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At least 19 recordsLinked to original sources

Problem of standardising growth rates for animals suckled in separate litters.

The tendency of animals suckled in different litters to grow at different rates is already known to be a serious problem for experimental design in developmental biology. However, the contribution made by avoidable technical practices, such as failure to standardise litter size, to this litter effect is not clear from the literature. The present study sought to minimise the litter effect by carefully contriving five litters of rats to be similar in many respects likely to affect growth rate. These litters were raised simultaneously by mutually similar maternal animals in the same room. Their growth rates were not, in fact, equal: significant effects of litter were resolved on three growth rate dependent variables by the thirtieth postnatal day. The extent of this effect (as great as the between animal variance, despite the attempts to minimise it), and its implications for the interpretation of publications in which it is ignored are briefly discussed. Solutions are offered for the problem litter effects cause for experimental design.

Animals↗

Postnatal development of lipid-clearing enzymes in the suckling animal.

Age-related changes in the enzyme activities in the storage and secretory pools of extrahepatic lipoprotein lipase and hepatic triglyceride lipase were determined during a primed/constant infusion of heparin for 2 hr in puppies between birth and 18 wk of life. Lipoprotein lipase activity was low in the first 4 wk of suckling. Its storage pool increased 6-fold in the next 14 wk, with a less dramatic rise in the secretory pool. Sustained increases in the activity of this enzyme were seen late when (1) the pup was being weaned, and (2) the insulin-dependent glucoregulatory mechanism had matured. Both phases of hepatic triglyceride lipase were well developed at birth reflecting the metabolic maturity of the liver at birth. The ability to clear intravenous lipid during a 2-hr infusion was also measured in the pups. The rate of Intralipid utilization increased from 198 +/- 43 mg/kg/hr in the first week of life to 424 +/- 20 mg/kg/hr at 12 wk. Blood Intralipid homeostasis was causally related to increased activity in the storage and secretory pools of lipoprotein lipase. The progressive increase in lipoprotein lipase activity and the maintenance of the secretory capacity was dependent on the growth of the muscle mass and its capillary bed. Endogenous insulin rather than the fat content of the feed appeared significant in the postnatal development of the heparin-releasable lipid clearing enzymes.

Aging↗

Influence of bombesin on gastrointestinal and pancreatic cell growth in adult and suckling animals.

Chronic administration of bombesin in the adult rat affects cell growth and enzyme activities in the pancreas. It also induces hyperplasia of the fundic mucosa, increases antral gastrin content, and stimulates gastrin cell proliferation in the antral mucosa. These effects could be explained by the release of hormones such as gastrin and CCK, whose trophic roles on the digestive tract are well proven. Some arguments raise the possibility that bombesin may also act directly on these organs (i.e., the presence of specific receptors for bombesin, pancreatic changes induced by bombesin and not blocked by a potent, specific CCK receptor antagonist). It may well be that both mechanisms exist simultaneously. In addition, bombesin has a growth-promoting effect on the gastric mucosa and pancreas of suckling rats when administered either subcutaneously or orogastrically. Keeping in mind that the maternal milk contains a bombesin-like immunoreactant peptide, we consider that the latter finding raises questions about the possible physiological role of such a peptide in the regulation of the postnatal development of the gastrointestinal tract.

Animals↗

Colostrum-induced enteric mucosal growth in beagle puppies.

To evaluate the role of artificial feeding and natural feeding in early growth of enteric mucosa, we determined enteric mucosal mass, protein and DNA content, and disaccharidase activities in beagle puppies at birth, and after 24 h of either natural or artificial feeding. Despite similar increases in body weight over the first 24 h of life, neither mucosal mass, DNA content, nor protein content of the artificially fed animals was different from that of newborn animals. In contrast, mucosal mass of the suckled animals was 75% greater, DNA content was 56% greater, and protein content was 93% greater than that of newborn animals. The mucosal protein/DNA ratio of the suckled animals was greater than that of newborn, but not artificially fed animals. The greater DNA, protein, and protein/DNA ratio in this group suggest that the greater mucosal mass is a result of both cellular hyperplasia and hypertrophy. Sucrase specific activity of the suckled animals was less than that of the artificially fed but not the newborn animals. Other disaccharidase activities were not different among the three groups. These data extend the findings of Widdowson et al.(25) to another species and demonstrate that this rapid enteric growth over the first day of life results only from natural feeding. They strongly suggest, therefore, that rapid early enteric growth, mediated perhaps by a factor in natural milk that stimulates enteric mucosal growth, is an important heretofore unappreciated phase of intestinal development.

