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J B Schnog

Publications and source records attributed to J B Schnog.

11 recordsLinked to original sources
PubMed2004

Plasma levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, are elevated in sickle cell disease.

In recent years an important role has been ascribed to a reduced nitric oxide (NO) availability in the pathophysiology of sickle cell disease (SCD). Endogenously produced inhibitors of NO synthase, in particular asymmetric dimethylarginine (ADMA), are currently considered of importance in various vascular disease states characterized by reduced NO availability. We determined ADMA levels in plasma of 12 adult sickle cell patients (eight HbSS and four HbSC), and compared these to plasma levels in race- and age-matched controls. Sickle cell patients were characterized by strongly elevated levels of ADMA [HbSS: median 0.63 micromol/l (interquartile range 0.54-0.85), HbSC: 0.43 micromol/l (0.40-0.46), HbAA: 0.33 micromol/l (0.32-0.35) p<0.001]. ADMA levels were highest in HbSS patients with lowest hemoglobin levels and highest leukocyte counts, and in HbSS patients ADMA levels were positively associated with serum levels of soluble vascular cell adhesion molecule-1. These results suggest an important role of ADMA in limiting NO availability in SCD, and its role in the pathophysiology of SCD should be further investigated.

Adult↗
PubMed2004

Protein C and S and inflammation in sickle cell disease.

Reduced activity of naturally occurring anticoagulants (NOAC) protein C and protein S may contribute to vaso-occlusion in sickle cell disease (SCD). We studied whether protein C and S are related to clinical vaso-occlusion, hematological markers of disease severity (hemoglobin levels, leukocyte counts, and percentage of fetal hemoglobin), and inflammation in SCD. Protein C activity, protein S (free and total) antigen, endothelial activation markers (soluble vascular cell adhesion molecule-1 [sVCAM-1], von Willebrand antigen [vWF]), and high sensitive C-reactive protein (hsCRP) levels were measured in 30 HbSS and 20 HbSC patients and in race-matched HbAA controls. NOAC levels were reduced in patients, and endothelial activation markers and hsCRP were elevated (except vWF in HbSC patients). Protein C activity and vWF levels were lower in HbSC patients who experienced painful crises compared to HbSC patients who were clinically asymptomatic. No other differences were observed between patients who did and did not experience vaso-occlusive events (painful crises, stroke, acute chest syndromes) or leg ulcers. A significant positive correlation between total protein S with hemoglobin levels and a significant negative correlation between total and free protein S and sVCAM-1 were detected in HbSS patients. Except perhaps for protein C in relation to painful crises in HbSC patients, these markers were not associated with the occurrence of clinical events. The protein S, hemoglobin, and sVCAM-1 associations may suggest decreased endothelial protein S production due to the more severe endothelial perturbation in HbSS patients with lower hemoglobin levels.

Adult↗
PubMed2004

Sickle cell disease; a general overview.

Sickle cell disease (SCD) is a heterogeneous disorder, with clinical manifestations including chronic haemolysis, an increased susceptibility to infections and vaso-occlusive complications often requiring medical care. Patients with SCD can develop specific and sometimes life-threatening complications, as well as extensive organ damage reducing both their quality of life and their life expectancy. Proven effective treatment options for sickle cell patients are limited to hydroxyurea, blood transfusions and bone marrow transplantation. With the increasing prevalence of SCD in the Netherlands, a fundamental understanding of its pathophysiology and clinical syndromes is of importance for local medical practitioners.

Anemia, Sickle Cell↗
PubMed2003

Erythropoiesis and serum sVCAM-1 levels in adults with sickle cell disease.

Sickle cell patients are characterized by stress erythropoiesis involving cytokines, growth factors, and adhesion molecules. We set out to determine whether serum soluble vascular cell adhesion molecule-1 (sVCAM-1) levels, which are inversely related to red blood cell counts in sickle cell disease (SCD), reflect erythropoietic activity in adult HbSS patients. Serum levels of sVCAM-1 were compared to erythropoietin (EPO), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and soluble transferrin receptor (sTfR) levels in 29 adults with HbSS, and their respective levels were also compared to 29 race- and age-matched HbAA controls. EPO and sTfR levels were increased as compared to healthy controls, whereas IL-3 and GM-CSF were not. No significant correlation of sVCAM-1 levels could be detected with any of the measured erythropoietic markers. Patients, but not controls, with detectable IL-3 levels had lower sTfR and GM-CSF levels as compared to patients with undetectable IL-3 levels. Even though a link of sVCAM-1 to erythropoiesis could not be established, it cannot be ruled out that sVCAM-1 levels reflect the release of young red blood cells into the circulation. IL-3 and GM-CSF levels suggest that different rates of erythropoiesis may be characterized by specific cytokine profiles in SCD. Further research should focus on the potential cytokines and adhesion molecules involved in sickle cell erythropoiesis, as this may increase our understanding of sickle cell complications and may provide us with potential markers for risk assessment in sickle cell disease as well.

Adult↗
PubMed2003

Steady-state sVCAM-1 serum levels in adults with sickle cell disease.

