Biomedical subjects

A Flyvbjerg

Publications and source records attributed to A Flyvbjerg.

At least 145 records · Page 8Linked to original sources

PubMed1996

Insulin-like growth factor I as a predictor of cortical bone mass in a long-term study of ovariectomized and estrogen-treated rats.

The relationship between serum insulin-like growth factor I (IGF-I) and cortical bone mass, formation and resorption and length of bone in a long-term experiment on intact, ovariectomized and estrogen-treated/substituted rats was studied by using multiple linear regression analysis. The study comprised intact rats killed at 2, 6, 9, 12, 15, and 24 months of age, rats ovariectomized 6 months old and killed at 9, 12, 15, and 24 months of age, and intact and ovariectomized rats treated with a low dose of estrogen for 8 months before they were killed at 24 months of age. Serum IGF-I, bone length and total, subperiosteal and subendocortical bone mass in mid-diaphyseal cross sections of the femur were determined. Changes in the latter two variables, respectively, represent the net result of subperiosteal bone formation and subendocortical bone resorption. Multiple linear regression analysis showed that IGF-I was a positive determinant of cortical bone mass and subperiosteal bone formation. In aged rats, IGF-I was also a positive determinant of bone length, whereas IGF-I was not found to be a determinant of subendocortical bone resorption. The analyses showed that long-term treatment of aged rats with a low dose of estrogen had a dual effect on cortical bone by inhibiting subperiosteal formation and subendocortical resorption. The results revealed a relationship between endogenous circulating IGF-I and local anabolic actions of the growth factor in bones. Thus, IGF-I may be a valuable serum marker of cortical bone formation and length of long bones when considering estrogen-depleted and estrogen-treated rats.

Animals↗

PubMed1996

Serum concentrations of free and total insulin-like growth factor-I, IGF binding proteins -1 and -3 and IGFBP-3 protease activity in boys with normal or precocious puberty.

OBJECTIVE: Circulating IGF-I and IGF binding protein-3 (IGFBP-3) levels both increase in puberty where growth velocity is high. The amount of free IGF-I is dependent on the IGF-I level and on the concentrations of the specific IGFBPs. Furthermore, IGFBP-3 proteolysis regulates the bioavailability of IGF-I. However, the concentration of free IGF-I and possible IGFBP-3 proteolytic activity in puberty has not previously been studied. SUBJECTS AND MEASUREMENTS: We investigated serum levels of easily dissociable IGF-I concentrations and ultrafiltrated free IGF-I levels by specific assays in 60 healthy boys and in 5 boys with precocious puberty before and during GnRH agonist treatment. In addition, total serum IGF-I, IGFBP-1 and IGFBP-3 levels as well as IGFBP-3 protease activity were determined. RESULTS: Free (dissociable and ultrafiltrated) IGF-I concentrations were significantly higher in pubertal boys than in prepubertal children and correlated significantly with the molar ratio between IGF-I and IGFBP-3 (r = 0.69, P < 0.0001 and r = 0.54, P = 0.0008, respectively) and inversely with IGFBP-1 (r = -0.47, P < 0.0001 and r = -0.43, P = 0.0003, respectively). Multiple regression analysis suggested that IGFBP-3 level, and not IGFBP-1, was the major determinant of the free IGF-I serum level in normal boys. Free IGF-I levels were elevated in boys with precocious puberty and decreased during GnRH treatment. IGFBP-3 proteolysis was constant throughout puberty (mean 20%). CONCLUSIONS: We conclude that easily dissociable and ultrafiltrated free IGF-I serum levels are increased in boys with normal and precocious puberty and suggest that the increased free IGF-I serum concentration in puberty primarily reflects changes in total concentrations of IGF-I and IGFBPs secondary to increased GH secretion, but that it is not influenced by changes in IGFBP-3 proteolysis.

Adolescent↗

PubMed1996

Effects of heparin on renal morphology and albuminuria in experimental diabetes.

