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Biomedical subjects

D Wiggins

Publications and source records attributed to D Wiggins.

16 recordsLinked to original sources
PubMed1992

The lipolysis/esterification cycle of hepatic triacylglycerol. Its role in the secretion of very-low-density lipoprotein and its response to hormones and sulphonylureas.

In hepatocyte cultures maintained in the absence of extracellular fatty acids, at least 70% of the secreted very-low-density lipoprotein (VLDL) triacylglycerol was derived via lipolysis of intracellular triacylglycerol. This proportion was unchanged when the cells were exposed for 24 h to insulin or glucagon, hormones which decreased the overall secretion of intracellular triacylglycerol, or to chloroquine or tolbutamide, agents which inhibit lysosomal lipolysis. The rate of intracellular lipolysis was 2-3-fold greater than that required to maintain the observed rate of triacylglycerol secretion. Most of the fatty acids released were returned to the intracellular pool. Neither insulin nor glucagon had any significant effect on the overall lipolysis and re-esterification of intracellular triacylglycerol. In these cases a greater proportion of the released fatty acids re-entered the cellular pool, rather than being recruited for VLDL assembly. Tolbutamide inhibited intracellular lipolysis, but suppressed VLDL secretion to a greater extent. 3,5-Dimethylpyrazole did not affect lipolysis or VLDL secretion. The increased secretion of VLDL triacylglycerol observed after exposure of cells to insulin for 3 days was not accompanied by an increased rate of intracellular lipolysis. However, a larger proportion of the triacylglycerol secreted under these conditions may not have undergone prior lipolysis.

Carbon Radioisotopes↗
PubMed1992

Clinical, cognitive, and neurophysiological effects of alprazolam in children and adolescents with overanxious and avoidant disorders.

In a double-blind, placebo-controlled study, the efficacy and safety of alprazolam was investigated in childhood and adolescent anxiety disorders. Thirty patients (mean, 12.6 years) diagnosed with overanxious or avoidant disorders participated in the study. Evaluations included clinical, laboratory, cognitive, and qualitative EEG measurements. On a clinical global rating, there was no statistical difference between alprazolam and placebo. Relative to baseline EEG, acute alprazolam administration increased beta power in the right occipital lead, and chronic administration increased beta power in both leads. Alprazolam was well tolerated, and adverse effects were few, mild, and transient.

Adolescent↗
PubMed1991

Ultrasound for the detection of foreign bodies.

STUDY OBJECTIVE: To determine the ability of an emergency physician to detect a variety of foreign bodies in an experimental model using a portable ultrasound device. DESIGN: Ten pieces of beef were sliced into cubes approximately 6 cm on each side. Six different groups of foreign bodies were examined: gravel, cactus spine, glass, metal, wood, and plastic. An independent observer placed the objects in a random fashion into the beef cubes. One hundred twenty observations were made using sets of ten beef cubes at a time. Five foreign bodies were placed into each set of ten beef cubes. INTERVENTIONS: A blinded emergency physician used a portable ultrasound with a 7.5-MHz transducer to determine the presence or absence of a foreign body in each cube. MEASUREMENTS AND MAIN RESULTS: Ultrasound detected 59 of 60 foreign bodies, including all cubes of meat embedded with gravel, cactus spine, plastic, metal, and wood. Glass was detected nine of ten times. Of the 60 cubes of meat with no foreign bodies, one false-positive was recorded. This yielded sensitivity, specificity, positive predictive value, and negative predictive value of 98%. Positive determinations by ultrasound were significantly greater in the meat cubes with foreign bodies compared with the control group with no foreign bodies (P less than .001 by chi 2). Although the subset of glass foreign bodies had one false-positive and one false-negative, it was not significantly different in comparison with the other groups (P greater than .05 by chi 2). CONCLUSION: Ultrasound has promise as a diagnostic tool for the detection of a variety of foreign bodies. Further clinical studies using ultrasound for the detection of foreign bodies are warranted.

Emergencies↗
PubMed1990

Maintenance of energy-linked functions in rat liver mitochondria.

EGTA and EDTA are compared with respect to their ability to preserve ATP-requiring reactions in rat liver mitochondria. The presence of EGTA sustains the high ATP requirement of citrulline synthesis. EDTA does not, even with excess Mg2+. Carboxylation of pyruvate, which has a lower ATP demand, is not influenced by the type of chelating agent. In mitochondria stored for 24 h at 4 degrees C, EGTA is more effective than EDTA in preventing loss of these energy-linked functions.

