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H Oxlund

Publications and source records attributed to H Oxlund.

At least 37 records · Page 2Linked to original sources

Administration of a glucocorticoid with depot effect counteracts the stimulating effect of growth hormone on cancellous and cortical bone of the vertebral body in rats.

Our earlier studies have shown that growth hormone administration could not counteract decreased longitudinal growth and cortical osteopenia of rat femora induced by a glucocorticoid with depot effect. In the present study we examined the effects of glucocorticoid on vertebral bone as well as the effect of growth hormone on vertebral bone in young growing animals also given glucocorticoid injections. Five groups of female rats (3 1/2 months) were treated for 80 days as follows: (1) saline, (2) prednisolone: Delcortol 5 mg/kg/day, (3) growth hormone: 5 mg/kg/day, (4) prednisolone and growth hormone, (5) food restriction. Vertebral dimensions, histomorphometry, and mechanical competence of the vertebral bone were examined. Growth hormone administration increased body weight, vertebral height, cross-sectional area, and volume. The compressive strength of the L4-corpus cylinder was also increased due to an increase in cancellous bone volume and an increase in the area of cortical bone surrounding the vertebral body. Glucocorticoid administration decreased body weight, height, and volume of the intact vertebrae. Histological examination revealed that glucocorticoid administration decreased the area of cortical bone surrounding the vertebral body but had no effect on the cancellous bone volume. No effect of glucocorticoid administration on mechanical strength of the L4 corpus cylinder could be detected. In agreement with our findings in cortical bone, we found no effect of growth hormone on vertebral bone when given to animals also receiving glucocorticoid injections. Growth hormone increases longitudinal growth, cortical and cancellous bone mass, and mechanical competence of the vertebral body. Glucocorticoid administration decreases longitudinal growth of the vertebrae and cortical bone mass without affecting cancellous bone mass of the vertebral body. Despite this, administration of a glucocorticoid with depot effect totally inhibits the effect of growth hormone on vertebral bone.

Aging↗

Inhibition of cross-links in collagen is associated with reduced stiffness of the aorta in young rats.

Collagen and elastin fibres are of major importance in providing the aorta with tensile strength and elasticity. The presence of cross-links in collagen and elastin is essential for the mechanical stability of collagen and elastin fibres. beta-aminopropionitrile (BAPN) reduces the formation of cross-links by inhibiting the enzyme lysyloxidase. Young rats were injected with BAPN to inhibit the formation of cross-links, and the changes in the biomechanical and biochemical properties of the thoracic aorta were studied. The biomechanical analyses of aortic samples from BAPN-treated rats showed a significantly increased diameter (1.64 +/-0.02 mm), a significantly reduced maximum load (1.08+/-0.08 N), and a significantly reduced maximum stiffness (3.34+/-0.10 N) compared with controls (1.57+/-0.02 mm, 1.55+/-0.04 N and 4.49 +/-0.14 N, respectively). No changes in the concentrations of collagen and elastin were found. The content of pyridinoline, a mature collagen cross-link, was significantly decreased by 49% in the BAPN-treated group compared with controls. No changes in the concentration of desmosine + isodesmosine, the major cross-links of elastin. were found. The present study shows that cross-links are essential in providing mechanical stability of the aorta. Even a partial inhibition of the cross-linking processes results in a destabilisation of the aortic wall with increased diameter and reduced strength and stiffness.

Aging↗

Growth hormone administration can improve growth in glucocorticoid-injected rats without affecting the lymphocytopenic effect of the glucocorticoid.

