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Biomedical subjects

H Orskov

Publications and source records attributed to H Orskov.

At least 73 records · Page 4Linked to original sources
PubMed1997

Growth hormone binding protein and growth hormone availability in acromegalic patients treated with long-acting octreotide (Sandostatin-LAR).

OBJECTIVE: In the medical treatment of acromegaly different factors are influential; among these the impact on growth hormone binding protein (GHBP) has not been clarified. DESIGN: Twenty acromegalic patients and nineteen age- and gender-matched normal subjects participated in this study. The patients were treated for 21 months with depot long-acting microsphere-enclosed octreotide (Sandostatin-LAR). Previously, all the patients were treated s.c. with octreotide t.i.d. After a 2-week wash-out period (baseline) the patients received the first i.m. injection of the long-acting octreotide. The first two injections were administered at 60-day intervals; thereafter the injections were at 28-day intervals. METHODS: The levels of GHBP, complexed GHBP, growth hormone (GH) and insulin-like growth factor-I (IGF-I) were determined in fasting serum samples. RESULTS: In the 2-week wash-out period GHBP levels decreased from 1.13 +/- 0.17 to 0.92 +/- 0.15 nmol/l (P < 0.05). During the 21-months treatment, GHBP increased again to 1.10 +/- 0.16 nmol/l. In the age- and gender-matched control group GHBP levels were significantly higher at all times (1.95 +/- 0.21 nmol/l. P(all) < 0.02). Mean levels of 8-h GH decreased from 12.6 +/- 2.58 microg/l at baseline to 1.97 +/- 0.20 microg/l after 21 months of treatment (P < 0.05). Mean 8-h GH levels were unchanged during long-acting octreotide treatment compared with levels during s.c. treatment (1.97 +/- 0.20 microg/l and 1.90 +/- 0.20 microg/l respectively). In fasting blood samples GH-complexed GHBP ranged from 13.8 +/- 2.4% (9 months) to 25.4 +/- 4.5% (baseline) of total GHBP. Serum IGF-I increased from 367 +/- 45 to 764 +/- 80 microg/l (P < 0.05) during the 2-week wash-out period and decreased to 290 +/- 35 microg/l (P < 0.05) after 21 months of treatment with long-acting octreotide. IGF-I levels after 21 months were significantly lower than during s.c. octreotide treatment (P < 0.05). CONCLUSION: Serum GHBP levels are similar during treatment with long-acting octreotide as compared with regular octreotide. Furthermore, significant changes in GHBP can occur within 2 weeks. Finally, in addition to the lowering effect on GH levels, the induced increase in GHBP levels may imply a further advantage in octreotide treatment of acromegaly. circulating GH bound to GHBP may less readily reach the tissues.

Acromegaly↗
PubMed1997

Serum free insulin-like growth factor-I in growth hormone-deficient adults before and after growth hormone replacement.

The objective of the present study was to compare fasting levels of free IGF-I in serum from patients with adult onset growth hormone deficiency (GHD) and from healthy volunteers, and to examine the effect of GH replacement therapy in GHD on serum free IGF-I. Free IGF-I was measured using separation of free IGF-I by ultrafiltration in serum samples from 42 healthy volunteers and 27 patients with GHD, in the latter before and after 1 year of treatment with GH (2 IU/m2) (n = 13) or placebo (n = 14). Free IGF-I was significantly decreased in patients with GHD (700 +/- 100 ng/l (mean +/- S.E.M.), range 55-2618 ng/l) compared with controls (1010 +/- 70 ng/l, range 231-2431 ng/l; P = 0.0016). Total IGF-I was 85 +/- 10 micrograms/l (GHD) and 160 +/- 10 micrograms/l (controls) (P < 0.0001). The ratio of free over total IGF-I was increased in GHD to 0.85 +/- 0.08% compared with 0.66 +/- 0.05% in controls (P = 0.04). In both GHD and controls, free IGF-I correlated significantly (P < 0.05) with total IGF-I (GHD r = 0.78; controls r = 0.42), IGFBP-1 (GHD r = -0.67; controls r = -0.46) and the molar ratio of total IGF-I over IGFBP-3 (GHD r = 0.58; controls r = 0.62). After 1 year of GH treatment, free IGF-I was increased to 2780 +/- 320 ng/l (P = 0.003) and total IGF-I was increased to 270 +/- 30 micrograms/l (P = 0.006) both of which values were greater than those in healthy volunteers. There were no changes in free or total IGF-I in the placebo-treated group. In conclusion, levels of free IGF-I are decreased in GHD, but measurements of free IGF-I in a single, fasting serum sample do not offer a better separation of patients with GHD from individuals with normal GH status than can be achieved by measurement of total IGF-I. One year of treatment with 2IU/m2 GH caused an increase of serum free IGF-I to supraphysiological levels.

