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Biochemical, functional, and histopathologic characterization of lomustine-induced liver injury in dogs
2020
Dedeaux, Andrea M. | Flesner, Brian K. | Reinhart, Jennifer M. | Langohr, Ingeborg M. | Husnik, Roman | Geraci, Shawn N. | Toboada, Joseph | Rademacher, Nathalie | Thombs, Lori A. | Bryan, Jeffrey N. | Trepanier, Lauren A. | Boudreaux, Bonnie B.
OBJECTIVE To characterize the biochemical, functional, and histopathologic changes associated with lomustine-induced liver injury in dogs. ANIMALS I0 healthy purpose-bred sexually intact female hounds. PROCEDURES Dogs were randomly assigned to receive lomustine (approx 75 mg/m2, PO, q 21 d for 5 doses) alone (n = 5) or with prednisone (approx 1.5 mg/kg, PO, q 24 h for 12 weeks; 5). For each dog, a CBC, serum biochemical analysis, liver function testing, urinalysis, and ultrasonographic examination of the liver with acquisition of liver biopsy specimens were performed before and at predetermined times during and after lomustine administration. Results were compared between dogs that did and did not receive prednisone. RESULTS 7 of the I0 dogs developed clinical signs of liver failure. For all dogs, serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, bile acid concentrations, and liver histologic score increased and hepatic reduced glutathione content decreased over time. Peak serum ALT (r = 0.79) and ALP (r = 0.90) activities and bile acid concentration (r = 0.68) were positively correlated with the final histologic score. Prednisone did not appear to have a protective effect on histologic score. CONCLUSIONS AND CLINICAL RELEVANCE In dogs, liver enzyme activities, particularly ALT and ALP activities, should be closely monitored during lomustine treatment and acute increases in those activities may warrant discontinuation of lomustine to mitigate liver injury. Nonspecific ultrasonographic findings and abnormal increases in liver function tests were not detected until the onset of clinical liver failure. Glutathione depletion may have a role in lomustine-induced hepatopathy and warrants further investigation.
Afficher plus [+] Moins [-]Randomized controlled trial to evaluate a novel two-catheter technique for urethral catheterization in anesthetized healthy female cats and small dogs
2020
Abrams, Brittany E. | Selmic, Laura E. | Howard, James | Horvath, Stephen J. | Bednarski, Linda | McLoughlin, Mary A. | Wavreille, Vincent A.
OBJECTIVE To evaluate a novel 2-catheter technique for urethral catheterization in female cats and small dogs and compare the time required for and success rates achieved by use of the novel technique versus traditional methods (blind technique in cats and digital palpation in dogs) as performed by personnel (catheter placers [CPs]) with different levels of experience in urinary catheter placement. ANIMALS 39 healthy sexually intact female animals (24 cats and 15 dogs weighing < 10 kg). PROCEDURES 2 CPs were board certified in veterinary surgery, 1 of whom had experience with the novel technique, and the other did not. The third CP was a veterinary surgical intern who was unfamiliar with the novel technique. For each animal enrolled in the study, 1 CP performed catheterization with the novel technique and traditional methods. Data recorded included the time required for successful catheterization and whether a successful catheterization was achieved within a 3-minute time limit. RESULTS The overall success rates were 79.5% (31/39 animals) with the novel technique and 43.6% (17/39 animals) with traditional methods. Median times for successful catheter placement were 48 seconds for the novel technique and 41 seconds for traditional methods. Among CPs, success rates or times to successful catheter placement did not differ significantly. CONCLUSIONS AND CLINICAL RELEVANCE Study results suggested that the novel 2-catheter technique for urethral catheterization may be a more efficient option than traditional methods for gaining access to the urinary bladder in cats and small dogs, particularly when patient size limits use of instrumentation or digital palpation.
Afficher plus [+] Moins [-]Salmonella enterica serovar Typhimurium gene sseK3 is required for intracellular proliferation and virulence
2020
Du, Fuyu | Liao, Chengshui | Yang, Yadong | Yu, Chuan | Zhang, Xiaojie | Cheng, Xiangchao | Zhang, Chunjie
Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the most significant zoonotic pathogens that poses a threat to humans. Previous studies have identified that Salmonella-secreted effector K3 (SseK3) is a novel translated and secreted protein of S. Typhimurium. The objective of this study was to determine whether deletion of the sseK3 gene can attenuate the virulence of S. Typhimurium. To do this, we constructed an sseK3 deletion mutant using the double-exchange allele of the suicide plasmid pRE112ΔsseK3 and assessed the virulence and intracellular proliferation of the mutant. The sseK3 deletion mutant exhibited adhesion and invasion properties similar to those of wild-type (WT) S. Typhimurium, although the virulence and intracellular proliferation of the mutant were significantly reduced compared to that of the WT strain. Furthermore, the observed increase in the median lethal dose (LD(50)) reflects a decrease in the pathogenicity of the sseK3 deletion mutant in a murine model. In summary, we concluded that disruption of sseK3 can attenuate the intracellular proliferation and reduce the virulence of S. Typhimurium.
