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Biomedical subjects

M F Aillaud

Publications and source records attributed to M F Aillaud.

At least 91 records · Page 5Linked to original sources

Correction by insulin added in vitro of abnormal membrane fluidity of the erythrocytes from type 1 (insulin-dependent) diabetic patients.

Filtrability of erythrocytes obtained from uncontrolled Type 1 (insulin-dependent) diabetic patients is abnormal, but is corrected by insulin added in vivo or in vitro. As erythrocyte filtrability depends on several determinants, we chose to study a membrane property of erythrocytes from diabetic subjects. Membrane fluidity was studied by fluorescence polarization using a lipophilic probe, the diphenyl-hexatriene and the Coulter Epics V together with a laser Spectra-physics 2000. Fluorescence polarization values obtained for 31 normal subjects (0.253 +/- 0.043 SD) and 31 uncontrolled Type 1 diabetic patients (0.231 +/- 0.043 SD) were significantly different (p less than 0.01). Insulin (2.5.10(-9) mol/l) added in vitro increased the fluorescence polarization values of red cell membranes from diabetic patients (without insulin, fluorescence polarization values = 0.210 +/- 0.032 SD; with insulin, fluorescence polarization values = 0.253 +/- 0.024 SD, p less than 0.001, n = 15), but had no effect on normal membranes (without insulin fluorescence polarization values = 0.255 +/- 0.037 SD, with insulin, fluorescence polarization values = 0.251 +/- 0.026 SD; n = 12). Given a relationship between the lipid bilayer and membrane cytoskeleton proteins, this insulin-correctable abnormality of erythrocyte membrane fluidity may be an important determinant of the rheological behaviour of erythrocytes from diabetic patients.

Adult↗

Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level, and relative body weight in normal and obese subjects.

This study was undertaken to obtain further information on the mechanism by which blood fibrinolytic activity, a balance between plasminogen activators and inhibitors, is lowered in obese subjects. Fasting blood samples were collected from 35 subjects, aged 15 to 45 years, with normal glucose tolerance and a Body Mass Index (BMI) varying widely between 16 and 45 (normal, 19 to 25). Euglobulin Fibrinolytic Activity (EFA) did not correlate with the level of tissue type plasminogen activator (t-PA) related antigen but exhibited a negative correlation with the level of PA inhibitor (r = -.609, P less than 0.01). EFA was negatively and PA inhibitor positively correlated with both BMI (r = -.381, P less than 0.02 and .664, P less than 0.01, respectively) and plasma insulin level (r = .410, P less than 0.02 and .521, P less than 0.01, respectively). Stepwise analysis showed that these correlations were independent. As expected, plasma insulin was correlated with BMI (r = .512, P less than 0.01) and triglyceride level (r = .38, P less than 0.02), total cholesterol with age (r = .379, P less than 0.02). Ten obese subjects were submitted to a 24-hour fast. While body weight did not change appreciably, plasma insulin decreased from 22.3 +/- 2.2 to 16.3 +/- 1.1 microU/ml, EFA increased from 3.6 +/- .8 to 4.9 +/- .67 mm, and PA inhibitor decreased from 4.52 +/- .76 to 3.44 +/- .63 IU/mL. All these differences were significant. T-PA-related antigen did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Thromboembolic disease and anomalies of fibrinolysis].

Quantitative abnormalities of fibrinolytic system factors (tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PA-inhibitor) are often found in the patients exhibiting an idiopathic thromboembolic pathology. Exploration of fibrinolytic system is performed by taking blood samples prior and after stimulation (after venous occlusion or DDAVP injection). Patients can be "good responders" (that is presenting with an increase of fibrinolytic activity after stimulation) or "bad responders". Among these latter (that is 30 p. 100 of cases), there are two groups: patients exhibiting an increase of PA inhibitor level, this concealing fibrinolytic role of t-PA released by stimulation (20 p. 100 of cases), patients failing to present any t-PA release through endothelial cells stimulation (10 p. 100 of cases). Furthermore, an hypofibrinolysis was demonstrated a long time ago, in certain thrombogenic conditions (post-operative period, obesity, elderly patients). Hypofibrinolysis was recently demonstrated, according to such conditions, as liable to an increase in the PA inhibitor levels. As pathogenic role of hypofibrinolysis is then demonstrated, therapeutic studies reducing the PA inhibitor level or increasing the t-PA rate produced and released by endothelial cells are to be developed.

