Estimation of the probability for exceeding thresholds of urine specific gravity and plasma concentration of furosemide at various intervals after intravenous administration of furosemide in horses

OBJECTIVE: To estimate the probability of concurrently exceeding thresholds for plasma concentration of furosemide and urine specific gravity after IV administration of furosemide in horses. ANIMALS: 12 mature healthy Thoroughbred (n = 6) or Quarter Horse (6) mares. PROCEDURE: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after IV administration of 250 mg (first experiment) or 500 mg (second experiment) of furosemide. Urine was collected hourly between 1 and 6 hours after administration of furosemide at both doses. Concentrations of furosemide were determined by use of an ELISA. Concentration of furosemide and urine specific gravity was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic and specific gravity data, the probability of exceeding a concentration of 100 ng of furosemide/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess the inherent variation in this estimated probability. RESULTS: The estimated probability of exceeding the threshold of 100 ng of furosemide/ml and urine specific gravity < 1.012 was approximately 0% between 4.0 and 5.5 hours after IV administration of 250 mg of furosemide/horse, and ranged from 0 to 1% between 4 and 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified as in violation of regulatory concentrations was inversely associated with time. CONCLUSIONS AND CLINICAL RELEVANCE: Coupling plasma furosemide concentration with urine specific gravity testing will greatly reduce the chance that some horses are misclassified as being in violation of regulatory concentrations.     

Effects of exercise on tenocyte cellularity and tenocyte nuclear morphology in immature and mature equine digital tendons

REASON FOR PERFORMING STUDY: The injury-prone, energy-storing equine superficial digital flexor tendon (SDFT) of the mature performance horse has a limited ability to respond to exercise in contrast with the noninjury-prone, anatomically opposing common digital extensor tendon (CDET). Previous studies have indicated low levels of cellular activity in the mature SDFT, but in foal tendons the tenocytes may still have the ability to adapt positively to increased exercise. OBJECTIVES: To measure tenocyte densities and types in histological sections from the SDFT and CDET of horses from controlled long-term, short-term and foal exercise studies. METHODS: Specimens were collected from mid-metacarpal segments of the CDET and SDFT for each horse and processed for histology; central and peripheral regions of the SDFT cross-section were analysed separately (SDFTc, SDFTp). Tenocyte nuclei were counted in a total area of 1.59 mm(2) for each tendon region in each horse. Each nucleus was classified as type 1 (elongate and thin), type 2 (ovoid and plump) or type 3 (chondrocyte-like); type 1 cells are proposed to be less synthetically active than type 2 cells. RESULTS: No significant differences were noted between exercise and control groups in any of the studies, with the exception of an exercise-related reduction in the proportion of type 1 tenocytes for all tendons combined in the long-term study. There were tendon- and site-specific differences in tenocyte densities and proportions of type 1 and 2 cells in all 3 studies. CONCLUSIONS AND POTENTIAL RELEVANCE: There was no indication that exercise increased tenocyte density or proportions of the (theoretically) more active type 2 cells in immature horses (short-term and foal studies), perhaps because the training regimens did not achieve certain threshold strain levels. In the foal study these findings can still be interpreted positively as evidence that the training regimen did not induce subclinical damage.     

Insulin Sensitivity in Thoroughbred Geldings: Effect of Weight Gain,Diet, and Exercise on Insulin Sensitivity in Thoroughbred Geldings

The effects of dietary energy source, controlled weight gain, and exercise restriction on insulin sensitivity (SI) were studied in mature Thoroughbred geldings with body condition scores (BCS) of 4.3 ± 0.1. Two dietary energy sources were used, one high in starch and sugar (HS; n = 9) and one high in fat and fiber (HF; n = 7), and horses were fed 20 Mcal digestible energy (DE)/day above maintenance requirements to encourage weight gain. Using the minimal model of glucose and insulin dynamics, no differences in SI between groups were noted before initiation of treatment concentrate feeding. After dietary acclimation, SI was decreased in HS (P < 0.01) as compared with HF. After 32 weeks of controlled weight gain (90.8 kg; final BCS, 7.0 ± 0.1), SI remained lower in HS (P = 0.07) but did not change from the preweight gain value. SI in HF did not change between the start and end of weight gain. After completion of weight gain, exercise was restricted for 2 weeks, resulting in a reduction in SI in HF (P = 0.03) but no change in HS. It was concluded that dietary energy source may be more influential than weight gain on SI in the mature Thoroughbred gelding between BCS 4 and 7. The higher SI found in horses consuming the HF diet appeared to be partially dependent on some level of physical activity.     

