Interferon Gamma Targeted Therapy: Is It Justified in Primary Sjögren's Syndrome?

Background: The pathomechanism of primary Sjögren syndrome (pSS) is multifactorial. Many cytokines take part in this process, including interferon. The study aimed to quantify certain cytokines involved in the pathomechanism of primary Sjögren syndrome (IL2, IL5, IL6, IL10, IL13, TNFα, IFNγ) and determine their common clinical correlation. On this basis, we discuss the potential use of anti-cytokine drugs in pSS therapy. Methods: The study group consisted of adult patients with a confirmed diagnosis of pSS. Results: The most frequently detected cytokines were IFNγ (82% of patients), TNFα (70%), IL6 (50%), and IL2 (42.5%). In all patients, except for one patient, IFNγ was found in the presence of other specific cytokines. There was no difference in clinical symptoms, age, and laboratory test results between the group of patients with IL-6 + TNFα + IFNγ positive cytokine, and the group of patients in whom they were not detected. There was no correlation between the presence of IL5, IL13, IL2, IL6, IL10, TNFα and musculoskeletal symptoms, skin lesions, glandular domains, pulmonary neurological, lymphadenopathy, biological and hematological domains in ESSDAI (p > 0.05). Conclusions: IFNγ most likely plays a central role in the pathomechanism of the disease. We have not noticed a clinical correlation between the three most common cytokines (IL6, IFNγ and TNFα), preliminary research results open up the possibility of searching for new treatments for pSS. The lower percentage of patients with detectable levels of TNFα and IL6 may explain the ineffectiveness of drugs targeting cytokines in clinical trials to date.

Cardiovascular Risk and Endothelial Dysfunction in Primary Sjogren Syndrome Is Related to the Disease Activity.

The aim of our study was to evaluate if endothelial-dysfunction (ED) occurs in patients with primary Sjogren syndrome (pSS) and whether it is associated with the disease characteristics and activity. A total of 46 patients with pSS and 30 controls, without known cardiovascular disease, were enrolled in this study. A flow-mediated-dilation (FMD) of the brachial artery, plasma concentrations of the nitric oxide (NO) metabolic pathway (ADMA, L-arginine, SDMA, cGMP), and markers of endothelial inflammatory function (PAI-1, sE-selectin) and angiogenesis (angiostatin, VEGF) were analyzed. The FMD was significantly lower in pSS patients (7.56 ± 3.08 vs. 10.91 ± 1.02%, p = 0.043) and positively correlated with the Ro/SS-A-antibodies (r = 0.34, p = 0.03), pulmonary involvement (r = 0.52, p = 0.001) and inversely with ADMA (r = -0.35, p = 0.04). Plasma ADMA, L-arginine and angiostatin levels were significantly higher in pSS patients (0.39 ± 0.08 vs. 0.36 ± 0.06 µmol/L, p = 0.05; 29.07 ± 6.7 vs. 25.4 ± 5.23 µmol/L, p = 0.01; 152.25 ± 60.99 vs. 120.07 ± 38.7 pg/mL, p = 0.0, respectively). ADMA was associated with ESSDAI (r = 0.33, p = 0.02), SCORE (r = 0.57, p = 0.00003) and focus score (r = 0.38, p = 0.04). In the multiple regression analysis, the ESSDAI was significantly and independently associated with plasma ADMA levels (ß = 0.24, p = 0.04). Moreover, plasma cGMP concentrations were negatively correlated with the disease duration (r = -0.31, p = 0.03). Endothelial function is impaired in patients with pSS and associated with the measures of disease activity, which supports the key-role of inflammation in developing and maintaining accelerated atherosclerosis.

The Clinical and Immunological Activity Depending on the Presence of Interferon γ in Primary Sjögren's Syndrome-A Pilot Study.

