Enhancement of Spontaneous Fibrinolytic Activity in Diabetic Retinopathy

1992 ◽  
Vol 68 (04) ◽  
pp. 400-403 ◽  
Author(s):  
Helmut Ostermann ◽  
Diethelm Tschöpe ◽  
Wolfgang Greber ◽  
Hans-Werner Meyer-Rüsenberg ◽  
Jürgen van de Loo
Keyword(s):  
Fibrinolytic Activity ◽  
Type I Diabetes ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Fibrinolytic System ◽  
Clot Lysis ◽  
Diabetic Patients ◽  
Type I ◽  
Activated State

SummaryThe fibrinolytic system was studied in 96 patients with type I diabetes mellitus. Patients were grouped according to their degree of retinopathy; 38 patients with no evidence of retinopathy, 28 patients with background retinopathy and 30 patients with proliferative retinopathy. Thirty healthy individuals served as controls. The basal fibrinolytic activity as measured by clot lysis time and t-PA activity was increased in diabetic patients. This was associated with low levels of plasminogen activator inhibitor. Increased levels of D-dimer in diabetic patients further indicate enhanced in vivo fibrinolysis. The increase in fibrinolytic activity was highest in diabetics without retinopathy, and decreased with increasing retinopathy. Endothelial release of t-PA after venous occlusion was not different between controls and all diabetic groups. These findings suggest that in type I diabetics the fibrinolytic system is in an activated state. With worsening of retinopathy this increase in fibrinolytic activity diminishes.

Type I diabetes suppresses intracellular calcium ion increase normally evoked by heat stress in rat skeletal muscle

2021 ◽  
Author(s):  
Ryo Ikegami ◽  
Hiroaki Eshima ◽  
Toshiaki Nakajima ◽  
Shigeru Toyoda ◽  
David C. Poole ◽  
...  
Keyword(s):  
Heat Stress ◽  
Protein Expression ◽  
Type I Diabetes ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Type I ◽  
Male Wistar Rats ◽  
Intracellular Calcium Ion ◽  
And Function

Heat stress, via its effects on muscle intracellular Ca2+ concentrations ([Ca2+]i), has been invoked as a putative therapeutic countermeasure to Type 1 diabetes-induced muscle atrophy. Using in vivo muscle preparation we tested the hypothesis that impaired muscle Ca2+ homeostasis in type I diabetic rats is due to attenuated heat stress tolerance mediated via TRPV1. Male Wistar rats were assigned to 1 of 4 groups: 1.control 30oC (CONT 30oC), 2.CONT 40oC, 3.diabetes 30oC (DIA 30oC), 4.DIA 40oC. 40oC was selected because it just exceeds the TRPV1 activation threshold. Spinotrapezius muscles were exteriorized in vivo and loaded with the fluorescent Ca2+ probe Fura-2AM. [Ca2+]i was estimated over 20min using fluorescence microscopy in quiescent muscle held at the required temperature using calibrated heat source applied to the ventral muscle surface. Western blotting was performed to determine the protein expression levels of TRPV1 in spinotrapezius muscle. After 20min of heat stress, the CONT 40oC condition induced a 12.3% [Ca2+]i elevation that was absent from the DIA 40oC or other conditions. Thus, no significant differences were found among DIA 40oC, DIA 30oC and CONT 30oC. TRPV1 protein expression was decreased by 42.0% in DIA compared with CONT (P<0.05) and, unlike CONT, heat stress did not increase TRPV1 phosphorylation. In conclusion, diabetes suppresses TRPV1 protein expression and function and inhibits the elevated myocyte [Ca2+]i evoked normally by heat stress. These results suggest that capsaicin or other therapeutic strategies to increase Ca2+ accumulation via TRPV1 might be more effective than hyperthermic therapy for Type I diabetic patients.

