Cardiac changes induced by excess exogenous growth hormone in juvenile miniature poodles

The transient elevated plasma growth hormone (GH) levels that occur at a young age in giant breed dogs may have consequences in adult life. The aim of this study was to investigate whether excess juvenile GH has consequences for cardiac function and morphology. To simulate the naturally occurring juvenile hypersomatotropism in giant breed dogs, elevated plasma GH and insulin-like growth factor-I (IGF-I) concentrations were induced in six miniature poodles (GH dogs) by daily administration of supraphysiological doses of GH starting at 12 weeks of age. Eight miniature poodles of the same age that received vehicle only served as controls. Cardiac anatomy and function were evaluated by echocardiography. After euthanasia at 21 weeks of age, the hearts were examined for weight, myocyte dimensions and collagen fraction. The hearts of the GH dogs had larger atria (+22%), a thicker left ventricular wall (+21%), greater weight (+84%), and their cardiomyocytes were 15% longer, 25% thicker, and 92% greater in volume than those of control dogs. The mean collagen fraction was also higher in the GH dogs (5.6%) than in the controls (3.1%). In conclusion, excess GH in juvenile miniature poodles resulted in myocardial hypertrophy and increased collagen content. These findings are consistent with observations in acromegalic human patients and in rats treated with GH.     

Effect of Physiological Determinants and Cardiac Disease on Plasma Adiponectin Concentrations in Dogs

Background

In humans, a high concentration of adiponectin is associated with a favorable cardiovascular risk profile whereas, in patients with heart failure (HF), a high concentration of adiponectin is associated with a less favorable prognosis.

Hypothesis/Objectives

To evaluate the physiological determinants of plasma adiponectin concentration in dogs and the influence of heart disease, myxomatous mitral valve disease (MMVD), and dilated cardiomyopathy (DCM).

Animals

One hundred and fourteen client‐owned dogs and 9 Beagles from the research colony of the Clinical Veterinary Unit of the University of Liège.

Methods

We prospectively measured circulating adiponectin concentration in healthy control dogs (n = 77), dogs with MMVD (n = 22) and dogs with DCM (n = 15) of various degrees of severity. Diagnosis was confirmed by Doppler echocardiography. Plasma adiponectin concentration was measured by a canine‐specific sandwich ELISA kit.

Results

An analysis of covariance showed an association between adiponectin concentration and age, neuter status, and heart disease. No association between adiponectin concentration and class of HF, sex, body condition score, body weight, circadian rhythm, or feeding was found. Plasma adiponectin concentration was negatively correlated with age (P = .001). Adiponectin was lower in neutered (P = .008) compared to intact dogs. Circulating adiponectin concentration was increased in dogs with DCM compared to healthy dogs (P = .018) and to dogs with MMVD (P = .014).

Conclusions and Clinical Importance

Age and neutering negatively influence circulating adiponectin concentration. Plasma adiponectin concentration increased in dogs with DCM. Additional research is required to investigate if this hormone is implicated in the pathophysiology of DCM and associated with clinical outcome.     

Excretion of loline alkaloids in urine and faeces of sheep dosed with meadow fescue (Festuca pratensis) seed containing high concentrations of loline alkaloids

Abstract

AIM: To determine the effect of oral dosing of sheep with loline alkaloids on their excretion in urine and faeces, and to monitor for any toxic effects.

METHODS: In Experiment 1, six 9-month-old ewe lambs were given a single oral dose of loline alkaloids (52 mg/kg bodyweight (BW); acute exposure) as a suspension of ground meadow fescue (Festuca pratensis) seed in water. In Experiment 2, on six consecutive days, six ewe lambs were given three doses of loline (68 mg/kg BW/day; chronic exposure). Blood was collected at variable intervals up to 72 h in Experiment 1, and up to 8 days in Experiment 2, for haematology and measurement of alkaline phosphatase, aspartate aminotransaminase, creatine kinase and γ-glutamyl transferase in plasma. Urine and faecal samples were collected at similar times for measurement of creatinine in urine and loline alkaloid analysis. A post mortem with histopathology was carried out on two animals at the end of each experiment.

