Prognostic usefulness of IL-6 and VEGF for the occurrence of changes in coronary arteries of patients with stable angina and implanted stents.

AIM: The aim of this study was to determine the prognostic significance of interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) in patients with chronic coronary artery disease treated who underwent percutaneous coronary intervention with stent implantation, for assessing the risk of restenosis and the occurrence of de novo lesions. PATIENTS AND METHODS: 498 patients with stable angina were examined during 18 months. 50 patients with significant (> 70%) stenosis of one coronary artery, eligible for the implantation of one stent, were enrolled to the study. Il-6 and VEGF level was measured using ELISA immunoassays during the initial coronary angiography with simultaneous angioplasty and stent implantation and 4 weeks after stent implantation. Coronary angiography was carried out 8-12 months after stent implantation. RESULTS: Statistically significant increase in IL-6 (from 4.02 ± 4.40 to 10.90 ± 8.23) and VEGF (from 310.13 ± 50.90 to 392.32 ± 106.84) level was observed 4 weeks after stent implantation in the group with restenosis. CONCLUSIONS: Increased levels of IL-6 and VEGF in the peripheral blood of patients with chronic stable angina pectoris, measured 4 weeks after coronary angioplasty with stent implantation, may indicate an increased risk of angiographic restenosis and de novo coronary artery lesions.

Supplementation with L-arginine does not influence arterial blood pressure in healthy people: a randomized, double blind, trial.

BACKGROUND AND OBJECTIVES: It cannot be excluded that supplementation with L-arginine, by improving function of endothelium and hypotensive effect, can be advantegeous in prevention of cardiovascular diseases in healthy people. However, reports about hypotensive effect of L-arginine in healthy people are unclear. Moreover, no research including ambulatory blood pressure measurement (ABPM) has been conducted so far. Therefore, the aim of our study was to show if 4-week supplementation of healthy people with L-arginine influences blood pressure measured with ABPM. MATERIALS AND METHODS: The study was carried out on 19 healthy people randomized to 6 g/24-hour, 12 g/24-hours of L-arginine or placebo. ABPM was carried out 4 times: before randomization, after 2 and 4 weeks of supplementation and 2 weeks after finishing supplementation. RESULTS: It was found that 4 weeks of supplementation of healthy people with L-arginine (6 or 12 g/24-hour) led to nonsignificant decrease of systolic and diastolic blood pressure; the decrease was greater during night. CONCLUSION: These findings showed that supplementation with L-arginine is not necessarily advantageous in healthy people.

Intense acute phase response in ischemic patients.

The aim of this study was to estimate the qualitative and quantitative changes of acute phase proteins in patients suffering from coronary heart disease. The study was carried out on 74 patients and 12 healthy volunteers. The patients were divided into three groups as follows: patients with myocardial infarction (n=37), Group I--without heart failure, Group II--with heart failure (II-III NYHA), Group III--patients with unstable angina pectoris (n=35); controls-healthy volunteers (n=12). The immunological measurements were performed at the beginning of hospitalisation (point 0), after 4, 8, 12 and 72 h, and after 6, 9 and 12 days of hospitalisation. The concentrations of C-reactive protein (CRP), alpha1-acid glycoprotein (AGP) and alpha1-antichymotrypsin (ACT) were measured using rocket immunoelectrophoresis according to Laurell. Glycosylation profiles of AGP and ACT were determined using crossed affinity immunoelectrophoresis with Con A as ligand according to Bøg-Hansen. Between Groups I and II statistically significant differences were observed for all investigated parameters. Highest concentration values were observed for Groups II and III; for Group II they appeared earlier than for Group III. The maximal values for reactivity coefficients (AGP-RC and ACT-RC) were observed earlier than the respective maximal values of concentrations. Continuous activation occurring in unstable angina leads to a more rapid increase in the concentrations of acute phase proteins and more marked alterations in their glycosylation profiles. In a way these patients seem to be 'primed' with constant stimulation, so that they respond dramatically to the stimulus of ischemia.

Different molecular mechanisms for Rho family GTPase-dependent, Ca2+-independent contraction of smooth muscle.

