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Effects of gamma radiation and azathioprine on Brucella abortus infection in BALB/c mice
1991
Elzer, P.H. | Rowe, G.E. | Enright, F.M. | Winter, A.J.
Sublethal irradiation of BALB/c mice 4 hours prior to inoculation with 5 X 10(4) virulent Brucella abortus, caused significant (P < 0.01) reductions in bacterial numbers in comparison with numbers in unirradiated controls. Numbers of brucellae in the spleen were significantly lower by 5 days after inoculation and decreased thereafter, so that at 2 and 3 weeks after inoculation, there were up to 1,000-fold fewer organisms in the spleen of irradiated mice. The number of brucellae in the spleen increased in irradiated mice thereafter. The course of events in the liver was similar, but developed more slowly, and peak differences in bacterial numbers were about 1 log less. These phenomena were not attributable to differences in implantation of brucellae in the liver or spleen, nor to an abnormal distribution of organisms in other organs of irradiated mice. Irradiation of mice during the plateau phase of infection also resulted in significant (P < 0.05) reductions in bacterial counts in the spleen during the succeeding 4 weeks. Macrophage activation in the spleen, measured by a Listeria monocytogenes-killing assay, was significantly (P < 0.01) increased by irradiation alone at 1 week after inoculation and at that time was significantly (P < 0.01) greater in B abortus-infected, irradiated mice than in B abortus-infected controls. Histologic, cytologic, and immunologic studies revealed that the decrease in numbers of organisms between 1 and 2 weeks after inoculation in irradiated mice occurred at a time when their immune response to B abortus was suppressed and when numbers of neutrophils and monocytes infiltrating the spleen were significantly (P < 0.01) diminished. The increase in numbers of B abortus in organs of irradiated mice that began after the third week coincided with recovery of the immune response and an increase in numbers of neutrophils and monocytes in the infected organs. The course of B abortus infection was not substantially altered during the first 11 days after inoculation in mice infected at the height of a profound monocytopenia and neutropenia induced by azathioprine, a drug that by itself failed to activate macrophages. We hypothesized that, in irradiated mice, a rapid radiation-induced activation of resident macrophages to a brucellacidal state was coupled with an absence of newly formed monocytes in which virulent strains of B abortus could establish persistent infection, and that as susceptible monocytes emerged in mice recovering from the effects of irradiation, chronic infection became established.
Show more [+] Less [-]Evaluation of edetate and thiamine for treatment of experimentally induced environmental lead poisoning in cattle
1991
Coppock, R.W. | Wagner, W.C. | Reynolds, J.D. | Vogel, R.S. | Gelberg, H.B. | Florence, L.Z. | Wolff, W.A.
Twenty mature Holstein cows were randomized into 5 treatment groups. Cows of groups 2 to 5 were given 2 mg of elemental Pb/kg of body weight for 28 days. Clinical signs of plumbism were scored, and blood for Pb, progesterone, and hematologic analyses was collected weekly. Cows also were examined weekly for anomalous ovarian cycles. Starting on study day 28, cows in group 3 were treated once daily with 2 mg of thiamine HCl/kg (IM) for 13 days, cows in group 4 were treated twice daily with 62 mg of Na2,Ca-EDTA/kg (IV) for 4 days, and cows in group 5 were given thiamine (dosage regimen the same as for group 3) plus Na2,Ca-EDTA (dosage regimen the same as for group 4). On study days 96 through 139, cows were slaughtered in a commercial abattoir and samples of blood, skeletal muscles, bones, liver, and kidneys were collected and assayed for Pb concentration. Thiamine was not effective in reducing blood Pb concentration, and treatment with Na2,Ca-EDTA and thiamine plus Na2,Ca-EDTA was effective in reducing the concentration of Pb in blood. However, treatment with thiamine was more effective than treatment with Na2,Ca-EDTA or thiamine plus Na2,Ca-EDTA in inducing remission of clinical signs of plumbism. The concentration of Pb in blood was significantly (P < 0.05) correlated to the concentration of Pb in liver, kidneys, skeletal muscles, and bones. Significant (P < 0.05) relationship existed between number of days from Pb exposure to slaughter and concentration of Pb in blood, liver, and skeletal muscles. Exposure to Pb did not significantly alter CBC values. On the basis of progesterone analysis and ovarian examination, exposure to Pb and treatment for plumbism did not induce changes in the ovarian cycle.
