Local hyperhemia to heating is impaired in secondary Raynaud's phenomenon

Accurate and sensitive measurement techniques are a key issue in the quantification of the microvascular and endothelial dysfunction in systemic sclerosis (SSc). Thermal hyperhemia comprises two separate mechanisms: an initial peak that is axon reflex mediated; and a sustained plateau phase that is nitric oxide dependent. The main objective of our study was to test whether thermal hyperhemia in patients with SSc differed from that in patients with primary Raynaud's phenomenon (RP) and healthy controls. In a first study, we enrolled 20 patients suffering from SSc, 20 patients with primary RP and 20 healthy volunteers. All subjects were in a fasting state. Post-occlusive hyperhemia, 0.4 mg sublingual nitroglycerin challenge and thermal hyperhemia were performed using laser Doppler flowmetry on the distal pad of the third left finger. In a second study, thermal hyperhemia was performed in 10 patients with rheumatoid arthritis and 10 patients with primary RP. The thermal hyperhemia was dramatically altered in terms of amplitude and kinetics in patients with SSc. Whereas 19 healthy volunteers and 18 patients with primary RP exhibited the classic response, including an initial peak within the first 10 minutes followed by a nadir and a second peak, this occurred only in four of the SSc patients (p < 0.0001). The 10 minutes thermal peak was 43.4 (23.2 to 63), 42.6 (31 to 80.7) and 27 (14.7 to 51.4) mV/mm Hg in the healthy volunteers, primary RP and SSc groups, respectively (p = 0.01), while the 44°C thermal peak was 43.1 (21.3 to 62.1), 42.6 (31.6 to 74.3) and 25.4 (15 to 52.4) mV/mm Hg, respectively (p = 0.01). Thermal hyperhemia was more sensitive and specific than post-occlusive hyperhemia for differentiating SSc from primary RP. In patients with rheumatoid arthritis, thermal hyperhemia was also altered in terms of amplitude. Thermal hyperhemia is dramatically altered in patients with secondary RP in comparison with subjects with primary RP. Further studies are required to determine the mechanisms of this altered response, and whether it may provide additional information in a clinical setting.     

Local hyperemia to heating is impaired in secondary Raynaud's phenomenon

Accurate and sensitive measurement techniques are a key issue in the quantification of the microvascular and endothelial dysfunction in systemic sclerosis (SSc). Thermal hyperemia comprises two separate mechanisms: an initial peak that is axon reflex mediated; and a sustained plateau phase that is nitric oxide dependent. The main objective of our study was to test whether thermal hyperemia in patients with SSc differed from that in patients with primary Raynaud's phenomenon (RP) and healthy controls. In a first study, we enrolled 20 patients suffering from SSc, 20 patients with primary RP and 20 healthy volunteers. All subjects were in a fasting state. Post-occlusive hyperemia, 0.4 mg sublingual nitroglycerin challenge and thermal hyperemia were performed using laser Doppler flowmetry on the distal pad of the third left finger. In a second study, thermal hyperemia was performed in 10 patients with rheumatoid arthritis and 10 patients with primary RP. The thermal hyperemia was dramatically altered in terms of amplitude and kinetics in patients with SSc. Whereas 19 healthy volunteers and 18 patients with primary RP exhibited the classic response, including an initial peak within the first 10 minutes followed by a nadir and a second peak, this occurred only in four of the SSc patients (p < 0.0001). The 10 minutes thermal peak was 43.4 (23.2 to 63), 42.6 (31 to 80.7) and 27 (14.7 to 51.4) mV/mm Hg in the healthy volunteers, primary RP and SSc groups, respectively (p = 0.01), while the 44 degrees C thermal peak was 43.1 (21.3 to 62.1), 42.6 (31.6 to 74.3) and 25.4 (15 to 52.4) mV/mm Hg, respectively (p = 0.01). Thermal hyperemia was more sensitive and specific than post-occlusive hyperhemia for differentiating SSc from primary RP. In patients with rheumatoid arthritis, thermal hyperemia was also altered in terms of amplitude. Thermal hyperemia is dramatically altered in patients with secondary RP in comparison with subjects with primary RP. Further studies are required to determine the mechanisms of this altered response, and whether it may provide additional information in a clinical setting.     

