The Kidney and Intravascular Coagulation in Myelomatosis

In 15 out of 35 patients with myelomatosis histological examination showed intravascular fibrin within the glomeruli, and this was associated with proliferation of the mesangial complex in 12. The presence of intravascular fibrin and mesangial proliferation was not associated with any specific immunoglobulin abnormality or with the presence or absence of Bence Jones proteinuria. In addition to fibrin being present within glomerular capillaries it was also shown in intertubular capillaries in three cases of myelomatosis with acute tubular necrosis. It is suggested that intraglomerular coagulation and fibrin deposition may contribute to the genesis of renal failure in myelomatosis.     

Modification by Drugs of Urinary Fibrin Fibrinogen Degradation Products in Glomerulonephritis

Treatment with indomethacin, aspirin, or prednisone has been shown to reduce urinary fibrin/fibrinogen degradation products (F.D.P.) in approximately two-thirds of patients with proliferative glomerulonephritis. This reduction which is dose-dependent for prednisone but not for indomethacin or aspirin in the range of doses used occurs within two to three days of beginning treatment and is thought to result from decreased intraglomerular fibrin deposition rather than alteration of glomerular permeability to F.D.P. In patients who responded in this manner treatment was associated with reductions in the degree of proteinuria and maintenance or improvement in renal function.     

Urinary Fibrinogen Derivative Excretion and Intraglomerular Fibrin Deposition in Glomerulonephritis

The relations between glomerular fibrin deposition, urinary excretion of fibrinogen derivatives (F.D.), and proteinuria were explored in 81 patients with glomerulonephritis. A positive correlation existed between proteinuria and F.D. excretion even when no fibrin could be detected in the glomerulus. In two patients with tubular proteinuria F.D. excretion was also raised, suggesting that tubular reabsorption or catabolism of F.D. or both normally occur.Disproportionately high titres of F.D. were observed when fibrin was deposited in an extracapillary site, but mesangial fibrin deposition was not accompanied by a higher excretion of F.D. than that observed in patients in whom intraglomerular fibrin was not detected. These observations suggest that the immunofluorescent findings on renal biopsies should be the major criteria on which a trial of anticoagulants in proliferative glomerulonephritis might be instituted and that measurement of urinary F.D. is likely to be of value in monitoring therapy in patients with extracapillary fibrin deposition.     

Serum and Urinary Fibrin/Fibrinogen Degradation Products in Glomerulonephritis

The serum and urine concentrations of fibrin/fibrinogen degradation products (F.D.P.) were estimated in 172 patients with glomerulonephritis. In each case the diagnosis was established on the basis of clinical, renal histological, and ultrastructural findings. Serum F.D.P. concentrations were often raised in all types of glomerulonephritis, though more consistently in active proliferative forms. The urinary concentration provided a reliable and sensitive index of activity, progression, and natural history in proliferative glomerulonephritis. In these forms the urinary F.D.P. content was thought to reflect predominantly lysis of intraglomerular fibrin deposits. In minimal lesion and membranous glomerulonephritis low but abnormal concentrations of urinary F.D.P. were consistently found. It is suggested that in these cases the products are derived from limited proteolysis of fibrinogen filtered through an abnormally permeable basement membrane.Daily measurement of urinary F.D.P. concentration is of potential value in the differential diagnosis of patients with glomerulonephritis and at the same time provides a sensitive assessment of the activity and natural history of proliferative disease.     

Tissue distribution of Neutrophils in postischemic acute renal failure

Polymorphonuclear neutrophil granulocytes (PMNs) seem to participate in the pathogenesis of renal ischemic reperfusion injury. The kidneys from male Sprague Dawley rats were immersion-fixed after 45 min of renal artery clamping followed by reperfusion for 0, 5, 20, and 120 min, respectively. The tissue distribution of PMNs in the kidneys was studied histochemically using naphthol AS-D chloroacetate esterase as a specific marker for these cells. Neutrophil counts per unit sectional area were obtained for renal cortex, outer and inner medulla. In the cortex separate intraglomerular and peritubular counts, and in the outer medulla separate outer and inner stripe counts were made. After 120 min of reperfusion the total renal PMN counts were 488 ±62 (n = 4) compared with 54 ±4 (n = 4) per cm² in nonischemic controls. Within 120 min of reperfusion PMN counts increased by a factor of 8 in the cortex, of 12 in the outer medulla and of 14 in the inner medulla, compared with controls. The ratio of intraglomerular against peritubular PMN counts was approximately 2 in controls, but 0.5 after a 120-min reperfusion interval. The outer stripe of the outer medulla contained only a small number of PMNs whereas PMN counts of 923 ±197 (n = 4) per cm² were found in the inner stripe after 120 min reperfusion. Interestingly, there was a marked increase in PMNs in the inner stripe during the first 5 min of reperfusion but no extravasation of PMNs was observed. Taken together, these data provide the first evidence that PMNs accumulate particularly within peritubular capillaries in the cortex and within the inner stripe of the outer medulla. This distribution pattern is consistent with the hypothesis that PMN-augmented cell injury occurs in the early phase of postischemic acute renal failure. In addition the steady increase in PMNs during reperfusion may further contribute to impaired renal function.     

