[Role of obesity in the development of osteoarthrosis and concomitant diseases].

AIM: To specify the association between obesity and the frequency of concomitant states, fat metabolic disturbances, and progressive osteoarthrosis (OA) at various sites. SUBJECTS AND METHODS: The study included 298 patients with manifest knee and hip osteoarthrosis in whom the body mass index (BMI) and waist and hip circumferences were measured calculating the waist-hip index. The association of these indices with the severity of OA and the development of concomitant states was analyzed. RESULTS: Both women and men were found to have overweight and first-second-degree obesity at equal ratios - 61.6 and 59%, respectively. There was an evident rise in the prevalence of cardiovascular diseases (arterial hypertension, coronary heart disease) and diabetes mellitus with a higher BMI. Stages II-III gonarthrosis was predominant (97.1%) in the obesity group (BMI 30.0-35.0 or greater). With a BMI of > 40, X-ray stages III-IV OA were revealed in 83.3% of the patients. CONCLUSION: Our findings support the important role of obesity as a risk factor in the development of OA. Fat metabolic disturbances also make a considerable contribution in the development of concomitant states and in the progression of OA of both knee and hand joints.

[Statistics on rheumatic conditions in the Russian Federation in early 2000es].

The analysis of rheumatic disease morbidity in the Russian Federation in early XXI century is presented.

[Effect of metformin on the clinical course of gout and insulin resistance].

UNLABELLED: The aim of this prospective study was to evaluate results of metformin (MF) therapy during 1 year of uric acid (UA) metabolism and the clinical course of gout with insulin resistance (IR). The study included 30 patients (28 men and 2 women) of mean age 51 yr and duration of he disease 4-11 yr. IR was diagnosed based on the HOMA index. INCLUSION CRITERIA: the absence of anti-gout therapy, normal renal and hepatic function, abstinence. The patients were given 1500 mg MF/day. The measured parameters included anthropometric and clinical characteristics, 24 hour AP, plasma UA, glucose, insulin, urea, creatinine, ALT, AST, lipid spectrum at the first and subsequent visits. UA clearance and excreted UA fraction were calculated. UA level decreased from 569 +/- 109.5 to 442.8 +/-107.4 mcmol/l (p < 0.01) after 12 months of MF therapy. Normouricemia ( < 360 mcmol/l) was achieved in 11 patients. Fasting insulin level dropped by 35% (from 23.9 to 15.9 mcU/ml, p < 0.01), HOMA index from 6.5 to 3. 7(p < 0.01). Serum glucose, cholesterol, triglycerides, and LDL cholesterol decreased while HDL cholesterol increased. Parameters of renal UA regulation and anthropometry remained unaltered. MF therapy resulted in a decrease of serum UA, insulin, and the degree of IR. The hypouricemic effect of MF was unrelated to renal UA excretion, reduced AP and body weight. It is hypothesized that MF reduces production of UA in patients with gout due to inhibition of synthesis of free fatty acids.

[The analysis of genomic mutations and structural chromosome aberrations in irradiated human lymphocytes].

The lymphocytes of healthy donors were exposed to 60Co gamma-rays in doses ranging 0.5 to 6.0 Gy, and were incubated with PHA and 5-bromodeoxyuridine at 37 degrees C for 72 h. In the course of five consecutive in vitro divisions of cultured lymphocytes, the frequency of polyploid metaphases were determined, and chromosome structural aberrations in polyploid and diploid metaphases were analyzed. Dose dependence of polyploid formation was investigated, and patterns of polyploid cells were analyzed at various DNA replication cycles post exposure and 5-bromodeoxyuridine addition. Radiation is most effective induces of polyploid metaphase of the second and of the third mitotic divisions. In metaphases of the fourth mitotic divisions radiation does not enlarge authentically frequency of polyploid cells. In metaphases of the fifth divisions was not retrieved of polyploid cells. Was shown, that 84.8% of polyploid metaphases compound of tetraploids, while of octoploids and the cells with endoreduplicated chromosomes compound, accordingly, 8.4 and 6.8%. The analysis of chromosome aberrations have shown that the percentage of aberrant cells was higher in polyploid metaphases than in diploids, which indicated that chromosome lesions were involved in formation of polyploid metaphases.

