Biomedical subjects

E A Carter

Publications and source records attributed to E A Carter.

At least 55 records · Page 3Linked to original sources

PubMed1991

Effect of haemolysis on reticuloendothelial system (RES) phagocytic activity in rats.

The role of haemolysis of blood in the alterations in the uptake of [99mTc]SC ([99mTc]-sulphur colloid) in vivo in the rat has been examined. When the haemolysed blood (produced by first freezing the blood in liquid nitrogen) was infused into synergenic Lewis rats via the tail vein, there was a significant reduction in the uptake of the [99mTc]SC by the spleen, but lung, liver and kidney uptake remained constant. These results suggest that haemolysis of the blood may play a role in the alterations in RES phagocytic activity observed in the spleen following thermal injury.

Animals↗

PubMed1991

Proteoglycan synthesis in human skin and burn scar explant cultures.

The synthesis of proteoglycans (PG) by normal human skin, and normal and hypertrophic scars were compared using tissue explants in culture. Newly synthesized PG were labelled with [35S]Na2SO4. Significant differences were found in the proportion of [35S]-radio-labelled incorporation of PG in the tissue and accumulation of [35S]PG in culture medium in the different tissues. The rate of PG biosynthesis in all three tissue types occurred in two phases. There was an initial phase of PG synthesis occurring at 0-3 h and a later phase that occurred at 3-18 h [35S]-labelled PG were isolated and characterized by Sepharose CL-6B chromatography and cellulose acetate electrophoresis. The results showed that the hypertrophic scar tissue and its culture medium contained higher proportions of dermatan sulphate (DS), chondroitin sulphate (CS) and DS' PG than the normal skin fractions. These results suggest that abnormal scarring is related to a change in the level of PG synthesis during the burn injury repair process.

Burns↗

PubMed1991

Effect of platelet activating factor on reticuloendothelial system function.

The effect of platelet activating factor (PAF) injections on the uptake of 99mTc-SC (99mTc-SC (99mTc-sulphur colloid) was determined in vivo. PAF (2 micrograms) injected intravenously into unanaesthetized, unrestrained rats was associated with the development of lesions in the small intestine and alteration of 99mTc-SC uptake in vivo. 99mTc-SC uptake into the lung was increased while spleen uptake was decreased. Pretreatment of the animals with a PAF antagonist, SRI-64-441, prevented the intestinal lesions and alterations of 99mTc-SC uptake. Macrophages, isolated from lung lavage of the PAF-treated rats, demonstrated a decreased generation of hydrogen peroxide in vitro. The present results suggest that, in addition to its other effects on the immune system, PAF can also alter the in vivo phagocytic activity of the reticuloendothelial system in the rat.

Animals↗

PubMed1991

The rat lung organotypic culture: an in vitro model for studying surfactant metabolism abnormalities.

The amount of surfactant present in the intra-alveolar space is mainly regulated by the synthesis and recycling of surfactant by type II pneumocytes. Biochemical analyses have shown that the surfactant level is frequently diminished and that protein-rich exudate can further interfere with surfactant function in the lungs of adult respiratory distress syndrome (ARDS) patients. The microenvironmental changes that occur in the alveoli of burned patients, who are prone to developing ARDS, are unclear. Therefore, using an in vitro rat lung organotypic culture, we showed that the sera of rats with a 3-day old, third-degree thermal injury (25-30% total body surface area) inhibited surfactant synthesis in organotypically cultured rat lung cells. Surfactant precursor, 3H-choline, incorporation into the surfactant was 58% of control. Using liposomes made of dipalmitoyl phosphatidylcholine and phosphatidylglycerol (8:1, v/v) or surfactant we showed that surfactant endocytosis by purified type II alveolar cells is an active, temperature-dependent process, and correlates with the quantity of surfactant present in the milieu. We also found that plasma protein-rich fluid interfered with surfactant endocytosis by the purified type II pneumocytes. These two processes of inhibition of surfactant synthesis and its reutilization by these cells may contribute to the pathogenesis of ARDS.

Animals↗

PubMed1990

Injury-induced inhibition of small intestinal protein and nucleic acid synthesis.

