fibrin and Ulcer

To assess thrombin generation, fibrin formation, and structure together with the fibrinolytic status in patients with systemic sclerosis (SSc) in relation to the occurrence of digital ulcers (DUs) during the course of disease.. We studied variables of endothelial dysfunction, thrombin generation, overall hemostatic potential, and fibrin clot turbidity in plasma from 58 patients with SSc (39 with DU history and 19 DU-naïve) and 46 matched healthy controls (HCs). Fibrin structure was visualized using scanning electron microscopy (SEM). Finally, 39 patients with a history of DUs were followed for 1.5 years and the predictive value of all investigated markers for new DU onset was explored.. Significantly enhanced endogenous thrombin potential (ETP) and prolonged clot lysis time (CLT) were found in patients with DUs compared to HCs. CLT was prolonged in patients with DUs compared to those without, showing good validity in identifying DUs with an area under the curve of 0.7 (95% CI 0.6-0.8). The levels of ETP and intercellular adhesion molecule 1 were independently associated with CLT. Over the follow-up period, 20 patients developed new DUs. CLT was prolonged (. Our results suggest that impaired fibrinolysis might have an emerging role in underlying digital vasculopathy and its progression in SSc.

Topics: Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Humans; Scleroderma, Systemic; Skin Ulcer; Thrombin; Thrombosis; Ulcer

The objective was to study the effectiveness of a commercially available collagen conduit filled with fibrin-agarose hydrogels alone or with fibrin-agarose hydrogels containing autologous adipose-derived mesenchymal stem cells (ADMSCs) in a rat sciatic nerve injury model.. A 10 mm gap was created in the sciatic nerve of 48 rats and repaired using saline-filled collagen conduits or collagen conduits filled with fibrin-agarose hydrogels alone (acellular conduits) or with hydrogels containing ADMSCs (ADMSC conduits). Nerve regeneration was assessed in clinical, electrophysiological and histological studies.. Clinical and electrophysiological outcomes were more favorable with ADMSC conduits than with the acellular or saline conduits, evidencing a significant recovery of sensory and motor functions. Histological analysis showed that ADMSC conduits produce more effective nerve regeneration by Schwann cells, with higher remyelination and properly oriented axonal growth that reached the distal areas of the grafted conduits, and with intensely positive expressions of S100, neurofilament and laminin. Extracellular matrix was also more abundant and better organized around regenerated nerve tissues with ADMSC conduits than those with acellular or saline conduits.. Clinical, electrophysiological and histological improvements obtained with tissue-engineered ADMSC conduits may contribute to enhancing axonal regeneration by Schwann cells.

Topics: Adipose Tissue; Amputation, Surgical; Animals; Biocompatible Materials; Cells, Cultured; Electromyography; Electrophysiological Phenomena; Fibrin; Hydrogels; Immunohistochemistry; Laminin; Male; Mesenchymal Stem Cells; Nerve Regeneration; Neurofilament Proteins; Peripheral Nerves; Rats; Rats, Wistar; S100 Proteins; Sciatic Nerve; Sepharose; Ulcer

Combining complementary nonviral gene delivery vehicles such as tissue engineering scaffolds and liposomes not only is a promising avenue for development of safe and effective gene delivery system but also provides an opportunity to design dynamic extended release systems with spatiotemporal control. However, the DNA loading capacity of scaffolds such as fibrin is limited. Fibrin microspheres carrying DNA complexes can be utilized to extend the capacity of fibrin scaffold. Here, in a proof of concept study, the feasibility of fibrin microspheres for extending gene delivery capacity is described. Toward this goal, fibrin microspheres encapsulating lipoplexes were fabricated. The structural and functional integrity of DNA was assessed respectively by gel electrophoresis and an in vivo pilot study, using endothelial nitric oxide synthase (eNOS) as a model therapeutic gene in a rabbit ear ulcer model of compromised wound healing. The results confirmed structural integrity and successful delivery and functional integrity, assessed qualitatively by angiogenic effect of eNOS. Finally, as a step toward development of a "fibrin in fibrin" temporal release system, fibrin microspheres were shown to degrade and release DNA differentially compared to fibrin scaffold. It can thus be concluded that fibrin microspheres can be utilized for gene delivery to extend the capacity of a fibrin scaffold and can form a component of a "fibrin in fibrin" temporal release system.