Reperfusion After Venous Occlusion Caused Transient Increase in Plasminogen Activator Inhibitor-1 in Systemic Circulation

1998 ◽  
Vol 4 (2) ◽  
pp. 133-137
Author(s):  
Nobuo Nagai ◽  
Tetsumei Urano ◽  
Yumiko Takada ◽  
Akikazu Takada
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Plasminogen Activator Inhibitor ◽  
Systemic Circulation ◽  
Venous Occlusion ◽  
Transient Increase ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Euglobulin Clot Lysis Time ◽  
Pai 1

From the point of local regulation, we investigated fibrinolytic activity both in local and systemic circulations, using a venous occlusion test as a stimulus of tissue plasmin ogen activator (t-PA) release in human volunteers. Blood samples were taken before, during, and after venous occlusion from the occluded arm as trapped blood and the unoccluded arm as blood of systemic circulation. In these samples, fibri nolytic activity by euglobulin-clot lysis time and related factors in t-PA and plasminogen activator inhibitor-1 (PAI-1) were measured. Venous occlusion increased fibrinolytic activity ac companied by an increase in t-PA without an increase in PAI-1 on the occluded arm. The fibrinolytic activity on the unoc cluded arm did not change. Five minutes after reperfusion, however, a transient increase in PAI-1 and no change of fibri nolytic activity were observed in the unoccluded arm. Transient increase of PAI-1 after reperfusion was also observed in the occluded arm. These results suggested that increased t-PA by venous occlusion was neutralized by released PAI-1 after reperfusion. Key Words: Tissue-plasminogen activator— Euglobulin-clot lysis time—Fibrinolysis.

IDENTIFICATION OF A FIBRINOLYTIC DEFECT IN TWO FAMILIES WITH A TENDENCY TO THROMBOSIS

1987 ◽  
Author(s):  
H Ostermann ◽  
S Koenig ◽  
H Pollmann ◽  
U Schmitz-Huebner
Keyword(s):  
Venous Thrombosis ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
Clot Lysis ◽  
Normal Range ◽  
Before And After ◽  
Euglobulin Clot Lysis Time

We identified two families in whom one member each suffered from deep venous thrombosis and subsequent pulmonary emboli at the age of 15 and 17. We were able to investigate several members of both families with regard to their fibrinolytic system. Blood sampling was done before and after ten minutes of venous occlusion. Parameters measured were euglobulin clot lysis time (ECLT), tissue-type plasminogen activator (t-PA) activity, t-PA concentration and plasminogen activator inhibitor (PAI) activity, besides several other constituents of the coagulation and fibrinolytic system commonly associated with thrombophilia.In the first family six persons could be evaluated. A prolonged ECLT was found in four probands. Three of them had no measurable t-PA activity after stasis, t-PA concentration after stasis was below the normal range in two and borderline in one of them.In the second family 13 members could be invest-gated. Three adults were found to have a prolonged ECLT. Two of these had very low t-PA activity after stasis, with normal increase in t-PA antigen. Their PAI was increased above the normal range. Six children showed no measurable PAI and increased levels of t-PA activity before stasis. After stasis four children had a prolonged ECLT. Two of them had low t-PA antigen levels, while all of them showed normal t-PA activity increases.These findings suggest, that there may be hereditary defects related to activators and inhibitors of the fibrinolytic system in the investigated families. These could possibly be responsible for the occurence of venous thrombosis early in life. However, results in the second family show that not all of the prolonged ECLT values can be explained by changes of t-PA and PAI.

Diurnal Variation of the Fibrinolytic System

1988 ◽  
Vol 59 (03) ◽  
pp. 495-499 ◽  
Author(s):  
V Grimaudo ◽  
J Hauert ◽  
F Bachmahh ◽  
E K O Kruithof
Keyword(s):  
Diurnal Variation ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Significant Proportion ◽  
Plasminogen Activator Inhibitor ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
Clot Lysis ◽  
Euglobulin Clot Lysis Time ◽  
Pai 1