Small intestinal mucosal weight and nutrient absorption are significantly diminished early after cutaneous thermal injuries. Because these intestinal properties are highly dependent on rates of nucleic acid and protein synthesis, in vivo incorporation of thymidine, uridine, and leucine into small intestinal deoxyribonucleic acid, ribonucleic acid, and proteins were measured. Deoxyribonucleic acid synthesis was markedly decreased with the lowest thymidine incorporation in the jejunum (p less than 0.01); these findings were confirmed by autoradiographic identification of radiolabeled nuclei in the intestinal crypts. Protein synthesis was decreased by 6 h postinjury (p less than 0.01) but had returned to normal by 48 h. Consistent with a decreased rate of protein synthesis, ribonucleic acid synthesis was also decreased 18 h postinjury (p less than 0.01). These decreased deoxyribonucleic acid, ribonucleic acid, and protein synthesis rates are not likely a result of ischemia because in other studies of this injury model, intestinal blood flow was not significantly changed by the burn injury. Potentially, factors initiating the acute inflammatory reaction may directly inhibit nucleic acid and protein synthesis and lead to alterations in nutrient absorption and intestinal barrier function after injury.

Animals↗

PubMed1990

Prevention of necrotizing enterocolitis in the rat with prenatal cortisone.

Cortisone acetate is known to accelerate maturation of the immature intestine. The effect of prenatal administration of cortisone acetate on the morbidity and mortality of necrotizing enterocolitis was examined in a rat pup model. Pregnant rats were administered cortisone acetate, 20 mg/100 g of body weight, or normal saline by daily IP injection from day 18-21 of gestation. Rat pups were taken from the mothers before suckling was initiated, fed a simulated rat milk formula, and subjected to daily ischemic insults to produce an animal model of necrotizing enterocolitis. Both morbidity and the mortality rates were significantly improved with prenatal cortisone treatment. Maturation of the intestinal mucosal barrier was accelerated with the cortisone treatment as measured by decreased serum concentrations of a fed antigen, ovalbumin. Aerobic bacterial colonization of the small intestine and translocation of bacteria to the liver were decreased in the pups pretreated with steroids. These changes observed in a rat model of necrotizing enterocolitis may explain the decreased incidence of necrotizing enterocolitis in human infants born to mothers who received corticosteroids late in gestation.

Animals↗

PubMed1990

Role of neutrophils in the intestinal alterations associated with thermal injury.

We have examined the role of neutrophils in the alterations observed in the intestines of rats subjected to 40 per cent surface area scald injury. Histologically, there was no evidence of neutrophilia in the intestinal tissue, and myeloperoxidase activity in mucosal scrapings was not elevated. The distribution of labelled human neutrophils injected into the burned rats showed no enhancement of uptake in the intestines, although there was increased uptake by the lung. The present data suggest that neutrophil migration may not play a role in the alterations in small intestinal function and morphology seen in burn trauma in the rat, but may be a factor in lung damage associated with thermal injury.

Acute Disease↗

PubMed1990

Effect of acute burn trauma on reticuloendothelial system phagocytic activity in rats. II: Comparison of uptake of radiolabelled colloid and bacteria.

The uptake of radiolabelled colloid or bacteria was compared in normal rats and animals subjected to acute burn trauma. The uptake of colloid by the liver was unaffected by burn trauma, but uptake of the labelled bacteria was reduced. Spleen uptake of both colloid and bacteria was reduced by burn trauma while lung uptake was increased. These data are consistent with the hypothesis that acute burn trauma alters reticuloendothelial system phagocytic activity in the rat towards both inert particles and live bacteria.

Acute Disease↗

PubMed1990

Role of skin in the burn-induced reduction of reticuloendothelial phagocytic activity in rats.

Acute burn trauma has been demonstrated to depress reticuloendothelial system (RES) phagocytic activity, which could partially explain the development of septicaemia in burn patients. In the present study we have attempted to determine the role that skin plays in the depression of the RES. One group of Lewis rats was subjected to a 100 degrees C scald burn for 10 s. Eschar was then removed and implanted onto the backs of a second group of normal controls. A third group of Lewis rats were subjected to sham treatment; the eschar of these animals was removed and implanted onto the back of a fourth group of normal rats. The excision sites of the donor animals were immediately covered with Biobrane. Twenty-four hours later the technetium-99m sulphur colloid [( 99mTS]SC) method described earlier (Trop et al., 1989) was used to determine phagocytosis in these four groups of animals. Acute burn trauma produced a marked reduction in colloid uptake by the spleen and a marked increase in the uptake of colloid material by the lung, although no effect was observed on liver or kidney uptake. Implantation of the burn eschar into normal control rats had no statistically significant effect upon colloid uptake. These data suggest that alterations in phagocytic activity of the spleen and lung occur within minutes after burn injury and may be unrelated to the presence of the burn eschar itself.

