fibrin and Sclerosis

Drawing from diverse sources including epidemiological and clinical data, surgical observations, histopathology, serosal healing responses to fibrin and fibrinolysis, tissue reaction to chronic exposure, and to exo- and endotoxins, new information on mesothelial stem cells, autocrine and paracrine influences on their proliferation and collagen synthesis, and the effect of glucose on fibroconnective tissue, we have begun to piece together the pathogenetic jigsaw of fibrosis in continuous ambulatory peritoneal dialysis (CAPD). The reaction of peritoneal mesothelium and stroma to the stress of continual dialysis results in a spectrum of alterations ranging from opacification through a tanned peritoneum syndrome to sclerosing encapsulating peritonitis (SEP). Any agent that causes irritation of the mesothelial layer and induces serositis, or single severe or multiple episodes of peritonitis resulting in mesothelial loss, predisposes the peritoneum to fibroneogenesis. An accurate definition of the histopathological changes of peritoneal thickening is a prerequisite for defining pathogenesis. This paper is the first attempt to create such a framework. It is evident from many areas of study that fibrin deposition and fibrinolysis, hyalinization of the superficial stromal collagen possibly tanned through nonenzymatic glycosylation by dialysate glucose and the proliferative potential of mesothelial stem cells play an important and possibly interdependent role in excessive fibroneogenesis in certain patients on CAPD. Many of the pieces of the jigsaw are obviously still missing, and the picture is most surely incomplete. Nevertheless, the outline of the pathologic and etiologic landscape should now be discernible.

Topics: Acetates; Adrenergic beta-Antagonists; Anti-Infective Agents, Local; Catheters, Indwelling; Dialysis Solutions; Fibrin; Fibrinolysis; Fibrosis; Humans; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Peritonitis; Sclerosis; Stem Cells

Aortic valve disease is the most common valvular heart disease leading to valve replacement. The efficacy of pharmacological therapy for aortic valve disease is limited by the high mechanical stress at the aortic valves impairing the binding rate. We aimed to identify nanoparticle coating with entire platelet membranes to fully mimic their inherent multiple adhesive mechanisms and target the sclerotic aortic valve of apolipoprotein E-deficient (ApoE. Considering the potent interaction of platelet membrane glycoproteins with components present in sclerotic aortic valves, platelet membrane-coated nanoparticles (PNPs) were synthetized and the binding capacity under high shear stress was evaluated in vitro and in vivo.. PNPs demonstrated effectively adhering to von Willebrand factor, collagen and fibrin under shear stresses in vitro. In an aortic valve disease model established in ApoE. PNPs could provide a promising platform for the molecular diagnosis and targeting treatment of aortic valve disease.

Topics: Animals; Aortic Valve; Apolipoproteins E; Bicuspid Aortic Valve Disease; Blood Platelets; Cell Membrane; Collagen; Disease Models, Animal; Fibrin; Heart Defects, Congenital; Heart Valve Diseases; Human Umbilical Vein Endothelial Cells; Humans; Male; Mice, Inbred C57BL; Mice, Knockout, ApoE; Nanoparticles; Polylactic Acid-Polyglycolic Acid Copolymer; Sclerosis; Stress, Mechanical; von Willebrand Factor

Dating the traumatic event is usually done on subdural hematoma (SDH). After infant deaths due to Abusive head trauma (AHT) without SDH available, the magistrates still ask experts to date the traumatic event. To do so, the expert only has tools based on adult series of AHT. We aimed to develop a subarachnoid hemorrhage (SAH) and retinal hemorrhage (RH) dating system applicable to infants aged under 3 years.. We studied a retrospective multicenter collection of 235 infants who died between the ages of 0 and 36 months, diagnosed with SAH and/or RH by forensic pathological examination and with known posttraumatic interval (PTI). Two pathologists assessed blindly and independently 12histomorphological features in 83 infants (35 girls, 48 boys) whose median age was 3.8 months. For SAH, histopathological changes were significantly correlated with PTI for the appearance of red blood cells, of fibrino-plaquetted organization, the quantity of lymphocytes and macrophages and the presence or absence of siderophages, collagen and fibroblast formation and presence or absence of neovascularization. For RH, histopathological changes were significantly correlated with PTI for the appearance of red blood cells, the presence or absence of siderophages and sclerosis of the retina.. Our HAS dating system improves the precision and reliability of forensic pathological expert examination of AHT, when SDH are not available, for age estimation in infants. The study of RH histomorphological changes does not allow for reliable dating.

