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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 16 (1979), S. 125-128 
    ISSN: 1432-0428
    Keywords: Experimental diabetes ; blood glucose control in rats ; Streptozotocin dibates in rats ; kidney weight ; glomerular volume ; stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Kidney weight and glomerular volume have been studied in groups of insulin-treated streptozotocin diabetic rats maintained at high, or nearly normal plasma glucose levels. Kidney weight and glomerular volume in these groups were compared to a non-diabetic control group. — Rats with nearly normal plasma glucose levels (95±35 to 182±20 mg/100ml) had the same kidney weight as the non-diabetic controls, 1.04±0.14 and 1.07±0.09 g, respectively. In the rats with constant high plasma glucose (338±71 to 555±86 mg/100ml) kidney weight was significantly increased, 1.73±0.20 g, compared to each of the two other groups. Glomerular volume was 0.599 Mμ3 in the diabetic animals with nearly normal plasma glucose, a value very close to that of the non-diabetic controls, 0.587 Mμ3. In animals with high plasma glucose concentrations glomerular volume was 0.775 Mμ3, 2 p〈0.03 compared with both other groups. — The study indicates that good diabetic control for 6 months prevents the development of large kidneys and large glomeruli in dibatic rats.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 16 (1979), S. 185-190 
    ISSN: 1432-0428
    Keywords: Streptozotocin diabetes ; blood glucose control ; rat ; insulin treatment ; diurnal plasma glucose ; long acting insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diurnal plasma glucose levels have been studied two hourly in streptozotocin diabetic rats during insulin treatment. Protamine Zinc Insulin induced a very steep fall in plasma glucose level from 359±100 (SD) mg/100 ml to 91± 49 mg/100 ml within two hours. Plasma glucose was then low (13–60 mg/100 ml) until after 18 hours when an equally steep rise in glucose concentration ocurred. Six other insulin preparations and several insulin treatment regimens were tested with the aim of normalising the 24 hour plasma glucose profile of streptozotocin diabetic rats. One preparation, a non-commercial, very long acting Ultralente NOVO (Mc, ox pH 5.5) yielded a diurnal plasma glucose profile reasonably close to normal when it was administered once a day and when the dose was based on daily blood glucose measurements. Mean plasma glucose was 122±55 mg/100 ml with a nadir of 55±15 and a maximal of 187±99 mg/100 ml.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 18 (1980), S. 413-416 
    ISSN: 1432-0428
    Keywords: Urine albumin in rats ; radioimmunoassay ; Streptozotocin diabetes in rats ; blood glucose control in rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A single antibody radioimmunoassay has been used to measure albumin excretion in 3 groups of female Wistar rats. Two groups had Streptozotocin diabetes and were treated daily with insulin for 6 months. In one of the diabetic groups good glycaemic control was attempted and throughout the 6 months plasma glucose levels were fairly close to normal (92 ± 33 mg/100 ml at 2300 h and 186 ± 9 mg/100 ml at 0800 h). In the other diabetic group poor control was intended and the group had consistent high plasma glucose levels (576 ± 89 mg/100 ml and 460 ± 43 mg/100 ml). The third group was a non-diabetic control group. — Albumin excretion was measured on two occasions: before the induction of diabetes and after 6 months of diabetes. The geometric mean albumin excretion increased from 0.38 to 2.56 mg/24 h in the 18 non-diabetic controls. In the 20 diabetic rats in “good” control the geometric mean albumin excretion increased from 0.37 to 1.58 mg/ 24 h (NS compared with controls) and in the group of 22 rats in poor control albumin excretion increased from 0.35 to 6.54 mg/24 h. — The increase in albumin excretion in rats in poor control differed significantly both from that of the non-diabetic controls (2p = 0.023) and from that of the “well-controlled” diabetic rats (2p = 0.00011).
