Thyroid Hormone Concentrations in Dogs With Chronic Weight Loss, With Special Reference to Cancer Cachexia

Serum concentrations of thyroxine (T₄), 3,5,3'-triiodothyronine (T₃), free thyroxine (fT₄), and free 3,5,3'-triiodothyronine (fT₃) were compared between tumor-bearing dogs (with and without chronic weight loss) and non—tumor-bearing dogs (with and without chronic weight loss) (n = 83). Serum T₄, T₃, and fT₃ concentrations were lower ( P < .05) in dogs with weight loss, whether or not they were tumor-bearing, than in dogs without weight loss. Serum fT₄ concentrations did not vary among the groups. Serum albumin concentrations were lower ( P < .05) in cachectic dogs than in dogs not experiencing weight loss, regardless of their tumor-bearing status. Percentage of weight loss was found to be associated ( P < .05) with T₄, T₃, and fT₃ concentrations. It appears that the low thyroid hormone concentrations are related to either an abnormal nutritional state or to the severity of illness, rather than to a tumor-related phenomenon.     

Plasma Taurine Concentrations in Normal Dogs and in Dogs With Heart Disease

Plasma taurine concentrations were determined in 76 dogs with dilated cardiomyopathy (DCM), 28 dogs with acquired valvular disease (AVD), and 47 normal (control) dogs. The data were collected at 2 referral centers. The Animal Medical Center, New York, NY (AMC), and the University of California, Davis (UCD), and the studies were conducted independently. Different anticoagulants (sodium citrate at AMC and lithium heparin at UCD) were used to collect the plasma samples. Paired analysis of samples showed a significant difference in plasma taurine concentrations, depending on the anticoagulant used. Consequently, results from each clinic were analyzed separately. Plasma taurine concentrations were significantly higher in dogs with AVD (median, 133 nmol/mL; range, 25 to 229 nmol/mL) than in control dogs (median, 63 nmol/mL; range 44 to 224 nmol/mL) and dogs with DCM (median, 72 nmol/mL; range, 1 to 247 nmol/mL) at AMC (P= .001). The number of dogs with AVD at UCD was too small to draw meaningful conclusions. At UCD, the median plasma taurine concentration was 98 nmol/mL (range, 28–169 nmol/mL) in dogs with AVD, 75 nmol/mL (range, 0.1–184 nmol/mL) in dogs with DCM, and 88 nmol/mL (range 52–180 nmol/mL) in control dogs. There were no significant differences in plasma taurine concentrations between dogs with DCM and the control dogs at either hospital. Congestive heart failure and administration of cardiac medication had no significant effect on plasma taurine concentrations. Plasma taurine concentration was low (<25 nmol/mL) in 17% (13/76) of the dogs with DCM. Seven of the 13 dogs with low plasma taurine concentrations were Cocker Spaniels or Golden Retrievers. It was concluded that most dogs with DCM do not have low plasma taurine concentrations. However, certain breeds or individual dogs may have low plasma taurine concentrations in association with DCM. Whether this association is causal or not is unknown. The significance of the high plasma taurine concentrations in dogs with AVD is also unknown.     

酸性成纤维细胞生长因子与肿瘤细胞生长的相关性

将 p RSV- a FGF(含 a FGF基因的劳斯肉瘤病毒载体 )与 HL - 6 0细胞 (人急性早幼粒细胞白血病细胞系 )悬液直接转移至裸鼠背部肌肉 ,11d后出现了可视肿瘤。比较病理学观察结果显示 ,试验组肿瘤组织内血管再生明显增多 ,2例裸鼠肝脏出现转移性 HL- 6 0细胞 ,表明酸性成纤维细胞生长因子 (a FGF)具有促进肿瘤组织内血管形成的作用 ,从而促进了 HL - 6 0细胞生长与转移。提示应用 FGF抗体对抑制肿瘤的生长与转移可能有一定的作用     

Basal and Glucagon-Stimulated Plasma C-PeDtide Concentrations in Healthy Dogs, Dogs With Diabetes Millitus, and Dogs With Hyperadrenocorticism

Serum glucose and plasma C-peptide response to IV glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5,10,20,30, and (for healthy dogs) 60 minutes after IV administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after IV glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after IV glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased (P < .001) at all blood sarnplkg times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .001) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .011 in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline C-peptide concentrations also were significantly higher (P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concentrations greater than 2 SD (ie, >0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired β-cell function (ie, diabetes mellitusl, and dogs with increased β-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of β-cell loss in dogs with type-1 diabetes. J Vet Intern Med 1996;10:116–122. Copyright © 1996 by the American College of Veterinary Internal Medicine.     

