Search PubMed⌕ Search

Biomedical subjects

H A W Hazewinkel

Publications and source records attributed to H A W Hazewinkel.

12 recordsLinked to original sources
PubMed2006

Growth hormone stimulates bone healing in a critical-sized bone defect model.

Growth hormone plays an important role in bone metabolism. Treating bone deficits is a major topic in orthopaedic surgery. Our hypothesis was that local continuous growth hormone administration stimulates bone healing in a canine critical-sized bone defect model. Bone formation in the defects was quantified using densitometric image analysis and histomorphometry. After growth hormone treatment, expression levels of insulin-like growth factors-I and II, and growth hormone receptor were determined in the bone regenerate of the original defects. Circulating plasma concentrations of insulin-like growth factors-I and II, and insulin- like growth factor binding proteins-4, and 6 were measured during treatment. Growth hormone administration resulted in healing of bone defects but without an additional effect of local infusion. Expression of insulin-like growth factor-I in the bone regenerate was lower in the growth hormone-treated dogs, whereas insulin-like growth factor-II and growth hormone receptor expression were not increased. Growth hormone increased circulating insulin-like growth factor-I and growth factor-II plasma concentrations. Continuous infusion of growth hormone stimulated bone healing in a canine critical-sized bone defect model. Local delivery of growth hormone did not additionally enhance bone healing. Increased circulating plasma concentrations of insulin-like growth factors-I and II most likely induced bone formation.

Animals↗
PubMed2005

[Puppy feed].

Explore the source record for details and available documents.

Animal Feed↗
PubMed2004

Different effects of physiologically and pharmacologically increased growth hormone levels on cholecalciferol metabolism at prepubertal age.

The aim of the study was to investigate the influence of physiologically and pharmacologically increased plasma growth hormone (GH) levels on cholecalciferol metabolism at prepubertal age. Three groups of dogs raised on the same diet were studied from weaning till 21 weeks of age, i.e., small breed dogs (n = 7, control group); large breed dogs with 15-fold greater growth rates compared to the control group (n = 8, LB-group); and small breed dogs treated with pharmacological doses of growth hormone (n = 6, GH-group; 0.5IU GH per kg body per day) from 12 to 21 weeks of age. Excess of GH had the expected anabolic effect on growth rate and phosphate sparing. Increased plasma GH levels in the LB- and GH-groups versus the control group were accompanied by (1) greater plasma insulin-like growth factor I (IGF-I) levels, (2) greater plasma 1,25-dihydroxycholecalciferol (1,25(OH)(2)D(3)) levels, and (3) lower plasma 24,25(OH)(2)D(3) levels. In the LB-group, excess of GH favored plasma 1,25(OH)(2)D(3) levels by decreasing the clearance of 1,25(OH)(2)D(3), whereas in the GH-group by increasing the production of 1,25(OH)(2)D(3). The lowered plasma 24,25(OH)(2)D(3) levels in the LB- and GH-groups were likely attributed to a competitive inhibition of the production of 24,25(OH)(2)D(3) by GH and/or IGF-I.

Animals↗
PubMed2003

Reduced dosage of ketoprofen for the short-term and long-term treatment of joint pain in dogs.

Two studies were conducted under laboratory conditions with 16 dogs to investigate the analgesic effectiveness of a low dose of ketoprofen in a short-term sodium urate crystal-induced synovitis model of arthritis. The effect of the treatment, defined as the improvement in peak vertical force weight bearing was evaluated in the first study at three dose levels. A single oral dose of 0.25 mg/kg ketoprofen was significantly better (P < 0.01) than the control (0 mg), but doses of 0.5 and 0.75 mg/kg did not improve the dogs' weight bearing further. The second study investigated the efficacy and safety of the 0.25 mg/kg dose administered daily for 30 days. The beneficial effects of ketoprofen at this dose were constant, with the treated dogs bearing 89.1 per cent of the baseline vertical force four hours after the induction of arthritis on day 1 and 92.2 per cent on day 29, compared with 42 per cent and 34 per cent of the baseline in the untreated dogs. No gastrointestinal or other side effects were observed during the treatment.

Animals↗
PubMed2003

Dietary 135-fold cholecalciferol supplementation severely disturbs the endochondral ossification in growing dogs.