Novel mode of action of iloprost: in vitro down-regulation of endothelial cell adhesion molecules

Iloprost is a stable prostacyclin analog commonly employed in the treatment of peripheral vascular disease and also indicated in the treatment of patients affected by systemic sclerosis (SSc) in the presence of severe Raynaud's phenomenon (RP). Several mechanisms of action of the drug other than vasodilation and antiplatelet effect have been demonstrated that may be involved in the exertion of its clinical efficacy. Aim of the present study was to investigate whether iloprost down-regulated lymphocyte adhesion to endothelium through a modulation of adhesion molecule expression on the surface of endothelial cells. In the presence of iloprost, both lymphocyte adhesion and IL-1 stimulated expression of ICAM-1 and ELAM-1 exhibited a significant reduction, while unstimulated adhesion molecule expression was not significantly affected. Our results confirm that iloprost is able to down-regulate lymphocyte adhesion to endothelial cells and indicate that endothelium itself could be target of iloprost administration. Attenuation of the inflammatory response through modulation of cellular interactions could be suggested as a potential mechanism of action of iloprost, when used in the treatment of pathological conditions characterized by endothelial activation.     

Atypical clinical presentation of a subset of patients with anti-RNA polymerase III - non-scleroderma cases associated with dominant RNA polymerase i reactivity and nucleolar staining

Introduction

Anti-RNA polymerase III (RNAP III) antibodies are highly specific markers of scleroderma (systemic sclerosis, SSc) and associated with a rapidly progressing subset of SSc. The clinical presentation of anti-RNAP III positive patients, onset of Raynaud's phenomenon (RP) and SSc in unselected patients in a rheumatology clinic were evaluated.

Methods

Autoantibodies in sera from 1,966 unselected patients (including 434 systemic lupus erythematosus (SLE), 119 SSc, 85 polymyositis/dermatomyositis (PM/DM)) in a rheumatology clinic were screened by radioimmunoprecipitation. Anti-RNAP III positive sera were also tested by immunofluorescence antinuclear antibodies and anti-RNAP III ELISA. Medical records of anti-RNAP III positive patients were reviewed.

Results

Among 21 anti-RNAP III positive patients, 16 met the American College of Rheumatology (ACR) SSc criteria at the initial visit but 5 did not; diagnoses were vasculitis, early polyarthritis, renal failure with RP, interstitial lung disease, and Sjögren's syndrome. The first two patients developed rapidly progressive diffuse SSc. An additional case presented with diffuse scleroderma without RP and RP developed two years later. Anti-RNAP III antibodies in these 6 cases of atypical clinical presentation were compared with those in 15 cases of typical (SSc with RP) cases. Anti-RNAP III levels by ELISA were lower in the former group (P = 0.04 by Mann-Whitney test) and 3 of 6 were negative versus only 1 of 15 negative in the latter (P < 0.05 by Fisher's exact test). Three cases of non-SSc anti-RNAP III positive patients had predominant reactivity with RNAP I with weak RNAP III reactivity and had a strong nucleolar staining. Three anti-RNAP III patients, who did not have RP at the initial visit, developed RP months later. Scleroderma developed prior to RP in 5 out of 16 (31%) in the anti-RNAP III group, but this was rare in patients with other autoantibodies. The interval between the onset of RP to scleroderma was short in anti-RNAP III positive patients.

Conclusions

Anti-RNAP III antibodies are highly specific for SSc; however, a subset of anti-RNAP III positive patients do not present as typical SSc. The interval between RP and scleroderma in this group is short, and 31% of patients developed scleroderma prior to RP in this group. Anti-RNAP III positive patients may not present as typical SSc and detecting anti-RNAP III may have predictive value.     

Gene expression profiling in circulating endothelial cells from systemic sclerosis patients shows an altered control of apoptosis and angiogenesis that is modified by iloprost infusion

Introduction  

Circulating endothelial cells are increased in patients affected by systemic sclerosis (SSc) and their number strongly correlates with vascular damage. The effects of iloprost in systemic sclerosis are only partially known. We aimed at studying the gene expression profile of circulating endothelial cells and the effects of iloprost infusion and gene expression in patients with systemic sclerosis.     

