Functional Consequences of PDK4 Deficiency in Doberman Pinscher Fibroblasts.

A splice site mutation in the canine pyruvate dehydrogenase kinase 4 (PDK4) gene has been shown to be associated with the development of dilated cardiomyopathy (DCM) in Doberman Pinchers (DPs). Subsequent studies have successfully demonstrated the use of dermal fibroblasts isolated from DPs as models for PDK4 deficiency and have shown activation of the intrinsic (mitochondrial mediated) apoptosis pathway in these cells under starvation conditions. For this study, we sought to further explore the functional consequences of PDK4 deficiency in DP fibroblasts representing PDK4wt/wt, PDK4wt/del, and PDK4del/del genotypes. Our results show that starvation conditions cause increased perinuclear localization of mitochondria and decreased cell proliferation, altered expression levels of pyruvate dehydrogenase phosphatase (PDP) and pyruvate dehydrogenase (PDH), dramatically increased PDH activity, and an impaired response to mitochondrial stress in affected cells. In sum, these results show the broad impact of PDK4 deficiency and reveal mechanistic pathways used by these cells in an attempt to compensate for the condition. Our data help to elucidate the mechanisms at play in this extremely prevalent DP disorder and provide further support demonstrating the general importance of metabolic flexibility in cell health.

ECHOCARDIOGRAPHIC FINDINGS OF BIDIMENSIONAL MODE, M-MODE, AND DOPPLER OF CLINICALLY NORMAL BLACK-RUMPED AGOUTI (DASYPROCTA PRYMNOLOPHA, WAGLER 1831).

The black-rumped agouti ( Dasyprocta prymnolopha , Wagler 1831) is currently under intense ecologic pressure, which has resulted in its disappearance from some regions of Brazil. Echocardiography is widely used in veterinary medicine but it is not yet part of the clinical routine for wild animals. The objective of the present study was to assess the applicability of the echocardiographic exam in nonanesthetized agouti and to establish normal reference values for echocardiographic measurements in bidimensional mode (2D), M-mode, and Doppler for this species, and a lead II electrocardiogram was simultaneously recorded. Twenty agouti were used in this study. All the echocardiographic measurements were positively correlated with weight (P < 0.05), and there were no significant differences between sexes (P > 0.05). Blood flow velocities in the pulmonary and aortic artery ranged from 67.32-71.28 cm/sec and 79.22-101.84 cm/sec, respectively. The isovolumic relaxation time was assessed in all the animals and ranged from 38.5 to 56.6 ms. The maximum value for the nonfused E and A waves and the Et and At waves was 158 beats/min for both. The results obtained for the morphologic and heart hemodynamic measurements can guide future studies and help in the clinical management of these animals in captivity.

Clearance of plasma ivermectin with single pass lipid dialysis in 2 dogs.

OBJECTIVE: To describe the use of single pass lipid dialysis (SPLD) for treatment of ivermectin toxicosis in 2 Australian Shepherd dogs with the ABCB1-1Δ gene mutation. CASE SERIES SUMMARY: Two Australian Shepherd dogs were presented for treatment of ivermectin toxicosis. Dogs were initially treated with intravenous lipid emulsion and supportive care, without improvement of clinical signs. They both developed respiratory paralysis and required mechanical ventilation. In order to increase the clearance of circulating ivermectin, SPLD was performed using dialysate containing 5% lipid. Blood samples were obtained immediately before and after dialysis and analyzed for serum ivermectin concentration. Ivermectin reduction ratio was calculated at 29% and 39% for each dog, respectively. When compared to intrinsic total body ivermectin clearance, only the second dog had a relative improvement of plasma clearance following SPLD. Both dogs were confirmed to be homozygous for ABCB1-1Δ gene mutations. Both dogs remained ventilator dependent for several days and ultimately made a full recovery. NEW OR UNIQUE INFORMATION PROVIDED: SPLD may be an adjunctive detoxification strategy for highly lipophilic toxins such as ivermectin.

Ophthalmic abnormalities secondary to periocular or ocular snakebite (pit vipers) in dogs--11 cases (2012-2014).

