Perspectives on the interlinked nature of systemic sclerosis and reflux disease.

INTRODUCTION: Systemic sclerosis (SSc) is a multisystem connective tissue disease, characterized by chronic inflammation and vascular changes that result in esophageal smooth muscle atrophy and fibrosis. Subsequent progressive loss of peristalsis in the distal esophagus and loss of lower esophageal sphincter function lead to problems with the protective barrier and exposure of sensitive tissues to the gastroduodenal contents, a disorder called reflux disease. Areas covered: Depending on the range, nature and symptoms of the disease, the term 'reflux disease' may refer to gastroesophageal reflux, laryngopharyngeal reflux, microaspiration into the airways and silent reflux. Despite the links between these visceral complications, this connection remains controversial. This is due to a lack of complete understanding, the asymptomatic nature of the disease and the limited diagnostic accuracy of tests, which can delay diagnosis. Such delays are problematic, given that the early detection of GERD in SSc patients, the timing of assessment, the treatment of the organs involved are critical aspects of patient prognosis and disease outcome. Expert commentary: This review summarizes the most recent knowledge about the pathophysiology, diagnosis and prospective treatment of GERD in SSc patients and highlights how innovative technologies applied through an integrative, interdisciplinary approach may soon lead to effective treatment strategies.

The Profile of Serum Transferrin Isoforms in Rheumatoid Arthritis.

INTRODUCTION: Transferrin, a microheterogeneous iron-transporting N-glycoprotein, is an optimal model for the analysis of the glycosylation profile in rheumatoid arthritis (RA). The aim of this study was to assess the transferrin isoforms profile in RA patients at the time of diagnosis and then look into their associations with disease activity. METHODS: Serum samples were collected from 48 patients with RA. The patients were males (6) and females (42) (age range: 33-85 years). Control group consisted of 30 healthy volunteers. Transferrin isoforms were analysed by capillary electrophoresis on MINICAP electrophoretic system. RESULTS: There was a significant decrease in the relative concentrations of trisialo- (mean ± SD; 2.130 ± 1.112) and pentasialotransferrin (13.562 ± 3.088), and significant increase in tetrasialotransferrin (83.640 ± 3.165) in RA patients when compared to the control group (3.615 ± 1.156; 76.840 ± 5.621; 18.610 ± 6.027, respectively) (U Mann-Whitney test: p < 0.001 for all comparisons). There were no significant changes in the disialotransferrin concentrations in RA patients. Trisialotransferrin concentration correlated with RA activity expressed as DAS 28 in RA patients (p < 0.001). The low trisialotransferrin concentration was also associated with high platelet count and high ESR (p < 0.001 for both). Disialo-, tetrasialo- and pentasialotransferrin concentrations did not correlate with DAS 28. CONCLUSIONS: In patients with RA the serum profile of transferrin isoforms is altered. We predict that the levels of trisialylated isoforms of transferrin will serve as a useful biochemical marker of the RA activity.

Pain, fatigue and functional disability are associated with higher educational needs in systemic sclerosis: a cross-sectional study.

In the process of the planned and systematic education of patients/families, it is extremely important to identify patients' health problems as well as their needs and expectations. The objective of this study was to determine the relationship between functional disability, health problems and perceived educational needs in people with systemic sclerosis (SSc). This was a cross-sectional analytic study conducted in six rheumatology centers in Poland. Functional disability was measured using HAQ-DI, and the magnitude of other health problems (pain, fatigue, intestinal problems, breathing problems, Raynaud's phenomenon, finger ulcerations) was measured using 0-100 mm visual analogue scales. The educational needs were measured using the Polish version of the Educational Needs Assessment Tool (Pol-ENAT). Spearman's correlation coefficient (rs) was used to report associations. The sample comprised 140 patients, 125 (89.28%) were women. They had a mean (SD) age of 54 (14.23) and disease duration of 11 (10.27) years. The median (IQR) HAQ-DI was 1.12 (0.62-1.62) and mean ENAT score was 71.54 (SD 27.72). Patients needed to know more about the disease process, self-help measures and managing pain. All health problems had significant correlations with the overall educational needs, pain, functional disability and fatigue having the highest rs = 0.359, p < 0.0001; rs = 0.314, p < 0.001 and rs = 0.270, p = 0.001, respectively. Health problems in people with SSc are associated with considerable educational needs; therefore, health professionals should take this into account when planning patient education. Group interventions should consider providing patient education related to disease process as a minimum.

