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PubMed2004

Albicidin pathotoxin produced by Xanthomonas albilineans is encoded by three large PKS and NRPS genes present in a gene cluster also containing several putative modifying, regulatory, and resistance genes.

Xanthomonas albilineans, which causes leaf scald disease of sugarcane, produces a highly potent pathotoxin called albicidin. We report here sequencing and homology analysis of the major gene cluster, XALB1 (55,839 bp), and a second, smaller region, XALB2 (2,986 bp), involved in albicidin biosynthesis. XALB1 contains 20 open reading frames, including i) three large genes with a modular architecture characteristic of polyketide synthases (PKSs) and nonribosomal peptide synthases (NRPSs) and ii) several putative modifying, regulatory, and resistance genes. Sequencing and complementation studies of six albicidin-defective mutants enabled us to confirm the involvement of the three PKS and NRPS genes encoded by XALB1 in albicidin production. XALB2 contains only one gene that is required for post-translational activation of PKS and NRPS enzymes, confirming the involvement of these enzymes in albicidin biosynthesis. In silico analysis of these three PKS or NRPS enzymes allowed us to propose a model for the albicidin backbone assembly and to gain insight into the structural features of this pathotoxin. This is the first description of a complete mixed PKS-NRPS gene cluster for toxin production in the genus Xanthomonas.

Amino Acid Sequence↗
PubMed2003

Aging enhances lymphocyte cytokine defects after injury.

Mortality and sepsis after a traumatic injury is greater in the elderly than in young individuals. The altered lymphocyte response observed to occur in healthy aged individuals is proposed to be a contributing factor to increased mortality. The immune response associated with the increased mortality was explored using a murine scald injury model. In the absence of injury, aged mice had depressed delayed-type hypersensitivity (DTH) and splenocyte proliferative responses relative to young mice. There was also an increase with age in the production of the TH2 cytokines interleukin (IL)-4 and IL-10 by splenocytes. There was no change in the TH1 cytokines IFNgamma or IL-12 with age. However, IL-2 production was significantly lower. Following injury, there was a further decrease in the DTH response of aged injured mice, compared with aged sham mice. In addition, there was a decrease in all of the cytokines examined, regardless of age. In contrast, IFNgamma and IL-2 were significantly lower in the aged injured animals compared with the young injured animals. These results suggest that the lack of an adequate amount of TH1 cytokines shortly after injury in the aged mice may parallel the increased incidence of sepsis and death that occurs in aged burn patients.

Aging↗
PubMed1996

Small-volume resuscitation using hypertonic saline improves organ perfusion in burned rats.

Resuscitation using small volumes (3-5 mL/kg) of 7.5% hypertonic saline (HTS) is effective for hemorrhagic shock. Whether HTS is beneficial for the initial resuscitation of burn injury is not clear. We compared the hemodynamic effects of HTS versus lactated Ringer's solution (LR) and examined organ tissue perfusion during burn resuscitation (R). Full thickness scald burn (35% of total body surface area) was induced in pentobarbital-anesthetized rats. Regional blood flows were measured using radioactive microspheres before and 30 min after burn, and after R with either HTS (4 mL/kg) or LR (at a dose required for equivalent restoration of arterial blood pressure). Data from the HTS-or LR-resuscitated groups were compared to those from a nonresuscitated group (n = 10 in each group). Mean arterial pressure decreased 30% after burn (from 120 +/- 4 to 84 +/- 5 mm Hg, mean +/- SEM) and returned toward baseline (112 +/- 7 mm Hg) at 10 min after R with HTS (4 mL/kg) or LR (22.6 +/- 0.7 mL/kg), but subsequently decreased to 100 +/- 7 mm Hg with HTS and 105 +/- 5 mm Hg with LR at 30 min. In contrast to LR, resuscitation using HTS was associated with tachycardia. Blood flows to the skin and muscle of the normal or burn regions did not change after fluid resuscitation as compared to a nonresuscitated group. Fluid resuscitation transiently increased intestinal perfusion. Similar improvements in blood flow to the spleen were observed with HTS and LR at 10 min after R (from 128 +/- 10 to 156 +/- 15 and from 113 +/- 10 to 145 +/- 26 mL.min-1 x 100 g-1, respectively). However, at 30 min after R, splenic perfusion in the LR group was not different from that in the nonresuscitated group. Blood flows to the brain and kidney increased 39% and 42%, respectively, with HTS. HTS was also associated with pronounced improvements in blood flows to the heart (from 346 +/- 20 to 631 +/- 37 mL.min-1 x 100 g-1), liver (from 36 +/- 2 to 62 +/- 4 mL.min-1 x 100 g-1), and testis (from 29 +/- 2 to 43 +/- 2 mL.min-1 x 100g-1). Resuscitation using HTS was associated with rapid improvement in organ tissue perfusion in anesthetized rats subjected to burn injury. In comparison to LR, greater increases in blood flows to the heart, kidney, liver, and testis were observed with HTS. The results suggest that significant improvement in blood flow distribution can be achieved using HTS at less than one fifth the volume of LR for the initial treatment of burn shock.

