XJZT12Z06.

No abstract

Summary: The importance of nitric oxide (NO) for CBF variations associated with arterial carbon dioxide changes was investigated in halothane-anesthetized rats by using an inhibitor of nitric oxide synthase, NJ-nitro-L-arginine (NOLAG). CBF was measured by intracarotid injection of 133Xe. In normocapnia, intracarotid infusion of 1.5, or 7.5, or 30 mg/kg NOLAG induced a dose-dependent in crease of arterial blood pressure and a decrease of nor mocapnic CBF from 85 ± 10 to 78 ± 6, 64 ± 5, and 52 ± 5 ml l00g -I min -I, respectively. This effect lasted for at least 2 h. Raising P aco 2 from a control level of 40 to 68 mm Hg increased CBF to 230 ± 27 ml 100g -I min -I , correspopdiRg to a percentage CBF response (C0 2 reac tivity) C!l3.7 ± 0.6%/mm Hg P aco 2 in saline-treated rats.NOLAG att enuated this reactivity by 32, 49, and 51% at the three-dose levels. Hypercapnia combined with an giotensin to raise blood pressure to the same level as the The endothelium-derived relaxing factor nitric oxide (NO) or a closely related NO-containing com pound (Ignarro et aI., 1987; Palmer et aI., 1987) is currently being studied intensively. In vitro studies have shown that the amino-nitrogen of the guani dino group of L-arginine is the precursor (Palmer et aI., 1988a; Sakuma et aI., 1988; Schmidt et aI., 1988). NO synthase is also located in the brain tis sue as well as in perivascular nerves (Bredt et aI., 947highest dose of NO LAG did not affect the CBF response to hypercapnia. L-Arginine significantly prevented the ef fect of NOLAG on normocapnic CBF as well as blood pressure and also abolished its inhibitory effect on hyper capnic CBF. o-Arginine had no such effect. Decreasing p aco 2 to 20 mm Hg reduced control CBF to 46 ± 3 ml lOOg -1 min-I with no further reduction after NOLAG. Furthermore, NOLAG did not change the percentage CBF response to an extracellular acidosis induced by ac etazolamide (50 mg/kg). The results suggest that NO or a closely related compound is involved in the regulation of CBF in normocapnia and even more so in hypercapnia.

CUEDC2, a CUE-domain-containing protein, modulates inflammation, but its involvement in tumorigenesis is still poorly understood. Here, we report that CUEDC2 is a key regulator of macrophage function and critical for protection against colitis-associated tumorigenesis. CUEDC2 expression is dramatically upregulated during macrophage differentiation, and CUEDC2 deficiency results in excessive production of proinflammatory cytokines. The level of CUEDC2 in macrophages is modulated by miR- 324-5p. We find that Cuedc2 KO mice are more susceptible to dextran-sodium-sulfate-induced colitis, and macrophage transplantation results suggest that the increased susceptibility results from the dysfunction of macrophages lacking CUEDC2. Furthermore, we find that Cuedc2 KO mice are more prone to colitis-associated cancer. Importantly, CUEDC2 expression is almost undetectable in macrophages in human colon cancer, and this decreased CUEDC2 expression is associated with high levels of interleukin-4 and miR-324-5p. Thus, CUEDC2 plays a crucial role in modulating macrophage function and is associated with both colitis and colon tumorigenesis.