Afficher plus [+] Moins [-]Pathogenesis, detection, and control of scrapie in sheep
2020
Cassmann, Eric D. | Greenlee, Justin J.
In sheep, scrapie is a fatal neurologic disease that is caused by a misfolded protein called a prion (designated PrPSc). The normal cellular prion protein (PrPC) is encoded by an endogenous gene, PRNP, that is present in high concentrations within the CNS. Although a broad range of functions has been described for PrPC, its entire range of functions has yet to be fully elucidated. Accumulation of PrPSc results in neurodegeneration. The PRNP gene has several naturally occurring polymorphisms, and there is a strong correlation between scrapie susceptibility and PRNP genotype. The cornerstone of scrapie eradication programs is the selection of scrapie-resistant genotypes to eliminate classical scrapie. Transmission of classical scrapie in sheep occurs during the prenatal and periparturient periods when lambs are highly susceptible. Initially, the scrapie agent is disseminated throughout the lymphoid system and into the CNS. Shedding of the scrapie agent occurs before the onset of clinical signs. In contrast to classical scrapie, atypical scrapie is believed to be a spontaneous disease that occurs in isolated instances in older animals within a flock. The agent that causes atypical scrapie is not considered to be naturally transmissible. Transmission of the scrapie agent to species other than sheep, including deer, has been experimentally demonstrated as has the transmission of nonscrapie prion agents to sheep. The purpose of this review is to outline the current methods for diagnosing scrapie in sheep and the techniques used for studying the pathogenesis and host range of the scrapie agent. Also discussed is the US scrapie eradication program including recent updates.
Afficher plus [+] Moins [-]Expression of microRNAs in plasma and in extracellular vesicles derived from plasma for dogs with glioma and dogs with other brain diseases
2020
Narita, Momoko | Nishida, Hidetaka | Asahina, Ryota | Nakata, Kohei | Yano, Hirohito | Dickinson, Peter J. | Tanaka, Toshiyuki | Akiyoshi, Hideo | Maeda, Sadatoshi | Kamishina, Hiroaki
OBJECTIVE To measure expression of microRNAs (miRNAs) in plasma and in extracellular vesicles (EVs) derived from plasma for dogs with glioma and dogs with other brain diseases. SAMPLE Plasma samples from 11 dogs with glioma and 19 control dogs with various other brain diseases. PROCEDURES EVs were isolated from plasma samples by means of ultracentrifugation. Expression of 4 candidate reference miRNAs (let-7a, miR-16, miR-26a, and miR-103) and 4 candidate target miRNAs (miR-15b, miR-21, miR-155, and miR-342-3p) was quantified with reverse transcription PCR assays. Three software programs were used to select the most suitable reference miRNAs from among the 4 candidate reference miRNAs. Expression of the 4 target miRNAs was then calculated relative to expression of the reference genes in plasma and EVs, and relative expression was compared between dogs with glioma and control dogs with other brain diseases. RESULTS The most suitable reference miRNAs were miR-16 for plasma and let-7a for EVs. Relative expression of miR-15b in plasma and in EVs was significantly higher in dogs with glioma than in control dogs. Relative expression of miR-342-3p in EVs was significantly higher in dogs with glioma than in control dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that miR-15b and miR-342-3p have potential as noninvasive biomarkers for differentiating glioma from other intracranial diseases in dogs. However, more extensive analysis of expression in specific glioma subtypes and grades, compared with expression in more defined control populations, will be necessary to assess their clinical relevance.
