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W Schumer

Publications and source records attributed to W Schumer.

At least 19 recordsLinked to original sources
PubMed1990

Alterations in the activities of DNA topoisomerase enzymes and O6-methylguanine-DNA-methyltransferase in septic rat liver.

To understand the genomic changes contributing to the various metabolic derangements in sepsis and septic shock, we measured the activities of the following liver enzymes intimately associated with DNA function: (1) DNA topoisomerases I and II (topo I and topo II) controlling DNA conformation in mammalian nuclei, and (2) O6-methylguanine-DNA-methyltransferase (MT) capable of removing the methyl groups from the O6-position of guanine in DNA. We found that in septic rat livers the specific activities (units/mg protein) of topo II and MT were elevated by 1.4- and 1.6-fold, respectively, over the sham-operated controls (P less than 0.001). There was no significant difference in topo I activity. We believe that peritonitis sepsis alters topo II levels modulating the selective pretranscriptional changes in chromatin and that MT functions as a cellular stress protein.

Animals↗
PubMed1989

Lung and muscle water after crystalloid and colloid infusion in septic rats: effect on oxygen delivery and metabolism.

We compared the effect of crystalloid infusion with that of colloid infusion on extravascular lung water and muscle water in septic rats. We also examined the relationship of lung and muscle edema to arterial oxygenation and muscle energy metabolism during sepsis. Cecal ligation and perforation were used to induce sepsis. Five animals served as sham-operated controls. Five animals were infused with 0.9% saline solution and five with 10% low molecular weight hydroxyethyl starch (hetastarch). Thermodilution cardiac output, plasma colloid osmotic pressure, and arterial blood gases were sequentially measured over a 6-hour interval. At 6 hours, a biopsy specimen was taken from the rectus femoris and the lungs and adductor magnus muscle harvested for gravimetric analysis (wet-dry/dry weight ratio). The colloid osmotic pressure was 16.1 +/- 1.2 mm Hg in the control animals, 9.3 +/- 0.5 mm Hg in the saline solution-infused animals, and 21.6 +/- 0.5 mm Hg in the hetastarch-infused animals at 6 hours (p less than 0.05 saline vs control, hetastarch). The lung wet-dry/dry weight ratio was 3.46 +/- 0.11 in the control animals, 3.74 +/- 0.13 in the saline group, and 3.64 +/- 0.11 in the hetastarch group (difference not significant). Arterial oxygenation was not significantly different in the three groups. Muscle wet-dry/dry weight ratio was 3.11 +/- 0.16 in the control animals, 2.75 +/- 0.12 in the hetastarch-infused animals, and 3.06 +/- 0.08 in the saline-infused group (not significant). There were no significant differences in skeletal muscle energy production or lactate/pyruvate ratio between the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Early impairment of oxidative metabolism and energy production in severe sepsis.

We investigated the relationship of systemic blood flow to skeletal muscle tissue oxygenation, lactate production, and energy production during rat peritonitis established by cecal ligation and perforation. The study included five sham rats, five septic rats, and five septic rats infused with 5% albumin. Thermodilution cardiac output and skeletal muscle tissue oxygen tension were sequentially measured over a 6 hr interval. At 6 hr the rectus femoris was biopsied. In sham rats, there was no change in cardiac output or tissue oxygen tension. Skeletal muscle lactate/pyruvate ratio was 10.4 +/- 0.6, ATP was 5.39 +/- 0.23 mumol/g and total tissue adenine nucleotides were 6.41 +/- 0.21 mumol/g. In septic rats, significant decreases in cardiac output and tissue oxygen tension were associated with a lactate/pyruvate ratio of 25.7 +/- 3.7, an ATP level of 4.38 +/- 0.08 mumol/g and tissue adenine nucleotides of 5.59 +/- 0.08 mumol/g (P less than 0.01 vs. sham). In albumin infused septic rats, cardiac output and tissue oxygen tension were maintained at control levels. Skeletal muscle lactate/pyruvate ratio was 14.8 +/- 1.0, ATP was 4.70 +/- 0.12 mumol/g and tissue adenine nucleotides were 5.80 +/- 0.12 mumol/g (P less than 0.05 vs. sham). Despite the maintenance of systemic blood flow and tissue oxygenation in albumin infused septic rats, the increase in lactate/pyruvate ratio and decrease in high energy phosphates suggest impaired oxidative metabolism and energy production early in the course of severe sepsis.

Adenine Nucleotides↗
PubMed1988

Liver gluconeogenic metabolites in young and old rats during septic shock.