Long-term glucocorticoid therapy as it is found in children with kidney transplants results in retarded longitudinal growth. The aim of the present study was to evaluate if growth hormone could improve longitudinal growth in glucocorticoid-injected experimental animals without affecting the immuno-suppressive effect of the glucocorticoid. 117 female Wistar rats were injected from the ages of 2-5 months with either saline, growth hormone (5 mg/kg/day), or glucocorticoid (methylprednisolone 1,3,6 or 9 mg/kg/day), alone or in combination with growth hormone (5 mg/kg/day). Body weight, nose-tail length and length of the lower extremity were measured continuously during the study. After death, femoral and tibial lengths, growth at the proximal, epiphyseal growth plate, muscle mass and immunological parameters were examined. Glucocorticoid administration dose-dependently decreased weight gain and growth (nose-tail length, growth of the lower extremity), lengths of femur and tibia, growth at the proximal, epiphyseal growth plate and muscle mass. Glucocorticoid administration decreased spleen and thymus weight as well as the white blood cell count (WBC count), mainly due to a decrease in lymphocyte number. For all glucocorticoid doses examined, growth hormone increased weight gain and growth (nose-tail length, growth of the lower extremity), lengths of femur and tibia, and muscle mass. The effects of growth hormone were, however, dose-dependently decreased by glucocorticoid administration. Growth hormone injection alone increased the WBC count due to an increase in the number of lymphocytes and monocytes. When the two hormones were administered concomitantly, growth hormone did not, however, reverse the lymphocytopenic effect induced by glucocorticoid administration. In conclusion, growth hormone can increase longitudinal growth and increase muscle mass in glucocorticoid-injected rats, if a glucocorticoid preparation of a short half-life is used. Growth hormone does not reverse the lymphocytopenic effect of glucocorticoid injections.

Animals↗

Withdrawal of parathyroid hormone treatment causes rapid resorption of newly formed vertebral cancellous and endocortical bone in old rats.

When administered intermittently, parathyroid hormone (PTH) is a strong anabolic agent, increasing both bone mass and bone mechanical strength and competence. This study evaluates the fate of PTH-induced bone in vertebral bodies after withdrawal of PTH treatment in normal old rats. Sixty-seven 21-month-old male rats were treated with 62 microg/kg/day PTH(1-34) for 8 weeks, followed by saline or bisphosphonate (risedronate, 5 microg/kg twice a week) for another 8 weeks. The rats were scanned by dual-energy X-ray absorptiometry at intervals. The bone mineral content (BMC) of L2-5 increased by 33% during the PTH treatment. The BMC started decreasing shortly after withdrawal of PTH and continued to decline during the 8 weeks after withdrawal of PTH. Risedronate, however, prevented this decrease in BMC. All rats were labeled with tetracycline and calcein 3 weeks and 1 week before the cessation of PTH therapy. In the cancellous bone, PTH increased the mineralized surface: 32.9% +/- 2.8% (mean +/- standard error of the mean) vs. controls 12.0% +/- 1.5%, the mineral appositional rate (0.65 +/- 0.02 to 0.88 +/- 0.06 microm/day), and the cancellous bone volume (BV/TV: 14.5% +/- 0.7% to 27.5% +/- 1.7%). Withdrawal of PTH induced a fast and pronounced bone resorption, decreasing both the extent of the fluorochrome labels and the cancellous bone volume to control values. Risedronate prevented this resorption. In the cortical bone of the vertebral shell, PTH induced large increases in the endocortical mineralized surface, mineral appositional rate, and cortical area. The endocortical fluorochrome labels were, however, resorbed after withdrawal of PTH. Risedronate maintained both the fluorochrome labels and the cortical area. At the periosteum, the response to PTH was less evident, however, and hardly any labeling was seen at the periosteum facing the vertebral canal either in the controls or in the PTH-treated rats. The compressive strength of the vertebral body specimens increased with PTH treatment whether measured in newtons (317 +/- 23 to 623 +/- 54 N), normalized to cross-sectional area (23.0 +/- 1.4 to 44.7 +/- 2.5 N/mm2), or to ash content per millimeter height (58 +/- 2 to 76 +/- 2 N x mm/mg). Withdrawal of PTH decreased the compressive strength and competence to control values. Risedronate, however, maintained the PTH-induced mechanical strength and competence. The study discloses that even in very old rats withdrawal of PTH treatment causes a rapid and pronounced decline in the bone mass deposited during PTH treatment; treatment with risedronate can, however, maintain the PTH-induced bone properties in the axial skeleton of old rats.

