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Biomedical subjects

R L Gamelli

Publications and source records attributed to R L Gamelli.

At least 19 recordsLinked to original sources
PubMed2001

The impact of antithrombin (H) concentrate infusions on pulmonary function in the acute phase of thermal injury.

BACKGROUND: Pulmonary complications occur frequently after thermal injury. OBJECTIVE: This open pilot study was performed as an initial assessment of the safety and efficacy of antithrombin H [AT(H)] concentrate in ameliorating the respiratory morbidity during the acute phase of injury. MATERIALS & METHODS: Thirty-two patients were eligible for the study; of these, nine opted for treatment with q8 h [AT(H)]. The mean daily peak values of pulmonary parameters such as PaO(2)/FiO(2) ratio, and RAW scores were computed for days 1-8. RESULTS: Control and AT(H)-treated patients were similar in age, % total burn surface area, inhalation injury, and mortality. Forty-three percent of the burn controls, and 23% of the AT(H)-treated patients had pneumonia, p<0.01. The median hospital stay for both groups was 42 days; however, the median number of ventilatory days for burn controls was 23 days vs 10 days for AT(H)-treated patients. The AT(H)-treated patients had admission AT plasma levels of 46+/-14% vs 49+/-18% in burn controls, (normal=100+/-20%). The AT plasma level was maintained at 120+/-24% in the AT(H)-treated patients vs 50+/-15% in the burn control group for the first four days following the acute injury, p<0.002. Thrombate(R) concentrate infusions were, in general, well tolerated by patients. The median dose was 97 u/kg/dose q8 h. Compared to burn controls, AT(H)-treated patients had higher PaO(2)/FiO(2) ratios between days 4-6, p<0.01. In comparing these two groups with and without inhalation, airway resistance (assessed by the RAW score) was significantly lower in the AT(H)-treated group with inhalation compared to the burn controls with inhalation on days 2 and 6, p<0.02. CONCLUSIONS: With a trend toward decreased airway resistance during AT(H) concentrate infusions, and increased oxygenation, AT(H)-treated patients had significantly fewer episodes of pneumonia compared to controls. AT(H) concentrates may modify the impact of thrombin on acute inflammation, and improve respiratory function in the acute phase of thermal injury.

Adult↗
PubMed2001

Myeloid commitment shifts toward monocytopoiesis after thermal injury and sepsis.

OBJECTIVE: To demonstrate enhanced bone marrow monocytopoiesis in response to thermal injury and sepsis and to provide a mechanism for this observation. SUMMARY BACKGROUND DATA: Although monocyte activation and the resultant dysregulated cytokine production are now the accepted hallmarks of systemic inflammatory response syndrome, no information is available on the status of bone marrow monocyte production under injury conditions; neither has the balance between the two arms of myelopoiesis (monocytopoiesis and granulocytopoiesis) been delineated. METHODS: Peripheral blood absolute neutrophil and monocyte counts were determined 72 hours after the initial injury in sham, burn, and burn sepsis mice. Colony-forming potential in response to colony-stimulating factors (granulocyte, macrophage, and granulocyte/macrophage) was determined in both total nucleated and monocyte progenitor enriched bone marrow cells. Dual color flow cytometry was used to document the distribution pattern of monocyte progenitors. Macrophage colony-stimulating factor receptor density in monocyte progenitors was assessed by 125I macrophage colony-stimulating factor binding assay. RESULTS: Burn sepsis induced circulating monocytosis and granulocytopenia. Colony-forming assays demonstrated an increase in the growth potential of monocyte progenitors and a significant decrease in granulocyte progenitors after burn and burn sepsis. Flow cytometric analysis of early (ER-MP12) and late (ER-MP20) monocyte progenitors showed an increase in monocyte lineage growth in burn sepsis. Radioligand binding assay demonstrated an increase in macrophage colony-stimulating factor receptor expression in monocyte progenitors in burn sepsis. CONCLUSIONS: The data validate the premise that enhanced monocytopoiesis in thermal injury and sepsis results from an imbalance in myelopoiesis that is driven by the increased expression of macrophage colony-stimulating factor receptor.

Analysis of Variance↗
PubMed2001

Norepinephrine modulates myelopoiesis after experimental thermal injury with sepsis.

OBJECTIVE: To determine whether thermal injury and sepsis cause an increase in bone marrow norepinephrine release and whether such a release influences bone marrow monocytopoiesis. SUMMARY BACKGROUND DATA: The authors previously demonstrated enhanced bone marrow monocytopoiesis after burn with sepsis. They also showed that physiologic stress and bacterial challenge without injury could lead to a dynamic release of norepinephrine from the bone marrow compartment. In this study, they sought to determine the potential cause-and-effect relationship of bone marrow norepinephrine release on increased monocytopoiesis after burn sepsis. METHODS: Norepinephrine release from bone marrow was determined by traditional pulse-chase methods. Tissue and bone marrow norepinephrine content was ablated by chemical sympathectomy with 6-hydroxydopamine treatment. Clonogenic potential in response to colony-stimulating factors was determined in total nucleated bone marrow cells. Dual color flow cytometry was used to document the distribution pattern of monocyte progenitors. RESULTS: Burn sepsis induced increased norepinephrine release in bone marrow, spleen, and heart. Colony-forming assays demonstrated an increase in responsive colonies, which was significantly attenuated when norepinephrine content was reduced in animals before burn sepsis. Flow cytometric analysis of early and late monocyte progenitors showed a significantly altered distribution profile of monocyte progenitors in norepinephrine-depleted mice compared with norepinephrine-intact mice. Abrogation of bone marrow norepinephrine content resulted in a 62% survival rate in burn septic mice compared with no survivors in norepinephrine-intact mice. CONCLUSIONS: These data suggest that enhanced bone marrow norepinephrine release after burn sepsis may play a role in bone marrow monocytopoiesis, thus contributing to the sustenance of inflammation.

Animals↗
PubMed2000

Outcome for older burn patients.

BACKGROUND: Physicians will be increasingly responsible for an aging society whose members demonstrate a notable striving for independence. HYPOTHESIS: With standard treatment of burns, older patients will have a survival rate of more than 70%, with at least 60% of patients becoming fully functional 6 months after hospital discharge. METHODS: A 7-year retrospective medical review of burn unit patients was performed, and 221 ( 11%) of 1957 patients who were at least 59 years old were identified. RESULTS: Of 97 women (44%) and 124 men (56%), 64 (29%) had an associated smoke inhalation injury; 146 (66%), flame injury; and 44 (20%), scald injury. The bedroom and/or living room were the most common areas of injury (90 [41%]), followed by outdoors and the workplace (62 [28%]), the kitchen (40 [18%]), the bathroom ( 18 [8%]), and the garage or basement (11 [5%]) (P<.005). One hundred twenty-six injuries (57%) were associated with impaired judgment, mobility, or both. On hospital admission, 74 patients (36%) were intubated, 60 (30%) required intubation postoperatively, and 34 (18%) required both. The survival rate was 159 patients (72%) overall. Findings from an ethanol screening and a drug toxicology screening were positive in 22 and 32 patients (10% and 29%) on admission, respectively. Of the survivors, most were discharged to home with (87 [64%) or without visiting nurse supervision, and at 6 months after discharge, 16 patients (50%) in transitional care facilities were able to return to an independent level of functioning. Of the 59- to 69-year-old age group, 83 (86%) survived compared with 59 (69%) in the 70- to 79-year-old age group and 18 (47%) in the 80 years and older age group. CONCLUSIONS: In contrast to the usual male preponderance in patients with thermal injury, older women, many of whom are widowed, constituted almost half of the older patients admitted to the hospital. Modalities for injury prevention are necessary to provide optimal and safe household environments for a growing population of older persons.

Age Factors↗
PubMed2000

Antithrombin III concentrate in the acute phase of thermal injury.

BACKGROUND: Thermal injury disrupts homeostasis by inducing subclinical disseminated intravascular coagulation, fibrinolysis. and an acquired deficiency of Antithrombin III (ATIII), a natural anticoagulant. As a result, thermally injured patients have a high incidence of hypercoagulability and thrombosis. OBJECTIVE: ATIII (Human) concentrate was given to a thermally injured patient to evaluate safety, and dosage requirements in this setting. DESIGN: The patient was a 40 yr old male with a 68% total burn surface area, right femoral comminuted fracture, and C5-C6 subluxation sustained in a vehicular crash. He received nine infusions of AT III (H) concentrate (100-50 u/kg) within the first four days of injury. RESULT: The ATIII plasma level increased from 45% on admission (normal = 100+/-20%) to 120+/-25% in the next four days. During the 64 day hospitalization, there were 11 grafting procedures with an estimated blood loss (EBL)/procedure: 1140 cc; and EBL/grafted surface area ratio: 0.6 cc cm2. The average time to healing of the meshed autograft was 6.4 days. CONCLUSION: ATIII (H) concentrate can be safely utilized in the acute phase of thermal injury: no excessive bleeding or prolongation of wound healing was documented.

Acute Disease↗
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↗
PubMed2000

Chlorpromazine modulates cytokine expression in the liver and lung after burn injury and endotoxemia.

BACKGROUND: Previous data from our laboratory have demonstrated that alterations in cytokine production occur in the lung and liver as the result of a two-hit model of injury, i.e., burn with subsequent endotoxin administration. The purpose of this study was to determine whether the phenothiazine derivative chlorpromazine would alter cytokine production in a sequential model of injury. METHODS: By using a sublethal burn/endotoxemia model, B2D6F1 mice (n = 40) were assigned to two groups and subjected to a 15% full-thickness burn. Three days after burn injury, one group (BURN/ETX) received 2.5 mg/kg Escherichia coli endotoxin intraperitoneally, and the other group (CPZ) received 4 mg/kg chlorpromazine 1 hour before the administration of 2.5 mg/kg E. coli endotoxin intraperitoneally. At selected time points, the animals were killed and lung and liver were removed and processed for protein and total RNA. Northern blots and enzyme-linked immunosorbent assays were used to assess the production of tumor necrosis factor-alpha, macrophage inflammatory protein-1alpha, and interleukin-10. RESULTS: Chlorpromazine significantly reduced tumor necrosis factor-alpha mRNA and protein expression in the liver. Macrophage inflammatory protein-1alpha mRNA was reduced by chlorpromazine in both liver and lung. Interleukin-10 production was not altered by chlorpromazine. CONCLUSION: The reduction of tumor necrosis factor-alpha and macrophage inflammatory protein-1alpha by chlorpromazine in the liver and lungs may have potential as a pharmaceutical agent that may dampen the inflammatory response in a model of sequential injury.

Animals↗
PubMed2000

Prostaglandin E2 receptor antagonist (SC-19220) treatment restores the balance to bone marrow myelopoiesis after burn sepsis.

BACKGROUND: Although prostaglandin E2 (PGE2) has been shown to be immunosuppressive, its role in the development of specific bone marrow myeloid lineages after thermal injury and sepsis has yet to be elucidated. The purpose of this study was to demonstrate that alterations in bone marrow progenitor proliferation favoring monocytopoiesis in burn sepsis can be restored by blocking the cellular interactions of PGE2. METHODS: A murine model of burn sepsis with and without treatment with SC-19220, a PGE2 receptor antagonist, was used to determine peripheral monocyte and neutrophil counts as well as the colony forming potential of colony-stimulating factor responsive bone marrow progenitors. RESULTS: Burn sepsis augmented the growth of the early colony-forming unit granulocyte-macrophage and monocyte progenitors and the number of circulating monocytes, whereas granulocyte progenitors and circulating neutrophils demonstrated an opposite response. Treatment with SC-19220 nearly reversed these alterations. CONCLUSION: These data indicate that abrogating PGE2's actions during burn sepsis can restore the balance in bone marrow granulocyte and monocyte production, further consolidating the pivotal role PGE2 plays in the pathogenesis of burn sepsis.

Animals↗
PubMed2000

Expression of the lactate transporter MCT1 in macrophages.

This study evaluated macrophage expression of the stereospecific lactate transporter, MCT1, and the effects of lipopolysaccharide (LPS), tumor necrosis factor (TNFa), or nitric oxide (NO) on MCT1 mRNA and protein levels and lactate transporter activity. Peritoneal and J774.1 macrophages were treated with either saline, LPS (10 or 100 ng/mL), dexamethasone (100 nM), and dexamethasone + LPS. Cells were harvested at 4, 8, and 16 h after treatment and processed for total RNA and protein isolation. LPS treatment significantly increased macrophage MCT1 mRNA expression at 4 and 8 h compared with the saline-treated cells. Dexamethasone did not alter MCT1 mRNA levels. Treatment of J774.1 macrophages with TNFalpha (1 ng/mL) or nitric oxide (DETA-NO, 100 microM) also significantly increased MCT1 mRNA levels at 4 and 8 h after treatment. LPS and TNFalpha treatment significantly increased MCT1 protein levels at 8 and 16 h after treatment. Lactate transporter activity in J774.1 macrophages was measured by uptake of 14C-labeled lactate. LPS and TNFalpha treatment significantly augmented lactate uptake, 12 h after administration; however, nitric oxide treatment did not affect lactate uptake. Thus, our data demonstrated that stimulated peritoneal and J774.1 macrophages express the lactate transporter, MCT, and that LPS and TNFalpha regulate MCT1 mRNA and protein levels.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

Role of neutrophils in burn-induced microvascular injury in the intestine.

The present study evaluated burn-induced vascular permeability alterations of rat small intestine in vivo and assessed the effect of neutrophil depletion in burn-injured rats on the altered intestinal microvascular permeability. 125I-labeled bovine serum albumin (125I-BSA) was injected intravenously, and its leakage from circulation into the intestinal tissue was determined by measuring tissue counts of 125I-BSA. Compared with sham, vascular albumin permeability increased 1.7-fold on day 1 post-burn and 3.0-fold on day 3 post-burn in ileum. In the jejunum, albumin permeability increased 1.8- and 2.5-fold on day 1 and day 3 post-burn, respectively. Intestinal tissue edema, determined as increases in tissue water contents, was noted in both intestinal segments on day 1 post-burn; no further increase in edema was found on day 3 post-burn. Neutrophil depletion before burn injury prevented the vascular leakage of albumin and edema in the ileum and jejunum on day 1 post-burn. On day 3 post-burn, the effect of prior neutrophil depletion on vascular permeability was less marked, and edema formation was not affected at all. These findings indicate that an absence of neutrophils prevents the loss of intestinal vascular barrier properties only in the initial periods after burns.

Animals↗
PubMed2000

Neutrophil depletion prevents intestinal mucosal permeability alterations in burn-injured rats.

Cutaneous thermal injury increases intestinal mucosal permeability. The mechanisms of this functional disturbance are not fully understood. We investigated whether accumulation of neutrophils in the intestine contributes to the increase in mucosal permeability. Labeled and unlabeled lactulose and mannitol were infused into a segment of rat ileum or jejunum. Blood concentrations of [(3)H]lactulose and [(14)C]mannitol were measured after 30, 60, and 90 min. On day 1 postburn, lactulose permeability increased fourfold in the ileum and twofold in the jejunum compared with sham-burned rats; mannitol permeability increased twofold in the ileum and 1. 5-fold in the jejunum. A greater increase in permeability occurred on day 3 postburn in the ileum, but not in the jejunum. The depletion of neutrophils in burned rats prevented the increase in permeability in both segments on day 1 postburn. Histological studies of intestines from burned, with or without neutrophil depletion, and sham-burned rats showed similar morphology. However, numerous neutrophils were found in the extravascular compartment in day 1 postburn, but not in neutrophil-depleted and sham-burned rats. These findings support the concept that the burn-induced increase in mucosal permeability is produced during the accumulation of neutrophils in the intestine and can be abrogated by the depletion of neutrophils.

Animals↗
PubMed2000

How well do third-year medical students learn key objectives in a case-based surgical lecture series?

Faculty members were asked to list major and minor concepts of their case-based session presented during the 12-week 3rd-year surgical clerkship. After each session, students were queried to list the key concepts presented. Data were collected from two groups: one at the end of an academic year and a second at the beginning of the next academic year. Faculty members listed a median of 10 major and 15 minor concepts. The mean number of matched major concepts ranged from 0.2 to 4, and from 0.2 to 3.4 for minor concepts. In a comparative analysis, the end-of-the-year students listed a higher number of matched concepts for 17 of the 20 sessions than the beginning of the year students (8 sessions reached statistical significance, P < 0.05). The current case-based teaching method is not effective in emphasizing key concepts to students. Reformatting cases to better align with key concepts may be one solution to enhance a student's ability to grasp key concepts. Students at the end of the academic year outperformed those at the beginning of the year. This additional variable needs to be considered by faculty and incorporated into their teaching techniques.

Clinical Clerkship↗
PubMed1999

Heparin and heparan sulphate protect basic fibroblast growth factor from non-enzymic glycosylation.

Non-enzymic glycosylation of basic fibroblast growth factor (bFGF, FGF-2) has recently been demonstrated to decrease the mitogenic activity of intracellular bFGF. Loss of this bioactivity has been implicated in impaired wound healing and microangiopathies of diabetes mellitus. In addition to intracellular localization, bFGF is also widely distributed in the extracellular matrix, primarily bound to heparan sulphate proteoglycans (HSPGs). Nonetheless, it is not clear if non-enzymic glycosylation similarly inactivates matrix-bound bFGF. To investigate this, we measured the effect of non-enzymic glycosylation on bFGF bound to heparin, heparan sulphate and related compounds. Incubation of bFGF with the glycosylating agents glyceraldehyde 3-phosphate (G3P; 25 mM) or fructose (250 mM) resulted in loss of 90% and 40% of the mitogenic activity of bFGF respectively. Treatment with G3P and fructose also decreased the binding of bFGF to a heparin column. If heparin was added to bFGF prior to non-enzymic glycosylation, the mitogenic activity and heparin affinity of bFGF were nearly completely preserved. A similar protective effect was demonstrated by heparan sulphate, low-molecular-mass heparin and the polysaccharide dextran sulphate, but not by chondroitin sulphate. Whereas non-enzymic glycosylation of bFGF with G3P impaired its ability to stimulate c-myc mRNA expression in fibroblasts, no such impairment was noticeable when bFGF was glycosylated in the presence of heparin. Taken together, these results suggest that HSPG-bound bFGF is resistant to non-enzymic glycosylation-induced loss of activity. Therefore, alteration of this pool probably does not contribute to impaired wound healing seen in diabetes mellitus.

Animals↗
PubMed1999

Effect of topical local anesthetic application to skin harvest sites for pain management in burn patients undergoing skin-grafting procedures.

OBJECTIVE: To determine if topical administration of local anesthesia, applied to fresh skin-harvest sites, reduces pain and analgesic requirements after surgery. SUMMARY BACKGROUND DATA: Nonopioid treatments for pain after therapeutic procedures on patients with burns have become popular because of the side effects associated with narcotics. The topical administration of local anesthesia originally offered little advantage because of poor epidermal penetration. METHODS: This study compares 2% lidocaine with 0.5% bupivacaine or saline, topically applied after skin harvest, to determine what effect this may have on pain and narcotic use. Sixty patients with partial- or full-thickness burns to approximately 10% to 15% of their body were randomly divided into three groups: group 1 received normal saline, group 2 had 0.5% bupivacaine, and group 3 had 2% lidocaine sprayed onto areas immediately after skin harvest. Blood samples were subsequently obtained to measure concentrations of the local anesthetic. Hemodynamic variables after surgery, wake-up times, emetic symptoms, pain, and narcotic use were compared. RESULTS: Higher heart rates were noted in the placebo group than in those receiving lidocaine or bupivacaine. No differences were noted in recovery from anesthesia or emetic symptoms. Pain scores were lower and 24-hour narcotic use was less in patients who received lidocaine. Plasma lidocaine levels were greater than bupivacaine at all time points measured. CONCLUSIONS: Topical lidocaine applied to skin-harvest sites produced an analgesic effect that reduced narcotic requirements compared with patients who received bupivacaine or placebo. Local anesthetic solutions aerosolized onto skin-harvest sites did not affect healing or produce toxic blood concentrations.

Adolescent↗
PubMed1999

Multicenter trial to evaluate the safety and potential efficacy of pooled human fibrin sealant for the treatment of burn wounds.

