We evaluated the efficacy of treating eccentric muscle damage with IGF-1 PEGylated to a fibrin biomatrix. With one injection, delivered one hour after the induction of eccentric muscle damage we saw an attenuation of force loss early in recovery, maintenance of muscle weight, and progression to the repair/regeneration of the damaged fibers at a greater speed and magnitude in the first week of recovery. As opposed to introducing an unbound bolus of IGF-1, we believe the ability of the PEGylated-fibrin to stabilize and sustain delivery of the molecule results in significantly better recovery. Coupling IGF-1, which has multiple beneficial effects in tissue repair, with this system of delivery provides a simple and easy to administer treatment for eccentric muscle damage. With this form of damage being the most prevalent of all skeletal muscle damage types, since it is underlies all muscle strain, a simple and effective treatment is important for increasing functional recovery after injury. / text

Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are associated with increased risk of atherothrombotic disease. Lp(a) is a unique lipoprotein consisting of a low density lipoprotein-like moiety covalently linked to apolipoprotein(a) (apo(a)), a homologue of the fibrinolytic proenzyme plasminogen. Apo(a) is extremely heterogeneous in size with small isoforms being independently associated with increased cardiovascular risk. Several in vitro and in vivo studies have shown that Lp(a)/apo(a) can inhibit tissue-type plasminogen activator (tPA)-mediated plasminogen activation on fibrin surfaces, although the mechanism of inhibition by apo(a) remains controversial. Essential to fibrin clot lysis are a number of plasmin-dependent positive feedback reactions that enhance the efficiency of plasminogen activation, including the plasmin-mediated conversion of Glu1-plasminogen to Lys78-plasminogen. Additionally, abnormal fibrin clot structures have been associated with both an increased risk of cardiovascular disease and elevated Lp(a) levels. Similarly, oxidized phospholipids have been implicated in the development of cardiovascular disease, and are not only preferentially carried by Lp(a) in the plasma but have also been shown to covalently-modify both apo(a) and plasminogen. In this thesis, we built upon the understanding of the role of apo(a) in plasminogen activation on the fibrin/degraded fibrin surface by determining that: (i) apo(a) inhibits plasmin-mediated Glu1-plasminogen to Lys78-plasminogen conversion and identifying the critical domains in apo(a) responsible for this effect, (ii) apo(a) isoform size does not affect either the inhibition of tPA-mediated plasminogen activation or the inhibition of plasmin-mediated Glu1-plasminogen to Lys78-plasminogen conversion, (iii) apo(a) modifies fibrin clot structure to form more dense clots with thinner fibers and reduced permeability, modifications that enhance the ability of apo(a) to inhibit tPA-mediated plasminogen activation and (iv) the phosphorus content of apo(a) affects its ability to inhibit tPA-mediated plasminogen activation and the phosphorus content of plasminogen affects its ability to be activated by tPA. By understanding these individual reactions, each of which has the potential to affect the broader fibrin clot lysis process, we have expanded our understanding of the overall effect of Lp(a)/apo(a) in the inhibition of plasminogen activation on the fibrin/degraded fibrin surface and thus broadened our understanding of how Lp(a)/apo(a) may mediate the inhibition of thrombolysis in vivo. / Thesis (Ph.D, Biochemistry) -- Queen's University, 2011-12-14 08:26:54.99

Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [134]-154).

Dissertation (Ph.D.) -- Worcester Polytechnic Institute. / Keywords: Ligament; ACL; Collagen; Fibrin; Microthread; Fiber; Thread; FGF-2; Fibroblast; Tissue regeneration; Tissue engineering. Includes bibliographical references.

Este trabalho tem por objetivo comparar a eficácia da cola biológica de fibrina e da drenagem de aspiração pós-operatória na prevenção de complicações cirúrgicas como hematoma e seroma após a realização de ritidoplastia pela equipe da Clínica Rezende no Hospital Moinhos de Vento, na cidade de Porto Alegre/RS. Realizou-se estudo prospectivo, controlado, randomizado e duplo cego. Foram analisadas 72 pacientes, divididas em dois grupos de 36, sendo que no grupo dreno utilizou-se drenagem de aspiração e no grupo cola utilizou-se cola de fibrina. Quarenta e oito horas após a realização dos procedimentos, todas as pacientes foram submetidas a aferição ecográfica da lâmina de exsudato presente sob os retalhos cutâneos da face. O volume total médio foi de 3,21 mL no grupo dreno e 1,02 mL no grupo cola, com magnitude de efeito de 68,1% e intervalo de confiança de 55,3 a 77,2 e p <0,001. Com esses resultados, comprovou-se que a cola apresenta eficácia significativa, demonstrando que sua utilização é 68,1 % mais efetiva que a drenagem de aspiração na prevenção de hematomas ou seromas em ritidoplastia. / This study aimed to compare the efficacy of fibrin glue and suction drainage in preventing postoperative complications such as hematoma and seroma following rhytidoplasties conducted by the staff of Clínica Rezende at Hospital Moinhos de Vento in Porto Alegre, Brazil. A prospective, controlled, randomized, double-blind trial was conducted. The 72 patients assessed in the study were divided into two groups of 36 each, one treated with suction drainage and other with fibrin glue. Forty-eight hours after the procedures, all patients underwent ultrasound evaluation of the volume of exudate under facial skin flaps. The average volume of exudate was 3.21 mL in the drainage group and 1.02 mL in the fibrin glue group, with a size effect of 68.1%, 95% confidence interval of 55.3 to 77.2, and p <0.001. The results of this investigation significant favor the use of fibrin glue, showing that was 68.1 % more effective than suction drainage in preventing hematoma or seroma following rhytidoplasty.

