Search

Background: Methylmercury (CH 3 Hg) toxicity causes irreversible inhibition of selenium (Se)-dependent enzymes, including those that are required to prevent and reverse oxidative damage in the brain. Fish consumption provides numerous essential nutrients required for optimal health, but is also associated with CH 3 Hg exposure risks, especially during fetal development. Therefore, it is necessary to assess the amounts of both elements in seafood to evaluate relative risks or benefits. Consumption of ocean fish containing Se in molar excess of CH 3 Hg will prevent interruption of selenoenzyme activities, thereby alleviating Hg-exposure risks. Because dietary Se is a pivotal determinant of CH 3 Hg's effects, the Selenium Health Benefit Value (HBV) criterion was developed to predict risks or benefits as a result of seafood consumption. A negative HBV indicates Hg is present in molar excess of Se and may impair Se availability while a positive HBV indicates consumption will improve the Se status of the consumer, thus negating risks of Hg toxicity., Objective: This study examined the Hg and Se contents of varieties of seafood to establish those with positive HBV's offering benefits and those having negative HBVs indicating potential consumption risks., Methods: The Hg and Se molar concentrations in samples of meat from pilot whale, mako shark, thresher shark, swordfish, bigeye tuna, and skipjack tuna were used to determine their HBV's in relation to body weight., Results: The HBVs of pilot whale, mako shark, and swordfish were typically negative and inversely related to body weight, indicating their consumption may impair Se availability. However, the HBV's of thresher shark, bigeye tuna, and skipjack tuna were uniformly positive regardless of body weights, indicating their consumption counteracts Hg-dependent risks of selenoenzyme impairment., Conclusions: The HBV criterion provides a reliable basis for differentiating seafoods whose intake should be limited during pregnancy from those that should be consumed to obtain health benefits., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Public health concerns have been raised over the risk of parasitic helminth (roundworm, tapeworm and fluke) infections from eating raw fish, an increasing US consumer trend. Hawai'i consumers eat seafood at nearly 3 times the US national average rate, with a long tradition and high level of raw fish consumption. The local fish species commonly eaten raw in Hawai'i include tuna (bigeye, yellowfin, albacore and skipjack), marlin (blue and striped) and deepwater snappers (long-tailedred, pink and blue green). Forty-eight Hawai'i-based physicians (gastroenterologists, internists, general and family practitioners) were surveyed to count known cases of parasitic worm infection linked to raw fish consumption and to explore physicians' perceptions of risk associated with the consumption of fresh, never frozen local fish with an emphasis on raw tuna and skipjack. No single known case of helminth infection due to consumption of raw tuna or skipjack, or other local fish species caught in Hawai'i was reported. The majority of the physicians surveyed reported that they eat raw yellowfin and bigeye tuna, also eat raw skipjack and do not think that these fish present a significant health risk of helminthic parasites. The survey results support the conclusion that the risk of parasitic helminth infection from the consumption of Hawai'i-caught tuna, skipjack, marlin and deepwater snappers is negligible.

Mercury distribution in the oceans is controlled by complex biogeochemical cycles, resulting in retention of trace amounts of this metal in plants and animals. Inter- and intra-specific variations in mercury levels of predatory pelagic fish have been previously linked to size, age, trophic position, physical and chemical environmental parameters, and location of capture; however, considerable variation remains unexplained. In this paper, we focus on differences in ecology, depth of occurrence, and total mercury levels in 9 species of commercially important pelagic fish (Thunnus obesus, T. albacares, Katsuwonus pelamis, Xiphias gladius, Lampris guttatus, Coryphaena hippurus, Taractichthys steindachneri, Tetrapturus audax, and Lepidocybium flavobrunneum) and in numerous representatives (fishes, squids, and crustaceans) of their lower trophic level prey sampled from the central North Pacific Ocean. Results indicate that total mercury levels of predatory pelagic fishes and their prey increase with median depth of occurrence in the water column and mimic concentrations of dissolved organic mercury in seawater. Stomach content analysis results from this study and others indicate a greater occurrence of higher-mercury containing deeper-water prey organisms in the diets of the deeper-ranging predators, X. gladius, T. obesus, and L. guttatus. While present in trace amounts, dissolved organic mercury increases with depth in the water column suggesting that the mesopelagic habitat is a major entry point for mercury into marine food webs. These data suggest that a major determinant of mercury levels in oceanic predators is their depth of forage.

