Thrombospondin-1 Type 1 Repeats in a Model of Inflammatory Bowel Disease: Transcript Profile and Therapeutic Effects

Thrombospondin-1 (TSP-1) is a matricellular protein with regulatory functions in inflammation and cancer. The type 1 repeats (TSR) domains of TSP-1 have been shown to interact with a wide range of proteins that result in the anti-angiogenic and anti-tumor properties of TSP-1. To ascertain possible functions and evaluate potential therapeutic effects of TSRs in inflammatory bowel disease, we conducted clinical, histological and microarray analyses on a mouse model of induced colitis. We used dextran sulfate sodium (DSS) to induce colitis in wild-type (WT) mice for 7 days. Simultaneously, mice were injected with either saline or one form of TSP-1 derived recombinant proteins, containing either (1) the three type 1 repeats of the TSP-1 (3TSR), (2) the second type 1 repeat (TSR2), or (3) TSR2 with the RFK sequence (TSR2+RFK). Total RNA isolated from the mice colons were processed and hybridized to mouse arrays. Array data were validated by real-time qPCR and immunohistochemistry. Histological and disease indices reveal that the mice treated with the TSRs show different patterns of leukocytic infiltration and that 3TSR treatment was the most effective in decreasing inflammation in DSS-induced colitis. Transcriptional profiling revealed differentially expressed (DE) genes, with the 3TSR-treated mice showing the least deviation from the WT-water controls. In conclusion, this study shows that 3TSR treatment is effective in attenuating the inflammatory response to DSS injury. In addition, the transcriptomics work unveils novel genetic data that suggest beneficial application of the TSR domains in inflammatory bowel disease

Electrochemically synthesized polymers in molecular imprinting for chemical sensing

This critical review describes a class of polymers prepared by electrochemical polymerization that employs the concept of molecular imprinting for chemical sensing. The principal focus is on both conducting and nonconducting polymers prepared by electropolymerization of electroactive functional monomers, such as pristine and derivatized pyrrole, aminophenylboronic acid, thiophene, porphyrin, aniline, phenylenediamine, phenol, and thiophenol. A critical evaluation of the literature on electrosynthesized molecularly imprinted polymers (MIPs) applied as recognition elements of chemical sensors is presented. The aim of this review is to highlight recent achievements in analytical applications of these MIPs, including present strategies of determination of different analytes as well as identification and solutions for problems encountered

Effects of circadian disruption on physiology and pathology: from bench to clinic (and back)

Nested within the hypothalamus, the suprachiasmatic nuclei (SCN) represent a central biological clock that regulates daily and circadian (i.e., close to 24 h) rhythms in mammals. Besides the SCN, a number of peripheral oscillators throughout the body control local rhythms and are usually kept in pace by the central clock. In order to represent an adaptive value, circadian rhythms must be entrained by environmental signals or zeitgebers, the main one being the daily light?dark (LD) cycle. The SCN adopt a stable phase relationship with the LD cycle that, when challenged, results in abrupt or chronic changes in overt rhythms and, in turn, in physiological, behavioral, and metabolic variables. Changes in entrainment, both acute and chronic, may have severe consequences in human performance and pathological outcome. Indeed, animal models of desynchronization have become a useful tool to understand such changes and to evaluate potential treatments in human subjects. Here we review a number of alterations in circadian entrainment, including jet lag, social jet lag (i.e., desynchronization between body rhythms and normal time schedules), shift work, and exposure to nocturnal light, both in human subjects and in laboratory animals. Finally, we focus on the health consequences related to circadian/entrainment disorders and propose a number of approaches for the management of circadian desynchronization.Fil: Chiesa, Juan José. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Duhart, José Manuel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Casiraghi, Leandro Pablo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paladino, Natalia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bussi, Ivana Leda. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andrés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Single Center Experience With Veno-Venous Extracorporeal Membrane Oxygenation in Patients With Traumatic Brain Injury

