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Biomedical subjects

R Dyer

Publications and source records attributed to R Dyer.

At least 37 records · Page 2Linked to original sources

Palmitic acid is absorbed as sn-2 monopalmitin from milk and formula with rearranged triacylglycerols and results in increased plasma triglyceride sn-2 and cholesteryl ester palmitate in piglets.

Milk fatty acids contain 20-30% palmitic acid (16:0), with approximately 70% of the 16:0 esterified to the sn-2 position of the milk triacylglycerol. Formulae containing vegetable and oleo oils contain different amounts of 16:0, but all have unsaturated fatty acids esterified to the triacylglycerol sn-2 position. Intraluminal triacylglycerol hydrolysis by endogenous lipases produces sn-2 monoacylglycerols and free fatty acids, which are absorbed and re-esterified in the enterocyte for secretion to plasma. The extent of absorption and re-esterification of sn-2 monoacylglycerols from milk or formula fats in infants is unknown. This was studied by feeding piglets sow milk or formulae containing similar total saturated fat, 18:1, 18:2(n-6) and 18:3(n-3) with unsaturated fatty acids at the sn-2 position or with rearranged triacylglycerols containing approximately 30% 16:0, with 70% 16:0 in fatty acids at the sn-2 position. Feeding milk or 16:0 on the sn-2 position of formula with rearranged triacylglycerols resulted in higher 16:0 esterified to the plasma triacylglycerol sn-2 position and in cholesteryl esters than feeding formulae with 0.4 to 4.4% 16:0 in the sn-2 position fatty acids. The absorption of 16:0 as monopalmitin from milk and any metabolic importance in human infants has yet to be determined.

Animals↗

Evidence that palmitic acid is absorbed as sn-2 monoacylglycerol from human milk by breast-fed infants.

Milk fatty acids consist of about 20-25% palmitic acid (16:0), with about 70% of 16:0 esterified to the sn-2 position of the milk triacylglycerols. Hydrolysis of dietary triacylglycerols by endogeneous lipases produces sn-2 monoacylglycerols and free fatty acids, which are absorbed, reesterified, and then secreted into plasma. Unesterified 16:0 is not well absorbed and readily forms soaps with calcium in the intestine. The positioning of 16:0 at the sn-2 position of milk triacylglycerols could explain the high coefficient of absorption of milk fat. However, the milk lipase, bile salt-stimulated lipase, has been suggested to complete the hydrolysis of milk fat to free fatty acids and glycerol. These studies determined whether 16:0 is absorbed from human milk as sn-2 monopalmitin by comparison of the plasma triacylglycerol total and sn-2 position fatty acid composition between breast-fed and formula-fed term gestation infants. The human milk and formula had 21.0 and 22.3% of 16:0, respectively, with 54.2 and 4.8% 16:0 in the fatty acids esterified to the 2 position. The plasma triacylglycerol total fatty acids had 26.0 +/- 0.6 and 26.2 +/- 0.6% of 16:0, and the sn-2 position fatty acids had 23.3 +/- 3.3 and 7.4 +/- 0.7% of 16:0 in the three-month-old exclusively breast-fed (n = 17) and formula-fed (n = 18) infants, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Feeding↗

Dietary saturated, monounsaturated, n-6 and n-3 fatty acids, and cholesterol influence platelet fatty acids in the exclusively formula-fed piglet.

Platelet lipid composition is important to normal platelet morphology and function, and is influenced by dietary fatty acids and cholesterol. The fatty acid composition and cholesterol content of infant formulas differs from those of human milk, but the possible effects on platelet lipids in young infants is not known. This was studied in piglets fed from birth to 18 d of age with one of eight formulas differing in saturated fatty acid chain length, or content of 18:1, 20:5n-3 plus 22:6n-3, or cholesterol. A reference group of piglets fed sow milk was also studied. Sow milk has a fatty acid composition and cholesterol content similar to that of human milk. Piglets fed formulas high in 18:1 (34.9-40.8% wt fatty acids) and low in 16.0 (< or = 6.5% wt fatty acids) had lower platelet counts and greater platelet size than piglets fed sow milk (40.4% 18:1, 30.7% 16:0). Piglets fed formulas high in 16:0 (27-29.6%) and 18:1 (40-40.6%), or low in both 16:0 (5.9-6.1%) and 18:1 (10.8-11.2%), had similar platelet counts and size to piglets fed sow milk. Platelet phospholipid % 20:4n-6 was lower in all the groups of piglets fed formula than in the group fed sow milk. Addition of fish oil with 20:5n-3 plus 22:6n-3 to the formula further decreased platelet phospholipid 20:4n-6. Addition of cholesterol to the formula increased the platelet phospholipid % 20:4n-6 and platelet volume.

