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Biomedical subjects

A D Morrison

Publications and source records attributed to A D Morrison.

At least 19 recordsLinked to original sources
PubMed1990

Effect of inhibition of polyol pathway activity on aortic smooth muscle metabolism.

The relationship was examined between increased polyol pathway activity and the changes in water content, respiration, and glycolysis that occur when tubular segments of rabbit aortic smooth muscle cells are incubated with elevated glucose concentrations. The presence of 1.0 mmol/L ibuprofen resulted in a 65% reduction in fructose production by tissue incubated with 50 mmol/L glucose. This was associated with an increase in intracellular glucose and decreases in aortic smooth muscle sorbitol and fructose consistent with an inhibition of aldose reductase. Inhibition of increased polyol pathway activity usually observed in tissue incubated with 50 mmol/L glucose, is accompanied by a decrease in tissue water, an increase in oxygen uptake, and a decrease in lactate production. This suggests a causal relationship between increased polyol pathway activity and the changes in the aortic water content and metabolism induced by an elevated medium glucose concentration, although this would not be predicted by the osmotic hypothesis. The mechanism(s) responsible for the prevention of metabolic changes seen in an elevated glucose concentration by the aldose reductase inhibitor remain to be elucidated.

Adenosine Triphosphate↗
PubMed1987

Glucose concentration in the dialysate and lipid abnormalities in chronic hemodialysis patients.

In order to assess the effect of varying glucose concentrations on plasma lipids, we first compared the hormonal response of nine non-diabetic patients during dialysis with a high (200 mg/dl) and a low (100 mg/dl) glucose bath. Insulin and growth hormone production increased (p less than 0.05) only with the high glucose bath, and no hemodynamic differences were noted during either dialyses. We then compared lipid profiles of 18 patients for 6 months, changing the glucose dialysate concentrations in each patient after three months. We found that all patients had hypertriglyceridemia, mild hypercholesterolemia, low HDL, normal LDL, and high VLDL cholesterol. We therefore conclude that episodic hyperinsulinemia and episodic excessive growth hormone secretion do not contribute significantly to the lipid abnormalities of the dialysis patients.

Adult↗
PubMed1986

Oral sulfonylureas for the treatment of type II diabetes: an update.

Oral hypoglycemic agents have been in clinical use since 1956 in the United States. Two new second-generation sulfonylureas, glipizide and glyburide, have been marketed recently. This article reviews the pharmacology of the oral sulfonylureas, compares the drugs from a safety and efficacy standpoint, and provides updated information regarding their use in the management of type II non-insulin-dependent diabetes mellitus.

Administration, Oral↗
PubMed1986

Rapid glucose-dependent increases in phosphatidic acid and phosphoinositides in rat pancreatic islets.

Glucose effects on islet phospholipids were examined during direct incubation or after 3 days of 32P prelabeling in primary culture. In both cases, glucose increased the 32P content of phosphatidic acid (PA), phosphatidylinositol (PI), and polyphosphoinositides (PPI). Glucose-induced increases in PA, PI, and PPI in the culture-prelabeling experiments were evident within 1 min, dose related, and reflective of increases in phospholipid mass, which was confirmed in direct incubations by measurement of PI phosphorus. Thus, in addition to increasing PI-PPI hydrolysis, glucose increases de novo phospholipid synthesis in pancreatic islets. The latter may result from enhanced glycolysis and substrate availability for PA-PI-PPI synthesis, since glyceraldehyde and pyruvic acid also increased PI levels. Our findings raise the possibility that increases in PA, PI, and PPI synthesis could serve as a mechanism to enhance the generation of intracellular mediators, which are purported to regulate insulin secretion.

Animals↗
PubMed1978

Glucose-induced alterations of the metabolism of an isolated capillary preparation.

A preparation of blood capillaries was isolated from the rete mirabile of the eel swin bladder. The capillaries, incubated for two hours at 37 degrees C. in Krebs-Ringer bicarbonate buffer with 5 mM glucose, contained 29.3 +/- 4.6 nmoles of sorbitol per gram and released in the medium 725 +/- 60 nmoles of fructose per gram. When glucose in the medium was raised from 5 to 30 mM, capillary sorbitol and medium fructose rose by approximately 100 per cent. There were no accompanying changes in capillary water content as determined by the ratio of wet weight to dry weight and by the difference between water-3H space and inulin-14C space. Respiration of capillary tissue was lower at 30 mM glucose than at 5 mM glucose. The addition of 30 mM mannitol to a medium containing 30 mM glucose did not restore the oxygen uptake by capillary tissue to values obtained with a medium containing 5 mM glucose alone. It is concluded that the polyol pathway is operative in vertebrate blood capillaries. At high medium glucose concentration, the activity of the pathway is enhanced, respiration is depressed, and water content is unchanged

Animals↗
PubMed1978

Release of lysosomal enzymes from human polymorphonuclear leukocytes by soluble intermediate immune complexes.

