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Biomedical subjects

A A Novikov

Publications and source records attributed to A A Novikov.

At least 19 recordsLinked to original sources

Mechanism of activation of cytochrome C peroxidase activity by cardiolipin.

In this work, the actions of bovine heart cardiolipin, synthetic tetraoleyl cardiolipin, and a nonspecific anionic detergent sodium dodecyl sulfate (SDS) on cytochrome c (Cyt c) peroxidase activity recorded by chemiluminescence in the presence of luminol and on the Fe...S(Met80) bond whose presence was estimated by a weak absorption band amplitude with peak at 695-700 nm (A(695)) were compared. A strict concurrency between Fe...S(Met80) breaking (A(695)) and cytochrome peroxidase activity enhancement was shown to exist at cardiolipin/Cyt c and SDS/Cyt c molar ratios of 0 : 1 to 50 : 1 (by chemiluminescence). Nevertheless, when A(695) completely disappeared, Cyt c peroxidase activity under the action of cardiolipin was 20 times more than that under the action of SDS, and at low ligand/protein molar ratios (=4), SDS failed to activate peroxidase activity while cardiolipin enhanced Cyt c peroxidase activity 16-20-fold. A(695) did not change on Cyt c binding with liposomes consisting of tetraoleyl cardiolipin and phosphatidylcholine (1 : 10 : 10), while peroxidase activity was enhanced by a factor of 8. Breaking of 70% of the Fe...S(Met80) bonds resulted in only threefold enhancement of peroxidase activity. Cardiolipin-activated Cyt c peroxidase activity was reduced by high ionic strength solution (1 M KCl). The aggregated data suggest that cardiolipin activating action is caused, first, by a nonspecific effect of Fe...S(Met80) breaking as the result of conformational changes in the protein globule caused by the protein surface electrostatic recharging by an anionic amphiphilic molecule, and second, by a specific acceleration of the peroxidation reaction which is most likely due to enhanced heme accessibility for H(2)O(2) as a result of the hydrophobic interaction between cardiolipin and cytochrome.

Animals↗

Cardiolipin activates cytochrome c peroxidase activity since it facilitates H(2)O(2) access to heme.

In this work, the effect of liposomes consisting of tetraoleyl cardiolipin and dioleyl phosphatidylcholine (1 : 1, mol/mol) on the rate of three more reactions of Cyt c heme with H2O2 was studied: (i) Cyt c (Fe2+) oxidation to Cyt c (Fe3+), (ii) Fe...S(Met80) bond breaking, and (iii) heme porphyrin ring decomposition. It was revealed that the rates of all those reactions increased greatly in the presence of liposomes containing cardiolipin and not of those consisting of only phosphatidylcholine, and approximately to the same extent as peroxidase activity. These data suggest that cardiolipin activates specifically Cyt c peroxidase activity not only because it promotes Fe...S(Met80) bond breaking but also facilitates H2O2 penetration to the reaction center.

Animals↗

Optimal spectral coordination of subantennae in natural antennae as an efficient strategy for light harvesting in photosynthesis.

This work continues a series of our investigations on efficient strategies of functioning of natural light-harvesting antennae, initiated by a concept of rigorous optimization of photosynthetic apparatus by functional criterion, and deals with the problem of an optimal spectral coordination of subantennae in photosynthetic superantenna of the green bacterium Oscillochloris trichoides from a new family of green bacteria Oscillochloridaceae based in 2000. At present, two subantennae were identified surely: chlorosomal BChl c subantenna B750 and membrane BChl a subantennae B805-860. Some indirect experiments indicated on the presence of minor amounts of BChl a in isolated chlorosomes which allowed us to propose on the existence of an intermediate-energy subantenna which can connect the chlorosomal BChl c and the membrane BChl a ones. However, in the absorption spectra of isolated chlorosomes, this BChl a subantenna was not visually identified. This promoted us to perform a theoretical analysis of the optimality of spectral coordination of Oscillochloris trichoides subantennae. Using mathematical modeling for the functioning of the natural superantenna, we showed that an intermediate-energy subantenna, connecting B750 and B805-860 ones, allows one to control superantenna efficiency, i.e. to optimize the excitation energy transfer from B750 to B805 by functional criterion, and hence, the existence of such intermediate-energy subantenna is biologically expedient.

Chloroflexi↗

[Atheroscleotic vascular lesion in systemic lupus erythematosus and antiphospholipid syndrome in men].

