Recipient Organization
UNIV OF PENNSYLVANIA
(N/A)
PHILADELPHIA,PA 19104
Performing Department
School Of Veterinary Medicine
Non Technical Summary
One strategy to prevent newborn calves from becoming infected with Johne's Disease is to treat them with an antimicrobial agent during the period of high susceptibility and high exposure. However, the use of antibiotics for this purpose is unattractive, because of the concern for development of antibiotic resistance. Gallium, a naturally occurring semi-metal that shares many similarities with ferric iron and functions as an iron mimic, has been shown to have antimicrobial activity against various microorganisms. The use of gallium in cattle is particularly attractive as it is not an antibiotic, and thus concerns about the public health impact of antimicrobial resistance could be avoided. The use of this drug, administered as a chemoprophylactic agent to calves during the period of greatest susceptibility would represent a novel control strategy to reduce MAP transmission on infected farms. However, work is needed to determine the bioavailability and safety of oral GaN administration in calves, and to determine the optimal dose of GaN that would be sufficient in suppressing the growth of or kill MAP in neonatal calves.
Animal Health Component
(N/A)
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Goals / Objectives
The main objective of this study is to find the optimal dose of GaN that could be administered to calves prophylactically during the neonatal period, in order to effectively suppress the growth of, or kill MAP. The more specific objectives of the study are: 1. To determine the bioavailability of GaN when administered orally to neonatal calves. 2. To determine if GaN is safe to use in neonatal calves. 3. To measure serum, fecal and tissue concentrations of Ga following its administration at 2 different dosages in neonatal calves.
Project Methods
Eight (8) male calves will be purchased from a nearby Johne's disease negative commercial dairy within 72 hours of birth, and transported to New Bolton Center where they will be housed in individual pens and fed milk replacer according to normal husbandry methods. Calves will be randomly assigned to 1 of 2 treatment groups (4 calves/group). Depending on their group assignment, calves will either receive 50 mg/kg or 100 mg/kg of gallium nitrate (GaN) orally once daily for 5 days. Throughout the study period, calves will be monitored for signs of adverse reaction. For each calf, blood samples will be collected for measurement of serum gallium concentrations prior to administration (time 0) and at 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after GaN administration on study day 1, and at times 4 and 24 hours after GaN administration on study days 2, 3, and 4. On study day 5, blood samples will be collected at times 4, 8, 12, and 24 hours post-administration. Fecal samples will also be obtained daily for gallium level determination. Calves will be euthanized on study day 6 by intravenous injection of barbiturate. At necropsy, 2 tissue samples per calf (ileum and ileocecal lymph node) will be collected for gallium level determination. Serum, feces, and tissues will be stored at -70 C, and all samples will be assayed for gallium at the same time. Determination of gallium concentrations: Gallium concentrations will be measured by mass spectrophotometry. Pharmacokinetic Analysis: The area under the curve, maximum serum concentration, time to reach maximum serum concentration, mean residence time, and terminal half-life will be determined by use of software program.