Animals↗
PubMed1982

Toxic epidermal necrolysis-case report and review of the literature.

A patient who developed toxic epidermal necrolysis secondary to a sulfonamide derivative is presented. Treatment consisted of fluid resuscitation and silver nitrate soaks to the affected areas. Silver nitrate was selected over silver sulfadiazine (Silvadene) and mafenide in view of the nature of the offending agent. Tissue biopsy helps in the differentiation of toxic epidermal necrolysis from staphylococcal scalded skin syndrome. A biopsy is especially useful if the offending agent is not known so that appropriate treatment can be started promptly. The mortality associated with toxic epidermal necrolysis is in the neighborhood of 30%. The priniciples of burn wound management are the key to treatment of this disease. The wound usually heals by epithelialization without the need of skin grafting.

Adult↗
PubMed1988

Salvage of the severely injured ear.

We present three cases of severe external ear injuries and their management. The first patient's ear, amputated in an automobile accident, was revascularized microsurgically. Replantation, when possible, offers the ultimate result. However, disadvantages include the length of the operation and prolonged hospitalization. The second patient sustained a human bite ear amputation. Salvage consisted of immediate coverage with a vascularized temporoparietal fascial flap and split-thickness skin graft. Revision of the external auditory meatus and postauricular sulcus was required. This technique is relatively simple and reliable when microvascular revascularization is not possible. In the third case the patient's ear suffered a full-thickness burn as part of a larger scalding injury to the patient's body, face and scalp. Acute salvage was accomplished in one stage with a technique similar to that used for the second patient. Secondarily, skin was regrafted to achieve an improved color match and cartilage contour.

Adolescent↗
PubMed1977

Changes in humoral components of host defense following burn trauma.

Serum opsonic activity for E. coli 075, conversion of C3 by inulin, total hemolytic complement (CH(50)), levels of native C3, factor B, C3b inactivator (KAF), properdin (P), and immunoglobulins (Ig) were determined in 14 patients with burns involving 13% to 91% body surface during 6 to 8 weeks postburn. In the 12 uninfected patients, levels of IgG and IgA were reduced during the first 10 days postburn, and decreased concentrations of P and IgM were demonstrated from three to 6 weeks postburn. C3 conversion was reduced from 10 days to 6 weeks postburn. Levels of C3, factor B, and KAF were normal or elevated for the entire study period. No difference in the occurrence of humoral abnormalities was noted in patients with burns caused by flame, immersion scald, or acid contact. Reduction in C3 conversion and P concentration were the only abnormalities which correlated with increasing burn size. Bacteremia and/or fungemia was documented in the other two patients. In one of these patients, reduction in CH(50) occurred during septicemia due to S. aureus, and in the other, reduction in all measurements of complement was associated with candidemia and Pseudomonas septicemia and occurred prior to the development of shock. Serum opsonic activity was only reduced significantly during sepsis, suggesting that this abnormality occurred as a result rather than a cause of infection. These results indicate that consumption of components of the classical and/or alternative pathways of complement activation may be an important mechanism by which infection is perpetuated in the burn patient. They also emphasize the importance of the clinical management of the burn patient in preventing the development of septic complications.

Adolescent↗
PubMed1983

Synthetic immunomodulators for prevention of fatal infections in a burned guinea pig model.

