Biomedical subjects

H Oxlund

Publications and source records attributed to H Oxlund.

At least 55 records · Page 3Linked to original sources

PubMed1995

Reduced concentrations of collagen cross-links are associated with reduced strength of bone.

The known cross-links of bone collagen are derived from lysine and hydroxylysine. The first step in the enzymatic cross-linking process is a deamination by lysyl oxidase producing an aldehyde which then may condense with a lysyl or hydroxylysyl residue of a neighbouring collagen molecule. Some of the resulting divalent aldimine and oxo-imine cross-links may later on be incorporated in trivalent hydroxylysyl-pyridinoline and lysyl-pyridinoline cross-links. In bone collagen prepared from the cancellous bone of vertebral bodies of osteoporotic individuals we found a reduced stability towards acetic acid and pepsin, and a substantial reduction in the concentration of the divalent collagen cross-links compared with sex- and age-matched controls. To what extent do the collagen cross-links influence the mechanical properties of bone? beta-amino-propionitrile (BAPN) irreversibly inhibits the enzyme lysyl oxidase and therefore, the formation of cross-links between the collagen molecules. In the present study female rats, 70 days old, injected subcutaneously two times daily with BAPN (333 mg/kg/day) for 1 month and saline injected control rats were studied. The concentration of the hydroxypyridinium cross-links of femoral mid-diaphyseal cortical bone was determined by HPLC with fluorescence detection and the mechanical properties of the rat femoral diaphyses were analyzed by a materials testing machine. The BAPN injections resulted in a 45% reduction in the concentration of the hydroxypyridinium cross-links and a 31% decrease in the stability of the bone collagen towards acetic acid and pepsin compared with the control rats. No changes were found in ash or collagen concentrations of the cortical bone.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopropionitrile↗

PubMed1995

Parathyroid hormone (1-34) increases vertebral bone mass, compressive strength, and quality in old rats.

Human parathyroid hormone 1-34 (PTH) exerts an anabolic effect on bone in younger rats. The aim of the present study was to examine the effect of PTH on vertebral bone in 2-year-old male rats. The rats were treated with daily injections of 15 nmol/kg PTH or vehicle (V) for 56 days. Tetracycline and calcein were injected on day 15 and day 40 of the treatment period, respectively. The PTH treatment did not influence the body weights of the rats, the volumes of whole vertebra, or the vertebral body heights. However, the PTH treatment induced profound changes in the bone structure. Histomorphometric analyses of the vertebral bodies (L-6) revealed an approximate doubling of the cancellous bone volume after PTH treatment from 24.6 +/- 1.3% to 54.9 +/- 2.0% (p < 0.001) as well as a doubling of the trabecular thickness while the bone surface/bone volume decreased by 60%. PTH treatment also increased bone formation as indicated by an increase in mineral apposition rate (from 0.42 +/- 0.01 to 0.89 +/- 0.01 microns/day, p < 0.01), increased mineralizing surface (from 7.8 +/- 1.4 to 43.8 +/- 1.9%, p < 0.01) and an increase in both volume-related and surface-related bone formation rates (5 and 11 times, respectively). The biomechanical properties were analyzed using standardized bone specimens from the vertebral bodies of L-4 by applying cranial-caudal compression in a materials testing machine. The PTH treatment induced a substantial increase in the strength of the vertebral body: ultimate load increased by 66%, ultimate stiffness by 47%, and energy absorption by 98%. The increase in vertebral body strength was also evident after normalizing the parameters to the cross sectional area and the ash content of the vertebral body specimens. PTH treatment increased ultimate stress from 26 +/- 3 to 44 +/- 3 N per mm2 (p < 0.01) and increased ultimate load normalized to ash content per mm specimen height from 59 +/- 4 to 72 +/- 4 N (mm/mg) (p < 0.05). The PTH treatment induced an increase in dry defatted bone density and ash density of both the vertebral body specimen (L-4) and the whole vertebra (L-5). In conclusion, PTH showed a remarkable ability to stimulate bone formation in the vertebral body of old rats. Furthermore, the biomechanical analysis revealed an enhanced compressive bone strength, even after correction for the increased bone mass, indicating an improved bone quality after the PTH treatment.

