PubMed Health⌕ Search

Biomedical subjects

W E van den Brom

Publications and source records attributed to W E van den Brom.

At least 19 recordsLinked to original sources

Effect of octreotide on plasma concentrations of glucose, insulin, glucagon, growth hormone, and cortisol in healthy dogs and dogs with insulinoma.

The inhibitory effect of the somatostatin analogue octreotide on the secretion of insulin could be used in the treatment of insulinoma. However, current information on the effectiveness of octreotide in dogs is conflicting. Therefore, the endocrine effects of a single subcutaneous dose of 50 microg octreotide were studied in healthy dogs in the fasting state (n=7) and in dogs with insulinoma (n=12). Octreotide did not cause any adverse effects. In healthy dogs in the fasting state, both plasma insulin and glucagon concentrations declined significantly. Basal (non-pulse related) GH and ACTH concentrations were not affected. A slight but significant decrease in the plasma glucose concentrations occurred. Dogs with insulinoma had significantly higher baseline insulin concentrations and lower baseline glucose concentrations than healthy dogs in the fasting state. Plasma glucagon, GH, ACTH, and cortisol concentrations did not differ from those in healthy dogs. Baseline plasma insulin concentrations decreased significantly in dogs with insulinoma after octreotide administration, whereas plasma concentrations of glucagon, GH, ACTH, and cortisol did not change. In contrast to the effects in the healthy dogs, in the dogs with insulinoma plasma glucose concentrations increased. Thus, the consistent suppression of plasma insulin concentrations in dogs with insulinoma, in the absence of an suppressive effect on counter-regulatory hormones, suggests that further studies on the effectiveness of slow-release preparations in the long-term medical treatment of dogs with insulinoma are warranted.

Animals↗

Immunophenotyping of the cutaneous cellular infiltrate after atopy patch testing in cats with atopic dermatitis.

Cats with spontaneously occurring atopic dermatitis have clinical and immunocytochemical characteristics compatible with these in humans with atopic dermatitis (AD). The atopy patch test (APT) has proven to be a valuable tool in elucidating the disease process in humans. Additionally, the APT is very specific and bypasses the problem of conflicting results due to differences in chronicity of lesions of AD patients. We adapted the APT for use in cats to explore the suitability of the APT as a tool to study the onset of allergic inflammation in cats with atopic dermatitis. APT were performed in AD cats (n = 6) and healthy cats (n = 10). All cats were patch tested with two allergens in three different dilutions and a diluent control. The allergens for the APT were selected from positive intradermal test and /or prick test results and consisted of: Dermatophagoides farinae, D. pteronyssinus, Tyrophagus putrescentiae, and a grass pollen mixture. APT were read after 10, 24 and 48 h, and punch biopsies for immunohistochemical evaluation were collected at these time points. Macroscopically positive APT reactions were observed in three out of six cats at 24 and/or 48 h with allergen concentrations of 25,000 and 100,000 NU/ml. Reactions were not observed at negative control sites and neither in control animals. A significantly increased number of IL-4+, CD4+, CD3+, MHC class II+ and CD1a+ cells was found in one AD cat with positive APT reactions. Five out of six AD cats had significantly increased IL-4+ T cell numbers at 24 and/or 48 h. Our data indicate that in cats, macroscopically positive patch test reactions can be induced, which have a cellular infiltrate similar to that in lesional skin. We found a high specificity and a macroscopically positive APT reaction in half of the cats, which is similar to what is seen in humans. Hence, the APT in cats might be a useful tool in studying the immunopathogenesis of feline atopic dermatitis.

Allergens↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

The rat vertex-middle latency auditory-evoked potential as indicator of anaesthetic depth: a comparison with evoked-reflex testing.

We investigated whether components from the rat Vx-MLAEP could be used to assess depth of anaesthesia induced by propofol. Propofol decreased MLAEP amplitudes and increased latencies. We propose that the P(16)-N(22) wave in the rat MLAEP is similar to the human P1, and that recovery of this wave during propofol anaesthesia correlates with behavioural measures of the regaining of consciousness.

Anesthesia↗

Ground reaction force analysis of large breed dogs when walking after the amputation of a limb.

