Search PubMed⌕ Search

Biomedical subjects

R D Saunders

Publications and source records attributed to R D Saunders.

At least 73 records · Page 4Linked to original sources
PubMed1987

Effects of methylprednisolone and the combination of alpha-tocopherol and selenium on arachidonic acid metabolism and lipid peroxidation in traumatized spinal cord tissue.

Traumatic injury of the spinal cord leads to a series of pathological events that result in tissue necrosis and paralysis. Among the earliest biochemical reactions are hydrolysis of fatty acids from membrane phospholipids, production of biologically active eicosanoids, and peroxidation of lipids. This study examines the effect of agents purported to improve recovery following spinal cord trauma, methylprednisolone sodium succinate (MPSS) and the combination of alpha-tocopherol and selenium (Se), on the posttraumatic alterations of membrane lipid metabolism. Pretreatment with either MPSS or alpha-tocopherol and Se reduced the trauma-induced release of total FFA including arachidonate in the injured spinal cord tissue. In addition, these agents decreased the postinjury levels of prostanoids. Pretreatment with either MPSS or alpha-tocopherol and Se also completely prevented the trauma-induced loss of cholesterol while inhibiting the increase of a cholesterol peroxidation product, 25-hydroxycholesterol. These data suggest that: perturbation of membrane lipid metabolism may contribute to the tissue necrosis and functional deficit of spinal cord injury and MPSS or the combination of alpha-tocopherol and Se may protect injured spinal cord tissue, at least in part, by limiting these posttraumatic membrane lipid changes.

Animals↗
PubMed1986

The effects of low-level radiofrequency and microwave radiation on brain tissue and animal behaviour.

There has been much public interest and controversy about the effects of exposure to low levels of microwave and radiofrequency radiation. Of particular interest are reports of radiation-induced changes in brain tissue and animal behaviour. This review considers the evidence supporting some of these effects. The main conclusions of the review are: The levels of tracer substances in the brain tissue of conscious or anaesthetized animals can be altered by acute exposure to microwave radiation that is sufficient to raise the brain temperature by several degrees Celsius. However, the results of such experiments are difficult to interpret, being in some cases contradictory or influenced by various confounding factors, and the data cannot be considered sufficient to recommend a threshold for human tolerance. The evidence that calcium ion exchange in living nervous tissues is affected by amplitude-modulated radiofrequency and microwave radiation is inconclusive. Exposure sufficient to cause an increase in core temperature of about 1 degree C, corresponding to specific energy absorption rates of about 2-8 W kg-1 may adversely affect animal behaviour.

Animals↗
PubMed1986

Cytogenetic effects of microwave irradiation on male germ cells of the mouse.

Hybrid male mice were exposed to 2.45 GHz microwaves for 30 min/day, 6 days a week for two consecutive weeks at power densities of 1.0, 100 or 400 W m-2, with sham-exposed controls. Rectal temperatures before and after exposure were measured on days 1, 6 and 12. Measurements made on day 1 were treated with caution because of heterogeneity in rectal temperatures taken before exposure between the groups of mice given different treatments. On days 6 and 12, rectal temperatures rose by approximately 1 degree C in mice sham exposed, or exposed to 1 W m-2 or 100 W m-2. Only in the group of mice exposed to 400 W m-2 was the mean rise in rectal temperature during exposure (about 3 degrees C) significantly increased above the sham value. In groups killed 2-3 days after treatment (mainly meiotic exposure) frequencies of chromosome aberrations in spermatocytes showed no significant heterogeneity although the highest frequency of 1.5 per cent was at the highest (400 W m-2) power density. Another group killed 30 days after 100 W m-2 exposures (spermatogonial sampling) showed no significant increase over controls in chromosome aberration frequency. There was a small but significant increase in sperm count with increasing power density in mice killed 12-13 days after exposure, but a non-significant one in those exposed as spermatogonia (killed 41 days later). Thus effects were markedly less severe than those reported previously by Manikowska-Czerska et al. (1985) with a very similar radiation regime and were probably caused by the temperature enhancement.

Animals↗
PubMed1985

Spinal cord injury and protection.

Subsequent to traumatic injury of the spinal cord, a series of pathophysiological events occurs in the injured tissue that leads to tissue destruction and paraplegia. These include hemorrhagic necrosis, ischemia, edema, inflammation, neuronophagia, loss of Ca2+ from the extracellular space, and loss of K+ from the intracellular space. In addition, there is trauma-initiated lipid peroxidation and hydrolysis in cellular membranes. Both lipid peroxidation and hydrolysis can damage cells directly; hydrolysis also results in the formation of the biologically active prostaglandins and leukotrienes (eicosanoids). The time course of membrane lipid alterations seen in studies of antioxidant interventions suggests that posttraumatic ischemia, edema, inflammation, and ionic fluxes are the result of extensive membrane peroxidative reactions and lipolysis that produce vasoactive and chemotactic eicosanoids. A diverse group of compounds has been shown to be effective in ameliorating spinal cord injury in experimental animals. These include the synthetic glucocorticoid methylprednisolone sodium succinate (MPSS); the antioxidants vitamin E, selenium, and dimethyl sulfoxide (DMSO); the opiate antagonist naloxone; and thyrotropin-releasing hormone (TRH). With the exception of TRH, all of these agents have demonstrable antioxidant and/or anti-lipid-hydrolysis properties. Thus the effectiveness of these substances may lie in their ability to quench membrane peroxidative reactions or to inhibit the release of fatty acids from membrane phospholipids, or both. Whatever the mode of action, early administration appears to be a requirement for maximum effectiveness.

