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Effect of heart failure on dipeptidyl peptidase IV activity in plasma of dogs. 心力衰竭对犬血浆二肽基肽酶IV活性的影响。
IF 2.6 2区 农林科学 Pub Date : 2012-07-01 Epub Date: 2012-05-18 DOI: 10.1111/j.1939-1676.2012.00942.x
N Gomez, V Matheeussen, C Damoiseaux, A Tamborini, A C Merveille, P Jespers, C Michaux, C Clercx, I De Meester, K Mc Entee

Background: In congestive heart failure (HF), plasma B-type natriuretic peptide (BNP) seems devoid of biological effectiveness. BNP(1-32) could be truncated into BNP(3-32) by dipeptidyl peptidase IV (DPP4), and BNP(3-32) has reduced biological activities.

Hypothesis: Increased DPP4 activity is associated with pathophysiology of HF.

Animals: One hundred twenty-eight client-owned dogs and 9 experimental Beagles from the Clinical Veterinary Unit of the University of Liège.

Methods: We prospectively measured plasma DPP4 activity in 5 groups of dogs: normal growing dogs (n = 21), normal adult dogs (n = 60), healthy Beagle (n = 9), dogs with myxomatous mitral valve disease (n = 35), and dogs with dilated cardiomyopathy (n = 12). The final diagnosis and the severity of HF were determined by Doppler echocardiography. Plasma DPP4 activity was measured kinetically by a fluorimetric method.

Results: In growing dogs, DPP4 activity was higher than in adults (P < .001) and inversely correlated with age (r = -0.57, P < .01). In adults, DPP4 activity increased linearly with body weight (r = 0.39, P < .01), but there was no influence of age or sex. No effect of the circadian rhythm was noted. DPP4 activity was significantly higher in HF ISACHC I (16.3 ± 1.14 U/L) compared with healthy adults (12.4 ± 0.65 U/L, P < .05) and HF ISACHC III (11.0 ± 1.50 U/L, P < .05). Mean DPP4 activity in ISACHC II was 15.1 ± 1.4 U/L.

Conclusion and clinical importance: We did not find evidence that plasma DPP4 activity is responsible for the "BNP resistance" in overt congestive HF, but it may be implicated in early stages.

背景:在充血性心力衰竭(HF)中,血浆b型利钠肽(BNP)似乎缺乏生物学有效性。BNP(1-32)可被二肽基肽酶IV (DPP4)截断为BNP(3-32), BNP(3-32)的生物活性降低。假设:DPP4活性升高与HF的病理生理有关。动物:128只客户拥有的狗和9只来自li大学临床兽医部门的实验小猎犬。方法:前瞻性测定5组犬的血浆DPP4活性:正常生长犬(n = 21)、正常成年犬(n = 60)、健康比格犬(n = 9)、二尖瓣黏液瘤病犬(n = 35)、扩张型心肌病犬(n = 12)。通过多普勒超声心动图确定HF的最终诊断和严重程度。用荧光法动态测定血浆DPP4活性。结果:生长犬DPP4活性高于成年犬(P < 0.001),且与年龄呈负相关(r = -0.57, P < 0.01)。在成人中,DPP4活性随体重呈线性增加(r = 0.39, P < 0.01),但不受年龄和性别的影响。没有注意到昼夜节律的影响。心衰ISACHCⅰ组(16.3±1.14 U/L)和心衰ISACHCⅲ组(11.0±1.50 U/L, P < 0.05) DPP4活性显著高于健康成人(12.4±0.65 U/L, P < 0.05)。ISACHCⅱ中DPP4的平均活性为15.1±1.4 U/L。结论和临床意义:我们没有发现血浆DPP4活性与明显充血性HF患者的“BNP抵抗”有关的证据,但它可能在早期阶段就有关联。
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引用次数: 17
Cardiac troponin I in calves with congenital heart disease. 先天性心脏病犊牛心肌肌钙蛋白I的研究
IF 2.6 2区 农林科学 Pub Date : 2012-07-01 Epub Date: 2012-06-11 DOI: 10.1111/j.1939-1676.2012.00953.x
K Suzuki, E Uchida, K E Schober, A Niehaus, M D Rings, J Lakritz

Background: The association between plasma cardiac troponin I (cTnI) and the magnitude of cardiac enlargement in calves with congenital heart disease (CHD) are not well defined.

Objective: To investigate the relationship between plasma cTnI concentrations and cardiac size in healthy calves and calves with CHD.

Animals: A total of 19 healthy calves (control) and 12 Holstein calves with CHD (patent ductus arteriosus, ventricular septal defect, tetralogy of Fallot or double outlet right ventricle).