[The analysis of chromosome lesions in lymphocytes of Hodgkin's lymphoma patients after chemotherapy and radiation therapy].

The analysis of chromosome lesions in peripheral blood lymphocytes of Hodgkin's lymphoma (HL) patients after chemotherapy and chemotherapy with the subsequent course of radiation therapy is carried out. Is shown, that the mean aberration frequency was significantly higher in HL patients after chemotherapy (7.20 +/- 0.58 per 100 metaphases) than in non-treated HL patients (4.80 +/- 0.54, p < 0.01). The subsequent carrying out of radiation therapy enlarges number of chromosome aberrations on 100 metaphases up to 46.7 +/- 10.7 (p < 0.05), of which chromosome-type aberrations (43.2 +/- 10.3 on 100 metaphases) averaged 92.5%. In lymphocytes of 37 out of 43 HL antitumoral treatment patients, we found, in addition to ordinary aberrant cells, a large number of multiaberrant (MA-cells) cells, i.e. metaphases carrying multiple (at least four) chromosome-type exchange aberrations. In 30 non-treated HL patients only one MA-cell was found. From 171 MA-cells which were in 43 HL patients after antitumoral treatment, 114 MA-cells were found at inspection of 9766 diploid metaphases, and the remaining 57 MA-cells were found at inspection of 196 polyploid metaphases. The carrying out after chemotherapy of radiation therapy enlarges in lymphocytes frequency of appearance of MA-cells. The analysis of MA-cells in diploid and polyploid metaphases shown, that the MA-cells could be formed both in vivo, and in vitro in absence of influence of clastogenic factors, and could survive at least two rounds of in vitro replication.

[Development and relapse of gastroduodenal ulcer in patients taking nonsteroid anti-inflammatory drugs: effects of standard risk factors].

AIM: To investigate incidence and recurrence rate of endoscopic ulcers in patients with rheumatic diseases (RD) taking NSAID in respect to factors of NSAID gastropathy risk. MATERIAL AND METHODS: Endoscopic findings in the gastrointestinal tract were analysed for 6103 patients (age 50.1 +/- 14.6 years, 83.1% females) with RD taking NSAID regularly, 1642 of them took also glucocorticoids (GC). Control RD patients (n = 504) matched by age and sex took no NSAID, GC and low dose aspirin a month and more before the trial. RESULTS: Gastric or duodenal ulcers were detected in 763 (12.5%) RD patients treated with NSAID, in 20 (4.0%) in the control group, p < 0.0001. Ulcers were more frequent in older patients (65 years of age and older) with ulcer history treated with nonselective NSAID in combination with low aspirin doses (15.1 and 12.0, p < 0.05; 27.3 and 9.7%, p < 0.001; 13.1 and 9.8%, p < 0.001; 19.1 and 12.2%, p < 0.001; respectively). No significant difference in ulcer occurrence was observed in patients given NSAID+GC and NSAID only (11.3 and 12.9%, respectively; p = 0.041). The recurrence rate was assessed in 407 patients with NSAID-induced ulcer 12 months later. Control consisted of 1640 patients having no ulcer, multiple erosions after 12 months of regular intake of NSAID. Ulcer recurrence rose in 163 of 407 patients (40%) while only in 107 f 1640 controls (6.5%, p < 0.0001). Old age and GC administration had no impact on the recurrence rate. Recurrences were less frequent in patients taking nonselective NSAID than those taking nonselective ones (23.4 and 46.5%, respectively; p < 0.001) and in patients treated with NSAID in combination with proton pump inhibitors (24.6 and 42.6%, respectively; p < 0.001). Prophylactic intake of H-2 blockers did not reduce recurrence rate. CONCLUSION: Old age, ulcer history and intake of nonselective NSAID increased the risk of endoscopic GI ulcer. Combined use of NSAID and GC did not increase the risk of ulcer development or recurrence. In a year or later of NSAID continuation recurerences arose in 40% patients with NSAID-induced ulcers. Recurrence risk was reduced by selective NSAID and proton pump inhibitors.

[Neutralisation of interferon gamma--a new trend in therapy of rheumatoid arthritis].