Angiogenic and angiostatic factors in systemic sclerosis: increased levels of vascular endothelial growth factor are a feature of the earliest disease stages and are associated with the absence of fingertip ulcers

To examine whether the lack of sufficient neoangiogenesis in systemic sclerosis (SSc) is caused by a decrease in angiogenic factors and/or an increase in angiostatic factors, the potent proangiogenic molecules vascular endothelial growth factor (VEGF) and basic fibroblast growth factor, and the angiostatic factor endostatin were determined in patients with SSc and in healthy controls. Forty-three patients with established SSc and nine patients with pre-SSc were included in the study. Serum levels of VEGF, basic fibroblast growth factor and endostatin were measured by ELISA. Age-matched and sex-matched healthy volunteers were used as controls. Highly significant differences were found in serum levels of VEGF between SSc patients and healthy controls, whereas no differences could be detected for endostatin and basic fibroblast growth factor. Significantly higher levels of VEGF were detected in patients with Scl-70 autoantibodies and in patients with diffuse SSc. Patients with pre-SSc and short disease duration showed significant higher levels of VEGF than healthy controls, indicating that elevated serum levels of VEGF are a feature of the earliest disease stages. Patients without fingertip ulcers were found to have higher levels of VEGF than patients with fingertip ulcers. Levels of endostatin were associated with the presence of giant capillaries in nailfold capillaroscopy, but not with any other clinical parameter. The results show that the concentration of VEGF is already increased in the serum of SSc patients at the earliest stages of the disease. VEGF appears to be protective against ischemic manifestations when concentrations of VEGF exceed a certain threshold level.     

Application of the 2013 ACR/EULAR classification criteria for systemic sclerosis to patients with Raynaud’s phenomenon

IntroductionWe investigated how many patients, who presented with Raynaud’s phenomenon (RP) and who had not been classified as systemic sclerosis (SSc), would be reclassified as SSc, if the 2013 American College of Rheumatology (ACR)/the European League Against Rheumatism (EULAR) classification criteria were used. We also analyzed the predictive values of the reclassification as SSc in those patients.MethodsWe consecutively enrolled 64 patients with RP and 60 patients with SSc. We applied the new classification criteria to them, reclassified them, and compared variables between those who were newly classified as SSc and those who were not or previously classified as SSc.ResultsSeventeen of 64 patients (26.5%), who presented with RP, but did not fulfill the 1980 ACR classification criteria, were newly classified as SSc by the 2013 ACR/EULAR classification criteria. The newly classified patients as SSc showed increased frequencies of sclerodactyly, digital tip ulcer, telangiectasia, abnormal nailfold capillaries and the presence of anti-centromere antibody, compared to those not and telangiectasia and anti-centromere antibody, compared to the previously classified patients. For the reclassification as SSc, the variables with independent predictive value were sclerodactyly (odds ratio (OR) 60.025), telangiectasia (OR 13.353) and the presence of anti-centromere antibody (OR 11.168).ConclusionsOverall, 26.5% of the patients, who presented with RP, but who did not fulfill the 1980 ACR classification criteria, were newly classified as SSc according to the 2013 ACR/EULAR classification criteria. Sclerodactyly, telangiectasia, and the presence of anti-centromere antibody had independent predictive value for reclassifying patients with RP as SSc.     

Volunteer and clinical studies with carfecillin: a new orally administered ester of carbenicillin.

Blood and urine levels of carbenicillin were measured in 10 healthy volunteers and four patients with renal failure after single and multiple oral dose of carfecillin. Urinary levels after 1000-mg doses in healthy subjects were considered sufficient for treatment of Pseudomonas aeruginosa urinary infections, but the serum levels were too low for chemotherapy of systemic infections with this organism even in severe renal failure. Urinary infections were treated in 35 inpatients with a seven-day course of carfecillin. The infection was eradicated in 21 cases (60%). In 12 cases the pathogen was Ps. aeruginosa, which was eradicated from eight patients (67%). Many patients had severe urinary tract disease. Side effects were virtually absent.     