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) use in patients following traumatic injury continues to increase. Some consider traumatic brain injury (TBI) as an absolute contraindication for VV-ECMO because of the concern for systemic anticoagulation (A/C) worsening intracranial injury. We evaluated outcomes and complications in patients with TBI treated with VV-ECMO. Methods We retrospectively reviewed TBI patients >= 18 years of age treated with VV-ECMO. The primary outcome was survival to discharge. Secondary outcomes included progression of intracranial hemorrhage, bleeding complications, and episodes of oxygenator thrombosis requiring exchange. Medians and interquartile ranges were reported where appropriate. Results 13 TBI patients received VV-ECMO support during the study period. The median age was 28 years (Interquartile range (IQR) 25-37.5) and 85% were men. Median admission Glasgow coma scale was 5 (IQR 3-13.5). Median injury severity score (ISS) was 48 (IQR 33.5-66). Median pre-ECMO PaO2:FiO2 ratio was 58 (IQR 47-74.5). Five (38.4%) patients survived to discharge. Six patients (46%) received systemic A/C while on ECMO. No patient had worsening of intracranial hemorrhage on computed tomography imaging. There were two bleeding complications in patients on A/C, neither was related to TBI. Four patients required an oxygenator change; 2 in patients on A/C. Conclusion VV-ECMO appears safe with TBI. We have demonstrated that A/C can be withheld without increased complications. Traumatic brain injury should not be considered an absolute contraindication to the use of VV-ECMO for severe respiratory failure and should be decided on a case by case basis. Additional research is needed to confirm these preliminary findings

The lung rescue unit-Does a dedicated intensive care unit for venovenous extracorporeal membrane oxygenation improve survival to discharge?

BACKGROUND: The use of venovenous extra corporeal membrane oxygenation (VV ECMO) for acute respiratory failure (ARF)/acute respiratory (ARDS) has increased since 2009. Specialized units for patients requiring VV ECMO are not standard and patients are often cohorted with other critically ill patients. The purpose of this study was to report the outcome of adult patients admitted in 2015 to the lung rescue unit, which, to our knowledge, is the first intensive care unit in the United States that has been specifically created to provide care for patients requiring VV ECMO. METHODS: Data were collected on all patients admitted to the lung rescue unit on VV ECMO between January 1, 2015, and December 31, 2015. Demographics, medical history, pre-ECMO data, indication for VV ECMO as well as duration of ECMO and survival to decannulation and discharge were recorded. Means (+/- standard deviation) and medians (interquartile range [IQR]) were reported when appropriate. RESULTS: Forty-nine patients were enrolled. Median age was 48 years (IQR, 32-57). Median PaO2/FIO2 ratio before cannulation was 66 (IQR, 53-86). Median ventilator days before cannulation was 2 (IQR, 1-4). Median time on VV ECMO for all patients was 311 hours (IQR, 203-461). Thirty-eight (78%) patients were successfully decannulated with 35 (71%) patients surviving to hospital discharge. CONCLUSION: The use of VV ECMO for ARF/ARDS is increasing. We have demonstrated that a dedicated multidisciplinary intensive care unit for the purpose of providing standardized care with specialized trained providers can improve survival to discharge for patients that require VV ECMO for ARF/ARDS. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved

Incidence of Cannula-Associated Deep Vein Thrombosis after Veno-Venous Extracorporeal Membrane Oxygenation

Limited literature regarding the incidence of cannula-associated deep vein thrombosis (CaDVT) after veno-venous extracorporeal membrane oxygenation (VV ECMO) exists. The purpose of this study was to identify the incidence of post decannulation CaDVT and identify any associated risk factors. Forty-eight patients were admitted between August 2014 and January 2016 to the Lung Rescue Unit were included in the study. Protocolized anticoagulation levels (partial thromboplastin time [PTT] 45-55 seconds) and routine post decannulation DVT screening were in place during the study period. Forty-one (85.4%) patients had CaDVT. Of those with CaDVT, 31 (76%) patients were treated with full anti-coagulation therapy. Thirty-four (76%) patients with right internal jugular (RIJ) cannulation had CaDVT at cannula site. Twenty-five (61%) patients had CaDVT in the lower extremity (18 associated right femoral vein cannulation and 7 left femoral vein cannulation). Eighteen (44%) patients had both upper and lower extremity CaDVT. Overall, patients with CaDVT tended to be older, have a higher body mass index (BMI), and on ECMO longer (p = NS). Mean PTT during time on ECMO between patients that did and did not have CaDVT did not differ. No clinical evidence of pulmonary embolism (PE) was seen