Fibronectin‐α4β1 Interactions in Hepatic Cold Ischemia and Reperfusion Injury: Regulation of MMP‐9 and MT1‐MMP via the p38 MAPK Pathway

Liver ischemia‐reperfusion injury (IRI) remains a challenging problem in clinical settings. The expression of fibronectin (FN) by endothelial cells is a prominent feature of the hepatic response to injury. Here we investigate the effects of the connecting segment‐1 (CS‐1) peptide therapy, which blocks FN‐α4β1 integrin leukocyte interactions, in a well‐established model of 24‐h cold liver IRI. CS‐1 peptides significantly inhibited leukocyte recruitment and local release of proinflammatory mediators (COX‐2, iNOS and TNF‐α), ameliorating liver IRI and improving recipient survival rate. CS1 therapy inhibited the phosphorylation of p38 MAPK, a kinase linked to inflammatory processes. Moreover, in addition to downregulating the expression of matrix metalloproteinase‐9 (MMP‐9) in hepatic IRI, CS‐1 peptide therapy depressed the expression of membrane type 1‐matrix metalloproteinase (MT1‐MMP/MMP‐14) by macrophages, a membrane‐tethered MMP important for focal matrix proteolysis. Inhibition of p38 MAPK activity, with its pharmacological antagonist SB203580, downregulated MMP‐9 and MT1‐MMP/MMP‐14 expressions by FN‐stimulated macrophages, suggesting that p38 MAPK kinase pathway controls FN‐mediated inductions of MMP‐9 and MT1‐MMP/MMP‐14. Hence, this study provides new insights on the role of FN in liver injury, which can potentially be applied to the development of new pharmacological strategies for the successful protection against hepatic IRI.     

In vitro study on the schedule-dependency of the interaction between pemetrexed, gemcitabine and irradiation in non-small cell lung cancer and head and neck cancer cells

Background  

Based on their different mechanisms of action, non-overlapping side effects and radiosensitising potential, combining the antimetabolites pemetrexed (multitargeted antifolate, MTA) and gemcitabine (2',2'-difluorodeoxycytidine, dFdC) with irradiation (RT) seems promising. This in vitro study, for the first time, presents the triple combination of MTA, dFdC and irradiation using various treatment schedules.     

A case report of pulmonary coinfection of Strongyloides stercoralis and Pneumocystis jiroveci

A case of pulmonary coinfection by Strongyloides stercoralis and Pneumocystis jiroveci has been detected in an AIDS patient treated in the Respiratory Intensive Care Unit of the Muñiz Hospital. At diagnosis, the patient presented cough with mucopurulent expectoration, dyspnea, fever, bilateral pulmonary infiltrates on the chest X-ray, negative bacilloscopy for acid fast bacteria and a CD4⁺ T lymphocytes count of 52 cells/µL. The microbiological diagnosis was achieved by microscopic observation of the respiratory secretions obtained by bronchoalveolar lavage, while the wet mount examination revealed rhabditiform and filariform larvae of the nematode and foamy exudates, pathognomonic of the pulmonary pneumocystosis. It was the unique case of this association among about 3 000 samples performed in our laboratory in the last 10 years and diagnosed by microscopy. Other complementary stains (a rapid modification of Grocott, Kinyoun and Giemsa) were applied to the smears after the diagnosis of mycotic and parasitary infections achieved by fresh microscopy. Both physicians and microbiologists should take into account the possible coexistence of respiratory pathogens in immunocompromised patients, such as those with AIDS.     

Natural Orifice Transluminal Endoscopic Surgery

Natural orifice transluminal endoscopic surgery (NOTES) has generated healthy and vigorous debate about the introduction of an entirely novel method of surgical therapy. Although there are many reasons for scepticism, there is undoubted interest in this field from both the medical profession and general public. Those Associations currently involved in laparoscopic and endoscopic surgery wish to safeguard patients and the reputation of the profession by issuing clear guidance and support for those wishing to undertake NOTES. The purpose of this document is to review the current status of both NOTES and hybrid NOTES, while at the same time identifying obstacles in both clinical research and training. Furthermore, it aims to provide a consensus statement on behalf of the main UK specialty associations involved in this field of surgery. The primary aim of this consensus statement is to provide a framework within which to develop, safely and effectively, what must still be considered an experimental technique.