Interindividual variability in plasma concentrations after systemic exposure of swine to dietary doxycycline supplied with and without paracetamol: a population pharmacokinetic approach

Anorexigenic substances released during infection may hinder the therapeutic efficacy of in-feed antibiotics. Paracetamol (acetaminophen; PARA) inhibits the anorexia of infection and seems to improve the clinical efficacy of doxycycline (DOX) against bacterial respiratory disease in swine herds. In order to verify whether PARA selectively stimulates intake of DOX-medicated feed in diseased pigs, we documented the pharmacokinetics (PK) of DOX when coadministered with PARA and examined the effect of in-feed PARA on the interindividual variability in plasma concentrations after systemic exposure to in-feed DOX in swine herds with respiratory disease. Systemic exposure to DOX was measured with the area under the curve (AUC) of its plasma concentrations over time. First, a rich-sampling PK study of in-feed and i.v. DOX (10 mg/kg of BW) and PARA (30 and 10 mg/kg of BW, respectively) was performed on 5 pigs. The PK profiles of in-feed DOX were used in mathematical simulations to determine 5 optimal sampling times for the farm-based population PK study. A randomized, blind, parallel PK study was performed in 2 herds with bacterial respiratory disease, where liquid feed was fortified with DOX alone (5 mg x kg of BW(-1) x meal(-1)) or combined with PARA (15 mg x kg of BW(-1) x meal(-1)). Medicated meals were given twice, 12 h apart, to group-housed growing pigs (n > 50 pigs x treatment(-1) x herd(-1), totaling 215 pigs). Plasma concentrations of DOX and PARA were measured with HPLC. At variance with our expectations, PARA decreased (P = 0.069) mean AUC of in-feed DOX and did not decrease its variability (P > 0.34). Mean AUC of DOX increased with feed intake and with initial exposure to DOX, and was greater in sick animals. Therefore, symptomatic PARA-induced improvement in bacterial respiratory disease control with DOX is more likely caused by its analgesic/antipyretic effects than by its orexigenic effect. Interindividual variation in the AUC of DOX was large in pigs given group medication, even when sufficient feeding space was allowed and the amount of feed offered was greater than their requirements. Therefore, future studies to improve the efficacy of group antibiotic therapy should focus on feeding behavior characteristics as well as biopharmaceutical properties of medicated feeds.     

Spontaneous retrograde movement of ureteroliths in two dogs and five cats

CASE DESCRIPTION: 2 dogs and 5 cats were evaluated for treatment of ureteroliths. CLINICAL FINDINGS: Spontaneous retrograde movement of 1 or more ureteroliths was detected by radiography, ultrasonography, fluoroscopy, and a combination of fluoroscopy and ultrasonography. The ureteroliths moved retrograde up to 4 centimeters. Retrograde movement of ureteroliths into the renal pelvis resulted in improved renal function in some patients but made complete surgical removal of all uroliths more difficult. TREATMENT AND OUTCOME: Medical management was not successful, and ureteroliths were surgically removed. Surgical management of ureteroliths was complicated by retrograde movement of ureteroliths in the perioperative period. CLINICAL RELEVANCE: Ureteroliths can move retrograde within the ureter and even back into the renal pelvis. Retrograde movement of ureteroliths may make surgical planning more difficult.     

Effects of dihydroheptaprenol on neutrophil functions in calves

Microemulsified dihydroheptaprenol (DHP) was administered intramuscularly to clinically healthy calves at doses of 4, 6 and 8 mg/kg body weight. Marked increase of neutrophil counts was observed 0.5, 1 and 2 days after the injection at a dose of 6 mg/kg. Nitroblue tetrazolium reducing activity of neutrophils was also obviously enhanced 1, 2 and 3 days after DHP administration. Phagocytic killing of Staphylococcus aureus by neutrophils was further enhanced markedly 1, 2 and 3 days after the drug injection at 6 mg/kg.     

Ultrastructure of the gastrocnemius tendon and sheath from broilers infected with reovirus

Gastrocnemius tendon and sheath from male broilers infected with reovirus at 1 day of age were evaluated ultrastructurally at 1, 2, 3, 4, 5, 10, 15, and 20 weeks postinoculation (PI). Although virus particles were not identified, degenerative changes in sheath and tendon fibroblasts were characterized by cytoplasmic vacuolization, disruption of membranes, and loss of ribosomes from rough endoplasmic reticulum, mitochondrial degeneration, and cell disruption.     

In vitro reactivity of digital arteries and veins to vasoconstrictive mediators in healthy horses and in horses with early laminitis

The in vitro reactivity of vasoconstrictive mediators that are implicated in acute laminitis was determined in palmar and plantar digital arteries and veins obtained from healthy horses and in palmar digital vessels of horses with early laminitis (Obel grade I). To obtain baseline reactivity data, 3 experiments were conducted, using healthy horses: (1) the reactivity of palmar and plantar digital arteries and veins to angiotensin II, norepinephrine, and 5-hydroxytryptamine (serotonin) were compared; (2) the direct effects of bacterial endotoxin on vascular reactivity were assessed; and (3) the reactivity of palmar digital arteries and veins to angiotensin II, norepinephrine, prostaglandin F2 alpha (PGF2 alpha), serotonin, and a thromboxane-endoperoxide analog (U46619) were determined. The vascular reactivity of these same 5 vasoconstrictors then was determined in horses with early laminitis and was compared with data from healthy (control) horses. Obel grade-I laminitis was experimentally induced in horses, using carbohydrate overload. Dose responses were conducted for each agent at concentrations between 10(-8)M and 10(-4)M. The potency of a drug was defined as the mean effective concentration necessary to induce 50% of maximal contraction (EC50). There were no differences in EC50 concentrations and in maximal contractions between forelimb and hind limb arteries and veins for angiotensin II, norepinephrine, and serotonin. Incubation with endotoxin had no effect on the reactivity of arteries and veins to angiotensin II, norepinephrine, and serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)     

