Interleukins: Biological Properties and Therapeutic Potential

Interleukins are biologically active glycoproteins derived primarily from activated lymphocytes and macrophages. Tremendous insight into the biochemical and biological properties of interleukins has been gained with advances in recombinant DNA technology, protein purification, and cell-culture techniques. The biological properties of interleukins include induction of T-lymphocyte activation and proliferation, augmentation of neutrophil, macrophage, and T-lymphocyte cytotoxicity, and promotion of B lymphocyte and multilineage bone marrow stem-cell precursor growth and differentiation. Interleukins may play a role in the pathogenesis of several important diseases. Interleukin therapy is likely to play an important role in the treatment of cancer, infectious diseases, and immunodeficiency syndromes.     

Use of a flexed dorsoplantar radiographic view of the talocrural joint to evaluate lameness in two dogs.

A flexed dorsoplantar radiographic view of the talocrural joint was a useful additional view to diagnose abnormalities of the lateral trochlear ridge of the talus of 2 dogs. This view outlined the subchondral bone of both trochlear ridges of the talus and the apposing cochlea tibiae of the distal portion of the tibia. The tarsus was flexed at the level of the talocrural joint, and an x-ray beam was centered on the joint. With this additional view, fractures of the lateral trochlear ridge were readily diagnosed. This view would help to demonstrate osteochondral lesions of the lateral trochlear ridge.     

Effects of treatment with aspirin or aspirin/dipyridamole combination in heartworm-negative, heartworm-infected, and embolized heartworm-infected dogs.

To determine the drug dose required to inhibit platelet reactivity by at least 50%, 2 drug regimens were evaluated in heartworm-negative, heartworm-infected, and heartworm-infected dogs embolized with dead heartworms. Aspirin, or a combination of aspirin and dipyridamole, were administered to 2 groups of Beagles (n = 5 each) for 5 to 9 days; a third group of 5 Beagles served as nontreated controls. For heartworm-negative dogs, mean (+/- SD) aspirin dosage that inhibited collagen-induced platelet reactivity by at least 50% was 6 (+/- 2) mg/kg of body weight given once daily. The aspirin/diphridamole combination dosage was 1 mg of each drug/kg given every 12 hours. All dogs (n = 15) were implanted with 7 adult heartworms each and remedicated (or not treated) beginning at 21 days after heartworm implantation. In heartworm-infected dogs, mean aspirin dosage required to inhibit collagen-induced platelet reactivity greater than or equal to 50% was 10 (+/- 6) mg/kg. Mean dosage of aspirin/dipyridamole combination was 1.6 +/- (0.5) mg of each drug/kg given every 12 hours. When platelet reactivity in response to collagen was determined to be inhibited by at least 50% in all medicated dogs, each dog (n = 15) was embolized with 7 dead adult heartworms to mimic heartworm adulticidal treatment. Platelet reactivity was monitored for 21 days after treatment, and drug dose was adjusted to maintain platelet inhibition by at least 50%. In embolized dogs, mean aspirin dosage was 17 (+/- 14) mg/kg given once daily. Mean dosage of the aspirin/dipyridamole combination was 2.8 (+/- 1.3) mg of each drug/kg given every 12 hours. All dogs (n = 15) were euthanatized 21 days after heartworm embolization. Each lung lobe was evaluated for severity of lesions and presence of organized or fibrinous thrombi. Lesion severity in the aspirin- and aspirin/dipyridamole-treated dogs was not significantly different from that in control dogs.     

Effects of treatment with ticlopidine in heartworm-negative, heartworm-infected, and embolized heartworm-infected dogs.

Ticlopidine hydrochloride was evaluated for its effectiveness in inhibiting platelet aggregation and serotonin release in 5 laboratory Beagles before and after heartworm implantation with 7 adult Dirofilaria immitis, and after embolization with 7 dead heartworms to mimic what happens after heartworm adulticide treatment. Five other laboratory Beagles, similarly implanted and embolized with heartworms, were used as nonmedicated controls. During the heartworm-negative stage, the dosage of ticlopidine that inhibited adenosine diphosphate (ADP)-induced platelet aggregation in 5 dogs by at least 50% after 5 days of treatment was 62 mg/kg of body weight once a day. In the same dogs implanted with 7 adult heartworms 21 days previously, mean (+/- SD) ticlopidine dosage required to obtain similar results was 71 (+/- 13) mg/kg given once daily. During the 21 days after dead heartworms were implanted in heartworm-infected dogs, mean ticlopidine dosage was 108 (+/- 35) mg/kg (range, 62 to 150 mg/kg). Ticlopidine treatment was associated with increased platelet numbers in all 5 dogs during the heartworm-negative stage and in 4 of 5 dogs during the heartworm implantation and heartworm embolization stages. Mean platelet volume tended to decrease as platelet numbers increased. At necropsy, gross and histologic pulmonary lesions were less severe in ticlopidine-treated dogs than in nonmedicated control dogs.     