The upregulation of IFN pathways and their stimulated genes is associated with primary Sjögren's syndrome (pSS). The recent studies also indicate the involvement of interferon γ (IFNγ) in the pathogenesis of pSS. The study aimed to assess the clinical and immunological activity depending on the concentration of IFNγ in the peripheral blood in pSS patients. METHODS: The study group consisted of patients over 18 years of age with a confirmed diagnosis of pSS. Based on the collected data, disease activity was assessed using the EULAR Sjögren's syndrome disease activity index (ESSDAI) and the EULAR Sjögren's syndrome patient reported index (ESSPRI). RESULTS: Among 40 pSS patients, 33 (82%) showed increased levels of IFNγ. The group with positive IFNγ was younger (43 years) than the group with negative IFNγ (57 years) (p < 0.05). In the positive IFNγ group, the time to diagnosis was shorter (p < 0.05). There was a difference in ESSDAI among patients with and without IFNγ (p < 0.05). There were no differences between the groups in ESSPRI and the presence of cryoglobulins, specific anti-SSA, and anti-SSB antibodies and in C3 and C4 hypocomplementemia. RF occurred in both groups with a similar frequency (p = 0.6), but in patients with IFNγ presence, significantly higher RF titers were observed (34.9 vs. 10.5; p < 0.05). CONCLUSION: In the group of patients with positive IFNγ, the mean value of RF and ESSDAI was higher. This group was also younger than patients with pSS without IFNγ.

Role of the eNOS Uncoupling and the Nitric Oxide Metabolic Pathway in the Pathogenesis of Autoimmune Rheumatic Diseases.

Atherosclerosis and its clinical complications constitute the major healthcare problems of the world population. Due to the central role of endothelium throughout the atherosclerotic disease process, endothelial dysfunction is regarded as a common mechanism for various cardiovascular (CV) disorders. It is well established that patients with rheumatic autoimmune diseases are characterized by significantly increased prevalence of cardiovascular morbidity and mortality compared with the general population. The current European guidelines on cardiovascular disease (CVD) prevention in clinical practice recommend to use a 1,5-factor multiplier for CV risk in rheumatoid arthritis as well as in other autoimmune inflammatory diseases. However, mechanisms of accelerated atherosclerosis in these diseases, especially in the absence of traditional risk factors, still remain unclear. Oxidative stress plays the major role in the endothelial dysfunction and recently is strongly attributed to endothelial NO synthase dysfunction (eNOS uncoupling). Converted to a superoxide-producing enzyme, uncoupled eNOS not only leads to reduction of the nitric oxide (NO) generation but also potentiates the preexisting oxidative stress, which contributes significantly to atherogenesis. However, to date, there are no systemic analyses on the role of eNOS uncoupling in the excess CV mortality linked with autoimmune rheumatic diseases. The current review paper addresses this issue.

Silicon intake and plasma level and their relationships with systemic redox and inflammatory markers in rheumatoid arthritis patients.

BACKGROUND: The nutritional significance of silicon for the human body is highlighted by a continually growing body of evidence. In conditions of excessive reactive oxygen species and upregulated immune response, silicon has been observed to provide benefits, but its role in redox and inflammatory status has not yet been examined in rheumatoid arthritis (RA). OBJECTIVES: The aim of this study was to assess the relationship of silicon intake and plasma level to systemic indices of redox status and inflammation in patients with RA. MATERIAL AND METHODS: Silicon intake and plasma levels were measured in 115 RA subjects and 129 control subjects. Serum antioxidant and oxidant levels, antioxidant enzyme activity, and albumin, uric acid, TBARS, hs-CRP, and IL-6 levels were measured and compared to the intake and plasma levels of silicon. RESULTS: Silicon intake and plasma silicon levels were higher in RA subjects than in the controls. In the RA group, a generally favorable correlation to redox and inflammatory markers was found for silicon in diet and in plasma; however, albumin level, smoking status, and gender interfered with these results. In the control subjects, a significant relationship was observed only between plasma silicon and non-enzymatic markers of redox status. CONCLUSIONS: There are suggestions of silicon's involvement in managing redox and inflammatory status in RA, though further studies are warranted.

Diet Quality and Its Relationship with Antioxidant Status in Patients with Rheumatoid Arthritis.