Female nondiabetic and streptozotocin diabetic Wistar rats received 200 units heparin two times daily by subcutaneous injection for 6 mo. Mesangial volume fraction was reduced in heparin-treated control (CH) compared with untreated control (C) animals (CH 0.18 +/- 0.02 vs. C 0.24 +/- 0.02, P < 0.05), but other histological parameters were similar. In the heparin-treated diabetic (DH) group, wet kidney weight was increased compared with the untreated diabetic (D) group (DH 1,156 +/- 39 vs. D 1,050 +/- 30 mg, P < 0.05), as were absolute, but not fractional, glomerular volume (P < 0.05) and capillary volume (P < 0.05). Basement membrane thickness (DH 193 +/- 3 vs. D 231 +/- 9 nm, P < 0.01) and mesangial/glomerular volume fraction (P < 0.001) were decreased. Urinary albumin excretion was increased in the heparin-treated control animals compared with control animals [CH 980 (range 150-4,448) vs. C 221 (range 86-654) micrograms/24 h, P < 0.001] and in the heparin-treated diabetic animals compared with the diabetic animals [DH 12,785 (range 4,495-29,520) vs. D 899 (range 450-1,335) micrograms/24 h, P < 0.001]. Thus the possibly deleterious increases in glomerular capillary volume and albumin excretion may negate the beneficial effects of heparin on mesangial and basement membrane structures.

Albuminuria↗

PubMed1996

Increased number of myocardial voltage-gated Ca2+ channels and unchanged total beta-receptor number in long-term streptozotocin-diabetic rats.

In order to elucidate further the abnormal myocardial Ca2+ metabolism in diabetes mellitus, voltage-gated Ca2+ channels and beta-receptors were quantified in myocardial membranes of short- and long-term diabetic rats. Diabetes was induced by an injection of streptozotocin (STZ). Animals were killed 2, 4, 7, 90 and 200 days after STZ. A group of diabetic animals were treated with insulin for 20 days following 180 days of untreated diabetes. Diabetic animals developed low triiodothyronine syndrome. During short-term diabetes, the maximum binding capacity (MBC) for Ca2+ channels was reduced by 25% at day 4 (p < 0.05) and the beta-receptor MBC was reduced by 48% (p < 0.05). A normalizing tendency was observed at day 7 for both receptor types; insulin-treated rats did not differ from controls at that time. After 90 and 200 days of untreated diabetes the Ca2+ channel MBC had increased by 36% and 27%, respectively (p < 0.05). Twenty days of strictly regulated blood glucose following 180 days of untreated diabetes totally normalized the Ca2+ channel MBC. This is in contrast to a previous report where insulin treatment did not normalize the Ca2+ channel MBC. Total beta-receptor MBCs did not differ from control values 90 and 200 days after STZ. In conclusion, an increase in rat myocardial Ca2+ channel MBC during long-term diabetes was fully normalized by short-term insulin treatment. The increase in sarcolemmal Ca2+ channels could serve to compensate for a defect coupling of the beta-receptor to adenylate cyclase. An elevated Ca2+ channel number may, at least theoretically, lead to increased Ca2+ flow across the cardiac sarcolemma and in this way contribute to the diabetic cardiomyopathy by increasing the intracellular Ca2+ concentration.

Animals↗

PubMed1996

The effect of epidermal growth factor on circulating levels of IGF and IGF-binding proteins in adult Goettingen minipigs.

It has recently been demonstrated that epidermal growth factor (EGF) administration to neonatal rodents causes growth retardation with concomitant reductions in circulation levels of IGF-I. We describe the effects of systemic EGF administration for 4 weeks on circulating levels of IGF-I and IGF-binding proteins (IGFBPs) and on thyroid hormones (tri-iodothyronine, T3; thyroxine, T4) in sexually mature pigs. Goettingen minipigs of either sex were treated with placebo (n = 5) or EGF (30 micrograms/kg per day, n = 6) s.c. for 4 weeks (in relation to an oesophageal sclerotherapy regimen). Blood samples were taken under anaesthesia before and after 1, 2, 3 and 4 weeks of treatment. Circulating levels of IGF-I, insulin, glucose, T3 and T4 were analysed every week and IGFBPs every second week. IGF-I was not reduced significantly after 1 week but significantly reduced after 2 and 3 weeks of EGF treatment. A similar decline was observed for the major IGFBP, IGFBP-3, which was reduced after 2 and 4 weeks. IGFBP-1, IGFBP-2 and IGFBP-4 increased throughout the treatment period (all significantly at week 4). EGF treatment induced increased circulating T3 after 2, 3 and 4 weeks of EGF treatment. In conclusion, we report that EGF treatment for 4 weeks in Goettingen minipigs reduces circulating IGF-I and IGFBP-3, increases circulating IGFBP-1, IGFBP-2 and IGFBP-4, and induces a slight hyperthyroidism as judged from increased circulating levels of T3.