Show more [+] Less [-]Effect of colostrum ingestion on gamma-glutamyltransferase and alkaline phosphatase activities in neonatal pups
1991
Center, S.A. | Randolph, J.F. | ManWarren, T. | Slater, M.
Analysis of hepatic enzyme activities in serum samples from 1- to 3-day-old pups revealed alkaline phosphatase (ALP) activities that were 30 times higher and gamma-glutamyltransferase (GGT) activities that were 100 times higher than activities in clinically normal adult dogs. A study was conducted to investigate high enzyme activity in pups and to determine whether there is any association between serum enzyme activity and colostrum ingestion, passive transfer of maternal serum enzyme (in colostrum or in utero), or excessive renal or hepatic tissue enzymes. Serum enzyme activity was quantified in 15 neonatal pups before and after ingestion of colostrum and in 3 colostrum-deprived neonates fed a milk substitute. Serum samples were collected on postpartum days 0, 1, 10, 15, and 30. Enzyme activity was also quantified in serum from pregnant and lactating bitches (collected on days - 2, 0, 1, 10, 30), hepatic and renal tissue from clinically normal adult dogs and 1-day-old pups, colostrum, milk (collected on days 10 and 30), and milk replacer. Significant (P < 0.01) differences in serum GGT and ALP activities between colostrum-deprived and suckling pups did not exist before initial feeding. Significant (P < 0.001) increases in serum GGT and ALP activities developed within 24 hours in suckling pups, but not in the colostrum-deprived pups. At 10 and 30 days after birth, serum GGT and ALP activities were less than values before suckling in all pups. Enzyme activities in bitches' serum remained within the normal range for adult dogs throughout whelping and lactation. Renal GGT and ALP activities were substantially greater than hepatic enzyme activities in neonates and adults. Renal tissue from adults contained 3 times greater GGT and 2 times greater ALP activities than that from neonates. Hepatic tissue from neonates contained 5 times more GGT activity than did hepatic tissues from clinically normal adults; however, hepatic ALP activity was similar in adults and neonates. Colostrum and milk bad substantially higher enzyme activities than did bitches' serum. Activities of GGT and ALP in milk were 100 times and 10 times greater, respectively, than activities in serum through day 10. By day 30, GGT and ALP activities in milk were less than before suckling. Enzyme activity was not detected in the milk substitute. These studies reveal an association between colostrum ingestion by suckling and acute, profound increases in serum GGT and ALP in 1- to 3-day-old pups. Although this phenomenon might be useful as an indicator of colostrum ingestion, it precludes the diagnostic use of either enzyme as an indicator of hepatobiliary disease in 3-day-old pups.
Show more [+] Less [-]Effect of left hepatic vein ligation on hepatic circulation, function, and microanatomy in dogs
1991
Payne, J.T. | Martin, R.A. | Moon, M.L. | Saunders, G.K. | Donaldson, L. | Richey, M. | Clutton, R.E. | Shires, P.K.
Eighteen healthy dogs were allotted to 3 groups (n = 6 dogs each). All dogs were evaluated at the beginning of the study by complete physical examination; total and differential WBC counts; serum biochemical analysis (alanine transaminase and alkaline phosphatase activities and bilirubin and albumin concentrations); sulfobromophthalein excretion, ammonia tolerance, and glucagon response testing; portal and intraparenchymal pressure determinations; operative mesenteric portography; and histologic assessment of hepatic biopsy specimens. The left hepatic vein was ligated completely in dogs of groups 1 and 2. Group-3 (control) dogs had a ligature placed loosely around the left hepatic vein. Dogs of groups 1 and 3 were reevaluated 24 hours after surgery by use of the aforementioned hematologic and biochemical tests. Group-1 dogs were reevaluated by use of portal and intraparenchymal pressure determinations, jejunal vein portography, and complete necropsy at 48 hours after surgery. At 4 weeks after surgery, dogs of groups 2 and 3 were reevaluated by use of all aforementioned tests. Results indicated transient hepatic congestion, which resolved by the fourth postoperative week. Longstanding effect on hepatic structure, circulation, or function was not found. We concluded that left hepatic vein ligation in clinically normal dogs does not cause severe or permanent liver damage.