Kinetic study of serum gentamicin concentrations in baboons after single-dose administration

This study establishes preliminary pharmacokinetic data on the use of gentamicin sulfate administered IM to baboons. Serum concentrations greater than or equal to 12 micrograms/ml are generally agreed to cause toxicosis in human beings. On the basis of preliminary test results suggesting that the manufacturer's recommended dosage for dogs of 4.4 mg/kg of body weight caused potentially toxic serum concentrations, a dosage of 3 mg/kg was chosen to conduct a single-dose kinetic study in 6 baboons. Using a single-compartment model, the gentamicin serum half-life for IM administration of 3 mg of gentamicin/kg was 1.58 hours, and serum concentrations remained below the potentially toxic concentrations reported for human beings. We suggest that a dosage of 3 mg/kg is safer than a dosage of 4.4 mg/kg administered IM to baboons. Minimal inhibitory concentrations for 2 Pseudomonas aeruginosa isolates were less than or equal to 1 micrograms/ml. On the basis of our measured elimination half-life of 1.58 hours, it is reasonable to suppose that dosing q24 h will be inadequate to maintain therapeutic serum concentrations. We calculate that serum concentrations will remain at or above our measured minimal inhibitory concentration for P aeruginosa (1 micrograms/ml) for 100% of the treatment time if the animal is dosed q 6h, 78% for dosing q 8h, and 52% for dosing q 12h. Therefore, we suggest 3 mg/kg, q 8h or q 6h as appropriate dosing schedules for the use of gentamicin sulfate administered IM to baboons.     

Attraction of newborn piglets to auditory, visual, olfactory and tactile stimuli

Newborn piglets were removed from their dam and their responses to a variety of sensory stimuli were tested in four experiments. Test stimuli were presented simultaneously in multiple-choice arenas. Piglets allowed to choose among recordings of sow vocalizations, piglet vocalizations or white noise in a 5-min test spent more time in proximity to vocalizations of sows and piglets than near white noise. This was significant for males (P less than .01) but not for females. Piglets choosing among illumination levels (bright, dim or dark) in a 5-min test showed a strong preference for either dim or dark areas over bright light (P less than .01), with no difference between attractivity of dim and dark areas. Piglets choosing among birth fluids, sow's milk or tap water during a 5-min test spent more time with maternal odors than with water (P less than .05). No difference in attractivity between birth fluids and sow's milk was apparent. Preferences of piglets to move either with or against the direction of hair growth were tested using the mid-back area of the sow as a test surface. Piglets moved with the direction of hair growth twice as often as against the growth of hair (P less than .01). Results of these experiments indicate that piglets can discriminate among auditory, olfactory, visual and tactile stimuli immediately after birth.     

Efficacy of parenteral antibiotics for disease prophylaxis in feedlot calves

Trimethoprim-sulfadoxine (TMPSDX) and two formulations of oxytetracycline (OTC) were examined for their prophylactic efficacy in feedlot calves when given by intramuscular injection on arrival at a large commercial feedlot. The study included 2,112 high-risk feeder calves that developed disease early in the feeding period. Both formulations of OTC reduced bovine respiratory disease morbidity during the first two weeks on feed and for the entire feeding period by 15-19% (p<0.05), and they also reduced all fatal fibrinous pneumonia by 67% and 84% (p<0.05). All three drugs significantly reduced all fatal disease in animals first treated during the second week on feed, but not for the overall feeding period. Oxytetracycline with 2-pyrrolidone reduced the incidence of all fatal disease by 44% (p<0.05) during the entire feeding period. The case fatality risk for calves first treated during the second week on feed was lower (p<0.05) in the TMPSDX group and in the OTC with polyvinyl-pyrrolidone group.     

