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Biomedical subjects

J Monasterio

Publications and source records attributed to J Monasterio.

At least 19 recordsLinked to original sources
PubMed2001

Matrix metalloproteinase expression is related to hemorrhagic transformation after cardioembolic stroke.

BACKGROUND AND PURPOSE: In animal models of cerebral ischemia, matrix metalloproteinase (MMP) expression was significantly increased and related to blood-brain barrier disruption, edema formation, and hemorrhagic transformation (HT). MMP inhibitors reduce HT after embolic ischemia in tissue-type plasminogen activator-treated animals. We aimed to determine the relationship between MMPs and HT after human ischemic stroke. METHODS: Serial MMP-2 and MMP-9 determinations were performed by means of ELISA in 39 cardioembolic strokes in the middle cerebral artery territory. Hemorrhagic events were classified according to clinical and CT criteria (hemorrhagic infarction [HI] and parenchymal hematoma [PH]). HT was evaluated on CT at 48 hours (early HT) and again between day 5 and 7 (late HT). RESULTS: HT was present in 41% of the patients (43.75% early HI, 25% early PH and 31.25% late HI). MMP-2 values were within normal range and were unrelated to HT. Increased expression of MMP-9 (normal range <97 ng/mL) was found among patients with and without HT (159.3+/-82 versus 143.9+/-112.6 ng/mL; P=0.64). According to HT subtypes, the highest baseline MMP-9 levels corresponded to patients with late HI (240.4+/-111.2 versus 102.5+/-76.7 ng/mL for all other patients, P=0.002). Baseline MMP-9 was the only variable associated with late HI in the multiple logistic regression model (OR 9; CI 1.46, 55.24; P=0.010). Peak of MMP-9 at the 24-hour time point (250.6 ng/mL) was found before appearance of PH. CONCLUSIONS: MMPs are involved in some subtypes of HT after human cardioembolic stroke. Baseline MMP-9 level predicts late HI and a 24-hour peak precedes early PH.

Aged↗
PubMed2001

Matrix metalloproteinase expression after human cardioembolic stroke: temporal profile and relation to neurological impairment.

BACKGROUND AND PURPOSE: Uncontrolled expression of matrix metalloproteinases (MMPs) can result in tissue injury and inflammation. In animal models of cerebral ischemia, the expression of MMP-2 and MMP-9 was significantly increased. However, their role in human stroke in vivo remains unknown. Therefore, we sought to determine the temporal profile of MMP expression in patients with acute ischemic stroke and to investigate its relationship to stroke severity, location of arterial occlusion, and total infarct volume. METHODS: Serial MMP-2 and MMP-9 determinations were made in 39 patients with cardioembolic strokes that involved the middle cerebral artery territory by means of enzyme-linked immunosorbent assay. Blood samples, transcranial Doppler recordings, and National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and at 12, 24, and 48 hours after stroke onset. Infarct volume was measured with CT scanning at 48 hours. RESULTS: No correlation was found between MMP-2 and NIHSS score at any time point, although a close relation appeared between mean MMP-9 and final NIHSS score (r=0.486, P=0.002). MMP-9 value was the only factor associated with the final NIHSS score in the multiple logistic regression model (OR 4.54, 95% CI 1.5 to 13.75). A cut-point of MMP-9 142.18 ng/mL had a positive predictive value of 94.4% to assess a patient's NIHSS (<8 or >/=8) by the end of the study. Final MMP-2 and MMP-9 levels were significantly lower when recanalization occurred (528+/-144.3 versus 681.4+/-239.2 ng/mL, P=0.031 for MMP-2; 110.2+/-100.9 versus 244.8+/-130 ng/mL, P=0.004 for MMP-9). A positive correlation was found between mean MMP-9 and infarct volume (r=0.385, P=0.022). CONCLUSIONS: MMPs are involved in the acute phase of human ischemic stroke. MMP-9 levels are associated with neurological deficit, middle cerebral artery occlusion, and infarct volume.

Acute Disease↗
PubMed2000

Hypercoagulation and hypofibrinolysis in horses with colic and DIC.