Acute Disease↗

PubMed1990

Acute alcohol ingestion reduces fatty acid extraction of the heart, liver, and small intestine.

Ethanol may have profound effects on both the distribution of perfusion and substrate utilization by the liver and heart due to its vasodilating properties and the generation of high levels of circulating acetate and lactate. Since fatty acids are highly extracted by the heart and liver under normal circumstances, changes in the relationship of perfusion/fatty acid uptake may be a sensitive indicator of both altered perfusion and changes in metabolic substrate availability. To test this hypothesis, studies were performed in rats fed 3.1, 6.2, and 9.3 g/kg doses of ethanol. Fatty acid uptake was estimated with a 3-methyl substituted reagent with a chain length equivalent to 17 carbons. The methyl group in the three position prevented beta oxidation and prolonged the residence of fatty acids in the tissue. Eighteen hours after acute alcohol administration, fatty acid uptake was reduced in the heart and the small intestine; in the liver uptake was increased or unchanged. Acute ethanol administration also resulted in increased perfusion, as indicated by enhanced uptake of 201thallium by the heart, liver, and small intestine. The fatty acid extraction of the heart, liver, and small intestine, defined as the concentration of fatty acid divided by the concentration of 201thallium, was markedly decreased by alcohol ingestion. These alcohol effects were dose-dependent and temporally related. The data suggest that ethanol ingestion could potentially alter heart function during exercise or following a prolonged fast, when the heart relies primarily upon fatty acids extracted from the circulation to generated adenosine triphosphate (ATP).

Acetates↗

PubMed1990

Cutaneous thermal injury alters macromolecular permeability of rat small intestine.

The intestinal epithelium normally provides a barrier function that prevents absorption of potentially harmful materials from the intestinal lumen. It has been postulated but never demonstrated that a cutaneous thermal injury will result in increased small-intestinal permeability. In a standardized 20% body surface area full-thickness scald injury, with polyethylene glycol 3350 and horseradish peroxidase used as permeability probes, small-intestinal permeability was examined regionally in an everted intestinal sac model. In the normal animals, the upper (proximal) and lower (distal) small intestine were less permeable to these probes than the middle segment. Within 6 hours after the injury, an increase in the mucosal uptake and transmural permeability was seen in all three small-intestinal segments; the most dramatic increase in permeability occurred in the ileum, p less than 0.01. The maximum increase in permeability was seen at 18 hours, and permeability was normal by 72 hours after the injury. This increase in intestinal permeability may represent a transient failure of the intestinal barrier function and may allow absorption of potentially toxic macromolecules from the intestinal lumen into the portal circulation early after thermal injury. Absorption of these macromolecules, such as endotoxin, may be potentially harmful by direct toxic actions or potentially helpful by activation of the immune system.

Animals↗

PubMed1989

Inhibition of in vivo DNA synthesis in regenerating rat liver following thermal injury.

Hepatic repair and regeneration which is extremely important after thermal injuries can be inhibited by the acute inflammatory reaction. Since thermal injury initiates this acute inflammatory reaction, DNA synthesis was studied in the regenerating liver following this injury. In vivo incorporation of [3H]-thymidine into hepatic DNA, autoradiographic determination of a labeling index, and thymidine kinase activity were determined. Incorporation of [3H]-thymidine into hepatic DNA and labeling indices were markedly diminished at 24 hours if partial hepatectomy and thermal injury were carried out concurrently. After partial hepatectomy, the expected elevations in thymidine kinase activity were inhibited by the thermal injury (p less than 0.01) and elevation of serum fibrinogen, a marker of the acute phase reaction that normally follows thermal injury, was blunted by the partial hepatectomy (p less than 0.05). The combination of thermal injury and partial hepatectomy resulted in a greatly diminished DNA replicative response as compared to partial hepatectomy alone and suggests that multiplicative injury is more likely to result in multi-system failure.