AIM: To evaluate objectively therapeutic potentialities of a novel method of biological therapy--blocking interferon gamma (IF-gamma)--by means of a comparative analysis of using antibodies to IF-g (anti-IF-gamma) and tumor necrosis factor alpha (anti-TNF-alpha) in resistant rheumatoid arthritis (RA). MATERIAL AND METHODS: A double blind trial included 55 patients with resistant RA. They received 5 intramuscular injections of anti-IF-gamma (n = 20), anti-TNF-alpha (n = 20) and placebo (15 patients). The results were assessed on the treatment day 7 and 28. RESULTS: 16 patients withdrew because of the treatment uneffectiveness (2 from the group on anti-IF-g, 3--on anti-TNF-alpha, 11--on placebo). To the treatment day 28 the patients given anticytokines achieved significant improvement of all clinical indices while placebo group had no improvement. The highest response was observed in the group on anti-IF-gamma (ACR 70). As shown by ultrasound investigation, a significant reduction of the synovial membrane thickness took place also in administration of anti-IF-gamma. Most frequent side effect of the anticytokine therapy was mild dermatitis at injection site on treatment day 8-11. CONCLUSION: Therapeutic efficacy of anti-IF-gamma was comparable with efficacy of anti- TNF-alpha and even was superior in some aspects. The block of IF-gamma holds much promise in the treatment of RA.

[Comparison of the time to analgetic and anti-inflammatory effect in the treatment of gouty arthritis with nimesulide and sodium diclofenac].

AIM: To compare the time to presentation of the analgetic and anti-inflammatory effects of granulated and tablet nimesulide and sodium diclofenac since the start of therapy for gouty arthritis (GA). MATERIAL AND METHODS: Ninety males with gout were randomized into 3 equal groups. The patients were included in the study by the following criteria: a documented diagnosis of gout (Wallace S. criteria), age over 18 years, acute arthritis for less than 3 weeks, affection of 4 and more joints. For 7 days patients of group 1 received nimesil (200 mg/day), those of group 2--aponil (200 mg/day), group 3 --sodium diclofenac (150 mg/day). Swelling, articular, pain indices were estimated daily for 7 days. RESULTS: Patients of group 1 (nimesil) experienced pain relief on min 20; patients taking nimesulide (aponil) experienced pain attenuation within the first hour. Pain (at rest and movement) and the indices declined faster in group 1 than in group 2 as well as in groups 1 and 2 compared to group 3. Arthritis was arrested in 24 (80%) patients of group 1, 11 (36%) of group 2 and 4 (13%) of group 3. CONCLUSION: Efficacy of nimesulide for arrest of an acute gout attack exceeds that of sodium diclofenac. Granulated nimesulide has advantages over tablets.

[The genome instability in the descendants of the Chinese hamster of the cells, irradiated by the low dose and by various intensities of gamma-radiation].

The V-79 Chinese hamster cells were irradiated by gamma-rays in dose of 0.5 Gy at powers of doses 0.48 Gy/min (an acute irradiation) and 0.0485 MGy/min (a prolonged irradiation). The acute and prolonged irradiation in a dose of 0.5 Gy enlarges frequency of the appearance of micronucleus (MN). Subsequent cultivation of the irradiated cells during 20 generations enlarges frequency of MN, and for prolonged an irradiation the boosted frequency of MN, is saved during 40-60 generations. After an acute irradiation the number of MN starts to reduce after 20 doublings.

[Action of mixed gamma-neutron radiation with various dose rates on the number of cells in thymus and chromosomes of mice bone marrow and human lymphocytes].

The irradiation with mixed gamma-neutron radiation was carried out at the pulse nuclear reactor on fast neutrons BARS-6 in a regimen of one pulse (100 micros) and in a regimen of continuous irradiation during 60 minutes. Was shown, that the irradiation of mice with pulse radiation was 1.3-1.8 times more effective in the induction of the chromosome aberrations in bone marrow cells in comparison with the continuous regimen of irradiation. At the same time, other biological tests (yield of chromosome aberrations in human lymphocytes, decreasing the number of cells in thymus) demonstrated that pulsed and continuous regimens have almost equal biological effectiveness.

[Radioprotective and antistressful properties of nitric oxide production modulators].

