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Biomedical subjects

B Woodward

Publications and source records attributed to B Woodward.

At least 109 records · Page 6Linked to original sources

An investigation of the importance of the adrenal gland to the action of dopamine in the rat kidney.

1 In the rat, administration of dopamine is associated with diuresis, natriuresis and a decreased excretion of K+. The site of action of dopamine in mediating these responses has been investigated. 2 Urine volume, and urinary Na+, K+, Cl- and dopamine concentrations have been measured in adrenalectomized and sham-operated male Wist ar rats. 3 As expected, adrenalectomy decreased urine volume and increased Na+ and Cl- excretion; at the same time the amount of dopamine excreted fell, and K+ excretion did not change. 4 Administration of either 3% NaCl (20 ml/kg orally) or frusemide (100 mg/kg s.c.) significantly elevated dopamine excretion after adrenalectomy. 5 When dopamine, 1, 10 and 30 mg/kg (s.c.) was given to adrenalectomized rats, the diuresis and fall in K+ excretion seen in control animals was still present. No further natriuresis, over and above the already high urinary Na+ levels, was observed. 6 The results show that the three actions of dopamine in inducing diuresis and natriuresis, and decreasing K+ excretion, are clearly separable. 7 It is further argued that in mediating these effects the main site of action of dopamine is the kidney rather than the adrenal gland.

Adrenal Glands↗

The effect of severe protein deficiency on serum zinc concentration of mice fed a requirement level or a very high level of dietary zinc.

The objective of the present study was to determine the effect of severe dietary protein deficiency on serum zinc concentration in weanling animals fed either a requirement level or a very high level of dietary zinc. Weanling (21-day-old) male and female CBA/J mice were randomly assigned to be fed one of four diets containing either 1.7% or approximately 18.5% protein and either 7 micrograms (predetermined requirement level) or about 200 micrograms zinc per gram of formulation. Serum zinc levels were measured after a 14-day feeding period. Dietary zinc content, over the range tested, did not influence the serum zinc level of protein deficient mice, and these animals exhibited serum zinc concentrations which were much lower than the levels found in adequately nourished mice fed the requirement level of zinc (7 micrograms/g diet). These results indicate that dietary zinc supplementation is unable to restore to normal the zinc status of severely protein-deficient animals. This may be an important factor to consider when studying the effect of protein deficiency on zinc-sensitive physiological processes.

Animals↗

Riboflavin supplementation of diets for rainbow trout.

The present study was designed to determine whether a modern practical trout grower diet requires riboflavin supplementation and whether the levels of this vitamin currently included in trout diets may be within a toxic range. Six diets differing only in the level of riboflavin supplementation (0, 4, 10, 25, 50 and 100 mg/kg diet) were formulated from a basal mix, which supplied 8.2 mg/kg. The diets were fed in a randomized complete block design to 18 tanks of 100 fish, and the experiment continued for 5 periods of 28 days. The fish fed a supplement of 4 mg/kg diet achieved a greater final liveweight than those fed supplements of 0, 50 or 100 mg/kg. Other growth parameters (condition factor and carcass composition) as well as food consumption and feed-conversion efficiency were unaffected by the level of dietary riboflavin. The unsupplemented basal diet supported flavin saturation of liver and heart but not of spleen, head kidney or posterior kidney, a finding consistent with the inability of this diet to promote maximal liveweight gain. The results suggest that, although riboflavin supplementation of practical trout diets is advisable, an optimal level of supplementation exists. The rainbow trout may exhibit sensitivity to high levels of dietary riboflavin.

Animals↗

Strain and sex differences in serum alpha-fetoprotein levels in Mus musculus.

Normal levels of circulating serum alpha-fetoprotein (AFP) in different inbred strains of mice, as determined by radioimmunoassay, are reported. These strains show different and characteristic values for the mean serum AFP concentration, suggesting genetic control of the serum level of this protein. Furthermore, within each strain a difference in serum levels of the protein is observed between sexes; males have a significantly higher serum AFP concentration.

Animals↗

A study of the influence of the ambient microflora on the structure of lung alveolar macrophages and an ultrastructural comparison of lung and peritoneal macrophages in germ-free and conventionally reared mice.