Individuals who have suffered severe trauma, such as burns, have a high incidence of infection associated with impaired host resistance. Nonspecific stimulators of host defense mechanisms, i.e., immunomodulators, may be of benefit in such situations. A small animal model (guinea pigs) was developed to study the efficacy of immunomodulators in burns. Anesthetized animals received a 20% total body surface area, full-thickness, scald burn. There was no mortality associated with this injury, but these animals were highly susceptible to challenge with Pseudomonas aeruginosa strain 1244 by direct injection into the burn wound within 24 hours of injury. This susceptibility persisted about 7 days. The standard model adopted was to injure animals, then challenge with 1 median lethal dose (LD50) of P. aeruginosa 96 hours after injury. Using this model, six synthetic immunomodulators were tested: CP-20,961, CP-46,665, muramyl dipeptide, thymopoietin pentapeptide (TP-5), levamisole, and lithium. Drug administration began 24 hours after injury and ended prior to challenge with P. aeruginosa at 96 hours. CP-20,961, muramyl dipeptide, levamisole, and lithium all had no beneficial effect on survival. A single dosage (0.3 mg/kg, I.V.) of CP-46,665, administered 24 hours postinjury, increased the survival rate from 50% to 85% and mean survival time (MST) from 8.2 days to 12.4 days. TP-5, given in four doses (0.1 mg/kg, I.V. each) every 24 hours, increased the survival rate from 40% to 80% and MST from 6.9 days to 11.6 days. These data show that immunomodulators could be of benefit in burns, but also that not all agents are effective in this particular situation.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Lymphoid subpopulation changes after thermal injury and thermal injury with infection in an experimental model.

Subpopulation analysis of peripheral blood lymphocytes is a frequently used measure of immunocompetence. Yet, little is known about the lymphocyte subpopulations in the circulation and lymphoid organs after severe trauma. Blood, spleen, and lymph node (LN) subpopulations were compared in a rat model of burn injury (B) and burn injury with infection (BI). B and BI rats received 30% total body surface scald burns. Infection was induced by seeding wounds with Pseudomonas aeruginosa. Subpopulations were identified by flow cytometry 48 hours after burn. Helper lymphocytes were selectively depleted from the circulation of BI but not B animals, which caused the ratio of helper to suppressor cells (HSR) in BI animals to decrease significantly compared with the unburned controls. Both LN helper and suppressor cells were decreased in BI animals and the HSR was unchanged, but a selective reduction in suppressor cells in B LN increased the HSR relative to unburned controls. Spleen subpopulations were unchanged for both B and BI groups. Subpopulation changes after trauma and infection were different for each tissue examined.

Animals↗
PubMed1990

Early burn wound excision significantly reduces blood loss.

The hypothesis that near-total early excision of large burns in children can be performed safely with a reduction in blood loss was tested. Of 1662 acutely burned patients admitted to this institution between 1982 and 1989, 594 underwent near-total excision of cutaneous flame or scald burn injuries in a single procedure. Operations took less than 3 hours and there were no operative deaths. Blood losses in burns of more than 30% total body surface area (TBSA) were significantly less at 0.40 +/- 0.06 mL/cm2 and 0.49 +/- 0.49 mL/cm2 excised when surgery was performed within the first 24 hours or after the 16th day after burn, respectively, when compared to 0.75 +/- 0.02 mL/cm2 for those excised between 2 and 16 days after burn (p less than 0.05). Blood loss for burns of less than 30% TBSA was of 1.19 +/- 0.13 mL/cm2. Early excision did not increase mortality rate when compared to later excision times. We suggest that near-total excision of large burns within the first 24 hours reduces blood requirements and morbidity without adversely altering hemodynamic stability or increasing mortality risks.

Blood Transfusion↗
PubMed1990

Effects of recombinant human growth hormone on donor-site healing in severely burned children.

The beneficial effects of growth hormone on wound healing in severely burned children were studied. Forty patients who were 2 to 18 years old, with 40% or more total body surface area (TBSA) and 20% or more TBSA full-thickness flame or scald burns, were randomized in a double-blind study to receive placebo or 0.1 mg/kg/day recombinant human growth hormone (rHGH) until the first donor site healed or to receive 0.2 mg/kg/day rHGH or placebo from admission throughout hospitalization. Patients receiving 0.2 mg/kg/day rHGH demonstrated significantly higher serum IGF-1 levels at 4.8 +/- 1.7 U/mL compared to placebos at 1.6 +/- 0.4 U/mL (p less than 0.05) and a significant decrease in donor-site healing times compared to placebo (p less than 0.05). Length of hospital stay (LOS/%TBSA) was decreased from 0.80 +/- 0.10 days/%TBSA burned in the placebo group to 0.54 +/- 0.04 days/%TBSA burned in the 0.2 mg/kg/day treatment group (p less than 0.05). This translates, for the average 60% TBSA burned patient, to a decrease in LOS from 46 to 32 days.