Changes in haemostasis in horses with colic were assessed by using specific and sensitive markers of coagulation and fibrinolysis activity. Blood samples from 41 horses with severe colic and from 30 healthy control horses were tested. Diagnosis of DIC was based on the findings of at least 3 of 6 abnormalities: thrombocytopenia, prolonged clotting times (PT and APTT), increased polyclonal FDPs, decreased fibrinogen and decreased AT-III activity. Plasma thrombin-antithrombin III complexes (TAT), monoclonal fibrin degradation products fragment D (D-dimer) and monoclonal fibrinogen degradation products (FgDP) were also tested by using ELISA kits. DIC was diagnosed in 16 of 41 horses with colic. Compared to control and non-DIC colic values, TAT was significantly (P < 0.000) greater in horses with colic and DIC (Control group, mean +/- s.d. 2.6 +/- 2; non-DIC colic group, 7.5 +/- 9, and DIC colic group, 30.9 +/- 36 ng/ml). Also, D-dimer was significantly (P < 0.000) less in the DIC group when compared to control and non-DIC colic values (mean +/- s.d. 677 +/- 119, 682 +/- 220 and 399 +/- 234 ng/ml, respectively). Compared to non-DIC colic values, FgDP was significantly (P < 0.05) lower in the DIC group (363 +/- 111, 437 +/- 230 and 293 +/- 187 ng/ml respectively). Both PT and APTT showed a significant positive correlation with TAT. DIC was more common among nonsurvivors and horses with ischaemic bowel. We conclude that a hypercoagulative state was detected in horses with colic, which was stronger in horses with colic and DIC. Hypofibrinolysis was present only in horses with DIC. Therefore, marked hypercoagulation together with hypofibrinolysis are associated with DIC in horses.

Animals↗
PubMed1999

Tissue factor levels and high ratio of fibrinopeptide A:D-dimer as a measure of endothelial procoagulant disorder in pre-eclampsia.

To assess coagulation activation and endothelial cell injury in normotensive and pre-eclamptic pregnant women, a comparison was made of plasma levels of tissue factor, fibronectin, fibrinopeptide A and D-dimer. Samples were taken from 50 nonpregnant women, 40 normotensive pregnant women in the third trimester and 27 women with pre-eclampsia after diagnosis and before treatment. High levels of fibrinopeptide A and D-dimer were found in pre-eclamptic women. Moreover, the ratio fibrinopeptide A:D-dimer was much greater in the pre-eclampsia group than in normotensive pregnant women. The levels of fibronectin and tissue factor were also higher in the pre-eclampsia group. The increase of tissue factor levels suggests an alteration of the extrinsic coagulation pathway in pre-eclampsia. The increase of fibrinopeptide A:D-dimer ratio shows that the activation of coagulation is associated with a relative hypofibrinolysis in pre-eclampsia.

Adult↗
PubMed1998

Endothelial cell markers and fibrinopeptide A to D-dimer ratio as a measure of coagulation and fibrinolysis balance in normal pregnancy.

OBJECTIVE: Changes in hemostatic system were evaluated in healthy pregnant women. METHODS: Blood was sampled in the 1st, 2nd and 3rd trimesters of gestation, during delivery and 3 days postpartum and plasma factors were measured using commercial tests. RESULTS: Thrombin-antithrombin III complexes, fibrinopeptide A and D-dimer were higher during pregnancy. The endothelial cell markers, fibronectin and tissue factor, remained within the normal reference values in the healthy nonpregnant population. This result suggests no endothelial injury and shows no activation of extrinsic coagulation pathway during pregnancy. The balance coagulation/fibrinolysy is maintained during pregnancy and delivery, as shown by the ratio fibrinopeptide A/D-dimer, however, a tendency towards coagulation process is developed in the early puerperium.

Adult↗
PubMed1998

Heparin cofactor II: a new marker for pre-eclampsia.

