Evaluation of a Hydrogel Liquid Embolic Agent in a Porcine Mesenteric Hemorrhage Model.

PURPOSE: To evaluate the ability to achieve hemostasis of a new liquid embolic agent in a porcine mesenteric artery hemorrhage model. MATERIALS AND METHODS: An anticoagulated porcine mesenteric artery hemorrhage model was created using a transarterial approach. Arterial hemorrhage was the result of aspiration needle punctures and simultaneous radiofrequency current application. Ten injured mesenteric arteries in 8 swine were treated. The hydrogel liquid embolic agent under investigation, an aqueous-based and in situ polymerizing liquid embolic agent, was used to treat actively bleeding sites. At 7 days, confirmation angiography was performed, followed by necropsy. RESULTS: The mesenteric arterial injuries produced persistent and angiographically visible hemorrhage before initiating embolic therapy. Arteriovenous fistulae were observed in 4 cases. Embolization led to hemostasis in 10 of the 10 bleeds (100%). The mean embolic agent delivery time was 5.3 minutes (range, 1-15 minutes) with a mean embolic agent volume of 2.9 mL (range, 0.8-5.2 mL) delivered to achieve hemostasis. Notably, 40% of the treatments embolized the injury in the artery at the treatment site while leaving the native arterial lumen patent for the 7-day term of survival. All animals survived with no clinical evidence of hemorrhage through 7 days. Necropsy did not reveal evidence of ischemia within the bowel, liver, or lung. CONCLUSIONS: A new hydrogel liquid embolic agent was found to achieve rapid and durable hemostasis in an animal model of acute mesenteric hemorrhage.

The Uterus Duplex Bicollis, Vagina Simplex of Female Chinchillas.

The available literature describing the morphology of the female chinchilla's uterine cervix varies and includes phrases such as 'the cervical canal,' 'a single cervix,' and 'the cervix;' alternatively, some publications describe 2 cervices. In this report, we provide an anatomically correct and definitive description of the uterine cervical morphology of the laboratory chinchilla. We further propose revised, anatomically precise nomenclature to characterize the female chinchilla reproductive tract as a whole.

Dosing of adult pigeons with as little as one #9 lead pellet caused severe δ-ALAD depression, suggesting potential adverse effects in wild populations.

Avian wildlife species commonly ingest lead (Pb) spent shot or bullet fragments as grit or mistakenly as food. In previous studies in our laboratory and others, the toxicity varied based on the diet as well as type and quantity of Pb ingested. In the current study, domestic pigeons were gavaged with 1, 2, or 3 Pb pellets and then followed with weekly radiographs and blood physiologic endpoints for 28 days. Pellet retention decreased by roughly 50 % per week as pellets were either absorbed or excreted, except for week 4 where pellet number no longer was diminished. Size of retained pellets visually decreased over retention time. Birds dosed with a single #9 pellet showed mean blood Pb levels over 80 times higher than those of the controls, verifying Pb pellet absorption from the gut. A single Pb pellet also reduced plasma δ-aminolevulinic acid dehydratase (δ-ALAD) activity by over 80 % compared to controls, suggesting the potential for population injury in Pb pellet-exposed pigeons.

Oral lead bullet fragment exposure in northern bobwhite (Colinus virginianus).

Lead (Pb) is a worldwide environmental contaminant known to adversely affect multiple organ systems in both mammalian and avian species. In birds, a common route of exposure is via oral ingestion of lead particles. Data are currently lacking for the retention and clearance of Pb bullet fragments in gastrointestinal (GI) tract of birds while linking toxicity with blood Pb levels. In the present study, northern bobwhite quail fed a seed-based diet were orally gavaged with Pb bullet fragments (zero, one or five fragments/bird) and evaluated for rate of fragment clearance, and changes in peripheral blood, renal, immune, and gastrointestinal parameters. Based on radiographs, the majority of the birds cleared or absorbed the fragments by seven days, with the exception of one five-fragment bird which took between 7 and 14 days. Blood Pb levels were higher in males than females, which may be related to egg production in females. In males but not females, feed consumption, body weight gain, packed cell volume (PCV), plasma protein concentration, and δ-aminolevulinic acid dehydratase (δ-ALAD) activity were all adversely affected by five Pb fragments. Birds of both sexes that received a single Pb fragment displayed depressed δ-ALAD, suggesting altered hematologic function, while all birds dosed with five bullet fragments exhibited greater morbidity.