OBJECTIVE: To describe ophthalmic abnormalities secondary to periocular and ocular snakebite in dogs. ANIMAL STUDIED: Retrospective review of medical records from dogs presenting to the Small Animal Hospital at University of Florida following snakebites to the face (2012-2014). Two groups were identified: periocular bites (PB) and ocular bites (OB). RESULTS: Records from eleven dogs matched the search criteria and were included in the study (PB=9, 81.8%; OB=2, 18.2%). Both OB cases involved the cornea. Facial edema, blepharospasm, chemosis, and conjunctival hyperemia occurred in all cases (100%). Hemorrhage from the eyelids occurred in eight cases (72.7%; PB=7, OB=1). Subconjunctival hemorrhage occurred in seven cases (63.6%; PB=6, OB=1). Third eyelid laceration and nictitans gland prolapse occurred in 1 case each (9%; PB=1). Lagophthalmia was present in three cases (27.3%; PB=3), with secondary corneal ulcer in two cases (18.2%; PB=2). Corneal ulcer due to direct corneal bite occurred in two cases (18.2%-partial thickness with melting (1) and full thickness (1) ). Uveitis was present in 6 cases (54.5%; PB=4, OB=2), with flare and miosis in 4 cases (36.4%; PB=2, OB=2). Hyphema, fibrin in anterior chamber, and cataract occurred in one case (9%; OB=1). Vision loss occurred in two cases (18.2%; PB=2), secondary to retinal degeneration (PB=1) and amaurosis (PB=1). Mean follow-up time was 7 weeks (range: 3 days-11 months). Most clinical signs had resolved by last examination. CONCLUSIONS: Periocular symptoms were more commonly observed than ocular alterations, regardless of bite location. Appropriate supportive therapy should be instituted according to clinical signs.

Penile amputation and scrotal urethrostomy followed by chemotherapy in a dog with penile hemangiosarcoma.

A 7 yr old castrated male standard poodle weighing 25 kg was presented with a 5 day history of hematuria, dysuria, and the presence of a 2.5 cm, firm swelling within the prepuce. Abdominal radiographs revealed a soft-tissue mass on the distal prepuce and lysis of the cranial margin of the os penis. The patient was sedated and an ulcerated hemorrhagic mass was identified at the tip of the penis. The mass was diagnosed as hemangiosarcoma via incisional biopsy. A penile amputation with scrotal urethrostomy was performed followed by chemotherapy with doxorubicin.

Treatment of ibuprofen toxicosis in a dog with IV lipid emulsion.

A 3 yr old spayed female mixed-breed dog weighing 19.4 kg was evaluated for ingestion of 1,856 mg/kg (180 tablets) of ibuprofen, a human formulated nonsteroidal anti-inflammatory drug (NSAID). At the time of presentation, the patient was alert and hypersalivating, but her mental status rapidly declined to obtunded, stuporous, and then comatose within 30 min of presentation. Initial treatment included supportive therapy with prostaglandin analogs and antiemetics. An IV lipid emulsion (ILE) was administered as a bolus, followed by a constant rate infusion. Clinical signs began to improve approximately 3 hr after completion of the lipid infusion. The patient required supportive care for 3 days before discharge. This case report demonstrates the use of ILE for treatment of ibuprofen toxicosis in a dog. ILE infusion may be a therapeutic option for patients with toxicosis due to lipid-soluble drugs.

Methocarbamol CRI for symptomatic treatment of pyrethroid intoxication: a report of three cases.

Pyrethroids are popular for use in companion animals due to their relatively low mammalian toxicity and efficacy against arthropods. Nonetheless, pyrethroid intoxication has been reported in cats and dogs, and cats appear to be more susceptible due to difficulty in biotransformation and excretion of pyrethroids. Pyrethroid intoxications are generally due to either the improper use or accidental ingestion of approved products. Methocarbamol, given as intermittent injections, is a common first-line treatment choice for the tremors associated with pyrethroid intoxication. Two cats and one dog were treated with a methocarbamol continuous rate infusion (CRI) for pyrethroid intoxication. Clinical signs of toxicity resolved within a few hr in all three cases, with no adverse drug effects. A methocarbamol CRI can be considered in animals presenting with pyrethroid intoxication.

Relação dos músculos papilares com os segmentos anátomo-cirúrgicos do ventrículo esquerdo e ramos marginais da artéria coronária esquerda em cães (Canis familiaris, Linnaeus, 1758) / Relación de los músculos papilares con los segmentos anatómicos y quirúrgicos del ventrículo izquierdo y ramas marginales de la arteria coronaria izquierda en perros (Canis familiaris, Linnaeus, 1758) / Relation of papillary muscles with anatomic surgical segments of the left ventricule and marginal branches of the left coronary artery of dogs (Canis familiaris, Linnaeus, 1758)

