The effects of neonatal infection, perinatal malnutrition, and crowding on the metabolism of brain catecholamine were studied in specific pathogen-free mice. Metabolic turnover of catecholamine was determined by measuring the incorporation of precursor tyrosine-(14)C into brain tissue, catabolic activity of norepinephrine-(3)H at various times after intracisternal injection, and tissue levels of dopamine and norepinephrine. The rate of tyrosine incorporation was decreased by neonatal infection but was increased by perinatal malnutrition and crowding. There was no difference in catabolic activity of norepinephrine between infected, crowded, and control groups. In the malnourished group, however, the total radioactivity from norepinephrine was significantly higher than in the control group (1/2) and 2 hr after injection. The brain contents of dopamine and norepinephrine were depressed in the malnourished group. There was no significant difference in catecholamine levels between infected, crowded, and control groups. In the malnourished group, treatment of the mothers with growth hormone prevented almost completely weight loss during lactation, and also resulted in higher fetal weight. Hormone treatment restored to normal the levels of brain catecholamine and the enzymatic activity of brain tyrosine hydroxylase in progeny of malnourished mothers.

Animals↗

PubMed1972

Lasting biological effects of early environmental influences. VII. Metabolism of adenosine in mice exposed to early environmental stress.

The metabolism of adenosine 3',5'-monophosphate (cyclic AMP) was studied in specific pathogen-free mice exposed to neonatal infection with mouse enterovirus or to malnutrition during early life. Metabolic activity was determined by measuring the turnover of cyclic AMP-8-(14)C to respiratory (14)CO(2), its incorporation into various organs and plasma, and the binding activity of synaptosome for cyclic AMP. Early malnutrition increased the catabolism of cyclic AMP as measured by expiration in respiratory CO(2). The level of cyclic AMP was lower in plasma and its incorporation into various tissues was decreased in infected and malnourished animals. Metabolic products of cyclic AMP were isolated from plasma by ion exchange chromatography. Cyclic AMP-8-(14)C had completely disappeared 9 hr after injection. Fewer metabolites of cyclic AMP were detected in infected or malnourished groups than in controls and the metabolic reaction from 5'-AMP to adenosine seemed to be slow in these animals. The ability to incorporate cyclic AMP to synaptosome was also impaired in the experimental groups. The concentrations of brain cyclic AMP were lower in infected or malnourished animals than in controls. Depression of accumulation of cyclic AMP probably resulted from excessive activity of phosphodiesterase, rather than from impairment of adenyl cyclase. Intraperitoneal administration of theophylline brought the activity level of phosphodiesterase to normal in infected or malnourished mice; this fact probably accounted for enhanced accumulation of brain cyclic AMP.

Animal Nutritional Physiological Phenomena↗

PubMed1971

Toxic factors in enzymes used in laundry products.

Autolyzates of Bacillus subtilis used as enzymes in laundry products contain several potentially toxic substances.

Animals↗

PubMed1971

The mouse intestinal microflora with emphasis on the strict anaerobes.

The various components of the intestinal microflora in the mouse become established according to a definite time sequence; the strict anaerobes are the last groups of bacteria to reach their maximum population levels, 14-16 days after birth. The multiplication of these strict anaerobes in the mouse intestine seems to depend upon the prior multiplication of other bacterial species, and coincides with the ingestion of food other than maternal milk. These two conditioning factors may correspond to the establishment of a suitably reduced Eh potential and to the provision of certain metabolites. Once established, the strict anaerobes constitute by far the largest percentage of the total intestinal microflora; most of them are associated in a viable form with the mucosa. In normal animals they persist at very high levels throughout the life span. However, their populations can be drastically reduced by dietary manipulation of the animal, by administration of vancomycin, or by certain disease processes of the intestine. The strict anaerobic bacteria seem to play an important, and perhaps essential role in the maintenance of the anatomic structures and physiological functions of the intestine. They also seem to hold in check several species of intestinal bacteria, in particular the coliform bacilli.

Age Factors↗

PubMed1971

Lasting biological effects of early environmental influences. VI. Effects of early environmental stresses on metabolic activity and organ weights.

