Feline ureteral obstructions Part 1: medical management

Feline ureteral obstructions are an increasingly recognised and challenging diagnostic and management problem. Many cats with ureteral obstructions are critically ill at the time of diagnosis, especially if there is dysfunction of the contralateral kidney. They may present with varying severities of acute kidney injury, electrolyte disturbances, and may have comorbidities such as heart disease that complicate perioperative and long‐term management. Medical management, which may consist of rehydration and restoration of intravascular volume with intravenous fluid therapy, osmotic diuresis, ureteral muscle relaxation, and antimicrobials for infection, is important in feline ureteral obstruction patients. Despite medical management, many cats with ureteral obstructions will require decompression of the obstructed kidney to relieve pressure‐nephropathy and restore urine flow. However, some cats may be too unstable for traditional medical management and require more emergent intervention to relieve the obstruction and address the life‐threatening sequelae to acute kidney injury, such as hyperkalaemia and fluid overload. Both surgical and interventional methods to address ureteral obstructions have been described in veterinary medicine, though debate continues as to the ideal approach.     

The evolution and application of enzymes in the animal feed industry: the role of data interpretation

ABSTRACT

1. Enzymes have been used commercially for nearly 40 years and save significant costs through sparing of expensive nutrients but the mechanism by which this is achieved is still debated.

2. The research focused on non-starch polysaccharidase (NSPase) enzymes is used as an example of where greater progress could have been made if the details of the work had been described more fully and the analysis of the data generated had been broader in scope and more critical.

3. Lack of standardisation of the details presented in the materials and methods has been identified as a significant barrier to meaningful retrospective analysis and thus limits advances in the understanding of the mode of action of these enzymes.

4. The identity of the enzyme employed and its activity is often lacking, and more importantly the purity is rarely disclosed. Contaminant activities which are neither listed nor assayed could play a significant role in the responses observed.

5. The dose optimum of most enzymes is often considerably higher than that employed in most studies. Thus studies claiming synergy between two ‘activities’ should ensure that the response is not related to each enzyme simply augmenting the dose of just one activity in the finished feed. This is a common problem, and coupled with the lack of factorial experiments to justify the presence of each enzyme in a multi-enzyme product, it is not surprising that there is still debate as to whether single or multi-enzymes are best suited poultry rations.

6. The three proposed mechanisms for NSPases (viscosity, cell wall and prebiotic) are discussed, and along with their strengths and weaknesses it is suggested that a re-evaluation of each is needed. Viscosity may have to be re-evaluated as being a function not only of the cereal being fed, but of the age of the animal as well. The cell wall theory as described is poorly modelled in vitro and hence the validity of these data is questioned. The prebiotic theory may need significant modification as it appears that the quantities of oligomers produced are insufficient to generate the additional volatile fatty acids (VFA)’s reported. It is likely that all three mechanisms play a role in the responses observed, but the prebiotic mechanism probably plays by far the most important part in low viscosity diets.

7. Future research would be improved if it considered all potential mechanisms when designing a trial. Significant failings are apparent as a result of adherence to tenets in explanation of the results. Most importantly, it should be emphasised that a hypothesis is there to be tested, not defended.     

Efficacy of a mephentermine‐based product as a vasopressor and a cardiac performance enhancer when given intramuscularly to cattle

The goal of this study was to confirm the vasopressor and cardiac effects of POTENAY^® INJETÁVEL (POT), a mephentermine‐based product, given to cattle with induced vascular/cardiac depression. Ten healthy Holstein cattle (206 ± 13 kg) followed a randomized‐complete‐block design (RCBD) utilizing crossover study design. Each animal randomly received (1 ml/25 kg, IM) of either POT (n = 10) or volume‐matched placebo control (0.9%NaCl, CP, n = 10). A subset of animals (n = 5) received POT first (day 0) while the remaining (n = 5) received CP; after a six‐day washout period, cattle received the opposite compound. Animals were anesthetized and catheterized for systemic/left ventricular hemodynamic monitoring. Myocardial dysfunction/hypotension was induced by increasing the end‐tidal isoflurane concentration until arterial blood pressure was 20% lower than at baseline and remained stable. Once the animal was determined to be hypotensive and hemodynamically stable, steady‐state hypotensive baseline data (BL2) were acquired, and treatment with either POT or CP was given. Data were acquired post‐treatment at every 15 min for 90 min. POT improved cardiac output (+68 L/min, ±14%, p < 0.05), MAP (+14 mmHg, ±4%, p < 0.05), HR (+22 bpm, ±8%, p < 0.05), and peak rates of ventricular pressure change during both systole (dP/dt_max: +37 mmHg/s ±13%, p < 0.05) and diastole (dP/dt_min: +31 mmHg/s, ±7%, p < 0.05). No improvements were noted following placebo‐control administration. Results indicate that POT improves cardiac performance and systemic hemodynamics in cattle with induced cardiovascular depression when given as single intramuscular injection.     