Adolescent↗
PubMed1992

Reduction in biliary IgA after burn injury. Role of diminished delivery via the thoracic duct and of enhanced loss from the systemic circulation.

The concentration of biliary IgA is greatly reduced after scald burn injury in the rat, thereby contributing to a deficiency in upper intestinal immune defense. This reduction in biliary IgA might have several explanations, including failure of the transhepatic transport of polymeric IgA (pIgA) from the circulation, decreased delivery of pIgA to the hepatocyte, or decreased local synthesis of IgA in the liver. The authors examined whether burn injury reduces circulating pIgA available for delivery to the hepatocyte. In initial studies, they demonstrated that burn injury induces a decrease in circulating pIgA in bile-duct-ligated rats. They then sought to determine whether this decrease in pIgA was due to increased loss from the circulation or to a decreased supply of pIgA to the circulation through the thoracic duct. After injection of purified 125I-pIgA into bile duct-ligated rats, radioactivity was removed more rapidly from the circulation of burn-injured compared with control rats. The radioactivity localized in the skin and muscle at the site of burn injury. In another group of rats with patent bile ducts, the thoracic duct was cannulated and lymph collected for 12 hours. The total amount of IgA protein in lymph was found to be reduced in burn-injured compared with control animals. Thus, burn injury is accompanied by reduced circulating pIgA, which may be attributed to its enhanced loss from the circulation and to decreased delivery of pIgA from the intestinal mucosa to the systemic circulation via the thoracic duct.

Animals↗
PubMed1999

Posttranslational modifications of cardiac and skeletal muscle proteins by reactive oxygen species after burn injury in the rat.

OBJECTIVE: To determine the involvement of oxidative damage in muscle wasting after burn injury. SUMMARY BACKGROUND DATA: Burn injury damages tissue at the site of the burn and also affects peripheral tissue. There is evidence to suggest that reactive oxygen species may be generated in increased amounts after burn, and these may contribute to wound healing and to posttranslational modifications of tissue constituents distant from the wound site. METHODS: The oxidation of muscle proteins was assessed, using the dinitrophenylhydrazine assay for carbonyl content, in muscles of rats after a full-thickness skin scald burn covering 20% of the total body surface area, over a 6-week period. In this model, rats failed to incur normal body weight or muscle weight gain. RESULTS: Soleus, extensor digitorum longus, diaphragm, and heart ventricle proteins were oxidatively damaged after injury. The extent of tissue protein oxidation, however, differed depending on the time points studied. In general, higher levels of protein carbonyl group formation, an indicator of oxidative damage, were found to occur within 1 to 5 days after injury, and the oxidized protein content of the various tissues decreased during the later stages. Both sarcoplasmic and myofibrillar carbonyl-containing proteins accumulated in diaphragm 3 days after burn injury and were rapidly removed from the tissue during a 2-hour in vitro incubation. This coincided with increased proteolytic activity in diaphragm. CONCLUSIONS: These observations suggest that the loss of proteins modified by reactive oxygen species may contribute to the burn-induced protein wasting in respiratory and other muscles by a proteolytically driven mechanism.

Animals↗
PubMed1999

Caspase-3-dependent organ apoptosis early after burn injury.

