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At least 253 records · Page 14Linked to original sources

[Compressive hematoma complicating percutaneous catheterization of the axillary vein].

A 41-year-old woman was admitted in the intensive care unit with ruptured oesophageal varices. She had already had two similar events, six and four months previously. She had a haemoglobin concentration of 56 g.l-1, 20% prothrombin, 228 s activated cephalin time for a control time of 60 s, 0.9 g.l-1 of fibrinogen and a platelet count of 53 G.l-1. Because of the poor condition of her peripheral veins, it was decided to insert a central venous catheter. The axillary vein was chosen because of the coagulopathy. The axillary artery was accidentally punctured during the second attempt. Despite manual compression for 15 min, a small haematoma arose. The catheter was inserted in the right internal jugular vein. At the same time, a very large oedema of the left arm was noticed. The axillary haematoma had spread to the breast and lumbar fossa. The humeral and radial pulse amplitudes were decreased, and the patient complained of paraesthesiae. At phlebography, a vast haematoma was seen to compress the axillary vein. The patient's condition rapidly worsened, and she died 19 hours after admission with a probable cerebral haemorrhage. Although complications of axillary venous catheterization are rare, this case demonstrates that, in patient with very abnormal coagulation tests, central venous access should be obtained via a peripheral vein.

Adult↗

[Role of acute normovolemic hemodilution in treating retinal venous occlusions].

The supposed state of retinal venous occlusions by a thrombus has led to the use of diverse antithrombotic treatments (heparin, fibrinolytic agents). This theory being considered at the moment as controversial, haemorheological theories being more particularly favoured, other treatments are proposed in an attempt to better retinal microcirculation, and this by changing the blood viscosity parameters. The study reported here compared the effects on recovery of visual acuity of retinal venous occlusion patients of anticoagulant treatment alone, haemodilution alone, or both together. After initial ophthalmic assessment, twenty-five patients were randomly assigned to one of three groups: group I (n = 5; mean age 62 +/- 14 yr) received heparin for 21 days, followed by antivitamin K drugs for a further 30 days; group II (n = 10; mean age 54 +/- 16 yr) were acutely hemodiluted with 40,000 daltons molecular weight dextran, bringing the haematocrit to between 0.25 and 0.30; on day 2, the same anticoagulant treatment as in group I was associated; group III (n = 10; mean age 58 +/- 18 yr) were only hemodiluted. The hemodiluted state was maintained for 21 days. A biological assessment was carried out for the three groups on days 1, 2, 7, 14, 21 and 30 (haematocrit, fibrinogen level, platelet count, kaolin-cephalin time, heparin level). The evolution of visual acuity was assessed on days 7, 14, 21, 30, 60 and 90. Mean visual acuity was assessed on days 7, 14, 21, 30, 60 and 90. Mean visual acuity was virtually the same for the three groups on day 0.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Macrophage activation syndrome after treatment with infliximab for fistulated Crohn's disease].

INTRODUCTION: Macrophage activation syndrome has never been reported as an adverse effect of infliximab. CASE: Treatment with infliximab was prescribed for a 37-year-old man with fistulated Crohn's disease unresponsive to azathioprine. Three months after the last injection, he developed macrophagic activation syndrome, with febrile pancytopenia, hyperferritinemia, hypertriglyceridemia and an activated cephalin time twice the control level. DISCUSSION: Elimination of the known causes of macrophage activation syndrome suggests it is related to the infliximab treatment, but its pathogenesis remains a mystery.

Adult↗

Chloroquine effects on intrauterine and postnatal dendritic maturation of hippocampal neurons and on lipid composition of the developing rat brain.

The aim of the study was to analyse the intrauterine effects of Chloroquine on the dendritic maturation in the hippocampal region under considering of the lipid composition in brain tissue. 131 brains of rat pups from day 22 of pregnancy and 49 brains from offsprings from day 7 of life were investigated. The findings indicate changes in the geometric dendritic architecture of the CA3 neurons on the 7th day of life. The length of apical shaft, apical dendrites and basilar dendrites of the CA3 neurons showed a significant elongation (p < 0.05) under low doses of Chloroquine. Furthermore a early considerable formation of dendritic spines during the intrauterine period could be observed for CA1 spines at the day 22 p.c. A significant increase of the fatty acids, a reduced amount of sphingomyelines, cephalines and gangliosides was found. These results underline the fact of a mild toxic effect under a low dosis of Chloroquine in our model.

