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Biomedical subjects

D P Muller

Publications and source records attributed to D P Muller.

At least 19 recordsLinked to original sources
PubMed1992

Plasma clearance and net uptake of alpha-tocopherol and low-density lipoprotein by tissues in WHHL and control rabbits.

The mechanism(s) of uptake of vitamin E (alpha-tocopherol) by tissues is poorly understood. It has, however, been suggested from studies in vitro that the apolipoprotein B/E (apo B/E) receptor pathway for low-density lipoprotein (LDL) may be involved. To investigate the role of the apo B/E receptor pathway in vivo, we have studied the transport and uptake of alpha-tocopherol by tissues in Watanabe Heritable Hyperlipidaemic (WHHL) rabbits, which lack functional LDL (apo B/E) receptors, and controls. [3H]alpha-Tocopherol incorporated within LDL labelled with [14C]sucrose was used in these studies, as this enabled the uptake of both alpha-tocopherol and LDL to be studied independently. The principal findings were as follows. (1) Concentrations of the circulating lipids (including alpha-tocopherol) and LDL were increased and the plasma fractional disappearance rates of alpha-tocopherol and LDL decreased in the WHHL rabbits. (2) The WHHL rabbits clear more LDL and alpha-tocopherol from the circulation than controls do, because of their increased pool sizes of alpha-tocopherol and LDL. (3) The lipoprotein composition of the WHHL rabbits differed from that of the controls, and there was exchange of alpha-tocopherol between the lipoprotein fractions in vivo and in vitro. (4) High-affinity apo B/E receptors were not essential for the uptake of alpha-tocopherol by tissues. (5) Evidence from the plasma-clearance and tissue data suggest that alpha-tocopherol can be taken up by tissues in association with, and also independent of, LDL. We conclude that there are several different mechanisms for the uptake of alpha-tocopherol by tissues, which include receptor-dependent and receptor-independent pathways, independent transport and co-transport of alpha-tocopherol and LDL, and uptake from a number of different lipoproteins.

Animals↗
PubMed1992

Vitamin E therapy in retinopathy of prematurity.

Vitamin E is a fat soluble antioxidant and as a result it is able to scavenge free radicals derived from oxygen. The premature infant and the retina are likely to be particularly vulnerable to the deleterious effects of these oxygen derived free radicals, and as a result prophylactic vitamin E has been suggested for the management of retinopathy of prematurity (ROP). However, despite numerous trials, prophylactic supplementation with vitamin E remains controversial. This paper will critically review the use of vitamin E in ROP and consider the risk/benefit relationship of such treatment in premature infants.

Free Radicals↗
PubMed1991

Abnormalities of the electroretinogram and visual-evoked potential in vitamin E deficient rats.

Flash electroretinograms, retinal oscillatory and cortical visual-evoked potentials were recorded in 10-month vitamin E deficient rats and in age-matched controls. A significant increase in the latency (P less than 0.0001) and decrease in amplitude (P less than 0.0001) of the electroretinogram a- and b-waves were observed in the vitamin E deficient rats compared with controls. The vitamin E deficient rats also showed a significant delay (P less than 0.002) in early oscillatory potentials. No significant group differences were obtained in the P1 latency or P1-N1 amplitude of the visual-evoked potential; however, the N1 peak was significantly delayed (P = 0.01) in the vitamin E deficient rats. This study shows, for the first time, that the electroretinogram and visual-evoked potential to flash stimulation provide a sensitive index for monitoring the visual effects of vitamin E deficiency in the rat.

Animals↗
PubMed1991

Experimental vitamin E deficiency in rats. Morphological and functional evidence of abnormal axonal transport secondary to free radical damage.

