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Background Trazodone is a serotonin antagonist/reuptake inhibitor medication commonly used for anxiety in dogs. Therapy with selective serotonin reuptake inhibitors in humans is associated with bleeding disorders and increased arrhythmogenesis. Hypothesis/Objectives To evaluate markers of primary hemostasis and corrected QT (cQT) interval in dogs before and after oral administration of standard dosages of trazodone or placebo. Animals Fifteen apparently healthy, client‐owned dogs. Methods A single‐blinded, randomized placebo‐controlled crossover study was performed. Dogs were administered trazodone (5 to 7.5 mg/kg PO Q12h) or placebo. [Correction added after first online publication on 14 October 2023. In the (methods) section (57.5 mg/kg PO Q12h) changed as (5 to 7.5 mg/kg PO Q12h).] Buccal mucosal bleeding time (BMBT), platelet count, platelet aggregation via Plateletworks, PFA‐100 closure time and cQT interval were measured. A Shapiro‐Wilk test was performed followed by either a paired t test or a Wilcoxon signed‐rank test. Results No significant difference was detected in the BMBT, PFA‐100 closure times, platelet counts, and cQT interval between trazodone or placebo. However, using Plateletworks, there was a significant decrease in platelet aggregation after administration of trazodone (95%; 81‐97 vs 62%; 39‐89, P = .002) and not placebo (95%; 81‐97 vs 91%; 81‐96, P = .21). Conclusions It is unknown if this represents a clinically relevant change or if dogs with preexisting impairment in primary hemostasis or receiving higher dosages or longer durations of trazodone could have a more substantial change in hemostatic variables.

Global warming has the potential to reduce arctic sea ice and thereby increase the length of summer–fall fasting when polar bears (Ursus maritimus) lose access to most marine mammals. To evaluate the consequences of such changes, we compared the cost of fasting by polar bears with hibernation by brown bears (U. arctos), American black bears (U. americanus), and polar bears and made projections about tissue reserves polar bears will need to survive and reproduce as fasts become longer. Hibernating polar bears expend energy at the same rate per unit mass as do brown bears and black bears. However, daily mass losses, energy expenditures, and the losses of lean mass are much higher in fasting, active polar bears than in hibernating bears. The average pregnant polar bear living around Hudson Bay during the 1980s and 1990s could fast for 10.0 ± 2.3 months (X̄ ± SD), and the average lactating female with cubs born during the preceding winter could fast for 4.2 ± 1.9 months. Thus, some pregnant or lactating females with lower levels of body fat content were already approaching or beyond the constraint of being able to produce cubs and survive the required 8 months of fasting if producing new offspring or 4 months if accompanied by older offspring. Pregnant or lactating females and their dependent offspring have the most tenuous future as global warming occurs. Thus, we predict a significant reduction in productivity with even modest increases in global warming for polar bears living in the very southern part of their range and are concerned about more northern populations depending on their ability to accumulate increasing amounts of fat.

At Animals Asia’s Vietnam Bear Rescue Center (VBRC), 40% of the current population has been diagnosed with systemic hypertension. Systemic hypertension lesions have led to fatal consequences in the form of aortic aneurysm and rupture. Historically, veterinarians were only able to diagnose systemic hypertension by identifying validated secondary structural heart and retinal lesions during annual health checks of anesthetized bears. In 2021, the VBRC began training bears for cooperative conscious blood pressure measurements to increase monitoring frequency and expedite the diagnosis of systemic hypertension in affected bears. The objective of this study was to evaluate a noninvasive method of blood pressure measurement in trained, cooperative Asiatic black bears. Indirect blood pressure measurements, using the oscillometric technique, were validated with direct arterial measurements in nine bears (6 male, 3 female, ages 13–22 years) undergoing anesthesia for annual health checks. Eleven trained bears at the VBRC without secondary lesions of systemic hypertension (6 male, 5 female, ages 7–23 years) were used to develop normal systolic ranges for Asiatic black bears using the indirect technique. Mean blood pressure measurements for this group of trained bears (n = 11) were 180.65 +/− 37 mmHg (95% CI: 126–255) systolic. These results suggest that indirect blood pressures may be a useful tool to monitor blood pressure in cooperative conscious bears at the VBRC.

