Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is over-expressed in approximately 95% of cases of clear cell renal cell carcinoma (ccRCC), the most common renal cancer. We synthesized and performed in vitro and in vivo evaluation of a dual-motif ligand, [64Cu]XYIMSR-06, for imaging CAIX expression on ccRCC tumors using positron emission tomography (PET). [64Cu]XYIMSR-06 was generated in yields of 51.0 ± 4.5% (n=5) and specific activities of 4.1 – 8.9 GBq/μmol (110-240 Ci/mmol). Tumor was visualized on PET images by 1 h post-injection with high tumor-to-background levels (>100 tumor-to-blood and -muscle) achieved within 24 h. Biodistribution studies demonstrated a maximum tumor uptake of 19.3% injected dose per gram of radioactivity at 4 h. Tumor-to-blood, -muscle and -kidney ratios were 129.6 ± 18.8, 84.3 ± 21.0 and 2.1 ± 0.3, respectively, at 8 h post-injection. At 24 h a tumor-to-kidney ratio of 7.1 ± 2.5 was achieved. These results indicate pharmacokinetics superior to those of previously reported imaging agents binding to CAIX. [64Cu]XYIMSR-06 is a new low-molecular-weight PET ligand targeting CAIX, which can image localized and metastatic ccRCC.
Four nonlactating ruminally cannulated Holstein cows were used in a 4 x 4 Latin square experiment with 4 21-d periods to determine if the effects of dietary fat would be affected by hay particle length. Treatments consisted of two levels of tallow (0 and 5%) and two hay particle lengths (short-cut and long-cut) in a 2 x 2 factorial. Diets contained alfalfa hay, corn silage, and concentrate [1:1:2, dry matter (DM) basis] fed as a total mixed ration (TMR) once per day. Samples of the 0 and 5% tallow TMR were ground and incubated in situ in polyester bags for 24 and 48 h. Ruminal samples were taken on day 21 at 0800 h and at 2-h intervals until 1600 h. The total tract digestibilities of acid detergent fiber (ADF) and neutral detergent fiber (NDF) were not affected by tallow or by hay by tallow interactions. There was a trend for tallow to improve total tract digestibility of crude protein (CP) (70.2 vs. 74.7%). After 48 h of ruminal incubation, tallow significantly decreased the digestibilities of DM, ADF, and NDF. No hay length by tallow interactions for DM, NDF, ADF or CP digestibilities occurred after 24 or 48 h. Tallow increased concentrations of propionate and decreased concentrations of acetate and valerate and the acetate-to-propionate ratio. Total volatile fatty acids increased when tallow was added to diets with short-cut hay, which suggests that when unprotected fat is added to diets with a high level of hay, a short-cut hay length may be advantageous. This result may be due to shorter rumen retention time of feed particles, which reduces the time for fatty acids to exert antimicrobial effects. Or, it may because the increased surface area of the hay particle provides more area for microbial attachment and increased fermentation.
Mean blood loss from percutaneous cryoablation in this model was between that for RF ablation with the single electrode and that for RF ablation with the electrode cluster.
Plasmodium mexicanum is a malaria parasite that naturally infects the western fence lizard, Sceloporus occidentalis , in northern California. We set out to determine whether lizards naturally infected with this malaria parasite have different leukocyte profiles, indicating an immune response to infection. We used 29 naturally infected western fence lizards paired with uninfected lizards based on sex, snout-to-vent length, tail status, and the presence-absence of ectoparasites such as ticks and mites, as well as the presence-absence of another hemoparasite, Schellackia occidentalis. Complete white blood cell (WBC) counts were conducted on blood smears stained with Giemsa, and the proportion of granulocytes per microliter of blood was estimated using the Avian Leukopet method. The abundance of each WBC class (lymphocytes, monocytes, heterophils, eosinophils, and basophils) in infected and uninfected lizards was compared to determine whether leukocyte densities varied with infection status. We found that the numbers of WBCs and lymphocytes per microliter of blood significantly differed (P< 0.05) between the 2 groups for females but not for males, whereas parasitemia was significantly correlated with lymphocyte counts for males, but not for females. This study supports the theory that infection with P. mexicanum stimulates the lizard's immune response to increase the levels of circulating WBCs, but what effect this has on the biology of the parasite remains unclear.
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