Aging↗

PubMed1995

Growth hormone is not able to counteract osteopenia of rat cortical bone induced by glucocorticoid with protracted effect.

UNLABELLED: Osteopenia and inhibited longitudinal growth in childhood are serious side effects during glucocorticoid therapy. The effects of glucocorticoids on bone have been confirmed in animal experiments. Long-term glucocorticoid administration to rats results in reduced body weights, reduced bone growth (length and cross-sectional area), and bone strength. Glucocorticoid treatment also resulted in a reduced bending stress, indicating reduced bone quality. Growth hormone, on the other hand, increased body weights, bone dimensions, and bone strength. The aim of the present study was to evaluate if growth hormone administration would have an anabolic effect on rat bone when given to animals also receiving a high dosage of glucocorticoid. Five groups of female rats, 3.5 months old, were treated as follows: (1) saline control; (2) glucocorticoid (prednisolone: Delcortol 5 mg/kg/day); (3) growth hormone (recombinant human growth hormone 5 mg/kg/day); (4) glucocorticoid and growth hormone; and (5) food restriction, consisting of restricted access to food to reduce their weight gain to match that of the glucocorticoid injected rats. After 80 days of hormone administration the animals were sacrificed. The right femur was removed and tested biomechanically in a three-point bending procedure. The left femur was used for determination of bone dimensions. Biomechanical parameters (ultimate load and ultimate stiffness) were then normalized to diaphyseal cross-sectional diameters of the femur, giving the values of ultimate bending stress and Young's modulus. RESULTS: administration of both hormones simultaneously could not reverse the decrease in body weights, bone length, and diameters, or the decreased bone strength induced by glucocorticoid administration. In conclusion, growth hormone cannot prevent cortical osteopenia in female rats induced by a high dose of glucocorticoid with protracted effect.

Animals↗

PubMed1995

Biosynthetic growth hormone increases the collagen deposition rate in rat aorta and heart.

Disorders of the cardiovascular system often are associated with alterations in the metabolism of the collagens of these tissues. A method for in vivo determination of collagen deposition rate in small tissue samples is delineated and used for assessment of the effect of biosynthetic growth hormone (GH) injections on the collagen deposition rate in rat aorta and cardiac musculature. Rats were injected with GH, and the controls with saline, twice daily for 7 days. The in vivo collagen deposition rate was measured by injecting iv a large dose of [3H]-proline with a flooding dose of "cold" proline, followed by determination of the production of [3H]-hydroxyproline during a 4-h labelling period. Extractable collagens that were not bound in the tissue and therefore do not contribute mechanical strength to it were removed from the samples. 3H-Labelled- and "cold" amino acids were assessed by reversed-phase HPLC combined with simultaneous flow scintillation detection on the same sample. In the control group the deposition per hour was 0.13 +/- 0.02% (mean +/- SEM) in aortic intima media and 0.72 +/- 0.09% in cardiac left ventricular musculature. Growth hormone induced a threefold increase (p < 0.001 and p < 0.01, respectively) in the collagen deposition rate: 0.45 +/- 0.06% in aortic intima media and 2.43 +/- 0.45% in cardiac left ventricular musculature. The method described enables a rapid and sensitive determination of collagen deposition per hour in small tissue samples from experimental animals. The collagen deposition rate of cardiac musculature is fivefold higher compared with that of aortic intima media.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Relaxin (hRLX-2)-induced weakening of human fetal membranes in vitro.

