Pretaping of the Aorta Prior to Patent Ductus Arteriosus Ligation

SURGICAL repair of the patent ductus arteriosus (PDA) is one of the most common cardiovascular procedures performed in veterinary and human medicine.^1–3 The techniques have been well documented and used successfully.^2–5     

Effects of transforming growth factor-α on parathyroid hormone- and parathyroid hormone-related protein- mediated bone resorption and adenylate cyclase stimulation in vitro

The effects of transforming growth factor-alpha (TGF alpha) were determined on the ability of parathyroid hormone (PTH) or parathyroid hormone-related protein (PTHrP) to stimulate bone resorption and adenylate cyclase in vitro. Bovine PTH-(1-34) and human PTHrP-(1-34) were equipotent in their ability to stimulate bone resorption in neonatal mouse calvaria with maximal stimulation (2.9 and 2.8-fold increases in 45Ca release, respectively) at a concentration of 10 nM. Combinations of TGF alpha with bPTH-(1-34) or hPTHrP-(1-34) had additive effects on their ability to stimulate bone resorption when submaximal concentrations of the agonists were used. There was no evidence of synergism between TGF alpha bPTH-(1-34) or hPTHrP-(1-34) in their ability to stimulate bone resorption in vitro, nor was TGF alpha able to increase bone resorption induced by maximal concentrations of bPTH-(1-34) or hPTHrP-(1-34). TGF alpha potentiated the effects of either bPTH-(1-34) or hPTHrP-(1-34) on the stimulation of adenylate cyclase in osteoblast-like ROS 17/2.8 cells. These data indicate that TGF alpha has additive effects with submaximal concentrations of PTH or PTHrP on their ability to stimulate bone resorption which may be important in the pathogenesis of humoral hypercalcemia of malignancy.     

Fatty acid supplementation and skin disease

The importance of dietary fatty acids to the health of the skin was recognized more than 60 years ago. Fatty acids are important in providing membrane fluidity and maintaining the cutaneous water permeability barrier. Fatty acids function as precursors of eicosanoids. Eicosanoids, which include prostaglandins and leukotrienes, influence cellular interactions, cellular proliferation, and inflammation. Certain diseases, such as atopy and hypothyroidism, are characterized by abnormalities in fatty acid metabolism. Dietary manipulations may be useful in the treatment of diseases mediated by eicosanoids.     

Absorption of equations for non-parents for an animal model with maternal effects and genetic groups

Rules for forming the mixed-model equations for the reduced animal model with all relationships and including maternal effects have been set out by Quaas and Pollak. They also have shown how to simplify the mixed-model equations when genetic group effects are included in the model with what has become known as the Q-P transformation. Westell has given rules for calculating the coefficients for the Q-P transformed equations that are associated with the inverse of the numerator relationship matrix and genetic group effects. Those rules can be extended to include maternal effects and genetic groups for maternal as well as direct effects. As with the rules of Quaas and Pollak for the equations for the reduced animal model, a similar set of rules can be obtained for the genetic groups model after the Q-P transformation. The rules are derived easily by examining the algebraic results of absorbing the direct and maternal breeding value equations for non-parents into the parent breeding value, group and fixed effects equations. These rules involve Westell's rules and the inverse elements of the genetic (co)variance matrix for direct and maternal additive genetic effects. The rules make calculation of breeding values for parents for models including direct and maternal genetic group effects nearly as easy as for models without genetic group effects. Back solution for direct and maternal breeding values of non-parents similarly is as simple as when genetic group effects are not in the model.     

Pharmacokinetics and dose selection of a novel, long-acting transdermal fentanyl solution in healthy laboratory Beagles

A novel, transdermal fentanyl solution (TFS) was developed that delivers sustained concentrations of fentanyl for days following a single application. The pharmacokinetics following a single topical dose was examined. Eighteen adult Beagle dogs were divided into three groups of six dogs (3M, 3F). Each group was administered a single dose of 1.3 (25), 2.6 (50), or 5.2 mg/kg (100 μL/kg) of TFS. The dose was applied to the clipped, ventral abdominal skin using a 1-mL tuberculin syringe. Immediately following dosing, collars were placed on each dog through 72 h to prevent direct licking of the application site. Serial jugular venous blood samples were collected at 0 (predosing), 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 240, 336, 408, and 504 h after dosing and assayed for plasma fentanyl concentration. Fentanyl was rapidly detected following application with a mean absorption lag time (t(lag) ) of 0.333 h in the 1.3 mg/kg group and 0 in the other two groups. The mean C(max) increased with dose and were 2.28, 2.67, and 4.71 ng/mL in the 1.3, 2.6 and 5.2 mg/kg dose groups, respectively. Mean terminal half-lives were 53.7, 69.6, and 103 h in the 1.3, 2.6, and 5.2 mg/kg dose groups, respectively. The mean AUC(0-LLOQ) from lowest to highest dose groups were 157, 268, and 645 ng·h/mL and were dose proportional with a R(2) value of 0.9818. Adverse reactions were limited to the highest dose group and included sedation (four of six dogs) and decreased food and water intake (one dog). A dose of 2.6 mg/kg (50 μL/kg) is proposed for further development studies based on the lack of adverse events that were observed compared to the 5.2 mg/kg group and a more rapid onset of action and longer duration of action compared to the 1.3 mg/kg group.