Protective effects of selenium against mercury toxicity have been demonstrated in all animal models evaluated. As interactions between selenium and mercury and their molar ratios in seafood are essential factors in evaluating risks associated with dietary mercury exposure, considering mercury content alone is inadequate. In this study, the absolute and molar concentrations of mercury and selenium were determined in edible portions from 420 individual fish representing 15 species of pelagic fish collected from the central North Pacific Ocean near Hawaii. Selenium was in molar excess of mercury in almost all fish species evaluated. The rank order of mean Se/Hg molar ratios was striped marlin (17.6) > yellowfin tuna (14.1) > mahimahi (13.1) > skipjack tuna (12.8) > spearfish (11.4) > wahoo (10.8) > sickle pomfret (6.7) > albacore tuna (5.3) > bigeye tuna (5.2) > blue marlin (4.1) > escolar (2.4) > opah (2.3) > thresher shark (1.5) > swordfish (1.2) > mako shark (0.5). With a Se/Hg molar ratio of less than 1, mako shark was the only fish containing a net molar excess of mercury. A selenium health benefit value based on the absolute amounts and relative proportions of selenium and mercury in seafood is proposed as a more comprehensive seafood safety criterion.

A study of the physiologic and ecologic factors involved in a spontaneous seasonal gallstone cycle of deer mice (Peromyscus maniculatus gambelii) was conducted at the Tulelake National Wildlife Refuge (California, USA) from March 1991 to June 1992. The specific hypothesis examined was whether or not seasonal increases in dietary fiber intake provides the necessary conditions for a solubility defect, or supersaturation mechanism, resulting in precipitation of cholesterol gallstones. Results indicated that in addition to the seasonal gallstone prevalence cycle, these deer mice exhibit significant seasonal cycling in serum cholesterol, serum bile acids, fecal bile acids, and diet composition. These physiologic and dietary cycles were phase-advanced 3 mo over the gallstone prevalence cycle, indicating an approximate 3 mo time period for gallstone formation under field conditions. Further, seasonal dietary fiber (plant material and seeds) was positively correlated with both serum cholesterol and the fecal bile acids. This suggests that in wild deer mice, variations in dietary fiber may significantly affect the resorption of bile acids, thereby providing a potential physiologic and nutritional mechanism for spontaneous cholesterol gallstone formation.

The objectives of this study were to determine the time course of copper (Cu) absorption in the Bedlington Terrier (BT) dog after duodenal infusion of Cu and to determine the onset of Cu accumulation in BT puppies. At 80 minutes after infusion, Cu was present in the bile and liver at 26.1 and 2675 microg/g dry weight (dw), as compared with 598 and 224 microg/g dw, respectively, in the control. In the puppies, the mean liver Cu concentrations were 443 +/- 216 microng/g dw as compared with 54 +/- 34 microg/g dw in their controls. The BT puppies had large numbers of Cu granules in their hepatic lysosomes, with very few in the bile canaliculi. In contrast, the controls had few granules in their lysosomes and large numbers in their canaliculi. These results suggest that hepatic Cu accumulation occurs rapidly and in utero in the BT.

Biliary obstruction was produced by surgical ligation of the common bile duct to observe alterations in serum bile acid composition. The percent composition of serum bile acids was found to change with time. Taurocholic acid increased on day 3 and accounted for more than 90% of the total bile acids in all dogs, however it decreased after day 7. The percentage of taurochenodeoxycholic acid (TCDC) and taurodeoxycholic acid (TDC) decreased to 4.2-6.0% and 0.2-0.7% on day 3, respectively. However, the percentage of TCDC increased after day 7 in all dogs and reached greater than 20% on day 14 in 2 dogs, whereas the percent TDC after bile duct ligation remained low in all dogs. Glycolithocholic acid, which was not identified in normal dog sera, was detected on day 3 and remained throughout the study in all dogs. Bile acid composition of gallbladder bile sampled on day 35 was similar to the serum bile acid composition on the same day. This indicates that the bile acids refluxed into the circulation in these dogs. In the present study, total cholic acid to chenodeoxycholic acid (C:CDC) ratio increased to 15.5-22.3 at three days post bile duct ligation and after the day 14, the C:CDC ratio decreased to its pre-ligation value or below. In contrast, the glycine conjugated to taurine conjugated bile acids (G:T) ratio did not change. Therefore, at this time, the G:T ratio would not be usable as an indicator of liver disease in dogs while it may be possible to use the C:CDC ratio.

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 C and for 2 weeks at -20 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.