Afficher plus [+] Moins [-]Effects of intervertebral distraction screw fixation of the lumbosacral joint on the adjacent lumbar segments in Beagles
2020
Tanoue, Hirofumi | Uchiyama, Rika | Fukuda, Hideyuki | Ichinohe, Tom | Kanno, Nobuo | Suzuki, Shūji | Harada, Yasuji | Hara, Yasushi
OBJECTIVE To investigate the effects of intervertebral distraction screw (IDS) fixation of the lumbosacral joint (LSJ) on the intervertebral foraminal area (IFA) and intervertebral stabilization of the LSJ and adjacent lumbar segments in dogs. ANIMALS 7 healthy Beagles. PROCEDURES Dorsal laminectomy was performed at the LSJ in each dog to expose the intervertebral disk. The IDS was then inserted into the L7-S1 disk. Computed tomography was performed before and after laminectomy and after IDS insertion (intact, laminectomy, and IDS conditions, respectively) to measure the intervertebral range of motion (ROM) and intervertebral distance (ID) at L7-S1, L6-7, and L5-6 with the LSJ in a flexed and extended position. The intervertebral foramina stenosis rate was calculated from the intervertebral foramina area in entrance, middle, and exit zones. Results were compared among conditions. RESULTS The ROM at L7-S1 after IDS insertion was lower than that observed before and after laminectomy; no other differences were identified among conditions. With the LSJ in the flexed position, the ID at L7-S1 was larger after IDS insertion than before and after laminectomy; no other differences in ID were identified. In all evaluated zones, the stenosis rate was lower after IDS insertion than before and after laminectomy. No differences in ROM, ID, and stenosis rate were identified among conditions at L6-7 or L5-6. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that IDS fixation of the LSJ restricted lumbosacral ROM and prevented decreases in lumbosacral ID and IFA in healthy dogs. There were no changes at L6-7 and L5-6.
Afficher plus [+] Moins [-]Radiographic localization of the attachments of soft tissue structures in the tarsal region of horses
2020
Casillas, Jose M. | Jacobs, Carrie C. | Manfredi, Jane M.
OBJECTIVE To identify radiographic locations of soft tissue attachments in the tarsal region of horses and describe any variability in the gross anatomy of those attachments. SAMPLE 15 cadaveric limbs from 8 adult horses. PROCEDURES 8 limbs were used for dissection and radiography of soft tissue structures, with metallic markers used to identify radiographic locations of soft tissue attachments. The remaining 7 limbs were used to evaluate anatomic variations in the insertion of the tendon of the fibularis tertius muscle. A consensus list of preferred radiographic views for evaluating each soft tissue attachment was created. RESULTS The dorsoplantar, dorsoproximolateral-plantarodistomedial oblique (35° proximal and 45° lateral), dorsoproximomedial-plantarodistolateral oblique (10° proximal and 15° medial), and plantaroproximal-plantarodistal oblique (70° proximal; flexed) views were preferred for evaluating the collateral ligaments. The standard oblique views and plantaroproximal-plantarodistal oblique (70° proximal; flexed) view were preferred for evaluating the tendinous attachments of the gastrocnemius and superficial digital flexor muscles. All 4 standard views were necessary for evaluating the tendinous attachments of the cranial tibial and fibularis tertius muscles, the dorsal tarsal ligament, and the origin of the suspensory ligament. Three configurations of the insertion of the fibularis tertius tendon were identified grossly. In limbs with osteoarthritis of the distal tarsal joints, the dorsal tarsal ligament firmly adhered to the centrodistal tarsal joint. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that attachments of soft tissue structures in the tarsal region of horses were in distinct radiographically identifiable locations and that visualization of individual soft tissue attachments could be optimized with certain radiographic views, including some nonstandard views.
Afficher plus [+] Moins [-]Ex vivo modeling of the airflow dynamics and two-and three-dimensional biomechanical effects of suture placements for prosthetic laryngoplasty in horse
2020
Lynch, Nicola P. | Jones, Sarah A. | Bazley-White, Lucy G. | Wilson, Zoe F. | Raffetto, Jennifer | Pfau, Thilo | Cheetham, Jonathon | Perkins, Justin D.
OBJECTIVE To identify the degree of left arytenoid cartilage (LAC) abduction that allows laryngeal airflow similar to that in galloping horses, assess 2-D and 3-D biomechanical effects of prosthetic laryngoplasty on LAC movement and airflow, and determine the influence of suture position through the muscular process of the arytenoid cartilage (MPA) on these variables. SAMPLE 7 equine cadaver larynges. PROCEDURES With the right arytenoid cartilage maximally abducted and inspiratory airflow simulated by vacuum, laryngeal airflow and translaryngeal pressure and impedance were measured at 12 incremental LAC abduction forces (0% to 100% [maximum abduction]) applied through laryngoplasty sutures passed caudocranially or mediolaterally through the left MPA. Cross-sectional area of the rima glottis and left-to-right angle quotient were determined from photographs at each abduction force; CT images were obtained at alternate forces. Arytenoid and cricoid cartilage markers allowed calculation of LAC roll, pitch, and yaw through use of Euler angles on 3-D reconstructed CT images. RESULTS Translaryngeal pressure and impedance decreased, and airflow increased rapidly at low abduction forces, then slowed until a plateau was reached at approximately 50% of maximum abduction force. The greatest LAC motion was rocking (pitch). Suture position through the left MPA did not significantly affect airflow data. Approximately 50% of maximum abduction force, corresponding to a left arytenoid angle of approximately 30° and left-to-right angle quotient of 0.79 to 0.84, allowed airflow of approximately 61 ± 6.5 L/s. CONCLUSIONS AND CLINICAL RELEVANCE Ex vivo modeling results suggested little benefit to LAC abduction forces > 50%, which allowed airflow similar to that reported elsewhere for galloping horses.