Background Some studies in humans show that the concurrent use of clopidogrel and omeprazole decreases plasma clopidogrel active metabolite (CAM) concentrations and clopidogrel antiplatelet effects. Whether this drug interaction occurs in cats is unknown. Hypothesis We hypothesized that administration of clopidogrel with omeprazole would decrease plasma CAM concentrations and decrease clopidogrel antiplatelet effects in healthy cats. Animals Ten domestic cats. Methods In this 2‐sequence, 2‐period, 2‐treatment randomized crossover study, healthy cats were randomly assigned to receive clopidogrel only (18.75 mg PO q24h) or clopidogrel with omeprazole (1 mg/kg PO q12h) for 10 days, followed by a 2‐week washout period, and then the opposite treatment for another 10 days. Blood was collected by jugular venipuncture on days 0, 5, and 10. Plasma CAM concentrations were measured using high‐performance liquid chromatography‐tandem mass spectrometry. Platelet function was evaluated using Plateletworks, Multiplate Analyzer, and Platelet Function Analyzer‐100 (PFA‐100). Results Multiplate Analyzer and PFA‐100 detected no difference in platelet function between days or treatment groups. Plateletworks detected a significant difference (P < .001) in platelet function from day 0 to 5 and day 0 to 10 in both treatment groups but no difference between treatment groups. Plasma CAM concentrations were significantly lower on day 10 (P < .02) in cats receiving both medications versus clopidogrel only. Conclusions and Clinical Importance Concurrent omeprazole and clopidogrel administration was associated with altered pharmacokinetics on day 10, but no difference in pharmacodynamics between the 2 treatment groups. The short‐term use of clopidogrel and omeprazole does not seem to alter platelet function significantly.

Revealing the mechanisms underlying the reversible physiology of hibernation could have applications to both human and animal health as hibernation is often associated with disease-like states. The present study uses RNA-sequencing to reveal the tissue and seasonal transcriptional changes occurring in grizzly bears ( Ursus arctos horribilis ). Comparing hibernation to other seasons, bear adipose has a greater number of differentially expressed genes than liver and skeletal muscle. During hyperphagia, adipose has more than 900 differentially expressed genes compared to active season. Hibernation is characterized by reduced expression of genes associated with insulin signaling, muscle protein degradation, and urea production, and increased expression within muscle protein anabolic pathways. Across all three tissues we find a subset of shared differentially expressed genes, some of which are uncharacterized, that together may reflect a common regulatory mechanism. The identified gene families could be useful for developing novel therapeutics to treat human and animal diseases. Jansen, Trojahn, Saxton, et al. examine the transcriptional changes that occur during the seasonal cycle in grizzly bears. They find that during hibernation, adipose tissue has the largest number of differentially expressed genes of the three tissues examined, revealing potential therapeutic targets for human diseases.

The number, size, and survival of bear cubs emerging from winter dens depend on maternal condition prior to entering the den. We hypothesized that delayed implantation provides flexibility in timing of birth such that pregnant females are able to track environmental or body conditions long after conception to optimize reproductive output in a changing environment. We tested the hypotheses that causative links between maternal condition and size of newly emerging brown bear (Ursus arctos) cubs were females in superior condition give birth earlier and, thereby, lactate longer in the den than females in poorer condition; and females in superior condition produce more milk or higher quality milk, which accelerates cub growth relative to females in poorer condition. No brown bear with a body fat content ≤ 20% produced cubs even though breeding occurred. Brown bears that were fat gave birth earlier than those that were lean. Cubs nursing from fat mothers grew faster than those nursing from lean mothers. The combination of an earlier birth date and faster growth by cubs produced from fat mothers increased mass of brown bear and polar bear (U. maritimus) twins at den emergence by 330–360 g for each unit increase in percent maternal body fat content when entering hibernation.

Approximately 17,000 bears undergo bile extraction in facilities across Asia for traditional medicines despite the availability of proven alternatives. Bears are confined to cages and bile harvested from the gallbladder via needle aspiration, implanted catheters, or transabdominal fistulas. Bile-extracted bears develop numerous detrimental conditions, including abnormal repetitive behaviors, emaciation, dental disease, cholecystitis, hernias, abscesses, and neoplasia. A high prevalence of aortic dilation, commonly seen with systemic hypertension, was reported in bile-extracted bears, and aortic aneurysm rupture/dissection was the third leading cause of death in a population of 600 formerly bile-extracted bears. A high incidence of renal disease, a common cause of systemic hypertension in other species, was also identified in this population. We hypothesized that renal disease was positively correlated with lesions of systemic hypertension in bile-extracted bears. Archived medical records, imaging, and samples from 180 formerly bile-extracted bears were analyzed. Hypertensive retinopathy, left ventricular hypertrophy, and aortic dilation were used as validated correlates of systemic hypertension. The majority (76.1%) of bears exhibited at least one systemic hypertension lesion, and 62.8% had two or more lesions. Left ventricular hypertrophy was most common, followed by aortic dilation/aneurysm. Lesions of systemic hypertension were positively correlated to renal disease parameters of serum creatinine and renal histopathology. Understanding the etiology of systemic hypertension in this population is critical due to consequent comorbidities and increasing numbers of bile-extracted bears finding their way to sanctuary.