Evaluation of twice-daily, low-dose trilostane treatment administered orally in dogs with naturally occurring hyperadrenocorticism

OBJECTIVE: To evaluate the effects of twice-daily oral administration of a low-dose of trilostane treatment and assess the duration of effects after once-daily trilostane administration in dogs with naturally occurring hyperadrenocorticism (NOH). DESIGN: Prospective study. ANIMALS: 28 dogs with NOH. PROCEDURES: 22 dogs received 0.5 to 2.5 mg of trilostane/kg (0.23 to 1.14 mg/lb) orally every 12 hours initially. At intervals, dogs were reevaluated; owner assessment of treatment response was recorded. To assess drug effect duration, 16 of the 22 dogs and 6 additional dogs underwent 2 ACTH stimulation tests 3 to 4 hours and 8 to 9 hours after once-daily trilostane administration. RESULTS: After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [3]). At 3 to 4 hours and 8 to 9 hours after once-daily dosing, mean post-ACTH stimulation serum cortisol concentrations were 2.60 and 8.09 Pg/dL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with NOH, administration of trilostane at low doses every 12 hours was effective, although 2 dogs became ill during treatment. Drug effects diminished within 8 to 9 hours. Because of potential adverse effects, lower doses should be evaluated.     

Risk factors for epiploic foramen entrapment colic: an international study

REASON FOR PERFORMING STUDY: Epiploic foramen entrapment (EFE) is one of the most common causes of small intestinal strangulation in the horse. Identification of risk factors would generate hypotheses about causation and may suggest preventive strategies. HYPOTHESIS: Horses exhibiting certain behavioural patterns and those exposed to particular management practices are at increased risk of EFE. METHODS: A matched case-control study was conducted on EFE cases admitted to hospitals in the UK, Ireland and USA. Data on 109 cases and 310 control horses were obtained by telephone questionnaire and conditional logistic regression was used to identify associations between horse- and management-level variables and the risk of EFE. RESULTS: Crib-biting/windsucking behaviour was strongly associated with increased risk of EFE (OR 67.3, 95%CI 15.3-296.5). A history of colic in the previous 12 months (OR 4.4, 95%CI 1.5-12.7) and horses of greater height (OR/cm 1.05, 95%CI 1.01-1.08) were also at increased risk. The person(s) responsible for horses' daily care (nonowner/relative/spouse OR 5.5, 95%CI 2.3-13.3) and a number of behavioural features, including response to a stimulus causing fright (easily frightened OR 0.4, 95%CI 0.1-1.0) or excitement (sweats up easily/occasionally OR 0.3, 95%CI 0.1-0.8), reaction to their surroundings (inquisitive OR 0.4, 95%CI 0.2-0.8) and feeding behaviour when stressed (goes off food in full/part OR 0.3, 95%CI 0.1-1.0) were also associated with altered risk of EFE. CONCLUSIONS: The association between horses of greater height and those with a previous history of colic and increased risk of EFE suggests that some horses may be inherently predisposed to EFE. Furthermore, a behavioural pattern has been characterised that is common to horses at increased risk of EFE. Further research is required to investigate the causal pathway linking behavioural traits with gastrointestinal dysfunction and to determine whether behavioural modification reduces the risk of EFE. POTENTIAL RELEVANCE: The findings of the present study have relevance to horses in the UK, Ireland and USA.     

Evaluation of immunoglobulin G concentration in colostrum of mares by ELISA, refractometry and colostrometry

In 360 samples of colostrum and 36 samples of blood of warmblood mares, the concentration of immunoglobulin G (IgG) was evaluated in the post partal period with an ELISA and the results were compared to values obtained with 2 field methods--refractometry and colostrometry. A significant correlation (p < 0.0001) was determined between ELISA and colostrometry (r = +0.88) and between ELISA and refractometry (r = +0.93). So both field-methods seem suitable for evaluation of the colostral IgG-concentration in mares. Further the kinetic of the IgG concentration in colostrum, the volume of colostrum and the total amount of IgG was measured in the 12 hours post partum (p.p.) in each half udder of 36 mares of different parity. Immediately p.p. primiparous mares have a greater mean concentration of IgG (68 mg/ml) than multiparous mares (51 mg/ml). However, multiparous mares have a mean colostral volume of 1020 ml whereas, in primiparous mares, a mean volume of 527 ml was determined within the first three hours p.p. As a result of this the total amount of IgG was lower in primiparous (31.5 g) than in multiparous mares (48.5 g). A significant decrease of IgG concentration was measured in multiparous mares in the 1.5 hours following partum versus 3 hours in primiparous mares. The mean IgG concentration in the blood serum of the 36 mares immediately p.p. was 13.4 +/- 3.6 mg/ml. No significant correlation was observed between values of IgG concentration in the blood and in the colostrum of the mares.