We examined the effect of human relaxin (hRLX-2) on the biomechanical properties of human fetal membranes in vitro. Intact chorioamniotic membranes were obtained from twelve elective cesarean sections before the onset of labor. Membrane strips with a fixed width were biomechanically tested after incubation for 20 h with hRLX-2 in concentrations of 10(-7) mol/l and 10(-9) mol/l. Incubation with hRLX-2 (10(-9) mol/l) changed the load-strain values as the membrane stiffness was decreased by 19% when compared with controls: median 2.45 N (range, 0.81-4.31) versus 3.03 N (1.28-5.46), P = 0.02 (Mann-Whitney test). For description of the membrane material as such, the stress-strain values were calculated by dividing the load-strain values with the cross sectional area of the membranes. Incubation with hRLX-2 (10(-9) mol/l) decreased the tensile strength of the membranes by 30%-0.817 N/mm2 (0.282-1.139) vs. 0.575 N/mm2 (0.101-1.150), P = 0.03--and reduced the elastic modulus by 31%--2.26 N/mm2 (0.82-5.08) versus 1.57 N/mm2 (0.51-3.71), P = 0.002. Less pronounced effects were found after incubation with hRLX (10(-7) mol/l). No quantitative or qualitative changes of the membrane collagen were found after relaxin incubation. Although the mechanism for rupture of the fetal membranes remains unknown, the present results suggest that relaxin might be involved in the process leading to rupture of the membranes.

Amnion↗

PubMed1994

Human parathyroid hormone(1-34) increases bone formation and strength of cortical bone in aged rats.

The effect of parathyroid hormone (PTH(1-34)) on mid-diaphyseal femoral cortical bone was studied in 2-year-old male rats. The rats were treated with daily injections of 15 nmol/kg PTH(1-34) or vehicle for 56 days, and labelled with tetracycline and calcein on day 15 and day 40, respectively. The PTH(1-34) treatment did not affect the body weights or the lengths of the femora. Fluorescence microscopy showed large intracortical cavities in the old vehicle-treated rats. After PTH treatment, double labelling and new bone formation filling in these cavities were found. Furthermore, an increased bone formation rate was observed both at the periosteum and at the endosteum. This resulted in an increase in the cross-sectional area and a decrease in the medullary area. Three-point bending analysis revealed an increase in ultimate load, ultimate stiffness, energy absorption and ultimate stress after the PTH(1-34) treatment. No differences were found between the groups regarding the hydroxyproline concentration or apparent and real densities. The ash concentration was, however, slightly reduced after PTH(1-34) treatment. The PTH(1-34) treatment of old rats induced the formation of bone both from the periosteum and endosteum, with a pronounced filling in of intracortical cavities, and, furthermore, a marked increase in the biomechanical competence of the cortical bone.

Aging↗

PubMed1994

Local injection of TGF-beta increases the strength of tibial fractures in the rat.

The effect of Transforming Growth Factor beta (TGF-beta) administered locally around the fracture line of healing rat tibial fractures was investigated after 40 days of healing. TGF-beta in a dose of 4 ng or 40 ng was injected every second day during the healing period. The strength, stiffness, energy absorption and deflection of the fractures were measured in a materials-testing machine. Compared with placebo-treated animals, the ultimate load of the fractures increased in the group injected with 40 ng of TGF-beta, but not in those injected with 4 ng. TGF-beta induced a dose-dependent increase in the cross-sectional area of the callus and bone at the fracture line. Consequently, local treatment of fractures with TGF-beta increases the callus formation and strength. The energy absorption and deflection capacities of the healing fractures are preserved.

Animals↗

PubMed1994

Growth hormone increases the collagen deposition rate and breaking strength of left colonic anastomoses in rats.

BACKGROUND: The purpose was to investigate how growth hormone exerts its stimulating effect on the healing of experimental colonic anastomoses. METHODS: Rats were treated with biosynthetic growth hormone (bGH); the anastomotic breaking strength, collagen content, and collagen deposition rate (labeling of collagen with 14C-proline) were compared to saline treated controls. RESULTS: bGH increased the breaking strength when the rats were treated before and after the operation and when bGH treatment was started at operation and continued during the healing period. No effect on these parameters was seen, however, when treatment was given only before operation. The collagen deposition rate of the intact colon was accelerated from 0.6% to 1.0% per hour at operation after 7 days of preoperative treatment. The anastomotic collagen deposition rate was increased on day 4 from 4.4% in the controls to 9.0% in the anastomosed rats given bGH from operation and to 12.9% in rats given bGH from 7 days before operation until day 4 after operation, resulting in a higher anastomotic collagen content. CONCLUSIONS: Treatment of rats with bGH in the healing phase increases the breaking strength of colonic anastomoses caused by a stimulation of the collagen deposition rate of the anastomotic segment.

