Biomedical subjects

R Rasch

Publications and source records attributed to R Rasch.

At least 19 recordsLinked to original sources

PubMed2004

The role of the RAS in programming of adult hypertension.

The aetiology of cardiovascular disease originally included two components: a genetic component and an environmental or lifestyle component. Increasing epidemiologic evidence has been accumulating during the last decades indicating the importance of a third component: the influence of the environment during foetal development. Poor living conditions resulted in a high infant mortality and influenced the incidence of cardiovascular diseases in adulthood despite better living conditions (A. Forsdahl. Br J Prev Soc Med 1977; 31, 91-95). An association between pre-natal growth pattern and the rate of death from cardiovascular disease in adulthood was reported (D.J. Barker, P.D. Winter, C. Osmond, B. Margetts & S.J. Simmonds. Lancet 1989; 2, 577-580). Men from Hartfordshire (UK), born between 1911 and 1930 were investigated. The investigations showed that men with the lowest weight at birth and at 1 year of age had the highest risks of death from cardiovascular disease (D.J. Barker, P.D. Winter, C. Osmond, B. Margetts & S.J. Simmonds. Lancet 1989; 2, 577-580). These findings suggested that factors in the perinatal environment could programme an individual for later risk of development of cardiovascular disease compared with someone born with a normal weight. Numerous studies have since confirmed these initial findings of an inverse relationship between early growth pattern and cardiovascular disease in adulthood.

Animals↗

PubMed2002

Inhibitory effects of octreotide on renal and glomerular growth in early experimental diabetes in mice.

It was recently discovered that the streptozotocin (STZ)-diabetic mouse model is characterised by GH hypersecretion in contrast to the STZ-diabetic rat, the former thus mimicking the changes in GH in human type 1 diabetes. Inhibition of circulating and renal IGF-I by long-acting somatostatin analogues reduces renal and glomerular growth and urinary albumin excretion in diabetic rats. The aim of the present study was to examine renal and glomerular growth in early experimental diabetes in mice along with changes in the GH/IGF-I axis following treatment with the somatostatin analogue octreotide. Balb/C(a) mice were randomised into non-diabetic controls, placebo-treated and octreotide-treated diabetic (50 microg/day) mice and examined 7 and 14 days after induction of diabetes. There was no effect of octreotide treatment on body weight, glycaemic control or food intake. However, octreotide treatment significantly inhibited renal and glomerular growth by the end of the study period when compared with placebo treatment. In addition, octreotide prevented an increase in kidney IGF-I by day 7. GH hypersecretion was observed in the diabetic groups but octreotide treatment reduced GH levels compared with placebo treatment by day 14. No significant differences in serum or kidney IGF-binding protein-3 levels were observed between placebo- and octreotide-treated diabetic mice. In conclusion, this new diabetic mouse model mimicking human type 1 diabetes is characterised by GH hypersecretion and the somatostatin analogue octreotide is able to prevent renal and glomerular growth, probably mediated through changes in circulating GH and local kidney IGF-I levels.

Analysis of Variance↗

PubMed2001

Hypertension after neonatal uninephrectomy in rats precedes glomerular damage.

The present study was designed to determine whether adult hypertension caused by a reduced number of nephrons from birth is due to preceding glomerular damage. Newborn male Sprague-Dawley rat pups were uninephrectomized during the first 24 hours after birth (UNX rats). At 20 weeks of age, chronically instrumented UNX animals were hypertensive on a normal-sodium (0.20%) diet compared with sham-operated controls (142+/-2 versus 124+/-2 mm Hg in controls). Body weights and the total kidney-to-body weight ratio were not significantly different in adult UNX animals compared with controls. Glomerular filtration rate (GFR) was reduced by 49% in UNX rats (1.85+/-0.24 versus 3.65+/-0.22 mL/min). Urine protein excretions were higher in UNX rats (20+/-2 versus 7+/-1 mg/d in controls). On a high-sodium (3.15%) diet, arterial pressure increased more in UNX than in controls (28+/-9 versus 3+/-1 mm Hg). In contrast, in animals studied at 8 weeks of age, GFR was only reduced by 26% in UNX animals (2.02+/-0.06 versus 2.73+/-0.07 mL/min). Their hypertension (125+/-2 versus 117+/-2 mm Hg) was also salt sensitive (increase on high-sodium diet of 35+/-11 versus 8+/-2 mm Hg in controls) but was not associated with proteinuria or histological signs of glomerular disease. Number of glomeruli per kidney in UNX animals was not different from controls, but individual glomerular volume increased by 41%. Thus, surgical removal of 50% of the nephrons, when done during development, causes reduced renal function and salt-sensitive hypertension in adulthood. Hypertension is present earlier in life than signs of glomerular disease, which suggests that hypertension is a major contributor to rather than primarily resulting from onset of renal disease.

