Effects of trilostane on the pituitary-adrenocortical and renin–aldosterone axis in dogs with pituitary-dependent hypercortisolism

The medical records of 63 dogs with pituitary-dependent hypercortisolism (PDH) before and during treatment with trilostane were reviewed retrospectively. The correct trilostane dosage in dogs with PDH was based on the resolution of clinical signs and the results of an adrenocorticotropic hormone (ACTH) stimulation test. The mean (±SD) dose rate of trilostane to achieve good clinical control was 2.8 ± 1.0 mg/kg bodyweight. Trilostane treatment resulted in a significant decline in basal plasma cortisol concentrations. The median plasma ACTH concentration (39 pmol/L, range 7–132 pmol/L; n = 60) at the optimal trilostane dosage time was significantly higher (P < 0.001) than before treatment (13 pmol/L, range 2–102 pmol/L). These values did not overlap with plasma ACTH concentrations (range 212–307 pmol/L) of five PDH dogs with trilostane-induced hypocortisolism.The median cortisol/ACTH ratio in well-controlled dogs (0.23, range 0.03–2.5; n = 46) was significantly lower (P < 0.001) than before treatment (2.59, range 0.27–13.25). Trilostane treatment resulted in an insignificant decrease in plasma aldosterone concentration (PAC), but the median plasma renin activity (PRA) at the time the trilostane dosage was considered optimal (265 fmol/L/s, range 70–3280 fmol/L/s; n = 18) was significantly higher (P < 0.001) than prior to treatment (115 fmol/L/s, range 15–1330 fmol/L/s). Similarly, the median PAC/PRA ratio during trilostane treatment (0.16, range 0.003–0.92; n = 17) was significantly lower (P < 0.001) than before treatment (median 0.44, range 0.04–1.33). Trilostane affected both the hypothalamic-pituitary-adrenocortical and the renin–aldosterone axes. The results also suggested that basal plasma ACTH concentration may be used to detect trilostane overdosage.     

Identification of feline monocytes and neutrophils as effector cells in antibody-dependent cellular cytotoxicity: sequential analysis, using light microscopy, histochemistry, and scanning electron microscopy

Feline monocytes and neutrophils functioned as effector cells in antibody-dependent cellular cytotoxicity (ADCC) against antibody-coated chicken erythrocytes. Using light microscopy, effector cell populations were identified in effector-target cell interactions, with further characterization of these identical individual effector cells by histochemical evaluations and scanning electron microscopy. Monocytes and neutrophils, but not lymphocytes, were observed attacking target cells. Carbonyl iron depletion of monocytes and neutrophils from peripheral blood leukocytes caused a marked reduction from a mean of 62% to 3.6% lysis in ADCC as measured by a 4-hour 51Cr release assay. Effector cells functioning in the ADCC reaction were visualized, using sequential analysis and light microscopy, histochemistry, and scanning electron microscopy.     

Polyglandular deficiency syndrome in a boxer dog: Thyroid hormone and glucocorticoid deficiency

Summary

Primary hypothyroidism and partial primary adrenocortical deficiency (isolated glucocorticoid deficiency) were diagnosed in an 8‐year‐old spayed female boxer dog, presented because of progressive symmetrical truncal alopecia, lethargy, and intolerance to cold. The diagnosis was based upon the combination of low, non‐TSH‐responsive concentrations of plasma thyroxine and low urinary excretion of corticoids together with high plasma concentrations of ACTH. Normal suppressibility of ACTH concentrations by a low dose of dexamethasone indicated an intact feedback system. Plasma growth hormone levels were elevated, most probably because somatostatin release was depressed by the glucocorticoid deficiency.

The dog improved during oral replacement therapy with thyroxine until death ensued after 9 months as a result of intercurrent disease. Autopsy revealed thyroid atrophy and lymphocytic adrenalitis with complete destruction of the zona fasciculata and zona reticularis of the adrenal cortex.

