A subpopulation of collie dogs is extremely sensitive to neurotoxicity induced by ivermectin. The aim of this study was to determine the mechanistic basis for this phenomenon. The multi-drug-resistance gene (mdr1) encodes a large transmembrane protein, P-glycoprotein (P-gp), that is an integral part of the blood-brain barrier. P-gp functions as a drug-transport pump at the blood-brain barrier, transporting a variety of drugs from the brain back into the blood. Since ivermectin is a substrate for P-gp, we hypothesized that ivermectin-sensitive collies had altered mdr1 expression compared with unaffected collies. We report a deletion mutation of the mdr1 gene that is associated with ivermectin sensitivity. The 4-bp deletion results in a frame shift, generating several stop codons that prematurely terminate P-gp synthesis. Dogs that are homozygous for the deletion mutation display the ivermectin-sensitive phenotype, while those that are homozygous normal or heterozygous do not display increased sensitivity to ivermectin.
The relationship between serum protein concentration in the 1st week of life and survival to 16 weeks of age was examined in 3,479 Holstein replacement heifers over a period of 10 years on a farm with endemic salmonellosis. Thirty-four percent of calves studied had serum protein concentrations <5.0 g/dL and 60.5% of calves had serum protein concentrations <5.5 g/dL. Cumulative mortality was 7.9%, indicating that calves with marginal passive transfer status can be reared successfully under conditions of endemic salmonellosis. Optimal survival was observed in calves with serum protein concentrations >5.5 g/dL. Calves with serum protein concentrations of 5.0-5.4 g/dL had only a slightly increased relative risk (RR) of mortality (RR = 1.3) compared to calves with serum protein concentrations >5.5 g/dL. The highest RR was experienced by calves with serum protein concentrations <4 g/dL (RR = 4.6) and 4.0-4.4 g/dL (RR = 3.1). Calves with inadequate passive transfer (serum protein concentration <5.0 g/dL), experienced increased mortality until at least 10 weeks of age, indicating that failure of passive transfer has an effect on calf health that extends into the juvenile period. Models in which serum protein concentration was treated either as a continuous variable or as a categorical variable failed to demonstrate any significant interaction between baseline mortality and the RR of mortality. This finding suggests that the RR derived in the present study should be applicable to farms with dramatically different baseline mortality rates.Key words: Calves; Colostrum; Passive transfer; Refractometry; Serum proteins.revious studies have shown that refractometry is an ac-P curate predictor of passive transfer status in young calves. Reported r' values for models predicting serum immunoglobulin G (IgG) concentration as a function of serum protein concentration range from 0.6 to OX.'-' Accuracy of refractometry in prediction of calf health and survival has been less clear. Although calves with low serum protein or immunoglobulin concentrations generally are accepted to be at greater risk for morbidity and mortality,4-I1 some studies have failed to identify any significant increase in risk associated with lower serum protein or immunoglobulin concentrations.12J3 In some instances, small sample size was hypothesized as a primary cause for the failure to identify increased risk of m0rta1ity.l~ The purpose of this study was to characterize the association between passive transfer status, as determined by refractometric determination of serum protein concentration, and mortality in mixed-source dairy replacement heifers. Furthermore, this study examined whether the relationship between passive transfer status and mortality was dependent or independent with regard to baseline mortality risk in calves. Lastly, the present study attempted to determine the upper age limit at which inadequate passive transfer status was related to the ongoing risk of mortality. Materials and Methods Study SiteThe study farm was a contract calf-rearing ...
Feline-specific amino acid changes in ABCG2 cause a functional defect of the transport protein in cats. This functional defect may be owing, in part, to defective cellular localization of feline ABCG2. Regardless, dysfunction of ABCG2 at the blood-retinal barrier likely results in accumulation of photoreactive fluoroquinolones in feline retina. Exposure of the retina to light would then generate reactive oxygen species that would cause the characteristic retinal degeneration and blindness documented in some cats receiving high doses of some fluoroquinolones. Pharmacological inhibition of ABCG2 in other species might result in retinal damage if fluoroquinolones are concurrently administered.
The study objective was to identify probable sources and modes of transmission of 91 Staphylococcus aureus isolates obtained from the colostrum of 76 heifers at parturition. Sources cultured were milk (including colostrum), heifer body sites (teats, muzzle, rectum, vagina, and lacteal secretions), and environmental sites (bedding, insects, housing, water, feedstuffs, humans, nonbovine animals, air, and equipment). Staphylococcus aureus isolates were characterized by 63 phenotypic traits. A similarity coefficient was calculated by herd to identify the S. aureus that most closely resembled the S. aureus obtained from heifer colostrum. Staphylococcus aureus from a heifer's colostrum was compared with all preexisting S. aureus isolates from that heifer's herd. Isolates that were > or = 90% similar were considered to be identical. Because 30 (of the 91) S. aureus isolates from heifer colostrum were collected prior to environmental sampling, only 61 S. aureus isolates from heifer colostrum were available for comparison among all three sources. Possible sources of S. aureus from heifer colostrum at parturition were milk (70%, 43 of 61 isolates), heifer body sites (39%, 24 of 61), environmental sites (28%, 17 of 61), or no identified source (16%, 10 of 61). Three heifers with intramammary infection (IMI) from S. aureus at parturition had the same S. aureus on their teats prior to parturition. Milk was the only source identified for 41% (25 of 61) of isolates from heifer colostrum. Isolates from heifer body sites were the only source identified for 5% (3 of 61) of heifer colostrum isolates. Staphylococcus aureus from the environment was never the sole possible source for S. aureus from heifer colostrum. Data suggest that the major sources of S. aureus IMI in heifers at parturition are milk and heifer body sites. Contact among heifers may be an important mode of transmission of S. aureus leading to IMI in heifers at parturition.
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