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The assay of overall haemostasis potential used to monitor the low molecular mass (weight) heparin, dalteparin, treatment in pregnant women with previous thromboembolism.

The present study aimed to assess whether the determination of overall haemostasis potential (OHP) in plasma is powerful enough to monitor the prophylactic effect of low molecular mass heparin (dalteparin, Fragmin) in patients with increased risk of thromboembolitic events. In five pregnant women who had a history of deep venous thrombosis, OHPs were kinetically investigated in gestation weeks 32-35 twice during 24 h (before injection and after 1, 2, 4, 6, 8, 10, 12, 14, 16 and 24 h). Levels of anti-activated factor X (anti-FXa), reflecting dalteparin activity, as well as prothrombin fragments 1 + 2 (F1 + 2) and soluble fibrin, were also measured. In converse relation to changes of anti-FXa, OHPs decreased reaching the lowest level between 2 and 8 h after the injection, and then rose again, returning to the levels around those before the administration. There were no significant variations in concentrations of F1 + 2 and soluble fibrin during the observation course. These findings indicate that the OHP assay can monitor the alteration of haemostatic balance under the dalteparin influence while anti-FXa only shows the activity of the drug present in plasma. Additionally, analyses of thrombin generation markers are not useful to screen immediate changes in the haemostatic system after dalteparin injection.

Adult↗

Micronucleus assay reveals no radiation effects among nuclear power plant workers.

The micronucleus assay was applied as biomarker for exposure effect and radiosensitivity in a group of 99 radiation workers of the Nuclear Power Plant Doel (Belgium). The difference in micronucleus frequency between the group of radiation workers with annual dose exceeding 2 mSv and a non-exposed control population was statistically not significant. With respect to the micronucleus frequency after an in vitro challenge dose of 2 Gy, which can be considered as biomarker for radiosensitivity, the data of present study can be represented by a normal distribution without a high frequency tail. This means that a subpopulation of workers with elevated radiosensitivity could not be identified in the population under study.

Adult↗

Relationship between physical activity and oxidative stress biomarkers in women.

PURPOSE: To examine the relationship between physical activity and levels of plasma lipid peroxides, superoxide dismutase in erythrocytes (SOD), and glutathione peroxidase (GSH-Px) in whole blood activities. METHODS: Cross-sectional study in 488 Spanish women. Two categories of leisure time physical activity were defined according to their intensity: low ( 6 METs). Energy expenditure in household activities was also recorded. Multivariate linear regression analyses were used to adjust for the effect of physical activity on lipid peroxides and SOD and GSH-Px for confounding variables. RESULTS: The amount of leisure time physical activity was associated with high activity levels of SOD (P = 0.022) and GSH-Px (P = 0.002). Similar results were obtained when physical activity in household activities was added to total leisure physical activity. Physical activity of low intensity was associated with high SOD activity levels (P = 0.002) and that of high intensity with high GSH-Px activity levels (P = 0.001). CONCLUSION: The amount and intensity of leisure physical activity were directly related to both antioxidant enzyme activity levels. The findings of this study suggest a modulatory effect of leisure physical activity intensity on antioxidative balance in the studied female population.

Adult↗

Correlation of serum aminotransferases with HCV RNA levels and histological findings in patients with chronic hepatitis C: the role of serum aspartate transaminase in the evaluation of disease progression.

OBJECTIVES: To investigate whether HCV RNA levels can be considered to be predictors of hepatocellular injury in patients with chronic hepatitis C, and whether aminotransferase levels are markers of liver damage. METHODS: We performed a retrospective study on 112 patients with chronic hepatitis C. For each patient, we considered the baseline alanine aminotransferase (ALT) and serum aspartate transaminase (AST) levels, baseline HCV RNA, HCV genotype, histological evaluation and the mean aminotransferase levels measured in the 6 months following liver biopsy. RESULTS: We found a statistically significant correlation between HCV RNA and aminotransferase levels measured during the follow-up (AST: r = 0.24, P = 0.01; ALT: r = 0.27, P = 0.004). We also observed a statistically significant correlation between HCV RNA levels and histological activity index (HAI) (r = 0.25, P = 0.008), as well as between the HAI and both baseline AST (r = 0.34, P = 0.0002) and ALT levels (r = 0.23, P = 0.01). These findings were confirmed by the mean aminotransferase values during follow-up. In the regression analysis, the fibrosis score was significantly and independently associated with baseline AST and ALT values. CONCLUSIONS: Our results demonstrate a statistically significant correlation of aminotransferase values with the histological parameters, and an even stronger correlation with the AST values. Our study therefore suggests that aminotransferase values, especially AST, may correlate with liver damage.

