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Opposite effects of one and three injections of cortisone or thyroxine on intestinal lactase activity in suckling mice.

A single injection of cortisone or thyroxine to 8-day-old suckling mice initiates a temporary decrease of lactase activity. On the contrary, 3 injections of cortisone or thyroxine provoke a significant increase of lactase activity. It appears that the mechanism which controls the postnatal development of lactase in suckling animals is more complex than expected.

Animal Population Groups

Interactions in vivo between oxidation of non-esterified fatty acids and gluconeogenesis in the newborn rat.

Metabolic interactions between fatty acid oxidation and gluconeogenesis were investigated in vivo in 16h-old newborn rats under various nutritional states. As the newborn rat has no white adipose tissue, starvation from birth induces a low rate of hepatic fatty acid oxidation. Hepatic gluconeogenesis in inhibited in the starved newborn rat when compared with the suckling rat, which receives fatty acids through the milk, at the steps catalysed by pyruvate carboxylase and glyceraldehyde 3-phosphate dehydrogenase. These inhibitions are rapidly reversed by triacylglycerol feeding. Inhibition of fatty acid oxidation by pent-4-enoate in the suckling animal mimics the effect of starvation on the pattern of hepatic gluconeogenic metabolites. It is concluded that, in the newborn rat in vivo, hepatic fatty acids oxidation can increase the gluconeogenic flux by providing the acetyl-CoA necessary for the reaction catalysed by pyruvate carboxylase and the reducing equivalents (NADH) to displace the reversible reaction catalysed by glyceraldehyde 3-phosphate dehydrogenase in the direction of gluconeogenesis.

Animals

Coxsackievirus B4 myocarditis in mice: valvular changes in virus-infected and control animals.

Suckling, weanling, and adult HaM/ICR and Swiss-Webster mice were inoculated intraperitoneally with the TC631 and Dowell strains of coxsackievirus B4. Vero cell-inoculated and uninoculated control mice were also studied under code. An intense, necrotizing myopericarditis was produced in suckling mice; it was less severe in weanlings. Myocarditis did not occur when coxsackievirus B4 was inoculated into adult mice. Progressive sclerosis and thickening of all valves in both strains of mice were observed with equal frequency in infected and control mice. There was no evidence that coxsackievirus B4 induced a specific valvular or endocardial lesion.

Animals

The development of ketogenesis at birth in the rat.

In the suckling newborn rat, blood ketone bodies begin to increase slowly 4h after birth and then rise sharply between 12 and 16h, whereas the major increase in plasma non-esterified fatty acids and liver carnitine occurs during the first 2h of life, parallel with the onset of suckling. In the starved newborn rat, which shows no increase in liver carnitine unless it is fed with a carnitine solution, the developmental pattern of the ketogenic capacity (tested by feeding a triacylglycerol emulsion, which increases plasma non-esterified fatty acids by 3-fold) is the same as in the suckling animal. This suggests that the increases in plasma non-esterified fatty acids and liver carnitine seen 2h after birth in the suckling animal are not the predominant factors inducing the switch-on of ketogenesis. Injection of butyrate to starved newborn pups resulted in a pattern of blood ketone bodies which was similar to that found after administration of triacylglycerols, but, at all time points studied, the hyperketonaemia was more pronounced with butyrate. It is suggested that, even if the entry of long-chain fatty acids into the mitochondria is a rate-limiting step, it is not the only factor controlling ketogenesis after birth in the rat. As in the adult rat, there is a reciprocal correlation between the liver glycogen content and the concentration of ketone bodies in the blood.

Animals

Intestinal neuraminidase activity of suckling rats and other mammals. Relationship to the sialic acid content of milk.

1. The neuraminidase activity of homogenates of the mucosa of the middle and distal thirds of the small intestine of rats increased about 5-fold between birth and 4 to 8 days of age, and then gradually declined to the much lower adult activity by 24 days. No comparable changes occurred in the proximal third. 2. In 8-day-old rats, the neuraminidase activity of the middle and distal thirds of the small intestine was about 10 times greater than that of the proximal third, 20 times greater than that of the colon and at least 100 times greater than that of the liver, brain, gastric mucosa or pancreas. 3. In all other species investigated (mice, rabbits, cats and guinea pigs), the neuraminidase activity of the middle and distal thirds of the small intestine was greater in suckling animals than in adults. 4. The sialic acid content of rat milk increased about 2-fold between birth and 8 days post partum and then declined. 5. There was a highly significant positive correlation between the intestinal neuraminidase activity of suckling animals of various species and ages and the sialic acid content of milk obtained from the corresponding species and stage of lactation. 6. It is suggested that the intestinal neuraminidase of suckling mammals functions primarily to remove sialic acid from various components of milk, thus providing sialic acid for the synthesis of sialoglycoproteins and gangliosides by the young.