Anastomosis, Surgical↗

PubMed1993

Human parathyroid hormone (1-34) and (1-84) increase the mechanical strength and thickness of cortical bone in rats.

An anabolic effect on bone of intermittent parathyroid hormone (PTH) treatment has been found in patients with osteoporosis and also in experimental animals. Controversies exist, however, about whether the positive effect on the trabecular bone balance occurs at the expense of the cortical bone. We examined the biomechanical quality of cortical bone after intermittent treatment with different doses of PTH and, furthermore, compared the effects of PTH-(1-34) and PTH-(1-84). Groups of rats were treated with biosynthetic human PTH-(1-34) or PTH-(1-84), 1.1, 3.3, 10, or 30 nmol/kg/day for 30 days. No changes in the body weights and no changes in the lengths of the femora were observed after the PTH treatments. The biomechanical properties were analyzed by means of a materials-testing machine. A dose-related increase in the bending strength and stiffness of the femora was found, and this increase in mechanical strength corresponds with a 9-12% increase in the cross-sectional area of the femoral diaphyses. The deflection capability and energy absorption were not influenced by any of the PTH treatments. No differences were found between the effects of PTH-(1-34) or PTH-(1-84) on the biomechanical properties of the femora. Consequently, intermittent treatment with biosynthetic PTH-(1-34) or PTH-(1-84) increased the formation of cortical bone, and the biomechanical competence of the femora was found to be preserved.

Animals↗

PubMed1993

Different biomechanical properties of human fetal membranes obtained before and after delivery.

The aim of this study was to elucidate whether the mechanical properties of fetal membranes change during late pregnancy and labour. Membranes delivered by elective caesarean section in week 38 showed different load-strain curves to membranes obtained after spontaneous vaginal delivery at term. A major change in mechanical properties was a decrease in strength of the intact chorioamniotic membrane from 1.39 N to 0.98 N (width of biopsy 4 mm), mainly due to loss of strength of the amniotic component, from 1.27 N to 0.72 N. Moreover, the extensibility of the chorionic component (epsilon Fmax) increased after vaginal delivery from 0.42 to 0.54, resulting in a two-component behaviour of the intact chorioamniotic membrane and further decrease of strength. Based on these observations it is suggested that the amnion is attached to the chorion, act biomechanically in parallel and possess relatively high mechanical strength during pregnancy. After vaginal delivery the two membranes are separated, and pronounced changes are induced in their mechanical properties.

Amnion↗

PubMed1993

Parathyroid hormone (1-34) and (1-84) stimulate cortical bone formation both from periosteum and endosteum.

The anabolic effect of intermittent treatment with parathyroid hormone (PTH) on cortical bone was investigated. Groups of rats were injected with human PTH (1-34) or PTH (1-84), 1.1, 3.3, 10, and 30 nmol/kg/day for 30 days. A dose-related increase in bone formation rate at the femoral middiaphysis was found at both the periosteum and the endosteum and also an increase in bone mass, with no change in the bone lengths or body weight gain of the rats. The highest mineral apposition rate, as analyzed by tetracycline labeling, was found at the periosteal postero-medial aspect and at the endosteal anterior aspect. This pattern of bone modeling was also found in the PTH-treated animals, although more and more areas were included in bone mineral apposition. The PTH treatments did not change the porosity of the cortical bone nor the concentration and biochemical stability of the collagen. The highest doses of PTH resulted in a slight reduction in the ash concentration of cortical bone. No differences were found between the effects of PTH (1-34) and PTH (1-84) on bone formation rate, bone mass, porosity, and biochemical parameters. Consequently, intermittent treatment with PTH increased the formation of cortical bone dose dependently, at both the periosteum and the endosteum and increased the bone mass of these growing rats, with no change in the body weight gain or femoral growth rate compared with the control animals. The responses of the cortical bone modeling were increased by the PTH treatments without changing its direction or pattern.