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Streptozotocin diabetes ; uninephrectomy ; rat kidney ; thymidine ; autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Incorporation of 3H-thymidine into renal cortical tissue has been studied by light microscopic autoradiography in streptozotocin-diabetic rats, uninephrectomized rats, uninephrectomized diabetic rats, insulin-treated diabetic rats and control rats. The percentage of labelled cortical nuclei (the labelling index) was determined separately in glomeruli, proximal tubules and distal tubules after 2, 4 and 6 days on autoradiographs from 1 μm thick plastic embedded sections. The incorporation of thymidine in glomerular nuclei was consistantly low (〈 1%) and no differences were found between the control and experimental groups. In both proximal and distal tubules an increase in thymidine incorporation was seen on day 2 followed by a decline on days 4 and 6. The maximal labelling on day 2 in proximal tubules was 9.1% in the uninephrectomized diabetic group, 3.7% in the diabetic group and 1.4% in the uninephrectomized group. In distal tubules the corresponding values were 5.2, 3.5 and 1.1%. The increase in kidney weight after 6 days was 83, 62 and 37%, respectively. Estimates of the net increase in the number of cortical tubular cells in the different experimental groups showed that the kidney enlargement followed different patterns with respect to the extent of cellular hyperplasia and hypertrophy. The kidney growth in uninephrectomized diabetic rats was dominated by tubular cellular hyperplasia, in the diabetic group hyperplasia and hypertrophy participated to approximately the same extent, whereas cellular hypertrophy was most pronounced in the uninephrectomized animals. Nuclear labelling in the insulin-treated diabetic rats was not different from that of control rats and consequently a hyperplastic effect of streptozotocin can be ruled out. It is concluded that combined tubular cellular hyperplasia and hypertrophy is involved in the kidney cortical enlargement seen in the present experimental groups and that each group follows different cellular reactions. In glomerular enlargement, however, no cellular hyperplasia is obserbed.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 17 (1979), S. 243-248 
    ISSN: 1432-0428
    Keywords: Mesangial region ; streptozotocin diabetes ; glucose control in rats ; diabetic glomerulopathy ; stereology ; insulin treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A quantitative morphological study of the mesangial regions has been performed on the kidneys of two groups of insulin treated diabetic rats 6 months after the induction of diabetes. In one group reasonably good control of plasma glucose levels (182±20 (SD) mg/l00ml at 0800 h; 95±35 mg/100 ml at 2300 h) was achieved. This group showed no mesangial changes when compared to a non-diabetic control group. In the second diabetic group poor control was intended (plasma glucose 452±41mg/100 ml and 555±86mg/100 ml respectively). The following differences were noted when this group was compared to the non-diabetic controls and to the rats in which the blood glucose was well-controlled: 1. Increase in total mesangial volume per glomerulus by 42% and 38% (2p = 0.025 and 0.037); 2. Increase in the total amount of basement membrane-like material (BMLM) per glomerulus by 30 and 27% (2p = 0.030 and 0.046); 3. Increase in the total mesangial cell volume per glomerulus by 46 and 43% (2p = 0.033 and 0.048); 4. Increase in volume of electron dense material in the BMLM by about 200% compared to both groups (2p = 0.001 and 0.0003). The study has shown that the mesangial regions also are involved in the diabetic glomerulopathy of experimental diabetes. The morphological changes including increased amounts of basement membrane material are prevented by proper glycaemic control.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Key words Diabetes mellitus ; kidneys ; thick ascending limb of the loop of Henle ; Tamm ; Horsfall glycoprotein.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tamm–Horsfall glycoprotein, present only in the kidney thick ascending limb of Henle's loop, was studied here in streptozotocin diabetic rats. Tamm–Horsfall glycoprotein mRNA in situ hybridization was performed on snap-frozen left kidneys; the right kidneys were perfusion-fixed with 4 % paraformaldehyde and embedded either in paraffin, for Tamm–Horsfall glycoprotein immunohistochemistry, or in Epon for stereologic measurements. The length of the thick ascending limb of Henle's loop and the amount of glycogen were measured and the ultrastructure of the cells was evaluated. Urinary excretion of Tamm–Horsfall glycoprotein, calcium, magnesium and albumin was measured. After 10 and 50 days' duration of diabetes, kidney weight increased 20 and 41 %, respectively and the length of the thick ascending limb of Henle's loop increased 28 and 56 %, respectively, compared with controls. Substantial glycogen accumulations were present in the thick ascending limb of Henle's loop, and electron microscopy revealed a significant decrease in organelles and basolateral membranes. After 10 and 50 days' duration of diabetes, in situ hybridization of Tamm–Horsfall glycoprotein mRNA revealed a fourfold decrease, and the immunostaining for Tamm–Horsfall glycoprotein showed a threefold decrease as measured by densitometry. However, urinary Tamm–Horsfall glycoprotein excretion rate was increased fivefold and urinary concentration about twofold. Urinary calcium excretion increased threefold and magnesium twofold, but urinary albumin excretion was not significantly increased. The increased amount of Tamm–Horsfall glycoprotein, calcium and magnesium in the urine in diabetes occurs here concomitant with severe cellular damage in the thick ascending limb of Henle's loop. [Diabetologia (1995) 38: 525–535]
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 40 (1997), S. 802-809 
    ISSN: 1432-0428
