Purine metabolism during strenuous muscular exercise in man.

This study was designed to examine the influence of exercise on purine metabolism in man. In 15 men, the plasma uric acid concentration increased from 6.9 to 8.5 mg/dl following a 5000-m race and from 6.2 to 7.9 mg/dl in 11 men following a 42-km marathon. During a progressive exercise test on a cycle ergometer, the plasma uric acid ocnentration did not change significantly in 11 subjects. However, the plasma oxypurines increased from 19 micrM at rest to 50 microM at exhaustion and the urinary excretion of oxypurines increased from 140 to 400 mumol/g creatinine. Intracellular ATP decreased from 5.17 to 2.91 mumol/g and ADP and AMP increased from 0.85 to 1.29 and from 0.12 to 0.15 mumol/g wet weight, respectively. These observations suggest that there is an accelerated degradation of purine nucleotides to the precursors of uric acid in skeletal muscle during vigorous exercise.

Effects of prenatal stress and ethanol on cerebellar fiber tract maturation in B6D2F2 mice: an image analysis study.

Two studies were carried out to evaluate the role of prenatal stress in the outcome of prenatal ethanol exposure on central nervous system maturation in offspring. B6D2F1 mice were paid-fed liquid diets containing either 25% ethanol-derived calories or an isocaloric amount of maltose-dextrin on days 12 to 17 of gestation. During this period, half of the dams in each dietary condition also underwent two daily one-hour periods of restraint stress. A fifth group, provided with lab chow and water ad lib, was left undisturbed throughout pregnancy. At birth, all pups were fostered to untreated dams. Neither prenatal ethanol nor prenatal stress affected the maturation of cerebellar fiber tracts as indicated by membrane lipid staining either on day 32 post-conception or at weaning, nor was there an interactive effect of ethanol and stress combined. On the other hand, fiber tract maturation was significantly retarded on both days by prenatal undernutrition caused by treatment-induced reductions in maternal food intake. In the second study, pregnant dams were divided into three groups, all of which were fed lab chow and water. One group underwent the same stressing procedure as in the first study while a second group was unrestrained but pair-fed to the stressed group. A third group was undisturbed and allowed food and water ad lib. The offspring of both prenatally stressed and pair-fed dams did not differ from each other in terms of cerebellar fiber tract maturation, but both groups exhibited immature fiber tract development relative to the offspring of ad lib-fed dams. These data suggest that alterations in maternal nutritional status due to the ethanol and stress treatments can affect cerebellar fiber tract maturation in developing offspring.

Prenatal ethanol and stress in mice: 1. Pup behavioral development and maternal physiology.

On days 12 to 17 of pregnancy, B6D2F1 mice were pair-fed liquid diets containing either 25% ethanol-derived calories or an isocaloric amount of maltose-dextrin. During this period, half the mice in each dietary condition also underwent two daily one-hour periods of restraint stress. A fifth group, given lab chow and water ad lib, was left undisturbed throughout gestation. Neither treatment affected offspring body weight on days 22 or 32 postconception, but undernutrition produced by the pair feeding procedure reduced day 32 body weight in all groups relative to the ad lib-fed group. Both prenatal ethanol and pair feeding led to delayed neurobehavioral development on day 32, while prenatal stress significantly reduced the degree of developmental delay caused by these factors. In a second study, restraint stress significantly reduced blood alcohol concentrations in pregnant dams on day 15 of gestation while elevating plasma corticosterone concentrations, and this elevation was consistent regardless of the dietary condition of the dam. The pair feeding procedure also produced corticosterone elevations but the effect of ethanol was not significant. These results suggest that prenatal stress in the presence of other physiological insults may act to counter the actions of those insults.

Prenatal ethanol and stress in mice: 2. Development and behavior of fostered offspring.

