Cytological comparison of fine-needle aspirates of liver and spleen of normal dogs and of dogs with cutaneous mast cell tumours and an ultrasonographically normal appearing liver and spleen.

Staging of dogs with cutaneous mast cell tumours (MCTs) is an important diagnostic step. Aspiration of the liver and the spleen is often part of routine staging. This study cytologically compared mast cell numbers in fine-needle aspirates of liver and spleen of clinically normal unaffected dogs with those of dogs with cutaneous MCT and an ultrasonographically normal appearing liver and spleen. The unaffected dogs (n = 32) were selected from humane society dogs, and the affected dogs (n = 51) were selected from hospital cases. There were no statistically significant differences in each of the parameters evaluated for the liver aspirates. For splenic aspirates, affected dogs showed significantly more mast cells per cluster (P = 0.04) and more isolated mast cells per slide (P = 0.03) compared with unaffected dogs. However, no clinically important difference existed between the unaffected and affected dogs; thus, routine aspiration of an ultrasonographically normal appearing liver and spleen of dogs with cutaneous MCT does not appear to be a clinically useful staging tool.

Effect of omega-3 fatty acids on canine atopic dermatitis.

Twenty-nine dogs were included in a double-blinded, placebo-controlled, randomised trial and were orally supplemented for 10 weeks with either flax oil (200 mg/kg/day), eicosapentaenoic acid (50 mg/kg/day) and docosahexaenoic acid (35 mg/kg/day) in a commercial preparation, or mineral oil as a placebo. For each dog, clinical scores were determined based on a scoring system developed prior to the trial. Total omega-6 and omega-3 intake and the ratio of omega-6:omega-3 (omega-6:3) were calculated before and after the trial. The dogs' clinical scores improved in those supplemented with flax oil and the commercial preparation, but not in the placebo group. No correlation was identified between total fatty acid intake or omega-6:3 ratio and clinical scores. Based on the results of this study, the total intake of fatty acids or the omega-6:3 ratio do not seem to be the main factors in determining the clinical response.

Cardiac troponin I in canine patients with lymphoma and osteosarcoma receiving doxorubicin: comparison with clinical heart disease in a retrospective analysis.

The cumulative cardiotoxicity that occurs as a result of doxorubicin chemotherapy is irreversible and can affect both quality and quantity of life for the cancer patient. Cardiac troponin I (cTnI) is a sensitive and specific marker of cardiomyocyte death. The purpose of this retrospective study was to evaluate serum concentrations of cTnI in dogs with lymphoma or osteosarcoma given doxorubicin chemotherapy, and with known cardiac outcome, based on a minimum assessment by physical examination and thoracic radiography. Serum samples were also available for cTnI measurement from seven healthy dogs given intracoronary doxorubicin. Serial serum samples obtained before, during and after doxorubicin chemotherapy showed increased cTnI concentrations in some clinical patients following chemotherapy (P = 0.0083 compared to baseline), but this did not correlate with clinical signs of cardiomyopathy. In dogs that subsequently developed cardiomyopathy however, serum cTnI concentrations were elevated before clinical signs became evident (confirmed with echocardiography).

Treatment of feline diabetes mellitus using an alpha-glucosidase inhibitor and a low-carbohydrate diet.

The purpose of this study was to determine the effect of an alpha-glucosidase inhibitor (acarbose), combined with a low-carbohydrate diet on the treatment of naturally occurring diabetes mellitus in cats. Eighteen client-owned cats with naturally occurring diabetes mellitus were entered into the study. Dual-energy X-ray absorptiometry (DEXA) was performed prior to and 4 months after feeding the diet to determine total body composition, including lean body mass (LBM) and percent body fat. Each cat was fed a commercially available low-carbohydrate canned feline diet and received 12.5mg/cat acarbose orally every 12h with meals. All cats received subcutaneous insulin therapy except one cat in the study group that received glipizide (5mg BID PO). Monthly serum glucose and fructosamine concentrations were obtained, and were used to adjust insulin doses based on individual cat's requirements. Patients were later classified as responders (insulin was discontinued, n=11) and non-responders (continued to require insulin or glipizide, n=7). Responders were initially obese (>28% body fat) and non-responders had significantly less body fat than responders (<28% body fat). Serum fructosamine and glucose concentrations decreased significantly in both responder and non-responder groups over the course of 4 months of therapy. Better results were observed in responder cats, for which exogenous insulin therapy was discontinued, glycemic parameters improved, and body fat decreased. In non-responders, median insulin requirements decreased and glycemic parameters improved significantly, despite continued insulin dependence. The use of a low-carbohydrate diet with acarbose was an effective means of decreasing exogenous insulin dependence and improving glycemic control in a series of client-owned cats with naturally occurring diabetes mellitus.