Cytokines and adhesion molecules play an important role in the pathophysiology of vaso-occlusion in sickle cell disease (SCD), and their in vivo profiles are potential tools for assessing SCD severity. We compared steady-state soluble vascular cell adhesion molecule-1 (sVCAM-1) serum levels to clinical (painful crisis frequency, occurrence of acute chest syndrome, leg ulcers, and cerebrovascular disease) and related hematological parameters of SCD severity (such as HbF%, hemoglobin levels, and leukocyte counts) in 29 HbSS adults. Serum sVCAM-1 levels were not related to clinical severity, but an inverse correlation was demonstrated between sVCAM-1 and hemoglobin levels (r=-0.71, p<0.001) with a positive correlation to serum lactate dehydrogenase levels (r=0.59, p=0.008). Based upon these results, steady-state serum sVCAM-1 levels do not seem to reflect clinical disease severity. However, as VCAM-1 is involved in hematopoiesis, sVCAM-1 levels might reflect bone marrow activity in SCD. This underlies the pleiotropic nature of adhesion molecules in vivo and the need for further research in this area, especially since therapies targeting (cellular) adhesive interactions involving the endothelium are emerging for SCD.

Adult↗
PubMed2002

No effect of acenocoumarol therapy on levels of endothelial activation markers in sickle cell disease.

Sickle cell patients are characterized by a chronic inflammatory and hypercoagulable state, depicted by elevated levels of pro-inflammatory cytokines, endothelial adhesion molecules, and elevated markers of thrombin generation. We set out to determine whether anticoagulation with a coumadin derivative reduces inflammation in sickle cell disease. Therefore, serum levels of NFkappaB-regulated endothelial adhesion molecule soluble vascular cell adhesion molecule-1 and serum levels of non-NFkappaB-dependent markers of endothelial activation (soluble cellular fibronectin and von Willebrand factor antigen) were compared during treatment with acenocoumarol (INR 1.6-2.0) and placebo. No effect on circulating levels of the measured parameters was observed during treatment with acenocoumarol as compared to placebo. In the targeted INR range, anticoagulation of sickle cell patients with acenocoumarol does not seem to reduce endothelial activation.

Acenocoumarol↗
PubMed2001

Low adjusted-dose acenocoumarol therapy in sickle cell disease: a pilot study.

Vasoocclusion is a continuous process in sickle cell disease (SCD) and accumulates to significant end organ damage, mostly irrespective of the occurrence of manifest acute vasoocclusive events. As there are indications that reversing the hypercoagulable state may be of clinical benefit in sickle cell patients, we performed a randomized, double blind, placebo-controlled, cross-over pilot study to assess the efficacy and safety of low-adjusted dose acenocoumarol therapy (International Normalized Ratio: 1.6-2.0) in SCD. Treatment consisted of either acenocoumarol or placebo for 14 weeks, after which treatment was discontinued for a period of five weeks. Then, patients initially on acenocoumarol received placebo (and vice versa) for 14 weeks. Therapy efficacy was assessed by comparing the frequency of vasoocclusive complications, the occurrence of bleeding, and clotting activation between acenocoumarol and placebo treatment of each individual patient. Twenty-two patients (14 homozygous [HbSS] and 8 double heterozygous sickle-C [HbSC]; aged 20-59 years) completed the entire study. Acenocoumarol treatment did not result in a significant reduction of acute vasoocclusive events (three painful crises during acenocoumarol, five painful crises during placebo). There was a marked reduction of the hypercoagulable state (depicted by a decrease in plasma levels of prothrombin F1.2 fragments [P = 0.002], thrombin-antithrombin complexes [P = 0.003], and D-dimer fragments [P = 0.001]) without the occurrence of major bleeding. Even though no clinical benefit (pertaining to the frequency of painful crises) was detected in this pilot study, the value of low adjusted-dose acenocoumarol for preventing specific events (such as strokes) and as a long-term treatment of sickle cell patients should be subject of further study.

Acenocoumarol↗
PubMed2000

Duffy phenotype does not influence the clinical severity of sickle cell disease.

The red blood cell Duffy antigen receptor for chemokines serves as a sink for the clearance of chemokines such as interleukin-8 (IL-8) from the circulation. We analyzed the impact of the Duffy phenotype on sickle cell disease (SCD) severity and serum IL-8 levels in 15 Duffy-positive and 36 Duffy-negative sickle cell patients. There was no difference in clinical severity between Duffy-positive and Duffy-negative sickle cell patients. In asymptomatic sickle cell patients the upward deviation of mean serum IL-8 levels was significantly greater in Duffy-negatives (n = 20) than in Duffy-positives (n = 8) (P = 0.011). However, during a vasoocclusive episode, serum IL-8 levels were similar between Duffy-negatives (n = 11) and Duffy-positives (n = 3). Although the Duffy phenotype seems to influence steady-state serum IL-8 levels, it does not seem to have an effect on SCD severity.

Adolescent↗
PubMed1998

Elevated IL-8 levels during sickle cell crisis.

The vaso-occlusive process (VOC) in sickle cell disease is of a complex nature. It involves intricate interactions between sickle red blood cells, endothelium and probably also leukocytes. As these interactions are regulated by cytokines, we analyzed the role of the potent neutrophil chemokine IL-8 by measuring serum levels in sickle cell patients during sickle cell crisis. These results were compared to nonsymptomatics and healthy controls. In patients having a vaso-occlusive crisis both HbSS and HbSC patients showed significantly enhanced serum IL-8 levels compared to healthy controls. Several of these patients showed extremely elevated serum IL-8 levels which were independent of the crisis inducing factor. Furthermore, a sickle cell patient with VOC as a complication of rhGM-CSF treatment similarly showed high IL-8 serum levels at crisis onset. Nonsymptomatic sickle cell patients serum IL-8 levels were comparable to healthy controls. These results implicate a role for IL-8 at or during (the initiation of) sickle cell crisis.

Anemia, Sickle Cell↗