PubMed Health⌕ Search

Biomedical subjects

A G Dawson

Publications and source records attributed to A G Dawson.

At least 19 recordsLinked to original sources
PubMed2004

Tsunami hazards in Europe.

Tsunami represents one of the most potentially serious forms of coastal flood risk. Although much is known on the recorded history of tsunamis for given areas of the world, very little information is available on the occurrence of palaeotsunamis during prehistory. This is of fundamental importance in calculating tsunami flood risk for any given coastal area. Given sufficient information on past tsunami activity for a particular coastal area, the numerical calculation of aggregate coastal flood risk (including tsunami) for a coastal area is very difficult to estimate since one needs also to take into account the risk of a tsunami and a storm surge taking place simultaneously during a high tide. Estimates of coastal flood risk also need to consider future changes in relative sea level caused by the combined effects of global climate change and vertical movements of the lithosphere.

Disasters↗
PubMed1993

A double-blind trial of melatonin as a treatment for jet lag in international cabin crew.

This study investigated the efficacy of oral melatonin in alleviating jet lag in flight crew after a series of international flights. The optimal time for taking melatonin in this group was also investigated. In a double-blind placebo-controlled trial, 52 international cabin crew were randomly assigned to three groups; early melatonin (5 mg started 3 days prior to arrival until 5 days after return home); late melatonin (placebo for 3 days then 5 mg melatonin for 5 days); and placebo. Daily ratings showed a trend in jet lag, mood, and sleepiness measures toward an improved recovery in the late melatonin group and a worse recovery in the early melatonin group as compared to placebo. Retrospective ratings made 6 days after arrival showed the late melatonin group reported significantly less jet lag and sleep disturbance following the flight compared to placebo. The late melatonin group also showed a significantly faster recovery of energy and alertness than the early melatonin group, which reported a worse overall recovery than placebo. These findings show melatonin may have potential benefits for international aircrew.

Adult↗
PubMed1986

Increased ketogenesis in hyperthyroid rats metabolizing ethanol.

The levels of various metabolites were measured in freeze-clamped samples of liver from triiodothyronine-treated and control rats to which either saline or ethanol (2.5 g/kg body weight) had been administered 2 hours earlier. It was found that ethanol led to a sharp increase in the hepatic acetate concentration in both hyperthyroid and euthyroid rats whereas lactate and pyruvate concentrations were lowered in both groups. The lactate/pyruvate ratio rose significantly in euthyroid animals that had received ethanol but the ratio remained relatively low in hyperthyroid rats. The adenine nucleotide phosphorylation potential, already low in hyperthyroid rats, was further lowered by ethanol. However, the most remarkable difference between the responses of euthyroid and hyperthyroid rats to ethanol was in the hepatic concentrations of ketone bodies, particularly 3-hydroxybutyrate. In control animals, administration of ethanol did not affect either the acetoacetate or 3-hydroxybutyrate concentration but, although the level of ketone bodies in the livers of hyperthyroid rats that had not received ethanol was the same as that of controls, there was a greater than fivefold increase in the 3-hydroxybutyrate level when ethanol was given. While this increase in ethanol-dependent ketogenesis is not explicable at this stage, hyperthyroidism did not increase the activity of cytoplasmic acetyl-CoA synthetase, an enzyme that is probably involved in the formation of ketone bodies from ethanol-derived acetate.

3-Hydroxybutyric Acid↗
PubMed1985

Effect of triiodothyronine on alcohol dehydrogenase and aldehyde dehydrogenase activities in rat liver. Implications for the control of ethanol metabolism.