On days 12 to 17 of gestation, B6D2F2 mice were pair-fed liquid diets containing either 25% ethanol-derived calories or an isocaloric amount of maltose-dextrin. During this time, half the mice in each dietary condition also underwent two daily one-hour periods of restraint stress. All pups were fostered at birth to untreated mothers whose pups, in turn, were fostered to the treated mothers. Two additional groups of untreated dams were included, the pups in one group being fostered to other untreated dams while the rest remained with their biological mothers. Prenatal ethanol retarded neurobehavioral development on day 32 postconception and also decreased pup body weight at birth and at weaning, and brain weight on day 32 and at weaning. Prenatal stress decreased body weight at birth in the pair-fed controls only, increased open field activity at weaning and affected retention of a learned passive avoidance task. Undernutrition due to the pair feeding procedure decreased pup birth weight. There were a few effects on untreated pups fostered to treated dams, but these were marginal. These results do not support a role of stress-induced physiological changes in ethanol teratogenicity.

Reductions in maternal food and water intake account for prenatal stress effects on neurobehavioral development in B6D2F2 mice.

This study evaluated the role of stress-induced reductions in food intake in pregnant B6D2F1 mice in the production of developmental abnormalities in the offspring. One group of dams underwent one hour of physical restraint stress twice daily from days 12 to 17 of gestation. A second group was not restrained but, during this period, each dam was pair-fed to a weight-matched partner in the stressed group. A third group was left undisturbed and allowed unlimited access to lab chow and water. The restraint stress procedure reduced the average daily food and water intake in the dams, resulting in lower maternal weights, with the unstressed pair-fed group being affected more severely than the stressed group. The offspring of both the stressed and pair-fed dams were lighter than the offspring of the dams fed ad lib on day 20 postconception, and exhibited lower brain weights on day 32 postconception. Neurobehavioral development, as assessed on a battery of sensorimotor tests on day 32 postconception, was retarded in the prenatally stressed pups in comparison to the ad lib pups, while the pair-fed pups did not differ from either group. There were no differences among any of the groups on day 50 body or brain weight, body or tail length, anogenital distance, or locomotion, rearing and defecation in the open field.(ABSTRACT TRUNCATED AT 250 WORDS)

Exposure to ethanol and nicotine during the brain growth spurt: spatial DMP performance in male rats.

Male Long-Evans rats were reared artificially and, using a 2x2 design, were exposed from postnatal days (PD) 6-9 to ethanol (ET: 6.5 g kg(-1) day(-1) "binge" exposure) and/or nicotine bitartrate (NIC: 6 mg kg(-1) day(-1) continuous exposure) via gastrostomy tubes. Controls were administered maltose-dextrin in amounts isocaloric to ET and/or sodium bitartrate. A fifth suckled-control group was reared normally. NIC accelerated eye opening on PD 14; whereas ET delayed eye opening and hindlimb support on PD 16. Beginning in postnatal week 7, rats were tested on a spatial delayed matching-to-place (DMP) version of the Morris water maze, which entailed a series of problems, each consisting of search and recall trials, that required the rats to use extra-maze cues to locate a hidden escape platform. In Phase 1 of testing, the ET-exposed groups were impaired in the recall trials, but there was no effect of NIC. A longer encoding time (45 vs. 10 s) improved performance across all groups. In contrast, acute administration of NIC (0.1 mg/kg ip) immediately prior to testing in Phase 2 failed to improve performance in any group. In conclusion, these results confirm previous findings of impaired spatial DMP-task performance in ET-exposed rats and further suggest that these memory deficits are amenable to amelioration.

Effects of postnatal ethanol exposure on brain growth and lipid composition in n-3 fatty acid-deficient and -adequate rats.

The artificial rearing model was used to investigate the effects of short-term exposure to ethanol on growth and fatty acid composition of forebrain (FB) and cerebellum (CB) during the brain growth spurt in either n-3 fatty acid-adequate (AD) or n-3 deficient (DEF) rat pups. On postnatal day 5, offspring of female rats that had been fed AD or DEF diets from day 5 of life were assigned to three groups: members of two groups were gastrostomized and artificially fed formulas appropriate for their maternal history, and the third group (suckled control) was fostered to lactating dams of a similar dietary history. Half of the artificially reared pups in each dietary condition were fed ethanol in their formula (7% vol/vol) in one-quarter of their daily feedings, while the others received maltose-dextrin substituted isocalorically for ethanol. Blood alcohol concentrations did not differ between the dietary groups. FB weight on postnatal day 9 was lower in ethanol-exposed offspring in both dietary conditions. Brain fatty acid composition reflected dietary history in that, compared with AD pups, DEF pups had lower percentages of docosahexaenoic acid, higher percentages of 22:5n-6, and a higher n-6/n-3 fatty acid ratio. However, the effects of ethanol exposure were inconsistent, lowering the n-6/n-3 ratio in the phosphatidylethanolamine (PE) fraction in FB but not in CB, while increasing this ratio in the phosphatidylcholine (PC) fraction in FB of the DEF pups only. Thus, while ethanol had some effects on lipid composition, there was no difference between the dietary groups in their vulnerability to the effects of early short-term ethanol exposure on brain growth.