Absorptiometry, Photon↗

Biomechanical properties of normal and varicose internal spermatic veins.

To investigate possible differences in biomechanical properties between varicose spermatic veins and controls. During surgery on 12 patients for grade 3 left-sided varicocele testis, 2 cm of the vein was obtained for comparison with: (i) samples of the left internal spermatic vein taken from the same anatomical localization from 8 patients without scrotal disease, and (ii) samples from the right internal spermatic vein from 7 other patients also without scrotal disease. The biomechanical properties of ring-shaped venous specimens were investigated by loading the specimen at a constant deformation rate until rupture. The relative amounts of collagen in the specimens were determined as the contents of hydroxyproline. There was a significant difference between varicocele testis/right spermatic vein in UC (unit collagen), F-max (maximum strength), Strain (ultimate extensibility) and E-fail (relative failure energy), but not in LD (diameter) and Tan-a (stiffness of the specimen). There were no significant differences between left and right spermatic vein in LD, UC, F-max, Strain, Tan-a and E-fail. There was a significant difference in LD between varicocele testis/left spermatic vein, but no relationship in UC, F-max, Strain, Tan-a and E-fail. Biomechanical analyses of the spermatic veins from patients operated for varicocele seem to support the hypothesis that a difference in biomechanical properties plays a part in the development of varicocele because a significant increase in extensibility of varicocele samples was found compared with normal right spermatic vein samples.

Adult↗

Biomechanical properties of the internal spermatic vein in the normal population and patients with left-sided varicocele testis.

OBJECTIVE: The aim of the study was to investigate a possible decreased strength of the wall of the left internal spermatic vein between patients with varicocele testis and controls. MATERIALS: From 14 patients with varicocele testis, 2 cm of the vein was obtained during operation per varicocele and compared to samples of the left internal spermatic vein taken from the same anatomical localization of 19 patients with no varicocele testis or other conditions with relation to the scrotum; additionally, samples from the right internal spermatic vein similar to those described above were taken from 12 patients. The biomechanical properties of ring-shaped venous specimens were investigated by loading the specimens at a constant deformation rate until rupture. MAIN RESULTS: The regression coefficient, standard error and p value revealed no significant differences in ID (diameter), UC (unit collagen/ID), E-max (ultimate extensibility), Max (maximum strength), Tan-a (maximum stiffness), E-fail (relative failure energy). The trend to significance was shown in ID between the varicocele and left-sided veins (p = 0.05) and between left- and right-sided veins (p = 0.05). CONCLUSIONS: These biomechanical tests of the spermatic veins from healthy subjects and patients operated for varicocele showed that biomechanical differences were associated with age and could play a part in the development of varicocele testis in an age-matched group.

Adult↗

Growth hormone and mild exercise in combination markedly enhance cortical bone formation and strength in old rats.

The effects of a combination of mild exercise and GH injections on bone were studied in old female rats. Biosynthetic human GH, 2.7 mg/kg/day, was injected s.c. for 73 days. Exercised rats ran 8 m/min on a treadmill for 1 h/day. All rats (age 21 months old) were labeled with a tetracycline injection 56 days and a calcein injection 11 days before killing. The GH injections resulted in an 11-fold increase in femoral middiaphyseal bone formation rate and a 12% increase in cross-sectional area compared with the saline-injected group. The mild exercise doubled the mineralizing surface but did not influence the bone formation rate significantly. The combination of GH injections plus exercise, however, resulted in a further increase of 39% in bone formation rate, primarily at the anterolateral aspects, and an increase of 5% in cross-sectional area compared with the group injected with GH only. The femur ultimate breaking load was increased by 37% and the stiffness by 42% in the group injected with GH compared with the saline-injected group. Exercise alone did not influence the femur mechanical properties. The combination of GH injections plus exercise induced a 4% further increase in ultimate breaking load and 7% further increase in stiffness compared with the group injected with GH alone. The GH injections induced a 117% increase in serum insulin-like growth factor I. The GH-insulin-like growth factor I axis stimulates recruitment of osteoblast precursor cells, resulting in increased bone formation at the periosteal surface. GH injections and mild excercise in combination modulate and increase further the formation and strength of cortical bone in old female rats.

