Intraoperative Ultrasound Applications in Intracranial Surgery.

The methods and use of intraoperative ultrasound in 33 canine and five feline patients and its ability to localize and identify anatomical structures and pathological lesions in canines and felines undergoing intracranial surgery are described from a case series. All were client-owned referral patients admitted for neurologic evaluation, with an advanced imaging diagnosis of an intracranial lesion, and underwent surgical biopsy or surgical removal of the lesion. Medical records, retrieval and review of imaging reports, and characterization of findings for all canine and feline patients show that intraoperative ultrasound guidance was used in intracranial procedures during the period of 2012 and 2019. Twenty-nine of the canine patients had intracranial tumors. The remainder had various other conditions requiring intracranial intervention. Three of the feline patients had meningiomas, one had a depressed skull fracture, and one had an epidural hematoma. The tumors appeared hyperechoic on intraoperative ultrasound with the exception of cystic portions of the masses and correlated with the size and location seen on advanced imaging. Statistical comparison of the size of images seen on ultrasound and on MRI for 20 of the canine tumors revealed no statistical differences. Neuroanatomical structures, including vascular components, were easily identified, and tumor images correlated well with preoperative advanced imaging. The authors conclude that intraoperative ultrasound is a valuable asset in intracranial mass removals and can augment surgical guidance in a variety of intracranial disorders that require surgery. This is the first known publication in veterinary surgery of using intraoperative ultrasound as a tool in the operating theater to identify, localize, and monitor the removal/biopsy of intracranial lesions in small animals undergoing craniotomy/craniectomy.

Beneficial impact of exogenous arginine, cysteine and methionine on postharvest senescence of broccoli.

This study examined the ability of l-arginine, l-cysteine and l-methionine, to inhibit postharvest senescence of broccoli. Florets were dipped in aqueous solutions of the amino acids at concentrations from 1.0 to 100 mM and stored at 10 °C. A 5 mM dip was found to be optimal in delaying senescence as measured by retention of green colour, vitamin C and antioxidant activity, and a lower level of ethylene production, respiration, weight loss, phenylalanine ammonia lyase (PAL) activity and ion leakage with the benefits being similar for all three amino acids. Arginine, cysteine and methionine have Generally Recognised As Safe (GRAS) status and should have few impediments in obtaining regulatory approval for commercial use if similar effects were found for other leafy vegetables.

Overturning circulation, nutrient limitation, and warming in the Glacial North Pacific.

Although the Pacific Ocean is a major reservoir of heat and CO2, and thus an important component of the global climate system, its circulation under different climatic conditions is poorly understood. Here, we present evidence that during the Last Glacial Maximum (LGM), the North Pacific was better ventilated at intermediate depths and had surface waters with lower nutrients, higher salinity, and warmer temperatures compared to today. Modeling shows that this pattern is well explained by enhanced Pacific meridional overturning circulation (PMOC), which brings warm, salty, and nutrient-poor subtropical waters to high latitudes. Enhanced PMOC at the LGM would have lowered atmospheric CO2-in part through synergy with the Southern Ocean-and supported an equable regional climate, which may have aided human habitability in Beringia, and migration from Asia to North America.

Evaluation of SNAP cPL, Spec cPL, VetScan cPL Rapid Test, and Precision PSL Assays for the Diagnosis of Clinical Pancreatitis in Dogs.

BACKGROUND: The sensitivity, specificity, and agreement of 4 diagnostic assays (SNAP canine pancreatic lipase (cPL), specific cPL (Spec cPL), VetScan cPL Rapid Test, and Precision PSL) for pancreatitis in dogs have not been directly compared. HYPOTHESIS/OBJECTIVES: To determine the level of agreement among each of the 4 assays and a clinical suspicion score, level of agreement among the assays, and sensitivity and specificity of each assay in a clinically relevant patient group. ANIMALS: Fifty client-owned dogs with clinical signs of gastrointestinal disease. METHODS: Prospective study. History, physical examination, complete blood count, serum biochemistry, abdominal ultrasound examination, and the 4 diagnostic assays for pancreatitis were performed. Intraclass correlation coefficients (ICC) were used to determine the level of agreement between each assay and a clinical suspicion score determined by a panel of 5 board-certified veterinary internists. RESULTS: The ICC between the clinical suspicion score and the 4 assays were SNAP cPL, 0.61; Spec cPL, 0.68; VetScan cPL Rapid Test, 0.68; and Precision PSL, 0.60. The sensitivities of the assays ranged from 73.9 to 100.0%, whereas the specificities were SNAP cPL, 71.1-77.8%; Spec cPL, 74.1-81.1%; VetScan cPL Rapid Test, 76.9-83.8%; and Precision PSL, 64.0-74.3%. CONCLUSIONS AND CLINICAL IMPORTANCE: A good to excellent level of agreement was demonstrated among the 4 assays. The previously unreported sensitivity and specificity of the VetScan cPL Rapid Test were 73.9-83.3% and 76.9-83.8%, respectively. Results of any of the 4 diagnostic assays alone, in the absence of supporting clinical findings, are insufficient to establish a diagnosis of clinical pancreatitis in dogs.