The relation of the glycated serum protein, fructosamine, to serum protein, albumin, and glucose concentrations was examined in healthy dogs, dogs with hypo- or hyperproteinemia, and diabetic dogs. Fructosamine was determined by use of an adaptation of an automated kit method. The reference range for fructosamine in a composite group of control dogs was found to be 1.7 to 3.38 mmol/L (mean +/- SD, 2.54 +/- 0.42 mmol/L). Fructosamine was not correlated to serum total protein, but was highly correlated to albumin in dogs with hypoalbuminemia. To normalize the data with respect to albumin, it is suggested that the lower limit of the reference range for albumin concentration (2.5 g/dl) be used for adjustment of fructosamine concentration and only in hypoalbuminemic dogs. In 6 hyperglycemic diabetic dogs, fructosamine concentration was well above the reference range. It is concluded that although fructosamine may be a potentially useful guide to assess the average blood glucose concentration over the preceding few days in dogs, further study is required to establish its value as a guide to glucose control in diabetic dogs.

Serum bile acids were fractionated by high-performance liquid chromatography (HPLC) in 13 control and 8 cases of liver disease in horses. The severity and type of liver injury was determined by histopathological examination of biopsy and/or necropsy specimens. The total serum bile acids (tSBA) were determined in these horses by an enzymatic method (SBA-EA) and by summation of the bile acids (SBA-LC) as fractionated by the HPLC. The SBA-LC were generally higher than the SBA-EA in both the controls and liver disease and they did not parallel each other. The primary bile acids, total cholates and total chenodeoxycholates accounted for most of the tSBA increases in liver disease. There was a shift in profile from taurocholate to free (unconjugated) cholate in direct relation to the severity of the liver injury. Among the secondary bile acids, total deoxycholates and total taurodeoxycholates increased at random. The pattern of the SBA profile in relation to the severity of the liver disease suggested that hepatocellular excretion is the most sensitive step in the enterohepatic circulation of the bile acids.

The fatty acid composition of the intramuscular lipids of cattle, pigs and birds were determined relative to breed and feeding regime. The cattle included Yellow Cattle, Hereford and Japanese Black; pigs included Wild-boar, Touyuens and Yorkshires; the birds were Wild-birds, Jungle-fowl and broilers. The pen fed animals such as Japanese Black cattle and Yorkshire pigs had a higher amounts of oleic acid, palmitic acid and palmitoleic acid. On the other hand, wild or pasture fed animals such as the Herefords, Wild-boars and Touyuens had higher amounts of omega-3 fatty acids such as alpha-linolenic acid, icosapentaenoic acid and omega-6 fatty acids such as linoleic acid and arachidonic acid. Among Wild-fowl, open-yard fed birds or broilers, there was no difference in fatty acid composition. It is suggested the meat of pasture fed or wild fed animals such as Herefords, Yellow Cattle and Wild-boar is better for health than meat from pen fed animals.

The fractionation of serum bile acids was performed in the dog, cow, horse, and human by high performance liquid chromatography equipped with an immobilized 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) column. There were significant differences in the bile acid compositions, conjugation patterns and quantities of each bile acid among these animals. Cholic acid was the major primary bile acid in the dog and cow, which constituted 62.9% and 83.5%, respectively, whereas chenodeoxycholic acid was the major acid in the horse and human, which constituted 68.4% and 46.3%, respectively. Taurine conjugates were predominant in the dog and horse, which constituted 94.4% and 85.3%, respectively, whereas glycine conjugates were predominant in the cow and human, which constituted 31.0% and 49.4%, respectively. Although there were several unidentified peaks, it was confirmed that they had a hydroxy group at the C-3 alpha position by chromatographing the samples without the 3 alpha-HSD column.

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.

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.

The hematocrits of 258 Holstein-Friesian and Jersey calves were determined during the first 3 days following birth. Hematocrit values of 25% or less were observed in 15.8% of the calves and hematocrits of 20% or less were observed in 6.9% of calves from apparently normal dams. The serum iron concentration of neonatal calves with hematocrits of 25% or less was significantly lower than the value recorded in calves with hematocrits above 25% and there was a direct correlation between PCV and serum iron concentration. The data presented suggested that prenatal development of iron deficiency is an important cause of anemia in neonatal dairy calves. Factors which may be important in pathogenesis are discussed.

The anemia of inflammatory disease(AID) in the dog is an almost invariable complication of infection, inflammation and disseminated or necrotizing neoplastic disease. Clinically innocuous, it is important only in the greater understanding of the mechanisms controlling circulating erythrocyte quantity and quality. The etiology and pathogenesis include a shortened red cell life-span, disordered iron metabolism, depressed bone marrow response to the anemia and a disordered iron storage. The laboratory features of a moderate anemia, normal bone marrow cellular pattern, depression iron metabolism and reticuloendothelial iron sequestration make a final diagnosis of AID dependent on ruling out other etiologic mechanisms which may obscure or aggravate the anemia of the inflammatory disease in the dog.