Aging↗

No effects of human relaxin on the active and passive biomechanical properties of isolated cervical specimens from nonpregnant women.

OBJECTIVE: To evaluate the effect of human relaxin (hRLX-2) on the active and passive biomechanical properties of cervical tissue in vitro. MATERIAL: Cervical samples were obtained from the middle part of the cervix in 22 nonpregnant women undergoing hysterectomy. METHODS: The effect of hRLX-2 (10(-7) M) on the active biomechanical properties was studied on vasopressin (10(-8) M) induced smooth muscle contractions in an organ bath model. The effect on the passive biomechanical properties were studied after incubation of the strips for 48 h with hRLX-2 (10(-8) M and 10(-9) M). Subsequently, the specimens were stretched in a material testing machine until they broke. The load applied and the elongation were simultaneously recorded and the results translated into stress-strain curves. RESULTS: hRLX-2 did not influence the vasopressin-induced contractility of cervical strips from nonpregnant women in this study. No synergistic effect of progesterone could be demonstrated. The passive biomechanical properties (tensile strength, extensibility, stiffness of failure energy) did not change significantly after relaxin incubation. The results obtained in vitro do not suggest an important physiological effect of relaxin on the human nonpregnant cervix.

Adult↗

Changes in biomechanical properties, composition of collagen and elastin, and advanced glycation endproducts of the rat aorta in relation to age.

During ageing and senescence the aorta becomes stiffer and its elasticity is reduced. The mechanism causing this increased stiffness of the aortic wall was studied using a rat model. Ring-shaped samples were prepared from the thoracic aorta of three groups of rats aged 4.5, 14 and 27 months, representing young, adult and old animals. Analysis of the static biomechanical properties showed increased diameter (2.20 +/- 0.03 mm) and increased stiffness (4.0 +/- 0.2 mN) of aortic samples from old rats compared with adult rats (1.82 +/- 0.02 mm and 3.0 +/- 0.1 mN, respectively). The total hydroxyproline and elastin content per sample was not changed. However, the hydroxyproline content/mm2 of the aortic wall was reduced by 20% and the elastin content/mm2 of the aortic wall was reduced by 19% comparing the old with the adult rats. No differences were found in the pyridinoline concentrations between old and adult rats. The collagen- and elastin-associated fluorescence was determined as a marker of advanced glycation endproducts (AGE). Both parameters were increased in the old rats compared with the adult rats by 42% and 17%, respectively, and positively correlated with stiffness at physiological loads. A positive correlation between collagen-associated fluorescence and maximum stiffness was found as well. In conclusion, the age-related increase in stiffness of the aorta was associated with increased diameter, reduced collagen and elastin contents/mm2 of the aortic wall, increased fenestration of elastic laminae and accumulation of fluorescent material in collagen and elastin.

Aging↗

The influence of growth hormone on cancellous and cortical bone of the vertebral body in aged rats.

The influence of growth hormone administration on cancellous and cortical bone of the vertebral body in 2-year-old male rats has been investigated. All rats were injected for 80 days, then killed. Controls were given saline, and three recombinant human growth hormone (rhGH) injected groups were given either rhGH (2.7 mg/kg/day) for the first 20 or 40 days, followed by saline injection, or rhGH for all 80 days. Tetracycline labeling was performed on days 41 and 69. In all groups given rhGH, an increase in the cortical bone volume was found. In the rhGH 40-day group, single labeling corresponding to injection on day 41 was seen all around the anterior surface of the vertebral body wall (toward the abdominal cavity). In the rhGH 80-day group, double labeling was seen all around the anterior surface of the vertebral body, and a substantial increase in the mineralizing surface/total surface, mineral apposition rate, and mineralized bone formation rate was found. In the cortical bone of the anterior wall, cavities had developed in the rhGH 40- and 80-day groups. In the cancellous bone, no differences in bone volume, bone volume/total volume, or bone surface/bone volume were seen, but in the middle part of the vertebral body a decrease in the mineralizing surface/total surface was found in the rhGH 80-day group. The height of the vertebral body was not influenced by rhGH administration, whereas the transversal and midsaggital diameters were increased in the rhGH 80-day group. The compressive mechanical strength of the vertebral body specimens was increased in the rhGH 80-day group, and this increase most likely could be explained by formation and deposition of cortical bone.