Show more [+] Less [-]Comparison of antibody response by use of synthetic adjuvant system and Freund complete adjuvant in rabbits
1991
Mallon, F.M. | Graichen, M.E. | Conway, B.R. | Landi, M.S. | Hughes, H.C.
Two commercially available synthetic adjuvant systems, trehalose dimycolate (TDM) and TDM + monophosphoryl lipid A (MPL), were compared with Freund complete adjuvant (FCA) for the ability to stimulate antibody production in New Zealand White rabbits (Oryctolagus cuniculus). In addition, each animal was evaluated for adverse reactions. The antigen, rat liver microsomal epoxide hydrolase, was administered sc emulsified with FCA, TDM, or TDM + MPL. Serum antibody titers were stimulated with all 3 adjuvant-antigen combinations. The highest titer was produced by use of FCA; TDM + MPL produced an intermediate response, and TDM produced the lowest titer. All of the rabbits immunized with FCA developed sterile subcutaneous abscesses. Rabbits immunized with TDM or TDM + MPL developed no abscesses, and only slight reactions at the injection sites. The synthetic adjuvant system TDM + MPL is recommended for use in rabbits, considering its adequate stimulation of antibody production with minimal adverse reactions.
Show more [+] Less [-]Serum liver enzyme and histopathologic changes in calves with chronic and chronic-delayed Senecio jacobaea toxicosis
1991
Craig, A.M. | Pearson, E.G. | Meyer, C. | Schmitz, J.A.
Progressive changes in serum enzyme activity and liver histologic features were monitored in calves fed tansy ragwort (Senecio jacobaea)-contaminated pellets. The experiments were designed to simulate natural intoxicant ingestion conditions in relationship to the dose and duration of exposure to the toxic plant to correlate early laboratory diagnostic changes with the natural progression of the disease, thereby facilitating early diagnosis and intervention by veterinary clinicians. Eight calves were fed tansy ragwort and 4 additional calves served as controls. In group 1, 4 calves were continuously fed dried tansy ragwort mixed in a pelleted feed at a 5% concentration by dry weight until terminal liver disease developed. Serum liver enzyme (alkaline phosphatase, glutamate dehydrogenase, and gamma-glutamyltransferase) activities were monitored at weekly intervals in these calves and in the 2 controls. In group 2, 4 calves were fed the same contaminated feed for only 60 days, with return to normal feed for the duration of the trial. Two additional calves served as controls. Their liver enzyme activities were monitored every other week in conjunction with percutaneous liver biopsies. All 8 calves fed tansy ragwort-contaminated pellets developed terminal hepatopathy in either a chronic pattern (n = 6) or a chronic-delayed pattern (n = 2), with the onset of a moribund state or sudden death at 11 to 17 weeks and 27 to 51 weeks, respectively. The calves were euthanatized when classic terminal signs of hepatic encephalopathy first became evident. The clinicopathologic patterns of chronic and chronic-delayed toxicoses were typical of over 5,000 cases of field tansy toxicosis diagnosed at the diagnostic laboratory. Serum glutamate dehydrogenase was the first enzyme to increase in most animals, with a short-term increase to peak values followed by a rapid return to normal. This enzyme change was followed by increases in alkaline phosphatase and gamma-glutamyltransferase. Serum enzyme changes preceded development of recognizable histologic lesions. Vacuolar changes in hepatocyte nuclei, biliary hyperplasia, and fibrosis sequentially developed in liver biopsy specimens from each animal, whereas megalocytosis was not a predominant feature until necropsy. On the basis of our finding we suggest that the optimal tests for diagnosis of pyrrolizidine alkaloid intoxication should consist of liver biopsy and determination of concurrent serum liver-enzyme activities.
Show more [+] Less [-]High sulfide concentrations in rumen fluid associated with nutritionally induced polioencephalomalacia in calves
1991
Gould, D.H. | McAllister, M.M. | Savage, J.C. | Hamar, D.W.