Methods: Case control study. All animals underwent a comprehensive transthoracic echocardiographic study to document cardiac health or presence of CHD. The vertebral heart score (VHS) was determined in each animal using right lateral survey radiographic images. Blood samples were collected via jugular venipuncture and plasma cTnI concentration and creatine kinase (CK) activity were determined by a 3rd generation immunoassay and an automatic biochemical analyzer, respectively. Groups were compared using Mann-Whitney U-test and receiver-operating characteristics (ROC) curve analysis.

Results: Calves with CHD had significantly larger VHS values and higher plasma cTnI concentrations (P < .001) compared to control. Creatine kinase activity was not different between the control and CHD groups of calves. Diagnostic cutoffs of VHS and plasma cTnI for discrimination of groups were 8.9 vertebrae and 0.035 ng/mL, respectively. The cTnI concentration in plasma was significantly correlated with VHS (r (2) =0.512, P < .001).

Conclusion and clinical relevance: Our results suggest that determination of plasma cTnI concentrations in calves with clinical signs compatible with CHD might prove useful as a guide to quantify cardiac remodeling associated with increased cardiac size.

背景:血浆心肌肌钙蛋白I (cTnI)与先天性心脏病(CHD)犊牛心脏增大程度之间的关系尚不明确。目的:探讨健康犊牛和冠心病犊牛血浆cTnI浓度与心脏大小的关系。动物:19头健康犊牛(对照组)和12头患有冠心病(动脉导管未闭、室间隔缺损、法洛四联症或右心室双出口)的荷斯坦犊牛。方法:病例对照研究。所有的动物都进行了全面的经胸超声心动图研究,以记录心脏健康或冠心病的存在。每只动物的椎体心脏评分(VHS)采用右侧放射图像测量。颈静脉穿刺采血,采用第三代免疫分析法和全自动生化分析仪分别测定血浆cTnI浓度和肌酸激酶(CK)活性。各组间比较采用Mann-Whitney u检验和受试者工作特征(ROC)曲线分析。结果:与对照组相比,冠心病犊牛的VHS值和血浆cTnI浓度显著升高(P < 0.001)。犊牛肌酸激酶活性在对照组和冠心病组之间无显著差异。VHS和血浆cTnI对组间区分的诊断临界值分别为8.9和0.035 ng/mL。血浆cTnI浓度与VHS有显著相关性(r (2) =0.512, P < 0.001)。结论和临床意义:我们的研究结果表明,测定具有冠心病临床症状的犊牛血浆cTnI浓度可能有助于量化与心脏大小增加相关的心脏重构。
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引用次数: 13
Seasonal changes in the combined glucose-insulin tolerance test in normal aged horses. 正常老年马葡萄糖-胰岛素耐量试验的季节变化。
IF 2.6 2区 农林科学 Pub Date : 2012-07-01 Epub Date: 2012-05-18 DOI: 10.1111/j.1939-1676.2012.00939.x
R A Funk, A A Wooldridge, A J Stewart, E N Behrend, R J Kemppainen, Q Zhong, A K Johnson

Background: Equine metabolic syndrome (EMS) is an increasingly recognized problem in adult horses. Affected horses are often obese and predisposed to the development of laminitis, especially in the spring and summer months. In addition, in the summer and fall months, increases in endogenous insulin concentrations, a marker of EMS, have been reported.

Hypothesis/objectives: The purpose of this study was to evaluate seasonal changes in results of the combined glucose-insulin tolerance test (CGIT), a diagnostic test for EMS.

Animals: Nine healthy, aged horses with no history of laminitis and no clinical signs of EMS.

Methods: Horses were given dextrose (150 mg/kg) and insulin (0.1 U/kg) IV. Plasma glucose concentrations were measured at 0, 1, 5, 15, 30, 45, 60, 75, 90, and 150 minutes and serum insulin concentrations at 0, 5, and 75 minutes. Testing was performed in February, May, June, August, September, and November. Mean glucose concentrations, characteristics of the curve, and insulin concentrations during the CGIT were compared across months using repeated measures ANOVA (P < .05).

Results: No CGIT parameters indicated insulin resistance, but mean area under the curve for glucose concentrations was significantly lower in August and November compared to February and in November compared to June, indicating increased insulin-mediated glucose clearance. Glucose nadir was significantly lower in November compared to that in February.

Conclusions and clinical importance: No clinically relevant differences were seen in the results of the CGIT, suggesting that season minimally affects results of this test in normal aged horses in the southeastern United States.

