Viera Štvrtinová

Treatment of rat adjuvant arthritis with flavonoid (Detralex®), methotrexate, and their combination.

In both adjuvant arthritis and rheumatoid arthritis, edema and inflammation appear in synovial joints. Edema or effusion reflects an imbalance in lymph dynamics. Purified micronized flavonoid fraction is mainly used in the treatment of chronic venous insufficiency. This compound improves lymphatic drainage with a significant increase in lymphatic flow and lymphatic pulsality. It is suggested that the beneficial effect of purified micronized flavonoid fraction may be involved in the treatment of adjuvant arthritis in rats. In this study treatment of adjuvant arthritis in rats with Detralex, methotrexate, and their combination were evaluated. Groups of rats with adjuvant arthritis were treated with methotrexate (0.6 mg/kg/week), Detralex (20 mg/kg/day), and their combination for 50 days from adjuvant application. Hind paw swelling, arthrogram scores, serum albumin level, serum nitrite/nitrate concentrations, and whole‐body mineral density were evaluated as markers of inflammation and destructive changes associated with arthritis. Long‐term prophylactic treatment with low‐dose methotrexate significantly inhibited the markers of both inflammation and arthritis. Detralex administered alone slightly decreased both the hind paw swelling and the arthritic score. Other inflammatory and arthritic markers were not significantly influenced. However, Detralex combined with methotrexate markedly potentiated the beneficial effects of methotrexate, which resulted in a more significant reduction in hind paw swelling, arthritic scores, and serum concentrations of nitrite/nitrate. Interestingly, the arthritis‐induced decrease of bone mineral density in AA rats was significantly lower only in the group treated with the combination of Detralex and methotrexate. Our results indicate that Detralex increased the therapeutic efficacy of methotrexate basal treatment in AA. We suggest that this may be related to the beneficial effect of Detralex on microcirculation, especially on venules and lymphatic vessels.

Vasculitis of the Coronary Arteries and Atherosclerosis: Random Coincidence or Causative Relationship?

Publisher Summary The classical risk factors of atherosclerosis per se cannot be the reason for the enhanced atherosclerotic process observed in young patients with vasculitis. Inflammation plays an important role, although the exact mechanism through which acute or chronic inflammation results in acceleration of atherosclerosis remains unknown. Crucial is to timely seek for the various risk factors and attempt to eliminate or at least attenuate them. It seems rather important to instruct the patient correctly and to achieve a change in his/her unfavorable lifestyle. It has been recognized that atherosclerosis in general develops as a result of a combination of several risk factors. In the case of vasculitis, traditional risk factors get combined with inflammatory process, which is responsible for the acceleration of atherosclerotic alterations in young individuals. The clarification of the relationship between inflanmiation, vasculitis and atherosclerosis therefore represents a challenge to both the basic and the clinical research.

Mast cell infiltration in the wall of varicose veins

Varicose veins of the lower extremities are abnormally dilated, tortuous and elongated. The exact cause of vein dilatation has still not been established. Mast cells produce, store and release various types of vasoactive compounds (histamine, tryptase, prostaglandins, leukotrienes, and cytokines). Histamine enhances local vasopermeability and smooth muscle cell proliferation, leading to thickening of the intima. Tryptase can contribute to local vascular injury and subsequent weakness of the vascular wall causing varix formation. The aim of the present study was the comparison of mast cell infiltration in the wall of varicose and non-varicose veins. The mean mast cell density in the wall of varicose veins was 0.86 mast cell per mm2 and in healthy non-dilated vein walls, density was 1.23 mast cell per mm2. This difference was not statistically significant, therefore we could not confirm our hypothesis. Nevertheless, we suggest that mast cells could play an important role in the development of varices and the factor released by the mast cells should be further examined.

Thyroid-stimulating hormone concentration as an independent risk factor of venous thromboembolism regardless of thyroid function.

INTRODUCTION Thyroid dysfunction has been recognised as playing a role in the coagulation cascade, but the clinical implications of this phenomenon are unclear. The aim of our study was to assess the predictive power of TSH measurement on the presence or absence of venous thromboembolism (VTE). MATERIAL AND METHODS From January 2009 to August 2012, all consecutive patients hospitalised for suspected VTE were included in the study. VTE was confirmed either by pulmonary angiography or compressive ultrasound. We investigated the predictive power of TSH concentration on the risk of VTE in univariate and multivariate analysis including the existing risk factors (age, D-dimer). RESULTS A total of 232 patients were eligible for final analysis, with a median age of 70 years (IQR 58-80) and male-to-female ratio of 124:108. VTE was confirmed in 124 patients (53.4%). TSH concentration was significantly higher in cases with VTE (median 2.17 vs. 1.76 mIU/L, p = 0.0104), but free T4 concentrations were not found to be significantly different. Receiver operating curve analysis identified the cut-off of TSH > 2.686 mIU/L as a predictor of VTE with the prevalence of VTE 47.1 vs. 66.7% below and above this cut-off, p = 0.011. Multivariate logistic regression identified five independent predictors of VTE: male gender (odds ratio, OR = 2.22), D-dimer > 0.5 mg/L OR = 16.42), CRP > 5 g/L (OR = 9.178), TSH > 2.686 mIU/L (OR = 2.269), and age (OR = 0.9767/year). CONCLUSIONS Among patients with suspected venous thromboembolism TSH concentration was found to be an independent predictor of VTE in addition to gender, D-dimer, C-reactive protein (CRP), and age.