Adult↗

International Society on Thrombosis and Haemostasis score for overt disseminated intravascular coagulation predicts organ dysfunction and fatality in sepsis patients.

We evaluated the score for disseminated intravascular coagulation (DIC) recently published by the International Society for Thrombosis and Haemostasis (ISTH) in a well-defined series of sepsis patients. Thirty-two patients suffering from severe sepsis and eight patients with septic shock were evaluated following the ISTH DIC score. Fibrin monomer and D-dimer were chosen as fibrin-related markers (FRM), respectively. DIC scores for nonsurvivors (n = 13) as well as for septic shock patients were higher (P < 0.04) compared with survivors and patients with severe sepsis, respectively. Using fibrin monomer and D-dimer, 30 and 25% of patients suffered from overt DIC. Overt DIC was associated with significantly elevated thrombin-antithrombin complexes and plasminogen activator inhibitor type-1 levels as well as with significantly lower factor VII clotting activity. Patients with overt DIC had a significantly higher risk of death and of developing septic shock. Since more than 95% of the sepsis patients had elevated FRM, the DIC score was strongly dependent on prolongation of the prothrombin time and platelet counts. The ISTH DIC score is useful to identify patients with coagulation activation, predicting fatality and disease severity. It mainly depends on the prolongation of the prothrombin time and platelet counts.

Adult↗

Diffusion-weighted MR imaging for determination of hepatocellular carcinoma response to yttrium-90 radioembolization.

Early detection of the response of hepatocellular carcinoma (HCC) to yttrium-90 radioembolization therapy may be important to permit repeat radioembolization or alternative treatment options. Water-mobility measurements with use of diffusion-weighted (DW) magnetic resonance (MR) imaging are useful for noninvasive interrogation of microstructural tissue properties. Findings of DW MR imaging may serve as an early biomarker of HCC response. This study tested the hypothesis that DW MR imaging can detect changes in tumor tissue water diffusion in response to (90)Y therapy. In each of six patients with HCC included in the study, tumor water diffusion increased significantly after therapy. DW MR imaging is a promising technique for noninvasive assessment of tumor response to (90)Y radioembolization.

Adult↗

Carcinogenicity of methylurea or morpholine in combination with sodium nitrite in rat multi-organ carcinogenesis bioassay.

For carcinogenic risk assessment of combinations of N-nitroso precursors in man, the effects of feeding methylurea (MU) or morpholine (Mor) plus sodium nitrite (NaNO2) were investigated using a multi-organ carcinogenesis model. In experiment 1, to initiate multiple organs, groups of 10 or 20 male F344 rats were treated with 6 carcinogens targeting different organs. Starting a week after completion of this initiation phase, animals were given 0.1% MU or 0.5% Mor in their food and/or 0.15% NaNO2 in their drinking water for 23 weeks. The induction of tumors and/or preneoplastic lesions in the forestomach and esophagus was significantly increased in the group receiving MU plus NaNO2. The numbers and areas of liver glutathione S-transferase placental form (GST-P)-positive foci were significantly elevated with MU or Mor plus NaNO2. Experiment 2 was conducted to assess formation of N-nitroso compounds in the stomach, and to detect DNA adduct generation in target organs by immunohistochemical staining. Groups of 5 or 14 animals were starved overnight, then given 0.4% MU or 2.0% Mor in the diet, or basal diet alone for 1 h. Then NaNO2 or distilled water was given intragastrically. The mean gastric N-methyl-N-nitrosourea yield in the MU plus NaNO2 group was 7700 micrograms at 2 h after combined administration. The mean N-nitrosomorpholine yield in the group given Mor plus NaNO2 was 6720 micrograms. Immunohistochemically, N7-methyldeoxyguanosine-positive nuclei were evident in the forestomach epithelium at 8 h after the combination treatment with MU plus NaNO2.

Administration, Oral↗

Risk of recurrent venous thromboembolism or bleeding in relation to thrombophilic risk factors in patients receiving ximelagatran or placebo for long-term secondary prevention of venous thromboembolism.