Independence of carbohydrate-deficient isoforms of transferrin and cyclic citrullinated peptides in rheumatoid arthritis.

OBJECTIVE: The aim of this study was to assess the relationship between the two types of posttranslational modifications of proteins in RA: glycosylation on the example of carbohydrate-deficient transferrin and citrullination by means of autoantibodies to cyclic citrullinated peptides. METHODS: The study was carried out in 50 RA patients. CDT was measured using N Latex CDT immunonephelometric test, the results were presented in absolute and relative units. Anti-CCP were measured using the chemiluminescent method and rheumatoid factor by immunoturbidimetric method. RESULTS: 80% of RA patients were positive for anti-CCP, 70% for RF and 62% for both, anti-CCP and RF. The level of %CDT was significantly elevated, but absolute CDT level was not changed. The mean absolute CDT concentration was higher in anti-CCP positive patients than that in anti-CCP negative. CDT (absolute and relative concentration) did not correlate with anti-CCP and RF. However, serum RF significantly correlated with anti-CCP. %CDT did not correlate with anti-CCP, but absolute level correlated with anti-CCP only in anti-CCP negative and RF negative patients. CDT did not correlate with RF, but solely with anti-CCP in anti-CCP negative patients. Anti-CCP correlated with DAS 28 only in anti-CCP negative RA, but CDT (absolute and relative units) correlated with DAS 28 in all patients and in anti-CCP positive RA. CONCLUSIONS: These results suggest that the changes in CDT and anti-CCP concentrations are not associated with oneself and indicate on the independence of these posttranslational modifications in rheumatoid arthritis. Only the alterations in transferrin glycosylation reflected the activity of RA.

Independence of carbohydrate-deficient isoforms of transferrin and cyclic citrullinated peptides in rheumatoid arthritis / Independência de isoformas de transferrina deficiente em carboidrato e peptídeos citrulinados cíclicos na artrite reumatoide

ABSTRACT Objective: The aim of this study was to assess the relationship between the two types of posttranslational modifications of proteins in RA: glycosylation on the example of carbohydrate-deficient transferrin and citrullination by means of autoantibodies to cyclic citrullinated peptides. Methods: The study was carried out in 50 RA patients. CDT was measured using N Latex CDT immunonephelometric test, the results were presented in absolute and relative units. Anti-CCP were measured using the chemiluminescent method and rheumatoid factor by immunoturbidimetric method. Results: 80% of RA patients were positive for anti-CCP, 70% for RF and 62% for both, anti-CCP and RF. The level of %CDT was significantly elevated, but absolute CDT level was not changed. The mean absolute CDT concentration was higher in anti-CCP positive patients than that in anti-CCP negative. CDT (absolute and relative concentration) did not correlate with anti-CCP and RF. However, serum RF significantly correlated with anti-CCP. %CDT did not correlate with anti-CCP, but absolute level correlated with anti-CCP only in anti-CCP negative and RF negative patients. CDT did not correlate with RF, but solely with anti-CCP in anti-CCP negative patients. Anti-CCP correlated with DAS 28 only in anti-CCP negative RA, but CDT (absolute and relative units) correlated with DAS 28 in all patients and in anti-CCP positive RA. Conclusions: These results suggest that the changes in CDT and anti-CCP concentrations are not associated with oneself and indicate on the independence of these posttranslational modifications in rheumatoid arthritis. Only the alterations in transferrin glycosylation reflected the activity of RA.

