PubMed Health⌕ Search

Biomedical subjects

T T Andreassen

Publications and source records attributed to T T Andreassen.

At least 19 recordsLinked to original sources
PubMed2003

Low-intensity, high-frequency vibration appears to prevent the decrease in strength of the femur and tibia associated with ovariectomy of adult rats.

The effect of low-intensity, high-frequency vibration on bone mass, bone strength, and skeletal muscle mass was studied in an adult ovariectomized (OVX) rat model. One-year-old female rats were allocated randomly to the following groups: start control, sham OVX, OVX without vibration, OVX with vibration at 17 Hz (0.5g), OVX with vibration at 30 Hz (1.5g), OVX with vibration at 45 Hz (3.0g). Vibrations were given 30 min/day for 90 days. During vibration each group of rats was placed in a box on top of the vibration motor. The amplitude of the vibration motor was 1.0 mm. The animals were labeled with calcein at day 63 and with tetracycline at day 84. The tibia middiaphysis was studied by mechanical testing and dynamic histomorphometry and the femur distal metaphysis by mechanical compression. OVX without vibration increased the periosteal bone formation rate and increased the medullary cross-sectional area, i.e., increased the endocortical resorption and outward anteromedial and lateral drifts of cortical bone at the tibia middiaphysis. OVX also resulted in a reduced maximum bending stress of the tibia diaphysis and a reduced compressive stress of the femur distal metaphysis. Vibration at the highest intensity, i.e., 45 Hz, of OVX rats induced a further increase in periosteal bone formation rate and inhibited the endocortical resorption seen in OVX rats. Furthermore, vibration at 45 Hz inhibited the decline in maximum bending stress and compressive stress induced by OVX. Neither OVX nor OVX with vibration influenced skeletal muscle mass. In conclusion, the results support the idea of a possible beneficial effect of passive physical loading on the preservation of bone in OVX animals.

Animals↗
PubMed2001

The effect of monocyclic and bicyclic analogs of human parathyroid hormone (hPTH)-(1-31)NH2 on bone formation and mechanical strength in ovariectomized rats.

The [Leu27]cyclo(Glu22-Lys26)-hPTH-(1-31)NH2 lactam is a stronger stimulator of adenylyl cyclase activity and a better stimulator of trabecular bone in the ovariectomized (OVX) rat model of osteopenia than hPTH-(1-31)NH2. This enhanced activity is due in large part to the stabilization of the amphiphilic receptor-binding alpha-helix in the Ser17-Gln29 region. The goal of the present study was to determine whether further cyclization could produce a more active hPTH analog. To this end, we compared the relative bioactivities of the bicyclic hPTH analog [Glu17,Leu27]cyclo(Lys13-Glu17,Glu22-Lys26)-hPTH-(1-31)NH2, made by replacing Ser17 with Glu17 and introducing a second lactam linkage between Lys13 and Glu17. The relative EC50 for adenylyl cyclase stimulation by the bicyclic hPTH analog was similar to the EC50 of the monocyclic [Leu27]cyclo(Glu22-Lys26)-hPTH-(1-31)NH2, but the bicyclic analog was still more active than hPTH-(1-31)NH2. As expected from adenylyl cyclase stimulation being responsible for PTH's anabolic action, the bicyclic hPTH analog [Glu17, Leu27]cyclo(Lys13-Glu17, Glu22-Lys26)-hPTH-(1-31)NH2 was able to increase femoral trabecular volume and thickness and mechanical strength in OVX rats, but it was no more effective than [Leu27]cyclo(Glu22-Lys26)-hPTH-(1-31)NH2 when injected once daily in a dose of 0.8 nmol/100 g body weight. Thus, further constraint of the conformation of hPTH-(1-31)NH2 by introducing two lactam link-ages between Lys13-Glu17 and Glu22-Lys26 did not raise the osteogenicity above that of the monocyclic analog.

Adenylyl Cyclases↗
PubMed2001

Statin given perorally to adult rats increases cancellous bone mass and compressive strength.