背景:马代谢综合征(EMS)在成年马中越来越被认识到。受影响的马通常肥胖,易患足部炎,特别是在春季和夏季。此外,据报道,在夏季和秋季,内源性胰岛素浓度增加,这是EMS的一个标志。假设/目的:本研究的目的是评估葡萄糖-胰岛素耐量联合试验(CGIT)结果的季节性变化,CGIT是EMS的诊断试验。动物:9匹健康的老年马,无足板炎病史,无EMS临床症状。方法:给马注射葡萄糖(150 mg/kg)和胰岛素(0.1 U/kg)静脉注射,在0、1、5、15、30、45、60、75、90、150分钟测定血浆葡萄糖浓度,在0、5、75分钟测定血清胰岛素浓度。测试在2月、5月、6月、8月、9月和11月进行。使用重复测量方差分析(repeated measures ANOVA)比较CGIT期间的平均葡萄糖浓度、曲线特征和胰岛素浓度(P < 0.05)。结果:CGIT参数均未显示胰岛素抵抗,但葡萄糖浓度曲线下平均面积在8月和11月明显低于2月,11月明显低于6月,表明胰岛素介导的葡萄糖清除率增加。11月的血糖最低点明显低于2月。结论和临床重要性:CGIT的结果没有临床相关的差异,表明季节对美国东南部正常老年马的测试结果影响很小。
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引用次数: 26
The prevalence of leptospiral antibodies in free roaming cats in Worcester County, Massachusetts. 麻萨诸塞州伍斯特县流浪猫中钩端螺旋体抗体的流行。
IF 2.6 2区 农林科学 Pub Date : 2012-05-01 Epub Date: 2012-03-06 DOI: 10.1111/j.1939-1676.2012.00900.x
J E Markovich, L Ross, E McCobb

Background: Serosurveys of cats for exposure to or infection with leptospires have been published from other geographic areas, but none for cats in the United States in the past 4 decades.

Hypothesis/objectives: The purpose of this pilot study was to determine the prevalence of leptospiral antibodies in a population of free roaming cats in Worcester County, (central) Massachusetts.

Animals: Sixty-three free roaming cats presenting to a trap-neuter-return (TNR) program.

Methods: Prospective study. Serum was collected from 63 free roaming cats presented to a university associated TNR. Microagglutination titers to Leptospira interrogans serovars Autumnalis, Hardjo, Bratislava, Icterohaemorrhagiae, Canicola, Pomona, and L kirshneri Grippotyphosa were determined.

Results: A total of 3 of 63 cats (4.8%) had a titer of 1 : 100 or greater to one or more serovars, with Autumnalis being the most common. None of the cats were seropositive to Hardjo, Grippotyphosa, or Canicola.

Conclusions and clinical importance: These results are consistent with previously published seroprevalence rates in feral cats. Additional studies are required to determine the role of leptosporosis in clinical disease in the domestic cat.

背景:其他地区的猫接触或感染钩端螺旋体的血清调查已经发表,但在过去的40年里没有针对美国猫的调查。假设/目的:本初步研究的目的是确定马萨诸塞州伍斯特县(中部)流浪猫群体中钩端螺旋体抗体的流行情况。动物:63只自由漫游的猫参加了一个陷阱-绝育-回归(TNR)项目。方法:前瞻性研究。从63只流浪猫身上收集血清,这些猫被送到大学相关的TNR。测定了秋钩端螺旋体、哈德乔钩端螺旋体、布拉迪斯拉发钩端螺旋体、出血性钩端螺旋体、Canicola钩端螺旋体、Pomona钩端螺旋体和kirshneri钩端伤寒螺旋体的微凝集滴度。结果:63只猫中有3只(4.8%)对一种或多种血清型的滴度为1:1及以上,以秋猫最常见。没有猫对Hardjo、gripo伤寒菌或Canicola血清呈阳性。结论和临床意义:这些结果与先前发表的野猫血清患病率一致。需要进一步的研究来确定钩端孢子病在家猫临床疾病中的作用。
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引用次数: 51
Importance of the effective strong ion difference of an intravenous solution in the treatment of diarrheic calves with naturally acquired acidemia and strong ion (metabolic) acidosis. 静脉注射溶液强离子差在治疗腹泻小牛自然获得性酸血症和强离子(代谢性)酸中毒中的重要性。
IF 2.6 2区 农林科学 Pub Date : 2012-05-01 Epub Date: 2012-04-04 DOI: 10.1111/j.1939-1676.2012.00917.x
K R Müller, A Gentile, W Klee, P D Constable

Background: The effect of sodium bicarbonate on acid-base balance in metabolic acidosis is interpreted differently by Henderson-Hasselbalch and strong ion acid-base approaches. Application of the traditional bicarbonate-centric approach indicates that bicarbonate administration corrects the metabolic acidosis by buffering hydrogen ions, whereas strong ion difference theory indicates that the co-administration of the strong cation sodium with a volatile buffer (bicarbonate) corrects the strong ion acidosis by increasing the strong ion difference (SID) in plasma.

Objective: To investigate the relative importance of the effective SID of IV solutions in correcting acidemia in calves with diarrhea.