A direct contribution towards destructive, proliferative synovitis in rheumatoid arthritis (RA) has been attributed to reactive oxygen species action. Some nutrients are considered to be capable of improving the oxidant/antioxidant status in RA; however the impact of diet composition on the antioxidant capacity of serum has not yet been studied in this disease. The aim of the study was to assess the relationship between diet quality and antioxidant status in patients with RA and healthy controls. Nutritional assessment was performed, and antioxidant status in serum, without and with deproteinization (TAS and DSAS, resp.), was determined in 82 RA and 87 healthy subjects. The diet of the RA group was low-energy and imbalanced. TAS and DSAS were significantly lower in RA patients than in controls. Antioxidant status significantly correlated with the supply of foods and nutrients influencing antioxidant and anti-inflammatory defense in RA; however, in this group, TAS was more sensitive to diet than DSAS. In healthy subjects, the nonprotein pool of serum antioxidants was more tightly linked to diet. These outcomes indicate the need to monitor diet quality of patients with RA and the usefulness of TAS measurements in this monitoring.

The Safety of Intravenous Cyclophosphamide in the Treatment of Rheumatic Diseases.

BACKGROUND: The therapeutic effects of cyclophosphamide (CP) in the treatment of systemic rheumatic diseases are related to its immune suppressive activity. However effective, the application of CP is restricted due to multiple adverse effects. OBJECTIVES: This retrospective study was conducted to determine the frequency of adverse effects attributed to CP toxicity. MATERIAL AND METHODS: The study involved 65 patients (17 male; 48 female) receiving intravenous CP between October 2007 and December 2010. The mean age at onset was 51.2 years (range 19-77 years). The most common diagnoses were systemic sclerosis (20), systemic lupus erythematosus (13) and vasculitis (13). The indications for treatment with CP were interstitial lung disease in the course of systemic diseases (33), vasculitis (24), glomerulonephritis (5) and changes in the central nervous system (3). The patients were administered 400-1000 mg CP in intravenous infusions at 2-16 week intervals, with the addition of sodium 2-sulfanylethanesulfonate (mesna) before and after each pulse. RESULTS: Out of 65 patients 40 (60%) reported adverse effects: infections in 24 (37%), nausea in 19 (29%), vomiting in 11 (17%), abdominal pain in 7 (11%) and pancytopenia in one, leading to cessation of the therapy. No association was found between the frequency of side effects and the treatment duration (p = 0.632), age (p = 0.852), diagnosis (p = 0.171) or nominal dose (p = 0.321). CONCLUSIONS: As knowledge about CP continues to increase, this medication remains a safe way to treat many rheumatic diseases.

Disease Activity, Oxidized-LDL Fraction and Anti-Oxidized LDL Antibodies Influence Cardiovascular Risk in Rheumatoid Arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) have a shortened lifespan compared to the general population. The high rate of premature mortality in the RA population can be attributed to cardiovascular disease (CVD). OBJECTIVES: The aim of the study was to look for non-classic risk factors that can at least partially explain the enhanced cardiovascular (CV) risk in patients with RA. MATERIAL AND METHODS: This was an observational study with 37 RA patients and 24 healthy volunteers as controls. The participants' medical history was taken, and systematic coronary risk evaluation (SCORE) and carotid ultrasonography examinations were performed on all the participants. Laboratory tests included antibodies anti-cyclic citrullinated peptide (anti-CCP), inflammatory markers, lipid level, oxidized low-density lipoprotein (oxLDL) level and the level of anti-oxLDL antibodies. RESULTS: Both SCORE and oxLDL fraction were elevated in RA patients as compared to the healthy controls (3.1 ± 3.7 vs. 0.8 ± 1.2, p = 0.005; and 0.029 ± 0.033% vs. 0.014 ± 0.006%, p = 0.04, respectively). In the RA group, the presence of anti-CCP was associated with thickening of the carotid intima-media complex and SCORE elevation. In the RA group, significant correlations were found between SCORE and mean carotid intima-media thickness (IMT; RP = 0.34, p = 0.040), disease activity score (RP = 0.42, p = 0.011), erythrocyte sedimentation rate (ESR; RP = 0.35, p = 0.036), and disease duration (RP = 0.52, p = 0.002). In RA patients with carotid plaques, the oxLDL fraction was significantly elevated in comparison to those without plaques (0.055 ± 0.070% vs. 0.022 ± 0.018%, p = 0.033). In the RA group, there was a significant negative correlation between mean carotid IMT and the serum concentration of anti-oxLDL antibodies (RP = -0.38, p = 0.02). No association was noted between the presence of rheumatoid nodules and SCORE or carotid IMT. CONCLUSIONS: Among RA patients, disease activity, ESR, disease duration, the presence of anti-CCP antibodies, the oxLDL fraction and the level of anti-oxLDL antibodies influence CV risk.

