It is well established that hepatotoxicity is associated with an overdose of acetaminophen and that this hepatotoxicity can be increased by prior alcohol exposure in either humans or animal models. N-Acetylcysteine (NAC) has been developed as a tool to prevent the hepatotoxicity associated with acetaminophen overdosing. The present investigation observed that prior acute and chronic ingestion of alcohol to mice resulted in enhanced toxicity following acetaminophen injection. This increased toxicity was prevented by treatment with NAC. These results suggest that NAC may be a useful tool for combatting the enhanced acetaminophen toxicity associated with alcohol ingestion.

Acetaminophen↗

PubMedDate not supplied

Effect of ethanol administration on plasma glycerol levels in the rat.

Many mechanisms have been postulated as being responsible for the fatty liver resulting from ethanol ingestion. Lipid mobilization has been strongly implicated in both acute and chronic ethanol administration--the difference between the two lying in the source of the fat. In the acute situation, the lipid is mobilized from depot fat, whereas in the chronic situation, it apparently comes from the diet. One possibility not explored is the mobilization of glycerol. This substance is the backbone of triglyceride. Hence, an influx of glycerol to the liver coupled with increased amounts of fatty acids could help explain, in part, the fatty liver resulting from alcohol administration. The purpose of the following study was to determine if such an effect does occur.

Animals↗

PubMedDate not supplied

Thermal injury and gastrointestinal function. I. Small intestinal nutrient absorption and DNA synthesis.

The effect of acute burn trauma, produced by scalding hot water, on rat small intestinal nutrient absorption and DNA synthesis has been examined. Burned rats showed decreased small-intestine mucosal weight and altered small-intestine transport of nutrients (calcium, glucose, or amino acid) in vitro. In addition, there was decreased 3H-thymidine incorporation into intestinal DNA in vivo and decreased intestinal thymidine kinase activity in vitro 18 hours after acute burn. These data suggest that after the severe stress produced by acute burn trauma, there is altered small-intestine nutrient absorption and DNA synthesis. These alterations may affect delivery of nutrients by the gut to the burn patient.

Animals↗

PubMedDate not supplied

Thermal injury and gastrointestinal function. II. Evidence for the production of hepatic dysfunction in the rat following acute burn injury.

Following acute thermal injury to rats produced by scalding water, there was marked elevation of a number of plasma enzyme activities, including GOT, GPT, and 5'-nucleotidase, suggesting hepatic dysfunction. Changes in plasma enzyme activities were observed within minutes following application of acute burn trauma, and remained elevated for at least one month. The magnitude of the elevations of the plasma enzyme activities was dependent upon the length of time the acute burn trauma was applied to the skin and/or the percentage of skin surface area burned. These changes in plasma enzyme activity correlated with histologic examination of the hepatic tissue, indicating single cell necrosis. These data suggest that acute burn trauma to rats is associated with altered hepatic function.

5'-Nucleotidase↗

PubMedDate not supplied

Hepatic and intestinal blood flow following thermal injury.

Because cardiac output decreases after burn injuries, investigators have assumed, based upon dye clearance techniques, that hepatic and intestinal blood flow are also decreased following these injuries. Blood flow to the liver, stomach, small intestine, and kidney was determined by the uptake of 201thallium and 125I-labeled fatty acid (para-125I-phenyl-3-methyl pentanoic acid) in a 20% body surface area scald injury that also included plasma volume replacement resuscitation. Uptake of these radioisotopes was determined 15 minutes, 18 hours, and 72 hours after injury. The uptake of the 201thallium and 125I-labeled fatty acid by the gastrointestinal tissues was not statistically different at any of the time periods after comparison of the injured and control (sham-treated) animals. 201Thallium uptake by the kidney was significantly diminished 15 minutes after the burn injury (P less than 0.01). Based on these blood flow measurement techniques, the data suggest that the 20% body surface area scald injury did not alter blood flow to the liver or gastrointestinal tract within the initial 72 hours after the burn injury even though a decrease in renal blood flow was easily detected. These results suggest that the dysfunction of the gastrointestinal system or hepatic system observed after an acute burn injury is not simply the result of hypovolemic shock, which reduces both renal and mesenteric blood flow. These gastrointestinal and hepatic alterations may be related to a factor or factors other than intestinal ischemia.

Animals↗

PubMedDate not supplied

Effect of acute burn trauma on phagocytic activity of the reticuloendothelial system in rats.