Correlation of endostatin and tissue inhibitor of metalloproteinases 2 (TIMP2) serum levels with cardiovascular involvement in systemic sclerosis patients

Fibrosis of oesophagus, lungs, heart, and kidney in the course of systemic sclerosis (SSc) may lead to dysfunction of the above organs or even patients death. Recent studies point out the role of angiogenesis and fibrosis disturbances in the pathogenesis of SSc. Heart fibrosis is one of the most important prognostic factors in SSc patients. So, the aim of our study was to examine cardiovascular dysfunction in SSc patients and its correlation with serum levels of vascular endothelial growth factor (VEGF), endostatin, and tissue inhibitor of metalloproteinase 2 (TIMP2). The study group comprised 34 patients (19 with limited scleroderma (lSSc) and 15 with diffuse scleroderma (dSSc)). The control group consisted of 20 healthy persons, age and sex matched. Internal organ involvement was assessed on the basis of specialist procedures. Serum VEGF, endostatin, and TIMP2 levels were evaluated by ELISA. We found cardiovascular changes in 15 patients with SSc (8 with lSSc and 7 with dSSc). The observed symptoms were of different characters and also coexisted with each other. Higher endostatin serum levels in all systemic sclerosis patients in comparison to the control group were demonstrated (P < .05). Also higher serum levels of endostatin and TIMP2 were observed in patients with cardiovascular changes in comparison to the patients without such changes (P < .05). The obtained results support the notion that angiogenesis and fibrosis disturbances may play an important role in SSc. Evaluation of endostatin and TIMP2 serum levels seems to be one of the noninvasive, helpful examinations of heart involvement in the course of systemic sclerosis.     

Postocclusive reactive hyperemia inversely correlates with urinary 15-F2t-isoprostane levels in systemic sclerosis

Microvascular dysfunction and increased oxidative stress are major hallmarks of the systemic sclerosis disease process. The primary objective of this study was to test whether there is a link between peak postocclusive hyperemia and urinary levels of the F2-isoprostane 15-F2t-IsoP (8-iso-PGF2alpha) in patients suffering from systemic sclerosis. We enrolled 43 patients suffering from systemic sclerosis, 33 patients with primary Raynaud's phenomenon (RP), and 25 healthy volunteers. Microvascular function was assessed using the postocclusive hyperemia monitored by laser Doppler flowmetry. Endothelium-independent response was monitored after 0.4 mg sublingual nitroglycerin. Oxidative stress status was assessed by urinary levels of the F2-isoprostane 15-F2t-IsoP using GC-MS. The peak postocclusive vascular conductance was altered in subjects with systemic sclerosis and primary RP compared to controls (respectively 28 (7-48), 30 (13-48), and 39.9 (13-63) mV/mm Hg, p = 0.01). F2-isoprostanes were increased in the systemic sclerosis group compared to primary Raynaud's phenomenon and healthy controls (respectively 230 (155-387), 182 (101-284), and 207 (109-291) pg/mg, p = 0.006). In patients suffering from systemic sclerosis, there was a significant inverse correlation between F2-isoprostanes and postocclusive hyperemia, expressed as raw data (R = -0.45, p = 0.007) or as an increase over baseline (R = -0.28, p = 0.04). Conversely, no correlation was found with the nitroglycerin response. In conclusion, we provide evidence that there is an inverse correlation between postocclusive hyperemia and urinary F2-isoprostane levels in patients suffering from systemic sclerosis. Whether oxygen free radicals initiate the vascular dysfunction or whether there is an initial trigger that initiates both processes will need to be further clarified in future studies.     