Administration, Oral↗

Phosphatidylethanolamine augments factor VIIa-tissue factor activity: enhancement of sensitivity to phosphatidylserine.

The effect of phosphatidylethanolamine (PE) on the activity of the factor VIIa-tissue factor complex (fVIIa-TF) has been examined with respect to plasma clotting activity and activation of factor X (fX) in a purified system. Vesicles prepared by relipidating membrane-anchored TF (dcTF; TF1-244, lacking the C-terminal cytoplasmic tail) into phospholipid vesicles containing 6 mol % phosphatidylserine (PS) and increasing levels of PE up to 40 mol % (the balance consisting of phosphatidylcholine) were found to progressively shorten TF-initiated clotting in normal human plasma to levels comparable to those observed using dcTF relipidated with cephalin. The shortened clotting times were at least in part due to the ability of PE-containing membranes to better support the activation of fX by the fVIIa.TF complex, as vesicles with increased PE content yielded progressively higher initial rates of fX activation. Surprisingly, PE substantially altered the sensitivity of fX activation to low levels of PS, yielding near-maximal rates of activation at only 3 mol % PS compared to 15-20 mol % PS required in the absence of PE. The effect of PE was not synergistic with that of PS since PE did not increase fX activation rates at high levels of PS (20 mol %). Examination of the kinetic parameters for fX activation revealed that the majority of the effect of PE was in decreasing the apparent Km for fX.(ABSTRACT TRUNCATED AT 250 WORDS)

Factor VIIa↗

Human placental anticoagulant protein: isolation and characterization.

An anticoagulant protein was purified from the soluble fraction of human placenta by ammonium sulfate precipitation and column chromatography on DEAE-Sepharose, Sephadex G-75, and Mono S (Pharmacia). The yield of the purified protein was approximately 20 mg from one placenta. The purified protein gave a single band by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a molecular weight of 36,500. This protein prolonged the clotting time of normal plasma when clotting was induced either by brain thromboplastin or by kaolin in the presence of cephalin and Ca2+. It also prolonged the factor Xa induced clotting time of platelet-rich plasma but did not affect thrombin-induced conversion of fibrinogen to fibrin. The purified placental protein completely inhibited the prothrombin activation by reconstituted prothrombinase, a complex of factor Xa-factor Va-phospholipid-Ca2+. The placenta inhibitor had no effect on prothrombin activation when phospholipid was omitted from the above reaction. Also, it neither inhibited the amidolytic activity of factor Xa, nor did it bind to factor Xa. The placenta inhibitor, however, did bind specifically to phospholipid vesicles (20% phosphatidylserine and 80% phosphatidylcholine) in the presence of calcium ions. These results indicate that the placental anticoagulant protein (PAP) inhibits coagulation by binding to phospholipid vesicles. The amino acid sequences of three cyanogen bromide fragments of PAP aligned with those of two distinct regions of lipocortin I and II with a high degree of homology, showing that PAP is a member of the lipocortin family.

Amino Acid Sequence↗

Prostaglandin precursor fatty acids in serum and bile as influenced by oophorectomy, contraceptive steroids and pregnancy. An experimental study in the cat.

