Michael Leschnik

Impaired Heart Contractility in Apelin Gene–Deficient Mice Associated With Aging and Pressure Overload

Apelin constitutes a novel endogenous peptide system suggested to be involved in a broad range of physiological functions, including cardiovascular function, heart development, control of fluid homeostasis, and obesity. Apelin is also a catalytic substrate for angiotensin-converting enzyme 2, the key severe acute respiratory syndrome receptor. The in vivo physiological role of Apelin is still elusive. Here we report the generation of Apelin gene–targeted mice. Apelin mutant mice are viable and fertile, appear healthy, and exhibit normal body weight, water and food intake, heart rates, and heart morphology. Intriguingly, aged Apelin knockout mice developed progressive impairment of cardiac contractility associated with systolic dysfunction in the absence of histological abnormalities. We also report that pressure overload induces upregulation of Apelin expression in the heart. Importantly, in pressure overload–induced heart failure, loss of Apelin did not significantly affect the hypertrophy response, but Apelin mutant mice developed progressive heart failure. Global gene expression arrays and hierarchical clustering of differentially expressed genes in hearts of banded Apelin−/y and Apelin+/y mice showed concerted upregulation of genes involved in extracellular matrix remodeling and muscle contraction. These genetic data show that the endogenous peptide Apelin is crucial to maintain cardiac contractility in pressure overload and aging.

Subclinical Infection with Avian Influenza A H5N1 Virus in Cats

Infection without disease may occur under natural conditions after contact with infected birds.

Clinical symptoms and diagnosis of encephalitozoonosis in pet rabbits.

Infections with Encephalitozoon cuniculi in rabbits are observed at increasing frequency and are known as opportunistic infections in immunocompromised humans. 191 pet rabbits with suspected encephalitozoonosis, presented at the Animal Hospital of the Veterinary University of Vienna (Austria), were included in this study. Rabbits were serologically examined for antibodies against E. cuniculi (144 positive out of 184 rabbits with suspected encephalitozoonosis compared to 14 positive out of 40 clinically healthy rabbits tested as part of a standard health check) and Toxoplasma gondii (8 positive out of 157). Of the 144 seropositive rabbits with clinical signs, 75% showed neurological symptoms, 14.6% demonstrated phacoclastic uveitis and 3.5% suffered from renal failure. 6.9% of the animals had combined symptoms. Vestibular disease dominated within the rabbits that showed neurological symptoms. Polymerase chain reaction (PCR) could not detect parasite DNA in urine or cerebrospinal fluid (CSF), but did so in 4 out of 5 samples of liquefied lens material in cases with phacoclastic uveitis due to lens capsule rupture. Additionally further diagnostic procedures, such as inspection of the external ear canal (N=69), radiography of the tympanic bullae (N=65) were performed to rule out differential diagnosis. 54.2% of the patients exhibiting neurological symptoms recovered within a few days, while 87.5% of the rabbits suffering from renal failure died or had to be euthanized.

Tick-borne encephalitis (TBE) in dogs

Tick-borne encephalitis (TBE) is caused by a Flavivirus and transmitted by ticks. It is known in dogs for nearly 30 years and the number of TBE cases is increasing. In addition to fever, cerebrocortical, thalamic, and brainstem symptoms occur simultaneously. Not all TBE infections in dogs lead to clinical signs but peracute/lethal as well as subacute and chronic courses have been reported. TBE is a seasonal disease, depending on climate related tick activity. Infected ticks are spreading the virus over central Europe with a tendency to expand to new endemic areas in western Europe.

Complex partial cluster seizures in cats with orofacial involvement.

Seventeen cats were presented with acute onset of complex partial seizures with orofacial involvement (salivation, facial twitching, lip smacking, chewing, licking or swallowing), motor arrest (motionless starring) and behavioural changes. In 11 cats hippocampal necrosis (HN) was confirmed by histopathology. In a further six cats hippocampal changes were suggested by magnetic resonance imaging. The mean monitoring time of eight cats which were not euthanased in the acute phase of the disease, was 408 days (60–908): four cats are still alive. In all surviving cases, the owners reported a good quality of life. We conclude that an acute cluster of complex partial seizures with orofacial involvement are often associated with HN and that HN is not necessarily a fatal condition. Supportive and antiepileptic therapy can result in remission. The long-term outcome can be good to excellent; therefore, euthanasia should be avoided in the acute phase of the signs.

Ticks and haemoparasites of dogs from Praia, Cape Verde.

In February 2008 an epidemiological field study on arthropod-borne infections in dogs was carried out in Praia, the capital city of Cape Verde. For this purpose 130 dogs were included in the study. Of these, 94.6% were infested with ticks. Altogether, 1293 ticks of the genus Rhipicephalus (in all evaluated cases R. sanguineus) were collected. Examination for haemotropic parasites was performed via polymerase chain reaction (PCR). Lymph node fine-needle aspirates were screened by PCR for Leishmania infantum infections in 20 dogs with enlarged lymph nodes. Our investigation revealed two species of protozoa (Babesia canis vogeli and Hepatozoon canis) and two species of rickettsiae (Anaplasma platys and Ehrlichia canis). In 101 dogs (77.7%) DNA of one or more pathogens was detected. The PCR examination for H. canis was positive in 83 dogs (63.8%), for E. canis in 34 dogs (26.2%), for A. platys in 10 dogs (7.7%) and for B. canis in five dogs (3.8%), whereas neither B. gibsoni nor L. infantum DNA could be detected. Of the infected dogs, 71.3% had a monoinfection, 27.7% had infections with two pathogens and 1.0% with three pathogens. B. canis, H. canis, E. canis, A. platys and their vector tick R. sanguineus are endemic to Cape Verde and can be present in dogs in high prevalences. These results outline the risk of importing tropical canine diseases when Capeverdian stray dogs are taken to Europe.