RESULTS: The loline alkaloids, N-acetyl norloline, N-formyl loline, N-acetyl loline, N-methyl loline and loline base were detected in urine within 15 minutes after the single dosing. N-formyl loline and loline base were the predominant metabolites in urine in both experiments. The total quantity of lolines excreted in both urine and faeces was 10% and 4% of the amount dosed in Experiments 1 and 2, respectively. In both experiments, the clinical chemistry parameters in blood and urine were within normal ranges. Post-mortem and histopathological examination did not show any abnormalities.

CONCLUSIONS: This is the first report of loline alkaloid profiles in both urine and faeces of sheep. The appearance of loline alkaloids and the loline base in urine within 15 minutes suggests rapid uptake, metabolism and excretion. Loline alkaloids were non-toxic to sheep at the concentrations they are exposed to under New Zealand grazing conditions. The low recovery of loline alkaloids in urine and faeces in the absence of toxicity signs suggests lolines are extensively metabolised; probably to forms other than N-formyl loline, N-methyl loline, N-acetyl loline, N-acetyl norloline, and loline base in the digestive tract of sheep prior to absorption, and/or in the liver or other tissues following absorption.     

An in situ single-pass perfusion model for assessing absorption across the intestinal mucosa of the brushtail possum

AIM: To develop an in situ animal model for assessing absorption of molecules across the intestinal mucosa of possums.

METHODS: A surgical preparation was used to perfuse known concentrations of reference compounds (fluorescein and luteinising hormone-releasing hormone; LHRH) through measured sections of selected regions (jejunum, caecum, proximal colon) of the intestinal tract of 19 possums, over a 2-h period. Plasma concentrations of the compounds, which were perfused either with or without co-administration of a permeation enhancer (sodium deoxycholic acid; SDA), were determined in the perfusion effluent, peripheral and in some instances in the pre-hepatic circulation by spectrofluorometry (fluorescein) or radio-immunoassay (LHRH). Pharmacokinetic parameters of both compounds in the possum were determined over a period of up to 4 h in a further 30 animals (fluorescein, n=6; LHRH n=24), from their plasma profiles following intravenous (I/V) administration of a bolus dose.

RESULTS: In animals perfused with 25 mg/ml fluorescein (Perfusion Experiment (PE) 1), the mean plasma concentration was 2.8 (SE 0.12) µg/ml in post-hepatic blood samples. When possums were perfused with 2.5 mg/ml fluorescein and 7 µg/ml LHRH (PE 2), mean plasma concentrations were 0.3 (SE 0.01) and 7.8 (SE 1.64) µg/ml fluorescein and 0.1 (SE 0.02) and 6.3 (SE 0.45) ng/ml LHRH, in the absence and presence of permeation enhancer, respectively. There was a poor correlation between pre-hepatic and post-hepatic concentrations.

CONCLUSIONS: The single-pass in situ perfusion technique provided a useful model for investigating basic information on the absorption of biocontrol agents across the intestinal tract of possums, but had limitations that must be recognised.     

High Similarity Between Tomato Isolates of Pepino mosaic Virus Suggests a Common Origin

The almost simultaneous outbreaks of Pepino mosaic virus in tomato crops in different European and non-European countries, was reason to have a closer look at the relationship between these isolates and the original isolate from pepino. Fifteen isolates from tomato from different locations and the original pepino isolate, were compared on the basis of their symptomatology on a series of plant species. In addition, PCR fragments derived from the viral polymerase gene were sequenced and aligned. Both studies showed that the isolates from tomato clearly differed from the pepino isolate. The different tomato isolates, however, exhibited only minor differences to each other, both in symptomatology and nucleotide sequence. These results support the conclusion that the tomato isolates should be considered as a distinct strain (Mumford and Metcalfe (2001) Archives of Virology 146: 2455–2460; Van der Vlugt et al. (2000) Plant Disease 84: 103; Van der Vlugt et al. (2002) Bulletin OEPP/EPPO Bulletin 32: 503–508). Moreover, the high similarity of the different tomato isolates suggests the existence of a common source of infection for the recent outbreaks.     

Overgang Van Ringvuur(Verticillium Alboatrum) Bij Aardappelen Met De Knollen

European Journal of Plant Pathology -