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Objectives: Vitamin D modulates inflammation, and this may explain the observed associations between vitamin D status and disorders driven by systemic inflammation, such as coronary artery disease (CAD) and inflammatory rheumatic diseases (IRDs). The aims of this study were to assess vitamin D status in patients with CAD alone and in patients with CAD and IRD, and to explore potential associations between vitamin D status and the presence of mononuclear cell infiltrates (MCIs) in the aortic adventitia of these patients.Method: Plasma levels of 25-hydroxyvitamin D3 [(25(OH)D3] were determined by radioimmunoassay and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] by enzyme immunoassay in the 121 patients from the Feiring Heart Biopsy Study (FHBS) who had available histology data on adventitial MCIs; 53 of these had CAD alone and 68 had CAD and IRD.Results: In the crude analysis, vitamin D levels were similar in CAD patients with and without IRD. After adjustment for potential confounders, IRD was associated with an increase of 8.8 nmol/L [95% confidence interval (CI) 1.0-16.6; p = 0.027] in 25(OH)D3 and an increase of 18.8 pmol/L (95% CI 4.3-33.3; p = 0.012) in 1,25(OH)2D3, while MCIs in the aortic adventitia were associated with lower levels of 1,25(OH)2D3 (β = -18.8, 95% CI -33.6 to -4.0; p = 0.014).Conclusions: IRD was associated with higher levels of both 25(OH)D3 and 1,25(OH)2D3. These findings argue against the hypothesis that patients with high systemic inflammatory burden (CAD+IRD) should have lower vitamin D levels than those with less inflammation (CAD only). Of note, when controlled for potential confounders, low 1,25(OH)2D3 levels were associated with adventitial aortic inflammation. [ABSTRACT FROM AUTHOR]

Objective. Homocysteine measurements may be relevant in geriatric medicine as homocysteine has been identified as an independent risk factor for prevalent disorders such as occlusive arterial vascular disease, cognitive impairment and dementia. The aim of the present study was to study diagnostic correlates of plasma total homocysteine (tHcy) in geriatric in‐patients. Material and methods. Blood samples for the analysis of tHcy and related factors like serum vitamin B 12 , serum folate, red blood cell folate and clinical data were collected from geriatric patients ( n = 114) in stable clinical condition. Results. Almost 40 % of the patients had tHcy values above 20 µmol/L. tHcy correlated significantly with serum folate, serum vitamin B 12 , serum creatinine and congestive heart failure, but not with red blood cell folate, cerebrovascular disease, coronary heart disease or cognitive impairment. Conclusions. Hyperhomocysteinaemia seems to be frequent in geriatric patients and might primarily be an indicator of low folate and high creatinine values. [ABSTRACT FROM AUTHOR]

Running leads to biochemical and hematological changes consistent with an inflammatory reaction to tissue injury. We report changes in the plasma concentration of the leukocyte-derived protein calprotectin after long-distance running. Blood samples were collected from runners before and after a marathon, half-marathon, a 30-km cross-country run, a military ranger-training course and short-term maximal physical exercise until exhaustion, VO2max. Leukocyte counts, plasma calprotectin concentration and calprotectin per neutrophilic granulocyte were assayed using a new method. During the marathon, half-marathon, the 30-km run, the ranger-training course and the VO2max exercise, calprotectin levels increased 96.3-fold, 13.3-fold, 20.1-fold, 7.5-fold and 3.4-fold, respectively. These changes may reflect damage to the tissues or vascular endothelium, causing microthrombi with subsequent activation of neutrophils. These cells are known to phagocytose platelets in microthrombi and may contribute to the prevention of clinical thrombosis. The half-life of calprotectin in plasma was about 5 h. The content of calprotectin per neutrophil remained unchanged during exercise at a level similar to that in healthy blood donors: mean: 25 pg/cell, range 18.8-33.6. A reference interval (mean +/- 2 SD) of 18.6-31.4 pg/cell is suggested. [ABSTRACT FROM AUTHOR]