碱性成纤维细胞生长因子对牛骨骼肌卫星细胞增殖的影响

为研究碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)对牛骨骼肌卫星细胞增殖的影响,试验对牛骨骼肌卫星细胞进行体外分离培养,在生长培养基和分化培养基中分别添加bFGF,观察细胞生长及分化情况,绘制细胞生长曲线,并进行EDU细胞增殖检测试验。结果显示,添加了bFGF培养基的细胞生长状态较对照组良好,细胞增殖速度快,细胞增殖率显著高于对照组(P<0.05),说明bFGF对牛骨骼肌卫星细胞在生长培养基和分化培养基中增殖都具有良好的促进作用。本研究建立了一种高效的牛骨骼肌卫星细胞培养方案,为骨骼肌卫星细胞的研究利用提供参考。     

Effect of Basic Fibroblast Growth Factor on the Proliferation of Bovine Skeletal Muscle Satellite Cells

To investigate the effect of basic fibroblast growth factor (bFGF) on the proliferation of bovine skeletal muscle satellite cells,bovine skeletal muscle satellite cells were isolated and cultured in the medium with bFGF,the growth and differentiation state of muscle satellite cells were observed,and the growth curve and EDU cell proliferation assay were conducted.The results showed that cell morphology of bovine skeletal muscle satellite cells cultured in medium containing bFGF was better and proliferation rate was significantly higher than that in control group (P<0.05).The results indicated that bFGF could promote proliferation of bovine skeletal muscle satellite cells efficiently in growth medium and differential medium.Our study established an efficient method to culture bovine skeletal muscle satellite cells,which could provide reference for studying and using of skeletal muscle satellite cells.     

成纤维细胞生长因子对动物的营养研究

成纤维细胞生长因子是广泛存在于机体组织细胞的一类生长因子。它对动物具有十分重要的营养作用。它可以促进动物生长、刺激骨骼肌细胞增殖、抑制胫软骨发育不良等作用，现已知ＦＧＦ家族至少有１８名成员。该家庭存在２类受体：高亲和力受体具有酷氨酸蛋白激酶活性；抵亲和力受体为肝素样受体，它们对机体内激素的分泌以及多种细胞的生长和分化有一定的影响。     

Plasma Histamine and Gastrin Concentrations in 17 Dogs With Mast Cell Tumors

Dogs with mast cell tumors (MCT) are often affected with paraneoplastic syndromes such as gastrointestinal ulceration. The mechanism of ulceration is believed to be related to hyperhistaminemia. To test this hypothesis, plasma histamine and gastrin concentrations were measured in 17 dogs with MCT. Plasma histamine concentrations in dogs with MCT were significantly higher than those in normal dogs. Conversely, plasma gastrin concentrations in dogs with MCT were significantly lower than gastrin concentrations in normal dogs. Additionally, plasma gastrin concentrations were inversely related to plasma histamine concentrations, which provided indirect evidence for the presence of hyperacidity secondary to hyperhistaminemia (r2 = 57.7). Plasma histamine and plasma gastrin concentrations were not related to clinical stage of disease, tumor histologic grade, or tumor size. Median survival time was 245 days, with a range of 90 to 1315 days. Because the degree of hyperhistaminemia could not be predicted in this study from the clinical stage, histologic grade, or tumor size, these data suggest that hyperhistaminemia may occur in any dog with MCT.     

