Lack of evidence for perinatal transmission of canine granulocytic anaplasmosis from a bitch to her offspring.

Granulocytic anaplasmosis is an emerging infectious disease affecting dogs and humans in the United States and other regions of the world. Relatively few cases have been described in pregnant women, and perinatal transmission appears to occur infrequently in humans. Infection in pregnant dogs has not been reported. Diagnosis of infection during pregnancy poses therapeutic challenges, because doxycycline, the treatment of choice, is teratogenic. Also, infection during pregnancy may result in more severe disease. When infection is diagnosed after parturition, knowledge of the risk of perinatal transmission to offspring is important, because prophylactic therapy in neonates is also not without risk. In this report, we describe relatively severe clinical manifestations of Anaplasma phagocytophilum infection in a postpartum bitch and a lack of perinatal transmission to her puppies.

Insulin activation of the phosphatidylinositol 3-kinase/protein kinase B (Akt) pathway reduces lipopolysaccharide-induced inflammation in mice.

Insulin is used to control pro-inflammatory hyperglycemia in critically ill patients. However, recent studies suggest that insulin-induced hypoglycemia may negate its beneficial effects in these patients. It is noteworthy that recent evidence indicates that insulin has anti-inflammatory effects that are independent of controlling hyperglycemia. To date, the mechanism by which insulin directly reduces inflammation has not been elucidated. It is well established that insulin activates phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling in many cell types. We and others have shown that this pathway negatively regulates LPS-induced signaling and pro-inflammatory cytokine production in monocytic cells. We hypothesized that insulin inhibits inflammation during endotoxemia by activation of the PI3K/Akt pathway. We used a nonhyperglycemic mouse model of endotoxemia to determine the effect of continuous administration of a low dose of human insulin on inflammation and survival. It is noteworthy that insulin treatment induced phosphorylation of Akt in muscle and adipose tissues but did not exacerbate lipopolysaccharide (LPS)-induced hypoglycemia. Insulin decreased plasma levels of interleukin-6, tumor necrosis factor-alpha, monocyte chemotactic protein 1 (MCP1)/JE, and keratinocyte chemoattractant, and decreased mortality. The PI3K inhibitor wortmannin abolished the insulin-mediated activation of Akt and the reduction of chemokine and interleukin-6 levels. We conclude that insulin reduces LPS-induced inflammation in mice in a PI3K/Akt-dependent manner without affecting blood glucose levels.

Morphometric assessment of the proximal portion of the tibia in dogs with and without cranial cruciate ligament rupture.

Based on the clinical observation that dogs with a steep tibial plateau slope had variable tibial morphology, we hypothesized that these dogs could be further characterized using measurements developed by examining computer generated models of specific proximal tibial malformations. A 3D tibial model was created from a normal canine tibia. The model was manipulated to reproduce two specific proximal tibial anomalies representing deformities originating from the tibial plateau or the proximal tibial shaft. Data from these models were used to create specific measurements that would characterize the shape of these anomalies. These measurements included the diaphyseal tibial axis (DTA)/proximal tibial axis (PTA) angle, which defined the orientation of the proximal portion of the shaft in relation to the tibial mid-shaft. These measurements were then made on radiographs of dogs with and without cranial cruciate ligament (CCL) rupture. Models with tibial plateau and proximal shaft deformities had a steep tibial plateau slope (TPS). Models with proximal shaft deformity had a markedly increased DTA/PTA angle. The model with a 10 degree proximal shaft deformity had a DTA/PTA angle of 11.23 degrees. Six dogs (9.0%) had a DTA/PTA angle larger than 11.23 degrees (range, 11.4-13.9 degrees). Dogs in this group had ruptured CCL and a steep TPS. Dogs with CCL rupture had higher TPS (mean, 31.8 +/- 4.1 degrees) and DTA/PTA angle (mean, 6.0 +/- 3.3 degrees) than dogs without CCL rupture (means, 23.6 +/- 3.4 degrees and 4.1 +/- 2.2 degrees, respectively). Dogs with proximal shaft deformity represented a distinct group, which could not be identified using the magnitude of the TPS alone. Characterizing more precisely the shape of the proximal portion of the tibia in dogs contributes to our understanding of the pathogenesis of steep TPS and may facilitate the optimization of the surgical management of dogs with CCL rupture.

Cat red blood cell thiopurine S-methyltransferase: companion animal pharmacogenetics.

A common genetic polymorphism for thiopurine S-methyltransferase (TPMT) is a major factor responsible for individual variation in the toxicity and therapeutic efficacy of thiopurine drugs in humans. We set out to determine whether inheritance might also influence the level of TPMT activity in the domestic cat, Felis domesticus. As a first step, red blood cell (RBC) TPMT activity was measured in blood samples from 104 cats. The average level of cat RBC TPMT activity was lower than that observed in humans and was not related to either age or sex of the animal. We then cloned and characterized the F. domesticus TPMT cDNA and gene. Genotype-phenotype correlation analysis was performed by resequencing the cat TPMT gene using DNA samples from 12 animals with high and 12 with low levels of RBC TPMT activity. Thirty-one single nucleotide polymorphisms (SNPs) were observed in these 24 DNA samples, including five that altered the encoded amino acid, resulting in nine allozymes (six observed and three inferred). Twelve of the 31 feline TPMT SNPs were associated, collectively, with 56% of the variation in level of RBC TPMT activity in these 24 animals. When those 12 SNPs were assayed in all 89 cats for which DNA was available, 30% of the variation in level of RBC TPMT activity was associated with these 12 polymorphisms. After expression in COS-1 cells, five of the eight variant cat allozymes displayed decreased levels of both TPMT activity and immunoreactive protein compared with the wild-type allozyme. These observations are compatible with the conclusion that inheritance is an important factor responsible for variation in levels of RBC TPMT activity in the cat. They also represent a step toward the application of pharmacogenetic principles to companion animal thiopurine drug therapy.