Animals↗

Reliability and within subject variability of VE, VO2, heart rate and blood pressure during submaximum cycle ergometry.

To assess the reliability and within subject variability of steady-rate ventilation (VE), oxygen uptake (VO2), heart rate, systolic and diastolic blood pressure, 4 subjects exercised for 10 minutes at 3 work rates on a bicycle ergometer: 50 W, 125 W and 55% of maximum work rate (55% max). Each testing session included two work rates and only 2 testing sessions were scheduled per week. The order of the work rates was counterbalanced. In 8 to 10 weeks, 3 of the subjects completed 20 trials at 50 W while the fourth subject completed 11 trials, and all the subjects completed 10 trials at 125 W and 55% max. The within subject variability (S2w) was expressed as a percent of the mean steady-rate response. VO2 ranged from 21.2% to 27.5% of VO2max at 50 W, from 37.7% to 49.7% at 125 W and from 42.9% to 63.7% at 55% max. The S2w averaged 6.8% for VE, 4.3% for VO2, 3.2% for heart rate, 7.3% for systolic blood pressure and 10.5% for diastolic blood pressure. Reliability coefficients were calculated for the steady-rate scores by dividing the between subject variation by the total variation. The reliability was similar for VE, VO2 and heart rate and ranged from r = 0.69 to r = 0.97. Systolic and diastolic blood pressure reliabilities were lower and ranged from r = 0.27 and r = 0.80. In summary, the steady-rate ventilation, oxygen uptake and heart rate responses were reliable and consistent. The reliability of blood pressure was low. It is possible that this low reliability may result from variability in stroke volume or total peripheral resistance.

Adult↗

5-lipoxygenase inhibitory activity of zileuton.

Zileuton [N-(1-benzo[b]thien-2-ylethyl)-N-hydroxyure] inhibited 5-hydroxyeicosatetraenoic acid synthesis by rat basophilic leukemia cell 20,000 x g supernatant and rat polymorphonuclear leukocytes (PMNL) (IC50 = 0.5 and 0.3 microM) respectively. It also inhibited leukotriene (LT)B4 biosynthesis by rat PMNL (IC50 = 0.4 microM), human PMNL (IC50 = 0.4 microM) and human whole blood (IC50 = 0.9 microM). Inhibition of human PMNL LTB4 biosynthesis was removed readily by a simple wash procedure. At concentrations up to 100 microM, the compound produced little or no inhibition of several related enzymes, such as platelet 12-lipoxygenase, soybean and rabbit reticulocyte 15-lipoxygenase and sheep seminal vesicle cyclooxygenase. At p.o. doses from 0.5 to 5 mg/kg in the dog, zileuton produced a rapid and sustained inhibition of ex vivo blood LTB4 biosynthesis which correlated with the pharmacokinetic behavior of the compound. In a similar ex vivo study in the rat, the compound displayed an p.o. ED50 of 2 mg/kg. Zileuton was highly effective in preventing 6-sulfidopeptide LT formation in the rat peritoneal cavity triggered by an antigen-antibody reaction with an ED50 of 3 mg/kg. In experimental models of inflammation, zileuton significantly reduced arachidonic-acid induced mouse ear edema (ED50 = 31 mg/kg) and also attenuated inflammatory cell accumulation in the rat pleural Arthus reaction. The effectiveness of this compound for preventing LT formation in vitro, ex vivo and in vivo suggests its utility for preventing the pathophysiological effects of the LTs and other 5-lipoxygenase products in animals and in humans.

Administration, Oral↗

Fluid production by in vitro lungs from fetal guinea pigs.

