Efficacy and Safety of 4.7 mg Deslorelin Acetate Implants in Suppressing Oestrus Cycle in Prepubertal Female Dogs.

Our multicentric, masked, controlled and randomised study aimed to assess the efficacy and safety of Suprelorin® 4.7 mg (Virbac, Carros, France) regarding oestrus prevention in prepubertal intact bitches. Twelve- to eighteen-week-old females (n = 83) were allocated either a deslorelin implant (n = 62) or 0.9% sodium chloride (n = 21) group. Clinical assessment (heat signs), 17ß oestradiol and progesterone assays, and vaginal cytology were performed at day (D)0, D7, D21, month (M)3 and M6 after product administration, and were then performed every other month until reaching puberty. Trained owners assessed heat signs between each veterinary visit. All bitches (n = 83) reached puberty before M30. Deslorelin significantly extended the median time to sexual maturity when compared to the control group (377 days versus 217 days after D0, p < 0.0001). Three females, implanted between 16 and 18 weeks of age, expressed an induced oestrus. Additional descriptive data, collected over a 24 month-period, showed functional reproductive abilities in both deslorelin (n = 52) and control (n = 21) groups once puberty was achieved. In conclusion, Suprelorin® 4.7 mg seems to be an effective and safe option for postponing the onset of oestrus when administered to prepubertal female dogs aged from 12 to 16 weeks.

Double-Blind, Placebo-Controlled Trial of Cyproterone Acetate to Prevent Flare-Up Effect on Dogs Implanted With Deslorelin.

Deslorelin slow-released implants are registered in Europe for the reversible suppression of fertility in male dogs. After administration, a time-limited increase in sex hormones concentration and related behavioral problems may be observed. The aim of this work was to assess whether cyproterone acetate, a synthetic progestogen, can prevent this flare-up effect. Eighteen privately-owned entire male dogs were enrolled in this double-blind, placebo-controlled, randomized clinical trial. All subjects received a 4.7 mg deslorelin implant by SC route and 1-3 capsules containing either cyproterone acetate 2 mg/kg (N = 9) or a placebo (N = 9), by oral route BID for 14 days, depending on the dog's weight. The dogs were followed for 28 days. An increase in the blood testosterone concentration was observed in respectively 9/9 and 7/9 dogs of the control and cyproterone groups (p = 0.47). However, a worsening of the sex hormone related problems (i.e., urinary marking, mounting, aggressiveness toward other dogs and/or escape) was only observed in the placebo group, in 56 or 66% of the dogs as measured by respectively the veterinarian and the owners. Our study suggests that cyproterone acetate is effective and safe to supress the deslorelin induced behavioral flare-up effect, but not the rise in testosterone.

A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease.

Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. We examined the peripheral immune system and found widespread evidence of innate immune activation detectable in plasma throughout the course of HD. Interleukin 6 levels were increased in HD gene carriers with a mean of 16 years before the predicted onset of clinical symptoms. To our knowledge, this is the earliest plasma abnormality identified in HD. Monocytes from HD subjects expressed mutant huntingtin and were pathologically hyperactive in response to stimulation, suggesting that the mutant protein triggers a cell-autonomous immune activation. A similar pattern was seen in macrophages and microglia from HD mouse models, and the cerebrospinal fluid and striatum of HD patients exhibited abnormal immune activation, suggesting that immune dysfunction plays a role in brain pathology. Collectively, our data suggest parallel central nervous system and peripheral pathogenic pathways of immune activation in HD.

Glial cells in ALS: the missing link?

Amyotrophic lateral sclerosis (ALS) was initially known as Charcot's sclerosis, named after the French neurobiologist and physician Jean-Martin Charcot who first described this type of muscular atrophy in the early nineteenth century. In the United States, ALS became widely known as Lou Gehrig's disease after the famous baseball player who succumbed to the disease in the late 1930s. Currently, ALS is the most common motor neuron disease, with a worldwide incidence of 8 cases per 100,000 population per year. Familial forms constitute approximately 5% to 10% of all cases. Onset increases with age, with a peak in the seventh decade and a slight preponderance (relative risk, 1.3-1.5) among men compared with women. Rapid progression of motor neuron loss leads to death an average of 3 to 5 years after symptom onset. The cause of ALS remains unknown and there is still no curative therapy.