Recently, it has been shown that statins increased cancellous bone formation and volume in 3-month-old rats and induced a minor decrease in osteoclast number. In the present study, one-year-old female rats were given simvastatin (10 mg/kg) or placebo daily for 3 months by a gastric tube. Specimens, 2.0 mm high, were cut transversely from the 5th lumbar vertebral body. The cancellous bone core diameters within the cortical shell of each specimen were delineated by a micro-CT scanner and then the cancellous bone was compressed in a materials testing machine between an upper and a lower platen with a diameter corresponding to the diameter of the cancellous bone core of each specimen. The cancellous bone volume was determined histomorphometrically on transverse sections. The cancellous bone volume in the simvastatin group (52.7 +/- 1.6%, mean value +/- SEM) was increased by 23% compared with the placebo group (42.8 +/- 1.7%). The compressive stress of the cancellous bone from the simvastatin group (31.8 +/- 2.7 MPa) was increased by 24% compared with the placebo group (24.1 +/- 1.9 MPa). No changes were found in cortical bone mass and strength after the statin treatment. In conclusion, statin given perorally to adult rats increased cancellous bone mass and increased cancellous bone compressive strength. The cancellous bone was found to possess normal biomechanical competence after the statin treatment.

Administration, Oral↗
PubMed2001

The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats.

The ability of the growth hormone secretagogue (GHS) Ipamorelin to counteract the catabolic effects of glucocorticoid (GC) on skeletal muscles and bone was investigated in vivo in an adult rat model. Groups of 8-month-old female rats were injected subcutaneously for 3 months with GC (methylprednisolone) 9 mg/kg/day or GHS (Ipamorelin) 100 microg/kg three times daily, or both GC and GHS in combination. The maximum tetanic tension of the calf muscles was determined in vivo in a materials testing machine. The maximum tetanic tension was increased significantly, and the periosteal bone formation rate increased four-fold in animals injected with GC and GHS in combination, compared with the group injected with GC alone. In conclusion, the decrease in muscle strength and bone formation found in GC-injected rats was counteracted by simultaneous administration of the growth hormone secretagogue.

Animals↗
PubMed2001

Increases in callus formation and mechanical strength of healing fractures in old rats treated with parathyroid hormone.

We studied the effects of intermittent administration of parathyroid hormone (PTH(1-34)) on callus formation and mechanical strength of tibial fractures in 27-month-old rats after 3 and 8 weeks of healing. 200 microg PTH(1-34)/kg was administered daily during both periods of healing, and control animals with fractures were given vehicle. At 3 weeks, PTH treatment increased maximum load and external callus volume by 160% and 208%; at 8 weeks, by 270% and 135%. It also enhanced callus bone mineral content (BMC) by 190% and 388% (3 and 8 weeks). From week 3 to week 8, callus BMC increased by 60% in the vehicle-injected animals, and by 169% in the PTH-treated animals. In the contralateral intact tibia, PTH treatment increased BMC by 18% and 21% (3 and 8 weeks). No differences in body weight were found between the vehicle-injected and the PTH-treated animals during the experiment. In conclusion, PTH treatment enhances fracture strength, callus volume and callus BMC after 3 and 8 weeks of healing.

Animals↗
PubMed2001

Growth hormone treatment promotes guided bone regeneration in rat calvarial defects.

This study evaluated the biomechanical strength and bone formation in calvarial critical size bone defects covered with expanded polytetrafluoroethylene (e-PTFE) membranes in rats treated systemically with recombinant human growth hormone (rhGH). A full-thickness bone defect, 5 mm in diameter, was trephined in the central part of each parietal bone in 40 one-year-old female Wistar rats, which were randomly assigned to two groups of 20 animals each. The bone defects were covered with an exocranial and an endocranial e-PTFE membrane. From the day of operation, the rhGH-treated animals were given 2.7 mg rhGH/kg/day and the placebo-injected rats were given isotonic sodium chloride. The animals were killed 28 days after operation. The biomechanical test was performed by a punch out test procedure placing a 3.5-mm diameter steel punch in the centre of the right healed defect. After mechanical testing, the newly formed tissue inside the defect was removed and the dry and ash weights were measured. The left healed defects were used for three-dimensional (3D) reconstruction by means of micro-computer tomography (micro-CT). Ultimate load, ultimate stiffness, and energy absorption at ultimate load were significantly increased in the rhGH-treated group (P < 0.003). Also, tissue dry and ash weights were significantly augmented in the rhGH-treated group (P < 0.001). The 3D reconstruction of newly formed bone showed that there was almost twice as much bone volume present in the rhGH-treated defects compared with the placebo group. The experiment demonstrated that rhGH administration enhances bone deposition and mechanical strength of healing rat calvarial defects, covered with e-PTFE membranes.

Animals↗
PubMed2000

Strong effect of PTH (1-34) on regenerating bone: a time sequence study in rats.

