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Biomedical subjects

A Rijnberk

Publications and source records attributed to A Rijnberk.

At least 91 records · Page 5Linked to original sources
PubMed1991

Aging and the hypothalamus-pituitary-adrenocortical axis, with special reference to the dog.

Aging affects the hypothalamus-pituitary-adrenocortical (HPA) system in various ways. It affects the receptors for glucocorticosteroids in the limbic system, the hypothalamus and the pituitary; the basal and stress-induced secretion of proopiomelanocortin-derived peptides and glucocorticoids; and the neuronal integrity, especially in the hippocampus. The homeostatic actions of glucocorticoids occur through the glucocorticoid and the mineralocorticoid receptors. It has been hypothesized that the balance between these two receptors, which are co-localized in the hippocampus, determines the basal HPA activity and the magnitude of the response to challenges. Feedback actions of glucocorticoids are mediated via glucocorticoid receptors in the hypothalamus and the pituitary. In aged rats many changes in the binding capacity of the mineralocorticoid receptor and glucocorticoid receptor and in the regulation of the HPA activity have been reported, but the findings often seem contradictory. The only consistent finding has been that the binding capacity of mineralocorticoid receptor in the hippocampus is reduced. The number of glucocorticoid receptors may be increased, reduced or unchanged in senescent rats. In old dogs the receptor changes were largely confined to mineralocorticoid receptor, there being a 60% reduction in the binding capacity in the limbic system, but glucocorticoid receptor was unchanged in all brain regions. Senescent dogs also had an increased basal secretion of ACTH, and of cortisol. The old dogs had exaggerated responses to stress and to administered corticotropin-releasing hormone, but the termination of the response by the feedback mechanism was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1991

Progestins and growth hormone excess in the dog.

Chronic overproduction of growth hormone in man and the cat is most often caused by a GH-producing tumour of the pituitary gland. In dogs the usual cause is quite different. In this species endogenous progestins (during metestrus) and exogenous progestins (used to prevent estrus) cause excessive GH secretion that is reversible. For a better understanding of the mechanism of progestin-induced GH synthesis and secretion, studies were carried out in healthy dogs and in dogs presented with GH excess. The effectiveness of stimulation of GH secretion by hGHRH, and clonidine and of the inhibition with the somatostatin analogue SMS 201-995 were evaluated in healthy male dogs. SMS 201-995 had no influence on basal plasma GH levels, but significantly inhibited the hGHRH and clonidine-evoked GH release. In healthy female dogs the basal concentrations of plasma GH were significantly higher during metestrus than during anestrus. The elevated basal plasma GH levels were associated with a diminished responsiveness to stimulation with clonidine. In female dogs with experimental or spontaneous progestin-induced chronic overproduction of GH (and IGF-I), plasma GH levels were completely unresponsive to stimulation with hGHRH and clonidine and to inhibition with SMS 201-995. It is concluded that in the female dog the progestin-induced GH excess has characteristics of autonomous secretion.

Acromegaly↗
PubMed1990

Assessment of survey radiography and comparison with x-ray computed tomography for detection of hyperfunctioning adrenocortical tumors in dogs.

Results of abdominal survey radiography and x-ray computed tomography (CT) were compared in 13 dogs with hyperadrenocorticism histologically attributed to adrenocortical tumors. X-ray computed tomography enabled accurate localization of the tumor in all 13 dogs. Apart from 2 poorly demarcated irregular-shaped and mineralized carcinomas, there were no differences between adenoma (n = 3) and carcinoma (n = 10) on CT images. In 1 dog, invasion of the caudal vena cava by the tumor was suggested on CT images and was confirmed during surgery. Suspicion of adhesions between tumors of the right adrenal gland and the caudal vena cava on the basis of CT images was confirmed during surgery in only 2 of 6 dogs. Survey radiography allowed accurate localization of the tumor in 7 dogs (4 on the right side and 3 on the left). In 6 of these dogs, the tumor was visible as a well-demarcated soft tissue mass and, in the other dog, as a poorly demarcated mineralized mass. The smallest tumor visualized on survey radiographs had a diameter of 20 mm on CT images. Six tumors with diameter less than or equal to 20 mm were not visualized on survey radiographs. In 1 of these dogs, a mineralized nodule was found in the left adrenal region, without evidence of a mass. In a considerable number of cases, survey radiography can provide presurgical localization of adrenocortical tumors in dogs with hyperadrenocorticism; CT is redundant in these instances. In the absence of positive radiographic findings, CT is valuable for localization of adrenocortical tumors.