Titin is a giant protein that is in charge of the assembly and passive mechanical properties of the sarcomere. Cardiac titin contains a unique N2B region, which has been proposed to modulate elasticity of the titin filament and to be important for hypertrophy signaling and the ischemic stress response through its binding proteins FHL2 and αB-crystallin, respectively. To study the role of the titin N2B region in systole and diastole of the heart, we generated a knockout (KO) mouse deleting only the N2B exon 49 and leaving the remainder of the titin gene intact. The resulting mice survived to adulthood and were fertile. Although KO hearts were small, they produced normal ejection volumes because of an increased ejection fraction. FHL2 protein levels were significantly reduced in the KO mice, a finding consistent with the reduced size of KO hearts. Ultrastructural analysis revealed an increased extension of the remaining spring elements of titin (tandem Ig segments and the PEVK region), which, together with the reduced sarcomere length and increased passive tension derived from skinned cardiomyocyte experiments, translates to diastolic dysfunction as documented by echocardiography. We conclude from our work that the titin N2B region is dispensable for cardiac development and systolic properties but is important to integrate trophic and elastic functions of the heart. The N2B-KO mouse is the first titin-based model of diastolic dysfunction and, considering the high prevalence of diastolic heart failure, it could provide future mechanistic insights into the disease process.

Across China and Southeast Asia, over 17,000 bears are currently farmed for bile, predominantly for traditional Chinese medicines. Bears on farms in China are cage confined and undergo repeated daily bile extraction facilitated by surgically implanted catheters or gallbladder fistulas. Numerous health problems have been reported in bile-farmed bears including peritonitis, abdominal hernias, and extraction site abscessation. Between 2009 and 2014, five Asiatic black bears (Ursus thibetanus) and one Asiatic black/Eurasian brown bear (Ursus arctos arctos) hybrid, rescued from the bear bile industry in China, died from ruptured and/or dissecting aortic aneurysm. Medical records were reviewed and two bears exhibited no clinical signs prior to death. In four bears, clinical findings varied and included increased stereotypic behavior prior to death, epistaxis, retinal lesions, dysphagia, weight loss, and acute onset of hyporexia. On postmortem examination, hemopericardium with dissection and/or rupture of the ascending aorta and left ventricular wall hypertrophy were present in all cases. No evidence of infectious disease, connective tissue disorders, or congenital cardiac disease was identified. Based on these observations screening thoracic radiography was performed on all bears at the rescue center and aortic dilation was identified in 73 of 134 (54.5%) bile-extracted bears. To the authors' knowledge, aortic aneurysm, rupture, and/or dissection have not been previously reported in any bear species and the high prevalence in this population of bears suggests an association with bile-farming practices. Future studies are needed to investigate the etiopathogenesis of this condition to aid in early diagnosis and improved management of bears being rescued from bile farms across Asia.

Background Across China and Southeast Asia, an estimated 17,000 bears are currently farmed for bile, primarily for traditional medicines. Depending on country, bile is extracted daily via transabdominal gallbladder fistulas, indwelling catheters, or needle aspiration. Despite claims that bears do not develop adverse effects from bile extraction, health issues identified in bears removed from bile farms include bile-extraction site infections, abdominal hernias, peritonitis, cholecystitis, hepatic neoplasia, cardiac disease, skeletal abnormalities, and abnormal behaviors. We present a comprehensive assessment of the effects of bile farming by comparing serum biochemical and hematological values of bears from farms that were bile-extracted (BE) and bears from farms not bile-extracted (FNE) with bears from non-farm captive (ZOO) and free-range (FR) environments. We hypothesized BE bears would have significant laboratory abnormalities compared to all non-extracted bear groups. We also hypothesized BE bears would have reduced long-term survival compared to FNE bears despite removal from farms. Results BE bears exhibited the highest values and greatest variation (on a population level) in laboratory parameters compared to all non-extracted bear groups particularly for alanine transaminase, gamma glutamyltransferase (GGT), total bilirubin (TBIL), alkaline phosphatase (ALKP), blood urea nitrogen, creatinine (CREA), and total white blood cell count. Significant differences were detected between bear groups when accounting for season, sex, and/or age. BE bears exhibited greater mean serum GGT compared to all non-extracted bear groups, and the odds of having elevated TBIL were 7.3 times greater for BE bears, consistent with hepatobiliary disease. Biochemical parameter elevations in BE bears persisted up to 14 years post-rescue, consistent with long-term effects of bile-extraction. BE bears that arrived with elevated CREA and ALKP had median survival times of 1 and 4 years respectively, and regardless of laboratory abnormalities, BE bears had significantly shorter survival times compared to FNE bears. Conclusions Our results provide strong evidence that bile extraction practices not only represent a temporary constraint for bears’ welfare, but confer distinct long-term adverse health consequences. Routine laboratory panels may be insensitive to detect the extent of underlying illness in BE bears as these bears have significantly reduced survival regardless of biochemical assessment compared to FNE bears.