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Biomedical subjects

D Billington

Publications and source records attributed to D Billington.

At least 19 recordsLinked to original sources
PubMed2004

Effect of changing to a self-selected vegetarian diet on anthropometric measurements in UK adults.

BACKGROUND: Vegetarians are often a little leaner compared with nonvegetarians and suffer less from obesity and its associated complications than nonvegetarians. Whether this is because of not eating meat specifically is unclear. OBJECTIVE: We investigated whether changing to a self-selected vegetarian diet resulted in changes to anthropometric measurements. Design Subjects (n = 33; seven males and 26 females) who were in the earliest stages of becoming vegetarian were observed for 6 months. Data on dietary intake, using a 3-day estimated dietary diary, and body composition were obtained at baseline and after 6 months of following a self-selected vegetarian diet. RESULTS: Dietary calculations showed that on changing to a self-selected vegetarian diet, there was a significant reduction (P < 0.05) in energy intake (8.9 MJ day(-1) versus 8.1 MJ day(-1)), and in the proportion of energy from saturated fatty acids (12.9% versus 11.3%) and a significant increase (P < 0.05) in the proportion of energy from carbohydrates (44.9% versus 47.5%) and in intake of nonstarch polysaccharides (NSP) (1.6 g MJ(-1) versus 2.0 g MJ(-1)). Significant reductions in mid-upper arm circumference, calculated body fat, biceps and triceps skinfolds and waist and hip circumferences were observed. No reduction in body weight was observed. CONCLUSION: The findings of our study suggest that significant dietary changes, helping people to conform more closely to current dietary recommendations, occurred when people became vegetarian. In this study we did not find any significant change in body weight, but significant reductions were observed in skinfold thickness and waist : height ratio which imply that on changing to a self-selected vegetarian diet, the subjects became leaner.

Adipose Tissue↗
PubMed2003

Separation of bovine plasma lipoproteins by a rapid ultracentrifugation method.

The recently described method of centrifugation with iodixanol for the rapid separation of human plasma lipoproteins was adapted to separate bovine plasma lipoproteins. Density gradients were generated by mixing plasma with iodixanol 12% (w/v), followed by centrifugation at 350,000 g and 16 degrees C for 3 h 10 min in a vertical rotor. Gradients were unloaded dense-end first into 10 fractions. Human very low density lipoprotein (VLDL; density < 1.011 g/ml), low density lipoprotein (LDL; density = 1.016-1.039 g/ml) and high density lipoprotein (HDL; density = 1.039-1.090 g/ml) were resolved well at densities considerably lower than those traditionally reported in salt gradients. In gradients generated from 12% iodixanol, bovine LDL and HDL exhibited even lower densities (1.016-1.028 and 1.016-1.048 g/ml, respectively) with all lipoproteins occurring at the lower density region of the gradient. In contrast, density gradients generated from layers of equal volumes of 6% and 12% iodixanol readily separated bovine HDL from VLDL, whilst LDL still overlapped with HDL. The latter accounts for >80% of all bovine lipoproteins and exists as two populations, namely light and heavy HDL. Gradients generated from two layers of iodixanol recovered bovine HDL in five fractions. The hypercholesterolaemia associated with lactation resulted in a modest shift in the profile of HDL cholesterol towards lipoprotein particles of lower density (light HDL). Significant between-farm differences were also detected in the density profiles of bovine plasma cholesterol. This new method is suitable for use in research and diagnosis in relation to lipoprotein metabolism disorders in cows.

Animals↗
PubMed2002

Changing from a mixed to self-selected vegetarian diet--influence on blood lipids.

OBJECTIVE: To observe any changes in serum concentrations of lipids, when UK meat-eaters switch to a self selected vegetarian diet for 6 months. DESIGN: Observational study using capillary blood samples and 3-day estimated dietary diary. SETTING: Free-living subjects in the North-West of England. SUBJECTS: Twelve male and 31 female adult volunteers aged between 18 and 42 years. OUTCOME MEASURES: Serum lipids; nutrient intake and anthropometric measurements at baseline and 6 months after switching to a self-selected vegetarian diet. RESULTS: Total energy intake and amount of energy derived from saturated fatty acids decreased significantly after changing to a vegetarian diet (P < 0.05) whereas energy derived from carbohydrate, and intakes of nonstarch polysaccharide intake increased. On switching to a vegetarian diet, total cholesterol and triacylglycerol concentrations were not significantly changed, but HDL-C was 21% higher than at baseline (1.21 mmol L(-1) vs. 1.47 mmol L(-1); P = 0.001). CONCLUSIONS: These results suggest that beneficial changes to diet occurred on changing to a self-selected vegetarian diet. Changing to a self-selected vegetarian diet appears to be one way of achieving a better blood lipid profile.