Mediators and mechanisms of radiation nephropathy

Normal tissue radiation injury occurs after sufficient irradiation, thus limiting the curative potential of x-ray therapy. In the kidney, radiation injury results in fibrosis and, ultimately, renal failure. The mediators of fibrosis in radiation nephropathy have received scant attention. Therefore, we evaluated the sequential presence of alpha smooth muscle actin (alphasma), fibrin, collagen, and TGFbeta1 in a porcine model of radiation nephropathy using 9.8 Gy single-dose local kidney irradiation. During the 24-week study, there was progressive and significant collagen accumulation in glomeruli and in interstitium. In glomeruli, this was associated with significant mesangial alphasma expression by 2 weeks after irradiation, a further rise at 4 weeks, and then a gradual fall to baseline. Glomerular fibrin deposition was significant by 4 weeks after irradiation, and remained elevated thereafter. There was little or no glomerular TGFbeta1 expression at any time point. Tubular fibrin deposition was significant at 4 weeks after irradiation but declined thereafter. There was little or no tubulo-interstitial alphasma expression at any time after irradiation. At 6 weeks after irradiation, there was a significant peak of tubular epithelial TGFbeta1 expression that declined thereafter. The early glomerular injury is evident as mesangial alphasma expression but is not proceeded by TGFbeta1 expression. There is sustained glomerular fibrin deposition with deposition of fibrin in tubular lumens, suggesting that tubular fibrin derives and flows out from injured glomerular tufts. We conclude that i) alphasma expression is an early marker of glomerular radiation injury, presaging scarring; ii) fibrin deposition is involved in glomerular and tubular radiation injury; and iii) TGFbeta1 is not an early event in radiation nephropathy, and not apparent in glomeruli in this model, but may correlate with later tubulo-interstitial fibrosis. Thus, the mediators of scarring in this model differ according to time after injury and also according to the affected tissue compartment.     

Releasing of plasminogen-activator from the kidney to the blood (author's transl)]

When fibrinolytic activity in blood samples from various vessels was examined by the dilute-blood-clotlysis-time method (DBCLT), it was found to be noticeably high in the renal venous blood, though the activity was not detected by usual blood clotlysis time method. Plasmin was not detected in any blood samples examined, and the contents of fibrinogen and fibrin (or fibrinogen) breakdown products in the renal venous blood were not significantly different from those in the blood from other vessels. However, the high activity of plasminogen-activator was found only in the renal venous blood. Inhibitors on plasmin and plasminogen-activator (urokinase) were detected in almost the same amount in the blood samples from the various vessels. The amount of the inhibitors was sufficient to inhibit the plasminogen activation by urokinase, whose activity was equivalent to the plasminogen-activator activity in the renal venous blood. These results indicate that the high activity by DBCLT in the renal venous blood was derived from the high activity of plasminogen-activator, which was inactivated by inhibitors in undiluted blood. Plasminogen-activator may be released from the kidney to the blood, and immediately inactivated by the inhibitors in renal vein, and then diluted with systemic blood which contains little plasminogen-activator.     

