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Biomedical subjects

D P Dhall

Publications and source records attributed to D P Dhall.

At least 19 recordsLinked to original sources
PubMed1995

The permeability of fibrin network developed in human plasma.

Fibrin network permeability has an important role in thrombosis and inflammation since it influences the rate of transport of macromolecules through the network by convection. The conditions of polymerization of fibrin determine the network permeability and this has been attributed to variability in fibrin fibre thickness. Inconsistencies between values for fibrin fibre thickness derived from turbidity and permeability were examined. Networks were developed from human plasma by the addition of thrombin and network polymerization was modified pharmacologically. Dextran (MW 70,000) and poloxamer 188 both increased, and lauryl sulphate decreased, network permeability and network turbidity. Network fibre thickness was consistently higher when derived from permeability than from turbidity. Network permeability was significantly more susceptible to pharmacological manipulation by these agents than network turbidity. These inconsistencies were attributed to variation in the arrangement of the network fibres such as inhomogeneity of network fibre distribution and to fibre aggregation or alignment. Collectively these factors prohibit the derivation of fibrin fibre thickness from permeability. The dimensionless permeability (network permeability/(fibre radius)2) was used as an index of network fibre arrangement and found to be readily modified pharmacologically. Physiological and pharmacological regulation of fibrin network permeability may be predominantly mediated through modification of fibre arrangement and not through fibre thickness.

Biopolymers↗
PubMed1994

Complement activation: a new participant in the modulation of fibrin gel characteristics and the progression of atherosclerosis?

The activation of the complement system has been implicated as an important mechanism in the progression of atherosclerosis. The relationship between fibrin gel characteristics and complement activation has, however, not been investigated. Zymosan-treated plasma with 87% complement activation as measured by C3a production using radioimmunoassay was found to induce changes in biophysical characteristics of fibrin network developed in both plasma and purified fibrinogen solution. Using already established methods to measure fibre thickness (mu T), permeability (T) and compaction, it was found that these networks are made of thinner fibres with increased tensile strength arranged into a matrix which renders the networks less permeable. Such networks are resistant to streptokinase-induced lysis. Fibrin networks with thin fibres in turn induced 3.7 times higher production of C3a than unmodified networks. These observations suggest the existence of positive feedback; complement activation induces major alterations in fibrin structure which in turn can induce further activation of the complement system. The detailed mechanism underlying this interrelationship is not clear at present, but this positive feedback system may play an important role in establishing a fibrin infrastructure ultimately responsible for the progression of atherosclerosis.

Arteriosclerosis↗
PubMed1993

Effects of Poloxamer 188 on fibrin network structure, whole blood clot premeability and fibrinolysis.

The effects of Poloxamer 188 (0-5 mg/ml) on the permeability, turbidity, compaction, and fibrinolysis of fibrin network developed in human plasma, and on the permeability and fibrinolysis of network developed in whole blood were examined. Poloxamer 188 was found to increase network permeability and compaction in plasma. In networks in plasma, effects on the fibre mass-length ratio from turbidity and fibrinolysis with recombinant tissue plasminogen activator were small. Poloxamer did not alter the fibrinolysis with streptokinase. The increase in fibrin network permeability at low poloxamer concentrations was not attributable to an increase in fibre thickness, but results from alterations in the arrangement of fibrin fibres. Poloxamer also significantly increased the permeability of networks developed in whole blood. Studies with the platelet inhibitor cytochalasin B demonstrated that this effect in whole blood networks was partly from facilitation of platelet induced clot retraction. Poloxamer was not found to affect streptokinase induced fibrinolysis of whole blood networks. The effects of poloxamer support the hypothesis that depletion flocculation of fibrin intermediaries by soluble macromolecules is a significant determinant of network permeability. The therapeutic use of poloxamer will result in altered fibrin function in particular its permeability and mechanical stability. These alterations may contribute to its described antithrombotic and rheological effects.

Blood Coagulation↗
PubMed1991

Studies on fibrin network structure in human plasma. Part One: Methods for clinical application.

Methods based on turbidity and permeability, for measurement of mass-length ratio of fibrin fibres developed in pure fibrinogen solution, have been evaluated in respect of their applicability to human plasma. Theoretical assumptions made in the calculation of mass-length ratios in plasma have been critically examined. Methods of handling plasma, reproducibility of technique and the influence of age and sex have been investigated. The anticoagulant used, as well as other factors such as time, venepuncture and effects of calcium and fibrinolytic inhibitors are fully explored. With suitable standardization the methods are acceptable for application to clinical studies and are reproducible.