Adenine Nucleotides↗
PubMed1990

An ovine model of maternal iron poisoning in pregnancy.

An ovine model of maternal iron poisoning in pregnancy was used to examine the placental transport of deferoxamine and ferrioxamine and to follow maternal and fetal serum iron concentrations when maternal serum iron levels exceeded total iron-binding capacity. Ewes in the third stage of gestation underwent hysterotomy and delivery of the fetal head through an abdominal incision while under ketamine and halothane anesthesia. The fetal external jugular vein was catheterized for sampling of venous blood while the fetus remained in utero. Administration of deferoxamine mesylate or ferrioxamine mesylate IV to ewes was not accompanied by measurable deferoxamine or ferrioxamine in fetal blood. In a final experiment, four gravid ewes in a control group received 2 mg/kg maternal body wt iron IV over 60 minutes. An experimental group comprising another four ewes received similar doses of iron but then received 50 mg/kg deferoxamine mesylate IV over 15 minutes. Control and deferoxamine ewes reached similar peak maternal serum iron concentrations (2,479 +/- 266 and 2,121 +/- 343 micrograms/dL, respectively). The markedly elevated maternal serum iron concentrations were not accompanied by meaningful elevations in fetal serum iron levels over baseline values. Maternal deferoxamine infusion resulted in a more rapid fall in maternal serum iron concentrations but had no effect on fetal serum iron levels. The ovine fetus appears to be protected from elevated maternal serum iron concentrations in the last trimester of pregnancy. It could not be demonstrated that meaningful quantities of deferoxamine or ferrioxamine cross the placenta in the last trimester.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Treatment of adolescent obsessive-compulsive disorder with a clomipramine-fluoxetine combination.

Clomipramine has been reported to be effective in the treatment of obsessive-compulsive disorder (OCD). Children and adolescents, however, tolerate poorly the adverse effects of tricyclics. Fluoxetine and other serotonin re-uptake inhibitors also appear useful in OCD, and are safer than clomipramine. To maximize the therapeutic effects and minimize adverse effects, 6 adolescents with OCD were treated in single trials with a clomipramine-fluoxetine combination. Duration of combined drug therapy ranged from 4 weeks to more than 28 weeks. Patients were first treated with clomipramine alone; if improvement or adverse effects were unsatisfactory, they received the drug combination. Clinical global improvement with clomipramine alone was moderate in 3 patients and minimal in 3. With a combined clomipramine-fluoxetine therapy, improvements were marked in 5 patients, and moderate in 1. These improvements were obtained with relatively low daily doses: clomipramine at 25 to 50 mg, and fluoxetine at 20 to 40 mg. Adverse effects appeared greater and much less tolerable with clomipramine alone than with the clomipramine-fluoxetine combination. This drug combination was well tolerated. These preliminary data suggest that relatively low doses of a clomipramine-fluoxetine combination may potentiate therapeutic effects and minimize adverse effects in OCD patients. Larger controlled trials are suggested.

Adolescent↗
PubMed1989

Chelating agents and rat liver mitochondria.

The chelating agents (EGTA and EDTA) and inorganic phosphate (Pi) are the most variable components of experiments involving isolated liver mitochondria. In the absence of EGTA or EDTA, swelling induced by Pi leads to rapid loss of endogenous adenine nucleotides to adenosine. Chelating agents prevent swelling and loss of adenine nucleotides. Concentrations below about 0.1 mM are ineffective. The protective effects depend on the continuous presence of the chelating agent; they are lost on washing EGTA-containing suspensions with chelating-agent-free medium. We question the accepted view that chelating agents stabilize mitochondria by binding Ca2+ to prevent activation of phospholipase.

Adenine Nucleotides↗
PubMed1989

Comparative effects of tumour necrosis factor-alpha (cachectin), interleukin-1-beta and tumour growth on amino acid metabolism in the rat in vivo. Absorption and tissue uptake of alpha-amino[1-14C]isobutyrate.