Interactive effects of prenatal ethanol and N-3 fatty acid supplementation on brain development in mice.

This study assesses the combined effects on brain and behavioral development of ethanol administration and supplementation of the maternal diet with long chain n-3 polyunsaturated fatty acids. From day 7 to 17 of gestation, pregnant mice were fed equivalent daily amounts of isocaloric liquid diets; 20% of the energy was provided by either ethanol or maltose-dextrin, and a further 20% by either safflower oil (rich in linoleic acid, 18:2 n-6), or a combination of safflower oil with a fish oil concentrate (rich in eicosapentaenoic acid, 20:5 n-3, and docosahexaenoic acid, 22:6 n-3). On day 18 the liquid diets were replaced by lab chow; a fifth group was maintained on lab chow throughout the experiment. Measures on the pups included brain weight and the fatty acid composition of the brain phospholipids on days 22 and 32 post-conception (birth = day 19), as well as behavioral development. Maternal weight gain during gestation was decreased by ethanol relative to maltose-dextrin, and increased by fish relative to safflower oil. On day 32, the brain weight of ethanol-treated animals fed fish oil was greater than their safflower oil controls, whereas the reverse was true in the two maltose-dextrin groups; a similar trend was apparent on day 22. The brain phospholipid content of the longer chain fatty acids (20:4 n-6, 22:4 n-6, 22:5 n-6, 20:5 n-3, 22:5 n-3, 22:6 n-3) on day 22 reflected that of the prenatal diet, with the proportion of n-3 compounds being higher and that of n-6 lower in the fish oil than safflower oil groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of gamma-linolenic acid and docosahexaenoic acid in formulae on brain fatty acid composition in artificially reared rats.

This study evaluated the effects of dietary supplementation with gamma-linolenic acid (GLA, 18:3n-6) and docosahexaenoic acid (DHA, 22:6n-3) on the fatty acid composition of the neonatal brain in gastrostomized rat pups reared artificially from days 5-18. These pups were fed rat milk substitutes containing fats that provided 10% linoleic acid and 1% alpha-linolenic acid (% fatty acids) and, using a 2x3 factorial design, one of two levels of DHA (0.5 and 2.5%), and one of three levels of GLA (0.5, 1.0, and 3.0%). A seventh artificially reared group served as a reference group and was fed 0.5% DHA and 0.5% arachidonic acid (AA, 20:4n-6); these levels are within the range of those found in rat milk. The eighth group, the suckled control group, was reared by nursing dams fed a standard American Institute of Nutrition 93M chow. The fatty acid composition of the phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine/phosphatidylinositol membrane fractions of the forebrain on day 18 reflected the dietary composition in that high levels of dietary DHA resulted in increases in DHA but decreases in 22:4n-6 and 22:5n-6 in brain. High levels of GLA increased 22:4n-6 but, in contrast to previous findings with high levels of AA, did not decrease levels of DHA. These results suggest that dietary GLA, during development, differs from high dietary levels of AA in that it does not lead to reductions in brain DHA.

Investigative techniques and renal parenchymal damage in children with spina bifida.

The case records of 72 patients attending a multidisciplinary spina bifida clinic were reviewed to discover the prevalence of renal parenchymal damage. 19.4% of the total population had such damage. More detailed analysis of the group according to age showed that the prevalence of parenchymal damage in the over ten year olds (27.3%), was twice that of the under five year olds (13.3%) but the same as the prevalence of "at risk" patients (26.6%) in this group. On the basis that most renal parenchymal damage occurs early we conclude that the current approach to investigation and treatment is reducing the incidence of renal parenchymal damage in this population. Further reduction would require the early identification of the high risk bladder before the onset of hydronephrosis.