Treatment of rats with 20 micrograms of 3,3',5-triiodo-L-thyronine (T3) per 100 g body wt for a period of 6 days led to a 45% decrease in total liver alcohol dehydrogenase and a 36% decrease in total liver aldehyde dehydrogenase. Most of the latter decrease was directly attributable to a 57% fall in the level of the physiologically-important low Km mitochondrial isoenzyme. The high Km isoenzyme of the postmitochondrial and soluble fractions was much less affected by T3-treatment. T3, at concentrations up to 0.1 mM, did not inhibit the activity of aldehyde dehydrogenase in vitro. Despite these large losses of the two enzymes most intimately involved in ethanol metabolism, the rate of ethanol elimination in vivo was the same in T3-treated and control animals. Moreover, there was no difference between the two groups in the susceptibility of ethanol elimination to inhibition by 4-methylpyrazole, making it unlikely that an alternative route of ethanol metabolism had been significantly induced by treatment with T3. As it had been suggested that T3 might create a "hypermetabolic state" in which constraints normally imposed on alcohol dehydrogenase and aldehyde dehydrogenase are removed thereby compensating for any loss in total enzymic activity, 2,4-dinitrophenol (0.1 mmoles/kg body wt) was administered to rats in order to raise the general metabolic rate. However, the uncoupler proved to be lethal to T3-treated animals and did not stimulate ethanol elimination in controls. The results do not support the notion that ethanol elimination in vivo is normally governed either by the level of alcohol dehydrogenase or by that of hepatic aldehyde dehydrogenase. However, the mode of control remains unclear.

Alcohol Dehydrogenase↗
PubMed1983

Ethanol oxidation in systems containing soluble and mitochondrial fractions of rat liver. Regulation by acetaldehyde.

Systems containing soluble fraction of rat liver, with or without mitochondrial fraction, oxidised [1-14C] ethanol to acetaldehyde, 14CO2 and non-volatile 14C-products of which acetate was the principal, and possibly the only, component. Ethanol oxidation was stimulated by pyruvate which served as an electron sink thereby allowing rapid regeneration of NAD. When no mitochondria were present acetaldehyde accumulated, rapidly at first but eventually reaching a plateau. The rate of ethanol oxidation in these systems was much lower than the measured maximum activity of alcohol dehydrogenase (ADH) and it was concluded that ADH was inhibited by the accumulated acetaldehyde. Mitochondria, because of their relatively high aldehyde dehydrogenase (ALDH) activity, prevented the accumulation of acetaldehyde, or quickly removed acetaldehyde already accumulated. This action was accompanied by a sharp increase in the rate of ethanol oxidation, presumably due to the deinhibition of ADH. Cyanamide, an inhibitor of mitochondrial ALDH, blocked the stimulatory effect of mitochondria on ethanol oxidation. It was concluded that, in the reconstituted systems, acetaldehyde played a dominant role in controlling the rate of ethanol oxidation. The possible importance of acetaldehyde in governing ethanol oxidation in vivo is discussed.

Acetaldehyde↗
PubMed1982

Rapid oxidation of NADPH via the reconstituted malate-aspartate shuttle in systems containing mitochondrial and soluble fractions of rat liver: implications for ethanol metabolism.

In an attempt to assess whether hydrogen shuttle capacity might serve as the rate-limiting factor in the hepatic oxidation of ethanol, the malate-aspartate shuttle was reconstituted in systems containing mitochondrial and soluble fractions of rat liver. Oxidation of NADH was stimulated slightly by the addition of either glutamate or malate but when both substrates were added the stimulation was far stronger. This effect was greatly enhanced by aspartate indicating that, when not added to the system, extramitochondrial aspartate was limiting. It was found that the rate of oxidation of NADH was directly related to the amount of mitochondrial protein present but extramitochondrial reactions became restrictive when the 'soluble protein/mitochondrial protein' ratio fell below 0.8. When calculated on a whole tissue basis the maximum rate of oxidation of NADH by the reconstituted shuttle was substantially higher than reported rates of ethanol oxidation in vivo. The results are discussed in relation to the normal control of ethanol metabolism.

Animals↗
PubMed1980

Inhibition of glycolysis in boar sperm by alpha-chlorohydrin.