Em 20 corações de cães sem raça definida estudou-se a morfologia e a relação dos músculos papilares do ventrículo esquerdo com os segmentos anátomo-cirúrgicos e ramos marginais da artéria coronária esquerda na superfície externa do ventrículo esquerdo. O objetivo foi oferecer condições de localizá-los por meio da superfície externa do ventrículo esquerdo, evitando incluí-los no segmento muscular plicado ou seccionado. Após serem lavados, os corações foram fixados e conservados em solução de formol a 10%. Com auxílio de alfinetes, cada músculo papilar foi dividido transversalmente em 3 porções: dorsal, média e ventral. A artéria circunflexa emite ramos marginais ventricular caudo-lateral esquerdo (VCLE), intermédio (RI) e ventricular caudo-lateral direito (VCLD). No ventrículo esquerdo estão presentes os músculos papilares subauricular e subatrial. Em todas as preparações, o músculo papilar subauricular relacionou-se com o segmento anátomo-cirúrgico vascular ventricular ventral esquerdo (III); o músculo papilar subatrial com o segmento anátomo-cirúrgico vascular ventricular ventral direito (V) em 13 casos (65,0%); com o segmento anátomo-cirúrgico vascular ventricular marginal esquerdo (IV) em 3 peças (15,0%); com ambos os segmentos IV e V em 4 casos (20,0%). Nas 20 preparações (100%), o músculo papilar subauricular relacionou-se com o ramo VCLE e o músculo papilar subatrial relacionou-se com os ramos RI e VCLD em 18 peças (90,0%). Os músculos papilares apresentaram-se de três maneiras: simples, com uma ramificação ou com duas ramificações. De acordo com esses achados, torna-se mais seguro realizar as plicaturas no segmento anátomo-cirúrgico vascular ventricular marginal esquerdo (IV), orientando-se pelo ramo RI.

In 20 hearts of mongrel dogs, the morphology and the relation of the papillary muscles of the left ventricule with the anatomic-surgical segments and marginal branches of the left coronary artery on the external surface of the left ventricule were studied. The objective was to provide ways of localizing them through the external surface of the left ventricule in order to avoid its inclusion in the plicated or sectioned muscular segment. After being washed, the hearts were fixed and preserved in formaldehyde solution 10%. Using needles, each papillary muscle was separated transversally into three portions: dorsal, median and ventral. The circumflex artery had left caudal-lateral ventricular (LCLV), intermediate (I) and right caudal-lateral ventricular (RCLV) marginal branches. The subauricular and subatrial papillary muscles are found in the left ventricule. In all the preparations, the subauricular papillary muscle was related to the left ventral anatomic-surgical segment (III); the subatrial papillary muscle was related to the right ventral anatomic-surgical segment (V) in 13 cases (65.0%), to the left marginal anatomic-surgical segment (IV) in 3 pieces (15.0%), and to both IV and V segments in 4 cases (20.0%). In 20 preparations (100%), the subauricular papillary muscle was related to the LCLV branch, and the subatrial papillary muscle to I and RCLV branches in 18 pieces (90.0%). The papillary muscles were presented in three ways: single, with one branching or with two branchings. According to these findings, it is safer to apply the left ventricule plication in the left marginal anatomic-surgical segment (IV), oriented by I branch.

En 20 corazones de perros, sin raza definida, se estudió la morfología y la relación de los músculos papilares del ventrículo izquierdo, con los segmentos anatómicos quirúrgicos y ramas marginales de la arteria coronaria izquierda en la superficie externa del ventrículo izquierdo, evitando incluirlos en el segmento muscular doblado o seccionado. Después de lavados, los corazones fueron fijados y conservados en solución de formol a 10%. Con auxilio de alfileres, cada músculo papilar fue dividido transversalmente en 3 porciones: dorsal, mediana y ventral. La arteria circunfleja emite ramas marginales ventriculares caudal-lateral izquierdo (VCLI), intermedio (RI) y ventricular caudal-lateral derecho (VCLD). En el ventrículo izquierdo están presentes los músculos papilares subauricular y subatrial. En todas las preparaciones, el músculo papilar su- bauricular se relacionó con el segmento anatómico quirúrgico vascular ventricular ventral izquierdo (III); el músculo papilar subatrial con el segmento anatómico quirúrgico vascular ventricular ventral derecho (V) en 13 casos (65%); con el segmento anatómico quirúrgico vascular ventricular marginal izquierdo (IV) en 3 piezas (15%); con los segmentos IV y V en 4 casos (20%). En las 20 preparaciones (100%), el músculo papilar subauricular se relacionó con la rama VCLI y el músculo papilar subatrial se relacionó con las ramas RI y VCLD en 18 piezas (90,0%). Los músculos papilares se presentaron de tres formas: simples, con una ramificación o con dos ramificaciones. De acuerdo con esos hallazgos, se hace más seguro realizar las dobladuras en el segmento anatómico quirúrgico vascular ventricular marginal izquierdo (IV), orientándose por la rama RI.