Animals↗
PubMed1985

Membrane lipid changes in laminectomized and traumatized cat spinal cord.

Free fatty acid (FFA), diacylglycerol (acyl2Gro), icosanoid, phospholipid, and cholesterol levels were measured in samples of cat spinal cord (L2) that were frozen in situ with vertebrae intact, at various times after laminectomy, and at various times after laminectomy with compression trauma to the spinal cord. Tissue samples either were grossly dissected into gray and white portions prior to FFA and acyl2Gro analysis or were used whole for the other lipid types. Gray matter total FFA and acyl2Gro values were abnormally high in samples frozen with vertebrae intact and in those frozen 10 min after laminectomy. This indicates that the surgical procedures resulted in some perturbation of spinal cord lipid metabolism. If the experimental animals were allowed to recover for 90 min after laminectomy, the gray matter FFA and acyl2Gro levels were greatly reduced. Compression of the spinal cord with a 170-g weight for 1, 3, or 5 min (following 90 min of recovery after laminectomy) caused significant elevations of total FFA, acyl2Gro, icosanoids, and phosphatidic acid and significant decreases in ethanolamine plasmalogens and cholesterol. Among the total FFA, arachidonic acid was found to have the largest relative increase. Comparisons of gray and white matter demonstrate that, in general, changes in white matter FFA and acyl2Gro were similar to those seen in gray matter. However, the increases in white matter levels of FFA and acyl2Gro were delayed, occurring after the elevations in gray matter. For some FFA (e.g., arachidonate), the rise in white matter occurred as gray matter levels were decreasing. This suggests that the initial alteration in spinal cord lipid metabolism after trauma was in gray matter but, with time, spread radially into white matter.

Animals↗
PubMed1985

The degradation of phospholipids, formation of metabolites of arachidonic acid, and demyelination following experimental spinal cord injury.

Spinal cord injury has been studied using a cat compression model. Very early changes in lipid metabolism were found that compromise the integrity of the plasma membrane and decrease the activities of ATPases. Up to 18% of the ethanolamine plasmalogens are lost, with very marked elevations of the free fatty acids, arachidonic acid, diacylglycerols, prostaglandins, thromboxanes, and leukotrienes. These changes result in edema, inflammation, necrosis of oligodendroglia, demyelination, and paralysis.

Animals↗
PubMed1985

Lipid hydrolysis and peroxidation in injured spinal cord: partial protection with methylprednisolone or vitamin E and selenium.

Compression trauma of the cat spinal cord induces a very rapid alteration in the lipid metabolism of cellular membranes, including lipid hydrolysis with release of fatty acids including arachidonate, production of biologically active eicosanoids, and loss of cholesterol. This disturbance of cellular membranes can directly damage cells and can lead to the secondary development of tissue ionic imbalance, ischemia, edema, and inflammation with neuronophagia. Pretreatment with either the synthetic glucocorticoid methylprednisolone sodium succinate (MPSS) or the antioxidants vitamin E and selenium (Se) completely prevented the loss of cholesterol and partially inhibited lipolysis and prostanoid production. Treatment with MPSS significantly reduced the postinjury tissue necrosis and paralysis. Preliminary evidence indicates that pretreatment with vitamin E and Se also protected against the effects of spinal cord injury (SCI). We speculate that the ability of these agents to preserve function after SCI may, in part, reside in their capacity to limit the trauma-induced changes in lipid metabolism.

Animals↗
PubMed1985

The 45-kb unit of major urinary protein gene organization is a gigantic imperfect palindrome.

The multigene family which codes for the mouse major urinary proteins consists of about 35 genes. Most of these are members of two distinct groups, group 1 and group 2. The group 1 and group 2 genes are organized in head-to-head pairs within 12 to 15 remarkably uniform chromosomal units or domains about 45 kilobase pairs (kb) in size. The 45-kb units are located on chromosome 4, and many of them are adjacent to each other. We propose that the 45-kb unit is a unit both of organization and of evolutionary change. In this study the homologies within the unit were observed by examining, in an electron microscope, heteroduplex and foldback structures made from cloned major urinary protein genes. These show that the 45-kb unit is a gigantic imperfect palindrome. Each arm of the palindrome contains two regions of inverted symmetry of 9.5 and 4.5 kb separated by a 3-kb nonsymmetrical region. We argue that the nonsymmetrical regions arose by a series of deletion events in the two arms of the palindrome. The center of the 45-kb unit is an 8-kb sequence without inverted symmetry flanked by the 9.5-kb regions, which contain the 4-kb genes and their immediate 5' and 3' flanking regions. The junction between adjacent 45-kb units is a 2- to 4-kb sequence without inverted symmetry flanked by the 4.5-kb regions. Some of the 45-kb units are arranged as direct tandem repeats. Others appear to be in inverted orientation with respect to a neighboring unit. Cloned major urinary protein genes show few incidences of the repetitive elements B1, B2, R, and MIF. Two elements, a B1 and an R, may be a constant feature of the 45-kb units. If so, in those cases in which the units are in tandem array, both of these elements will occur with a 45-kb periodicity. A comparison of corresponding parts of different 45-kb units shows that they differ because of a number of deletion or insertion events, particularly in the regions 3' to the genes.