Animals↗

PubMed1992

Age-related alterations in the strength and collagen content of left colon in rats.

The biomechanical properties and intestinal wall composition of left colon were studied in 4-month-old, 14-month-old, and 27-month-old male rats. The hydroxyproline content and hydroxyproline concentration in old rats were increased by 36% and 26%, respectively, compared with young rats and by 20% and 17%, respectively, compared with middle-aged rats. In middle-aged rats the maximum load increased by 21%, compared with young rats. In old rats, however, the maximum load decreased by 13%, compared with middle-aged rats. Histological examination showed that the mean crypt height was 9% higher in middle-aged rats and 12% higher in old rats than in young rats. In conclusion, an accumulation of collagenous proteins was found in old rats compared with middle-aged rats and this was accompanied by a decrease in the strength, which may deteriorate the functional integrity of the left colonic wall with age.

Aging↗

PubMed1992

Aminoguanidine treatment reduces the increase in collagen stability of rats with experimental diabetes mellitus.

Alterations in the biophysical properties of connective tissues in diabetes mellitus have been attributed to the nonenzymatic glycation of the collagens and the subsequent formation of browning products, cross-linking the proteins. Aminoguanidine may bind to carbonyl groups of these nonenzymatic glycation products and thereby block the process. Rats with streptozotocin-induced diabetes were treated with aminoguanidine, 25 mg.kg-1.day-1, for 120 days. The aminoguanidine treatment did not counteract the increase in blood glucose concentrations, nor did it prevent the arrest in weight gain of diabetic rats. The increased stability in 7 mol/l urea and increased tensile strength of tail tendons from the diabetic rats, however, were prevented by the aminoguanidine treatment. Aminoguanidine did not reduce the formation of early nonenzymatic glycation products (aldimine and Amadori rearrangement products), whereas the amount of browning products (fluorescent compounds) was reduced in the tail tendon collagen of the diabetic rats. Aminoguanidine treatment of intact rats did not influence these parameters. These findings indicate that the biophysical alterations of collagens induced by experimental diabetes are caused by cross-links derived from the nonenzymatic glycation, and furthermore, that aminoguanidine treatment may prevent the concomitant changes in biophysical properties of connective tissues.

Animals↗

PubMed1992

Glucocorticoid treatment or food deprivation counteract the stimulating effect of growth hormone on rat cortical bone strength.

Growth hormone (GH) has been found to increase the length, thickness and bending strength of rat femora. The present study was designed to investigate if glucocorticoid treatment or food restriction would interfere with the effect of exogenous GH on bone growth. Male rats treated with GH for 30 days experienced a weight gain of 30-35% and longitudinal and periosteal femoral growth. A dose-related increase in the bending strength of the femora was found and was explained by an increased thickness of the femora. In spite of a reduced real density, biomechanical competence was preserved after GH treatment. GH treatment combined with a relatively small dose of glucocorticoid, which in itself had no significant effect on bone growth and strength, reduced the stimulating effect of GH on body weight gain, femoral growth and strength. GH-treated rats that were food restricted, so as to limit their body weight gain to that of the saline group, experienced significant longitudinal and periosteal femoral growth. Bone strength, however, was not increased, which conforms to a reduced mineralization and increased porosity of the femora. Young's modulus (normalized bone stiffness) was significantly decreased in this group, probably as a result of decreased mineralization. Furthermore, the combination of GH treatment and food restriction resulted in a reduced apparent density indicating increased bone resorption.

Animals↗

PubMed1992

Increased mechanical strength of left colon in old rats treated with growth hormone.