In vivo effects of aspirin and cyclosporine on regulatory T cells and T-cell cytokine production in healthy dogs.

Cyclosporine and aspirin are routinely used in combination to treat immune-mediated hemolytic anemia (IMHA) in dogs. Cyclosporine is a potent immunosuppressive agent that targets T cell production of the cytokines IL-2 and IFN-γ. Low-dose aspirin is often used to inhibit platelet function in dogs with IMHA, since these animals are prone to life-threatening thromboembolic disease. In rodents and humans, aspirin and cyclosporine have both been shown to variably affect T cell cytokine production, and also numbers of circulating regulatory T cells (Tregs). In dogs, it has not yet been determined if concurrent aspirin alters the effects of cyclosporine on T-cell cytokine expression, or if either drug influences Treg numbers. In a crossover study, seven healthy young adult dogs were given either oral high-dose cyclosporine (10 mg/kg Q12 h), oral low-dose aspirin (1 mg/kg Q24 h), oral high-dose aspirin (10 mg/kg Q12 h), or combined low-dose aspirin with cyclosporine, each for 8 days, with a washout of at least 2 weeks after each treatment. Activated T cell cytokine expression (IL-2 & IFN-γ) and percent CD4 + CD25 + FOXP3+ Tregs were evaluated using flow cytometry, both prior to and on the last day of treatment. The difference between pre- and post-treatment values for each group, as well as the difference between treatment groups, was evaluated. Cyclosporine significantly decreased IL-2 and IFN-γ expression when used alone or in combination with low-dose aspirin. High-dose aspirin, but not low-dose aspirin, also significantly decreased IL-2 expression, although the decrease was not as marked as that seen with cyclosporine alone or in combination with aspirin. Neither low-dose nor high-dose aspirin significantly affected IFN-γ expression. No drug or drug combination affected Treg numbers. Low-dose aspirin given with cyclosporine creates the same degree of T-cell cytokine suppression as does cyclosporine alone, suggesting that the two drugs can be used concurrently without significantly altering the immunosuppressive mechanism of action of cyclosporine.

Effects of aspirin dose escalation on platelet function and urinary thromboxane and prostacyclin levels in normal dogs.

Established "low" aspirin dosages inconsistently inhibit platelet function in dogs. Higher aspirin dosages consistently inhibit platelet function, but are associated with adverse effects. The objectives of this study were to use an escalation in dosage to determine the lowest aspirin dosage that consistently inhibited platelet function without inhibiting prostacyclin synthesis. Eight dogs were treated with five aspirin dosages: 0.5 mg/kg q24h, 1 mg/kg q24h, 2 mg/kg q24h, 4 mg/kg q24h and 10 mg/kg q12h for 7 days. Utilizing aggregometry and a whole-blood platelet function analyzer (PFA-100), platelet function was evaluated before and after treatment. Urine 11-dehydro-thromboxane-B2 (11-dTXB2 ) and 6-keto-prostaglandin-F1α (6-keto-PGF1α ), were measured. Compared to pretreatment, there were significant post-treatment decreases in the maximum aggregometry amplitude and increases in the PFA-100 closure times for all dosages expect 0.5 mg/kg q24h. There was no difference in amplitude or closure time among the 2 mg/kg q24h, 4 mg/kg q24h, and 10 mg/kg q12h dosages. Compared to pretreatment values, there was a significant decrease in urinary 11-dTXB2 -to-creatinine and 6-keto-PGF1α -to-creatinine ratios, but there was no dose-dependent decrease for either metabolite. An aspirin dosage of 2 mg/kg q24h consistently inhibits platelet function without decreasing prostacyclin synthesis significantly more than lower aspirin dosages.