Adult↗
PubMed1996

Lanreotide reduces serum free and total insulin-like growth factor-I after angioplasty.

BACKGROUND: Several experiments point to a participating role of insulin-like growth factor-I (IGF-I) in the vascular events leading to restenosis after percutaneous transluminal coronary angioplasty (PTCA). METHODS AND RESULTS: We measured fasting serum total (extractable) IGF-I in 553 patients in a controlled clinical trial. Half of the patients received continuous subcutaneous infusion of the somatostatin analogue lanreotide from the day before (baseline) and for 4 days after PTCA. We also measured ultrafiltrated serum free IGF-I and IGF-II, total IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-3, and insulin in a subgroup of 18 placebo-treated and 20 lanreotide-treated patients. Total IGF-I had decreased by 7% (P < .0001) 1 day after initiation of lanreotide infusion and stayed reduced, whereas no early changes occurred in placebo-treated patients. The same pattern was observed in the subgroup. Free IGF-I decreased significantly from baseline by 22% to 27% (P < .05) in lanreotide-treated patients and increased insignificantly by 10% to 30% (P = .054) in placebo-treated patients. IGFBP-1 increased (P < .05) in both groups postoperatively, but levels in lanreotide-treated patients exceeded (P < .05) those of placebo-treated patients. Lanreotide treatment resulted in minor reductions (P < .05) in free and total IGF-II and IGFBP-3, whereas insulin was unaltered. CONCLUSIONS: Lanreotide administration acutely decreases circulating total and free IGF-I, the latter relatively more, and increases IGFBP-1. These alterations in the IGF system may participate in the improvement of the long-term outcome after PTCA noted with lanreotide treatment.

Adult↗
PubMed1996

[Angiopeptin versus placebo for reductin of restenosis after PTCA treatment. A randomized, double-blind study].

Angiopeptin, a somatostatin analogue, inhibits intimal hyperplasia after (percutaneous transluminal coronary angioplasty) (PTCA) in several animal models. This pilot study sought to determine the effect of subcutaneous infusion of angiopeptin on clinical events and restenosis in patients undergoing successful PTCA. One hundred and twelve patients were randomized to receive continuous subcutaneous angiopeptin (750 micrograms/day) or placebo infusion from the day before PTCA and for the following four days in a double-blind study. Eighty patients had a successful PTCA, and 75 of these patients with 94 lesions underwent angiography 6 +/- 2 months after PTCA. All 112 patients underwent clinical follow-up at 12 months. The 12-month event rate (death, myocardial infarction, coronary artery bypass grafting and re-PTCA) was reduced from 34% to 25% (p = 0.30) by angiopeptin by intention to treat analysis. Restenosis (> or = 50% diameter stenosis) was significantly reduced in lesions treated with angiopeptin (12% vs 40%; p = 0.003). Late lumen loss was also significantly reduced after angiopeptin treatment (0.12 +/- 0.46 mm vs 0.52 +/- 0.64 mm; p = 0.003). In conclusion, continuous subcutaneous angiopeptin infusion for five days tended to decrease clinical events and restenosis after PTCA.

Adolescent↗
PubMed1996

Impaired growth hormone secretion and increased growth hormone-binding protein levels in subfertile males.

OBJECTIVE: To evaluate GH secretion in subfertile males. DESIGN: Comparing GH secretion to a GH stimulation test in two different patient groups and in a control group. PATIENTS: Nine oligozoospermic patients, nine asthenozoospermic patients, and nine age- and body mass index-matched fertile males with normal spermograms. INTERVENTION: All subjects underwent an IV arginine GH stimulation test. MAIN OUTCOME MEASURES: Serum levels of FSH, LH, PRL, E2, T, insulin-like growth factor I (IGF-I), and GH-binding protein were measured. RESULTS: Basal levels of GH were similar in all three groups and serum GH increased in all groups after arginine. However, there was a significant difference between the two patient groups and the control group characterized by an impaired GH response in the subfertile patients. Serum FSH and serum GH-binding protein were significantly higher in the patient groups compared with the controls. Serum LH, PRL, T, E2, and IGF-I were similar in all three groups. CONCLUSIONS: This study demonstrates that subfertile men may suffer from relative GH insufficiency, which could have therapeutical implications.

Adult↗
PubMed1996

Growth hormone treatment of subfertile males.

