Concentrations Of Acute-phase Reactants Research Articles

Blood Rheology and Hemodynamics.

Seminars in Thrombosis and Hemostasis (STH) celebrates 50 years of publishing in 2024. To celebrate this landmark event, STH is republishing some archival material. This article represents the most highly cited paper ever published in STH. The original abstract follows.Blood is a two-phase suspension of formed elements (i.e., red blood cells [RBCs], white blood cells [WBCs], platelets) suspended in an aqueous solution of organic molecules, proteins, and salts called plasma. The apparent viscosity of blood depends on the existing shear forces (i.e., blood behaves as a non-Newtonian fluid) and is determined by hematocrit, plasma viscosity, RBC aggregation, and the mechanical properties of RBCs. RBCs are highly deformable, and this physical property significantly contributes to aiding blood flow both under bulk flow conditions and in the microcirculation. The tendency of RBCs to undergo reversible aggregation is an important determinant of apparent viscosity because the size of RBC aggregates is inversely proportional to the magnitude of shear forces; the aggregates are dispersed with increasing shear forces, then reform under low-flow or static conditions. RBC aggregation also affects the in vivo fluidity of blood, especially in the low-shear regions of the circulatory system. Blood rheology has been reported to be altered in various physiopathological processes: (1) Alterations of hematocrit significantly contribute to hemorheological variations in diseases and in certain extreme physiological conditions; (2) RBC deformability is sensitive to local and general homeostasis, with RBC deformability affected by alterations of the properties and associations of membrane skeletal proteins, the ratio of RBC membrane surface area to cell volume, cell morphology, and cytoplasmic viscosity. Such alterations may result from genetic disorders or may be induced by such factors as abnormal local tissue metabolism, oxidant stress, and activated leukocytes; and (3) RBC aggregation is mainly determined by plasma protein composition and surface properties of RBCs, with increased plasma concentrations of acute phase reactants in inflammatory disorders a common cause of increased RBC aggregation. In addition, RBC aggregation tendency can be modified by alterations of RBC surface properties because of RBC in vivo aging, oxygen-free radicals, or proteolytic enzymes. Impairment of blood fluidity may significantly affect tissue perfusion and result in functional deteriorations, especially if disease processes also disturb vascular properties.

Toxicological Assessments of a Pandemic COVID-19 Vaccine-Demonstrating the Suitability of a Platform Approach for mRNA Vaccines.

The emergence of SARS-CoV-2 at the end of 2019 required the swift development of a vaccine to address the pandemic. Nonclinical GLP-compliant studies in Wistar Han rats were initiated to assess the local tolerance, systemic toxicity, and immune response to four mRNA vaccine candidates encoding immunogens derived from the spike (S) glycoprotein of SARS-CoV-2, encapsulated in lipid nanoparticles (LNPs). Vaccine candidates were administered intramuscularly once weekly for three doses at 30 and/or 100 µg followed by a 3-week recovery period. Clinical pathology findings included higher white blood cell counts and acute phase reactant concentrations, lower platelet and reticulocyte counts, and lower RBC parameters. Microscopically, there was increased cellularity (lymphocytes) in the lymph nodes and spleen, increased hematopoiesis in the bone marrow and spleen, acute inflammation and edema at the injection site, and minimal hepatocellular vacuolation. These findings were generally attributed to the anticipated immune and inflammatory responses to the vaccines, except for hepatocyte vacuolation, which was interpreted to reflect hepatocyte LNP lipid uptake, was similar between candidates and resolved or partially recovered at the end of the recovery phase. These studies demonstrated safety and tolerability in rats, supporting SARS-CoV-2 mRNA-LNP vaccine clinical development.