Objective. Pregnancy is characterized by haemostasis activation, and in preeclampsia endothelial dysfunction, platelet and leukocyte activation are further characteristic features. The aim of this study was to investigate to which extent platelets from normotensive pregnant women or those with preeclampsia are circulating as microparticles or platelet-platelet aggregates. We also investigated if platelet-leukocyte multiconjugates were differently present in nonpregnant and pregnant women.Study design. Using flow cytometry we investigated these parameters in basal samples and after in vitro stimulation with adenosine diphosphate (ADP) or thrombin receptor activation peptide. This was done in samples from 20 matched preeclamptic and normotensive pregnant women and in a group of 12 nonpregnant women.Results. In the basal state we found that women with preeclampsia had a smaller portion of microparticles circulating than the normotensive pregnant women, Upon ADP stimulation both pregnancy groups showed a higher percentage of monocytes and granulocytes with platelets attached and also a higher number of platelets attached to each monocyte and granulocyte than in the group of nonpregnant individuals.Conclusion. This article presents further evidence that changes from the nonpregnant to the pregnant state are associated with hemostasis activation as an integrated part of an inflammatory reaction that is even more pronounced when pregnancy is complicated with preeclampsia. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate intracellular levels of reactive oxygen species (ROS) in circulating leukocytes in populations at risk for atherosclerosis compared with in healthy individuals. The study populations consisted of 27 non-diabetic men (aged 40-69 years) with untreated hypercholesterolemia (HC), 13 individuals (aged 39-56 years) with well-controlled insulin-dependent diabetes mellitus (DM), and 20 healthy individuals (aged 26-61 years) (REF). Citrated whole blood was collected in fasting condition. Using flow cytometric techniques, the resting levels and the response upon phorbol 12-myristate 13-acetate (PMA, 100 ng/mL) stimulation of ROS were measured in circulating monocytes (MO) and granulocytes (GR). The relative mean fluorescence intensity (rMFI) in 10(4) leukocytes of fluorochromes mainly reflecting the levels of peroxynitrite (ONOO-) hydrogen peroxide (H2O2) and superoxide anion (O2-) was recorded. Significantly, higher basal levels of ONOO- in GR from the combined risk population compared with REF were found (1.4 vs. 1.5 rMFI, p<0.05). Upon PMA stimulation, significantly lower levels of O2 in GR in the risk populations compared to REF (119 vs. 90 Si, p<0.001) were observed. In conclusion, increased resting levels of ROS in circulating granulocytes, but reduced response to PMA stimulation could be demonstrated in populations at risk for atherosclerosis compared with in healthy individuals. This might indicate a higher degree of resting oxidative reactions, with partly exhausted cells and less capacity to host defence. [ABSTRACT FROM AUTHOR]

To elucidate the pathophysiology of infections with Streptococcus pyogenes we applied flow cytometric techniques to study dose-response and time-related effects of the streptococcal cell-wall-derived components lipoteichoic acid (LTA 0.005 to 50 μg/ml) and peptidoglycan (10 and 100 μg/ml) on the expression of leukocyte adhesion molecules, the CD14 receptor, and the production of leukocyte reactive oxygen species (ROS). LTA (50 μg/ml, 1-2 h) markedly increased the expression of CD11b (∼5-fold), CD11c (∼2-fold) and CD11a. Concomitantly, CD62L was downregulated (60%). Peptidoglycan alone or in combination with LTA had little effect on adhesion molecules, except for an amplification of the downregulation of CD62L to 90%. Monocyte CD14 expression was doubled by LTA. Leukocyte ROS production was 10-fold and 5-fold increased by peptidoglycan in granulocytes and monocytes, respectively. LTA alone had no effect, while the combination of peptidoglycan with LTA doubled the increase in ROS caused by peptidoglycan. Conclusion: LTA and peptidoglycan had marked and differential effects: LTA caused mainly adhesion molecule modulation, whereas peptidoglycan mainly increased ROS production. These changes are important in inflammatory cell activation and recruitment, intracellular microbial killing and adverse tissue injury. [ABSTRACT FROM AUTHOR]