The combination of primary hypothyroidism and primary adrenocortical deficiency in this dog is identical to the entity known as type II polyglandular autoimmunity or Schmidt's syndrome in humans. The adrenocortical insufficiency remained confined to glucocorticoid deficiency during the observation period; on no occasion did electrolyte concentrations in the plasma reach values suggestive of mineralocorticoid deficiency.     

Persistent Mullerian Duct Syndrome in a Miniature Schnauzer Dog with Signs of Feminization and a Sertoli Cell Tumour

A 5‐year‐old male Miniature Schnauzer was presented with unilateral cryptorchidism and signs of feminization. Abdominal ultrasonography revealed an enlarged right testis and a large, fluid‐filled cavity that appeared to arise from the prostate. Computed tomography revealed the cavity to be consistent with an enlarged uterine body, arising from the prostate, and showed two structures resembling uterine horns that terminated close to the adjacent testes. The dog had a normal male karyotype, 78 XY. Gonadohysterectomy was performed and both the surgical and the histological findings confirmed the presence of a uterus in this male animal, resulting in a diagnosis of persistent Mullerian duct syndrome (PMDS). The enlarged intra‐abdominal testis contained a Sertoli cell tumour. Computed tomography proved to be an excellent diagnostic tool for PMDS.     

High urinary corticoid/creatinine ratios in cats with hyperthyroidism

Measurement of the urinary corticoid : creatinine (C : C) ratio provides an assessment of cortisol secretion over a period of time. Therefore, this test is a very sensitive measure of adrenocortical function. The stress of the diagnostic procedure and nonadrenal disease may increase the urinary C : C ratio. In addition, diseases such as hyperthyroidism may influence the metabolic clearance of cortisol. To evaluate the effect of thyroid hormone excess, urinary C : C ratios were measured in 32 cats with hyperthyroidism and 45 healthy household cats. In 7 cats, urinary C : C ratios were measured both before and after treatment for hyperthyroidism. With data from the healthy cats, the reference range for the urinary C : C ratio was determined to be 8.0 to 42.0 X 10(-6). The urinary C : C ratios in the cats with hyperthyroidism (median, 37.5 x 10(-6); range, 5.9-169.5 x 10(-6)) were significantly (P = .001) higher than those in the healthy cats (median, 16 x 10(-6); range, 4.8-52.5 x 10(-6)). In 15 cats with hyperthyroidism, the urinary C : C ratios exceeded the upper limit of the reference range. Treatment for hyperthyroidism led to a marked decrease in urinary C : C ratios. The results of this study demonstrate that the urinary C : C ratio may be abnormally high in cats with hyperthyroidism, probably because of increased metabolic clearance of cortisol and activation of the pituitary-adrenocortical axis by disease. Although the clinical features of hyperthyroidism and hyperadrenocorticism in cats are different, hyperthyroidism should be ruled out when cats are suspected of hyperadrenocorticism on the basis of abnormally high urinary C : C ratios.     

Na(+), K(+)-ATPase content in skeletal muscle of dogs with pituitary-dependent hyperadrenocorticism