This study compares the effects of parathyroid hormone (PTH) treatment on new bone formation and normal baseline remodelling in rats. To study new bone formation we used a titanium bone chamber, and to study normal remodelling we used the femur and vertebrae from the same animals. One titanium bone chamber was inserted in the proximal tibia of each of 37 rats. The rats were randomly assigned to daily injections of human PTH (1-34) 60 microg/kg) or vehicle control and killed after 2, 4 or 6 weeks. The total distance of bone growth into the chamber was slightly increased by PTH. Body weight was not affected, and there was only a minor increase in trabecular density of the vertebral and femoral cancellous bone after 6 weeks. The only dramatic effect of PTH was seen in the chambers. In the controls, a marrow cavity formed in the chamber so that the cancellous density decreased from 44% to 24%, and 11% over 2, 4 and 6 weeks. In the PTH-treated animals, a dense network of bone trabeculae was found in the entire bone chamber at all times. The cancellous density increased from 48% to 60%, and 73% at 2, 4 and 6 weeks, respectively. The results suggest that PTH treatment can reduce the development of a resorption cavity. Thus, PTH in this model had a net antiresorptive effect, probably solely because it stimulated osteoblastic activity. Even though osteoclastic activity was present throughout the PTH specimens, it was not sufficient to resorb all newly formed bone. Since PTH seemed to have a greater effect on new bone formation in the chamber than on normal bone remodeling, it might become useful for improving the incorporation of orthopedic implants and stimulating fracture repair.

Animals↗
PubMed2000

Parathyroid hormone (1-34) increases the density of rat cancellous bone in a bone chamber. A dose-response study.

Intermittent treatment with parathyroid hormone I(PTH) has an anabolic effect on both intact cancellous and cortical bone. Very little is known about the effect of the administration of PTH on the healing of fractures or the incorporation of orthopaedic implants. We have investigated the spontaneous ingrowth of callus and the formation of bone in a titanium chamber implanted at the medioproximal aspect of the tibial metaphysis of the rat. Four groups of ten male rats weighing approximately 350 g were injected with human PTH (1-34) in a dosage of 0, 15, 60 or 240 microg/kg/day, respectively, for 42 days from the day of implantation of the chamber. During the observation period the chamber became only partly filled with callus and bone and no difference in ingrowth distance into the chamber was found between the groups. The cancellous density was increased by 90%, 132% and 173% in the groups given PTH in a dosage of 15, 60 or 240 microg/kg/day, respectively. There was a linear correlation between bone density and the log PTH doses (r 2= 0.6). Our findings suggest that treatment with PTH may have a potential for enhancement of the incorporation of orthopaedic implants as well as a beneficial effect on the healing of fractures when it is given in low dosages.

Animals↗
PubMed2000

The influence of combined parathyroid hormone and growth hormone treatment on cortical bone in aged ovariectomized rats.

The influence of combined parathyroid hormone (PTH) and growth hormone (GH) treatment on bone formation and mechanical strength was investigated in femoral middiaphysial cortical bone from 20-month-old ovariectomized (OVX) rats. The animals were OVX at 10 months of age, and at 18 months they were treated daily for 56 days with PTH(1-34) alone (60 microg/kg), recombinant human GH (rhGH) alone (2.7 mg/kg), or a combination of PTH(1-34) plus rhGH. Vehicle was given to OVX control rats. All animals were labeled at day 28 (calcein) and at day 49 (tetracycline) of the treatment period. PTH(1-34) alone gave rise to formation of a new zone of bone at the endocortical surface. rhGH alone caused substantial bone deposition at the periosteal surface without influencing the endocortical surface. Combined PTH(1-34) plus rhGH administration enhanced bone deposition at the periosteal surface to the same extent as that of rhGH alone. However, the combined treatment resulted in a more pronounced formation of new bone at the endocortical surface than was induced by PTH(1-34) alone. Both PTH(1-34) alone and rhGH alone increased the mechanical strength of the femoral diaphysis, and further increase in mechanical strength resulted from combined PTH(1-34) plus rhGH treatment. OVX by itself induced the characteristic increase in medullary cavity cross-sectional area and a minor decrease in the mechanical quality of the osseous tissue.

Age Factors↗
PubMed2000

Growth hormone and mild exercise in combination increases markedly muscle mass and tetanic tension in old rats.

