Harmonic scalpel versus flexible CO2 laser for tongue resection: A histopathological analysis of thermal damage in human cadavers

<p>Abstract</p> <p>Background</p> <p>Monopolar cautery is the most commonly used surgical cutting and hemostatic tool for head and neck surgery. There are newer technologies that are being utilized with the goal of precise cutting, decreasing blood loss, reducing thermal damage, and allowing faster wound healing. Our study compares thermal damage caused by Harmonic scalpel and CO2 laser to cadaveric tongue.</p> <p>Methods</p> <p>Two fresh human cadaver heads were enrolled for the study. Oral tongue was exposed and incisions were made in the tongue akin to a tongue tumor resection using the harmonic scalpel and flexible C02 laser fiber at various settings recommended for surgery. The margins of resection were sampled, labeled, and sent for pathological analysis to assess depth of thermal damage calculated in millimeters. The pathologist was blinded to the surgical tool used. Control tongue tissue was also sent for comparison as a baseline for comparison.</p> <p>Results</p> <p>Three tongue samples were studied to assess depth of thermal damage by harmonic scalpel. The mean depth of thermal damage was 0.69 (range, 0.51 - 0.82). Five tongue samples were studied to assess depth of thermal damage by CO2 laser. The mean depth of thermal damage was 0.3 (range, 0.22 to 0.43). As expected, control samples showed 0 mm of thermal damage. There was a statistically significant difference between the depth of thermal injury to tongue resection margins by harmonic scalpel as compared to CO2 laser, (p = 0.003).</p> <p>Conclusion</p> <p>In a cadaveric model, flexible CO2 laser fiber causes less depth of thermal damage when compared with harmonic scalpel at settings utilized in our study. However, the relevance of this information in terms of wound healing, hemostasis, safety, cost-effectiveness, and surgical outcomes needs to be further studied in clinical settings.</p

Heparin cofactor II in atherosclerotic lesions from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study

Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) that has been shown to be a predictor of decreased atherosclerosis in the elderly and protective against atherosclerosis in mice. HCII inhibits thrombin in vitro and HCII-thrombin complexes have been detected in human plasma. Moreover, the mechanism of protection against atherosclerosis in mice was determined to be the inhibition of thrombin. Despite this evidence, the presence of HCII in human atherosclerotic tissue has not been reported. In this study, using samples of coronary arteries obtained from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, we explore the local relationship between HCII and (pro)thrombin in atherosclerosis. We found that HCII and (pro)thrombin are co-localized in the lipid-rich necrotic core of atheromas. A significant positive correlation between each protein and the severity of the atherosclerotic lesion was present. These results suggest that HCII is in a position to inhibit thrombin in atherosclerotic lesions where thrombin can exert a proatherogenic inflammatory response. However, these results should be tempered by the additional findings from this, and other studies, that indicate the presence of other plasma proteins (antithrombin, albumin, and α1-protease inhibitor) in the same localized region of the atheroma

Bcl-2 Overexpression Leads to Increases in Suppressor of Cytokine Signaling-3 Expression in B Cells and De Novo Follicular Lymphoma

The t(14;18)(q32;q21), resulting in deregulated expression of B-cell-leukemia/lymphoma-2 (Bcl-2), represents the genetic hallmark in human follicular lymphomas. Substantial evidence supports the hypothesis that the t(14;18) and Bcl-2 overexpression are necessary but not solely responsible for neoplastic transformation and require cooperating genetic derangements for neoplastic transformation to occur. To investigate genes that cooperate with Bcl-2 to influence cellular signaling pathways important for neoplastic transformation, we used oligonucleotide microarrays to determine differential gene expression patterns in CD19+ B cells isolated from Eμ-Bcl-2 transgenic mice and wild-type littermate control mice. Fifty-seven genes were induced and 94 genes were repressed by ≥2-fold in Eμ-Bcl-2 transgenic mice (P \u3c 0.05). The suppressor of cytokine signaling-3 (SOCS3) gene was found to be overexpressed 5-fold in B cells from Eμ-Bcl-2 transgenic mice. Overexpression of Bcl-2 in both mouse embryo fibroblast-1 and hematopoietic cell lines resulted in induction of SOCS3 protein, suggesting a Bcl-2-associated mechanism underlying SOCS3 induction. Immunohistochemistry with SOCS3 antisera on tissue from a cohort of patients with de novo follicular lymphoma revealed marked overexpression of SOCS3 protein that, within the follicular center cell region, was limited to neoplastic follicular lymphoma cells and colocalized with Bcl-2 expression in 9 of 12 de novo follicular lymphoma cases examined. In contrast, SOCS3 protein expression was not detected in the follicular center cell region of benign hyperplastic tonsil tissue. These data suggest that Bcl-2 overexpression leads to the induction of activated signal transducer and activator of transcription 3 (STAT3) and to the induction of SOCS3, which may contribute to the pathogenesis of follicular lymphoma

Trp53 negatively regulates autoimmunity via the STAT3-Th17 axis

Emerging evidence suggests that the tumor suppressor p53 is also a crucial regulator for many physiological processes. Previous observations indicate that p53 suppresses inflammation by inhibiting inflammatory antigen-presenting cells. To investigate the potential role of p53 in autoimmune effector T cells, we generated p53nullCD45.1 mice by crossing p53nullCD45.2 and CD45.1 mice. We demonstrate that p53nullCD45.1 mice spontaneously developed autoimmunity, with a significant increase in IL-17-producing Th17 effectors in their lymph nodes (4.7±1.0%) compared to the age-matched counterparts (1.9±0.8% for p53nullCD45.2, 1.1±0.2% for CD45.1, and 0.5±0.1% for CD45.2 mice). Likewise, p53nullCD45.1 mice possess highly elevated serum levels of inflammatory cytokines IL-17 and IL-6. This enhanced Th17 response results largely from an increased sensitivity of p53nullCD45.1 T cells to IL-6-induced STAT3 phosphorylation. Administration of STAT3 inhibitor S31–201 (IC50 of 38.0±7.2 μM for IL-6-induced STAT3 phosphorylation), but not PBS control, to p53nullCD45.1 mice suppressed Th17 effectors and alleviated autoimmune pathology. This is the first report revealing that p53 activity in T cells suppresses autoimmunity by controlling Th17 effectors. This study suggests that p53 serves as a guardian of immunological functions and that the p53-STAT3-Th17 axis might be a therapeutic target for autoimmunity.—Zhang, S., Zheng, M., Kibe, R., Huang, Y., Marrero, L., Warren, S., Zieske, A. W., Iwakuma, T., Kolls, J. K., Cui, Y. Trp53 negatively regulates autoimmunity via the STAT3-Th17 axis