Several hormones regulate Na⁺, K⁺-ATPase content in the muscle cell membrane, which is essential for maintaining muscle cell excitability. Chronic glucocorticoid excess is associated with muscle weakness and reduced endurance. We hypothesized that chronic glucocorticoid excess affects Na⁺, K⁺-ATPase content in canine skeletal muscle, and contributes to reduced endurance and muscle weakness associated with pituitary-dependent hyperadrenocorticism (PDH) in dogs. Therefore, Na⁺, K⁺-ATPase content in skeletal muscle was evaluated before and after hypophysectomy and hormone replacement (cortisone and l-thyroxin) in dogs with PDH (n = 13), and in healthy controls (n = 6). In addition, baseline and exercise-induced changes in plasma electrolyte concentrations and acid–base balance were evaluated before and after hypophysectomy in dogs with PDH. Na⁺, K⁺-ATPase content of gluteal muscle in dogs with PDH was significantly lower than in control dogs (201 ± 13 pmol/g versus 260 ± 8 pmol/g wet weight; P < 0.01). Similar differences were found in palatine muscle. After hypophysectomy and on hormone replacement, Na⁺, K⁺-ATPase was increased (234 ± 7 pmol/g wet weight). Both plasma pH and base excess in dogs with PDH (7.44 ± 0.01; 1.7 ± 0.6 mmol/l, respectively) were significantly higher (P < 0.05) than after hypophysectomy and hormone replacement (7.41 ± 0.01; −0.2 ± 0.4 mmol/l, respectively). Exercise induced respiratory alkalosis, but did not result in hyperkalemia in dogs with PDH. In conclusion, chronic glucocorticoid excess in dogs with PDH is associated with decreased Na⁺, K⁺-ATPase content in skeletal muscle. This may contribute to reduce endurance in canine PDH, although dogs with PDH did not exhibit exercise-induced hyperkalemia. Na⁺, K⁺-ATPase content normalized to values statistically not different from healthy controls after hypophysectomy and hormone replacement.     

Integrated research in archaeology using soil micromorphology and palynology

Archaeologists often encounter problems in interpreting the genesis of layers and the context in which specific materials occur in excavations. Field visits of geologists, soil scientists or biologists can solve a number of questions, but often, problems remain that only can be studied by microscopic research as, for example, soil micromorphology and palynology. In the past, the employment of these two disciplines, one in earth science and one in biology, generally occurred independently of each other, also in interdisciplinary research and contract research. Consequently, results could not always be correlated, permitting only a restricted integration of data. It was realised that soils, as archives, contain much more information than generally utilised. A skillful employment and balancing of both specialties create a real integrated approach that offers a substantially improved interpretation potential without hardly additional efforts and costs. The results of 7 years of experience were very stimulating and presented here.In this article, the essence of soil micromorphology and palynology applied to archaeology is briefly outlined and illustrated by selected examples of the different research themes covered, showing the possibilities and results of integrated research. Both specialties generate essential information that, when combined and integrated properly, lead to improved understanding of the landscape genesis and human activities in the past. To be able to employ the full interpretive potential of this integrated approach, the research procedures followed by both specialties had to be compared. The key requirements for optimal integration of each other's databases comprised a combined effort to compare the pros and cons during the first four steps of the research procedure: defining research questions, field survey, selection of sampling locations and sampling. This approach enabled optimal correlation of the individual results, made cross-checking and references possible and led to higher levels of interpretation that would not have been possible otherwise. The integrated research elucidated lacunae in the other's discipline, resulting in a distinctly more complete reconstruction of paleoenvironments and past land uses, important research themes of archaeologists for the specialties concerned.     

Characterization of host tolerance to Striga hermonthica

Summary One of the most promising control options against the parasitic weed Striga hermonthica is the use of crop varieties that combine resistance with high levels of tolerance. The aim of this study was to clarify the relation between Striga infestation level, Striga infection level and relative yield loss of sorghum and to use this insight for exploring the options for a proper screening procedure for tolerance. In three pot experiments, conducted in Mali (2003) and The Netherlands (2003, 2004), four sorghum genotypes were exposed to a range of Striga infestation levels, ranging from 0.0625 to 16 seeds cm⁻³. Observations included regular Striga emergence counts and sorghum grain yield at maturity. There were significant genotype, infestation and genotype × infestation effects on sorghum yield. The relation between infestation level and infection level was density dependent. Furthermore, the relation between Striga infection level and relative yield loss was non-linear, though for the most resistant genotype Framida only the linear part of the relation was obtained, as even at high infestation levels only moderate infection levels were achieved. The results suggest that for resistant genotypes, tolerance can best be quantified as a reduced relative yield loss per aboveground Striga plant, whereas for less resistant genotypes the maximum relative yield loss can best be used. Whether both expressions of tolerance are interrelated could not be resolved. Complications of screening for tolerance under field conditions are discussed.