Efficacy of transsphenoidal hypophysectomy in treatment of dogs with pituitary-dependent hyperadrenocorticism

The long-term survival, disease-free fractions, and the complications of hypophysectomy in 150 dogs with pituitary-dependent hyperadrenocorticism (PDH) were examined in a prospective study. Long-term survival and disease-free fractions in relation to pituitary size were analyzed by the Kaplan-Meijer estimate procedure. The 1-, 2-, 3-, and 4-year estimated survival rates were 84% (95% confidence interval [CI], 76-89%), 76% (67-83%), 72% (62-79%), and 68% (55-77%), respectively. Treatment failures included procedure-related mortalities (12 dogs) and incomplete hypophysectomies (9 dogs). The 1-, 2-, 3-, and 4-year estimated relapse-free fractions were 88% (CI: 80-93%), 75% (64-83%), 66% (54-76%), and 58% (45-70%), respectively. Postoperative reduction of tear production (58 eyes in 47 dogs) was often reversible but remained low until death in 11 eyes of 10 dogs. Central diabetes insipidus (CDI) occurred more frequently (62%) in dogs with enlarged pituitaries than in dogs with nonenlarged pituitaries (44%). Survival and disease-free fractions after hypophysectomy were markedly higher in dogs with nonenlarged pituitaries than in dogs with enlarged pituitaries. Transsphenoidal hypophysectomy is an effective treatment for PDH in dogs. The survival and disease-free fractions after hypophysectomy decrease and the incidence of CDI increases with increasing pituitary size. Therefore, early diagnosis of PDH is important and transsphenoidal hypophysectomy is expected to have the best outcome when used as primary treatment for dogs with nonenlarged or moderately enlarged pituitaries.     

Acromegaly due to a somatroph adenoma in a dog

A 10-year-old uncastrated male Dalmatian dog was referred for gait abnormalities consisting of chronic progressive stiffness and rigidity. Other symptoms were polyphagia associated with weight gain, polyuria and polydipsia, excessive panting, and an inspiratory stridor. The owner had noticed progressive thickening of the skin and enlargement of the tongue over the last 3 years. Physical examination revealed thickening of the skin, redundant skin folds, and enlargement of the tongue. The only remarkable abnormalities found on routine laboratory examination were mild anaemia and an increased serum fructosamine concentration. Circulating concentrations of total thyroxine, free thyroxine, and cTSH, and the results of an ACTH stimulation test were all within reference ranges. The basal serum growth hormone (GH) concentration was markedly elevated (23microg/l) and did not decrease during a glucose tolerance test or after somatostatin administration. The serum insulin-like growth factor-1 concentration was also markedly elevated (1254microg/l). Basal serum insulin concentration was high (95mU/l) and insulin concentrations increased considerably after glucose loading, consistent with insulin resistance. Abdominal ultrasonography showed no abnormalities. Survey radiographs of the vertebral column showed severe spondylosis deformans extending from the cervical to the lumbosacral spine. CT scanning of the skull showed an enlarged pituitary gland with normal enhancement pattern. On post-mortem examination, the entire vertebral column appeared as a single and inflexible structure due to the presence of multiple fused osteophytes. The pituitary gland contained an acidophilic adenoma that immunostained positively for GH (and negatively for ACTH and alpha-MSH). In conclusion, this Dalmatian dog with acromegaly and insulin resistance represents the first case of GH hypersecretion proven to be due to a somatotroph adenoma.     

Hepatic carcinoid, hypercortisolism and hypokalaemia in a dog

A German Shepherd dog was diagnosed with periodic myopathy secondary to persistent hypokalaemia. Hormone analysis revealed excess cortisol secretion. A neuroendocrine carcinoma, thought to be a primary hepatic carcinoid, was detected in the liver. Ectopic adrenocorticotrophin hormone secretion was suspected as the cause of hypercortisolism and hypokalaemia, although this could not be confirmed by immunohistochemical staining.     

Hypocalcemia and hypovitaminosis D in dogs with induced endotoxemia

Background

Hypocalcemia is a documented electrolyte disturbance in people and animals with sepsis, but its mechanism is poorly understood.

Objective

To investigate mechanisms of hypocalcemia in dogs with experimentally induced endotoxemia.

Animals

Six healthy mixed breed dogs were included in this nonrandomized, placebo‐controlled, crossover study.