S-adenosylmethionine (SAMe) in a feline acetaminophen model of oxidative injury.

S-adenosylmethionine (SAMe) is reported to have hepatoprotective and antioxidant functions. Acetaminophen (paracetamol) was used to induce oxidative damage in cats, and to then determine the effect of SAMe treatment on erythrocyte morphology, PCV, liver histopathology, thiobarbituate reacting substances (TBARS), reduced glutathione (GSH), and oxidised glutathione (GSSG). Cats receiving acetaminophen had a significant increase in methemoglobin and Heinz body production. A significant effect for the interaction of time and treatment was found for Heinz body production and changes in PCV. No significant changes were found in blood or hepatic TBARS. Blood GSH increased significantly in all cats, while the blood GSH:GSSG ratio tended to increase the most in cats given acetaminophen only. The hepatic GSH:GSSG ratio tended to increase in cats given SAMe and decrease in cats given acetaminophen, but this effect was not significant. SAMe protected erythrocytes from oxidative damage by limiting Heinz body formation and erythrocyte destruction and maybe useful in treating acetaminophen toxicity.

A comparison of dobutamine infusion to exercise as a cardiac stress test in healthy horses.

This study was done to determine whether administration of dobutamine would produce echocardiographic and electrocardiographic alterations comparable to those induced by treadmill exercise in healthy horses. Fourteen horses received maximal treadmill exercise and, separately, intravenous dobutamine infusion up to a maximum rate of 50 microg/kg/min. Ten of the 14 horses were euthanized, and the myocardial tissues were examined grossly and histopathologically. No significant differences were found in the chronotropic effects of dobutamine and exercise (P = .905). Dobutamine induced greater interventricular septal thickening during systole (dobutamine = 4.78 cm, exercise = 4.03 cm; P = .004). and greater left ventricular diameters during diastole (dobutamine = 9.73 cm, exercise = 9.26 cm; P = .037), than did exercise treatment. Horses exhibited transient signs of sweating and restlessness during infusion of moderate to maximum doses of dobutamine. Ventricular ectopy seen in 11 of 14 horses was attributed to the arrhythmogenic properties of dobutamine, as well as to increased vagal tone present at low dobutamine doses. Myocardial lesions characteristic of catecholamine myotoxicity were present in 2 of the 10 horses examined. Although dobutamine induces chronotropic and inotropic changes similar to those induced by exercise, the use of high-dose dobutamine as a cardiac stressor in horses cannot be advocated because of potential development of arrhythmias or myotoxicity.

Metabolic alterations in dogs with osteosarcoma.

OBJECTIVE: To evaluate changes in resting energy expenditure (REE) as well as protein and carbohydrate metabolism in dogs with osteosarcoma (OSA). ANIMALS: 15 weight-stable dogs with OSA that did not have other concurrent metabolic or endocrine illness and twelve 1-year-old sexually intact female Beagles (control dogs). PROCEDURES: Indirect calorimetry was performed on all dogs to determine REE and respiratory quotient (RQ). Stable isotope tracers (15N-glycine, 4.5 mg/kg of body weight, IV; 6,6-deuterium-glucose, 4.5 mg/kg, IV as a bolus, followed by continuous-rate infusion at 1.5 mg/kg/h for 3 hours) were used to determine rate of protein synthesis and glucose flux in all dogs. Dual-energy x-ray absorptiometry (DEXA) scans were performed to determine total body composition. RESULTS: Accounting for metabolic body size, REE in dogs with OSA was significantly higher before and after surgery, compared with REE of healthy control dogs. The RQ values did not differ significantly between groups. Dogs with OSA also had decreased rates of protein synthesis, increased urinary nitrogen loss, and increased glucose flux during the postoperative period. CONCLUSIONS AND CLINICAL RELEVANCE: Alterations in energy expenditure, protein synthesis, urinary nitrogen loss, and carbohydrate flux were evident in dogs with OSA, similar to results documented in humans with neoplasia. Changes were documented in REE as well as protein and carbohydrate metabolism in dogs with OSA. These changes were evident even in dogs that did not have clinical signs of cachexia.