The effect of acute burn trauma on phagocytic activity of the reticuloendothelial system measured in vivo with technetium 99m sulfur colloid was examined in rats subjected to acute burn trauma. After the scald injuries (10-second, full-thickness burns) were induced, a reduction in phagocytic activity by the spleen took place with an accompanying increase in the uptake of colloid material by the lungs. Uptake of colloid material by the liver was essentially unchanged. These uptake changes, observed within hours after the inducement of acute burn trauma and apparently continuing for 7 days after burn injury, may explain, in part, the development of septicemia in patients with burns because altered phagocytic activity of the reticuloendothelial system can result in subsequent overabundance of microorganisms and bacteria in the blood.

Animals↗

PubMedDate not supplied

Effect of irreversible dermal necrosis on phagocytic activity of reticuloendothelial system.

A model of full-thickness dermal necrosis was produced in rats by the application of liquid nitrogen to a 20% total body surface area of the dorsal skin surface. In this model there was an alteration of reticuloendothelial system phagocytic activity of the lung and spleen as measured by the uptake of technetium 99m-labeled sulfur colloid in vivo. The present results suggest that marked alterations in reticuloendothelial system phagocytic activity can be produced by full-thickness dermal necrosis in the absence of heat.

Animals↗

PubMedDate not supplied

Core body temperature responses immediately after cutaneous thermal injury in rats.

Internal temperatures were continuously measured in rats that received 20% or 40% body surface area cutaneous scald injuries in 25 degrees C and 38.5 degrees C environments. In animals that received thermal injuries in the 25 degrees C environment, intraperitoneal, intraesophageal, and intrarectal temperatures rapidly rose to 40 degrees C within 5 minutes but returned to normal values within 15 minutes after injury. When 20% body surface area injuries were induced in a 25 degrees C environment, all of the animals survived. In the 25 degrees C environment, neither acute core body temperature elevations nor use of fluid resuscitation predicted survival. In contrast, in a 38.5 degrees C environment core body temperatures rapidly exceeded 41 degrees C with the 20% injury, and all of the animals died within minutes in spite of fluid resuscitation. These studies suggest that the ambient environmental temperature may significantly influence a thermally injured animal's ability to rapidly eliminate absorbed heat of injury and result in an elevated core body temperature, which may contribute to the immediate lethality of the injury.

Animals↗

PubMedDate not supplied

Injury-induced inhibition of fat absorption.

Burn injury inhibits lipoprotein lipase, which leads to an impeded clearance of triglycerides from the plasma and an increase in serum triglycerides. Intestinal brush border lipase, which hydrolyzes triglyceride to free fatty acids and is essential for absorption of triglycerides from the gastrointestinal tract, could also be inhibited by burn injury. In thermally injured rats, the absorption and oxidation of enterally administered 14C-palmitate triglyceride, brush border lipase activity, and small-intestinal and colonic content of fat were determined. Absorption of 14C-palmitate triglyceride and production of 14CO2 were reduced 50% 18 hours after injury (p < 0.01). In addition, brush border lipase activity was reduced 50% (p < 0.01). Because brush border lipase function is essential to the proper absorption of enterally administered fat, inhibition of intestinal lipase could be an important factor in enteral diet effectiveness.

Animals↗

PubMedDate not supplied

Arterial blood pressure immediately after thermal injury: the role of anesthesia.

Mean arterial blood pressure was measured in anesthetized rats. The duration that the rats were under anesthesia with ether or methohexital was brief, and the animals were allowed to awaken early after injury. Three hemodynamic measurements were compared: (1) lowest mean arterial blood pressure, (2) duration at lowest mean arterial blood pressure, and (3) time to recover initial mean arterial blood pressure. In these studies the anesthetic agents reduced mean arterial blood pressure by 36%, recovering to normal pressures within 24 to 39 minutes. During the hemodynamic observation period, no significant additional hemodynamic effects as a result of the thermal injury were seen. Administration of resuscitation fluid did not significantly affect hemodynamics during the observation period in this study. These studies demonstrate that anesthesia dominates the short-term cardiovascular effects of thermal injury, and therefore caution is required in the interpretation of acute cardiovascular effects immediately after thermal injuries with patients under general anesthesia.

Anesthesia, General↗

PubMedDate not supplied

Thermal trauma and gastrointestinal function: III. Effect of hot- and cold-burn trauma on small intestinal weight and mucosal mass of mice.

The effect of hot- and cold-burn trauma on small intestinal mass in mice has been examined. Hot-burn but not cold-burn caused a significant reduction in the intestinal mass 24 hours after application of the trauma. These data may suggest that the alterations produced in the small intestine associated with hot-burn injury, are related, in part, to factors released from the skin.

Animals↗

PubMedDate not supplied

Ethanol metabolism: oxidative and peroxidative mechanisms.

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Adenosine Diphosphate↗