Adenoma↗
PubMed1990

Binding characteristics of mineralocorticoid and glucocorticoid receptors in dog brain and pituitary.

A series of studies was started to gain insight into the functioning of the canine hypothalamo-pituitary-adrenocortical axis during normo- and hypercortisolemic states. In this first study, we have focused on the binding characteristics of the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) in the brain and pituitary of the adrenalectomized dog. In hippocampal cytosol at 0 C, corticosterone had the highest association rate, followed by cortisol and aldosterone. Cortisol had the most rapid rate of dissociation from MR at 0 C (t1/2 = 45.5 h), followed by aldosterone (70.4 h) and corticosterone (102 h). The selective glucocorticoid RU 28362 associated rapidly with hippocampal GR, attaining maximum binding within 4 h, and dissociated with a t1/2 of 34.8 h. Saturation binding of [3H]cortisol in adrenalectomized dog hippocampal cytosol produced a curvilinear Scatchard plot. After inclusion of RU 28362, [3H]cortisol bound solely to MR [dissociation constant (Kd) = 0.34 nM, Bmax = 72.8 fmol/mg]. GR capacity was determined with [3H]RU 28362 (Kd = 0.39 nM, Bmax = 120 fmol/mg). Competition binding analyses of various steroids for MR and GR revealed markedly different patterns of steroid binding specificity for these receptors. The rank order for displacement of [3H]aldosterone binding of MR was: corticosterone greater than aldosterone = cortisol greater than dexamethasone greater than ZK 91587 greater than RU 26752 greater than spironolactone much greater than RU 38486, and for displacement of [3H]RU 28362 binding of GR: RU 28362 much greater than corticosterone = cortisol greater than dexamethasone greater than aldosterone greater than ZK 91587 greater than RU 26752 = RU 38486 much greater than spironolactone. MR was located in all brain regions examined, with highest levels in the septo-hippocampal complex, whereas GR was rather evenly distributed. Substantial amounts of MR and GR were present in the anterior part of the pituitary as well as in the neurointermediate lobe. Our findings show that the ligand binding specificity of canine MR and GR is remarkably different from that of rodent MR and GR, but is similar to that of recombinant-derived human receptors. Spironolactone and RU 38486 are selective antagonists for MR and GR, respectively. In contrast to other species, the dog has relatively large quantities of MR widely distributed in the brain and pituitary, which makes this species an interesting animal model to study the role of corticosteroid receptor diversity in control of homeostasis.

Aldosterone↗
PubMed1990

Effects of a [Met]-enkephalin analogue ( [D-Ala2,N-Me-Phe4,Met-(O)5-ol]-enkephalin) on canine pituitary function.

In adult healthy beagle dogs, plasma concentrations of ACTH, cortisol, alpha-MSH, GH, prolactin and arginine vasopressin (AVP) were measured after i.v. administration of [D-Ala2,N-Me-Phe4,Met-(O)5-ol]-enkephalin (DAMME) at doses of 0.1, 0.5, 1, 5 and 10 micrograms/kg body weight. Significant dose-dependent increases occurred for ACTH, cortisol and GH at dose rates of 0.5, 1, 5 and 10 micrograms/kg body weight. Increments in plasma concentrations of prolactin were significant only at 5 and 10 micrograms DAMME/kg, and there was no significant effect on plasma concentrations of alpha-MSH and AVP. Prior i.v. administration of the opiate antagonist naloxone (0.1 mg/kg) attenuated the DAMME (10 micrograms/kg)-stimulated release of ACTH and cortisol. The results demonstrate that the [Met]-enkephalin analogue DAMME stimulates the release of ACTH, cortisol, GH and prolactin in dogs, and that this stimulation is, at least in part, mediated by mu-opioid receptors. The observations for ACTH and cortisol are different from those in man, where DAMME lowers their basal concentrations.

Adrenocorticotropic Hormone↗
PubMed1990

Heterogeneity in Cushing's disease.

Some patients with Cushing's disease respond to neuropharmacological treatment, whereas others do not. This apparent heterogeneity has been attributed to the existence of a separate form of Cushing's disease of putative neurointermediate lobe origin as opposed to Cushing's disease of anterior pituitary origin. The present review summarizes recent observations in human and canine Cushing's disease which mitigate against this view. We propose that heterogeneity in Cushing's disease is related to heterogeneity of the normal anterior pituitary corticotroph. However, the most fundamental questions concerning the pathogenesis of Cushing's disease remain unanswered.

Cushing Syndrome↗
PubMed1990

Nephrotomography and ultrasonography for the localization of hyperfunctioning adrenocortical tumors in dogs.