Animals↗

PubMed1989

MRI measurement of hepatocyte toxicity using the new MRI contrast agent manganese dipyridoxal diphosphate, a manganese/pyridoxal 5-phosphate chelate.

This study reports the first in vivo results using an MR contrast agent manganese dipyridoxal diphosphate (Mn-DPDP) designed to estimate the functional status of the hepatocyte. Thirty New Zealand white rabbits were studied in groups of 5 as follows: No. 1, control, MRI scans only; No. 2 MRI before and up to 90 min following 50 mumol/kg of Mn-DPDP iv; No. 3, rabbits received 9.3 g ethanol/kg and MRI; No. 4, as in No. 3 but following Mn-DPDP; No. 5, MRI as in No. 2 but 18 h. following 1000 mg/kg D-galactosamine used to induce hepatocyte necrosis; and No. 6, rabbits received D-galactosamine and MN-DPDP. In this study significant ethanol- and D-galactosamine-induced hepatocyte damage was indicated by the increased SGPt serum levels in the rabbit. The use of Mn-DPDP allowed detection of early hepatocyte necrosis in these animals whereas conventional spin-echo MRI did not. The fact that D-galactosamine curves with and without Mn-DPDP were not significantly different indicated virtually no membrane transport or metabolism of Mn-DPDP in the liver. Ethanol curves were not normal, but there was still considerable residual Mn-DPDP metabolism. Mn-DPDP appears to be an attractive agent in assessing hepatocyte function.

Animals↗

PubMed1989

Effect of thermal injury in the rat on transfer of IgA protein into bile.

Severe thermal injury is associated with bacterial sepsis; the intestine is considered a likely source of invasive organisms. Because IgA antibody in bile accounts for much of the specific immune defense of the upper intestinal tract in the rat, the effect of thermal injury on the quantity of IgA protein in bile was examined. Sprague-Dawley rats received a 20% to 30% body surface area burn under anesthesia. Eighteen hours later the common bile duct was cannulated and bile was collected for three hours. Total IgA protein in bile decreased 90% after thermal injury. The bile volume, the concentration of bile protein, and free secretory component did not change significantly. Although blood flow to the liver 18 hours after thermal injury was not changed, there was a significant reduction in total IgA concentration in the circulation; both monomeric (m-IgA) and polymeric IgA (p-IgA) were decreased. This finding may explain, in part, the reduced concentration of IgA protein in bile. Although not examined in this study, decreased local hepatic synthesis and/or transport of p-IgA across the hepatocyte may also contribute to the reduced IgA levels in bile.

Animals↗

PubMed1989

Factors influencing pharmacists' selection of their first practice setting.

Factors that influenced the choice of initial practice setting among pharmacists who had completed the majority of their experiential training in a hospital setting were determined. A questionnaire was mailed to all eligible pharmacists who successfully completed the Ohio pharmacist licensure examination in June or September 1987. Respondents were asked to (1) provide demographic data, (2) rate the importance of 23 factors that a pharmacist might consider when choosing a practice site, and (3) rate the desirability of a pharmacist position in their major hospital internship site, as well as positions they had considered in other hospitals and in community pharmacies. The predictive accuracy of four decision-making models--the weighted compensatory choice model, the unweighted compensatory choice model, the lexicographic model, and the conjunctive model--also was determined. Of 105 pharmacists surveyed, 53 returned usable questionnaires. Twenty-five had chosen to practice in hospital settings, and 28 had chosen community settings. The factor "is personally rewarding" was mentioned most often by hospital and community pharmacists as the factor that was most important when choosing their first position. The lexicographic model, which postulates that a pharmacist will choose the practice site with the highest performance rating for the most important factor, was the most accurate predictor of respondents' initial practice sites. Pharmacists' perception of how practice sites would rate in terms of the single job-related factor most important to them was the best predictor of whether they chose hospital or community practice initially and whether they chose to work in the hospital in which they served their internship, another hospital, or a community pharmacy.

Attitude of Health Personnel↗

PubMed1988

An S6 kinase activated during liver regeneration is related to the insulin-stimulated S6 kinase in H4 hepatoma cells.