Biomarkers of Inflammation in the Context of Acute Illness Among Children 12–24 Months of Age Living in the Urban Slums of Mumbai

Abstract Objectives To examine and compare the concentration of acute phase proteins, including nutritional and inflammation biomarkers, by morbidity status among children 12–24 months old living in urban slums of Mumbai. Methods 12–24-month-old children were screened for participation in a randomized controlled trial involving feeding of iron- and zinc-biofortified pearl millet complementary foods. Information on acute illness including fever, respiratory symptoms, and diarrhea on the day of screening, in the past 7 days, and the last 4 weeks was collected along with blood samples for analysis of concentrations of nutritional (ferritin, retinol) and inflammation biomarkers (C-reactive protein, alpha-1-glycoprotein) involved in the acute phase response. Difference in medians were compared by the Kruskal-Wallis Test. Results The mean age of children was 14.9 months; 51% were males. More than half the children (54%) had at least one or more symptoms such as fever, cough, or diarrhea at any timepoint in the 4 weeks prior to the interview. Among those with symptoms, fever and respiratory symptoms, either alone or in combination, were most common (44.8%), while diarrhea (alone or in combination with fever or respiratory symptoms) was present in only 11% of the population. More than a quarter had some illness in the 7 days before the interview (25.8%) with 2.5% having illness (fever and/or respiratory symptoms) on the day of the interview. Among those reporting no morbidity, 7% had elevated CRP. Among those reporting acute illness on the day of interview or in the past 7 days, 13% had elevated CRP. When compared across different kinds of acute illness and having no symptoms, there was no significant difference in the median concentrations of CRP, ferritin, and retinol. Similar results were observed on comparing the concentration of these acute phase reactants across children with no, one, two, or more symptoms. Conclusions Among this pediatric population, we did not observe any significant difference in the concentration of acute phase reactants by illness type or number of concurrent illnesses compared with apparently healthy children. Funding Sources HarvestPlus.

The Role of Blood Viscosity in Infectious Diseases.

Blood viscosity is increased by elevated concentrations of acute phase reactants and hypergammaglobulinemia in inflammation. These increase blood viscosity by increasing plasma viscosity and fostering erythrocyte aggregation. Blood viscosity is also increased by decreased erythrocyte deformability, as occurs in malaria. Increased blood viscosity contributes to the association of acute infections with myocardial infarction (MI), venous thrombosis, and venous thromboembolism. It also increases vascular resistance, which decreases tissue perfusion and activates stretch receptors in the left ventricle, thereby initiating the systemic vascular resistance response. This compensates for the increased vascular resistance by vasodilation, lowering hematocrit, and decreasing intravascular volume. This physiological response causes the anemias associated with malaria, chronic inflammation, and other chronic diseases. Since tissue perfusion is inversely proportional to blood viscosity, anemia may be beneficial as it increases tissue perfusion when erythrocyte aggregating factors or erythrocytes with decreased deformability are present in the blood.

Interaction between anthelmintic treatment and vaccine responses in ponies naturally infected with cyathostomins

Anthelmintics and vaccines are commonly given concurrently in routine equine management, but it is unknown to what extent an interaction between the two exists. Cyathostomins can modulate the local immune response by stimulating a type 2 helper T cell (Th2) response. In addition, anti-inflammatory effects of ivermectin have been found in rodent models. It is unknown whether these anti-inflammatory effects affect the acute phase response elicited by commonly used vaccines. This study evaluated how the acute phase inflammatory response, leukocyte expression of pro-inflammatory cytokines, and vaccine-specific titers induced by simultaneous injection of three vaccines (West Nile Virus, Equine Herpes Rhinopneumonitis, and Keyhole Limpet Hemocyanin) were modulated by concurrent administration of ivermectin or pyrantel pamoate in ponies naturally infected with cyathostomins. Mixed-breed yearling ponies were blocked by gender and fecal strongyle egg count, then randomly assigned to three treatment groups: ivermectin (n=8), pyrantel pamoate (n=8), and control (n=7). All ponies received vaccinations intramuscularly on days 0 and 29, and anthelmintics were administered on the same days. Whole blood, serum and plasma samples were collected one, three and 14 days after each vaccination. Samples were analyzed for concentrations of acute phase reactants (haptoglobin, serum amyloid A, fibrinogen and iron), mRNA expression levels of cytokines (interleukin (IL)-1β, IL-4, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ) in leukocytes, and vaccine-specific antibody titers. A marked acute-phase response was noted following both vaccinations. In contrast, the pattern of change in cytokine expression was less pronounced and more variable. Statistical differences were observed between groups for haptoglobin, fibrinogen, IL-1β, IL-4, and IL-10, but differences were generally small and none of the vaccine titers were different between the groups. Taken together, the study found some signs of modulation of immunologic or inflammatory responses to the administered vaccines, when anthelmintics were administered concurrently, but these are unlikely to have practical implications for vaccination routines.