Force plate analysis was used to measure ground reaction forces (GRF) and contact times, and calculate the centre of gravity at a walk of 10 dogs which had had a limb amputated, and the results were compared with the results from 22 normal dogs of the same weight. The loss of a limb caused significant changes in the GRF, impulses and contact times of the remaining limbs and in the location of the dogs' centre of gravity. The changes were greater in dogs which had lost a forelimb than in dogs which had lost a hindlimb.

Amputation, Surgical↗

Secretion pattern of thyroid-stimulating hormone in dogs during euthyroidism and hypothyroidism.

In as many as one third of dogs with primary hypothyroidism a plasma thyrotropin (TSH) concentration within the reference range for euthyroid dogs is found. To determine whether this is due to fluctuations in the release of TSH, the plasma profiles of TSH were analyzed in 7 beagle bitches by collecting blood samples every 10 min for 6 hr, both before and after induction of primary hypothyroidism. After induction of primary hypothyroidism, a 37-fold increase in mean basal plasma TSH concentration and a 34-fold increase in mean area under the curve for TSH were found. Analysis by the Pulsar program demonstrated pulsatile secretion of TSH in the hypothyroid state, characterized by relatively low amplitude pulses (mean [+/-SEM]) amplitude 41 +/- 3% of basal plasma TSH level) and a mean pulse frequency of 2.0 +/- 0.5 pulses/6 hr. In the euthyroid state, significant TSH pulses were identified in only 2 dogs. The mean basal plasma TSH level correlated positively (r = 0.84) with the mean amplitude of the TSH pulses, and correlated negatively (r = -0.88) with the TSH pulse frequency. The results of this study demonstrate pulsatile secretion of TSH in dogs during hypothyroidism and only small fluctuations in plasma TSH concentrations during euthyroidism. The findings also suggest that the low TSH values occasionally found in dogs with spontaneous primary hypothyroidism may in some cases in part be the result of ultradian fluctuations.

Animals↗

Clinical and radiographic findings compared with urodynamic findings in neutered female dogs with refractory urinary incontinence.

Possible correlations were investigated between the clinical and urodynamic findings in 77 neutered female dogs with urinary incontinence refractory to standard medical management. The clinical data used in the analysis were age, bodyweight, breed, the characteristics of the dribbling of urine and whether it developed before or after neutering, the type of response to previous treatments, signs of polyuria/polydipsia, and the results of urinalysis and culture. In 50 of the dogs, a standardised contrast radiographic examination was made to locate the neck of the bladder and to assess the morphology of the bladder. These findings were analysed for their correlation with the results of multichannel urethral pressure profilometry and diuresis cysto-urethrometry. Logistic regression analysis revealed that neither the clinical nor the radiographic findings could predict any of the abnormal urodynamic findings. Functional abnormalities of the bladder, such as a low compliance, detrusor instability, or a low bladder capacity may therefore be particularly difficult to detect in dogs with urinary incontinence.

Animals↗

Progressive remission of portosystemic shunting in 23 dogs after partial closure of congenital portosystemic shunts.

The congenital portosystemic shunts in 23 dogs were closed partially in 18 and completely in five with a single silk ligature. The clinical results were studied and the degree of portosystemic shunting was measured by a scintigraphic method, the results being expressed as the shunt index (SI). In 17 of the dogs, the mean (sd) SI decreased from 0.92 (0.16) before surgery to 0.34 (0.25) during surgery after the attenuation of the shunt, and then to 0.10 (0.12) one month later. The dogs' venous ammonia concentration decreased from 203 (122) microM before surgery to 36 (18) one month after surgery. At the same time the clinical scores improved significantly. There were positive correlations between the SI and the general evaluation of the dogs' well-being by their owners (rs = 0.60), the ammonia concentration (rs = 0.86), and the diameter of the shunt (rs = 0.86). In the other six dogs, the intraoperative and/or postoperative SI was high. In two of them the shunt was further attenuated during a second operation, which resulted in lower SI values; in two a second small shunt was responsible for the high SI; in one multiple portosystemic shunts were found postmortem; and one dog was lost to follow-up.