Piroxicam Therapy in 34 Dogs With Transitional Cell Carcinoma of the Urinary Bladder

Thirty-four dogs with histopathologically confirmed, measurable, nonresectable transitional cell carcinoma of the urinary bladder were treated with piroxicam (0.3 mg/kg PO sid) and were evaluated for tumor response and drug toxicity. Dogs were evaluated at the Purdue University Veterinary Teaching Hospital by means of physical examination, thoracic and abdominal radiography, cystography, complete blood count, serum biochemistry profile, and urinalysis. In selected cases, prostaglandin E₂ (PGE₂) concentrations in plasma and in supernatants of stimulated monocytes, and natural killer cell activity were quantified, Dogs were evaluated before therapy and at 28 and 56 days after initiation of therapy. Dogs with stable disease or remission at 56 days remained on the study and were evaluated at 1 to 2 month intervals. Tumor responses were 2 complete remissions, 4 partial remissions, 18 stable diseases. and 10 progressive diseases. The median survival of all dogs was 181 days (range, 28 to 720+ days), with 2 dogs still alive. Piroxicam toxicity consisted of gastrointestinal irritation in 6 dogs and renal papillary necrosis (detected at necropsy) in 2 dogs. Monocyte production of PGE₂ appeared to decrease with therapy in dogs whose tumors were decreasing in size, and increased in dogs with tumor progression. A consistent pattern in natural killer cell activity was not observed. In vitro cytotoxicity assays against 4 canine tumor cell lines revealed no direct antitumor effects of piroxicam. In summary, antitumor activity, which was not likely the result of a direct cytotoxic effect, was observed in dogs with transitional cell carcinoma of the bladder treated with piroxicam.     

Estimation of Quantitative Enzymuria in Dogs With Gentamicin-Induced Nephrotoxicosis Using Urine Enzyme/Creatinine Ratios From Spot Urine Samples

The correlation between 24-hour urinary excretion of N -acetyl-β- d -glucosaminidase (NAG) and γ-glutamyl transferase (GGT) with urine NAG and GGT/creatinine ratios was assessed in dogs with gentamicin-induced nephrotoxicosis. Eighteen 6-month-oid male Beagles with normal renal function were randomly divided into 3 groups of 6. Each group was fed a different concentration of protein (high protein, 27.3%; medium protein, 13.7%; and low protein, 9.4%) for 21 days. After dietary conditioning, gentamicin was administered at a dose of 10 mg/kg IM tid for 8 days and each group was continued on its respective diet. Endogenous creatinine clearance and 24-hour urinary excretion of NAG and GGT were determined after dietary conditioning (day 0) and on days 2, 4, 6, and 8 of gentamicin administration. In addition, urine NAG and GGT/creatinine ratios (IU/L ± mg/dL) were determined from catheterized spot urine samples obtained between 7 and 10 am on the same days. The correlation between 24-hour urinary enzyme excretion and urine enzyme/creatinine ratio in the spot urine samples was evaluated by simple linear regression analysis. Spot sample urine enzyme/creatinine ratios were significantly correlated with 24-hour urinary enzyme excretion through day 4 for dogs on low dietary protein, through day 6 for those on medium protein, and through day 8 for those on high dietary protein. Mean ± SD baseline values for urine NAG/creatinine ratio and 24-hour urinary NAG excretion were 0.06 ± 0.04 and 0.19 ± 0.14 IU/kg/24 hr, respectively. Baseline values for urine GGT/creatinine ratio and 24-hour urinary GGT excretion were 0.39 ± 0.18 and 1.42 ± 0.82 IU/kg/24 hr, respectively.     

Effect of Gelatin Hydrogel Sheet Containing Basic Fibroblast Growth Factor on Proximal Sesamoid Bone Transverse Fracture Healing in the Horse

Our objective in this study was to examine the effect of gelatin hydrogel (GH) sheets containing basic fibroblast growth factor (bFGF) on healing of proximal sesamoid bone transverse fractures in the horse. Ten healthy adult Thoroughbreds were used. The lateral proximal sesamoid bone of the left forelimb and the medial proximal sesamoid bone of the right forelimb were osteotomized, while the horses were under general anesthesia, and subsequently repaired by lag screw fixation using a single 4.5-mm cortical screw. A GH sheet containing 100 μg of bFGF was then sutured to the synovial membrane adjacent to the osteotomized proximal sesamoid bone. In the control group, the fracture was fixed with a lag screw, and the articular capsule was sutured. Fracture healing was assessed by radiographic examination once a week for 16 weeks after the operation. Radiographic examination of bone healing revealed significantly lower demineralization of the fracture line in the GH sheet-treated group than in the control group. The rate of demineralization of the fracture line in the GH sheet-treated group was significantly lower than that in the control group at 2, 4, and 8 weeks after the operation. In this study, we demonstrated that the use of a GH sheet containing bFGF promotes healing of proximal sesamoid bone fracture in the horse. Therefore, it is believed that this treatment strategy would be useful for quick recovery from bone fracture in the horse.     