Treatment with angiotensin II receptor blockers is associated with prolonged relapse-free survival, lower relapse rate, and corticosteroid-sparing effect in patients with giant cell arteritis

ObjectiveTo determine whether concomitant treatment with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) is associated with changes in the outcome of patients with giant cell arteritis (GCA). MethodsA study cohort of 106 patients with biopsy-proven GCA was longitudinally followed up for 7.8 ± 3.3 years. Patients were stratified according to their treatment with ACEI, ARB, or no ACEI/ARB. Time to first relapse, number of flares, time to achieve a stable prednisone dose <10mg/day and <5mg/day with no relapses, time required to completely discontinue prednisone, cumulative dose of prednisone received during the first year, and concentrations of acute-phase reactants at pre-defined time points (baseline, 6, 12, 18, and 24 months) were compared among the 3 groups. Cox proportional hazards models were performed to adjust for potential confounders. ResultsPatients receiving ARB presented a significantly longer relapse-free survival than patients treated with ACEI or patients not receiving ACEI/ARB (p = 0.02). The adjusted hazard ratio for relapses in patients treated with ARB was 0.32 (95% CI: 0.12–0.81, p = 0.017). In addition, patients who received ARB achieved a prednisone maintenance dose <10mg/day faster than all other patients (p = 0.0002). No significant differences were observed among groups in acute-phase reactant levels during follow-up. However, patients not receiving ACEI/ARB had significantly higher C-reactive protein and haptoglobin concentrations than those receiving ACEI or ARB at various time points. ConclusionsAddition of ARB to glucocorticoids is associated with lower relapse rate and more prolonged disease-free survival in patients with GCA.

AB0381 Safety and efficacy of rituximab in systemic lupus erythematosus

BackgroundRituximab (RTX) is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells. Originally developed for the treatment of B-cell non-Hodgkin’s lymphoma,...

Diabetes is a risk factor for pulmonary tuberculosis: a case-control study from Mwanza, Tanzania.

BackgroundDiabetes and TB are associated, and diabetes is increasingly common in low-income countries where tuberculosis (TB) is highly endemic. However, the role of diabetes for TB has not been assessed in populations where HIV is prevalent.MethodsA case-control study was conducted in an urban population in Tanzania among culture-confirmed pulmonary TB patients and non-TB neighbourhood controls. Participants were tested for diabetes according to WHO guidelines and serum concentrations of acute phase reactants were measured. The association between diabetes and TB, and the role of HIV as an effect modifier, were examined using logistic regression. Since blood glucose levels increase during the acute phase response, we adjusted for elevated serum acute phase reactants.ResultsAmong 803 cases and 350 controls the mean (SD) age was 34.8 (11.9) and 33.8 (12.0) years, and the prevalence of diabetes was 16.7% (95% CI: 14.2; 19.4) and 9.4% (6.6; 13.0), respectively. Diabetes was associated with TB (OR 2.2, 95% CI: 1.5; 3.4, p<0.001). However, the association depended on HIV status (interaction, p = 0.01) due to a stronger association among HIV uninfected (OR 4.2, 95% CI: 1.5; 11.6, p = 0.01) compared to HIV infected (OR 0.1, 95% CI: 0.01; 1.8, p = 0.13) after adjusting for age, sex, demographic factors and elevated serum acute phase reactants.ConclusionDiabetes is a risk factor for TB in HIV uninfected, whereas the association in HIV infected patients needs further study. The increasing diabetes prevalence may be a threat to TB control.

