Topics

exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets.

08:00 EDT 11th October 2019 | BioPortfolio

Summary of "exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets."

Perforations, anastomotic leak and subsequent intraabdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiologic healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We have previously demonstrated in both mice and humans that the commensal microbe 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 a novel collagenolytic virulence mechanism by which is able to bind and locally activate the human fibrinolytic protease plasminogen (PLG), a protein present in high concentrations in healing colonic tissue. -mediated PLG activation leads to supraphysiologic collagen degradation; in this study, we demonstrate this concept both and . This pathoadaptive response can be mitigated with the PLG inhibitor tranexamic acid (TXA) in a fashion that prevented clinically significant complications in validated murine models of both and mediated colonic perforation. TXA has a proven clinical safety record and is FDA approved for topical application in invasive procedures, albeit for the prevention of bleeding rather than infection. As such, the novel pharmacologic effect described in this study may be translatable to clinical trials for the prevention of infectious complications of colonic healing.

Affiliation

Journal Details

This article was published in the following journal.

Name: American journal of physiology. Gastrointestinal and liver physiology
ISSN: 1522-1547
Pages:

Links

DeepDyve research library

PubMed Articles [22563 Associated PubMed Articles listed on BioPortfolio]

Modulation of the mammalian coagulation system by venoms and other proteins from snakes, arthropods, nematodes and insects.

The mammalian hemostatic system involves complex interactions between protein components of the coagulation cascade and platelets. The fibrinolytic system removes the hemostatic plug. Dysregulation of...

Mixed fibrinolytic phenotypes in decompensated cirrhosis and ACLF with hypofibrinolysis in those with complications and poor survival.

Patients with liver disease acquire complex changes in their hemostatic system which results in a fragile rebalanced status. The status of the fibrinolytic system is controversial, as is the role of f...

Contribution of platelets, the coagulation and fibrinolytic systems to cutaneous wound healing.

Wound healing is a complex process that consists of multiple phases, each of which are indispensable for adequate repair. Timely initiation and resolution of each of these phases namely, hemostasis, i...

MASP-1 of the complement system alters fibrinolytic behaviour of blood clots.

The lectin pathway serine protease mannan-binding lectin-associated serine protease 1 (MASP-1) has been demonstrated to be a major link between complement and coagulation, yet little is known about it...

Respiratory Drive in Critically Ill Patients: Pathophysiology and Clinical Implications.

The respiratory drive, the intensity of the respiratory centers output, determines the effort exerted in each breath. The increasing awareness of the adverse effects of both strong and weak respirator...

Clinical Trials [8172 Associated Clinical Trials listed on BioPortfolio]

Female Sex is an Independent Predictor of Death and Bleeding Among Fibrinolytic Treated Patients With AMI

This study evaluated differences between men and women in the presentation, management and outcome of heart attacks within the GUSTO V study.

Genes and Fibrinolytic Capacity of Human Endothelium

To conduct several studies on genes and the fibrinolytic capacity of human endothelium.

Efficacy and Safety of Geneferm Nattokinase

Nattokinase, first found by Dr. Hiroyuki Sumi in 1980, is a potent fibrinolytic enzyme extracted from Natto, a popular soybean fermented food in Japan. It was confirmed that oral administr...

Treatment of Complicated Parapneumonic Effusion With Fibrinolytic Therapy Versus VATs Decortication

This study aims to standardize the treatment of pleural space (parapneumonic) infections by comparing the difference in outcomes between 2 methods of treatment: early VATS (Video Assisted ...

Fibrinolytic Therapy Versus Medical Thoracoscopy

The purpose of this prospective randomized clinical trial is to compare two currently accepted standard-of-care treatment strategies: medical thoracoscopy as compared to instillation of in...

Medical and Biotech [MESH] Definitions

A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response.

Substances, usually endogenous, that act as inhibitors of blood coagulation. They may affect one or multiple enzymes throughout the process. As a group, they also inhibit enzymes involved in processes other than blood coagulation, such as those from the complement system, fibrinolytic enzyme system, blood cells, and bacteria.

A condition caused by prolonged exposure to excess levels of cortisol (HYDROCORTISONE) or other GLUCOCORTICOIDS from endogenous or exogenous sources. It is characterized by upper body OBESITY; OSTEOPOROSIS; HYPERTENSION; DIABETES MELLITUS; HIRSUTISM; AMENORRHEA; and excess body fluid. Endogenous Cushing syndrome or spontaneous hypercortisolism is divided into two groups, those due to an excess of ADRENOCORTICOTROPIN and those that are ACTH-independent.

A branch of applied ethics that studies the value implications of practices and developments in life sciences, medicine, and health care.

A fibrinolytic and thrombolytic enzyme from Aspergillus oryzae. EC 3.4.99.-.

Quick Search


DeepDyve research library

Relevant Topics

Complementary and Alternative Medicine
Alternative medicine are whole medical systems that did not fit with conventional medicine as they have completely different philosophies and ideas on the causes of disease, methods of diagnosis and approaches to treatment. Although often overlapping, co...

Sepsis, septicaemia and blood poisoning
Septicaemia (another name for blood poisoning) refers to a bacterial infection of the blood, whereas sepsis can also be caused by viral or fungal infections.  Sepsis is not just limited to the blood and can affect the whole body, including the organ...


Searches Linking to this Article