Animals: Twenty-two Holstein-Friesian calves (4-21 days old) with naturally acquired diarrhea and strong ion (metabolic) acidosis.

Methods: Calves were randomly assigned to IV treatment with a solution of sodium bicarbonate (1.4%) or sodium gluconate (3.26%). Fluids were administered over 4 hours and the effect on acid-base balance was determined.

Results: Calves suffered from acidemia owing to moderate to strong ion acidosis arising from hyponatremia and hyper-D-lactatemia. Sodium bicarbonate infusion was effective in correcting the strong ion acidosis. In contrast, sodium gluconate infusion did not change blood pH, presumably because the strong anion gluconate was minimally metabolized.

Conclusions: A solution containing a high effective SID (sodium bicarbonate) is much more effective in alkalinizing diarrheic calves with strong ion acidosis than a solution with a low effective SID (sodium gluconate). Sodium gluconate is ineffective in correcting acidemia, which can be explained using traditional acid-base theory but requires a new parameter, effective SID, to be understood using the strong ion approach.

背景:氢碳酸钠对代谢性酸中毒中酸碱平衡的影响有两种不同的解释,一种是强离子酸碱法,另一种是Henderson-Hasselbalch法。应用传统的以碳酸氢盐为中心的方法表明,碳酸氢盐通过缓冲氢离子来纠正代谢性酸中毒,而强离子差理论表明,强阳离子钠与挥发性缓冲剂(碳酸氢盐)共同施用通过增加血浆中的强离子差(SID)来纠正强离子酸中毒。目的:探讨静脉注射液在纠正犊牛腹泻胃酸血症中的相对重要性。动物:22头荷斯坦-弗里西亚犊牛(4-21日龄),自然获得性腹泻和强离子(代谢性)酸中毒。方法:将犊牛随机分为碳酸氢钠(1.4%)和葡萄糖酸钠(3.26%)静脉注射组。给药4小时,测定对酸碱平衡的影响。结果:犊牛因低钠血症和高d -乳酸血症引起中重度离子酸中毒而发生酸血症。碳酸氢钠输注可有效纠正强离子酸中毒。相比之下,葡萄糖酸钠输注没有改变血液pH值,可能是因为强阴离子葡萄糖酸盐代谢最低。结论:含有高效SID(碳酸氢钠)的溶液比含有低效SID(葡萄糖酸钠)的溶液更有效地碱化患有强离子酸中毒的腹泻小牛。葡萄糖酸钠对酸血症的纠正是无效的,这可以用传统的酸碱理论来解释,但需要一个新的参数,即有效SID,用强离子方法来理解。
{"title":"Importance of the effective strong ion difference of an intravenous solution in the treatment of diarrheic calves with naturally acquired acidemia and strong ion (metabolic) acidosis.","authors":"K R Müller,&nbsp;A Gentile,&nbsp;W Klee,&nbsp;P D Constable","doi":"10.1111/j.1939-1676.2012.00917.x","DOIUrl":"https://doi.org/10.1111/j.1939-1676.2012.00917.x","url":null,"abstract":"<p><strong>Background: </strong>The effect of sodium bicarbonate on acid-base balance in metabolic acidosis is interpreted differently by Henderson-Hasselbalch and strong ion acid-base approaches. Application of the traditional bicarbonate-centric approach indicates that bicarbonate administration corrects the metabolic acidosis by buffering hydrogen ions, whereas strong ion difference theory indicates that the co-administration of the strong cation sodium with a volatile buffer (bicarbonate) corrects the strong ion acidosis by increasing the strong ion difference (SID) in plasma.</p><p><strong>Objective: </strong>To investigate the relative importance of the effective SID of IV solutions in correcting acidemia in calves with diarrhea.</p><p><strong>Animals: </strong>Twenty-two Holstein-Friesian calves (4-21 days old) with naturally acquired diarrhea and strong ion (metabolic) acidosis.</p><p><strong>Methods: </strong>Calves were randomly assigned to IV treatment with a solution of sodium bicarbonate (1.4%) or sodium gluconate (3.26%). Fluids were administered over 4 hours and the effect on acid-base balance was determined.</p><p><strong>Results: </strong>Calves suffered from acidemia owing to moderate to strong ion acidosis arising from hyponatremia and hyper-D-lactatemia. Sodium bicarbonate infusion was effective in correcting the strong ion acidosis. In contrast, sodium gluconate infusion did not change blood pH, presumably because the strong anion gluconate was minimally metabolized.</p><p><strong>Conclusions: </strong>A solution containing a high effective SID (sodium bicarbonate) is much more effective in alkalinizing diarrheic calves with strong ion acidosis than a solution with a low effective SID (sodium gluconate). Sodium gluconate is ineffective in correcting acidemia, which can be explained using traditional acid-base theory but requires a new parameter, effective SID, to be understood using the strong ion approach.</p>","PeriodicalId":17462,"journal":{"name":"Journal of Veterinary Internal Medicine","volume":"26 3","pages":"674-83"},"PeriodicalIF":2.6,"publicationDate":"2012-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1939-1676.2012.00917.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30561128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 33
Qualitative and quantitative characteristics of the electroencephalogram in normal horses after sedation. 正常马镇静后脑电图的定性和定量特征。
IF 2.6 2区 农林科学 Pub Date : 2012-05-01 Epub Date: 2012-04-10 DOI: 10.1111/j.1939-1676.2012.00921.x
D C Williams, M Aleman, B Tharp, D J Fletcher, P H Kass, E P Steffey, R A LeCouteur, T A Holliday

