Disease-induced alterations in plasma drug-binding proteins and their influence on drug binding percentages in dogs

Disease-induced variations of plasma albumin (ALB) and alpha 1-acid glycoprotein (AAG) levels were investigated in dogs. Lower ALB (sometimes > 50% reduction) and higher AAG (sometimes > 10-fold increase) levels were observed in dogs with various diseases. Drug binding was determined at therapeutic concentrations using normal, low-ALB and high-AAG dog plasma. The binding percentages of the ALB-binding drugs decreased in low-ALB plasma, resulting in a large increase in unbound drug, particularly for naproxen (a 13-fold increase). The binding percentages of all AAG-binding drugs investigated in this study increased in high-AAG plasma, resulting in a large decrease in unbound drug, particularly for quinidine (99% decrease). The fluctuation in the unbound fraction of drugs could affect their efficacy or could cause side-effects. Veterinary clinicians should monitor the ALB and AAG levels in the plasma of patients and correct dosage regimens according to these levels, where field conditions permit this, in order to ensure the proper usage of drugs with high affinity for ALB or AAG.     

Histopathology and physiopathology of gastric mucous hyperplasia in rats heavily infected with Taenia taeniaeformis.

Rats heavily infected with larval Taenia taeniaeformis show hyperplasia of the gastric mucosa accompanied by mucous cell proliferation, increase in the level of intragastric pH and hypergastrinemia. Sixty one rats were divided into 2 groups designed as infected (36 rats) and control (25 rats) group. These rats were examined with time course of the infection histopathologically and physiopathologically, during 14-112 days postinfection (DPI). In the infected rats, gastric mucosal hyperplasia began to be observed at 56 DPI, and the structural disturbance of zymogenic units in the corpus and mucous units in the antrum had increased with time. However, the degree of these changes in the antrum was weaker than those in the corpus. Alcianblue and/or PAS-positive cells increased in their numbers with time, and 4 types of cells other than typical surface mucous cell and mucous neck cell were observed by electron-microscopy. However, zymogenic and parietal cells decreased in their number after 56 DPI. Further, the infected rats showed changes in the serum concentration of alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, glucose and total protein. Some similarities with Menetrier's disease were discussed.     

Cross-reactivity between a monoclonal antibody that recognizes a tumor-associated antigen on bovine lymphosarcoma cells and blood lymphocytes from various mammalian species.

Tumor-associated antigens that are expressed in lymphosarcoma B cells of cattle with enzootic bovine leukosis had been analyzed in terms of their reactivity with 13 monoclonal antibodies (MAB). By use of flow cytometry and radioimmunoprecipitation, 1 of the MAB (c143) that recognized a tumor-associated antigen cross-reacted with blood lymphocytes (BL) from various mammalian species. By use of flow cytometry, the c143 MAB reacted with 10 to 49% of BL derived from human beings, mice, dogs, horses, pigs, llamas, sheep, goats, and cattle. Titer of the c143 MAB with BL from horses, pigs, human beings, and llamas ranged between 1:6.0 x 10(4) and 1:5.3 x 10(5); titer associated with BL of goats and sheep was 1:1.6 x 10(6); and that associated with BL of cattle was 1:4.3 x 10(7). The c143 MAB specifically immunoprecipitated 3 homologous proteins from cell extracts of caprine, ovine, and bovine BL (32-, 34-, and 36- to 37-kDa bovine proteins; 31-, 32-, and 36- to 37-kDa caprine proteins; and 31.5-, 33-, and 36- to 37-kDa ovine proteins), but none was immunoprecipitated from human, murine, canine, porcine, and llama BL. These results indicate that the avidity of the c143 MAB in binding to BL from ruminants (eg, goats, sheep, and cattle) is higher than that to BL from human beings, mice, dogs, horses, pigs, and llamas. In sheep, the c143 MAB could immunoprecipitate the aforementioned proteins from BL of the Suffolk breed, but not BL from the Corriedale breed, whereas the c143 MAB immunoprecipitated apparently identical proteins from BL of 4 breeds of cattle.