important step in glutathione depletion‐induced apoptosis in resting and inflammatory neutrophils. Regulation of caspase activity may represent a possible target to trigger apoptosis and resolve inflammatory disorders.

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

&NA;P‐selectin is an adhesion molecule expressed on activated endothelial and platelet membranes containing 9 short consensus repeats (SCRs) similar to the composition of complement regulatory proteins. In our murine model of intestinal ischemia and reperfusion where local injury is mediated by the classical complement pathway we hypothesized the SCRs would moderate the complement response. Confirmatory data were sought following hindlimb ischemia and reperfusion where injury is both complement and neutrophil‐mediated. Mice deficient in P‐selectin (P−/−) were found to have similar intestinal and hindlimb permeability compared to normal wild types mice (P+/+). When reconstituted with P+/+ platelets, but not P−/− platelets, P−/− mice subjected to intestinal ischemia had a significant 29% decrease in permeability (P< 0.05) and after hindlimb ischemia the decrease was 33% (P<0.05). Reperfusion after intestinal ischemia led to a 76% fall in CH50 in P−/− compared to sham animals (P< 0.05) indicating complement activation and consumption, but only a 36% fall in animals reconstituted with P+/+ platelets (P< 0.05). Full‐length, soluble P‐selectin (sPsel) derived from processed platelets, but not the truncated version of sPsel has been shown to adhere to a heat labile fraction of serum and sensitized red blood cells thereby reducing C1q adherence to the sensitized red cell. From these data we conclude that sPsel moderates complement activation by competing with C1q binding to antibody, thereby limiting activation of the classical pathway that mediates murine reperfusion injury.

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

&NA;Bolus infusion of of 7.5% NaCI/6% dextran‐70 (HSD‐B) improves outcome from controlled hemorrhage. In contrast, HSD‐B during uncontrolled hemorrhage increases bleeding and short‐term mortality. The purpose of this study was to compare the effects of bolus vs. slow infusion of HSD in a near‐fatal vascular injury hemorrhage model. Sixteen (15‐20 kg) swine with 4‐mm aortic tears were hemorrhaged to a pulse pressure of 5 mmHg. An ultrasonic flow probe was placed proximal to the aortic tear for continuous blood flow (AF) measurements. Group I (slow infusion; n = 8) was resuscitated with 8 mL/kg of HSD at 0.4 mL/kg/min. Group II (bolus infusion; n = 8) was resuscitated with 8 mL/kg of HSD at 1.33 mL/kg/min. In both groups, HSD infusion was followed by administration of 30 mL/kg of shed blood at 3 mL/kg/min. Hemorrhage volume and 90‐min mortality were greater in group II (79 ± 11 mL/kg; 75%) compared with group I (43 ± 9 mL/kg; 12.5%) (PHem< 0.001; PMort= 0.04). Mean arterial pressure (MAP) and AF were greater in group II compared with group I during the first 15 min of resuscitation. In group I, MAP, AF, cardiac indices, and O2delivery gradually returned to baseline levels and were significantly greater than group II at 30 min and throughout the remainder of the protocol. In this model of near‐lethal uncontrolled hemorrhage, slow infusion of HSD restored cardiodynamics while minimizing hemorrhage volume and mortality. Resuscitation regimens that cause early increases in blood flow and pressure may result in greater hemorrhage and mortality than those regimens that yield comparable flow and pressure increases late in resuscitation.

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

&NA;Studies have shown that cell mediated immunity is suppressed markedly following thermal injury. Macrophages and the activation of an inflammatory cascade that includes interleukin (IL)‐1, IL‐6, tumor necrosis factor‐alpha (TNF&agr;) and PGE2have been implicated as causative factors. Burn wound excision and grafting is a common clinical practice that decreases patient morbidity and mortality. It is not known, however, if the salutary effects of this procedure are related to modulation of macrophage activity post‐burn. Therefore, C57BL/6 female mice were subjected to a third‐degree scald burn covering 25% of their total body surface area followed by complete excision and allografting of the injury site at 8, 24, or 72 h post‐burn. Splenic macrophage function was assessed 7 days post‐burn. Thermal injury without burn excision and grafting significantly increased macrophage TNF&agr;, IL‐6, nitric oxide, and PGE2production in response to lipopolysaccharide stimulation, whereas IL‐1&bgr; production was not increased. Burn wound excision and grafting normalized TNF&agr; production to sham levels, independent of when post‐burn the procedure was conducted. In contrast, the elevated production of other inflammatory mediators (IL‐1&bgr;, IL‐6, nitric oxide, PGE2) post‐burn was unaffected by burn wound excision and grafting. Moreover, splenic T‐lymphocyte proliferation was also suppressed at 7 days post‐burn and was not improved by burn wound excision and grafting. These results, therefore, suggest that the beneficial effects of burn wound excision and grafting are likely to be related to the normalization of macrophage TNF&agr; production as well as the maintenance of skin barrier function.

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

&NA;Clostridium difficiletoxins A and B are the widely recognized etiologic agents of antibioticassociated diseases ranging from diarrhea to pseudomembranous colitis. We hypothesized thatC. difficiletoxins may alter intestinal epithelial permeability and facilitate bacterial penetration of the intestinal epithelial barrier. Experiments were designed to clarify the effects ofC. difficiletoxins A and B on the flux of inert particles across HT‐29 enterocyte monolayers, and to correlate these results with bacteria‐enterocyte interactions. In all experiments, mature, confluent HT‐29 cultures were preincubated 16 h with toxin A or B (1‐100 ng/mL). To study alterations in epithelial permeability, toxin‐treated enterocytes were incubated with 5 pM solutions of 10‐ and 40‐kD inert dextran particles. Toxin A, but not toxin B, was associated with increased dextran flux through enterocyte monolayers. To study bacteria‐enterocyte interactions, toxin‐treated enterocytes were incubated with 108Salmonella typhimurium, Proteus mirabilis,orEscherichia coli.Although numbers of internalized bacteria were generally unaffected, both toxins were associated with increased bacterial adherence, as well as increased bacterial transmigration through enterocyte monolayers. Bacterial transmigration was significantly greater using toxin A‐ compared to toxin B‐treated enterocytes, consistent with the observation that dextran flux was significantly greater using toxin A‐ compared to toxin B‐treated enterocytes. Thus intestinal colonization with toxigenicC. difficilemay facilitate bacterial penetration of the intestinal epithelium by a mechanism involving increased permeability of the intestinal epithelial barrier.

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID