Vicky L. Chappell

Effects of incremental starvation on gut mucosa.

Starvation induces gut mucosal atrophy, but the effects of progressive dietary restriction are not defined. The studys purpose was to determine the effects of incremental starvation on gut epithelial cell turnover. After food intake of mice was determined, they were divided into five groups: control (ad libitum fed), 75% normal intake, 50% intake, 25% intake, and fasted. Mice were killed after 48 hours, and the proximal small bowel were assessed for weight and protein content. Histologic specimens were examined for villus morphology, apoptosis, and proliferation. After 48 hr of diet restriction, bowel weight decreased in the 50% intake, 25% intake, and fasted groups. Villus density also decreased in the fasted group. Proliferation progressively decreased in the diet-restricted groups. Apoptosis increased in the fasted group, primarily in the villus tip. In conclusion, incremental starvation produces progressive small bowel atrophy. The mechanism involves both decreased gut epithelial cell proliferation and increased apoptosis.

Impact of discontinuing a hospital-based air ambulance service on trauma patient outcomes

BACKGROUND The clinical benefit of aeromedical transportation of injured patients in the civilian population has been debated. The purpose of this study was to examine the effects of discontinuing a hospital-based helicopter transport program on trauma patient outcomes, with the hypothesis that the loss of an air ambulance would result in increased transport time and increased mortality among severely injured patients. METHODS Data on injury severity and patient outcomes were collected prospectively for the 12 months immediately preceding and 24 months following discontinuation of the helicopter ambulance service. Transport time, mortality rate, and hospital length of stay was compared. RESULTS The number of trauma patient admissions decreased 12%, with a 17% decrease in admissions of severely injured patients. Transport time decreased, with no change in mortality. CONCLUSION Discontinuation of a hospital-based air ambulance service did not increase transport time or increase mortality for trauma patients.

Stat proteins play a role in tumor necrosis factor alpha gene expression

Trauma produces dysfunction in immunity, which appears to be partially related to alterations in the cytokine response. Signal transducer and activator of transcription proteins (STATs) mediate activation of several cytokine genes. However, the effect of STAT proteins on tumor necrosis factor-alpha (TNFalpha) activation is not fully defined. We identified binding sites for STAT 3 and STAT 5/6 within the promoter region of TNFalpha and hypothesize that alterations in these sites would affect TNFalpha expression. The TNFalpha promoter was inserted into the luciferase reporter vector, and binding sites for STAT 3, STAT 5/6, and activator protein-1 (AP-1) were mutated using site-directed mutagenesis. Murine macrophages were transfected with the resultant plasmids, then incubated with and without lipopolysaccharide (LPS) or IFNalpha. Gene expression was measured by dual luciferase assay. Mutation of the STAT 3 binding site was associated with decreased LPS-inducible activity. Mutation of the AP-1 and STAT 5/6 consensus binding sites alone had no effect on TNFalpha expression. However, combined mutation of both STAT 5/6 and AP-1 was associated with increased LPS-inducible activity. Mutations of the STAT binding sites in the promoter region of TNFalpha affect TNFalpha gene expression. These results suggest a regulatory role for STATs in TNF gene transcription.

Effect of bombesin on gut mucosal impairment after severe burn.

Severe cutaneous burn alters gut epithelial homeostasis. In previous studies, treatment with bombesin decreased mucosal atrophy and improved maintenance of gut mucosal integrity after severe burn. Our current hypothesis is that bombesin reduces burn-induced gut impairment by decreasing gut epithelial cell death. Fifty-four adult male Fisher-344 rats were randomly assigned to three groups: control, sham burn (I), burn (II), and burn + bombesin (III). Animals in groups II and III received a 60% total body surface area full thickness scald burn, and the treatment group (III) received bombesin subcutaneously (10 &mgr;g/kg, every 8 h) beginning immediately before the experiment. The proximal small bowel was harvested at 12 and 72 h after burn with measurement of wet and dry weight, mucosal weight, and protein content, and a 1-cm length of proximal end was excised and fixed in formalin for histological and immunohistochemical observation. Data are expressed as means ± SEM. Statistical analysis was by done by analysis of variance (significance at P < 0.05). Bombesin treatment attenuated mucosal atrophy demonstrated by restoration of the mucosal weight, mucosal protein content, and maintenance of mucosal height and total mucosal epithelial cell count. Gut epithelial cell apoptosis was, at least in part, inhibited by bombesin compared with a significant increase of gut cell apoptosis at 12 h after burn. Gut epithelial proliferation was not affected. Bombesin diminished burn-induced gut mucosal atrophy and gut epithelial cell apoptosis, suggesting that bombesin treatment may play an important role in the recovery of gut impairment after severe burn.

The role of tumor necrosis factor-α in gut mucosal changes after severe burn

Introduction: Gut mucosal homeostasis is maintained by a balance between epithelial cell proliferation and cell death. We previously showed increased gut epithelial cell death by apoptosis after severe burn which was associated with mucosal atrophy. Several membrane bound ligand-receptor interactions, such as tumor necrosis factoralpha (TNFa)/TNFa-receptor (TNFR), can initiate cell death. We hypothesized that TNFa/TNFR interactions play a role in gut epithelial homeostasis after severe burn. Methods: Anesthetized male C57BL6 mice were randomly assigned to sham control, 30% TBSA scald burn, and 30% TBSA scald burn with neutralizing anti-TNFa antibody (200 mg i.p.). Burn groups were resuscitated with 2 cc subcutaneous normal saline. After sham burn or burn, all groups were fasted and given water ad lib. The proximal small bowel was collected 12 hrs after injury and assessed for histologic measures of atrophy and cell number changes by a blinded observer. Statistical analysis of data was performed by one way analysis of variance with Tukey’s test. Results: Gut mucosal height significantly decreased after burn which was restored with anti-TNFa treatment. When villus and crypt were analyzed separately, only villus height was decreased by burn, which was again abrogated by anti-TNF-a. Crypt depth was not affected. Cell number in the villus and crypt followed a similar pattern.