scholarly journals FEATURES OF THE ABDOMINAL SEPSIS COURSE DEPENDING ON EXPRESSION OF MICROCIRCULATORY DISTURBANCES IN THE EXPERIMENT

2020 ◽  
Vol 4 (2) ◽  
pp. 326
Author(s):  
Yu. M. Solovey
Keyword(s):  
Abdominal Sepsis ◽  
Microcirculatory Disturbances

Chronic Abdominal Sepsis and Migratory Polyarthritis

Rheumatology ◽  
1995 ◽  
Vol 34 (5) ◽  
pp. 478-479
Author(s):  
A. FAROOQI
Keyword(s):  
Abdominal Sepsis ◽  
Migratory Polyarthritis

scholarly journals Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets

2020 ◽  
Vol 318 (1) ◽  
pp. G1-G9 ◽  
Author(s):  
Richard A. Jacobson ◽  
Kiedo Wienholts ◽  
Ashley J. Williamson ◽  
Sara Gaines ◽  
Sanjiv Hyoju ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Healing Process ◽  
Abdominal Sepsis ◽  
Infectious Complications ◽  
Fibrinolytic System ◽  
Clinical Safety ◽  
High Concentrations ◽  
Clinically Significant

Perforations, anastomotic leak, and subsequent intra-abdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiological healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We (Shogan, BD et al. Sci Trans Med 7: 286ra68, 2015.) have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive degradation. Here, we demonstrate for the first time, to our knowledge, a novel collagenolytic virulence mechanism by which E. faecalis is able to bind and locally activate the human fibrinolytic protease plasminogen (PLG), a protein present in high concentrations in healing colonic tissue. E. faecalis-mediated PLG activation leads to supraphysiological collagen degradation; in this study, we demonstrate this concept both in vitro and in vivo. This pathoadaptive response can be mitigated with the PLG inhibitor tranexamic acid (TXA) in a fashion that prevents clinically significant complications in validated murine models of both E. faecalis- and Pseudomonas aeruginosa-mediated colonic perforation. TXA has a proven clinical safety record and is Food and Drug Administration approved for topical application in invasive procedures, albeit for the prevention of bleeding rather than infection. As such, the novel pharmacological effect described in this study may be translatable to clinical trials for the prevention of infectious complications in colonic healing. NEW & NOTEWORTHY This paper presents a novel mechanism for virulence in a commensal gut microbe that exploits the human fibrinolytic system and its principle protease, plasminogen. This mechanism is targetable by safe and effective nonantibiotic small molecules for the prevention of infectious complications in the healing gut.

scholarly journals AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nathaniel B. Bone ◽  
Eugene J. Becker ◽  
Maroof Husain ◽  
Shaoning Jiang ◽  
Anna A. Zmijewska ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Inflammatory Responses ◽  
Abdominal Sepsis ◽  
Immune Defense ◽  
Bacterial Killing ◽  
Lung Infections ◽  
Sepsis Survivors ◽  
The Impact

AbstractMetabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK and Parkin ubiquitin ligase are known to regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it is not known if this evolutionarily conserved mechanism has been coopted by the host immune defense to eradicate bacterial pathogens and influence post-sepsis immunosuppression. Parkin, AMPK levels, and the effects of AMPK activators were investigated in human leukocytes from sepsis survivors as well as wild type and Park2−/− murine macrophages. In vivo, the impact of AMPK and Parkin was determined in mice subjected to polymicrobial intra-abdominal sepsis and secondary lung bacterial infections. Mice were treated with metformin during established immunosuppression. We showed that bacteria and mitochondria share mechanisms of autophagic killing/clearance triggered by sentinel events that involve depolarization of mitochondria and recruitment of Parkin in macrophages. Parkin-deficient mice/macrophages fail to form phagolysosomes and kill bacteria. This impairment of host defense is seen in the context of sepsis-induced immunosuppression with decreased levels of Parkin. AMPK activators, including metformin, stimulate Parkin-independent autophagy and bacterial killing in leukocytes from post-shock patients and in lungs of sepsis-immunosuppressed mice. Our results support a dual role of Parkin and AMPK in the clearance of dysfunctional mitochondria and killing of pathogenic bacteria, and explain the immunosuppressive phenotype associated Parkin and AMPK deficiency. AMPK activation appeared to be a crucial therapeutic target for the macrophage immunosuppressive phenotype and to reduce severity of secondary bacterial lung infections and respiratory failure.

scholarly journals Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach

2021 ◽  
Vol 22 (10) ◽  
pp. 5332
Author(s):  
Raquel G. Bardallo ◽  
Rui Teixeira da Silva ◽  
Teresa Carbonell ◽  
Emma Folch-Puy ◽  
Carlos Palmeira ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Fatty Liver ◽  
Liver Graft ◽  
Suitable Alternative ◽  
Graft Preservation ◽  
Preservation Solutions ◽  
Microcirculatory Disturbances ◽  
Organ Recovery ◽  
Surgical Manipulations