Hemodialysis in a dog with acute renal failure from currant toxicity

A 3 1/2-year-old Labrador retriever being presented for acute onset vomiting and lethargy was diagnosed with acute renal failure (ARF). The dog had ingested dried currants, a type of raisin. Hemodialysis was successfully performed to treat the ARE Raisin toxicity can cause ARF and warrants early recognition and aggressive treatment.     

Effect of Prophylactic Calcitriol Administration on Serum Ionized Calcium Concentrations after Parathyroidectomy: 78 Cases (2005–2015)

Background

Prophylactic administration of calcitriol has been suggested to mitigate the risk of hypocalcemia after parathyroidectomy. The effect of calcitriol on postoperative serum ionized calcium concentrations has not been evaluated in dogs after parathyroidectomy.

Hypothesis/Objectives

To determine the effect of prophylactic calcitriol administration on postoperative serum ionized calcium (iCa) concentrations in dogs with primary hyperthyroidism (PHPTH) treated by parathyroidectomy.

Animals

Seventy‐eight dogs with primary hyperparathyroidism treated surgically.

Methods

Multi‐institutional retrospective case study. Medical records from 2005 to 2015 were evaluated. Dogs were included if they had a diagnosis of PHPTH and had surgery to remove parathyroid tissue. Serum iCa concentrations were monitored for a minimum of 2 days postoperatively. Two study groups were evaluated: calcitriol administration and no calcitriol administration.

Results

Serial postoperative iCa concentrations measured at 12‐hour time intervals for 2 days postoperatively were positively associated with preoperative iCa concentrations. This association was evident at each time interval, and the effect of preoperative iCa concentrations on postoperative iCa concentrations decreased as time elapsed (12 hours, P < 0.0001; 24 hours, P < 0.0001; 36 hours, P < 0.04; and 48 hours, P = 0.01). Prophylactic calcitriol administration was not found to be significantly associated with postoperative iCa concentrations or its rate of decrease after parathyroidectomy.

Conclusion and Clinical Importance

We found no protective value in administering calcitriol prophylactically to prevent hypocalcemia in the immediate postoperative period (48 hours) after parathyroidectomy. Preoperative iCa concentrations had a significant positive association with postoperative iCa concentrations throughout the monitoring period.     

Modulation of innate and acquired immunity by an estrogenic dose of genistein in gonadectomized cats

Dietary genistein has potential as a surrogate estrogen to restore normal control of food intake in cats following gonadectomy. However, since genistein affects immunological responses in other species it is important to determine if there is any immunological effect of genistein in cats, before long-term feeding of it could be considered. It was hypothesized that the minimum estrogenic dose of genistein (peak serum concentration 0.276+/-0.055 microg/mL) would be associated with altered innate and acquired immunity in cats. Cats (n=8 per group) were surgically neutered then treated daily with either 0.5 microg estradiol subcutaneously, 100mg/kg genistein orally, or vehicle only for 38 days. Circulating CD4+ and CD8+ T cells, and CD21+ B cells were quantified using flow cytometry. Concanavalin-A induced lymphocyte proliferation was assayed using incorporation of tritiated thymidine. Indirect ELISA was used to assay serum IgG in response to a commercial vaccine. Neutrophil respiratory burst in response to opsonized zymosan was evaluated using flow cytometric detection of oxidized dihydrorhodamine. Delayed-type hypersensitivity was evaluated with formalin-killed Yersinia pseudotuberculosis. Genistein treatment decreased circulating CD8+ cells (P=0.006), increased neutrophil respiratory burst (P=0.034), and increased wheal formation at 24h (P=0.038) but decreased wheal formation at 72 h (P=0.012) following intradermal challenge with killed Y. pseudotuberculosis. There were no significant differences between genistein treated cats and the other treatment groups in any other parameters. It is concluded that the minimum estrogenic dose of genistein alters selected leukocyte responses in cats. Unexpected effects of genistein suggest that extrapolation from one species to other species may not be appropriate in regards to the effects of genistein on immunity.     