The effect of alpha-chlorohydrin (3-chloropropan-1,2-diol) on the metabolism of D-[U-14C]-fructose and L-[U-14C]-lactate by washed boar sperm has been investigated. Whereas alpha-chlorohydrin at concentrations as low as 0.1 mM inhibited the metabolism of fructose and led to an increase in the utilization of endogenous lactate, amounts up to 500 mM had no effect on the oxidation of added lactate. Low levels of alpha-chlorohydrin increased the cellular concentrations of fructose-1,6-bisphosphate and the triosephosphates, an effect consistent with the inhibition of glyceraldehyde-3-phosphate dehydrogenase. Although [U-14C]-glycerol was rapidly oxidized by boar sperm, [U-14C]-alpha-chlorohydrin was not metabolized to 14CO2, showing that it is not converted to glycerol. Extracts obtained by sonication of boar sperm after incubation with [3-36C1]-alpha-chlorohydrin, did not contain [3-36C1]-alpha-chlorohydrin-1-phosphate. This is contrary to the postulate that this phosphorylated compound is the inhibitory metabolite of alpha-chlorohydrin.

Animals↗
PubMed1980

Effects of indomethacin on the metabolism of glycerol by rat-kidney tubules: an alternative explanation for the enhancement of glycerol-induced acute renal failure by indomethacin.

1. The metabolism of glycerol by isolated rat-kidney tubules was investigated. 2. Indomethacin, at a concentration of 0.1 mmol/l, markedly inhibited the utilization of glycerol and its conversion into glucose and CO2. 3. The glycerol 3-phosphate production rose significantly when indomethacin was present, indicating a fall in the rate at which glycerol 3-phosphate was oxidized. 4. The results are discussed in relation to the observation that indomethacin increases the severity of glycerol-induced acute renal failure.

Acute Kidney Injury↗
PubMed1978

The oxidative activities of membrane vesicles from Bacillus caldolyticus. Energy-dependence of succinate oxidation.

1. The properties of membrane vesicles from the extreme thermophile Bacillus caldolyticus were investigated. 2. Vesicles prepared by exposure of spheroplasts to ultrasound contained cytochromes a, b and c, and at 50 degrees C they rapidly oxidized NADH and ascorbate in the presence of tetramethyl-p-phenylenediamine. Succinate and l-malate were oxidized more slowly, and dl-lactate, l-alanine and glycerol 1-phosphate were not oxidized. 3. In the absence of proton-conducting uncouplers the oxidation of NADH was accompanied by a net translocation of H(+) into the vesicles. Hydrolysis of ATP by a dicyclohexylcarbodi-imide-sensitive adenosine triphosphatase was accompanied by a similarly directed net translocation of H(+). 4. Uncouplers (carbonyl cyanide p-trifluoromethoxyphenylhydrazone or valinomycin plus NH(4) (+)) prevented net H(+) translocation but stimulated ATP hydrolysis, NADH oxidation and ascorbate oxidation. The last result suggested an energy-conserving site in the respiratory chain between cytochrome c and oxygen. 5. Under anaerobic conditions the reduction of cytochrome b by ascorbate (with tetramethyl-p-phenylenediamine) was stimulated by ATP hydrolysis, indicating an energy-conserving site between cytochrome b and cytochrome c. However, no reduction of NAD(+) supported by oxidation of succinate, malate or ascorbate occurred, neither did it with these substrates in the presence of ATP under anaerobic conditions, suggesting that there was no energy-conserving site between NADH and cytochrome b. 6. Succinate oxidation, in contrast with that of NADH and ascorbate, was strongly inhibited by uncouplers and stimulated by ATP hydrolysis. These effects were not observed when phenazine methosulphate, which transfers electrons from succinate dehydrogenase directly to oxygen, was present. It was concluded that in these vesicles the oxidation of succinate was energy-dependent and that the reoxidation of reduced succinate dehydrogenase was dependent on the outward movement of H(+) by the protonmotive force. 7. In support of the foregoing conclusion it was shown that the reduction of fumarate by NADH was an energy-conserving process. 8. If the activities of vesicles accurately represent those of the intact organism it appears that in B. caldolyticus the reduction of fumarate to succinate at the expense of reducing equivalents from NADH is energetically favoured over succinate oxidation even under aerobic conditions. This may be related to the need for an ample supply of succinate for haem synthesis in order to provide cytochromes for the organism.

Adenosine Triphosphate↗