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Anemia of inflammatory disease induced by injection of adjuvant was characterized by decreases in hematocrit (mean +/- 1 SD, 37.5 +/- 2.7%, as compared with base-line values of 49.8 +/- 2.4%) and hemoglobin (12.54 +/- 1.22 g/dl, as compared with base line of 16.87 +/- 0.96 g/dl) and was classified as unresponsive, normocytic, and normochromic. Disordered iron metabolism was manifest by decreases in serum iron (62.3 +/- 13.6 g/dl, as compared with base line or 113.0 +/- 8.2 g/dl) and shortened mean radioiron clearance half-times (50.0 +/- 12.6 minutes, as compared with base line of 74.0 +/- 13.6 minutes) in the presence of increased bone marrow reticuloendothelial iron. Shortened radioiron clearance half-times reflected maximal extraction of iron from the plasma by the erythroid marrow due to suboptimal iron supply, since extraction of iron by other tissues is minor. Shortened mean marrow transit times (2.79 +/- 0.46 days, as compared with base line of 5.4 +/- 0.64 days) were indicative of adequate erythropoietin stimulation in the anemia of inflammatory disease. Increases in plasma iron turnover rate over base line (1.73 +/- 0.33 mg/dl/day to 1.51 +/- 0.34 mg/dl/day), erythron iron turnover rate (1.50 +/- 0.27 mg/dl/day, as compared with base line of 0.99 +/- 0.27 mg/dl/day), and RBC iron utilization (86 +/- 8.3%, as compared with base-line utilization of 65 +/- 9.3%) indicated erythroid marrow proliferation was effective. The magnitude of erythroid response appeared to be limited mainly by iron supply.

The iron-chelating agent deferoxamine (DF) was administered as a single dose and also daily over a prolonged period to evaluate availability of storage iron in dogs with induced anemia of inflammatory disease. In a 6-hour period, total urinary ferrioxamine (measured as urinary iron) excretion in controls was 251.22 +/- 119.68 microgram (mean +/- 1 SD), a 5.32 +/- 2.64-fold increase over prechelation values. In anemia of inflammatory disease-affected dogs, excretion was diminished to 115.67 +/- 34.86 microgram, a 2.87 +/- 1.10-fold increase, indicating a restricted iron excretion and sequestration of iron in a less soluble, less chelatable form. During prolonged DF administration, a pattern of increasing total urinary iron excretion was observed. This pattern is consistent with iron being stored as an insoluble polynuclear hydroxide in protein of ferritin and hemosiderin. The increase in hemoglobin and serum iron concentrations during prolonged DF administration indicates that increased iron stores are present, but in a less labile form. During the process of chelation, iron is converted to a more readily utilized state, and the increased availability of iron promotes hemoglobin synthesis. Thus, storage iron in the form of hemosiderin and ferritin is released to the metabolizable pool.

Copper and iron are involved in protection of the aerobic cell from highly toxic oxygen by-products, one of which is the superoxide anion-free radical. This protection is associated with a copper-zinc enzyme, superoxide dismutase. Increased hepatic superoxide dismutase activity correlated directly with hepatic nonheme iron, serum zinc, and serum copper concentrations and inversely with hepatic copper, hepatic zinc, and serum iron concentrations (P less than 0.001). Decrease in hepatic ceruloplasmin concentration was correlated with the decrease in hepatic copper concentration (P less than 0.001).

Canine factor VIII was isolated by a cryoprecipitation method and injected into dogs with hemophilia A. Assays of factor VIII in the cryoprecipitate resulted in a range of 92 to 660% of the factor VIII level of normal dog plasma, with a mean of 266%. Half times of the cryoprecipitate in the hemophiliac dogs, as measured by the partial thromboplastin time (PTT) test, ranged from 7.7 to 32.3 hours, with a mean of 13.2 hours.