Analysis of Variance↗

PubMed2001

Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats.

Restriction of maternal protein intake during rat pregnancy produces offspring that are hypertensive in adulthood, but the mechanisms are not well understood. Our purpose was to determine whether this adult hypertension could be programmed during development by suppression of the fetal/newborn renin-angiotensin system (RAS) and a consequent reduction in nephron number. Pregnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) diet throughout gestation. Birth weight was reduced by 13% (p < 0.0005), and the kidney/body weight ratio was reduced in LP pups. Renal renin mRNA levels were significantly reduced in newborn LP pups; renal renin concentration and renin immunostaining were suppressed. Renal tissue angiotensin II levels were also suppressed in newborn LP (0.079 +/- 0.002 ng/mg, LP versus 0.146 +/- 0.016 ng/mg, NP, p < 0.01). Mean arterial pressure in conscious, chronically instrumented adult offspring (21 wk) was higher in LP (135 +/- 1 mm Hg, LP versus 126 +/- 1 mm Hg, NP, p < 0.00007), and GFR normalized to kidney weight was reduced in LP (p < 0.04). The number of glomeruli per kidney was lower in adult LP offspring (21,567 +/- 1,694, LP versus 28,917 +/- 2,342, NP, p < 0.03), and individual glomerular volume was higher (1.81 +/- 0.16 10(6) microm(3), LP versus 1.11 +/- 0.10 10(6) microm(3), NP, p < 0.005); the total volume of all glomeruli per kidney was not significantly different. Thus, perinatal protein restriction in the rat suppresses the newborn intrarenal RAS and leads to a reduced number of glomeruli, glomerular enlargement, and hypertension in the adult.

Animals↗

PubMed2001

The role of the IGF axis in IGFBP-1 and IGF-I induced renal enlargement in Snell dwarf mice.

Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is generally believed to inhibit IGF action in the circulation. In contrast, IGFBP-1 has been reported to interact with cell surfaces and enhance IGF-I action locally in some tissues. Renal IGFBP-1 levels are found elevated in various conditions characterized by renal growth (e.g. diabetes mellitus, hypokalemia). To test whether IGFBP-1 is a renotropic factor, IGFBP-1 was administered alone or in combination with IGF-I to Snell dwarf mice, an in vivo model without compensatory feedback effects on growth hormone (GH) secretion. In three control groups of Snell dwarf mice, placebo, GH or IGF-I was administered. Compared with placebo, kidney weight increased in all treated groups, however, with different effects on kidney morphology. Administration of IGF-I, alone or in combination with IGFBP-1, tended to increase glomerular volume, while no changes were seen in the other groups. Administration of IGFBP-1 or IGFBP-1+IGF-I both caused dilatation of the thin limbs of Henle's loop, while GH or IGF-I administration had no visible effect. Furthermore, IGF-I administration resulted in an increased mean number of nuclei per cortical area and renal weight, whereas GH, IGF-I+IGFBP-1 or IGFBP-1 caused a decreased renal nuclei number. In situ hybridization and immunohistochemistry showed specific changes of the renal IGF system expression patterns in the different groups. Particularly, IGFBP-1 administration resulted in extensive changes in the mRNA expression of the renal IGF system, whereas the other administration regimen resulted in less prominent modifications. In contrast, administration of IGFBP-1 and IGFBP-1+IGF-I resulted in identical changes in the protein expression of the renal IGF system. Our results indicate that IGFBP-1, alone or in combination with IGF-I, demonstrated effects on the renal tubular system that differ from the effects of IGF-I.

Animals↗

PubMed2001

Transforming growth factor-beta2 antibody attenuates fibrosis in the experimental diabetic rat kidney.