Specific pathogen-free mice were exposed to three different kinds of environmental stress during early life: (a) by infecting them with a mouse enterovirus on the second day after birth; (b) by placing the mother during pregnancy and lactation on a mildly deficient diet containing wheat gluten supplemented with See PDF for Structure small amounts of lysine and threonine; (c) by combining a (neonatal infection) and b (early malnutrition). All animals survived the three types of stresses, but all exhibited marked depressions of metabolic activity, and of body weights and organ weights. These depressions lasted throughout the experimental period even though all animals were placed under optimum conditions of nutrition and husbandry after weaning, and maintained under these same conditions thereafter. Metabolic activity was determined by measuring the turnover of (14)C-acetate and (14)C-glucose in respiratory CO(2), and their incorporation in total lipids of liver and brain. The utilization of (14)C-acetate was profoundly depressed in all experimental groups with regard to both elimination in respiratory CO(2) and their incorporation in total lipids of liver and brain. In contrast, the utilization of (14)C-glucose was much less affected; its incorporation into lipids was not decreased and its elimination in respiratory CO(2) was depressed only in animals having experienced both neonatal infection and early malnutrition. The extent of weight depression per 100 g of body weight differed according to the organ and the type of stress. Irrespective of the organ, however, depression of weight was largest in animals having experienced both neonatal infection and early malnutrition. And irrespective of the type of stress, the brain exhibited the smallest depression of weight relative to total body weight.

Acetates↗

PubMed1971

Man made environments.

Explore the source record for details and available documents.

Environment↗

PubMed1970

The anaerobic bacterial flora of the mouse cecum.

Refinements of the anaerobic technique such as the utilization of prereduced media and the removal of traces of oxygen from the gases used by passage through a hot copper oven resulted in quantitative and qualitative improvements in the recovery of anaerobic bacteria from the cecum of SPF mice. The commonest morphologic types of bacteria in the mouse cecum were tapered rods. These characteristically gave "speckled" colonies on agar plates. Those identified were species of the genera Fusobacterium, Eubacterium, and Clostridium. Several of the morphologic types seen with phase microscopy still could not be cultivated. The implications of these findings for the study of the intestinal flora are discussed.

Air↗

PubMed1969

Lasting biological effects of early environmental influences. IV. Notes on the physicochemical and immunological characteristics of an enterovirus that depresses the growth of mice.

Physicochemical and immunological techniques have been used in an attempt to characterize a filterable agent, separated from the intestines of mice raised under ordinary conditions of husbandry, which produces a lasting depression of weight in specific pathogen-free (SPF) mice when administered to them orally shortly after birth. Although this agent has not yet been identified, it will be tentatively designated here as enterovirus. The mouse enterovirus can be readily sedimented by ultracentrifugation and by precipitation at pH 4.3; it does not pass through cellophane membranes. Its infective power is completely destroyed by ultraviolet radiation, but is resistant to heating at 56 degrees C, exposure to ether, treatment with trypsin, ribonuclease, and deoxyribonuclease. Dialysis and treatment with ether and nucleases greatly increase the infective activity of the intestinal filtrates containing the enterovirus, a finding which suggests that these procedures eliminate or destroy some inhibitory substance(s). The mouse enterovirus causes hemagglutination of mouse red blood cells. When injected into rabbits, it elicits in them an immune response that renders their serum capable of neutralizing its weight-depressing activity. As measured by inhibition of hemagglutination or complement fixation, the sera of infected mice do not exhibit any significant activity against usual mouse viruses. Centrifugation of the mouse enterovirus in 50%-20% sucrose gradient gave almost complete recovery of the infectivity and of hemagglutinating activity in the same fraction. In contrast, the protein content of the material was distributed through the various fractions. Consequently, this procedure resulted in a marked increase of specific activity.

Animals↗

PubMed1969

Lasting biological effects of early environmental influences. V. Viability, growth, and longevity.

The effects of neonatal influences on the growth and longevity of mice were studied by using animals derived from a highly inbred germfree colony that had been reassociated with a microbial flora free of known pathogens. The size of the animals at weaning time could be conditioned predictably by manipulating the diet of their mothers during gestation and lactation or by shortening or lengthening the period of lactation. A deficient diet during gestation or during lactation decreased the metabolic efficiency of the adult animal, even if it was fed an optimum diet after weaning. The effect was greatest when malnutrition occurred during both pregnancy and lactation. In contrast, an optimum diet during gestation and lactation rendered the animal less susceptible to the depressing effects of nutritional deficiency during adult life. A marked and lasting growth depression could be reproducibly achieved by contaminating newborn mice orally with an unidentified enterovirus. But neonatal infection with enterobacteria or mycobacteria even though severe, did not significantly alter the growth rate. Regardless of its initial cause, the depression of the growth rate during the preweaning period persisted throughout the whole life span of the animals, even when they were placed under optimum sanitary and nutritional conditions after weaning. Agencies (nutritional or infectious) which brought about a depression of whole body weight also affected the absolute and relative sizes of the various organs, especially of the brain. By manipulating neonatal influences, it was possible to produce at will in a given colony of highly inbred mice a family of strikingly different growth curves. This could be done without causing the death of any animal or affecting longevity.

Animals↗