Protein kinase activity toward the 40 S ribosomal protein S6 is activated 6-fold in regenerating rat liver following 70% hepatectomy. The kinase is maximally activated within 2 h after surgery, remains active up to 36 h after surgery, and declines rapidly thereafter. The post-hepatectomy S6 kinase activity exhibits structural and functional similarity to an insulin-stimulated S6 kinase in H4 hepatoma cells. Both S6 kinase activities are cAMP- and Ca2+-independent, and have a requirement for [ethylenebis(oxyethylenenitrilo)]tetraacetic acid. The regenerating liver and the insulin-stimulated H4 hepatoma S6 kinase elute at similar positions when sequentially fractionated by anion-exchange and cation-exchange chromatography. Both enzymes migrate at Mr 70,000 on fast protein liquid chromatography Superose 12 gel filtration. In H4 hepatoma cells, activation of S6 kinase activity is reversed by removal of insulin, and the cells can then be restimulated. Freshly isolated hepatocytes from normal animals show low levels of S6 kinase activity which can be stimulated by epidermal growth factor and insulin. Hepatocytes prepared from regenerating liver remnant have constitutively high levels of S6 kinase activity, which is unresponsive to insulin plus epidermal growth factor and which remains elevated at least 2 h in the absence of exogenously added growth factors. These findings demonstrate S6 protein kinase activation in vivo, in the setting of regulated cell growth; as in cultured cells, activation of S6 kinase probably represents an early step in the pleiotypic response elicited by activation of growth factor receptors.

Animals↗

PubMed1988

Increase of sialyltransferase activity in the small intestine following thermal injury in rats.

The acute phase protein response following inflammation is associated with an increased total protein-bound carbohydrate content in plasma in the form of glycoproteins. Glycosyltransferases in liver may serve as a regulator of this increased glycosylation activity in the plasma and may also serve as a marker for the acute phase response. Sialyltransferase is an example of a glycosyltransferases in which sialic acid is transferred to oligosaccharides of glycopeptides in the Golgi prior to glycopeptide secretion. In this study, sialyltransferase activities were determined in plasma, liver, and intestinal mucosa following a standardized 25% body surface area thermal injury in the rat. A statistically significant increase in sialyltransferase activity was found in liver and small intestine which were maximal at 24 hours after the injury. These increased sialyltransferase activities were accompanied by a statistically significant 2 to 4 fold elevation in plasma sialyltransferase activity at 24 hours. The plasma and liver elevations in these activities were similar to elevations seen in other models of acute inflammation using turpentine injections and bacterial infections. The increased sialyltransferase activity within the rat intestine was comparable to increases in intestinal sialyltransferase activity following colchicine treatment and may represent a similar mechanism(s).

Animals↗

PubMed1988

Ethanol-induced inhibition of liver cell function: I. Effect of ethanol on hormone stimulated hepatocyte DNA synthesis and the role of ethanol metabolism.

We have studied a short term effect (96 hr) of ethanol on hormone-stimulated DNA synthesis in a primary rat hepatocyte culture system. Studies were also performed with respect to total RNA and protein synthesis as well as albumin secretion measured by a solid-phase radioimmunoassay. We found that ethanol, when added to cultured hepatocytes, resulted in a substantial reduction in hormone-stimulated hepatocyte DNA synthesis and this effect was concentration dependent and occurred in serum-free medium. Ethanol also had an inhibitory effect on total RNA synthesis but protein synthesis and albumin secretion remained essentially unchanged. We determined that hepatocytes exposed to ethanol during the first 24 hr of culture were the most susceptible to inhibition of DNA synthesis. During the first 24 hr, alcohol dehydrogenase (ADH) activity was present in the cells at higher levels than at 48 and 72 hr. In human hepatoma cell lines and differentiated primary and secondary chick fibroblasts, no ADH activity was demonstrable; such cells were not inhibited by 100 mM ethanol additions and DNA synthesis rates were similar to untreated cultures. Other alcohols found to be metabolized by hepatocyte ADH were inhibitory towards hormone-stimulated DNA synthesis whereas those with less metabolism had little effect. Hepatocytes treated with 4-methylpyrazole, an inhibitor of ADH, were partially protected from ethanol effects. Taken together our results are consistent with the hypothesis that a major physiological effect of ethanol on the hepatocyte is a direct impairment of DNA synthesis and that alcohol metabolism is required.

Alcohol Dehydrogenase↗