The effects of excessive non-toxic dietary Vitamin D(3) supplementation on Ca homeostasis with specific effects on endochondral ossification and skeletal remodeling were investigated in a group of growing Great Dane dogs supplemented with cholecalciferol (Vitamin D(3); HVitD) versus a control group (CVitD) (1350 microg versus 11.4 microg Vitamin D(3) per kilogram diet) from 6 to 21 weeks of age. There were no differences between groups in plasma concentrations of total Ca, inorganic phosphate, growth hormone, and insulin-like growth factor I and no signs of Vitamin D(3) intoxication in HVitD. For the duration of the study in HVitD compared to CVitD, plasma levels of parathyroid hormone (PTH) decreased, calcitonin (CT) increased, 25-hydroxycholecalciferol [25(OH)D(3)] increased 30- to 75-fold, 24,25-dihydroxycholecalciferol [24,25(OH)(2)D(3)] increased 12- to 16-fold, and 1,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)] decreased by approximately 40%. The latter was attributed to the two-fold increased metabolic clearance rate in the HVitD versus CVitD accompanied by the absence of the anabolic effect of PTH on the production of 1,25(OH)(2)D(3). Fractional Ca absorption (alpha) did not differ between groups at 8 and 14 weeks of age, whereas at 20 weeks of age alpha increased by only 16.4% in HVitD compared to CVitD. Excessive non-toxic Vitamin D(3) supplementation resulted in decreased bone remodeling and focal enlargement of the growth plate with morphology resembling those induced by administration of CT. Hypercalcitoninemia and the imbalanced relationship between 1,25(OH)(2)D(3) and 24,25(OH)(2)D(3) are potent candidates for the disturbed endochondral ossification.

24,25-Dihydroxyvitamin D 3↗
PubMed2003

Growth hormone modulates cholecalciferol metabolism with moderate effects on intestinal mineral absorption and specific effects on bone formation in growing dogs raised on balanced food.

The aim of the study was to investigate the influence of growth hormone (GH) on Vitamin D3 metabolism and the subsequent effects on calcium (Ca) homeostasis and skeletal growth in growing dogs. A group of Miniature Poodles received supraphysiological doses of GH (GH group; n = 6; 0.5 IU GH per kg body per day) from 12 to 21 weeks of age and was compared with a control placebo-treated group (n = 8). Biologic activity of GH in the GH compared to the control group was indicated by (a) the 2.5- to 3.5-fold increase in the plasma concentrations of insulin-like growth factor I (IGF-I), (b) the increased production of 1,25-dihydroxycholecalciferol as indicated by the significantly increased plasma 1,25-dihydroxycholecalciferol concentrations and the 12.9-fold increase in renal 1alpha-hydroxylase gene expression, and (c) the inhibited production of 24,25-dihydroxycholecalciferol as indicated by the significantly lower plasma 24,25-dihydroxycholecalciferol concentrations and the similar levels of renal 24-hydroxylase gene expression. Despite the distinct effects on Vitamin D(3) metabolism in the GH group, there were only moderate effects on the intestine, i.e. at 20 weeks of age there was a significant increase of 14.4 and 5.6% in fractional absorption of Ca and phosphate (Pi), respectively, compared to the control group. GH administration resulted in significantly elevated glomerular filtration rate, with no differences in Pi urine excretion as a result of a concomitant increase in the tubular reabsorption of Pi. GH had only limited disturbing effects on endochondral ossification as indicated by the maintenance of the regularity of the growth plates. However, GH had specific anabolic effects on bone formation without concomitant effect on bone resorption that may result in disorders of skeletal remodeling and manifestation of enostosis.

Analysis of Variance↗
PubMed2003

Hormonal regulation of calcium homeostasis in two breeds of dogs during growth at different rates.