OBJECTIVE: To examine the role played by endotoxin, tumor necrosis factor-alpha (TNF-alpha), and caspase-3 in the increased apoptosis seen in solid organs in the early period after a burn injury. SUMMARY BACKGROUND DATA: Burn injury is often associated with immune suppression. Bacterial translocation and systemic endotoxemia have been reported after a burn injury, and caspase-3 activation due to TNF-alpha and Fas ligand (FasL) are presumed to initiate apoptosis. We hypothesized that endotoxin-induced TNF-alpha expression and caspase-3 activation could be the stimulus for the apoptosis after burn injury. METHODS: A 20% full-thickness scald burn was used in C57BL/6 mice. Three hours after burn injury, tissue samples were obtained from the thymus, lung, liver, and spleen. Lipopolysaccharide-nonresponsive (C3H/HeJ) and TNFalpha null B6x129tnf-/- mice were also used. To detect apoptosis, hematoxylin and eosin stain, in situ TUNEL, DNA extraction, and gel electrophoresis were all performed. Caspase-3 activity and TNF-alpha and FasL mRNA were also measured. RESULTS: Increased apoptosis and caspase-3 activity were observed in the thymus and spleen 3 hours after burn injury but were not seen in liver or lung. In the thymus and spleen, increased expression of FasL mRNA was also observed, whereas increased TNF-alpha mRNA was not. Increased apoptosis in thymus and spleen were also observed in C3H/HeJ and B6x129tnf-/- mice after burn injury. An inhibitor of the caspase-3 (Z-VAD-fmk) reduced apoptosis in both thymus and spleen. CONCLUSIONS: In the early period after a burn injury, increased apoptosis is observed primarily in the lymphoid organs and is independent of endotoxin or TNF-alpha. The increased caspase-3 activity in thymus and spleen contributes to apoptosis in these organs.

Animals↗
PubMed2000

Insulin-like growth factor I in combination with insulin-like growth factor binding protein 3 affects the hepatic acute phase response and hepatic morphology in thermally injured rats.

OBJECTIVE: To modulate the hepatic acute phase response after a thermal injury by the administration of insulin-like growth factor I (IGF-I) in combination with its principal binding protein 3 (IGFBP-3). SUMMARY BACKGROUND DATA: The hepatic acute phase response is a cascade of events initiated to restore homeostasis after trauma; however, a prolonged response contributes to multiorgan failure, hypermetabolism, complications, and death. Although IGF-1 has been shown to improve cell recovery and play a major role in liver regeneration, its effect on the hepatic acute phase response is not known. METHODS: Sprague-Dawley rats (56 males) received a 60% total body surface area third-degree scald burn and were randomly divided to receive either rhIGF-I/BP-3 (10 mg/kg/day given subcutaneously) or saline (control). Rats were killed on postburn days 1, 2, 5, and 7 and serum glucose, electrolytes, acute phase reactant proteins, tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, and rat and human serum IGF-I and IGFBP-3 were measured. Hepatic protein concentrations, hepatocyte proliferation, and hepatocyte apoptosis were determined. RESULTS: No hypoglycemia or electrolyte imbalance could be shown in rats receiving the growth factor complex compared with saline. rhIGF-I/BP-3 increased serum protein on postburn days 2 and 7, albumin on days 5 and 7, and transferrin on days 1, 5, and 7, and decreased haptoglobin and alpha1-acid glycoprotein on postburn days 5 and 7 compared with controls. IGF-I/ BP-3 had no effect on type II acute phase proteins. Rats receiving IGF-I/BP-3 had lower serum levels of interleukin 1 beta and tumor necrosis factor alpha on the first day after burn compared with controls, whereas serum levels of interleukin 6 did not change. rhIGF-I/BP-3 significantly increased total liver protein content on postburn days 1, 2, 5, and 7 compared with controls. IGF-I/BP-3 increased hepatocyte proliferation and decreased hepatocyte apoptosis versus controls. CONCLUSION: In combination with its principal binding protein, rhIGF-I decreases the proinflammatory cytokines interleukin 1 beta and tumor necrosis factor alpha, followed by a decrease in type I acute phase proteins. IGF-I/BP-3 had no effect on interleukin 6 and type II acute phase proteins. Decreases in acute phase protein and proinflammatory cytokine synthesis were associated with increases in constitutive hepatic proteins, total liver protein content, and hepatocyte proliferation. IGF-I/BP-3 attenuates the hypermetabolic response after thermal injury and may improve the clinical outcome.

Acute-Phase Reaction↗
PubMed1994

Transport of fluorescent dextrans across the rat ileum after cutaneous thermal injury.