The impact of prothrombotic abnormalities on the risk of recurrent venous thromboembolism (VTE) and bleeding in patients receiving long-term anticoagulation remains unclear. This analysis evaluated the influence of potential prothrombotic risk factors (antithrombin, protein C, protein S, factor V Leiden mutation, prothrombin gene G20210A mutation, cardiolipin antibodies, number of risk factors) on the risk of recurrent VTE or bleeding during treatment with oral ximelagatran (24 mg twice daily) or placebo for 18 months [THRombin Inhibitor in Venous thromboEmbolism (THRIVE) III trial]. Of the 1223 patients in the intention-to-treat population, prothrombotic state was analysed in 559 patients receiving ximelagatran and 540 patients receiving placebo. It is possible that patients at a high risk of recurrent VTE were poorly represented in this analysis because of selection bias. Prothrombotic risk factors were reported in 41% of patients (8% had > or = 2 factors). No significant interactions were found between ximelagatran treatment and potential prothrombotic risk factors for the risk of recurrent VTE or bleeding by Cox proportionate hazard modelling. There was no clear evidence for a higher risk of recurrent VTE or bleeding across subgroups according to the potential prothrombotic factors analysed in this study.

Antibodies, Anticardiolipin↗

Serum surfactant protein D is elevated in allergic patients.

BACKGROUND: There is evidence that surfactant protein (SP)-D is important in the innate, as well as in the adaptive pulmonary immune response. Serum concentrations of SP-D have been proposed as parameter of the integrity of the blood-airspace barrier in interstitial lung diseases. We hypothesized that serum SP-D concentrations are affected in allergic patients and correlate with changes in allergic airway inflammation. OBJECTIVE: To determine levels of serum SP-D in allergic patients compared with non-allergic controls. Furthermore, to investigate associations between serum SP-D concentrations on the one hand and changes in commonly used markers of bronchial inflammation in allergic airways disease on the other hand. MATERIALS AND METHODS: Fifty allergic patients were studied and bronchial allergen challenge was used as a model to increase bronchial allergic inflammation in these patients. Serum SP-D concentrations, inflammatory parameters in induced sputum and bronchial hyper-responsiveness (BHR) were determined before and after allergen challenge. Twenty-five non-allergic volunteers served as controls. RESULTS: Baseline serum SP-D was significantly higher in allergic patients as compared with controls (mean serum SP-D concentration (95% confidence interval): 62.7 (55.5, 70.0) in allergic patients vs. 49.5 (36.7, 62.3) ng/mL in non-allergic controls, P=0.006). In addition, baseline serum SP-D appeared to be an independent predictor for the magnitude of the late asthmatic response after allergen challenge. Furthermore, serum SP-D was predictive for the sputum eosinophil cationic protein concentration after allergen challenge. CONCLUSION: We propose that serum SP-D concentrations are associated with allergic bronchial inflammation and may give additional information, beside BHR and sputum eosinophils, about the degree of bronchial inflammation in allergic patients.

Adult↗

cDNA cloning and substrate specificity of equine tryptase, a possible mediator in equine heaves.

BACKGROUND: Mast cell mediators are believed to play a central role in inflammatory lung disorders such as human allergic and occupational asthma. Equine heaves is characterized by reversible neutrophilic airway inflammation and airway obstruction, primarily due to bronchospasm and mucus hypersecretion, following exposure of susceptible horses to organic stable dusts. As such, heaves shares many similarities with human occupational dust-induced asthma and therefore it is proposed that mast cells may also be implicated in the pathogenesis of heaves. Tryptase, a mast cell-specific proteinase, can be used as an indicator of biological mast cell activity. OBJECTIVE: The aim of this study was to determine the cDNA sequence of equine tryptase and to investigate its substrate specificity in order to rationalize its enzymatic activity. METHODS: RT-PCR cloning was used to sequence equine tryptase. Substrate specificity of equine tryptase was investigated using arginine and lysine containing substrates. RESULTS: The cDNA and deduced amino acid (Aa) sequences for equine tryptase shared strong identity with other tryptases. Unusually for a trypsin-like proteinase however, equine tryptase has alanine at residue 216, rather than glycine, which confers increased arginine substrate specificity in vitro and may restrict fibrinogenolysis in vivo. CONCLUSION: Cloning and sequencing of the mast cell proteinase equine tryptase will allow molecular probing of its expression in the lung of control and heaves-affected horses. Further work is warranted to determine the biological relevance of the unique alanine 216 substitution in the molecular sequence of the equine tryptase substrate-binding pocket.