Animals↗

PubMed1996

Periosteal insulin-like growth factor I and bone formation. Changes during tibial lengthening in rabbits.

We investigated changes in periosteal insulin-like growth factor I (IGF-I) during tibial lengthening. In 37 rabbits, an osteotomy of the right middle tibia was made and fixed by a unilateral external fixator. The rabbits were randomized into 6 groups: the tibiae were distracted at 0.5 mm/day up to 4 weeks and the animals killed after 2 weeks, 4 weeks or 6 weeks, for each period there was a control group with no distraction. Periosteal IGF-I was measured by radioimmunoassay and bone formation was quantified by CT scanning. During bone lengthening, CT showed moderate bone formation, while IGF-I was increased. When lengthening was stopped, IGF-I returned to a basal level, and CT scanning showed considerable bone formation. Our study suggests that IGF-I plays a role in an early stage of bone formation.

Animals↗

PubMed1996

The effect of epidermal growth factor on circulating levels of free and total IGF-I and IGF-binding proteins in adult rats.

In neonatal rats, systemic administration of epidermal growth factor (EGF) results in reduced body weight gain and decreased levels of circulating IGF-I, which suggests that it be involved in the EGF-induced growth retardation. We investigated the effect of 4 weeks of EGF administration on circulating free and total IGF-I and IGF-binding proteins (IGFBPs) in adult rats treated with saline (controls), 30 (low dose group) and 150 (high dose group) microgram/kg/day EGF. Serum IGF-I was determined in ultrafiltrates (free) and acid-ethanol extracts (total), and serum IGFBPs using Western ligand blotting, which yielded four distinct molecular bands. The IGFBPs were tentatively identified as IGFBP-3 (a double band at 42 and 38 kDa), IGFBP-1 and/or IGFBP-2 (a single band at 30 kDa) and IGFBP-4 (a single band at 24 kDa). EGF administration did not change the body weight, tibia length, or liver, heart and lung weight. In contrast, serum total IGF-I and IGFBP-3 decreased dose-dependently: total IGF-I averaged 1470 +/- 100 micrograms/l (controls; mean +/- SEM), 1030 +/- 60 micrograms/l (low dose group; P < 0.005) and 760 +/- 40 micrograms/l (high dose group; P < 0.005), whereas differences between IGFBP-3 levels reached significance (P < 0.05) between controls and high dose rats, only. When compared to controls, levels of IGFBP-1 and/or IGFBP-2 were increased in the low dose group (P < 0.05), but unchanged in the high dose group. IGFBP-4 was unaffected by EGF. Free IGF-I averaged 74 +/- 6 micrograms/l in controls, and was reduced to 35 +/- 6 micrograms/l (low dose group; P < 0.005) and 57 +/- 5 micrograms/l (high dose group; P < 0.05). Free IGF-I was inversely correlated (r = -0.49, P < 0.05) with IGFBP-1 and/or IGFBP-2. We conclude that in adult rats prolonged EGF administration has a marked depressing effect on circulating total and free IGF-I. Nevertheless, we did not observe any somatic growth retardation.

Animals↗

PubMed1996

Streptozotocin induction of diabetes in rats leads to increased insulin-like growth factor-II/mannose-6-phosphate receptor mRNA expression in kidney but not in lung or heart.

