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Biomedical subjects

B Woodward

Publications and source records attributed to B Woodward.

At least 91 records · Page 5Linked to original sources
PubMed1989

Dietary biotin requirements of young rainbow trout (Salmo gairdneri) determined by weight gain, hepatic biotin concentration and maximal biotin-dependent enzyme activities in liver and white muscle.

The objective of the present work was to determine the dietary biotin requirements of young, rapidly growing rainbow trout according to independently measured parameters. Two experiments were conducted with a purified diet which had a basal biotin level of 0.01-0.02 mg/kg. A third study was done with a nonpurified diet with or without a supplement of 1.0 mg biotin/kg. Each study was initiated with fry weighing less than 2 g/fish, and was continued for 16-20 wk at 15 degrees C. The first experiment, a cross-over design with pair-feeding, showed that the unsupplemented purified diet produced a biotin-specific deficiency condition in the trout. Dietary requirements could therefore be estimated (expt 2): maximal weight gain and maximal liver biotin concentration, 0.08 mg/kg; maximal activity of hepatic pyruvate carboxylase and acetyl CoA carboxylase, 0.05 mg/kg; and maximal white muscle pyruvate carboxylase activity, 0.14 mg/kg. No differences were found between fish fed the supplemented nonpurified diet and fish fed its unsupplemented counterpart (expt 3). The biotin requirement of the trout for growth does not exceed that of other vertebrates. These results also raise a question as to the level of supplementation which may be necessary for trout diets under field conditions.

Acetyl-CoA Carboxylase↗
PubMed1989

Effects of endothelin-1 on the rat isolated heart.

This study shows that bolus injections of endothelin-1 (ET-1) (1-30 pmol) produce transient vasodilator and prolonged coronary vasoconstrictor actions. The initial effect on cardiac contractility was a positive inotropic action, but with repeated doses a negative inotropic action developed. Verapamil (0.1 microM) antagonized the vasoconstrictor action of Bay K 8644 but did not affect ET-1-induced vasoconstriction. In contrast, removal of extracellular calcium did block the vasoconstrictor action of ET-1. This suggests that vasoconstriction is due to activation of receptor-rather than potential-operated calcium channels. The ET-1-induced vasoconstriction was not due to the release of platelet-activating factor (PAF) or thromboxane A2 since it was not inhibited by WEB 2086 (0.5 microM), fluribiprofen (2 microM), or BW755C (7 microM). In addition, thromboxane B2 could not be detected in the effluent from the heart. The vasoconstrictor action of ET-1 was potentiated by passage of air through the coronary vascular bed, suggesting that an intact endothelium normally opposes this vasoconstrictor effect.

Animals↗
PubMed1988

Involution of thymic epithelium and low serum thymulin bioactivity in weanling mice subjected to severe food intake restriction or severe protein deficiency.

The volume of epithelium in the cortex and in the medulla of the thymus was compared in four groups of weanling male and female CBA/J mice. Well-nourished controls (C), food intake restricted (R), and animals given a low-protein diet ad libitum (LP) were fed from 23 to 37 days of age. Baseline controls (B) were studied at 23 days of age. Epithelial volume fraction was estimated for each group by point-counting morphometry on electron micrographs. Other mice were used to obtain group mean estimates of thymic index (mg/g live weight) and volume fraction of cortex and medulla (light microscope-level point-counting morphometry). Cortical and medullary epithelial volumes were calculated for each animal examined by electron microscopy by obtaining the live weight and applying, in sequence, the group mean thymic index, an assumed thymic density of 1.0 mm3/mg, the group mean cortical or medullary volume fraction, and the measured cortical or medullary volume fraction for that animal. Serum thymulin bioactivity was also measured in C, R, and LP mice. The results reveal thymic epithelial involution in the two most common rodent models of malnutrition, and suggest that this may contribute to the low serum thymulin levels found in malnourished experimental animals and humans.

Animals↗
PubMed1988

Dissociation of immune capacity from nutritional status by triiodothyronine supplements in severe protein deficiency.

Weanling mice were fed ad libitum from age 23 to 37 days either an 18 or an 0.6% protein diet. Half the animals in each dietary group received supplemental triiodothyronine (T3, 0.2 mg/kg diet). T3 increased the primary in vivo antibody response of protein-deficient mice to sheep red blood cells, as measured by both splenic plaque-forming cells (PFC) per 10(6) nucleated spleen cells and serum hemagglutinin titers. T3 also increased PFC/spleen in well-nourished mice. The effect on protein-deficient animals was achieved although nutritional status in these animals, as estimated by weight loss and carcass composition, was further impaired by T3 supplementation. These results support the hypothesis that immune functions can be improved independently of nutritional status in severe (wasting) malnutrition. Insofar as T3 was effective in a model of malnutrition that does not reduce serum total or free T3 levels, the phenomenon appears to represent a pharmacological action of the hormone.