OBJECTIVE: To study spermatogenesis and sperm motility during GH therapy in infertile men. DESIGN: Prospective open study. Each patient was treated with GH for 12 weeks and followed for a total of 36 weeks with sampling of blood and semen. SETTING: Outpatients studied at a clinical research unit of a university hospital. PATIENTS: Nine oligozoospermic (<5 x 10(6) sperm/mL) males and nine asthenozoospermic (percentage motile sperm <30 and >15 x 10(6) sperm/mL) males. The patient groups had a significantly lower GH response to an arginine GH stimulation test as compared with a control group. RESULTS: Serum insulin-like growth factor I (IGF-I) and serum IGF-binding protein 3 (IGFBP-3) levels increased significantly during GH treatment, as did seminal IGF-I. Serum E2, T, PRL, FSH, LH, and GH-binding protein were unchanged during the study. Sperm motility was increased significantly during GH treatment in both patient groups. There was no difference in sperm count during the treatment. There were three pregnancies in the nine couples from the asthenozoospermic group and no pregnancies in the oligozoospermic group. CONCLUSION: The biologic and clinical results in this study encourage the initiation of double-blind, placebo-controlled trials.

Adult↗
PubMed1996

Sandostatin LAR: a promising therapeutic tool in the management of acromegalic patients.

A stable and sustained suppression of growth hormone (GH) secretion was noted in 101 patients treated long term with individual doses (20 and 30 mg in 89 patients, 40 mg in 12 patients) of Sandostatin LAR (Sandoz Pharma Ltd, Basel, Switzerland). Doses of 20 mg and 30 mg at 4-week intervals delivered average octreotide concentrations of 1,348 +/- 483 ng/L and 2,631 +/- 1,026 ng/L, respectively, in steady-state conditions and provided adequate control of patients who had been well controlled during treatment with 0.1 mg and 0.2 mg thrice-daily subcutaneous (SC) Sandostatin. Suppression of GH serum concentrations to less than 5 micrograms, 2 micrograms, and even 1 microgram/L was recorded in more patients and more consistently during long-term treatment with Sandostatin LAR than Sandostatin. A marked decrease or even a normalization of insulin-like growth factor-1 (IGF-1) serum concentrations was observed after the first double-blind 10-, 20-, or 30-mg dose of Sandostatin LAR. A progressive improvement was recorded during long-term treatment, with normalization of IGF-1 serum concentrations in 65.3% of patients. A marked clinical improvement was observed in parallel, with 36 of 101 patients (35.6%) becoming asymptomatic after the nineteenth injection of Sandostatin LAR. A greater than 20% shrinkage of the GH-secreting adenoma was also recorded in 12 of 14 patients treated with Sandostatin LAR after receiving only 2 to 4 weeks of treatment with SC Sandostatin and in 11 of 18 patients receiving Sandostatin LAR as adjuvant therapy after failure of surgery. The systemic tolerability of Sandostatin LAR was good, and most adverse events were mild and short term (1 to 2 days). No impairment of thyroid function was detected. Newly occurring gallstones were recorded in four of 101 patients and microlithiasis in four of 101 after up to 30 months of treatment with Sandostatin LAR. Due to its excellent efficacy, good tolerability, convenience of administration, and acceptability by patients, Sandostatin LAR is considered a promising therapeutic tool in the management of acromegalic patients.

Acromegaly↗
PubMed1996

Somatostatin, growth hormone, insulin-like growth factor-1, and diabetes: friends or foes?

Major findings with regard to the somatostatin-growth hormone (GH)-insulin-like growth factor (IGF-1) axis and diabetes are summarized. GH hypersecretion and reduced circulating IGF-1 levels are prevalent in insulin-dependent diabetes. Somatostatin improves metabolism in insulin-dependent diabetics. Insulin resistance and poor metabolic regulation, which may partly be due to hypersecretion of GH, are believed to accelerate the development of diabetic angiopathy. Diabetic hypersomatotrophinemia may be due to hepatic resistance to GH and increased hepatic production of IGF-1-binding protein-1 (IGFBP-1), leading to reduced levels of circulating IGF-1 and further stimulation of GH production. Studies in vitro and in diabetics suggest a causal link between diabetic hypersomatotrophinemia and diabetic angiopathy. In vitro evidence for the involvement of IGF-1 in diabetic angiopathy is reviewed. Also reviewed is evidence, from rat and human studies, of the possible involvement of GH and IGF-1 in diabetic nephropathy. The role of somatostatin in late diabetic vascular complications remains to be elucidated.

Animals↗
PubMed1996

Bioavailability and bioactivity of intravenous vs subcutaneous infusion of growth hormone in GH-deficient patients.

