REGIONAL BINDING INDEX OF THE RADIOLABELED SELECTIVE 5-HT2A ANTAGONIST 123I-5-I-R91150 IN THE NORMAL CANINE BRAIN IMAGED WITH SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY

The pattern of the specific 5-HT2A (5-hydroxytryptamine 2A receptor) antagonist 123I-5-I-R91150 was measured in 10 healthy dogs without neurologic and behavior abnormalities. Eight cortical regions (left and right fronto-, temporo-, parieto-, and occipitocortical area), one global subcortical region (including the thalamic system) were compared with a reference region lacking receptors; that is, the cerebellum. The 123I labeled radioligand was injected intravenously 100-200 minutes before acquisition. Both transmission and emission data were obtained with a triple head gamma camera equipped with high-resolution fanbeam collimators. The emission data were corrected for scatter and attenuation. To delineate different cerebral regions more accurately, the regions of interest (ROI) defined in a former study on brain perfusion measured with 99mTc-ethyl cysteinate dimer (ECD) in the same dogs were used. The co-registration of the 99mTc-ECD and the 123I-5-I-R91150, obtained from each dog, was realized with the help of corresponding transmission maps. By normalizing each regional cerebral activity to the activity observed in the cerebellum, the regional radioactivity (binding index) could be relatively quantified. Highest brain uptake was noted in the frontocortical brain areas (right: 1.85, left: 1.89), followed by the temporocortical region (right: 1.58, left: 1.56). Least uptake was noted in the more caudal and middle brain regions [occipito- (right: 1.46, left: 1.41), parietocortical (right: 1.30, left: 1.26), and striatal region (1.19)]. No gender nor age influence was noted in this series. The 123I labeled serotonin-2A receptor ligand seems to have similar cortical binding in the normal canine brain, as shown in humans and other animal species. A frontocortical to occipitocortical (rostrocaudal) binding index gradient was identified within the dog, which has not been seen in imaging studies from humans and other animal species. The significance of these results will need further investigation. This normative data can be used to compare regional brain uptake of the 123I-radioligand to dogs with behavioral disorders related to the serotonergic system, in future studies.     

Echinococcus multilocularis in Austrian foxes from 1991 until 2004

The prevalence rates of Echinococcus multilocularis in foxes (n=5600) evaluated in several Austrian surveys conducted between 1991 and 2004 were analysed for spatial and temporal differences. Data from early studies (1993-1997) in which the intestinal scraping technique (IST) was utilized were compared with data from recent (1999-2004) investigations, which made use of the shaking in a vessel technique (SVT), and it was assessed whether or not the infection rates of Austrian foxes had increased between the investigated intervals. In total, data from 85 districts are presented and both the retrospective and recent data are available from 39 of these districts. A Bayesian hierarchical model of parasite prevalences is presented which (i) accounts for differences in the sensitivity of IST and SVT, (ii) incorporates spatial auto-correlation between neighbouring districts, (iii) investigates the possibility of a temporal shift in the infection status of foxes, and (iv) quantifies uncertainty at each level of the model. The national average prevalence rates in the mid-1990s and at the turn of the millennium were 2.4% (95% confidence intervals 1.1-4.8) and 3.9% (95% confidence intervals 1.5-8.4) respectively. Above average prevalence rates were observed in the western and the northern parts of the country. Evidence is also presented for a temporal augmentation of the prevalence rates in some districts in the northern and eastern parts of the country. These findings are in concordance with several investigations in other European states where both newly emerged areas and elevated levels of transmission in existing endemic areas have been found. None of the districts investigated here showed significant evidence of a drop in prevalence.     

The effect of medetomidine on the regional cerebral blood flow in dogs measured using Technetium-99m-Ethyl Cysteinate Dimer SPECT

Sedatives and anaesthetics are known to cause changes in the regional cerebral blood flow. In dogs intramuscular sedation with medetomidine, a potent sedative frequently used in veterinary medicine, is sometimes indicated prior to intravenous injection of ^99mTechnetium-Ethyl Cysteinate Dimer (^99mTc-ECD) in brain perfusion studies using Single Photon Emission Computed Tomography (SPECT). Based on the knowledge of the distribution of alpha₂-receptors in the brain, we hypothesized altered regional brain perfusion in dogs receiving medetomidine prior to ^99mTc-ECD. Two conditions were compared in 10 dogs; tracer injection before and after intramuscular sedation with medetomidine. In our study, medetomidine caused a significantly higher tracer uptake in all brain regions. Semi-quantification of brain perfusion rendered a lower perfusion index in the subcortical region and an imbalance between left and right cortical perfusion induced by medetomidine. This study shows that caution is needed when quantifying the brain perfusion indices under medetomidine sedation.     

Antimicrobial peptides and proteins of the horse - insights into a well-armed organism

ABSTRACT: Antimicrobial peptides play a pivotal role as key effectors of the innate immune system in plants and animals and act as endogenous antibiotics. The molecules exhibit an antimicrobial activity against bacteria, viruses, and eukaryotic pathogens with different specificities and potencies depending on the structure and amino-acid composition of the peptides. Several antimicrobial peptides were comprehensively investigated in the last three decades and some molecules with remarkable antimicrobial properties have reached the third phase of clinical studies. Next to the peptides themselves, numerous organisms were examined and analyzed regarding their repertoire of antimicrobial peptides revealing a huge number of candidates with potencies and properties for future medical applications. One of these organisms is the horse, which possesses numerous peptides that are interesting candidates for therapeutical applications in veterinary medicine. Here we summarize investigations and knowledge on equine antimicrobial peptides, point to interesting candidates, and discuss prospects for therapeutical applications.     