AbstractTo elucidate which component(s) of thei fibrinolytic system is (are) responsible for the diurnal variation of fibrinolytic activity we have studied several parameters of this system in 8 healthy male volunteers during a period of. 24 h. Blood was collected at 8 a. m., 10 a. m., 12 a. m., 4 p.m., 8 p.m. and 8 a. m. next morning. The following tests were performed: euglobulin clot lysis time (ECLT), fibrinolytic activity of euglobulins on fibrin plates in the presence and absence of blocking antibodies to tissue-type plasminogen activator (t-PA) and/or urokinase (u-PA), overall plasminogen activator inhibitor (PAI) activity, antigen levels of t-PA, u-PA and PAI-I and zymography of the euglobulin fraction after SDS-PAGE. From 8-10 a. m. to 4-8 p. m., total fibrinolytic activity increased by 1l3% (p <0.01) or 71%h (p <0.01) when measured by ECIX or by fibrin plate assay, respectively. The immunoquenching experiments showed that this increase was entirely due to t-PA related activity whereas u-PA activity and t-PA/u-PA independent activity remained constant during the day. Average antigen levels of u-PA and t-PA in the afternoon were 6% and 25% lower than those measured in the morning. During this period, overall PAI activity and PAI-1 antigen decreased by 3l% (p <0.01) and 52% (p <0.01) respectively. Electrophoretic-zymographic analysis of_ the euglobulins revealed that throughout the day the majority of t-PA was present in the form of the 110 kDa t-PA/PAI-I complex. The intensity of this cornplex was lowest in the afternoon. Free t-PA was almost undetectable in morning samples, but constituted a significant proportion of total t-PA in the afternoon. The diurnal increase of fibrinolytic activity, therefore, is not due to an augmentation of antigen levels of t-PA and/or u-PA but to a decline of those of PAI-1.

Fibrinolytic Activity in Chinese Patients with Diabetes or Hyperlipidemia in Comparison with Healthy Controls

1991 ◽  
Vol 65 (01) ◽  
pp. 003-006 ◽  
Author(s):  
Chao Hung Ho ◽  
Tjin Shing Jap
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Chinese Patients ◽  
Tissue Type ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Before And After ◽  
Patients With Diabetes

SummaryPlasma tissue-type plasminogen activator (tPA), plasminogen activator inhibitor (PAI) and euglobulin lysis time (ELT) were determined before and after the venous occlusion test (VOT) in 3 groups of patients with mean age about 60 years: 29 diabetic patients (D group), 8 hyperlipidemic patients (H group) and 19 healthy controls (C group). In the D and H groups, the mean of morning tPA was significantly higher than that of the C grogp, but the means of PAI were not significantly different among the 3 groups. ELI was significantly shortened and tPA was markedly increased after the VOT in all 3 groups whereas PAI had not significantly changed. In conclusion, high tPA activity and good fibrinolytic response without significant change of PAI .activity were found in the diabetic and hyperlipidemic patients, and no definite impairment of the fibrinolytic activity could be found in the Chinese patients with diabetes and hyperlipidemia. This might be one of the reasons why the Chinese has low incidence of thromboembolic diseases.

Platelet Factor 4, β-Thromboglobulin and Thrombospondin Levels in Type I Diabetes Mellitus Patients

1994 ◽  
Vol 22 (2) ◽  
pp. 90-94 ◽  
Author(s):  
M Bayraktar ◽  
S Dündar ◽  
S Kirazli ◽  
F Teletar
Keyword(s):  
Diabetes Mellitus ◽  
Type I Diabetes ◽  
Platelet Factor 4 ◽  
Type I Diabetes Mellitus ◽  
Control Group ◽  
Diabetic Patients ◽  
Type I ◽  
Platelet Factor ◽  
Release Reaction