Trypanosoma brucei EATRO 110 infection in deer mice (Peromyscus maniculatus) produced anemia in 15 of 42 mice between postinoculation days 14 and 70. The infected anemic (IA) mice had significantly higher reticulocyte counts (P less than 0.025), spleen (P less than 0.001) and liver (P less than 0.005) weights, and higher parasitemia than did infected nonanemic (INA) mice. gamma-Globulin concentrations of infected mice were markedly increased, and values for INA mice were 10% higher than values for IA mice. Erythrocyte hexokinase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione reductase, and pyruvate kinase activities were increased in infected mice, whereas phosphofructokinase was only slightly decreased in infected mice. Seemingly, development of anemia was not related to defects in erythrocyte metabolism. Serum iron values of infected mice were similar to those of controls. Storage iron (hemosiderin and ferritin) concentrations were increased in the spleen and to a lesser extent in the liver. The activity of superoxide dismutase, an enzyme that favors conversion of easily mobilized soluble ferritin to poorly mobilized insoluble hemosiderin, was decreased per unit weight of the enlarged spleen, although total activity was increased. The superoxide dismutase activity per unit weight of liver was not altered in infected mice although total liver activities were increased. These findings, as well as the marked reticulocytosis, indicate that lack of iron supply does not have a part in precipitating the anemia of T brucei infection. Leukocytosis was present in infected animals and was associated with lymphocytosis, eosinopenia, basophilia, and monocytosis; these changes were more marked in IA than in INA mice.

Glutathione reductase (GR) was studied in erythrocytes of horses, cats, dogs, and man. Glutathione reductase activity was measured in hemolysates with and without preincubation of hemolysates with flavinadenine dinucleotide. The percentage saturation of GR apoenzyme with cofactor (flavin-adenine dinucleotide) was lower in cats and dogs than in horses or man. The greatest amount of inactive apoenzyme was in feline erythrocytes. Total GR activity listed in order by species is cat greater than man greater than dog greater than horse. Kinetic constants for oxidized glutathione and reduced nicotinamide-adenine dinucleotide phosphate were determined in each species. Although kinetic constant (reduced nicotinamide-adenine dinucleotide phosphate) values for GR were similar, considerable species variation was observed in the kinetic constant (oxidized glutathione) for GR. The kinetic constant (oxidized glutathione) for equine GR was approximately 3 times that for human GR, with intermediate values determined for feline and canine GR.

A mild, stable diabetes mellitus was induced in dogs, using a small (20 mg/kg of body weight) dose of streptozotocin in a standard volume of 200 ml infused in 15 minutes. The stability of the diabetes was evidenced by the results of a standard intravenous glucose-tolerance test, insulin response to the glucose load, and urinary glucose excretion. The results of the urinary clearances for urea, creatinine, and phosphate indicated minimal renal toxicosis and that the toxicosis was localized to the tubules.

To determine the usefulness of information provided by measurement of serum amylase activity in the evaluation of dogs for pancreatitis, the relationship of amylase activity to lipase activity in 713 paired serum samples was investigated by statistical analysis. Little change in mean amylase concentration was found until lipase values exceeded 800 U/L. The ranges of amylase activity (mean +/- 2 SD) were essentially the same for dogs with no pancreatitis (0 to 100 U of lipase activity/L) as for dogs with a high probability for the disease (700 to 799 U of lipase activity/L), 0 to 4,029 U/L and 857 to 4,869 U/L, respectively. Pathologic findings from biopsy and necropsy reports from 92 dogs for which serum lipase determinations were done indicated that serum lipase increased not only with pancreatitis, but also with other medical problems, such as renal and hepatic disease. It was concluded that determination of serum amylase activity without knowledge of serum lipase activity was of little value to diagnose pancreatitis. High amylase activity was not specific for pancreatitis and low amylase activity could not rule out the disease. The results of this study also showed that low serum lipase values almost always eliminated the possibility of pancreatitis and that high values were often, but not always, diagnostic for pancreatitis.

Intravascular granulocyte kinetic values of normal developing calves were determined, using the chromium radioisotope 51Cr as the cell label. A total of 15 kinetic trials were conducted in the calves at 8 to 365 days of age. The clearance of labeled granylocytes from the circulation was an exponential function. The kinetic data from the oldest group of calves (7 experiments on 5 calves, 180 days of age and older) were remarkably similar to those reported for persons. Mean total blood granulocyte pool was 6.34 times 10-8 granulocytes/kg of body weight, of which 45.6% was in the circulating granulocyte pool. Mean clearance half-life (T1/2) was 8.9 hours, and mean granulocyte turnover rate was 12.44 times 10-8 granulocytes/kg of body weight/day. In the oldest calf group, there was significant correlation between the blood granulocyte count and the total blood granulocyte pool size. There was also significant correlation between the total blood granulocyte pool size and the clearance half-life. The youngest group of calves (4 experiments on 4 calves, 8 to 16 days of age) had significantly larger total blood granulocyte pool and shorter intravascular half-life than did the oldest group. These factors combined to yield a markedly greater granulocyte turnover rate of 39.91 times 10-8 granulocytes/kg of body weight/day in the youngest group of calves. Calves of an intermediate age group (70 to 127 days) had kinetic which were intermediate between those of the youngest and oldest groups of calves.