The aim of the study was to determine the prevalence of various clinical and subclinical manifestations of atherosclerosis (AS) in men with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APLS), as well as to evaluate correlations between vascular atherosclerotic lesions, risk factors, and the levels of C-reactive protein (CRP) and cardiolipin antibodies (CLA). The subjects of the study were 62 patients (mean age 35.7 +/- 11.6 years, disease duration 129 +/- 102 months). Conventional and disease-related risk factors were analyzed. Carotic ultrasonography (CU) was performed in order to reveal vascular atherosclerotic lesions. Serum CRP levels were measured by the high-sensitive immunonephelometric technique. IgG and IgM CLA were studied by solid-phase immunoenzyme assay. CU found carotic arterial involvement in 58% of the patients; clinical manifestations of AS were revealed in 42% of the patients. The patients were divided into two groups: group I included 19 patients with APLS signs, group II consisted of 43 patients without APLS symptoms. The disease duration and lesion index were higher in group I. The study revealed a significant correlation between CRP level and intima-media complex (IMC) thickness in patients suffering from SLE with or without APLS (p < 0.05). Patients with AS displayed higher levels of IgG CLA, although the difference was insignificant. The study demonstrates that men suffering from SLE with or without APLS have a high risk of AS. An increase in CRP level is associated with an increase in IMC thickness.

Adolescent↗

[Soluble receptors of TNF-alpha: association with atherosclerotic vascular affection in systemic lupus erythematosus in males].

AIM: To study association between concentration of soluble receptors of TNF-alpha (sTNFa-R1) and atherosclerotic vascular affection in systemic lupus erythematosus (SLE) in men. MATERIAL AND METHODS: The examination covered 75 patients (mean age 34.76 +/- 11.8 years), duration of the disease 126 +/- 110 months. Standard cardiovascular risk factors were analysed. SLE activity was estimated by SLEDAI and ECLAM scales, SLICC/ACR index was calculated. Atherosclerotic vascular affection was studied with ultrasonic scanning of the carotid arteries. sTNFa-RI concentration in blood serum was determined with enzyme immunoassay technique in 73 SLE patients and 20 healthy donors. RESULTS: By sTNFa-R1 concentration, the patients were divided into two groups. Group 1 consisted of patients with sTNFa-R1 < or = 2.87 ng/ml, group 2 > 2.87 ng/ml. Higher concentrations of the receptors were associated with higher mean values of the damage index and proteinuria occurrence, with older age and higher body mass, with signs of vascular atherosclerotic affection (atherosclerotic plaques and intima-media thickness > 0.9 mm. CONCLUSION: Concentration of sTNFa-R1 can be considered as a laboratory marker of atherosclerotic vascular lesions.

Adolescent↗

[Soluble CD40 ligand in systemic lupus erythematosus and antiphospholipid syndrome].

AIM: To investigate a clinical role of soluble (s) CD40 ligand in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). MATERIAL AND METHODS: A serum concentration of sCD40 ligand was measured with enzyme immunoassay (Bender Medsystems, Austria) in 21 patients with primary antiphospholipid syndrome (PAPS), in 25 patients with secondary APS (SAPS) associated with SLE, in 92 SLE patients and in 16 healthy donors. RESULTS: A sCD40 ligand concentration in sera of SAPS and SLE patients was significantly higher than in donors. Significant differences by the ligand level between the above patients were not seen. In PAPS sCD40 ligand concentration was normal. Elevated serum concentration of the ligand was observed in 9.5% patients with PAPS, 54.0%--with SAPS, 73.9%--with SLE. This rise in SLE and SAPS was not related with the disease activity or renal damage. Hyperexpression of the ligand in APS was associated neither with thromboses nor with a high concentration of IgG/IgM antibodies to cardiolipin. A direct correlation occurred between sCD40 ligand level and platelet count. In SLE and SAPS elevation of the ligand level correlated with increased thickness of carotid artery intima-media complex, hypercholesterinemia and diastolic dysfunction of left ventricular myocardium. CONCLUSION: Hyperexpression of sCD40L in SLE and SAPS is associated with developing cardiovascular diseases and atherosclerosis.

Adult↗

[Markers of chronic inflammation in patients with ischemic heart disease with in-stent restenosis].

Concentrations of interleukins 6 and 10, tumor necrosis factor alpha, transforming growth factor beta and C-reactive protein were measured in 42 patients before and in remote period after coronary stenting. Patients with angiographically documented in-stent restenosis compared with those without restenosis had higher initial levels of interleukin 6 and more often discontinued therapy with statins.

Aged↗

[Anti-phosphatidylethanolamine antibodies in patients with Sneddon's syndrome].

