Osteoarthritis (OA) is a degenerative joint disease with a high prevalence in dogs. Mesenchymal stem cells (MSCs) have been used to treat humans, dogs, and horses with OA. This report describes a prospective, randomized, blinded, and placebo-controlled clinical efficacy study of intraarticular allogeneic adipose stem cells for the treatment of dogs with OA. Health assessments and measurements of pain and activity impairment were performed at baseline and at selected time points through day 60. The primary outcome variable was the owner Client-Specific Outcome Measurement (CSOM) and secondary measures included veterinary pain on manipulation, veterinary global score, and owner global score. The dogs were treated with either a saline placebo or a single dose of allogeneic adipose-derived MSCs in either one or two joints. Seventy-four dogs were statistically analyzed for efficacy outcomes. Success in the primary outcome variable, CSOM, was statistically improved in the treated dogs compared to the placebo dogs (79.2 versus 55.4%, p = 0.029). The veterinary pain on manipulation score (92.8 versus 50.2%, p = 0.017) and the veterinary global score (86.9 versus 30.8%, p = 0.009) were both statistically improved in treated dogs compared to placebo. There was no detected significant difference between treated and placebo dogs in the incidence of adverse events or negative health findings. Allogeneic adipose-derived stem cell treatment was shown to be efficacious compared to placebo. This large study of dogs also provides valuable animal clinical safety and efficacy outcome data to our colleagues developing human stem cell therapy.

NCT00056563 and NCT01076452.

The effects of insulin and cortisol on saturated phosphatidylcholine synthesis are examined in fetal type II cell cultures and in mixed cell cultures containing type II cells and fibroblasts. In 19-day fetal rat lung type II cell cultures, 100 nM cortisol and 2 nM insulin have no significant effect. Fibroblast-pneumonocyte factor results in enhanced saturated phosphatidylcholine synthesis by fetal type II cells. The significant stimulatory effect of cortisol in mixed-cell cultures is abolished in the presence of insulin or of monoclonal antibodies to fibroblast-pneumonocyte factor. Incubation of type II cells with conditioned media from fibroblasts exposed to cortisol results in increased saturated phosphatidylcholine synthesis. This process is not stimulated when type II cells are incubated with conditioned media from fibroblasts exposed to insulin and cortisol (or to insulin alone). These observations demonstrate that insulin inhibits cortisol induction of lung maturation and suggest that this antagonism results from an inhibitory effect of insulin on the elaboration of fibroblast-pneumonocyte factor by fetal lung fibroblasts.

Normal rat pups and pups with septallesions produced at 7 days of age were reared after weaning under group and isolated housing conditions. Contact time between pairs of animals in the open fieldwas observed at 90·110days of age. Gregariousness was increased by both septaliesion treatment and isolated rearing conditions. The housing condition variable accounted for a greater proportion of treatment variance than did the lesion variable. These results stress the importance of housing conditions as a confounding variable in studies of recovery from infant brain damage.Jonason and Enloe (1971) reported a dramatic increase in open-field gregariousness of the rat following lesions of the septal forebrain. Johnson's (1972) studies indicated that the enhancement of gregariousness effect can be observed regardless of the age at the time the lesion was produced. Meyer, Ruth, and Lavond (1978) demonstrated that the impact of septal lesions on social contact in the rat is potent and lasting, A body of evidence has been produced primarily by Latane and his colleagues (Latane, Nesbitt, Ekman, & Roden, 1972) that isolated vs. social housing conditions is also a potent variable in the openfield gregariousness of rats. The Latane studies indicate that adult rats housed in isolation are more gregarious in the open field than are animals reared in group cages.In the Johnson (1972) experiment, following septal lesions, animals were housed individually from 45 days of age until open-field observations on adult animals were completed. It is possible that the isolated housing conditions might have confounded the data relevant to the lesion variable in that study. In order to more clearly view potential recovery of function following septal lesions, we need more Information on how septal lesions in infancy and housing conditions during development interact.The current study was designed to evaluate the interaction of housing conditions during development and septal lesions in infancy. METHonDellln, SubJeetl, .nd Rou1lnlEach litter was culled to eight male pups at 5 days of age. At 7 days of age, 48 pairs of animals were assigned to four groups (12 The authors' mailing address is:

Streptozotocin (Sz) given as a single dose of 50 mg/kg body wt. caused severe diabetes in Syrian hamsters. However, the level of blood glucose decreased gradually after 21 days post-Sz and reached the near normal level at 70 days in 90% of hamsters. The recovery from diabetes was associated with the regeneration of the beta-cells of islets and a reduction in the initially increased number of alpha- and delta-cells. Daily treatment of diabetic hamsters with insulin was associated with the persistence of severe diabetes, lack of or minimal tendency for beta-cell regeneration and sustained hyperplasia of alpha- and delta-cells in 90% of hamsters. Insulin also inhibited DNA synthesis (as measured by incorporation of tritiated thymidine), in ductal, ductular and acinar cells in Sz-pretreated hamsters but not in normoglycemic control hamsters treated with insulin alone. The results demonstrate a deleterious effect of exogenous insulin in the course of Sz-induced diabetes in hamsters.