Localization in situ of type VI collagen protein and its mRNA in mesangial proliferative glomerulonephritis using renal biopsy sections

 Extracellular matrix accumulation is crucial in the pathogenesis of glomerulosclerosis in mesangial proliferative glomerulonephritis (GN). In an attempt to explore the distribution of type VI collagen and its synthesizing cells in normal and diseased glomeruli, we investigated mRNA and protein expression of type VI collagen in renal biopsy sections, histologically diagnosed as mesangial proliferative GN. Five renal biopsies from patients diagnosed as having minor glomerular abnormalities and one surgical renal tissue were also simultaneously examined as controls. Immunohistochemical studies revealed type VI collagen immunostaining in the mesangium and glomerular basement membrane of the control glomeruli. Compared to the control, increased deposition of type VI collagen was noted in the mesangial proliferative and sclerotic lesions in GN. To identify the cells responsible for the synthesis of type VI collagen mRNA, renal sections were hybridized in situ with digoxigenin-labeled antisense oligo-DNA probe complementary to a part of α1 (VI) mRNA. Occasionally intraglomerular cells hybridized with digoxigenin-labeled antisense pro α1 (VI) oligo-DNA in control glomeruli. An increased number of intraglomerular cells (mostly epithelial cells) were, however, positive for α1 (VI) mRNA expression in GN sections. The present study documents the distribution of type VI collagen in the normal glomeruli and provides further evidence of accelerated synthesis of this collagen in mesangial proliferative GN. Accepted: 21 July 1998     

Protective effect of cicletanine on renal function in diabetic spontaneously hypertensive rats.

Hypertension and diabetes are commonly associated and strongly predispose to renal injuries. In general, antihypertensive therapies protect from these damages, but the effect of cicletanine, a new type of antihypertensive drug, is unknown. This study examines the effects of cicletanine on renal failure in spontaneously hypertensive rats with diabetes (SHRD). Diabetes mellitus was induced with streptozotocin in uninephrectomized SHR. Rats received the vehicle, 10 mg or 50 mg/kg per day of cicletanine for 6 weeks. Age-matched untreated Wistar-Kyoto rats were used as controls. Systolic blood pressure (SBP), microalbuminuria and proteinuria were assessed throughout the treatment. At the end of the study, creatinine clearance measurements and histological analysis of kidneys were performed. Cicletanine did not affect SBP but decreased the elevated albuminuria of diabetic SHR in a dose-dependent manner. Similar results were obtained for proteinuria. Treatment with the high dose of cicletanine also normalized the altered creatinine clearance of diabetic SHR. These results indicate that cicletanine has a renal-protective action, probably blood pressure-independent, in a model combining hypertension and diabetes. The mechanism of renal-protection of cicletanine is not clearly established but may be due to the stimulation of arterial prostacyclin synthesis and/or to the reduction of intraglomerular capillary pressure.     

Control of the renal microvasculature by vasoactive peptides

In recent years, numerous techniques have been developed to study renal microcirculation. These technical advances have provided new insight regarding the specificity of action of vasoconstrictor peptides (angiotensin II, arginine vasopressin, endothelin) and vasodilator peptides (bradykinin, atrial natriuretic peptide) at discrete sites within the renal vascular bed. Differential signal transduction mechanisms, particularly those related to calcium regulation, appear to mediate the renal vascular actions of these compounds, both in a segment-specific and agonist-specific manner. These observations substantiate the concept that regulation of intrarenal and intraglomerular dynamics is accomplished by selective changes in pre- and postglomerular resistance induced by different endogenous peptides. This microvascular selectivity allows precise regulation of glomerular and peritubular capillary function, and ultimately exerts great influence on the volume and composition of the final urine.     

Role for thromboxane A2 from glomerular thrombi in nephropathy with type 2 diabetic rats

We used rats (the Otsuka Long-Evans Tokushima Fatty strain) as a model of type 2 diabetes to find whether thromboxane (TX) A2 is involved in diabetic nephropathy, and if so, to identify where it is synthesized. We measured urinary excretion of TXB2 and 2,3-dinor-TXB2 in rats up to 60 weeks of age as markers of renal and platelet synthesis of TXA2, respectively. Some diabetic rats were given daily oral doses of OKY-046 (100 mg/kg), a TXA2 synthase inhibitor, starting when they were 10 weeks of age. Healthy Long-Evans Tokushima Otsuka rats served as the controls. Urinary excretion of protein was greater in diabetic rats at 26 weeks than in controls, and the difference increased with age. Urinary excretion of TXB2 by diabetic rats was about 150% that of controls at 14 weeks, and remained at that level. In diabetic rats, urinary excretion of 2,3-dinor-TXB2 increased with age in parallel to increases in proteinuria, but in controls, excretion of these metabolites did not change with age. In diabetic rats, OKY-046 prevented the increase in urinary excretion of both metabolites, and decreased the proteinuria. Histologic examination at 60 weeks showed intraglomerular thrombi in diabetic rats but not in controls. OKY-046 reduced intraglomerular thrombi formation and the score for glomerulosclerosis. When platelet aggregation began, more TXA2 than before was released from the thrombi that formed, and the TXA2 contributed to the progress of nephropathy in this rat model of type 2 diabetes.     

