Vacuolar hepatopathy in dogs: 336 cases (1993-2005)

OBJECTIVE: To determine disorders associated with vacuolar hepatopathy (VH), morphologic hepatic and clinicopathologic abnormalities, and affiliation with steroidogenic hormone excess in dogs. DESIGN: Retrospective case series. Animals-336 dogs with histologically confirmed moderate or severe VH. PROCEDURES: Information on signalment, results of diagnostic testing, definitive diagnoses, and exposure to glucocorticoids (ie, exogenous glucocorticoid administration or high endogenous concentrations of steroidogenic hormones) was obtained from medical records. Dogs were grouped by underlying disorder, glucocorticoid exposure, acinar zonal distribution of lesions, and histologic severity. RESULTS: 12 disease groups (neoplastic, acquired hepatobiliary, neurologic, immune-mediated, gastrointestinal tract, renal, infectious, cardiac disease, diabetes mellitus, portosystemic vascular anomaly, adrenal gland dysfunction, and miscellaneous disorders) were identified. There were 186 (55%) dogs with and 150 (45%) dogs without evidence of glucocorticoid exposure. Acinar zonal distribution of hepatic vacuolation and clinicopathologic values did not differ between dogs with and without evidence of glucocorticoid exposure. However, a 3-fold increased likelihood of severe VH was associated with steroidogenic hormone exposure. Of 226 dogs with high serum alkaline phosphatase activity, 102 (45%) had no evidence of glucocorticoid exposure. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that neoplasia and congenital or acquired hepatobiliary disease are common in dogs with VH and provide support for the suggestion that VH, high alkaline phosphatase activity, and illness-invoked physiologic stress may be associated. Histologic confirmation of VH should initiate a diagnostic search for a primary disease if glucocorticoid treatment and hyperadrenocorticism are ruled out.     

Pre-translational regulation of neutrophil L-selectin in glucocorticoid-challenged cattle.

L-selectin (CD62L) gene expression in neutrophils is commonly referred to as "constitutive" because circulating neutrophils require a constant supply of this adhesion molecule for continuous trafficking into peripheral tissues. Under normal circumstances, marginating blood neutrophils and neutrophils that become activated for migration into infected tissues rapidly shed surface CD62L that is ligated to the vascular endothelium. However, this does not shut down CD62L gene expression because these cells continue to express surface CD62L. In contrast, glucocorticoid challenges resulting from stress and hormone injections result in gradual and chronic down-regulation of CD62L on the surface of blood neutrophils. Rather than being associated with migration, this type of CD62L down-regulation associates with pronounced neutrophilia and increased susceptibility to infections. Nothing is currently known about glucocorticoid regulation of CD62L expression in neutrophils. In other cell systems, however, this steroid hormone binds to cytoplasmic glucocorticoid receptors (GR) that influence expression of glucocorticoid-responsive genes at multiple pre-translational levels. Thus, the hypothesis of the present study was that glucocorticoid challenge suppresses CD62L mRNA expression in blood neutrophils. Suppressed CD62L gene expression might help explain the chronic down-regulation of surface CD62L in neutrophils and accompanying neutrophilia. The main objectives of the study were to monitor neutrophil CD62L mRNA abundance before and during subtle and severe glucocorticoid challenges and to determine if CD62L mRNA expression correlates with degree of glucocorticoid challenge. Parturient dairy cows and dexamethasone-treated steers were used as models of subtle and severe (respectively) glucocorticoid challenges. Data presented from both models support the hypothesis and show for the first time that glucocorticoids regulate neutrophil CD62L at a pre-translational level. Results also showed that inhibited CD62L mRNA expression correlated precisely with down-regulated surface expression of CD62L on neutrophils and peak neutrophilia during severe glucocorticoid challenge. Therefore, results of this study indicate that bovine neutrophils are highly sensitive to the blood environment, displaying full capacity to alter CD62L gene expression and trafficking patterns in response to changing glucocorticoid levels. This may serve animals well when heightened inflammatory responses begin to lead to tissue damage, but may be detrimental to overall health if animals are exposed to opportunistic pathogens while stressed or undergoing glucocorticoid therapy. Although this study did not elucidate how glucocorticoids inhibit neutrophil CD62L mRNA expression, presented data implicate GR as possibly being involved because neutrophils from cattle in both models expressed GR mRNA. Further in vitro studies using purified populations of neutrophils will be required to determine if GR is directly involved in glucocorticoid regulation of CD62L gene expression and, if so, at what level.     