Lead pellet retention time and associated toxicity in northern bobwhite quail (Colinus virginianus).

Birds are exposed to Pb by oral ingestion of spent Pb shot as grit. A paucity of data exists for retention and clearance of these particles in the bird gastrointestinal tract. In the current study, northern bobwhite quail (Colinus virginianus) were orally gavaged with 1, 5, or 10 Pb shot pellets, of 2-mm diameter, and radiographically followed over time. Blood Pb levels and other measures of toxicity were collected, to correlate with pellet retention. Quail dosed with either 5 or 10 pellets exhibited morbidity between weeks 1 and 2 and were removed from further study. Most of the Pb pellets were absorbed or excreted within 14 d of gavage, independent of dose. Pellet size in the ventriculus decreased over time in radiographs, suggesting dissolution caused by the acidic pH. Birds dosed with one pellet showed mean blood Pb levels that exceeded 1,300 µg/dl at week 1, further supporting dissolution in the gastrointestinal tract. Limited signs of toxicity were seen in the one-pellet birds; however, plasma δ-aminolevulinic acid dehydratase (d-ALAD) activity was persistently depressed, suggesting possible impaired hematological function.

Antigenic modulation limits the efficacy of anti-CD20 antibodies: implications for antibody selection.

Rituximab, a monoclonal antibody that targets CD20 on B cells, is now central to the treatment of a variety of malignant and autoimmune disorders. Despite this success, a substantial proportion of B-cell lymphomas are unresponsive or develop resistance, hence more potent anti-CD20 monoclonal antibodies (mAbs) are continuously being sought. Here we demonstrate that type II (tositumomab-like) anti-CD20 mAbs are 5 times more potent than type I (rituximab-like) reagents in depleting human CD20 Tg B cells, despite both operating exclusively via activatory Fcgamma receptor-expressing macrophages. Much of this disparity in performance is attributable to type I mAb-mediated internalization of CD20 by B cells, leading to reduced macrophage recruitment and the degradation of CD20/mAb complexes, shortening mAb half-life. Importantly, human B cells from healthy donors and most cases of chronic lymphatic leukemia and mantle cell lymphoma, showed rapid CD20 internalization that paralleled that seen in the Tg mouse B cells, whereas most follicular lymphoma and diffuse large B-cell lymphoma cells were far more resistant to CD20 loss. We postulate that differences in CD20 modulation may play a central role in determining the relative efficacy of rituximab in treating these diseases and strengthen the case for focusing on type II anti-CD20 mAb in the clinic.

Interplay between function and structure in complex networks.

We show that abrupt structural transitions can arise in functionally optimal networks, driven by small changes in the level of transport congestion. Our results offer an explanation as to why so many diverse species of network structure arise in nature (e.g., fungal systems) under essentially the same environmental conditions. Our findings are based on an exactly solvable model system which mimics a variety of biological and social networks. We then extend our analysis by introducing a renormalization scheme involving cost motifs, to describe analytically the average shortest path across multiple-ring-and-hub networks. As a consequence, we uncover a "skin effect" whereby the structure of the inner multi-ring core can cease to play any role in terms of determining the average shortest path across the network.

Effect of congestion costs on shortest paths through complex networks.

We analyze analytically the effect of congestion costs within a physically relevant, yet exactly solvable, network model featuring central hubs. These costs lead to a competition between centralized and decentralized transport pathways. In stark contrast to conventional no-cost networks, there now exists an optimal number of connections to the central hub in order to minimize the shortest path. Our results shed light on an open problem in biology, informatics, and sociology, concerning the extent to which decentralized versus centralized design benefits real-world complex networks.