abstract: Thrombus (blood clot) formation is at the roots of hemostasis and pathological thrombosis. Although many studies have successfully elucidated the cellular and molecular mechanisms underlying thrombus formation, there is still a void in understanding the processes limiting thrombus growth beyond that needed for stabilization. As a hemostatic thrombus grows, its surface consisting primarily of platelets changes to that composed of fibrin, which mechanically stabilizes the thrombus. Formation of fibrin ceases after some time; however, it is unclear why this fibrin is non-thrombogenic. This is puzzling since fibrin is known to support strong integrin-mediated adhesion of both platelets and leukocytes in vitro. Therefore, it would be expected that the fibrin surface of hemostatic thrombi in the circulation also support accumulation of these cells and thus continuous thrombus growth or degradation. Nevertheless, many in vivo studies did not detect any accumulation of blood cells including platelets at the fibrin surfaces of thrombi. This finding suggests the existence of natural processes that modulate the adhesive properties of fibrin to ensure proper regulation of thrombus growth, stability and degradation. In this dissertation, I document and discuss the findings supporting the existence of anti-adhesive mechanisms and their physiological relevance in surface-mediated control of thrombus growth and stability. The studies discussed in my dissertation have the potential to establish a novel aspect of hemostasis. Furthermore, it may provide new insights into the intricate and dynamic interplay between the mechanisms underlying hemostatic balance, which is essential to understanding the dysfunction of this process during pathological conditions. / Dissertation/Thesis / Doctoral Dissertation Molecular and Cellular Biology 2016

Este trabalho tem por objetivo comparar a eficácia da cola biológica de fibrina e da drenagem de aspiração pós-operatória na prevenção de complicações cirúrgicas como hematoma e seroma após a realização de ritidoplastia pela equipe da Clínica Rezende no Hospital Moinhos de Vento, na cidade de Porto Alegre/RS. Realizou-se estudo prospectivo, controlado, randomizado e duplo cego. Foram analisadas 72 pacientes, divididas em dois grupos de 36, sendo que no grupo dreno utilizou-se drenagem de aspiração e no grupo cola utilizou-se cola de fibrina. Quarenta e oito horas após a realização dos procedimentos, todas as pacientes foram submetidas a aferição ecográfica da lâmina de exsudato presente sob os retalhos cutâneos da face. O volume total médio foi de 3,21 mL no grupo dreno e 1,02 mL no grupo cola, com magnitude de efeito de 68,1% e intervalo de confiança de 55,3 a 77,2 e p <0,001. Com esses resultados, comprovou-se que a cola apresenta eficácia significativa, demonstrando que sua utilização é 68,1 % mais efetiva que a drenagem de aspiração na prevenção de hematomas ou seromas em ritidoplastia. / This study aimed to compare the efficacy of fibrin glue and suction drainage in preventing postoperative complications such as hematoma and seroma following rhytidoplasties conducted by the staff of Clínica Rezende at Hospital Moinhos de Vento in Porto Alegre, Brazil. A prospective, controlled, randomized, double-blind trial was conducted. The 72 patients assessed in the study were divided into two groups of 36 each, one treated with suction drainage and other with fibrin glue. Forty-eight hours after the procedures, all patients underwent ultrasound evaluation of the volume of exudate under facial skin flaps. The average volume of exudate was 3.21 mL in the drainage group and 1.02 mL in the fibrin glue group, with a size effect of 68.1%, 95% confidence interval of 55.3 to 77.2, and p <0.001. The results of this investigation significant favor the use of fibrin glue, showing that was 68.1 % more effective than suction drainage in preventing hematoma or seroma following rhytidoplasty.

No description available.

