Post-Translational Oxidative Modifications of Hemostasis Proteins: Structure, Function, and Regulation.

Reactive oxygen species (ROS) are constantly generated in a living organism. An imbalance between the amount of generated reactive species in the body and their destruction leads to the development of oxidative stress. Proteins are extremely vulnerable targets for ROS molecules, which can cause oxidative modifications of amino acid residues, thus altering structure and function of intra- and extracellular proteins.

Electrospinning of biomimetic materials with fibrinogen for effective early-stage wound healing.

Electrospun biomimetic materials based on polyester of natural origin poly-3-hudroxybutyrate (PHB) modified with hemin (Hmi) and fibrinogen (Fbg) represent a great interest and are potentially applicable in various fields. Here, we describe formulation of the new fibrous PHB-Fbg and PHB-Hmi-Fbg materials with complex structure for biomedical application. The average diameter of the fibers was 3.

Antioxidant role of methionine-containing intra- and extracellular proteins.

Significant evidence suggests that reversible oxidation of methionine residues provides a mechanism capable of scavenging reactive species, thus creating a cycle with catalytic efficiency to counteract or mitigate deleterious effects of ROS on other functionally important amino acid residues. Because of the absence of MSRs in the blood plasma, oxidation of methionines in extracellular proteins is effectively irreversible and, therefore, the ability of methionines to serve as interceptors of oxidant molecules without impairment of the structure and function of plasma proteins is still debatable. This review presents data on the oxidative modification of both intracellular and extracellular proteins that differ drastically in their spatial structures and functions indicating that the proteins contain antioxidant methionines/the oxidation of which does not affect (or has a minor effect) on their functional properties.

Younger Age at Onset Is Associated With Worse Long-term Behavioral Outcomes in Anti-NMDA Receptor Encephalitis.

Background And Objectives: Anti-NMDA receptor encephalitis (anti-NMDARE) is one of the most common causes of encephalitis. It typically presents in adolescence and young adulthood, but little is known about its potential long-term consequences across the lifespan. Adaptive behavior describes an individual's ability to respond and adapt to environmental demands and unanticipated changes in daily routines.

The effect of hypochlorite- and peroxide-induced oxidation of plasminogen on damage to the structure and biological activity.

In this study, we examined for the first time the effect of the HOCl/OCl- and HO-induced oxidation of Glu-plasminogen on damage to its primary structure and the biological activity of plasmin. The consolidated results obtained with the aid of MS/MS, electrophoresis, and colourimetry, demonstrated that none of the oxidised amino acid residues found in the proenzyme treated with 25 μM HOCl/OCl or 100 μM HO were functionally significant for plasminogen. However, the treatment of plasminogen with increasing concentrations of HOCl/OCl from 25 μM to 100 μM or HO from 100 μM to 300 μM promoted a partial loss in the activity of oxidised plasmin.

Hypochlorite-induced oxidation of fibrinogen: Effects on its thermal denaturation and fibrin structure.

Background: Human fibrinogen, which plays a key role in plasma haemostasis, is a highly vulnerable target for oxidants. Fibrinogen undergoes posttranslational modifications that can potentially disrupt protein structure and function.

Methods: For the first time, by differential scanning calorimetry, dynamic and elastic light scattering and confocal laser scanning microscopy, the consequences of HOCl/OCl-induced oxidation of fibrinogen on its thermal denaturation, molecular size distribution and fibrin clot network have been explored.

The Structure of Blood Coagulation Factor XIII Is Adapted to Oxidation.

The blood coagulation factor XIII (FXIII) plays a critical role in supporting coagulation and fibrinolysis due to both the covalent crosslinking of fibrin polymers, rendering them resistant to plasmin lysis, and the crosslinking of fibrin to proteins of the fibrinolytic system. The hypochlorite-mediated oxidation of the blood coagulation factor XIII (FXIII) at the different stages of its enzymatic activation is studied for the first time in this paper. The consolidated results obtained with the aid of MS/MS, electrophoresis, and colorimetry demonstrate that in the process of FXIII's conversion into FXIIIa, the vulnerability of FXIII to hypochlorite-induced oxidation increased as follows: native FXIII < FXIII + Ca << FXIII + Ca/thrombin.

Ozone-induced damage of fibrinogen molecules: identification of oxidation sites by high-resolution mass spectrometry.

Fibrinogen is highly susceptible to oxidation compared to other plasma proteins. Fibrinogen oxidation damages its structure and affects the protein function. Ozone-induced oxidative modifications of the fibrinogen Aα, Bβ, and γ polypeptide chains upon addition of various amounts of the oxidiser were studied by mass spectrometry.

Binding of Coagulation Factor XIII Zymogen to Activated Platelet Subpopulations: Roles of Integrin αIIbβ3 and Fibrinogen.

Factor XIIIa (fXIIIa) is a transglutaminase that plays a crucial role in fibrin clot stabilization and regulation of fibrinolysis. It is known to bind to procoagulant platelets. In contrast, the zymogen fXIII interaction with platelets is not well characterized.

Oxidation-induced modifications of the catalytic subunits of plasma fibrin-stabilizing factor at the different stages of its activation identified by mass spectrometry.

Plasma fibrin-stabilizing factor (pFXIII) is a heterotetrameric proenzyme composed of two catalytic A subunits (FXIII-A) and two inhibitory/carrier B subunits (FXIII-B). The main function of the protein is the formation of cross-links between the polypeptide chains of the fibrin clot. The conversion of pFXIII into the enzymatic form FXIII-A* is a multistage process.