[Artefacts of questionnaire-based psychological testing of drivers]. / Artefakty w opartych na metodach kwestionariuszowych badaniach psychologicznych kierowców.

BACKGROUND: The purpose of this article is to draw attention to a significant role of social approval variable in the qustionnaire-based diagnosis of drivers' psychological aptitude. MATERIAL AND METHODS: Three questionnaires were used: Formal Characteristics of Behavior - Temperament Inventory (FCB-TI), Eysenck Personality Questionnaire (EPQ-R(S) and Impulsiveness Questionnaire (Impulsiveness, Venturesomeness, Empathy - IVE). Three groups of drivers were analyzed: professional "without crashes" (N = 46), nonprofessional "without crashes" (N = 75), and nonprofessional "with crashes" (N = 75). RESULTS: Nonprofessional drivers "without crashes" significantly stood up against other drivers. Their personality profile, indicating a significantly utmost perseveration, emotional reactivity, neuroticism, impulsiveness and the lowest endurance did not fit in to the requirements to be met by drivers. The driver safety profile was characteristic of professional drivers (the lowest level of perseveration, impulsiveness and neuroticism and the highest level of endurance). Similar profile occurred among nonprofessional drivers--the offenders of road crashes. Compared to the nonprofessional "without crashes" group, professional drivers and offenders of road crashes were also characterized by a significantly higher score on the Lie scale, determining the need for social approval. This is likely to result from the study procedure according to which the result of professional drivers testing had an impact on a possible continuity of their job and that of nonprofessional drivers "with crashes" decided about possible recovery of the driving license. CONCLUSIONS: The variable of social approval can be a significant artifact in the study of psychological drivers' testing and reduce the reliability of the results of questionnaire methods.

Validation of selected temperament and personality questionnaires for diagnosing drivers' aptitude for safe driving. A Polish study.

This paper presents the results of a study aimed at validating psychological questionnaires evaluating temperamental and personality features. It discusses their usefulness in diagnosing drivers' aptitude for safe driving and working as professional drivers. Three psychological questionnaires were validated: the Formal Characteristics of Behaviour - Temperament Inventory (FCB-TI), the Eysenck Personality Questionnaire - Revised and Short Scale (EPQ-R (S)) and the Impulsiveness Questionnaire (IVE). Three groups of drivers (n=246) aged 19-75 participated in the study. Group I (professional drivers; n=96) and Group II (nonprofessional drivers; n=75) had never been involved in road crashes, whereas Group III (nonprofessional drivers; n=75) were offenders involved in fatal injury road crashes. Criterion-related validity, Cronbach's alpha and Guttman split-half reliability coefficient were in assessing the psychometric properties of the questionnaires. There were some significant differences between Groups II and III for most traits. However, contrary to expectations, higher Emotional Reactivity, Perseveration and lower Endurance as well as higher Neuroticism, Impulsiveness and Venturesomeness were determined for Group II than for Group III. Additionally, the temperament and personality profile of Group II turned out to be less fitted to the profile of safe drivers than that of Group III, whose profile was actually similar to that of Group I. This seems to result from a high tendency for a positive self-presentation among Group I and Group III (a significantly higher result on the Lie scale in comparison with Group II). The results suggest that if psychological tests are to decide on whether a person may be a professional driver or may drive vehicles, the three questionnaires (FCB-TI, EPQ-R(S) and IVE) do not provide a valid diagnosis of professional drivers' aptitude because of drivers' high tendency for positive self-presentation. However, they can be used in job counselling and in screening high-risk drivers.

