Efficacy of a new topical formulation containing selamectin plus sarolaner against three common tick species infesting cats in the United States.

The efficacy of a single topical application of a combination product containing selamectin and sarolaner (selamectin/sarolaner; Revolution® Plus/Stronghold® Plus) was evaluated in seven laboratory studies against Ixodes scapularis (three studies), Dermacentor variabilis (two studies), or Amblyomma maculatum (two studies). In each study, cats were randomly allocated to treatment groups based on pre-treatment host-suitability tick counts. On Days -2, 5, 12, 19, 26 and 33, the cats were infested with unfed adult ticks. On Day 0, cats were treated with either a placebo (vehicle control) or with the spot-on solution at the minimum dose of 6.0 mg selamectin and 1.0 mg sarolaner/kg bodyweight. In one study with I. scapularis and one with D. variabilis an additional group of cats was treated with selamectin alone (Revolution®, Zoetis) at 6.0 mg/kg bodyweight. Tick counts were conducted after treatment and after each weekly re-infestation and efficacy determined relative to placebo-treated animals. There were no treatment-related adverse reactions in any of the studies. Geometric mean live tick counts were significantly (P < 0.05) lower in the selamectin/sarolaner-treated groups compared to the geometric mean tick counts in the placebo-treated groups at all time-points in all studies. For all species, a single topical administration of the selamectin/sarolaner combination resulted in>90% efficacy against existing infestations based on geometric means. Efficacy against weekly re-infestations was >90% based on geometric means for at least 5 weeks for I. scapularis and D. variabilis, and for at least 4 weeks against A. maculatum. Selamectin alone had no efficacy against I. scapularis, where counts on selamectin-treated cats were not significantly different from placebo at all time points (P > 0.05), and for D. variabilis, counts were not significantly different from placebo at 2, 3 and 5 weeks after treatment (P > 0.05) and efficacy was never greater than 85%. Thus, the activity of the sarolaner against three common tick species found on cats in the US is complementary to the existing broad-spectrum parasite control of selamectin. The inclusion of sarolaner with selamectin in a combination product (Revolution® Plus/Stronghold® Plus) provides for the treatment of existing tick infestations and gives at least one month of control against re-infestation following a single topical application.

The efficacy of a novel topical formulation of selamectin plus sarolaner (Revolution® Plus/Stronghold® Plus) in preventing the development of Dirofilaria immitis in cats.

Three controlled studies were conducted to investigate the efficacy of selamectin plus sarolaner (Revolution® Plus/Stronghold® Plus) in preventing feline heartworm disease in cats. In all studies, cats were inoculated with 100 Dirofilaria immitis third stage larvae on Day -30. In the first study, cats were treated with selamectin plus sarolaner as a single dose on Day 0 or as three consecutive monthly doses on Days 0, 28 and 56. In the second and third studies, cats were treated with either sarolaner alone on Day 0, selamectin plus sarolaner on Day 0 or selamectin plus sarolaner as three consecutive monthly doses on Days 0, 28 and 56. In all three studies, dosages were 6 mg/kg selamectin plus 1 mg/kg sarolaner or 1 mg/kg sarolaner alone. Control cats were given a placebo containing inert formulation ingredients (vehicle). All treatments were administered at a single site topically to the skin cranial to the scapulae. Cats were humanely euthanized on Day 145/146 (i.e., 175/176 post-inoculation), and adult D. immitis worms were recovered and enumerated. Across the three studies, adult heartworms were recovered from 87 to 100% of control cats, with geometric mean worm counts ranging from 2.1 to 5.4. No adult D. immitis worms were recovered from cats treated with selamectin plus sarolaner. Cats treated with sarolaner alone were not protected against D. immitis infection, showing geometric mean worm counts of 1.9 to 2.4. In these studies, selamectin (6 mg/kg) plus sarolaner (1 mg/kg) was 100% effective in preventing heartworm development in cats when administered topically as one dose 30 days after inoculation or as three consecutive monthly doses starting 30 days post-inoculation. These studies demonstrated that a single topical administration of selamectin plus sarolaner at the recommended dosage was completely effective in preventing the development of D. immitis in cats.

Efficacy of a new spot-on formulation of selamectin plus sarolaner against four common tick species infesting cats in Europe.