Accuracy of radiography, nuclear scintigraphy, and histopathology for determining the proximal extent of distal radius osteosarcoma in dogs.

OBJECTIVE: To compare the accuracy of radiography, nuclear scintigraphy, and histopathology for determining the proximal extent of distal radius osteosarcoma in dogs. STUDY DESIGN: Retrospective clinical study. SAMPLE POPULATION: Twenty client-owned dogs taken to Colorado State University with osteosarcoma of the distal radius. METHODS: Medical records of 20 dogs with confirmed osteosarcoma that underwent a limb-salvage procedure were reviewed. Measurements were performed directly from the lateral view of each radius, from both the scintigram and the radiograph, to determine the length of the radius and the distance from the proximal extent of the tumor to the distal radiographic or scintographic extent of the radius. The ratio of distal radial involvement to total radius length was calculated. A similar ratio was also determined using the macroslide, which included the entire portion of bone that was excised during the limb-salvage procedure. All 3 methods of measurement were compared. RESULTS: Nuclear scintigraphy significantly overestimated tumor length when compared with macroslide specimen measurements. Radiography also overestimated tumor length, but these results were not significantly different from macroslide specimen measurements. CONCLUSIONS: Both radiography and nuclear scintigraphy overestimate the extent of distal radius osteosarcoma in dogs when compared with histopathologic macroslides of the same lesions. Nuclear scintigraphy overestimated tumor extent to a larger degree than did radiography. CLINICAL RELEVANCE: Although radiography is a more accurate method of measurement of the extent of distal radius osteosarcoma, because nuclear scintigraphy overestimates tumor length to a greater degree, scintigraphy may provide a larger margin of safety for determining the site of proximal osteotomy during a limb-salvage procedure. However, caution should be taken when utilizing scintigraphy, because this method may overestimate length of radius involved to such an extent as to cause the surgeon to believe that a patient is not a suitable limb-salvage candidate.

Clinical outcome of dogs with grade-II mast cell tumors treated with surgery alone: 55 cases (1996-1999).

OBJECTIVE: To determine outcome for dogs with grade-II mast cell tumors treated with surgery alone. DESIGN: Retrospective study. ANIMALS: 55 dogs. PROCEDURES: Medical records were examined, and signalment; location and size of tumor; staging status; dates of local recurrence, metastasis, death, or last follow-up examination; status of surgical margins; previous surgery; postoperative complications; and cause of death were recorded. Follow-up information was obtained via reexamination or telephone conversations with owners or referring veterinarians. Univariate analysis was performed to identify prognostic factors. RESULTS: 60 tumors in 55 dogs were included. Median follow-up time was 540 days. Three (5%) mast cell tumors recurred locally; median time to local recurrence was 62 days. Six (11%) dogs developed another mast cell tumor at a different cutaneous location; median time to a different location was 240 days. Three (5%) dogs developed metastases; median time to metastasis was 158 days. Fourteen dogs died; 3 deaths were related to mast cell tumor, and 7 were unrelated. The relationship with mast cell tumor was not known for 4. Median survival times were 151, 841, and 827 days, respectively, for these 3 groups. Forty-six (84%) dogs were free of mast cell tumors during the study period. A reliable prognostic factor could not be identified. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that additional local treatment may not be required after complete excision of grade-II mast cell tumors and that most dogs do not require systemic treatment.

Putative uremic encephalopathy in horses: five cases (1978-1998).

