The scavenging of superoxide radicals by endogenous and therapeutically administered superoxide dismutases may prevent superoxide-mediated oxidative stress leading to lipid peroxidation, membrane lysis, and cell death in a wide variety of normal and pathologic states. Simple inorganic manganous salts such as MnCl2 also have superoxide dismutase-like activity and are extremely inexpensive, compared with enzymatic superoxide dismutase preparations. In this study, we explored the use of Mn salts as antioxidant drugs. We used the percentage of inhibition of nitroblue tetrazolium reduction by superoxide as a measure of the amount of superoxide dismutase-like activity. We found concentration-related increases in superoxide scavenging activity in simple buffer solutions upon addition of 1.25, 2.5, and 5.0 microM MnSO4. To determine whether Mn salts can inhibit oxidative damage in tissues, we used an in vitro model of lipid peroxidation in ischemic and reoxygenated rat liver slices. Concentrations of 10, 100, and 1000 micromoles MnCl2/L of buffer significantly decreased indicators of lipid peroxidation believed to be initiated by intracellular superoxide. We then determined the effectiveness of MnCl2 as a superoxide scavenger in conscious horses by measuring the superoxide scavenging ability of equine plasma before and during intravenous infusions of 1.0 L volumes of 0.9% saline solution containing 0, 12.5, or 25 mM MnCl2. Plasma Mn concentrations, which were determined by atomic absorption spectrophotometry, increased as a function of time and dose. Intravenously administered MnCl2 concomitantly produced dose-related increases in superoxide scavenging ability of equine plasma at 15, 30, 45, and 60 minutes after the onset of infusion, compared with preinfusion control values. Heart rate and blood pressure of the treated horses, which were monitored to measure toxicity of MnCl2, gradually increased in both treatment groups. Clinical adverse effects of MnCl2 administration included defecation, pawing, hyperexcitability, flank watching, and sweating. The results of this study indicate that simple Mn salts may scavenge superoxide radicals in vivo with minimal adverse reactions and at a trivial cost.

The effects of hypertonic saline solution (HTSS) combined with colloids on hemostatic analytes were studied in 15 dogs. The analytes evaluated included platelet counts, onestage prothrombin time, activated partial thromboplastin time, von Willebrand's factor antigen (vWF-Ag), and buccal mucosa bleeding times. The dogs were anesthetized, and jugular phlebotomy was used to induce hypovolemia (mean arterial blood pressure = 50 mm of Hg). Treatment dogs (n = 12) were resuscitated by infusion (6 ml/kg of body weight) of 1 of 3 solutions: HTSS combined with 6% dextran 70, 6% hetastarch, or 10% pentastarch. The control dogs (n = 3) were autotransfused. Hemostatic analytes were evaluated prior to induction of hypovolemia (baseline) and then after resuscitation (after 30 minutes of sustained hypovolemia) at 0.25, 0.5, 1, 6 and 24 hours. All treatment dogs responded rapidly and dramatically to resuscitation with hypertonic solutions. Clinically apparent hemostatic defects (epistaxis, petechiae, hematoma) were not observed in any dog. All coagulation variables evaluated, with the exception of vWF:Ag, remained within reference ranges over the 24-hour period. The vWF:Ag values were not statistically different than values from control dogs, and actual values were only slightly lower than reference ranges. Significant (P less than or equal to 0.04) differences were detected for one-stage prothrombin time, but did not exceed reference ranges. The results of this study suggested that small volume HTSS/colloid solutions do not cause significant alterations in hemostatic analytes and should be considered for initial treatment of hypovolemic or hemorrhagic shock.