Animals↗
PubMed1984

Simultaneous extraction and preparation for high-performance liquid chromatography of prostaglandins and phospholipids.

A method for the maximum recovery of prostaglandins from brain tissue with simultaneous recovery of neutral lipids and phospholipids was developed. Hexane:2-propanol was used to extract lipids from bovine brain. This method, which does not require a washing step to remove nonlipid contaminants, was compared to extraction according to Folch et al. [(1957) J. Biol. Chem. 226, 497-509] for efficiency of lipid extraction. Recoveries of prostaglandins were 12-37% greater with hexane:2-propanol than with the Folch extraction procedure with washing. The ratios of cholesterol to lipid phosphorus and absolute phospholipid recoveries were comparable for the two methods. A new elution sequence was devised for separation of lipid classes on silicic acid columns. The elution sequence was chloroform (neutral lipids and free fatty acids), methyl formate (prostaglandins and cerebrosides), acetone (remaining glycolipids), and methanol (phospholipids). Reverse-phase HPLC of the methyl formate fraction was used to separate the prostaglandins. The method permits simultaneous quantitative recovery of prostaglandins and phospholipids (which contain the 20:4(n-6) precursor for prostaglandin synthesis), and therefore allows changes in phospholipid composition and prostaglandin synthesis to be studied in the same tissue sample.

Animals↗
PubMed1984

No clastogenic effect from in vitro microwave irradiation of G0 human lymphocytes.

Specimens of human blood were exposed at specific energy absorption rates of 104 or 193 W kg-1 to 2.45 GHz microwave radiation at temperatures below 36 degrees C. Cultured lymphocytes were examined for induced unstable chromosome and chromatid aberrations and sister chromatid exchanges. The amount of chromosome damage observed did not exceed that found in controls.

Chromatids↗
PubMed1983

Sperm count and sperm abnormality in male mice after exposure to 2.45 GHz microwave radiation.

Adult male mice had the posterior halves of their bodies exposed at 44 W/kg in a waveguide system to 2.45 GHz microwave radiation for 30 min. They were killed sequentially over 10 weeks and assessed for decreased sperm count and abnormal sperm morphology. The response in each assay was maximal 2-4 weeks after the exposure. This corresponds to microwaves having their greatest effect on spermatids and spermatocytes. Male fertility, assessed as the proportion of normal sperm per epididymis, was compared with results of an earlier study on dominant lethality. It is concluded that reduced male fertility correlates well with reduced pregnancy rate but less well with pre-implantation survival. Whilst microwaves clearly induced abnormally shaped sperm, those which achieved fertilization cannot have possessed a dominant mutation which would result in the post-implantation death of the embryo.

Animals↗
PubMed1981

The effect of acute far field exposure at 2.45 GHz on the mouse testis.

Male C3H mice were exposed in an anechoic chamber to 2.45 GHz microwave radiation. The exposures ranged from 1000 Wm-2 for 5 min to 100 Wm-2 for 260 min, giving dose rates to the testis ranging from 66 Wkg-1 to 7 Wkg-1. The mice were killed six days later and the testes examined histologically. Quantitatively, no significant effects were seen on cells identified as X-ray sensitive (spermatogonia type B) or heat sensitive (early primary spermatocytes and late primary and secondary spermatocytes) or on the sperm count. Extrapolation of these results to man would suggest that acute exposure to the Maximum Permissible Exposure level of 100 Wm-2 has no effect on the testes in the ranges 1 to 3.5 MHz and 300 MHz to 100 GHz. There was insufficient data to comment on other frequencies.

Animals↗
PubMed1981

Effects of 2.45 GHz microwave radiation and heat on mouse spermatogenic epithelium.

The rear halves of the bodies of anaesthetized male C3H mice were exposed for 30 min to 2.45 GHz microwave radiation and the effects on the testes were compared to those produced by direct heating. Effects were observed which are consistent with the hypothesis that heat damage is the primary effect of microwave exposure. Damage measured six days after exposure ranged in severity from depletion of the spermatocytes to extensive necrosis of the germinal epithelium. Temperature-sensitive probes implanted in the testes revealed a threshold effect for depletion of the spermatocytes of approximately 39 degrees C and an LD50 6 (50 per cent cell death after 6 days) of about 41 degrees C after microwave exposure or direct heating. The corresponding effective threshold effect and LD50 6 expressed in terms of absorbed microwave power were 20 W kg-1 and 30 W kg-1. However, it is probable that a conscious animal is better able to regulate testicular temperature and hence adjust to higher dose-rates.

Animals↗