Methods

Dogs initially were injected with placebo (0.9% NaCl; 1 mL, IV) and then lipopolysaccharide (LPS; 2 μg/kg, IV) after a 5‐day washout period. Blood and urine samples were collected for measurement of serum total calcium (tCa), ionized calcium (iCa), total magnesium (tMg), ionized magnesium (iMg), parathyroid hormone (PTH), 25‐hydroxyvitamin D (vitamin D), venous blood gases, and fractional excretion (FE) of calcium.

Results

After LPS administration, body temperature increased and blood pressure decreased. Both iCa and tCa decreased (P < .01), but iMg was not significantly different between control and LPS treatments. PTH concentrations increased (P < .01) and vitamin D concentrations decreased (P < .01). Venous pH, bicarbonate, base excess, and blood glucose also decreased (P < .01). Urine tCa concentration was below the limit of detection for all dogs after LPS administration.

Conclusions

Hypocalcemia occurs during endotoxemia in dogs and is associated with hypovitaminosis D. Hypomagnesemia, hypoparathyroidism, alkalosis, and increased calciuresis are not associated with hypocalcemia in endotoxemic dogs.     

Clinical and microbiological characterization of subclinical bacteriuria and sporadic bacterial cystitis in dogs with spontaneous hypercortisolism

Study’s aims were to characterize subclinical bacteriuria (SB) and sporadic bacterial cystitis (SBC) in dogs with spontaneous hypercortisolism (HC). Prospective cross-sectional design divided patients as newly diagnosed (n = 27), poorly controlled (n = 21), well controlled (n = 34), and controls (n = 19). Urine culture positive results were identified by MALDI-TOF and submitted to antibiogram. Escherichia coli was the most common microorganism (36%). The majority of positive cultures in HC were SB (12.2%). All 4.1% SBC cases were in well controlled HC cases. Bacteriuria correlated with low urine specific gravity and low lymphocyte count. HC degree of control correlated with leukocyturia. SB/SBC cases were treated based in antimicrobial susceptibility leading to microbiological cure in 75% of HC cases. Persistent infections occurred only in SB cases, all by E. coli which became more resistant. SB/SBC prevalence in canine HC is actually lower. Further evidence for current ISCAID guideline contraindication for SB treatment due to HC were provided.     

甲基供体促仔猪生长的内分泌机制的探讨

试验将 72头始重为 1 0kg左右的杜长嘉仔猪随机分为 3组 ,以添加和不添加蛋氨酸为对照 ,试验组喂以添加 80 0mg/kg的甜菜碱。 3组的基础饲粮组成及营养水平相同 ,试验期为 3 6天。结果表明 ,与不添加蛋氨酸组相比 ,添加甜菜碱组猪的日增重和采食量分别提高了 1 1 .82 %(P <0 .0 5)和 8.71 %(P <0 .0 5) ,饲料转化率提高了 2 .79%(P <0 .0 5) ;与添加蛋氨酸组相比无显著差异 (P >0 .0 5)。此外 ,甜菜碱组肝脏中甜菜碱高半胱氨酸甲基转移酶 (BHMT)活较不添加蛋氨酸组高 61 .4 1 %(P <0 .0 5) ,较添加蛋氨酸组高 55.3 6%(P <0 .0 5) ,血样分析结果显示 ,添加甜菜碱组猪比不添加蛋氨酸组显著降低了血清尿素氮含量 (P <0 .0 1 )。提高了血清总铁结合力、GH和IGF -1水平 (P <0 .0 5)。但与添加蛋氨酸组相比 ,差异均不显著 (P >0 .0 5)。上述结果提示 ,甲基供体一方面通过肝脏BHMT酶的调控下为机体甲基化合成代谢提供甲基 ,发挥节约蛋氨酸的效应 ;另一方面通过增强机体GH和IGF -1的分泌 ,促进生长。     

Vitamin D metabolism in dogs and cats and its relation to diseases not associated with bone metabolism

Due to the presence of receptors in the cells of numerous body tissues, vitamin D is associated with several physiological functions that go beyond calcium and phosphorus homoeostasis and control of bone metabolism in the body. In humans, several studies have associated lower vitamin D concentrations with numerous diseases, such as cancer, heart disease, autoimmune diseases and infectious diseases, and also with an increase in the total mortality rate of the population. Recently, this nutrient started to gain importance in veterinary medicine, and several articles have shown a correlation between low vitamin D status and diseases unrelated to bone metabolism. The present review aims to highlight the recent publications that investigated this relationship, bringing the evidence that exists so far in dogs and cats.     