M.Phil. / Cataracts have been identified as one of the leading causes of blindness, especially in the developing world. The only presently known effective treatment for this growing problem is surgical removal of the opaque lens followed by replacement with an artificial intra ocular lens. Newer methods have brought greater success, and greater costs. For people in the developing world, these newer methods are not always an option. Together with the increased cost, there is a growing demand because of this worldwide problem. This increased need for surgery has lead to the development of waiting lists in the state funded hospitals. To qualify for a cataract extraction in most state funded hospitals, a best visual acuity of 6/60 is required, compared to the 6/12 to 6/24 levels required in the industrial countries and private practices. With these levels of visual impairment in the developing world, many patients are left functionally blind for long periods of time until cataract extraction can be performed. Older methods such as extra-capsular cataract extraction are still being used in the developing world. This is mostly due to the increased density of the cataracts at the time when the extraction can be performed because of the long waiting time leading to further maturation of the cataract. This method requires a large corneal incision, which is normally closed with nylon sutures. With this method of surgery meticulous wound closure is very important, and in many cases surgically induced astigmatism is one of the unwanted consequences. It was therefore decided, for the purpose of this study, to use autokeratometric data to explore the refractive effects of two different methods of corneal wound closure following planned extra-capsular cataract extraction (ECCE). Astigmatism is a major problem associated with extra capsular cataract extraction, especially when the wound is closed by means of sutures. Studies by Minassian et al. (2001), Jacobi (2003) and Dowler et al. (2000) all show that newer methods of cataract extraction making use of smaller incisions and therefore fewer sutures show faster recovery and less astigmatism. These methods are however mostly restricted to private practice, and therefore potentially unsuited for use in developing countries. The type of material used for wound closure is another very important factor. Depending on the method of suturing wound gape and wound compression can cause increased amounts of astigmatism. Using a method of wound closure that would cause less traction on the cornea could therefore cause less of a problem postoperatively. Tissue adhesives such as Tisseel® fibrin glue could be such an alternative. Studies by Henrick et al. (1987), Kim and Kharod (2007) and Bhatia (2006) show that fibrin glue forms a watertight, non irritating wound while promoting the healing process by the cross linking of collagen fibres.

Diabetes mellitus has emerged as a major public health problem with pandemic growth as the International Diabetes Federation estimates that there were 415 million diabetics in 2015 with that number reaching 642 million by 2040, affecting all regions of the world. Globally we are all interconnected when we deal with problems of climate change, water shortage, HIV or Ebola. The war against type 2 diabetes and other non-communicable diseases should be no different, as effective solutions will need expanded global engagement in science to win it. The risk of cardiovascular events in type 2 diabetes remains unchanged despite good control of diabetes and other cardiovascular risk factors. A better understanding of thrombogenicity in diabetes may help to identify novel therapeutic agents and a starting point would be to identify ultrastructural changes in diabetic erythrocytes, platelets and fibrin networks. In diabetes, thrombogenicity is enhanced and is characterised by: hyperactive platelets, higher levels of clotting factors and impaired fibrinolysis. Thus, in this research study, the technique of scanning electron microscopy (SEM) was used to identify ultrastructural abnormalities in erythrocytes, platelets and fibrin networks of diabetic subjects. Distinct abnormal morphological findings were observed in the erythrocytes, platelets and fibrin fibres of diabetic subjects in comparison to the controls. Physiological parameters such as platelet markers and tissue factor levels were also assessed. Flow cytometric analysis revealed hyperactive platelets in the diabetic subjects. The measurement of tissue factor in plasma was completed by using an ELISA. Tissue factor levels in the diabetic subjects were markedly elevated when compared to controls. Biomedical research has provided evidence that has led to the hypothesis that inflammation is the culprit behind almost most chronic illnesses. Hyperglycaemia, a key feature of diabetes, is known to promote a state of low-grade chronic inflammation. A natural method that can resolve acute and chronic inflammation is earthing. Earthing involves coupling your body to the Earth's surface energies by simply walking barefoot or being connected to a conductive device. When earthed, the electrons are conducted into the human body at the same electrical potential as the earth. It is also suggested that free electrons from the earth neutralize the positively charged free radicals that are the hallmark of chronic inflammation. In this study, earthing was accomplished with conductive adhesive patches placed on the sole of each foot and palm of each hand. An earthing cord was connected to the patches and led outdoors to be connected to a stainless-steel rod driven into the ground. Diabetic subjects were earthed for a session of two hours. Bloods were drawn before and just prior to the end of the two-hour session. Morphological SEM findings of the erythrocytes, platelets and fibrin networks at two-hours showed a remarkable difference when compared to findings at baseline. More importantly, the erythrocytes, platelets and fibrin findings revealed that they all almost reverted to looking like control erythrocytes, platelets and fibrin networks. It remains to be seen if earthing will reduce cardiovascular events in diabetics by improving morphology of cells involved in coagulation. / Thesis (PhD)--University of Pretoria, 2016. / Physiology / PhD / Unrestricted