Background: Biliary secretion of organic anions disturbs the proportional relationship normally pertaining between biliary lipid and bile acid secretion. The mechanism causing this uncoupling of biliary lipid from bile acid secretion is incompletely understood. Impaired micellization of membrane lipids by bile due to biliary contamination with organic anions or lowering of biliary bile acid concentration by enhanced bile acid-independent bile flow has been proposed as causative factors. Recently, we found that hepatic phosphoglycoprotein 3 (pgp3) activity was reduced in pigs during bilirubin-induced uncoupling of biliary lipid from bile acid secretion. Pgp3 is the phosphatidylcholine flippase in the canalicular membrane sustaining biliary phospholipid secretion in pigs. This investigation was undertaken to examine whether bilirubin, dibromosulfophthalein, and bromosulfophthalein uncouple biliary lipid from bile acid secretion by the same mechanism. Methods/Results: Hepatic bile was collected from 24 anesthetized pigs before and during infusion of 0.63 μmol·kg body wt[sup -1] · min[sup -1] intravenous bilirubin, dibromosulfophthalein, or bromosulfophthalein. Bile acid secretion was varied by intraportal cholic acid infusion. Hepatic pgp3 expression was measured by means of Western blot, using C219 antibody. Bilirubin > dibromosulfophthalein > bromosulfophthalein lowered biliary lipid secretion without altering hepatic pgp3 expression, increased bile acid-independent bile flow (bromosulfophthalein > dibromosulfophthalein > bilirubin), and enhanced the capacity of bile to micellize membrane lipids as assayed by means of erythrocyte lysis. Biliary bile acid concentration did not determine biliary lipid secretion. Conclusion: Bilirubin, dibromosulfophthalein, and bromosulfophthalein in bile uncouple biliary lipid from bile acid secretion by inhibiting hepatic pgp3 phosphatidylcholine flippase activity, putatively through diffusing into the pgp3 pore. [ABSTRACT FROM AUTHOR]

Endothelin (ET) induces hypertrophy of cardiomyocytes and increases synthesis of collagen in vitro. Interestingly, these features are hallmarks of the cardiac remodeling taking place in heart failure. The aim of the present study was to examine cardiac ET peptide and preproET-1 mRNA synthesis in human heart failure. Cardiac tissue was obtained from 11 patients with end-stage heart failure undergoing orthothopic heart transplantation (NYHA III-IV). Cardiac tissue from nine organ donors served as controls. The specimens were examined by immunohistochemistry and mRNA slot blot analyses. Significantly stronger ET-1-like immunoreactivity (ET-1-ir) was seen in the left atrial myocardium of failing hearts compared to the left atrial myocardium of donor hearts. Within each heart, the epicardium showed the strongest ET-1-ir. Left ventricular preproET-1 mRNA expression in the entire group of patients did not differ significantly from that of donor hearts. However, hypertrophic obstructive cardiomyopathy may be associated with a twofold increase in left ventricular preproET-1 mRNA. We report an increase in cardiac ET peptide in human heart failure. [ABSTRACT FROM AUTHOR]

Background: Large intravenous bilirubin loads cause loss of hepatic canalicular membrane microvilli and cholestasis. This study examines whether these untoward effects might be due to canalicular membrane injury from cytotoxic bile. Methods: The cytotoxicity of bile was assayed against pig erythrocytes before and throughout 4.5-h intravenous infusion of 170 μg[sup -1] kg body weight of bilirubin in anaesthetized pigs. The capacity to generate canalicular bile flow was tested before and after bilirubin infusion by means of short-term intraportal cholic acid infusion. Results: Bilirubin infusion increased the cytotoxicity of hepatic bile, reduced biliary phospholipid secretion by 90%, and caused cholestasis. Cholic acid infusion before bilirubin also increased the cytotoxicity of bile but increased bile flow and doubled biliary phospholipid output. Conclusion: Large intravenous bilirubin infusions increase the cytotoxicity of bile, suppress biliary phospholipid secretion, and render hepatic canalicular membrane microvilli susceptible to injury from cytotoxic bile so that cholestasis occurs. [ABSTRACT FROM AUTHOR]

The article presents a research which examines the efficacy of methotrexate (MTX) or methotrexate in combination with a tumor necrosis factor (TNF)-&#03B1 inhibitor treatment on endothelial function (EF) in rheumatoid arthritis (RA) patients. According to the research, since the treatment led to improvement in the EF after 6 weeks, compared to the expected 8 to 12 weeks, MTX can have subclinical anti-inflammatory or anti-atherogenic effects on the vascular system.

Investigates the effects of intravenous bilirubin infusion on biliary phospholipid secretion in pigs. Increase in the biliary cytotoxicity; Alterations in hepatic P-glycoprotein expression; Use of gas chromatography in determining biliary phospholipid fatty acid profile.