Infection, immunity and the neuroendocrine response

The Central Nervous (CNS) and Immune Systems (IS) are the two major adaptive systems which respond rapidly to numerous challenges that are able to compromise health. The defensive response strictly linking innate to acquired immunity, works continuously to limit pathogen invasion and damage. The efficiency of the innate response is crucial for survival and for an optimum priming of acquired immunity. During infection, the immune response is modulated by an integrated neuro-immune network which potentiates innate immunity, controls potential harmful effects and also addresses metabolic and nutritional modifications supporting immune function. In the last decade much knowledge has been gained on the molecular signals that orchestrate this integrated adaptive response, with focus on the systemic mediators which have a crucial role in driving and controlling an efficient protective response. These mediators are also able to signal alterations and control pathway dysfunctions which may be involved in the persistence and/or overexpression of inflammation that may lead to tissue damage and to a negative metabolic impact, causing retarded growth.This review aims to describe some important signalling pathways which drive bidirectional communication between the Immune and Nervous Systems during infection. Particular emphasis is placed on pro-inflammatory cytokines, immunomodulator hormones such as Glucocorticoids (GCs), Growth hormone (GH), Insulin-like Growth Factor-1 (IGF-1), and Leptin, as well as nutritional factors such as Zinc (Zn).Finally, the review includes up-to-date information on this neuroimmune cross-talk in domestic animals. Data in domestic animal species are still limited, but there are several exciting areas of research, like the potential interaction pathways between mediators (i.e. cytokine-HPA regulation, IL-6-GCS-Zn, cytokines-GH/IGF-1, IL-6-GH-Leptin and thymus activity) that are or could be promising topics of future research in veterinary medicine.     

Diurnal ACTH and plasma cortisol variations in healthy dogs and in those with pituitary-dependent Cushing's syndrome before and after treatment with retinoic acid

Daytime variations in ACTH and plasma cortisol were studied in healthy dogs and in dogs with pituitary-dependent hypercortisolism (PDH), before and after treatment with retinoic acid. In control dogs ACTH showed a higher concentration at 8.00 AM and between 2.00 and 6.00 PM, with the lowest concentration registered at 10.00 AM (p < 0.05 vs. 8.00 AM and 2.00 PM and p < 0.01 vs. 4.00 PM). Cortisol did not show significant differences. In dogs with PDH, ACTH was lower at 8.00 AM (ACTH: p < 0.01 vs. 2.00 and 4.00 PM; and p < 0.05 vs. 6.00 PM). The lowest cortisol concentration was registered at 8.00 AM and 8.00 PM and the highest at 4.00 PM (p < 0.05 vs. 8.00 AM and p < 0.01 vs. 8.00 PM). After treatment, the lowest ACTH concentration was registered at 10.00 AM (p < 0.01 vs. 2.00 and 4.00 PM). To conclude, the adrenal is desensitized in PDH possibly showing negative in diagnostic tests.     

Effects of short- and long-term fasting on plasma and stomach ghrelin,and the growth hormone/insulin-like growth factor I axis in the tilapia, Oreochromis mossambicus

Ghrelin is a highly conserved peptide hormone secreted by the stomach, which is involved in the regulation of food intake and energy expenditure. Ghrelin stimulates growth hormone (GH) release, and increases appetite in a variety of mammalian and non-mammalian vertebrates, including several fish species. Studies were conducted to investigate the effect of feeding and fasting on plasma and stomach ghrelin, and the growth hormone/insulin-like growth factor I (IGF-I) axis in the Mozambique tilapia, a euryhaline teleost. No postprandial changes in plasma and stomach ghrelin levels or stomach ghrelin mRNA levels were observed. Plasma levels of GH, IGF-I and glucose all increased postprandially which agrees with the anabolic roles of these factors. Fasting for 4 and 8 d did not affect ghrelin levels in plasma or stomach. Plasma GH was elevated significantly after 4 and 8 d of fasting, while plasma IGF-I levels were reduced. Plasma ghrelin levels were elevated significantly after 2 and 4 wk of fasting, but no change was detected in stomach ghrelin mRNA levels. Four weeks of fasting did not affect plasma GH levels, although plasma IGF-I and glucose were reduced significantly, indicating that GH resistance exists during a prolonged nutrient deficit (catabolic state). These results indicate that ghrelin may not be acting as a meal-initiated signal in tilapia, although it may be acting as a long-term indicator of negative energy balance.     