Tissue distribution of neutrophils in postischemic acute renal failure.

Polymorphonuclear neutrophil granulocytes (PMNs) seem to participate in the pathogenesis of renal ischemic reperfusion injury. The kidneys from male Sprague Dawley rats were immersion-fixed after 45 min of renal artery clamping followed by reperfusion for 0, 5, 20, and 120 min, respectively. The tissue distribution of PMNs in the kidneys was studied histochemically using naphthol AS-D chloroacetate esterase as a specific marker for these cells. Neutrophil counts per unit sectional area were obtained for renal cortex, outer and inner medulla. In the cortex separate intraglomerular and peritubular counts, and in the outer medulla separate outer and inner stripe counts were made. After 120 min of reperfusion the total renal PMN counts were 488 +/- 62 (n = 4) compared with 54 +/- 4 (n = 4) per cm2 in nonischemic controls. Within 120 min of reperfusion PMN counts increased by a factor of 8 in the cortex, of 12 in the outer medulla and of 14 in the inner medulla, compared with controls. The ratio of intraglomerular against peritubular PMN counts was approximately 2 in controls, but 0.5 after a 120-min reperfusion interval. The outer stripe of the outer medulla contained only a small number of PMNs whereas PMN counts of 923 +/- 197 (n = 4) per cm2 were found in the inner stripe after 120 min reperfusion. Interestingly, there was a marked increase in PMNs in the inner stripe during the first 5 min of reperfusion but no extravasation of PMNs was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of D and E domains in the migration of vascular smooth muscle cells into fibrin gels

The structure of fibrin plays an important role in the organization of thrombi, the development of atherosclerosis, and restenosis after PTCA. In this study, we examined the mechanisms of the migration of vascular smooth muscle cells (SMCs) into fibrin gels, using an in vitro assay system. Cultured SMCs from bovine fetal aortic media migrated into fibrin gels prepared with thrombin, which cleaves both fibrinopeptides A and B from fibrinogen, without other chemotactic stimuli. Both desA fibrin gels prepared with batroxobin, which cleaves only fibrinopeptide A, and desB fibrin gels prepared with Agkistrodon contortrix thrombin-like enzyme (ACTE), which cleaves only fibrinopeptide B, similarly induced the migration of SMCs compared to fibrin gels prepared with thrombin. These results suggest that the cleavage of fibrinopeptides is not necessary, but rather that the three-dimensional structure of the gel may be important for the migration of SMCs. Furthermore, gels prepared with protamine sulfate, which forms fibrin-like gels non-enzymatically, similarly induced the migration of SMCs compared to the gels prepared with thrombin. Both anti-fibrin(ogen) fragment D and anti-fibrin(ogen) E antibodies inhibited the migration of SMCs into fibrin gels, suggesting that both the D and E domains of fibrin(ogen) are involved in the migration of SMCs into fibrin gels. The addition of GRGDS, a synthetic RGD-containing peptide, but not that of GRGES, a control peptide, partially inhibited the migration of SMCs into fibrin gels, suggesting that the migration of SMCs into fibrin gels is at least in part dependent on the RGD-containing region of the alpha chain. The migration of SMCs into fibrin gels was also inhibited by a monoclonal antibody for integrin alpha v beta 3 and alpha 5 beta 1, indicating that migration is dependent on these integrins. Furthermore, both fibrin(ogen) fragments D and E inhibited the migration of SMCs into fibrin gels, suggesting that these fragments, generated during fibrino(geno)lysis, may be relevant in the regulation of SMC migration into fibrin gels.     