Topics: Blood Platelets; Child Abuse; Child, Preschool; Collagen; Erythrocytes; Female; Fibrin; Fibroblasts; Forensic Pathology; Humans; Infant; Infant, Newborn; Lymphocytes; Macrophages; Male; Neovascularization, Physiologic; Postmortem Changes; Retina; Retinal Hemorrhage; Retrospective Studies; Sclerosis; Subarachnoid Hemorrhage

Reports analyzing the histopathological differences between encapsulating peritoneal sclerosis (EPS) and simple peritoneal sclerosis (non-EPS) and those comparing the pathology of early and late EPS are limited. We present pathological comparisons between EPS and non-EPS, also between the early and late EPS stages. We compared peritoneal membrane (PM) samples (Group B) of 12 EPS patients (Group A) and 23 non-EPS cases regarding; mesothelial loss, submesothelial compact zone degenerated layer and compact zone thicknesses, densities of total and diseased vessels, fibrin stain, new membrane formation and degenerative changes. Group A was subdivided into 7 early (group A1) and 8 late (group A2) EPS cases; we compared both subgroups in the same manner and finally compared groups A1, A2, and B. No differences were found between groups A and B in the incidences of mesothelial detachment, new membrane formation and compact zone degenerative changes between the two groups. Furthermore, there were no differences in compact zone thickness, and vascular densities in the compact zone of respective vascular grade. Whereas, fibrin deposition and thickness of the submesothelial degenerated layer were significantly higher in group A than group B (P = 0.01 and 0.05, respectively), and the thickness of the compact zone was less in group A1 than in group A2 (P = 0.03). Positive fibrin stains and thick degenerative compact zone layers are important pathological findings in EPS. Angiogenesis, vasculopathy, new membrane formation, fibrosis and degenerative changes of the compact zone are not unique characteristics for EPS. Larger size studies are recommended to verify this issue.

Topics: Adult; Aged; Biopsy; Epithelium; Female; Fibrin; Fibrosis; Humans; Male; Middle Aged; Neovascularization, Pathologic; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Sclerosis; Time Factors

To evaluate the utility of peritoneal pathologic samples, unrelated to peritoneal dialysis (PD) treatment, for the study of peritoneal fibrosis and inflammation.. Comparative morphologic and immunohistochemical study of peritoneal pathologic samples unrelated to PD with peritoneal biopsies from PD patients with special emphasis on the expression of myofibroblastic and epithelial-to-mesenchymal transition markers.. Regarding morphology, PD-related simple fibrosis was less cellular, with greater stromal hyalinization, determining a homogeneous, hypocellular aspect of the submesothelium. In contrast, non-PD fibrosis was more cellular with an extracellular matrix showing a dense and fibrillar quality with wide bundles of collagen. Hylinazing vasculopathy was only present in PD samples. Myofibroblastic differentiation and epithelial-to-mesenchymal transition were common findings in all situations of peritoneal fibrosis. Calponin and calretinin are useful cellular markers to study such fibrogenic mechanisms and correlate with other well-known markers such as a -SMA and cytokeratins. Their expression was much more intense in those samples showing acute inflammation (peritonitis).. Non-PD models of peritoneal fibrosis seem very useful to evaluate important features of human peritoneal pathology such us fibrogenesis, and inflammation. Fibrogenic events such as myofibroblastic differentiation and epithelial-to-mesenchymal transition are evident in these tissue samples allowing us to use them as an accessible source for in vivo and ex vivo studies. Both events show their maximal expression in situations of acute inflammation supporting the important role that peritonitis episodes play in the progression of fibrosis.

Topics: Actins; Biomarkers; Biopsy; Calbindin 2; Calcium-Binding Proteins; Calponins; Case-Control Studies; Cell Differentiation; Edema; Epithelium; Fibrin; Fibroblasts; Fibrosis; Hernia, Inguinal; Humans; Hyalin; Keratins; Microfilament Proteins; Neutrophils; Peritoneum; S100 Calcium Binding Protein G; Sclerosis; Tissue Adhesions