Induction of osteoclast‐associated receptor, a key osteoclast costimulation molecule, in rheumatoid arthritis

Osteoclast-associated receptor (OSCAR) is a newly identified osteoclast-specific receptor and is of key importance in the process of osteoclast costimulation. This study was undertaken to define the role of costimulation in osteoclast differentiation during inflammatory arthritis. OSCAR expression was assessed in the synovium and peripheral blood monocytes of patients with rheumatoid arthritis (RA), and associations with disease activity were assessed. Serum levels of OSCAR were determined by enzyme-linked immunosorbent assay. In vitro osteoclast assays were performed to characterize the role of OSCAR in human osteoclastogenesis. Cytokine regulation of OSCAR was investigated by reverse transcriptase-polymerase chain reaction. OSCAR was expressed by osteoclasts at the erosion front and by mononuclear cells around synovial microvessels. Flow cytometry revealed enhanced expression of OSCAR in peripheral blood monocytes of RA patients as compared with healthy controls. OSCAR expression was correlated with disease activity and acute-phase reactant concentrations. Serum levels of soluble OSCAR were lower in RA patients than in healthy controls. Monocytes with high OSCAR expression exhibited an enhanced potential to differentiate into osteoclasts. Tumor necrosis factor alpha was identified as the main inducer of OSCAR expression in monocytes. These data suggest that the osteoclast costimulation pathway is activated in RA. OSCAR is induced in monocytes of RA patients, facilitating their differentiation into osteoclasts and bone resorption.

The genetic variation of the tenomodulin gene (TNMD) is associated with serum levels of systemic immune mediators—the Finnish Diabetes Prevention Study

PurposeWe have reported that the genetic variation of the tenomodulin gene (TNMD) is associated with the risk of type 2 diabetes (T2DM), central obesity, and impaired glucose metabolism and the TNMD mRNA levels correlate with serum and mRNA levels of inflammatory markers. Our objective was to investigate the genetic associations of the single nucleotide polymorphisms of the TNMD gene with the serum levels of systemic immune mediators. MethodsSeven single nucleotide polymorphisms were genotyped from 507 participants of the Finnish Diabetes Prevention Study. All subjects had body mass index >25 and impaired glucose tolerance. ResultsThe sequence variation of tenomodulin was consistently associated with the serum concentrations of acute phase reactants, macrophage migration inhibitory factor, and CCR5 receptor ligands. The genotype effects were modified by status of glucose metabolism and central obesity. Markers associated with increased risk of T2DM in our previous study were associated with serum concentrations of acute phase proteins in men so that the subjects possessing the genotypes associated with increased risk of T2DM had higher serum concentrations of acute phase reactants. ConclusionsThese results indicate that the genetic variation of TNMD is associated with low-grade inflammation. The putative link between TNMD and T2DM could be mediated through the effects on systemic immune mediators.

Reference maps of mouse serum acute-phase proteins: Changes with LPS-induced inflammation and apolipoprotein A-I and A-II transgenes

We present reference maps of the mouse serum proteome (run under reducing and non-reducing conditions), from control animals, from mice injected with lipopolysaccharide (LPS) to induce systemic inflammation, and from mice transgenic for human apolipoproteins A-I and A-II. Seventy-seven spots/spot chains from the reducing gels were identified by HPLC MS/MS, representing 28 distinct proteins, including a species-specific protease inhibitor, contrapsin, and high levels of carboxylesterase. The concentrations of acute-phase reactants were monitored for 96 h after LPS challenge. The greatest changes (four-fold 48 h after LPS administration) were observed for haptoglobin and hemopexin. Orosomucoid/alpha(1)-acid glycoprotein and apolipoprotein A-I increased steadily, to 50-60% above baseline at 96 h from stimulation. In mice transgenic for human apolipoprotein A-I the levels of expression of orosomucoid/alpha(1)-acid glycoprotein, alpha(1)-macroglobulin, esterase, kininogen and contrapsin were altered compared to knockout mice lacking apolipoprotein A-I. In contrast, except for the presence of apolipoprotein A-II, no statistically significant difference was observed in mice transgenic for human apolipoprotein A-II.