The IV glucose-tolerance test was performed in 71 diabetic dogs (fasting glycemia greater than 6.70 mmol/L) and in 20 healthy dogs. All diabetic dogs were characterized by various degrees of glucose intolerance as expressed by an abnormal glucose disappearance coefficient. On the basis of the fasting plasma insulin concentration (Io), insulin peak response (IPR), the insulinogenic index (delta I/delta G), and the total insulin secretion (TIS), the diabetic dogs were classified, as follows: Type I dogs (n = 32) which had the severe clinical signs of diabetes and an absence of certain diagnostic responses: Io, IPR, delta I/delta G, and TIS. Type II dogs (n = 15) which also had marked diabetic signs and an absence of IPR, delta I/delta G, and TIS responses. The dogs were further subdivided into obese and nonobese groups; the Io was within acceptable limits in the nonobese group (n = 8), but was markedly increased in the obese group (n = 7). Type III dogs (n = 24) had no diabetic signs and a fasting plasma glucose less than 12 mmol/L. They were also subdivided into obese and nonobese groups. The nonobese dogs (n = 13) had Io values within acceptable limits and decreased IPR, delta I/delta G, and TIS. In contrast, the obese dogs had increased Io, IPR, delta I/delta G, and TIS. Statistical analyses indicated that the TIS and IO were highly significant linear functions of obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-one healthy young non-anesthetized Dalmatian dogs (10 male, 11 female) were given IV glucose loads between 300 and 1,500 mg/kg of body weight in a standard time period of 30 s. The fractional glucose turnover rates and the insulin peak responses gradually increased with glucose loads to 1,000 mg/kg and the total insulin secretion with loads to 1,250 mg/kg and remained constant. The insulinogenic index (delta I/delta G) varied inversely with the size of the glucose loads. The pattern of responses indicates that the optimum glucose load is near 600 mg/kg for evaluating normal glucose metabolism in dogs by the IV glucose loading technique.

To characterize the erythroid homeostatic defect in canine inflammatory states, a single dose of Freund's complete adjuvant was injected subcutaneously to simulate naturally occurring infection and inflammation. After a latent period of 5 to 8 days, a generalized noninfectious inflammatory process was observed, followed by abscessation and drainage. This was accompanied by a modest anemia which decreased from base-line values by as much as 30%. In addition, a disordered iron metabolism was evidenced by depressed serum iron concentrations, total iron binding capacity (transferrin), percentage saturation of transferrin, and decreased numbers of bone marrow sideroblasts. Free RBC protoporphyrin concentrations were increased, as were serum copper, zinc, and ceruloplasmin. Bone marrow reticuloendothelial iron and hepatic nonheme iron were increased. Bone marrow myeloid-erythroid ratios were depressed. Throughout the course of the inflammatory period, the anemia remained normocytic and normochromic. A significant reticulocyte response was not observed.

Light microscopic and scanning and transmission electron microscopic studies demonstrated that Trypanosoma brucei EATRO 110 produced several alterations in RBC structure including microspherocytes, schistocytosis, vacuolation, doughnut-cell formation, and keratocytosis. Mature RBC and reticulocytes were constantly observed to adhere firmly to trypanosomes in heart blood and in blood vessels of the testes, heart, liver, and kidney, as well as in the sinuses and pulp cords of the spleen. Adhesion of RBC to trypanosomes was also observed by light microscopy in thin blood films. Except for a few platelets that adhered to trypanosomes, other blood cells were not involved. Minute pores were sometimes observed on the RBC membrane at the point of adhesion to the trypanosome, but effects were not seen on the parasite. Erythrophagocytosis was marked in the spleen and to a lesser extent in the liver; mature RBC, as well as reticulocytes, were engulfed. Erythrophagocytosis was presumed to arise from the mechanical injury to RBC, the damage caused by the adhesion phenomenon and the hyperactivity of the enormously enlarged spleen.

The influence of prednisolone on granulocyte kinetics in calves was evaluated under nonsteady state conditions, using chromium-51 as a cell label. The kinetic pattern observed was similar to that described for persons. Interpretation of results indicated that alteration from steady state to granulocytosis was the result of an increase in input from the storage pool and that shifts occurred in the distribution of cells between the marginating and circulating pools during the period of rapidly changing kinetic patterns. Granulocyte kinetic variables of a calf under induced physiologic stress demonstrated a kinetic pattern similar to that of the calves given prednisolone. There was a rapid enlargement of the total granulocyte pool size and a greater than twofold increase in clearance halftime compared with those in calves of a similar age group.