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Biomedical subjects

J Aznar

Publications and source records attributed to J Aznar.

At least 91 records · Page 5Linked to original sources
PubMed1996

Erythrocyte membrane cholesterol/phospholipid changes and hemorheological modifications in familial hypercholesterolemia treated with lovastatin.

Fourteen patients with familial hypercholesterolemia treated with lovastatin (40 mg/day) for three months were studied to find out whether the expected changes in plasma lipids are accompanied by modifications in the lipid composition of the erythrocyte membrane and whether these in turn induce changes in the rheological behavior of the red blood cell. Our results demonstrate the efficacy of lovastatin in reducing the plasma concentration of cholesterol and LDL cholesterol. The changes observed in the plasma lipids correlate with a significant decrease in the cholesterol/phospholipid ratio of the red blood cell membrane, from 1.19 +/- 0.19 in a basal situation to 0.92 +/- 0.23 (p < 0.01) at the end of treatment. These changes in the lipid composition of the cell are statistically related to a decrease in erythrocyte aggregability and an improvement in blood filterability, which means beneficial change in the patients' hemorheological situation.

Adult↗
PubMed1996

A modification of the APC resistance test and its application to the study of patients on coumarin therapy.

APC resistance appears to be caused, predominantly, by a mutation in coagulation factor V (nucleotide 1691: G to A). This phenomenon is usually studied by performing APTTs in the absence and presence of added APC. We studied a modification of the assay involving dilution of the test plasma in factor V deficient plasma, to render the assay more factor V specific. This modification was applied to 76 patients with venous thrombosis on coumarin treatment and to 45 controls. Two out of 45 controls (4.4%) showed abnormal results with the modified test. They also showed loss of factor V exon 10 Mnl I restriction site, associated to APC resistance. All remaining controls, with normal functional results by the modified assay, showed normal restriction profile. We detected 9 affected patients (11.8%), one of them homozygous or double heterozygous. In conclusion, the modified assay is very sensitive for factor V dependent APC resistance, and can successfully be applied to patients on coumarin therapy.

Adult↗
PubMed1996

Comparative in-vitro activity of sparfloxacin against genital pathogens.

The in-vitro activity of sparfloxacin against four pathogens commonly implicated in genital infections was compared with that of a number of other commonly administered antimicrobials. Sparfloxacin demonstrated excellent activity against Neisseria gonorrhoeae (MIC range of < or = 0.0002-5 mg/L for beta-lactamase producing strains, and < or = 0.0002-0.03 mg/L for non-beta-lactamase producing strains). This activity was similar to that of lomefloxacin and ciprofloxacin and was greater than that of ofloxacin. Sparfloxacin was more active against Ureaplasma urealyticum (MIC90 1 mg/L) than the other three quinolones (MIC90 4 mg/L). Sparfloxacin was much more active against Mycoplasma hominis (MIC90 0.06 mg/L) than the other quinolones (MIC90 1 mg/L). Sparfloxacin showed the most potent inhibitory and bactericidal activity of the quinolones against Chlamydia trachomatis with MIC and MBC of 0.06 mg/L (ofloxacin MIC and MBC 1 mg/L; ciprofloxacin and lomefloxacin MIC and MBC 2 mg/L). The results of this study and others performed by workers using different methods are consistently similar. Since sparfloxacin has broad activity against pathogens implicated in genital infections it may be a good therapeutic alternative for these syndromes.

Anti-Infective Agents↗
PubMed1996

Hemorheological profile in patients with cardiovascular risk factors.

In order to find out whether hemorheological alterations precede the atherosclerotic lesions and could constitute an atherothrombotic risk factor, we studied the hemorheological profile in 150 healthy normotensive offspring whose parents were diagnosed as having essential hypertension WHO I-II grade and in another group of 40 children with familial hypercholesterolemia (FH) but without vascular atherosclerosis lesions, whose parents also suffer from FH. In offspring of hypertensive individuals, a significant increase in the fibrinogen level with respect to the control group was found both in males and females. In addition, only the female offspring showed a higher leucocyte count. FH children showed increased erythrocyte aggregation and increased plasma viscosity with respect to the control group. The fact that the rheological alterations appear prior to the development of the vascular lesion suggests that they could play a role in the pathogenesis of the atherosclerotic process.