The proteins β-thromboglobulin, platelet factor 4 and thrombospondin are stored in platelet α-granules and released from the platelet by the release reaction. The assays of these proteins were studied in patients with type I diabetes mellitus ( n = 30) and a healthy control group ( n = 15). Platelet factor 4 and β-thromboglobulin levels were not significantly different in both groups but thrombospondin concentrations in diabetic patients were significantly higher than those of the control group (136.6 ± 14.2 ng/ml vs 91.2 ± 14.3 ng/ml, P < 0.05). When the diabetic patients were divided into those with or without complications, the diabetic patients with complications ( n = 11) had significantly elevated plasma thrombospondin concentrations compared with the control group (150.4 ± 23.7 ng/ml vs 91.2 ± 14.3 ng/ml, P < 0.05), while thrombospondin concentrations in the control group were not statistically different from the diabetic patients without complications. Plasma β-thromboglobulin and platelet factor 4 levels were not significantly different between the diabetic and the control group. It is suggested that thrombospondin may be a convenient marker of in vivo platelet release reaction.

Fibrinolysis in Normal Subjects - Comparison Between Plasminogen Activator Inhibitor and Other Components of the Fibrinolytic System

1988 ◽  
Vol 59 (02) ◽  
pp. 299-303 ◽  
Author(s):  
Grazia Nicoloso ◽  
Jacques Hauert ◽  
Egbert K O Kruithof ◽  
Guy Van Melle ◽  
Fedor Bachmann
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Plasminogen Activator Inhibitor ◽  
Venous Occlusion ◽  
Venous Stasis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Plate Assay ◽  
Fibrin Plate ◽  
Activator Inhibitor ◽  
Pai 1

SummaryWe analyzed fibrinolytic parameters in 20 healthy men and 20 healthy women, aged from 25 to 59, before and after 10 and 20 min venous occlusion. The 10 min post-occlusion fibrinolytic activity measured directly in diluted unfractionated plasma by a highly sensitive 125I-fibrin plate assay correlated well with the activity of euglobulins determined by the classical fibrin plate assay (r = 0.729), but pre-stasis activities determined with these two methods did not correlate (r = 0.084). The enhancement of fibrinolytic activity after venous occlusion was mainly due to an increase of t-PA in the occluded vessels (4-fold increase t-PA antigen after 10 min and 8-fold after 20 min venous occlusion). Plasminogen activator inhibitor (PAI) activity and plasminogen activator inhibitor 1 (PAI-1)1 antigen levels at rest showed considerable dispersion ranging from 1.9 to 12.4 U/ml, respectively 6.9 to 77 ng/ml. A significant increase of PAI-1 antigen levels was observed after 10 and 20 min venous occlusion. At rest no correlation was found between PAI activity or PAI-1 antigen levels and the fibrinolytic activity measured by 125I-FPA. However, a high level of PAI-1 at rest was associated with a high prestasis antigen level of t-PA and a low fibrinolytic response after 10 min of venous stasis. Since the fibrinolytic response inversely correlated with PAI activity at rest, we conclude that its degree depends mainly on the presence of free PAI.

Anti-thrombotic Effect of a PAI-1 Inhibitor in Rats Given Endotoxin

1996 ◽  
Vol 75 (01) ◽  
pp. 118-126 ◽  
Author(s):  
T Abrahamsson ◽  
V Nerme ◽  
M Strömqvist ◽  
B Åkerblom ◽  
A Legnehed ◽  
...  
Keyword(s):  
Plasminogen Activator Inhibitor ◽  
Rat Plasma ◽  
Clot Lysis ◽  
Fibrin Deposition ◽  
Plasminogen Activator Inhibitor 1 ◽  
Fab Fragment ◽  
Dose Dependent Decrease ◽  
Pai 1