Disease control through fertility control: Secondary benefits of animal birth control in Indian street dogs

We sought to (1) survey sexually intact street dogs for a wide range of diseases in three cities in Rajasthan, India and (2) evaluate links between the health of non-treated dogs and both the presence and duration of animal birth control (ABC) programs. ABC regimes sterilize and vaccinate stray dogs in an attempt to control their population and the spread of rabies. They are commonly suggested to improve the health of those dogs they serve, but here we provide evidence that these benefits also extend to untreated dogs in the community.     

The year-round distribution and habitat preferences of Campbell albatross (Thalassarche impavida)

1. The use of miniaturized electronic tracking devices has illuminated our understanding of seabird distributions and habitat use, and how anthropogenic threats interact with seabirds in both space and time. To determine the year-round distribution of adult Campbell albatross (Thalassarche impavida), a single-island endemic, breeding only at Campbell Island in New Zealand's subantarctic, a total of 68 year-long location data sets were acquired from light-based geolocation data-logging tags deployed on breeding birds in 2009 and 2010.
2. During the incubation and chick-guard phases of the breeding season, birds used cool (<10°C) waters over the Campbell Plateau, but also ranged over deeper, shelf-break and oceanic waters (4,000–5,500 m) beyond the Plateau. Later in the breeding season, during post-guard chick-rearing, Campbell albatrosses exploited generally deep waters (4,000–5,000 m) beyond the Campbell Plateau.
3. During the non-breeding period, adults tended to move northwards into warmer (approximately 15°C) waters and occupied areas beyond western Australia in the west to offshore from Chile in the east. Overall, about 30% of adults spent some of their non-breeding period in the central and eastern Pacific Ocean, substantially expanding the previously reported range for this species.
4. One bird, that failed in its breeding attempt in October 2009, departed Campbell Island and circumnavigated the southern oceans before being recaptured back at Campbell Island in October 2010. This is the first example of an annually-breeding albatross species completing a circumnavigation between breeding attempts.
5. Overlap with fishing effort, using data from the Global Fishing Watch database, was assessed on a monthly and seasonal basis. Generally, levels of overlap between Campbell albatross and fishing effort were relatively low during the breeding season but were approximately 60% higher during the non-breeding period, underlining the need for international initiatives to safeguard this species.

     

BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis

BAX and BAK are "multidomain" proapoptotic proteins that initiate mitochondrial dysfunction but also localize to the endoplasmic reticulum (ER). Mouse embryonic fibroblasts deficient for BAX and BAK (DKO cells) were found to have a reduced resting concentration of calcium in the ER ([Ca2+]er) that results in decreased uptake of Ca2+ by mitochondria after Ca2+ release from the ER. Expression of SERCA (sarcoplasmic-endoplasmic reticulum Ca2+ adenosine triphosphatase) corrected [Ca2+]er and mitochondrial Ca2+ uptake in DKO cells, restoring apoptotic death in response to agents that release Ca2+ from intracellular stores (such as arachidonic acid, C2-ceramide, and oxidative stress). In contrast, targeting of BAX to mitochondria selectively restored apoptosis to "BH3-only" signals. A third set of stimuli, including many intrinsic signals, required both ER-released Ca2+ and the presence of mitochondrial BAX or BAK to fully restore apoptosis. Thus, BAX and BAK operate in both the ER and mitochondria as an essential gateway for selected apoptotic signals.