Morphological and functional studies have been performed on experimental vitamin E deficient rats. The predominant morphological change was axonal dystrophy and degeneration in the rostral parts of the dorsal columns, particularly in the gracile fasciculi. The dystrophic changes comprised focal axonal swellings containing accumulations of normal and abnormal organelles which included tubulovesicular structures probably derived from the smooth endoplasmic reticulum, mitochondria, dense lamellar bodies, neurofilaments, multifascicular bodies and lysosomes. Similar but lesser changes were observed in distal peripheral nerves. The appearances suggested a disturbance of axonal transport with a defect of 'turnaround' in the distal axons. Studies on the axonal transport of endogenous acetylcholinesterase showed an impairment both of fast anterograde and retrograde transport. The changes were considered to be secondary to the lack of the antioxidant effect of vitamin E as the neurological deficits could be reduced by the concomitant dietary administration of the synthetic antioxidant ethoxyquin and were markedly aggravated by the administration of polyunsaturated fatty acids. It is suggested that the neurological syndrome produced by vitamin E deficiency could be the result of damage to the function of mitochondria and other intra-axonal membranous structures which would interfer both with fast anterograde transport and 'turnaround' and lead to a distal axonal degeneration.

Acetylcholinesterase↗
PubMed1990

A longitudinal study of somatosensory, brainstem auditory and peripheral sensory-motor conduction during vitamin E deficiency in the rat.

A severe deficiency of vitamin E causes a characteristic neurological syndrome in man and experimental animals. In this study a number of electrophysiological modalities in vitamin E deficient and control rats have been investigated over a period of one year to define the time of onset and severity of the abnormalities associated with vitamin E deficiency in the rat. The mean velocities (n = 10) of the sensory evoked potentials were slower at all time points in the vitamin E deficient rats, with the central conduction velocities being more severely affected than the peripheral. Central conduction velocities, following both tibial and median nerve stimulation, were significantly delayed (P less than 0.005) after 8 months of deficiency. Differences in peripheral conduction following tibial stimulation became significantly delayed (P less than 0.005) after 11 months of deficiency. There were no significant differences in the brainstem auditory evoked potentials or peripheral sensory motor responses between the vitamin E deficient and control rats over the 1 year period. These results in the rat are essentially similar to those previously reported in vitamin E deficient man.

Animals↗
PubMed1990

Neurochemical, neurophysiological, and neuropathological studies in vitamin E deficiency.

It is now recognized that vitamin E is essential for normal neurological structure and function in both man and experimental animals, with severe deficiency resulting in a characteristic neurological syndrome. The reasons why the neurological system should be particularly susceptible to a deficiency of this fat-soluble vitamin, and the mechanisms involved, are not known. In this review, the neurochemistry, neuropathology, and neurophysiology associated with vitamin E deficiency are described and correlated. A deficiency of vitamin E results in a "distal or dying back" axonal neuropathy which predominantly involves the centrally directed fibers of sensory neurons, with the large caliber myelinated fibers being particularly affected. Both the pathological and electrophysiological studies indicate that the primary abnormality is a degeneration of the axons which then results in a secondary demyelination. The mechanism(s) involved is assumed to involve lipid peroxidation of neuronal membranes as a consequence of a deficiency of the major lipid-soluble secondary (i.e., chain breaking) antioxidant in vivo.

Animals↗
PubMed1989

Vitamin E concentrations in human brain of patients with Alzheimer's disease, fetuses with Down's syndrome, centenarians, and controls.

The concentration of vitamin E (alpha-tocopherol) was measured in samples of cortex from patients with Alzheimer's disease (AD), fetuses with Down's syndrome (DS), and also in a group of centenarians. The mean tocopherol concentrations in the two patient groups did not differ significantly from appropriate controls. When expressed per lipid the mean tocopherol concentration of the centenarians was greater than that of the controls but this reflected a significant decrease in the lipid concentration of the former group. These results indicate that neither the normal aging processes, Alzheimer's disease, nor the increased in vitro lipid peroxidation reported in fetuses with Down's syndrome result from a gross lack of alpha-tocopherol, or cause a significant depletion of the vitamin.

Adult↗
PubMed1988

Longitudinal studies of the neurobiology of vitamin E and other antioxidant systems, and neurological function in the vitamin E deficient rat.