Dramatic Elevations of Interleukin-6 and Acute-Phase Reactants in Athletes Participating in the Ultradistance Foot Race Spartathlon: Severe Systemic Inflammation and Lipid and Lipoprotein Changes in Protracted Exercise

Plasma IL-6, the serum inflammatory markers C-reactive protein (CRP) and serum amyloid A (SAA), and the tissue destruction marker-free plasma DNA, as well as the circulating lipid profile, were examined in athletes participating in the ultradistance foot race of the 246-km Spartathlon. SETTING, DESIGN, AND PARTICIPANTS: This race consists of continuous, prolonged, brisk exercise. Blood samples were obtained from 15 male athletes, who finished the race in less than 36 h, taken before, at the end of, and 48 h after the end of the race. IL-6, CRP, SAA, and free plasma DNA levels markedly increased (by 8000-, 152- 108-, and 10-fold, respectively) over the baseline at the end of the race. However, IL-6 levels returned to normal by 48 h, whereas CRP, SAA, and free plasma DNA remained elevated. The mean values of cholesterol, triglycerides, low-density lipoprotein, and apolipoprotein B decreased to a minimum value at the end of the race and remained low 48 h after the race. High-density lipoprotein levels, on the other hand, were mildly increased at the end of the race (P < 0.015) and decreased to normal 48 h after the race. Apolipoprotein AI levels decreased significantly during the time course of the exercise and remained low 48 h after the race (P < 0.001). These observations suggest that continuous, prolonged, moderate-intensity exercise is associated with markedly elevated IL-6 and acute-phase reactant concentrations, peripheral tissue damage, and significant changes in serum lipid levels. The biochemical changes observed during the Spartathlon amount to a potent systemic inflammatory response, which might explain severe cardiovascular events that occur during prolonged exercise in compromised individuals.

Microinflammation in Renal Failure-Is Periodontal Disease One of the Culprits?: Periodontal Microbiota and Carotid Intima-Media Thickness: The Oral Infections and Vascular Disease Epidemiology Study (INVEST). Circulation 111: 576-582, 2005.