The radioprotective and antistressful activities of L-arginine and the "Pronumol" preparation, in which L-arginine is contained in the complex of proteins with nucleic acids, were studied. In mice repeated peroral intake of L-arginine and "Pronumol" partially prevented radiation-induced and stress-induced lipid peroxidation and DNA degradation in thymus, increased hemopoietic stem cell survival, and prevented an increase in chromosome aberration frequency in bone marrow cells of irradiated mice. When repeatedly administered per os before irradiation, "Pronumol" increased survival of intestinal stem cells in irradiated mice and prevented thymus cell devastation induced by radiation and stress.

[Severity of a female gout course].

AIM: Comparison of a gout course in males and females. MATERIAL AND METHODS: The trial enrolled 34 patients (17 females and 17 males). The patients were matched by age and the disease duration. Severity of a gout course was assessed by the disease history, articular syndrome, concomitant diseases, blood biochemistry. Statistical processing was made with a computer program "Statistica 6.0". RESULTS: Events predisposing to purin metabolism disturbances and, therefore, to development of gout occur more frequently in females than in males. For the most part this concerns arterial hypertension and intake of diuretics. Women often have endocrine pathology (artificial menopause, dysmenorrhea, euthyroid goiter). In women gout runs a more severe course manifesting in early chronization, polyarticularity, lingering arthritis, rapid formation of tophuses. Both groups demonstrated marked polymorbidity with accumulation of the diseases related to atherosclerosis. Distinct group differences by content of uric acid seem to arise from early onset of chronic renal failure in women. CONCLUSION: In the absence of sex- and age-related differences, a more severe course of gout is observed in women. This may be due to hyperuricemia and a trend to the disease chronization, high prevalence of arterial hypertension and renal failure.

Cytogenetic adaptive response in cultured human lymphocytes: dependence on the time of exposure to adapting and challenging doses of gamma-rays.

Human lymphocytes from 16 healthy donors were exposed in vitro to an adapting dose of gamma-rays (0.05 Gy) at G0, or G1, or G1/S stage of the cell cycle and subsequently to a challenging dose of gamma-rays at G1, or G1/S, or S (1 Gy), or G2 (0.5 Gy) stage. Frequencies and distributions of the induced chromosome aberrations were analyzed in first-division metaphases. The data averaged over the donors revealed the protective action of the adapting exposure under the irradiation schemes with the challenging dose delivered at S or G2 stage. The majority of aberrations induced at these stages belonged to the chromatid type, and their yield was significantly higher in G2-exposed cells than in S-exposed cells. However, the relative reduction of the challenging dose effect (about 34%) in the adapted cells did not depend on the magnitude of this effect, and its value remained the same (within the experimental error) if aberrations were subdivided into chromosome and chromatid types or grouped as total deletions and total fragments. The adaptive response was not revealed under the schemes with the challenging dose delivered at G1 or G1/S stage. Analysis of the individual results showed that, in one and the same donor, the adaptive response could be observed under one irradiation scheme and not observed under other schemes, the most effective schemes being those with the challenging dose delivered at G2 stage. Four donors, however, did not show the adaptive response even under such schemes. Data on aberration distributions suggested that different repair processes, rather than a unique one, may underlie the adaptive response.

In vivo optical coherence tomography imaging of human skin: norm and pathology.