Lungs from fetal guinea pigs (54-67 days of gestation) were supported in vitro, and lung liquid secretion rates were measured by a dye-dilution technique. The average secretion rate in the first hour was 2.14 +/- 0.08 (SE) mL x kg-1 body weight.h-1 (0.21 +/- 0.01 mL/h) (n = 450); this was comparable to intact preparations. In an independent study of 30 lungs, secretion continued unchanged for 3 h, with no significant change in fluid composition. Between 54 days and term, production appeared to fall in terms of millilitres per kilogram per hour. The following agents were placed in the supporting saline during the middle hour of incubation. (i) Sodium iodoacetate: at 10(-4) M this produced a fall in secretion (fall, succeeding hours; 55.4 +/- 23.0 and 64.9 +/- 17.5%; n = 6); at 10(-3) M it stopped secretion (fall, succeeding hours; 87.2 +/- 10.3 and 100%, n = 6). (ii) Ouabain: at 10(-5) M there was no change in production (n = 6); at 10(-4) M, four preparations were unaffected, two reduced production. (iii) Epinephrine (10(-7) M) produced a significant fall in production in all cases (n = 6); in four preparations secretion reduced (average fall, 64.4 +/- 10.8%); in two preparations there was reabsorption (average rate, -1.03 mL.kg-1.h-1). This extends the effect of epinephrine to the guinea pig, and suggests that the in vitro preparation is a useful model for studies of the fetal lung.

Animals↗

Electrophysiological measures of visual and auditory function as indices of neurotoxicity.

The application of auditory and visual evoked potentials (VEP) to neurotoxicity testing of humans and animals is reviewed. VEPs elicited by flash, reversing-checkerboard patterns, and sine wave grating are described. The flask evoked potential in rats is altered by exposure to many heavy metals, pesticides and solvents. The brainstem auditory evoked potential also appears to be sensitive to neurotoxic chemicals, but the evidence available is limited. The homology of auditory and visual evoked potentials in rats and humans is useful for cross-species extrapolation in neurotoxicology research.

Animals↗

Experiential factors in the expression of hypermotility produced by intradentate colchicine: lack of effect of GM1 ganglioside on colchicine-induced loss of granule cells and mossy fibers.

Adult male Fischer-344 rats were given bilateral injections of 2.5 micrograms colchicine or artificial cerebrospinal fluid into caudal and rostral sites of the dentate gyrus of the hippocampus. One group of rats received 21 consecutive daily injections of 20 mg/kg GM1 gangliosides, i.p., beginning the day prior to surgery. Another group received saline. Colchicine-induced hypermotility was not seen in animals repeatedly handled 21 d after surgery, in spite of significant decreases in granule cell number and decreases in the volume of hippocampal mossy fibers. Pretreatment with GM1 had no effect on behavior and it did not protect against the hippocampal damage produced by colchicine. Rats given colchicine, but not handled for 21 d, showed significant hypermotility, which was associated with decreases in hippocampal granule cells. These data underscore the importance of handling in postlesion functional recovery.

Animals↗

Radiation exposure to patients during extracorporeal shock wave lithotripsy.

Extracorporeal shock wave lithotripsy is rapidly becoming an accepted treatment of renal calculi. Since fluoroscopy is involved to image the stones it is important to know how much radiation the patient receives during this proCedure. Surface radiation exposure to the patient was measured in more than 300 fluoroscopic and radiographic procedures using thermoluminescent dosimeters. Initial results showed an average skin exposure of 10.1 rad per procedure for each x-ray unit, comparing favorably with exposure rates for percutaneous nephrostolithotomy and other routine radiological procedures. Factors influencing exposure levels include stone characteristics (location, size and opacity), physician experience and number of shocks required. Suggestions are given that may result in a 50 per cent reduction of radiation exposure.

Humans↗

Balloon dilatation of the prostatic urethra. Work in progress.

Balloon dilatation of the prostatic urethra was performed in eight dogs and one human with benign prostatic hyperplasia. This was done in vivo in six dogs and in vitro in two dogs and one human. Follow-up study at 1-23 weeks showed persistent dilatation, which was documented both radiographically and pathologically. Technical improvements limited complications to the early phase of the study. While results are encouraging, extrapolation to humans is difficult.

Animals↗

Osteopetrosis with calcifying tendinitis.

Osteopetrosis is a hereditary disease caused by cellular dysfunction. Calcifying tendinitis is a sequela of stress mediated by multinucleated cells in the tendon fibers. Our patient had both osteopetrosis and calcifying tendinitis. A related cellular dysfunction may predispose individuals with osteopetrosis to calcifying tendinitis.

Adult↗