Systemic iron reduction via an iron deficient diet decreases the severity of knee cartilage lesions in the Dunkin-Hartley guinea pig model of osteoarthritis.

OBJECTIVE: Iron accumulation is emerging as a player in aging-related disorders due to its propensity for generating reactive oxygen species (ROS). Studies investigating the role of iron in the pathogenesis of primary osteoarthritis (OA) are limited. We designed a proof-of-principle study to determine the effect of systemic iron deficiency, via an iron deficient diet, on knee OA in an animal model. METHODS: Twelve-week-old male Hartley guinea pigs received the standard diet (n = 6) or a diet devoid of iron (n = 6) for 19-weeks. Iron levels were determined in the serum, liver, and articular cartilage. Knees were collected to assess structural changes related to OA (microcomputed tomography, histopathology). Immunohistochemistry was performed to evaluate the presence and distribution of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) and ROS-driven 4-hydroxynonenal (4-HNE)-induced protein adducts. Transcript expression was also assessed. RESULTS: Relative to control animals, an iron deficient diet reduced the concentration of this mineral in serum, liver, and articular cartilage. Iron deficient animals had lower histologic OA scores; decreased subchondral bone mineral density was also noted. This reduction in knee joint pathology was accompanied by a decrease in: ADAMTS4 in synovium; and 4-HNE protein adducts from lipid peroxidation in both the menisci and articular cartilage of iron deficient animals. Expression of iron-related genes in these tissues was also altered in treated animals. CONCLUSIONS: Results from this study suggest that systemic iron levels may play a role in knee OA pathogenesis, with a short-term deficit in dietary iron reducing the severity of knee cartilage lesions.

Prevalence of portal vein thrombosis detected by computed tomography angiography in dogs.

OBJECTIVE: To evaluate dogs with computed tomography angiography of the abdomen for overall prevalence of portal vein thrombosis and prevalence of portal vein thrombosis based on different disease categories. To evaluate dogs with and without portal vein thrombosis for differences in outcome. To compare ultrasound to computed tomographic angiography for identification of portal vein thrombosis. METHODS: Abdominal computed tomography angiography of 223 client-owned animals was reviewed for evidence of portal vein thrombosis. Based on medical records, dogs were assigned to disease categories: (1) liver disease; (2) non-hepatic neoplasia; (3) pancreatitis; (4) infectious disease; (5) immune-mediated disease; (6) other; (7) multiple diseases. Different categories were compared for the prevalence of portal vein thrombosis. Outcome was evaluated in dogs with and without portal vein thrombosis. Ultrasound reports were reviewed to determine the detection of thrombosis on ultrasound. RESULTS: Twenty-eight dogs (13%) had portal vein thrombosis. The pancreatitis category contained the highest percentage of portal vein thrombosis among different categories (eight of 19; 42%). There was a similar outcome between dogs with and without portal vein thrombosis. Of 21 dogs with portal vein thrombosis that had ultrasound performed, ultrasound detected thrombosis in four of 21 (19%) cases. CLINICAL RELEVANCE: In this study, portal vein thrombosis prevalence was higher in dogs with pancreatitis compared to dogs with liver disease, non-hepatic neoplasia and other abdominal or systemic disease. The portal system should be carefully evaluated with imaging in dogs with pancreatitis. As compared to ultrasound, CT angiography is the imaging method of choice for detection of portal vein thrombosis in dogs.

Systemic iron overload exacerbates osteoarthritis in the strain 13 guinea pig.

OBJECTIVE: Iron is emerging as a key player in aging-associated diseases due to its propensity for driving free radical formation. Studies examining the role of iron in the pathogenesis of primary osteoarthritis (OA) are limited. Our objective was to establish a direct relationship between excess iron and OA by administering iron dextran to a guinea pig strain with decreased propensity for developing this disease. DESIGN: Twenty, 12-week-old Strain 13 guinea pigs received either iron dextran or dextran control intraperitoneally once weekly for 4 weeks; termination occurred at 16 weeks of age. Iron levels were determined systemically (serum and liver) and within diarthrodial joints [femoral head articular cartilage and infrapatellar fat pads (IFPs) of knee joints]. One knee was collected to score structural changes associated with OA via microcomputed tomography (microCT) and histology using published grading schemes. Articular cartilage and IFPs were harvested from contralateral knees for gene expression analyses. RESULTS: Iron overload was confirmed systemically via increased serum iron and liver iron concentration. Articular cartilage and IFPs in the iron dextran group also had higher levels of iron. Excess iron worsened knee OA using both microCT and histologic scoring systems. Gene analyses revealed that exogenous iron altered the expression of iron trafficking proteins, select cytokines, and structural components of cartilage. CONCLUSION: These results demonstrate that systemic iron overload caused cellular iron accumulation in the knee joint. This excess iron is associated with increased expression of local inflammatory mediators and early onset and progression of knee joint OA in Strain 13 animals.

Comparison of endoscopy and sonography findings in dogs and cats with histologically confirmed gastric neoplasia.