Abnormal smooth muscle contraction may contribute to diseases such as asthma and hypertension. Alterations to myosin light chain kinase or phosphatase change the phosphorylation level of the 20-kDa myosin regulatory light chain (MRLC), increasing Ca2+ sensitivity and basal tone. One Rho family GTPase-dependent kinase, Rho-associated kinase (ROK or p160(ROCK)) can induce Ca2+-independent contraction of Triton-skinned smooth muscle by phosphorylating MRLC and/or myosin light chain phosphatase. We show that another Rho family GTPase-dependent kinase, p21-activated protein kinase (PAK), induces Triton-skinned smooth muscle contracts independently of calcium to 62 +/- 12% (n = 10) of the value observed in presence of calcium. Remarkably, PAK and ROK use different molecular mechanisms to achieve the Ca2+-independent contraction. Like ROK and myosin light chain kinase, PAK phosphorylates MRLC at serine 19 in vitro. However, PAK-induced contraction correlates with enhanced phosphorylation of caldesmon and desmin but not MRLC. The level of MRLC phosphorylation remains similar to that in relaxed muscle fibers (absence of GST-mPAK3 and calcium) even as the force induced by GST-mPAK3 increases from 26 to 70%. Thus, PAK uncouples force generation from MRLC phosphorylation. These data support a model of PAK-induced contraction in which myosin phosphorylation is at least complemented through regulation of thin filament proteins. Because ROK and PAK homologues are present in smooth muscle, they may work in parallel to regulate smooth muscle contraction.

Activation of myosin-I by members of the Ste20p protein kinase family.

The heavy chain of myosin-ID isolated from Dictyostelium was identified as an in vitro substrate for members of the Ste20p family of serine/threonine protein kinases which are thought to regulate conserved mitogen-activated protein kinase pathways. Yeast Ste20p and Cla4p and mammalian p21-activated protein kinase (PAK) phosphorylated the heavy chain to 0.5-0.6 mol of Pi/mol and stimulated the actin-dependent Mg2+-ATPase activity to an extent equivalent to that of the Ste20p-like myosin-I heavy chain kinase isolated from Dictyostelium. PAK purified from rat brain required GTPgammaS-Cdc42 to express full activity, whereas recombinant mouse mPAK3 fused to glutathione S-transferase and purified from bacteria, and Ste20p and Cla4p purified from yeast extracts were fully active without GTPgammaS-Cdc42. These results suggest, together with the high degree of structural and functional conservation of Ste20p family members and myosin-I isoforms, that myosin-I activation by Ste20p family protein kinases may contribute to the regulation of morphogenetic processes in organisms ranging from yeast to mammalian cells.

The acetylation and oxidation phenotypes in insulin-dependent diabetes mellitus.

Polymorphism of the acetylation and oxidation phenotypes in patients with IDDM was evaluated. A greater statistically significant number of fast acetylators in IDDM was found.

Factor V is complexed with multimerin in resting platelet lysates and colocalizes with multimerin in platelet alpha-granules.

Factor V stored in platelets is an important source of factor Va for the prothrombinase complex. Investigations of potential platelet factor Va-binding proteins, using factor Va light chain affinity chromatography, identified a disulfide-linked multimeric protein with a reduced mobility of 155 kDa in the column eluate. Immunodepletion and immunoblotting indicated that this protein was multimerin. Multimerin specifically bound factors V and Va and the isolated factor Va light chain, but not the heavy chain of factor Va. Factor V stored in platelets, but not plasma factor V, was found to be complexed with multimerin. Multimerin immunodepletion of resting platelet lysates was associated with the removal of factor V and the loss of factor V coagulant activity. Immunoelectron microscopic studies colocalized factor V with multimerin in the alpha-granules of resting platelets. With thrombin-induced platelet activation, we observed dissociation of factor Va-multimerin complexes, multimerin-independent membrane binding of factor Va, and prothrombinase activity that was not inhibitable by multimerin antibodies. This study indicates that platelet factor V is stored as a complex with multimerin and suggests a possible role for multimerin as a carrier protein for factor V stored in platelets.

Coagulation factor Va is an actin filament binding and cross-linking protein.