Effect of dietary supplementation of chitosan and galacto-mannan-oligosaccharide on serum parameters and the insulin-like growth factor-I mRNA expression in early-weaned piglets

The study was to determine effects of dietary supplementation of chitosan (COS) and galacto-mannan-oligosaccharids (GMOS) on some serum biochemical indices, serum growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels, and hepatic and long gissimus muscle IGF-I mRNA expression in early-weaned piglets. Twenty six Duroc × Landrace × Yorkshire piglets at the age of 15 days were used. The piglets had access to creep feed during the suckling. Six piglets were sacrificed for sampling at the beginning of the study. The other 20 piglets were individually housed in metabolic cages and randomly allotted to four corn and soybean meal-based diets including the control group, the antibiotic group with 110 mg lincomycin/kg diet, the COS group containing 0.025% COS, and the GMOS group with 0.20% GMOS, respectively, in a 2-week feeding experiment. Blood urea nitrogen (BUN) level was reduced whereas serum total protein concentration was increased (P < 0.05) in responses to the COS and GMOS supplementation. Dietary supplementation of COS and GMOS also increased (P < 0.05) the serum GH and IGF-I levels along with enhanced hepatic and the muscle IGF-I mRNA abundance. Dietary supplementation of oligosaccharides such as COS and GMOS may improve growth and feed conversion efficiency by increasing plasma GH and IGF-I levels, in the early-weaned piglets.     

Activated Vitamin D3 and Pro-activated Vitamin D3 Attenuate Induction of Permanent Changes Caused by Neonatal Estrogen Exposure in the Mouse Vagina

Exposure of mice to a high dose of estrogens including diethylstilbestrol (DES) during the neonatal period modifies the developmental plan of the genital tract, which leads to various permanent changes in physiology, morphology and gene expression. These changes include development of an abnormal vaginal epithelium lined with hyperplastic mucinous cells accompanied by Tff1 gene expression in mice. Here, the influence of vitamin D on the direct effect of estrogen on the developing mouse vagina was examined. The mid-vagina of neonatal mice was cultured in a serum-free medium containing estradiol-17β (E₂) and various concentrations of 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D) ex vivo and then was transplanted under the renal capsule of ovariectomized host mice for 35 days. Exposure to E₂ alone caused the vaginal tissue to develop estrogen-independent epithelial hyperplasia and to express TFF1 mRNA, while addition of a low nanomolar amount of 1,25(OH)₂D added at the same time as E₂ to the culture medium attenuated the effects of estrogen. Expression of vitamin D receptor was also evident in the neonatal mouse vagina. Interestingly, addition of 25-hydroxyvitamin D₃, a pro-activated form of vitamin D, at the micromolar level was found to be potent in disrupting the developmental effects of E₂, while cholecalciferol was not at least at the dose examined. Correspondingly, expression of Cyp27B1, a kidney-specific 25-hydroxyvitamin D hydroxylase, was evident in the neonatal mouse vagina when examined by RT-PCR. In addition, simultaneous administration of 1,25(OH)₂D successfully attenuated DES-induced ovary-independent hyperplasia in the vagina in neonatal mice in vivo. Thus, manipulation of vitamin D influenced the harmful effects of estrogens on mouse vaginal development.     

Circulating concentrations of insulin-like growth factor-1 in dogs with naturally occurring mitral regurgitation

Insulin-like growth factor-1 (IGF-1), which mediates most effects of growth hormone, has effects on cardiac mass and function, and plays an important role in the regulation of vascular tone. In humans, an inverse relationship between degree of heart failure (HF) and circulating IGF-1 concentrations has been found in several studies. In dogs with HF, few studies have focused on IGF-1. We examined circulating IGF-1 concentrations in dogs with mitral regurgitation (MR) caused by myxomatous mitral valve disease. Study 1 included 88 Cavalier King Charles Spaniels (CKCSs) with a broad range of asymptomatic MR (median serum IGF-1: 76.7 microg/L; 25-75 percentile, 59.8-104.9 microg/L). As expected, standard body weight and percentage under- or overweight correlated directly with IGF-1. MR (assessed in 4 different ways) did not correlate with IGF-1. In study 2, 28 dogs with severe MR and stable, treated congestive HF had similar serum IGF-1 concentrations (median, 100.8 g/L; 25-75 percentile, 74.9-156.5 microg/L) as 11 control dogs (79.6 microg/L; 25-75 percentile, 64.1-187.4 microg/L; P = .84). In study 3, the plasma IGF-1 concentration of 15 untreated CKCSs with severe MR was 16.4 +/- 24.2 microg/L lower (P = .02) at the examination when decompensated HF had developed (80.8 +/- 30.9 microg/L) than at a visit 1-12 months earlier (97.2 +/- 39.8 microg/L), possibly in part due to an altered state of nutrition. The studies document that circulating IGF-1 concentrations are not altered before development of congestive HF in dogs with naturally occurring MR, but decrease by approximately 20% with the development of untreated HE In treated HF, circulating IGF-1 concentrations apparently return to within the reference range.     