Microcirculation and tolerability following i.v. infusion of PGE1 and iloprost: a randomized cross-over study in patients with critical limb ischemia

In a randomized cross-over study, the effect of PGE(1) and iloprost on microcirculation as well as the tolerability was investigated in 36 patients with peripheral arterial occlusive disease stage III and IV according to Fontaine. Patients received PGE(1) and iloprost by single 3-h i.v. infusions on two different days at doses recommended by the manufacturers or in previous studies (PGE(1): first hour 20 microg, next 2h 30 microg each. Iloprost: first hour 0.5 ng/kg/min, next 2h 1.0 ng/kg/min). Transcutaneous oxygen pressure (tcPO(2)) values increased much more with PGE(1). Median tcPO(2) increase over baseline 30 min after the end of infusion was 9 and 2 mmHg for PGE(1) and iloprost, respectively, corresponding to median AUC differences from baseline of 1050 and 210 min mmHg. Because of its exploratory character, the study was not powered to test for significance. Adverse effects occurred in 19.4% (PGE(1)) and 30.6% (iloprost) of patients. Dose reduction was required in 3 patients receiving iloprost (hypotension, nausea, irritation of the infused vein), and in none receiving PGE(1).     

Influence of acute alcohol intake and alcohol withdrawal on circulating levels of IL-6, IL-8, IL-10 and IL-12

Cytokine balance alterations are responsible for some of the systemic and hepatic manifestations of alcoholism. The present study was aimed to evaluate the influence of both acute alcohol abstinence (in alcoholics) and acute alcohol intake (in healthy subjects) on serum IL-6, IL-8, IL-10, and IL-12 levels. Serum cytokine concentrations were determined on admission and after a median of 6 days of ethanol abstinence in 29 patients with alcohol withdrawal syndrome. The same determinations were made in five healthy volunteers at baseline and after 36 h of a single 60 g-dose alcohol intake. Increased serum levels of IL-6, IL-10 and, to a lesser extent IL-8, declined in the few days after alcohol abstinence in patients with alcohol withdrawal syndrome. Serum IL-8 values increased after alcohol intake in healthy subjects. Rapid variation of serum cytokine levels along with alcohol intake or abstinence should be taken into account in cytokine studies in alcohol abusers.     

Nifedipine decreases sVCAM-1 concentrations and oxidative stress in systemic sclerosis but does not affect the concentrations of vascular endothelial growth factor or its soluble receptor 1

Microvascular injury, oxidative stress, and impaired angiogenesis are prominent features of systemic sclerosis (SSc). We compared serum markers of these phenomena at baseline and after treatment with nifedipine in SSc patients. Forty successive SSc patients were compared with 20 matched healthy subjects. All SSc patients stopped taking calcium-channel blockers 72 hours before measurements. Twenty SSc patients were also examined after 14 days of treatment with nifedipine (60 mg/day). Quantitative ELISA was used to measure the serum concentrations of vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGFR-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), carbonyl residues, and advanced oxidation protein products (AOPP). The median concentrations of VEGF, sVEGFR-1, sVCAM-1, carbonyl residues, and AOPP were significantly higher in SSc patients than in healthy subjects at baseline. A correlation was found between VEGF concentration and carbonyl residue concentration (r = 0.43; P = 0.007). Nifedipine treatment led to a significant decrease in concentrations of sVCAM-1, carbonyl residues, and AOPP but did not affect concentrations of VEGF and sVEGFR-1. Nifedipine treatment ameliorated endothelium injury in patients with SSc, as shown by the concentrations of adhesion molecules and oxidative damage markers. The fact that VEGF and sVEGFR-1 concentrations were not changed whereas oxidative stress was ameliorated by nifedipine is consistent with the hypothesis that VEGF signalling is impaired in SSc. However, more experimental evidence is needed to determine whether the VEGF pathway is intrinsically defective in SSc.     

Systemic Sclerosis Sera Impair Angiogenic Performance of Dermal Microvascular Endothelial Cells: Therapeutic Implications of Cyclophosphamide