The effects of treatment with 2.7 mg biosynthetic human growth hormone (b-hGH; 2.7 mg/kg b.w./day) for 80 days on the biomechanical properties and collagen deposition of the left colon were studied in 27-month-old male rats. The b-hGH-treated rats increased in body weight by 17%, and the wet weight of colon by 31%. The defatted dry weight and the hydroxyproline content of the left colon were increased by 41 and 29%, respectively, compared with controls. The biomechanical analysis showed that the maximum load and stiffness of the left colonic specimens in the b-hGH-treated group were enhanced by 27 and 60%, respectively, and the strain at maximum load was 24% less than in the control group. The maximum 'stress' and stiffness were 40 and 73% higher, respectively, than in the controls. Histological examination demonstrated that the mean crypt heights was 9% higher in the b-hGH-treated rats than in the controls. Consequently, treatment of old rats with b-hGH may increase the strength, collagen deposition and mucosal crypt height of the left colon.

Aging↗

PubMed1991

Postoperative biosynthetic human growth hormone increases the strength and collagen deposition of experimental colonic anastomoses.

This study examined the effects of preoperative treatment with 2.0 mg biosynthetic human growth hormone (b-hGH)/kg/day on the bursting strength and collagen deposition of experimental left colonic anastomoses, and of intact colon from sham-operated rats. The anastomotic bursting pressure was 55% higher in the b-hGH treated animals on day 2 (p less than 0.05) and 79% higher on day 4 (NS; p = 0.056), and the bursting wall tension was 65% higher on day 2 (p less than 0.05) and 112% higher on day 4 postoperatively (p less than 0.05), than saline-injected controls. The hydroxyproline content of the anastomotic segment in the b-hGH treated rats increased by 56% on day 4 (p less than 0.005) and by 30% on day 6 postoperatively (p less than 0.05), compared with controls. At 3 cm proximal to the anastomoses the defatted dry weight and hydroxyproline content of the healing colons were increased after 6 days compared with the sham-operated rats. There was, however, no difference between the b-hGH treated rats and the paired controls, indicating that growth hormone is not involved in this process.

Anastomosis, Surgical↗

PubMed1991

Biosynthetic growth hormone changes the collagen and elastin contents and biomechanical properties of the rat aorta.

The biomechanical and biochemical properties of aortas from female rats treated with biosynthetic human GH (b-hGH) for 80 days were investigated. b-hGH was administered at a dose of 5 mg.kg-1.d-1. Treatment with b-hGH increased the body weight by 75% and the diameter of the aorta by 14% compared with the control group. The concentration of collagen and the relative amount of collagen type I were increased, and the concentration of elastin was decreased. Aortas from the b-hGH-treated group showed increased extensibility in the regions corresponding to physiological load values (i.e. 100-200 mmHg), and increased stiffness in regions with higher load values. The increased extensibility at low load values corresponds well with the loss of elastin, and the increased stiffness at higher load values with the increase of collagen and relative increase of collagen type I. These alterations induced by the growth hormone treatment might influence the elasticity and recoiling properties of the aorta.

Animals↗

PubMed1991

Alterations in the cross-links of skin collagen of rats treated with biosynthetic growth hormone.

The effect of biosynthetic human growth hormone (b-hGH) treatment on rat skin collagen was investigated. Groups of rats were injected with b-hGH 0.16, 1.10 and 8.33 mg/kg/day for 90 days. The weight gain of the rats treated with b-hGH 1.10 and 8.33 mg/kg/day was 13% and 82% higher, respectively, compared with that of the placebo control group. The extractability of the skin collagen was studied by extraction with phosphate buffered saline (pH 7.4), followed by acetic acid (0.5 M) and acetic acid with pepsin. The reducible collagen cross-links were measured after reduction of the cross-links by KB3H4, followed by acid hydrolysis and ion-exchange chromatography. Furthermore, patterns of cyanogen bromide peptides were studied by SDS-poly-acrylamide-gel-electrophoresis. Peptides bound together by stable cross-links and the relative amounts of collagen type I and collagen type III were measured. Treatment with b-hGH 8.33 mg/kg/day resulted in increased extractability of the skin collagen in acetic acid, increased relative amounts of reducible collagen cross-links and reduced amounts of high molecular weight cyanogen bromide cleaved peptides of the collagen. These alterations probably reflect an increased synthesis of skin collagen induced by the highest dose of b-hGH. The relative amounts of collagen type I and collagen type III of the skin were not influenced by the b-hGH treatment.

Acetates↗