Acetylation and methylation of sperm histone 3 lysine 27 (H3K27ac and H3K27me3) are associated with bull fertility.

Epigenetic modifications in histones are crucial for proper sperm physiology, egg activation and reproductive development of males. The objectives of this study were to determine the conservation and interactomes of histone three (H3) and ascertain the expression dynamics of acetylated and methylated H3 lysine 27 (H3K27ac and H3K27me3) in spermatozoa from Holstein bulls with different fertility. Methods in immunocytochemistry and flow cytometry were used to evaluate the expression dynamics of H3K27ac and H3K27me3 in spermatozoa from 10 bulls with different in vivo fertility. Computational biology methods including Clustal Omega and Cytoscape were performed to determine the evolutionary conservation and interactome of H3. The post-translational modifications (PTM) of H3 (H3K27ac and H3K27me3) had different spatiotemporal dynamics in the sperm head. Intensities of methylation were higher than those of acetylation and inversely correlated between the two fertility groups (p = .0032). The interacting proteins of H3 are involved in critical subcellular processes such as regulation of methylation, nucleosome assembly, regulation of DNA replication and chromatin assembly. These results are significant because they help advance fundamental science and biotechnology of mammalian reproduction.

Effects of Leukoreduction and Storage on Erythrocyte Phosphatidylserine Expression and Eicosanoid Concentrations in Units of Canine Packed Red Blood Cells.

BACKGROUND: Storage of canine packed red blood cells (pRBCs) can increase erythrocyte phosphatidylserine (PS) expression and eicosanoid concentrations. HYPOTHESIS/OBJECTIVES: To determine the effects of leukoreduction on erythrocyte PS expression and eicosanoid concentrations in stored units of canine pRBCs. Our hypothesis was that leukoreduction would decrease PS expression and eicosanoid concentrations. ANIMALS: Eight healthy dogs. METHODS: In a cross-over study, units of whole blood were leukoreduced (LR) or non-LR and stored (10 and 21 days) as pRBCs. Samples were collected at donation, and before and after a simulated transfusion. PS expression was measured by flow cytometry, and concentrations of arachidonic acid (AA), prostaglandin F2α (PGF2α ), prostaglandin E2 (PGE2 ), prostaglandin D2 (PGD2 ), thromboxane B2 (TXB2 ), 6-keto-prostaglandin F1α (6-keto-PGF1α ), and leukotriene B4 (LTB4 ) were quantified by liquid chromatography-mass spectrometry. RESULTS: There was no change in PS expression during leukoreduction, storage, and simulated transfusion for non-LR and LR units. Immediately after leukoreduction, there was a significant increase in TXB2 and PGF2α concentrations, but during storage, these eicosanoids decreased to non-LR concentrations. In both LR and non-LR units, 6-keto-PGF1α concentrations increased during storage and simulated transfusion, but there was no difference between unit type. There was no difference in AA, LTB4 , PGE2 , and PGD2 concentrations between unit types. CONCLUSIONS AND CLINICAL IMPORTANCE: Leukoreduction, storage, and simulated transfusion do not alter erythrocyte PS expression. Leukoreduction causes an immediate increase in concentrations of TXB2 and PGF2α , but concentrations decrease to non-LR concentrations with storage. Leukoreduction does not decrease the accumulation of 6-keto-PGF1α during storage.

The effects of clopidogrel and omeprazole on platelet function in normal dogs.

Omeprazole is used concurrently with clopidogrel to reduce gastrointestinal adverse effects. In humans, the concurrent use of these two drugs can reduce the antiplatelet efficacy of clopidogrel. Our objective was to determine the effects of omeprazole and clopidogrel on platelet function in healthy dogs. A crossover study utilized turbidimetric aggregometry (ADP and collagen) and the PFA-100® with the collagen/ADP cartridge to evaluate platelet function in eight healthy dogs during the administration of clopidogrel (1 mg/kg/24 h p.o.), omeprazole (1 mg/kg/24 h p.o.), and a combination of clopidogrel and omeprazole. Drug metabolite concentrations were also measured. Compared to pretreatment, on Days 3 and 5, with ADP as the agonist, there was a significant decrease in maximum amplitude on aggregometry for both clopidogrel and clopidogrel/omeprazole groups. The following revealed no significant differences between clopidogrel and clopidogrel/omeprazole groups when compared on Days 3 and 5: maximum amplitude on aggregometry with ADP or collagen agonists, and PFA-100® closure times. When compared to the clopidogrel group, clopidogrel metabolite concentrations in the clopidogrel/omeprazole group were significantly higher on Days 3 and 5. The concurrent administration of omeprazole and clopidogrel in healthy dogs was associated with an increase in the plasma concentration of an inactive metabolite of clopidogrel, but does not significantly alter the antiplatelet effects of clopidogrel.