The plasma levels of heparin cofactor II were determined in pregnant women who were either normotensive, or had essential hypertension, gestational hypertension or pre-eclampsia during the third trimester and 72 h after delivery. Heparin cofactor II levels in the pre-eclampsia group were depressed. The clinical relevance of this finding is the potential utility of heparin cofactor II plasma levels in the differential diagnostic between non-proteinuric hypertension and pre-eclampsia.

Adult↗
PubMed1998

Hemorheological, coagulative and fibrinolytic changes during autologous blood donation.

BACKGROUND: Clinical data suggest that autologous blood donation may prevent postsurgical venous thrombosis. If confirmed, this is probably due to beneficial effects in rheologic and hematologic variables which may be changed in patients as a result of repeated bleeding. STUDY DESIGN AND METHODS: To ascertain this point, we studied variations in hematological, hemorheological, coagulative and fibrinolytic parameters in 30 patients undergoing autologous blood donation. RESULTS: Whole blood viscosity (WBV), plasma viscosity and blood viscosity adjusted to 40% hematocrit, progressively and substantially decreased throughout the successive bleeding at all the shear rates considered. WBV was further reduced by presurgical hemodilution with autologous plasma which decreased the platelet and leukocyte count. The hemostasis and fibrinolysis variables, however, underwent no clinically significative changes. CONCLUSION: Repeated bleedings change most hemorheological variables. By decreasing cytocrit and viscosity, reducing aggregability and increasing blood cell deformability an optimal milieu to help prevent thrombosis is artificially created.

Adult↗
PubMed1996

Evaluation of thrombin-antithrombin complexes and fibrin fragment D in carbohydrate-induced acute laminitis.

Carbohydrate-induced laminitis has been associated with decreased platelet survival, decreased blood flow to the hoof wall and with the deposition of platelets and microthrombi within venules in the dermal laminae. To evaluate further the systemic prothrombotic events occurring in the prodromal stages of laminitis, plasma samples from control and laminitis-affected ponies and horses were tested for the presence of thrombin-antithrombin (TAT) complexes and fibrin fragment D (D-dimer). No statistically significant differences between the control and laminitis-affected animals were observed for either the D-dimer or the TAT complexes. Few of the values for individual animals exceeded the reference ranges for control animals. These data indicate that the prothrombotic events observed in carbohydrate-induced laminitis may not be associated with systemic activation of the coagulation or fibrinolytic systems.

Acute Disease↗
PubMed1995

Effects of two different doses of hirudin on APTT, determined with eight different reagents.

The APTT has been considered the most suitable candidate to monitor the anticoagulant activity of hirudin. However, its use is hampered by problems of standardization, which make the results heavily dependent on the responsiveness of the reagent used. Our aim was to investigate if this different responsiveness of different reagents when added in vitro is to be confirmed in an ex vivo study. Two different doses of r-hirudin (CGP 39393), 0.3 mg/kg and 1 mg/kg, were administered subcutaneously to 20 New Zealand male rabbits, and the differences in prolongation of APTT 2 and 12 h later were compared, using 8 widely used commercial reagents. All groups exhibited a significant prolongation of APTT 2 h after sc administration of hirudin, both at low and high doses. But this prolongation persisted 12 h later only when the PTTa reagent (Boehringer Mannheim) was used. In general, hirudin prolonged the APTT most with the silica-based reagents. In a further study, we compared the same APTT reagents in an in vitro study in which normal pooled plasma was mixed with increasing amount of hirudin. We failed to confirm a higher sensitivity for silica-containing reagents. Thus, we conclude that subcutaneous administration of hirudin prolongs the APTT most with the silica-based reagents, but this effect is exclusive for the ex vivo model.

Animals↗
PubMed1993

[Normal values for hematological and hemostatic parameters in the rabbit. Determination of new parameters for experimental models of thrombosis and hemostasis].