Anti-phosphatidylethanolamine antibodies (aPE) belong to the group of anti-phospholipid antibodies (aPL) and are directed against neutral phospholipid, connected with co-factor protein, while cardiolipin antibodies (aKL) are directed against negative phospholipid. The paper presents a study of prevalence and clinical significance of IgG aPE in 28 patients (22 women and 6 men, mean age 47.6 +/- 11.6 years) with Sneddon's syndrome (SS), which consists in cerebrovascular disturbances and extensive livedo reticularis. IgG aPE were detected by immune-enzyme assay. The upper normal limit, calculated as mean + 3SD after studying 19 healthy donors, was 0.303 optic density units. aPE were found in 15 (54%), aKL and/or lupus anticoagulant (LA)--in 6 (21%) patients with SS. aPE were found in 10 (46%) out of 22 aKL- and LA-negative patients. Among the aPE-positive patients there was a higher incidence of cortic dementia (53% vs. 8%, p = 0.02), the widening of cortical sulci, detected by means of computed tomography and magnetic resonance imaging (73% vs. 31%, p = 0.05), and mild renal syndrome (73% vs. 16%, p = 0.03). Besides, they displayed a higher rate of headaches (87% vs. 62%), chorea (33% vs. 8%), epilepsy (27% vs. 8%), non-carrying of pregnancy (91% vs. 50%), peripheral venous thrombosis (27% vs. 15%), coronary heart disease (47% vs. 31%), cardiac valvular thickening, detected by means of EchoCG (93% vs. 69%), arterial hypertension (87% vs. 54%), thrombocytopenia (20% vs. 0), anemia (40% vs. 15%); however, the difference was not significant. The results show that aPE detection, performed in addition to detection of classic immunological antiphospholipid syndrome markers (aKL and LA), increases the portion of aPE-positive patients with SS by 33%. aPE are often (in 46% of cases) found in aKL- and LA-negative patients with SS. aPE is likely to be the most significant factor of thrombosis in small arteries of the brain cortex and kidneys, which could explain their association with dementia and renal syndrome.

Adult↗

[Neurological appearances of primary antiphospholipid syndrome].

Neurological disturbances frequently emerge in antiphospholipid syndrome (APS). One hundred and twenty four patients (100 women, 24 men, mean age 37.5 +/- 11.3 years) with primary APS (PAPS), including 76 patients with Sneddon's syndrome and positive antibodies to phospholipids (aPL), have been studied. A structure of neurological disturbances was as follows: ischemic lesions of cerebral blood flow (LCBF) which comprised stroke and transient LCBF (91%); thrombosis of brain venous sinuses (3%); epileptic seizures (24%); headache (65%); chorea (15%); visual neuropathy (9%); peripheral neuropathy (6%); multiple-sclerosis-like syndrome (10%); myasthenia syndrome (1%); syndrome of parkinsonism of non-vascular genesis (1%) and psychotic disorders (2%). 84% patients had main systemic APS symptoms (fetal loss, thrombosis), which preceded neurological appearances in 78% cases. All the patients had aPL: aPL to cardiolipin (aCL) and/or lupus coagulant (LC) and/or aPL to phosphatidyl serine, phosphatidyl inositol, phosphatidyl ethanolamine. In some patients, aCL titres ranged from positive to negative values and LC was not consistently detected. Thus, the presence of clinical symptoms of PAPS including neurological disturbances demands an investigation of different aPL types as well as a replicate study for immunological confirmation of PAPS.

Adult↗

[Atherosclerotic lesion of the vessels in systemic lupus erythematosus in males: relations with concentration of C-reactive protein].

AIM: To elicit prevalence of clinical and subclinical manifestations of atherosclerosis in men with systemic lupus erythematosus (SLE), to assess correlation between vascular atherosclerosis, risk factors and concentration of C-reactive protein (CRP). MATERIAL AND METHODS: Analysis of conventional and disease-related factors of risk, ultrasonic scanning of the carotid arteries, high-performance enzyme immunoassay for CRP were made in 37 patients (mean age 36.9 +/- 10.7 years, duration of the disease 130.2 +/- 108.2 months). RESULTS: Clinical symptoms of atherosclerosis were seen in 35% patients. By thickness of the intimamedia complex (IMC), the patients were divided into 2 groups. Group 1 consisted of 21 patients with vascular atherosclerosis (IMC > 0.9 mm), group 2--of 16 patients with IMC < 0.9 mm. Mean age, age of the disease onset, body mass index were greater in group 1. A mean CRP concentration in patients with athrosclerosis was significantly higher than in the group without vascular atherosclerosis (p = 0.004). CONCLUSION: SLE men comprise a group of high atherosclerosis risk. An elevated CRP level is associated with thicker IMC.

