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Biomedical subjects

R L Gamelli

Publications and source records attributed to R L Gamelli.

At least 37 records · Page 2Linked to original sources
PubMed1998

Improvement in survival with peptidyl membrane interactive molecule D4B treatment after burn wound infection.

OBJECTIVE: To examine the effects of peptidyl membrane interactive molecule D4B in a murine model of lethal burn wound infection. EXPERIMENTAL DESIGN: Four experiments were performed: (1) growth inhibition assays of Pseudomonas aeruginosa treated with D4B, 0 to 100 micromol/L; (2) in vitro coculture of bone marrow cells with D4B, 0 to 100 micromol/L; (3) D4B treatment survival studies after burn injury only or burn wound infection in mice; and (4) peripheral white blood cell count, burn wound tissue bacterial culture, and burn wound morphological analysis at days 1, 2, and 3 after injury. SETTING: University medical center laboratory. SUBJECTS: Groups of B6D2F1 male mice (20 each) were studied. INTERVENTIONS: Full-thickness scald burn, 15% of total body surface area, with P aeruginosa topical infection, and subeschar injections of D4B at 200 microg or 0.25 mL of placebo per mouse at 2 and 24 hours after injury. MAIN OUTCOME MEASURES: Animal survival after thermal burn wound bacterial infection, circulating leukocyte numbers, in vitro clonal cell culture of granulocyte-macrophage progenitor cells, and wound histopathological analysis. RESULTS: The survival rate in the D4B-treated group was nearly 2-fold greater than that in controls (P<.01) during 14 days of study. Bacterial quantitative wound cultures disclosed significant reductions in bacterial numbers at days 1, 2, and 3 in D4B-treated animals as compared with controls (P<.05 to <.01). D4B induced a dose-dependent inhibition of bacterial cell growth when added to in vitro P aeruginosa cultures (P<.01). Granulocyte-macrophage progenitor cell growth in culture was not altered by D4B treatment. D4B-treated animals displayed no signs of toxic effects or impairment in wound healing. CONCLUSIONS: The peptidyl membrane interactive molecule D4B had the ability to improve survival after gram-negative burn wound sepsis via direct antimicrobial effects. Peptidyl membrane interactive molecules may offer the potential of alternative treatments to standard topical agents or in patients with drug-resistant microbes.

Animals↗
PubMed1998

Mechanisms of neutropenia involving myeloid maturation arrest in burn sepsis.

OBJECTIVE: To determine the mechanisms that lead to the decrease in bone marrow production of neutrophils during burn sepsis. SUMMARY BACKGROUND DATA: Impaired bone marrow granulopoiesis during burn sepsis often results in neutropenia despite elevated circulating levels of granulocyte colony-stimulating factor (G-CSF). To date, neither the specific stages of neutrophil maturation involved in the bone marrow suppression nor the mechanisms for the impairment have been determined. METHODS: Peripheral blood absolute neutrophil count and G-CSF levels were determined in mice 3 days after randomization to control, burn alone, or burn plus a topical inoculation of Pseudomonas aeruginosa (1000 colony-forming units). Bone marrow aspirates were analyzed for their neutrophil differentiation patterns by Gr-1 antigen expression and their G-CSF receptor status. Histologic analysis of liver, lung, spleen, and wound site was performed. RESULTS: In burn sepsis, absolute neutrophil count was reduced whereas plasma G-CSF levels were elevated, and myeloid differentiation was significantly shifted toward the immature mitotic myeloid cells. Bone marrow G-CSF receptor mRNA levels and G-CSF-stimulated proliferation were substantially decreased in burn sepsis. Histologic analysis revealed no significant neutrophil infiltration into the tissues. CONCLUSIONS: In thermal injury with superimposed sepsis, neutropenia and myeloid maturation arrest, despite the elevated levels of G-CSF, correlate with the reduction in bone marrow G-CSF receptor expression. These observations may provide a potential mechanism for neutropenia in sepsis.

Animals↗
PubMed1998

Effect of prophylactic administration of recombinant human granulocyte colony-stimulating factor (filgrastim) on the frequency of nosocomial infections in patients with acute traumatic brain injury or cerebral hemorrhage. The Filgrastim Study Group.