Aging↗

Collagen deposition and mechanical strength of colon anastomoses and skin incisional wounds of rats.

The mechanical strength development of healing wounds depends on the formation of collagen fibrils bridging the wound cleft. A considerable deposition, degradation, and remodeling of these fibrils takes place influencing the mechanical strength of the healing wounds. A method for studies of wound collagen metabolism in vivo is delineated, enabling determination of collagen deposition per hour in rat colon anastomoses and skin incisional wounds. Labeled proline was incorporated into wound collagen with a flooding dose of unlabeled proline, reducing errors introduced by proline recycling and proline de novo synthesis. The mechanical strength was determined by a materials testing machine. In both colon anastomoses and skin wounds a substantial increase in collagen deposition was observed at Day 2, reached a maximum at Day 6, and was still relatively high at Day 12 during the remodeling of collagen fibers in the wound cleft. The collagen deposition in colon anastomoses at Day 6, however, was 10-fold higher compared with that of the skin incisional wounds. The time course of the collagen deposition was much alike in colon anastomoses and skin incisional wounds reaching a maximum at Day 6. The mechanical strength of these two rather different types of wounds was increased correspondingly and to the same level during the 1st week of healing. The measurements of collagen deposition, collagen content, and biomechanical strength indicated a substantial turnover of newly synthesized and deposited collagen during the early phases of wound healing. On the basis of this, it seems obvious that even small disturbances to the balance between collagen synthesis, deposition, collagen cross-linking, and collagen degradation/remodeling may result in defective wound healing.

Anastomosis, Surgical↗

The role of glycation cross-links in diabetic vascular stiffening.

Previous studies have shown that biomechanical analysis of aorta from diabetic subjects reveals a marked increase in stiffness compared to aorta from age-matched control subjects. In the present paper we have proposed that this increased stiffness can be attributed to glycation-induced inter-molecular cross-links based on a direct analysis of the two known glycation cross-links, the fluorescent pentosidine and the non-fluorescent NFC-1. There was a significant difference in the increase in concentration of both cross-links with increasing age for both the intima (p < 0.0025) and the media (p < 0.0005) from the diabetic compared to the control subjects, but no correlation with the mature enzymic cross-link hy droxylysyl-pyridinoline. Finally, we have obtained a significant correlation of stiffness with both glycation cross-links (NFC-1, r = 0.86; p < 0.005 and pentosidine r = 0.75, p < 0.05), but the concentration of NFC-1 is about 50 times greater than that of pentosidine, indicating that it is the major glycation cross-link responsible for the stiffening of the aorta.

Adult↗

Qualitative alterations of cortical bone in female rats after long-term administration of growth hormone and glucocorticoid.