In systemic sclerosis (SSc), dermal capillaries are progressively lost with consequent chronic tissue hypoxia insufficiently compensated by angiogenesis. Clinical studies reported that intravenous cyclophosphamide (CYC) may improve SSc-related peripheral microvascular damage. Recently, we showed that CYC treatment may normalize SSc sera-induced abnormalities in endothelial cell-matrix interactions. Our objective was to evaluate in vitro the effects of sera from treatment-naïve or CYC-treated SSc patients on dermal blood microvascular endothelial cell (dMVEC) angiogenesis, migration, proliferation and apoptosis. dMVECs were challenged with sera from 21 SSc patients, treatment-naïve (n = 8) or under CYC treatment (n = 13), and 8 healthy controls. Capillary morphogenesis on Geltrex matrix was significantly reduced upon challenge with sera from naïve SSc patients compared with healthy controls. When dMVECs were challenged with sera from CYC-treated SSc patients, their angiogenic capacity was comparable to that of cells treated with healthy sera. Wound healing capacity and chemotaxis in Boyden chamber were both significantly decreased in the presence either of naïve or CYC-treated SSc sera compared with healthy sera. WST-1 assay revealed that cell proliferation was significantly decreased in dMVECs challenged with sera from naïve SSc patients compared with healthy sera. Conversely, dMVEC proliferation was not impaired in the presence of sera from CYC-treated SSc patients. Accordingly, the percentage of TUNEL-positive apoptotic dMVECs was significantly higher in the presence of sera from naïve SSc patients than healthy controls, while CYC-treated SSc sera did not induce dMVEC apoptosis. Levels of the angiostatic mediators endostatin, pentraxin 3, angiostatin and matrix metalloproteinase-12 were all significantly elevated in sera from naïve SSc patients compared with sera from both healthy controls and CYC-treated SSc patients. In SSc, CYC treatment might boost angiogenesis and consequently improve peripheral microangiopathy through the normalization of the endothelial cell-matrix interactions, reduction of endothelial cell apoptosis and rebalance of dysregulated angiostatic factors.     

Intracellular free radical production by peripheral blood T lymphocytes from patients with systemic sclerosis: role of NADPH oxidase and ERK1/2

IntroductionAbnormal oxidative stress has been described in systemic sclerosis (SSc) and previous works from our laboratory demonstrated an increased generation of reactive oxygen species (ROS) by SSc fibroblasts and monocytes. This study investigated the ability of SSc T lymphocytes to produce ROS, the molecular pathway involved, and the biological effects of ROS on SSc phenotype.MethodsPeripheral blood T lymphocytes were isolated from serum of healthy controls or SSc patients by negative selection with magnetic beads and activated either with PMA or with magnetic beads coated with anti-CD3 and anti-CD28 antibodies. Intracellular ROS generation was measured using a DCFH-DA assay in a plate reader fluorimeter or by FACS analysis. CD69 expression and cytokine production were analyzed by FACS analysis. Protein expression was studied using immunoblotting techniques and mRNA levels were quantified by real-time PCR. Cell proliferation was carried out using a BrdU incorporation assay.ResultsPeripheral blood T lymphocytes from SSc patients showed an increased ROS production compared to T cells from healthy subjects. Since NADPH oxidase complex is involved in oxidative stress in SSc and we found high levels of gp91phox in SSc T cells, SSc T cells were incubated with chemical inhibititors or specific siRNAs against gp91phox. Inhibition of NADPH oxidase partially reverted CD69 activation and proliferation rate increase, and significantly influenced cytokine production and ERK1/2 activation.ConclusionsSSc T lymphocityes are characterized by high levels of ROS, generated by NADPH oxidase via ERK1/2 phosphorylation, that are essential for cell activation, proliferation, and cytokine production. These data confirm lymphocytes as key cellular players in the pathogenesis of systemic sclerosis and suggest a crucial link between ROS and T cell activation.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0591-8) contains supplementary material, which is available to authorized users.     

Interindividual variability in the enantiomeric disposition of ibuprofen following the oral administration of the racemic drug to healthy volunteers

The plasma disposition of the enantiomers of ibuprofen has been investigated following the oral administration of the racemic drug (400 mg) to 24 healthy male volunteers. The plasma elimination of (R)-ibuprofen was found to be more rapid than that of the S-enantiomer [plasma half-life: (R) 2.03 h; (S) 3.05 h; 2P less than 0.001], resulting in a progressive enrichment in the plasma content of this isomer, some 64% of the total area under the plasma concentration time curves (AUC) being due to the pharmacologically active enantiomer. The influence of dose on the pharmacokinetic characteristics of the enantiomers of ibuprofen, over the range 200-800 mg, was investigated in three subjects. Examination of dose-normalized AUC values and oral clearance indicate the dose dependence of (R)-ibuprofen disposition.     

