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.     

Canine serum protein patterns using high-resolution electrophoresis (HRE)

Serum protein values were determined in 26 healthy dogs using agarose gel electrophoresis (SPE), splitting the electrophoretic separation into six regions: albumin, alpha(1), alpha(2), beta(1), beta(2)and gamma globulins. High-resolution electrophoresis (HRE) was used to separate single proteins. Serum proteins from dogs (26 healthy and 20 affected by various diseases) were then characterized by electrophoretic immunofixation (IFE) and Sudan black staining on HRE film. Haemoglobin and normal canine plasma and serum were used to identify haptoglobin and fibrinogen, respectively.In the standard pattern, determined by HRE, the following proteins were identified: albumin, alpha(1)-lipoprotein (alpha(1)-region), haptoglobin and alpha(2)-macroglobulin (alpha(2)-region), beta -lipoprotein and C3 (beta(1)-region), transferrin and IgM (beta(2)-region), IgG (mostly in gamma -region and partly in beta(2)-region). The HRE pattern shown by healthy dogs could be compared with those of dogs affected by various diseases to obtain clinical information.     

Technical note: recombinant LHRH fusion protein suppresses estrus in heifers

A recombinant luteinizing hormone-releasing hormone (LHRH) fusion protein was evaluated for its effectiveness in suppression of estrus in heifers. Eight heifers were randomly assigned to two equal treatment groups. Treatments consisted of recombinant ovalbumin-LHRH-7 or recombinant ovalbumin (control). This recombinant chimeric fusion protein consisted of ovalbumin with seven LHRH peptides (ovalbumin-LHRH-7). The plasmid for this protein was expressed in E. coli and was collected and purified as an insoluble protein. One milligram of the respective proteins was suspended in 2 mL of Z-Max adjuvant and administered by intramammary injection three times at 7-wk intervals. Luteinizing hormone-releasing hormone antibody binding was elevated in heifers treated with ovalbumin-LHRH-7 compared to ovalbumin-treated heifers (P < .05). Serum progesterone concentrations (< 1 ng/mL) indicate that the estrous cycle of the four heifers treated with ovalbumin-LHRH-7 was suppressed for a time period ranging from 60 to 238 d, which was different from control heifers (P < .01). Serum progesterone for the control heifers continued to exhibit cyclic profiles over the experimental period. This preliminary study in heifers demonstrated that a chimeric LHRH fusion protein induced elevated concentrations of circulating LHRH antibodies that suppressed estrus for an average of 122 +/- 41 d.     

Digesta kinetics, energy intake, grazing behavior, and body temperature of grazing beef cattle differing in adaptation to heat

The objective of this study was to determine whether digesta kinetics, energy intake (EI, kcal ME intake x kg(-.75) x d(-1)), grazing behavior, or body temperature differed by breed, lactational state, or season of the year among cattle presumed to vary in adaptability to the subtropics. Two-year-old lactating and nonlactating Brahman x Angus (BA; n = 5, n = 5), Tuli x Angus (TA; n = 5, n = 4), and Angus (A; n = 4, n = 4) cows were used. During both early (ES) and late summer (LS), lactating cattle vs nonlactating cattle had greater gastrointestinal tract load (CM2) and EI (P < .01), although passage rate did not differ (P > .48). During LS, lactating cattle had decreased early morning rectal temperatures (P < .05) and spent more time grazing during the day compared with nonlactating cattle (P < .001). Among breeds, A had the largest CM2 (P < .01 compared with BA and P = .068 compared with TA) and accumulated the greatest heat during the day (P < .05). Due to greater daytime shading (P < .01) and less daytime grazing (P < .05), A had lower (P < .05) early morning and comparable (P > .26) late afternoon rectal temperatures compared with BA and TA. With data pooled over both grazing trials, BA cattle had the smallest CM2 (P < .01), and in ES they spent the least amount of time in the shade (P < .001). The TA spent more time in the shade than did BA (P < .001) during ES and less during LS (P < .001) and had similar (P > .28) early morning rectal temperatures compared with BA during ES and LS. During LS, TA spent more time in the sun and less time in the shade than did either A or BA (P < .001). During ES, EI did not differ among breeds (P > .50). During LS, EI for lactating A was greater than for BA and TA (P < .05), and EI for nonlactating BA was less than for A and TA (P < .05). Bite rate per minute for lactating cattle during ES was reduced (P < .03) by increased body condition score. Tuli x Angus cattle appear to be comparable to BA with respect to heat adaptation. It appears that EI demands are greater in a hot environment.     