OBJECTIVE: To determine historical, physical examination, clinicopathologic, and postmortem findings in horses with putative uremic encephalopathy. Design-Retrospective study. Animals-5 horses with renal failure and neurologic disease not attributable to abnormalities in any other organ system. PROCEDURE: Medical records from 1978 to 1998 were examined for horses with renal disease and neurologic signs not attributable to primary neurologic, hepatic, or other diseases. Signalment, history, physical examination findings, clinicopathologic data, renal ultrasonographic findings, and postmortem data were reviewed. RESULTS: Of 332 horses with renal disease, 5 met selection criteria. Historical findings, physical examination findings, clinicopathologic data, ultrasonographic data, and postmortem findings were consistent with chronic renal failure. Swollen astrocytes were detected in all 4 horses examined at necropsy. CONCLUSIONS AND CLINICAL RELEVANCE: A single criterion was not determined to be pathognomonic for uremic encephalopathy in horses. Uremic encephalopathy should be considered as a differential diagnosis in horses with evidence of chronic renal failure and encephalopathic neurologic sign not attributable to other causes. Astrocyte swelling, which was common to all 4 horses examined at necropsy, may serve as a microscopic indicator of uremic encephalopathy in horses.

Response of feline oral squamous cell carcinoma to palliative radiation therapy.

Seven cats with advanced oral squamous cell carcinoma were treated with palliative radiotherapy. Megavoltage radiation in 8 Gray (Gy) fractions was delivered on days 0, 7, and 21 for a total dose of 24 Gy. Treatment field included the mandible, oropharynx, retropharyngeal lymph nodes, and tonsils. Adjuvant treatment with chemotherapy was variable. Age ranged from 13 to 18 years old with a median age of 15 years. Three of the seven cats (43%) did not complete treatment. Six cats were euthanized due to tumor growth and/or radiation side effects with a median survival time of 60 days (range = 42 to 97 days, mean = 63 +/- 8.4 days). Radiotherapy complications or progression of disease occurred in 6 of 7 (85.7 %) cats and included adverse clinical signs, such as mucositis, serosanguinous oral discharge, pain, and dysphagia. These data suggest that coarse fractionation radiotherapy did not result in palliation in cats with inoperable oral squamous cell carcinoma.

Serum zinc, chromium, and iron concentrations in dogs with lymphoma and osteosarcoma.

We compared serum concentrations of zinc, chromium, and iron in dogs with cancer to those of normal dogs. Dogs with lymphoma (n = 50) and osteosarcoma (n = 52) were evaluated. Dogs with lymphoma had significantly lower (P = .0028) mean serum zinc concentrations (mean +/- SD; 1.0 +/- 0.3 mg/L) when compared to normal dogs (1.2 +/- 0.4 mg/L). Dogs with osteosarcoma also had lower mean serum zinc concentrations (1.1 +/- 0.4 mg/L), but this difference was not significant (P = .075). Serum chromium concentrations were significantly lower in dogs with lymphoma (2.6 +/- 2.6 microg/L, P = .0007) and osteosarcoma (2.4 +/- 3.1 microg/L, P = .0001) compared to normal dogs (4.7 +/- 2.8 microg/L). Serum iron concentrations and total iron-binding capacity were significantly lower in dogs with lymphoma (110.8 +/- 56.7 microg/dL, P < .0001, and 236.6 +/- 45.6 microg/dL, P < .0001, respectively) and osteosarcoma (99.6 +/- 49.3 microg/dL, P < .0001, and 245.0 +/- 43.8 microg/dL, P = .0011, respectively) when compared to normal dogs (175.1 +/- 56.7 microg/dL and 277.1 +/- 47.4 microg/dL). Mean ferritin concentration was significantly higher in dogs with lymphoma (1291.7 +/- 63.0 microg/L) than in normal dogs (805.8 +/- 291.1 microg/L, P < .0001) and dogs with osteosarcoma (826.5 +/- 309.2 microg/L, P < .0001). Further investigation is needed to explore the clinical significance of these mineral abnormalities in dogs with cancer.

Identification of matrix metalloproteinases in canine cutaneous mast cell tumors.