Primary hypoadrenocorticism in a dog receiving glucocorticoid supplementation

A 5-year-old, spayed, female husky-Labrador retriever cross was diagnosed with primary hypoadrenocorticism, an uncommon endocrine disorder caused by a deficiency of glucocorticoid and mineralocorticoid hormones. Subtle clinical signs and previous treatment with exogenous glucocorticoid drugs required an adrenocorticotropic hormone stimulation test to confirm the diagnosis.     

Synovial fluid total protein concentration as a possible marker for canine idiopathic polyarthritis

Idiopathic polyarthritis (IPA) is a very common inflammatory arthropathy in the dog. Canine IPA is diagnosed mainly by detecting increased number of leukocytes in the synovial fluid (SF), which is easily influenced by glucocorticoid therapy. We obtained 31 SF samples from 24 IPA dogs prior to (n=19) and/or after (n=12) 1 to 10 weeks of glucocorticoid therapy. The SF total protein concentrations of IPA dogs were significantly higher than those of dogs with non-arthritis diseases (n=34) and healthy controls (n=10). Our data revealed that the SF total protein concentrations are not influenced by several weeks of glucocorticoid therapy. Hence, the SF total protein concentration is applicable as a diagnostic marker of canine IPA even when the patients are receiving glucocorticoid therapy.     

Increased risk of select glucocorticoid adverse events in dogs of higher body weight

There are limited data on glucocorticoid treatment in dogs. The purpose of this study was to investigate whether dogs of higher body weight experienced more adverse events when receiving glucocorticoid therapy. Data pertaining to glucocorticoid therapy was abstracted from the records of 61 dogs that were prescribed glucocorticoids for treatment of immune-mediated thrombocytopenia or hemolytic anemia from 2014 to 2019. The odds of developing muscle atrophy and polyphagia during therapy were increased by 30% for each 5 kg of additional body weight. Almost half of the dogs (44.3%) fluctuated > 15% from baseline weight during therapy. Dogs whose body condition scored as above ideal were at increased risk (odds ratio = 4.2) for being diagnosed with urinary tract infection. Our findings suggest that standard linear glucocorticoid dosing may place higher body weight dogs at increased risk of developing adverse events. Accelerated glucocorticoid tapering and/or alternative dosing schemes in dogs with higher body weights may be prudent in efforts to improve tolerance and client compliance.     

Plasma glucocorticoid concentrations in calves as an indicator of stress during parturition

Plasma glucocorticoid concentrations and blood gas values were determined for 6 days in 47 newborn calves that had been subjected to various obstetrical procedures at term. Concentrations of glucocorticoids were uniformly high at birth (70 to 103 ng/ml). Increasing degrees of acidosis were accompanied by increasing glucocorticoid concentrations in plasma. Plasma glucocorticoid concentrations decreased sharply during the first 6 hours after delivery and reached a plateau at 48 hours after birth (14 to 21 ng/ml). The latter was taken as an indication that adaptation had been achieved. Calves subjected to severe pulling had higher glucocorticoid concentrations at birth (110.4 ng/ml) than calves requiring no assistance (88.3 ng/ml), calves requiring only slight assistance (83.8 ng/ml), or calves that had been delivered by cesarean section (82.9 ng/ml).     