OBJECTIVE: To determine whether the use of prophylactic recombinant human granulocyte colony-stimulating factor (filgrastim) reduces the frequency of nosocomial infections in patients with either acute traumatic brain injury or cerebral hemorrhage. DESIGN: Randomized, placebo-controlled, double-blind, multicenter phase II study. SETTING: Intensive care units of seven medical centers. PATIENTS: Patients with either acute traumatic brain injury or cerebral hemorrhage who were intubated within 6 hrs of admission and who were expected to be ventilated for >72 hrs. INTERVENTIONS: Patients were randomized to receive daily subcutaneous injections of placebo (n = 21) or one of two doses of filgrastim (75 microg [n = 20] or 300 microg [n = 20]) for 10 days or until the absolute neutrophil count was >75,000 cells/mm3 or until extubation. MEASUREMENTS AND MAIN RESULTS: End points included increase in absolute neutrophil count, safety of filgrastim, and frequency of nosocomial infections (pneumonia, bacteremia, and urinary tract infection). Filgrastim caused a dose-dependent increase in absolute neutrophil count. There were no differences in the frequency of pneumonia or urinary tract infection; however, there was a dose-dependent decrease in the frequency of bacteremias (p < .05). Adverse events were similar among the three groups. There was one case of acute respiratory distress syndrome in the placebo group. CONCLUSION: In this patient population, use of filgrastim was safe and the agent appeared to reduce the risk of primary bacteremias but had no beneficial effects on mortality, length of stay, or other nosocomial infections.

APACHE↗
PubMed1998

Human immune cells mediate catecholamine secretion from adrenal chromaffin cells.

OBJECTIVES: To determine the ability of human mononuclear cells to produce factors that cause catecholamine secretion from adrenomedullary chromaffin cells; to determine conditions that stimulate mononuclear cells to produce such factors; and to compare these results with catecholamine secretion in response to the cytokines interleukin (IL)-1 and IL-2. DESIGN: Randomized, controlled, prospective study using in vitro conditions. SETTING: University research laboratory. SUBJECTS: Human mononuclear cells and porcine chromaffin cells. INTERVENTIONS: Circulating human mononuclear cells were isolated and cultured overnight in RPMI media. Cell-free media from these cultures (conditioned media) were then tested for the ability to cause epinephrine secretion from porcine chromaffin cells. Mononuclear cells were stimulated with phytohemagglutinin or by mixing cells from two different individuals while suppression was tested with dexamethasone. Catecholamine secretion in response to IL-1 and IL-2 (50 and 500 units/well, respectively), or nicotinic agonist dimethylphenylpiperazinium (10 microM, which mimics the action of acetylcholine), was tested for comparison. MEASUREMENTS AND MAIN RESULTS: Isolated porcine chromaffin cells had stable catecholamine content at the time of secretion measurements, and catecholamine release from cells into the media was measured using electrochemical detection after high-performance liquid chromatography separation. Catecholamine secretion was expressed as a percentage of the total cellular content. Epinephrine secretion due to human conditioned media was 6.9 +/- 1.0% compared with 1.4 +/- 0.6% for control media (p < .05) and 14.6 +/- 3.3% for dimethylphenylpiperazinium (p < .05). Epinephrine secretion with conditioned media from mixed cells (mixed leukocyte reaction) was 16.6 +/- 1.2%, which was higher than the epinephrine secretion caused by media from a single donor (6.9% +/- 1.0, p < .001). Pretreatment with dexamethasone inhibited the formation of bioactive products from mixed mononuclear cell preparations. Cytokines IL-1 and IL-2 did not stimulate chromaffin cell epinephrine secretion above background release with control media incubation. In all cases, norepinephrine secretion was similar to that of epinephrine, and results are included in all figures. CONCLUSIONS: Factors released from human immune cells can mediate epinephrine and norepinephrine release from adrenomedullary cells through a nonneural mechanism. Such immune cell factor release can be modulated by immunostimulation and steroid suppression. Release of such factors in vivo may contribute to increased circulating epinephrine in response to infectious challenge and may be an important factor in the critically ill patient.

Animals↗
PubMed1998

Trauma care fellowships: current status and future survival.