Insulin and glucose are thought to act as important modulators of the expression of the IGFs, their binding proteins and their receptors. It has been postulated that changes of the IGF system after diabetes onset contribute to the development of diabetes late complications. We have measured the expression of IGF-II/M6P receptor mRNA in rat kidney, lung and heart after streptozotocin induction of diabetes. Adult rats were injected with streptozotocin, and, after the onset of diabetes, were treated with either insulin or vehicle. The rats were sacrificed on days 1, 2, 3, 4 and 9. Kidneys, lungs and hearts were removed aseptically and RNA was extracted from the tissues. In solution hybridization/RNAse protection experiments, specific IGF-II/M6P receptor and beta-actin transcripts were detected in the RNA samples from all tissues examined. To gain additional evidence for the expression of IGF-II/M6P receptor RNA in the tissues examined, Northern blotting experiments were performed: a major 9 kb RNA species was detected on the blots. Interestingly, streptozotocin-induced onset of diabetes led to a significant increase in the expression of IGF-II/M6P receptor mRNA in the kidney but not in lung and heart whereas no change in actin mRNA expression was measured. Insulin treatment did not prevent the increase of IGF-II/M6P receptor mRNA expression during short-term treatment (1-9 days). Alterations of the IGF system during diabetes onset might be of relevance for the development of early renal changes during the course of the disease.

Animals↗

PubMed1995

IGF-II receptors in luminal and basolateral membranes isolated from pars convoluta and pars recta of rabbit proximal tubule.

The binding of 125I-labeled insulin-like growth factor-II (125I-IGF-II) to luminal and basolateral membrane vesicles isolated from pars convoluta and the straight part (pars recta) of rabbit proximal tubule was investigated. Analyses of the binding data by use of the general stoichiometric binding equation revealed, that in all preparations IGF-II was bound to one high-affinity binding site and other sites with lower affinities. The specificity of the high-affinity 125I-IGF-II binding to the membrane vesicles assessed by displacement by unlabeled IGF-II, IGF-I and insulin showed that IGF-I displaced 125I-IGF-II in the range 22.5-47.9 nM (IC50) whereas insulin did not effect 125I-IGF-II binding at all. beta-Galactosidase inhibited the 125I-IGF-II binding with half-maximal inhibition of 20-30 nM beta-galactosidase. D-Mannose 6-phosphate increased the binding of 125I-IGF-II and reversed the inhibitory effect of beta-galactosidase. Analyses of 125I-IGF-II binding curves in the presence of beta-galactosidase or D-mannose 6-phosphate demonstrated that none of these compounds changed the binding affinity of 125I-IGF-II for the membrane vesicles. The IGF-II/M6P receptor content in the luminal membranes was in the range 0.21-0.34 pmol IGF-II/M6P receptor per mg protein and very low compared to 2.27-2.86 pmol IGF-II/M6P receptor per mg protein in basolateral membranes.

Animals↗

PubMed1995

Growth hormone stimulates bone formation and strength of cortical bone in aged rats.

The influence of growth hormone on bone formation, mechanical strength, and composition has been investigated in femur middiaphyseal cortical bone from 2-year-old male rats. The rats were given biosynthetic human growth hormone (bhGH) at 2.7 mg/kg/day in two daily injections for 20, 40, or 80 days, and all animals were killed 80 days after the start of bhGH administration. Control animals were given saline. All animals were labeled with tetracycline on days 41 and 69. Only in the bhGH-80-day group was subperiosteal tetracycline double labeling seen all around the femur diaphysis, and this pattern was found in all animals of the group. Double labeling subperiosteally at the posteromedial aspect was found in all animals of the experiment, but compared with the control group, a 400% and an 800% increase in mineral apposition rate was seen in the bhGH-40-day and bhGH-80-day groups, respectively. Light microscopy and polarization microscopy showed that this newly deposited bone was organized in the same concentric lammellae and had the same direction of the collagen fibers when compared with the surrounding bone formed before the start of bhGH injections. The cortical bone cross-sectional area was increased in the bhGH-40-day and bhGH-80-day groups. At the endosteum, scattered labeling was found in animals from all groups, and no differences in medullary cross-sectional areas were seen. The mechanical analysis revealed an increased mechanical strength of the whole diaphyseal bone after bhGH administration. When the data were corrected for dimensions of the diaphyseal bone, no differences in intrinsic mechanical properties of the bone tissue were found. No differences in apparent density of dry defatted bone, ash, and collagen were seen, whereas apparent density of dry defatted bone minus ash was decreased in all groups given bhGH. Correspondingly, a slight increase in ash concentrations of the bhGH-injected animals was seen. bhGH administration also increased the body weight, muscle mass, and total serum IGF-I and thyroxine concentrations.

Aging↗

PubMed1995

Short-term treatment with growth hormone stimulates osteoblastic and osteoclastic activity in osteopenic postmenopausal women: a dose response study.