RESUMO Objetivo: Avaliar a relação entre os dois tipos de modificações pós-translacionais de proteínas na AR: glicosilação no caso da transferrina deficiente em carboidrato (TDC) e citrulinação por meio dos anticorpos no caso do antipeptídeo citrulinado cíclico (anti-CCP). Métodos: O estudo foi feito em 50 pacientes com AR. A TDC foi medida com o teste imunonefelométrico N Latex CDT e os resultados foram apresentados em unidades absolutas e relativas. O anti-CCP foi mensurado com o método quimioluminescente e o fator reumatoide (FR) pelo método imunoturbidimétrico. Resultados: Dos pacientes com AR, 80% foram positivos para anti-CCP, 70% para FR e 62% para ambos (anti-CCP e FR). A percentagem de transferrina total (%TDC) esteve significativamente elevada, mas o nível absoluto de TDC não esteve alterado. A concentração média de TDC absoluta foi maior nos pacientes anti-CCP positivos do que naqueles anti-CCP negativos. A TDC (concentração absoluta e relativa) não se correlacionou com o anti-CCP e o FR. No entanto, o FR sérico se correlacionou significativamente com o anti-CCP. O percentual de TDC não se correlacionou com o anti-CCP, mas seu nível absoluto se correlacionou com o anti-CCP apenas em pacientes FR negativos e anti-CCP negativos. A TDC não se correlacionou com o FR, somente com o anti-CCP em pacientes anti-CCP negativos. O anti-CCP se correlacionou com o DAS 28 apenas nos pacientes com AR anti-CCP negativos, mas a TDC (unidades absolutas e relativas) se correlacionou com o DAS 28 quando considerados todos os pacientes com AR e em pacientes com AR anti-CCP positivos. Conclusões: Esses resultados sugerem que as alterações na TDC e as concentrações de anti-CCP não estão associadas e indicam a independência dessas modificações pós-translacionais na artrite reumatoide. Apenas as alterações na glicosilação da transferrina refletem a atividade da AR.

Comparative analysis of educational needs of patients with rheumatic diseases selected based on the Polish version of the Educational Needs Assessment Tool (Pol-ENAT).

OBJECTIVES: Chronic rheumatic diseases, which have a progressive course, lead to large deficits in physical, mental and social functioning. In the process of the planned and systematic education of patients/families, it is extremely important to identify patients' health problems as well as their needs and expectations. Study objectives: To assess the learning needs of patients with rheumatoid arthritis (RA) and systemic sclerosis (SSc). MATERIAL AND METHODS: This was a multicenter, cross-sectional study conducted in seven rheumatology centers in Poland. Health problems were defined as disability (HAQ-DI), pain (Pain VAS), fatigue (Fatigue VAS) and severity of disease (0-100). The educational needs were measured using the Pol-ENAT (0-156). Statistical analysis was performed using PQStat v.1.4.2 and Excel. RESULTS: The study involved 277 patients with rheumatoid arthritis and 140 with systemic sclerosis. The average age of respondents was comparable in RA (53.3 ±13.0 years) and SSc (54.1 ±14.2 years). Patients suffered from RA on average for 13.7 ±10.6 years and from SSc for 10.9 ±10.3 years. With age and duration of disease, the health problems worsened (p < 0.05). The reported needs of education (Pol-ENAT) were generally at the secondary level - RA 66.4 ±29.3 - younger people (p = 0.008) and those with early RA (r = -0.151, p = 0.011); SSc 71.5 ±27.7 - regardless of age and duration of SSc. Educational needs of patients with SSc correlated with the severity of certain health problems and health evaluation (pain r = 0.334, p < 0.001; fatigue r = 0.243, p = 0.004; severity of disease r = 0.242, p = 0.004 and disability r = 0.291, p < 0.001). CONCLUSIONS: All patients reported the need for education, although it was slightly higher in patients with SSc. There was a decline in interest in education with progressive disability in RA, while in SSc interest in education increased with the progress and severity of the disease.

Assessment of education requirements for patients with rheumatoid arthritis, based on the Polish version of the Educational Needs Assessment Tool (Pol-ENAT), in the light of some health problems - A cross-sectional study.