Animals↗

The postnatal development of sodium transport in the proximal small intestine of the rabbit.

To investigate the postnatal development of intestinal Na+ transport, a major determinant of fluid absorption, we measured spontaneous and glucose-coupled Na+ transport across short-circuited epithelium and in isolated villus enterocytes from rabbit jejunum at age intervals after birth. Villus cells from suckling animals actively transported Na+ and responded to glucose, but their capacity to do so was less than that of villus cells from older animals. Net Na+ fluxes across short-circuited epithelium from suckling animals failed to respond to glucose, remaining negligible and less than adult values. This lack of response to glucose in tissue from younger animals was associated with marked paracellular shunting as evidenced by greater unidirectional fluxes and greater tissue conductance. Villus enterocytes from suckling animals compared to those from adults had reduced (Na+-K+)ATPase activity, but were rich in thymidine kinase. We conclude that proximal intestinal epithelium in suckling animals has a limited capacity for active Na+ transport, is incompletely differentiated, and is leaky, with a greater permeability for ions compared with adult intestine.

Age Factors↗

Experimental infection of Akodon molinae (Rodentia, Cricetidae) with Junín virus.

Experimental infection with the XJ-Clone 3 strain of Junín virus in laboratory bred Akodon molinae, a cricetid rodent inhabiting the borders of endemic Argentine hemorrhagic fever areas, was studied. Suckling animals inoculated intracerebrally proved sensitive and became chronically infected. Sixty percent of the rodents showed neurologic involvement, with mortality reaching 60%. Virus was recovered from the brain at 7, 15, 21, 37, and 57 days postinfection (pi). By immunofluorescence (IF), viral antigens were observed up to 182 days pi in cells of the central nervous system (CNS). Concurrently, immunoglobulin deposits were detected in infected CNS cells from 21 up to 182 days pi. These deposits increased with the progression of the immune response as measured by IF antibodies. The detection of immune complexes in brain cells of apparently healthy animals suggests that neither viral replication nor the development of a humoral immune response are necessary requisites for neurovirulence in this host. Infection of adult rodents by different routes failed to induce disease or mortality and virus could not be recovered from oral swabs, blood, or organs. Our data suggest that Akodon molinae could play a role in nature as an alternative reservoir of Junín virus in addition to the main reservoir, Calomys musculinus.

Animals↗

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↗

Fatty acid synthesis in mouse brown adipose tissue. The influence of environmental temperature on the proportion of whole-body fatty acid synthesis in brown adipose tissue and the liver.

Fatty acid synthesis has been measured in vivo with 3H2O in mice acclimated at different environmental temperatures (33, 22, 4 degrees C), and the importance of brown adipose tissue and the liver to whole-body fatty acid synthesis at each temperature assessed. At 33 degrees C, when non-shivering thermogenesis is minimal, the rate of fatty acid synthesis in interscapular brown adipose tissue was lower than in the liver, but higher than in white adipose tissue and the carcass. At 4 degrees C, when non-shivering thermogenesis is maximal, the fatty acid synthesis rate in interscapular brown adipose tissue was many times greater than in any other tissue. High fatty acid synthesis rates were also found in other brown adipose tissue depots--subscapular, dorsocervical and axillary--of cold-acclimated mice. In mice maintained at 22 degrees C the rate of fatty acid synthesis was also higher in brown adipose tissue than in other tissues. Overall, the relative importance of brown adipose tissue as a site of fatty acid synthesis increased with lower environmental temperatures, while that of the liver decreased. It was calculated that brown adipose tissue in total accounted for approx. 5% of whole-body fatty acid synthesis at 33 degrees C, 10% at 22 degrees C and 30% at 4 degrees C. In contrast, hepatic synthesis amounted to 32% of whole-body fatty acid synthesis at 33 degrees C, 16% at 22 degrees C and only 11% at 4 degrees C. An estimate of the contribution that de novo synthesis makes to total fatty acid utilization by interscapular brown adipose tissue suggests that fatty acid synthesis and breakdown constitutes a significant heat-dissipating 'cycle' in brown adipose tissue of cold-acclimated mice. Such a cycle is not evident in suckling animals since fatty acid synthesis in brown adipose tissue is very low during early development.