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).

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 prevalence of agglutinating serum antibodies against Coxiella burnetii, the cause of Q fever in humans, was tested in a hospital population of companion animals and livestock in California during 1973--1975. A sample of stray dogs was also tested. Among the hospitalized animals 346 (48%) of 724 dogs, 7 (9%) of 80 cats, 9 (32%) of 28 cattle and 31 (26%) of 121 horses had antibodies against C. burnetii. Of 316 stray dogs 208 (66%) were seropositive. The overall prevalence of 53% among 1040 dogs tested was comparable to the 63% antibody prevalence found in an earlier survey among coyotes and foxes in wildlife areas of California. When the dog was considered as a sentinel animal for the presence of C. burnetii surrounding household environments, it was hypothesized that the common, low level exposures in the community are similar to those found in more remote wildlife areas.

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.

Chronic renal failure associated with hypercalcemia and hypophosphatemia was diagnosed in 6 horses. The renal lesions in 5 of the horses were classified as chronic glomerulonephritis and in the sixth, as chronic interstitial nephritis/pyelonephritis. There was no evidence of primary hyperparathyroidism or pseudohyperparathyroidism, thus suggesting that hypercalcemia associated with advanced renal failure in horses is related to a unique role of the equine kidney in calcium homeostasis.

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)

Alloxan-induced diabetes and platelet aggregation were studied in male Sprague-Dawley rats. Platelets from diabetic rats receiving insulin (one unit protamine-zinc insulin/100 g BW) were consistently more responsive to aggregating agents (ADP, thrombin) than platelets from control rats (with or without insulin administration). Also, serotonin release from platelets was consistently greater in diabetic compared to control rats following thrombin-stimulated platelet aggregation.

Total serum bile acid assay for the evaluation of liver function has been available for many years but its application has been limited primarily by factors such as methodology, equipment and cost. New and improved methods for bile acid assay such as the radioimmunoassay or the hydroxysteroid dehydrogenase techniques have brought the assay for bile acids into the realm of the clinical laboratory. The efficacy of bile acids for clinical diagnostic use in the evaluation of liver function has not been firmly established. Newer methods using high pressure liquid chromatography to develop a profile of the different bile acids may clarify its usefulness and define its role among the many available tests of liver function in animals.

Digoxin was administered orally and intravenously to seven healthy adult mares and geldings in two separate trials. At a dose of 44 microgram digoxin/kg body weight, the oral study was characterized by an absorption phase with a mean (+/- 1 standard deviation) peak serum digoxin concentration of 2.21 ng/ml (+/- 0.45) at a mean of 2.29 h (+/- 1.52) after administration. A second rise in serum digoxin concentration started about 6-8 h after administration and extended to about 20 h after administration. The mean bioavailability (F) was 23.38% (+/- 5.96). At a dose of 22 microgram digoxin/kg body weight, the intravenous study was characterized by a two-compartment model with the following mean pharmacokinetic measurements: distribution rate constant (alpha), 1.391 h-1 (+/- 0.1909); zero-time serum digoxin concentration determined from the distribution phase (A), 21.247 ng/ml (+/- 5.6614); elimination rate constant (beta), 0.0409 h-1 (+/- 0.0069); zero-time serum digoxin concentration determined from the elimination phase (B), 3.82 ng/ml (+/- 0.433); apparent specific volume of distribution uncorrected for protein binding (Vd beta), 5.003 l/kg (+/- 0.5177). The mean beta corresponded to a biological half-life (T1/2 beta) of 16.9 h. Based upon results of this study, theoretically achievable steady-state serum digoxin concentrations were calculated for maintenance doses given by oral and intravenous routes of administration with appropriate two-compartment, multiple-dose formulae. Loading doses were also calculated for each route. It is the opinion of the authors that the oral route of administration of digoxin is effective in the horse and may preclude the potential risks posed by the high serum digoxin concentrations immediately following intravenous administration.

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.

Under physiological conditions, erythrocytes of the horse metabolized 638 +/- 37 (+/-SE) nmoles glucose/ml cells/hr at 37 degrees C compared to 942 +/- 31 for the cat, 1,329 +/- 44 for the dog, and 1,485 +/- 43 for man. On an absolute basis, pentose phosphate metabolism was similar between species, with species differences in erythrocyte glucose tulization attributable to differences in Embden-Meyerhof pathway metabolism. By examining pentose phosphate pathway recycling, it appears that some functional compartmentation exists within erythrocytes.