Presence of matrix metalloproteinases has been associated with tumor invasion and metastasis in human neoplasia. The presence of matrix metalloproteinase 2 and matrix metalloproteinase 9 was determined in canine mast cell tumor tissue and normal stromal tissue from 24 dogs with spontaneously occurring cutaneous mast cell tumors. Seventeen of the mast cell tumors were of histologic grade 2, and 7 were of histologic grade 3. Gelatin zymography and computer assisted densitometry image analysis were used to quantify matrix metalloproteinase concentration. Bands from canine tissues migrated in the same location as human proenzyme and active enzyme matrix metalloproteinase 2 and matrix metalloproteinase 9 standards. A semiquantitative value for each patient sample was obtained by comparing the optical assessment density of each unknown band to the optical density of the human standard. The presence of matrix metalloproteinase 2 and matrix metalloproteinase 9 in histologic grade 2 mast cell tumors and histologic grade 3 mast cell tumors was compared, as was presence of matrix metalloproteinases in tumor and stromal tissue. There was dramatically more proenzyme matrix metalloproteinase 9 activity in histologic grade 3 mast cell tumors when compared to grade 2 tumors (P = .03). There was also dramatically more active enzyme matrix metalloproteinase 2 and active enzyme matrix metalloproteinase 9 activity in tumor tissue compared to stromal tissue (P = .02, P < .0001). This study demonstrates that the proenzyme and active enzyme forms of matrix metalloproteinase 2 and matrix metalloproteinase 9 are present in canine mast cell tumors. This appears to be related to the degree of histologic malignancy, although histologic grade 1 tumors were not evaluated.

Effects of diet on pharmacokinetics of phenobarbital in healthy dogs.

OBJECTIVE: To determine effects of various diets on the pharmacokinetics of phenobarbital and the interactive effects of changes in body composition and metabolic rate. DESIGN: Prospective study. ANIMALS: 27 healthy sexually intact adult female Beagles. PROCEDURE: Pharmacokinetic studies of phenobarbital were performed before and 2 months after dogs were fed 1 of 3 diets (group 1, maintenance diet; group 2, protein-restricted diet; group 3, fat- and protein-restricted diet) and treated with phenobarbital (approx 3 mg/kg [1.4 mg/lb] of body weight, p.o., q 12 h). Pharmacokinetic studies involved administering phenobarbital (15 mg/kg [6.8 mg/lb], i.v.) and collecting blood samples at specific intervals for 240 hours. Effects of diet and time were determined by repeated-measures ANOVA. RESULTS: Volume of distribution, mean residence time, and half-life (t1/2) of phenobarbital significantly decreased, whereas clearance rate and elimination rate significantly increased with time in all groups. Dietary protein or fat restriction induced significantly greater changes: t1/2 (hours) was lower in groups 2 (mean +/- SD; 25.9 +/- 6.10 hours) and 3 (24.0 +/- 4.70) than in group 1 (32.9 +/- 5.20). Phenobarbital clearance rate (ml/kg/min) was significantly higher in group 3 (0.22 +/- 0.05 ml/kg/min) than in groups 1 (0.17 +/- 0.03) or 2 (0.18 +/- 0.03). Induction of serum alkaline phosphatase activity (U/L) was greater in groups 2 (192.4 +/- 47.5 U/L) and 3 (202.0 +/- 98.2) than in group 1 (125.0 +/- 47.5). CONCLUSIONS AND CLINICAL RELEVANCE: Clinically important differences between diet groups were observed regarding pharmacokinetics of phenobarbital, changes in CBC and serum biochemical variables, and body composition. Drug dosage must be reevaluated if a dog's diet, body weight, or body composition changes during treatment. Changes in blood variables that may indicate liver toxicosis caused by phenobarbital may be amplified by diet-drug interactions.

Serum alhpa 1-acid glycoprotein concentrations in healthy and tumor-bearing cats.