Adaptation, Physiological↗

Ultrastructural localization of calcium, by electron-probe X-ray microanalysis, in the small intestine of suckling rats.

The subcellular distribution of calcium has been investigated in samples, from the intestinal mucosa of 10-day rats, prepared for X-ray microanalysis by various techniques designed to minimize the loss of this element. Calcium retention and its threshold of detection was most satisfactory in freeze-dried frozen thin sections. In resin-embedded samples the best retention of calcium was found in specimens fixed in absolute ethanol, embedded without osmication, and sectioned onto glycerol. The results of this investigation indicate the presence of calcium in the supranuclear vacuole of enterocytes in the distal intestine of the neonatal rat. This calcium is probably taken up during the endocytosis of material from the intestinal lumen. The same mechanism may also be important in the uptake of other metals by suckling animals.

Animal Population Groups↗

Brush border membrane sucrase-isomaltase, maltase-glucoamylase and trehalase in mammals. Comparative development, effects of glucocorticoids, molecular mechanisms, and phylogenetic implications.

1. Trehalase, sucrase-isomaltase and maltase-glucoamylase are three integral glycoproteins of the brush border membranes of the enterocytes. On the basis of a comparative study on alpha-glycosidase activities (sucrase, isomaltase, maltase, glucoamylase and trehalase) associated to these glycoproteins during neonatal development, mammals could be basically divided into three groups. 2. In rodents and rabbit alpha-glycosidase activities are low or undetectable during the suckling period and increase to adult levels during the weaning period. In cat, dog and the primates examined, alpha-glycosidase activities are well or fully developed at birth. 3. In ruminants and pinnipedia alpha-glycosidases are low or absent throughout life. 4. During the suckling period of rat, mouse and rabbit, glucocorticoids trigger a premature and dramatic increase of all alpha-glycosidases. 5. On the contrary, alpha-glycosidases development during the weaning period appears to be independent of glucocorticoids. Neither hypophysectomy nor adrenalectomy prevent the development of alpha-glycosidases; only the rate of increase is reduced. 6. Transplantations of intestinal isografts either in adult or suckling animal, have shown that (1) no systemic factor inhibits the expression of alpha-glycosidase, (2) alpha-glycosidases induction is neither triggered by luminal alimentary substances, nor by hormones, (3) alpha-glycosidase development is controlled by an intrinsic ontogenic program. 7. The use of an antiglucocorticoid failed to inhibit the spontaneous development of alpha-glycosidase activities. 8. The increase of maltase and sucrase activities triggered by glucocorticoids is associated with an increase of the concentration of two glycoproteins in the microvillous membrane: sucrase-isomaltase and maltase-glucoamylase. 9. After administration of glucocorticoids the increase of maltase, sucrase and trehalase is strongly inhibited by actinomycin-D and the increase of sucrase activity is associated with a parallel increase of sucrase-isomaltase mRNA. Transcription is most likely the primary site of control of alpha-glycosidase biosynthesis. 10. In the crypt cells, alpha-glycosidases biosynthesis appears to be triggered by a receptor-mediated glucocorticoid interaction. 11. The enterocytes synthesize more alpha-glycosidase molecules as they travel to the tip of the villi. 12. The simultaneous, biosynthesis of sucrase-isomaltase and maltase-glucoamylase triggered by glucocorticoids, as well as their simultaneous normal development suggest that they may be subjected to related control mechanisms. 13. It is suggested that sucrase-isomaltase and maltase-glucoamylase might have arisen by several cycles of partial gene duplication of an ancestor gene coding for a single site maltase-isomaltase; subsequent mutation would have transformed isomaltase into sucrase or glucoamylase.