Aged individuals have diminished resistance to severe sepsis and septic shock. Previous studies in young animals showed that the liver's gluconeogenic capacity was an important determinant of survival in shock states. This study compared hepatic carbohydrate intermediates from young rats and old rats to correlate changes during peritonitis septic shock with known differences in survival times. Old control rats had glucose 6-phosphate (G6P) concentrations two-fold higher than young controls, 354 +/- 49 nanomole/g wet liver vs 180 +/- 41, suggesting a reduced ability to convert hexose monophosphate precursor into blood sugar. There was a 53% increase in G6P levels in the peritonitis livers, to 540 +/- 155 nanomole/g liver while in young septic rats the G6P decreased 33 per cent. These opposite, highly significant changes in shock (P = 0.01) show the reduced ability of old animals to mobilize gluconeogenic precursors. Fructose 1,6-biphosphate (FBP) in old control liver was 14 +/- 3 nanomole/g liver and did not change in shock; in young rats, FBP was 7.0 +/- 3 nanomole and increased 230 per cent in shock, showing a different metabolic response in young and old animals. These data suggest older animals may be more vulnerable to shock because of lower gluconeogenic potential.

Aging↗
PubMed1987

Effect of aging on hepatic carbohydrate metabolism in septic rats.

Aged individuals have diminished resistance to severe sepsis and septic shock. Past work with animals suggested that an important determinant of survival was the ability of the liver to supply glucose. In this study, young adult (3 to 4 months) and old (24 months) Fischer 344 rats were fasted and subjected to cecal incisions producing a rapidly lethal peritonitis. We then determined gluconeogenic intermediates in the liver. In the old rats with peritonitis, hexosemonophosphates (HMP) increased 50% relative to control liver, whereas in the young animals with peritonitis, the substrate decreased 50%. The accumulation of HMP in the old rat liver cells indicates a failure to dephosphorylate glucose-6-phosphate (G6P). This increase in HMP is associated with a decline in hepatic glucose-6-phosphatase (G6Pase), the final enzyme in the gluconeogenic pathway, and is reflected in a significant reduction in serum glucose in old Fischer 344 rats when compared to young Fischer rats.

Aging↗
PubMed1986

Hepatic glycolytic intermediates in fed and fasted rats after severe hemorrhage.

The responses of key liver carbohydrate intermediates to severe hemorrhage were investigated in fed and fasted young adult male rats. Forty per cent of intravascular blood was withdrawn and liver was sampled by freeze-clamp at 0, 0.25, 1.0, 3.0, and 4.0-5.0 hours. Fed rats with abundant glycogen showed a threefold increase in glucose-6-phosphate (G6P) concentration, and fasted rats showed a 75% decline in G6P immediately after hemorrhage. This significant difference in response traces to the fact that G6P is one of the first catabolites in fed liver formed by glycogenolysis but is the last intermediate of the gluconeogenic pathway in fasted animals. Phosphoenolpyruvate (PEP), the high-energy intermediate, was markedly depleted in both fed and fasted rats at zero time. In the fasted animal, however, the PEP was rapidly restored, and by 1.0 hour was threefold above normal. The ability of fasted rats to rapidly synthesize glucose from accumulated lactate is attributed to increased amount of gluconeogenic enzymes induced by fasting. In prolonged shock states, this synthetic capacity plays a protective role. Contrariwise, in brief shock states such as hemorrhage, the immediate availability of glucose from stored glycogen appears to be a more important determinant of survival. In the present experiments, fed rats were more resistant to the hemorrhage protocol.

Animals↗
PubMed1986

Cellular metabolic alterations in shock.

Circulatory shock is considered one of the most severe stimulus of the pituitary adrenal axis, therefore causing profound physiologic and metabolic sequelae. It is defined as inadequate circulating blood volume producing decreased perfusion first to nonvital tissues (skin, connective tissue, bone, and muscle), and subsequently to vital organs (brain, heart, lungs, liver, and kidney). Decreased perfusion of nonvital tissues results in anaerobic metabolism because the nonvital tissue cell mass is significantly larger than the vital tissue cell mass. As circulating blood volume decreases, catecholamines and angiotensin are secreted which increases peripheral resistance thus producing low flow in the periphery. Later, baroreceptors in the auricles and carotid and aortic bodies stimulate the vasomotor center in the medulla oblongata via the sympathetic nerves. The vasomotor center compounds sympathetic vasoconstriction further, increasing peripheral resistance.

Animals↗
PubMed1986

Endotoxin lethality is intensified by inhibited gluconeogenesis.

