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  • 1
    ISSN: 1432-0428
    Keywords: Hyperglycaemia ; embryogenesis ; rat embryo culture ; malformation ; sorbitol ; myo-inositol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To demonstrate the myo-inositol depletion hypothesis in hyperglycaemia-induced embryopathy, rat conceptuses of 9.5 days of gestation in the early head-fold stage were grown in vitro during neural tube formation for 48 h with increasing amounts of glucose. The effects of an aldose reductase inhibitor and the myo-inositol supplementation were also investigated. Sorbitol and myo-inositol contents were measured in separated embryos and extra-embryonic membranes including yolk sac and amnion at the end of culture. After addition of 33.3 mmol/l and 66.7 mmol/l glucose to the culture media, the myo-inositol content of the embryos was significantly decreased by 43.1% (p〈0.05) and 64.6% (p 〈 0.01) of the control group, while a marked accumulation of sorbitol was observed (25 and 41 times that of the control). Although the addition of an aldose reductase inhibitor (0.7 mmol/l) to the hyperglycaemic culture media containing an additional 66.7 mmol/l glucose significantly reduced the sorbitol content of embryos to approximately one-eighth, the myo-inositol content of embryos remained decreased and the frequency of neural lesions was unchanged (23.1% vs 23.9%, NS). Supplementation of the myo-inositol (0.28 mmol/l) completely restored the myo-inositol content of the embryos and resulted in a significant decrease in the frequency of neural lesions (7.1% vs 23.9%, p 〈 0.01) and a significant increase in crown-rump length and somite numbers. Much less significantly, sorbitol accumulation was also observed in the extra-embryonic membrane in response to hyperglycaemia, neither hyperglycaemia nor the myo-inositol supplementation modified the myo-inositol contents of the extra-embryonic membrane. We conclude that the mechanism of hyperglycaemia-induced teratogenicity was mediated by the myo-inositol depletion of the embryo at a critical stage of organogenesis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Glucose transporter ; embryogenesis ; hyperglycaemia ; rat embryo culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated the expression of glucose transporter genes and protein in embryo and yolk sac during organogenesis and the regulation of glucose transporters during culture in hyperglycaemic media. Erythrocyte-type glucose transporter (GLUT 1) and brain-type glucose transporter (GLUT 3) mRNA were expressed in embryo and yolk sac. The expression of GLUT-1 and GLUT-3 mRNA was abundant on day 9–11 and day 9–10 in the embryo, respectively, and day 9–14 and day 10–11 in the yolk sac, respectively. The levels of GLUT-1 protein in the embryo increased in parallel with the expression of GLUT-1 mRNA during the corresponding period. Immunohistochemical staining of GLUT-1 protein was found principally in the neuroepithelial cells surrounding the neural tube in the embryo on day 10 and appeared in the microvessels surrounding the neural tube after day 12. To test whether the expression of glucose transporter genes and protein was suppressed during hyperglycaemia, conceptuses were cultured in high glucose medium. The abundant expression of GLUT-1 protein was not decreased during culture in high glucose media for 24 h (day 9–10) and was only down-regulated by prolonged exposure to this media for 48 h (day 9–11). We have demonstrated the predominant expression of the high affinity glucose transporter (GLUT 1 and GLUT 3) genes and (GLUT 1) protein in embryo during the early period of organogenesis. The persistently abundant expression of glucose transporter during the critical period of neural tube formation (day 9–10) even in the presence of hyperglycaemia may explain one of the mechanisms of increased glucose flux into the neuroepithelium, which may lead to neural tube defects.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 82 (1997), S. 5176-5184 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We propose an annealing method as an effective way of operating quantum-cellular-automaton (QCA) systems, which are devices for computation that utilize the minimum energy state of electrons in a quantum cell system. A QCA system has an energy function with many local minima and therefore cannot be operated as desired if placed under the conditions of a thermodynamically open system. Accordingly, for successful operation of a QCA system (i.e., making the QCA system converge successfully to its minimum-energy state), we propose a method of operation based on the concept of thermodynamic annealing. We simulate the dynamics of various QCA logic-gate systems operated by this annealing method, and show that data processing in QCA systems can be carried out accurately by means of this annealing method. The applicability of QCA systems to non-Neumann parallel-processing computation is also described. © 1997 American Institute of Physics.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Applied Surface Science 60-61 (1992), S. 702-709 
    ISSN: 0169-4332
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Hypoglycaemia ; rat embryo culture ; congenital malformation ; growth retardation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary As congenital malformations may be caused by perturbations of glycolytic flux on early embryogenesis [16], effects of hypoglycaemia were investigated by using rat embryo organ culture. Nine and one-half day old rat embryos were grown in vitro for 48 h (day 9 1/2 to 11 1/2) in the presence of hypoglycaemic serum for different hours during the culture period. Hypoglycaemic serum was obtained from rats given insulin intraperitoneally. On exposure to hypoglycaemic serum during the first 24 h of culture (day 9 1/2 to 10 1/2), embryos showed marked growth retardation and had increased frequencies of neural lesions (42.7% versus 0%, p〈0.01), in contrast to hypoglycaemic exposure during the second 24 h of culture (day 10 1/2 to 11 1/2), where only minor growth retardation and low frequencies of neural lesions (2.4% versus 0%, NS) were seen. Even exposure to hypoglycaemic serum for a relatively short period (8 h) during the first 24 h of culture resulted in neural lesions at the frequency of 9.3–13.3%. The embryos exposed to hypoglycaemia demonstrated decreased glucose uptake and lactic acid formation, indicating decreased energy production via glycolysis that constitutes the principal energy pathway at this stage of embryonic development. These results suggest that hypoglycaemia during critical periods of embryogenesis has adverse effects on the development of the embryo and these effects might be mediated through metabolic interruption of embryogenesis.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-5233
    Keywords: Embryogenesis ; Glucose transporter ; Growth retardation ; Hypoglycemia ; Neural tube defect ; Rat embryo culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the glucose transporter gene and protein expression during early organogenesis in the rat and in rat embryos cultured with hypoglycemic serum. Erythrocyte-type glucose transporter (GLUT-1) mRNA was expressed at a high level in embryos; peak levels were reached at days 10.5–11.5 and decreased as gestational age increased. In contrast, the insulin regulaable glucose transporter (GLUT-4) mRNA was not detected. The levels of GLUT-1 protein determined by Western blot analysis increased in parallel with expression of the glucose transporter (GLUT-1) gene and peak levels were observed on days 10.5 and 11.5, which correspond to the main periods of neural tube formation. Immunohistochemical staining of the embryo on day 10.5 showed that GLUT-1 protein was abundantly located in the tissue of neural tube. When embryos were cultured from day 9.5 to day 10.5 with insulin-induced hypoglycemic serum containing 2–3 mM glucose an increased frequency of anterior neural tube defects was observed in association with a significant reduction of the glycolytic flux. Increased levels of GLUT-1 mRNA and protein were not observed during the culture with hypoglycemic serum compared with the levels in embryos cultured in normal serum. Addition of insulin to normal serum (500 μU/ml) did not affect the GLUT-1 mRNA and protein levels. GLUT-1 mRNA and protein are strongly expressed in the embryo during early organogenesis, especially in the tissues of the neural tube, and the expression of the glucose transporter did not increase in response to prolonged glycopenia. This may account for the vulnerability of embryogenesis to hypoglycemia during these critical developmental periods.
    Type of Medium: Electronic Resource
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