Volvulus of the colon in a horse associated with a mesocolic-umbilical band     

TD MOGG †  S. GROENENDYK  RH SUTTON ‡ 《Australian veterinary journal》1992,69(1):11-12

A 7-years-old Clydesdale mare was presented with severe abdominal distension and acute colic. Dilated large intestine was palpated per rectum and a ventral midline exploratory laparotomy was performed. A 180 degrees volvulus of the pelvic flexure was present, associated with an inelastic band of tissue connecting the mesocolon to the umbilicus. The band was ligated and transected, and the volvulus reduced. Postoperative complications included hyponatraemia, metabolic acidosis and laminitis. The possible aetiology of the mesocolic-umbilical band is discussed.  相似文献   

Development of prednisone resistance in naïve canine lymphoma: Longitudinal evaluation of NR3C1α, ABCB1, and 11β-HSD mRNA expression     

Camille C. Hanot  Katrina L. Mealey  Janean L. Fidel  Neal S. Burke  Laura A. White  Rance K. Sellon 《Journal of veterinary pharmacology and therapeutics》2020,43(2):231-236

Prednisone resistance develops rapidly and essentially universally when dogs with lymphoma are treated with corticosteroids. We investigated naturally occurring mechanisms of prednisone resistance in seven dogs with naïve multicentric lymphoma, treated with oral prednisone; four dogs were administered concurrent cytotoxic chemotherapy. Expression of NR3C1α, ABCB1 (formerly MDR1), 11β-HSD1, and 11β-HSD2 mRNA was evaluated in neoplastic lymph nodes by real-time RT-PCR. Changes of expression levels at diagnosis and at time of clinical resistance to prednisone were compared longitudinally using a Wilcoxon signed-rank test. Clinical resistance to prednisone was observed after a median of 68 days (range: 7–348 days) after initiation of treatment. Relative to pretreatment samples, prednisone resistance was associated with decreased NR3C1α expression in biopsies of all dogs with high-grade lymphoma (six dogs, p=.031); one dog with indolent T-zone lymphoma had increased expression of NR3C1α. Resistance was not consistently associated with changes in ABCB1, 11β-HSD1, or 11β-HSD2 expression. Decreased expression of the glucocorticoid receptor (NR3C1α) may play a role in conferring resistance to prednisone in dogs with lymphoma. Results do not indicate a broad role for changes in expression of ABCB1, 11β-HSD1, and 11β-HSD2 in the emergence of prednisone resistance in lymphoma-bearing dogs.  相似文献   

Intravenous fat emulsion as treatment for ivermectin toxicosis in three dogs homozygous for the ABCB1–1Δ gene mutation     

Heather M. Wright DVM  Annie V. Chen DVM  MS  DACVIM  Patricia A. Talcott DVM  PhD  DABVT  Robert H. Poppenga DVM  PhD  DABVT  Katrina L. Mealey DVM  PhD  DACVIM  DACVCP 《Journal of Veterinary Emergency and Critical Care》2011,21(6):666-672

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Liquorice and canine Addison's disease     

RH Jarrett  EJ Norman  RA Squires 《New Zealand veterinary journal》2013,61(3)

Abstract

Extract

Hypoadrenocorticism, or Addison's disease, is an uncommon en-docrinopathy of dogs (Feldman and Nelson 2004 Feldman, EC and Nelson, RW. 2004. “Hypoadrenocorticism (Addison's disease)”. In Canine and Feline Endocrinology and Reproduction, 3rd, 394–439. Philadelphia, , USA: WB Saunders.  [Google Scholar]). Long-term management of affected dogs in New Zealand involves treatment with oral fludrocortisone acetate (Florinef tablets; Bristol-Myers Squibb (NZ) Ltd, Auckland, NZ), which is a relatively expensive synthetic adrenocortical steroid. Table salt may be added to the food, in an attempt to reduce the amount of fludrocortisone required. Despite fludrocortisone therapy, many Addisonian dogs remain hyponatraemic and hyperkalaemic and the required dose of fludrocortisone may need to be increased during the first year of treatment. Increasing the dose of fludrocortisone is not only expensive, but may also have undesirable effects through its potent glucocorticoid action.  相似文献   

Establishment of a cell line for assessing drugs as canine P‐glycoprotein substrates: proof of principle          下载免费PDF全文