Rickettsia parkeri and "Candidatus Rickettsia andeanae" in Questing Amblyomma maculatum (Acari: Ixodidae) From Mississippi.

Amblyomma maculatum Koch (Acari: Ixodidae), the primary vector for Rickettsia parkeri, may also be infected with a rickettsia of unknown pathogenicity, "Candidatus Rickettsia andeanae." Infection rates with these rickettsiae vary geographically, and coinfected ticks have been reported. In this study, infection rates of R. parkeri and "Ca. R. andeanae" were evaluated, and rickettsial DNA levels quantified, in 335 questing adult A. maculatum collected in 2013 (n = 95), 2014 (n = 139), and 2015 (n = 101) from Oktibbeha County, MS. Overall infection rates of R. parkeri and "Ca. R. andeanae" were 28.7% and 9.3%, respectively, with three additional A. maculatum (0.9%) coinfected. While R. parkeri-infected ticks were detected all three years (34.7% in 2013; 13.7% in 2014; 43.6% in 2015), "Ca. R. andeanae" was not detected in 2013, and was detected at rates of 10.8% in 2014, and 15.8% in 2015. Interestingly, rickettsial DNA levels in singly-infected ticks were significantly lower in "Ca. R. andeanae"-infected ticks compared to R. parkeri-infected ticks (P < 0.0001). Thus, both infection rates and rickettsial DNA levels were higher for R. parkeri than "Ca. R. andeanae." Infection rates of R. parkeri were also higher, and "Ca. R. andeanae" lower, here compared to A. maculatum reported previously in Kansas and Oklahoma. As we continue to monitor infection rates and levels, we anticipate that understanding temporal changes will improve our awareness of human risk for spotted fever rickettsioses. Further, these data may lead to additional studies to evaluate potential interactions among sympatric Rickettsia species in A. maculatum at the population level.

The Effects of Cyclosporine and Aspirin on Platelet Function in Normal Dogs.

BACKGROUND: Cyclosporine increases thromboxane synthesis in dogs, potentially increasing the thrombogenic properties of platelets. HYPOTHESIS/OBJECTIVES: Our hypothesis was that the concurrent administration of low-dose aspirin and cyclosporine would inhibit cyclosporine-associated thromboxane synthesis without altering the antiplatelet effects of aspirin. The objective was to determine the effects of cyclosporine and aspirin on primary hemostasis. ANIMALS: Seven healthy dogs. METHODS: A randomized, crossover study utilized turbidimetric aggregometry and a platelet function analyzer to evaluate platelet function during the administration of low-dose aspirin (1 mg/kg PO q24h), high-dose aspirin (10 mg/kg PO q12h), cyclosporine (10 mg/kg PO q12h), and combined low-dose aspirin and cyclosporine. The urine 11-dehydro-thromboxane-B2 (11-dTXB2 )-to-creatinine ratio also was determined. RESULTS: On days 3 and 7 of administration, there was no difference in the aggregometry amplitude or the platelet function analyzer closure time between the low-dose aspirin group and the combined low-dose aspirin and cyclosporine group. On day 7, there was a significant difference in amplitude and closure time between the cyclosporine group and the combined low-dose aspirin and cyclosporine group. High-dose aspirin consistently inhibited platelet function. On both days, there was a significant difference in the urinary 11-dTXB2 -to-creatinine ratio between the cyclosporine group and the combined low-dose aspirin and cyclosporine group. There was no difference in the urinary 11-dTXB2 -to-creatinine ratio among the low-dose aspirin, high-dose aspirin, and combined low-dose aspirin and cyclosporine groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Low-dose aspirin inhibits cyclosporine-induced thromboxane synthesis, and concurrent use of these medications does not alter the antiplatelet effects of aspirin.

Effects of oral cyclosporine on canine T-cell expression of IL-2 and IFN-gamma across a 12-h dosing interval.