Variations in the occurrence of prostaglandin precursor fatty acids might be of importance for the pathogenesis of gallstones. Pregnancy and use of contraceptive steroids increase the risk of gallstones. The present study reports the relative fatty acid composition in serum and biliary phospholipids studied by gas-liquid chromatography in four groups of female cats, which were on a standard diet: 1) oophorectomized animals, 2) animals on contraceptive steroids, 3) pregnant animals and 4) control animals. It was consistently found that the portions of palmitic and linoleic acid were higher and stearic and arachidonic acid were lower in biliary than in serum lecithin. In biliary lysolecithin, sphingomyelin and cephaline there were only small portions of linoleic and negligible amounts of arachidonic acid. Oophorectomy, contraceptive steroids or pregnancy did not induce any gross changes in the fatty acid pattern of lecithin in serum or bile. In animals treated with contraceptive steroids a reduced portion of linoleic acid was seen in the bile lecithin, and in pregnant animals there was a reduction of omega 3 and omega 6 fatty acids in biliary lecithin.

Animals↗

Effects induced by two different estrogens on serum individual phospholipids and serum lecithin fatty acid composition.

Eleven oophorectomized women (mean age 34.5 +/- 5.9) received two treatment cycles, one of the 17-C-alkylated ethinyl estradiol 20 microgram per day, and the second of the non-alkylated estrogen, estradiol valerate 2 mg per day for six weeks in separate periods preceded by six weeks without hormonal replacement therapy. Blood samples were drawn before and after six weeks on each estrogen. The samples were assayed for individual phospholipids i.e. cephalin, lecithin, lysolecithin and sphingomyelin after separation of these lipids by thin layer chromatography. The relative fatty acid composition of serum and high density lipoprotein lecithin and serum cholesterol ester was determined by gas liquid chromatography. Both estrogens reversed the symptoms of estrogen deficiency and had similar effects on serum individual phospholipids i.e. causing an increase in lecithin concomitant with a decrease in lysolecithin. It is suggested that this lecithin-lysolecithin shift could depend on an inhibition of the hepatic lipase and its phospholipase A1-activity. Both estrogens increased serum lecithin arachidonic acid without causing any change in linoleic acid (the major essential fatty acid), which indicates that this increase in arachidonic acid could be an estrogenic effect independent of dietary factors. Ethinyl estradiol caused an increase in palmitic and a decrease in stearic acid in the 1-position of serum lecithin while estradiol valerate did not influence these fatty acids at all. This palmitic-stearic acid shift induced by ethinyl estradiol is interpreted as a non-hormonal "drug-effect" linked to the liver toxicity of 17-C-alkylated steroids in spite of the lack of influence on routine liver function tests.

Adult↗

Superior sagittal sinus thrombosis: a clinical and experimental study.

Sinus-vein thrombosis is increasingly recognized as a much more frequent neurological disorder than was anticipated before. We examined the pathophysiology of superior sagittal sinus thrombosis (SSST) from 19 patients and a rat SSST model. We treated 19 cases with SSST who were diagnosed by angiography. The symptoms of nine patients, who suffered multiple intracerebral hemorrhage, were abrupt. In another ten patients who recovered satisfactorily, the condition progressed slowly and they were treated with heparin and urokinase. Multivariate analysis demonstrated that female, sudden onset (<24 hours) and posterior 1/3 occlusion are related to bad outcome. Experimentally, SSST was induced by ligation and slow injection of kaolin-cephalin suspension into SSS in rats. Regional cerebral blood flow (rCBF) and tissue hemoglobin oxygen saturation (Hb Sao(2)) using a "scanning" technique were measured at 48 locations, and fluorescence angiography was performed before and until 90 min after SSST induction. After 48 hours the animals were sacrificed for histological studies. Decrease of rCBF and tissue Hb SO(2) and brain damage were seen in group B (n = 10) with an extension of thrombosis from SSS into cortical veins. Brain injury was not observed in group A (n = 8) with SSS thrombus alone and sham-operated animals (n = 5). In conclusion, a brain with acute extension of thrombus from SSS into cortical veins becomes critical for cerebral blood supply and metabolism. CBF, tissue HbSO(2) and repeated angiography can be helpful monitors for the early detection of critical conditions after SSST. As to the therapy, restraint on the ongoing thrombus is essential to protect the brain with SSST, and we encourage the use of combination therapy of heparin and urokinase as early as possible in cases without intracerebral hemorrhage.

Journal Article↗

Electrostatic effects on lipid phase transitions: membrane structure and ionic environment.