To investigate the potential use of growth hormone (GH) in Activate-Depress-Free-Repeat treatment of postmenopausal osteoporosis, we measured changes in serum levels of biochemical markers of bone turnover, insulin-like growth factor-I (IGF-I), calciotropic hormones, and bone mineral density in 40 postmenopausal women with osteopenia (ages 52-73 years) in response to 7 days of treatment with either placebo or GH (0.05, 0.10, or 0.20 IU/kg/day) administered subcutaneously in the evening. GH treatment increased serum osteocalcin (p < 0.01) and C-terminal type-I procollagen propeptide (p < 0.01) and also serum levels of type-I collagen telopeptide (p < 0.001), fasting urinary hydroxyproline/creatinine (p < 0.05), pyridinoline/creatinine (p < 0.05), and deoxypyridinoline/creatinine (p < 0.01) in a dose-dependent fashion. Even the lowest dose of GH tested induced a significant increase in these parameters; however, the effects were transient lasting only 1-2 weeks. In the highest dose group, however, a somewhat prolonged effect (30 days) on serum osteocalcin was observed. Furthermore, GH increased serum levels of IGF-I, insulin, and tri-iodothyronin. No effect on serum 1,25-dihydroxyvitamin D3 or parathyroid hormone could be demonstrated. Adverse effects were mainly related to fluid retention. They were clearly dose-dependent and rapidly reversible. In conclusion, short-term GH treatment stimulates bone formation and bone resorption in postmenopausal women with osteopenia.

Aged↗

PubMed1995

Effect of diabetes and dietary ubiquinone supplementation on the post-translational modification of rat lens beta L crystallin.

The effect of streptozocin diabetes of 14 days duration on the integrity of lenticular crystallins has been determined by the measurement of characteristic markers of protein modification in the lens crystallins of rats. Further, the susceptibility of the crystallins to modification has also been determined by measurement of the same markers after the application of a metal-catalyzed oxidative insult in vitro. The results show that the previously reported increased post-translational modification of lens crystallins in vivo and increased susceptibility to modification in vitro of diabetic crystallins after 21 days of uncontrolled diabetes are also evident after just 14 days of diabetes. Treatment of the diabetic animals with the antioxidant ubiquinone by dietary supplementation was unable to prevent the post-translational modifications sustained by the crystallin when subjected to diabetes in vivo or the increase in susceptibility to an in vitro oxidative stress. While the present results support the proposal that cataract formation is initiated by protein post-translational modification factors such as glycation, ubiquinone supplementation does not appear to be beneficial in the inhibition of post-translational crystallin modification in diabetic cataractogenesis.

Animals↗

PubMed1995

Dose-response study of the effect of growth hormone on mechanical properties of skin graft wounds.

The aim of the study was to investigate the effect of growth hormone on compromised wound healing in a model without exogenously applied metabolic disturbances, e.g., diabetes mellitus. Female Wistar rats were injected with biosynthetic human growth hormone (b-hGH) at 2.0, 4.0, 8.0, and 16.0 mg/kg/day from 7 days before operation to 7 days after. Controls were given saline. On the left side of the dorsal skin a 35 x 20-mm full-thickness skin graft was raised and replaced in situ. After 7 days of healing the wound between the graft and the skin was tested mechanically. The maximum load and maximum stiffness showed a positive correlation with dose of b-hGH, being increased by 40 and 47% in the 8.0 mg group and 34 and 48% in the 16.0 mg group compared with the saline group. During the 7 days of injection before operation serum insulin-like growth factor I (IGF-I) decreased in the saline group, was unchanged in the group given 2.0 and 4.0 mg b-hGH, and was increased in the groups given 8.0 and 16.0 mg b-hGH. Postoperatively, no changes in se-IGF-I were seen in any of the groups when compared to the values at operation. Blood glucose was unaffected by b-hGH treatment. Postoperatively the saline-treated rats showed an 8% weight loss and the 2.0 mg b-hGH group a 3% weight loss, whereas no significant changes were seen postoperatively in the 4.0, 8.0, and 16.0 mg b-hGH groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1995

Effect of octreotide and insulin on manifest renal and glomerular hypertrophy and urinary albumin excretion in long-term experimental diabetes in rats.

