Baroreflex sensitivity and carotid intima-media thickness in risk stratification of prehypertensives and hypertensives.

BACKGROUNDː The aim of the study was to evaluate the clinical significance of baroreflex sensitivity (BRS) and carotid intima media thickness (IMT) in risk stratification of hypertensives and subjects with high normal blood pressure (SHNBP). METHODSː A total of 20 patients (61±13 years of age, 10 female/10 male) with essential, treated hypertension and 20 subjects (59±8 years of age, 10 female/10 male) with high normal blood pressure were enrolled. The interrelationship between BRS expressed in ms/mmHg (BRS) and IMT of common carotid artery (CCA) in hypertensives and subjects with high normal blood pressure (SHNBP, prehypertensives) was evaluated. BRS was determined by the sequence and spectral method: a five-minute non-invasive beat-to-beat recording of blood pressure (BP) and R-R interval with use of Collin CBM-7000 monitor, controlled breathing at a frequency of 0.1 Hz. Duplex ultrasonographic examination of the carotid wall and IMT of both CCA and carotid bulb were performed in all patients. RESULTSː Essential hypertension was associated with decreased BRS (r =-0.53, P<0.001). We found out that there was no significant difference between BRS and IMT CCA values in mild treated hypertensives and those in SHNBP. This finding was independent of age-dependent decrease of BRS. SHNBP and hypertensives with critical value BRS≤5 ms/mmHg have significantly increased IMT CCA. CONCLUSIONSː Decreased BRS is an early sign of autonomic dysfunction even in prehypertensive period. SHNBP and hypertensives with BRS≤5ms/mmHg have significantly increased IMT CCA. The principal result of this study showed that BRS and carotid IMT in relatively low-risk hypertensives and SHNBP could identify subjects at higher cardiovascular risk.

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.

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.

Effects of purified micronized flavonoid fraction (Detralex) on prophylactic treatment of adjuvant arthritis with methotrexate in rats.

BACKGROUND: 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 signicant 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. OBJECTIVES: To evaluate the effect of Detralex on methotrexate prophylactic treatment of adjuvant arthritis in rats. METHODS: 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. RESULTS: 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 BMD in AA rats was significantly lower only in the group treated with the combination of Detralex+methotrexate. CONCLUSION: 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.

Defects in regulation of local immune responses resulting in atherosclerosis.

Atherosclerosis is nowadays generally accepted as an inflammatory disease but the mechanism of its origin and development have not yet been fully clarified. The present review focuses on the role of the local immune system as one of the key players in the pathogenesis of the complex process. Its part represented by vascular-associated lymphoid tissue (VALT) within the arterial wall participates directly in the vascular wall's homeostatis. Its inordinate activation during ontogenic development of an individual, this formerly defensive and physiologic mechanism transform into a pathological process resulting in an impairing inflammation. Hsp60, CRP and oxidized or otherwise modified LDL are serious candidates for triggering these pathological changes. The principal role is played by anti-Hsp60 antibodies and by shear stress originating on the surface of endothelium due to blood flow. The experimental and clinical data supporting this immunological hypothesis of atherosclerosis are discussed.

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.