BACKGROUND/AIMS: Since the majority of skin diseases are known to be accompanied by structural alterations, research efforts are focused on the development of various novel diagnostic techniques capable of providing in vivo information on the skin structure. An essential parameter here is spatial resolution. In this paper we demonstrate the capabilities of optical coherence tomography (OCT) in detecting in vivo specific features of thin and thick skin. A particular focus is made on the identification of OCT patterns typical of certain pathological processes in skin, by performing parallel histological and tomographical studies. METHODS: To obtain images of the skin, we used a compact fiber OCT system developed at the Institute of Applied Physics of the Russian Academy of Sciences. A low coherence source (superluminescent diode) operated at a wavelength of 1280 nm; the output power was 0.5-2 mW. This power is low enough to conform to the ANSI safety standards for light exposure. The in-depth resolution limited by the spectral bandwidth (40-50 nm) of the probing light was approximately 20 &mgr;m. The lateral resolution determined by the probe light focusing ranged from 15 to 30 &mgr;m. In this series of experiments the maximum depth of imaging did not extend beyond 1.5 mm. Obtaining images of skin regions 2-6 mm long took 2-4 s. OCT capabilities for imaging normal skin of different localization and some skin diseases were studied in 12 healthy volunteers and 24 patients. RESULTS: OCT imaging of the skin can detect in vivo such general pathological reactions of the human body as active inflammation and necrosis. OCT is useful for in vivo diagnosis of some specific processes in the skin, including hyperkeratosis, parakeratosis and formation of intradermal cavities. OCT imaging is noninvasive and therefore allows frequent multifocal examination of skin without any adverse effects. OCT can perform monitoring of disease progress and recovery in the course of therapy. Morphometric studies, measurements of the depth and extension of skin pathology within the human body can be easily performed by OCT. CONCLUSIONS: OCT allows imaging of subsurface soft tissues with the spatial resolution of 15-20 &mgr;m, a resolution one order of magnitude higher than that provided by other clinically available noninvasive diagnostic techniques. An imaging depth of up to 1.5-2 mm, given by current OCT technology, is sufficient to examine the skin. Real time OCT imaging can provide information not only on the structure, but also on some specific features in the functional state, of tissues. OCT imaging is a noninvasive technique, i.e., OCT does not cause trauma and has no side effects since it utilizes radiation in the near infrared wavelength range at a power as low as 1 mW.

[Use of I125 labelled poly(I). poly(C) for determination of antibodies to double-stranded RNA by immune complex absorption to nitrocellulose filters]. / Ispol'zovanie mechennoi 125I poli(I). poli(C) dlia epredeleniia antitel k dvuspiral'noi RNK metodom adsorbtsii immunogo kompleksa na nitrotselliuloznykh fil'trakh

125I-labeled double-stranded polyribonucleotide complex was used for detection of antibodies to double-stranded RNA in sera from people and immunized animals by the method of immune complex adsorption by the nitrocellulose filters. The technique is simple and sensitive. Antibodies to double-stranded RNA WERE detected in sera from patients with different diseases and from normal individuals. Systemic lupus erythematosus sera contain as a rule higher amounts of antibodies to double-stranded RNA. Often these antibodies were measured together with those directed towards native and denatured DNA. Anti-double-stranded RNA antibodies from sera of immunised animals and patients with systemic lupus erythematosus are highly specific.

[Chromosome aberrations in human lymphocytes at a various duration of cultivation after irradiation]. / Aberratsii khromosom v limfotsitakh cheloveka pri razlichnoi prodolzhitel'nosti kul'tivirovaniia posle oblucheniia.

Human peripheral blood lymphocytes were exposed to 60Co gamma-rays (a dose of 3 Gy) and cultivated during seven days in the presence of PHA and BrdU. It was shown that the metaphases of the first and second mitosises occurred during cultivation of the irradiated and unirradiated lymphocytes, being evidence about of irregularity of the coming into division of various fractions of lymphocytes. The time of cultivation did not influence a rate of aberrations in metaphases of the first and second mitosises of the irradiated lymphocytes. During the first and the subsequent mitosises the number of exchange chromosome aberrations decreased and reached a control level in metaphases of the fourth and fifth mitosises. The number of paired fragments at second and third mitosises increased a little and started to decrease only in metaphases of the fourth and fifth mitosises. The decrease in chromosome aberrations with prolongation of the cultivation of lymphocytes after irradiating is a consequence of elimination of cells with chromosome damages during sequential mitotic divisions.

[The cytogenetic analysis of the adaptive response in the lymphocytes of donors living in areas with different levels of radioactive contamination]. / Tsitogeneticheskii analiz adaptivnogo otveta u limfotsitov donorov, prozhivaiushchikh na territoriiakh s razlichnym urovnem radioaktivnogo zagriazneniia.

The adaptive response was studied in peripheral lymphocytes of healthy donors residing at territories with various levels of radioactive contamination. For donors from a clean territory (the town of Obninsk), the adaptive response depended on the cell cycle stage at which lymphocytes had been exposed to adaptive and challenge doses. The most expressed adaptive response was observed if lymphocytes had been exposed to the adaptive dose 0.05 Gy at G0 or G1 stage and to the challenge dose 0.5 Gy at G2 stage. Lymphocytes of donors from a contaminated territory (the town of Novozybkov) did not show an adaptive response in the conditions described above.