The duration of immunosuppressive effects following oral cyclosporine in dogs is unknown. This study used flow cytometry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to evaluate the effects of high-dose oral cyclosporine across a 12-h dosing interval. Expression of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) was compared before and after 8 days of cyclosporine at 10 mg/kg every 12 h in six healthy dogs. Samples were collected at 0, 2, 4, and 8 h postdosing for analysis of unactivated and activated T-cell and whole blood cytokine expression using flow cytometry and qRT-PCR, respectively, and at 0, 2, 4, 6, 8, and 10 h postdosing for measurement of cyclosporine concentrations. Flow cytometry and qRT-PCR both demonstrated significant marked reductions in IL-2 and IFN-γ levels at 0, 2, 4, and 8 h after dosing compared to pretreatment levels (P < 0.05) for activated samples, with less consistent effects observed for unactivated samples. Both flow cytometry and qRT-PCR are viable techniques for measuring cyclosporine pharmacodynamics in dogs, yielding comparable results with activated samples. Two hours postdrug administration is the preferred time for concurrent assessment of peak drug concentration and cytokine expression, and T-cell activation is needed for optimal results.

Use of the cortisol-to-ACTH ratio for diagnosis of primary hypoadrenocorticism in dogs.

BACKGROUND: The ACTH stimulation test is currently required for definitive diagnosis of hypoadrenocorticism. Increased cost of synthetic ACTH (cosyntropin) has prompted a search for alternative diagnostic methods. OBJECTIVE: The purpose of this study was to determine whether a cortisol-to-ACTH ratio (CAR) can be used to differentiate dogs with hypoadrenocorticism from normal dogs and those with nonadrenal illness. ANIMALS: Eight healthy dogs (H), 19 dogs with nonadrenal illness (NAI), and 15 dogs with hypoadrenocorticism (HAD). METHODS: Dogs in the HAD group were retrospectively identified from PUVTH medical records. The NAI group consisted of hospitalized dogs with clinical signs, clinicopathologic findings, or both, consistent with a diagnosis of hypoadrenocorticism, but in which hypoadrenocorticism was ruled out based on ACTH stimulation test results. Healthy dogs were recruited from hospital staff and students. Endogenous ACTH concentrations and cortisol concentrations before and after ACTH stimulation were measured in all dogs. RESULTS: Baseline cortisol concentration was significantly lower, and ACTH concentration was significantly higher, in the HAD group versus the H and NAI group (P < .001). However, there was overlap among groups. Cortisol-to-ACTH ratio was significantly lower in the HAD group versus the H and NAI groups (P < .001), and there was no overlap between the HAD group and the other 2 groups. CONCLUSIONS AND CLINICAL IMPORTANCE: CAR can be used for definitive diagnosis of primary hypoadrenocorticism.

Tensile properties in collagen-rich tissues of Quarter Horses with hereditary equine regional dermal asthenia (HERDA).

REASONS FOR PERFORMING STUDY: Hereditary equine regional dermal asthenia (HERDA) is an autosomal recessive disorder of Quarter Horses characterised by skin fragility. Horses with HERDA have a missense mutation in peptidyl-prolyl cis-trans isomerase B (PPIB), which encodes cyclophilin B and alters folding and post translational modifications of fibrillar collagen. OBJECTIVES: The study aimed to test the hypothesis that tendons, ligaments and great vessels, which, like skin, are rich in fibrillar collagen, will also have abnormal biomechanical properties in horses with HERDA. STUDY DESIGN: Ex vivo biomechanical study comparing horses with and without a diagnosis of HERDA. METHODS: Forelimb suspensory ligament, superficial and deep digital flexor tendons; withers, forelimb and abdominal skin; the main pulmonary artery and the aortic arch were harvested from 6 horses with HERDA and 6 control horses without the HERDA allele. Tissues were distracted to failure. Tensile strength (TS), elastic modulus (EM) and energy to failure (ETF) were compared. RESULTS: Horses with HERDA had significantly lower TS and EM in tendinoligamentous tissues and great vessels, respectively. The TS, EM and ETF were significantly lower in skin from horses with HERDA. Differences in TS and ETF were more extreme at the withers than at the forelimb or abdomen. CONCLUSIONS: Tendinoligamentous tissue, great vessels and skin are significantly weaker in horses with HERDA than in horses lacking the PPIB mutation, substantiating that diverse tissues with high fibrillar collagen content are abnormal in HERDA and that the HERDA phenotype is not limited to the integument.