The purpose of this study was to evaluate alpha 1-acid glycoprotein (AGP) concentrations in tumor-bearing and healthy cats. The hypothesis of the present study was that AGP concentrations would be significantly increased in tumor-bearing cats. Serum from 51 healthy and 97 tumor-bearing, client-owned cats was harvested at the time of presentation and stored at -80 degrees C until assayed. Cats with measurable, histologically confirmed malignancies, and healthy cats of similar ages were included. Serum was assayed for AGP concentration by using a radial immunodiffusion method. AGP concentrations were significantly (P = .0051) higher in tumor-bearing (763 +/- 595 microg/mL; mean +/- SD) when compared to healthy cats (501 +/- 377 microg/mL; mean +/- SD). Of the tumor-bearing cats, 35 had carcinomas, 33 had sarcomas, and 26 had discrete, round cell tumors. AGP concentrations were 645 +/- 62 microg/mL, 660 +/- 540 microg/mL, and 967 +/- 860 microg/mL, respectively, and there were no significant differences among the groups.

Effect of fish oil, arginine, and doxorubicin chemotherapy on remission and survival time for dogs with lymphoma: a double-blind, randomized placebo-controlled study.

BACKGROUND: Polyunsaturated n-3 fatty acids have been shown to inhibit the growth and metastasis of tumors. This double-blind, randomized study was designed to evaluate the hypothesis that polyunsaturated n-3 fatty acids can improve metabolic parameters, decrease chemical indices of inflammation, enhance quality of life, and extend disease free interval and survival time for dogs treated for lymphoblastic lymphoma with doxorubicin chemotherapy. METHODS: Thirty-two dogs with lymphoma were randomized to receive one of two diets supplemented with menhaden fish oil and arginine (experimental diet) or an otherwise identical diet supplemented with soybean oil (control diet). Diets were fed before and after remission was attained with up to five dosages of doxorubicin. Parameters examined included blood concentrations of glucose, lactic acid, and insulin in response to glucose and diet tolerance tests; alpha-1 acid glycoprotein; tumor necrosis factor; interleukin-6; body weight; amino acid profiles; resting energy expenditure; disease free interval (DFI); survival time (ST); and clinical performance scores. RESULTS: Dogs fed the experimental diet had significantly (P < 0.05) higher mean serum levels of the n-3 fatty acids docosahexaenoic acid (C22:6) and eicosapentaenoic acid (C20:5) compared with controls. Higher serum levels of C22:6 and C20:5 were associated with lesser (P < 0.05) plasma lactic acid responses to intravenous glucose and diet tolerance testing. Increasing C22:6 levels were significantly (P < 0.05) associated with longer DFI and ST for dogs with Stage III lymphoma fed the experimental diet. CONCLUSIONS: Fatty acids of the n-3 series normalize elevated blood lactic acid in a dose-dependent manner, resulting in an increase in DFI and ST for dogs with lymphoma.

Dietary instead of pharmacological management to counter the adverse effects of physiological adaptations to space flight.

The development of pharmacological counter-measures to the adverse effects of physiological adaptation to microgravity has received relatively more attention than alternatives such as dietary management. The manipulation of dietary cation-anion balance, and its subsequent effects on acid-base metabolism, have been routinely used for some time in managing domestic animal health. More recently, dietary intake by humans of alkalinizing potassium salts has been demonstrated to exert profound beneficial effects on calcium balance, bone mineralization, predisposition to calcium oxalate nephrolithiasis, and overall nitrogen balance. Dietary sodium restriction has also been shown to improve calcium balance, bone mineralization, and the effectiveness of neurohumoral defenses against orthostatic hypotension. It is proposed that these simple alterations in the astronauts' diets may be easily implemented to lessen the adverse effects of physiological adaptations to space flight, and to enhance or even replace prescribed pharmacological counter-measures.

Platelet function in dogs treated for lymphoma and hemangiosarcoma and supplemented with dietary n-3 fatty acids.

A prospective randomized, double-blind clinical trial was performed to test the hypothesis that dogs with malignancies that are supplemented with n-3 fatty acids do not have clinical or laboratory evidence of coagulation disorders or altered platelet function when compared with unsupplemented dogs with similar malignancies. Thirteen dogs with hemangiosarcoma and 66 dogs with lymphoma were evaluated. Coagulation status of the dogs with lymphoma and hemangiosarcoma was evaluated with prothrombin time, partial thromboplastin time, platelet count, and in vitro platelet aggregometry using the whole-blood method. These tests were performed at 5 time points: before beginning the diet (week 0), at weeks 3, 15, and 21, and at 1 year or when progressive disease was evident. Alterations in platelet function in dogs receiving a diet supplemented with dietary n-3 fatty acids were not identified when compared to dogs fed a control diet. Dietary n-3 fatty acid supplementation using this dosage and ratio in dogs with lymphoma or hemangiosarcoma did not induce clinically significant hemorrhage in these animals. Therefore, supplementation with n-3 fatty acids did not result in clinical or laboratory evidence relating to uncontrolled hemorrhage in these dogs.

