Impact of Human FcγR Gene Polymorphisms on IgG-Triggered Cytokine Release: Critical Importance of Cell Assay Format.

Monoclonal antibody (mAb) immunotherapy has transformed the treatment of allergy, autoimmunity, and cancer. The interaction of mAb with Fc gamma receptors (FcγR) is often critical for efficacy. The genes encoding the low-affinity FcγR have single nucleotide polymorphisms (SNPs) and copy number variation that can impact IgG Fc:FcγR interactions.

Engineered hexavalent Fc proteins with enhanced Fc-gamma receptor avidity provide insights into immune-complex interactions.

Autoantibody-mediated diseases are currently treated with intravenous immunoglobulin, which is thought to act in part via blockade of Fc gamma receptors, thereby inhibiting autoantibody effector functions and subsequent pathology. We aimed to develop recombinant molecules with enhanced Fc receptor avidity and thus increased potency over intravenous immunoglobulin. Here we describe the molecular engineering of human Fc hexamers and explore their therapeutic and safety profiles.

An assessment of the statistical methods used to analyse toxicology studies.

The Statisticians in the Pharmaceutical Industry Toxicology Special Interest Group has collated and compared statistical analysis methods for a number of toxicology study types including general toxicology, genetic toxicology, safety pharmacology and carcinogenicity. In this paper, we present the study design, experimental units and analysis methods.

Effect of acarbose on milk yield and composition in early-lactation dairy cattle fed a ration to induce subacute ruminal acidosis.

Subacute ruminal acidosis reduces lactation performance in dairy cattle and most often occurs in animals fed a high concentrate:forage ration with large amounts of readily fermentable starch, which results in increased production of volatile fatty acids and lactic acid and a reduction in ruminal pH. Acarbose is commercially available (Glucobay, Bayer, Wuppertal, Germany) and indicated for the control of blood glucose in diabetic patients. In cattle, acarbose acts as an alpha-amylase and glucosidase inhibitor that slows the rate of degradation of starch to glucose, thereby reducing the rate of volatile fatty acid production and maintaining rumen pH at higher levels.

Effect of acarbose on acute acidosis.

A challenge model was used to evaluate a new approach to controlling acute acidosis. Acute acidosis reduces performance in both dairy and beef cattle and most often occurs as a consequence of ingestion of large amounts of readily fermentable starch, resulting in increased production of volatile fatty acids (VFA) and lactic acid and a reduction in ruminal pH. Acarbose is an alpha-amylase and glucosidase inhibitor that slows the rate of degradation of starch to glucose, thereby reducing the rate of VFA production and maintaining rumen pH at a more stable level.

Efficacy and safety of cefovecin for the treatment of urinary tract infections in cats.

Objectives: To determine the efficacy and safety of cefovecin (Convenia); Pfizer Animal Health) in the treatment of urinary tract infections in cats.

Method: A multi-centre, masked, randomised study was conducted in cats presenting with clinical signs indicative of urinary tract infections. Cephalexin (Rilexine); Virbac) administered orally twice daily at 15 mg/kg bodyweight for 14 days was compared with a single subcutaneous injection of cefovecin in cats.

The efficacy and safety of cefovecin in the treatment of feline abscesses and infected wounds.

Objectives: To determine the efficacy and safety of cefovecin for the treatment of bacterial abscesses and wounds in cats at clinics in Germany, France, Spain and the UK.

Method: Cats with abscesses or wounds were enrolled. Cats (217) were randomised to treatment with either cefovecin administered by subcutaneous injection at 14 day intervals or amoxicillin/clavulanic acid as twice-daily oral tablets for 14 days.

An evaluation of dirlotapide to reduce body weight of client-owned dogs in two placebo-controlled clinical studies in Europe.

The clinical efficacy for weight loss and safety of dirlotapide in dogs were evaluated in two multi-centre studies with parallel designs. Overweight, adult dogs (n = 245) of various breeds were randomized to treatment with dirlotapide or placebo in a 2:1 ratio. Dirlotapide was administered orally once daily to dogs at an initial dose of 0.

Evaluation of dirlotapide for sustained weight loss in overweight Labrador retrievers.

The effects of dirlotapide on body weight (BW) reduction were investigated in overweight Labradors in two parallel-design studies. Study A involved 42 dogs randomized to 0.0, 0.

Clinical efficacy and safety of cefovecin in the treatment of canine pyoderma and wound infections.

Objectives: To determine the efficacy and safety of cefovecin in the treatment of bacterial skin infections in dogs.

Method: Dogs with superficial or deep pyoderma or wounds/abscesses were enrolled in three separate studies. Dogs (354) were randomised to treatment and received either cefovecin administered by subcutaneous injection at 14 day intervals, as clinically necessary, or amoxicillin/clavulanic acid as oral tablets twice daily for 14 days.

Efficacy and safety of cefovecin (Convenia) for the treatment of urinary tract infections in dogs.

Objectives: To determine the efficacy and safety of cefovecin (Convenia); Pfizer Animal Health) in the treatment of urinary tract infections in dogs.

Methods: A multi-centre, blinded, randomised study was conducted in 129 dogs with urinary tract infections. Cephalexin (Rilexine) administered twice daily at 15 mg/kg bodyweight orally for 14 days was compared with a single, subcutaneous injection of cefovecin (Convenia) in dogs.

Pharmacokinetics of cefovecin in cats.

The pharmacokinetics of the novel cephalosporin cefovecin were investigated in a series of in vivo, ex vivo and in vitro studies following administration to adult cats at 8 mg/kg bodyweight. Bioavailability and pharmacokinetic parameters were determined in a cross-over study after intravenous (i.v.