Cyclooxygenase expression and platelet function in healthy dogs receiving low-dose aspirin.

BACKGROUND: Low-dose aspirin is used to prevent thromboembolic complications in dogs, but some animals are nonresponsive to the antiplatelet effects of aspirin ("aspirin resistance"). HYPOTHESIS/OBJECTIVES: That low-dose aspirin would inhibit platelet function, decrease thromboxane synthesis, and alter platelet cyclooxygenase (COX) expression. ANIMALS: Twenty-four healthy dogs. METHODS: A repeated measures study. Platelet function (PFA-100 closure time, collagen/epinephrine), platelet COX-1 and COX-2 expression, and urine 11-dehydro-thromboxane B(2) (11-dTXB(2)) were evaluated before and during aspirin administration (1 mg/kg Q24 hours PO, 10 days). Based on prolongation of closure times after aspirin administration, dogs were divided into categories according to aspirin responsiveness: responders, nonresponders, and inconsistent responders. RESULTS: Low-dose aspirin increased closure times significantly (62% by Day 10, P < .001), with an equal distribution among aspirin responsiveness categories, 8 dogs per group. Platelet COX-1 mean fluorescent intensity (MFI) increased significantly during treatment, 13% on Day 3 (range, -29.7-136.1%) (P = .047) and 72% on Day 10 (range, -0.37-210%) (P < .001). Platelet COX-2 MFI increased significantly by 34% (range, -29.2-270%) on Day 3 (P = .003) and 74% (range, -19.7-226%) on Day 10 (P < .001). Urinary 11-dTXB(2) concentrations significantly (P = .005, P < .001) decreased at both time points. There was no difference between aspirin responsiveness and either platelet COX expression or thromboxane production. CONCLUSIONS AND CLINICAL IMPORTANCE: Low-dose aspirin consistently inhibits platelet function in approximately one-third of healthy dogs, despite decreased thromboxane synthesis and increased platelet COX expression in most dogs. COX isoform expression before treatment did not predict aspirin resistance.

Analytical validation of a quantitative reverse transcriptase polymerase chain reaction assay for evaluation of T-cell targeted immunosuppressive therapy in the dog.

Cyclosporine is an immunosuppressive agent that inhibits T-cell function by decreasing production of cytokines such as interleukin-2 (IL-2) and interferon-γ(IFN-γ). In dogs, there is currently no reliable analytical method for determining effective cyclosporine dosages in individual patients. Our laboratory has developed a quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) assay that measures IL-2 and IFN-γ gene expression, with the goal of quantifying immunosuppression in dogs treated with cyclosporine. This study focuses on analytical validation of our assay, and on the effects of sample storage conditions on cyclosporine-exposed samples. Heparinized whole blood collected from healthy adult dogs was exposed to a typical post-treatment blood concentration for cyclosporine(500 ng/mL) for 1 h, and then stored for 0, 24, and 48 h at both room temperature and 4 ◦C.The study was then repeated using a cyclosporine concentration of 75 ng/mL, with sample storage for 0, 24, and 48 h at 4 ◦C. Cytokine gene expression was measured using RT-qPCR,and assay efficiency and inter- and intra-assay variability were determined. Storage for upto 24 h at room temperature, and up to 48 h at 4 ◦C, did not significantly alter results compared to samples that were processed immediately. Validation studies showed our assay to be highly efficient and reproducible and robust enough to be feasible under standard practice submission conditions.

The effects of cyclosporine on platelet function and cyclooxygenase expression in normal dogs.