[An analysis of the cellular distribution of chromosome aberrations induced in human lymphocytes after a single irradiation and under conditions of preliminary adaptive exposure]. / Analiz raspredeleniia po kletkam aberratsii khromosom, indutsirovannykh v limfotsitakh cheloveka posle odnokratnogo oblucheniia i v usloviiakh prevaritel'nogo adaptiruiushchego vozdeistviia.

Irradiation by an adaptive dose 0.05 Gy at the G0 stage decreased the number of chromosome aberrations induced in lymphocytes by a challenge dose 0.5 Gy at the G2 stage. Adaptive response was not observed at the G1 stage, when the cells were exposed to adaptive dose 0.05 Gy and challenge dose 1.0 Gy respectively after 24 h and 29 h incubation with PHA. In lymphocytes exposed to 1.0 Gy at the G1 stage, cellular distribution of chromosomal aberrations followed the Poisson distribution, while in lymphocytes exposed to 0.5 Gy at the G2 stage, the distribution of aberrations differed from the Poisson distribution and was nearer to the degenerated Poisson distribution. The adaptive dose 0.05 Gy did not alter the distribution of chromosome aberrations induced by the challenge dose at the G1 or the G2 stages. The role of independent and whole-cellular repair in the formation of chromosome and chromatid aberration is discussed.

[Suppressive action of bone marrow and spleen cells on antibody genesis and lymphoid cell proliferation in an in vitro culture of autoimmune mice (NZB.NZW)F1]. / Supressivnoe deistvie kletok kostnogo mozga i selezenki na antitelogenez i proliferatsiiu limfoidnykh kletok v kul'ture in vitro u autoimmunnykh myshei (NZB.NZW)F1.

The ability of bone marrow and spleen cells of autoimmune (NZB.NZW) F1 strain of mice of various age to suppress the immune response and spleen cells proliferation of young syngeneic mice in vitro was studied. The SRBC were used as an antigen. The proliferation rate was measured by the intensiveness of 3H-thymidine incorporation into DNA of cells being in the process of division. It has been found out that the bone marrow supressive activity in (NZB.NZW) F1 strain of mice undergoes age-associated changes. In mice 4-5 months of age the temporary reduction of suppressor-cell activity in the bone marrow is observed. The bone marrow suppressive activity recovers by 8-10 months, reaching the level of that observed in mice 1.5-2 months of age. In the spleens of (NZB.NZW) F1 strain of 8-10 months old mice suppressor cells appear lacking in young animals. The possibility of bone marrow B-suppressor participation in the development of the autoimmune process in (NZB.NZW) F1 strain of mice is discussed.

[Electron microscopic characteristics and polypeptide composition of the nuclear matrix of liver cells in mice with autoimmune disease]. / Elektronno-mikroskopicheskaia kharakteristika i polipeptidnyi sostav iadernogo matriksa kletok pecheni myshei s autoimmunnym zabolevaniam.

A study was made of the ultrastructure and polypeptide composition of liver cell nuclear matrix of F1NZB/NZW hybrid mice imitating human systemic Lupus erythematosus. Electron microscopy reveals enlargement in fibrous lamina diameter and increase in pore complex density up to the age of 8-9 months. In the terminal stages of the disease (12-13 months of age) a gradual attenuation of the intranuclear matrix and disappearance of pore complexes is observed along with a segregation and subsequent fragmentation of residual nucleoli which results eventually in the general degradation of the nuclear matrix. 30-35 polypeptide bands with molecular weight from 200 to 10 kD are revealed in polyacrylamide gel electrophoresis of the liver cell nuclear matrix of hybrid mice. Several protein bands in the high molecular weight region of 200-150 kD are strongly enhanced, and a triplet with molecular weight 70-60 kD is distinctly visible. The results obtained are interpreted as an indication of a protecting cellular reaction against antinuclear autoantibodies in the earlier stages, and a degradation of the nuclear matrix in terminal stages of the disease. It is supposed that the electron microscopic and electrophoretic patterns of the nuclear matrix indicate an accumulation of collagenous proteins.