Serum and Urine Blastomyces Antigen Concentrations as Markers of Clinical Remission in Dogs Treated for Systemic Blastomycosis

Background

Serum and urine Blastomyces antigen concentrations can be used to diagnose blastomycosis in dogs.

Objectives

Blastomyces antigen concentrations correlate with clinical remission in dogs during antifungal treatment, and detect disease relapse after treatment discontinuation.

Animals

21 dogs with newly diagnosed blastomycosis monitored until clinical remission (Treatment Phase), and 27 dogs monitored over 1 year from the time of antifungal discontinuation or until clinical relapse (After Treatment Phase).

Methods

Prospective study. Dogs were monitored monthly during treatment and every 3 months after treatment discontinuation, with a complete history, physical exam, chest radiographs, and ocular exam. Urine and serum Blastomyces antigen concentrations were measured at each visit using a quantitative enzyme immunoassay.

Results

At enrollment in the Treatment Phase, Blastomyces antigen was positive in all 21 urine samples (100% sensitivity; 95% CI 85–100%), and in 18 of 20 serum samples (90% sensitivity; 95% CI 70–97%). At 2–4 months of treatment, urine antigen was more sensitive for clinically detectable disease (82%; CI 60–94%) than serum antigen (18%; CI 6–41%). The sensitivity of the urine test for clinical relapse was 71% (CI 36–92%), with close to 100% specificity (CI 84–100%) during after treatment surveillance in this population.

Conclusions

Urine Blastomyces antigen testing has high sensitivity for active disease at the time of diagnosis and during treatment, and moderate sensitivity but high specificity for clinical relapse. Urine testing should be useful at the time of diagnosis, when treatment discontinuation is being considered, and anytime there is poor clinical response or suspicion of relapse.     

纤维蛋白粘合剂在犬小肠端端吻合术中对吻合口Hyp、VEGF与bFGF含量的影响

为探讨纤维蛋白粘合剂(FG)在犬小肠端端吻合术中对吻合口处羟脯氨酸(Hyp)、血管内皮生长因子(VEGF)与碱性成纤维细胞生长因子(bFGF)含量的影响,将30只试验犬随机分为试验组和对照组两组,试验组采用简易缝合配合纤维蛋白粘合剂,对照组采用常规手术肠线缝合;分别于术后第3、5、7、14和28天每组随机选取3只测定吻合口处Hyp、VEGF与bFGF的含量。术后试验组Hyp含量在第5天显著高于对照组(P0.05),bFGF的含量在第3天、第5天、第7天显著高于对照组(P0.05),VEGF含量在第3天和第5天高于对照组(P0.01),在第14天和第28天显著低于对照组(P0.01)。结果表明,应用简易缝合配合纤维蛋白粘合剂吻合肠管,可促进吻合口处小肠组织内羟脯氨酸、血管内皮因子和碱性成纤维细胞生长因子的分泌,从而加速吻合口的愈合。     

Plasma Concentrations and Cardiovascular Influence of Lidocaine Infusions During Isoflurane Anesthesia in Healthy Dogs and Dogs With Subaortic Stenosis