OBJECTIVE: The primary purpose of this multicenter study was to evaluate the safety and potential efficacy of a solvent/detergent-treated commercial fibrin sealant (human) for topical hemostasis in skin grafting. METHODS: The study involved a prospective evaluation of changes in viral titers in patients with burns less than 15% after treatment with fibrin sealant (human). Each patient served as his/her own control for an unblinded, randomized comparison of donor site hemostasis and healing. Preoperative serum was obtained to screen for viral titers. At autografting, the recipient site and one of two randomly chosen donor sites were treated with fibrin sealant (human). The use of other hemostatic agents, including epinephrine was prohibited. Each donor site was covered with gauze to collect blood for estimation of the relative amount of bleeding. The healing of the graft and donor sites was observed. Viral titers and wounds were checked monthly for 6 months, and at 9 and 12 months postoperatively. RESULTS: Viral titers for human immunodeficiency virus; hepatitis A, B, and C; Epstein-Barr virus; and cytomegalovirus were obtained before and after treatment. Of 47 patients, 34 completed the full year of observation. After treatment, there were no seroconversions to any of the aforementioned viruses. Bleeding at the recipient site appeared well controlled with fibrin sealant (human). Although investigators felt that fibrin sealant (human) improved donor site hemostasis, differences in hemoglobin measurements of blood-soaked dressings failed to reach significance. No differences were noted with regard to acceleration of donor site healing, graft take, or scar maturation at the two groups of donor sites. Anecdotally, the maturation of the recipient site appeared to be accelerated. CONCLUSION: Fibrin sealant (human) is safe for use during excision and grafting, and its topical hemostatic potential needs to be examined in patients with larger burns. Its role in scar maturation also needs to be investigated.

Adolescent↗
PubMed1999

Burn injury with infection alters prostaglandin E2 synthesis and metabolism.

OBJECTIVE: The aim of this study was to examine the relationship between prostaglandin synthesis and prostaglandin degradation in a model of burn injury with infection. METHODS: Male B2D6F1 mice were assigned to control, burn (16% dorsal scald burn), or burn with infection (burn with topical application of 1,000 colony forming units of Pseudomonas aeruginosa) groups. Lung tissue was harvested at 1, 2, and 3 days after burn injury and subsequently processed for total RNA and protein. Northern and Western blot analyses were used to examine differences in cyclooxygenase 2 (COX-2) and prostaglandin 15-OH dehydrogenase (PGDH) protein and mRNA expression. Total RNA was probed with the riboprobe for murine PGDH and COX-2 and the 100,000g protein fraction was immunoblotted by using an rabbit anti-murine PGDH and anti-murine COX-2 antibody. RESULTS: COX-2 expression was elevated in the burn with infection animals on day 1 and day 2 after burn injury. At these time points in the burn + infection group, PGDH was significantly depressed. Burn injury increased COX-2 expression on day 1, but by day 2, COX-2 expression had decreased to control values. A corresponding increase in PGDH expression was observed on day 2 in the burned mice. The mRNA expression of COX-2 was followed by a similar increase in COX-2 protein expression at all time points in the injured animals. This was not the case with PGDH expression. On day 1, PGDH mRNA expression was depressed in the burn with infection mice with no change in PGDH protein expression. This finding indicates that PGDH is subject to regulation at both the transcriptional and posttranscriptional levels. CONCLUSION: Burn wound infection depressed both PGDH mRNA and protein expression and increased COX-2 mRNA and protein expression. Therefore, increases in circulating prostaglandin E2 levels during septic injury are derived from alterations in synthesis and degradation of prostaglandin E2.

Animals↗
PubMed1999

Enhanced expression of neutrophil NADPH oxidase components in intestine of rats after burn injury.

We have evaluated the accumulation of neutrophils in the gut and their infiltration into the intestinal extravascular spaces in rats subjected to a 25% total body surface area scald burn. The accumulation of neutrophils was assessed via measurements of myeloperoxidase (MPO) activity in the intestinal homogenates, and the immunohistochemical localization of neutrophil NADPH oxidase component proteins (p47phox and p67phox) within the intestinal extravascular spaces determined neutrophil tissue infiltration. MPO measurements demonstrated a 12- and 21-fold increase above the control value in the intestinal tissue at day 1 and day 3 post-burn, respectively, suggesting that a substantial total tissue accumulation of neutrophils occurs in the gut after burn injury. The immunohistochemical staining procedures showed both a definitive presence of the neutrophil in the intestinal extravascular spaces and an enhanced immunoreactivity in neutrophils accumulating in intestine after burn injury. There was no evidence of either the presence of neutrophils in the extravascular regions or any significant neutrophil immunoreactivity to NADPH oxidase component proteins in the intestines of sham control rats. These findings indicate that burn injury causes an enhanced migration of circulating neutrophils into the intestinal interstitial spaces and an upregulation of NADPH oxidase activity in the infiltrating neutrophils.

Animals↗