The incidence of chronic headache in children with shunted hydrocephalus.

Report of chronic headache amongst children with shunted hydrocephalus is frequent, and often leads to investigation for raised intra-cranial pressure and shunt malfunction, and much debate has appeared in the literature concerning possible cause. However headache is a common neurological symptom amongst children, and studies of prevalence indicate incidence of frequent non-migrainous headache to be 6.8%, and migrainous headache 4% in the general child population. A relationship between stress and anxiety and headache is recognised, and the hydrocephalic child has many reasons above those of his/her peers to be subject to stress. It is also hypothesised that this group may be more vulnerable than peers to developing a migraine-like condition in the face of adequate shunt function. The clinician dealing with complaint of chronic headache in a hydrocephalic child must therefore be wary of over-investigation in a child with a working shunt, or missing possible shunt malfunction when the only symptom is chronic headache. It was speculated therefore that incidence of non-shunt related chronic headache in this group would be high, and an attempt was made to document incidence of migrainous and non-migrainous headache in the medical notes, and in replies to postal questionnaire sent to a sample of 130 children with shunted hydrocephalus of varying aetiology. Incidence of migrainous headache was documented in the medical notes in 8.5% of cases, with incidence rising to 21.5% using self-report. Incidence of non-migrainous headache was also very high (15.4%) and the overlap between migraine and tension headache, combined with difficulty of diagnosis in children may indicate migraine to be more frequent still. The concept of "Shunt Migraine" is therefore worthy of consideration. Report of chronic headache led to investigation in a large proportion of cases, but symptomatology often continued. Even when shunt malfunction was indicated, shunt revision did not "cure" complaint of headache. Headache was not found to be related to diagnosis associated with hydrocephalus, to presence of seizure disorder, or to the sex of the child, although in common with other studies, there was a strong trend towards girls being statistically more likely to experience headache than boys. There was a relationship however between report of chronic headache, and the sort of school a child was likely to attend; children who attended mainstream school without the support of a Statement of Special Educational Need were more likely to report headache than their peers, and it is hypothesised that these children may be suffering sufficient stress to contribute to maintenance of headache. The importance of the multi-disciplinary team in assessment of children's physical, intellectual and emotional status is stressed, in order that medical interventions have the greatest chance of success.

Combined effects of moderate ethanol consumption and a low-protein diet during gestation on brain development in BALB/c mice.

We investigated whether or not moderate ethanol consumption during gestation would interact with the effects of a low-protein diet in affecting brain development in BALB/c mice. The independent variables included fetal body and brain weights and cross-sectional area in midsagittal sections of the corpus callosum (CC) and anterior commissure (CA). Pregnant animals were fed either ethanol 12% v/v or an isocaloric sucrose solution from days 5 to 19 of gestation, when fetal development was assessed. In addition, the animals were fed semisynthetic isocaloric diets containing either 8 or 20% casein. All animals were pair-fed to those in the group receiving ethanol and 20% casein; an additional control group was fed lab chow ad libitum. There was clearly an interactive effect of diet and ethanol consumption on blood alcohol concentrations: those in the low-protein group were significantly higher than in the normal-protein group. Similarly, the effect on body weight in the group receiving low protein plus ethanol was greater than the additive effect of either treatment alone, although this may have been due partly to differences in litter size. Brain weight in this group was also significantly less than in the other three groups, which did not differ from each other. Covariance analysis, adjusting brain weight for body weight, suggested a brain-sparing effect of low protein but not ethanol. Neither treatment affected the incidence of the CC being absent at midline. The low-protein treatment decreased the cross-sectional area of both the CC and CA; the effect on the CC was independent of brain weight. There was no effect of ethanol on either of those measures.

gamma-Linolenic acid fails to prevent the effects of prenatal ethanol exposure on brain and behavioral development in B6D2F2 mice.

