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.     

Short-term effects of ecadotril in dogs with induced congestive heart failure

OBJECTIVE: To evaluate short-term hemodynamic effects of ecadotril in a model of congestive heart failure in dogs. ANIMALS: 6 conscious adult male dogs. PROCEDURES: Instruments were placed in dogs to measure left ventricular, aortic, and atrial blood pressures. Heart failure was induced by repeated coronary embolization with latex microspheres. Four times, and in random order, dogs were given vehicle or active drug (3, 10, or 30 mg/kg of body weight) orally. Hemodynamic variables, urine flow, and urinary electrolyte excretion were measured before and 30, 90, and 150 minutes, and 10 and 21 hours after drug administration. RESULTS: Changes in urine flow, heart rate, mean arterial pressure, or peak positive and negative rate of change in ventricular pressure were not apparent. Urinary sodium excretion significantly increased in response to the low and high doses of ecadotril but not in response to the 10 mg/kg dose. Left ventricular end diastolic pressure (LVEDP) consistently decreased in dose- and time-dependent manner. Maximal group-averaged reductions in LVEDP were 5.2, 8.1, and 10 mm Hg for the low, middle, and high doses, respectively. The magnitude of the decrease in LVEDP was not related to cumulative change in urine flow. CONCLUSIONS AND CLINICAL RELEVANCE: Orally administered ecadotril reduced left ventricular filling pressures in these dogs by a mechanism that does not require a substantial diuretic effect. Ecadotril may be effective for alleviating clinical signs in dogs with left-sided heart failure and may be particularly beneficial for use in dogs that are refractory to traditional diuretic therapy.     

Approaches to modeling intramammary infections in dairy cattle

In this paper, three approaches (Markov processes, discrete-event simulation, and differential equations) to modeling intramammary infections (IMI; focusing on the dynamic changes between uninfected, subclinical, and clinical udder-health states) are described. The objectives were to describe the various approaches to modeling intramammary infections, determine if simulations of the examples of the three approaches yield stable prevalences, and discuss the approaches' limitations. The literature review showed that there is no agreement on the proportion of animals that change health states. The approach of discrete-event simulation modeling included the most cow-level risk factors and udder-health states (hence, was judged to replicated best the dynamics of the infection process) and yielded stable prevalences for all udder-health states. However, there remain parts of the dynamics that need further research. These include the pathogen-specific probabilities and times of occurrence for: regression of clinical IMI to subclinical IMI, flare-up of subclinical IMI to clinical IMI, and incidence of subclinical IMI. Also, the assumption in all current approaches of homogenous mixing is violated because the primary contact structure for contagious pathogens during milking is either between cows through residual infectious milk in the milking machine or within a cow by vacuum fluctuations or teat-cup liner slips. Better contact structures should be incorporated so that the effects of control strategies can be better-estimated. Moreover, the three modeling approaches discussed assumed that all non-infected quarters are susceptible to infection—which might be denied by work in genetic resistance.     

Characteristics and risk factors for failure of horses with acute diarrhea to survive: 122 cases (1990-1996)

OBJECTIVE: To characterize horses with acute diarrhea and determine risk factors for failure to survive. DESIGN: Retrospective study. ANIMALS: 122 adult horses admitted for acute diarrhea at the teaching hospital between Jan 1, 1990 and Dec 31, 1996. PROCEDURE: Medical records of horses with acute diarrhea were reviewed to abstract information regarding signalment, history, physical examination, clinicopathologic testing, treatment, and outcome. RESULTS: 91 of 122 (74.6%) horses lived and were discharged from the hospital. Horses with history of administration of antimicrobials for a problem preceding diarrhea were approximately 4.5 times less likely to survive. The following variables that had been determined at the time of admission were significantly associated with failure to survive: administration of antimicrobial drugs for another illness, serum creatinine concentration > 2.0 mg/dl, PCV > 45%, tachycardia (heart rate > 60 beats/min), and low serum total protein concentration. Prevalence of laminitis was 11.5%. CLINICAL IMPLICATIONS: Diarrheic horses that are azotemic and have clinicopathologic findings consistent with hemoconcentration and hypoproteinemia have a poor prognosis for survival. Antimicrobial administration may induce diarrhea, and antimicrobial-associated diarrhea may have a worse prognosis than other types of acute diarrhea.     

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.     