BACKGROUND AND METHODS: To determine the current status and future direction of trauma care fellowships, a phone survey was conducted with the 45 program directors reporting information to the American Association for the Surgery of Trauma and the Eastern Association for the Surgery of Trauma. RESULTS: Forty programs (89%) were operational, with 86 positions. The duration of the fellowship was 1 year for 16 (40%) and 2 or more years for 24 (60%). Accreditation Council for Graduate Medical Education accreditation (ACGME) (for surgical critical care) was held by 28 (70%). Mean salary was $39,600 at the first-year level. A funding shift from institutional to practice revenue sources is foreseen. Thirteen directors (32.5%) saw future recruitment potential as increasing and 11 (27.5%) saw it as decreasing. CONCLUSION: The essence, structure, and funding of trauma fellowships are changing. One-year exclusive trauma fellowships are being replaced by 1- to 2-year trauma or surgical critical care fellowships with Accreditation Council for Graduate Medical Education accreditation increasingly seen as essential. The challenge for fellowships in an era of budgetary constraints will be to provide adequate training in the full spectrum of tramatology within a reasonable time frame supported by a predictable funding mechanism.

Accreditation↗
PubMed1998

Trauma and thermal injury: comparison of hemostatic and cytokine changes in the acute phase of injury.

BACKGROUND: Initiated either by thermal injury or mechanical trauma, the systemic inflammatory response syndrome stimulates activation of coagulation and fibrinolysis, evolving into a subclinical disseminated intravascular coagulation. METHOD: Hemostatic parameters, interleukin-6, and endothelin plasma levels were compared in burn and trauma patients. Nineteen patients with major burn injury (> or = 40% total body surface area) were compared with 35 trauma patients with Injury Severity Scores > 25 on day 1 and days 5 to 8. RESULTS: Thrombin-antithrombin levels were significantly higher in trauma patients than in burn patients (p < 0.0001) on day 1, and endothelin was significantly higher on days 1 and 5 (p < 0.0001) in trauma patients than in burn patients. Interleukin-6 plasminogen activator inhibitor-1, and tissue plasminogen activator levels were elevated above normal limits on both days in both groups. CONCLUSION: There was a difference in the degree and level to which homeostasis was perturbed between the two groups. The mechanism of injury did not affect the initiation of subclinical disseminated intravascular coagulation and cytokine release, and the physiologic response remained the same.

Adult↗
PubMed1998

Burn wound infection-induced myeloid suppression: the role of prostaglandin E2, elevated adenylate cyclase, and cyclic adenosine monophosphate.

Suppressed granulocyte and macrophage growth after burn infection or endotoxicosis appears to be mediated by macrophage-derived products. In this study, we found that after burn, burn plus infection, or endotoxicosis, peritoneal-elicited macrophages or bone marrow cells released increased amounts of prostaglandin E2 (PGE2) and inhibited growth of granulocyte-macrophage progenitor cells (GM-CFC). PGE2, when added in culture, inhibited in vitro GM-CFC growth in a dose-dependent manner. Pretreatment of bone marrow cells with either dibutyryl cyclic adenosine monophosphate or Forskolin in vitro mimicked the PGE2 inhibition, further aggravated the inhibition induced by burn, burn plus infection, or endotoxicosis, and was not blocked by co-culture with indomethacin. Pretreatment of bone marrow cells with SQ22536, an adenylate cyclase inhibitor, significantly restored the suppressed GM-CFC growth found after burn, burn plus infection, or endotoxicosis. Alterations in myeloid production after burn infection appear to be related in part to the level of intracellular cyclic adenosine monophosphate for the GM-CFC and are responsive to PGE2.

Adenylyl Cyclases↗
PubMed1998

Prostaglandin E2 alterations during sepsis are partially mediated by endotoxin-induced inhibition of prostaglandin 15-hydroxydehydrogenase.