Ergonomics assessment of composite ballistic inserts for bullet- and fragment-proof vests.

Personal protective equipment worn by uniformed services (e.g., the police and the military) must ensure protection against bodily injuries. However, a high degree of protection is always associated with significant discomfort. This article presents the results of an assessment of the ergonomics parameters of new special purpose products, ballistic inserts with improved ballistic resistance, and an assessment of the impact of the burden related to their use on the psychomotor performance of the subjects. An obstacle course and subjective ergonomics assessment questionnaires were used in tests. Thermal discomfort was also assessed. Psychological testing included tests enabling an assessment of the subjects' cognitive and psychomotor performance, and a subjective assessment of mental load. The tests did not show any decrease in the comfort of use of the new inserts with improved ballistic resistance compared to the inserts currently used.

The beneficial impact of fasudil and sildenafil on monocrotaline-induced pulmonary hypertension in rats: a hemodynamic and biochemical study.

Pulmonary arterial hypertension (PAH) still cannot be cured effectively, hence the search for novel treatments continues. The effects of sildenafil (25 mg/kg body weight) and fasudil (30 mg/kg body weight) given alone or in combination, on normalization of right ventricular pressure (RVP), right ventricle mass, as well as the levels of several biomarkers (HDL-C, BNP, VEGF-A), were assessed in a rat model of monocrotaline (MCT)-induced PAH. MCT (60 mg/kg body weight) induced clear PAH in male Wistar rats. After 21 days, a significant decrease in RVP accompanied by a reduction of right ventricular hypertrophy - a significant decrease in the right ventricle/left ventricle plus septum ratio - as a result of sildenafil or fasudil administration was assessed. The administration of fasudil and sildenafil alone or in combination caused a significant decrease in plasma BNP level as compared to MCT-treated rats. Fasudil alone or with sildenafil, but not sildenafil alone, significantly increased HDL-C level as compared to MCT-treated rats. Fasudil and sildenafil given alone or in combination caused a significant increase in plasma VEGF-A level as compared to rats exposed to MCT.

Methods of estimating the effect of integral motorcycle helmets on physiological and psychological performance.

This article proposes a method for a comprehensive assessment of the effect of integral motorcycle helmets on physiological and cognitive responses of motorcyclists. To verify the reliability of commonly used tests, we conducted experiments with 5 motorcyclists. We recorded changes in physiological parameters (heart rate, local skin temperature, core temperature, air temperature, relative humidity in the space between the helmet and the surface of the head, and the concentration of O(2) and CO(2) under the helmet) and in psychological parameters (motorcyclists' reflexes, fatigue, perceptiveness and mood). We also studied changes in the motorcyclists' subjective sensation of thermal comfort. The results made it possible to identify reliable parameters for assessing the effect of integral helmets on performance, i.e., physiological factors (head skin temperature, internal temperature and concentration of O(2) and CO(2) under the helmet) and on psychomotor factors (reaction time, attention and vigilance, work performance, concentration and a subjective feeling of mood and fatigue).

[Coexistence of systemic sclerosis and gout? Hyperuricemia in systemic sclerosis: case report and literature review]. / Wspólwystepowanie twardziny ukladowej oraz dny moczanowej? Znaczenie hiperurykemii u pacjenta z rozpoznaniem twardziny ukladowej--opis przypadku. Przeglad pismiennictwa.