There is consensus that microinflammation is common in patients on dialysis (1,2). The evidence for microinflammation consists of increased concentrations of acute phase reactants (3) such as high-sensitivity C reactive protein (hsCRP) (4,5); of cytokines (6), particularly IL-6 (7,8); and of oxidative stress indicators (9,10). Novel markers include fetuin (11) and adiponectin (12,13). Many factors have been suspected or documented to be responsible for microinflammation. They are related to renal replacement therapy (e.g., exposure to proinflammatory stimuli such as bacterial toxins or bacterial DNA in the dialysate, bioincompatibility of dialysis membranes and tubing, etc.) or terminal renal failure (e.g., uremic toxins, advanced glycosylation end (AGE) products, hypervolemia with intestinal leak of endotoxin [14)] etc.). Nevertheless it is of note that increased markers of microinflammation and endothelial cell dysfunction can be found even in nondialysed patients with renal failure early in the course of chronic kidney disease (CKD) (15–17). In that stage of CKD one also finds accelerated atherogenesis (18), possibly triggered by increased oxidative stress (14), providing a link between microinflammation and cardiovascular risk. It is unlikely, however, that one single cause accounts for all microinflammation. In this context it is of interest that a high prevalence of periodontal disease is found in chronic hemodialysis patients (19), particularly in diabetic patients (20). Unpublished preliminary data even suggest that periodontal disease is predicitive of survival (21). Is there a causal link between periodontitis and microinflammation? Following the observations of Ridker and colleagues (22,23) that CRP concentrations predict cardiovascular events, it is of interest to examine whether periodontal disease contributes to the inflammatory burden. Indeed, inflammation markers are found in patients with periodontal disease: Increased hsCRP concentrations, together with reduced flow-mediated vasodilatation of the brachial artery, were noted by Amar et al. (24), although not confirmed by others (25), and higher IL-1β, TNFα, and IL-2 levels are also common (26). After periodontal treatment, white blood cell, neutrophil, and platelet counts decrease significantly (27). Antibodies against and T cells reactive with heat shock protein of Porphyromonas gingivalis were found in the circulation and in atherosclerotic plaques of patients with periodontitis (28). How about cardiovascular risk? A correlation, though modest, was found between periodontal disease and coronary artery calcification as a surrogate marker (29). In the Third National Health and Nutrition Examination Survey (NHANES III), the odds ratio for a heart attack increased with increasing clinical severity of periodontitis (29), and such a relationship was confirmed in the Atherosclerosis Risk in Communities (ARIC) study (30). Sceptics will be impressed by the observation that radical elimination of periodontitis by extraction of all teeth failed to lower cardiovascular risk, however (31). So criticisms had been definitively justified that the available evidence was soft and that more sensitive and comprehensive measures of periodontal disease were required (32). It is the sophisticated methodology used by Desvarieux in the Oral Infection and Vascular Disease Epidemiology Study (INVEST) that now provided more scientifically convincing evidence. Six hundred fifty-seven patients without history of cardiovascular events and with teeth were studied. Subgingival plaque samples were collected and quantitatively assessed by DNA–DNA checkerboard hybridization targeting 11 bacterial species known to be involved in periodontal disease. In addition, the carotid artery intima-media thickness (IMT) was measured and white blood cell counts as well as CRP values were obtained. The main result is that increasing tertiles of overall periodontal bacterial burden, but more importantly increasing tertiles of the burden of causative bacteria (i.e., bacteria involved in plaque formation) were correlated to the carotid IMT. The adjusted IMT values across tertiles of etiologic bacterial burden were 0.84, 0.85, and 0.88—a modest, but statistically significant, increase (P < 0.02). White blood cell counts, but not CRP values, were similarly correlated. The strength of the study is that rigorous molecular bacteriological techniques were used. The weakness is that a surrogate marker (i.e., IMT) but not hard endpoints (i.e., events) were assessed. Nevertheless, the study identifies periodontitis as a definite candidate for, although not yet a convicted culprit in, the genesis of microinflammation and cardiovascular risk. Against the background of the high prevalence of malnutrition, inflammation, and atherosclerosis (MIA syndrome) (1) and of periodontal disease (19,21) in dialysis patients, it is a reasonable hypothesis to propose a link between periodontal disease and microinflammation in these patients. Rigorous studies are currently underway to test this hypothesis. What are the practical consequences? When examining uremic patients it is not medical malpractice but a most sensible procedure to check whether the patient has periodontal disease. And the patient is not hurt by the advice to adopt careful oral hygiene.

Pathophysiological response of cytokines and vasoactive agents in patients undergoing total gastrectomy.

To investigate the involvement of vasoactive agents, endothelin (ET)-1, and atrial natriuretic peptide (ANP), and the responses of cytokines in patients undergoing total gastrectomy. Prospective study. University hospital, Japan. 20 patients with advanced gastric cancer who had undergone total gastrectomy with lymph node dissection. Serum or plasma samples collected on the day before the operation, at the time of skin closure, and on postoperative days 1, 3, 5, and 7. Concentrations of acute phase reactants, cytokines (interleukin (IL)-1, tumour necrosis factor (TNF) and interleukin (IL)-6), and vasoactive agents (ET-1 and ANP). There were significant increases in concentrations of IL-6 and acute phase reactants postoperatively. ET-1 and ANP concentrations did not change significantly. There was no correlation between concentrations of the vasoactive agents ET-1 and ANP, and those of acute phase reactants or cytokines in serum or plasma in patients undergoing total gastrectomy.

