Anatomical and physiological basis for the allometric scaling of cisplatin clearance in dogs

Cisplatin is a platinum‐containing cytotoxic drug indicated for the treatment of solid tumors in veterinary and human patients. Several of the algorithms used to standardize the doses of cytotoxic drugs utilize allometry, or the nonproportional relationships between anatomical and physiological variables, but the underlying basis for these relationships is poorly understood. The objective of this proof of concept study was to determine whether allometric equations explain the relationships between body weight, kidney weight, renal physiology, and clearance of a model, renally cleared anticancer agent in dogs. Postmortem body, kidney, and heart weights were collected from 364 dogs (127 juveniles and 237 adults, including 51 dogs ≥ 8 years of age). Renal physiological and cisplatin pharmacokinetic studies were conducted in ten intact male dogs including two juvenile and eight adult dogs (4–55 kg). Glomerular filtration rate (GFR), effective renal plasma flow, effective renal blood flow, renal cisplatin clearance, and total cisplatin clearance were allometrically related to body weight with powers of 0.75, 0.59, 0.61, 0.71, and 0.70, respectively. The similar values of these diverse mass exponents suggest a common underlying basis for the allometry of kidney size, renal physiology, and renal drug handling.     

Risk factors for Thoroughbred racehorse fatality in jump starts in Victoria, Australia (1989-2004)

REASONS FOR PERFORMING STUDY: The risk of fatality is greater in jump than in flat racing in Victoria, Australia. This is the first study to identify risk factors specific to jump starts in Victoria. OBJECTIVE: To identify risk factors for fatality of Thoroughbred racehorses in jump starts on all racecourses in Victoria, Australia between 1989 and 2004. METHODS: Fatalities comprised all horses that died during or immediately after a jump (hurdle or steeplechase) race or official jump trial and all horses that were subjected to euthanasia within 24 h of an event in which an injury was sustained. The retrospective study involved 191 case starts and 2324 control starts. Univariable and multivariable backward stepwise logistic regression was used to identify risk factors for fatality at any one start. A multiple level model was used with racecourse included as a random effect. RESULTS: In the final multivariable model, the duration of the racing career of the horse, the number of flat, hurdle and steeple starts accumulated in the 60 days prior to the case or control start, the number of flat and jump starts accumulated over the racing career, if the horse had had a start between 1 and 14 days prior to the case or control start, the type of jump race (hurdle or steeple), the calendar year of the start and the location of the racecourse were associated with fatality. CONCLUSIONS: The findings highlight the need to investigate further the differences between hurdle and steeplechase events and the adverse effect of prolonged prior flat racing careers on the risk of fatality in jump starts. POTENTIAL RELEVANCE: This is the first study to examine risk factors for fatality in jump starts in Victoria. The results should shape the development of interventions to reduce the risk in jump starts in the future.     

Cardiovascular effects of acute pulmonary obstruction in horses with recurrent airway obstruction

BACKGROUND: Recurrent airway obstruction (RAO) is common in horses. Although pulmonary artery (PA) pressure increases during RAO, cardiac function in horses with RAO has received limited attention. HYPOTHESIS: The purpose of this study was to noninvasively determine the cardiovascular effects of acute pulmonary obstruction (APO) in horses with RAO and their reversibility. ANIMALS: Five geldings with RAO, inducible by exposure to moldy hay, were studied. METHODS: Pulmonary mechanics, echocardiography, serum troponin I concentrations, arterial blood gases, and hematocrit were obtained before and after 7 days of APO. Heart rate, PA diameter and flow characteristics, right and left ventricular luminal dimensions and wall thicknesses, global cardiac performance, and evidence of myocardial damage were evaluated. Pulmonary mechanics and echocardiography were reevaluated during remission. RRESULTS: Severe, transient APO did not induce chronic cor pulmonale in horses, because cardiac anatomy and function were normal between episodes. An acute episode of APO produced anatomical and functional cardiac changes in both the right and left heart (including increased PA diameter, abnormal septal motion, and decreased left ventricular diameter and estimated stroke volume), possibly because of the development of pulmonary hypertension, without apparent myocardial damage. The decrease in stroke volume was offset by the increase in heart rate. CONCLUSIONS AND CLINICAL IMPORTANCE: With APO of 7 days' duration, cardiovascular abnormalities and the functional airway changes that produce them are reversible when the offending allergens are removed.     