Bovine coagulation cofactor factor Va is shown to bind to filament of skeletal muscle actin with a dissociation constant of 40-50 nM in the presence of 50 mM NaCl. At saturation, approximately one molecule of factor Va was bound for every two actin molecules. The binding of factor Va to F-actin was inhibited by increasing ionic strength, being approximately 20-fold weaker at 150 mM NaCl. Addition of factor Va dramatically increased both the low-speed sedimentation and the low-shear viscosity of actin filament solutions, indicating that factor Va cross-linkis actin filaments. Factor Va bound to actin filaments saturated with myosin. The isolated 74-kilodalton light chain of factor Va displayed actin binding and cross-linking properties indistinguishable from those of intact factor Va. The procofactor factor V bound weakly to F-actin, indicating that proteolytic activation is required to uncover the actin binding sites within the light chain domain. Actin filaments had only a slight inhibitory effect on the prothombinase activity of the factor Va-factor Xa-phospholipid complex. Since high concentrations of actin filaments can be exposed to the circulation when cells are damaged, the interaction of factor Va with actin may be of physiological relevance.

Studies of thrombin-induced proteoglycan release in the degradation of human and bovine cartilage.

Because fibrin is commonly observed within arthritic joints, studies were undertaken to determine whether purified coagulation and fibrinolytic proteases degrade cartilage in vitro and to seek evidence for the activation of coagulation in arthritic joints through measurements of the levels of inhibitor-enzyme complexes and several other proteins associated with coagulation and fibrinolysis. The concentrations of 13 plasma proteins and complexes of thrombin and Factor Xa with antithrombin III were measured in synovial fluids recovered at the time of knee replacement surgery. All zymogens necessary to constitute the coagulation cascade were present. Thrombin and the combination of prothrombin plus prothrombinase induced proteoglycan release from both normal and arthritic cartilages. Factor Xa and plasmin induced release from diseased cartilage only, and urokinase, tissue plasminogen activator, and activated protein C were without effect at the levels used. At saturating levels of thrombin (> or = 2.0 microM) 80% of the proteoglycan content of normal cartilage was released within 24 h. Thrombin, which is cationic, reversibly binds cartilage with Kd = 7.0 +/- 1.0 microM and Bmax = 820 +/- 70 ng/mg of human cartilage. Levels of thrombin-antithrombin III complexes in synovial fluids and arthritis were 4-fold higher in osteo (OA) and 43-fold higher in rheumatoid (RA) than in controls (0.98 nM). Factor Xa-antithrombin III complex levels were threefold lower in OA and fivefold higher in RA than in controls (0.24 nM). These elevated levels of enzyme-inhibitor complexes imply a history of activation of coagulation within the joint, especially in RA. Since thrombin degrades cartilage in vitro and had been generated in vivo, as inferred by the existence of thrombin-antithrombin III complexes, intraarticular activation of coagulation may both contribute to the pathology of arthritis and comprise a target for therapy and diagnosis.

[Assessment of bioavailability of magnesium preparations]. / Ocena biodostepnosci preparatów magnezu.

The bioavailability was studied of three magnesium preparations-Asmag, Slow-Mag and magnesium oxide (wafer)-administered to healthy volunteers for two weeks. The observed increase of magnesium level in the serum was not statistically significant.

On the existence of platelet receptors for factor V(a) and factor VIII(a).

The surface of the platelet expresses procoagulant phospholipids that bind coagulation factors and contribute to the procoagulant activity of the cell. The evidence, however, also suggests that platelets may possess specific receptors for coagulation Factors V(a) and VIII(a). Examination of a limited set of the available data could lead to the controversial position that the procoagulant surface of platelets is defined exclusively by either procoagulant phospholipids, or specific receptors for the cofactors and proteases. At the present time insufficient data exist to exclusively support one or the other of these possibilities. Further work, however, should indicate clearly whether the putative receptors exist and what role they play, either alone or in concert with surface phospholipids, in the expression and regulation of platelet procoagulant activity.

[The effect of blood pressure changes during hemodialysis on left ventricular systolic function]. / Wplyw zmian cisnienia tetniczego w czasie hemodializy na czynnosc skurczowa lewej komory serca.