Function and structure of peritoneal membrane (PM) are impaired on peritoneal dialysis (PD). Peritoneal sclerosis is a common finding in peritoneal biopsies (PB) of PD patients. The aim of this study was to examine the impact of peritoneal sclerosis on peritoneal function and clinical parameters in PD patients submitted to peritoneal biopsy.. A PB was performed on 31 PD patients during catheter removal due to malfunction or after drop-out from treatment. For each patient PM transport was evaluated by the last peritoneal equilibration test before PB. Each daily glucose load was calculated. Tissue was formalin-embedded and stained for histological and immunohistochemical studies.. Patients with submesothelial sclerosis and those with impairment of submesothelial basement membrane and subendothelial vascular membrane were submitted to a larger daily glucose load. Peritoneal sclerosis > 50 microns was more frequent in high transporters, who were exposed to larger daily glucose load compared to medium-high transporters. Mesothelial loss is correlated to peritoneal sclerosis and vascular injuries.. Peritoneal sclerosis is not constant in PD patients: it is related to the loss of mesothelium integrity, to the daily glucose load of PD treatment and to vascular injuries, but apparently not to the presence of inflammatory infiltrate. It remains a matter of debate how much the peritoneal sclerosis modifies the function of PM and how new more biocompatible PD solutions could reduce PM injury.

Topics: Actins; Antibodies; Biopsy; Dialysis Solutions; Epithelium; Fibrin; Fibroblasts; Glucose; Humans; Macrophages, Peritoneal; Neovascularization, Pathologic; Peritoneal Dialysis; Peritoneum; Sclerosis

To establish histologic criteria for a diagnosis of encapsulating peritoneal sclerosis (EPS), we investigated 69 peritoneal biopsy specimens histologically and immunohistochemically. The specimens included cases of EPS (n = 12), suspected cases of EPS without later manifestation (n = 5), cases of infectious peritonitis (n = 20), cases of ultrafiltration failure (n = 25), and peritoneum at the start of peritoneal dialysis (n = 7). For each specimen, we evaluated these histologic parameters: fibrin deposition, mesothelial denudation, interstitial fibrosis, peritoneal fibroblast swelling, perivascular bleeding capillary angiogenesis, microvascular sclerosis, and interstitial mononuclear cell infiltration. We also evaluated these immunohistochemical markers: macrophage migration inhibitory factor (MIF), fibroblast growth factor (FGF), FGF receptor 2 (FGFR2), alpha smooth muscle actin (alpha SMA), MIB1, and BCL2. The most characteristic histologic findings for EPS were fibrin deposition and fibroblast swelling. The presence of capillary angiogenesis and mononuclear cell infiltration were also associated with EPS. Expression of FGF, FGFR2, MIF, MIB1, and BCL2 in peritoneal fibroblasts was frequently observed in EPS. Our results suggest that fibrin deposition and peritoneal fibroblast activation or proliferation (or both) are useful findings for the early diagnosis of EPS. Careful histologic observation of the peritoneal biopsy after withdrawal of peritoneal dialysis is required for the early diagnosis and prevention of EPS.

Topics: Adult; Female; Fibrin; Fibrosis; Humans; Immunohistochemistry; Male; Middle Aged; Neovascularization, Pathologic; Peritoneal Dialysis, Continuous Ambulatory; Peritoneal Diseases; Peritoneum; Sclerosis

Nonmalignant lymphoid tissue and tissue from patients with nodular sclerosis, Hodgkin's disease, and large cell lymphocytic lymphoma was examined by immunohistochemical techniques for the occurrence in situ of components of coagulation and fibrinolysis reaction pathways. Staining for material interpreted as fibrinogen was observed in abundance in both malignant and reactive lymphoid tissue. Fibrin also occurred to a variable extent but focally in all tissues. Components of coagulation pathways, including tissue factor, factor VII, factor X, and factor XIII ("a" subunit), were restricted to tissue macrophages. Double-labeling techniques revealed fibrin in direct apposition to tissue macrophages. We conclude that fibrinogen and fibrin occur in both benign and malignant lymphoid tissue and that the transformation of fibrinogen to fibrin is attributable to macrophage-initiated thrombin formation. We postulate that both systemic and local hypercoagulability associated with these disorders may be attributable to macrophage activation resulting in expression of procoagulant activity.

Topics: Adolescent; Adult; Aged; Factor VII; Factor VIII; Factor X; Female; Fibrin; Fibrinogen; Fibrinolysis; Hodgkin Disease; Humans; Immunohistochemistry; Leukemia, Lymphocytic, Chronic, B-Cell; Lymph Nodes; Lymphoid Tissue; Lymphoma, Large B-Cell, Diffuse; Macromolecular Substances; Macrophages; Male; Middle Aged; Sclerosis; Thromboplastin

Otic capsule osteogenesis is a common finding in temporal bones from autoimmune disease individuals. However, the underlying cellular mechanisms are poorly understood. Therefore, to better understand this relationship of autoimmune disease and otic capsule pathology, inner ear sclerotic lesions of the Palmerston North autoimmune disease mouse were histochemically stained to identify their content and potential osteogenic processes. Lesions stained positive for calcium, amyloid, fibrinoid, and glycoproteins (PAS), but negative for collagen, calcium oxalate, reticular fibers and glycosaminoglycans (Alcian Blue). Amyloid and fibrinoid deposition are associated with other immune disease, which suggests these local processes may provide a protein substructure that calcifies in lesion progression. Similar cellular mechanisms may underlie certain types or phases of human autoimmune otic capsule disease.

