Duodenal-jejunal bypass surgery does not increase skeletal muscle insulin signal transduction or glucose disposal in Goto-Kakizaki type 2 diabetic rats.

BACKGROUND: Duodenal-jejunal bypass (DJB) has been shown to reverse type 2 diabetes (T2DM) in Goto-Kakizaki (GK) rats, a rodent model of non-obese T2DM. Skeletal muscle insulin resistance is a hallmark decrement in T2DM. The aim of the current work was to investigate the effects of DJB on skeletal muscle insulin signal transduction and glucose disposal. It was hypothesized that DJB would increase skeletal muscle insulin signal transduction and glucose disposal in GK rats. METHODS: DJB was performed in GK rats. Sham operations were performed in GK and nondiabetic Wistar-Kyoto (WKY) rats. At 2 weeks post-DJB, oral glucose tolerance (OGTT) was measured. At 3 weeks post-DJB, insulin-induced signal transduction and glucose disposal were measured in skeletal muscle. RESULTS: In GK rats and compared to sham operation, DJB did not (1) improve fasting glucose or insulin, (2) improve OGTT, or (3) increase skeletal muscle insulin signal transduction or glucose disposal. Interestingly, skeletal muscle glucose disposal was similar between WKY-Sham, GK-Sham, and GK-DJB. CONCLUSIONS: Bypassing of the proximal small intestine does not increase skeletal muscle glucose disposal. The lack of skeletal muscle insulin resistance in GK rats questions whether this animal model is adequate to investigate the etiology and treatments for T2DM. Additionally, bypassing of the foregut may lead to different findings in other animal models of T2DM as well as in T2DM patients.

Cost per day of patency: understanding the impact of patency and reintervention in a sustainable model of healthcare.

BACKGROUND: Healthcare resource utilization is an understudied aspect of vascular surgery. Initial cost of a given procedure is not an accurate reflection of resource utilization because it does not account for procedural durability and efficacy. Herein we describe an amortized cost model that accounts for procedural costs, durability, and re-intervention costs. METHODS: A cost model was developed using patency data endpoints and total hospital costs (direct and indirect) associated with an inital revascularization and subsequent re-interventions. This model was applied to a retrospective database of femoropopliteal reconstructions. One hundred and eighty-three open cases were compared with 198 endovascular cases; and the endpoints of initial cost, amortized cost at 12 months, and assisted patency were examined. RESULTS: The open and endovascular cases were not statistically different with respect to indication, patient co-morbid profiles, or post-procedural pharmacotherapy. Primary assisted patency was better in the open revascularization group at 12 months (78% versus 66%, P < .01). There was a statistically significant higher initial cost for open reconstruction when compared with endovascular ($12,389 +/- $408 versus $6,739 +/- $206, P < .001). However, at 12 months post-procedure, the initial cost benefit was lost for endovascular patients ($229 +/- $106 versus $185 +/- $124, P = .71). There was, however, a trend for endovascular cost savings in claudicants, though this did not reach significance ($259 +/- $189 versus $86 +/- $52, P = .31). For patients with critical limb ischemia, renal dysfunction, and end stage renal disease, the trend favored open surgery. CONCLUSIONS: An amortized cost model provides insight into the healthcare resource utilization associated with a particular revascularization and assistive procedures. The initial cost savings of endovascular therapies are not sustained over time. Cost-savings trends were noted, however, longer follow-up is required to see if these will reach statistical significance.

Antibody-mediated p53 protein therapy prevents liver metastasis in vivo.

To evaluate the clinical efficacy of monoclonal antibody (mAb) 3E10 Fv antibody-mediated p53 protein therapy, an Fv-p53 fusion protein produced in Pichia pastoris was tested on CT26.CL25 colon cancer cells in vitro and in vivo in a mouse model of colon cancer metastasis to the liver. In vitro experiments showed killing of CT26.CL25 cells by Fv-p53 but not Fv or p53 alone, and immunohistochemical staining confirmed that Fv was required for transport of p53 into cells. Prevention of liver metastasis in vivo was tested by splenic injection of 100 nmol/L Fv-p53 10 min and 1 week after injection of CT26.CL25 cancer cells into the portal vein of BALB/c mice. Mice were sacrificed 1 week after the second injection of Fv-p53 and assigned a quantitative metastasis score. Control mice had an average metastasis score of 3.3 +/- 1.3, whereas mice treated with Fv-p53 had an average metastasis score of 0.8 +/- 0.4 (P = 0.004). These results indicate that Fv-p53 treatment had a profound effect on liver metastasis and represent the first demonstration of effective full-length p53 protein therapy in vivo. mAb 3E10 Fv has significant clinical potential as a mediator of intracellular and intranuclear delivery of p53 for prevention and treatment of cancer metastasis.