Gillian Dank

Radiopaque iodinated polymeric nanoparticles for X-ray imaging applications

Recently we described iodinated homopolymeric radiopaque nanoparticles of 28.9+/-6.3 nm dry diameter synthesized by emulsion polymerization of 2-methacryloyloxyethyl(2,3,5-triiodobenzoate) (MAOETIB). The nanoparticle aqueous dispersion, however, was not stable and tended to agglomerate, particularly at weight concentration of dispersed nanoparticles above approximately 0.3%. The agglomeration rate increases as the concentration of nanoparticles in aqueous phase rises and prevents the potential in vivo use as contrast agent for medical X-ray imaging. Here we describe efforts to overcome this limitation by synthesis of iodinated copolymeric nanoparticles of 25.5+/-4.2 nm dry diameter, by emulsion copolymerization of the monomer, MAOETIB, with a low concentration of glycidyl methacrylate (GMA). The surface of resulting copolymeric nanoparticles is far more hydrophilic than that of polyMAOETIB (PMAOETIB) nanoparticles. Therefore, P(MAOETIB-GMA) nanoparticles are significantly more stable against agglomeration in aqueous continuous phase. After intravenous injection of P(MAOETIB-GMA) nanoparticles in rats and mice (including those with a liver cancer model) CT-imaging revealed a significant enhanced visibility of the blood pool for 30 min after injection. Later, lymph nodes, liver and spleen strongly enhanced due to nanoparticle uptake by the reticuloendothelial system. This favorably enabled the differentiation of cancerous from healthy liver tissue and suggests our particles for tumor imaging in liver and lymph nodes.

Clinical characteristics, treatment, and outcome of dogs with presumed primary hepatic lymphoma: 18 cases (1992–2008)

OBJECTIVE-To determine outcome of dogs with presumed primary hepatic lymphoma treated with various multiagent, doxorubicin-based chemotherapeutic protocols and identify factors associated with prognosis. DESIGN-Retrospective case series. ANIMALS-18 dogs with presumed primary hepatic lymphoma. PROCEDURES-Medical records were reviewed for information on signalment, treatment, and outcome. RESULTS-8 dogs had a complete remission (CR), with a median remission duration of 120 days. Dogs with leukocytosis, neutrophilia, hypoalbuminemia, hyperbilirubinemia, or a combination of hypoalbuminemia and hyperbilirubinemia were less likely to achieve a CR. Overall median survival time (MST) was 63 days (range, 2 to 402 days). In a multivariate analysis, response to treatment and serum albumin concentration were associated with MST. Dogs that did not achieve a CR had a significantly shorter MST than did dogs that did achieve a CR (13 vs 283 days, respectively). Dogs with serum albumin concentration < 2.5 g/dL at the time treatment was initiated had a significantly shorter MST than did dogs with serum albumin concentration within reference limits (10 vs 128 days, respectively). There was also a positive correlation between serum albumin concentration and survival time (r = 0.74). CONCLUSIONS AND CLINICAL RELEVANCE-Results suggested that dogs with primary hepatic lymphoma that underwent chemotherapy had a poor prognosis, with a low response rate. Dogs that responded to treatment had a better prognosis, and dogs with hypoalbuminemia had a poorer prognosis.

Follow-up study comparing necropsy rates and discrepancies between clinical and pathologic diagnoses at a veterinary teaching hospital: 2009 versus 1989 and 1999