    Keywords: Keywords Diabetes mellitus ; experimental ; kidney ; diabetic nephropathy ; morphometry.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A morphometric study was performed on moderately hyperglycaemic streptozotocin diabetic rats after 10 and 50 days of diabetes, and on groups of rats that, after initial hyperglycaemia for 50 days, were insulin treated for 2 h or for 5, 15 or 38 days. A group of hyperglycaemic diabetic animals were fasted for 18 h. Another group of rats had acute hyperglycaemia induced by intravenous glucose injection. After 10 and 50 days of diabetes, kidney weight was increased by 55 and 93 %. Glomerular volume, tubule length, and tubular and interstitial volume increased in diabetic animals compared with controls. After 4 h insulin treatment, the kidney weight was 20 % decreased; after 5 days it was 31 % decreased. After 38 days the kidney weight was still 26 % greater than in controls. In diabetic animals, 18 h fasting induced a 30 % decrease in kidney weight. In normal animals, acute hyperglycaemia induced a 22 % increase in kidney weight. Volume fractions of most kidney structures remained similar in all groups. However, the glomerular volume fraction was smaller during kidney enlargement, and the tubular volume fraction was larger after induced hyperglycaemia compared with controls. In conclusion, high blood glucose levels in diabetic and normal animals are associated with increased kidney weight. In hyperglycaemic diabetic animals, normalization of blood glucose after insulin treatment or fasting was followed by a decrease in kidney weight. [Diabetologia (1997) 40: 802–809]
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 9 (1973), S. 483-485 
    ISSN: 1432-0428
    Keywords: Capillaryfragility ; Doxium ; calcium-Dobesilate ; diabetes mellitus ; diabetic retinopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of Doxium on capillary resistance has been investigated in a 7 month double-blind clinical trial on 16 long-term diabetics with retionpathy. Quantitative measurements were performed every 5–6 weeks. The drug showed no effect on capillary resistance.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Distal tubules ; experimental diabetes mellitus ; insulin ; kidney ; proximal tubules ; rats ; stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetic renal growth, regression and regrowth was studied using stereological methods on perfusion-fixed rat kidneys. The study lasted 13 weeks and comprised one control group and three diabetic groups. The first diabetic group was hyperglycaemic for 13 weeks. The second group was hyperglycaemic for 10 weeks and then normoglycaemic for 3 weeks. The third group was similar to the second group except that during the last week the animals were again hyperglycaemic. Using an optical disector on the plastic-embedded kidney slices, the number and size of proximal and distal tubular cells were estimated. The number of proximal and distal tubular cells increased by 37% and 36% during 13 weeks of experimental diabetes and the mean volume of the proximal tubular cells increased by 12% whereas the 16% increase in mean tubular cell volume was only borderline significant as compared to the control group. Normoglycaemia for 3 weeks normalized the mean volume of distal tubular cells but the proximal tubular cells tended to be 7% smaller than those in control rats. The number of proximal cells remained increased by 21% compared with the control rats and the number of distal tubular cells retained a 17% insignificant increase. After regrowth the volume of proximal tubular cells was 20% greater than in the second diabetic group and the other parameters were unchanged. In conclusion, 13 weeks of experimental diabetes induced formation of 36% more tubular cells that were enlarged only by about 14%. Normoglycaemia for 3 weeks failed to normalize the cell number. Repeated hyperglycaemia for 1 week after 2 weeks of normoglycaemia increased the size of the proximal tubular cells.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; kidneys ; thick ascending limb of the loop of Henle ; Tamm-Horsfall glycoprotein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tamm-Horsfall glycoprotein, present only in the kidney thick ascending limb of Henle's loop, was studied here in streptozotocin diabetic rats. Tamm-Horsfall glycoprotein mRNA in situ hybridization was performed on snap-frozen left kidneys; the right kidneys were perfusion-fixed with 4% paraformaldehyde and embedded either in paraffin, for Tamm-Horsfall glycoprotein immunohistochemistry, or in Epon for stereologic measurements. The length of the thick ascending limb of Henle's loop and the amount of glycogen were measured and the ultrastructure of the cells was evaluated. Urinary excretion of Tamm-Horsfall glycoprotein, calcium, magnesium and albumin was measured. After 10 and 50 days' duration of diabetes, kidney weight increased 20 and 41%, respectively and the length of the thick ascending limb of Henle's loop increased 28 and 56%, respectively, compared with controls. Substantial glycogen accumulations were present in the thick ascending limb of Henle's loop, and electron microscopy revealed a significant decrease in organelles and basolateral membranes. After 10 and 50 days' duration of diabetes, in situ hybridization of Tamm-Horsfall glycoprotein mRNA revealed a fourfold decrease, and the immunostaining for Tamm-Horsfall glycoprotein showed a threefold decrease as measured by densitometry. However, urinary Tamm-Horsfall glycoprotein excretion rate was increased fivefold and urinary concentration about twofold. Urinary calcium excretion increased threefold and magnesium twofold, but urinary albumin excretion was not significantly increased. The increased amount of Tamm-Horsfall glycoprotein, calcium and magnesium in the urine in diabetes occurs here concomitant with severe cellular damage in the thick ascending limb of Henle's loop.
    Type of Medium: Electronic Resource
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