Prostaglandin E2 (PGE2) is significantly elevated in the plasma of septic or injured patients and is thought to be a component of the resultant immune suppression associated with augmented rates of infection and mortality. Many studies have examined the effect of burn injury and sepsis on PGE2 synthesis. However, the effect of sepsis or burn injury on the expression of prostaglandin 15-hydroxydehydrogenase (PGDH), the key enzyme responsible for PGE2 degradation, has not been explored. The aim of this study was to examine the effect of endotoxin treatment and/or burn injury on the expression of PGDH. Male BDF1 mice were assigned to four groups (n = 4/group): sham, lipopolysaccharide (LPS) (2.5 mg/kg, Escherichia coli LPS, i.p.), burn (15% body surface area scald injury), and burn + LPS (15% body surface area + 2.5 mg/kg LPS, i.p.). Lung tissue was harvested at specific time points after treatment and subsequently was processed for total RNA and protein. Northern and Western blot analyses were used to examine differences in PGDH protein and mRNA expression. Total RNA was probed with the riboprobe for murine PGDH, and the 100,000 g protein fraction was immunoblotted using an rabbit antimurine PGDH antibody. PGDH was expressed in lung at t = 0 in both the saline and LPS-treated animals. A decrease in mRNA expression was initially observed at 2 hours after LPS treatment. The decrease was also significant (p < 0.05) at 3 hours after LPS and maximal decrease in mRNA and protein expression was observed at 6 hours. At 24 hours after LPS administration, the PGDH mRNA and protein expression was still significantly depressed to 49% of control expression. PGDH expression was similar and not statistically different in both burn and burn + LPS treatment at t = 0. At 2 hours after LPS, PGDH mRNA expression in the burn + LPS treatment group had significantly decreased to 47% in comparison with the burn alone group. Maximal decrease in PGDH mRNA and protein expression in lung from burn + LPS was observed at 6 hours after LPS treatment. This change represents a 73% decrease in mRNA in comparison with the time-matched burn control. At 24 hours after LPS administration, PGDH mRNA but not protein expression in the lung from burn + LPS treated mice was still significantly decreased. In summary, LPS treatment alters PGDH mRNA expression at the transcriptional and protein levels. Consequently, sepsis-induced increases in PGE2 levels may not be only due to increased PGE2 synthesis but also due to decreased PGDH expression and, hence, PGE2 degradation.

Animals↗
PubMed1998

Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing.

Angiogenesis is an essential component of normal wound repair, yet the primary mediators of wound angiogenesis have not been well described. The current study characterizes the contribution of vascular endothelial cell growth factor (VEGF) to the angiogenic environment of human surgical wounds. Surgical wound fluid samples (n = 70) were collected daily for up to 7 postoperative days (POD) from 14 patients undergoing mastectomy or neck dissection. VEGF levels in surgical wound fluid were lowest on POD 0, approximating values of serum, but increased steadily through POD 7. An opposite pattern was noted for basic fibroblast growth factor-2. Fibroblast growth factor-2, which has been previously described as a wound angiogenic factor, exhibited highest levels at POD 0, declining to near serum levels by POD 3. Surgical wound fluid form all time points stimulated marked endothelial cell chemotaxis and induced a brisk neovascular response in the rat corneal micropocket angiogenesis assay. Antibody neutralization of VEGF did not affect the in vitro chemotactic or the in vivo angiogenic activity early wound samples (POD 0). In contrast, VEGF neutralization significantly attenuated both chemotactic activity (mean decrease 76 +/- 13%, P < 0.01) and angiogenic activity (5 of 5 samples affected) of later wound samples (POD 3 and 6). The results suggest a model of wound angiogenesis in which an initial angiogenic stimulus is supplied by fibroblast growth factor-2, followed by a subsequent and more prolonged angiogenic stimulus mediated by VEGF.

Aged↗
PubMed1997

Ischemic necrotic bowel disease in thermal injury.