In order to investigate quantitatively and objectively the influence of the normal microbial flora on the ultrastructure of the alveolar macrophage, three groups of mice were studied stereologically: germ-free (GF), conventionally reared under non sterile isolation conditions (IC), and conventionally reared in an open environment (OC). The alveolar macrophages of GF mice possess a smaller mitochondrial compartment, possibly with fewer organelles, than the macrophages of conventional mice. Other influences of the normal microflora on alveolar macrophage substructure are obscured by the effects of nonmicrobial stimuli such as droplets of lung surfactant. No previous comparison exists of alveolar and peritoneal macrophage ultrastructure. Lung macrophages are larger than the phagocytes of the peritoneum, but the difference in size is much less than is commonly believed. Alveolar macrophages are rounder than peritoneal macrophages, and exhibit much less rough endoplasmic reticulum (RER) as well as differences in mitochondrial morphometry. No difference in mitochondrial volume fraction exists between the two types of macrophage even though alveolar macrophages represent the extreme of aerobic adaptation in the mononuclear phagocyte system. Phagosomes occupy a significant fraction of cellular volume only in the alveolar macrophages. Moreover alveolar phagocytes contain fewer but larger represent the first objective, quantitative structural evidence confirming the common belief that alveolar macrophages experience greater physiological stimulation than peritoneal macrophages. The normal microflora accounts for only a small proportion of the differing degree of stimulation exerted on the two types of macrophage.

Animals↗

A model of ventricular fibrillation in the isolated rat heart.

A simple technique is described for the induction of reversible ventricular fibrillation in the isolated rat heart. Fibrillation is induced by doubling the calcium chloride and halving the sodium chloride concentration of the perfusate. Fibrillation can be prevented by Class I antiarrhythmic drugs and verapamil.

Animals↗

Factors affecting the release and excretion of dopamine in the rat.

The effects of inorganic salts and of diuretic agents on the excretion of dopamine (DA) were examined in the rat. Both types of treatment evoked significant increases in urinary DA excretion, urine volume and urinary sodium excretion. In the salt-treated animals a significant correlation was observed between DA excretion and urine volume, whereas after diuretic treatment there was better correlation between DA and urinary sodium excretion. The salt-treated animals showed a high correlation between administered chloride and DA excretion. Subcutaneous administration of DA produced a significant diuresis and an increase in sodium excretion. The mechanisms responsible for these responses are discussed with reference to the possibility that DA has a physiological role in the kidney.

Animals↗

A stereological ultrastructural study of stimulated peritoneal macrophages in the germ-free mouse.

Peritoneal macrophage ultrastructure was analysed stereologically in germ-free mice given a single intraperitoneal injection of sterile, pyrogen-free saline. Thus the stimulant was non-particulate, non-antigenic and inorganic, and effects of immune reactions were minimal. Macrophages were recovered 1, 6, 24 and 72 h after stimulation. A sequence of structural alterations is reported which may be fundamental to macrophage activation. The plasma membrane and nuclear envelope increased in area within only 1 h of saline injection. During the next 5 h loss of plasma membrane, probably by pinocytosis, caused cellular "rounding" and clear-cut alteration in surface configuration. At the same time lysosome-like granules enlarged but decreased in number. By 24 h most cellular structures and compartments (including the plasma membrane) were enlarged. Morphological evidence of nuclear activation accompanied a rather modest enlargement of the nucleus at this stage. The RER hypertrophied last and must, therefore, be judged sufficient in resident macrophages to support the initial growth response which results after stimulation. Thus hypertrophy was observed eventually in every structure examined. Even the minimally activated macrophages resident in the peritoneum of germ-free mice respond readily to stimulation.

Animals↗

The peritoneal leukocytes of the germ-free mouse.

The cytology of the lavage-recoverable peritoneal cell population of germ-free mice is similar to that of conventional controls. The microbial status has no effect on the total counts, differential counts or 3H-thymidine labelling index of peritoneal leukocytes.

Animals↗

A stereological ultrastructural study of peritoneal macrophages from germ-free and conventionally-reared mice.

The reported work is the first direct ultrastructural comparison of resident peritoneal macrophages from germ-free and conventional animals. Three groups of mice were studied: germ-free (GF), conventionally-reared under isolation conditions (IC), and conventionally-reared in an open environment (OC). The macrophages from the three groups of animals are closely similar morphologically. Particularly noteworthy are the electron-dense, lysosome-like granules which are numerous in the macrophages of germ-free mice and which provide a structural foundation for the presumed microbicidal capability of the phagocytes. Morphometric estimates showed that the "average macrophage" from GF mice is smaller and possesses a smaller, rounder nucleus, a smaller volume fraction of mitochondria and more lysosome-like granules per unit of cytoplasmic volume than the "average macrophage" from conventional mice. Moreover, granules and mitochondria are smaller, on average in the GF phagocytes than in macrophages from conventional mice. The results suggest that peritoneal macrophages from the germ-free mouse represent, more truly than those from the conventional mouse, the nature of the fully differentiated but as yet unstimulated mononuclear phagocyte.

Animals↗

Membrane potential changes induced by 5-hydroxytryptamine in the rabbit superior cervical ganglion.