Objective—To determine the plasma concentrations and cardiovascular changes that occur in healthy dogs and dogs with aortic stenosis that are given an infusion of lidocaine during isoflurane anesthesia. Study Design—Phase 1, controlled randomized cross-over trial; Phase 2, before and after trial Animals—Phase 1, 6 healthy dogs (4 female, 2 male) weighing 23.8 ± 7.4 kg; Phase 2, 7 dogs (4 female, 3 male) with moderate to severe subaortic stenosis (confirmed by Doppler echocardiography) weighing 31.1 ± 14.5 kg. Methods—After mask induction, intubation, and institution of positive pressure ventilation, instrumentation was performed to measure hemodynamic variables. After baseline, measurement at an end-tidal isoflurane concentration of 1.9% (phase 1) or 1.85% (phase 2), a loading dose infusion of lidocaine at 400 μg/kg/min was given. Phase 1: Maintenance doses of lidocaine were administered consecutively (40, 120, and 200 μg/kg/min) after the loading dose (given for 10, 10, and 5 minutes, respectively) in advance of each maintenance concentrations. Measurements were taken at the end of each loading dose and at 25 and 35 minutes during each maintenance level. The same animals on a different day were given dextrose 5% and acted as the control. Phase 2: Dogs were studied on a single occasion during an infusion of lidocaine at 120 μg/kg/ min given after the loading dose (10 minutes). Measurements occurred after the loading dose and at 25 and 35 minutes. A blood sample for lidocaine concentration was taken at 70 minutes. Data were compared using a one-way ANOVA for phase 1, and between phase 1 and 2. Statistical analysis for phase 2 was performed using a paired r-test with a Bonferroni correction. A P value ± .05 was considered significant. Results—Phase 1: Plasma lidocaine concentrations achieved with 40, 120, and 200 μg of lidocaine/kg/min were 2.70, 5.27, and 7.17 μg/mL, respectively. A significant increase in heart rate (HR) (all concentrations), central venous pressure (CVP), mean pulmonary areterial pressure (PAP), and a decrease in stroke index (SI) (200 μg/kg/min) were observed. An increase in systemic vascular resistance (SVR) and mean PAP, and a decrease in SI also followed the loading dose given before the 200 μg/kg/min infusion. No other significant differences from the control measurements, during dextrose 5% infusion alone, were detected. Phase 2: Plasma lidocaine concentrations achieved were 5.35, 4.23, 4.23, and 5.60 μg/mL at 10, 25, 35, and 70 minutes, respectively. They were not significantly different from concentrations found in our healthy dogs at the same infusions. A significant but small increase in CVP compared with baseline was noted after the loading dose. There were no significant differences from baseline shown in all other cardiovascular data. There were no statistically significant differences in any measurements taken during the lidocaine infusion between the dogs in phase 1 and phase 2. Dogs with aortic stenosis tended to have a lower cardiac index than healthy dogs at baseline (88 v 121 mL/kg/min) and during lidocaine infusion (81 v 111 mL/kg/min). A small, statistically significant difference in systolic PAP was present at baseline. Conclusions—There does not appear to be any detrimental cardiovascular effects related to an infusion of lidocaine at 120 μg/kg/min during isoflurane anesthesia in healthy dogs or dogs with aortic stenosis. The technique used in this study resulted in therapeutic plasma concentrations of lidocaine. Clinical Relevance—Methods shown in the study can be used in clinical cases to achieve therapeutic lidocaine levels without significant cardiovascular depression during isoflurane anesthesia.     

Salivary Cortisol Concentrations in Healthy Dogs and Dogs with Hypercortisolism

Background: Measurement of salivary cortisol is a useful diagnostic test for hypercortisolism (HC) in humans. Objectives: To determine whether measurement of salivary cortisol concentration is a practical alternative to plasma cortisol to diagnose HC, to validate the use of salivary cortisol, and to examine the effect of time of day and sampling location on salivary cortisol. Animals: Thirty healthy dogs and 6 dogs with HC. Methods: Prospective, observational clinical trial including healthy volunteer dogs and dogs newly diagnosed with HC. Salivary and plasma cortisol concentrations were measured with an immunoassay analyzer. Intra‐ and interassay variability, linearity, and correlation between salivary and plasma cortisol concentrations were determined. Results: The required 300 μL of saliva could not be obtained in 88/326 samples from healthy dogs and in 15/30 samples from dogs with HC. The intra‐assay variability for measurement of salivary cortisol was 5–17.7%, the interassay variability 8.5 and 17.3%, and the observed to expected ratio 89–125%. The correlation (r) between salivary and plasma cortisol was 0.98. The time of day and location of collection did not affect salivary cortisol concentrations. Dogs with HC had significantly higher salivary cortisol values than healthy dogs (10.2 ± 7.3 nmol/L versus 1.54 ± 0.97 nmol/L; P < .001). Conclusions and Clinical Importance: The ROCHE Elecsys immunoassay analyzer correctly measured salivary cortisol in dogs. However, a broad clinical application of the method seems limited, because of the large sample volume required.