BACKGROUND: Gastrointestinal tract (GI) complications are a well-recognized entity following burn injury. OBJECTIVE: To determine whether there was a change in the incidence and type of GI complications in individuals with thermal injuries requiring operative intervention and whether this might be related to changes in patient management. DESIGN: A retrospective 8-year study of patients admitted with burn injuries. SETTING: A university medical center burn unit. METHODS: Statistical analysis and pathological review of 2 groups of patients: those with ischemic necrotic bowel disease (INBD group) and those with other GI complications (other GI complication group), identified among 2114 patients admitted with burn injuries during an 8-year period (1988-1995). RESULTS: Of 2114 patients admitted with burn injuries, 19 patients were identified retrospectively as having had either INBD (n = 10) or other GI complications (n = 9). Statistical analysis showed no difference between the 2 groups in duration of hospitalization, age, sex, pneumonia, mortality, peritonitis or gastric ulcer disease, inhalation injury, ventilator use, grafting procedures, or infections. The patients in the INBD group had a statistically significant mean (+/- SD) increase in the percentage of total burn surface area compared with those in the other GI complication group (53% +/- 10% vs 22% +/- 7%; P < .02) and sepsis prior to the GI complication (32% vs 5%; P < .03). A statistically significant decrease was noted in the incidence of paralytic ileus (17% vs 69%; P < .03). Enteral nutritional support became the primary mode of treatment, and GI hemorrhage and ulcer disease decreased during this period. Patients with total burn surface area greater than 40% and sepsis were at increased risk of INBD during their hospitalization. CONCLUSIONS: The severity of thermal injury and systemic infection are risk factors for the development of INBD. This entity is more frequent currently because of increased survival of the more severely injured patients. Systemic infection may alter the integrity of the bowel, which becomes less "tolerant" of enteral feedings. The role of large-volume high-density enteral feedings as a usually associated event in these patients remains speculative.

Adolescent↗
PubMed1997

Down-regulation of tissue specific tumor necrosis factor-alpha in the liver and lung after burn injury and endotoxemia.

Burn injury and endotoxin lead to the development of a systemic inflammatory response. Because tumor necrosis factor-alpha (TNF-alpha) is a component of the proinflammatory response, we have determined the effect of burn injury and endotoxin in a murine model of thermal on tissue specific TNF-alpha levels in the liver and lung. Male mice were divided into four groups and injected with endotoxin (ETX) (2.5 mg/kg intraperitoneally) or saline (CNTL) or subjected to a 16% full-thickness scald burn (B), or ETX administration 72 hours after burn injury (B+ETX). Animals were killed at 0 to 24 hours after ETX or CNTL, 0 to 72 hours after B, and 72 to 96 hours after B+ETX (ETX administration 72 hours after B). TNF-alpha mRNA by Northern blot and protein analysis by enzyme-linked immunosorbent assay were determined and protein expressed as nanogram per gram of tissue. Statistical analysis was performed using analysis of variance with significance at p < 0.05. Burn injury did not result in detectable levels of liver or lung TNF protein or mRNA. Endotoxin administration resulted in a near six-fold rise in liver TNF protein compared with controls at 1, 2, and 6 hours after ETX (p < 0.05 to p < 0.001). Liver mRNA remained elevated from 20 minutes to 24 hours after ETX versus CNTL (p < 0.05). Endotoxin injection produced a persistent lung TNF protein elevation reaching significance at 1 and 2 hours (p < 0.001) and a rise in mRNA at 40 minutes to 6 hours (p < 0.05) versus CNTL. The liver showed a trend of reduced mRNA after B+ETX versus ETX (p = NS), whereas protein levels were reduced by 50 to 60% at 1 and 2 hours (p < 0.01). Lung mRNA values after B+ETX were only 40% compared with ETX at nearly all time points (p < 0.001) but were 15 times above CNTL values at 2 hours (p < 0.05). Based on these results, we conclude that burn injury did not cause an increase in liver or lung tissue specific TNF-alpha. However, the presence of a preexisting burn injury dramatically altered the response to endotoxin and the primary point of regulation appears to be at the posttranscriptional level.

Animals↗
PubMed1997

Molsidomine increases endotoxic survival and decreases cytokine production.