PURPOSES: Assessment of normal haematological values in the rabbit using a semi-automatic analyser. Evaluation of new haemostatic parameters necessary for experimental models in thrombosis and haemostasis. MATERIAL AND METHODS: 20 New Zealand male rabbits of 2-2.5 kg were anaesthetized and blood was collected from the jugular vein. The following haematological determinations were carried out using a semi-automatic analyser: red blood cells count, haemoglobin, haematocrit, indexes, white blood cells count, platelet count and mean platelet volume. The parameters used to assess the physiological haemostasis in rabbit were: bleeding time, fibrinogen, prothrombin time, activated partial thromboplastin time, thrombin time; and others not yet determined in the rabbit: antithrombin III, thrombin-antithrombin complexes and F1+2 fragments to measure the basal thrombin-formation activity, and fibrin D-dimer and fibrinogen degradation products for fibrinolysis activity. RESULTS: The haematological results obtained were similar than with other techniques, but with no stress influence. Normal values for haemostatic parameters studied are shown, including the parameters for the determination of physiological thrombin-formation and fibrinolysis activity. F1+2 fragments and fibrinogen degradation products could not be evaluated. CONCLUSIONS: The haematological results obtained were completely normal. All the haemostatic parameters studied were found useful to determine the physiological activity of coagulation and fibrinolysis in the rabbit, and specially for experimental models of hypercoagulability and hyperfibrinolisys states.

Animals↗
PubMed1993

[Platelet hyperactivity in diabetic retinopathy: etiologic factor or epiphenomenon of microangiopathy?].

In order to analyze the etiologic and pathogenic meaning of platelet activity in diabetic retinopathy, Plasmatic Beta-Thromboglobulin (BTG) has been determined in 42 diabetics without retinopathy, 14 diabetics with non proliferative retinopathy and in 29 health controls. BTG showed higher values in diabetic patients with retinopathy in comparison with diabetics with no retinopathy (46.4 +/- 10.7 versus 37.6 +/- 13.4 ng/ml; p < 0.05 and with controls (31 +/- 18.8; p < 0.005). There were no differences between diabetics with no retinopathy and controls. No relation was found between BTG and the glycemic control grade, neither with lipoproteic profile. In resume, platelet hyperactivity found in patients with retinopathy seems to be an epiphenomenon of the microangiopathic lesion and not an etiologic factor, however this not precludes that it can play a role in the progression on retinal lesions.

Adult↗
PubMed1992

[Resistance to antivitamins K].

Resistance to oral anticoagulant is a rare phenomenon. We report the case of a 32-year-old woman who required anticoagulation due to a deep venous thrombosis. She gradually developed resistance to acenocumarol and warfarin. Although the HPLC (high performance liquid chromatography) method proved satisfactory acenocumarol levels in plasma, therapeutic anticoagulation was not achieved. The mechanisms of resistance are discussed.

Acenocoumarol↗
PubMed1991

Comparative study on the antithrombotic efficacy of four low-molecular-weight heparins in three different models of experimental venous thrombosis.

In a randomized, blind study, both the antithrombotic efficacy (reduction of thrombus weight) and potency (anti-Xa activity) of several commercially available low-molecular-weight heparins (LMWHs) were compared with those of unfractioned heparin (UFH) and placebo. Three different thrombogenic challenges were used: venous thrombosis was induced by direct endothelial damage in 60 New Zealand rabbits (group I), intracarotid injection of bovine thrombin in an additional series of 60 rabbits (group II), or after inferior-vena-cava ligature in 60 Wistar rats (group III). The drugs were administered subcutaneously 2 h before surgery in a blind fashion. The doses recommended for clinical practice were used (adjusted by body weight), except in group II animals, in whom doses were doubled. No differences were found between UFH and most LMWHs in terms of reduction of thrombus weight in group I animals. But UFH showed a weaker antithrombotic efficacy in the other two models. Similarly, one of the LMWHs used (Clexane) proved to be not as effective as the remainder. However, only clinical studies will provide enough information to verify these differences. Additionally, our findings confirm that the antithrombotic efficacy of a given drug differs according to the stimulus used to induce venous thrombosis.

Animals↗
PubMed1989

Platelet aggregation in transient global amnesia.

We found a correlation between increased platelet aggregation parameters and transient global amnesia and no differences between patients with transient global amnesia and transient ischemic attacks. Our findings support the theory of a vascular mechanism for transient global amnesia.

Amnesia↗