Growing giant-breed dogs are more susceptible to developing skeletal disorders than small-breed dogs when raised on diets with deficient or excessive Ca content. Differential hormonal regulation of Ca homeostasis in dogs with different growth rates was investigated in Great Danes (GD, n = 9) and Miniature Poodles (MP, n = 8). All animals were raised on the same balanced diet and under identical conditions. Calciotropic and growth-regulating hormones were measured. Production and clearance of 1,25-dihydroxycholecalciferol (1,25[OH]2D3) were investigated with the aid of [3H]-1,25(OH)2D3 and renal messenger RNA abundance of 1 alpha-hydroxylase and 24-hydroxylase. Intestinal, renal, and skeletal Ca handling were evaluated with the aid of 45Ca balance studies. Skeletal development was evaluated by radiology and histomorphometry. Great Danes had greater (P < 0.001) growth rates than MP, as indicated by the 17-fold greater body weight gain, by increased longitudinal growth reflected in the increased (P < 0.05) gain in length of the radius and ulna, and by increased (P < 0.001) growth plate thickness. These findings were accompanied in GD by greater (P < 0.05) plasma GH and IGF-I concentrations. Effects were observed for vitamin D3 metabolism, such as greater (P < 0.01) plasma 1,25(OH)2D3 concentrations due to decreased (P < 0.01) clearance rather than increased production of 1,25(OH)2D3, and decreased (P < 0.01) plasma 24,25-dihydroxycholecalciferol (24,25[OH]2D3) concentrations likely due to competitive inhibition of the production of 24,25(OH)2D3. These findings were accompanied in both breeds by a limited hormonal regulation of Ca and P absorption at the intestinal level, and in GD by increased (P < 0.05) renal reabsorption of inorganic P (Pi) compared with MP, resulting in greater (P < 0.01) Pi retention and greater (P < 0.01) plasma Pi concentrations. Bone turnover, resorption, and formation were greater (P < 0.01) in GD than in MP. In addition, GD had more irregular (P < 0.01) growth plates than MP, accompanied by disorders of endochondral ossification. It is suggested that in GD, increased calcitonin levels and/or a relative deficiency in 24,25(OH)2D3 at the growth-plate level may both be responsible for the retarded maturation of chondrocytes, resulting in retained cartilage cones and osteochondrosis, and this may be a pathophysiological factor for the increased susceptibility of large breed dogs to developing skeletal disorders.

Aging↗
PubMed2002

Vitamin D3 metabolism in dogs.

Plasma concentrations of the main vitamin D(3) metabolites (i.e., 25(OH)D(3), 1,25(OH)(2)D(3), and 24,25(OH)(2)D(3)) were measured in 14 weeks old large- and small-breed dogs (adult body weight 60 kg vs. 6 kg), raised under the same conditions. Levels of 25(OH)D(3) (approx. 22 microg/l) and 1,25(OH)(2)D(3) (approx. 40 ng/l) were similar in both groups, whereas plasma 24,25(OH)(2)D(3) concentrations were lower in large-breed dogs (7 microg/l vs. 70 microg/l, large- vs. small-breed dogs, respectively). The lower plasma 24,25(OH)(2)D(3) concentrations could be explained by the higher plasma GH and IGF-I concentrations in the large- vs. small-breed dogs, and these hormones are known to suppress 24-hydroxylation. Plasma 24,25(OH)(2)D(3) concentrations increased during Ca supplementation in small-breed but not in large-breed dogs (100 microg/l vs. 7 microg/l, respectively). Hypophosphatemia induced by a high dietary Ca content was only seen together with increased plasma 1,25(OH)(2)D(3) concentrations in euparathyroid dogs and not in hypoparathyroid dogs. Hyperparathyroidism due to Ca deficiency was accompanied by increased plasma 1,25(OH)(2)D(3) concentrations and decreased plasma 24,25(OH)(2)D(3) concentrations in both large- and small-breed dogs, together with generalized osteoporosis. Large-breed pups fed on a standard diet supplemented with Ca and P had decreased plasma concentrations of both 25(OH)D(3) and 1,25(OH)(2)D(3), which may indicate an increased clearance of these metabolites; the low plasma concentrations of the di-hydroxylated vitamin D metabolites were considered responsible for the disturbance in cartilage maturation (i.e., osteochondrosis) in these dogs. Even lower concentrations of all vitamin D(3) metabolites were seen in young dogs raised on a vitamin D(3)-deficient diet, and led to disturbed osteoid and cartilage mineralization (i.e., rickets). These studies indicate that there is a hierarchy of factors regulating vitamin D(3) metabolism in dogs, i.e., GH and IGF-I suppress 24-hydroxylase more than hypercalcemia or hypophosphatemia does; 1,25(OH)(2)D(3) and 24,25(OH)(2)D(3) are only reciprocally related in hyperparathyroidism; excessive Ca and P intake increases the turnover of vitamin D(3) metabolites; and the synergism between parathyroid hormone and 1,25(OH)D(3) seems to play a role in skeletal mineralization. The low plasma 24,25(OH)(2)D(3) concentrations in large-breed dogs raised on standard dog food may play a role in the etiology of disturbances in endochondral ossification during the rapid growth phase.

Animals↗
PubMed2002

24-Hydroxylase: potential key regulator in hypervitaminosis D3 in growing dogs.