Effect of dasatinib in a xenograft mouse model of canine histiocytic sarcoma and in vitro expression status of its potential target EPHA2

Canine histiocytic sarcoma (HS) is an aggressive and highly metastatic tumor. Previously, the kinase inhibitor dasatinib was shown to have potent growth inhibitory activity against HS cells in vitro, possibly via targeting the EPHA2 receptor. Here, the in vivo effect of dasatinib in HS cells was investigated using a xenograft mouse model. Moreover, the expression status of EPHA2 was examined in six HS cell lines, ranging from insensitive to highly sensitive to dasatinib. In the HS xenograft mouse model, dasatinib significantly suppressed tumor growth, as illustrated by a decrease in mitotic and Ki67 indices and an increase in apoptotic index in tumor tissues. On Western blot analysis, EPHA2 was only weakly detected in all HS cell lines, regardless of sensitivity to dasatinib. Dasatinib likely results in the inhibition of xenograft tumor growth via a mechanism other than targeting EPHA2. The findings of this study suggest that dasatinib is a targeted therapy drug worthy of further exploration for the treatment of canine HS.     

Review of triazine antiprotozoal drugs used in veterinary medicine

Triazines are relatively new antiprotozoal drugs that have successfully controlled coccidiosis and equine protozoal myeloencephalitis. These drugs have favorably treated other protozoal diseases such as neosporosis and toxoplasmosis. In this article, we discuss the pharmacological characteristics of five triazines, toltrazuril, ponazuril, clazuril, diclazuril, and nitromezuril which are used in veterinary medicine to control protozoal diseases which include coccidiosis, equine protozoal myeloencephalitis, neosporosis, and toxoplasmosis.     

Noninferiority trial investigating the efficacy of a nonantibiotic intramammary therapy in the treatment of mild‐to‐moderate clinical mastitis in dairy cows with longer lasting udder diseases

A nonblinded, positively controlled, noninferiority trial was conducted to evaluate the efficacy of an alternative, nonantibiotic therapy with Masti Veyxym^® to reduce ineffective antibiotic usage in the treatment of nonsevere clinical mastitis (CM) in cows with longer lasting udder diseases. The solely intramammary treatment with Masti Veyxym^® (three applications, 12 hr apart) and the combined treatment with Masti Veyxym^® and antibiotics as usual on the farm according to label of the respective product were compared with the reference treatment of solely antibiotic therapy. The matched field study was conducted on eight free‐stall dairy farms located in Eastern Germany. Cases of mild‐to‐moderate CM in cows with longer lasting high somatic cell counts in preceding dairy herd improvement test days and with previous CM cases in current lactation were randomly allocated to one of the three treatment groups. A foremilk sample of the affected quarter was taken before treatment and again approximately 14 days and 21 days after the end of therapy for cyto‐bacteriological examination. Primary outcomes were clinical cure (CC) and no CM recurrence within 60 days after the end of treatment (no R60). Bacteriological cure (BC) and quarter somatic cell count (QSCC) cure were chosen as secondary outcomes although low probabilities of BC and QSCC cure for selected cows were expected. The study resulted in the following findings: the pathogens mostly cultured from pretreatment samples were Streptococcus uberis, followed by Staphylococcus aureus and coagulase‐negative staphylococci. There were no significant differences between the two test treatments in comparison with the reference treatment regarding all outcome variables. The sole therapy with Masti Veyxym^® resulted in a numerically lower likelihood of BC without significant differences to the reference treatment. The combined therapy group showed a numerically higher nonrecurrence rate than the two other treatment groups and noninferiority compared to the reference treatment was proven. Having regard to the selection criteria of cows in this study, the findings indicated that sole treatment with Masti Veyxym^® in nonsevere CM cases may constitute an alternative therapy to reduce antibiotics. However, noninferiority evaluations were mostly inconclusive. Further investigations with a larger sample size are required to confirm the results and to make a clear statement on noninferiority.