BACKGROUND: Cyclosporine has been shown to alter platelet plasma membranes and have a hypercoagulable effect in humans, leading to thromboembolic complications. HYPOTHESIS/OBJECTIVES: Our hypothesis was that by modulating platelet reactivity, cyclosporine increases the risk of thromboembolic complications. The objective was to determine the effects of cyclosporine on primary hemostasis in normal dogs. ANIMALS: Eight healthy, intact female dogs. METHODS: A repeated-measures design utilized flow cytometry to evaluate platelet expression of platelet reactivity markers (P-selectin and phosphatidylserine) and COX-1 and COX-2 during the administration of 2 cyclosporine dosages (19 mg/kg q12h [immunosuppressive dosage] and 5 mg/kg q24h [atopy dosage]). Urine 11-dehydro-thromboxane-B(2) (11-dTXB(2) ) concentration was normalized to urine creatinine concentration, and platelet function was analyzed by PFA-100. RESULTS: After a week of the immunosuppressive dosage, all platelet reactivity markers showed a significant decrease in mean fluorescent intensity (MFI). After the atopy dosage, only P-selectin and COX-2 MFI demonstrated a change from baseline, decreasing by 29% (P = .013) and 31% (P = .003), respectively. Urinary 11-dTXB(2) -to-creatinine ratio significantly increased at all time points during the immunosuppressive dosage, but no significant change occurred during administration of the atopy dosage. PFA-100 closure times using collagen/ADP cartridges increased by 62% (P = .008) with the immunosuppressive dosage and decreased by 45% with the atopy dosage (P = .035). No significant changes in closure times occurred with collagen/epinephrine cartridges. CONCLUSIONS AND CLINICAL IMPORTANCE: Our study suggests that, similar to what is observed in humans, cyclosporine alters the platelet plasma membrane and increases thromboxane production in dogs, especially at immunosuppressive dosages.

Evaluating interventions against Salmonella in broiler chickens: applying synthesis research in support of quantitative exposure assessment.

A scoping study and systematic review-meta-analyses (SR-MAs) were conducted to evaluate the effectiveness of various interventions for Salmonella in broiler chicken, from grow-out farm to secondary processing. The resulting information was used to inform a quantitative exposure assessment (QEA) comparing various control options within the context of broiler chicken production in Ontario, Canada. Multiple scenarios, including use of two separate on-farm interventions (CF3 competitive exclusion culture and a 2% lactose water additive), a package of processing interventions (a sodium hydroxide scald water disinfectant, a chlorinated post-evisceration spray, a trisodium phosphate pre-chill spray and chlorinated immersion chilling) a package consisting of these farm and processing interventions and a hypothetical scenario (reductions in between-flock prevalence and post-transport concentration), were simulated and compared to a baseline scenario. The package of on-farm and processing interventions was the most effective in achieving relative reductions (compared to baseline with no interventions) in the concentration and prevalence of Salmonella by the end of chilling ranging from 89·94% to 99·87% and 43·88% to 87·78%, respectively. Contaminated carcasses entering defeathering, reductions in concentration due to scalding and post-evisceration washing, and the potential for cross-contamination during chilling had the largest influence on the model outcomes under the current assumptions. Scoping study provided a transparent process for mapping out and selecting promising interventions, while SR-MA was useful for generating more precise and robust intervention effect estimates for QEA. Realization of the full potential of these methods was hampered by low methodological soundness and reporting of primary research in this area.

Platelet cyclooxygenase expression in normal dogs.

BACKGROUND: Human platelets express both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Variation in COX-2 expression could be a mechanism for variable response to aspirin. HYPOTHESIS/OBJECTIVES: The hypotheses were that circulating canine platelets express COX-1 and COX-2, and that aspirin alters COX expression. The objective was to identify changes in platelet COX expression and in platelet function caused by aspirin administration to dogs. ANIMALS: Eight female, intact hounds. METHODS: A single population, repeated measures design was used to evaluate platelet COX-1 and COX-2 expression by flow cytometry before and after aspirin (10 mg/kg Q12h for 10 days). Platelet function was analyzed via PFA-100(®) (collagen/epinephrine), and urine 11-dehydro-thromboxane B(2) (11-dTXB(2)) was measured and normalized to urinary creatinine. Differences in COX expression, PFA-100(®) closure times, and urine 11-dTXB(2 ): creatinine ratio were analyzed before and after aspirin administration. RESULTS: Both COX-1 and COX-2 were expressed in canine platelets. COX-1 mean fluorescent intensity (MFI) increased in all dogs, by 250% (range 63-476%), while COX-2 expression did not change significantly (P = 0.124) after aspirin exposure, with large interindividual variation. PFA-100(®) closure times were prolonged and urine 11-dTXB(2) concentration decreased in all dogs after aspirin administration. CONCLUSIONS AND CLINICAL IMPORTANCE: Canine platelets express both COX isoforms. After aspirin exposure, COX-1 expression increased despite impairment of platelet function, while COX-2 expression varied markedly among dogs. Variability in platelet COX-2 expression should be explored as a potential mechanism for, or marker of, variable aspirin responsiveness.