A systematic review of randomized controlled trials for prevention or treatment of atopic dermatitis in dogs: 2008–2011 update

Background – The management of atopic dermatitis (AD) in dogs relies mainly on the use of interventions to reduce pruritus and skin lesions. Objectives – To provide a critical analysis of recent clinical trials reporting the efficacy and safety of interventions for canine AD. Methods – Systematic review of randomized controlled trials (RCTs) published, presented or completed between 2008 and 2011, which enrolled dogs with AD. The search was done using electronic databases, reviewing published meeting abstracts and sending queries to professional email lists. Trials reporting the efficacy of interventions aimed at treating, preventing or reducing glucocorticoid usage in atopic dogs were selected. Results – Twenty‐one RCTs were included. We found further moderate‐quality evidence of efficacy and safety of oral glucocorticoids and ciclosporin for treatment of canine AD. There was additional moderate‐quality evidence of the efficacy of a topical glucocorticoid spray containing hydrocortisone aceponate. Low‐quality evidence was found for the efficacy and safety of injectable recombinant interferons, a budesonide leave‐on conditioner, a ciclosporin topical nano‐emulsion and oral fexofenadine. There is low‐quality evidence of efficacy of oral masitinib, with a need for monitoring for protein‐losing nephropathy. Finally, we uncovered low‐quality evidence of efficacy of a commercial diet as a glucocorticoid‐sparing intervention and of a glucocorticoid spray as a flare‐delaying measure. Very low‐quality evidence was found for the efficacy of other interventions. Conclusions and clinical importance – Topical or oral glucocorticoids and oral ciclosporin remain the interventions with highest evidence for efficacy and relative safety for treatment of canine AD.     

Glucocorticoid therapy and the risk of equine laminitis

Although glucocorticoids have been used successfully for the treatment of noninfectious inflammatory diseases of horses for more than 35 years, their use has been attended by a fear of the induction of laminitis. This paper reviews the evidence for this fear and the possible mechanisms whereby glucocorticoids could participate in laminitis induction. Although the association of laminitis with elevated serum cortisol in pituitary pars intermedia dysfunction suggests that chronic exposure to glucocorticoids may be part of laminitis pathogenesis, review of published reports and databases suggests that glucocorticoid‐induced laminitis is a relatively rare occurrence. However, several of the actions of glucocorticoids are similar to those known to be involved in laminitis pathogenesis. Glucocorticoid administration can induce insulin resistance, lead to vascular dysfunction that potentiates vasoconstriction, and interfere with keratinocyte proliferation and differentiation as well as matrix integrity, all mechanisms that could possibly induce laminitis. Drug formulation, dose and route of administration, and the systemic and hoof disease history of the horse must all be considered when assessing laminitis risk during glucocorticoid treatment. Generally, local glucocorticoid administration presents little risk as does systemic treatment of recurrent airway obstruction without concurrent disease. Caution should be used however in horses that are overweight and/or insulin resistant, or have had a recent bout of acute laminitis of alimentary or endotoxic origin. Overall, however, the risk of laminitis after glucocorticoid treatment, especially local use, is acceptable compared to the many benefits of these drugs.     

VC和VE对应激梅花鹿血液中白细胞及糖皮质激素的影响

将30只试验鹿随机分为3组,Ⅰ组为对照组,Ⅱ组和Ⅲ组为试验组,分别在日粮中添加400mg/kgVC和166.64IU/kgVE。观测“保定与锯茸”应激状态下,梅花鹿血液白细胞的数量和组成、血浆总糖皮质激素、皮质醇浓度及淋巴细胞糖皮质激素受体含量的变化。结果表明,VC和VE均可显著提高应激鹿血液白细胞总数(P<0.01);VC和VE均可显著提高应激鹿血液中淋巴细胞百分率(P<0.01),降低N/L值(P<0.01)。VC和VE可显著降低应激鹿血浆总糖皮质激素、皮质醇浓度,提高应激鹿血液淋巴细胞糖皮质激素受体含量(P<0.01)。综合比较,VC的作用效果较VE好。     

The splayleg disease: A form of congenital glucocorticoid myopathy?