Adult↗

[Effect of small-dose glucocorticoids on the course of early rheumatic arthritis].

The study was undertaken to evaluate the effect of small-dose glucocorticoids (GCs) in combination with essential drugs used in early rheumatic arthritis (RA) on the clinical and laboratory activity and progression of joint destruction. Sixty-two patients aged 18-63 years who had active RA (its history being 1.5 to 24 months) and had not received basic therapy before were given methotrexate (MT) in a dose of 7.5-10.0 mg/week. Prednisolone (P) was randomly used in a dose equal or more than 10 mg/day). The efficiency of treatment was evaluated every 3 months by the ACR criteria 20/50/70. X-ray study of the hand and foot joints (the Larsen procedure by erosion calculations) was performed and the serum levels of C-reactive protein (C-RP) and interleukin-6 (IL-6) were measured before and 12 months after therapy. In the MT group, the patients' mean age was 52.0 +/- 10.5 years, the history of RA was 8.4 +/- 6.8 months; 82% of the patients were seropositive in terms of rheumatoid factor; the DAS 28 index was 5.2 +/- 0.8; in the P+MT group, the above parameters were 51.9 +/- 11. 7 years, 9.1 +/- 6.0 months, 83%, and 5.4 +/- 0.8, respectively (p > 0.05). Throughout one-year follow-up, the patients whose parameters corresponded to ACR 70 were more in the P+MT group than in the MT group (p < 0.05). The level of IL-6 and C-RP significantly decreased only in the P+MT group. There was a significant in the Larsen scores in both groups. A much fewer number of new erosions was revealed in the P+MT group than that in the MT group. According to the ACR 70 criteria, the efficiency of treatment with small-dose GCs was much higher than that in MT monotherapy. The small doses of GCs significantly lowered the laboratory activity of RA (C-RP, IL-6) and the occurrence of erosions.

Adolescent↗

[Antibodies to cyclic citrullinized peptide in rheumatoid arthritis].

AIM: To estimate a diagnostic value of antibodies to cyclic citrullinized peptide (CCP) in rheumatoid arthritis (RA). MATERIAL AND METHODS: The study was made of 85 RA patients. Of them, 48 patients had early RA, i.e. of 8 month and less duration. The control group consisted of 35 patients with non-differentiated arthritis (NDA) and 8 healthy donors. Concentrations of CCP antibodies, rheumatoid factor (RF) IgM and RF IgA were measured with enzyme immunoassay (EIA). RESULTS: The level of CCP antibodies in RA patients (76.3 +/- 43.8; median 100.0 U/ml) was significantly higher than in NDA patients (25.1 +/- 43.9; median 0.8 U/ml; p < 0.05) or in donors (0.38 +/- 0.36; median 0.2 U/ml; p < 0.05). A correlation was found between the CCP antibodies level and that of RF IgM (chi2 = 15.4; p = 0.001) and RF IgA (chi2 = 10.3; p = 0.001). Sensitivity (82%) and specificity (90%) of CCP antibodies in RA diagnosis was higher than these parameters for RF IgM and IgA (78%, 86% and 72%, 83%, respectively). Simultaneous tests for CCP antibodies, RF IgM and RF IgA led to a 93% specificity. CCP antibodies were detected in 50% patients seronegative by RF IgM and in 62% patients seronegative by IgA. Detection of CCP antibodies was closely associated with early RA (chi2 = 30.8; p = 0.0001). CONCLUSION: The EIA for CCP antibodies is a sensitive and specific serological test for early RA diagnosis.

Adult↗

[Antibodies to beta2-glycoprotein I and antibodies to cardiolipin in antiphospholipid syndrome: analysis of sensitivity and specificity].