OBJECTIVE: To determine the time course and spatial distribution of uptake of macromolecules in the small intestine of rats subjected to cutaneous thermal injury. DESIGN: Prospective, controlled animal study. SUBJECTS: Fifty-five female Sprague-Dawley (CD) rats subjected to scald burn injury covering 20% (small injury; n = 29) and 40% (large injury; n = 6) of the total body surface area between 3 and 72 hrs after injury. Animals subjected to sham injury (n = 20) were used as controls. INTERVENTIONS: The intestine was cannulated near the distal ileum and incised 7 cm upstream. After perfusion with physiologic buffer, this intestinal loop was filled with the same buffer containing fluorescent-labeled dextrans (3 and 70 kilodaltons molecular weight) and ligated 4 cm from the injection point. After a 2-hr incubation period, the tissues were fixed with paraformaldehyde and cryosections were examined by laser confocal microscopy. The mesentery was also observed by laser confocal microscopy during incubation with the permeability probes. The disappearance of fluorescence was studied after washing the dextran probes from the gut lumen. MEASUREMENTS AND MAIN RESULTS: In small injuries, there was a transient uptake of the 3-kilodalton dextran by the epithelium in focal regions of the ileum with the effects seen between 7 and 21 hrs after injury. In large injuries, epithelial staining was visible within 3 hrs, and the marker was seen to translocate both to the lymphatics and the blood vessels of the mesentery. In comparison, the 70-kilodalton dextran was visible within the intercellular spaces. Little or no epithelial staining was seen in sham-injured animals. CONCLUSIONS: These results suggest that a transcellular pathway for the translocation of small macromolecules from the lumen to the mesentery can be activated after burn injury. The novel techniques described here will be useful to examine intestinal transport in various pathologic situations.

Animals↗
PubMed1996

Burn injury alters beta-adrenergic receptor and second messenger function in rat ventricular muscle.

OBJECTIVES: The molecular pharmacologic bases for the attenuated cardiovascular and metabolic responses to catecholamines, after burn injury, have not been elucidated. In the present study, myocardial tissues were used as a model of beta-adrenergic receptors to study burn injury-induced alterations in receptors and in signal transduction. DESIGN: Prospective study, randomized to treatment and control groups. SETTING: University-hospital research laboratory. SUBJECTS: Male Sprague-Dawley rats (180 to 210 g). INTERVENTIONS: A 50% body surface area burn or sham-burn was administered to the rats. MEASUREMENTS AND MAIN RESULTS: Myocardial membranes were isolated at 24 hrs, 7 days and 14 days after 50% body surface area scald or sham injury. (-)125I-iodocyanopindolol was used to assess maximal binding capacity and affinity of the beta-adrenergic receptor. Basal and stimulated concentrations of second messenger, cyclic adenosine monophosphate (cAMP), were also assessed. Production of cAMP during isoproterenol stimulation tested the integrity of the beta-adrenergic receptor-mediated signal transduction. Forskolin, which stimulates adenylate cyclase enzyme directly (bypassing the receptor and G protein) to produce cAMP, tested the efficacy of the enzyme itself. Maximal binding capacity was unaltered between the experimental and control groups, but the affinity (mean +/- SEM) was significantly decreased in burned animals at 7 days (125.4 +/- 15.5 picomoles [pmol]; p = .01) and at 14 days (216.7 +/- 50.7 pmol; p = .001) compared with controls (75.5 +/- 8.4 pmol). In different set experimental and control groups, basal concentrations of cAMP in myocardial membranes were significantly decreased in burned animals at 7 days (control 38.6 +/- 4.2 vs. 5.8 +/- 0.9 pmol/mg of protein/min; p = .003) and at 14 days (control 47.4 +/- 3.2 vs 28.3 +/- 6.6 pmol/mg of protein/min; p = .002). The forskolin (direct)-stimulated synthesis of cAMP was decreased in burned animals at 24 hrs (control 339.0 +/- 40.5 vs. 214.4 +/- 16.6 pmol/mg of protein/min; p = .01), at 7 days (control 289.0 +/- 34.4 vs. 32 +/- 13.0 pmol/mg of protein/min; p = .01), and at 14 days (control 322.9 +/- 28.6 vs. 137.0 +/- 46.1 pmol/mg of protein/min; p = .01). The isoproterenol or receptor-mediated stimulation of cAMP production was also significantly (p < .001) impaired in burned animals compared with controls at 24 hrs (control 134.7 +/- 11.9 vs. 83.1 +/- 13.3 pmol/mg of protein/min), and at 14 days (control 128.2 +/- 7.2 vs. 92.8 +/- 17.7 pmol/mg of protein/min). CONCLUSION: The etiology of the decreased responses in the myocardium to exogenous and endogenous beta-adrenergic receptor agonists after burn injury may be attributed to decreased affinity for ligands, and also to impaired receptor-mediated signal transduction and to decreased adenylate cyclase enzyme activity, resulting in decreased basal and stimulated second messenger (cAMP) production.