Adolescent↗
PubMed1996

Effect of HMG-CoA reductase inhibitors on red blood cell membrane lipids and haemorheological parameters, in patients affected by familial hypercholesterolemia.

Eighteen patients with familial hypercholesterolemia treated with lovastatin (40 mg/day) for three months were studied to find out whether the drug induces modifications in the lipid composition of the erythrocyte membrane and whether these induce changes in the rheological behaviour of the red blood cell. Our results show that the changes observed in plasma lipids correlate with a significant decrease in the cholesterol/phospholipid ratio of the red blood cell membrane. These changes in the lipid composition of the cell are statistically related to a decrease in the erythrocyte aggregability and an improvement in blood filterability probably due to an increase in the red blood cell deformability.

Adult↗
PubMed1996

Quantification of circulating activated protein C in human plasma by immunoassays--enzyme levels are proportional to total protein C levels.

We have developed a simple assay that measures the circulating activated protein C (APC) in plasma. The assay requires collection of duplicate blood samples, one in citrate plus heparin and the other in citrate plus inhibitors of the enzyme. In the heparin tube, APC reacts completely and irreversibly with its major plasma inhibitors, protein C inhibitor (PCI) and alpha 1-antitrypsin (alpha 1AT), and the complexes formed are measured by ELISAs. The amount of circulating APC is calculated from the difference between the total amount of complexed APC (sample in citrate plus heparin) and the amount of APC complexed in vivo (sample in citrate plus inhibitor). Over 95% of the APC added to blood collected with heparin was recovered in the assay. The assay can easily be performed in four hours, and had a detection limit of 0.1 ng/ml APC. The mean APC level in 18 protein C heterozygous members from seven kindreds was significantly lower (0.6 +/- 0.3 ng/ml) than in 20 healthy controls (1.1 +/- 0.3 ng/ml) (p < 0.001), whereas the mean level in 10 non-affected members from the kindreds studied was 1.5 +/- 0.3 ng/ml. In the group of 12 nonanticoagulated heterozygous protein C-deficient individuals, the three patients with a history of venous thrombosis had a mean APC level significantly lower than the nine asymptomatic members (p < 0.01), both subgroups showing similar protein C levels. There was a significant correlation in all groups between the levels of APC and the levels of protein C antigen (r = 0.758, p < 0.0001) and activity (r = 0.745, p < 0.0001), which means that APC circulating levels are proportional to protein C levels and suggests that the protein C level is the limiting factor in the rate of protein C activation in vivo.

Adolescent↗
PubMed1996

Abnormal expression of plasminogen activator inhibitors in patients with gestational trophoblastic disease.

We previously reported significantly elevated levels of plasminogen activator inhibitor type 1 (PAI-1) in plasma and placenta from pregnant women with severe pre-eclampsia, and pre-eclampsia is a frequent problem in molar pregnancies. As increases in PAI-1 may contribute to the placental alterations that occur in pre-eclampsia, we have begun to investigate changes in PAI-1 as well as PAI-2 and several other components of the fibrinolytic system in patients with trophoblastic disease. Significant increases in plasma PAI-1 and decreases in plasma PAI-2 levels were observed in molar pregnancies when compared with the levels in normal pregnant women of similar gestational age. PAI-1 antigen levels also were increased, and PAI-2 levels were decreased in placenta from women with molar pregnancies compared with placenta obtained by spontaneous abortion. Immunohistochemical analysis revealed strong positive and specific staining of PAI-1 in trophoblastic epithelium in molar pregnancies and relatively weak staining of PAI-2. No association between the distribution of PAI-1 and vitronectin was found, and no specific signal for tissue type PA, urokinase type PA, tumor necrosis factor-alpha, or interleukin-1 was detected. In situ hybridization revealed an increase in PAI-1 but not PAI-2 mRNAs in placenta from molar pregnancies in comparison with placenta from abortions. These results demonstrate increased PAI-1 protein and mRNA in trophoblastic disease and suggest that localized elevated levels of PAI-1 may contribute to the hemostatic problems associated with this disorder.