Adolescent↗
PubMed2000

Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans.

Garlic has been widely reported to protect against cardiovascular disease by reducing serum cholesterol concentrations and blood pressure and by inhibiting platelet aggregation. However, most of these studies have been performed in hypercholesterolemic subjects or in animal models. We performed a 13-wk study in normolipidemic subjects who ingested 5 mL of aged garlic extract (AGE, Kyolic) per day. Blood was drawn from these subjects at the beginning and end of the study. Aggregation of platelet-rich plasma was induced by ADP; full lipid profiles and liver function tests were determined on serum, and plasma concentrations of eicosanoids were also measured. Dietary supplementation with AGE significantly inhibited both the total percentage and initial rate of platelet aggregation at concentrations of ADP up to 10 micromol/L. The K:(M) for ADP-induced aggregation were approximately doubled after supplementation with AGE, whereas the maximum rate of aggregation was unaffected. No significant changes in plasma thromboxane B(2) and 6-ketoprostaglandin F(1alpha) concentrations or serum lipid profiles were observed. We conclude that AGE, when taken as a dietary supplement by normolipidemic subjects, may be beneficial in protecting against cardiovascular disease as a result of inhibiting platelet aggregation.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

The use of orbital morphine for postoperative analgesia in pterygium surgery.

A prospective double-blind study compared the analgesic effectiveness of peribulbar lignocaine with peribulbar morphine and lignocaine for postoperative analgesia in pterygium surgery. Twenty patients were randomly divided to receive a peribulbar injection preoperatively of either 1% lignocaine 2 ml or 1% lignocaine 1.6 ml and 4 mg morphine. Effects on pain at injection and pain at 24 hours and 48 hours postoperatively were measured with a visual analog pain scale. Effects of the injections on sedation, pupil size and unwanted side-effects were also recorded. The groups were comparable for age, weight and surgical technique. There was a significantly lower pain score at 24 hours after operation in the morphine group (P = 0.035). There were no significant differences in sedation or side-effects between the groups. The physiological effects of morphine on the eye are reviewed. The study suggests that orbital morphine may be an effective and safe form of analgesia for corneal surgery and further investigation is warranted.

Adult↗
PubMed1999

Treatment with aged garlic extract protects against bromobenzene toxicity to precision cut rat liver slices.

Precision-cut liver slices from phenobarbital-induced rats were incubated for 6 h with the model hepatotoxin bromobenzene (BB) at a final concentration of 1 mM. Severe toxicity was indicated by a decreased K+, adenosine triphosphate and glutathione (GSH) content of the slices, increased release of alanine aminotransferase and lactate dehydrogenase into the medium, and increased formation of thiobarbituric acid reacting substances. Pretreatment of animals for 7 days with aged garlic extract (AGE) (Kyolic) at doses of 2 and 10 ml/kg/day dramatically reduced the toxicity of BB in a dose-dependent manner. The GSH content of liver slices from rats treated with AGE at 2 or 10 ml/kg/day increased by 50 and 80%, respectively. The BB-induced decrease in GSH content was less in slices derived from AGE-treated rats compared with slices from control rats. Pretreatment with AGE did not affect cytochrome P450 when assayed as 7-ethoxycoumarin O-deethylase and 7-pentoxyresorufin O-depentylase activities in hepatic microsomes. Thus, the mechanism by which pretreatment with AGE protects against BB hepatotoxicity involves both an elevation of hepatic GSH content, and a GSH sparing effect, possibly due to conjugation of organosulphur compounds in AGE with toxic BB metabolites. Only this GSH sparing effect was seen in our earlier study on the in vitro hepatoprotective effect of AGE [Wang et al., 1998. Toxicology 126, 213-222].

Adenosine Triphosphate↗
PubMed1999

Carotenoid composition and antioxidant potential in subfractions of human low-density lipoprotein.

Carotenoids and vitamin E are transported in human plasma complexed with lipoproteins. The bulk of them are associated with low-density lipoprotein (LDL), in which form they may act as antioxidants and thus delay the onset of atherosclerosis. We used a simple, rapid, ultracentrifugation technique to fractionate plasma lipoproteins in self-generating gradients of iodixanol (Optiprep), a non-ionic iodinated density gradient medium. The carotenoid content and composition of a number of LDL subfractions was determined by reversed-phase high-performance liquid chromatography. Lycopene, beta-carotene and beta-cryptoxanthin were mainly located in the larger, less-dense LDL particles whereas lutein and zeaxanthin were found preferentially in the smaller, more dense LDL particles. When the antioxidant content of these fractions was expressed per milligram of LDL protein, significantly lower concentrations of carotenoid and vitamin E were found to be associated with the smaller, protein-rich fractions of LDL. Strong positive correlations were found between total carotenoid and vitamin E plasma concentrations and the lag-time of Cu(2+)-mediated oxidation of LDL subfractions. The more dense LDL subfractions, which had lower levels of these antioxidants, were more readily oxidized, highlighting their possible role in atherosclerotic events.