Effects of dietary cysteine on blood sulfur amino acid, glutathione, and malondialdehyde concentrations in cats.

OBJECTIVE: To determine effects of dietary cysteine on blood sulfur amino acids (SAA), reduced glutathione (GSH), oxidized glutathione (GSSG), and malondialdehyde (MDA) concentrations in cats. ANIMALS: 12 healthy adult cats. PROCEDURE: Cats were fed diets with a nominal (0.50 g/100 g dry matter [DM]), moderate (1.00 g/100 g DM), or high (1.50 g/100 g DM) cysteine content in a 3 X 3 Latin square design with blocks of 8 weeks' duration. Venous blood samples were collected after each diet had been fed for 4 and 8 weeks, and a CBC and serum biochemical analyses were performed; poikilocyte, reticulocyte, and Heinz body counts were determined; and MDA, GSH, GSSG, and SAA concentrations were measured. RESULTS: Blood cysteine and MDA concentrations were not significantly affected by dietary cysteine content. Blood methionine, homocysteine, and GSSG concentrations were significantly increased when cats consumed the high cysteine content diet but not when they consumed the moderate cysteine content diet, compared with concentrations obtained when cats consumed the nominal cysteine content diet. Blood GSH concentrations were significantly increased when cats consumed the moderate or high cysteine content diet. CONCLUSIONS: Increased dietary cysteine content promotes higher blood methionine, homocysteine, GSH, and GSSG concentrations in healthy cats. CLINICAL RELEVANCE: Supplemental dietary cysteine may be indicated to promote glutathione synthesis and ameliorate adverse effects of oxidative damage induced by disease or drugs.

Comparison of the effects of asparaginase administered subcutaneously versus intramuscularly for treatment of multicentric lymphoma in dogs receiving doxorubicin.

OBJECTIVE: To determine the effectiveness and safety of asparaginase administered s.c. versus i.m. for treatment of multicentric lymphoma in dogs receiving doxorubicin. DESIGN: Prospective study. ANIMALS: 49 dogs with multicentric lymphoma. PROCEDURE: Dogs were treated with doxorubicin every 3 weeks, for a total of 5 treatments, and were given 3 weekly treatments of asparaginase, s.c. or i.m. Using high-performance liquid chromatography, mean plasma asparagine, aspartic acid, glutamine, and glutamic acid concentrations were determined in dogs before and during treatment with asparaginase (10,000 U/m2 of body surface area, once a week for 3 weeks). Asparaginase was administered s.c. in 23 dogs and i.m. in 26 dogs. Variables evaluated included time to response to chemotherapy, remission and survival times, and clinical and serum biochemical indicators of toxicoses. RESULTS: Using the World Health Organization's staging system for lymphoma, 30 dogs were in clinical stage III and 19 were in clinical stage IV. One week after asparaginase treatment, plasma asparagine concentrations were low and plasma aspartic acid, glutamine, and glutamic acid concentrations were high. Differences in plasma amino acid concentrations were not found between s.c. and i.m. groups. For dogs in clinical stage IV, i.m. administration of asparaginase significantly decreased the number of days to complete remission, compared with s.c. administration (8 vs 17 days, respectively). For dogs in clinical stage III, i.m. administration favorably increased the duration of first remission (191 vs 103 days) and survival time (289 vs 209 days). Overall, dogs treated i.m. had a faster response to chemotherapy (9 vs 15 days), a longer remission (191 vs 109 days), and a longer survival time (286 vs 198 days), compared with all dogs treated s.c. Asparaginase toxicoses were not observed regardless of the route of administration. CLINICAL IMPLICATIONS: For dogs with multicentric lymphoma that are receiving doxorubicin, i.m. treatment with asparaginase is more effective than s.c. treatment.