1. Changes in resting membrane potential induced by 5-hydroxytryptamine (5-HT) have been measured in the excised ganglion by the sucrose-gap technique. 2. 5-HT produced a rapid depolarization, the threshold concentration for depolarization being around 10 muM. With concentrations of 100 muM or greater, repolarization began during the course of the superfusion; this was followed by prolonged tachyphylaxis. 3. Tachyphylaxis was largely avoided by making injections into the superfusion stream. Standard injections of 0.2 mumol 5-HT dissolved in 0.2 ml of Krebs solution were used routinely and could be given at 20-30 min intervals to evoke relatively constant responses. 4. The response to an injection consisted of a rapid depolarization, followed by a rapid repolarization and subsequent after-hyperpolarization. The threshold quantity for depolarization was around 0.01 mumol, while the ED50 estimated from 6 dose-response curves was 0.12 +/- 0.02 mumol (mean +/- s.e. mean). 5. Injections of 5-HT (0.2 mumol), choline (10 mumol) and acetylcholine (9.9 mumol) produced depolarizations of similar magnitude. 6. Monoamine oxidase inhibitors failed to alter substantially the amplitude of depolarizations to 5-HT. 7. 5-HT depolarizations were unaltered in amplitude when the impermeant anion benzenesulphonate was substituted for the chloride ion in Krebs solution, but were initially markedly reduced in amplitude in a sodium-deficient medium; some recovery of the response subsequently occurred. The depolarization which persisted in sodium-deficient solutions was much reduced or abolished when calcium ions were then removed from the superfusion medium. Removal of either calcium ions alone or potassium ions from the superfusion fluid did not reduce depolarization amplitude. 8. The after-hyperpolarization was abolished in sodium-deficient solutions, usually increased in potassium-free solutions, reduced or abolished by ouabain or nicotine, but unaffected by calcium free solutions. 9. A depolarizing action of 5-HT on presynaptic terminals in the ganglion appears probable.

Acetylcholine↗

Divergent effects of excess dietary vitamin A on alimentary cholesterolemia in cockerels of different genetic backgrounds.

The variable effect of excessive vitamin A intake on alimentary cholesterolemia was investigated in cockerels of strains of White Leghorns and New Hampshires. With the New Hampshire cockerels, the feeding of 0.5% of dietary cholesterol resulted in greater cholesterolemia when the diet contained 1700 I.U. of vitamin A per kilogram than when it contained 22000 I.U. of vitamin A per kilogram. With the White Leghorn cockerels, on the other hand, cholesterolemia was enhanced with the higher level of dietary vitamin A. Absorption of a single oral dose of cholesterol was increased in birds of both breeds when vitamin A had been given previously by injection. In the White Leghorn cockerels the percentage of newly absorbed cholesterol in the hepatic pool was reduced by vitamin A administration, whereas in the New Hampshire cockerels the percentage was increased. It was concluded that excess vitamin A may have divergent effects on alimentary cholesterolemia in chickens of different genetic backgrounds as a result of opposite effects on the liver-blood ratio of a large load of cholesterol.

Animals↗

The facilitatory actions of 5-hydroxytryptamine and bradykinin in the superior cervical ganglion of the rabbit.

1 The effects of 5-hydroxytryptamine (5-HT) on ganglionic transmission and on intrinsic modulation of transmission have been re-examined and compared with the effects of bradykinin by means of electrophysiological techniques.2 Early facilitation, which is maximal 40-75 ms after a conditioning stimulus, was considerably enhanced by 5-HT. This enhancement was concentration-dependent, the threshold concentration lying between 0.1 and 1 muM. With concentrations of 5-HT 10 muM or greater, there was some depression of the Sa response to the conditioning stimulus.3 5-HT reduced or abolished the inhibition of a test response induced by a conditioning response 100-300 ms earlier. Facilitation was observed at these intervals at concentrations of 5-HT of 25 muM or greater.4 Late facilitation, which is maximal 700-2000 ms after a conditioning stimulus, was increased by 5-HT, but the effect was not as great as on early facilitation and was not always seen with a concentration of 1 muM.5 Bradykinin reduced early facilitation but increased the amplitude of the transmitted action potential in response to a single stimulus. The threshold concentration producing these effects was between 1 and 2 muM.6 5-HT produced a rapid depolarization of the ganglion cell membrane which was followed by an after-hyperpolarization.7 Bradykinin either produced no measurable change in ganglion cell resting potential or only very small, transient depolarizations.8 The depression of transmission, enhancement of intrinsic facilitation and the depolarization of the ganglion cell membrane induced by 5-HT may indicate more than one mode of action of this amine at the ganglionic synapse.

Action Potentials↗