K. L. Mealey  S. Dassanayake  N. S. Burke 《Journal of veterinary pharmacology and therapeutics》2017,40(5):545-551

P‐glycoprotein (P‐gp), encoded by the ABCB1 (MDR1) gene, dramatically impacts drug disposition. P‐gp is expressed in the intestines, biliary canaliculi, renal tubules, and brain capillaries where it functions to efflux substrate drugs. In this capacity, P‐gp restricts oral absorption, enhances biliary and renal excretion, and inhibits central nervous system entry of substrate drugs. Many drugs commonly used in veterinary medicine are known substrates for canine P‐gp (vincristine, loperamide, ivermectin, others). Because these drugs have a narrow therapeutic index, defective P‐gp function can cause serious adverse drug reactions due to enhanced brain penetration and/or decreased clearance. P‐gp dysfunction in dogs can be intrinsic (dogs harboring ABCB1‐1Δ) or acquired (drug interactions between a P‐gp inhibitor and P‐gp substrate). New human drug candidates are required to undergo assessment for P‐gp interactions according to FDA and EMA regulations to avoid adverse drug reactions and drug–drug interactions. Similar information regarding canine P‐gp could prevent adverse drug reactions in dogs. Because differences in P‐gp substrates have been documented between species, one should not presume that human or murine P‐gp substrates are necessarily canine P‐gp substrates. Thus, our goal was to develop a cell line for assessing drugs as canine P‐gp substrates.  相似文献   

Vincristine-induced central neurotoxicity in a collie homozygous for the ABCB1Δ mutation     

Krugman L  Bryan JN  Mealey KL  Chen A 《The Journal of small animal practice》2012,53(3):185-187

A six-year-old, neutered, female collie was presented to an oncology specialty service after developing tetraparesis and self-mutilation that progressively worsened while receiving chemotherapy for lymphoma. Neurologic examination revealed ataxia, paresis and diminished conscious proprioception in all limbs with entire spinal reflexes. Magnetic resonance imaging of the brain and spinal cord was normal. Electromyography of the limbs ruled out a vincristine-induced peripheral neuropathy. Cerebrospinal fluid analysis and cerebrospinal fluid and serum testing for Neospora and Toxoplasma were normal. Results of MDR1 genotyping revealed that the dog was homozygous for the ABCB1-1Δ (MDR1) mutation. This clinical presentation strongly resembled the effects seen from inadvertent intrathecal administration of vincristine in humans. Dogs that are homozygous for the ABCB1-1Δ (MDR1) mutation should not receive standard dosages of chemotherapy drugs known to be eliminated by P-glycoprotein, the gene product of ABCB1. Testing for this mutation is strongly recommended before chemotherapy initiation for at-risk breeds.  相似文献   

ABCG2 transporter: therapeutic and physiologic implications in veterinary species     

Mealey KL 《Journal of veterinary pharmacology and therapeutics》2012,35(2):105-112

Drug transporters significantly influence drug pharmacokinetics and pharmacodynamics. While P-glycoprotein, the product of the MDR1 (ABCB1) gene, is the most well-characterized ABC transporter, the pharmacological importance of a related transporter, ABCG2, is starting to be realized in veterinary medicine. Based primarily on human and rodent studies, a number of clinically relevant, structurally and functionally unrelated drugs are substrates for ABCG2. ABCG2 is expressed by a variety of normal tissues including the intestines, renal tubular cells, brain and retinal capillary endothelial cells, biliary canalicular cells, and others, where it functions to actively extrude substrate drugs. In this capacity, ABCG2 limits oral absorption of substrate drugs and restricts their distribution to privileged sites such as the brain and retina. ABCG2 is also expressed by tumor cells where it functions to limit the intracellular accumulation of cytotoxic agents, contributing to multidrug resistance. Several ABCG2 polymorphisms have been described in human patients, some of which result in altered drug disposition, increasing susceptibility to adverse drug reactions. Additionally, ABCG2 polymorphisms in humans have been associated with disease states such as gout. Feline ABCG2 has recently been demonstrated to have several amino acid differences at conserved sites compared with 10 other mammalian species. These amino acid differences adversely affect transport function of feline ABCG2 relative to that of human ABCG2. Furthermore, these differences appear to be responsible for fluoroquinolone-induced retinal toxicity in cats and may play a role in acetaminophen toxicity as well. Studies in rodents and sheep have determined that ABCG2 expressed in mammary tissue is responsible for the secretion of many compounds (both therapeutic and toxic) into milk. Finally, data in rodent models suggest that ABCG2 may play an important role in regulating a number of physiologic pathways involved in protecting erythrocytes from oxidative damage.  相似文献   

Relationship between the melanocortin-1 receptor (MC1R) variant R306ter and physiological responses to mechanical or thermal stimuli in Labrador Retriever dogs     

Tania E. Perez  Katrina L. Mealey  Neal S. Burke  Tamara L. Grubb  Michael H. Court  Stephen A. Greene 《Veterinary anaesthesia and analgesia》2017,44(2):370-374

Objective

Variants in the MC1R gene have been associated with red hair color and sensitivity to pain in humans. The study objective was to determine if a relationship exists between MC1R genotype and physiological thermal or mechanical nociceptive thresholds in Labrador Retriever dogs.