In countries with modern pig industries an increasing percentage of newborn piglets is affected by congenital myofibrillar hypoplasia, also called splayleg or spraddleleg. The main pathomorphological features of this disease are myofibrillar hypoplasia and degeneration. Glucocorticoid myopathy induced in immature muscles of early postnatal rats and rabbits has a pathomorphology very similar to that of splayleg disease. Also in other respects the splayleg disease resembles the glucocorticoid myopathy, as summarized in this contribution. It is suggested that splayleg might represent a congenital form of glucocorticoid myopathy resulting from stress and hormonal imbalance of pregnant sows which affect the fetuses.     

Effects of glucocorticoids on endocrine function in the dog

There are a multitude of possible side effects when using high levels of or chronic administration of glucocorticoid treatment. Several of the studies referred to in this discussion used large amounts of glucocorticoids for rather lengthy periods. The endocrine, as well as nonendocrine, effects of glucocorticoids are minimized when the lowest effective doses are used, when treatment is terminated as soon as reasonably possible, and when an alternate-day therapy schedule is followed. However, an occasional individual may appear with a particular susceptibility to one or more of the side effects of glucocorticoid treatment even when these measures are followed.     

Use of modified ciclosporin in the management of feline pemphigus foliaceus: a retrospective analysis

Background – Glucocorticoids as sole therapy for pemphigus foliaceus (PF) in cats are not always successful, and it is common to need additional immunomodulating agents to manage the disease. Hypothesis/Objectives – This retrospective study evaluated the use of modified ciclosporin as an adjuvant or sole immunomodulating drug in cats with PF and compared their response to PF cats managed with chlorambucil. Animals – Fifteen client‐owned cats diagnosed with PF that received ciclosporin and/or chlorambucil as part of their treatment and had adequate follow‐up to assess treatment response were evaluated. Methods – Records were reviewed from feline PF patients presented between the years of 1999 and 2009. Cats were divided into two treatment groups: those treated with ciclosporin and those treated with chlorambucil. Most cats in both groups also received concurrent systemic glucocorticoids. Each group contained six patients. Three cats were treated with both medications and are discussed separately. Time to disease remission, remission‐inducing glucocorticoid dose, maintenance or final glucocorticoid dose, disease response and adverse effects were assessed. Results – There was no significant difference in remission times or disease response between groups. All six patients maintained with ciclosporin for PF management were weaned off systemic glucocorticoids, while glucocorticoid therapy was stopped in only one of the six cats receiving chlorambucil. Conclusions and clinical importance – Modified ciclosporin is effective in the management of feline pemphigus foliaceus and is glucocorticoid sparing.     

Frequency of urinary tract infection among dogs with pruritic disorders receiving long-term glucocorticoid treatment

OBJECTIVE: To determine frequency of urinary tract infection (UTI) among dogs with pruritic disorders that were or were not receiving long-term glucocorticoid treatment. DESIGN: Observational study. ANIMALS: 127 dogs receiving glucocorticoids for > 6 months and 94 dogs not receiving glucocorticoids. PROCEDURE: Bacterial culture of urine samples was performed in dogs receiving long-term glucocorticoid treatment, and information was collected on drug administered, dosage, frequency of administration, duration of glucocorticoid treatment, and clinical signs of UTI. For dogs not receiving glucocorticoids, a single urine sample was submitted for bacterial culture. RESULTS: Multiple (2 to 6) urine samples were submitted for 70 of the 127 (55%) dogs receiving glucocorticoids; thus, 240 urine samples were analyzed. For 23 of the 127 (18.1%) dogs, results of bacterial culture were positive at least once, but none of the dogs had clinical signs of UTI. Pyuria and bacteriuria (present vs absent) were found to correctly predict results of bacterial culture for 89.9% and 95.8% of the samples, respectively. Type of glycocorticoid, dosage, frequency of administration, and duration of treatment were not associated with frequency of UTI. None of the urine samples from dogs not receiving glucocorticoids yielded bacterial growth. The frequency of UTI was significantly higher for dogs treated with glucocorticoids than for dogs that had not received glucocorticoids. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that dogs receiving long-term glucocorticoid treatment have an increased risk of developing a UTI. On this basis, we recommend that urine samples be submitted for bacterial culture at least yearly for such dogs.     