Ordered --> fluid phase transitions in bilayers of charged lipids are accompanied by a decrease in electrostatic free energy mainly as a result of bilayer expansion. For uniform charge distribution the Gouy-Chapman theory of the electrical double layer predicts a decrease of the transition temperature with increasing charge density. We studied the effects of pH and mono- and divalent cations on the phase transition of lecithin, cephalin, phosphatidylserine, and phosphatidic acid bilayers. Phosphatidic acid with two ionizable protons was selected for a systematic investigation. A change in pH from 7 to 9 increases the charge per polar group from one to two elementary charges. This lowers the transition temperature by about 20 degrees C in agreement with the theory. In this pH region rather small changes in pH suffice to induce the phase transition at constant temperature. Divalent cations (Mg(++) and Ca(++)) increase the transition temperature by charge neutralization and thus can be used to induce the fluid --> ordered transition at constant temperature. In contrast, monovalent cations (Li(+), Na(+), K(+)) lower the transition temperature, or fluidize the bilayer structure at a given temperature. Rather small changes in ionic environment can induce gross alterations in bilayer structure; divalent and monovalent cations have antagonistic effects. This result parallels current theories on nerve excitation and sensory transduction where cation-induced structural changes in biomembranes are invoked.

Calcium↗

Binding of factors IX and IXa to cultured vascular endothelial cells.

Factor IX and its activated form IXa have been found to bind to confluent cultured bovine aortic and human umbilical vein endothelial cells. Binding of bovine factors IX and IXa to the bovine endothelial cells was saturable and specific and reached a plateau in 75 min at 4 degrees C and 30 min at 37 degrees C. Binding was half-maximal at a total factor IX or IXa concentration of 2.3 +/- 0.2 nM. At 4 degrees C, a maximum of 42 fmol of tritiated factor IX or IXa bound to 10(6) cells (an average of 20,000 molecules per cell). The binding of tritiated factor IX or IXa was inhibited by excess unlabeled factor IX or IXa but not by factor X, prothrombin, or thrombin. Competition studies indicated that factors IX and IXa interacted with the same site. Binding was reversible, with 50% of the specifically bound factor IX or IXa eluted in 40 min by a 400-fold excess of unlabeled protein. Specific binding required Ca2+ with half-maximal binding at 1.2 mM CaCl2. Factor IXa bound to the cells was tested for procoagulant activity in a clotting assay with factor IX-deficient plasma, cephalin, and CaCl2. Cell-bound factor IXa was at least 3-fold more active than was factor IXa in solution. The retention of procoagulant activity by cell surface-bound factor IXa provides a mechanism for the localization of clot-promoting activity.

Animals↗

Protein C inhibitor secreted from activated platelets efficiently inhibits activated protein C on phosphatidylethanolamine of platelet membrane and microvesicles.

Protein C inhibitor (PCI) was detected in human platelets (2.9 ng/10(9) cells) and megakaryocytic cells (1.5 ng/10(6) cells). PCI mRNA was also detected in both platelets and megakaryocytic cells using nested polymerase chain reaction. PCI was found to be located in the alpha-granules of resting platelets. Approximately 30% of the total amount of PCI in platelets was released after stimulation with ADP, collagen, adrenalin, thrombin, or thrombin receptor-activating peptide. Secreted PCI was detected on the surface of activated platelets and phospholipid microvesicles. PCI secreted from thrombin receptor-activating peptide-stimulated platelets inhibited activated protein C (APC) efficiently. PCI significantly inhibited APC in the presence of phospholipid vesicles prepared using rabbit brain cephalin (RBC) or a mixture of 40% phosphatidylethanolamine (PE), 20% phosphatidylserine (PS), and 40% phosphatidylcholine (PC) with a second order rate constant of 1.0 x 10(6) M-1.min-1. Of these phospholipids, PE was critical for this inhibition. The dissociation constants of the binding of APC or PCI to solid phase phospholipids showed that APC binds more preferably to PE than to RBC or PS, and PCI to PE or RBC than to PS or PC. PCI binding to solid phase phospholipids depended on the presence of PE. RBC- or PE-bound PCI inhibited APC significantly but only weakly the gamma-carboxyglutamic acid domainless APC. The gamma-carboxyglutamic acid fragment of protein C suppressed the PCI-mediated inhibition of APC on solid phase RBC or PE. Most of the APC.PCI complex formed on solid phase RBC or PE was released into the soluble phase. These findings suggest that PCI secreted from activated platelets binds preferably to PE of platelet membrane and microvesicles and that it inhibits phospholipid-bound APC efficiently.