Topics: Amyloid; Animals; Autoimmune Diseases; Calcium; Collagen; Ear, Inner; Fibrin; Glycoproteins; Glycosaminoglycans; Histocytochemistry; Mice; Mice, Mutant Strains; Sclerosis

Sclerosing peritonitis is a severe complication after CAPD treatment. The visceral peritoneum is thickened and interenteric adhesive parts are found. Myofibroblasts are proliferated and the collageneous tissue is hyperplastic. The mean clinical symptom is the mechanical obstruction of the small bowel. We observed this illness in three out of sixty patients under CAPD. These patients had higher incidence of bacterial peritonitis. In the ascites high concentrations of PG E2 and Thromboxan B2 were observed. After treatment of the infection the concentrations fell down to normal values. Electronoptical observations from peritoneal biopsies showed a proliferation of myofibroblasts and extracellular lysosomes. It is known from these lysosomes that they are able to set free proteasis. These lead to degredation of fibrin and fibrinogen. These splits are mitogen to myofibroblasts. release from HIT cells could also be evoked by the sulphonylureas glibenclamide and tolbutamide and by an increase in concentration of extracellular K+ to 40 mmol/l. The content of cyclic AMP in HIT cells was increased modestly by glucose but not by an increase in extracellular K+. Forskolin elicited a 4-fold increase in cyclic AMP content. We conclude that HIT cells retain the essential features of the insulin secretory response of normal B cells and represent an important tool for further biochemical characterisation of the secretory system.

Topics: Adult; Bacterial Infections; Dinoprostone; Female; Fibrin; Humans; Intestinal Obstruction; Intestine, Small; Male; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Peritonitis; Prostaglandins E; Sclerosis; Thromboxane B2

The association of fibrin and tumour cells on a sclerosed mitral valve in a 62-year-old woman is described. This was the first indication of malignant disease but bilateral ovarian cancer was proved two months later. ino further tumour deposits have been found in fifteen months. The tumour deposit on the valve was most likely a metastasis but primary heart valve sarcoma has not been positively excluded. If the lesion was a secondary deposit this has possible implications for the role of fibrin in metastasis in humans.

Topics: Female; Fibrin; Heart Neoplasms; Heart Valve Diseases; Humans; Middle Aged; Mitral Valve; Neoplasm Metastasis; Neoplastic Cells, Circulating; Ovarian Neoplasms; Ovary; Sarcoma; Sclerosis

Topics: Capillaries; Fibrin; Humans; Hypertension; Sclerosis; Skin; Varicose Ulcer; Venous Pressure

Topics: Adolescent; Adult; Anemia, Sickle Cell; Arthritis; Bone and Bones; Child; Child, Preschool; Erythrocytes, Abnormal; Female; Fibrin; Hemoglobin C Disease; Humans; Infarction; Joint Diseases; Male; Middle Aged; Mucins; Necrosis; Osteoporosis; Radiography; Sclerosis; Synovial Fluid; Synovial Membrane; Thalassemia; Uric Acid

Topics: Chlorambucil; Complement Fixation Tests; Complement System Proteins; Eosinophils; Female; Fibrin; Humans; Hyalin; Immunoglobulin G; Immunoglobulin M; Infant; Infant, Newborn; Kidney Glomerulus; Kidney Tubules; Male; Nephrotic Syndrome; Prednisone; Prognosis; Renal Dialysis; Sclerosis

Topics: Acute Kidney Injury; Aged; Bronchopneumonia; Diagnosis, Differential; Fibrin; Humans; Hypertension, Portal; Kidney Cortex Necrosis; Kidney Glomerulus; Liver Cirrhosis; Male; Mesenteric Veins; Portal Vein; Sclerosis; Shwartzman Phenomenon; Splenic Vein; Thrombosis

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

Topics: Blood Coagulation; Coronary Artery Disease; Coronary Disease; Coronary Thrombosis; Fibrin; Fibrinolysis; Heart; Humans; Sclerosis