A single application of a new spot-on formulation of selamectin plus sarolaner (Stronghold®Plus, Zoetis) was evaluated for efficacy against the most common tick species infesting cats in Europe. In each of the seven laboratory studies, 16 adult and purpose-bred cats were randomly allocated to one of two treatment groups based on pre-treatment tick counts. Weekly infestations with 50 unfed adult Ixodes ricinus (2 studies), Ixodes hexagonus (1 study), Dermacentor reticulatus (2 studies), or Rhipicephalus sanguineus (2 studies) were scheduled on Days -2, 5, 12, 19, 26 and 33. Cats were treated on Day 0 with the spot-on formulation at the minimum recommended label dose of 6.0mg selamectin and 1.0mg sarolaner per kg bodyweight or with a placebo. Ticks were counted 48h after treatment and after each re-infestation. No treatment-related adverse reactions were recorded in any of the studies. Geometric mean live tick counts were significantly (P≤0.0012) lower in the selamectin/sarolaner-treated group compared to the placebo-treated group at all time-points. Against I. ricinus and I. hexagonus, efficacy was ≥97.2% against existing infestations and ≥97.4% against weekly re-infestations for at least 5 weeks. Treatment was 100% effective against existing R. sanguineus infestations and was ≥95.8% for at least 4 weeks. Against D. reticulatus treatment resulted in ≥94.4% efficacy for at least 4 weeks. Thus, a single application of the new spot-on formulation of selamectin plus sarolaner at the minimum dose provides rapid treatment of existing infestations and is at least one month effective against re-infestation by all relevant European tick species in cats.

European surveillance for pantropic canine coronavirus.

Highly virulent pantropic canine coronavirus (CCoV) strains belonging to subtype IIa were recently identified in dogs. To assess the distribution of such strains in Europe, tissue samples were collected from 354 dogs that had died after displaying systemic disease in France (n = 92), Hungary (n = 75), Italy (n = 69), Greece (n = 87), The Netherlands (n = 27), Belgium (n = 4), and Bulgaria (n = 1). A total of 124 animals tested positive for CCoV, with 33 of them displaying the virus in extraintestinal tissues. Twenty-four CCoV strains (19.35% of the CCoV-positive dogs) detected in internal organs were characterized as subtype IIa and consequently assumed to be pantropic CCoVs. Sequence and phylogenetic analyses of the 5' end of the spike protein gene showed that pantropic CCoV strains are closely related to each other, with the exception of two divergent French viruses that clustered with enteric strains.

A pantropic canine coronavirus genetically related to the prototype isolate CB/05.

We report the genetic and biological characterisation of a novel pantropic canine coronavirus (CCoV), strain 450/07, which caused the death of a 60-day-old miniature pinscher. At the genetic level, this virus was strictly related to the prototype strain CB/05, but displayed some unique features. After experimental infection with the new pantropic isolate, most inoculated dogs showed diarrhoea and acute lymphopenia. Gross lesions and histological changes were mainly evident in the gut and lymphoid tissues, although some animals showed remarkable changed also in parenchymatous organs. The viral RNA was detected in the faeces and/or internal organs of most pups. These findings seem to indicate that strain 450/07 is able to spread to internal organs (mainly lymphoid tissues), causing lymphopenia but inducing a mild disease.

Is the fetal lung a mineralocorticoid receptor target organ? Induction of cortisol-regulated genes in the ovine fetal lung, kidney and small intestine.