Fibrinolysis↗

Increased PA-inhibitor levels in the postoperative period--no cause-effect relation with increased cortisol.

It has been reported that the level of PA-inhibitor increases in postoperative patients and on the other hand that glucocorticoids increase the PA-inhibitor level in cell culture. Because surgery is associated with increased plasma cortisol level, a relation between the postoperative increase in plasma cortisol and PA-inhibitor levels was looked for. Blood samples were collected from 8 patients undergoing extensive abdominal surgery, before operation and postoperatively at 2 hr, 4 hr, 24 hr and daily for 7 days. Plasma cortisol and PA-inhibitor were increased 2 hr after surgery, when there was a significant correlation (p less than 0.05). The maximum increase was at 24 hr and the values fell to normal on day 6. An increase in t-PA related antigen (t-PA R:Ag) and a decrease in euglobulin fibrinolytic activity (EFA) also occurred. In 7 controls 0.25 mg ACTH was given intravenously and blood was collected after 1/2, 1, 2, 4, 6 hr. Although the increase in plasma cortisol level following ACTH was comparable to that observed after surgery the increase was not associated with significant change in PA-inhibitor level, t-PA R:Ag or EFA. A cause-effect relationship between the increased plasma cortisol and PA-inhibitor level could not be shown. The mechanism of the postoperative increase in PA-inhibitor thus remains unknown.

Abdomen↗

[Immunologic determination of the protein C of coagulation: detection of deficiencies].

Protein C, discovered by Stenflo in 1976, plays a major role in the regulation of thrombogenic processes. Even moderate deficiencies (0.40 to 0.60 U/ml) can be responsible for serious thromboembolic accidents. The authors evaluated the kits for the immunological assay of protein C, produced by Laboratoire Diagnostica Stago: a immuno-enzymatic method (ELISA) and Laurell's method. Despite the very different characteristics in terms of practicability, threshold of sensitivity and precision, the authors obtained an excellent correlation between these two techniques. The concentrations of protein C Ag obtained in 22 normal plasmas were 0.70 to 1.40 U/ml. In 32 patients with recurrent thrombosis with no apparent cause, 5 had a concentration of protein C Ag less than 0.70 U/ml. The identification of a deficiency of protein C Ag (Vitamin K depend protein) is often made difficulty by the fact that the patients are treated with anti-vitamin K drugs. The ratio between the vitamin K depend pro-coagulation factors and Protein C Ag may provide information about a possible deficiency.

4-Hydroxycoumarins↗

Plasma levels of a specific inhibitor of tissue-type plasminogen activator (and urokinase) in normal and pathological conditions.

Rapid inhibition of tissue-type plasminogen activator (t-PA) in human plasma was measured by addition of 5 IU (50 ng) of purified t-PA per ml plasma and measurement of residual t-PA in the euglobulin precipitate after 5 min incubation at 37 degrees C. The recovery of both t-PA activity and t-PA related antigen in pooled plasma from healthy individuals was approximately 90 percent, indicating that one ml of pooled normal plasma inhibits less than 1 IU or 10 ng of t-PA within 5 min. Of 20 control subjects 13 had less than 1 IU inhibitor activity; 5 subjects inhibited between 1 and 3 IU of t-PA and 2 subjects inhibited around 4.5 IU. The inhibitor titer in the latter two had however decreased to 1.8 and 2.7 IU after two days. Markedly increased rapid inhibition of t-PA (greater than 4 IU per ml) was found in plasma of patients with severe liver disease (3 of 8), pancreatitis (4 of 8), malignancy (5 of 26), but only very occasionally and transiently in that of patients with myocardial infarction (5 of 28) or deep vein thrombosis (2 of 9). Increased inhibition was observed on the first day following coronary bypass (22 of 42) or open heart (16 of 27) surgery but this had disappeared in 15 of 16 patients on the fifth postoperative day. Titration of inhibitor levels revealed maximal amounts of 30 to 50 IU per ml plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Gel↗

Effect of 24 hours of normoglycaemia on tissue-type plasminogen activator plasma levels in insulin-dependent diabetes.

