Pharmacokinetics and pharmacodynamics of three formulations of firocoxib in healthy horses

The objectives of this study were to compare the pharmacokinetics and COX selectivity of three commercially available formulations of firocoxib in the horse. Six healthy adult horses were administered a single dose of 57 mg intravenous, oral paste or oral tablet firocoxib in a three‐way, randomized, crossover design. Blood was collected at predetermined times for PGE₂ and TXB₂ concentrations, as well as plasma drug concentrations. Similar to other reports, firocoxib exhibited a long elimination half‐life (31.07 ± 10.64 h), a large volume of distribution (1.81 ± 0.59L/kg), and a slow clearance (42.61 ± 11.28 mL/h/kg). Comparison of the oral formulations revealed a higher C_max, shorter T_max, and greater AUC for the paste compared to the tablet. Bioavailability was 112% and 88% for the paste and tablet, respectively. Maximum inhibition of PGE₂ was 83.76% for the I.V. formulation, 52.95% for the oral paste formulation, and 46.22% for the oral tablet formulation. Pharmacodynamic modeling suggests an IC₅₀ of approximately 27 ng/mL and an IC₈₀ of 108 ng/ mL for COX2 inhibition. Inhibition of TXB₂ production was not detected. This study indicates a lack of bioequivalence between the oral formulations of firocoxib when administered as a single dose to healthy horses.     

Pathological findings and probable causes of the death of Stejneger’s beaked whales (Mesoplodon stejnegeri) stranded in Japan from 1999 and 2011

One hundred and twenty stranding events of Stejneger’s beaked whales were reported in Japan between 1999 and 2011. The purpose of this study is to introduce pathological data and to discuss probable causes of death for 44 Stejneger’s beaked whales among them. The significant pathological findings were the pulmonary edema, parasitic granulomatous nephritis, emaciation, amyloidosis, suppurative bronchopneumonia and so on. The probable causes of death were categorized as noninfectious in 43 of the cases, which included drowning, starvation and secondary amyloidosis. One individual was diagnosed with septicemia, which was the only example of an infectious disease. Because we could not always perform advanced analyses, such as microbiology tests, biotoxin examinations or contaminant analyses, the finality of our findings may be impaired. However, the present study has broad implications on the causes of death of Stejneger’s beaked whales of the seas around Japan, which are valuable for the future studies and for the detection of emerging diseases.     

Determination of capsaicinoids in habanero peppers by chemometric analysis of UV spectral data

A novel spectrophotometric method for the determination of capsaicinoids in habanero pepper extracts is described that does not require prior analyte separation. The method uses partial-least-squares (PLS-1) multivariate regression modeling techniques in conjunction with ordinary UV absorption spectral data obtained on alcoholic extracts of habanero peppers (Capsicum chinese). The PLS-1 regression models were developed by correlating the known total concentration of the two major capsaicinoids (capsaicin and dihydrocapsaicin) in the extracts as determined by high-performance liquid chromatography with the spectral data. The regression models were subsequently validated with laboratory-prepared test sets. The validation studies revealed that the root-mean-square error of prediction varied from 4 to 8 ppm, based on the results obtained from models prepared from nine test sets. Once a regression model has been developed and validated, analyses of the extracts can be accomplished rapidly by ordinary spectrophotometric procedures without any prior separation steps.     

The integration of a telemental health service into rural primary medical care

Mental health care shortages in rural areas have resulted in the majority of services being offered through primary medical care settings. The authors argue that a paradigm shift must occur so that those in need of mental health care have reasonable, timely access to these services. Changes proposed include integrating mental health services into primary medical care settings, moving away from the traditional view of mental health care services (one therapist, one hour, and one client), and increasing the consultative role of psychologists and other mental health care providers in primary medical care. Characteristics of mental health providers that facilitate effective integration into primary medical care are presented. The results of a needs assessment survey and an example of a telemental health project are described. This project involved brief consultations with patients and their physicians from a shared care model using a broadband internet telecommunications link between a rural clinic and mental health service providers in an urban area.     

