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Clinical efficacy and toxicity of doxorubicin encapsulated in glutaraldehyde-treated erythrocytes administered to dogs with lymphosarcoma.
1994
Matherne C.M. | Satterfield W.C. | Gasparini A. | Tonetti M. | Astroff A.B. | Schmidt R.D. | Rowe L.D. | DeLoach J.R.
Doxorubicin was encapsulated in canine erythrocytes, treated with 0.32% glutaraldehyde, and administered at a dosage equivalent to 30 mg of free doxorubicin/m(2) of body surface area to dogs with diagnosis of lymphosarcoma. Compared with administration of free doxorubicin, this method of drug delivery substantially reduced peak plasma concentration and prolonged higher plasma concentration of doxorubicin. As such, this method was comparable to continuous IV infusion. Previous studies have indicated this method's potential for reduction in toxic side effects, particularly cardiotoxicosis, while allowing higher total doses of doxorubicin to be administered. In this study, doxorubicin encapsulated in glutaraldehyde-treated erythrocytes induced a triphasic exponential decay of doxorubicin from plasma, the highest relative contribution to the total area of the curve being the terminal phase. The treatment was effective in inducing complete and partial remissions of lymphosarcoma, with minimal acute toxicosis and no evidence of cardiotoxicosis. However, substantial, unanticipated, chronic, nonregenerative myelosuppression developed, and was most strikingly expressed as profound thrombocytopenia. Efforts to ameliorate or circumvent this toxic effect will be required prior to further consideration of this doxorubicin delivery system for treatment of systemic neoplasia.
Afficher plus [+] Moins [-]Pharmacokinetic properties of doxorubicin encapsulated in glutaraldehyde-treated canine erythrocytes.
1991
Tonetti M. | Astroff A.B. | Satterfield W. | De Flora A. | Benatti U. | DeLoach J.R.
Canine erythrocytes were loaded with the antineoplastic drug doxorubicin and then treated with 0.16% glutaraldehyde. This procedure has been previously shown to slow down the efflux of doxorubicin from erythrocytes and to result in the selective targeting of the carrier erythrocytes to liver. Three dogs were treated each with 2 different schedules of IV bolus administration of doxorubicin (0.4 mg/kg of body weight): free drug and doxorubicin encapsulated in glutaraldehyde-treated erythrocytes. The 2 treatments yielded consistent differences in the plasma pharmacokinetic properties of doxorubicin and of its only metabolite, doxorubicinol. A triphasic exponential decay of doxorubicin plasma concentrations was observed on injection of the free drug. Conversely, in the case of erythrocyte-encapsulated doxorubicin, 4 phases of plasma concentrations of doxorubicin were found. The plasma concentrations of doxorubicinol, after a steady increase during the first hour, followed patterns of decay comparable to those of the parent drug. On the basis of the kinetic variables calculated with the 2 administration schedules, area under curve concentrations of plasma doxorubicin were 136 microgram.h/L (free infusion) and 734 microgram.h/L erythrocyte-encapsulated drug). Significant alterations of hematologic and hematochemical factors were not observed in the 3 dogs during and after the 2 treatments. On the basis of our findings, doxorubicin-loaded and glutaraldehyde-treated erythrocytes may potentially be used in the treatment of systemic and hepatic tumors in dogs.
Afficher plus [+] Moins [-]Development of an enzyme-linked immunosorbent assay to detect IgG, IgM, and complement (C3) on canine erythrocytes.
1989
Porter R.E. Jr. | Weiser M.G. | Callahan G.N.
An ELISA was used to detect IgG, IgM, and complement (C3) on the surface of canine erythrocytes. Erythrocytes were placed in wells of a microtitration plate and incubated with affinity purified, alkaline phosphatase-conjugated anti-canine IgG, IgM, or C3. Results of the ELISA were compared with the direct antiglobulin test (DAT) by preparing standard reference curves from canine blood type A erythrocytes that had been incubated with serial dilutions (1:2 to 1:8,192) of canine anti-A serum. The ELISA detected increased erythrocyte-bound immunoglobulin and complement at two- to fourfold dilutions greater than thoe required for positive results with the DAT. The ELISA required small sample and reagent volumes and detected lower concentrations of immune components than did the DAT.
Afficher plus [+] Moins [-]Increased peroxidation of erythrocytes of stress-susceptible pigs: an improved diagnostic test for porcine stress syndrome.
1989
Duthie G.G. | Arthur J.R. | Bremner P. | Kikuchi Y. | Nicol F.
When incubated with solutions of hydrogen peroxide, erythrocytes of stress-susceptible pigs produced more by-products of lipid peroxidation (as measured as thiobarbituric acid-reactive substances [TBARS]) than did erythrocytes from stress-resistant pigs. Using this technique, discrimination between the 2 pig types was absolute at hydrogen peroxide concentrations of 0.9 and 1.5%. This was in contrast to other methods of identifying stress-susceptible pigs, such as osmotically induced erythrocyte lysis and the determination of plasma pyruvate kinase and creatine kinase activities, for which considerable overlap of data was observed between pig types. The increased TBARS production by erythrocytes was further evidence for the existence of an antioxidant abnormality in stress-susceptible pigs. However, because there were no discernible differences in the major blood antioxidant-related values between stress-susceptible and stress-resistant pigs, the nature of the defect remains unclear. The production of TBARS by erythrocytes when incubated with hydrogen peroxide provides an improved method for identifying stress-susceptible pigs.
Afficher plus [+] Moins [-]Inhibition of lacteal leukocyte phagocytosis by colostrum, nonlactating secretion, and mastitic milk.