OBJECTIVE: The bioavailability of GH immunoreactive serum concentrations is reduced following subcutaneous (s.c.) as compared with intravenous (i.v.) administration. Whether this difference also translates into a different biological activity remains to be investigated. The aim of the present study was to evaluate the short-term metabolic effects of GH following i.v. and s.c. delivery. DESIGN AND MEASUREMENTS: In a cross-over design 10 GH-deficient patients were randomized to receive GH (0.03 microgram (0.1 mU/kg/min) as a continuous i.v. or s.c. infusion for 39 hours on two different occasions. Preceding each study GH therapy was discontinued for 5 days. Serum profiles of GH, IGF-I, IGF-II, IGF binding protein 3 (IGFBP-3), insulin, glucose and non-esterified fatty acids (NEFA) were recorded during the studies. Serum GH was measured by a polyclonal radio-immunoassay (RIA) and by a double monoclonal immunofluorimetric assay (DELFIA). RESULTS: Higher mean integrated values (AUC) of serum GH (mU/l) were obtained with i.v. GH delivery [47.4 +/- 5.1 (i.v.), 33.3 +/- 3.0 (s.c.), P < 0.05]. The two GH assays showed qualitatively similar results, but higher mean GH concentrations were measured by RIA following both s.c. (P < 0.001) and i.v. infusion (P < 0.001). Serum IGF-I levels displayed different patterns following i.v. and s.c. GH infusion (P < 0.05 by ANOVA) and mean IGF-I levels (micrograms/l) were lower following s.c. GH infusion [159.5 +/- 21.8 (s.c.), 185.2 +/- 27.7 (i.v.), P = 0.002]. Serum IGF-II levels were unaffected by short-term GH treatment and by the route of GH administration. Serum IGFBP-3 levels increased in response to GH administration (P < 0.001), irrespective of route (P = 0.76). The IGF-I/IGFBP-3 molar ratio increased significantly following GH administration (P < 0.001), and a higher ratio was obtained following i.v. infusion (P < 0.005). Subcutaneous GH infusion resulted in significantly lower mean levels of serum NEFA (P < 0.02), whereas similar mean levels of serum insulin (P = 0.54), blood glucose (P = 0.24), energy expenditure (P = 0.13), and respiratory exchange ratio (P = 0.09) were observed on the two occasions. CONCLUSIONS: A reduced bioavailability of s.c. as compared with i.v. administered GH has been recorded with two independent GH assays, and this was also accompanied by a significant, albeit modest, reduction in biological activity.

Adult↗
PubMed1996

A simple, rapid immunometric assay for determination of functional and growth hormone-occupied growth hormone-binding protein in human serum.

We present a sensitive time-resolved fluorometric immunofunctional assay (TR-FIA) for direct quantitation of functional growth hormone-binding protein (GHBP), using an immunoassay kit for growth hormone (GH-DELFIA). In addition to the immobilized GH antibody, one monoclonal antibody against GHBP was used. This anti-GHBP was labelled with the chelate of europium. The assay was performed in one step. The detection limit for GHBP was 0.044 nmol L-1 (NBS + 3 SD). The calibration curve was linear in the interval 0.11-8.03 nmol L-1. Average intra-assay coefficient of variation (CV) was 3.44%. Average interassay CV at GHBP concentrations 0.563 nmol L-1 and 1.40 nmol L-1 were 12% and 6.3% respectively. Analytical recovery in serum ranged from 76% to 127% with a mean of 101 +/- 3.6%. Serum GHBP in 102 normal subjects ranged from 0.513 to 3.772 nmol L-1 and was positively related to body mass index (P < 0.001). In growth hormone-deficient sera GHBP was higher than in control subjects (1.751 +/- 0.179 nmol L-1 and 1.257 +/- 0.140 nmol L-1 respectively, P < 0.001). Acromegalic patients had lower levels of GHBP than controls (0.946 +/- 0.251 and 1.234 +/- 0.144 nmol L-1 respectively, P = 0.005). This assay also allowed detection of GH-complexed GHBP in serum. These results were in agreement with theoretical values calculated from the measured GH and the functional GHBP concentrations. Results were compared with data obtained by a recently reported, validated ligand immunofunctional assay (LIFA), which is fundamentally different. There was a significant linear relationship between the results from the two assays (r = 0.89, P = 0.001). The slope of the regression line was 0.65. In conclusion, this new convenient GHBP TR-FIA provides a sensitive and precise method for detecting total GHBP as well as complexed GHBP in human serum, and allows easy processing of large numbers of samples.

Acromegaly↗
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

Factors modifying growth hormone estimates in immunoassays.