Female↗
PubMed1996

Decreased expression of PAI-2 mRNA and protein in pregnancies complicated with intrauterine fetal growth retardation.

An increase in plasma plasminogen activator inhibitors (PAIs), fundamentally PAI type 2 (PAI-2), has been described in normal pregnancy probably because the placenta is the main source of the high plasma levels of this protein. Although we have previously described plasmatic alterations of these inhibitors in pregnancies complicated with intrauterine fetal growth retardation (IUGR), no reports have been published about placental PAI-2 mRNA expression. In the present study, the placental PAI-2 expression determined in pregnancies complicated with IUGR and in severe preeclamptic patients was compared with that of normal pregnancies in order to identify the placental cell types expressing PAI-2 and to determine whether the production of PAI-2 is altered in placentas from IUGR. In situ hybridization analyses show that the syncytiotrophoblasts are the cells with the greatest PAI-2 expression in placenta. We report that the significant decrease in plasma and placental PAI-2 levels in IUGR groups is fundamentally due to a diminished expression of PAI-2 mRNA in placenta.

Adult↗
PubMed1996

Heparin stimulation of the inhibition of activated protein C and other enzymes by human protein C inhibitor--influence of the molecular weightof heparin and ionic strength.

The ability of unfractionated (UF) heparin and low-molecular-weight heparin (LMWH) to potentiate the inhibition of fibrinolytic and coagulation factors by protein C inhibitor (PCI) was studied. Inhibition of activated protein C (APC), urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), thrombin, factor Xa (Xa), factor XIa (XIa) and plasma kallikrein (KK) by PCI was found to be dependent on the size of the polysaccharide. In general, maximal stimulation was reached with UF heparin, except in the case of KK. Differences in heparin stimulation were more pronounced for thrombin, APC, uPA, tPA and XIa, whereas inactivation of Xa by PCI was less dependent on the presence of heparin, and kallikrein showed higher potentiation with LMWH than with UF heparin. The second-order rate constants for enzyme inhibition by PCI were strongly dependent on the ionic strength, and, in general, with an ionic strength higher than 0.15 the heparin stimulation of the inhibition reactions was drastically reduced. These results may explain the large discrepancies in the literature on the effect of heparin on the stimulation of enzyme inhibition by PCI. They also show that LMWH is less efficient in stimulating the PCI inhibition of APC, uPA and tPA, which could contribute to the antithrombotic effect of these enzymes.

Animals↗
PubMed1995

Activation of the protein C pathway in acute sepsis.

To obtain quantitative information on the in vivo activation of the protein C system during the acute phase of sepsis, several components of the protein C pathway were studied in 18 patients. Blood samples were obtained one day after diagnosis (day 1) and, in 11 patients, also on the fourth and tenth days after diagnosis (days 4 and 10). On day 1, patients showed laboratory signs of haemostatic alterations such as positive fibrinogen/fibrin degradation products, and increased thrombin:antithrombin-III (TAT) complex levels. Compared with the control group, patients on day 1 had significantly decreased (p < 0.001) antigenic protein C (69 +/- 28%) and protein C inhibitor (PCI) (33 +/- 22%) whereas a significant increase in the levels of activated protein C (APC) complexed with alpha 1-antitrypsin (alpha 1AT) (APC:alpha 1AT, 26 +/- 15 ng/mL) and APC:PCI complex (3.0 +/- 2.0 ng/mL), and in the level of plasma kallikrein (KK) complexes with PCI (KK:PCI) (31 +/- 22 ng/mL) was observed. There was a positive correlation between APC:alpha 1AT and TAT complex levels (r = 0.597, p = 0.009). In the follow-up a trend toward normal values in antigenic protein C and PCI, and in APC:PCI and KK:PCI complex levels was found. However, PCI remained significantly decreased compared to normal values. C4b-binding protein, alpha 1AT, and TAT and APC:alpha 1AT complexes did not show any significant variations during the course of the disease, suggesting the contribution of the inflammatory and haemostatic responses, in spite of the good recovery of the patients. This study shows that in the course of sepsis, patients experience a generalized activation of the protein C pathway which was more prominent on day 1, resulting in the consumption of protein C and PCI and in the increase of APC:inhibitor complexes. Moreover, these data provide further evidence that KK:PCI circulating complexes occur in vivo.