INTRODUCTION: Patients with chronic rheumatoid arthritis (RA) need advice in order to face the problems of everyday life, as well as suffering associated with the disease. Health professionals should attempt to raise the level of resourcefulness and independence of the patient. OBJECTIVE: To assess the relationship between the deficit of knowledge about RA and the degree of pain, fatigue, morning stiffness, assessment of disease activity as well as functional efficiency. MATERIALS AND METHOD: The study was conducted on 277 patients with RA in 7 rheumatologic centres in Poland. The method applied was the questionnaire Pol-ENAT (0-156); HAQ DI (0-3); analog scales (0-100). RESULTS: Mean (SD) age was 53.28 (13.01) and disease duration 13.70 (10.63) years. The mean (SD) value was 54.93 (23.17) for pain, 52.97 (21.98) for fatigue, 48.28 (24.76) for morning stiffness (0-100 mm). HAQ DI was 1.40 (0.66), with an upward trend with duration of disease (p<0.001). There was a positive correlation between the demand for knowledge about the movement (r=0.194; p=0.001), self-care (r=0.134; p=0.026), assistance/support(r =0.163; p=0.006) and morning stiffness experienced. There was a negative correlation between the need for knowledge concerning managing pain, feelings and the arthritis process and daily ability assessed with HAQ DI. CONCLUSIONS: The study shows that health education should be targeted at young patients with early RA. In the case of the severity of morning joints stiffness, there is a need to increase knowledge about the methods of mobility aids, self-care and the possibility of obtaining support.

Changes of glycosylation of IgG in rheumatoid arthritis patients treated with methotrexate.

PURPOSE: In patients with active rheumatoid arthritis (RA) decrease of galactosylation is correlated with disease activity. The aim of our study was to evaluate an effect of methotrexate therapy on glycosylation disturbances of IgG in RA patients. MATERIALS/METHODS: IgG glycosylation in 40 patients with active RA treated with methotrexate for 12 months prior to and after treatment were compared. The control group consisted of 20 healthy volunteers. IgG glycosylation was assessed using biotinylated lectins and immunosorbent ELISA assay. For galactose specificity Datura stramonium lectin (DSA), for sialic acid Sambucus nigra (SNA) and Maackia amurensis (MAA) and for fucose residue Areulia auranta (AAA) lectins were used. RESULTS: In RA-cases N-glycan galactosylation and sialylation of IgG before treatment were significantly lower than in healthy subjects (for DSA, MAA lectins p<0.001 and SNA p<0.05). Significant increase of IgG galactosylation and sialylation in RA patients after therapy (for DSA, MAA and SNA lectin p<0.05) was detected. Moreover the glycosylation disturbances of N-glycan IgG were strongly associated with changes of disease activity based on disease activity score. For fucose residues significantly higher absorbency of AAA lectin in RA patients before treatment was observed compared to control subjects (p<0.05) and slightly, not significantly decreased after MTX therapy. CONCLUSIONS: Defect of galactosylation of IgG in RA patients is a useful marker of disease activity that may be used for the assessment of therapy effectiveness. The role of IgG fucosylation and sialylation in RA pathogenesis has still to be determined.

The onset of lipid peroxidation in rheumatoid arthritis: consequences and monitoring.

Several epidemiological studies propose the association of rheumatoid arthritis (RA) with oxidative stress. The aim of this study was to estimate the possible onset of systemic lipid peroxidation in RA patients and its relevance for pathophysiology and monitoring of RA. Seventy-three patients with RA and 73 healthy subjects were included in the study. Lipid peroxidation was estimated by the measurement of 4-hydroxynonenal (4-HNE), 4-hydroxyhexenal, malondialdehyde, acrolein, crotonaldehyde, 4-oxononenal, and isoprostanes (8-isoPGF(2α)) levels. Cytosolic phospholipase A(2) (cPLA(2)), platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase (GSH-Px) activities and vitamin E levels were also determined. In parallel, the plasma levels of phospholipid arachidonic acid (AA), linoleic acid (LA), and 4-HNE-protein adducts were monitored. Plasma of RA patients had increased vitamin E levels, but decreased GSH-Px activity and phospholipid AA and LA levels when compared to levels of the healthy subjects. The levels of aldehydes were significantly increased in the plasma of the RA patients and even more in urine. Significant increases in HNE-modified protein adducts was observed for the first time in plasma of RA patients, while the activities of PAF-AH and cPLA(2) were decreased. The 8-isoPGF(2α) levels were 9-fold higher in plasma and 3-fold higher in urine of RA patients and were related to the severity of disease. The levels of lipid peroxidation products in plasma and in urine suggest the relationship between lipid peroxidation and the development of RA. Additionally, urine 8-isoPGF(2α), plasma 4-HNE and 4-HNE-protein adducts appear to be convenient biomarkers to monitor progression of this autoimmune disease.