Growth hormone (GH) in human serum has been measured for more than 30 years and during this period it has been used diagnostically in growth disturbances and GH disorders. The first GH determinations were by radioimmunoassays using polyclonal antibodies. Due to the low specificity of these assays and the variable molecular appearance of GH, higher levels were obtained than with later assays employing two highly specific monoclonal antibodies. Because of this variability between assays, empiric GH cutoff levels had to be developed in different laboratories. However, with the growing need for more sophisticated diagnosis, especially in adulthood GH deficiency, knowledge of factors influencing the individual GH assays is required. Since GH deficiency in adulthood is now treated with GH substitution therapy, the relevance of factors influencing GH estimates has become increasingly evident, because no specific symptoms exist in adult GH deficiency.

Adult↗
PubMed1996

Calorigenic effects of growth hormone: the role of thyroid hormones.

GH administration increases energy expenditure, independent of changes in lean body mass, in healthy, obese, and GH-deficient subjects. This may be causally linked to the well known GH-induced increase in peripheral T4 to T3 generation, but experimental data are sparse. In this study we have addressed whether 1) the calorigenic effects of GH administration could be reproduced by oral supplementation of T3 in a dose selected to mimic the GH-induced increase in peripheral T3 levels; and 2) combined GH and T3 administration have a synergistic effect on resting energy expenditure (REE). Eight normal male subjects (aged 21-27 yr; body mass index, 21.11-27.17 kg/m2) were randomly studied during four 10-day treatment periods with 1) daily sc placebo injections and placebo tablets, 2) daily sc GH injections (0.1 IU/kg x day) and placebo tablets, 3) daily T3 administration (40 microg on even dates, 20 microg on uneven dates) plus placebo injections, and 4) daily GH injections plus T3 administration. GH administration increased both free T3 (FT3) levels [mean +/- SE, 6.2 +/- 0.3 (control) vs. 7.3 +/- 0.5 (GH) pmol/L; P < 0.05] and REE [mean +/- SE, 1959 +/- 67 (control) vs. 2164 +/- 55 (GH) Cal/24 h; P < 0.01]. T3 administration yielded comparable levels of FT3 (7.7 +/- 0.5 pmol/L; T3 vs. GH, P = 0.37), but did not increase REE (2015 +/- 48 Cal/24 h; T3 vs. control, P = 0.23). Combined GH and T3 administration increased REE to a level higher than that seen with T3 alone (2279 +/- 68 Cal/24 h; T3 vs. GH plus T3, P < 0.01). Significant increments in serum levels of insulin-like growth factor I and insulin were recorded with GH administration, but not with T3 alone. Resting heart rate increased to a similar degree after GH administration and T3 supplementation, respectively. Tympanic temperature remained unaltered in all four studies. The results suggest that the calorigenic effect of GH is not mediated solely through increased conversion of T4 to T3.

Adult↗
PubMed1996

Free and total insulin-like growth factors and insulin-like growth factor binding proteins during 14 days of growth hormone administration in healthy adults.

The objective was to investigate the effect of growth hormone (GH) administration on circulating levels of free insulin-like growth factors (IGFs) in healthy adults. Eight healthy male subjects were given placebo and two doses of GH (3 and 6 IU/m2 per day) for 14 days in a double-blind crossover study. Fasting blood samples were obtained every second day. Free IGF-I and IGF-II were determined by ultrafiltration of serum. Total IGF-I and IGF-II were measured after acid-ethanol extraction. In addition, GH, insulin, IGF binding protein 1 (IGFBP-1) and IGFBP-3 were measured. Serum-free and total IGF-I increased in a dose-dependent manner during the 14 days of GH administration. After 14 days, serum-free IGF-I values were 610 +/- 100 ng/l (mean +/- SEM) (placebo), 2760 +/- 190 ng/l (3 IU/ m2) and 3720 +/- 240 ng/l (6 IU/m2) (p = 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.004 for 3 IU/m2 vs 6 IU/m2). Total IGF-I values were 190 +/- 10 micrograms/l (placebo), 525 +/- 10 (3 IU/m2), and 655 +/- 40 micrograms/l (6 IU/m2) (p < 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.04 for 3 IU/m2). There were no differences in the levels of free or total IGF-II during the three study periods. Insulin-like growth factor binding protein 1 was decreased during GH administration (p = 0.04 for placebo vs 3 IU/m2; p = 0.006 for placebo vs 6 IU/m2). In conclusion, fasting serum free IGF-I increased dose dependently during GH administration and free IGF-I increased relatively more than total IGF-I. This may partly be due to the decrease in IGFBP-1.

Adult↗
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

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↗