Diabetic nephropathy is characterised by an increase in glomerular and tubular fibrosis that compromises kidney function. The transforming growth factor-betas (TGF-betas) have been shown to play a major role in fibrosis and we have shown that TGF-beta2, in particular, increases co-ordinately with fibrogenesis in the diabetic kidney. The aim of this study was to investigate the changes in expression of extracellular matrix molecules in the diabetic kidney, with and without systemic administration of a recombinant human monoclonal antibody to TGF-beta2. Streptozotocin-induced diabetic rats were split into two groups. The first were treated with 5 mg/kg irrelevant control IgG4 (placebo) and the second treated with 5 mg/kg isoform-specific recombinant monoclonal anti-TGF-beta2 IgG4 (termed CAT-152) systemically every second day for 14 days. A further group of six non-diabetic rats was also used as a control. Various biological parameters were measured daily throughout the experimental period, and on termination of the experiment at 14 days Western blotting was performed on kidney cortices for procollagen-I C-propeptide, which is an indicator of the rate of collagen-I synthesis within the kidney. In the placebo-treated diabetic rats, blood glucose, food consumption, urinary albumin excretion (UAE) and kidney weights were all significantly higher than in the non-diabetic group (P<0.05, n=24, by ANOVA). In the anti-TGF-beta2-treated diabetic rats, kidney weights and UAE levels were decreased when compared with those in placebo-treated diabetics. Western blotting for the procollagen-I C-propeptide in kidney cortices showed a significant increase in levels in placebo-treated diabetic rats compared with non-diabetic controls over the 14 day diabetic period, indicating initiation of fibrogenesis. By contrast, in anti-TGF-beta2-treated diabetic rats, levels of the propeptide remained at non-diabetic levels. In summary, a significant suppression of kidney fibrosis was seen in anti-TGF-beta2-treated diabetic rats, compared with placebo-treated diabetic rats. We conclude that systemic delivery of CAT-152, a neutralising anti-TGF-beta2 antibody, during the acute stages of diabetic nephropathy reduces the rate of pathogenic fibrosis in the kidney.

Albuminuria↗

PubMed1999

Compensatory renal growth in uninephrectomized adult mice is growth hormone dependent.

UNLABELLED: Compensatory renal growth in uninephrectomized adult mice is growth hormone dependent. BACKGROUND: Growth hormone (GH) and insulin-like growth factors (IGFs) have been implicated as pathogenic factors in compensatory renal growth (CRG) following unilateral nephrectomy in rodents. CRG in adult rats has been suggested to be GH dependent and GH independent in immature rats. However, the exact role of GH as a regulating or permissive factor in CRG in adult rodents has not been fully resolved to date. METHODS: To elucidate a possible direct, permissive role of GH in CRG, we examined the effect of a newly developed specific GH receptor (GHR) antagonist (G120K-PEG) on kidney IGF-I accumulation and renal/glomerular hypertrophy over seven days after uninephrectomy in adult mice. RESULTS: Placebo-treated uninephrectomized mice were characterized by a transient increase in kidney IGF-I concentration preceding CRG and an increase in glomerular volume. In G120K-PEG-treated uninephrectomized animals, increased kidney IGF-I levels, kidney weight, and glomerular volume were fully abolished. No differences were seen between the two uninephrectomized groups with respect to body weight, food intake, blood glucose, serum GH, IGF-I, or IGFBP-3 levels. CONCLUSIONS: The administration of a GHR antagonist in uninephrectomized adult mice has renal effects without affecting circulating levels of GH/IGFs, indicating that the effect of G120K-PEG may be mediated through a direct inhibitory effect on renal IGF-I accumulation through the renal GHR. This study shows, to our knowledge for the first time, that CRG in adult mice is strictly GH dependent.

Age Factors↗

PubMed1999

Growth hormone receptor antagonism prevents early renal changes in nonobese diabetic mice.

The growth hormone (GH)/insulin-like growth factor (IGF) axis is involved in diabetic renal disease. The role of a specific GH receptor (GHR) antagonist in the development of early renal changes in nonobese diabetic (NOD) mice was investigated. Female diabetic (nonketotic) NOD mice treated with a polyethylene glycol-treated GHR antagonist (2 mg/kg, every other day) (DA group) or saline (D group) and their nonhyperglycemic age-matched littermates (control animals) were euthanized 3 wk after the onset of diabetes. Body weights at euthanasia were similar among the groups. Serum GH levels were markedly elevated, and serum IGF-I levels were significantly decreased in D and DA animals, compared with controls. The increases in kidney weights and glomerular volumes observed for the D group were absent in the DA group. Albuminuria was increased in the D group but was normalized in the DA group. Extractable renal IGF-I protein levels were increased in the D group but were partially normalized in the DA group. Renal IGF-binding protein 1 mRNA levels were increased in the D group but returned to almost normal levels in the DA animals. Kidney IGF-I and GHR mRNA levels were decreased in both the D and DA groups. Renal GH-binding protein mRNA levels remained unchanged in both diabetic groups. GHR antagonism had a blunting effect on renal/glomerular hypertrophy and albuminuria in diabetic NOD mice. These salutary effects were associated with concomitant inhibition of increased renal IGF-I protein levels and were obtained without affecting either somatic growth or circulating GH and IGF-I levels. Therefore, modulation of GH effects may have beneficial therapeutic implications in diabetic nephropathy.

