[Effectiveness and safety of selective and non - selective factor Xa inhibitors in antiphospholipid syndrome and systemic lupus erythematosus: anti - Xa - activity range].

The aim of the study was to evaluate the anti - Xa - activity (aXa) of selective and non - selective factor Xa inhibitors in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) patients according to clinical implications and laboratory parameters. MATERIALS AND METHODS: Clinical and laboratory data were analyzed retrospectively in SLE and APS patients who protractedly received low weight molecular heparins (LWMH) and selective factor Xa inhibitors fondaparinux and rivaroxaban. The study included 70 patients in the middle age 39 [31; 43] years: 15/70 (21%) - with SLE, 10/70 (14%) - with APS and 45/70 (65%) - with SLE and APS (SLE+APS). All the patients received anticoagulants: 29 patients - nadroparin (98.3 [67.8; 129.5] IU/kg/day), 29 patients - fondaparinux (5 [5; 7.5] mg/day), 3 patients - enoxaparin (1.2 [0.8; 1.5] mg/day) and 9 patients - rivaroxaban (20 mg/day). All the patients signed informed consents. RESULTS: aXa therapeutic range of 0.1-1.5 IU/ml was found in 43/70 (61%) patients, low aXa - in 14/70 (20%) and high aXa - in 13/70 (19%) patients. Patients with low aXa underwent anticoagulant dose correction. There were not any major bleedings and thrombosis relapses in the study. Increased aXa was more common in patients, who took fondaparinux (31%), than in those, who took nadroparin (7%) and rivaroxaban (23%), p=0.02. Patients with enoxaparin had normal aXa range. In the absence of bleeding in SLE and APS patients, received anticoagulants in standardized therapeutic dose, the next factors influenced the aXa range excess: valvular heart disease (VHD) with the 3rd stage of mitral valve insufficiency as a result of aseptic Libman-Sacks endocarditis (odds ratio - OR 9.02, 95% confidential interval - CI [1.53; 53.12], p=0.015), peripheral artery disease in analogy with arteritis obliterans (AO) (OR 6.86, 95% CI [1.25; 37.71], p=0.027), and also triple - positivity of all types of antiphospholipid antibodies (OR 4.93, 95% CI [1.11; 21.99], p=0.036). According to found logistic regression model, aXa range excess risk can be prognosticated by the next formula: Z = -3.98 + 2.2 × VHD (yes-1/no-0) + 1.9 × AO (yes-1/no-0) + 1.6 × Triple - positivity (yes-1/no-0). Classified function value Z=0.39 defines the patients group with aXa range excess. Thus the value Z>0.39 indicates aXa range excess in the absence of bleeding, herewith sensibility is of 77% and specificity is 86%, positive prognostic value is 84.3%. CONCLUSION: In SLE and APS patients the next clinical and immunologic manifestations influenced the aXa therapeutic range excess: peripheral artery disease in analogy with AO, earlier aseptic Libman-Sacks endocarditis with the 3rd stage of mitral valve insufficiency and triple - positivity of all types of antiphospholipid antibodies, that does not need LWMH and fondaparinux dose correction. In contrast, anticoagulant dose reduction can cause clinical symptoms progression. Therapeutic aXa range in such patients should be extended.

[Evaluation of methotrexate effect on the acute-phase response in rheumatoid arthritis after 12-week treatment].

UNLABELLED: DAS28 index calculated with regard for ESR, the number of swollen/painful joints and evaluation of the patient's condition by VAS is universally used to estimate activity of rheumatoid arthritis (RA). There is a variant of calculation using C-reactive protein (CRP) instead of ESR. Our experience indicates that ESR decreases more slowly than CRP during treatment and better reflects dynamics of patients' condition. From the practical standpoint it is important to estimate activity of RA because therapeutic modalities are chosen based on the DAS28 value. AIM: To study the influence of pharmaceutical form of methotrexate on the acute-phase response in rheumatoid arthritis. MATERIALS AND METHODS: The study included 32 patients (24 women, 8 men) aged 19-76 (mean 47.5 +/- 28.5) yr with active RA (DAS28 > 3.2) 4-30 months (11.5 +/- 7.4, median 8) in duration. Diagnosis was made using AXR criteria (1987), none of the patients previously received methotrexate injections. Inclusion criteria: initially high ESR (Westegren, mm/hr) and/or CRP (mg/l measured by a highly sensitive method). All patients were given methotrexate subcutaneously for 12 weeks as monotherapy (initial dose 10 mg, maximum one 25 mg/week). The cumulative dose was 211.36 +/- 17.2 mg. RESULTS: Side effects did not require withdrawal of methotrexate. CRP level decreased faster than ERS: a 70% decrease of CRP by week 12 was recorded more frequently than that of ESR. Slow dynamics of the number of swollen joints compared with CRP may be due to the low cumulative dose of methotrexate. Duration of the disease had no effect on dynamics of acute phase characteristics. CONCLUSION: Methotrexate injections resulted in markedly delayed development of clinical signs of improvement compared with laboratory values. CFP levels fell down much faster than ESR, Remission or low activity of RA (estimated from DAS28) occurred only in 38% of the cases after 3 month monotherapy by methotrexate injections. It is concluded that efficacy of this drug should be estimated no sooner than 4 months after the onset of the treatment.