Genetic Variation in Bovine Neutrophil Sensitivity to Glucocorticoid Challenge

Blood neutrophils use CD62L and CD18 adhesion molecules to contact and migrate rapidly through blood vessels in defense against infections in underlying tissues. Previous work showed that glucocorticoid hormones repress expression of CD62L and CD18, causing neutrophilia and increased mastitis susceptibility in dairy cows. The aim of this study was to determine whether bovine neutrophil sensitivity to glucocorticoids exhibits genetic variability. Test animals included 60 pedigreed Holstein bulls treated on 3 consecutive days with a synthetic glucocorticoid (dexamethasone) and five untreated control bulls. Five indicator traits of neutrophil glucocorticoid sensitivity were monitored, including circulating neutrophil counts and two measures on each of CD62L and CD18 expression. Random regression models with treatment-specific serial correlation were used to estimate genetic and non-genetic sources of variation before, during and after glucocorticoid administration. Significant genetic variation was observed for neutrophil CD18 expression, with longitudinal heritability estimates ranging from 0.10 to 0.54 and influenced by dexamethasone. Significant genetic variation was also observed for blood neutrophil counts (heritability estimates ranging from 0.11 to 0.24) but was not influenced by dexamethasone administration. Estimated genetic correlations between circulating neutrophil counts and various indicators of CD62L and CD18 expression were large and negative (-0.44 to - 0.78). These results imply significant genetic variability and pleiotropic effects for neutrophil traits that are important for stress-induced disease susceptibility in dairy cattle and might be exploited by genetic selection.     

Effect of a glucocorticoid on the post-operative course following experimental orthopaedic surgery in dogs

The capability of a single i.m. injection of betamethasone (Celeston Chronodose®) to modulate a post-operative course was investigated in a placebo-controlled crossover trial with 8 dogs. Two »identical« soft tissue/bone operations were performed on the forelimbs of each animal with an interval of 28 days, to allow a paired comparison of the inflammatory signs and healing process. Significantly less swelling, but not less pain and limping, was observed when the glucocorticoid was administered. No adverse effect of the glucocorticoid was seen on wound and bone healing. The present experimental model is suggested useful for evaluation of anti-inflammatory drug effects in accidental trauma and orthopaedic surgery.     

肾上腺糖皮质激素节律性分泌及主要受控因素

机体在维持内环境稳态和适应外环境的过程中,各种生理机能和代谢活动按照一定的时间顺序发生周而复始的节律变化,称为生物节律。肾上腺糖皮质激素作为机体内维持稳态的一种核心内分泌激素,在维持机体内生命活动发生和营养物质代谢的有序性方面扮演着重要角色。自然状态下,外源受控因素(食物和光照等)通过丘脑的视交叉上核和生物钟之间的复杂的同步反馈调控,使肾上腺糖皮质激素的产生、分泌及生物学作用都具有了节律性特征。本文主要就糖皮质激素的合成、分泌及其内在作用机制的节律性变化特点等方面进行综述,以期为机体内生物节律机制的研究及其对动物生产的指导提供参考。     

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.     

Seasonal variations in plasma glucocorticoid levels in yaks (<Emphasis Type="Italic">Poephagus grunniens L</Emphasis>.) (<Emphasis Type="Italic">Bos grunniens</Emphasis>)

The changes of glucocorticoid concentrations were measured by highly sensitive enzymeimmunoassay procedures using second antibody coating technique and cortisol -HRP amplified system for one whole calendar year in yaks. The year was divided into seasons of cool, intermediate and hot seasons. The glucocorticoid values were lower (P < .01) in hotter months than in cool and intermediate seasons. Rectal temperature and respiration rates were indicative of heat stress in the hot temperature season and gave significant negative correlation with circulating corticoid concentration.