Animals↗

PubMed1999

Inhibitory effect of a growth hormone receptor antagonist (G120K-PEG) on renal enlargement, glomerular hypertrophy, and urinary albumin excretion in experimental diabetes in mice.

Growth hormone (GH) and IGFs have a long and distinguished history in diabetes, with possible participation in the development of renal complications. To investigate the effect of a newly developed GH receptor (GHR) antagonist (G120K-PEG) on renal/glomerular hypertrophy and urinary albumin excretion (UAE), streptozotocin-induced diabetic and nondiabetic mice were injected with G120K-PEG every 2nd day for 28 days. Placebo-treated diabetic and nondiabetic animals were used as reference groups. Placebo-treated diabetic animals were characterized by growth retardation, hyperphagia, hyperglycemia, increased serum GH levels, reduced serum IGF-I, IGF-binding protein (IGFBP)-3, and liver IGF-I levels, increased kidney IGF-I, renal/glomerular hypertrophy, and increased UAE when compared with nondiabetic animals. No differences were seen between the two diabetic groups with respect to body weight, food intake, blood glucose, serum GH, IGF-I, and IGFBP-3 levels or hepatic IGF-I levels. Kidney IGF-I, kidney weight, and glomerular volume were normalized, while the rise in UAE was partially attenuated in the G120K-PEG-treated diabetic animals. No effect of G120K-PEG treatment on any of the parameters mentioned above was seen in nondiabetic animals. In conclusion, administration of a GHR antagonist in diabetic mice has renal effects without affecting metabolic control and circulating levels of GH, IGF-I, or IGFBP-3, thus indicating that the effect of G120K-PEG may be mediated through a direct inhibitory effect on renal IGF-I through the renal GHR. The present study suggests that specific GHR blockade may present a new concept in the treatment of diabetic kidney disease.

Albuminuria↗

PubMed1998

Quantitative changes in rat renin secretory granules after acute and chronic stimulation of the renin system.

In order to study the cellular mode of renin secretion, stereological methods were used to estimate number and volume of rat renin secretory granules during stimulation of the renin system. An acute decrease in renal perfusion pressure to 40 mmHg for 5 min increased plasma renin concentration (PRC) twofold, but did not significantly change the number of renin granules per arteriole or the renin-containing volume of the arteriole. Chronic stimulation was achieved by a combination of low-salt diet and inhibition of angiotensin-converting enzyme (ACE) for 14 days, and resulted in a 36-fold increase in PRC, a 20-fold increase in the number of granules per arteriole, and a 17-fold increase in the arteriolar volume that contained renin. An acute decrease in renal perfusion pressure to 40 mmHg for 5 min in the chronically stimulated rats increased PRC further (1.6-fold), and significantly reduced the number of granules per arteriole by 4000 (45% reduction), but did not change the renin-containing arteriolar volume significantly. The average renin granule size was 0.35 microm3 with no significant differences among the groups. We conclude that recruited granular cells contribute significantly to renin release, and that all granular cells along the arteriole participate in secretory responses. The reduced number of renin granules after acute stimulation is compatible with exocytosis as the dominating mechanism of renin release.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Perinatal ANG II programs adult blood pressure, glomerular number, and renal function in rats.