There are two major etiologies regarding the lethal element in the pathophysiology of endotoxemia and severe gram-negative sepsis: 1) metabolic lesions culminating in terminal hypoglycemia and 2) circulatory deficits resulting in early peripheral and late vital organ perfusion failure. Although not mutually exclusive, a direct test of the relative importance of either hypothesis is needed. The impact of inhibited gluconeogenesis on endotoxin lethality in young adult male rats (180-220 g) was investigated. Fasted rats received 20 mg/kg intravenous E. coli endotoxin (LD10) simultaneously with 500 mg/kg intraperitoneal L-tryptophan. This amino acid rapidly forms quinolinic acid, which blocks liver glucose synthesis. Endotoxin together with tryptophan caused hypoglycemic convulsions, killing 22 of 24 rats, 75% within 6 hours. In parallel studies, liver intermediates were assayed in freeze-clamped samples obtained at 5 hours from ether anesthetized rats. The high-energy intermediate phosphoenolpyruvate was 222 +/- 79 nmole/gm +/- 1 S.D. wet liver in the moderately endotoxic rats (N = 8). In the endotoxin-plus tryptophan group (N = 7), the PEP intermediate had fallen to 58 +/- 24 nmole/gm liver (P = 0.005). Liver lactate was increased 2.8-fold over the value in the endotoxin-only group, to 4390 nmole/gm wet tissue, showing the failure to utilize gluconeogenic precursors. Tryptophan given alone was not lethal. It is concluded that inhibited gluconeogenesis greatly intensifies the hepatic metabolic derangement of endotoxemia.

Animals↗
PubMed1979

Septic shock.

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Emergencies↗
PubMed1979

Hypovolemic shock.

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Acid-Base Imbalance↗
PubMed1979

Phenothiazine effect on gastrointestinal tract function.

Clinical evidence indicates that phenothiazines, specifically chlorpromazine (CPZ), used extensively in the treatment of patients with mental and/or neurologic disorders produce an ileus characterized by pseudoobstruction with an extended barium transit time of eight to ten days. Postoperatively, these patients have a protracted ileus, lasting from ten to fourteen days. In our present study we investigated the mechanism of action by which phenothiazines block gastrointestinal tract function as well as the possible reversal of this effect by pharmacologic agents. Guinea pigs were injected intraperitoneally with CPZ at a dose of 30 mg/kg/day for five to seventeen days. This caused deleterious effects in the gastrointestinal tract, such as cessation of peristalsis of small intestine and colon, and marked distension of the cecum. In vitro pharmacologic studies were performed on the electrically stimulated longitudinal muscle-myenteric plexus of the guinea pigs. We found that phenothiazines interfered with the neuromuscular mechanism of the intestine, as exemplified by a lack of response to electrical current stimulation. The effect was protracted, lasting at least 24 hours. These effects were reversed by the administration of the anticholinesterase, physostigmine (PGM), provided the block was less than 80 per cent. The paralytic ileus produced was similar to that found in man.

Animals↗
PubMed1978

Endotoxin-challenged monkeys and rats.

Studies in our laboratory with both the monkey and the rat showed that, after three hours of endotoxemia, there was a significant decrease in the number of circulating platelets, total hemolytic complement (CH 50 units), and blood serotonin (5-HT) levels. Administration of dexamethasone sodium phosphate in the clinical dose range at the time of endotoxin challenge significantly attenuated the decrease in blood 5-HT levels when compared to the untreated groups in both the monkey and the rat experiments. In the monkey, CH 50 units remained at a higher level when dexamethasone was administered; however, the difference between the treated and untreated groups was not statistically significant. The number of circulating white blood cells and platelets did not appear to be significantly altered by corticosteroid treatment. It is suggested that glucocorticoids may interfere with lipopolysaccharide-induced alterations in complement components or factors regulating hemostasis that influence platelet 5-HT release.

Animals↗
PubMed1976

Glucocorticoid effect on hepatic carbohydrate metabolism in the endotoxin-shocked monkey.

This study investigated the effect of glucocorticoid treatment on survival, on hepatic carbohydrate metabolism, and on levels of hepatic adenine nucleotides in the endotoxin-shocked monkey. Dexamethasone sodium phosphate (DMP) administered either at the time of endotoxin challenge or up to 90 minutes afterward significantly increased the survival rates. Endotoxin administered alone caused profound hypoglycemia and lactic-acidemia, which were alleviated by the administration of DMP. Endotoxin administered alone significantly decreased the hepatic levels of glucose-6-phosphate, fructose-6-phosphate, phospho-enolpyruvate, adenosine triphosphate, adenosine diphosphate, and glycogen; and it significantly increased the hepatic levels of fructose-1,6-diphosphate, lactate, and adenosine mono-phosphate. The administration of DMP at the time of endotoxin challenge maintained the levels of all these metabolites at or near the control levels.

Adenosine Diphosphate↗