Blood rheology and hemodynamics.

Blood is a two-phase suspension of formed elements (i.e., red blood cells [RBCs], white blood cells [WBCs], platelets) suspended in an aqueous solution of organic molecules, proteins, and salts called plasma. The apparent viscosity of blood depends on the existing shear forces (i.e., blood behaves as a non-Newtonian fluid) and is determined by hematocrit, plasma viscosity, RBC aggregation, and the mechanical properties of RBCs. RBCs are highly deformable, and this physical property significantly contributes to aiding blood flow both under bulk flow conditions and in the microcirculation. The tendency of RBCs to undergo reversible aggregation is an important determinant of apparent viscosity because the size of RBC aggregates is inversely proportional to the magnitude of shear forces; the aggregates are dispersed with increasing shear forces, then reform under low-flow or static conditions. RBC aggregation also affects the in vivo fluidity of blood, especially in the low-shear regions of the circulatory system. Blood rheology has been reported to be altered in various physiopathological processes: (1) Alterations of hematocrit significantly contribute to hemorheological variations in diseases and in certain extreme physiological conditions; (2) RBC deformability is sensitive to local and general homeostasis, with RBC deformability affected by alterations of the properties and associations of membrane skeletal proteins, the ratio of RBC membrane surface area to cell volume, cell morphology, and cytoplasmic viscosity. Such alterations may result from genetic disorders or may be induced by such factors as abnormal local tissue metabolism, oxidant stress, and activated leukocytes; and (3) RBC aggregation is mainly determined by plasma protein composition and surface properties of RBCs, with increased plasma concentrations of acute phase reactants in inflammatory disorders a common cause of increased RBC aggregation. In addition, RBC aggregation tendency can be modified by alterations of RBC surface properties because of RBC in vivo aging, oxygen-free radicals, or proteolytic enzymes. Impairment of blood fluidity may significantly affect tissue perfusion and result in functional deteriorations, especially if disease processes also disturb vascular properties.

Lipoprotein (a) in Behçet's disease as an indicator of disease activity and in thrombotic complications.

To evaluate the utility of plasma concentrations of lipoprotein (a) (Lp(a)) as an indicator of disease activity in Behçet's disease and to investigate its role in thrombotic complications of this disease. 30 patients (19 male, 11 female) with Behçet's disease (8 active, 22 inactive) were enrolled in the study group and 30 healthy individuals (16 male, 14 female) in the control group. Seven of the inactive Behçet's disease patients had a history of thrombotic complications. The disease activity was evaluated by clinical manifestations (oral aphthous lesions, genital ulcerations, uveitis and vasculitis) and laboratory investigations (leucocyte count, lipoprotein (a), C-reactive protein (CRP), complement 3 (C3) and complement 4 (C4) concentrations). Plasma Lp(a) and other acute phase reactant concentrations were significantly higher in the study group than in the controls (p < 0.01). These concentrations were also higher during the active period of the disease than during the inactive phase (p < 0.01). Lp(a) concentrations were significantly correlated with concentrations of other acute phase reactants. There was no difference between the groups with and without thrombotic complications for any of these measurements. CONCLUSIONS. Plasma levels of Lp(a) might be an indicator of disease activity in Behçet's disease. There is no correlation between Lp(a) levels and thrombotic sequela in inactive Behçet's disease. However, further studies are needed on the thrombogenic role of Lp(a) during the active phase of thrombophlebitis, and in larger series.