Afficher plus [+] Moins [-]Investigation for correction formulas on the basis of packed cell volume for blood glucose concentration measurements obtained with portable glucometers when used in rabbits
2020
Cutler, Daniel C. | Koenig, Amie | Di Girolamo, Nicola | Mayer, Jörg
OBJECTIVE To determine effects of PCV on blood glucose (BG) concentration measurements obtained with a human portable blood glucometer (HPBG) and a veterinary portable blood glucometer (VPBG) on canine (cVPBG) and feline (fVPBG) settings (test methods) when used in rabbits and to develop correction formulas to mitigate effects of PCV on such measurements. SAMPLE 48 resuspended blood samples with known PVCs (range, 0% [plasma] to 92% [plasma and packed RBCs]) from 6 healthy research rabbits (experimental sample set) and 252 historic measurements of BG concentration and PCV in 84 client-owned rabbits evaluated at a veterinary hospital (validation data set). PROCEDURES Duplicate measurements of BG concentration with each test method and of PCV were obtained for each sample in the experimental sample set, and the mean results for each variable for each test method and sample were compared with results from a clinical laboratory analyzer (reference method) used to determine the true BG concentration for each sample. Mean ± SD differences in measurements between the reference and test methods were calculated. Linear regression and modified Clarke error grid analysis were used to develop correction formulas for the test methods given known PCVs, and these formulas were evaluated on the validation data set with linear regression and a modified Clarke error grid. RESULTS Blood glucose concentrations were falsely low for cVPBG and fVPBG used on samples with PCV < 31% and were falsely high for all test methods used on samples with PCV > 43%. Compared with original measurements, formula-corrected measurements overall had better agreement with reference method measurements for the experimental sample set; however, only the formula-corrected HPBG measurements had improved agreement for the validation data set. CONCLUSIONS AND CLINICAL RELEVANCE Findings indicated that, in rabbits, HPBG measurements had improved accuracy with the use of the correction formula HPBG measurement of BG concentration + ([0.75 × PCV] − 15); however, the correction formulas did not improve the accuracy of VPBG measurements, and we believe that neither the cVPBG nor fVPBG should be used in rabbits.
Afficher plus [+] Moins [-]Effects of kernel and window setting combinations on assessments of small and complicated vasculature in computed tomography angiographic images of dogs with and without tumors
2020
Yoon, Sooa A. | Park, Seungjo J. | Choi, Jihye H.
OBJECTIVE To evaluate the effect of kernel and window settings on the assessment of small and complicated vasculature in CT angiographic (CTA) images of kidneys, jejunum with mesentery, and tumors in dogs. ANIMALS 20 healthy dogs and 20 dogs with tumors. PROCEDURES Images from CTA performed previously in dogs were reconstructed with 3 different combinations of kernel and window settings (soft kernel with soft tissue window, soft kernel with bone window, and sharp kernel with bone window), and reconstructed images of the left kidney and the jejunum with the mesentery in healthy dogs and tumors in affected dogs were evaluated by reviewers blinded to the settings. RESULTS For images of kidney and jejunum with mesentery, reviewers’ scores for the conspicuity of vascularity in the arterial phase and the differentiation of the organs from the adjacent structures were significantly higher when viewed in bone window (vs soft tissue window) regardless of kernel setting. For images of head and gastrointestinal tumors, reviewers’ scores for differentiation of intratumoral vasculature were higher when viewed in sharp kernel with bone window versus other setting combinations. However, the conspicuity of gastrointestinal, hepatic, or splenic tumoral vessels from the adjacent structures had higher reviewer scores for images in soft kernel with soft tissue window, compared with other setting combinations. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that reconstruction of CTA images with sharp kernel combined with bone window settings might have clinical utility in evaluating and planning treatments for dogs with various tumors; however, additional research is warranted to further identify effects of various kernel and window setting combinations on assessments of small and complicated vasculature in larger and more diverse populations of dogs with and without tumors.
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