To study sensitivity and specificity of antibodies to beta 2-glycoprotein I (B2GP-I) and antibodies to cardiolipin (CL) in diagnosis of antiphospholipid syndrome (APS), we examined 19 patients with primary antiphospholid syndrome (PAPS), 23 patients with secondary APS (SAPS) and systemic lupus erythematosus (SLE) and 73 patients with SLE. Antibodies to B2GP-I and CL of IgG isotype were measured at enzyme immunoassay. The levels of IgG aCL and IgG aB2GP-I in the serum of PAPS patients were 69.9 +/- 116.0 GPL, 74.1 +/- 117.4 SGU, respectively; of SAPS and SLE patients 60.5 +/- 68.9 GPL and 66.2 +/- 88.3 SGU, respectively. These values were significantly higher than in SLE patients (19.5 +/- 27.6 GPL, p = 0.0025 and p = 0.0012; 14.5 +/- 41.9 SGU, p = 0.0001, respectively) and donors (3.9 +/- 3.8 GPL, p = 0.0001; 5.7 +/- 1.2 SGU, p = 0.001). By IgG aCL and IgG-aB2GP-I, PAPS and SAPS patients differed insignificantly (p > 0.05), but these values correlated positively (r = 0.85; p < 0.0005 for PAPS and r = 0.9, p < 0.005 for SAPS). Simultaneous detection of IgG aCL and IgG aB2GP-I occurred in 36.8% in PAPS, 52.4% in SAPS and 12.3% in SLE. 10.5% PAPS patients were positive by IgG aCL as well as 9.5% with SAPS and 13.4% with SLE. Isolated rise of IgG aB2GP-I concentration was observed in 21.1% patients with PAPS, in 9.5% patients with SAPS and 9.6% patients with SLE. Of 43 patients with a history of thrombosis, 46.5% were positive by IgG aCL and IgG aB2GP-I, 7.0% positive only by IgG aCL and 11.6% only by IgG aB2GP-I. Levels of IgG aCL and IgG aB2GP-I in patients with thrombosis (64.7 +/- 87.5 GPL and 66.0 +/- 94.8 SGU, respectively) were significantly higher than in patients without them (19.6 +/- 3.8 GPL, p = 0.009 and 16.4 +/- 52.2 SGU, p = 0.0001). In venous thrombosis IgG aCL and IgG aB2GP-I were higher than in arterial thrombosis (p < 0.004). For diagnosis of APS sensitivity and specificity of IgG aB2GP-I and IgG aCL were 60.0 and 83.8%; 57.1 and 73.5% (p > 0.05), respectively. As to thrombosis, the sensitivity and specificity were 58.1 and 84.6%; 54.5 and 72.7% (p > 0.005), respectively. Thus, IgG aB2GP-I is an essential additional marker of APS. In the presence of APS symptoms, but in negative results of APS test it is justified to confirm APS diagnosis by aB2GP-I test results. To make APS diagnosis more accurate, it is valid to make simultaneous measurements of aCL using standard B2GP-I dependent enzyme immunoassay and aB2GP-I.

Adult↗

[Age variation of the phenotypic expression and the inheritance of the IgG system of immunoglobulin allotypes in the pig].

The specificity of phenotypic expression and inheritance of immunoglobulin allotypes IgG1a and IgG2b in pigs are discussed. It was shown that a negative state by both these allotypes is repeatedly found among newborn pigs but is extremely rare in pigs older than one month. A model, which simultaneously describes the genetic determination of allogroups formed by allotypes IgG1a and IgG2b and the dynamics of ontogenetic expression of individual genotype by system IgG with a result of a visually registered phenotype, was developed. Allele frequencies by system IgG were assessed in populations of domestic pigs of productive breeds, laboratory miniature pigs, and wild Eurasian pigs.

Age Factors↗

[Soluble adhesion molecules in antiphospholipid syndrome associated with systemic lupus erythematosus and in primary antiphospholipid syndrome].

AIM: To evaluate clinical implications of measurements of the level of soluble cell molecules of adhesion (sCMA) in systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS) and primary APS (PAPS). MATERIAL AND METHODS: Serum levels of sP-selectine, sE-selectine, sVCAM-1 were determined with enzyme immunoassay (R&D, USA) in 23 SLE with APS, 15 SLE patients free of APS and 19 patients with PAPS. RESULTS: Mean levels of sE-selectine and sVCAM-1 in SLE patients with APS, PAPS and SLE was higher than in donors. Elevated mean levels of sP-selectine were observed only in SLE patients free of APS. These patients also showed a correlation between sVCAM-1 level and the disease activity (p < 0.01). CONCLUSION: The development of immunopathological process in APS is associated with increased concentration of sCMA.

Adult↗

[Soluble vascular adhesion-1 molecule in Sneddon syndrome: clinical and prognostic value].

Clinical significance of a soluble vascular adhesion-1 molecule (pVCAM-1) in Sneddon's syndrome (SS) was studied in 48 SS patients by examination of serum pVCAM-1 level using enzyme immunoassay (R&D, USA). High serum concentration of pVCAM-1 registered in 62.6% of SS patients was associated with extracerebral thromboses, not with severity of cerebral vessel damage. Lethal outcomes for 2 years of follow-up occurred more frequently in patients with a high basal level of pVCAM-1 than in patients with normal level. Thus, development of the pathological process in SS is associated with elevated concentration of serum pVCAM-1 and may serve an additional laboratory indicator of developing extrabrain thrombotic disorders and marker of unfavourable prognosis.

Female↗