Adult↗
PubMed1991

Studies on fibrin network structure in human plasma. Part II--Clinical application: diabetes and antidiabetic drugs.

Using measurements of fibrin fibre thickness (microT) derived from turbidity and permeability (tau) of clotted plasma, it has been found that glucose in vitro added to plasma decreases permeability of the network despite unaltered fibrinogen conversion. Fibrin fibre thickness (microT) in uncontrolled diabetes is found significantly reduced. In diabetic plasma the degree of conversion to fibrin is similar to that in age and sex matched plasma from non-diabetics: the effect on fibrin network and fibre thickness probably arises from glycosylation of fibrinogen. Studies with Gliclazide, Metformin, Glibenclamide and insulin have shown that while all other drugs tested have no effect, Gliclazide increases fibrin fibre thickness (microT) significantly, diminishes tensile strength and reduces permeability. In separate experiments lysability of 125I-labelled fibrin networks developed in the presence of all four hypoglycaemic agents by tissue activator was tested. Networks developed in the presence of Metformin were found to lyse more quickly, followed by insulin and Gliclazide. Alterations induced in fibrin networks in diabetes may be nullified by some oral hypoglycaemic agents such as Gliclazide and not by others. Whether nullification of such changes has long-term effects in reducing the incidence of vascular disease in diabetics remains to be established.

Adult↗
PubMed1991

Studies on fibrin network structure: the effect of some plasma proteins.

Significant differences were found between characteristics of networks developed in plasma and those developed in pure fibrinogen solution. Networks in plasma have thicker fibres, are more permeable and have lower tensile strength. In this investigation determinants of network structure under physiological conditions of clotting have been examined in an attempt to account for the differences in network structure in plasma and fibrinogen solution. Effect of antithrombin III and of physiological concentrations of fibronectin, albumin and gamma-globulin on fibrin network structure was examined using mass-length ratio (microT) from turbidity, bulk permeability of networks (tau) and kinetics of network development. At physiological concentrations effect of ATIII was too pronounced to allow this method to quantify changes in network characteristics. Whilst fibronectin and gamma-globulins increased fibrin fibre thickness and network permeability, albumin caused opposite effects. It is concluded that the final network structure is determined by kinetics of fibrin fibre growth and is highly responsive to the presence of plasma proteins.

Antithrombin III↗
PubMed1990

The effects of some plasma proteins on fibrin network structure.

Pronounced differences are found between characteristics of networks developed in plasma and those developed in pure fibrinogen solution. Networks in plasma have thicker fibres, are more permeable and have lower tensile strength. In this investigation the role of some plasma proteins as determinants of network structure under physiological conditions of clotting has been examined in an attempt to account for the differences in network structure in plasma and fibrinogen solution. The effect of physiological concentrations of antithrombin III, fibronectin, albumin, alpha globulin and gamma globulin on fibrin network structure was examined using mass-length ratio (muT) from turbidity, bulk network permeability (tau) and kinetics of network development. It was found that differences in fibrin network structure developed in plasma and pure fibrinogen solution could not be accounted for by alterations induced in network properties by albumin, gamma globulin, alpha globulin, fibronectin and antithrombin III. It is concluded that the final network structure is determined by the kinetics of fibrin fibre growth and is highly responsive to the presence of plasma proteins.

Antithrombin III↗
PubMed1987

Comparison of fibrin networks in plasma and fibrinogen solution.

Mass-Length ratio of fibrin fibres (microT and microP) derived independently from turbidity and permeability respectively, in networks made in fibrinogen solution and plasma, have been compared under similar conditions of clotting. Amount of fibrinogen conversion to fibrin was similar in both systems when high thrombin concentrations were used. But networks in plasma had significantly thicker fibres (higher microT and microP) than those in fibrinogen solution. This difference arises from differing kinetics of fibrin assembly in the two systems. When lower thrombin concentration is used, fibrin fibre thickness (as indicated by microP and microT) is increased in fibrinogen solution but the fibrin content of the network remains unaltered. In plasma, on the other hand, the fibrin content of the network is decreased, microT remains relatively unchanged while microP increases. The thrombin concentration dependence of the fibrin content of the network in plasma and the bimodal distribution of fibrin fibre thickness explain the breakdown in correlation between microP and microT.

Blood Coagulation↗
PubMed1986

Effect of temperature, pH and ionic strength and composition on fibrin network structure and its development.