We have previously demonstrated that a short period of normoglycaemia obtained through an artificial pancreas in uncontrolled insulin-dependent diabetics improves parameters of the functional microangiopathy such as erythrocyte deformability and platelet aggregation. Because recently an immunoradiometric assay for tissue plasminogen activator (t-PA) was developed we measured t-PA levels in 18 uncontrolled insulin-dependent diabetics before and after 24 hr of normoglycaemia induced by insulin to look for a modification of endothelial cells function. After 24 hr of strict control, plasma free insulin levels rose significantly, total t-PA R-Ag, its active fibrin binding fraction and euglobulin fibrinolytic activity were significantly decreased. These results suggest a responsibility for insulin in the decrease in t-PA blood level and could explain at least partially the relation between hyperinsulinism, thrombosis and atherogenesis.

Adolescent↗

Anticoagulants and erythrocyte filterability.

Positive-pressure and initial-flow-rate (Hémorhéomètre) filtration systems were used to study the deformability of erythrocytes from whole blood stored in EDTA or heparin. When all contaminating platelets and leucocytes were removed from the erythrocyte suspension there was no significant anticoagulant effect on erythrocyte filtration. Blood may therefore be stored in K2EDTA (1.5 mg/ml blood) or lithium heparin (15 IU/ml blood) for up to 6 hours at room temperature prior to measurement of erythrocyte filterability.

Anticoagulants↗

Fibrinolytic activity in experimental vascular grafts.

The effects of grafting segments of femoral vein in the dog have been studied. The venous segments, either reversed or left in situ, were interposed in the course of the femoral artery; these 'arterialized grafts' were compared with a segment of vein grafted into the venous stream, with normal femoral artery and vein. Histological changes and alterations in fibrinolytic activity were studied after 15, 30 and 90 days. The two types of arterialized venous graft showed similar aspects: normal endothelium (scanning electron microscopy and F VIII immunofluorescence), marked thickening of the smooth muscle cell layer, disappearance of intimal fibrinolytic activity (Todd's technique, quantified by morphometric analysis), associated with a marked increase of antiplasmin activity (Noordhoek Hegt's technique), increase in the activity of vascular plasminogen activator (measured with chromogenic substrates). The venous grafts in the venous stream showed no changes compared to the normal femoral vein. The proliferation of smooth muscle cells following exposure of a segment of vein to arterial conditions appears to be associated with increased synthesis of both an inhibitor of fibrinolysis (antiplasmin), and of vascular plasminogen activator. The contribution of these two factors to the development of the morphological changes in the vessel requires further study.

Animals↗

[Prevention of deep venous thrombosis of the leg by a very low molecular weight heparin fraction (CY 222) in patients with hemiplegia following cerebral infarction: a randomized pilot study (30 patients)].

The effectiveness and safety of a very low molecular weight heparin fraction were evaluated in the prevention of deep-vein thrombosis in patients confined to bed due to hemiplegia consecutive to a recent cerebral infarction. CY 222 was administered within 48 hours of the stroke by one single daily subcutaneous injection of 0.6 ml (= 15,000 U AXa IC) during 14 days. This randomized pilot study involved 30 patients. The effects of CY 222 were assessed in a group of 15 patients compared with a control group of 15 untreated patients. No deep-vein thrombosis was detected by the labelled fibrinogen test in the treated group, as against 12 patients in the control group. Six patients (3 in each group) died during the study. One case of lethal pulmonary embolism was observed and confirmed at autopsy in the control group. In the remaining 5 patients, no systematic autopsy which would have asserted the absence of pulmonary embolism or drug-induced haemorrhage was performed. Numerous standard laboratory tests confirmed that CY 222 was well tolerated.

Aged↗

Formation, inhibition and clearance of plasmin in vivo.

A 5 microg/kg bolus of tissue plasminogen activator (t-PA) was infused into 11 healthy subjects followed by measurement of t-PA activity and antigen, PAI-1 activity and antigen, t-PA/PAI-1 complex, plasmin/antiplasmin (PAP) complex and D-dimer over 4 h. Infusion of t-PA resulted in a rise in PAP levels in all subjects from a baseline of 2.4 +/- 1.1 nmol/l to a peak of 5.1 +/- 2.3 nmol/l, but had no effect on plasminogen, antiplasmin or D-dimer levels. Using a kinetic model of plasminogen activation in vivo, the second-order rate constant for t-PA binding to plasminogen was estimated to be 3,100 +/- 1,300 mol(-1)l x s(-1), 200-500 times slower than t-PA accelerated by fibrin. The half-life of PAP was 4.5 +/- 1.6 h. In healthy subjects, the PAP level in plasma represents the average rate of plasminogen activation over the last 2-8 h.

Adult↗