Early growth and ecophysiological responses of Koa (Acacia koa A. Gray) seedlings to reduced water and phosphorus

Sites in need of restoration typically have one or more environmental factors that limit seedling establishment. Identifying ecophysiological responses to environmental stressors can provide important insights into mitigating measures that would allow seedlings to overcome such constraints to survival. Koa (Acacia koa A. Gray) is a nitrogen-fixing tree species endemic to Hawai?i that is highly valued in restoring degraded forest ecosystems, which are often limited in available water and phosphorus. This study examined how koa seedlings respond to conditions of reduced water (65 W) and no phosphorus (0P). After 17 weeks, seedlings subjected to 65 W or 0P accumulated less biomass, smaller root-collar diameters, and lower nitrogen and phosphorus contents. Combined reductions in water and P resulted in seedlings with increased root to shoot dry biomass and shorter shoots. Seedlings subjected to 65 W also had lower instantaneous rates of CO₂ assimilation, but higher instantaneous water-use efficiencies following irrigation, suggesting that koa responds to water deficits by decreasing water loss via reduced stomatal conductance. Seedlings subjected to 0P had similar rates of CO₂ assimilation relative to those grown with adequate P, suggesting that koa is able to employ strategies to avoid physiological impairment from conditions of inadequate P. Future research should assess whether subjecting koa seedlings to reduced water before planting on water-limited sites cues increased drought resistance and whether uptake and storage of P by seedlings in the nursery better supports growth following outplanting, particularly on sites with anticipated low plant-available water.

     

Transient Fanconi syndrome in Quarter horses

Two Quarter horses with weight loss had glucosuria, euglycemia, and a mild metabolic acidosis suggesting a proximal renal tubular defect. Further testing revealed transient generalized aminoaciduria, lactic aciduria, and glucosuria, indicating Fanconi syndrome. Both horses recovered with supportive therapy. This is the first report of acquired Fanconi syndrome in horses.     

Pharmacokinetics and safety of firocoxib after oral administration of repeated consecutive doses to neonatal foals

The purpose of this study was to determine the pharmacokinetics and safety profile of firocoxib in neonatal foals. Seven healthy foals were administered 0.1 mg/kg firocoxib orally q24 h for nine consecutive days, commencing at 36 h of age. Blood was collected for firocoxib analysis using high‐pressure liquid chromatography with fluorescence detection at 0 (dose #1 only), 0.25, 0.5, 1, 2, 4, 8, 16, and 24 h after doses 1, 5, and 9. For all other doses (2, 3, 4, 6, 7, and 8), blood was collected immediately prior to the next dose (24 h trough). Elimination samples (36, 48, 72, 96, 120, and 144 h) were collected after dose 9. Safety was assessed via physical examinations, body weight measurements, gastroscopy, complete blood count, plasma biochemistry and urinalysis. Firocoxib was rapidly absorbed following oral administration with minimal accumulation after repeat dosing. After the final dose, the terminal half‐life was approximately 11 h. Firocoxib was below the limit of detection (<2.5 ng/mL) in plasma 72 h after the final dose. No significant abnormalities were found on blood analyses, urinalysis, or gastroscopy. This study demonstrated that firocoxib is absorbed in neonatal foals with no demonstrable adverse effects after repeated doses of 0.1 mg/kg.     

Septic funiculitis caused by Streptococcus equi subspecies equi infection with associated immune‐mediated haemolytic anaemia

A 2‐year‐old Quarter Horse gelding presented for anaemia, icterus, depression and intermittent colic 2 weeks after routine castration. Bilateral septic funiculitis with Streptoccocus equi ssp. equi with secondary immune‐mediated haemolytic anaemia were diagnosed. A blood transfusion was required to facilitate general anaesthesia for surgical excision of the septic funiculitis. Antibiotic therapy was provided initially with chloramphenicol and later enrofloxacin. Immunosuppressive therapy was provided with dexamethasone and later azathioprine. The horse responded well to treatment and was discharged 8 weeks after presentation. Streptococcus equi ssp. equi should be considered in cases with septic funiculitis and the potential for a secondary immune‐mediated haemolytic anaemia exists with this bacterial species.