OBJECTIVE: To compare sonographic and endoscopic findings in a group of dogs and cats with histologically confirmed gastric neoplasia. METHODS: Retrospective analysis of cases with concurrent abdominal ultrasound and endoscopy to evaluate the presence of gastric wall abnormalities, location and tumour appearance between the two examinations. Sonographic findings of the small intestines, liver, spleen and lymph nodes were recorded. Comparison of the findings from each test and assessment of predictive characteristics for neoplasia was evaluated. RESULTS: In total 17 dogs and 5 cats were included, Sonography identified 50% and endoscopy identified 95% of all gastric neoplasms. Lymphoma was the most commonly missed tumour by sonography. There was sonographic and endoscopic tumour location agreement in 36% of cases (Cohen's kappa = 0 · 25). Animals with sonographically normal small intestines had a statistically greater probability of gastric neoplasia (P = 0 · 035). All cats had lymphoma (P < 0 · 001). CLINICAL SIGNIFICANCE: Sonography and endoscopy are useful for the diagnosis of gastric neoplasia. Endoscopy is more accurate in identifying gastric neoplasia; however, sonography can raise the clinical suspicion for gastric neoplasia and may provide a less invasive means of gathering information before endoscopy. Intraluminal gastric gas or fluid may limit diagnostic capabilities of sonographic evaluation.

Computed tomographic angiography under sedation in the diagnosis of suspected canine pancreatitis: a pilot study.

BACKGROUND: Computed tomography (CT) is highly accurate for diagnosing pancreatitis in humans. The diagnosis of pancreatitis in dogs is based on clinical signs, laboratory findings, and ultrasonographic (US) changes. There are, however, inherent limitations in relying on laboratory and ultrasound findings for the clinical diagnosis of pancreatitis in dogs. HYPOTHESIS/OBJECTIVES: We hypothesized that CT angiography would be a rapid and reliable method to confirm pancreatitis in dogs compared to ultrasonography. The aim was to describe the CT characteristics and compare them to ultrasound findings and correlate the CT appearance to the severity of the patients' clinical course. ANIMALS: A prospective pilot case series; 10 dogs with pancreatitis were enrolled if the history, clinical signs, laboratory, and ultrasonographic findings were indicative of pancreatitis. METHODS: A 3-phase angiographic CT was performed under sedation. Afterward, each dog had US-guided aspirates of the pancreas collected and blood drawn for cPLi assay. Images were evaluated for portion of visible pancreas, pancreatic size and margin, pancreatic parenchyma, presence of peripancreatic changes and contrast enhancement pattern. The results were compared with outcome. RESULTS: An enlarged, homogeneously to heterogeneously attenuating and contrast-enhancing pancreas with ill-defined borders was identified in all dogs. CT identified more features characterizing pancreatic abnormalities compared to US. Thrombi were found in 3/10 dogs. Three dogs with heterogeneous contrast enhancement had an overall poorer outcome than those with homogenous enhancement. CONCLUSIONS AND CLINICAL IMPORTANCE: CT angiography under sedation was used in dogs to confirm clinically suspected pancreatitis and identified clinically relevant and potentially prognostic features of pancreatitis in dogs.

Effects of FSH and LH on ovarian and follicular blood flow, follicular growth and oocyte developmental competence in young and old mares.

Objectives of the experiment were to determine the effects of mare age and gonadotropin treatments on dominant follicle vascularity, ovarian blood flow and dominant follicle growth and to associate follicular vascularity with oocyte developmental capacity. Growing follicles >30 mm from young (4-9 years) and old (>20 years) mares were assessed for blood flow using color Doppler ultrasonography before maturation induction with recombinant equine LH (eLH) and immediately prior to oocyte collection at 20-24 h after eLH. Pulsed Doppler was used to obtain resistance indices of ovarian arteries ipsilateral to preovulatory follicles. For eFSH-treated estrous cycles, eFSH administration was started after detection of a cohort of follicles ≥20 to <25 mm and continued until a follicle >30 mm. Oocytes were harvested using transvaginal, ultrasonic-guided aspirations and cultured and injected with sperm at 40 ± 1 h after eLH. Presumptive zygotes were incubated, and rates of cleavage (≥2 cells) and blastocyst formation were obtained. Embryos were transferred nonsurgically into recipients' uteri, and pregnancy rates were assessed. Vascularity (number of color pixels per total pixels) was higher (P=0.003) in the follicles of old compared to young mares, with no significant interaction of eFSH or eLH. Effects of eFSH and time from eLH on follicle vascularity were not significant. The vascularity of follicles associated with oocytes that did compared to those that did not form blastocysts was greater (P=0.048), although follicular vascularity was less (P=0.02) for follicles associated with oocytes that did compared to those that did not develop into pregnancies. Resistance indices were not different for age, eFSH treatment, time after eLH administration and oocyte developmental potential. Growth of the dominant follicle was not associated with vascularity, although advanced age tended (P=0.09) to have a negative effect on follicle growth.