[Systemic sclerosis. Part 2. Epigenetic factors in the pathogenesis of clinical manifestations]. / Twardzina ukladowa. Czesc 2. Czynniki epigenetyczne w patogenezie objawów klinicznych.

Systemic sclerosis is a complex autoimmune disease characterized by immune activation, fibrosis of the skin and internal organs and vasculopathy affecting predominantly the microvessels with a predilection for women. The genetic background of systemic sclerosis is still full of unanswered questions, with classical genetics able to explain only some systemic sclerosis cases. Novel advances concerning epigenetics give us new insight into pathogenesis of systemic sclerosis. This review focuses on results of recent reports on epigenetic modifications of the gene functions and X inactivation changes in pathogenesis of systemic sclerosis. Current evidence demonstrates DNA heavy methylation (FLI1, NOS3, BMPRII) and hypomethylation of regulatory genes (CD40L, CD70), histone code modifications, abnormal expression of large spectrum of microRNAs.

Developing the Polish Educational Needs Assessment Tool (Pol-ENAT) in rheumatoid arthritis and systemic sclerosis: a cross-cultural validation study using Rasch analysis.

OBJECTIVES: To undertake cross-cultural adaptation and validation of the educational needs assessment tool (ENAT) for use with people with rheumatoid arthritis (RA) and systemic sclerosis (SSc) in Poland. METHODS: The study involved two main phases: (1) cross-cultural adaptation of the ENAT from English into Polish and (2) Cross-cultural validation of Polish Educational Needs Assessment Tool (Pol-ENAT). The first phase followed an established process of cross-cultural adaptation of self-report measures. The second phase involved completion of the Pol-ENAT by patients and subjecting the data to Rasch analysis to assess the construct validity, unidimensionality, internal consistency and cross-cultural invariance. RESULTS: An adequate conceptual equivalence was achieved following the adaptation process. The dataset for validation comprised a total of 278 patients, 237 (85.3 %) of which were female. In each disease group (145, RA and 133, SSc), the 7 domains of the Pol-ENAT were found to fit the Rasch model, X (2)(df) = 16.953(14), p = 0.259 and 8.132(14), p = 0.882 for RA and SSc, respectively. Internal consistency of the Pol-ENAT was high (patient separation index = 0.85 and 0.89 for SSc and RA, respectively), and unidimensionality was confirmed. Cross-cultural differential item functioning (DIF) was detected in some subscales, and DIF-adjusted conversion tables were calibrated to enable cross-cultural comparison of data between Poland and the UK. CONCLUSION: Using a standard process in cross-cultural adaptation, conceptual equivalence was achieved between the original (UK) ENAT and the adapted Pol-ENAT. Fit to the Rasch model, confirmed that the construct validity, unidimensionality and internal consistency of the ENAT have been preserved.

Regulation of serum matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 following rituximab therapy in patients with rheumatoid arthritis refractory to anti-tumor necrosis factor blockers.

In our article, we evaluated the regulatory effects of the infusions of rituximab, a monoclonal antibody directed against CD20(+) B cells, on the serum matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in patients with active rheumatoid arthritis (RA) not responding to anti-tumor necrosis factor (anti-TNF) therapy. Twelve RA patients were planned to receive four infusions of 1,000 mg of rituximab at weeks 0, 2, 24 and 26. The therapy was combined with methotrexate (MTX) (20-30 mg/week). Seven patients were refractory to previously received infliximab, and five to etanercept. Serum concentrations of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9) and TIMP-1 were measured by ELISA on weeks 0, 2, 12, 24, 36 and 52. Initial infusion of rituximab downregulated serum MMP-1 (p < 0.01), MMP-3 (p < 0.001), MMP-9 (p < 0.001) and TIMP-1 (p < 0.05) levels. Second drug administration caused even more remarkable reduction of measured MMPs (p < 0.001 in all cases) and TIMP-1 level (p < 0.01). These findings were accompanied by significantly decreased ratios of measured MMPs to TIMP-1. Next rituximab infusions on weeks 24 and 26 sustained the suppression of serum MMPs levels. Prior to the initial rituximab infusion, serum concentrations of studied MMPs and TIMP-1 significantly correlated with markers of RA activity such as disease activity score (DAS28) and CRP levels. Rituximab therapy, beside a rapid clinical improvement, reduced serum MMPs concentrations in RA patients refractory to anti-TNF treatment. Repeated infusions of rituximab maintained initial serum MMPs suppression.