Animals↗
PubMed1988

Physiological and supraphysiological supplements of triiodothyronine do not influence the primary in vitro antibody response to trinitrophenylated Brucella abortus by spleen cells in serum-containing media.

T3 supplements enhance splenic primary thymus-independent antibody responses in the mouse in vivo. The purpose of the present investigation was to determine whether this effect may be mediated, in part, by direct influences on the lymphocytes and/or accessory cells involved in the response. A range of T3 levels (3 x 10(-10) to 10(-5) mol/l) was tested in microcultures of separated spleen cells from CBA/J mice 33 days of age. The immune reaction examined in vitro was the primary antibody response to trinitrophenylated Brucella abortus (TNP-BA). T3 was without influence, throughout the concentration range tested, on the number of anti-TNP plasma cells generated per culture. This result was obtained using splenocytes either from well-nourished or from malnourished mice, and using both optimal and suboptimal numbers of TNP-BA. On the basis of the present results and a reinterpretation of previous published work, it is concluded that the influence of T3 supplements on splenic antibody responses in vivo is mediated indirectly. Direct influences of T3 on the T-independent antibody response, if such occur, must be maximized by subphysiological levels of the hormone.

Animals↗
PubMed1987

The effects of ischaemia, lysophosphatidylcholine and palmitoylcarnitine on rat heart phospholipase A2 activity.

Phospholipase A2 activity was studied in the isolated rat heart following coronary artery ligation. In both the homogenate and mitochondrial fractions phospholipase A2 activity was significantly depressed at 20 min post ligation in the ischaemic region only. This is at a time of peak lysophospholipid concentration and severity of arrhythmias. No such depression of activity was seen in a crude sarcolemmal fraction, possibly due to washout of inhibitory factors during isolation. Lysophosphatidylcholine and palmitoylcarnitine, two amphiphiles known to accumulate during ischaemia, were both shown to be capable of inhibiting phospholipase A2. It is suggested that lysophospholipid and palmitoylcarnitine accumulation during ischaemia may contribute to the depression of phospholipase A2 activity seen and that the decreased metabolism of lysophospholipids may be of more importance in their accumulation than increased production by phospholipase A2.

Animals↗
PubMed1987

The effect of triiodothyronine on evanescent delayed hypersensitivity to sheep red blood cells and on the primary antibody response to trinitrophenylated Brucella abortus in severely undernourished weanling mice.

Two experiments were conducted using weanling male CBA/J mice. Animals were fed for 14 days a nutritionally complete diet, either ad libitum, or in restricted amounts such that they lost about 30% of their weaning weight during the feeding period. Half the animals from each food intake group received 0.2 mg triiodothyronine (T3)/kg diet. Evanescent delayed hypersensitivity to sheep red blood cells (SRBC) was depressed by malnutrition but not influenced by T3 supplementation. T3 increased nucleated spleen cell number in mice immunized with trinitrophenylated Brucella abortus (TNP-BA). The number of splenic anti-TNP direct plaque-forming cells (PFCs) was decreased by malnutrition when expressed on a per spleen basis. T3 supplements increased splenic PFC number of malnourished mice when results were expressed either per spleen or per 10(6) cells, and increased PFCs per spleen in well-nourished mice. Serum anti-TNP agglutinin titres were unaffected by malnutrition and by T3. The results extend our previous observations as to the improvement by T3 of the primary anti-SRBC antibody response of malnourished weanling mice, and suggest that therapeutic hormonal treatment could be used to improve antibody responses of malnourished individuals. The mechanism of the effect of T3 is unknown, but the lack of effect on delayed hypersensitivity to SRBC implies that T3 (when administered at the dosage of the present protocol) acts on only some immune cells and does not exert a generalized adjuvant effect.

Animals↗
PubMed1987

Epithelial and pillar cell replacement in gills of juvenile trout, Salmo gairdneri Richardson.

Young rainbow trout, Salmo gairdneri (Richardson) were injected intraperitoneally with tritiated thymidine, and killed at intervals between 2 hr and 16 days after inoculation. Labelled epithelial cells were first detected autoradiographically along the base of gill lamellae. Epithelial cells proliferated here and then migrated toward the tips of the lamellae. Uniform labelling along the length of the filaments at the base of lamellae indicated that cells were dividing at a constant rate. Transverse sections of filaments showed that epithelial proliferation was also uniform across the base of the lamellae. The interior of the lamellae often had labelled pillar cells, indicating that these cells also divide. The high intensity of the label in animals killed 16 days after inoculation with tritiated thymidine suggests that division probably occurs slowly, less than once every 16 days.

Animals↗
PubMed1987

Triiodothyronine improves the primary antibody response to sheep red blood cells in severely undernourished weanling mice.

