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  • lipoprotein composition  (2)
  • thromboxane  (2)
  • ATP  (1)
  • 1
    ISSN: 1432-0428
    Keywords: Keywords Extracellular matrix ; transforming growth factor-β ; prostaglandins ; thromboxane ; mesangial cell ; diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Accumulation of extracellular matrix in the mesangium and altered renal eicosanoid synthesis are two prominent features of diabetic glomerular disease. We investigated the relationship between eicosanoid and extracellular matrix production in rat mesangial cells cultured under high glucose vs normal glucose conditions. Long-term exposure of rat mesangial cells to high glucose, but not to iso-osmolar mannitol, significantly increased extracellular matrix accumulation and gene expression and transforming growth factor-β (TGF-β) mRNA levels, and decreased prostaglandin (PG) E2 synthesis without affecting production of either thromboxane (TX) B2 or PGF2 a, with respect to cells incubated in normal glucose. Addition of exogenous PGE2 resulted in a dose-dependent reduction of matrix protein and mRNA levels and TGF-β gene expression in cells cultured in either normal or high glucose conditions, whereas exposure to exogenous PGF2α produced a significant increment in matrix production and matrix and TGF-β gene expression in cells grown in normal glucose, but only a slight increase in those cultured in high glucose. Stimulation of endogenous endoperoxide metabolism towards PGE2 and PGF2α synthesis with FCE-22,178, a drug originally developed as TXA2 synthase inhibitor, resulted in a dose-dependent decrease in matrix accumulation and matrix and TGF-β gene expression which was suppressed by co-incubation with the cyclo-oxygenase inhibitor fenoprofen blocking the FCE-22,178-enhanced PG production. In both cell lines, the rate of synthesis of TXA2 was very low and the selective blockade of its synthesis (by two other TXA2 synthase inhibitors, OKY-046 and Ridogrel) or action (by the TXA2 receptor antagonist BM-13,177) did not alter matrix production or TGF-β mRNA levels. These results suggest that the cyclo-oxygenase pathway is involved in the regulation of matrix changes induced by high glucose in rat mesangial cells; the reduced production of PGE2 may enhance the synthesis or potentiate the effect of stimulators of ECM formation such as TGF-β, whereas TXA2 does not appear to be involved. These data also indicate that glucose-enhanced mesangial matrix accumulation may be prevented by exogenous PGE2 or by drugs capable of increasing endogenous PGE2 synthesis. [Diabetologia (1996) 39: 1055–1062]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Extracellular matrix ; transforming growth factor-Β ; prostaglandins ; thromboxane ; mesangial cell ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Accumulation of extracellular matrix in the mesangium and altered renal eicosanoid synthesis are two prominent features of diabetic glomerular disease. We investigated the relationship between eicosanoid and extracellular matrix production in rat mesangial cells cultured under high glucose vs normal glucose conditions. Long-term exposure of rat mesangial cells to high glucose, but not to iso-osmolar mannitol, significantly increased extracellular matrix accumulation and gene expression and transforming growth factor-Β (TGF-Β) mRNA levels, and decreased prostaglandin (PG) E2 synthesis without affecting production of either thromboxane (TX) B2 or PGF2α, with respect to cells incubated in normal glucose. Addition of exogenous PGE2 resulted in a dose-dependent reduction of matrix protein and mRNA levels and TGF-Β gene expression in cells cultured in either normal or high glucose conditions, whereas exposure to exogenous PGF2α produced a significant increment in matrix production and matrix and TGF-Β gene expression in cells grown in normal glucose, but only a slight increase in those cultured in high glucose. Stimulation of endogenous endoperoxide metabolism towards PGE2 and PGF2α synthesis with FCE-22,178, a drug originally developed as TXA2 synthase inhibitor, resulted in a dose-dependent decrease in matrix accumulation and matrix and TGF-Β gene expression which was suppressed by co-incubation with the cyclo-oxygenase inhibitor feno-profen blocking the FCE-22,178-enhanced PG production. In both cell lines, the rate of synthesis of TXA2 was very low and the selective blockade of its synthesis (by two other TXA2 synthase inhibitors, OKY-046 and Ridogrel) or action (by the TXA2 receptor antagonist BM-13,177) did not alter matrix production or TGF-Β mRNA levels. These results suggest that the cyclo-oxygenase pathway is involved in the regulation of matrix changes induced by high glucose in rat mesangial cells; the reduced production of PGE2 may enhance the synthesis or potentiate the effect of stimulators of ECM formation such as TGF-Β, whereas TXA2 does not appear to be involved. These data also indicate that glucose-enhanced mesangial matrix accumulation may be prevented by exogenous PGE2 or by drugs capable of increasing endogenous PGE2 synthesis.