The purpose of this study was to obtain a quantitative assessment of the behavioral retardation caused by prenatal ethanol exposure in mice and to test the hypothesis that gamma-linolenic acid (GLA) supplementation would prevent such effects. Pregnant B6D2F1 mice were fed liquid diets containing 25% ethanol-derived calories from days 7-17 of gestation. The experimental groups were given GLA via subcutaneous injection; the control was administered vehicle only. All groups were pair fed to this ethanol control, including a second control group which received sucrose substituted isocalorically for ethanol. Additional control groups included one fed lab chow ad libitum and two further ethanol groups, one treated with coconut oil, the other with arachidonic acid (AA). Behavioral development of the pups was measured on day 32 postconception and open field behavior was measured on day 50. Body and brain weight were also measured. The results indicated that reproductive outcome, as measured by animals which produced live pups, was worse in the GLA- and AA-treated groups. Ethanol produced significant behavioral retardation of the order of 1.7 days. Body and brain weight were lower in ethanol-treated pups. Covariance analysis indicated that the effect on brain weight was independent of the effect on body weight. Open field scores suggested that ethanol-treated males were more active then sucrose controls. The data did not support the hypothesis that GLA would prevent the deleterious effects of prenatal ethanol exposure; in no instance was a GLA-treated group different from the ethanol control.

Varying physiological response to arm-crank exercise in specific spinal injuries.

The purpose of this arm-crank ergometry (ACE) study was to provide a greater understanding of the influence to which specific cervical and thoracic spinal cord injuries contribute to reduction in optimal cardio-respiratory and metabolic function. Twenty five male volunteers aged 20 to 47 years participated. Twenty disabled wheelchair-confined spinal cord injured (SCI) subjects were equally divided into four 'site-specific' groups based on the lesion being within either high- or low- cervical or thoracic anatomical regions. Five physically non-disabled controls (As) were included. Measured variables tended to decrease progressively from As to high-level quadriplegics. Analysis revealed a high variance in maximum cardio-respiratory performance levels between groups (P < 0.001). These findings confirm that limitation to upper body physical capabilities in the SCI during high-intensity ACE is dependent on specific lesion site. Considerable variability in performance levels were measured in those suffering lesions within closely approximating anatomical regions. Results also suggest a greater importance in the location of cervical rather than thoracic injuries in contributing towards higher relative losses in maximal cardio-respiratory and metabolic potential. Alterations in body composition and varying severity of muscle paralysis likely also play a contributing role in reducing optimal metabolic function in SCI individuals. The importance for stringent classification techniques of spinal cord lesion site in predicting upper body physical exercise potential in the SCI has therefore been highlighted in this study.

An empirical comparison of Maslow's and Murray's needs systems.

The Work Motivation Inventory (WMI), a measure of Maslow's hierarchy of needs, and the Edwards Personal Preference Schedule (EPPS), a measure of Murray's manifest needs, were administered to 372 undergraduates. The two instruments were compared using canonical analysis. The analysis revealed three significant relationships between components of the two instruments. The first relationship supported Maslow's need hierarchy in general and its measurement by the WMI. The second suggested a fluctuating relationship between giving and receiving help and the levels of Maslow's hierarchy. The third relationship suggested that need for Achievement is associated with the intermediate levels of Maslow's hierarchy.

Muscle glycogen repletion after high-intensity intermittent exercise.

Six subjects exercised to exhaustion on a cycle ergometer at intensities corresponding to approximately 140% of their maximal aerobic power. Subjects attempted to pedal for 1-min intervals with 3-min rest periods between, and continued until 30 s of exercise could no longer be maintained. Venous blood was sampled for lactate and glucose analysis. Muscle biopsies were extracted from the quadriceps before and immediately after exercise and at 2-, 5-, 12-, and 24-h intervals thereafter for total glycogen analysis. Three subjects consumed a mixed controlled diet (approx. 3,100 kcal) during the 24 h after exercise, and three consumed the same diet plus an additional 2,500/kcal carbohydrate. Following exercise, glycogen concentration had dropped to a mean value of approximately 28% of its preexercise value. After 2 h, it had recovered to 39%, at 5 h to 53%, at 12 h to 67%, and at 24 h to 102% of its preexercise value, with no difference in resynthesis rate between the two groups. It was concluded that, following glycogen depletion through intense intermittent exercise, complete recovery to preexercise values may be accomplished within 24 h; and that within this time period, the rate of resynthesis cannot be accelerated by a higher than normal carbohydrate intake.