Nephrotomography and ultrasonography were used in 11 dogs with hyperadrenocroticism to assess the value of these techniques for the localization of biochemically diagnosed hyperfunctioning adrenocortical tumors. Both techniques enabled accurate localization of a unilateral adrenal mass in each of the dogs. Cross-sectional diameters of the masses ranged from 1 to 4 cm. In 1 dog, expansion of tumor into the caudal vena cava was revealed by caudal venacavography and ultrasonography. Mineralization in the tumor mass in 2 dogs was easily recognized by nephrotomography, but not by ultrasonography. Paracostal laparotomy confirmed the presence of an adrenocortical tumor in each dog, and expansion of tumor into the caudal vena cava in 1 dog. Cross-sectional diameters of the tumors ranged from 1.2 to 4.5 cm and corresponded well with cross-sectional measurements by nephrotomography and ultrasonography. It was concluded that nephrotomography and ultrasonography have similar diagnostic accuracies for the detection and localization of hyperfunctioning adrenocortical tumors.

Adrenal Cortex Neoplasms↗
PubMed1989

Corticosteroid-induced alkaline phosphatase isoenzyme in the diagnosis of canine hypercorticism.

Corticosteroid-induced isoenzyme of alkaline phosphatase (AP) can easily be demonstrated in canine plasma as a routine procedure because of its greater heat stability at 65 degrees C in comparison with that of other AP-isoenzymes. In this study the accuracy of this test for the diagnosis of hypercorticism was investigated. The AP-65 degrees C test had its highest efficiency when applied to plasma AP levels exceeding 150 units/litre. In a group of 146 dogs, clinically suspected of having hyperadrenocorticism, the test had a sensitivity of 0.92 and a positive predictive value for a positive test result of 0.89. Its lack of specificity (0.44) makes it unsuitable as a diagnostic test. The main application of AP-65 degrees C is in detecting hypercorticism in dogs by routine laboratory measurements, as was demonstrated in 711 dogs, in which a positive predictive value for the presence of hypercorticism of 0.89 was found.

Adrenocortical Hyperfunction↗
PubMed1989

Thyroidal radioiodine uptake in hyperthyroid cats.

Thyroidal radioiodine uptake was measured in 10 healthy domestic cats and in 20 hyperthyroid cats. Compared with those in the healthy cats, the uptake curves in the hyperthyroid cats were characterised by elevated uptake and rapid thyroidal iodine turnover. For diagnostic purpose uptake measurements at 4 hours after administration of the tracer were found to be preferable to measurements at 24 hours or later.

Animals↗
PubMed1989

Persistent polyuria in two dogs following adrenocorticolysis for pituitary-dependent hyperadrenocorticism.

In two dogs with pituitary-dependent hyperadrenocorticism, adrenocorticolysis with o.p'-DDD led to the disappearance of the signs and symptoms except for the polyuria. After a modified water-deprivation test the osmoregulation of vasopressin release was studied by hypertonic saline infusion. In both dogs the hypertonicity, thus induced, resulted in very minimal responses of the vasopressin secretion.

Adrenal Cortex Hormones↗
PubMed1988

An alternative protocol for the medical management of canine pituitary-dependent hyperadrenocorticism.

As an alternative to the o,p'-DDD treatment aimed at the selective destruction of the adrenal cortices, the authors have introduced a protocol aimed at the complete destruction of the adrenal cortices. It consists of a longer period of daily treatment with o,p'-DDD and lifelong substitution for primary hypoadrenocorticism. The results obtained in 41 dogs, with a minimum follow-up period of one year, indicate that this approach has advantages over lifelong maintenance therapy with o,p'-DDD.

Adrenal Cortex↗
PubMed1988

Assessment of two tests for the diagnosis of canine hyperadrenocorticism.

The low-dose dexamethasone suppression test and the urinary corticoid/creatinine ratio were assessed in 166 and 150 dogs, respectively, for their value in the diagnosis of hyperadrenocorticism. The diagnostic accuracy of the low-dose dexamethasone suppression test was 0.83, with a 95 per cent confidence interval from 0.76 to 0.88. The urinary corticoid/creatinine ratio had a diagnostic accuracy of 0.91 with a 95 per cent confidence interval from 0.85 to 0.95. The high predictive value of a negative corticoid/creatinine ratio (0.98; confidence interval 0.80 to 1.00) and the low cost of this test makes it preferable for screening purposes to the low-dose dexamethasone suppression test for which the predictive value of a negative test was calculated as 0.5g (confidence interval 0.43 to 0.73).