Coagulation and Fibrinolytic Systems in Pre-eclampsia and Eclampsia

The coagulation and fibrinolytic mechanisms were investigated in a group of patients with severe pre-eclampsia and eclampsia and the findings were compared with those of healthy women in late pregnancy. In patients with pre-eclampsia the following significant differences were found: (1) greater depression of plasma fibrinolytic activity (euglobulin lysis time) than in normal pregnancy, (2) a higher level of inhibitor to urokinaseinduced lysis, (3) increased levels of serum fibrin degradation products, and (4) reduced platelet counts.In patients with eclampsia a progressive increase of the level of serum fibrin degradation products was found over the three days following eclamptic seizures. No such increase occurred after grand mal seizures in late pregnancy. The findings in this study support the view that intravascular clotting is taking place in pre-eclampsia and that this disturbance of the balance between coagulation and fibrinolysis may be localized to certain areas of the vascular compartment, particularly the placental and renal circulations. Fibrin deposition in the maternal vessels supplying the placenta would impair the placental blood flow, which may explain the placental insufficiency which occurs in pre-eclampsia. Likewise fibrin deposition in the renal vasculature will result in glomerular damage and proteinuria. Hypertension may be related to the renal ischaemic changes or a compensatory response to the presence of fibrin deposition in the vascular compartment. This evidence of intravascular fibrin deposition raises the question of the possible therapeutic value of antithrombotic agents to inhibit the clotting process. On a theoretical basis such treatment might be expected to improve blood flow to the placenta and thereby fetal growth.     

Increased class I and class II MHC products and mRNA in kidneys of MRL-lpr/lpr mice during autoimmune nephritis and inhibition by cyclosporine

The expression of MHC products in the kidneys of MRL-1pr/1pr mice was investigated. As previously described, these mice develop lupus-like nephritis with intraglomerular and peritubular Ig deposition, vasculitis, and interstitial mononuclear cell infiltration at about 12 wk of age. As the nephritis appeared, the expression of MHC class I and II products rose, as demonstrated by absorption and by specific binding of radiolabeled antibodies. Hybridization of kidney RNA with specific probes revealed an increase in specific mRNA for MHC class I and II genes and for beta2 microglobulin. Using rat monoclonals against mouse class I and II MHC products, and goat anti-rat Ig as second antibody, we showed that the increase in renal class I and II expression was localized to the basolateral membranes of tubular cells, and, in the case of class I, in arteries and glomeruli. The sites of tubular MHC expression corresponded closely to the sites of extensive peritubular Ig deposition. High doses of cyclosporine given for 6 to 8 wk reduced the peritubular Ig deposits, renal Ia and H-2K expression, and specific mRNA for beta 2-microglobulin and MHC genes, but did not reduce anti-DNA antibody levels in serum. Thus the peritubular Ig deposits and tubular MHC induction coincided in timing and location, and in their resolution with cyclosporine. The results raise the possibility that the increase in renal MHC expression not only accompanies the renal lesions, but may play a role in their pathogenesis.     

Volodymyr Oleksandrovych Bielitser--a gifted scientist and outstanding biochemist, a founder of the scientific school

Professor V. O. Belitser, Doctor of Science (biology), (30.09.1906, Ryazan, RF-04.03.1988 Kyiv, Ukraine), Member of the National Academy of Sciences of Ukraine, graduated from the physico-mathematical faculty of the Moscow University in speciality "physico-chemical biology". In 1934-1943 he worked at the All-Union Institute of Experimental Medicine (Moscow) where he was engaged in research of the relation between the respiratory system and glycolytic reactions in the animal tissues. V. O. Belitser established the effect of creatin on the muscular respiration on the role of creative phosphate in this process. He was the first to demonstrate that the anaerobic phosphorylation is bound to respiration. He investigated stechiometric relations between the joint phosphate binding and oxygen absorption and estimated thermodynamic importance of this process, he showed that the energy of electron transfer from the substrate to oxygen is a source of formation of three ATP molecules per one atom of absorbed oxygen. From 1944 to 1988 V. O. Belitser worked at the Institute of Biochemistry of the Academy of Sciences of the Ukr.SSR (Kyiv), where he headed the Laboratory of Enzymes (then proteins), and from 1966 he headed the Department of Protein Structure and Function; for a certain period (1969-1972) he headed the Institute as its director. Investigations of properties of native and denaturated proteins jointly with K. I. Kotkova led to the creation of blood substitute from blood serum proteins of cattle--BK-8. The school of V. O. Belitser is known by studying the molecular mechanism of one of the basic reactions of blood coagulation--fibrinogen transformation to fibrin, by finding out the organization and function of fibrinogen and fibrin. It was proved experimentally that the specific polymerization centres significance for the fibrin lattice formation are of essential significance for the fibrin lattice formation, that fibrinogen to fibrin transformation occurs in two stages--enzymatic and polymerizational ones. V. O. Belitser proposed the mechanism of fibrinogen transformation to fibrin, as soon as he had substantiated the kinetic theory of this reaction; domain structure of fibrinogen has been investigated. Such diagnostic tests as the methods of definition of the products of fibrinogen and fibrin splitting in urine (for differential diagnosis of cardiovascular diseases) were developed and put into medical practice under his guidance. V. O. Belitser and members of his school have published above 300 scientific works, prepared 5 doctors and 25 candidates of science. The selfless work of the scientists was honoured with high state awards--the Orders of Lenin, the Order of the Labour Red Banner, the Order of Oktober Revolution, that of Friendship of Peoples and with numerous medals.     