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Lipoproteins ; Type 1 (insulin-dependent) diabetes ; blood glucose control ; lipoprotein composition ; atherosclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma lipoprotein compositional abnormalities were investigated in eight normolipidaemic (plasma cholesterol 〈5.70 mmol/l; triglyceride 〈2.03 mmol/l) young male Type 1 (insulin-dependent) diabetic patients (before and after a short period of optimised blood glucose control) and in nine healthy control subjects, matched for sex, age and body mass index. Free and esterified cholesterol, triglyceride, phospholipids were assayed in all lipoprotein classes (VLDL, IDL, LDL) and in HDL subclasses (HDL2 and HDL3); apoB was measured only in very low density lipoproteins (VLDL). All VLDL constituents were increased in the diabetic group, the differences being more striking for apoB (6.0±1.1 mg/dl vs 2.0±0.1 mg/dl, p〈0.02), free cholesterol (0.27±0.04 mmol/l vs 0.13±0.02 mmol/l, p〈0.02) and esterified cholesterol (0.32±0.08 mmol/l vs 0.13±0.01 mmol/l, p〈0.05). Also HDL subfractions showed differences between the two groups: all HDL2 constituents were increased, while in HDL3 only triglyceride was significantly increased (0.11±0.01 mmol/l vs 0.08±0.004 mmol/l, p〈0.02). After two weeks of optimised blood glucose control all VLDL constituents were reduced and particularly: esterified cholesterol (−39%, p〈0.02), free cholesterol (−37%, p〈0.05), apoB (− 35%, p〈0.05). Expressing each VLDL constituent as percent of the total lipoprotein mass, it was evident that the diabetic VLDL was rich in cholesterol both esterified (8.4±1.0% vs 5.4±0.5%, p〈0.02) and free (8.5±0.7% vs 5.5±0.3%, p〈0.001), apo B (5.1±0.6% vs 2.6±0.3%, p〈0.001) and depleted in triglyceride (57.0±1.7% vs 64.1±1.7%, p〈0.001). Two weeks of optimised blood glucose control were not able to correct the abnormal composition of VLDL. In conclusion, Type 1 (insulin-dependent) diabetic patients, although normolipidaemic, show an abnormal VLDL composition suggesting an increased prevalence of smaller and, possibly, more atherogenic VLDL particles. This abnormality is not corrected by a short period of blood glucose optimisation.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Keywords Dietary cholesterol ; plasma lipoproteins ; lipoprotein subclasses ; lipoprotein composition ; IDDM patients.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To compare the effects of dietary cholesterol supplementation in insulin-dependent diabetic (IDDM) patients and normal subjects, 10 male IDDM patients in good glycaemic control (HbA1 c 7.3 ± 0.9 %) (mean ± SD) and normal plasma lipid levels, and 11 control male subjects of similar age, body mass index and lipid plasma levels underwent a double blind, cross-over, sequential study. Cholesterol supplementation of 800 mg/day or placebo were given for consecutive periods of 3 weeks. The concentration of plasma total cholesterol increased significantly with the dietary cholesterol supplementation compared to placebo in IDDM patients by 6 % (p 〈 0.05) and in control subjects by 9 % (p 〈 0.05). No changes were observed in the concentration of plasma triglycerides in either group. The LDL cholesterol level increased by 12 % (p 〈 0.01) in patients and by 7 % (p 〈 0.05) in control subjects. In patients plasma HDL cholesterol concentration remained the same, while in control subjects it tended to increase after cholesterol supplementation (from 1.14 ± 0.26 to 1.23 ± 0.27 mmol/l, p = 0.06). During the cholesterol intake period the mean concentration of LDL1, LDL2 and LDL3 subclasses in patients showed a significant increase by 21.0 (p 〈 0.05), 20.4 (p 〈 0.001) and 11.1 % (p 〈 0.05), respectively, resulting in an 18.0 % increase in mean total LDL mass (p 〈 0.001) without major changes in LDL composition. In the control subjects the changes in the concentrations of LDL subclasses during cholesterol intake were less and not significant. In the IDDM patients the cholesterol intake did not affect the concentration or composition of HDL subclasses or total HDL mass. In contrast, in control subjects cholesterol intake increased the mean concentration of HDL2 a by 12.2.% (p 〈 0.05) and this increase was significantly different if compared to changes obtained in the patients. In conclusion, compared to normal subjects, in IDDM patients, dietary cholesterol intake increased the LDL particle mass significantly and had no positive effect on HDL. [Diabetologia (1998) 41: 193–200]
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-136X
    Keywords: Embryonic development ; Diapause ; O2 consumption ; ATP ; Copepod ; Pontella mediterranea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Oxygen consumption and ATP content are reported for the planktonic marine copepod Pontella mediterranea during normal and diapause embryonic development. In subitaneous embryos that hatched without delay within 48 h, O2 uptake increased linearly after spawning to reach maximum levels about 25 h later. By contrast, ATP levels were initially very high but decreased rapidly within the next 5 h to reach stable values thereafter. In diapause embryos, O2 consumption followed the typical U-shaped curve described for insect diapause. An initial period of prediapause, which lasted for about 25 days, was characterized by elevated O2 uptake. This was followed by a period of diapause in which O2 consumption dropped to 25% of the values recorded during prediapause. This protracted period of dormancy, which lasted about 4 to 5 months, was followed by a period of high O2 consumption possibly due to the breaking of diapause and resumption in development. ATP content during the pre-diapause period showed a similar trend as in subitaneous embryos with high initial levels that decreased with time for the first 20 days and remained stable afterwards.
    Type of Medium: Electronic Resource
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