The effects of 3 commonly used dosages (0.3, 0.5, and 1.1 mg/kg of body weight, IV) of xylazine on ventilatory function were evaluated in 6 Thoroughbred geldings. Altered respiratory patterns developed with all doses of xylazine, and horses had apneic periods lasting 7 to 70 seconds at the 1.1 mg/kg dosage. Respiratory rate, minute volume, and partial pressure of oxygen in arterial blood (PaO2) decreased significantly (P < 0.001) with time after administration of xylazine, but significant differences were not detected among dosages. After an initial insignificant decrease at 1 minute after injection, tidal volume progressively increased and at 5 minutes after injection, tidal volume was significantly (P < 0.01) greater than values obtained before injection. Partial pressure of carbon dioxide in arterial blood (PaCO2) was insignificantly increased. After administration of xylazine at a dosage of 1.1 mg/kg, the mean maximal decrease in PaO2 was 28.2 +/- 8.7 mm of Hg and 22.2 +/- 4.9 mm of Hg, measured with and without a respiratory mask, respectively. Similarly, the mean maximal increase in PaCO2 was 4.5 +/- 2.3 mm of Hg and 4.2 +/- 2.4 mm of Hg, measured with and without the respiratory mask, respectively. Significant interaction between use of mask and time was not detected, although the changes in PaO2 were slightly attenuated when horses were not masked. The temporal effects of xylazine on ventilatory function in horses should be considered in selecting a sedative when ventilation is inadequate or when pulmonary function testing is to be performed.

Beagles were exposed to aerosols of (239)PuO2, (238)PuO2, or (239)Pu(NO3)4. Exponential growth constants for 50 primary lung tumors (23 bronchioloalveolar carcinomas, 22 papillary adenocarcinomas, 5 adenosquamous carcinomas) were calculated in 37 dogs, using sequential thoracic radiography. A wide range in doubling time (6 to 287 days) was observed. Mean +/- SEM doubling time was 93 +/- 10 days for bronchioloalveolar carcinoma, 107 +/- 13 days for papillary adenocarcinoma, and 101 +/- 36 days for adenosquamous carcinoma. Lung tumor growth rate in dogs was comparable to that in human patients with similar histologic tumor types. Linear regression analysis revealed significant (P less than or equal to 0.0001) correlation between doubling time and survival of individual dogs. Doubling time was not significantly dependent on tumor type, sex, age at time of diagnosis, initial lung deposition, or isotope. Extrapolating time to tumor onset from tumor doubling time cannot be used to reliably predict the onset of malignancy.

Three available differential stains, Camco-Quik, Diff-Quik, and Wright-Giesma were compared for detection of intraerythrocytic Anaplasma marginale in bovine blood smears. In samples where < 1% to more than 51% of the RBC were infected, statistical analysis of the data indicated no significant difference in the detection of A marginale with Camco-Quik or Diff-quik stains. However, a significantly lower percentage of infected RBC were detected when blood smears were stained with the Wright-Giemsa stain, compared with the other 2 methods.

Twelve nonlactating dairy cows, free of signs of liver disease and with normal serum activities of liver-derived enzymes and normal liver biopsy tissue, were examined over a 72-hour period for serum total bile acid concentrations. The cattle were fed hay twice daily, and blood samples were obtained every hour for 24 hours, every other hour for 24 hours, then every hour for 24 hours. After 3 weeks, the study was repeated on 6 of the cattle, thus providing data for eighteen 72-hour periods. Serum bile acid concentration varied greatly over the 72 hours, with the range being from one third to 3 times the median. There were variations by as much as 60 micromol/L from 1 hour to the next. After another 3 weeks, 8 of the cattle were deprived of hay for 48 hours and then fed hay morning and afternoon of the third (last) day of the study. There was no significant reduction in bile acid concentration after withholding the hay, but the variability was reduced (P = 0.02) during the last 20 hours of the haydeprivation period. In 3 ancillary studies, serum bile acid concentrations were examined over a 48-hour period in 2 cows in early lactation, 3 cows in midlactation, and two 6-month-old heifers. The cows were fed hay and grain twice daily, and the heifers were fed only hay twice daily. In comparison with values for the 12 nonlactating cows fed hay twice daily, mean serum bile acid concentration in the recently freshened cows was significantly (P < 0.002) higher (62.9 vs 22.0 micromol/L). The cows in midlactation had hourly fluctuations as great as 65 micromol/L. Values for the heifers varied less than values in older cattle.