Initial plasmin-degradation of fibrin as the basis of a positive feed-back mechanism in fibrinolysis

This study deals with the effect of fibrin on the transformation of Glu-plasminogen to Glu-plasmin during fibrinolysis. It focuses particularly on changes in fibrin effector function caused by plasmin-catalysed fibrin degradation. Conversion of 125I-labelled Glu-plasminogen to Glu-plasmin was catalysed by urokinase or tissue plasminogen activator, in the presence of different preparations of progressively degraded fibrin. Plasmin catalysis of Glu-plasminogen and the fibrin (derivative) effector was inhibited by aprotinin. The presence of intact fibrin enhanced the rate of Glu-plasmin formation catalysed by tissue plasminogen activator, but not by urokinase. The presence of initially plasmin-cleaved fibrin, however, increased the rates of Glu-plasmin formation with both activators, as compared to those found with intact fibrin. The rate enhancements induced by initial plasmin degradation of the fibrin effector were associated with an increase in its affinity to both Glu-plasminogen and tissue plasminogen activator, suggesting causal relationships. The weak binding of urokinase was unaffected by fibrin degradation, indicating that effector function was solely exerted on the Glu-plasminogen moiety of urokinase-activated systems. Further degradation of fibrin decreased the stimulating effect on Glu-plasmin formation. This decrease occurred at an earlier stage of degradation with tissue plasminogen activator than with urokinase, indicating that greater integrity of the fibrin effector is necessary for its optimal interaction with the tissue plasminogen activator than with Glu-plasminogen. Concentrations of tranexamic acid that saturate low-affinity lysine-binding sites nearly completely dissociated the binding of Glu-plasminogen to degraded fibrin, but not to intact fibrin. In analogy with the binding of lysine analogues to these sites, the conformation of Glu-plasminogen may be altered by binding to degraded fibrin, thus giving rise to the increased activation rate.     

Nature of Hyperacute (Accelerated Second Set) Rejection in Dog Renal Allographs and Effects of Heparin on Rejection Process

Renal allografts were exchanged between unrelated mongrel dogs after previous sensitization with skin and kidney grafts from the same donors. Rapid rejection of the renal allografts was associated with the accumulation of platelets and leucocytes in the peritubular and glomerular capillaries but fibrin deposition was not demonstrated.Heparin infusion delayed but did not prevent the rejection process.     

Cells Actively Stiffen Fibrin Networks by Generating Contractile Stress

During wound healing and angiogenesis, fibrin serves as a provisional extracellular matrix. We use a model system of fibroblasts embedded in fibrin gels to study how cell-mediated contraction may influence the macroscopic mechanical properties of their extracellular matrix during such processes. We demonstrate by macroscopic shear rheology that the cells increase the elastic modulus of the fibrin gels. Microscopy observations show that this stiffening sets in when the cells spread and apply traction forces on the fibrin fibers. We further show that the stiffening response mimics the effect of an external stress applied by mechanical shear. We propose that stiffening is a consequence of active myosin-driven cell contraction, which provokes a nonlinear elastic response of the fibrin matrix. Cell-induced stiffening is limited to a factor 3 even though fibrin gels can in principle stiffen much more before breaking. We discuss this observation in light of recent models of fibrin gel elasticity, and conclude that the fibroblasts pull out floppy modes, such as thermal bending undulations, from the fibrin network, but do not axially stretch the fibers. Our findings are relevant for understanding the role of matrix contraction by cells during wound healing and cancer development, and may provide design parameters for materials to guide morphogenesis in tissue engineering.     

Early postischaemic renal fibrin deposition and reduction of glomerular filtration rate in the rat: effect of the defibrinating agent Arwin

The correlation between the extent of intrarenal fibrin deposition induced by 15, 20 and 30-min bilateral occlusion of the renal arteries and the reduction of glomerular filtration rate (GFR) has been studied. The tissue level of fibrin was estimated by 125I-labelled human fibrinogen. There was a significant negative correlation between cortical and medullary fibrin content and GFR. In rats pretreatment with the defibrinating agent Arwin failed to prevent postischaemic coagulation in the kidney and the reduction of GFR.