Animals↗

The inefficient transfer of maternally fed alcohol to nursing rats.

The growth of rat pups nursed by ethanol-drinking mothers or pups exposed daily to ethanol/vapor was monitored for the first three weeks of life. Pups nursed by mothers fed either a 6% ethanol containing liquid diet or a 10% ethanol/water mixture had significantly lower body weights after the 2nd postnatal week than controls. This decrease in pup growth occurred despite pup blood alcohol levels that did not exceed 20 mg%. Only a small fraction of the alcohol fed to mothers ever reached suckling animals. In contrast, pups exposed daily to ethanol vapor regularly achieved blood alcohol concentrations in excess of 250 mg%, but experienced only minimal growth retardation. These results suggest that maternal alcohol feeding cannot be used to study the effects of ethanol upon postnatal development.

Animals↗

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↗

The ingestion of proteins and colloidal materials by columnar absorptive cells of the small intestine in suckling rats and mice.

Proteins and colloidal materials, administered orally to suckling rats and mice, were ingested by columnar absorptive cells of the jejunum and ileum, but not of the duodenum. Bovine gamma globulin and ovalbumin were identified in the apical cytoplasm by staining with fluorescent antibody; trypan blue, Evans blue, saccharated iron oxide, and colloidal gold were detected intracellularly by their color, specific staining, and appearance in the electron microscope. Each substance was segregated in membrane-enclosed vacuoles, apparently part of a system of potentially interconnecting vacuoles and tubules in the apical cytoplasm which is continuous in places with the apical cell membrane. We postulate that ingestion of foreign materials was accomplished by pinocytosis, that is, by invagination of the apical cell membrane to form vacuoles containing material from the intestinal lumen. Approximately 18 days after birth columnar absorptive cells lost the ability to ingest proteins and colloids, and no longer contained large vacuoles and numerous tubules. At this age rats and mice lose the ability to absorb antibodies from the intestine in an immunologically intact form, and we conclude that cellular ingestion is part of the mechanism of absorption of intact proteins in suckling animals. Particulate fat apparently is absorbed in both newborn and adult animals by micropinocytosis. Thus adult animals may not have lost the capacity for pinocytosis, but rather have become selective as to what substances provoke it. Cortisone acetate, administered subcutaneously to rats 8 to 10 days old alters the columnar absorptive cells within 72 hours so that they resemble the cells in adult animals and no longer ingest proteins.

Animals↗

Oral neurotensin increases gastrointestinal transit in suckling rats.

Several neuropeptides known to alter gastrointestinal motility are present in milk. We investigated the effect of gastric administration of neurotensin, bombesin, somatostatin, and vasoactive intestinal polypeptide on gastrointestinal motility in suckling rats. We gavage fed 7- to 10-day-old rats with a meal consisting of 10 microliters/g of body weight of 0.9% NaCl with 51Cr tracer and one of the peptides (0, 0.1, 10, and 1,000 ng/ml). We estimated the rates of gastric emptying and the small intestinal transit from the distribution of the radioactivity in the gut. Approximately one-half of the counts emptied from the stomach in 15 min. Both gastric emptying and small intestinal transit were time dependent and were accelerated by metoclopramide and inhibited by butylscopolamine. Neurotensin 1 micrograms/ml accelerated the gastric emptying by 35% (p less than 0.02). Small intestinal transit was also accelerated (p less than 0.05). The other neuropeptides had no effect on gastric emptying and small intestinal transit. Neurotensin did not change either the gastric emptying or small intestinal transit in weaned rats, 40-50 days old, studied in the same manner. These data suggest that the intraluminal administration of neurotensin may increase gastrointestinal motility in suckling animals.

Administration, Oral↗