Longitudinal studies were carried out over 55 weeks in vitamin E deficient and control rats. It was shown that neurological tissues (brain, cord and nerve) retained a greater percentage of vitamin E (alpha-tocopherol) than other tissues (serum, liver and adipose tissue), and that there was no evidence for compensation by other antioxidant enzyme systems (superoxide dismutase and glutathione peroxidase). An increased uptake of alpha-[3H]tocopherol (150% of controls) was observed in peripheral nerve of deficient animals from 11 weeks, whereas similar increases were not found in brain and cord until 36 weeks. These results were correlated with tests of neurological function which included electrophysiological studies and measurement of axonal transport. Recordings of somatosensory evoked potentials showed a significant delay (P less than 0.001) of central conduction velocity after 40 weeks of deficiency, whereas peripheral conduction was unchanged. After 40 weeks of deficiency, abnormal electromyographic activity of the hind limbs was obtained which was suggestive of chronic partial denervation. By 52 weeks there were significant reductions of both fast anterograde (P less than 0.02) and retrograde (P less than 0.05) transport of acetylcholinesterase in the deficient rats.

Acetylcholinesterase↗
PubMed1988

Pancreatic exocrine and endocrine function after subtotal pancreatectomy for nesidioblastosis.

Pancreatic exocrine and endocrine function was assessed in seven patients 1 to 2 years after 95% pancreatectomy (group A) and three patients 9 to 11 years after 75% pancreatectomy (group B). In all cases surgery was undertaken for the treatment of hyperinsulinism and the histologic diagnosis was nesidioblastosis. The activities of pancreatic enzymes and bicarbonate concentrations were generally normal in group B, but were reduced in approximately half the children in group A. One child in group A had significant exocrine failure and poor weight gain. Blood glucose levels and fasting insulin levels were normal during a standard glucose tolerance test in all of the group B patients. One had a low fasting blood glucose level. In the group A patients three had low fasting glucose levels and one a frankly diabetic glucose tolerance test. C peptide and insulin levels were comparable but inappropriate insulin levels were noted in one patient, suggesting that the control of glucose-stimulated insulin release may remain abnormal. The results suggest that pancreatic function is not seriously impaired in the majority of patients 1 to 2 years after 95% pancreatectomy and that it is comparable to that noted in 75% pancreatectomy patients followed over a longer period of time.

Amylases↗
PubMed1988

Lumbar and cortical somatosensory evoked potentials in rats with vitamin E deficiency.

Somatosensory evoked potentials (SEPs) from lumbar and cortical areas and electromyographic activity (EMG) were recorded in 40-42 week vitamin E deficient rats and in age matched controls. A significant increase in the latency (p less than 0.001) of the cortical SEP and a significant reduction in the lumbar to cortical conduction velocity (p less than 0.001) were observed in vitamin E deficient rats compared with controls. No significant differences were obtained in the latency of the lumbar SEP or in the peripheral conduction velocity from the ankle to lumbar region. All the vitamin E deficient rats had abnormal EMG findings (fibrillation potentials, positive sharp waves and polyphasic activity), whereas none of the controls showed any of these signs of dysfunction.

Afferent Pathways↗
PubMed1988

Genetic evidence from two families that the apolipoprotein B gene is not involved in abetalipoproteinemia.

Abetalipoproteinemia (ABL) is a recessive disorder in which affected individuals have extremely low or undetectable levels of serum apo B-containing lipoproteins. Using restriction fragment length polymorphisms, we have studied two families, each with two children with classical ABL born of normal parents. In each of these families, the two affected children have inherited different apo B alleles from at least one parent, whereas the siblings would be anticipated to share common alleles if this disorder were due to an apo B gene mutation. This linkage study shows that in these families, the apo B gene is discordant with ABL and therefore the disorder is caused by a defect in another gene, which is important for the normal synthesis or secretion of apo B-containing lipoproteins from both the liver and intestine.

Abetalipoproteinemia↗
PubMed1987

Vitamin E remains the major lipid-soluble, chain-breaking antioxidant in human plasma even in individuals suffering severe vitamin E deficiency.

The chain-breaking (peroxyl radical-trapping) antioxidant activity of plasma obtained from several patients with a very severe vitamin E deficiency has been measured. The total chain-breaking antioxidant activity in lipid extracts has been shown to be approximately equal to the concentration of vitamin E. For whole plasma there is no significant difference in the concentrations of water-soluble, chain-breaking antioxidants between the E-deficient patients and healthy adults. It is concluded that even in cases of very severe vitamin E deficiency the requirement for this vitamin is not met by some other exogenous or endogenous antioxidant.

Antioxidants↗