ANG II is known to be important in normal renal development, but the long-term consequences of a suppressed renin-angiotensin system (RAS) during the developmental period are not completely understood. This study tested the hypothesis that the RAS in the developing animal is important in long-term regulation of renal function and arterial pressure. Newborn Sprague-Dawley rat pups were given the ANG II AT1 receptor antagonist losartan (25 mg . kg-1 . day-1 sc) for the first 12 days of postnatal life (Los). Body weights at weaning (22 days) were significantly reduced in Los (53.4 +/- 3.2 vs. 64.5 +/- 3.6 g in controls); however, at the time of study (approximately 22 wk), body weights and the kidney-to-body weight ratios were not different. In chronically instrumented conscious animals, glomerular filtration rate and effective renal plasma flow were reduced by 27 and 20%, respectively, in Los; the filtration fraction was not different. Maximal urine concentrating ability was also reduced in Los (1,351 +/- 45 vs. 2,393 +/- 52 mosmol/kg in controls). Mean arterial pressure was significantly higher in Los (134 +/- 3 vs. 120 +/- 1 mmHg). The number of glomeruli per kidney was reduced by 42% in Los, but the total glomerular volume was unchanged. Thus perinatal blockade of ANG II AT1 receptors results in fewer but enlarged glomeruli, reduced renal function, and an increased arterial pressure in adulthood. These data indicate that perinatal ANG II, acting via AT1 receptors, plays an important role in renal development and long-term control of renal function and arterial pressure. Physiological conditions that cause suppression of the RAS in the developing animal may have long-term consequences for renal function and blood pressure.

Aging↗

PubMed1997

Quantitative morphology of the rat kidney during diabetes mellitus and insulin treatment.

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.

Animals↗

PubMed1997

Giant renin secretory granules in beige mouse renal afferent arterioles.

The mutant beige mouse (C57BL/6 bg) has a disease characterised by abnormally enlarged cytoplasmic granules in a variety of cells. With the purpose of establishing a suitable cellular model for studying renin secretion, the present study was undertaken to compare renin granule morphology in beige mice with that of control (NMRI) mice. Immunohistochemistry with an antibody specific for renin revealed intense staining of the juxtaglomerular part of the afferent arterioles in both strains of mice. Plasma renin concentrations were higher in the controls than in the beige mice (4.4+/-0.6 vs 2.5+/-0.3 mGoldblatt units/ml). The total volume of renin granules per afferent arteriole was similar in the two mice strains (1114 microm3 in the controls and 1507 microm3 in the beige mice). The total number of renin granules per arteriole as assessed by stereological techniques was about 1900 in controls (average granular volume 0.681 microm3), whereas 1-2 large granules were present per cell in beige mice. The volume of afferent arteriole that contained secretory granules was lower in the beige mice. We conclude that the beige mouse synthesizes, stores and releases active renin. Renin secretory granules in beige mice are grossly enlarged with 1-2 granules per juxtaglomerular cell. Compared with control mice, a similar amount of total renin granule volume per afferent arteriole is contained in a smaller part of beige mouse afferent arteriole. Granular cells from beige mice could therefore be a valuable tool in the study of renin release.

Animals↗

PubMed1997

Relationship between MRI and morphometric kidney measurements in diabetic and non-diabetic rats.

The aim of the present study was to determine the applicability of magnetic resonance imaging (MRI) as a non-invasive measure of kidney volume in vivo in diabetic and non-diabetic rats. Magnetic resonance, T1 weighted Spin Echo, images were obtained after injection of contrast in anesthetized control (N = 14) and hyperglycemic streptozotocin (STZ)-diabetic rats (N = 14). On MRI imaging the total kidney, cortex, medullary and pelvic volumes were calculated. Immediately after MRI measurements the left kidneys were removed before weighing either as a clamped kidney weight (that is, the kidney containing blood and urine) or as a wet kidney weight (the kidney drained of blood and urine), while the right kidneys were perfusion-fixed for morphometric measurements. On thin kidney slices obtained from perfusion-fixed kidneys the cortex, medullary and pelvic fractions were measured and subsequently the cortex, medulla and pelvic volumes were calculated. The cortical volume was measured according to three different approaches. The corticomedullary boundary was defined either to the arcuate arteries, to a curved line following the glomeruli, or to a line at the top of the medullary rays. Both in control and diabetic rats, MRI measured kidney volumes were similar to the volume of perfusion-fixed kidneys, while the clamped kidney weight, and in particular the wet kidney weights, were smaller than the MRI obtained volumes. Good agreement was found between the MRI measured cortex and medulla volumes when the cortex was defined to the top of the medullary rays in the morphometric analysis. In conclusion, the present study demonstrates that MRI allows a reliable non-invasive estimate of renal morphology at a macroscopic level in both diabetic and non-diabetic rats.

Animals↗

PubMed1996

Effects of heparin and aminoguanidine on glomerular basement membrane thickening in diabetic rats.