Serum ferritin: a predictor of early spontaneous preterm delivery

To identify biochemical indices for iron and protein nutriture as well as acute-phase reactants as predictors of preterm delivery. In this nested case-control study, serum samples were obtained at about 24 weeks' gestation from 94 indigent multiparas. These cases were defined based on having a spontaneous delivery of 32 weeks or less (n = 31) with two control groups, one delivering spontaneously at 33-36 weeks (n = 32) and the other delivering spontaneously at 37 weeks or more (n = 31). The concentrations of iron, ferritin, transferrin, transferrin saturation, and transferrin receptor were measured as indices of iron status. The concentrations of acute-phase reactants, including C-reactive protein, alpha-2-macroglobulin, beta-2-microglobulin and ceruloplasmin, were also measured, along with albumin, prealbumin, retinol-binding protein, copper, and zinc. Serum ferritin concentrations were negatively correlated with gestational age at birth (P = .034). For subjects having serum ferritin levels above the median compared with those below, the odds ratio of having an early spontaneous preterm delivery was 2.99 (95% confidence interval 1.13-7.89). The other indices, including iron status and the acute-phase reactants, were not significantly associated with gestational age at birth. Elevated serum ferritin levels during the second trimester are predictive of early spontaneous preterm delivery, possibly because these reflect an acute-phase reaction to subclinical infections that are closely associated with premature delivery.

Alpha-fetoprotein and the acute phase response. A study using acute pelvic inflammatory disease as a model system

Alpha-fetoprotein (AFP) is used as a tumor marker for hepatomas and germ cell tumors. In healthy non-pregnant adults the serum concentration (S-AFP) is very low and we examined whether it was affected when the acute phase response was activated, using patients with acute pelvic inflammatory disease (PID) as a model system. In 70 PID patients the median S-AFP was 1.2 kIU/1(range: 0.5-5.9 kIU/1), within the normal range. S-AFP did not correlate with the clinical grade of disease nor with the serum concentrations of acute phase reactants and albumin. Thus, S-AFP is not significantly affected by activation of the acute phase response and presence of infection should not per se interfere with the use of S-AFP as a tumor marker. However, a negative correlation was found with the serum concentration of α-2-macroglobulin ( P = 0.05), but whether this has any biological significance remains to be clarified.

Changes in Lp(a) lipoprotein and other plasma proteins during acute myocardial infarction.

The sequential changes of Lp(a) lipoprotein concentrations in patients (n = 59) suffering acute myocardial infarction (AMI) were examined and compared with other plasma proteins. The temporal and quantitative characteristics of the responses in concentration of acute phase reactants (CRP, haptoglobin, alpha 1-antitrypsin, alpha-acid glycoprotein), lipids (total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol) and apolipoproteins AI and B were similar to previous reports. Lp(a) lipoprotein showed transient changes with an initial decrease of 10-25% compared to the 3-month control value, followed by rebound on day 7-11 above admission level, before again declining. We were able to demonstrate a quantitative relationship between infarct size and alterations in plasma levels of acute phase reactants. However, in addition to rather unusual significant fluctuations during AMI, Lp(a) lipoprotein changes seemed unrelated to infarct size. These findings do not support the view that Lp(a) lipoprotein acts as an acute phase reactant.

Is there an acute-phase response in steady-state sickle cell disease?

Metabolic and serum changes during steady-state homozygous sickle cell (SS) disease are consistent with an acute-phase response and raise the possibility that inflammation occurs in SS disease even during the steady state. To test this hypothesis, we measured concentrations of acute phase reactants in patients with SS disease, in patients with sickle cell haemoglobin C (SC) disease, and in normal (AA) control subjects. The concentrations of C-reactive protein and serum amyloid A were increased above 10 mg/L and 5 mg/L, respectively (our definition of an acute-phase response) in 18% (26/143) of subjects with SS disease even when they were symptom free, in 17% (6/35) of subjects with SC disease, and in 1% (1/80) of AA controls (p<0·001). We suggest that subclinical vaso-occlusion may generate a covert inflammatory response and that the cytokine mediators of this response may contribute to the metabolic abnormalities and growth failure in sickle cell disease.