Inflammation-attenuating effect of carbon dioxide versus room-air environment in a rat laparotomy model.

Background: The mechanism by which laparoscopic operations induce lower post-operative inflammatory response compared to open surgery was investigated with regard to the effect of the type of gas environment.

Methods: Rats were subjected to midline laparotomy at either CO (group CO) or room-air environment (group Air) or to anesthesia only (group Control) under atmospheric pressure conditions. At various timepoints after surgery (1, 3, 6, 24, or 48 h), the expression of inflammation biomarkers interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), and nuclear factor-κΒ (NFκΒ) were assessed immunohistochemically in tissue samples excised from the liver, intestine, and kidneys, accompanied by histopathologic analysis, and their levels were measured by ELISA in blood samples.

Inhibition of Clostridioides difficile toxins TcdA and TcdB by the amiodarone derivative dronedarone.

The dreaded nosocomial pathogen Clostridioides difficile causes diarrhea and severe inflammation of the colon, especially after the use of certain antibiotics. The bacterium releases two deleterious toxins, TcdA and TcdB, into the gut, which are mainly responsible for the symptoms of C. difficile-associated diseases (CDADs).

Synthesis of biologically active Shiga toxins in cell-free systems.

Shiga toxins (Stx) produced by pathogenic bacteria can cause mild to severe diseases in humans. Thus, the analysis of such toxins is of utmost importance. As an AB toxin, Stx consist of a catalytic A-subunit acting as a ribosome-inactivating protein (RIP) and a B-pentamer binding domain.

Trauma-toxicology: concepts, causes, complications.

Trauma and toxic substances are connected in several aspects. On the one hand, toxic substances can be the reason for traumatic injuries in the context of accidental or violent and criminal circumstances. Examples for the first scenario is the release of toxic gases, chemicals, and particles during house fires, and for the second scenario, the use of chemical or biological weapons in the context of terroristic activities.

Exploring the inhibitory potential of the antiarrhythmic drug amiodarone against toxins TcdA and TcdB.

The intestinal pathogen is the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis in humans. The symptoms of -associated diseases (CDADs) are directly associated with the pathogen's toxins TcdA and TcdB, which enter host cells and inactivate Rho and/or Ras GTPases by glucosylation. Membrane cholesterol is crucial during the intoxication process of TcdA and TcdB, and likely involved during pore formation of both toxins in endosomal membranes, a key step after cellular uptake for the translocation of the glucosyltransferase domain of both toxins from endosomes into the host cell cytosol.

The C2 Toxin Subunit C2IIa Delivers Enzymes with Positively Charged N-Termini into the Cytosol of Target Cells.

The binary () C2 toxin consists of two non-linked proteins. The proteolytically activated binding/transport subunit C2IIa forms barrel-shaped homoheptamers, which bind to cell surface receptors, mediate endocytosis, and translocate the enzyme subunit C2I into the cytosol of target cells. Here, we investigate whether C2IIa can be harnessed as a transporter for proteins/enzymes fused to polycationic tags, as earlier demonstrated for the related anthrax toxin transport subunit PA.

Domperidone Protects Cells from Intoxication with Toxins by Inhibiting Hsp70-Assisted Membrane Translocation.

infections cause severe symptoms ranging from diarrhea to pseudomembranous colitis due to the secretion of AB-toxins, TcdA and TcdB. Both toxins are taken up into cells through receptor-mediated endocytosis, autoproteolytic processing and translocation of their enzyme domains from acidified endosomes into the cytosol. The enzyme domains glucosylate small GTPases such as Rac1, thereby inhibiting processes such as actin cytoskeleton regulation.

Prospective multicenter external validation of postoperative mortality prediction tools in patients undergoing emergency laparotomy.

Background: Accurate preoperative risk assessment in emergency laparotomy (EL) is valuable for informed decision making and rational use of resources. Available risk prediction tools have not been validated adequately across diverse health care settings. Herein, we report a comparative external validation of four widely cited prognostic models.

Inhibition of Toxins TcdA and TcdB by Ambroxol.

produces the exotoxins TcdA and TcdB, which are the predominant virulence factors causing associated disease (CDAD). TcdA and TcdB bind to target cells and are internalized via receptor-mediated endocytosis. Translocation of the toxins' enzyme subunits from early endosomes into the cytosol depends on acidification of endosomal vesicles, which is a prerequisite for the formation of transmembrane channels.

The Compound U18666A Inhibits the Intoxication of Cells by Toxins TcdA and TcdB.

The intestinal pathogen is a major cause of diarrhea both in hospitals and outpatient in industrialized countries. This bacterium produces two large exotoxins, toxin A (TcdA) and toxin B (TcdB), which are directly responsible for the onset of clinical symptoms of -associated diseases (CDADs), such as antibiotics-associated diarrhea and the severe, life-threatening pseudomembranous colitis. Both toxins are multidomain proteins and taken up into host eukaryotic cells via receptor-mediated endocytosis.

The cytotoxic effect of Clostridioides difficile pore-forming toxin CDTb.

Clostridioides (C.) difficile is clinically highly relevant and produces several AB-type protein toxins, which are the causative agents for C. difficile-associated diarrhea and pseudomembranous colitis.

The enzyme subunit SubA of Shiga toxin-producing E. coli strains demonstrates comparable intracellular transport and cytotoxic activity as the holotoxin SubAB in HeLa and HCT116 cells in vitro.