Animals↗

Lyotropic phase transitions in phospholipids as evidenced by small-angle synchrotron X-ray scattering.

Hydration is an important factor in regulating the phase behaviour of lipids and besides affects their interactions with other compounds relevant for biological membranes. We present a reliable and fast method to detect and characterise hydration-induced phase transitions in phospholipids by means of small-angle synchrotron X-ray scattering. Films consisting of aggregations of representatives of the two important lipid classes lecithins (DPPC a, POPC and OPPC,a for abbreviations, see below) and cephalins (DPPE and DOPE) were investigated at room temperature in dependence on relative humidity. Qualitative changes in the sets of the diffraction patterns obtained in dynamic hydration/dehydration scans were taken as markers indicating the existence of lyotropic phase transitions. The efficiency of this methodology is demonstrated by illustrating the course of hydration-driven phase transitions between lamellar as well as nonlamellar phases. In detail, this was realised for chain melting in the mixed-chain lipids, POPC and OPPC, and for a novel nonlamellar-phase transition for DOPE between a disordered inverted ribbon phase designated as Palpha and the canonical H(II), phase, respectively.

Macromolecular Substances↗

Targeted inhibition of intrinsic coagulation limits cerebral injury in stroke without increasing intracerebral hemorrhage.

Agents that restore vascular patency in stroke also increase the risk of intracerebral hemorrhage (ICH). As Factor IXa is a key intermediary in the intrinsic pathway of coagulation, targeted inhibition of Factor IXa-dependent coagulation might inhibit microvascular thrombosis in stroke without impairing extrinsic hemostatic mechanisms that limit ICH. A competitive inhibitor of native Factor IXa for assembly into the intrinsic Factor X activation complex, Factor IXai, was prepared by covalent modification of the Factor IXa active site. In a modified cephalin clotting time assay, in vivo administration of Factor IXai caused a dose-dependent increase in time to clot formation (3.6-fold increase at the 300 micrograms/kg dose compared with vehicle-treated control animals, P < 0.05). Mice given Factor IXai and subjected to middle cerebral artery occlusion and reperfusion demonstrated reduced microvascular fibrin accumulation by immunoblotting and immunostaining, reduced 111In-labeled platelet deposition (42% decrease, P < 0.05), increased cerebral perfusion (2.6-fold increase in ipsilateral blood flow by laser doppler, P < 0.05), and smaller cerebral infarcts than vehicle-treated controls (70% reduction, P < 0.05) based on triphenyl tetrazolium chloride staining of serial cerebral sections. At therapeutically effective doses, Factor IXai was not associated with increased ICH, as opposed to tissue plasminogen activator (tPA) or heparin, both of which significantly increased ICH. Factor IXai was cerebroprotective even when given after the onset of stroke, indicating that microvascular thrombosis continues to evolve (and may be inhibited) even after primary occlusion of a major cerebrovascular tributary.

Animals↗

Preparation of thrombokinase from bovine plasma.