Fibroblast-Like Synovial Cells in Rheumatoid Arthritis--the Impact of Infliximab on Hexosaminidase Activity.

BACKGROUND: The effect of multiple infusions of infliximab (INF), a chimeric anti-tumor necrosis factor alpha antibody, on the concentration of hexosaminidase (HEX) activity in a synovial cell culture derived from human synovial inflamed fluid obtained from patients suffering from rheumatoid arthritis (RA) has been evaluated. OBJECTIVES: The aim of this study was to prove INF efficacy in RA. MATERIAL AND METHODS: Inflamed synovial fluid was taken from RA patients (a study group) and patients who had undergone knee trauma within 7 days (a control group). The following solutions of infliximab were used: 40, 60 and 140 µg/mL. Determination of the concentration of HEX activity in cell cultures was performed after 24, 48, 72 and 96 h of infliximab administration. To identify synoviocytes in cell culture immunohistochemical staining with vimentin and pancytokeratin was performed. RESULTS: A predominance of fibroblast-like synovial cells has been observed in the study group. In the control group the concentration of HEX activity without adding infliximab to the cell culture was 283.00 nkat/mL. After 96 h of incubation with infliximab, the concentrations of HEX activity in cultured synoviocytes according to infliximab doses of 40, 60 and 140 µg/mL were respectively: 280.00, 271.50 and 293.50 nkat/mL. In the study group, the concentration of HEX activity without adding infliximab to the cell culture was 542.27 nkat/mL. The final concentrations of HEX activity of cultured fibroblast-like synovial cells measured after 96 h of incubation with infliximab were: 471.72, 498.27 and 556.72 nkat/mL, according to infliximab doses of 40, 60 and 140 µg/mL. In all groups (besides the infliximab concentration of 140 µg/mL after 96 h of incubation), the level of concentration of HEX activity was significantly higher in the study group compared to the control group, irrespective of infliximab concentration and time of infliximab incubation. CONCLUSIONS: Infliximab changes the concentration of HEX activity depending on the drug dose and time of administration.

[Pulmonary manifestations in rheumatoid arthritis]. / Manifestacje plucne w reumatoidalnym zapaleniu stawów.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by destructive cartilages, bones and other structures formed joints. RA belongs to connective tissue diseases represented by systemic nature, internal illness, extra-articular features and rapidly progress of atherosceirosis. The extra-articular complications cause the reduction of patient longevity. The frequency of symptoms in patient with RA and respiratory disorders occur in 10-20% of cases. Pulmonary complications are the second most common cause of premature of patient deaths. Respiratory disorders associated with RA are devided into 3 groups: infection, lung disease caused by drugs and pulmonary manifestation connected by RA. These last affect interstitial tissue, bronchioli, pulmonary vessels, pleura, also are presented by pulmonary rheumatoid nodules and pulmonary hypertension.

Salivary: flow and proteins of the innate and adaptive immunity in the limited and diffused systemic sclerosis.

BACKGROUND: However, there are some informations on the salivary glands involvement in systemic sclerosis, and there is a lack of any data about salivary glands function depending on systemic sclerosis subsets. METHODS: The unstimulated and stimulated salivary flow, the activity of peroxidase, the total amount of lactoferrin, lysozyme and sIgA were determined in two subgroups of systemic sclerosis and healthy controls. RESULTS: In the unstimulated saliva of both patients groups, the salivary flow, the output of total protein and peroxidase activity were significantly lower; the total: sIgA and lactoferrin were significantly higher as compared with the control. In the stimulated saliva of the patients with limited form, the total lysozyme and peroxidase activity were significantly higher than in the control. In the stimulated saliva of the patients with diffused form, the salivary flow was significantly lower and the total sIgA and peroxidase activity were significantly higher than in the control. CONCLUSION: Systemic sclerosis regardless of its subset affects salivary defense system of human unstimulated and stimulated saliva. Patients with the limited form experience the same impairment of the submandibular glands function as compared with patients with the diffused form. Only patients with the diffused form are deficient in respect of stimulated saliva secretion; the parotid glands of the patients with the limited form have a good secretory capacity in comparison with the healthy control.