Networks were developed in fibrinogen solution under pathophysiological conditions of clotting. Mass-length ratio (a measure of fibre thickness) was derived independently from the turbidity (microT) and from the permeability (microP) of the network. Kinetics of network growth were investigated turbidimetrically. Physiological concentrations of Ca++and Mg++increased microT while those of K+, Na+, Cl-, HCO-3, H2PO-4 and SO--4 had no effect. As pH and ionic strength were increased stepwise within the pathophysiological range, network development was delayed. Under these conditions the turbidity curves did not cross and both microT and microP were progressively decreased. When temperature was lowered, although network growth was delayed, the turbidy curves crossed: the equilibrium turbidity was higher at lower temperatures. It appears that while pH and ionic strength affect network structure by influencing fibrin assembly, lowering the temperature influences both the rate of fibrin monomer generation and fibrin assembly.

Fibrin↗
PubMed1986

A comparative study of transplant sites for endocrine tissue transplantation in the pig.

Thyroid and thymus tissue autografts were used to examine the suitability of different transplant sites in the pig for endocrine tissue transplantation. The omental pouch, gall bladder fossa and renal subcapsular space showed optimal implantation, preservation and vascularisation of graft tissue. Marked dissemination of graft tissue was observed at intramuscular sites and graft viability at subcutaneous sites in the ear was poor. The omental pouch represents a potentially suitable site for pancreatic islet tissue transplantation studies in the pig.

Animals↗
PubMed1986

Induction and management of diabetes mellitus in the pig.

Insulin-dependent diabetes mellitus was induced in the pig by pancreatectomy or by administration of intravenous streptozotocin (150 mg/kg). High post-operative morbidity and mortality in the pancreatectomised animals made this method of inducing diabetes unsuitable for animals to be used in long term studies. By contrast, the good clinical state of animals after streptozotocin and the permanence of their diabetes indicated that these animals were suitable for long term studies such as those involving transplantation of pancreatic islet tissue. Techniques designed to facilitate the assessment and management of these animals included placement of an indwelling jugular venous catheter to enable blood samples to be obtained for metabolic studies, denervation of an area on the flank of the animal to enable insulin administration with minimum discomfort and denervation of an ear to enable blood samples to be obtained from the animal for glucose estimation in long term studies.

Animals↗
PubMed1985

Physiological studies on fibrin network structure.

Networks were developed in fibrinogen solution under pathophysiological conditions of clotting and their permeability and turbidity were measured. Mass-Length ratio of fibrin fibres (a measure of fibre thickness) was derived from two independent methods based on turbidity (mu T) and permeability (mu P). Both mu T and mu P increased as thrombin concentration was decreased. Data are in agreement with the concept that the fibrin network develops initially as a mesh of protofibrils. Fibrin monomer generated subsequently is incorporated into the existing network making individual fibres thicker. Consequently, slow fibrin monomer generation promotes thicker fibres. When the concentration of thrombin or fibrinogen was altered systematically, mu T and mup were found to mirror each other except when the fibrinogen concentration was increased at low thrombin concentrations. This breakdown between the two derivations of mass-length ratio is discussed in terms of the two network model.

Blood Coagulation↗
PubMed1983

Fibrin network structure: modification by platelets.

Platelets play a fundamental role in haemostasis and thrombosis. They are known to undergo characteristic changes including release of subcellular material during clotting. The effect of subcellular platelet material on fibrin network structure, however, has not previously been investigated. Using opacity ratio, syneresis, permeation and electron microscopy it was found that subcellular platelet material extracted into NaCl is able to influence fibrin network structure of clots made from purified fibrinogen as well as platelet-poor plasma. Such clots had higher opacity ratio, reduced syneresis and lower permeability than control clots. Further, the responsible platelet material is heat labile and is released from the platelets during their aggregation with several common aggregating agents. Morphometric analysis of transmission electron micrographs has shown that fibrin fibres in plasma clots made in the presence of platelet subcellular material are thinner than those in control clots. In addition, plasma clots made in the presence of platelet extract had a higher resistance to fibrinolytic digestion than control clots. Thus, platelets play a hitherto undescribed role in regulating fibrin network structure.

Blood Coagulation↗
PubMed1982

Preoperative blood tests in prediction of postoperative deep vein thrombosis.

Fifty six patients undergoing elective abdominal surgery were investigated preoperatively with tests of coagulation, platelet function and fibrinolysis. Ten patients developed postoperative deep vein thrombosis, detected by the labelled fibrinogen uptake test and confirmed by ascending phlebography. None of the tests showed a statistically significant difference between the group mean of patients who developed DVT and of those who did not. Potential discriminators were used to derive a prognostic index for prediction of patients who would develop postoperative DVT. An index based on two preoperative blood tests i.e. three hour fibrin digestion and APTT had a successful prediction rate of 59 percent.

Blood Coagulation Tests↗