OBJECTIVE: A decline of skeletal muscle mass and strength is seen with aging and immobilization. Growth hormone (GH) has been shown to increase muscle mass. In the present study the effects of a combination of mild exercise and GH on skeletal musculature tetanic tension, dry defatted weight (DDW), volume, water, fat and collagen concentrations were investigated in old rats. DESIGN: Recombinant human GH (2.7mg/kg per day) was injected subcutaneously for 73 days in 21-month-old female rats. Exercised rats ran on a treadmill, 8 m/min for 1 h/day. The in vivo maximal tetanic tension of the calf musculature (m. soleus, m. plantaris, m. gastrocnemius together) was analysed in anaesthetized rats by stimulating the ischiadic nerve. RESULTS: The maximal tetanic tension was increased by 23% in GH-injected compared to saline-injected rats. Mild exercise + GH in combination resulted in a further 18% increase in maximal tetanic tension. The mild exercise by itself did not influence the maximal tetanic tension significantly when compared with saline injected rats. The GH administration and/or mild exercise did not change skeletal muscle endurance, measured as tetanic tension during 30s of stimulation. Serum IGF-I concentration was increased twofold in GH-injected rats. CONCLUSION: The increased muscle mass induced by GH + mild exercise was associated with a corresponding increase in maximal tetanic tension. Combination of GH + mild exercise resulted in a substantial further increase of muscle mass and maximal tension compared with GH injections alone in these old rats.

Adipose Tissue↗
PubMed1999

Strength of colonic anastomoses and skin incisional wounds in old rats - influence by diabetes and growth hormone.

The influence of advanced age on the mechanical strength of colonic anastomoses and skin incisional wounds in diabetic rats was investigated after 0 (suture binding capacity) and after 7 days of healing. Furthermore, the effects of growth hormone (GH) injections to old diabetic rats were investigated. Diabetes in old rats did not influence the strength of colonic anastomoses after 0 and 7 days. However, in these diabetic animals, the strength of skin incisional wounds was reduced by 27% after 7 days of healing (P< 0.01). GH injections administered to old diabetic rats doubled the mortality compared with that of saline-injected old diabetic rats (P< 0.01). GH injections did not influence the strength formation of either colonic anastomoses or skin incisional wounds in old normal rats. In conclusion, the healing of colonic anastomoses in diabetic rats was not compromised by old age, while the strength of skin wounds was decreased.

Abdominal Injuries↗
PubMed1999

Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats.

Ipamorelin is a new and potent synthetic pentapeptide which has distinct and specific growth hormone (GH)-releasing properties. With the objective of investigating the effects on longitudinal bone growth rate (LGR), body weight (BW), and GH release, ipamorelin in different doses (0, 18, 90 and 450 microg/day) was injected s.c. three times daily for 15 days to adult female rats. After intravital tetracycline labelling on days 0, 6, and 13, LGR was determined by measuring the distance between the respective fluorescent bands in the proximal tibia metaphysis. Ipamorelin dose-dependently increased LGR from 42 microm/day in the vehicle group to 44, 50, and 52 microm/day in the treatment groups (P<0.0001). There was also a pronounced and dose-dependent effect on BW gain. The treatment did not affect total IGF-I levels, IGFBPs, or serum markers of bone formation and resorption. The number of tartrate-resistant acid phosphatase-positive multinuclear cells in the metaphysis of the tibia did not change significantly with treatment. The responsiveness of the pituitary to a provocative i.v. dose of ipamorelin or GHRH showed that the plasma GH response was marginally reduced (P<0.03) after ipamorelin, but unchanged after GHRH. The pituitary GH content was unchanged by ipamorelin treatment. Whether ipamorelin or other GH secretagogues may have a place in the treatment of children with growth retardation requires demonstration in future clinical studies.

Animals↗
PubMed1999

Effect of experimental diabetes and growth hormone administration on the strength of colonic anastomoses in rats.

The influence of growth hormone (GH; 2 mg/kg/day) administration on the mechanical breaking strength of colonic anastomoses in diabetic rats has been investigated on the day of operation (suture binding capacity) and after 4 and 7 days of healing. In diabetic rats, the suture binding capacity was decreased by 26% in both ultimate load and relative failure energy. After 4 days of healing, no difference was observed between control and diabetic animals. After 7 days, relative failure energy in the diabetic animals was reduced by 33%. GH administration to diabetic animals did not alter strength during the first week of healing. We found an increased circumference (33%) and defatted dry weight (22%) of the colon in diabetic rats. In conclusion, diabetes impairs the suture-binding capacity of the colon in rats, while there is only little influence on healing in the following week. GH administration could not influence the strength of colonic anastomoses in diabetic animals.

Anastomosis, Surgical↗
PubMed1999

Growth hormone increases cortical and cancellous bone mass in young growing rats with glucocorticoid-induced osteopenia.

