Nonredundant roles of antibody,cytokines, and perforin in the eradication of established Her-2/neu carcinomas

Since the mechanisms by which specific immunity destroys Her-2/neu carcinoma cells are highly undetermined, these were assessed in BALB/c mice vaccinated with plasmids encoding extracellular and transmembrane domains of the protein product (p185(neu)) of the rat Her-2/neu oncogene shot into the skin by gene gun. Vaccinated mice rejected a lethal challenge of TUBO carcinoma cells expressing p185(neu). Depletion of CD4 T cells during immunization abolished the protection, while depletion of CD8 cells during the effector phase halved it, and depletion of polymorphonuclear granulocytes abolished all protection. By contrast, Ig mu-chain gene KO mice, as well as Fcgamma receptor I/III, beta-2 microglobulin, CD1, monocyte chemoattractant protein 1 (MCP1), IFN-gamma, and perforin gene KO mice were protected. Only mice with both IFN-gamma and perforin gene KOs were not protected. Although immunization also cured all BALB/c mice bearing established TUBO carcinomas, it did not cure any of the perforin KO or perforin and IFN-gamma KO mice. Few mice were cured that had knockouts of the gene for Ig mu-chain, Fcgamma receptor I/III, IFN-gamma, or beta-2 microglobulin. Moreover, vaccination cured half of the CD1 and the majority of the MCP1 KO mice. The eradication of established p185(neu) carcinomas involves distinct mechanisms, each endowed with a different curative potential.     

Defining High Risk: Cost-Effectiveness of Extended-Duration Thromboprophylaxis Following Major Oncologic Abdominal Surgery

Purpose

Extended-duration thromboprophylaxis (EDTPPX) is the practice of prescribing antithrombotic therapy for 21 days after discharge, commonly used in surgical patients who are at high risk for venothromboembolism (VTE). While guidelines recommend EDTPPX, criteria are vague due to a paucity of data. The criteria can be further informed by cost-effectiveness thresholds. This study sought to determine the VTE incidence threshold for the cost-effectiveness of EDTPPX compared to inpatient prophylaxis.

Methods

A decision tree was used to compare EDTPPX for 21 days after discharge to 7 days of inpatient prophylaxis with base case assumptions based on an abdominal oncologic resection without complications in an otherwise healthy individual. Willingness to pay was set at $50,000/quality-adjusted life year (QALY). Sensitivity analyses were performed to assess uncertainty within the model, with particular interest in the threshold for cost-effectiveness based on VTE incidence.

Results

EDTPPX was the dominant strategy when VTE probability exceeds 2.39 %. Given a willingness to pay threshold of $50,000/QALY, EDTPPX was the preferred strategy when VTE incidence exceeded 1.22 and 0.88 % when using brand name or generic medication costs, respectively.

Conclusions

EDTPPX should be recommended whenever VTE incidence exceeds 2.39 %. When post-discharge estimated VTE risk is 0.88–2.39 %, patient preferences about self-injections and medication costs should be considered.     

Corticotropin-releasing hormone antagonists possess anti-inflammatory effects in the mouse ileum

BACKGROUND & AIMS: Corticotropin-releasing hormone (CRH) released at local sites of inflammation promotes inflammation in the periphery. We investigated its effects in the intestinal responses caused by toxin A from Clostridium difficile, the causative agent of antibiotic-associated colitis. METHODS: Ileal loops were injected with 10 microg of toxin A, and enterotoxic responses were measured at various time points. RESULTS: Pretreatment of mice with 2.5 microg/kg of the CRH receptor antagonist alpha-helical CRH((9-41)) that blocks both CRH receptor subtypes reduced toxin A-mediated ileal secretion, epithelial cell damage, mucosal edema, neutrophil infiltration, and mucosal content of interleukin 1 beta and tumor necrosis factor alpha. Pretreatment with the specific CRH(1) receptor antagonist antalarmin (20 mg/kg, IP) also inhibited toxin A-induced fluid secretion and toxin A-associated histologic changes. CRH messenger RNA and protein were increased in mouse ileum 30 minutes after intraluminal toxin A administration. In situ hybridization and immunohistochemistry demonstrated that toxin A at 1 hour caused a substantial increase in the expression of both CRH receptor subtypes in the ileal mucosa. CONCLUSIONS: Peripheral CRH may play a proinflammatory role in toxin A-induced intestinal secretion and inflammation and that CRH(1) receptor, at least in part, is important in the mediation of these responses.     

Dinámica de la infección por Helicobacter pylori en lactantes durante los primeros 6 meses de vida

Introduction

Mainly due to the high percentage of infection and the ineffectiveness of treatments, Helicobacter pylori is a global health problem. Knowing the age at acquisition is key to preventing the infection.

Behaviour of Impurities during Electron Beam Melting of Copper Technogenic Material

The current study presents the electron beam melting (EBM) efficiency of copper technogenic material with high impurity content (Se, Te, Pb, Bi, Sn, As, Sb, Zn, Ni, Ag, etc.) by means of thermodynamic analysis and experimental tests. On the basis of the calculated values of Gibbs free energy and the physical state of the impurity (liquid and gaseous), a thermodynamic assessment of the possible chemical interactions occurring in the Cu-Cu₂O-Me_x system in vacuum in the temperature range 1460–1800 K was made. The impact of the kinetic parameters (temperature and refining time) on the behaviour and the degree of removal of impurities was evaluated. Chemical and metallographic analysis of the obtained ingots is also discussed.