Background: The administration of certain sedatives has been shown to promote sleep in humans. Related agents induce sleep-like behavior when administered to horses. Interpretation of electroencephalograms (EEGs) obtained from sedated horses should take into account background activity, presence of sleep-related EEG events, and the animal's behavior.

Hypothesis: Sedatives induce states of vigilance that are indistinguishable on EEGs from those that occur naturally.

Animals: Six healthy horses.

Methods: Digital EEG with video was recorded after administration of 1 of 4 sedatives (acepromazine, butorphanol, xylazine, or detomidine). Serum drug concentrations were measured. Recordings were reviewed, states were identified, and representative EEG samples were analysed. These data were compared with data previously obtained during a study of natural sleep.

Results: Butorphanol was associated with brief episodes resembling slow wave sleep in 1 horse. Acepromazine led to SWS in 3 horses, including 1 that also exhibited rapid eye movement sleep. Periods of SWS were observed in all horses afer xylazine or detomidine administration. Normal sleep-related EEG events and heart block, occurred in association with SWS regardless of which sedative was used. Spectral data varied primarily by state, but some differences were observed between sedative and natural data.

Conclusions and clinical importance: Qualitatively, EEG findings appeared identical whether sedation-induced or naturally occurring. The startle response and heart block associated with some sedatives may be related to sleep. Alpha(2) agonists can be used to obtain high quality EEGs in horses, but acepromazine does not promote a relaxed state in all animals.

背景:某些镇静剂的使用已被证明能促进人类睡眠。当给马施用相关药剂时,会诱发类似睡眠的行为。对镇静马的脑电图(EEG)的解释应考虑到背景活动、与睡眠相关的脑电图事件的存在以及动物的行为。假设:镇静剂诱导的警觉状态在脑电图上与自然状态难以区分。动物:六匹健康的马。方法:给药4种镇静剂(乙酰丙嗪、丁托啡诺、噻嗪、托托咪定)中的1种后,记录数字脑电图录像。测定血清药物浓度。回顾记录,确定状态,并分析代表性脑电图样本。这些数据与之前在自然睡眠研究中获得的数据进行了比较。结果:布托啡诺与1匹马类似慢波睡眠的短暂发作有关。乙酰丙嗪导致3匹马出现SWS,其中1匹马也表现出快速眼动睡眠。在给药后观察到所有马的SWS期。无论使用哪种镇静剂,正常睡眠相关脑电图事件和心脏传导阻滞均与SWS相关。光谱数据主要随状态而变化,但在镇静和自然数据之间观察到一些差异。结论和临床意义:定性地说,无论是镇静诱导的还是自然发生的脑电图结果都是相同的。一些镇静剂引起的惊吓反应和心脏传导阻滞可能与睡眠有关。α(2)激动剂可用于马获得高质量的脑电图,但乙酰丙嗪并不能在所有动物中促进放松状态。
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引用次数: 30
A randomized trial investigating the efficacy and safety of water soluble micellar paclitaxel (Paccal Vet) for treatment of nonresectable grade 2 or 3 mast cell tumors in dogs. 一项随机试验,研究水溶性胶束紫杉醇(Paccal Vet)治疗犬体内不可切除的 2 级或 3 级肥大细胞瘤的有效性和安全性。
IF 2.6 2区 农林科学 Pub Date : 2012-05-01 Epub Date: 2012-03-06 DOI: 10.1111/j.1939-1676.2012.00897.x
D M Vail, H von Euler, A W Rusk, L Barber, C Clifford, R Elmslie, L Fulton, J Hirschberger, M Klein, C London, M Martano, E A McNiel, J S Morris, N Northrup, B Phillips, G Polton, G Post, M Rosenberg, D Ruslander, A Sahora, S Siegel, D Thamm, S Westberg, J Winter, C Khanna

Background: Effective treatments for dogs with advanced stage mast cell tumors (MCT) remain a pressing need. A micellar formulation of paclitaxel (paclitaxel [micellar]) has shown promise in early-phase studies.