Nine 115- to 180-kg, hay-adapted, Holstein steers were fed an experimental diet with added sodium sulfate that induces polioencephalomalacia (PEM). Five calves developed the disease. Thiamine concentrations in blood, CSF, brain, and liver were not indicative of thiamine deficiency. The odor of hydrogen sulfide in eructated rumen gas was associated with the onset of PEM. Sulfide concentrations in rumen fluid were measured 1 or 2 times a week by 2 techniques. Sulfide concentrations progressively increased in all 9 calves after the feeding of the PEM-inducing diet commenced. The highest concentrations coincided with the onset of clinical signs of PEM and were significantly higher in the calves that developed PEM than in those that did not. This suggests that PEM can result from sulfide toxicosis following excess production of sulfide in the rumen.
Show more [+] Less [-]A new type of lesion associated with severe fur damage in Canadian ranch foxes and an investigation of possible causes
1991
Hardy, M.H. | Tackaberry, L.E. | Goldberg, M.T.
In the silver fox, as in its wild ancestor, the red fox (Vulpes vulpes L.), the annual growing phase (anagen) of guard hair follicles occupies at least four months. Severe damage to the hair coat near the end of this growing period was reported in 1985 on many ranches in New Brunswick and Nova Scotia. A histological analysis of serial sections of skin biopsies showed a marked increase in nuclear aberrations in the hair matrix of anagen guard hair follicles. These nuclear aberrations indicated that cells were undergoing apoptosis, a controlled form of cell death. Tissues from affected and unaffected foxes for histological and toxicological analysis, as well as other data, were obtained during visits to 26 ranches in 1986 and 34 ranches in 1987. Histological sections of the 1987 skin samples showed the mean percentage of nuclear aberrations in 43 unaffected foxes to be 0.08 +/- 0.01 (SEM), while that for 49 affected foxes was 0.51 +/- 0.23. The four foxes with the most severe coat damage also had the highest incidences of guard hair matrix cells with nuclear aberrations, ranging from 20 to 100 times greater than the mean for unaffected foxes. The mitotic index of the hair matrix, which normally remains fairly constant during the hair growth phase, was similar for unaffected and affected foxes (1.83 + 0.06 and 1.97 +/- 0.07 respectively). Although our analyses of field data have not established a specific environmental factor associated with increased nuclear aberrations, the possible involvement of toxic agents in follicle damage may warrant further investigation.
Show more [+] Less [-]Pathologic changes, tissue distribution, and extent of conversion to ethylenethiourea after subacute administration of zinc ethylene-bis-dithiocarbamate (zineb) to calves with immature rumen function
1991
Nebbia, C. | Ferrero, E. | Valenza, F. | Castagnaro, M. | Re, G. | Gennaro Soffietti, M.
The toxicity of zinc ethylene-bis-dithiocarbamate (zineb), a widely used fungicide, was studied in four 4-week-old Friesian calves with immature rumen function. Calves were first subjected to liver biopsy, and thereafter, 3 of them were orally administered 200 mg of zineb/kg of body weight daily for 80 days, whereas the fourth calf served as control and remained untreated. Clinical, hematologic, and pathologic (including ultrastructural) findings were recorded. The distribution in body fluids and tissues of the parent compound and one of its main metabolites, ethylenethiourea (ETU), also was examined. Treated calves had unthrifty appearance and reduction in weight gain. They also had remarkable impairment of thyroid function, as reflected by reduction in serum concentrations of triiodothyronine and thyroxine and increase in weight of the thyroid gland associated with epithelial vacuolization and foci of hyperplasia. Moderate increase in liver glycogen content and impairment in maturation of germ cells were recorded consistently. Whereas zineb was widely distributed in body tissues, ETU accumulated mainly in the liver and the thyroid gland, although noticeable concentrations also were attained in muscle. Data were consistent with involvement of ETU mainly in the pathogenesis of thyroid gland lesions, and indicate that unweaned calves given zineb develop a clinicopathologic syndrome that does not differ qualitatively from that already described in adult cattle exposed to zineb.
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