Showing papers by "Shriners Hospitals for Children - Galveston published in 2000"

Gut epithelial apoptosis after severe burn: effects of gut hypoperfusion.

Abstract: Background: Severe cutaneous burn causes transient mesenteric vasoconstriction and altered gut mucosal integrity. We recently showed that burn also increases gut epithelial cell death by apoptosis. The goal of this study was to determine whether changes in gut perfusion after burn contribute to burn-associated gut apoptosis. Study Design: We first correlated superior mesenteric artery blood flow with measurement of gut perfusion at the tissue level by laser doppler in four nonburned rats before, during, and after arterial clamping to validate our measurements of gut perfusion. We then characterized gut perfusion sequentially over time after burn; gut perfusion was measured 3 cm from the ligament of Treitz before burn and hourly for 6 hours. A group of control rats underwent the exact same protocol without the burn to exclude effects of anesthesia and laparotomy on tissue perfusion (n = 4). We studied a third group of rats with hypoperfusion of the same duration and magnitude induced mechanically without burn (n = 7). Sections of the proximal gut from all three groups (control without burn, burn, and hypoperfusion without burn) were examined for epithelial apoptosis. Results: Linear regression analysis demonstrated a strong correlation between superior mesenteric artery blood flow and intestinal tissue perfusion measured by laser doppler under both low and high flow conditions (r = 0.85). Laser doppler measurements of gut perfusion after burn showed deceased gut perfusion that was maximal at 2 hours postburn (p Conclusions: We conclude that burn-induced gut hypoperfusion is insufficient to cause burn-related increased gut epithelial apoptosis. We speculate that the signal for increased gut epithelial apoptosis is primarily related to proinflammatory mediators induced by the burn wound.

Influence of glucose kinetics on plasma lactate concentration and energy expenditure in severely burned patients.

Abstract: Background: In critically ill patients, elevation in the plasma lactate concentration has traditionally been interpreted as indicating a deficiency in oxygen availability and is often an impetus to increase oxygen delivery clinically. However, another possible basis for increased lactate concentrations may be simply a mass effect from increased pyruvate availability (i.e., accelerated glycolysis). Methods: In six hypermetabolic burned patients, the rates of glucose production and oxidation were quantified using a tracer infusion of 6,6 d 2 glucose combined with indirect calorimetry. Measurements were obtained after a 9-hour fast and after a 3-hour infusion of unlabeled glucose at 30 μmol/kg/min. No patient was overtly septic, hypoxic, or hypovolemic. Results: The infusion of glucose significantly increased the arterial glucose concentration and rate of glucose oxidation, with a corresponding increase in the arterial plasma concentration of lactate and pyruvate. Resting energy expenditure and oxygen consumption were not affected by the infusion of glucose. Conclusions: These findings show that elevations in plasma lactate in severely injured patients may, in part, be related to increases in glucose flux and not entirely a reflection of any deficit in oxygen availability. Such findings highlight a potential pitfall for interpreting plasma lactate concentrations as an index of tissue oxygen availability in hypermetabolic patients.

Measurement of skin protein breakdown in a rat model.

Abstract: Whereas skin protein synthesis can be measured with different approaches, no method potentially applicable in humans is available for measurement of skin protein breakdown. To that end, we measured...

Comparative morphology of the marrow sac.

Abstract: Electron microscopic techniques have been used to profile the morphologies of marrow sacs in different laboratory species These structures all comprise a condensed layer of overlapping fibroblast-like stromal cells and apparently confine the medullary and endosteal osteoblast/lining cells to separate histiotypic compartments There were some variations in the morphology of the sac cells in the different species In rats, cats, and sheep, scanning electron microscopy (SEM) showed a seamless arrangement of marrow sac cells which resembled a thin, flat simple squamous epithelium; they displayed few intercellular cytoplasmic processes In the rabbit and pigeon, the sac comprised a more woven, multilayered fabric of broadly elongate flat fibroblast-like cells which displayed numerous intercellular processes Transmission electron microscopy (TEM) showed that all marrow sac cells were attenuated with elongated nuclei, a few small round mitochondria, and a sparse rough endoplasmic reticulum In the majority of animals, the sac was one to two cell layers thick The rabbit and pigeon sacs were multilayered, and never less than three to four cells deep The cell layers were not closely apposed Tight or gap junctions were absent at the points of intercellular contact These morphological results suggest that marrow sacs are common elements of the vertebrate skeleton with species specific morphologies

Increased Small Bowel Epithelial Turnover in Interleukin-1 Receptor Knockout Mice

Abstract: Mucosal epithelium is maintained by a balance in turnover between cell proliferation and cell death by apoptosis. Dysregulation of gut cellular turnover has been implicated in several diseases, among them the modulation of sepsis and multiorgan failure after injury, inflammatory bowel disease, and cancer. Severe cutaneous burn has been shown to cause atrophy of small bowel mucosa, 1–3 which is associated with accelerated turnover of gut epithelial cells. 4 The causes of the increased rates of cellular apoptosis and proliferation are not known. Burn injury increases expression of several cytokines, one of which is interleukin-1β (IL-1β). 5 IL-1β plays a role in both cell death and survival under appropriate conditions: 1. IL-1β pretreatment rendered glomerular mesangial cells more susceptible to apoptotic death from oxidant stress. 6 2. IL-1β induced thyrocyte apoptosis, which was blocked by the addition of Fas antibodies. 7 3. Treatment of pancreatic islet cells with a combination of IL-1β, tumor necrosis factor (TNF)-α, and interferon-γ increased cell death by apoptosis. 8 4. IL-1β type I receptor antagonist inhibited apoptosis in neurons and fibroblasts. 9 5. Pretreatment with mature IL-1β provided an antiapoptotic effect for induced apoptosis, which was attributed to downregulation of the receptor and thus the signal. 9 Others have shown that IL-1 is a growth factor for a variety of cells. 10,11 For example, IL-1 protects fibroblasts against TNF-mediated cell death by arresting cell cycling. 12 With these findings, we wondered whether IL-1β plays a role in gut mucosal cell turnover by influencing apoptotic cell death. Our hypothesis was that loss of the IL-1 signal would decrease gut epithelial cell apoptosis and improve cell survival. We chose to test this hypothesis in vivo in IL-1 receptor type I knockout mice.