Topics: Alloxan; Animals; Blotting, Western; DNA; Ear; Fibrin; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Immunoenzyme Techniques; Mice; Mice, Obese; Microspheres; Nitric Oxide; Nitric Oxide Synthase Type III; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Ulcer; Wound Healing

Diabetic healing is marked by a reduced nitric oxide (NO) production at the wound site. This study aimed to investigate whether a fibrin scaffold would enhance the delivery of adenovirus encoding endothelial nitric oxide synthase (eNOS), one of the enzymes responsible for NO production, resulting in more NO production, and enhanced healing. An alloxan rabbit ear ulcer model was used to investigate healing, in response to the following treatments: fibrin containing AdeNOS, AdeNOS alone, fibrin alone and no treatment. Immunohistochemistry to detect eNOS expression and histological evaluation of healing were assessed at 7 and 14 days. eNOS expression was significantly greater in the fibrin containing AdeNOS group at 14 days compared to all other groups. Furthermore, this group showed a significantly faster rate of epithelialisation than all other groups. The volume of inflammatory cells was highest in the fibrin containing AdeNOS group at 7 days, which dropped significantly by 14 days. Likewise, the surface area and length of vessels reduced significantly in the fibrin containing AdeNOS group between 7 and 14 days indicating tissue remodelling, but remained stable in all other groups. Regression analysis showed that the epithelialisation rate was significantly affected by change in eNOS expression, inflammation, and surface area and length of vessels over time in the fibrin containing AdeNOS group. It was concluded that fibrin delivery of AdeNOS resulted in enhanced eNOS expression, inflammatory response, and a faster rate of re-epithelialisation.

Topics: Adenoviridae; Animals; Blood Vessels; Collagen; Ear; Fibrin; Genetic Therapy; Immunohistochemistry; Inflammation; Nitric Oxide; Nitric Oxide Synthase Type III; Rabbits; Time Factors; Tissue Scaffolds; Transfection; Ulcer; Wound Healing

Haemophilus ducreyi causes the sexually transmitted genital ulcer disease chancroid. In human inoculation experiments, bacteria colocalize with neutrophils and macrophages but remain extracellular. The organism also colocalizes with collagen and fibrin but not with keratinocytes, fibroblasts, laminin, or fibronectin. These relationships are established by 48 h postinoculation and persist through the pustular stage of disease. To extend these observations to the ulcerative stage of disease, and to compare results in the human model with those of natural disease, we obtained biopsies from patients with naturally acquired chancroid. All ulcers were culture positive for H. ducreyi and histologically very similar to pustules from the human model. Staining with H. ducreyi-specific monoclonal antibodies demonstrated H. ducreyi within 5 biopsies. The organism was chiefly found within the granulocytic infiltrate of the ulcer. Dual staining for H. ducreyi and eukaryotic tissue components showed that H. ducreyi colocalized with neutrophils and fibrin at the ulcerative stage of disease. No bacteria were associated with keratinocytes, fibroblasts, or collagen. Overall, these findings are consistent with results from the human model. This is the first reported study to localize bacteria specifically identified as H. ducreyi within naturally acquired chancroid.

Topics: Chancroid; Fibrin; Haemophilus ducreyi; Humans; Neutrophils; Ulcer

Pooled donor fibrin with an ultimate fibrinogen concentration of 60 mg/ml was used to study its effect on wound healing of surgically created ulcers in a rabbit ear. Water soluble polymer (PEG Mw = 20 KD) beads of 100-150 microns were added (12% by volume) to the fibrinogen to obtain a porous and rough structure. Five 6 mm-diameter ulcers to the depth of bare cartilage were created on each rabbit ear. There were two periods of study (4 and 8 days), with 15 ulcers in each time period, 5 of which were treated with a modified fibrin scaffold, 5 with a non-modified fibrin scaffold, and 5 served as control ulcers. The ulcer sites were subjected to routine histological processing and histomorphometrical quantification. Data analysis revealed significant increases in volume fraction of fibroblast and number of blood vessels in the modified fibrin scaffold treated ulcers over control and non-modified fibrin scaffold treated groups.

Topics: Animals; Biocompatible Materials; Ear; Fibrin; Humans; Microscopy, Electron, Scanning; Rabbits; Ulcer; Wound Healing

A few studies have indicated that repeated dosing of acidic fibroblast growth factor (FGF-1) is essential to be effective in modulating the wound-healing response. However, little investigation has been done to determine the effective dosing regimen of FGF-1 or the appropriate carrier vehicle for this growth factor. The main objective of this study was to determine the effective angiogenic stimulatatory dose of FGF-1 delivered through a modified fibrin matrix, using a rabbit ear ulcer model. Specifically, the aim was to test the effects of FGF-1 on the angiogenic, fibroblastic, and epithelial responses in a wound model. Five 6-mm diameter ulcers to the depth of bare cartilage were created on each rabbit ear. Four different combinations (0.8, 8, 80, and 800 micrograms/ml) of the growth factor were examined across two periods of study. Pooled modified fibrin was used to deliver the growth factor. Histomorphometrical quantification was conducted after routine histological processing of the ulcers sites. Data analysis indicated a strong correlation between concentration and the histomorphometric response. In general, the growth factor treatments affected the healing response and exhibited a dose-dependent behavior. The addition of FGF-1 led to an increase in the angiogenic and fibroblastic responses, as well as an increase in the epithelialization rate. The preferred dose of 8 micrograms initiated a high epithelialization rate, fibroblastic, and angiogenic responses, and was the lowest dose required to initiate these responses.

