Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia.

Glycogen storage disease type Ia (GSD-Ia) stems from glucose-6-phosphatase (G6Pase) deficiency and causes hypoglycemia, hepatomegaly, hypercholesterolemia and lactic acidemia. Three dogs with GSD-Ia were initially treated with a helper-dependent adenovirus encoding a human G6Pase transgene (HDAd-cG6Pase serotype 5) on postnatal day 3. Unlike untreated dogs with GSD-Ia, all three dogs initially maintained normal blood glucose levels. After 6-22 months, vector-treated dogs developed hypoglycemia, anorexia and lethargy, suggesting that the HDAd-cG6Pase serotype 5 vector had lost efficacy. Liver biopsies collected at this time revealed significantly elevated hepatic G6Pase activity and reduced glycogen content, when compared with affected dogs treated only by frequent feeding. Subsequently, the HDAd-cG6Pase serotype 2 vector was administered to two dogs, and hypoglycemia was reversed; however, renal dysfunction and recurrent hypoglycemia complicated their management. Administration of a serotype 2 HDAd vector prolonged survival in one GSD-Ia dog to 12 months of age and 36 months of age in the other, but the persistence of long-term complications limited HDAd vectors in the canine model for GSD-Ia.

Simplified hypoosmotic swelling testing (HOST) of fresh and frozen-thawed canine spermatozoa.

The clinical use of the hypoosmotic swelling test (HOST) to identify spermatozoa with a functional intact membrane has been reported for humans and domestic species, including the dog. Currently, it is recommended that canine spermatozoa be incubated with the hypoosmotic solution for periods that range from 30 to 60 min. In an attempt to simplify the test, it was hypothesized that the degree of the hypoosmotic response at 1 min of incubation would not be different from the response documented at 60 min after incubation in the hypoosmotic solution at 37 degrees C. The hypoosmotic response of spermatozoa from 50 fresh and 16 frozen-thawed semen samples obtained from 22 adult dogs was recorded at 1 and 60 min of incubation. There were no significant differences between the hypoosmotic response recorded at 1 and 60 min for all evaluated semen samples (P>0.10). The hypoosmotic response recorded for canine spermatozoa from fresh semen samples were greater than that recorded for spermatozoa from frozen-thawed semen, both at 1 min (86.2% compared with 65.2%; P<0.001) and 60 min (85.6% compared with 61.8%; P<0.001). Based on the results of this study, it is recommended to decrease the incubation time of the HOST for canine spermatozoa to as short a period as 1 min. This incubation time should encourage the application of this relatively simple and inexpensive test of canine sperm membrane function in a clinical setting.

Serum and milk concentrations of leptin in gilts fed a high- or low-energy diet during gestation.

Concentrations of leptin in serum and milk were assessed in gilts fed diets during gestation that differed in energy level. Beginning at day 45 and continuing throughout pregnancy, gilts received either a high-energy (6882 kcal metabolizable energy (ME) per day) or low-energy (5221 kcal ME per day) diet (n = 9 per group). All gilts had ad libitum access to a standard lactation diet throughout a 21 day lactation. During gestation, gilts consuming the high-energy diet gained more body weight (P < 0.01) and backfat thickness (P = 0.03) than gilts fed the low-energy diet; however, serum concentrations of leptin remained similar between groups (P = 0.35). Within 24 h after farrowing, gilts fed the high-energy diet had greater levels of leptin in serum and milk than gilts that consumed the low-energy diet during gestation (P < 0.07); Across treatments, backfat thickness and leptin levels in serum were positively correlated (r(2) = 0.51; P = 0.03). At weaning, backfat thickness (P < 0.07), but not body weights or serum and milk levels of leptin (P > 0.1), were greater for gilts fed the high-energy, versus the low-energy, diet during gestation. Gilts that were fed the low-energy diet during gestation consumed more feed during week 2 of lactation (P = 0.06). Our results suggest that altering the level of energy in the diets of gestating swine can influence circulating and milk concentrations of leptin, as well as feed consumption, during lactation.