Ammonia↗

Excessive Ca and P intake during early maturation in dogs alters Ca and P balance without long-term effects after dietary normalization.

Calcium (Ca) and phosphorus (P) balance is important for skeletal development. Although the effects of deficiencies are well known, reports on the effects of excessive Ca and P supply are relatively scarce. Epidemiologic data and a few controlled studies have shown that skeletal abnormalities may develop when Ca intake is excessive, particularly in periods of rapid growth. Changes in Ca and P balance during and/or after a high Ca intake are thought to underlie this phenomenon. In this study, the effects of excessive Ca (3.1 g/kg dry matter) or Ca and P (Ca 3.1 g/kg, P 2.8 g/kg) intake on Ca and P balance in young, rapidly growing dogs during (for the period from 3 to 17 wk of age) and after (for the period from 17 to 27 wk of age) high Ca and P intake were compared with findings in age-matched controls with normal Ca and P intakes (Ca 1.0 g/kg, P 0.8 g/kg). Dogs fed a high Ca diet developed hypercalcemia, and food intake and fractional absorption of Ca and P were significantly lower at 15 wk of age, whereas endogenous fecal and renal Ca excretion were significantly higher than in controls. This resulted in significantly higher Ca retention than in controls only at 9 wk of age, and in disproportionate absorption of Ca and P. In dogs fed a high Ca and P diet, normocalcemia was maintained, fractional absorption of Ca and P were significantly lower at 9 and 15 wk of age, but retention of both was significantly higher at 9 wk than in controls. The endogenous fecal Ca and renal P losses were significantly higher, but renal Ca excretion was not different from that in controls. After normalization of Ca and P intake, Ca and P balance did not differ among groups. In conclusion, excessive Ca and P intake during early maturation alters Ca and P balance, but does not influence Ca and P balance after dietary normalization.

Absorption↗

EEG evaluation of reflex testing as assessment of depth of pentobarbital anaesthesia in the rat.

Electroencephalography (EEG) was applied to evaluate the validity of the paw pinch reflex as an indicator of anaesthetic depth in rats which are anaesthetized with a single intraperitoneal dose of pentobarbital. After induction of the anaesthesia, characterized by the rapid loss of the animals' ability to maintain upright posture, the EEG of 10 out of 11 rats was dominated by paroxysmal (burst suppression) activity, associated with unconsciousness. In seven out of 11 rats, the paw pinch reflex was lost after onset of paroxysmal electroencephalographic activity. However, the paw pinch reflex remained present in four out of 11 animals, demonstrating that the response is independent of cortical activity. In five out of seven rats, the EEG still showed paroxysmal activity when the paw pinch reflex was regained. However, in two other rats the EEG returned to a pattern similar to that shown by awake animals, 4 and 21 min respectively, before the reflex was regained. These data indicate that in the pentobarbital-anaesthetized rat, presence of the paw pinch reflex is not related to the level of depression of electrical activity in the cerebral cortex, and consequently is probably not related to the level of consciousness. Based upon these findings it is concluded that the paw pinch reflex is unreliable as a sole indicator of anaesthetic depth.

Analgesics, Opioid↗

Comparison of air- and bone-conducted brain stem auditory evoked responses in young dogs and dogs with bilateral ear canal obstruction.

Brain stem responses to air- and bone-conducted stimuli were analyzed in 11 young dogs, using an in-the-ear transducer and a vibrator designed for human hearing tests, respectively. The mean thresholds were 0 to 10 dB for air-conducted stimuli and 50 to 60 dB for bone-conducted stimuli. The wave forms and inter-peak latencies of the waves of the auditory evoked responses elicited by air-conducted and bone-conducted stimuli were similar. This indicated that the signals had the same origin and thus both the air-conducted and the bone-conducted responses could be considered to be auditory responses. Measurement of air-conducted and bone-conducted brain stem-evoked responses in five dogs with bilateral chronic obstructive ear disease revealed thresholds of 50 to 60 dB for air-conducted stimuli and 60 to 70 dB for bone-conducted stimuli. By comparison of these results with those in the 11 young dogs, it could be concluded that there was hearing loss other than that caused by obstruction of the ear canals.

Aging↗