[Clinical significance of heart rate variability in patients with systemic lupus erythematosus].

AIM: To evaluate clinical significance of heart rate variability (HRV) in patients with systemic lupus erythematosus (SLE). MATERIAL AND METHODS: HRV was investigated by means of time-domain analysis of 24 hour ambulatory ECG of 122 SLE patients under 55 years of age and 32 age-matched healthy controls. In addition to clinical manifestations and activity of SLE, we assessed the presence of basic conventional cardiovascular risk factors (hypertension, smoking, body mass index, dyslipidemia), performed common carotid duplex scanning with measurement of intima-medial thickness (IMT). Inflammatory markers (ESR, CRP, IL-6) were assessed in all the patients. RESULTS: Significantly lower HRV and the trend to tachycardia were detected in SLE patients when compared to the control group. There was a significant positive correlation between HRV and a cumulative dose of cyclophosphamide, a high density lipoprotein cholesterol level, a negative correlation between HRV and cumulative dose of azathioprine, standard risk factors (hypertension, smoking, body mass index, triglyceride level), markers of inflammation (ESR, CRP, IL-6) and IMT. CONCLUSION: Measurement of HRV in combination with routine cardiovascular risk factors and level of inflammatory markers can be used for identification of subjects at risk for faster progression of atherosclerosis in SLE patients.

[The significance of cardiovascular risk factors and C-reactive protein to the development of atherosclerosis in women with systemic lupus erythematosus].

Compared with general population, women suffering from systemic lupus erythematosus (SLE) have signs of coronary artery disease (CAD) five to eight times more often, especially in young age. Early development of atherosclerosis in patients with SLE is caused by conventional cardiovascular risk factors and specific ones, associated with the disease and its therapy. A slight increase in such an inflammatory marker as C-reactive protein (CRP) is thought to reflect the presence of subclinical inflammation in the vascular wall, connected with atherosclerotic process. The authors analyzed the frequency of clinical and subclinical (an increase in the thickness of intima-media complex (IMC)) atherosclerotic manifestations, the summary coronary risk, the prevalence of conventional risk factors, and CRP level in 133 female patients with SLE and in 50 healthy donors. Compared to the control group, SLE patients were younger, developed cardiovascular diseases (CAD, stenocardia, myocardial infarction, and cerebral stroke (p = 0.05) as well as arterial hypertension more often, had higher levels of hs-CRP and triglycerides, and lower levels of high density lipoprotein cholesterol (HDLC). There was a positive correlation between hs-CRP level and the activity of the disease according to ECLAM score, ES value, IgG and IgM levels, hematological disturbances (anemia, leucopenia, and/or thrombocytopenia) , and a negative correlation with total cholesterol level, HDLC there was a moderate correlation between hs-CRP and a maximal IMC value.

Phospholipids and glycosphingolipids in cultured skin fibroblasts from patients with progressive systemic sclerosis (scleroderma).

OBJECTIVE: A comparative investigation of glycosphingolipids and phospholipids of cultured skin fibroblasts from healthy donors and patients with progressive systemic sclerosis (SSc) was performed. METHODS: Culture techniques, qualitative and quantitative lipid analyses, determination of neuraminidase activity, and immunofluorescence microscopy were used. RESULTS: The quantitative content of individual phospholipids in the fibroblasts of SSc patients (PF) was equally elevated, on the average 2.8 times in comparison with the fibroblasts of healthy donors (DF). The total content of neutral glycosphingolipids was slightly elevated only because of a 1.5-fold increase of monoglucosylceramide in PF. A decrease in the amount of the gangliosides GM3 and GM1 and the absence of the disialogangliosides in PF in comparison with DF, were demonstrated. Immunofluorescent assay also showed a decrease of ganglioside epitopes on the cellular surface of PF in comparison with DF. The GM3-neuraminidase activity of PF homogenates was increased two-fold in comparison to normal values. CONCLUSIONS: These results are discussed in connection with abnormalities in membrane receptor functions, alterations in the cell phenotype and AMP-cyclase system activity, as well as hyperproduction of extracellular matrix proteins by PF.