BACKGROUND: Lung, kidney and small intestine are involved in fetal volume regulation and amniotic fluid secretion and play a pivotal role in the transition from intrauterine to extrauterine life. OBJECTIVE: This study was performed to determine the ontogeny of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR), and of MR- and GR-regulated genes and proteins, serum and glucocorticoid-induced kinase (Sgk-1), epithelial sodium channel (ENaC alpha), and Na,K-ATPase alpha1. METHODS: Lung, renal cortex and medulla, and small intestine were collected from fetuses at 80, 100, 120, 130 and 145 days' gestation and from day 1 and 7 neonatal lambs. Real-time PCR was performed to determine mRNA concentration for MR, GR, the 11 beta-hydroxysteroid dehydrogenases (11 beta-HSD1 and 2), Sgk-1, ENaC alpha, and Na,K-ATPase alpha1. Protein expression of ENaC alpha and Na,K-ATPase alpha1 in whole cell and membrane fractions was determined by immunoblotting. RESULTS: Expression of corticosteroid-induced genes in renal cortex increases at term; in small intestine the induction occurs postnatally. In contrast, in lung expression of MR and GR mRNAs were greater at 100 days to term than postnatally and 11 beta-HSD1 peaked at 145 days; the corticosteroid-induced genes also increased prenatally: Sgk-1 and ENaC alpha increased by 120 days, peaking at 145 days, and Na,K-ATPase alpha1 was greatest at 130 days. CONCLUSIONS: The expression of high levels of MR and 11 beta-HSD1 in preterm fetal lung suggest low endogenous fetal cortisol may exert actions at the high affinity MR in vivo, leading to increases in expression of sodium channels important in the regulation of lung liquid secretion and reabsorption.

c-Fos expression in the midbrain periaqueductal gray after chemoreceptor and baroreceptor activation.

The pattern of Fos-like immunoreactivity (FLI) in the periaqueductal gray (PAG) associated with activation of arterial chemoreceptors versus baroreceptor afferents was examined in urethane-anesthetized rats. Chemoreflex responses elicited by repeat intravenous injections of potassium cyanide (KCN; 90 microg/kg) significantly increased FLI in all columns of the PAG relative to saline-injected animals. Pressor responses elicited by intravenous phenylephrine (PE) produced a similar pattern of increased FLI throughout the PAG except in the dorsomedial and lateral columns of the caudal PAG, where FLI was minimal. Chemoreflex responses were unaltered by blockade of excitatory amino acid receptors in the dorsomedial PAG, and < 10% of the neurons of the caudal PAG that expressed FLI after KCN stimulation were retrogradely labeled from the A5 region of the caudal ventrolateral pons. These results indicate that integration of chemoreceptor inputs occurs primarily in the dorsal and lateral columns of the caudal PAG, but these neurons have little direct descending influence over lower brain stem regions integral to the central arterial chemoreflex arc.

Aberrations in uterine contractile patterns in mares with delayed uterine clearance after administration of detomidine and oxytocin.

An experiment was conducted to determine whether the uterotonic effects of oxytocin, a drug used to treat mares that have a delay in uterine clearance were affected by the sedative detomidine (an alpha2-agonist), a drug used to treat fractious mares. An additional objective was to identify propagation patterns of uterine contractions and determine whether these patterns differed between normal mares and mares with delayed uterine clearance (DUC). Intrauterine pressure was measured in five reproductively normal mares and four mares with DUC during estrus using an 8-F Milar catheter with two discrete pressure sensors. Mares received one of three treatments in random order: detomidine (0.001 mg/kg; i.v.); detomidine followed in 10 min by oxytocin (10 IU; i.v.); and saline (0.9% NaCl 0.5 ml; i.v.) followed in 10 min by oxytocin. All treatments induced waves of contractions; however, only three mares with DUC exhibited contractions after administration of detomidine. Normal mares experienced more uterine contractions (P < 0.01) that tended to last longer (P < 0.06), and were of greater intensity (P < 0.04) than mares with delayed clearance. Administration of detomidine before oxytocin increased the number of contractions (P < 0.02) and increased the maximum intrauterine pressure in the uterine horn (P < 0.05) in normal mares as compared to response after administration of saline and oxytocin. Detomidine had no effect in mares with delayed clearance. All mares had more propagating than non-propagating uterine contractions (74 +/- 8 versus 25 +/- 8%, respectively). Normal mares exhibited a normal propagation pattern more frequently (P < 0.0001) than mares with DUC. Simultaneous (P < 0.05) and inverted (P < 0.03) contractions occurred more frequently in mares with DUC. Administration of detomidine increased the number (P < 0.01), and tended to increase the percentage (P < 0.07) of normal propagating uterine contractions in normal mares, but did not affect propagation patterns in mares with DUC. In conclusion, detomidine augmented the uterotonic effect of oxytocin in normal mares but not in mares with DUC. Data suggest that mares with DUC have a defect in myoelectrical signaling and a decrease in the contractile strength of the uterine muscle.