High prevalence of mycoplasmas in the genital tract of asymptomatic stallions in Austria

Mycoplasma equigenitalium and M. subdolum have been implicated in genital disorders and infertility of horses. The reported cytopathic effects of M. equigenitalium observed in vitro underscore its potential pathogenic role in reproductive dysfunction in mares. This study was initiated to determine the prevalence of mycoplasmas in the genital tract of stallions in relationship to age, clinical signs, geographic location and semen quality. For this purpose the mycoplasma flora of the genital tract of 116 stallions of the Noric breed was determined by isolation and colony immunoblotting and by polymerase chain reaction (PCR) assays. Of 438 swabs from the genital tract, pre-ejaculatory fluid and semen samples, 352 (80%) samples were positive by PCR and 125 (29%) were positive by culture. Mycoplasmas were isolated predominantly from the fossa glandis and urethra and less frequently from the penis shaft and from semen. M. equigenitalium (89 isolates) and M. subdolum (70 isolates) were the predominant species identified. M. equirhinis and M. felis were detected in 27 and 8 samples, respectively. Comparison of these isolations with clinical signs, semen quality, and age of the stallions revealed no significant correlation. However, geographical location of the stallion significantly correlated with mycoplasma detection. These results suggest that mycoplasmas are present as commensals in the genital tract of stallions. Thus, clinically healthy stallions may present a permanent reservoir for infection of mares via venereal transmission.     

Testicular blood flow and plasma concentrations of testosterone and total estrogen in the stallion after the administration of human chorionic gonadotropin

The goal of this study was to investigate for the first time a possible association between plasma concentrations of testosterone and total estrogen and testicular blood flow in the stallion. Correlations between these variables were calculated before and after administration of human chorionic gonadotropin (hCG). Eight mature warmblood stallions received 5,000 IU hCG intravenously, and four stallions received solvent only. Testicular blood flow in the left and right testicular arteries was assessed using colour Doppler sonography by measuring blood flow volume (BFV) and pulsatility index (PI) immediately before (time 0) and 1, 3, 6, 12, 24, 72, 120 and 168 h after hCG administration. EDTA blood samples were collected after each examination from a jugular vein to measure plasma testosterone and total estrogen concentrations. After treatment, the BFV increased and was elevated at 1 h and between 12 and 24 h. The profile of the PI was contrary to that of the BFV throughout the study period. Following hCG, there was a biphasic increase in testosterone concentration with maxima between 1 and 3 h and between 24 and 72 h, and there was a monophasic increase in the total estrogen concentration with a maximum between 6 and 24 h. At time 0, the total estrogen concentration correlated significantly with BFV (r=0.90; P<0.05) but the testosterone concentration did not (P>0.05). The testosterone and total estrogen concentrations did not correlate with PI (P>0.05). The total estrogen concentration, but not testosterone, correlated well with BFV after injection of hCG (P<0.05). The results of this study indicated that the testicular blood flow volume of the stallion may be regulated by estrogens, but additional studies are necessary to investigate whether there is a causal relationship.     

Neuro-imaging the serotonin 2A receptor as a valid biomarker for canine behavioural disorders

The serotonergic system is disturbed in different mood and affective disorders, with especially the serotonin (5-HT) 2A receptor involved in impulsive aggressiveness and anxiety. The aim of the study was to evaluate the involvement of the brain 5-HT 2A receptor in dogs with different behavioural disorders. Three groups of drug naive dogs were studied: 22 dogs showing impulsive aggressive behaviour, 22 showing normal behaviour, and 22 showing anxious behaviour. The serotonin 2A receptor was evaluated with Single Photon Emission Computed Tomography (SPECT) and the serotonin 2A receptor-selective radiopharmaceutical (123)I-R91150. A serotonin 2A receptor binding index (BI), proportional to the cortical receptor density, was calculated. A receiver operating characteristic (ROC) analysis was performed to determine cut-off values at which optimal sensitivity and specificity are achieved and to evaluate the general performance of the BI in reflecting the state of the dog, i.e., impulsive aggressive, normal or anxious. Significantly (P<0.0056) altered 5-HT 2A receptor binding indices were found in bilateral frontal, temporal and occipital cortical brain areas of the dogs behaving abnormally, with consistently increased BI in impulsive aggressive dogs and decreased BI in anxious dogs. These results provide clear evidence for a disturbed serotonergic balance in canine impulsive aggression and anxiety disorders. A right frontal cut-off value of ≥1.92 with 86.4% sensitivity and 2.3% (1-specificity) was obtained for the impulsive aggressive dogs. Differentiating the anxious dogs from the rest of the population was possible with a cut-off value of ≤1.73 with 86.4% sensitivity and 18.2% (1-specificity). We conclude that SPECT imaging with the radioligand (123)I-R91150 can be a helpful tool in evaluating the involvement of the serotonin 2A receptor in the complex mechanisms of impulsive aggressive and anxious behaviour. The 5HT-2A binding index of the right frontal cortex appears to be a valid biomarker in differentiating the studied canine behavioural disorders.