Antioxidants↗
PubMed1998

Dissection of hepatic receptor-mediated endocytic pathways using self-generated gradients of iodixanol (Optiprep).

Iodixanol is a new, nonionic, iodinated density gradient medium which has an advantage over other similar media in that it rapidly forms self-generated gradients in vertical or near-vertical rotors. Endocytosis of 99mTc-labeled neogalactosyl albumin (99mTc-NGA), a synthetic ligand for the asialoglycoprotein receptor, was studied by administering the ligand as a short pulse to perfused rat livers operating under single-pass conditions. Intracellular processing was arrested at various times after the pulse and the resultant homogenate cleared of nuclei and heavy mitochondria by centrifugation at 3000 g for 10 min. After adjustment to 12.5% (w/v) iodixanol, the 3000 g supernatants were centrifuged at 350,000 g for 60 min to form the gradients in which early, clathrin-containing vesicles, low-density endosomes, and lysosomes were well-resolved. 99mTc-NGA bound to the sinusoidal membrane could be partially resolved from clathrin-containing vesicles by inclusion of 1 mM CaCl2 in the homogenization and gradient buffers. Two populations of early clathrin-containing vesicles could be resolved by rate-zonal centrifugation in preformed iodixanol gradients. Thus, iodixanol is an excellent density gradient medium for the rapid and efficient resolution of endosome compartments.

Albumins↗
PubMed1998

Protective effects of aged garlic extract against bromobenzene toxicity to precision cut rat liver slices.

Precision-cut liver slices from phenobarbital-treated rats were incubated for up to 8 h with the industrial solvent and hepatotoxin bromobenzene at a final concentration of 1 mM. Phenobarbital pretreatment potentiates bromobenzene hepatotoxicity by inducing those P450 isoforms responsible for the formation of the active hepatotoxin, namely bromobenzene-3,4-oxide. A reduction in cell viability was indicated by a decrease in the K+, ATP and glutathione content of the slices and the increased release of the intracellular enzymes, lactate dehydrogenase and alanine aminotransferase, into the medium. Furthermore, levels of lipid peroxidation as judged by the formation of thiobarbituric acid reactive substances, were increased approximately 5-fold. Aged garlic extract (AGE) at concentrations of 1-5% (v/v) reduced the toxicity of bromobenzene in a concentration-dependent manner as judged by all of the parameters of viability studied, with the exception of lipid peroxidation which was reduced to control levels even at the lowest concentration of garlic extract used. AGE was found to cause partial inhibition of cytochrome P450 when assayed as both 7-ethoxycoumarin O-deethylase and 7-pentoxyresorufin O-depentylase activities, but even the highest concentration used inhibited both activities by less than 50%. It is suggested that the hepatoprotective effects of AGE are due primarily to the reduced glutathione-sparing properties of its constituents, most probably its organosulphur compounds.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1997

Effects of cyclosporin A on paracellular and transcellular transport of horseradish peroxidase in perfused rat livers.

The immunosuppressive agent cyclosporin A (CsA) is known to cause cholestasis. Transcellular and paracellular transport of macromolecules contribute, albeit to a minor extent, to bile formation, but little is known about the effects of CsA on these pathways. The aims of this study were to investigate the influence of CsA on tight junction (paracellular) permeability and on transcytotic vesicular pathways labeled with horseradish peroxidase (HRP) in perfused rat liver. Livers from male Sprague-Dawley rats were perfused with Krebs-Henseleit buffer (albumin 1%, RBC 20%, and amino acid mixture). Taurodehydrocholate (1 microM/min) was coinfused into the portal vein; 1 microg/ml of CsA, dissolved in Cremophor-EL (CsA livers), or the vehicle alone (CEL livers), was added to the medium. Tight junction permeability was assessed by administering HRP (25 mg) as a short pulse to perfused rat livers, operating under single-pass conditions. Under such conditions, HRP output into the bile shows two components: an initial peak at approximately 3-5 min, corresponding to paracellular transfer across tight junctions, and a second peak at approximately 15 min, corresponding to vesicular transport. Furthermore, we assessed the vesicular transport pathway by examining HRP-labeled vesicles in the perisinusoidal (PS) and pericanalicular (PC) areas using ultrastructural morphometric analysis. To analyze HRP in hepatocytes and to study rapid and late transcytotic vesicular pathways, a 1-min pulse of a high dose of HRP (500 and 200 mg, respectively) was given. Two and 18 min after single-pass perfusion the livers were fixed with 2.5% glutaraldehyde-0.8% paraformaldehyde in 0.1 mM cacodylate buffer, pH 7.8. The total pericanalicular area, the HRP-containing structures, were quantified morphometrically in liver samples. At concentrations of 1.2 microg/ml, CsA produced a twofold increase in the paracellular transfer of HRP to bile. The areas under the second peak (transcellular vesicular pathway) of the biliary HRP secretion curve were similar in CEL- and CsA-treated livers. Morphometric analysis confirmed that CsA treatment did not affect the percentage area of HRP-labeled vesicles in either the pericanalicular or in the perisinusoidal area at 2 min (rapid pathway) and 18 min (late pathway). These results indicate that CsA increases tight junctional permeability whereas it does not inhibit rapid or late transcytotic vesicle pathways.