Hypothesis/objectives: The objective was to demonstrate greater activity for paclitaxel (micellar) compared with lomustine. The null hypothesis was μ(p) = μ(L) (ie, proportion of responders for the paclitaxel [micellar] and lomustine groups, respectively).

Animals: Two hundred and fifty-two dogs with advanced stage nonresectable grade 2 or 3 MCT.

Methods: Prospective multicenter randomized double-blind positive-controlled clinical trial. The primary endpoint was confirmed overall response rate (CORR) at 14 weeks. A secondary endpoint, biologic observed response rate (BORR), also was calculated. Safety was assessed by the characterization and grading of adverse events (AE).

Results: Overall CORR (7% versus 1%; P = .048) and BORR (23% versus 10%; P = .012) were greater for paclitaxel (micellar) compared with lomustine. Paclitaxel (micellar)-treated dogs were 6.5 times more likely to have a confirmed response and 3.1 times more likely to experience a biologic observed response. The majority of AE with paclitaxel (micellar) were transient and clinically manageable. Twenty-seven dogs (33%) receiving lomustine were discontinued because of hepatopathy compared with 3 dogs (2%) receiving paclitaxel (micellar) (P < .0001; odds ratio 26.7).

Conclusions and clinical importance: Paclitaxel (micellar)'s activity and safety profile are superior to lomustine. The addition of an active and novel taxane to the veterinary armamentarium could fill a substantial need and, as its mechanism of action and AE profile do not overlap with currently available TKI, its availability could lead to effective combination protocols.

背景:对患有晚期肥大细胞瘤(MCT)的狗进行有效治疗仍是一项迫切需要。紫杉醇的胶束制剂(紫杉醇[胶束])在早期阶段的研究中显示出良好的前景:假设/目的:目的是证明紫杉醇(胶束)与洛莫司汀相比具有更强的活性。零假设为μ(p) = μ(L)(即紫杉醇[胶束]组和洛莫司汀组的应答者比例):方法:前瞻性多中心随机对照研究:前瞻性多中心随机双盲阳性对照临床试验。主要终点是14周时的确诊总反应率(CORR)。次要终点为生物观察反应率(BORR)。安全性通过对不良事件(AE)的定性和分级进行评估:结果:与洛莫司汀相比,紫杉醇(胶束)的总体CORR(7%对1%;P = .048)和BORR(23%对10%;P = .012)更高。接受紫杉醇(胶束)治疗的狗出现确诊反应的几率是洛莫司汀的6.5倍,出现生物观察反应的几率是洛莫司汀的3.1倍。紫杉醇(胶束)引起的AE大多是一过性的,临床上可以控制。接受洛莫司汀治疗的27只狗(33%)因肝病而停药,而接受紫杉醇(胶束)治疗的3只狗(2%)因肝病而停药(P < .0001;几率比26.7):紫杉醇(胶束)的活性和安全性均优于洛莫司汀。由于其作用机制和AE特征与目前可用的TKI并不重叠,它的可用性可促成有效的联合方案。
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引用次数: 0
Comparative potential therapeutic effect of sesame oil and peanut oil against acute monocrotaline (Crotalaria) poisoning in a rat model. 芝麻油和花生油对大鼠急性小檗碱中毒的潜在治疗效果比较。
IF 2.6 2区 农林科学 Pub Date : 2012-05-01 Epub Date: 2012-03-23 DOI: 10.1111/j.1939-1676.2012.00909.x
P Srinivasan, M-Y Liu

Background: Many Crotalaria plant species contain hepatotoxic pyrrolizidine alkaloids (such as monocrotaline) that can cause acute and chronic poisoning in cattle and other animals.

Hypothesis: Peanut oil, atropine sulfate, and antidiarrheal agents are used to treat acute monocrotaline poisoning. The effect of sesame on acute monocrotaline poisoning has never been investigated.

Animals: Fifty male Sprague-Dawley rats were used for toxicity studies.

Methods: Experiment 1: Group I, control. Groups II-IV were given monocrotaline (205.2 mg/kg) and euthanized 6, 12, and 24 hours later. Experiment 2: Group I, control. Group II monocrotaline alone (205.2 mg/kg). Groups III-VI were given monocrotaline (205.2 mg/kg) and 1 hour later, Groups III and IV were given sesame oil (1 and 2 mL/kg) and Groups V and VI were given peanut oil (1 and 2 mL/kg).

Results: Monocrotaline significantly decreased (P < .05) serum amylase activity, but, over time, increased (P < .05) pancreatic and lung injury. AST and ALT activity and liver injury peaked at 24 hours. Sesame oil and peanut oil (P < .05) inhibited the changes in all tested parameters in acute monocrotaline poisoning. Although peanut oil inhibited acute monocrotaline poisoning, it induced steatosis, but sesame oil did not.