[Articular lesions in Ixodes tick-borne borreliosis (Lyme disease)]. / Porazhenie sustavov pri iksodovykh kleshchevykh borreliozakh (laimskoi bolezni).

Articular lesions in 157 patients infected with ixodes tick-borne borreliosis (ITB) in a central Russia's region set on, on the average, in 4 months after tick attack; they were associated with systemic signs of an early disseminated infection and set on less seldom in a late period. The most often encountered systemic signs were as follows: secondary erythema (32% of patients), neurological syndrome (13%), cardio-vascular lesions (22%), ocular lesions (13%) and hepatic lesions (8%). The articular syndrome manifested itself through arthralgia (53 patients) and arthritis (104 patients), which set on quite often in the tick-attack area. There was a peculiarity typical of articular lesions, which made it possible to distinguish them from other rheumatic disease. A dynamic follow-up revealed different clinical variations of Lyme's arthritis and peculiarities of the genetic profile, i.e. a higher prevalence of HLA A2, HLA-B15 and HLA-DR4 as well as of haplo-types HLA A2-B15 and HLAB15-DR4. The articular lesions were associated with an intensive specific humoral immune response. The instrumental examination methods, i.e. ultrasonography of joints as well as scintigraphy of bones and joints, did not reveal any qualitative differences between arthralgia and arthritis, which is indicative of a common nature different-intensity manifestations of arthropathy in thick-borne borreliosis.

[The effect of cyclic nucleotides on the specific binding of estradiol by skin fibroblasts in the normal state and in systemic scleroderma]. / Vliianie tsiklicheskikh nukleotidov na spetsificheskoe sviazyvanie éstradiola fibroblastami kozhi v norme i pri sistemnoi sklerodermii.

Specific binding of estradiol E2 was studied in homogenates of cultivated skin fibroblasts from healthy persons and patients with systemic sclerodermia as well as effect of cAMP and cGMP on the hormone binding was evaluated. Binding of estradiol E2 was decreased 4-fold in systemic sclerodermia. cAMP and cGMP were of importance in activation of the estradiol specific binding. Under conditions of normal state cAMP 10(-6) elevated 2-fold the estradiol specific binding, while the stimulation was not observed in systemic sclerodermia. However, cGMP 10(-6) M did not affect distinctly the estradiol E2 binding by fibroblasts of healthy volunteers but stimulated the hormone binding in systemic sclerodermia as a result of which the binding values were increased practically up to the basal level of normal state.

[Significance of estradiol in the development of fibrosis in systemic scleroderma (bases of sexual predisposition to the disease)]. / Znachenie éstradiola v razvitii fibroza pri sistemnoi sklerodermii (osnovy polovoi predraspolozhennosti k zabolevaniiu).

The influence of estradiol (E2) was studied on the production of type III procollagen by cultivated fibroblasts from the skin of healthy donors and SSD patients. It has been found that when in the norm E2 (concentration 10(-8) and 10(-7) M) inhibits the production of type III procollagen. In SSD the hormone's effect is not found. Here the quantity of E2 receptors in cells from SSD patients is 1.96 time lower than the norm. The resulted data testify to the fact that the decrease of E2 receptors in fibroblasts from SSD patients may be one of the factors contributing to the increase in the functional activity of cells and to the fibrosis progression.

[Phospholipids and glycosphingolipids in cultured skin fibroblasts from healthy donors and patients with systemic scleroderma]. / Fosfolipidy i glikosfingolipidy kul'tiviruemykh fibroblastov kozhi zdorovykh donorov i bol'nykh sistemnoi sklerodermiei.

A comparative study of phospho- and glycosphingolipids of cultured skin fibroblast from healthy donors and from patients with systemic sclerodermia (SSD) was carried out. It was shown that the total phospholipid content in SSD fibroblasts is elevated. No significant changes in the concentration of neutral glycosphingolipids were observed. The ganglioside composition of SSD cell cultures differs significantly from that of healthy donor cells. The concentration of the gangliosides, GM3 and GM1, is decreased; no ganglioside GD1a was found in SSD fibroblasts. The data obtained are suggestive of changes in the properties of fibroblast surface which can be manifested both in the impaired reception of matrix proteins and in the impairment of basic properties of the membrane. These changes are well correlated with the results of previous studies on the AMP cyclase system.