OBJECTIVES A follow-up, retrospective study to determine whether the proportion of discrepancies between clinical and pathological diagnoses made during 2009, 1999 and 1989 and the proportion of dogs necropsied have changed. METHODS Medical records of 148 hospitalised dogs that died or were euthanased in a veterinary medical teaching hospital during 2009 were reviewed. Clinical and pathological diagnoses were recorded, categorised and compared to historical controls using a data set of 623 dogs from a previous study. RESULTS The proportion of discrepancies was significantly (P<0·001) lower in 2009 (14·9%), compared to both 1999 (37%) and 1989 (39·8%). There was also a significant (P<0·001) decrease in the number of necropsies performed during 2009 (21·4%) compared to both 1999 (48·4%) and 1989 (58·9%). CLINICAL SIGNIFICANCE There was a marked improvement in the ante-mortem diagnosis of patients in 2009 compared with both 1989 and 1999 as evidenced by the decrease in the proportion of discrepancies between the clinical and pathological diagnoses. Necropsies should still be regarded as a vital tool for teaching, determining the pathological basis of disease, identification of new and emerging diseases, and for an individual animal determining the cause of death.

Induction of Nitric-Oxide Metabolism in Enterocytes Alleviates Colitis and Inflammation-Associated Colon Cancer

Summary Nitric oxide (NO) plays an established role in numerous physiological and pathological processes, but the specific cellular sources of NO in disease pathogenesis remain unclear, preventing the implementation of NO-related therapy. Argininosuccinate lyase (ASL) is the only enzyme able to produce arginine, the substrate for NO generation by nitric oxide synthase (NOS) isoforms. Here, we generated cell-specific conditional ASL knockout mice in combination with genetic and chemical colitis models. We demonstrate that NO derived from enterocytes alleviates colitis by decreasing macrophage infiltration and tissue damage, whereas immune cell-derived NO is associated with macrophage activation, resulting in increased severity of inflammation. We find that induction of endogenous NO production by enterocytes with supplements that upregulate ASL expression and complement its substrates results in improved epithelial integrity and alleviation of colitis and of inflammation-associated colon cancer.

Non‐skeletal multicentric chondrosarcoma in the hindlimb of a dog

An eight-year-old, spayed, female golden retriever was presented with progressive right hindlimb lameness and polyuria/polydipsia. Multiple soft tissue masses were palpable within the hindlimb muscles. A tentative diagnosis of sarcoma was made on fine needle aspiration. A computed tomography scan of the hindlimb and thorax confirmed the presence and location of the masses, none of which were associated with the bones of the hindlimb. In addition, two pulmonary lesions were identified in the right cranial lung lobe. A diagnosis of chondrosarcoma was confirmed on histopathology with a final diagnosis of extraskeletal chondrosarcoma. A high, hindlimb amputation was performed, and chemotherapy was initiated. Polyuria and polydipsia resolved 2 weeks postoperatively. Numerous lung lesions, suspected to be metastases were found on routine followup radiographs, 73 days post surgery after which the dog was lost to follow-up.

Association of cancer-related mortality, age and gonadectomy in golden retriever dogs at a veterinary academic center (1989-2016).

Golden retriever dogs have been reported to have an increased prevalence of cancer compared to other breeds. There is also controversy over the effect spay or neuter status might have on longevity and the risk for developing cancer. The electronic medical records system at an academic center was searched for all dogs who had a necropsy exam from 1989–2016. 9,677 canine necropsy examinations were completed of which 655 were golden retrievers. Age was known for 652 with a median age of death 9.15 years. 424 of the 652 (65.0%) were determined to have died because of cancer. The median age for dying of a cause other than cancer was 6.93 years while those dying of cancer had a median age of 9.83 years (p<0.0001). There was no significant difference in the proportion of intact males and castrated males dying of cancer (p = 0.43) but a greater proportion of spayed females died of cancer compared to intact females (p = 0.001). Intact female dogs had shorter life spans than spayed female dogs (p<0.0001), but there were no differences between intact and castrated males. Intriguingly, being spayed or neutered did not affect the risk of a cancer related death but increasing age did. The most common histologic diagnosis found in golden retrievers dying of cancer was hemangiosarcoma (22.64%) followed by lymphoid neoplasia (18.40%). Overall golden retriever dogs have a substantial risk of cancer related mortality in a referral population and age appears to have a larger effect on cancer related mortality than reproductive status.