The effects of heparin and aminoguanidine on glomerular basement membrane thickening were studied in streptozotocin diabetic Sprague-Dawley rats. A placebo-treated group and a non-diabetic group served as controls. All diabetic rats remained severely hyperglycaemic (23 mmol/l) throughout the 8-month study period. At the end of this time relative kidney weight was significantly increased in diabetic control rats (4.9 +/- 0.5 g/kg b.w.) compared with non-diabetic rats (3.3 +/- 0.3 g/kg). This increase was not affected by the intervention treatments. Glomerular basement membrane thickness increased 32% in diabetic control rats (240 +/- 24 nm) compared with non-diabetic rats (182 +/- 20 nm). This increase was prevented by s.c. treatment with both unfractionated and low molecular weight heparins, while basement membrane thickness was the same in animals treated with oral heparins and aminoguanidine and untreated diabetic rats. Macroscopic malignant kidney tumours were seen in three aminoguanidine-treated rats. In conclusion, subcutaneously administered heparin prevents diabetes-induced glomerular basement membrane thickening.

Administration, Oral↗

PubMed1995

Tamm-Horsfall glycoprotein in streptozotocin diabetic rats: a study of kidney in situ hybridization, immunohistochemistry, and urinary excretion.

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 three-fold 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.

Albuminuria↗

PubMed1995

Presence of antibodies reacting with porcine circovirus in sera of humans, mice, and cattle.

Antibodies reacting with porcine circovirus (PCV) were found in sera of humans, mice, and cattle by means of an indirect immunofluorescence assay (IFA) and an ELISA. In man, the highest seroprevalence (23.9% in IFA and 30.2% in ELISA) was found among hospitalized patients with fever of partially unclear etiology. Non-hospitalized "healthy" persons of the former German Democratic Republic showed a significantly higher number of positive sera (IFA = 20%) than blood donors from Berlin-West (IFA = 8.6%). Murine sera reacted positive with PCV in IFA between 12 to 69% in different breeding groups and about 35% of cattle sera were found reactive with PCV in IFA. Double-staining IFAs, immuno-electron microscopy and immunoblotting showed that non-porcine antibodies reacted with PCV structural antigen. Mathematical analysis revealed that in ELISA, non-porcine antibodies reacted specifically with PCV. Loss of binding specificity of non-porcine antibodies in ELISA after storage of sera and lower maximal optical densities obtained at equal titers in ELISA with non-porcine than with porcine sera suggest that antibodies in man, mice and cattle are caused by related species specific viruses sharing antigenic epitopes with PCV.

Adult↗

PubMed1995

Morphometric analysis of effects of angiotensin II on glomerular structure in rats.

Micropuncture and morphometric studies related the effects of angiotensin II (ANG II) on glomerular function and structure. Compared with control animals, rats receiving an intrarenal infusion of ANG II at 40 ng.kg-1.min-1 exhibited a marked reduction in the glomerular ultrafiltration coefficient (Kf) (0.84 +/- 0.13 vs. 1.43 +/- 0.05 microliters.s-1.mmHg-1, ANG II vs. control), which caused a decrease in glomerular filtration rate (GFR) (1.04 +/- 0.11 vs. 1.27 +/- 0.11 ml/min) despite an increase in glomerular transcapillary hydraulic pressure difference (46 +/- 1 vs. 40 +/- 1 mmHg). Morphometric studies showed that these hemodynamic changes were not associated with any reduction in glomerular volume (1.27 +/- 0.05 vs. 1.31 +/- 0.07 x 10(6) microns3, ANG II vs. control), glomerular capillary volume (4.25 +/- 0.36 vs. 4.41 +/- 0.33 x 10(5) microns3), or glomerular peripheral capillary surface area (2.24 +/- 0.11 vs. 2.29 +/- 0.30 x 10(5) microns2). Higher-power electron micrographs showed that ANG II also did not alter mean foot process width (478 +/- 14 vs. 491 +/- 18 nm, ANG II vs. control), reduce the total filtration slit length overlying the peripheral capillary wall (7.0 +/- 0.6 vs. 6.6 +/- 0.5 x 10(5) microns), or reduce the average width of individual filtration slits (45 +/- 2 vs. 43 +/- 2 nm). ANG II infusion thus caused a 40% reduction in the value of Kf without causing detectable changes in epithelial cell or filtration slit structure.

Angiotensin II↗