The efficacy of soluble immune complexes (1C) of different sizes prepared in vitro or present in RA sera and synovial fluids to induce the release of beta-glucuronidase (BG) and neutral protease (NP) from PMN has been examined. Immune complexes of human HGG-rabbit anti-human HGG prepared in 5, 10 and 20 times excess of antigen equivalence were fractionated into three pools, PI (22S--13S), PII (13S--7S) and PIII (7S) using Sephadex G-200 column chromatography. NP and BG-releasing activity was mostly associated with PII. Similar fractions were obtained from RA sera and synovial fluids. BG-releasing activity was again predominantly associated with PII. PII fractions from normal sera and from 2 non-RA IC disease sera showed less BG-releasing activity than the RA PII fractions. Negligible NP release was observed with all three serum pools. Further investigation demonstrated the presence of NP inhibitor(s) in PI and PII from human sera.

Antigen-Antibody Complex↗
PubMed1977

The effects of anoxia on the morphology and composite metabolism of the intact aortic intima-media preparation.

Paired samples of an intact rabbit aortic intima-media preparation were incubated for short periods under aerobic or anoxic conditions in Krebsbicarbonate buffer containing 6% albumin and 5 mM glucose. During aerobic incubation for as long as 1 h the preparation retained an electron microscopic (EM) appearance similar to that of tissue fixed in situ, and scanning EM confirmed the presence of an uninterrupted endothelial surface. After 2.5 min of anoxia there was widespread endothelial swelling, but the alterations in the EM appearance of these cells were not striking and did not progress during a subsequent 30 min aerobic incubation in fresh medium. After 10 min of anoxia there were marked and widespread alterations in endothelial cell structure, including loss of cell integrity, and numerous discrete interruptions in the endothelium were consistently observed on both transmission and scanning EM. After a subsequent 30 min aerobic incubation in fresh buffer, a major fraction of the luminal surface was denuded of endothelium. The aortic vascular smooth muscle cells did not exhibit evidence of irreversible anoxic injury after 2.5 or 10 min of anoxia or after subsequent aerobic incubation for 30 min. Exposure to anoxia for 10 min induced persistent alterations in the composite metabolism of the preparation during subsequent aerobic incubation in fresh medium; O(2) uptake was reduced, and the fraction of the glucose uptake that was accounted for by lactate production increased approximately 100%. The observations suggest that aortic endothelial cells are dependent upon respiration for the preservation of normal ultrastructure and cell integrity, and probably derive the major fraction of their energy requirements from reactions linked to respiration. Under the conditions employed in these experiments, short periods of anoxia did not induce EM evidence of irreversible anoxic injury in aortic vascular smooth muscle cells; this negative result is not incompatible with other data suggesting that these cells normally derive the major fraction of their energy requirements from respiration. Aortic intima-media does not exhibit a high rate of aerobic glycolysis under aerobic conditions which preserve a normal EM appearance of the preparation, but this pattern of metabolism can be induced by prior anoxic exposure.

Aerobiosis↗
PubMed1976

Morphology and metabolism of an aortic intima-media preparation in which an intact endothelium is preserved.

An in vitro preparation of rabbit aortic "intima-media" previously shown to exhibit stable rates of respiration and glucose metabolism and the high rate of aerobic glycolysis considered characteristic of the metabolism of this tissue was subjected to electron microscopic examination. In samples examined immediately after the aortae were dissected free of adipose tissue and adventitia, under conditions similar to those now in common use, marked and widespread alterations in endothelial cell structure were present, including loss of cell integrity. The vascular smooth muscle cells retained a normal electron microscopic (EM) appearance. During subsequent incubation with 5 mM glucose in Krebs-Ringer bicarbonate (KRB), pH 7.4, under the conditions usually employed in studies of this preparation, large zones of the luminal surface were rapidly denuded of endothelium, and the remaining endothelial cells exhibited a wide range of ultrastructural alterations. The smooth muscle cells, however, continued to maintain a normal EM appearance. A method was developed to prepare segments of rabbit aortic intima-media which retained an intact layer of endothelium resembling that observed in tissue fixed in situ. During a 1-h incubation with 5 mM glucose in KRB, pH 7.4, gas phase 5% CO2/95% O2, containing 6% bovine serum albumin, the intact aortic intima-media preparation retains an essentially unmodified EM appearance and exhibits linear rates of respiration. Under these conditions the intact aortic intima-media preparation exhibits significantly higher rates of O2 uptake and glucose uptake than those observed in our previous preparation or in other reported aortic intima-media preparations. The intact aortic intima-media does not exhibit the high rate of aerobic glycolysis during in vitro incubation that has been considered characteristic of the metabolism of rabbit, rat, and swine aortic intima-media. In addition, the magnitude of the Pasteur effect was far greater than that observed in other aortic intima-media preparations. The data suggest that component cells of the aortic intima-media may derive a major fraction of their energy requirements from respiration; they raise further questions concerning the significance of the high rate of aerobic glycolysis observed when aortic intima-media preparations are incubated in vitro, and they suggest that documentation of the EM appearance of the endothelium in such preparations is desirable.

Aerobiosis↗