We hypothesized that nitric oxide (NO) may exert feedback regulatory control over cytokine production and improve survival in endotoxin (ETX) shock. To test this hypothesis, we evaluated the pre-endotoxin effect of the NO donor molsidomine (MOL) on circulating tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6 levels, the production of these cytokines in the perfused liver, and endotoxic lethality in mice. Male BDF mice weighing 28-32 g were administered either 100 mg/kg MOL or saline (SAL) i.p. Thirty minutes later, the mice received either 50 mg/kg Salmonella enteriditis ETX or SAL i.p. Mice were killed at 90 min after ETX or SAL, for either the determination of plasma cytokine levels by enzyme-linked immunosorbent assays or for use in the perfused liver assessment of cytokine production. MOL treatment significantly reduced the post-ETX circulating levels of TNF to 84%, IL-1 to 65%, and IL-6 to 56%, as compared with SAL-treated ETX controls. Endotoxic livers from MOL-pretreated mice produced 82% less TNF, 88% less IL-1, and 54% less IL-6 over a 2 h perfusion, as compared with SAL-treated ETX controls. MOL pretreatment also decreased lethality in ETX shock from 90 to 50% (p < .05). Therefore, NO may provide a beneficial effect during sepsis by inhibiting hepatic cytokine production, and thus providing survival benefits.

Animals↗
PubMed1997

Glucocorticoid regulation of hepatic TNF production following cecal ligation and puncture sepsis.

Tumor necrosis factor-alpha (TNF) is a critical early mediator in the genesis of a systemic inflammatory response during a septic insult. Many of the harmful effects evident during sepsis are ascribed to excessive endogenous TNF production. Because the liver is an important source of circulating TNF during endotoxicosis, and because glucocorticoids are believed to have a regulatory role in suppressing endogenous TNF production, we evaluated the effect of adrenalectomy on the hepatic production of TNF in an isolated perfused liver model after cecal ligation and puncture (CLP) sepsis. Fasted, male Holtzman rats (n = 4/group) underwent CLP alone, adrenalectomy (ADREX) alone, or CLP plus ADREX (CLP/ADREX). Two hours after the operation, the rat livers were explanted and perfused in an isolated recirculating model. Serum TNF levels were greater in CLP/ADREX rats than in both other groups. TNF production in the perfused liver was greater in the CLP/ADREX rats when compared with either CLP alone or ADREX alone. A separate mortality study was performed (N = 35) that demonstrated a CLP induced mortality of 45%, and a CLP/ADREX mortality of 100%. Thus, adrenalectomy increased circulating TNF and hepatic TNF production as well as mortality in CLP sepsis. These findings suggest an important role for endogenous glucocorticoids in modulating hepatic TNF production during CLP-induced sepsis.

Adrenalectomy↗
PubMed1997

Elevated expression of p47phox and p67phox proteins in neutrophils from burned rats.

The molecular control of neutrophil respiratory burst in burn injury was investigated through quantitation of protein factors, p47phox and p67phox, which are required for the activation of the phagocyte plasma membrane NADPH-oxidase. Circulating neutrophils were isolated from rats with 30% body surface area covered with full thickness burns. Neutrophil O2- generation, and p47phox and p67phox expressions, respectively, were determined using spectrophotometric and immunoblot techniques. Formylmethionyl-leucyl-phenylalanine stimulated superoxide anion generation was approximately 50% higher in neutrophils from rats 24 and 72 h after burns compared with that in sham control rats. The level of superoxide production was .47 +/- .05 nanomoles per minute per 10(6) cells (mean +/- SE, n = 6) at 24 h and .45 +/- .05 (n = 6) at 72 h postburn, whereas in sham control animals it was .32 +/- .02 (n = 8). Compared with the sham group p47phox levels, p47phox expression was 5.7-fold, 4.4-fold, and 4.5-fold higher, respectively, at 24, 36 and 72 h postburn. The levels of p67phox in burned animals were 2-fold higher than in the sham group, (p < .05) at 24 h postburn, and approximately 50% higher than sham at 36 h after the burn. The p67phox levels in rats 72 h after the burn were not significantly different from the sham values. These data support the occurrence of an up-regulation of p47phox and p67phox expressions accompanying the enhanced neutrophil respiratory burst activity during the early stages of burn injury. The up-regulation of p47phox and p67phox could be responsible for the priming of neutrophil O2- production leading to host tissue injury.

Animals↗
PubMed1997

The effects of different corticosteroids on the healing colon anastomosis and cecum in a rat model.