Factors influencing the germination of seeds of the potato

American Journal of Potato Research -     

Development of an ex vivo model to study adherence of Mannheimia haemolytica serovar 1 to mucosal tissues of the respiratory tract of cattle

OBJECTIVE: To develop and validate an ex vivo model for study of adherence of Mannheimia haemolytica (formerly Pasteurella haemolytica) to respiratory tract mucosa of cattle and to use this model to confirm adherence of M haemolytica serovar 1 (Mh1) to several relevant respiratory mucosal surfaces. SAMPLE POPULATION: Excised nasal, nasopharyngeal, turbinate, and tonsillar mucosal tissue from the bovine upper respiratory tract. PROCEDURE: Mh1 was radiolabeled by use of tritiated leucine. Various concentrations of labeled bacteria were incubated with bovine upper respiratory tract tissues for various times. Tissue was washed to remove nonadherent bacteria, and percentage of bacteria adhered (percentage of adherence) was estimated using radioactivity. Using an optimal inoculum concentration and incubation time, percentage of Mh1 adherence was compared on nasal, nasopharyngeal, turbinate, and tonsillar mucosal tissue, and adherence to nasopharyngeal tissue was confirmed by scanning and transmission electron microscopy. RESULTS: The optimal Mh1 inoculum concentration was 1 X 10(7) colony forming units/ml and incubation time was 3 hours. Percentage of adherence of Mh1 to nasopharyngeal tissue was greater than adherence to other tissue types. CONCLUSIONS AND CLINICAL RELEVANCE: The ex vivo model maintained the functional and structural integrity of bovine upper respiratory tract mucosa, as confirmed by light and electron microscopy. Electron microscopy revealed participation of epithelial cell cilia and surface mucus in adherence of Mh1 to nasopharyngeal tissue. Adherence of Mh1 was confirmed in repeated assays, indicating that this organism adheres to upper respiratory tract mucosa of cattle.     

Intrathoracic lipoma in a Labrador retriever

Pyrexia, granulocytosis and hyperglobulinaemia were the main clinical findings in an unusual case of intrathoracic lipoma in a 12-year-old male Labrador retriever. The response to antibiotic and anti-inflammatory treatment was poor, prompting further investigation. Survey radiographs and ultrasonography revealed a cavitated, fluid-filled soft tissue mass in the right hemithorax, which was successfully removed resulting in rapid resolution of clinical signs. Lipomas are rare intrathoracic extrapulmonary tumours. Previously reported clinical signs are dyspnoea and coughing, attributed to the mass effect of the lipoma. The unusual presentation in this case was caused by necrosis of the lipoma, probably owing to torsion of the pedicle attaching it to the cranial mediastinum.     

A patch—clamp study of the action of a nitromethylene heterocycle insecticide on cockroach neurones growing in vitro

The mode of action of a nitromethylene heterocycle (NMH) insecticide was studied by patch–clamp techniques using cockroach embryonic cultures as an experimental model. Under whole-cell recordings, this compound elicited inward currents resembling those induced by O-acetylcholine (ACh). The reversal potentials for both ACh and the NMH were similar, suggesting that the inward currents induced by both were carried by the same species of ion. Pharmacological investigations of NMH-induced responses revealed that the insecticidal action of this compound is exerted through agonistic action at the nicotinic acetylcholine receptor. Single-channel studies were also performed to study the interaction of NMH with the nicotinic-receptor-coupled ion channel.