A group of growing dogs supplemented with cholecalciferol (vitamin D(3); HVitD) was studied vs. a control group (CVitD; 54,000 vs. 470 IU vitamin D(3)/kg diet, respectively) from 3 to 21 wk of age. There were no differences in plasma levels of P(i) and growth-regulating hormones between groups and no signs of vitamin D(3) intoxication in HVitD. For the duration of the study in HVitD vs. CVitD, plasma 25-hydroxycholecalciferol levels increased 30- to 75-fold; plasma 24,25-dihydroxycholecalciferol levels increased 12- to 16-fold and were accompanied by increased renal 24-hydroxylase gene expression, indicating increased renal 24-hydroxylase activity. Although the synthesis of 1,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)] was increased in HVitD vs. CVitD (demonstrated by [(3)H]1,25(OH)(2)D(3) and increased renal 1alpha-hydroxylase gene expression), plasma 1,25(OH)(2)D(3) levels decreased by 40% as a result of the even more increased metabolic clearance of 1,25(OH)(2)D(3) (demonstrated by [(3)H]1,25(OH)(2)D(3) and increased gene expression of intestinal and renal 24-hydroxylase). A shift of the Ca set point for parathyroid hormone to the left indicated increased sensitivity of the chief cells. Effective counterbalance was provided by hypoparathyroidism, hypercalcitoninism, and the key regulator 24-hydroxylase, preventing the development of vitamin D(3) toxicosis.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed2002

Intestinal calcium absorption in growing dogs is influenced by calcium intake and age but not by growth rate.

The effects of calcium (Ca) intake (V(I)), age and growth rate on intestinal Ca absorption were studied in growing dogs. Two breeds of dogs differing in their growth rate (67 Great Danes and 23 Miniature Poodles) were raised on diets differing only in their Ca content (range 0.33 to 3.3 g/100 g diet on a dry matter basis). Repetitive Ca balance studies were performed with the aid of (45)Ca from 6 wk (i.e., after weaning) until 6 mo of age. Several models were investigated expressing true Ca absorption (V(a)) as a function of V(I), breed and age. V(a) was directly proportional to a function close to V(I)(0.82) being a continuation of the high Ca needs for mineralization of the growing skeleton. This curvilinear relationship between V(a) and V(I) and the inverse relationship between fractional Ca absorption and V(I) indicated the presence of active and passive Ca absorption in weaned growing dogs. A model in which these two components of Ca absorption can be discerned revealed that active Ca absorption underwent age-dependent changes, whereas passive absorption remained constant and accounted for 53% absorption of the V(I). At low V(I), active absorption contributed to a significant part of the V(a), whereas at excessive V(I) active absorption was negligible and passive absorption was the driving force for causing supra positive Ca balance. Intestinal Ca handling did not differ between breeds with dramatically different mature body size and growth rates.

Aging↗
PubMed2002

Moderate cholecalciferol supplementation depresses intestinal calcium absorption in growing dogs.

Hormonal regulation of calcium (Ca) absorption was investigated in a cholecalciferol (vitamin D(3))-supplemented group (hVitD) vs. a control group (cVitD) of growing Great Danes (100 vs. 12.5 micro g vitamin D(3)/kg diet). Although Ca intakes did not differ, fractional Ca absorption was significantly lower in the hVitD group than in the cVitD group. There were no differences in plasma concentrations of Ca, inorganic phosphate, parathyroid hormone, growth hormone or insulin-like growth factor I between groups. Plasma 25-hydroxycholecalciferol [25(OH)D(3)] concentrations were maintained in the hVitD dogs at the same levels as in the cVitD dogs due to increased turnover of 25(OH)D(3) into 24,25-dihydroxycholecalciferol [24,25(OH)(2)D(3)] and 1,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)]. In hVitD dogs, the greater plasma 24,25(OH)(2)D(3) concentration and the enhanced metabolic clearance rate (MCR) of 1,25(OH)(2)D(3) indicated upregulated 24-hydroxylase activity. The increased MCR of 1,25(OH)(2)D(3) decreased plasma 1,25(OH)(2)D(3) concentrations. In hVitD dogs, the greater production rate of 1,25(OH)(2)D(3) was consistent with the 12.9-fold greater renal 1alpha-hydroxylase gene expression compared with cVitD dogs and compensated to a certain extent for the accelerated MCR of 1,25(OH)(2)D(3). The moderately decreased plasma 1,25(OH)(2)D(3) concentration can only partially explain the decreased Ca absorption in the hVitD dogs. Intestinal vitamin D receptor concentrations did not differ between groups and did not account for the decreased Ca absorption. We suggest that 24,25(OH)(2)D(3) may downregulate Ca absorption.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