The effect of exhaustive exercise on the antioxidant enzyme system in skeletal muscle from calcium-deficient rats

 The aim of the current study was to elucidate the synergism of dietary calcium restriction and exhaustive exercise in the antioxidant enzyme system of rat soleus muscle, and to investigate the involvement of neutrophils in exercise-induced muscle damage. Forty-eight male Wistar rats were assigned to the following groups: control (C) or calcium-restricted [1 month (1 M) or 3 months (3 M)]. Each group was subdivided into acutely exercised or non-exercised groups. Soleus muscle from each rat was analysed to determine the levels of antioxidant enzymes [Mn-superoxide dismutase (SOD), Cu,Zn-SOD, glutathione peroxidase (GPX), and catalase (CAT)]. Dietary calcium restriction resulted in calcium deficiency and upregulated the antioxidant enzymes examined except GPX. Conversely, exhaustive exercise significantly decreased GPX and CAT, but not SODs activities in the calcium-restricted (1 M and/or 3 M) rats. Contents of immunoreactive Mn-SOD and Cu,Zn-SOD were only increased in the 3 M rats. During calcium restriction, the mRNA expression of both forms of SOD showed initial upregulation, followed by downregulation. Exhaustive exercise significantly increased the mRNA expressions only in the 3 M rats. Moreover, exhaustive exercise markedly increased myeloperoxidase activity in soleus muscles from the 1 M and 3 M rats compared with the C rats, and significantly enhanced the ability of neutrophils to generate superoxide in the 3 M rats. The results demonstrate that dietary calcium restriction upregulates certain antioxidant enzyme activities in rat soleus muscle, indicating an enhanced resistance to potential increases in intracellular reactive oxygen species. The results also suggest that exhaustive exercise may cause oxidative damage in soleus muscle of calcium-deficient rats through the activation of neutrophils. Received: 4 August 1997 / Received after revision: 29 September 1997 / Accepted: 26 November 1997     

Long-lived alphaMUPA transgenic mice show reduced SOD2 expression, enhanced apoptosis and reduced susceptibility to the carcinogen dimethylhydrazine

Calorie restriction (CR) extends the life span of various species through mechanisms that are as yet unclear. Recently, we have reported that mitochondrion-mediated apoptosis was enhanced in alphaMUPA transgenic mice that spontaneously eat less and live longer compared with their wild-type (WT) control mice. To understand the molecular mechanisms underlying the increased apoptosis, we compared alphaMUPA and WT mice for parameters associated with SOD2 (MnSOD), a mitochondrial antioxidant enzyme that converts superoxide radicals into H(2)O(2) and is also known to inhibit apoptosis. The SOD2-related parameters included the levels of SOD2 mRNA, immunoreactivity and enzymatic activity in the liver, lipid oxidation and aconitase activity in isolated liver mitochondria, and the sensitivity of the mice to paraquat, an agent that elicits oxidative stress. In addition, we compared the mice for the levels of SOD2 mRNA after treatment with bacterial lipopolysaccharides (LPS), and for the DNA binding activity of NFkappaB as a marker for the inflammatory state. We extended SOD2 determination to the colon, where we also examined the formation of pre-neoplastic aberrant crypt foci (ACF) following treatment with dimethylhydrazine (DMH), a colonic organotypic carcinogen. Overall, alphaMUPA mice showed reduced basal levels of SOD2 gene expression and activity concomitantly with reduced lipid oxidation, increased aconitase activity and enhanced paraquat sensitivity, while maintaining the capacity to produce high levels of SOD2 in response to the inflammatory stimulus. alphaMUPA mice also showed increased resistance to DMH-induced pre-neoplasia. Collectively, these data are consistent with a model, in which an optimal fine-tuning of SOD2 throughout a long-term regimen of reduced eating could contribute to longevity, at least in the alphaMUPA mice.     

The effects of subdiaphragmatic vagotomy on circadian corticosterone rhythmicity in rats with continuous or restricted food access

Plasma corticosteroid circadian periodicity was determined in three groups of individual adult male rats. Categories were: postsubdiaphragmatic vagotomy, sham-operated, and controls. Blood was sampled every 4 hours over a 48-hour period with ad lib feeding and after a 13-day period on daytime (0930–1330) restriction of food and water availability. Plasma corticosterone circadian periodicity was normal under ad lib conditions in control, sham-operated, and vagotomized animals. Under food-restricted conditions, both the sham-operated and vagotomized animals exhibited the 12-hour shift in the circadian peak of plasma corticosterone levels that we have previously described in normal animals under such conditions. There were no differences between groups in the total amount of food and water consumed or the percentage of nocturnal food intake on an ad lib feeding schedule. Both vagotomized and sham-operated animals manifested reductions in food intake under conditions of food restriction, although vagotomized consumed less than sham-operated animals. The present data indicate that an intact vagus nerve is not necessary for the establishment of circadian periodicity of plasma corticosterone levels or the shift in the periodicity of corticosteroid secretion produced by a restricted feeding regimen.     