Animals↗
PubMed1996

Hepatic inactivation of Leu-enkephalin.

Leu-enkephalin radiolabelled at the N-terminal tyrosine by two different methods was presented to isolated perfused rat livers. Approximately 10% of a pulse of tritiated Leu-enkephalin was taken up first-pass; this was increased to 62% when the peptide was iodinated with Bolton and Hunter reagent. Uptake of both forms of radiolabelled Leu-enkephalin was inhibited by taurocholate in a concentration-dependent manner. The proportion of internalised radioactivity secreted into bile also differed but in both cases showed a very rapid time-course similar to that of [24-(14)C]taurocholate and suggestive of non-endocytic transfer via membrane transport proteins. Pre-perfusion with the aminopeptidase inhibitor bestatin increased uptake of 3H-labelled Leu-enkephalin from 10% to 23%; no further increase occurred when the endopeptidase 24.11 inhibitor thiorphan was also present. On infusion of the native peptide into rat livers, 80% of Leu-enkephalin immunoreactivity was lost between the pre- and post-hepatic perfusate; this was reduced to 65% in the presence of 10(-5) M bestatin. The almost total release of the N-terminal tyrosine from 3H-labelled Leu-enkephalin which escaped first-pass uptake confirmed that substantial sinusoidal metabolism had occurred. Low levels of aminopeptidase N were visualised in the sinusoidal membrane using a specific monoclonal antibody coupled to peroxidase staining. Thus, hepatic inactivation of Leu-enkephalin is primarily via hydrolysis mediated by cell surface peptidase (including aminopeptidases) whilst uptake of the intact peptide, probably by a bile salt transport protein, is quantitatively minor unless the N-terminus is blocked by Bolton and Hunter reagent or peptidase inhibitors are present.

Animals↗
PubMed1996

A novel method for the rapid separation of plasma lipoproteins using self-generating gradients of iodixanol.

We describe a new method for the rapid fractionation of plasma lipoproteins, which makes use of a new non-ionic, iodinated, density gradient medium, iodixanol, commercially available as Optiprep(TM). The method is simple: plasma or serum is mixed with iodixanol followed by centrifugation in a vertical or near vertical rotor. Separation of VLDL, LDL and HDL can be achieved in 3 h and the lipoprotein fractions are comparable in density and composition with those prepared using conventional salt based gradients. Each class of lipoprotein can be removed in a single fraction, or a profile of lipoprotein distribution can be obtained using a gradient fractionator. Because the medium is inert, fractions from the gradient can be analysed by agarose gel electrophoresis or assayed for lipid content or apolipoprotein composition by SDS-PAGE without removing the iodixanol. Small differences in electrophoretic mobility of HDL and LDL across several gradient fractions suggest that subfractionation of these classes may occur. The new method is simple, rapid and versatile with potential application for preparation of lipoproteins and for analysis of lipoprotein profiles in the research or clinical laboratory.

Apolipoproteins↗
PubMed1996

Intestinal permeability and orocaecal transit time in elderly patients with Parkinson's disease.

The aetiology of weight loss in patients with Parkinson's disease is likely to be multifactorial. We studied 15 patients with Parkinson's disease and 15 age- and sex-matched controls and looked for evidence of malabsorption due to small bowel bacterial overgrowth or alteration of intestinal permeability. There was a marked increase in orocaecal transit time in the patients with Parkinson's disease, although lactulose hydrogen breath testing did not show evidence of small bowel bacterial contamination. Intestinal permeability measured by the differential sugar absorption test was also deranged. There was reduced absorption of mannitol in patients with Parkinson's disease while lactulose absorption was similar in both groups, suggesting decreased non-mediated uptake across the enterocyte brush border membrane in patients with Parkinson's disease.

Aged↗