1986
Targowski S.P. | Niemialtowski M.
Modified indirect fluorescent antibody test for the serodiagnosis of Anaplasma marginale infections in cattle.
1985
Montenegro James S. | James M.A. | Ristic M.
Role of an intramammary device in protection against experimentally induced staphylococcal mastitis in ewes.
1993
Penades J.R. | Albizu I. | Baselga R. | Marco J. | Barberan M. | Amorena B.
An intramammary device (IMD) was adapted for use in ewes; this device was made of abraded poly. ethylene material (1.7 mm in diameter, 47 mm long) and formed a 15-mm-diameter loop in the gland cistern. The IMD was inserted in 1 gland in each of 43 ewes. A significant (P < 0.0001) increase in milk somatic cell count (SCC) was observed in glands provided with an IMD. This increase was attributable to an increase in neutrophil numbers and was observed during the first 12 weeks after insertion. The IMD had a protective effect against experimentally induced staphylococcal mastitis (Staphylococcus aureus and S epidermidis), although different milk SCC were required for protection from each bacterial species in most ewes (10(6) and 2 X 10(5) cells/ml, respectively). Histologic studies revealed that the IMD induced local squamous metaplasia in the glandular part of the lactiferous sinus. Erythrocytes were found in milk from glands provided with an IMD throughout the studied period (35 days of the 45-day lactation) and, in some cases, blood clots were observed during the first 2 weeks of lactation. Glands with IMD also had lower milk production and quality at 30 and 32 days of lactation. Eight ewes with IMD were studied throughout a subsequent lactation. Milk from the IMD-containing glands had an increase in SCC, as in the previous lactation period; did not contain blood clots or erythrocytes; and had normal composition (similar to that in glands without the IMD).
Afficher plus [+] Moins [-]Hemagglutination and hemagglutination inhibition of turkey red blood cells with Mycoplasma hyopneumoniae.
1989
Young T.F. | Erickson B.Z. | Ross R.F. | Wannemuehler Y.
The ability of Mycoplasma hyopneumoniae to agglutinate RBC was evaluated to develop an in vitro cytadsorption assay. Using swine RBC in a microtitration hemagglutination test, no agglutination or partial agglutination was detected. Comparison of RBC from various other species indicated that improved hemagglutination was obtained with RBC from turkeys. This hemagglutination was detected only when mycoplasma cells used in the assay had been frozen and thawed, heated at 50 C for 30 minutes, or treated with trypsin. Treatment of RBC with trypsin or neuraminidase enhanced hemagglutination. Possible surface lectin activity in M hyopneumoniae was evaluated by use of carbohydrates in a blocking assay; hemagglutination was not inhibited by any of 13 carbohydrates evaluated. Mycoplasma hyopneumoniae convalescent porcine serum and monoclonal antibodies against 2 M hyopneumoniae immunogens of molecular weights of 64,000 and 41,000 inhibited hemagglutination.
Afficher plus [+] Moins [-]Equine neonatal isoerythrolysis: evidence for prevention by maternal antibodies to the Ca blood group antigen.
1988
Bailey E. | Albright D.G. | Henney P.J.
Foals with the Ca blood group antigen on their RBC were given colostrum with anti-Ca antibodies (6 foals) or colostrum without anti-Ca antibodies (6 foals). The PVC were determined at birth and 2, 4, and 6 days after birth for the foals in each group. Significant differences were not observed for the PCV between the 2 groups, indicating that foals were not adversely affected by ingesting colostrum with the anti-Ca antibody. Standardbred mares without the Aa blood group antigen were evaluated to determine whether production of anti-Ca antibodies influenced production of anti-Aa antibodies. Of 266 mares without the Aa antigen, 3 of 61 (5%) mares without the Ca blood group antigen produced anti-Aa antibodies and 43 of 205 (21%) with the Ca blood group antigen produced anti-Aa antibodies. These 2 groups of mares were significantly (p = 0.006) different; Ca-negative mares were less likely to produce antibodies to Aa than were mares with the Ca blood group antigen. This observation was consistent with a hypothesis of antibody-mediated immunosuppression of immune response to the As blood group antigen by antibodies to the Ca blood group antigen, ie, when a mare is exposed to her foal's RBC and already has antibodies to the Ca blood group antigen on the foal's RBC, then she is less likely to initiate an immune response to the Aa blood group antigen also on the foal's RBC.
Afficher plus [+] Moins [-]Hereditary nonspherocytic hemolytic anemia in Beagles.
1988
Maggio Price L. | Emerson C.L. | Hinds T.R. | Vincenzi F.F. | Hammond W.R.
Three Beagles with chronic anemia and reticulocytosis were studied. The dogs originated from a large breeding colony and appeared clinically normal with the exception of splenomegaly. The PCV ranged from 30 to 39% (normal, 46 to 56%), with reticulocyte indices of 2.3 to 9.9. Red blood cells were morphologically normal, and examination of marrow aspirates revealed erythroid hyperplasia. Shortened chromium-51 RBC life-spans (7.2 to 15.4 days in anemic dogs; 22.2 to 25.2 days in control dogs) documented a hemolytic anemia. Acquired causes of hemolytic anemia were ruled out. Red blood cells had normal glycolytic enzyme activities, no evidence of unstable or abnormal hemoglobin, and had altered osmotic fragility curves. The breeding of 2 anemic dogs resulted in off-spring with anemia and reticulocytosis. Polyacrylamide gel electrophoresis revealed no abnormalities in RBC membrane cytoskeletal proteins in all anemic adult dogs and in 3 offspring.
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