Electrical self-stimulation of single and multiple loci: long term observations

Rats with chronic hypothalamic electrodes were allowed continuous access to self-stimulation, food and water in a 3 lever chamber. A prolonged burst of self-stimulation, with little food and water intake, was followed by bursts of activity on all 3 levers. A 12 hr light-dark cycle imposed a diurnal periodicity on all behaviors except in animals self-stimulating at the highest daily rates where self-stimulation was equal in dark and light. Under constant light conditions there was a 30 min daily shift in the peak periodicity of all behaviors. Increasing the current by 10 μA led to another continuous self-stimulation session for one day, with a subsequent decline and stabilization after three days. Reduction of the current to its original setting abolished self-stimulation for one day, but within 5 days rates returned to control values. Animals with electrodes in the septal, anterior and posterior hypothalamic areas allowed continuous access to self-stimulation on all 3 electrodes displayed similar behavior in that after a long initial self-stimulation session alternating on all 3 electrodes, periodic bursts of activity occurred on all three electrodes. The diurnal periodicity of self-stimulation seemed to be determined by the current intensity. The similarity of self-stimulation to normal drive mechanisms is discussed.     

The structuring of an allergy index based on IgE-mediated skin sensitivity to common environmental allergens

We computed skin-test sensitivity levels in 485 adults puncture-tested with eight standardized, high-quality inhalant allergens tested at single concentrations. In order to quantitate the "average" IgE-mediated skin sensitivity of each subject, we used both nonparametric and parametric statistical methods to generate two "allergy indices" (Allergy Index I and Allergy Index II) based on sensitivity end-point data from the subpopulations of individuals positive to six of the eight allergens. For the 192 skin test-positive subjects, Allergy Index I and Allergy Index II were significantly correlated with each other (rs = 0.98, p less than 0.001) and with the number of positive skin-test reactions (rs congruent to 0.9, p less than 0.001) as well as with log[total serum IgE] (r congruent to 0.4, p less than 0.01). In 102 ragweed-positive subjects, log[specific IgE to ragweed] was significantly correlated with ragweed-specific "ragweed indices I and II" (r congruent to 0.6, p less than 0.01). Furthermore, the average daily symptom scores reported by 14 ragweed-positive subjects during the ragweed pollination season were significantly correlated with ragweed indices I and II (p less than 0.05). We propose the use of Allergy Index II in epidemiologic and genetic studies of allergic phenotypes as well as in clinical decisions for diagnosis and immunotherapeutic intervention.     

Comparison of gastric, duodenal and jejunal contributions to the inhibition of food intake in the rat

Rats equipped with tubes leading to their stomach, duodenum or jejunum were infused with a liquid diet for 9 hr (4 ml/hr) and were allowed to eat during the last 8 hr of infusion. All rats ate significantly less on diet infusion days than on saline or no infusion days. A second study showed that a taste aversion could not be conditioned to flavored water associated with diet infusion. Apparently, intrajejunal injection of nutrients produces satiety and not discomfort. Infusion of the diet for 5 consecutive days into the stomach, duodenum or jejunum consistently and significantly lowered food intake by reducing meal size, not meal frequency. Results suggest that the small intestine below the infusion site contributes to normal satiety.     

Rhythmic patterns of food and water intake in the dog: preliminary study (author's transl)]

The spontaneous rhythmic patterns of food and water intake in the dog during periods of 24 hr have been studied under three experimental conditions: natural light, continuous light and artificial light with day and night sequences. Under natural light there is a rhythmic pattern in the frequency of food intake and the amount of food consumed. During the night, periods of food consumption are numerous and the amount of food ingested is significant. During the day both the number of periods of food intake and the amount of food consumed is less. Similar results were obtained under continuous light. Under artificial light, with day and night sequences, there is a tendency to equalize the amount of food consumed through the 24 hr. This produced a displacement of frequency curves. In these three situations there seems to be an important relationship between the amount of food consumed and the time intervals following periods of food intake. Generally, similar results were obtained for water intake.     

Hypothalamic self-stimulation in the female rat: effects of oestrus and food deprivation.

Natural oestrus (147 cycles) had no overall effect in a longitudinal study of self-stimulation in a group of rats with hypothalamic electrodes (n = 20), though some individual animals showed significant increases in response rate at oestrus or at dioestrus. Animals were significantly more likely to show peak rates at prooestrus or oestrus if their electrodes were located in hypothalamic feeding areas; the effects in these rats were therefore probably indirect and non-sexual, caused by the decrease in food intake that accompanies oestrus. In ovariectomized rats, however, self-stimulation of feeding areas was usually unaffected by oestradiol injections, and increases in response rate reported after oestradiol injections in ovariectomized animals may therefore be a direct effect of the hormone; replicated study of the only animal showing unequivocal oestrogen-sensitive enhancement of self-stimulation showed that the effect was specific to oestrogenic (and not androgenic) steroids, and that the minimum effective dose was within the physiological range. These findings indicate both direct and indirect effects of oestrus on hypothalamic self-stimulation.     

Adaptive modification of ingestive behavior in beach mice (Peromyscus polionotus).

The ability of an inland and beach race of the old-field mouse to use increasing concentrations of NaCl solutions was compared. Inland mice drank significantly more fluid at all concentrations than did beach mice. These differences became more pronounced as the salt concentration was increased. Food consumption was similar in both races while drinking water or a dilute salt solution, but beach mice ate significantly greater amounts when the concentration of salt was increased above 0.2 M. Weight losses on salt solutions were approximately equal in both races, although beach mice survived longer and tolerated the higher concentrations better. There was no difference in the ability of the races to concentrate urine or excrete Na⁺. When given a choice of distilled water or two salt solutions, beach mice consumed significantly more water (77%) than salt solutions (23%) whereas inland mice drank approximately equal amounts of water (54%) and salt solutions (46%). When deprived of anything to drink, beach mice almost stopped eating for the first two days while inland mice did not reduce their food consumption as quickly and died sooner. Thus, it appears that adaptive modifications of ingestive behavior are important for survival in habitats where salt accumlates and summer droughts may be a problem.