Amino Acid Sequence↗

Effects of inhaled ciclesonide on circulating T-helper type 1/T-helper type 2 cells in atopic asthmatics after allergen challenge.

BACKGROUND: The predominance of T-helper type 2 (Th2) lymphocytes is thought to underlie the pathogenesis of asthma. Allergen inhalation challenge in atopic asthmatic subjects is associated with decreased interferon-gamma (IFN-gamma) positive CD4+ and CD8+ lymphocytes in peripheral blood and induced sputum. OBJECTIVE: This study examined the effects of an inhaled corticosteroid on these previously described allergen-induced changes in circulating Th1 and Th2 lymphocytes. METHODS: Subjects were randomized to 7 days of placebo, 40 or 80 micro g ciclesonide in a crossover study. Airway responses and peripheral blood were measured before and after treatment, and 24 h after allergen challenge. RESULTS: Ciclesonide 40 and 80 micro g significantly attenuated the late response and sputum eosinophils at 8 h post-allergen (P<0.05). Circulating IFN-gamma positive CD4+ lymphocytes decreased after allergen challenge with placebo (P<0.05), and this was inhibited by 40 micro g ciclesonide treatment (P<0.05). There was no effect of allergen inhalation or ciclesonide on IL-4-positive CD4+ lymphocytes or IFN-gamma and IL-4-positive CD8(high) lymphocytes. The allergen-induced change of IFN-gamma/IL-4 ratio on CD4+ cells correlated with the allergen-induced change of peripheral blood eosinophils. CONCLUSIONS: The results of this study suggest that attenuation of allergen-induced airway responses by ciclesonide may be mediated through regulation of IFN-gamma-positive CD4+ cells.

Administration, Inhalation↗

An increase in creatine kinase secondary to acute pancreatitis: a case report.

Creatine kinase (CK) activity is found in high concentrations in skeletal muscle, cardiac muscle and brain. Here, we describe a 64-year-old woman with acute pancreatitis and elevated serum CK activity. This association is extraordinarily rare. In particular, laboratory findings which were found to be abnormal were serum CK 4.150 U/l (peaked 1 day after admission) with the CK-MB fraction being less than 5%, lactate dehydrogenase (LDH) 424 U/l, serum lipase 1.265 U/I and serum amylase 1.105 U/l. Some data regarding the phenomenon of acute pancreatitis and elevated serum CK activity are given.

Acute Disease↗

Cysteinyl-leukotrienes contribute to sputum eosinophil chemotactic activity in asthmatics.

BACKGROUND: Cysteinyl-leukotrienes are lipid derived mediators involved in asthma. They are able to stimulate eosinophil chemotaxis in vitro. Induced sputum from asthmatics has been shown to contain eosinophil chemotactic activity. The purpose of our study was to evaluate the contribution of cysteinyl-leukotrienes to sputum eosinophil chemotactic activity in asthmatics and to seek whether there might be differences between asthmatics free of inhaled corticosteroids vs those regularly receiving this treatment. METHODS: Twenty-two patients (11 corticosteroid free, mean FEV1 99% predicted, 11 corticosteroid-treated, mean FEV1 77% predicted) recruited from our asthma clinic underwent a sputum induction. Sputum was processed according to standard procedure. Eosinophil chemotactic activity contained in the fluid phase was assessed using Boyden microchamber model and expressed as chemotaxis index (CI). Cysteinyl-leukotrienes were measured in sputum supernatant by ELISA and their role in sputum eosionophil chemotactic activity was evaluated by using montelukast, a selective antagonist of a cys-LT1 receptor. RESULTS: Cysteinyl-leukotrienes were well detectable in sputum supernatants from both steroid-naive (247 +/- 42 pg/ml) and steroid-treated (228 +/- 26 pg/ml) asthmatics. Sputum eosinophil chemotactic activity was indiscriminately present in both corticosteroid-naive (CI: 2.61 +/- 0.22) and corticosteroid-treated (2.98 +/- 0.35) asthmatics. Montelukast (100 microM) significantly inhibited the eosinophil chemotactic activity in both groups achieving a mean inhibition of 54.2 +/- 9.2% (P < 0.001) and 64.7 +/- 7.8% (P < 0.001) in steroid-naive and steroid-treated asthmatics respectively. CONCLUSION: Cysteinyl-leukotrienes actively participate in sputum eosinophil chemotactic activity found in asthmatics irrespective of whether they are or not under treatment with inhaled corticoids.

Adult↗