Treatment of diabetic rats with octreotide can inhibit early diabetic renal hypertrophy. Octreotide administration for 6 months from the day of diabetes induction inhibits renal hypertrophy and diminishes increase in urinary albumin excretion. To investigate the effect of octreotide on manifest diabetic renal changes, octreotide treatment was given for 3 weeks after an untreated diabetic period of 3 or 6 months. In addition, following 6 months of diabetes, a group of diabetic rats was treated with insulin for 3 weeks. Renal and glomerular hypertrophy, and increased urinary albumin excretion were observed in diabetic rats compared to non-diabetic control rats from 3 months and throughout the study period. Octreotide treatment did not affect body weight, food intake, blood glucose or serum fructosamine levels. We observed no effect of octreotide treatment on renal and glomerular hypertrophy or urinary albumin excretion compared to placebo-treated diabetic rats. Insulin treatment for 3 weeks after 6 months of untreated diabetes normalized blood glucose and serum fructosamine levels, and furthermore renal hypertrophy was significantly diminished compared to the placebo-treated diabetic rats. However, insulin treatment had no effect on glomerular hypertrophy or urinary albumin excretion. In conclusion, octreotide treatment for 3 weeks following an untreated diabetic period of 3 or 6 months is unable to reduce the increased renal and glomerular volume or urinary albumin excretion. However, insulin treatment for 3 weeks with induction of euglycaemia diminishes the renal hypertrophy but has no effect on glomerular volume or urinary albumin excretion.

Albuminuria↗

PubMed1995

The role of growth hormone, insulin-like growth factors (IGFs), and IGF-binding proteins in experimental diabetic kidney disease.

Early renal changes in type I diabetes are characterized by an increase in renal size, glomerular volume, and kidney function, and later by development of mesangial proliferation, accumulation of glomerular extracellular matrix, and increased urinary albumin excretion (UAE). Growth hormone (GH) and insulin-like growth factors (IGFs) have a long and distinguished history in diabetes mellitus, with possible participation in the development of long-term complications. In experimental diabetes in dwarf rats with isolated GH and IGF-I deficiency, a slower and lesser renal and glomerular hypertrophy is observed as compared with diabetic control animals with intact pituitary. Furthermore, diabetic dwarf rats with a diabetes duration of 6 months display a smaller increase in UAE, indicating that GH and IGF-I may be involved in the development of diabetic kidney changes. In line with this, administration of octreotide to streptozotocin (STZ)-diabetic animals with normal pituitary inhibits initial renal growth without affecting blood glucose levels, and 6 months' administration of octreotide to diabetic rats reduces long-term renal/glomerular hypertrophy and UAE. In addition, the initial increase in renal size and function in experimental diabetes is preceded by an increase in renal IGF-I, IGF-binding proteins (IGFBPs), and IGF-II/mannose-6-phosphate receptor (IGF-II/Man-6-P receptor) concentration. Finally, specific changes occur in renal GH-binding protein (GHBP) mRNA, IGF-I receptor mRNA, and IGFBP mRNA expression in long-term diabetes. In conclusion, the knowledge we have today indicates that GH and IGFs, through a complex system consisting of GHBP, IGFs, IGF receptors, and IGFBPs, may be responsible for both early and late renal changes in experimental diabetes.

Animals↗

PubMed1995

Inhibition of renal ornithine decarboxylase activity fails to reduce kidney size and urinary albumin excretion in diabetic rats with manifest kidney hypertrophy.

Formation of polyamines has previously been shown to play an important role for initial kidney growth in experimental diabetes, as treatment of diabetic rats with a selective ornithine decarboxylase (ODC) inhibitor, initiated immediately after diabetes induction, abolishes the initial kidney growth. In order to investigate the role of polyamine formation for the maintenance of diabetic kidney hypertrophy, ODC inhibition was initiated after manifest kidney hypertrophy had occurred. The kidney weight in diabetic rats was significantly larger than in control rats after a diabetes duration of 7, 14, 50 and 71 days and the total glomerular volume was increased in kidneys from diabetic rats after a diabetes duration of 71 days. Renal activity of ODC was increased in diabetic rats throughout the study period of 71 days. Treatment of diabetic rats with the selective ODC inhibitor di-fluoro-methyl-ornithine (DFMO) was maintained for two periods (days 7-14 and days 50-71). DFMO treatment had no effect on 24-h food consumption, blood glucose concentration or body weight. However, despite almost total inhibition of the kidney ODC activity, there was no effect on kidney growth or total glomerular volume in the DFMO treated diabetic rats compared to placebo treated diabetic rats. Finally, the urinary albumin excretion was markedly increased in diabetic rats with no effects of ODC-inhibition. In conclusion, inhibition of ODC initiated in diabetic rats with manifest kidney enlargement had no effect on renal size, glomerular volume or urinary albumin excretion. These findings together with our previous findings indicate that the role of polyamines in diabetic kidney enlargement is restricted to the first week after diabetes induction.