Topics: Animals; Cattle; Disease Models, Animal; Ear; Epithelium; Fibrin; Fibroblast Growth Factor 1; Fibroblasts; Humans; Macrophages; Microcirculation; Neovascularization, Physiologic; Neutrophils; Rabbits; Ulcer; Wound Healing

We investigated the effect of dexamethasone on indomethacin-induced ulceration in the rat.. Groups of four rats received oral indomethacin (15 mg/kg) and the jejunal mucosa was examined 24 h later for mucosal ulceration. Three of the groups received oral dexamethasone (1, 3 and 6 mg/kg) 0.5 h prior to indomethacin, while the fourth received vehicle. Haematological evaluation was performed and ulcers were assessed both histologically and immunohistochemically.. Indomethacin caused multifocal jejunal ulceration that was reduced only by the highest dose of dexamethasone (6 mg/kg). Indomethacin caused a significant fall in the blood haemoglobin concentration that was prevented by dexamethasone at all doses. The ulcers induced by indomethacin alone were deep, punched-out and haemorrhagic while the ulcers arising in rats pre-treated with dexamethasone (all doses) were 'plugged' by a white fibrino-purulent exudate. Histologically, the dexamethasone ulcer exudate was composed of bacteria, fibrin, mucus and a significant increase in the numbers of neutrophils. Dexamethasone alone had no significant pathological effect on the small intestine.. We report the observation that dexamethasone at high doses inhibits indomethacin-induced jejunal ulceration in the rat while at low doses it promotes 'plugging' of ulcers with bacteria, fibrin, mucus and neutrophils that probably reduces haemorrhage from the ulcer base.

Topics: Animals; Dexamethasone; Enteritis; Fibrin; Hematologic Tests; Indomethacin; Intestinal Mucosa; Jejunal Diseases; Male; Mucus; Neutrophils; Rats; Rats, Sprague-Dawley; Ulcer

Pericapillary fibrin deposition is thought to contribute to the pathogenesis of venous ulceration. To our knowledge, however, there is no previous evidence that pericapillary fibrin is deposited in the tissue adjacent to venous ulcers. We prospectively studied patients with ulcers of the lower extremities for the presence of dermal pericapillary fibrin in the skin adjacent tot he ulcers. On direct immunofluorescence, pericapillary fibrin was found in 14 (93%) of the 15 patients with venous ulceration but in only one (7%) of the 14 subjects with ulcers due to other causes. We also confirmed the presence of dermal pericapillary fibrin in legs with venous disease without ulcerations. We conclude that the pericapillary fibrin is easily demonstrable in the dermis adjacent to venous ulcers. In the evaluation of ulcers due to uncertain causes, the presence of dermal pericapillary fibrin may provide additional diagnostic help.

Topics: Biopsy; Blood Gas Monitoring, Transcutaneous; Capillaries; Fibrin; Fluorescent Antibody Technique; Humans; Leg; Skin; Ulcer; Vascular Diseases; Veins; Wound Healing

Lesions are described in the vocal cords of an unselected group of 91 infants dying as "cot deaths", 11 stillbirths and 107 infants and children dying from conventional diseases. The lesions have been classified into six types. After allowances for the effects of intubation, the same incidence and type of change was present in all but the stillbirths. This argues against them being a specific pathogenic mechanism confined to the cot death situation. The aetiology and pathogenesis are unexplained but indicate the existence of an unsuspected laryngeal disorder that merits further study in mechanism leading to child death.

Topics: Autopsy; Basement Membrane; Female; Fetal Death; Fibrin; Humans; Infant; Infant, Newborn; Intubation, Intratracheal; Laryngeal Diseases; Necrosis; Pregnancy; Sudden Infant Death; Ulcer; Vocal Cords

Topics: Arteriosclerosis Obliterans; Arteritis; Biomedical Research; Celiac Artery; Fibrin; Gastrectomy; Glycosaminoglycans; Humans; Sclerosis; Stomach Ulcer; Takayasu Arteritis; Thromboangiitis Obliterans; Ulcer