Effects of tryptophan supplementation on cashmere fiber characteristics, serum tryptophan, and related hormone concentrations in cashmere goats

This study was designed to investigate the effects of tryptophan (Trp) supplementation on cashmere fiber characteristics and on serum Trp, melatonin (MEL), prolactin (PRL), insulin-like growth factor 1 (IGF-1), triiodothyronine (T(3)), and thyroxine (T(4)) concentrations in cashmere goats during the cashmere fast-growth period. Thirty-six Liaoning cashmere wether goats were stratified on the basis of body weight (28 ± 0.8 kg) and assigned randomly to 1 of the following 4 rumen-protected Trp treatments: 0, 2.0, 4.0, and 6.0 g per goat per day. The experimental period lasted 137 d. Blood samples were collected monthly during the daytime (8:00 AM) and at night (8:00 PM). Tryptophan supplementation improved cashmere growth rates, cashmere weight, and body weight (P = 0.001) and increased serum Trp levels, nighttime MEL concentrations, IGF-1, and T(3) and T(4) concentrations (P < 0.05). Across the treatments and sampling months, a highly positive correlation between cashmere growth rate and nighttime serum MEL concentrations was observed (r = 0.879, P = 0.001). A moderately negative correlation between cashmere growth rates and serum PRL concentrations during the day and at night (r(day) = -0.645, P = 0.007; r(night) = -0.583, P = 0.018) was observed. A moderately positive correlation between the cashmere growth rate and the daytime serum IGF-1 concentration (r = 0.536, P = 0.032) was observed, and no correlation was found between the cashmere growth rate and the other serum hormone concentrations. These data indicate that changes in serum concentrations of MEL, IGF-1, and PRL are related to cashmere growth in Liaoning cashmere goats during the cashmere fast-growth period. Under the experimental conditions of the current trial, we suggest that Trp may promote cashmere growth by increasing daytime IGF-1 and nighttime MEL secretion.     

Anti-insulin antibodies in diabetic dogs before and after treatment with different insulin preparations

Background: Anti‐insulin antibodies (AIA) occur in diabetic dogs after insulin therapy, although their clinical significance is unclear. Hypothesis: Treatment of diabetic dogs with heterologous insulin is more likely to stimulate production of AIA than is treatment with homologous insulin. Animals: Diabetic dogs sampled before insulin therapy (n = 40), diabetic dogs sampled following treatment with porcine (homologous) insulin (n = 100), bovine (heterologous) lente insulin (n = 100), or bovine protamine zinc (PZI) insulin (n = 20), and nondiabetic control dogs (n = 120). Methods: Prospective observational study. Sera were analyzed by ELISA for antibodies against porcine insulin, bovine insulin, insulin A, B, or C peptides, and control antigens; canine distemper virus (CDV) and canine thyroglobulin (TG). Canine isotype‐specific antibodies were used to determine total and anti‐insulin IgG1 : IgG2 ratios. Results: There was no difference in CDV or TG reactivity among the groups. AIA were detected in 5 of 40 newly diagnosed (untreated) diabetic dogs. There was no significant difference in AIA (ELISA optical density reactivity) comparing control and porcine insulin‐treated diabetic dogs (P > .05). Anti‐insulin reactivity was most prevalent in bovine PZI insulin‐treated dogs (90%; P < .01), and bovine lente insulin‐treated dogs (56%; P < .01). AIA induced by treatment were enriched for the IgG1 isotype. Conclusions and Clinical Importance: This study indicates that bovine insulin is more immunogenic than porcine insulin when used for treatment of diabetic dogs.