Corticosteroids are known to adversely affect wound healing in experimental skin models; however, their effect on healing colonic anastomoses is still disputed. Different steroids have not been compared to each other in the same study. We studied the effect of equipotent doses of dexamethasone, hydrocortisone, and methylprednisolone on healing colon anastomoses in a rat model. High-dose steroid therapy was started 2 days prior to the operation and continued until the bursting pressures were measured at 5 and 7 days after the surgery. Anastomotic bursting pressure was not decreased for any of the steroid treatments when compared to the control, but the frequency of anastomotic rupture in the dexamethasone group at day 5 was significantly higher than either of the other steroid groups or the control group (P < 0.01). Bursting pressures of the intact cecum were lower in all the steroid-treated groups compared with the control group. We concluded that dexamethasone slows the rate of wound healing, but short-term high-dose steroid therapy does not decrease the strength of the anastomoses as measured by bursting pressure.

Adrenal Cortex Hormones↗
PubMed1996

Augmentations of glucose uptake and glucose transporter-1 in macrophages following thermal injury and sepsis in mice.

Glucose is the primary metabolic substrate of macrophages, which are critical components of the host response to injury and infection. We have carried out a series of studies to examine macrophage glucose uptake and the status of glucose transporter 1 (GLUT1) at both the mRNA and protein level. Peritoneal macrophages that were obtained from mice undergoing sham burned (S), 15%TBSA burn (B) +/- Pseudomonas aeruginosa burn infection (B + I) and lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha) administration. [3H]deoxyglucose uptake was significantly increased (B, 157 +/- 9%; B + I, 243 +/- 19%; S + LPS, 231 +/- 24%; S + TNF-alpha, 379 +/- 18%; B + LPS, 230 +/- 13%; and B + TNF, 305 +/- 23%, P< 0.01 vs. sham). GLUT1 mRNA and protein levels were increased as well (mRNA: B, 135 +/- 13%; B + I, 250 +/- 33%; S + LPS, 282 +/- 29%; S + TNF-alpha, 193 +/- 19%; B + LPS, 378 +/- 20%; and B + TNF-alpha, 204 +/- 16%; protein: B, 159 +/- 27%; B + I, 181 +/- 17%; S + LPS, 219 +/- 26%; S + TNF-alpha, 343 +/- 51%; B + LPS, 366 +/- 41%; and B + TNF-alpha, 415 +/- 44, P< 0.01 vs. sham). Macrophages co-cultured with LPS or TNF-alpha in vitro demonstrated a similar response pattern. Following burn injury and infection, macrophages augment their cellular glucose uptake, which is facilitated by an increased GLUT1 mRNA and protein levels. TNF-alpha elicited by LPS may mediate this enhanced carbohydrate metabolism at the point of glucose entry into the cell.

Animals↗
PubMed1996

Basic fibroblast growth factor mediates angiogenic activity in early surgical wounds.

BACKGROUND: Wound angiogenesis is believed to be initiated by the early rapid release of performed growth factors such as basic fibroblast growth factor (bFGF). However, neither the angiogenic environment of early surgical wounds nor the potential contribution of bFGF to early surgical wound angiogenesis has been investigated. METHODS: We collected surgical drain fluid (SDF) from closed suction drains 6 hours to 6 days after operation. SDF was tested for endothelial cell (EC) proliferative and chemotactic activity and for the capacity to stimulate angiogenesis in vivo in the rat corneal assay. bFGF levels of SDF were determined with enzyme-linked immunosorbent assay. Neutralizing antibody to bFGF was used to determine the contribution of bFGF to SDF activity. RESULTS: The EC proliferative activity of SDF was maximal on postoperative day 0 (POD 0, 390% that of normal serum) and then fell by 41% on POD 1 and to near serum levels thereafter. SDF from PODs 0 and 1 also showed marked EC chemotactic activity and stimulated rapid formation of new vessels without signs of inflammation when implanted into rat corneas. The temporal appearance of bFGF in these exudates showed a pattern similar to EC proliferative activity, peaking on POD at 854 pg/ml and decreasing 80% by POD 2. Neutralizing antibody to bFGF decreased he proliferative activity of SDF from PODs 0 and 1 to near serum levels and substantially decreased the chemotactic and the in vivo neovascular response to SDFs. CONCLUSIONS: Surgical wounds are characterized by a rapid and early angiogenic environment that is mediated in part by bFGF, suggesting that tissue or platelet stores of bFGF may initiate wound repair.

Adult↗