A serious side effect of glucocorticoid treatment is the development of osteoporosis. We have earlier shown that long-term glucocorticoid administration results in a decrease in longitudinal bone growth, cortical bone mass, and biomechanical strength, while growth hormone administration increases these parameters. The result of biomechanical testing also indicates that glucocorticoid administration reduces the quality of bone. The glucocorticoid-induced osteopenia could not be inhibited by concomitant administration of large doses of growth hormone. The aim of the present study was to evaluate why glucocorticoid administration decreases the quality of cortical bone and why growth hormone administration had no beneficial effect on glucocorticoid-induced osteopenia. Five groups of female rats (3 1/2 months old) were treated for 80 days as follows: (1) glucocorticoid (prednisolone: Delcortol 5 mg/kg/day); (2) glucocorticoid and growth hormone; (3) saline; (4) growth hormone (recombinant human growth hormone 5 mg/kg/day); (5) Food restriction (consisting of restricted access to food to reduce their weight gain to match with that of the glucocorticoid injected rats). The animals were injected with tetracycline (15 mg/kg), 18 and 3 days before sacrifice, respectively. Furthermore, a baseline group (3 1/2-month-old female rats) was examined in order to enable us to differentiate between age-related changes and changes due to the hormone administration. Cortical mid-diaphysial cross sections of the femora were prepared and used for histological examination including determination of bone porosity, bone formation rate, and determination of the area of endosteal cavities as an indication of bone resorption. Furthermore, a cortical bone cylinder was cut from the mid-diaphysis and used for examinations of wet weight, dry weight, ash weight, volume, collagen content, and apparent density. Glucocorticoid administration resulted in an almost complete arrest of bone formation as shown by a decreased bone formation rate and a decreased periosteal mineralizing surface. Glucocorticoid administration also increased the porosity of bone indicating increased osteoclast activity. The increased porosity was due to a glucocorticoid-induced increase in the number of endosteal cavities in the mid-diaphysial cross section of the femora. The decreased bone formation and the increased bone resorption can explain the decrease in bone mass (volume and ash weight) found after glucocorticoid administration. Growth hormone administration, on the other hand, resulted in a marked increase in bone formation as shown by a marked increase in bone formation rate and periosteal mineralizing surface. In agreement with this, we found an increase in cortical bone mass (volume and ash weight). When the two hormones were given concomitantly, growth hormone administration did not increase bone formation. Our findings indicate the reason why growth hormone has no beneficial effect on cortical osteopenia induced by a high dose of glucocorticoid with protracted effect.

Administration, Oral↗

The effect of oophorectomy on mechanical properties of rabbit cerebral and coronary isolated small arteries.

OBJECTIVE: Our purpose was to study the effect of oophorectomy on the passive and active mechanical characteristics of rabbit small cerebral and small coronary arteries. STUDY DESIGN: Ring preparations of small cerebral and small coronary arteries from rabbits that had undergone oophorectomy and sham operation were mounted on myographs 6 weeks after operation. Experiments were performed as follows. (1) concentration-response relations for vasopressin (10(-11) to 10(-7) mol/L), U46619 (10(-10) to 10(-6) mol/L), 5-hydroxytryptamine (10(-7) to 10(-5) mol/L), and endothelin (10(-13) to 10(-7) mol/L); (2) relaxing effects of acetylcholine (10(-8) to 10(-4) mol/L); (3) length-tension relations after addition of high potassium (124 mmol/L), vasopressin (10(-7) mol/L), and a mixture composed of potassium (124 mmol/L), vasopressin (10(-7) mol/L), and prostaglandin F 2 alpha (10(-5) mol/L); (4) calculation of vessel morphologic features and determination of hydroxyproline as a measure of collagen content. RESULTS: Oophorectomy did not influence basal tone, relaxant effects of acetylcholine, vessel morphologic features, elastic characteristics, or hydroxyproline content of the vessels. However, in cerebral arteries at a normalized lumen diameter, oophorectomy induced a marked increase in the force development after stimulation with agonists but not after depolarization with high potassium. The reason for this was a leftward shift in the active length-tension curves (vasopressin activation). In coronary arteries none of these changes were seen after oophorectomy. CONCLUSION: These data demonstrate that withdrawal of ovarian hormones changes the position of the active length-tension curve for pharmacomechanical but not electromechanical coupling of small cerebral arteries without interference with the elastic characteristics of these vessels.

Acetylcholine↗

Reduced concentration of collagen reducible cross links in human trabecular bone with respect to age and osteoporosis.