Oxidation of proteins: is it a programmed process?

Proteins represent extremely susceptible targets for oxidants. Oxidative modifications of proteins may bring about violation of their structure and functionality. It implies that the structures of proteins are not infallible in terms of their antioxidant defence.

Fibrin self-assembly is adapted to oxidation.

Fibrinogen is extremely susceptible to attack by reactive oxygen species (ROS). Having been suffered an oxidative modification, the fibrinogen molecules, now with altered spatial structure and function of fibrin network, affect hemostasis differently. However, the potential effects of the oxidative stress on the early stages of the fibrin self-assembly process remain unexplored.

Covalent structure of single-stranded fibrin oligomers cross-linked by FXIIIa.

FXIIIa-mediated isopeptide γ-γ bonds are produced between γ polypeptide chains of adjacent monomeric fibrin. Despite the use of the different methodological approaches there are apparently conflicting ideas regarding the orientation of γ-γ bonds. To identify the orientation of these bonds a novel approach has been applied.

Ozone-induced oxidative modification of fibrinogen: role of the D regions.

Native fibrinogen is a key blood plasma protein whose main function is to maintain hemostasis by virtue of producing cross-linked fibrin clots under the influence of thrombin and fibrin-stabilizing factor (FXIIIa). The aim of this study was to investigate mechanisms of impairment of both the molecular structure and the spatial organization of fibrinogen under ozone-induced oxidation. FTIR analysis showed that ozone treatment of the whole fibrinogen molecule results in the growth of hydroxyl, carbonyl, and carboxyl group content.

Cannabinoids for neuropathic pain.

Treatment options for neuropathic pain have limited efficacy and use is fraught with dose-limiting adverse effects. The endocannabinoid system has been elucidated over the last several years, demonstrating a significant interface with pain homeostasis. Exogenous cannabinoids have been demonstrated to be effective in a range of experimental neuropathic pain models, and there is mounting evidence for therapeutic use in human neuropathic pain conditions.

The endocannabinoid system, cannabinoids, and pain.

The endocannabinoid system is involved in a host of homeostatic and physiologic functions, including modulation of pain and inflammation. The specific roles of currently identified endocannabinoids that act as ligands at endogenous cannabinoid receptors within the central nervous system (primarily but not exclusively CB 1 receptors) and in the periphery (primarily but not exclusively CB 2 receptors) are only partially elucidated, but they do exert an influence on nociception. Exogenous plant-based cannabinoids (phytocannabinoids) and chemically related compounds, like the terpenes, commonly found in many foods, have been found to exert significant analgesic effects in various chronic pain conditions.

Ozone-induced oxidative modification of plasma fibrin-stabilizing factor.

The plasma fibrin-stabilizing factor (pFXIII) function is to maintain a hemostasis by the fibrin clot stabilization. The conversion of pFXIII to the active form of the enzyme (FXIIIа) is a multistage process. Ozone-induced oxidation of pFXIII has been investigated at different stages of its enzyme activation.

Presenting the improved possibility for staying well might be better than talking about change in risk: use of the non-occurrence probability increase (NOPI).

Objective: Talking about risk with patients is problematic since the individual's risk is not addressed and is usually very low. This study aimed to see how fact presentation influenced the decision-making process for general practitioners concerning treatment for the prevention of cardiovascular disease. Rather than looking at the risk of becoming ill, often presented as high figures of relative risk reduction (RRR), it could be useful to present the probability of staying well, i.

Active involvement and intervention in patients exposed to whiplash trauma in automobile crashes reduces costs: a randomized, controlled clinical trial and health economic evaluation.

Study Design: To examine and compare the costs and consequences in a partial economic evaluation of two competing interventions in patients exposed to whiplash trauma in automobile crashes. The interventions were an active involvement and intervention using early mobilization and a standard intervention of rest, recommended short-term immobilization in a cervical collar and a cautious, gradual self-exercise program according to a leaflet. The study was randomized and controlled.

A review of treatment interventions in whiplash-associated disorders.

In recent years, there has been much debate on the treatment of whiplash-associated disorders (WAD). It is not clear if the treatments commonly employed are effective, and concerns have been raised on the available scientific evidence of many of these treatments. The aim of this study was to review the literature systematically to analyze the evidence basis of many commonly used treatments for patients suffering from WAD, both in the acute and the chronic state.

Active intervention in patients with whiplash-associated disorders improves long-term prognosis: a randomized controlled clinical trial.

Study Design: Three-year follow-up of a prospective randomized trial in 97 patients exposed to whiplash trauma in motor vehicle collisions.

Objectives: To compare the long-term efficacy of active intervention with that of standard intervention and the effect of early versus delayed initiation of intervention.

Summary Of Background Data: There is no strong evidence for many treatments for whiplash-associated disorders.

Laboratory implementation of human papillomavirus testing.

Human papillomavirus testing is becoming an integral component of cervical cancer screening. Market forces will require most laboratories that perform Papanicolaou tests to develop a system for handling human papillomavirus testing also. Data and information are presented that may facilitate laboratories when addressing the following issues in the process of developing a human papillomavirus testing service: Which methodology is the best fit for the laboratory? Is it better to develop an in-house testing service or to send it out? How do I get started? What are the financial and economic issues, and how should they be managed?