THROMBOKINASE IS PREPARED FROM BOVINE PLASMA BY A PROCEDURE INVOLVING: treatment with diatomaceous silica, adsorption on barium sulfate, flowing elution with two successive phosphate buffers, ammonium sulfate fractionation, "spontaneous" activation in concentrated solution, and isoelectric precipitation. The yield of nitrogen is 0.002 per cent, corresponding to 1.2 mg. protein per liter of plasma. When diluted back to the volume of parent plasma, and complemented by calcium plus cephalin, the product causes appreciable activation of prothrombin in 1 minute. Thus, the quantity of thrombokinase obtainable is compatible with a physiologic role. In the more complex system used for routine assay, thrombokinase can be supplied by crude plasma at a dilution of 1/500. In parallel tests, the product appears to be more active than its parent plasma, although it contains only 0.002 per cent of the nitrogen. However, the thrombokinase of the product has been activated, whereas the thrombokinase of the plasma is probably in an inactive precursor state. When diluted back to the volume of parent plasma, to a concentration of 0.2 microgram nitrogen per ml., thrombokinase can slowly activate prothrombin in the presence of oxalate, and without the addition of accessory factors. Activation of prothrombin in the presence of oxalate is faster with higher concentrations of thrombokinase.

Animals↗

The electrophoretic velocity of human red cells, of their ghosts and mechanically produced fragments, and of certain lipid complexes.

Ghosts prepared in CO(2)-saturated water from unwashed human red cells can be fragmented mechanically, but ghosts from thrice washed cells cannot. If the ghosts are prepared by freezing and thawing, this difference is not observed. The electrophoretic velocity varies also with the way in which the ghosts are prepared. The pH-mobility dependence of washed red cells flatten off to a plateau at pH 9, and the electrophoretic velocity is zero at about pH 2. Ghosts prepared by freezing and thawing have almost the same pH-mobility dependence, but if the ghosts are prepared in CO(2)-saturated hyptonic saline, the mobility at pH 9.4 is 0.75 times that of washed cells. Fragments of ghosts of unwashed red cells have a smaller mobility than that of the red cells. Trypsin reduces the mobility of washed red cells and of ghosts. Sols of lipid complexes (lecithin, cephalin, and lipositol), at varying pH's, have a mobility 1.2 times that of the washed red cell. The pH-mobility relation is otherwise similar. These complexes can be coated with dextran and trypsin.

Erythrocyte Membrane↗

Phospholipidcholesterol membrane model. Control of resistance by ions or current flow.

A cephalin-cholesterol membrane model is described whose electrical resistance can be reversibly raised by CaCl(2) or lowered by KCl or NaCl whether these ions are added to the membrane by mechanical immersion or are driven in electrically. Either KCl or NaCl acts antagonistically to CaCl(2). Experiments with controlled pH indicate that the above effects depend somehow on combination of the cations with the phospholipid acidic groups. Also, they are correlated with decreased membrane hydration in CaCl(2) solutions, and increased hydration in KCl or NaCl solutions. It is conjectured that cells may regulate their transsurface ion pathways and fluxes by K-Ca competition for negatively charged binding sites on plasma membrane phospholipid. It is regarded as a corollary to say that a fundamental event in excitation is displacement of membrane Ca from such a site by catelectrotonically propelled K.

Cations↗

Behavior of diluted activated partial thromboplastin time in pregnant women with a lupus anticoagulant.

The present study was developed to verify whether a reduction in phospholipid concentration could increase the activated partial thromboplastin time (APTT) sensitivity to detect lupus anticoagulant (LA) during pregnancy. The authors studied 38 pregnant women (10 normal subjects and 28 patients with associated clinical complications) and 40 nonpregnant control subjects. Tests to detect LA, including APTT, platelet neutralization procedure (standard APTT), the kaolin clotting time, the diluted Russell viper venom test neutralized by lysed platelets, and factor assays, were performed. Positive results were found in 5 of 28 pregnant women with associated clinical complications. The APTT, using three different phospholipid concentrations (standard and more diluted cephalin), was performed on plasma samples and on its 1:1 mixture with normal plasma. The behavior of standard and diluted APTT was similar in negative LA pregnant women and nonpregnant control subjects. The mean values showed nonsignificant differences. Four of five pregnant women with positive LA findings had a prolonged APTT, which was not corrected by the addition of normal plasma using standard conditions. When diluted phospholipids were used, only one of them had a prolonged APTT that was corrected by the addition of normal plasma. Therefore, the highest sensitivity (80%) and specificity (100%) of the APTT to detect LA in pregnant women were obtained using the standard conditions.

Female↗