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.

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.

Thirteen dogs with hepatic encephalopathy were found to have hyperammonemia and increased retention of plasma sulfobromophthalein. Six dogs had abnormal portal circulatory systems and 4 had heptic disease. The cause of illness was undetermined in 3.

A standard intravenous glucose tolerance test (IVGTT) and the insulin response to the glucose loads were studied in 14 cases of diabetes mellitus in dogs. In addition, urinary glucose excretion, and clearances of urea, creatinine and phosphate were also determined in these dogs. All diabetic dogs were characterized by glucose intolerance as expressed by an abnormal half-time (T 1/2) or fractional clearance rate (k-value) and were further classified as Types I, II or III diabetes on the basis of their insulin responses. Renal functional impairment was observed in about 60 percent of the cases and was generally mild. There appeared to be no apparent relationship between advanced chronic renal disease and severity of diabetes in dogs.

A macrocytic hypochromic anemia with marked reticulocytosis was observed at each of 10 examinations during a 4 month period of a male Beagle dog that was 11 months old when first examined. The owner had noticed pale mucous membranes from the time the dog was purchased at 7 weeks of age. Based on the clinical history and negative LE, ANA and Coombs tests, an intrinsic erythrocyte defect was suspected. Erythrocyte osmotic fragility and hemoglobin electrophoresis were normal. Autohemolysis of incubated erythrocytes was marked. Hemolysis was uncorrected by glucose but partially corrected by ATP. With the exception of pyruvate kinase (PK), all of the erythrocyte enzymes measured had greater activities than those of control Beagle erythrocytes. In comparison to moderately reticulocyte-rich controls. PK activity was low in the affected Beagle. Erythrocyte phosphoenolpyruvate content was increased significantly as expected in PK deficiency. The kinetic constant (Km) for phosphoenolpyruvate was lower than that of normal control dogs, a finding in agreement with studies of PK from deficient Basenjis. On these bases a diagnosis of PK deficiency was made.

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.

Inherited or acquired hematologic disease is the most prevalent of all human disease when we include the hematologic disorders which are secondary to disease of other systems. It follows that the study of the fundamental mechanisms of the disease processes affecting the hematopoietic system is of prime importance and much remains to be done when one considers that in only 25% of ail hemolytic anemias is the fundamental cause eventually discovered [150]. In the current climate of societal pressures on experimental animal research, animals with spontaneous inherited disease mimicking diseases of the various physiological systems assume proportionately greater importance. These animal models have been extremely valuable in the study of fundamental questions of molecular genetics, metabolic aberrations of the cell and its membrane, synthetic mechanisms of the cell as well as clinical questions of disease manifestations, pathogenetic mechanisms and management. Exploration of differences between normal animal species offer a secondary avenue of investigation into these same fundamental questions. New animal models are being uncovered constantly and this augurs well for the future of biomedical research and the ultimate benefit to humankind and to animals in their own right.

The results of light and electron microscopic studies demonstrated that Trypanosoma brucei infection produced marked testicular degeneration in deer mice (Peromyscus maniculatus) with highly significant (p less than 0.001) decreases in testicular weight, seminiferous tubular diameter, and epithelial thickness. Lesions in seminiferous tubules consisted of necrosis of spermatids, spermatocytes, and sometimes the spermatogonia. Sertoli's cells had marked vacuolation and accumulation of phagocytic material. Orchitis was present in most infected mice, particularly those with severe seminiferous tubular degeneration. There was marked folding of the basal laminae of the seminiferous tubule and myoid layer, and a consistent increase in the layers of the basal laminae of the seminiferous tubule. Trypanosomes were present in the intertubular tissues of seminiferous tubules, and they occasionally crossed the myoid layer but never the basal lamina of seminiferous tubules. Inflammatory and other cells in the interstitium consisted of lymphocytes (35.2%), Leydig's cells (25.1%), macrophages (18.1%), plasma cells (12.3%), neutrophils (5.6%), eosinophils (3.2%), and mast cells (0.5%). Inflammatory cells including lymphocytes (51.6%), macrophages (43.9%), plasma cells (3.0%), and eosinophils (1.5%) occasionally breached the myoid layer and occupied the space between it and the basal lamina of the seminiferous tubule. Leydig's cells usually existed in clusters, had decreased mitochondrial size and secretory granules, and folding of the nuclear membrane.

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.