The effects of growth hormone (GH) on linear growth, bone formation, and bone mass have been examined in glucocorticoid (GC)-injected young growing rats. Two-month-old female Wistar rats were injected for 90 days with 1, 3, 6, or 9 mg of methylprednisolone alone or in combination with 5 mg of GH. Bone mass and bone formation parameters were examined in the femoral cortical bone and in cortical bone and cancellous bone of the lumbar vertebra. GC administration dose dependently decreased growth, longitudinal growth of the vertebra, as well as the modeling drift of the cortical bone of the vertebral body and femoral diaphysis. In the vertebral cancellous bone, GC also decreased the mineralizing surface and inhibited the growth-related increase in cancellous bone volume. GH increased growth, longitudinal growth of the vertebra, as well as the modeling drift of the vertebral body and the femoral diaphysis, resulting in an increased cortical bone mass. GH also increased cancellous bone volume and the mineralizing surface of the vertebral body. In GC-injected animals, GH normalized and further increased growth, longitudinal growth, and the modeling drift of both the femoral diaphysis and the vertebral body, resulting in an increased cortical bone mass at both locations. GH also increased cancellous bone volume of the vertebral body in GC-injected animals, but GH did not, however, reverse the decreased mineralizing surface of cancellous bone induced by GC injections. In conclusion, GC administration to growing rats retards normal growth, longitudinal growth, and cortical bone modeling drift. It also decreases the cancellous bone mineralizing surface and inhibits the normal age-related increase in cancellous bone volume of the vertebral body. In the growing rat skeleton, GH can counteract these GC-induced side effects, except for the GC-induced decrease in the mineralizing surface of cancellous bone of the vertebral body, which remained unaffected by GH administration.

Animals↗
PubMed1999

Intermittent parathyroid hormone (1-34) treatment increases callus formation and mechanical strength of healing rat fractures.

The influence of intermittent parathyroid hormone (PTH(1-34)) administration on callus formation and mechanical strength of tibial fractures in rats was investigated after 20 and 40 days of healing. A dose of 60 microg of PTH(1-34)/kg/day and 200 microg of PTH(1-34)/kg/day, respectively, was administered during the entire periods of healing, and control animals with fractures were given vehicle. The dose of 200 microg of PTH(1-34)/kg/day increased the ultimate load and the external callus volume of the fractures by 75% and 99%, respectively, after 20 days of healing and by 175% and 72%, respectively, after 40 days of healing. The dose of 60 microg of PTH(1-34)/kg/day did not influence either ultimate load or external callus volume of the fractures after 20 days of healing, but the ultimate load was increased by 132% and the external callus volume was increased by 42% after 40 days of healing. During the healing period, the callus bone mineral content (BMC) increased in all groups. After 40 days of healing, the callus BMC was increased by 108% in the 200 microg of PTH(1-34)/kg/day group and by 76% in the 60 microg of PTH(1-34)/kg/day group. Both doses of PTH(1-34) steadily augmented the contralateral intact tibia BMC (20 days and 40 days: 60 microg of PTH (1-34)/kg/day 9% and 19%, respectively; 200 microg of PTH (1-34)/kg/day 12% and 27%, respectively) and bone mineral density (20 days and 40 days: 60 microg of PTH(1-34)/kg/day 11% and 12%, respectively; 200 microg of PTH(1-34)/kg/day 11% and 15%, respectively).

Animals↗
PubMed1998

Bisphosphonate maintains parathyroid hormone (1-34)-induced cortical bone mass and mechanical strength in old rats.

This study was designed to determine the fate of new parathyroid hormone (PTH)-induced cortical bone after withdrawal of PTH treatment, and to evaluate whether subsequent treatment with a bisphosphonate would influence this. Six groups of 21-month-old rats were used: a baseline group killed at the beginning of the experiment, three groups injected with human PTH (1-34) (62 mug/kg) daily for 8 weeks (day 1-56), then one group was killed and the other two groups were injected for another 8 weeks (day 57-112) with either saline or bisphosphonate (risedronate 5 mug/kg twice a week). Two control groups were injected with vehicle for the first 8 weeks, then one group was killed and the other group injected with saline the next 8 weeks. All animals were labeled with tetracycline and calcein on day 35 and day 49 of the experiment, respectively. PTH increased periosteal (35%) and in particular endosteal mineralizing surfaces (188%), mineral appositional rates, and bone formation rates at the femur diaphysis, leading to an increase in cortical cross-sectional area of 31%. Withdrawal of PTH induced a fast and pronounced endosteal bone resorption whereas risedronate prevented this resorption. No differences were seen in apparent density of dry defatted bone and ash among the groups. PTH increased the mechanical strength of the femur diaphysis; ultimate load increased by 64% and ultimate stress by 25%. A pronounced decrease in mechanical strength and competence was found after withdrawal of PTH: ultimate load decreased by 31% and ultimate stress by 21%. Risedronate, however, prevented this decrease in mechanical strength and competence in these 2-year-old rats.

Animals↗
PubMed1998

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↗