Acute Disease↗
PubMed1995

The effect of estrogen replacement therapy with or without progestogen on the fibrinolytic system and coagulation inhibitors in postmenopausal status.

OBJECTIVE: The aim of this study was to analyze several fibrinolytic components and coagulation inhibitors in postmenopausal women and had to evaluate the effect of hormone replacement therapy. STUDY DESIGN: Several hemostatic parameters were evaluated in 75 postmenopausal women before and after 3 to 4 and 12 months of hormone therapy. RESULTS: An increase in plasma fibrinolytic activity primarily related to a significant increase in tissue-type plasminogen activator and a decrease in plasminogen activator inhibitor type 1 was observed in women receiving hormone replacement therapy. A significant decrease in protein S and lipoprotein(a) was detected under therapy. No modifications in tissue-type plasminogen activator/plasminogen activator inhibitor-1 and activated protein C/alpha 1-antitrypsin complexes, urokinase activity, plasminogen, and antithrombin III were detected. CONCLUSIONS: The increase in fibrinolytic activity and the decrease in lipoprotein(a) levels observed in women receiving hormone replacement therapy could help decrease the risk of coronary disease associated with the postmenopausal state.

Administration, Cutaneous↗
PubMed1995

Fibrinolytic system and reproductive process with special reference to fibrinolytic failure in pre-eclampsia.

Here we summarize the recent progress in research on the role of the fibrinolytic system in reproduction, with a special emphasis on the role of the plasminogen activator inhibitors in fetal development. Trophoblasts produce fibrinolytic proteins that can promote normal implantation and regulate blood flow to the fetus and placenta throughout pregnancy. Normal pregnancy is associated with a hypofibrinolytic state that is fundamentally caused by an increase in plasminogen activator inhibitors types 1 and 2. In pre-eclampsia, a fibrinolytic failure, resulting from an increase in plasma and placental concentrations of plasminogen activator inhibitor-1, was observed. The localized elevated concentrations of placenta plasminogen activator inhibitor-1 protein and mRNA observed in pre-eclamptic patients would be expected to foster the deposition of fibrin and thus play a role in the complications associated with this disease. The decreased plasminogen activator inhibitor-2 concentrations in placenta and plasma from intrauterine fetal growth retardation pregnancies and the positive correlation between plasma/placenta plasminogen activator inhibitor-2 concentration and birthweight suggest that this inhibitor could be considered an adequate marker of placental function.

Cell Movement↗
PubMed1995

Nosocomial transmission of tuberculosis infection in pediatrics wards.

Analysis of restriction fragment length polymorphisms is a well-established method of "DNA fingerprinting" that has been used to trace the transmission of particular strains of Mycobacterium tuberculosis during investigations of outbreaks. This report describe the use of restriction fragment length polymorphisms and arbitrarily primed polymerase chain reaction analysis to investigate two outbreaks of tuberculosis that affected six children who attended two pediatric wards in our hospital. In both outbreaks a history of household exposure to an adult with M. tuberculosis was obtained and suspected tuberculous contacts were identified. We have demonstrated unequivocally the strain relationship among the isolates in all the cases by restriction fragment length polymorphisms and arbitrarily primed polymerase chain reaction analysis. These techniques are very useful for performing epidemiologic studies of tuberculosis in children where natural history of tuberculosis infection is different from that in adults in that it is almost always primary infection rather than reactivation.

Child↗