Comparison Between a γ-IFN Assay and Intradermal Tuberculin Test for the Diagnosis of Bovine Tuberculosis in Field Trials in Brazil

Bovine tuberculosis is a major problem in Brazil. The intradermal tuberculin test is the standard test for detection of bovine tuberculosis in Brazil but can lack both sensitivity and specificity. The purpose of this study was to compare a bovine γ-IFN assay with the tuberculin test under field conditions in Brazil. A total of 1632 animals from 13 dairy farms were tested using the single cervical tuberculin test (SCTT). Among those animals, about 15% of each herd, 220 in total, represented a high-risk group and were selected to be tested using the γ-IFN test. Of the 1632 animals tested, 207 presented significant reactions representing 12.7% of the cattle studied. In the selected group the number of animals positive by the γ-IFN assay was 126/220 (57.3%) and the total number of reactive cows on SCTT was 106/220 (48.2%). The real number of infected cattle, following standards, was 120/220 (54.5%). From these results the relative sensitivity rate of γ-IFN test was 100% including the false-positive results and 88.3% for the SCTT — a significant (P < 0.01) difference in favour of the γ-IFN test of 11.7%. The γ-IFN assay also identified some positive animals 60–120 days earlier than the SCTT. In conclusion, we believe that the γ-IFN assay can be used alone or in combination with the SCTT, as a valuable tool for the control of bovine tuberculosis in the Brazilian national herd.     

Influence of storage time and processing on chemical composition and in vitro ruminal fermentation of olive cake

Olive oil extraction generates olive cake (OC) that could be used in ruminant feeding. However, the chemical composition of OC is affected by multiple factors, being therefore highly variable. The objective of this study was to analyse the influence of storage time and further processing: crude, exhausted (subjected to a second oil extraction) and cyclone (obtained from a cyclone separator) on nutritive value of OC samples. Twelve samples (six crude and six exhausted) were obtained monthly from the same pond from 1 to 6 storage months, and nine samples (three crude, three exhausted and three cyclone) were obtained monthly from a different pond from 6 to 9 months storage. Chemical composition was analysed, and OC samples were fermented in vitro with sheep rumen fluid. Increasing storage time up to 6 months decreased sugars and total soluble polyphenols content but increased fibre content in OC. Dry matter effective degradability (DMED) decreased linearly (p < 0.001) by 35.9 and 45.5% as storage time augmented from 1 to 6 months for crude and exhausted OC, respectively. Crude OC had lower DMED values than exhausted OC (averaged values 0.255 and 0.294 g/g, respectively). Both potential production and rate of gas production were lower (p ≤ 0.018) in crude compared with exhausted OC, which was attributed to the high fat content of crude OC (≥86 g/kg dry matter). For samples stored longer than 6 months, cyclone had greater (p < 0.05) DMED than crude and exhausted OC (averaged values 0.207, 0.164 and 0.164 g/g, respectively). The results indicate that ruminal degradability of OC is reduced with advancing storage time, but only subtle changes were observed during the first two months. Cyclone showed greater degradability than crude and exhausted OC, but differences between crude and exhausted OC became negligible after five storage months.     

Genetic diversity among Australian and New Zealand isolates of Leptospira interrogans serovar pomona

Restriction endonuclease analysis of 16 Australian and 4 New Zealand isolates of Leptospira interrogans serovar pomona showed that they could be divided into 3 genetic groups. Most of the isolates closely resembled the serovar kennewicki reference strain, and they all differed from the reference strain of serovar pomona. Based on these findings, it is suggested that vaccine manufacturers re-evaluate their choice of serovar pomona vaccine strain.     

ANGIOGRAPHIC EVALUATION OF BOVINE FOOT ABNORMALITIES

Angiography of normal and diseased feet in cattle was carried out. In osteomyelitis of distal phalanx there was a narrowing of the digital artery with diminished vascular supply to the affected digit. An area of bone necrosis was found to be avascular. With overgrown hooves, narrowing of both the medial and lateral digital arteries with ill-defined laminar vessels was seen. The vascular pattern in cattle with cork screw claws was characterized by a dilated tortuous digital artery and a crowded arterial network resulting in increased vascular supply in the affected claw. Abrupt stricture of common digital artery, a crowded vascular network in the area of the middle phalanx and filling defects of terminal arches were demonstrated in animals with exostosis