Aging

The effect of age upon the influx of glucose into the brain.

1. Rats aged from 1 to 116 weeks were studied. 2. Influx of glucose into the brain is low in suckling rats but rises after weaning, to reach its highest level in the young adult, thenceforward declining slowly as age increases. 3. The blood-brain barrier for glucose is fully developed in the rat by the age of 18 days and glucose enters the brain, at this stage, by carrier-mediated transport, as in the adult. 4. The results show that the low influx of glucose into the brain of the suckling animal is due to a low maximum rate of transport of glucose rather than to a low affinity of the carrier-molecule for glucose. 5. In the young adult rat, efflux of glucose back from the brain into the blood is greater than in either the suckling or the old animals. Thus the margin of safety, i.e. the extent to which the blood glucose can be reduced without affecting the utilization of glucose by the brain, is highest in the young adult. 6. The lower margin of safety in the suckling animals is compensated for by the high influx of the ketone bodies which provide an alternative source of energy at this age. In the old animals there is no alternative source of energy, so that the older brain is at greatest risk in hypoglycaemia.

Aging

Effect of dam's diet on PCB accumulation in nursing Osborne Mendel pups.

Upon parturition, dams were fed high fat or high carbohydrate diets to which 1, 10, and 30 ppm of Aroclor 1254 were added to study the effect of diet on fat and PCB accumulation in nursing pups. The percentage of body fat in the carcasses of 0, 8, and 16 day old pups ranged from 2.2 to 18.2% and from 1.2 to 12.0% for animals suckled by dams fed high fat and high carbohydrate rations, respectively. Accumulation of Aroclor 1254 expressed as ppm wet weight or as total PCB's per pup was similar for animals nursed by dams fed either the high fat or high carbohydrate ration, but pups from dams fed a high carbohydrate ration also had significantly less body fat. Therefore, transfer of PCBs via the milk appears to be more a function of the amounts of PCB's consumed by the dam than the diet's ability to increase the percentage of body fat in the pups.

Adipose Tissue

Immunomodulation of host resistance to experimental viral infections in mice: effects of Corynebacterium acnes, Corynebacterium parvum, and Bacille calmette-guérin.

Resistance to a representative group of experimental virual infections in mice was significantly enhanced by nonspecific modulation of host defense mechanisms. Corynebacterium acnes, Corynebacterium parvum, and bacille Calmette-Guérin were effective in enhancing host resistance. Animals treated seven to 10 days before inoculation of virus were protected against a lethal infection with Herpesvirus hominis type 2, encephalomyocarditis virus, murine cytomegalovirus, or Semliki Forest virus. The protection of experimental animals against encephalomyocarditis virus infection intitiated by either the intraperitoneal or the respiratory route indicated that C. acnes exerted a systemic, rather than local, effect. A maturation process was required for host defense mechanisms stimulated by C. acnes, as indicated by the failure to enhance resistance in suckling animals. Involvement of cells of the lymphoreticular system was demonstrated by transfer of enhanced resistance against H. hominis type 2 to recipient animals with peritoneal exudate cells harvested from mice pretreated with C. acnes. Finally, these same cells inhibited the progression of herpetic infection in tissue culture. The data suggest that immunomodulation, possibly through activation of macrophages, may offer a method for enhancement of host resistance to viral infections.

Animals

Experimental alterations of endorphin levels in rat pituitary.

Endorphin (END) levels in rat pituitary were assessed with the opiate receptor binding assay. Procedures reported to alter hormone secretion from END-rich intermediate or anterior lobes were examined for their effect on END content. Lesions of the paraventricular nucleus (PVN) had no significant effect on END content. Ingestion of 2% NaCl reduced END levels in a significant majority of the animals. Suckling, a natural physiological stimulus, significantly elevated neurointermediate lobe END. Footshock and immobilization each evoked 40--50% reductions in anterior lobe END content. Pituitary ENDs are thus affected by many of the same stimuli that also promote release of a number of peptide hormones derived from the same biosynthetic precursor. However, separate mechanisms likely exist for control of secretion of these peptides from anterior and neurointermediate lobe.

Animals

Development of intestinal brush border membrane proteins in the rat.