Animals↗
PubMed1988

Inappropriate vasopressin secretion in two dogs.

Two dogs with hyponatremia due to inappropriate arginine vasopressin (AVP) secretion are described. Threshold and sensitivity of AVP secretion were investigated by increasing plasma osmolality with hypertonic saline infusion. In one dog, osmoregulation of AVP secretion occurred at normal sensitivity but at a low threshold. The other dog had a relatively high plasma AVP concentration under (resting) hypotonic conditions with an otherwise normal response to increasing plasma tonicity. In the absence of evidence for associated disease, it is suggested that both dogs have an idiopathic form of the syndrome of inappropriate AVP secretion.

Animals↗
PubMed1988

Effects of bromocriptine on corticotrophin, melanotrophin and corticosteroid secretion in dogs with pituitary-dependent hyperadrenocorticism.

Dogs with spontaneous pituitary-dependent hyperadrenocorticism were divided into two groups, one with normal plasma concentrations of alpha-MSH (normal alpha-MSH dogs, n = 26) and the other with high plasma concentrations of alpha-MSH (high alpha-MSH dogs, n = 14), on the presumption that high alpha-MSH concentrations indicated a parent cell of pars intermedia origin. The urinary corticoid/creatinine ratios of the high alpha-MSH dogs were significantly higher than those of the normal alpha-MSH dogs. The percentage decrease of the corticoid/creatinine ratios following dexamethasone administration was significantly higher in the normal alpha-MSH dogs than in the high alpha-MSH dogs. Dexamethasone resistance occurred in both the normal alpha-MSH dogs (4 out of 26) and the high alpha-MSH dogs (7 out of 14), indicating a relative rather than an absolute difference. The short-term effect of orally administered bromocriptine, at a dose (10 micrograms/kg body weight) known to be effective in lowering prolactin concentrations in dogs, was investigated by measuring concentrations of cortisol, ACTH and alpha-MSH in plasma at 4, 6 and 8 h after administration. Significant decreases were observed for cortisol in both groups and for alpha-MSH only in the high alpha-MSH dogs. The effect of 5 days of bromocriptine administration (10 micrograms at 12-h intervals) was assessed by measurements of urinary corticoid/creatinine ratios. Considering both groups as a whole, only the corticoid/creatinine ratios of the high alpha-MSH dogs decreased significantly on the first day of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1987

Organization of ovine corticotropin-releasing factor immunoreactive neurons in the canine hypothalamo-pituitary system.

The distribution of corticotropin-releasing factor immunoreactive (CRF-i) cell bodies and varicose fibers in the hypothalamus and the pituitary of the canine brain was studied by indirect immunofluorescence. CRF-i cell bodies were demonstrated mainly in the periventricular zone of the third ventricle, while some CRF-i cell bodies were scattered throughout the ventral part of the caudomedial hypothalamus. CRF-positive fibers were mostly situated in the median eminence. In addition some CRF-positive fibers were detected in the ventromedial aspect of the lateral hypothalamus forming a pathway arising from the CRF-i cell bodies, running via the median eminence through the infundibular stalk and terminating in the pars nervosa of the pituitary. The localization of the cell bodies and their projection points towards a possible (patho)physiological role of this peptide-transmitter system in the release of ACTH and beta-endorphin.

Animals↗
PubMed1987

Some functional aspects of canine corticotrophs.

To examine the regulation and functional significance of canine pituitary pars intermedia corticotrophs, ACTH and cortisol responses to CRF were studied in healthy dogs before and after treatment with dexamethasone. In addition the effects of the dopamine agonist bromocriptine and the dopamine antagonist pimozide were investigated. In the latter two instances prolactin concentrations were also measured. Finally the pituitaries were studied immunocytochemically for ACTH and alpha-MSH. No response of ACTH or cortisol to bromocriptine was observed. Pimozide caused a slight rise in ACTH levels in some dogs. However, prolactin levels significantly decreased with bromocriptine and increased with pimozide. Injection of synthetic ovine CRF to dogs was followed by sharp increases in ACTH and cortisol values. These responses were obliterated by prior treatment with dexamethasone. In 1 of 4 dogs given dexamethasone before euthanasia, there were few pars distalis cells with ACTH(1-24) immunopositivity, although persistence of ACTH(1-24) reaction was noted within cells of the pars intermedia. The results indicate that none of the CRF-induced ACTH secretion in dogs is derived from pars intermedia corticotrophs. Dosages of bromocriptine and pimozide that clearly alter prolactin secretion do not consistently affect ACTH levels.

Adrenocorticotropic Hormone↗