Study design

Prospective experimental study.

Animals

Thirty-four Labrador Retriever dogs were included in the study following public requests for volunteers. Owner consent was obtained and owners verified that their dog was apparently not experiencing pain and had not been treated for pain during the previous 14 days. The study was approved by the Institutional Animal Care and Use Committee.

Methods

Nociceptive thresholds were determined from a mean of three thermal and five mechanical replications using commercially available algometers. Each dog was genotyped for the previously described MC1R variant (R306ter). Data were analyzed using one-way anova with post hoc comparisons using Tukey’s test (p < 0.05).

Results

Thirteen dogs were homozygous wild-type (WT/WT), nine were heterozygous (WT/R306ter), and eight were homozygous variant (R306ter/R306ter) genotype. Four dogs could not be genotyped. A significant difference (p = 0.04) in mechanical nociceptive thresholds was identified between dogs with the WT/WT genotype (12.1 ± 2.1 N) and those with the WT/R306ter genotype (9.2 ± 2.4 N).

Conclusion

A difference in mechanical, but not thermal, nociceptive threshold was observed between wild-type and heterozygous MC1R variants. Differences in nociceptive thresholds between homozygous R306ter variants and other genotypes for MC1R were not observed.

Clinical relevance

Compared with the wild-type MC1R genotype, nociceptive sensitivity to mechanical force in dogs with a single variant R306ter allele may be greater. However, in contrast to the reported association between homozygous MC1R variants (associated with red hair color) and nociception in humans, we found no evidence of a similar relationship in dogs with the homozygous variant genotype.  相似文献   

Comparison of chemotherapeutic drug resistance in cells transfected with canine ABCG2 or feline ABCG2          下载免费PDF全文

R. S. Lewis  J. Fidel  S. Dassanayake  M. H. Court  N. S. Burke  K. L. Mealey 《Veterinary and comparative oncology》2017,15(2):411-420

ABCG2 (ATP binding cassette subfamily G, member 2) mediates resistance to a variety of cytotoxic agents. Although human ABCG2 is well characterized, the function of canine ABCG2 has not been studied previously. Feline ABCG2 has an amino acid substitution in the adenosine triphosphate‐binding domain that decreases its transport capacity relative to human ABCG2. Our goal was to compare canine ABCG2‐mediated chemotherapeutic drug resistance to feline ABCG2‐mediated chemotherapeutic drug resistance. HEK‐293 cells stably transfected with plasmid containing canine ABCG2, feline ABCG2 or no ABCG2 were exposed to carboplatin, doxorubicin, mitoxantrone, toceranib or vincristine, and cell survival was subsequently determined. Canine ABCG2 conferred a greater degree of chemotherapy resistance than feline ABCG2 for mitoxantrone. Neither canine nor feline ABCG2 conferred resistance to doxorubicin, vincristine or toceranib. Canine, but not feline, ABCG2 conferred resistance to carboplatin, a drug that is not reported to be a substrate for ABCG2 in other species.  相似文献   

Increased toxicity of P-glycoprotein-substrate chemotherapeutic agents in a dog with the MDR1 deletion mutation associated with ivermectin sensitivity     

Mealey KL  Northrup NC  Bentjen SA 《Journal of the American Veterinary Medical Association》2003,223(10):1453-5, 1434

Lymphoma was diagnosed in a 4-year-old spayed female Collie, and treatment with a combination chemotherapy protocol incorporating prednisone, L-asparaginase, vincristine, vinblastine, doxorubicin, and cyclophosphamide was initiated. The dog had signs of gastrointestinal tract toxicosis and myelosuppression after treatment with P-glycoprotein-substrate drugs (vincristine, vinblastine, and doxorubicin) even when dosages were reduced, but did not have signs of toxicosis after treatment with cyclophosphamide, a non-P-glycoprotein-substrate drug, even when administered at the full dosage. It was postulated that a deletion mutation in the canine MDR1 gene (deltaMDR1 295-298) could be responsible for the drug toxicoses in this dog. This mutation has been identified as the cause of a functional P-glycoprotein defect in Collies susceptible to the toxic effects of ivermectin, another P-glycoprotein-substrate drug. The MDR1 genotype of this dog consisted of 1 normal and 1 mutant MDR1 allele. Because P-glycoprotein contributes to renal, biliary, and intestinal excretion of P-glycoprotein-substrate drugs, it is possible that drug excretion was delayed in this patient, resulting in clinical signs of toxicosis.  相似文献