Three experiments were conducted in which weanling mice were fed a nutritionally complete diet either ad libitum or in restricted quantities such that they lost about 30% of their initial weight over a 14-day period. In Experiments 1 and 2, half the animals from each group received dietary triiodothyronine (T3) supplements. In Experiment 3, food-intake-restricted mice were fed graded levels of potassium iodide. Malnutrition reduced the number of nucleated cells per spleen, the number of splenic IgG plaque-forming cells (PFC) per 10(6) cells, and the serum antibody titers against sheep red blood cells. T3 supplements increased antibody titers, the number of nucleated cells per spleen, and both IgM and IgG PFC per 10(6) spleen cells in malnourished mice, but had no effect on well-nourished mice. The beneficial effect of T3 was not a result of improved protein, energy, or iodine status in the malnourished mice.

Animals↗
PubMed1986

The role of catecholamines in the production of ischaemia-induced ventricular arrhythmias in the rat in vivo and in vitro.

The role of catecholamines in the production of ischaemia-induced ventricular arrhythmias in vivo and in vitro was studied using coronary artery ligation in the rat. Increases in plasma catecholamine concentrations during coronary artery ligation in pentobarbitone-anaesthetized animals were prevented by either acute adrenalectomy or chronic adrenal demedullation, but these procedures did not protect against the occurrence of ventricular arrhythmias. Thus plasma catecholamines were not obligatory mediators of arrhythmogenesis. Three protocols were used in vitro to evaluate the possible influence of intramyocardial release of noradrenaline, produced by the local conditions of ischaemia, on the production of ventricular arrhythmias. During coronary artery ligation in isolated perfused hearts, no enhanced output of 3H could be detected from [3H]-noradrenaline loaded hearts, even in the presence of inhibitors of catecholamine uptake processes, although washout of lactate from ischaemic regions was readily demonstrable. Both optical isomers of propranolol were equally effective in reducing the incidence of arrhythmias, implying a non-specific effect, since the (+)-isomer possesses considerably less beta-adrenoceptor blocking activity. The equipotency of optical isomers of propranolol combined with a lack of effect of atenolol suggested that arrhythmia production was not a consequence of beta-adrenoceptor stimulation. The alpha-adrenoceptor blockers phentolamine and prazosin, both exerted antiarrhythmic actions of similar potency, but phenoxybenzamine and trimazosin had no significant effects. An evaluation of the pharmacological properties of the alpha-adrenoceptor blockers showed that those drugs which had demonstrable local anaesthetic properties also exerted significant antiarrhythmic effects. No relationship was found between potency of alpha-adrenoceptor blockade and antiarrhythmic efficacy. The overall conclusion from these multifaceted approaches was that catecholamines were not necessary mediators of the early phase of ventricular arrhythmias in the rat.

Adrenal Medulla↗
PubMed1985

Effect of some free radical scavengers on reperfusion induced arrhythmias in the isolated rat heart.

The possible role of oxygen free radicals in the development of reperfusion arrhythmias was investigated using a 10-min period of coronary ligation followed by reperfusion in the isolated rat heart. Superoxide dismutase (5 to 20 u/ml) glutathione (10(-5) to 10(3)M) and ascorbic acid (10(-4) to 5 X 10(-4) M) when given before coronary ligation attenuated the development of reperfusion arrhythmias. Mannitol (2 X 10(-2)M) and catalase (100 and 300 u/ml) did not have any significant effect on reperfusion arrhythmias when given alone but they did potentiate the antiarrhythmic effect of superoxide dismutase. Glutathione, and a combination of superoxide dismutase, catalase and mannitol also reduced the incidence of reperfusion induced ventricular fibrillation when given just before reperfusion. By perfusing hearts with ferricytochrome C it was possible to show an increased reduction of ferricytochrome C during the first minute of reperfusion which could be prevented by the addition of superoxide dismutase. These results provide evidence that oxygen free radicals are produced and may be important in the genesis of reperfusion induced arrhythmias in the isolated rat heart.

Animals↗
PubMed1985

Riboflavin requirement for growth, tissue saturation and maximal flavin-dependent enzyme activity in young rainbow trout (Salmo gairdneri) at two temperatures.

Two temperatures (10 degrees and 15 degrees C) and two fish stocks differing in growth potential were used to determine the dietary riboflavin requirement of young rainbow trout (Salmo gairdneri) on the basis of growth parameters, tissue saturation and a flavin-dependent biochemical function. Two experiments were conducted with purified diets based on vitamin-free casein. In experiment 1, fry (initially 2.0 g/fish) were fed, for 16 wk at 15 degrees C, diets containing 0.6, 2.6, 3.6, 4.6, 5.6 or 6.6 mg riboflavin per kilogram diet. In experiment 2, fry (initially 1.7-1.8 g/fish) were held at either 10 degrees or 15 degrees C and fed, for 10 wk, diets containing 0.7, 2.7, 3.7, 4.7, 6.7 or 8.7 mg riboflavin per kilogram. The riboflavin requirements for maximal growth rate, liver flavin saturation, spleen and head kidney flavin saturation and maximal hepatic D-amino-acid oxidase activity were 3.6, 4.6, 6.6 and 5.6 mg/kg diet, respectively, in a diet containing 40% crude protein and 15% ether extract. The requirements were not affected by temperature or by genetically determined differences in maximal growth rate. When expressed on a dietary energy basis, the riboflavin requirements of the trout for maximal growth rate and liver flavin saturation appear similar to those of several homeothermic species.