The subtilase cytotoxin (SubAB) is secreted by certain Shiga toxin-producing Escherichia coli (STEC) strains and is composed of the enzymatically active subunit SubA and the pentameric binding/transport subunit SubB. We previously demonstrated that SubA (10 µg/ml), in the absence of SubB, binds and intoxicates the human cervix cancer-derived epithelial cell line HeLa. However, the cellular and molecular mechanisms underlying the cytotoxic activity of SubA in the absence of SubB remained unclear.

Human α-Defensin-5 Efficiently Neutralizes Toxins TcdA, TcdB, and CDT.

Infections with the pathogenic bacterium are coming more into focus, in particular in hospitalized patients after antibiotic treatment. produces the exotoxins TcdA and TcdB. Since some years, hypervirulent strains are described, which produce in addition the binary actin ADP-ribosylating toxin CDT.

"A journey towards acceptance": The process of adapting to life with HIV in Greece. A Qualitative study.

Unlabelled: Aim To identify the experiences related to adaptation for people living with HIV in Greece and to explore different adaptation stages as well as their individual reactions.

Background: Receiving an HIV positive diagnosis leads to major changes in an individual's life and it can trigger an array of emotions including fear, despair and loss of control. As the profile of the disease has changed due to its transition into a chronic disease and extended life expectancy, adaptation to life and coping with uncertain events is of paramount importance.

Inverse control of Rab proteins by ADP-ribosyltransferase and glycosyltransferase related to clostridial glucosylating toxins.

We identified a glucosyltransferase (YGT) and an ADP-ribosyltransferase (YART) in , highly related to glucosylating toxins from , the cause of antibiotics-associated enterocolitis. Both toxins consist of an amino-terminal enzyme domain, an autoprotease domain activated by inositol hexakisphosphate, and a carboxyl-terminal translocation domain. YGT -acetylglucosaminylates Rab5 and Rab31 at Thr and Thr, respectively, thereby inactivating the Rab proteins.

Human peptide α-defensin-1 interferes with Clostridioides difficile toxins TcdA, TcdB, and CDT.

The human pathogenic bacterium Clostridioides difficile produces two exotoxins TcdA and TcdB, which inactivate Rho GTPases thereby causing C. difficile-associated diseases (CDAD) including life-threatening pseudomembranous colitis. Hypervirulent strains produce additionally the binary actin ADP-ribosylating toxin CDT.

The Antibiotic Bacitracin Protects Human Intestinal Epithelial Cells and Stem Cell-Derived Intestinal Organoids from Toxin TcdB.

Bacitracin is an established antibiotic for local application and inhibits the cell wall synthesis of Gram-positive bacteria. Recently, we discovered a completely different mode of action of bacitracin and reported that this drug protects human cells from intoxication by a variety of medically relevant bacterial protein toxins including CDT, the binary actin ADP-ribosylating toxin of () . Bacitracin prevents the transport of CDT into the cytosol of target cells, most likely by inhibiting the transport function of the binding subunit of this toxin.

Inappropriate Use of Public Hospitals Emergency Departments in Greece: Magnitude and Associated Factors.

The aim of this study was to evaluate the appropriateness of use of the Emergency Departments (EDs) and to identify the reasons for inappropriate use. A study with 805 patients visiting the EDs of four large-scale public hospitals in Athens was conducted using the Hospital Urgencies Appropriateness Protocol (HUAP). 38.

Revisiting an old antibiotic: bacitracin neutralizes binary bacterial toxins and protects cells from intoxication.

The antibiotic bacitracin (Bac) inhibits cell wall synthesis of gram-positive bacteria. Here, we discovered a totally different activity of Bac: the neutralization of bacterial exotoxins. Bac prevented intoxication of mammalian cells with the binary enterotoxins Clostridium botulinum C2, C.

Cytotoxicity of Clostridium difficile toxins A and B requires an active and functional SREBP-2 pathway.

Clostridium difficile is associated with antibiotic-associated diarrhea and pseudomembranous colitis in humans. Its 2 major toxins, toxins A and B, enter host cells and inactivate GTPases of the Ras homologue/rat sarcoma family by glucosylation. Pore formation of the toxins in the endosomal membrane enables the translocation of their glucosyltransferase domain into the cytosol, and membrane cholesterol is crucial for this process.

Human Serum Albumin Is an Essential Component of the Host Defense Mechanism Against Clostridium difficile Intoxication.

Background: The pathogenic effects of Clostridium difficile are primarily attributable to the production of the large protein toxins (C difficile toxins [Tcd]) A (TcdA) and B (TcdB). These toxins monoglucosylate Rho GTPases in the cytosol of host cells, causing destruction of the actin cytoskeleton with cytotoxic effects. Low human serum albumin (HSA) levels indicate a higher risk of acquiring and developing a severe C difficile infection (CDI) and are associated with recurrent and fatal disease.

Targeting oncogenic Ras by the toxin TpeL.

toxin TpeL belongs to the family of large clostridial glycosylating toxins. The toxin causes N-acetylglucosaminylation of Ras proteins at threonine35 thereby inactivating the small GTPases. Here, we show that all main types of oncogenic Ras proteins (H-Ras, K-Ras and N-Ras) are modified by the toxin and .