The effects of acute administration of either tumour necrosis factor-alpha (cachectin) (TNF) or interleukin-1-beta (IL-1), or of tumour growth (Walker-256 carcinosarcoma), on blood amino acid concentrations and tissue alpha-amino[1-14C]isobutyrate (AIB) uptake in virgin and lactating rats were compared. Both monokines decreased the blood concentrations of those amino acids (serine, glycine, alanine and proline) transported via the A system. Tumour growth decreased the blood concentrations of serine, proline and histidine, whereas the concentrations of glutamine and leucine were increased. IL-1 decreased the intestinal absorption of AIB in all groups studied; TNF or tumour growth had no effect. Tissue AIB uptake was increased (1.5-2.5-fold) in liver, whereas it was decreased in heart and skeletal muscle of the three treatment groups (except skeletal muscle of the IL-1-treated rats). Lactating rats had lower hepatic uptake of AIB compared with livers of virgin rats. IL-1 increased the hepatic uptake of AIB in lactating rats, but not to the values seen in virgin rats treated with IL-1; there was no effect of the cytokine on muscle or mammary-gland uptake. In adrenalectomized rats, the stimulatory effect of IL-1 on hepatic AIB uptake was diminished, whereas that of TNF still persisted. IL-1 caused a marked decrease of AIB uptake in muscle and heart of adrenalectomized rats, which was accompanied by an increase in the blood concentrations of branched-chain amino acids. These effects did not occur with TNF. It is concluded that the effects of the cytokines on tissue amino acid metabolism may depend on a differential endocrine response involving glucagon and/or glucocorticoids.

Absorption↗
PubMed1988

Preservation of hepatocyte suspensions at 4 degrees C.

Suspensions of rat hepatocytes are resistant to hypoxia for at least 24 hr at 4 degrees C. After storage for 24 hr with xylitol, sorbitol, or glycerol, their subsequent capacity for glucogenesis from these substrates is increased. Even storage under N2/CO2 as the gas phase has little deleterious effect.

Animals↗
PubMed1987

Inhibition of carbamoyl-phosphate synthase (ammonia) by Tris and Hepes. Effect on Ka for N-acetylglutamate.

The apparent Ka for N-acetylglutamate of rat liver carbamoyl-phosphate synthase is 11 microM in phosphate buffer, a value 10-fold lower than reported in other buffer systems. Tris and Hepes inhibit competitively with N-acetylglutamate. The proportion of carbamoyl-phosphate synthase in the active enzyme-acetylglutamate complex in vivo may be higher than previous calculations suggest, which re-opens the question of the involvement of N-acetylglutamate in the regulation of urea synthesis.

Animals↗
PubMed1987

The matrix water space of mitochondria in situ in isolated hepatocytes.

The intracellular and mitochondrial matrix water-permeable spaces were measured in intact, respiring hepatocytes from normal fed, 48 h starved, and protein fed rats. The mitochondrial matrix constitutes 15-20% of the total intracellular water, a proportion greater than has generally been assumed.

Animals↗
PubMed1987

Amino acid profiles during development of the fetal rat.

Umbilical blood venous-arterial differences for amino acids across the rat fetus show uptake of disproportionately large amounts of glutamine, alanine and lysine relative to their contribution to total body protein. Free amino acid concentrations in fetal liver tend to increase during development, but show a rapid adjustment to near-adult values within 24 h after birth.

Amino Acids↗
PubMed1986

The ornithine requirement of urea synthesis. Formation of ornithine from glutamine in hepatocytes.

In hepatocytes, urea synthesis from glutamine is independent of added ornithine, even when rates are high after stimulation of glutamine metabolism by dibutyryl cyclic AMP, phenylephrine or vasopressin. Incubation with glutamine increases tissue [ornithine]. The increases parallel those of [N-acetylglutamate] under different conditions. The ornithine requirement of urea synthesis increases with increasing supply of ammonia. A function of the unique, highly regulated, glutaminase of liver may be to regulate ornithine synthesis.

Ammonium Chloride↗
PubMed1978

Phosphorylation of adenosine monophosphate in the mitochondrial matrix.

The origin of the GTP needed for th phosphorylation of AMP in the mitochondrial matrix was investigated. When short-chain fatty acids are metabolized by hepatocytes, AMP is readily formed within the matrix by the butyryl-CoA ligase (AMP-forming) reaction (EC 6.2.1.2). The rate of matrix AMP formation in rat hepatocytes was calculated from the rate of ketone-body formation. The rate of the reconversion of matrix AMP into ADP by GTP-AMP transphosphorylase is limited by the rate of supply of GTP. GTP can be formed either by succinic thiokinase (EC 6.2.1.4) or by nucleoside diphosphokinase (EC 2.7.4.6). The rate of the succinic thiokinase reaction was calculated from turnover of the tricarboxylic acid cycle and this was calculated from the rate of O2 consumption and ketone-body formation. The results show that nucleoside diphosphokinase can make a major contribution (up to 80%) to the supply of GTP under the test conditions.

Adenosine Monophosphate↗