SummaryThe aim of this study was to investigate the anti-thrombotic effects of an inhibitor of the plasminogen activator inhibitor-1 (PAI-1) in rats given endotoxin. In studies in vitro, PRAP-1, a Fab-fragment of a polyclonal antibody against human PAI-1, was shown to inhibit PAI-1 activity in rat plasma as well as to stimulate clot-lysis of the euglobulin fraction derived from rat plasma. Endotoxin administered to anaesthetised rats produced a marked increase in plasma PAI-1 activity. To study fibrin formation and lysis in vivo after intravenous (i. v.) injection of the coagulant enzyme batroxobin, 125I-fibrinogen was administered to the animals. The thrombi formed by batroxobin were rapidly lysed in control animals, while the rate of lysis was markedly attenuated in rats given endotoxin. PRAP-1 was administered i.v. (bolus + infusion) to rats given endotoxin and batroxobin and the PAI-1 inhibitor caused a dose-dependent decrease in the 125I-fibrin deposition in the lungs. An immunohistochemical technique was used to confirm this decrease in density of fibrin clots in the tissue. Furthermore, PRAP-1 decreased plasma PAI-1 activity in the rats and this reduction was correlated to the decrease in lung 125I-fibrin deposition at the corresponding time point. It is concluded that in this experimental model the PAI-1 antibody PRAP-1 may indeed inhibit thrombosis in animals exposed to endotoxin.

The Roles of α2-Antiplasmin and Plasminogen Activator Inhibitor 1 (PAI-1) in the Inhibition of Clot Lysis

1993 ◽  
Vol 70 (02) ◽  
pp. 301-306 ◽  
Author(s):  
Linda A Robbie ◽  
Nuala A Booth ◽  
Alison M Croll ◽  
Bruce Bennett
Keyword(s):  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Plasminogen Activator Inhibitor 1 ◽  
Dependent Inhibition ◽  
Activator Inhibitor ◽  
Pai 1

SummaryThe relative importance of the two major inhibitors of fibrinolysis, α2-antiplasmin (α2-AP) and plasminogen activator inhibitor (PAI-1), were investigated using a simple microtitre plate system to study fibrin clot lysis in vitro. Cross-linked fibrin clots contained plasminogen and tissue plasminogen activator (t-PA) at concentrations close to physiological. Purified α2-AP and PAI-1 caused dose-dependent inhibition. All the inhibition due to normal plasma, either platelet-rich or poor, was neutralised only by antibodies to α2-AP. Isolated platelets, at a final concentration similar to that in blood, 2.5 × 108/ml, markedly inhibited clot lysis. This inhibition was neutralised only by antibodies to PAI-1. At the normal circulating ratio of plasma to platelets, α2-AP was the dominant inhibitor. When the platelet:plasma ratio was raised some 20-fold, platelet PAI-1 provided a significant contribution. High local concentrations of PAI-1 do occur in thrombi in vivo, indicating a role for PAI-1, complementary to that of α2-AP, in such situations.

Stem Cell-Based Therapies: A New Ray of Hope for Diabetic Patients

2019 ◽  
Vol 14 (2) ◽  
pp. 146-151 ◽  
Author(s):  
Junaid Khan ◽  
Amit Alexander ◽  
Mukta Agrawal ◽  
Ajazuddin ◽  
Sunil Kumar Dubey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Drug Therapy ◽  
Type I Diabetes ◽  
Embryonic Stem ◽  
Health Concern ◽  
Future Research ◽  
Diabetic Patients ◽  
Successful Implementation ◽  
Type I

Diabetes and its complications are a significant health concern throughout the globe. There are physiological differences in the mechanism of type-I and type-II diabetes and the conventional drug therapy as well as insulin administration seem to be insufficient to address the problem at large successfully. Hypoglycemic swings, frequent dose adjustments and resistance to the drug are major problems associated with drug therapy. Cellular approaches through stem cell based therapeutic interventions offer a promising solution to the problem. The need for pancreatic transplants in case of Type- I diabetes can also be by-passed/reduced due to the formation of insulin producing β cells via stem cells. Embryonic Stem Cells (ESCs) and induced Pluripotent Stem Cells (iPSCs), successfully used for generating insulin producing &#946; cells. Although many experiments have shown promising results with stem cells in vitro, their clinical testing still needs more exploration. The review attempts to bring into light the clinical studies favoring the transplantation of stem cells in diabetic patients with an objective of improving insulin secretion and improving degeneration of different tissues in response to diabetes. It also focuses on the problems associated with successful implementation of the technique and possible directions for future research.

Sign in / Sign up

Export Citation Format

Share Document