Lesions and effects of location for administration of clostridial bacterin-toxoid vaccines on growth performance and eating and drinking behaviors in newly arrived calves at a feedlot

OBJECTIVES: To determine the effect of location for administration of clostridial vaccines on behavior, growth performance, and health of calves at a feedlot, the relative risk of calves developing an injection-site reaction or being misdiagnosed as having bovine respiratory disease complex (BRDC), and the percentage of subcutaneous injection-site reactions that were detectable on carcasses after the hides were removed. ANIMAL: 170 newly arrived calves at a feedlot. PROCEDURE: Eating and drinking behaviors of calves during the initial 57 days after arrival were observed at a commercial feedlot, using an electronic monitoring system. Calves were assigned randomly to receive a clostridial vaccine (base of ear or neck). Data on reactions at the injection site were collected. RESULTS: Mean daily gain (MDG) for the initial 57 days did not differ significantly between treatments. Risk of being misdiagnosed as having BRDC was not associated with location for administration of vaccine. Calves vaccinated in the base of the ear were at higher risk of having an injection-site reaction at day 57 or at slaughter. Eighty-nine percent (95% confidence interval, 52 to 100%) of injection-site reactions in the neck could not be located on the carcasses after hides were removed. Calves vaccinated in the neck drank significantly fewer times per day during the first 57 days than calves vaccinated in the base of the ear. CONCLUSIONS AND CLINICAL RELEVANCE: Location for administration of a clostridial vaccine did not significantly affect health, growth performance, or eating behavior. Most subcutaneous injection-site reactions were not detectable after the hide was removed.     

An encephalopathy with argyrophilic inclusions in a Holstein-Friesian cow

The brain of a 6-year-old Holstein cow, which showed progressive neurologic symptoms during several months, was examined by histopathologic methods. Many round or oval-shaped cytoplasmic inclusions were observed, mainly in neurons of the temporal lobe and the hippocampus. Those inclusions were faintly eosinophilic with hematoxylin and eosin and positive with Bielschowsky's silver stain. Immunohistochemically, the inclusions were recognized by antiubiquitin and antiphosphorylated tau antibodies. Ultrastructurally, the inclusions were globular and well demarcated from the rest of the cytoplasm, lacked limiting membranes, and were mainly composed of straight fibrils about 15 nm in width. The structure of the inclusions was similar to that of Pick bodies in Pick's disease of humans. The pathogenesis of this bovine condition is not known.     

Hendra and Nipah virus infections.

The most important clinical and pathological manifestation of Hendra virus infection in horses and humans is that of severe interstitial pneumonia caused by viral infection of small blood vessels. The virus is also capable of causing nervous disease. Hendra virus is not contagious in horses and is spread by close contact with body fluids, such as froth from infected lungs. Diagnosis should be based on the laboratory examination of blood, lung, kidney, spleen, and, if nervous signs are present, also of the brain. Evidence of infection with the more recently identified and related Nipah virus was found in the brain of one horse in which there was inflammation of the meningeal blood vessels. Fruit bats, especially Pteropus s., have been incriminated as the natural and reservoir hosts of both Hendra and Nipah viruses.     

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.     

Antibodies produced by mice immunized with recombinant vaccinia viruses expressing two different types of a major Theileria sergenti surface antigen (p32) react with the native surface antigen.

A 32 kDa major surface antigen, p32, of Theileria sergenti at the piroplasm stage is the main target of the host immune response. The immunogenic property of the p32 varies in some strains among the population of Theileria sergenti in Japan where the Chitose type and the Ikeda type are the most common varieties. We have constructed vaccinia virus recombinants vv/p32C and vv/p32I which harbor the Chitose and Ikeda types of p32 gene, respectively. It was found that vv/p32C and vv/p32I produced type-specific p32 which did not cross react with the monoclonal antibodies (mAbs) against the other type of p32. When mice were immunized with vv/p32C and vv/p32I, antibodies against p32 were detectable 2 weeks after the immunization, and these antibodies reacted with the native surface antigen in purified T. sergenti merozoite.