Lipid peroxidation in Rheumatoid arthritis; consequences and monitoring.

The epidemiological studies have shown that rheumatoid arthritis (RA) leads to oxidative stress formation. Therefore the aim of this study has been to estimate the lipid peroxidation in RA patients. Moreover the reasons and consequences of changes in lipid peroxidation were estimated. 73 patients with RA and 62 healthy subjects were included into the study. Lipid peroxidation was estimated by the measurement of phospholipid arachidonic acid (AA) and linoleic acid (LA) as well as aldehydes: 4-hydroxynonenal (4-HNE), 4-hydroxyhexenal (4-HHE), malondialdehyde (MDA), acrolein, crotonaldehyde, and 4-oxononenal (4-ONE) that were determined by GC and GCMS, while 8-isoprostanes (8-isoPGF2a) - was determined by LCMS. Phospholipase A2 (PLA2), platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase (GSH-Px) activity were determined spectrophotometrically, while vitamin E was determined by HPLC. Plasma of RA patients was characterized by higher vitamin E level and decreased GSH-Px activity as well as the level of phospholipid AA and LA compared to healthy subjects. The level of all examined aldehydes was significantly increased in plasma patients but higher increase was observed in urine of RA patients in comparison with control group. The 8-isoprostanes level was approximately 9-fold higher in the plasma and 3-fold higher in the urine of RA patients compared to healthy subjects, but in the urine the changes in 8-isoprostanes level was correlated with RA progression. A significant increase in 4-HNE-modified protein adducts level as well as a decrease in the activity of PAF-AH and PLA2 were observed in the plasma of RA patients. The level of lipid peroxidation products in the plasma and the urine may be the indicator of RA, but additionally urine 8-isoprostanes may be the useful and reliable biomarker of RA progression.

Salivary antioxidants in patients with systemic sclerosis.

BACKGROUND: In spite of relatively large amount of evidence that oxidative stress is implicated in the pathogenesis of systemic sclerosis, there is no study analyzing antioxidants profile of the saliva of these patients. The aim of this study was to compare salivary antioxidants in subjects with systemic sclerosis and the healthy controls. METHODS: The unstimulated and stimulated salivary flow and the specific activity of peroxidase, superoxide dismutase 1, the total amount of uric acid, and total antioxidant status were determined in two subgroups of systemic sclerosis women and healthy controls. RESULTS: A significant increase in the specific activity of peroxidase, a significant decrease in the total amount of uric acid and total antioxidants status in unstimulated saliva as well as a significant increase in all antioxidants examined in stimulated saliva of group with normal salivary flow rate as compared to the healthy controls were observed. Our results showed a significant decrease in the specific activity of peroxidase in unstimulated and a significant decrease in all antioxidants examined in stimulated saliva of the group with hyposalivation as compared to the group with normal salivary flow rate. CONCLUSIONS: Our results prove that impairment of the salivary glands in the course of systemic sclerosis may be attributed to free radicals, and it is correlated with disease duration.

Sialic acid level reflects the disturbances of glycosylation and acute-phase reaction in rheumatic diseases.

In the rheumatic diseases, the changes in the carbohydrate part of serum glycoproteins occur and these abnormalities can be monitored by serum level of total and free sialic acid. The aim of this study was to evaluate the total and free sialic acid level as a marker of inflammation activity (TSA) and the changes in glycosylation of blood glycoproteins (FSA) in rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). Studies were carried out in 50 patients with RA, 24 with SLE and 32 with SSc. TSA concentration was measured with an enzymatic, colorimetric method and FSA with a thiobarbituric method. The serum levels of TSA in RA and SLE patients were significantly increased compared to controls and in RA patients were higher than that in SSc patients. The mean serum level of FSA in RA patients was significantly higher, but in SSc patients significantly lower than that in the controls, and in RA patients was significantly higher than in SLE and in SSc patients. All acute-phase proteins were changed: Positive acute-phase proteins were elevated, and the negative protein was decreased. The positive acute-phase proteins positively correlated with the levels of TSA and FSA in RA and SSc patients. In SLE patients, TSA positively correlated with haptoglobin and α1-antitrypsin. In RA patients, there was the positive correlation of TSA and FSA with DAS 28. The changes in the serum levels of TSA and FSA in the course of rheumatic diseases could reflect the abnormalities in glycosylation/sialylation patterns of glycoproteins induced by acute-phase response.