Expression of Constitutive Nitric Oxide Synthase Isoforms in Varicose Vein Wall; Preliminary Results

There are conflicting findings in literature about the structural changes of the primary varicose veins. NO (a potent vasodilatator) is synthesized by nitric oxide synthase (NOS). From 3 known NOS isoforms the two are constitutional: eNOS (endothelial NOS) and nNOS (neuronal NOS). 10 varicose and 10 control vein samples were processed by standard light microscopy and immuno-histochemica techniques using rabbit polyclonal antibodies against eNOS and nNOS. Antibodies expression was evaluated semiquantitatively and proved morphometrically by 2D-image analysis. total area of NOS isoforms expressions was determined by color analysis and color digital subtraction. The results showed discontinuous and significantly lower expression of both NOS isoforms the in the tunica media of varicose veins compared with the control group. For the statistical analysis the unpaired t-test was used. Our results suppose lower NO levels in varicose vein wall, deducing that varicose dilatation is due to other mechanism, and they contradict the results of previously published similar works.

Polymyalgia Rheumatica and Giant Cell Arteritis — an overview with a focus on important factors contributing to the severity of the disease

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) can be regarded quite rare systemic inflammatory diseases in the general population, however, their incidence increases with increasing age, and it may be anticipated that those disorders are frequently under-recognised. To diagnose both, PMR and GCA, extensive clinical experience in rheumatology as well as in general internal medicine is mandatory. The most important prerequisite, though, is to consider the possibility of existing PMR or GCA in the respective patients. Although commonly considered typically for elderly patients (70 and above), the most recent surveys reported development of PMR and GCA also in 4th and 5th decade. Moreover, also juvenile temporary arteritis and GCA has been reported in neonates and infants with fatal consequences (1, 2).

Coronary involvement and atherosclerosis in Giant Cell Arteritis

Myocardial ischemia and its extreme consequence, acute myocardial infarction are generally accepted to be a result of transient or prolonged discrepancy between real myocardial needs for oxygen and the actual blood flow through the coronary arteries into the cardiac muscle. There may be a variety of reasons for insufficient blood supply into the coronary arteries. In industrialized countries, coronary heart disease (CHD) is caused by atherosclerosis in more than 90% of the cases: it should be borne in mind however that there is a wide range of other pathological processes that eventually may result in myocardial infarction (1) (Table 2). Open image in new window Table 2 Causes of myocardial ischemia (adjusted according to Cheitlin and Virmani)

Polymyalgia Rheumatica, Giant Cell Arteritis, and Vascular Complications

Polymyalgia rheumatica (PMR) may be associated with vascular complications for a number of reasons: 1/the inflammatory nature of the disease itself, 2/strong association with giant cell arteritis (GCA – which has a direct inflammatory effect on arteries and may result in either stenosis or aneurysm within affected segments), 3/side effect of the corticosteroid treatment (including arterial hypertension, dyslipidemia and/or diabetes mellitus). GCA is a systemic granulomatous vasculitis, typically affecting branches of carotid artery mainly temporal artery; however, any other medium or large artery can be affected. This fact complicates diagnosis of the disease. Diagnostic possibilities of GCA are discussed in this chapter.

Coronary Artery Vasculitis and Atherosclerosis in Giant Cell Arteritis

Increased incidence of coronary artery disease (CAD) has been observed in several chronic vasculitic and inflammatory syndromes. Inflammatory affection of the coronary arteries may present a life-threatening condition and the underlying reason for CAD in all age groups. On the other hand, underlying vasculitis may enhance atherogenesis and the development of atherothrombosis. In our group of 23 patients (15 females and 8 males) with the diagnosis of giant cell arteritis four patients developed myocardial infarction, 2 patients suffered stroke and 1 patient both myocardial infarction and stroke.

Involvement of the Aorta in GCA

Giant cell arteritis involving aorta, can be a lethal disease and it is often manifested in a dramatic way in the elderly: by dissection or rupture of aorta. Early diagnostics, correct treatment and life-long checks of patients in whom GCA was diagnosed can prevent them from development of such a severe complication as aortic aneurysm. That is why it is necessary to actively seek aneurysms in all GCA patients - make regular duplex ultrasonography examinations, CT or MR examinations if possible, too. Patients with diagnosed GCA shall be carefully and properly treated, since in most of the patients in which aortal dissection developed the treatment was not adequate.