The decrease of bone strength in relation to age and osteoporosis is more pronounced than would be expected from the relative deficit in the amount of bone. Besides bone mass, the mechanical properties of cancellous bone also depend on the microarchitecture and possibly on the molecular structure of inorganic and organic components. The present study examines the bone collagen, especially the collagen cross links, in relation to age and osteoporosis. Samples of vertebral trabecular bone were taken at autopsy from 43 normal individuals, aged 15-90 years. Eleven of these served as sex- and age-matched controls for similar samples from 11 osteoporotic individuals, 70-90 years. The volume of each trabecular bone sample was estimated. After removal of the marrow, the trabeculae were ground to powder and decalcified. The extractability of the bone collagen was studied by repeated extractions with acetic acid and pepsin. The divalent reducible collagen cross-links, dehydro-dihydroxylysinonorleucine (DHLNL) and dehydro-hydroxylysinonorleucine (HLNL), were determined by reducing the bone collagen with tritiated potassium borohydride followed by ion-exchange chromatography. The mature trivalent pyridinium cross links were determined by reverse-phase HPLC with fluorescence detection. The extractability of collagen prepared from the vertebral trabecular bone of control individuals was increased with age. Bone collagen of osteoporotic individuals showed increased extractability and a substantial decrease in the concentration of the divalent reducible collagen cross links (DHLNL reduced by 30% and HLNL by 24%) compared with the sex- and age-matched controls. No alterations were observed in the concentration of the pyridinolines. The divalent reducible cross-links are the most frequent known cross links in bone (2-4 times the concentration of the pyridinium cross links). These changes would therefore be expected to reduce the strength of the bone trabeculae and could explain why the osteoporotic individuals had bone fractures even though the collagen density (mg/cm3) did not differ from that of the sex- and age-matched controls. The microarchitecture of the cancellous bone was not assessed. The osteoporotic and control individuals seemed to have the same amount of trabecular bone, but the quality of the osteoporotic bone collagen was reduced.

Acetic Acid↗

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↗

Morphological, stereological, and biochemical analysis of the mini-pig urinary bladder after chronic outflow obstruction and after recovery from obstruction.

Chronic partial bladder outlet obstruction was created in nine mini-pigs by implanting a 6-7 mm ring around the proximal urethra. After a median obstruction period of 63 days, the ring was removed and after a recovery period of median 60 days the animals were sacrificed. Changes in muscle and connective tissue were assessed by unbiased, modern morphometry and biochemical analysis. After obstruction the results were as follows: (1) a 6-fold increase in bladder weight, (2) a 2.5-fold increase in smooth muscle cell size, (3) a 3-fold increase in smooth muscle cell number, (4) unchanged proportions between muscle and connective tissue, (5) unchanged hydroxyproline concentrations, (6) an 8-fold increase in total collagen content, (7) an increase in the ratio of type I/III collagen, and (8) a 7-8-fold increase in total content of type I and III collagen. All changes were markedly, though incompletely, reversed after recovery, except smooth muscle cell number and the ratio of type I/III collagen.

Animals↗

Collagen structural organization of healing colonic anastomoses and the effect of growth hormone treatment.

PURPOSE: This experimental study was designed to investigate the collagen fibrils of colonic anastomoses in rats and to compare normal healing with rats treated with biosynthetic growth hormone (bGH). METHODS: The healing zone of left colonic anastomoses was studied at days 2, 4, and 6 after surgery by means of scanning electron microscopy. RESULTS: After four days of healing a normal anastomosis was filled with loosely packed and unorganized collagen fibrils, which were organized into collagen fibers after six days. Compared with normal anastomoses, rats treated with bGH showed a more organized healing, characterized by a dense structure of a new-formed collagen framework of fibrils and immature collagen fibers after six days. CONCLUSIONS: Healing colonic anastomoses are characterized by new-formed collagen fibrils at postoperative day 4, and bGH seems to stimulate structural organization of the anastomotic collagen fibrils into fibers.

Anastomosis, Surgical↗