Conclusion and clinical importance: We hypothesize that early pancreatic and lung injury and late liver injury contribute to acute monocrotaline poisoning and that sesame oil is more efficacious than peanut oil against acute monocrotaline poisoning in rats. However, additional studies are needed to confirm that these oils have the same effects in cattle and other animals.

背景:许多Crotalaria植物含有肝毒性吡咯利西啶生物碱(如monocrotaline),可引起牛和其他动物的急性和慢性中毒。假设:花生油、硫酸阿托品和止泻剂用于治疗急性单芥碱中毒。芝麻对急性单芥碱中毒的影响从未被研究过。动物:50只雄性Sprague-Dawley大鼠用于毒性研究。方法:实验一:第一组,对照组。II-IV组给予205.2 mg/kg的单苦参碱,6、12、24 h后实施安乐死。实验2:第一组,对照组。II组单藜碱(205.2 mg/kg)。III ~ VI组给予单芥碱(205.2 mg/kg), 1 h后,III、IV组给予香油(1、2ml /kg), V、VI组给予花生油(1、2ml /kg)。结果:苦杏仁碱显著降低血清淀粉酶活性(P < 0.05),但随着时间的推移,增加胰腺和肺损伤(P < 0.05)。AST和ALT活性与肝损伤的关系在24小时达到高峰。芝麻油和花生油对急性苦杏仁碱中毒各指标的变化均有抑制作用(P < 0.05)。花生油虽能抑制急性单芥碱中毒,但能诱导脂肪变性,而香油则无此作用。结论及临床意义:我们推测早期胰脏、肺损伤和晚期肝损伤是大鼠急性苦杏仁碱中毒的重要机制,芝麻油对大鼠急性苦杏仁碱中毒的治疗效果优于花生油。然而,还需要进一步的研究来证实这些油对牛和其他动物有同样的效果。
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引用次数: 11
Long-term follow-up of renal function in dogs after treatment for ACTH-dependent hyperadrenocorticism. acth依赖性肾上腺皮质亢进症治疗后犬肾功能的长期随访。
IF 2.6 2区 农林科学 Pub Date : 2012-05-01 Epub Date: 2012-03-30 DOI: 10.1111/j.1939-1676.2012.00915.x
P M Y Smets, H P Lefebvre, B P Meij, S Croubels, E Meyer, I Van de Maele, S Daminet

Background: Systemic hypertension and proteinuria are frequent complications in dogs with Cushing's syndrome and do not always resolve after treatment of hypercortisolism. Therefore, dogs with Cushing's syndrome may be at risk for renal dysfunction before and after treatment.

Hypothesis/objectives: To assess renal function in dogs with ACTH-dependent hyperadrenocorticism (ADHAC) before and after treatment.

Animals: A total of 19 dogs with ADHAC and 12 control dogs.

Methods: Renal function was assessed before and at 1, 3, 6, and 12 months after treatment. Twelve dogs were treated with trilostane and 7 dogs by transsphenoidal hypophysectomy. Routine renal markers were measured and urinary albumin (uALB), immunoglobulin G (uIgG), and retinol-binding protein (uRBP) were assessed by ELISA. Urinary N-acetyl-β-D-glucosaminidase (uNAG) was determined colorimetrically. All urinary markers were indexed to urinary creatinine concentration (c). Plasma clearance of creatinine (Cl(creat)), exo-iohexol (Cl(exo)), and endo-iohexol (Cl(endo)) was used to measure glomerular filtration rate (GFR). Data were analyzed using a general linear model.

Results: Serum creatinine and urea concentrations increased post-treatment, but remained within reference ranges. Plasma Cl(creat) and Cl(endo) were significantly lower post-treatment, whereas Cl(exo) was not different. Urinary protein-to-creatinine ratio (UPC), uALB/c, uIgG/c, and uRBP/c were decreased post-treatment, but at 12 months 5/13 dogs remained proteinuric. Urinary NAG/c did not change significantly.

Conclusions and clinical importance: A decrease in GFR and persistent proteinuria post-treatment may warrant the clinician's attention. Future research including renal histopathology of dogs with persistent proteinuria or low GFR is needed to further assess renal outcome.