The total damage inflicted on the liver before transplantation is associated with several surgical manipulations, such as organ recovery, washout of the graft, cold conservation in organ preservation solutions (UW, Celsior, HTK, IGL-1), and rinsing of the organ before implantation. Polyethylene glycol 35 (PEG35) is the oncotic agent present in the IGL-1 solution, which is an alternative to UW and Celsior solutions in liver clinical transplantation. In a model of cold preservation in rats (4 °C; 24 h), we evaluated the effects induced by PEG35 on detoxifying enzymes and nitric oxide, comparing IGL-1 to IGL-0 (which is the same as IGL-1 without PEG). The benefits were also assessed in a new IGL-2 solution characterized by increased concentrations of PEG35 (from 1 g/L to 5 g/L) and glutathione (from 3 mmol/L to 9 mmol/L) compared to IGL-1. We demonstrated that PEG35 promoted the mitochondrial enzyme ALDH2, and in combination with glutathione, prevented the formation of toxic aldehyde adducts (measured as 4-hydroxynonenal) and oxidized proteins (AOPP). In addition, PEG35 promoted the vasodilator factor nitric oxide, which may improve the microcirculatory disturbances in steatotic grafts during preservation and revascularization. All of these results lead to a reduction in damage inflicted on the fatty liver graft during the cold storage preservation. In this communication, we report on the benefits of IGL-2 in hypothermic static preservation, which has already been proved to confer benefits in hypothermic oxygenated dynamic preservation. Hence, the data reported here reinforce the fact that IGL-2 is a suitable alternative to be used as a unique solution/perfusate when hypothermic static and preservation strategies are used, either separately or combined, easing the logistics and avoiding the mixture of different solutions/perfusates, especially when fatty liver grafts are used. Further research regarding new therapeutic and pharmacological insights is needed to explore the underlying mitochondrial mechanisms exerted by PEG35 in static and dynamic graft preservation strategies for clinical liver transplantation purposes.

scholarly journals Development of a minimal invasive and controllable murine model to study polymicrobial abdominal sepsis

All Life ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 265-276
Author(s):  
Folkert Steinhagen ◽  
Tobias Hilbert ◽  
Nina Cramer ◽  
Sebastian Senzig ◽  
Marijo Parcina ◽  
...  
Keyword(s):  
Murine Model ◽  
Abdominal Sepsis ◽  
Minimal Invasive

Intra-abdominal sepsis: the role of radiology

1991 ◽  
Vol 5 (3) ◽  
pp. 587-609 ◽  
Author(s):  
E.Jane Adam ◽  
Janet E. Page
Keyword(s):  
Abdominal Sepsis

Radicicol, an Hsp90 inhibitor, inhibits intestinal inflammation and leakage in abdominal sepsis

2013 ◽  
Vol 182 (2) ◽  
pp. 312-318 ◽  
Author(s):  
Yilin Zhao ◽  
Zheng-Jie Huang ◽  
Milladur Rahman ◽  
Qi Luo ◽  
Henrik Thorlacius
Keyword(s):  
Intestinal Inflammation ◽  
Abdominal Sepsis ◽  
Hsp90 Inhibitor

scholarly journals CE3 COST-EFFECTIVENESS OF POLYMYXIN B IMMOBILIZED FIBER COLUMN AND CONVENTIONAL MEDICAL THERAPY IN THE MANAGEMENT OF SEVERE ABDOMINAL SEPSIS IN ITALY

2010 ◽  
Vol 13 (3) ◽  
pp. A5
Author(s):  
P Berto ◽  
M Antonelli ◽  
C Ronco ◽  
D Cruz ◽  
RM Melotti
Keyword(s):  
Cost Effectiveness ◽  
Medical Therapy ◽  
Polymyxin B ◽  
Abdominal Sepsis ◽  
Conventional Medical Therapy

Glyprolines and Semax Prevent Stress-Induced Microcirculatory Disturbances in the Mesentery

2003 ◽  
Vol 136 (5) ◽  
pp. 441-443 ◽  
Author(s):  
G. N. Kopylova ◽  
E. A. Smirnova ◽  
L. Ts. Sanzhieva ◽  
B. A. Umarova ◽  
T. V. Lelekova ◽  
...  
Keyword(s):  
Microcirculatory Disturbances

In intra-abdominal sepsis a rapid decline of serum interleukin 6 levels within 48 h of surgery predicts successful outcome and preceeds clinical improvement

2000 ◽  
Vol 118 (4) ◽  
pp. A1353
Author(s):  
Samir Qamar Latifi ◽  
Anthony Stallion ◽  
Alan D. Levine
Keyword(s):  
Clinical Improvement ◽  
Interleukin 6 ◽  
Abdominal Sepsis ◽  
Successful Outcome ◽  
Rapid Decline
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