Albuminuria↗

PubMed1995

Insulin-like growth factor I (IGF-I) and IGF binding proteins in seminal plasma before and after vasectomy in normal men.

OBJECTIVE: To examine the levels and origins of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) in the human male genital tract. DESIGN: Examining seminal plasma before and 3 months after vasectomy. SUBJECTS: Fifteen men who were candidates for vasectomy were included in the study. MAIN OUTCOME MEASURES: Seminal plasma and serum levels of IGF-I, IGFBP-1, and IGFBP-3 were determined by commercially available assays, furthermore, samples were subjected to Western ligand blotting. RESULTS: Seminal plasma concentrations of IGF-I were significantly lower after vasectomy: 18.0 +/- 2.4 micrograms/L (before) and 12.5 +/- 1.2 micrograms/L (after). When the total ejaculate content of IGF-I was calculated, the figures were reduced by 50% after vasectomy: 45.64 +/- 7.8 ng (before) and 23.45 +/- 3.8 ng (after). The patterns observed for seminal plasma IGFBP-3 concentrations were 844.9 +/- 59 micrograms/L (before) and 816.5 +/- 65 micrograms/L (after). When the total ejaculate IGFBP-3 content was calculated there was a 36% reduction after vasectomy: 2,300 +/- 251 ng (before) and 1,474 +/- 217 ng (after). CONCLUSIONS: A considerable amount of seminal plasma IGF-I and IGFBP-3 may be of testicular origin. Although the physiological significance of IGF-I and IGFBPs in the male reproductive system still remains uncertain, the demonstration of their presence in the testes add support to a functional role in the regulation of gonadal function.

Adult↗

PubMed1995

Elective laparoscopic cholecystectomy nearly abolishes the postoperative hepatic catabolic stress response.

OBJECTIVE: Surgery results in a catabolic state of postoperative stress, where the efficiency of the liver to convert amino acids to urea is increased. This study measured the metabolic consequences of the less traumatic laparoscopic surgery in elective cholecystectomy compared with traditional open surgery technique. SUMMARY BACKGROUND DATA: The authors previously have shown that open cholecystectomy doubles the urea synthesis measured by the means of the functional hepatic nitrogen clearance. Glucagon and cortisol increased by 50% (p < 0.05) and 75% (p < 0.05), respectively, after open cholecystectomy. METHODS: Patients undergoing uncomplicated elective laparoscopic cholecystectomies were included. Preoperatively and on the first postoperative day, blood and urine samples were drawn every hour under basal conditions and during amino acid infusion. The urea synthesis rate was calculated from the urea excreted in urine and accumulated in total body water. Functional hepatic nitrogen clearance was quantified as the slope of the linear relation between blood amino-N concentration and the urea synthesis rate. The results were compared with an historic matched group of patients who underwent open cholecystectomies and were studied by the same protocol. RESULTS: The laparoscopic cholecystectomy increased the functional hepatic nitrogen clearance by only 25% (from 8.7 +/- 0.9 to 11.1 +/- 1.5 mL/sec [mean +/- SEM; p < 0.05]), compared with a doubling after open cholecystectomy (from 9.4 +/- 0.9 to 17.6 +/- 3.3 mL/sec [p < 0.05]). The difference between the groups was significant (p < 0.05). Neither glucagon nor cortisol increased significantly after laparoscopic cholecystectomy. CONCLUSIONS: The laparoscopic technique results in a much smaller postoperative hepatic catabolic stress response and probably reduced tissue loss of amino-N. This may be important for the more rapid convalescence and reduced postoperative fatigue.

Adult↗