Echocardiographic study was performed in 31 uremic patients on maintenance hemodialysis (HD) with no apparent heart failure, valvular heart disease, pericardial effusion or coronary artery disease. On the basis of blood pressure patients were classified into two groups: 1) patients with normal arterial pressure (group I) (n = 19), 2) patients with blood hypertension (group II) (n = 12). Cardiac function was assessed immediately before and after HD session. Left ventricular end-diastolic diameter (EDD), left ventricular end-systolic diameter (ESD) and ejection fraction (EF) were calculated. Body weight, heart rate and mean blood pressure (mBP) were also measured. A significant decrease of EDD was noted in both groups during HD but it was less evident in group II (p < 0.05). ESD decreased significantly in group II (p < 0.01) when it did not change in group I. EF increased significantly only in group II (p < 0.05). Blood pressure decreased during HD in both groups. A significant inverse linear association between EF and ESD was noted during HD in both groups (r = -0.685; p < 0.001) but was more evident in group II. There was no association between and EDD (r = 0.199; NS). Similar analysis shows that ESD was significantly with mBP (group II--r = 0.914; p < 0.001, group I--r = 0.565; p < 0.05). Such association were not found for EDD and RR. Only in group II the decrease in mBP was statistical significantly correlated with the increase in EF. The decrease in EDD during HD exists probably due to changes in intravascular volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein S enhances C4b binding protein interaction with neutrophils.

Protein S, an inhibitor of coagulation, interacts reversibly with C4b binding protein (C4bBP). The physiologic role of this complex formation remains unknown. In this study we examined the possibility that protein S would facilitate C4bBP binding to the surface of neutrophils where, in turn, this complex could help protect the cell from complement-mediated damage at the site of inflammation. Neutrophils bind approximately 60,000 protein S molecules per cell (kd = 140 nmol/L) in a Ca(2+)-dependent fashion. C4bBP also binds to neutrophils (23,000 sites per cell at physiologic C4bBP concentration), but this binding is not Ca2+ dependent. Protein S approximately doubled C4bBP binding, but protein S only influenced C4bBP binding in the presence of Ca2+. Protein S binding to neutrophils decreased approximately twofold in the presence of saturating concentrations of C4bBP. Neutrophil activation had only minor effects on the affinity and number of sites for protein S or the protein S-C4bBP complex. These results indicate that the protein S-C4bBP complex binds to the neutrophil surface where it can presumably modulate complement assembly on the cell surface.

[Unusually large thrombus in the left cardiac ventricle in a patient with a history of anterior wall infarction]. / Niezwyklych rozmiarów skrzeplina w lewej komorze u pacjenta z przebytym zawalem sciany przedniej.

The giant size thrombus like a swallow's nest in the left cardiac ventricle in the patient with a history of anterior infarction was reported. In the autopsy a significant narrowing of the left coronary artery and two critical narrowings of the anterior interventricular artery were revealed. The relation between the localization of the pathological changes in the coronary arteries and the thrombi occurring during cardiac infarction was discussed.

[Unusually large vegetation on the mitral valve in a patient with bacterial endocarditis]. / Niezwyklych rozmiarów wegetacja na zastawce mitralnej u chorej z bakteryjnym zapaleniem wsierdzia.

We present a case history of 29-year old female with infective endocarditis, who was admitted 15 months after neurosurgical treatment of disruption of cerebral aneurysm. The diagnosis of organic heart disease had been established in her childhood. 6 months after discharge from neurosurgery she developed marked dyspnoea on exertion and became febrile (up to 39.0 C). The presumptive diagnosis of infective endocarditis was established 6 months later, when she developed the symptoms and signs of severe anaemia with ESR 170 mm/hr although blood cultures were negative. The patient underwent treatment with Penicillin and Debecillin. On admission to our Institute echocardiography showed a very large, mobile vegetation in the left ventricle, connected to the anterior leaflet of mitral valve. Decision of mitral valve replacement was made, but rupture of the next cerebral aneurysm was the reason of unexpected, sudden death of the patient. The postmortem examination revealed 7 x 4 cm large vegetation, with the mass of 7.0 g. Histologically the vegetation consisted of mass of fibrin strands, platelets and blood cell with inflammatory cells. On its base the signs of the process of organization were marked. This vegetation was the largest one that we found in literature on this subject.