Adrenergic beta-Agonists↗
PubMed2000

Hepatocyte growth factor modulates the hepatic acute-phase response in thermally injured rats.

OBJECTIVE: Hepatocyte growth factor (HGF) has been shown to modulate the acute-phase response in vitro. The specific in vivo role of HGF in this multifactorial response, however, remains unknown. This study examines the effects of exogenous HGF on the acute-phase response in thermally injured rats. DESIGN: Prospective, randomized, laboratory study. SETTINGS: Shriners Hospital for Children and University of Texas Medical Branch laboratories. SUBJECTS: Fifty-six male Sprague-Dawley rats (weight range, 300-325 g). INTERVENTION: Animals received a 60% total body surface area third-degree scald burn and were randomly divided to receive either 400 microg/kg/day i.v. HGF or saline (control). MEASUREMENTS AND MAIN RESULTS: Serum acute-phase proteins, cytokines, and insulin-like growth factor (IGF)-I concentrations, as well as liver weight, protein and triglyceride content, IGF-I concentrations, and cytokine gene expression were measured 1, 2, 5, or 7 days after burn. Serum albumin was increased on days 2, 5, and 7 after burn, and transferrin was increased on day 7 after burn in HGF-treated rats compared with controls (p<.05). HGF increased alpha2-macroglobulin concentrations on postburn days 2, 5, and 7 compared with controls (p<.05). Serum interleukin-6 and tumor necrosis factor-alpha were significantly higher within 2 days of burn in rats treated with HGF (p<.05). HGF increased the hepatic gene expression of tumor necrosis factor-alpha compared with controls (p<.05). Serum IGF-I decreased in rats receiving HGF 1, 2, and 5 days after burn, whereas liver IGF-I concentrations were higher on days 1 and 7 after burn compared with controls (p<.05). Hepatic protein concentrations were higher in the HGF group compared with controls on postburn days 1, 2, and 7, with a concomitant increase in total liver weight (p<.05). HGF exerted a strong mitogenic effect on hepatocytes 1 and 2 days after thermal injury compared with controls (p<.05). CONCLUSIONS: These findings suggest that HGF modulates the acute-phase response in vivo after burn and causes changes in liver morphology.

Acute-Phase Proteins↗
PubMed2000

Neutrophil depletion in rats reduces burn-injury induced intestinal bacterial translocation.

OBJECTIVE: To determine whether neutrophil depletion could eradicate intestinal bacterial translocation in bum-injured rats. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: The rats were intravenously administered a rabbit anti-rat neutrophil antibody causing profound neutropenia and subjected to a 30% total body surface area scald burn. MEASUREMENTS AND MAIN RESULTS: The depletion of neutrophils from the intestine was assessed via measurements of myeloperoxidase (MPO) activity in the intestinal homogenates. In addition, the presence of activated/extravasated neutrophils in intact intestines was determined via immunohistochemical localization of neutrophil nicotinamide adenine dinucleotide phosphate (NADPH) oxidase component protein p47phox. Bacterial translocation was measured using agar cultures and by determining Escherichia coli beta-galactosidase gene via polymerase chain reaction/Southern blot analyses of mesenteric lymph node and spleen, liver, lung, and blood. MPO measurements demonstrated a six-fold increase above the control value in the intestinal tissue in rats on day 1 postburn. The presence of activated neutrophils (expression of p47phox protein) was also markedly increased in the intestines of these rats. The increased MPO activity and p47phox expression accompanied a translocation of indigenous E. coli into the mesenteric lymph node without a spread to other organs. The administration of anti-neutrophil antibody to burn animals prevented an increase in MPO activity and bacterial translocation. CONCLUSION: These studies indicate that enhanced intestinal bacterial translocation caused by burn injury could be related to the increased infiltration of activated neutrophils into the intestinal tissue after bum. The release of neutrophil products such as superoxide anion may effect intestinal tissue damage leading to bacterial translocation of indigenous E. coli.

Animals↗