Fructosamine, a glycated serum protein, was evaluated as an index of glycemic control in normal and diabetic cats. Fructosamine was determined manually by use of a modification of an automated method. The within-run precision was 2.4 to 3.2%, and the day-to-day precision was 2.7 to 3.1%. Fructosamine was found to be stable in serum samples stored for 1 week at 4 degrees C and for 2 weeks at -20 degrees C. The reference range for serum fructosamine concentration in 31 clinically normal colony cats was 2.19 to 3.47 mmol/L (mean, 2.83 +/- 0.32 mmol/L). In 27 samples from 16 cats with poorly controlled diabetes mellitus, the range for fructosamine concentration was 3.04 to 8.83 mmol/L (mean, 5.93 +/- 1.35 mmol/L). Fructosamine concentration was directly and highly correlated to blood glucose concentration. Fructosamine concentration also remained high in consort with increased blood glucose concentration in cats with poorly controlled diabetes mellitus over extended periods. It is concluded that measurement of serum fructosamine concentration can be a valuable adjunct to blood glucose monitoring to evaluate glycemic control in diabetic cats. The question of whether fructosamine can replace glucose for monitoring control of diabetes mellitus requires further study.

Ultrasonography of the ovaries of 10 bitches was performed daily, using a 7.5-Mhz transducer with a built-in stand-off pad, from the onset of proestrus until the onset of metestrus. Ovarian size, shape, location, echogenicity, follicular development, and apparent ovulation were monitored. Blood samples were collected twice daily for luteinizing hormone determination and daily for progesterone determination. Vaginal smears were made daily for cytologic evaluation. Ultrasonograms were evaluated independent of hormonal and cytologic data, and the day of ovulation was noted. Initially, the ovaries were uniform and had an echogenicity that was equal to or slightly greater than that of the renal cortex. Follicles appeared as focal hypoechoic to anechoic rounded structures. Ovaries were easier to identify as follicular development progressed. Ovarian size increased with time. Apparent ovulation was characterized by a decrease in number of follicles seen from 1 day to the next, but 1 or more follicles remained in at least 1 ovary of 7 of 10 bitches. The ovaries had an oval shape that became rounded after ovulation. At some time after ovulation, all bitches had cystic (anechoic) structures indistinguishable from follicles. These structures increased in echogenicity and decreased in size with time and may have been follicles that did not ovulate, corpora hemorrhagica, fluid-filled corpora lutea, or cyctic luteinized follicles. Time of ovulation determined by ultrasonography paralleled that predicted on the basis of hormonal data in 9 of 10 bitches and with cytologic findings in all bitches.

Pituitary cells, collected from five healthy dogs, were cultured and treated with various doses of ovine corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), oxytocin (OT), or angiotensin II (AII) to determine which of these hypothalamic peptides affected adrenocorticotropin (ACTH) secretion. Of the 4 peptides, only CRH significantly increased ACTH secretion from cultured canine anterior pituitary cells. The lowest dose of CRH tested, 0.01 nM, significantly stimulated ACTH release. Co-addition of AVP, OT, or AII with CRH did not increase ACTH secretion beyond that caused by addition of CRH alone. Similarly, neither co-addition of AVP with OT, AVP with AII, or OT with AII significantly stimulated ACTH secretion. These results support a role for CRH in the physiologic regulation of ACTH secretion from the canine anterior pituitary, but do not support regulatory roles for AVP, OT, or AII.

The B1 strain of Newcastle disease virus (NDV-B1), which is nonpathogenic for newly hatched chickens, killed embryos when it was used to inoculate chicken eggs at embryonation day 18. Treatment of NDV-B1 with an alkylating agent, ethylmethane sulfonate (EMS) markedly reduced the pathogenicity of the virus for 18-day-old chicken embryos. Eggs inoculated with the modified virus (NDV-B1-EMS) hatched, and the virus was isolated from lungs and spleen of 1-day-old chickens. The hatched chickens developed antibody to NDV and were protected against challenge exposure (at 4 weeks of age) with a highly virulent GB-Texas strain of NDV. Presence of maternal antibody to NDV in embryonating eggs did not influence the protective ability of NDV-B1-EMS, which also induced protective immunity when administered to 4-week-old chickens. The 50% protective dose of NDV-B1-EMS in maternal antibody-negative and -positive embryos was calculated to be 10.77 and 17.70 embryo 50% lethal doses, respectively. Results of the study indicated that NDV-B1-EMS may be used as an embryo vaccine to protect chickens against Newcastle disease.