INTRODUCTION: There are few reports in the literature on the coexistence of systemic sclerosis with gout. Gout is the most common cause of arthritis among men past the age of 40 years. Elevated levels of uric acid may be associated with the metabolic syndrome, administration of diuretics, and kidney or cardiovascular disease. MATERIAL AND METHODS: We present the case of a 47-year-old male who was diagnosed with arterial hypertension, hypertrophic cardiomyopathy, systemic sclerosis with interstitial lesions in lungs, and hyperuricemia. Large nodules resembling tophi were present on the right elbow and knee. Radiographs of these sites revealed numerous calcifications. CONCLUSIONS: Coexistence of gout should be considered in a patient with systemic sclerosis and hyperuricemia. The authors draw attention to the potential effect of elevated levels of uric acid on the prognosis, particularly in the context of cardiovascular complications. There are data in the literature on the relationship of hyperuricemia with pulmonary arterial hypertension in patients with systemic sclerosis.

Injured professional drivers in Poland - an analysis of the causes and effects in relation to the time of the road accident.

INTRODUCTION: The objective of the paper was to present the results of an analysis of road accidents in professional drivers in Poland, from the point of view of their age, tenure, accident causes and effects in relation to the time of the accidents they were involved in. METHOD: Data were obtained from a database of the Central Statistical Office. Accidents recorded in statistical accident cards from 6 consecutive years were analysed. RESULTS: The overall number of injured professional drivers generally decreased over the 6 years, except for the last year of the period when the tendency to fatal and severe accidents between 23:00 and 6:59 increased. The highest percentage of fatal and severe accidents was found between 23:00 and 6:59 and was caused by medical emergencies and unsafe behaviour. The tenure of 70.89% of the injured drivers was under 10 years. Drivers who had worked for over 20 years had fewest injuries between 23:00 and 6:59. CONCLUSION: The results of the analysis may be used in changing work schedules to reduce the accident risk of the occupational groups at greatest risk.

A study of annoyance caused by low-frequency noise during mental work.

This article presents the results of an analysis of annoyance caused by low-frequency noise (including infrasonic noise) that occurs at work stations located in offices. The tests covered measurements of acoustic parameters specific for this type of noise and a survey conducted in the working environment and in laboratory conditions at a model of a work station.

Longitudinal changes in critical flicker fusion frequency: an indicator of human workload.

The aim of the study was to verify a hypothesis that critical flicker fusion frequency (CFFF) is season-related because of changes in the intensity and duration of sunlight. CFFF has a wide application in different fields, generally as an indicator of human workload. Therefore, confirmation of previous observations that CFFF is subject to a seasonal rhythm could make theoretical as well as practical sense. The analysis was based on data obtained from 23 male participants, aged 28-60 years. The study lasted 12 months. CFFF was measured with the flicker test. The results of statistical analysis indicate that CFFF changes over time. There are two forms of those changes: a linear trend and oscillations around the trend. Moreover, individual differences in the longitudinal course of CFFF (in trends as well as in oscillations) are observed. The conclusion is that CFFF is subject to longitudinal changes, whose pattern depends on individual differences. Additionally, the individual character of the CFFF changes over time allow the assumption that sunlight is probably not as significant a factor as expected, one that can modify the hypothetical pattern of season-related CFFF fluctuation. The obtained results are important for the methodology of experiments with CFFF and for the interpretation of the results of the flicker test.

Flicker Test as a Load Measurement During the Combined Effect of Heat and Noise.

This study was a joint physiological and psychological experiment undertaken to determine changes in physiological and psychological human functions under the combined influence of heat, noise, and physical activity. Seven experimental situations were simulated in a climatic chamber with different configurations of three independent variables: heat (40 °C), noise (98 dB), and physical effort (30% of maximum volume of oxygen uptake-V02 max). Five psychological variables (critical flicker fusion-CFF, hand tremor, reaction time, subjective climate evaluation, and subjective evaluation of the given condition load) and two physiological variables (heart rate and rectal temperature) were monitored. Results indicate that CFF changed (increased) significantly when more than one experimental variable was applied. These changes coincided with significant changes in both subjective climate evaluation and subjective evaluation of a given condition load. There were no significant changes in psychomotor functions (hand tremor and reaction time). None of the observed physiological parameters were above the critical value. The results suggest that CFF can be treated as a psychophysical load indicator.