Pharmacokinetics and pharmacodynamics of cefovecin in dogs.

A series of in vivo, ex vivo and in vitro studies were conducted to determine the pharmacokinetic and pharmacodynamic properties of cefovecin, a new injectable cephalosporin, in dogs. Absolute bioavailability was determined in a two-phase cross-over study in dogs receiving 8 mg/kg bodyweight (b.w.

Antimicrobial activity and spectrum of cefovecin, a new extended- spectrum cephalosporin, against pathogens collected from dogs and cats in Europe and North America.

Cefovecin is a new extended-spectrum semisynthetic cephalosporin indicated for the treatment of bacterial infections in dogs and cats. This study evaluated the in vitro activity and spectrum of cefovecin against 2,641 recent clinical isolates (1,660 canine and 981 feline isolates) from Europe and the United States. MIC determinations against cefovecin and other reference antimicrobials were performed by broth microdilution methods recommended by the Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS).

Evaluation of the therapeutic activity of tulathromycin against swine respiratory disease on farms in Europe.

The clinical efficacy of tulathromycin in the treatment of natural outbreaks of swine respiratory disease (SRD) was evaluated at five European sites. Pigs (1 to 6 months of age) exhibiting clinical signs of SRD were treated intramuscularly with tulathromycin (n = 247) at 2.5 mg/kg on day 0 versus either tiamulin (n = 102) at 15 mg/kg on days 0, 1, and 2 (Germany, the Netherlands, and the United Kingdom) or florfenicol (n = 20) at 15 mg/kg on days 0 and 2 (France).

Evaluation of tulathromycin for the treatment of pneumonia following experimental infection of swine with Mycoplasma hyopneumoniae.

Tulathromycin was evaluated in the treatment of pneumonia in weaned pigs inoculated intranasally with Mycoplasma hyopneumoniae. Five days postchallenge, the pigs were randomized to treatment with a single IM administration of saline, a single IM administration of tulathromycin (2.5 mg/kg; day 0), or three IM administrations of enrofloxacin (5.

Efficacy of tulathromycin in the treatment and prevention of natural outbreaks of bovine respiratory disease in European cattle.

The efficacy of tulathromycin in the treatment (phase 1) and prevention (phase 2) of bovine respiratory disease (BRD) was evaluated on commercial farms in France, Germany, Italy, and Spain. In phase 1, commingled cattle with clinical BRD were treated with tulathromycin (n = 128) or florfenicol (n = 125) on day 0. Similar percentages of animals showed sustained clinical improvement at day 14 (tulathromycin 83.

Pharmacokinetics and lung tissue concentrations of tulathromycin in swine.

The absolute bioavailability and lung tissue distribution of the triamilide antimicrobial, tulathromycin, were investigated in swine. Fifty-six pigs received 2.5 mg/kg of tulathromycin 10% formulation by either intramuscular (i.

Pharmacokinetics and lung tissue concentrations of tulathromycin, a new triamilide antibiotic, in cattle.

The pharmacokinetics of the new triamilide antibiotic tulathromycin was investigated in two cattle studies. Following a single subcutaneous injection, the drug was rapidly absorbed and bioavailability was excellent. High and persistent levels of the drug in lung tissue were observed as well.

Studies of the field efficacy and safety of a single-dose Mycoplasma hyopneumoniae vaccine for pigs.

The field efficacy and safety of a single-dose Mycoplasma hyopneumoniae vaccine were evaluated in three-to five-week-old pigs. Two field efficacy studies were conducted, one in England with 673 pigs, and one in Germany with 719 pigs. The pigs were injected intramuscularly with either the vaccine or saline (control) at a ratio of 2:1 and reared under commercial conditions to slaughter weight.

Efficacy of selamectin administered topically to pregnant and lactating female dogs in the treatment and prevention of adult roundworm (Toxocara canis) infections and flea (Ctenocephalides felis felis) infestations in the dams and their pups.

The efficacy of selamectin in the treatment and prevention of naturally acquired Toxocara canis infections and experimentally induced flea (Ctenocephalides felis felis) infestations in dams and their suckling pups was evaluated by administering selamectin to the adult females only, approximately 40 and 10 days before parturition and 10 and 40 days after parturition. Unit doses of the commercial formulation of selamectin were administered to the dams to provide at least the minimum recommended dosage of 6mgkg(-1) (range, 6-12mgkg(-1)). Dams and their pups were housed in carpeted environments able to support the flea life cycle.

Helminth parasites of the wild rabbit Oryctolagus cuniculus near Malham Tarn, Yorkshire, UK.

Between 1992 and 1996, 95 rabbits from the immediate locality of Malham Tarn, North Yorkshire, UK were examined for the presence of helminth parasites. All the examinations took place in late September or October. Three species of nematodes, Graphidium strigosum, Passalurus ambiguus and Trichostrongylus retortaeformis and two species of cestodes, Taenia pisiformis and Cittotaenia pectinata were identified.

Factors affecting morbidity and mortality on-farm and on-station in the Ethiopian highland sheep.

Factors affecting morbidity and mortality of the Ethiopian highland sheep were studied both on-farm and on-station at Debre Berhan between 1989 and 1990. Primary causes of infectious origin resulted in high proportional morbidity (88.4% on-farm) and mortality (72.

Effects of formalin footbathing on foot disease and claw quality in dairy cows.

Two experiments on the effect of routine footbathing in 5 per cent formalin in preventing foot diseases and improving claw horn quality of dairy cows are described. Treatment four times a week significantly (P less than 0.05) reduced the incidence of interdigital lesions but had no significant effect on the incidence of the individual interdigital lesions or on the incidence of individual or overall diseases of the claw horn.