牛子宫复旧过程中胶原蛋白和肌浆球蛋白降解规律的研究

本实验监测8头围产期奶牛外周血浆中胶原蛋白和肌浆球蛋白的代谢产物——羟基脯氨酸(HP)和3甲基组氨酸(3MH)的含量,借以找出这两种蛋白质的代谢规律和子宫复旧的关系。结果表明:荷兰黑白花牛和娟珊牛血浆中HP的含量和子宫角直径分别呈显著及极显著正相关(r=0.41,P<0.05和r=0.57 P<0.01),而3MH分别呈极显著和显著正相关(r=0.52 P<0.01和r=0.39(P<0.05)。此外,黑白花牛血浆中3MH的含量极显著高于娟珊牛(P<0.001)。两个品种牛子宫复旧的平均时间,黑白花牛为37.4±3.1天,娟珊牛32.3±2.1天。结果说明牛产后子宫体积的缩小与子宫肌肉的胶原蛋白和肌浆球蛋白降解成氨基酸排出体外有关,子宫复旧的速度可能决定于这两种蛋白质的降解速度。     

Gastrointestinal parasites presence during the peripartum decreases total milk production in grazing dairy Holstein cows

Parasitism in cattle is known to impair growth and development. Recent findings suggest that productivity of adult animals is also affected, but little is known about the physiological mechanisms involved. Furthermore, development of nematode resistance to drugs makes imperative the search of management practices that avoid whole herd treatment. We undertook an epidemiological and endocrine study in a grass based dairy farm in Argentina to study the effect of parasites on milk production and the underlying mechanisms involved, and identify individual animals that would benefit from antiparasitic treatment. All the cows in the dairy were followed monthly for egg parasite output in feces. Samples were cultured for genera determination. Milk production and reproductive results were recorded and periodical bleedings for hormone determination were performed. Nematode egg output (EPG) was maximal in late Summer and Autumn and minimal in Spring in coincidence with the Ostertagia inhibition-disinhibition cycle as this genus had the highest prevalence in all the study. The highest proportion of positive samples was found in the high producing herd and maximal counts were found in the peripartal period. Milk production did not correlate with EPG mean values but, when cows were grouped by EPG positivity around parturition, a significant difference in total milk production between EPG null and positive cows was observed. Positive cows produced 7%, 12% or 15% less milk than null EPG cows, depending on the sampling month/s chosen for classification. The highest difference was seen when both prepartum and postpartum samples were taken into account. No difference in lactation length and a marginal effect on partum to first service interval were encountered. Endocrine studies revealed a decrease in serum growth hormone (GH), type I insulin-like growth factor (IGF-I) and prolactin during lactation in cows with positive EPG in the first postpartum sample with respect to null EPG cows at that time. GH levels decreased and prolactin and IGF-I levels increased in both groups of cows from month 0 to 6 in milk. Serum insulin levels remained stable throughout lactation and were similar in both groups of cows. In conclusion, EPG around parturition may be a useful tool for identifying cows that will have a decrease in productivity due to parasite effects and would possibly benefit from an antiparasitic treatment. Besides, our results suggest that detrimental effect of parasites on milk production may be mediated by GH, IGF-I and prolactin serum levels.     

The effect of flaxseed supplementation on growth, carcass characteristics, fatty acid profile, retail shelf life, and sensory characteristics of beef from steers finished on grasslands of the northern Great Plains

The objective of this trial was to determine if daily supplementation of flaxseed for 85 d to steers finished on grasslands of the northern Great Plains would influence growth and carcass characteristics or the fatty acid profile, tenderness, and sensory characteristics of beef steaks. Eighteen Angus yearling steers (initial BW 399 ± 21 kg) were randomly divided into 3 groups. Steers in treatment 1 (FLX; n = 6) received a daily supplement of ground flaxseed (0.20% of BW), whereas steers in treatment 2 (CSBM; n = 6) received a daily supplement of ground corn and soybean meal (0.28% of BW), with contents of CP and TDN being similar to the supplement for FLX. Control steers (CONT; n = 6) were not supplemented. Treatments were given to each individual steer in side-by-side stalls and were fed from mid-August to November 7, 2007, the day before slaughter. All steers grazed growing forage from early May through the first week of November. Growth rate of steers fed FLX was 25% greater (P < 0.01) than that of steers fed CONT, but was similar (P = 0.45) to that of steers fed CSBM. No differences were observed for carcass characteristics (P ≥ 0.14), tenderness (Warner-Bratzler shear force; P ≥ 0.24), or sensory attributes (P ≥ 0.40) except for a slight off-flavor detected in steaks from steers fed FLX compared with CONT (7.4 vs. 7.8, respectively, with 8 indicating no off-flavor and 1 indicating extreme off-flavor; P = 0.07) and CSBM (7.9; P = 0.01). The n-3 fatty acids α-linolenic acid and eicosapentaenoic acid were 62 and 22% greater, respectively, in beef from steers fed FLX compared with those fed CONT (P < 0.001). The ratio of n-6 to n-3 fatty acids was smaller (P < 0.001) in beef from steers fed FLX compared with the ratios in beef from steers fed CONT and CSBM. Daily supplementation of flaxseed to steers grazing growing vegetation on the northern Great Plains may improve growth rate and enhance the n-3 fatty acid profile of the steaks.