Activin,a Grape Seed-derived Proanthocyanidin Extract,Reduces Plasma Levels of Oxidative Stress and Adhesion Molecules (ICAM-1, VCAM-1 and E-selectin) in Systemic Sclerosis

This study evaluated whether a new generation antioxidant Activin derived from the grape seed proanthocyanidins, could reduce the induction of the adhesion molecules as a result of inflammatory response in the plasma of systemic sclerosis (SSc) patients. SSc patients were divided into two groups: one group was treated with Activin, a grape seed‐derived proanthocyanidins, while the other group served as control. Patients were given Activin 100 mg/day orally for one month after which the blood samples were withdrawn from both groups of the patients. Blood was also taken from normal human volunteers. Plasma was obtained in fasting state between 8 to 9 A.M. from two groups of SSc patients and controls. Soluble adhesion molecules including ICAM‐1, VCAM‐1, E‐selectin and P‐selectin as well as malonaldehyde, a marker for oxidative stress, were measured. The results of our study demonstrated up‐regulation of these soluble adhesion molecules except for P‐selectin, in the plasma of the SSc patients compared to those obtained from human volunteers. Activin significantly attenuated the increased expression of these adhesion molecules. In addition, there was a significant increase in the amount of malondialdehyde formation in the plasma of the SSc patients, which was also attenuated by Activin. The results of this study demonstrated that Activin could reduce the inflammatory response and the oxidative stress developed in SSc patients.     

Personal Authentication Analysis Using Finger-Vein Patterns in Patients with Connective Tissue Diseases—Possible Association with Vascular Disease and Seasonal Change -

Objective

To examine how connective tissue diseases affect finger-vein pattern authentication.

Methods

The finger-vein patterns of 68 patients with connective tissue diseases and 24 healthy volunteers were acquired. Captured as CCD (charge-coupled device) images by transmitting near-infrared light through fingers, they were followed up in once in each season for one year. The similarity of the follow-up patterns and the initial one was evaluated in terms of their normalized cross-correlation C.

Results

The mean C values calculated for patients tended to be lower than those calculated for healthy volunteers. In midwinter (February in Japan) they showed statistically significant reduction both as compared with patients in other seasons and as compared with season-matched healthy controls, whereas the values calculated for healthy controls showed no significant seasonal changes. Values calculated for patients with systemic sclerosis (SSc) or mixed connective tissue disease (MCTD) showed major reductions in November and, especially, February. Patients with rheumatoid arthritis (RA) and patients with dermatomyositis or polymyositis (DM/PM) did not show statistically significant seasonal changes in C values.

Conclusions

Finger-vein patterns can be used throughout the year to identify patients with connective tissue diseases, but some attention is needed for patients with advanced disease such as SSc.     

Activin,a grape seed-derived proanthocyanidin extract,reduces plasma levels of oxidative stress and adhesion molecules (ICAM-1, VCAM-1 and E-selectin) in systemic sclerosis

This study evaluated whether a new generation antioxidant Activin derived from the grape seed proanthocyanidins, could reduce the induction of the adhesion molecules as a result of inflammatory response in the plasma of systemic sclerosis (SSc) patients. SSc patients were divided into two groups: one group was treated with Activin, a grape seed-derived proanthocyanidins, while the other group served as control. Patients were given Activin 100 mg/day orally for one month after which the blood samples were withdrawn from both groups of the patients. Blood was also taken from normal human volunteers. Plasma was obtained in fasting state between 8 to 9 A.M. from two groups of SSc patients and controls. Soluble adhesion molecules including ICAM-1, VCAM-1, E-selectin and P-selectin as well as malonaldehyde, a marker for oxidative stress, were measured. The results of our study demonstrated up-regulation of these soluble adhesion molecules except for P-selectin, in the plasma of the SSc patients compared to those obtained from human volunteers. Activin significantly attenuated the increased expression of these adhesion molecules. In addition, there was a significant increase in the amount of malondialdehyde formation in the plasma of the SSc patients, which was also attenuated by Activin. The results of this study demonstrated that Activin could reduce the inflammatory response and the oxidative stress developed in SSc patients.