Rheumatoid arthritis patients with xerostomia have reduced production of key salivary constituents.

OBJECTIVE: The aim of this study was to assess the relationship between complaints of xerostomia in patients with rheumatoid arthritis (RA) with the total output of the salivary proteins of innate and adaptive immunity. STUDY DESIGN: The salivary output and specific activity of peroxidase and specific contents of lysozyme, lactoferrin, and secretory immunoglobulin A (sIgA) were determined in xerostomic RA patients, nonxerostomic RA patients, and healthy control subjects. RESULTS: Compared with nonxerostomic RA and healthy control groups, xerostomic RA patients had significantly decreased output of saliva and protein, decreased peroxidase activity, and a significantly lower specific content of peroxidase and sIgA. Compared with the RA control group, xerostomic RA patients had significantly lower specific content of all salivary proteins examined. CONCLUSIONS: The results indicate that xerostomia in patients with RA may be a harbinger of diminished saliva production regarding quantity and quality, and may be indicative of impairment of the salivary immune system of the oral cavity in xerostomic RA patients.

[Monocytic parameters in patients with rheumatologic diseases reflect intensity of depressive disorder]. / Liczba monocytów we krwi chorych reumatologicznych odzwierciedla nasilenie zaburzen depresyjnych.

UNLABELLED: Last years have brought important informations about the changes in white blood cell parameters in patients with depressive disorder and furthermore changes in the levels of cytokine production. The concept of bidirectional communications between the immune system and the central nervous system has been expressed as the 'macrophage theory of depression' and the 'cytokine hypothesis of depression' that described greater expression of monocyte-associated Interleukin-1beta (IL-1beta), Interleukin-1(see text for symbol) (IL-1(see text for symbol)), tumor necrosis factor-alpha (TNF-alpha), Interleukin-6 (IL-6), Interleukin-8 (IL-8) etc., in patients suffering from depression. It was supported by many findings e.g. administration of proinflammatory cytokines in the treatment of cancer and hepatitis C, that induced depressive symptomatology. Generally Depression accompanies a number of illnesses characterized by chronic inflammatory response. The aim of this study was to investigate the association between intensity of depression and blood cells counts in patients attending Rheumatology Department. MATERIALS AND METHODS: Research included 56 patients hospitalized in Department of Rheumatology (Medical University of Bialystok), by the reason of rheumatic arthritis (RA), systemic lupus erythematosus (SLE), ankylosing Spondylitis (AS), systemic scleroderma, Churg-Strauss syndrome (CSS) and psoriatic arthritis (PA). Researched group was presenting by 46 women (mean age 51 years; range 18-73) and 10 men (mean age 50 years; range 27-78). Depressive symptoms were assessed using the Beck Depression Inventory (BDI) and Hamilton Depression Scale (HAM-D). Peripheral blood samples were obtained from all 56 patients for standard blood cell counts. Statistical analysis was performed using Statistica 9.0 pl (Statsoft, Cracov, Poland). Spearman's rank correlation coefficient was used to estimate associations between variables. P-values < 0.05 were considered statistically significant. RESULTS: The mean BDI value was found to be 12 +/- 8 and the mean HAM-D 14 +/- 9. Monocytes ratio significantly correlated with the intensity of depressive symptoms. CONCLUSIONS: Stress and pain increase with illness progression are only fragments of the analyzed problem ground. Although monocytes value remained within the upper limit of normal value, their correlation with depressive symptoms suggests that the serious reason for such a depressive mood state is a high level of monocytes. It indicates on necessity of early diagnosis and treatment of depression associate with chronic proinflammatory diseases. It may be also speculated potential efficiency of an adjunctive treatment with cytokine inhibitors and oxidative stress inhibitory factors in the therapy of depressive disorders.