1. The proteins of the intestinal microvillus membrane have been studied during post-natal development in the rat (days 12--37). 2. In suckling animals (up to age 20 days), the majority of alkaline phosphatase, glucoamylase and lactase activities in the distal half of the intestine were located in the supernatant fraction (100000 X g, 60 min). These enzymes were attached to the membrane from the proximal intestine at all ages. 3. Alkaline phosphatase, maltase and lactase activities in the supernatant fractions chromatographed in Sephadex G-200 in positions similar to the corresponding membrane enzyme. Corresponding activities for lysosomal counter-parts of maltase and lactase present in the supernatant fraction chromatographed differently. Moreover, pH optimum of the soluble enzymes was 9.2 for phosphatase and 5.5--6.0 for glycoamylase and lactase. The soluble lactase and alkaline phosphatase were inhibited minimally by p-chloromercuribenzoate, and sodium fluoride respectively. L-Phenylalanine (20 mM) did inhibit the soluble phosphatase by 90%. Thus, the soluble enzymes are not mainly of the lysosomal origin, but have characteristics of membrane-bound enzymes. 4. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate revealed 18 protein bands which were present in adult membranes. Two other proteins were unique for membranes of distal intestine in suckling rats. The proteins corresponding to known enzyme activity changed as expected with age (e.g. sucrase, maltase increased, lactase decreased). Most of the other proteins were also altered in amount during development. Thus, the changes in the microvillus membrane during development in the rat are not limited to specific enzymes.

Aging

Response of the organs of rabbits to feeding during the first days after birth.

An experiment described previously showed a large increase in weight and protein of the intestinal mucosa of suckling piglets during the first 24 h after birth. This did not take place in piglets that were starved. The results might have been partly due to the inclusion of protein molecules in the mucosa in process of absorption. Rabbits do not absorb large quantities of protein after birth, and the experiment has now been repeated on them. The gastrointestinal tract of suckled rabbits also grew rapidly in the first 24 h, but again not in those that were given only water, which is in line with the suggestion that colostrum contains a factor which stimulates the growth of the gastrointestinal tract. The brain gained weight in the suckled animals, due to incorporation of lipid and protein. It gained weight too in the starving rabbits, demonstrating its high priority for nutrients at a time when its growth velocity is at its peak.

Adipose Tissue

Heterologous radioimmunoassay for rabbit prolactin.

A highly specific heterologous double-antibody RIA has been developed to measure rabbit PRL by using guinea pig antiserum to human PRL and ovine [125 I]iodo-PRL. Rabbit pituitary PRL and serum give parallel dose-response curves in the assay and no cross-reaction (less than 0.1%) occurs with GH, placental lactogens, LH, FSH, or TSH from several different species. The assay is suitable for the measurement of human, ovine, bovine, caprine, and canine PRL in addition to rabbit PRL, but shows no cross-reaction with rat PRL. Reproducibility and precision of the assay are within acceptable limits. Gel filtration of rabbit pituitary PRL and rabbit serum on Sephadex G-100 revealed coincident peaks of activity measured by RIA and by PRL radioreceptor assay. The molecular weight of rabbit PRL appeared similar to that of ovine PRL. Serum PRL levels increased after the injection of both TRH and chlorpromazine and were reduced by CB154 (Bromocriptine). Venepuncture stress caused an increase in PRL in nonpregnant or postpartum non-suckled animals, but small or no increases were seen in lactating female rabbits.

Animals

Coenzyme-A-dependent esterification of cholesterol in intestinal mucosa from guinea-pig. Influence of diet on the enzyme activity.

Guinea-pig intestinal mucosa contains a microsomal enzyme which catalyses the esterification of cholesterol. The enzyme is CoA-dependent and probably an acyl-CoA-cholesterol acyltransferase (ACAT) (E.C. 2.3.1.26). The apparent Km for the CoA in the combined enzyme reaction is 3.3 x 10(-5)M. The specific activity of cholesterol esterification is about five times higher in young suckling animals than in ordinary fed adult animals. Feeding fat and fat/cholesterol diets increases the activity two- to five-fold. Concomitantly the fat/cholesterol fed animals get a marked accumulation of free and esterified cholesterol in mucosal cells.

Acyltransferases

Serum lipids in suckling and post-weanling iron-deficient rats.

Serum lipids were studied in iron-deficient and control rats during suckling and after weaning at 21, 30, and 60 days of age. Diets providing 5 or 307 ppm iron were fed to dams and their offspring during gestation, lactation, and after weaning. Rats on the deficient diet throughout the experimental period developed a hyperlipidemia characterized by elevated triglycerides, cholesterol, and phospholipids which was present at 21, 30, and 60 days. Control pups weaned to the deficient diet developed anemia at 30 days of age and hypertriglyceridemia at 60 days of age. Repletion of deficient rats with iron after weaning caused a rapid decline in serum lipid levels after only 9 days on the control diet. The hyperlipidemia of iron deficiency thus appears to be reversible with iron supplementation. The time required to develop hypertriglyceridemia in iron deficiency is longer postweaning than during suckling.

Animals