背景:全身性高血压和蛋白尿是库欣综合征犬的常见并发症,并不能在高皮质醇血症治疗后得到解决。因此,患有库欣综合征的狗在治疗前后可能存在肾功能不全的风险。假设/目的:评估acth依赖性肾上腺皮质亢进(ADHAC)犬治疗前后的肾功能。动物:共19只ADHAC犬和12只对照犬。方法:分别于治疗前、治疗后1、3、6、12个月评估肾功能。12只犬采用三叶曲烷治疗,7只犬采用经蝶窦垂体切除术。检测常规肾脏标志物,ELISA检测尿白蛋白(uALB)、免疫球蛋白G (uIgG)、视黄醇结合蛋白(uRBP)。用比色法测定尿n -乙酰-β- d -氨基葡萄糖酶(uNAG)。所有尿液标志物均与尿肌酐浓度(c)相关。血浆肌酐(Cl(creat))、外碘己醇(Cl(exo))和内碘己醇(Cl(endo))清除率用于测量肾小球滤过率(GFR)。数据分析采用一般线性模型。结果:治疗后血清肌酐和尿素浓度升高,但仍在参考范围内。治疗后血浆Cl(creat)和Cl(endo)显著降低,而Cl(exo)无显著差异。治疗后尿蛋白与肌酐比(UPC)、uALB/c、uIgG/c和uRBP/c均下降,但12个月时仍有5/13只狗保持蛋白尿。尿NAG/c无明显变化。结论和临床意义:治疗后GFR下降和持续性蛋白尿可能值得临床医生注意。未来需要对持续性蛋白尿或低GFR犬进行肾脏组织病理学研究,以进一步评估肾脏预后。
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引用次数: 41
Sonoclot® evaluation of single- and multiple-dose subcutaneous unfractionated heparin therapy in healthy adult dogs. Sonoclot®评估健康成年犬单次和多次皮下无分级肝素治疗。
IF 2.6 2区 农林科学 Pub Date : 2012-05-01 Epub Date: 2012-03-22 DOI: 10.1111/j.1939-1676.2012.00907.x
D M Babski, B M Brainard, A G Ralph, J R Pittman, A Koenig

Background: Heparin therapy is difficult to monitor due to variation in animal response. While laboratory measurements of activated partial thromboplasin time (aPTT) and Anti-Xa activity (AXA) accurately describe heparin effect, their availability is limited.

Hypothesis: Sonoclot analysis would be as sensitive as AXA and aPTT to monitor effects of unfractionated heparin (UFH) in healthy adult dogs.

Animals: Six adult mixed-breed dogs.

Methods: A prospective study design was employed. On day 1, baseline samples were collected (CBC, PT, aPTT, and Sonoclot), and UFH (300 U/kg SC) was administered to 6 dogs following an IV loading dose of 50 U/kg. Sonoclot and aPTT were performed hourly for 12 hours. AXA was assayed at hours 3, 6, 9, and 12. UFH (300 U/kg q8 h SC) was administered at 12 hours, and subsequently (q8 h) for 2 additional days. On day 4, a final dose of UFH was administered, and a sampling protocol identical to day 1 was performed.

Results: Sonoclot activated clotting time (ACT) and clot rate (CR) correlated with AXA (R = 0.69, R = 0.65, respectively, P < .001), although to a lesser degree than aPTT (R = 0.75, P < .001). Linear regression using ACT and CR as covariates indicated a stronger correlation with AXA (R = 0.73, P < .001). ACT values strongly correlated with aPTT (R = 0.87, P < .001).

Conclusions and clinical importance: Administration of UFH to healthy dogs results in progressive changes in Sonoclot values. AXA was correlated with a combination of ACT and CR and with aPTT. Sonoclot may play a role in monitoring UFH therapy; however, prospective studies evaluating its utility in clinical cases are warranted.

背景:由于动物反应的差异,肝素治疗很难监测。虽然实验室测量的活化部分凝血酶时间(aPTT)和抗xa活性(AXA)准确地描述肝素的作用,他们的可用性是有限的。假设:超声凝血分析与AXA和aPTT一样灵敏,可以监测未分离肝素(UFH)对健康成年犬的影响。动物:6只成年混血狗。方法:采用前瞻性研究设计。第1天,收集基线样本(CBC、PT、aPTT和Sonoclot),并在静脉给药剂量为50 U/kg的情况下给6只狗注射UFH (300 U/kg SC)。Sonoclot和aPTT每小时进行12小时。在第3、6、9和12小时检测AXA。在12小时给药UFH (300 U/kg q8 h SC),随后(q8 h)再给药2天。在第4天,给予最后剂量的UFH,并执行与第1天相同的采样方案。结果:Sonoclot活化凝血时间(ACT)和凝血率(CR)与AXA相关(R = 0.69, R = 0.65, P < 0.001),但程度低于aPTT (R = 0.75, P < 0.001)。以ACT和CR为协变量的线性回归显示,与AXA有较强的相关性(R = 0.73, P < 0.001)。ACT值与aPTT呈正相关(R = 0.87, P < 0.001)。结论及临床意义:健康犬服用UFH可导致超声心动图值进行性变化。AXA与ACT、CR联合用药及aPTT相关。速凝剂可能在监测UFH治疗中发挥作用;然而,评估其在临床病例中的效用的前瞻性研究是必要的。
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引用次数: 14
期刊
Journal of Veterinary Internal Medicine
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