Clinical comparison of primary versus secondary epilepsy in 125 cats

In the present study 125 cats with recurrent seizures were analysed. The main goal was to investigate the aetiology and compare primary epilepsy (PE) with secondary epilepsy (SE) regarding signalment, history, ictal pattern, clinical and neurological findings. Seizure aetiology was classified as PE in 47 (38%) and SE in 78 (62%) cats. SE was caused mainly by intracranial neoplasia (16), hippocampal necrosis (14), toxicosis (eight), and encephalitis (seven). A significant difference between PE and SE was found in: age, body weight, duration of seizure, occurrence of status epilepticus and neurological deficits. Status epilepticus, altered interictal neurological status and seizure onset over the age of 7 years indicated SE more frequently than PE. If the seizures occurred during resting conditions and rapid running occurred the aetiology was more likely to be PE than SE.

Suspected limbic encephalitis and seizure in cats associated with voltage-gated potassium channel (VGKC) complex antibody.

BACKGROUND Treatment-resistant complex partial seizures (CPS) with orofacial involvement recently were reported in cats in association with hippocampal pathology. The features had some similarity to those described in humans with limbic encephalitis and voltage-gated potassium channel (VGKC) complex antibody. HYPOTHESIS/OBJECTIVES The purpose of this pilot study was to evaluate cats with CPS and orofacial involvement for the presence of VGKC-complex antibody. ANIMALS Client-owned cats with acute orofacial CPS and control cats were investigated. METHODS Prospective study. Serum was collected from 14 cats in the acute stage of the disease and compared with 19 controls. VGKC-complex antibodies were determined by routine immunoprecipitation and by binding to leucine-rich glioma inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2), the 2 main targets of VGKC-complex antibodies in humans. RESULTS Five of the 14 affected cats, but none of the 19 controls, had VGKC-complex antibody concentrations above the cut-off concentration (>100 pmol/L) based on control samples and similar to those found in humans. Antibodies in 4 cats were directed against LGI1, and none were directed against CASPR2. Follow-up sera were available for 5 cats in remission and all antibody concentrations were within the reference range. CONCLUSION AND CLINICAL IMPORTANCE Our study suggests that an autoimmune limbic encephalitis exists in cats and that VGKC-complex/LGI1 antibodies may play a role in this disorder, as they are thought to in humans.

Loss of LAP2α Delays Satellite Cell Differentiation and Affects Postnatal Fiber‐Type Determination

Lamina‐associated polypeptide 2α (LAP2α) is a nucleoplasmic protein implicated in cell cycle regulation through its interaction with A‐type lamins and the retinoblastoma protein. Mutations in lamin A/C and LAP2α cause late onset striated muscle diseases, but the molecular mechanisms are poorly understood. To study the role of LAP2α in skeletal muscle function and postnatal tissue homeostasis, we generated complete and muscle‐specific LAP2α knockout mice. Whereas overall muscle morphology, function, and regeneration were not detectably affected, the myofiber‐associated muscle stem cell pool was increased in complete LAP2α knockout animals. At molecular level, the absence of LAP2α preserved the stem cell‐like phenotype of Lap2α−/− primary myoblasts and delayed their in vitro differentiation. In addition, loss of LAP2α shifted the myofiber‐type ratios of adult slow muscles toward fast fiber types. Conditional Cre‐mediated late muscle‐specific ablation of LAP2α affected early stages of in vitro myoblast differentiation, and also fiber‐type determination, but did not change myofiber‐associated stem cell numbers in vivo. Our data demonstrate multiple and distinct functions of LAP2α in muscle stem cell maintenance, early phases of myogenic differentiation, and muscle remodeling. STEM CELLS 2010;28:480–488

Detection of Dirofilaria in Austrian dogs

A recent increase in the occurrence of Dirofilaria repens and Dirofilaria immitis has been reported from the eastern neighbouring countries of Austria (Slovakia, Hungary). In order to obtain data from Austria--especially from the areas bordering these countries--blood samples of dogs from Gänserndorf (northeastern Austria, bordering Slovakia) and Neusiedl (eastern Austria, bordering Hungary) were examined for the presence of Dirofilaria spp.-DNA by quantitative real-time PCR (qPCR). For D. repens one (out of eight) and six (out of ninety) positive dogs were found, respectively. D. immitis-DNA was not detected. Most of the positive dogs had previously been abroad in known Dirofilaria endemic areas. Two dogs, however, had never been abroad and presumably became infected in Austria. To investigate an autochthonous focus, 1366 mosquitoes from the eastern part of Austria were also examined by qPCR. Although positive mosquitoes could not be found, an emerging endemic occurrence of D. repens in Austria due to positive dogs seems possible.