Animal Nutritional Physiological Phenomena↗
PubMed1985

Carbachol and dibutyryl cyclic GMP on the vulnerability to ventricular fibrillation in rat isolated hearts.

The hypothesis that elevation of intracellular guanosine 3':5' cyclic monophosphate (cyclic GMP) concentrations may increase electrical stability of the myocardium was examined by determination of ventricular fibrillation thresholds (VFT) on isolated perfused hearts of the rat. Hearts were paced to circumvent any complicating effects of bradycardia. Using this system, carbachol produced a concentration-related reduction in VFT. The reduction in VFT produced by carbachol was not significantly modified by a high concentration of atenolol (10(-5)M), indicating that the increased vulnerability to ventricular fibrillation was not an indirect consequence of catecholamine release from intramyocardial stores. Atropine (10(-6)M) blocked the carbachol-induced reduction in VFT. At the concentrations of carbachol used to reduce VFT, myocardial cyclic GMP concentrations were also elevated. The dibutyryl analogue of cyclic GMP (10(-4)M) mimicked the effect of carbachol in reducing VFT. Carbachol potentiated the adrenaline (3 X 10(-7)M)-induced reduction in VFT.

Animals↗
PubMed1985

High prevalence of intermittent acute porphyria in a psychiatric patient population.

The authors screened 3,867 psychiatric inpatients for intermittent acute porphyria by use of a spot test to detect diminished activity of the erythrocyte enzyme porphobilinogen (PBG) deaminase. Eighteen individuals so identified also had persistently diminished quantitative activity of PBG deaminase. Eight of these appeared to have intermittent acute porphyria by the added criteria of increased urinary delta-aminolevulinic acid or PBG or a family history of intermittent acute porphyria. The overall prevalence of intermittent acute porphyria was 0.21%, a considerably higher rate than that in the general population. Most of the subjects with the disorder had periods of agitated psychosis and apathetic or depressed withdrawal, with signs of neuropsychological impairment. Neurologic abnormalities were not prevalent.

Acute Disease↗
PubMed1985

Thymic epithelial cells of severely undernourished mice: accumulation of cholesteryl esters and absence of cytoplasmic vacuoles.

The thymic epithelium was compared in weanling male and female CBA/J mice when fed ad libitum and when subjected to severe food intake restriction for 14 days. The restriction protocol elicited predominantly a metabolic response to caloric deficit rather than to protein deficiency. Electron microscopy revealed intracytoplasmic accumulations of large, circular, homogeneously electron-dense profiles (with no limiting membrane) in a high proportion of cortical and medullary epithelial cells of thymuses from restricted mice, but not from controls. The electron-dense material was not preserved in the absence of osmium. Thin-layer chromatography (TLC) indicated elevated levels of free and esterified cholesterol, particularly the latter, in whole thymus extracts of restricted mice. Measurements of total cholesterol levels in the thymic extracts were consistent with the results obtained by TLC. In addition, cryostat sections of thymuses from restricted mice, but not from controls, exhibited numerous stained foci throughout the cortex and medulla when treated with oil red O (a general neutral lipid stain) or by the Schultz procedure which is specific for cholesterol. Collectively the results suggest accumulations of cholesteryl esters, together with some free cholesterol, as non-membrane-bound droplets in the cytoplasm of thymic epithelial cells of undernourished mice. It is also of interest that the lipid-laden epithelial cells exhibited none of the cytoplasmic vacuoles observed in controls and believed to be important in thymic hormone secretion. This work provides the first direct evidence of thymus epithelial abnormalities in severe protein-energy malnutrition.

Animals↗
PubMed1983

A waveguide pulse-echo system for ultrasonic absorption measurements in biological media.

The system described has been designed for measurements of ultrasonic absorption in suspensions of biological cells. A novel feature of the design is the provision of a wave-guide sample tube which prevents beam diffraction. This ensures that the ultrasonic energy is wholly constrained between a single transducer and a moveable air-backed reflector, and is lost only by absorption in the sample. The associated electronics comprises a simple ultrasonic generator with variable power output, carrier frequency and mark-space ratio, and a digital thermometer with a thermistor probe for measuring the sample temperature.

Absorption↗