[Human pathologies associated with mutations of mitochondrial genome].

In this revue different mitochondrial cytopathys were characterized. For each cytopathy we named mutations associated with this type of human pathology. This article may be useful for practicing doctors who are trying to find the cause of the patient's disease and for medical geneticists that are going to provide research in area of mitochondrial cytopathies.

[Current aspects of glucocorticoid therapy of rheumatic diseases. Pulse-therapy].

Mechanisms of action, clinical efficacy and safety of superhigh doses of methylprednisolone (pulse-therapy) in patients with SLE, RA, systemic vasculitis, Sjogren's disease are outlined.

[Advances and prospects in the treatment of systemic lupus erythematosus].

AIM: To reveal the priorities of Russian rheumatology to develop treatment options for systemic lupus erythematosus (SLE). MATERIALS AND METHODS: The data available in the Russian and foreign literature, the archives and publications by the researchers of the Institute of Rheumatology on systemic lupus erythematosus in 1958 to 2008 were analyzed. RESULTS: Analyzing the literature references has ascertained that the researchers of the Institute of Rheumatology, Russian Academy of Medical Sciences, have initiated studies to develop therapy methods for SLE since 1958. Diagnostic criteria for and SLE course type definitions and classification have been first developed in Russian and foreign medicine; the principles of optimal glucocorticoid, cytostatic therapy, and follow-up of patients with SLE have been proposed on the basis of a long-term observation. In Russian medicine, the Institute's researchers have first developed an algorithm of therapy for lupus nephritis, by using plasmapheresis, pulse therapy with methylprednisolone and cyclophosphan, and suppressing and maintaining doses of glucocorticoids. The practical application of the SLE treatment methods developed at the Institute have reduced mortality and increased 10-year survival in patients with SLE up to 90%. The Institute of Rheumatology has first provided data on the efficiency of anti-B-cell therapy for SLE in Russian rheumatology. CONCLUSION: Prognosis in patients with SLE has substantially changed in the past 50 years. The Russian rheumatologists have studied the clinical manifestations of the disease in detail; its diagnosis has improved; the specific features of SLE have been revealed; the treatment methods adequate to the clinical manifestations of the disease have been developed. Multicomponent therapy for SLE, monitoring, and follow-ups have solved the problem of curing SLE.

[Synovial membrane in the early stage of rheumatoid arthritis: clinico-morphological comparisons]. / Sinovial'naia obolochka na rannei stadii revmatoidno artrita: kliniko-morfologicheskie sopostavleniia.

AIM: To evaluate implications of pathomorphological alterations of synovial membrane at an early stage of rheumatoid synovitis (RS) for further course of rheumatoid arthritis (RA) and prognosis of the disease. MATERIAL AND METHODS: 92 new cases of RA (22 males, 70 females, mean age 31.1 +/- 10.5 years, mean duration of RA 5.99 +/- 3.27) subjected to puncture biopsy of the synovial membrane of the knee joint in 1967-1983. At admission to hospital 54.3, 45.7 and 29.3% patients had polyarthritis, mono- and oligoarthritis, rheumatoid factor, respectively. The RA diagnosis was confirmed in 68 (73.9%) patients, 26 (28.3%) of them were observed for 1-2 years, 42 (45.6%)--for 11.8 +/- 8.8 years, on the average. In 9 (9.8%) patients the diagnosis was changed for Bechterew's disease (n = 6), polymyositis (n = 1), rheumatism (n = 1), reactive arthritis (n = 1), 15 (16.3%) patients with seronegative oligoarthritis of large joints were lost for follow-up. Now (the beginning of 2002) synovial biopsies were investigated in "blind" mode by one morphologist (using the semiquantitative method) and compared to clinical and x-ray evidence. RESULTS: The most frequent changes were the following: proliferation of lining synovial cells (82.6%), lymphoid infiltration (64.1%), angiomatosis (60.9%), fibrinoid changes (60.9%). Accumulation of large amounts of macrophages and lymphocytes in the infiltrate was detected in RA significantly more often than in non-RA patients. Among 68 patients with definite RA morphological picture in biopsies obtained from the knee joints with manifest synovitis (69.1%) and from clinically intact joints (30.9%) was practically the same. The most important morphological sign was angiomatosis associated with early polyarticular involvement, early development of joint erosions and early disability (patients with marked angiomatosis were disabled after 4 years of illness, on the average, without angiomatosis--after 11 years). Statistically significant associations of parameters of RA development with other histological signs of synovitis were not detected. CONCLUSION: Angiomatosis in the synovial membrane occurs at early (including preclinical) stages of RA and, as a manifestation of angiogenesis, is an unfavorable prognostic factor of early polyarticular involvement, early development of joint erosions and early disability. Synovial biopsy at an early stage of arthritis is of differential-diagnostic value and helps to define a long-term outcome. Therefore, synovial biopsy of the knee joint must be in the list of standard examinations of patients with early RA.

[Significance of damage index in predicting systemic lupus erythematosus outcome]. / Znachenie indeksa povrezhdeniia v prognozirovanii iskhoda sistemnoi krasnoi volchanki.

AIM: To determine the significance of the damage index (SLICC/ACR DI) in the prognosis of the outcome of systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Correlations between the disease activity, cumulative damage and outcome were studied in 103 patients with SLE divided into two groups by the disease duration (21 to 60 months--group 1, 62 to 488 months--group 2). SLE activity was determined by Nasonova's classification, SLEDAI-1 and ECLAM. Cumulative damage was assessed by the damage index (systemic lupus international collaborating clinics/ACR damage index). RESULTS: We found the direct correlation between the age of the disease onset, SLE duration, degree of SLE activity and the damage index and between the maximal dose of glucocorticosteroids and the damage index. CONCLUSION: The results indicate that SLICC/ACR DI may be useful for outcome prediction in SLE.

[Deforming hand arthropathy in systemic lupus erythematosus]. / Deformiruiushchaia artropatiia kistei pri sistemnoi volchanke.

A case of systemic lupus erythematosus with deforming hand arthropathy (DHA) is reported in a woman observed for 15 years. DHA was presented with stable ulnar deviation, deformation of the fingers. This resulted in functional insufficiency of the hand of the third degree.

[The effect of bemetil on the production of DNA antibodies in patients with systemic lupus erythematosus]. / Vliianie bemetila na produktsiiu antitel k DNK u bol'nykh sistemnoi krasnoi volchankoi.

The levels of autoantibodies against DNA in blood serum and severity of the disease were evaluated prior to, during, and after 8-week treatment of patients suffering from lupus erythematosus systemicus (LES) with prednisolonum (daily dose of 5-60 mg/kg, 15 patient) and with prednisolonum in combination with cyclophosphane (CP) (a total dose of 2-4 mg/kg per os. 15 patients), or bemithyl doses of 500-750 mg/day per os (15 patients) or bemithyl in combination with CP (the same doses, 16 patients). It was shown that introduction of bemithyl into LES treatment schedule significantly lowered the level of autoantibodies against DNA evaluated in immunoassay and reduced LES severity assessed using standard SLEDAI-1 and ECLAM scales.

Receptor-mediated transport of foreign DNA into preimplantation mammalian embryos.

Mouse and rabbit preimplantation embryos with intact zona pellucida were incubated for 3 hr with DNA-carrying constructs containing insulin as an internalizable ligand: (insulin-polylysine)-DNA and (insulin-polylysine)-DNA-(streptavidin-polylysine)-(biotinylated adenovirus). Video-intensified microscopy demonstrated that the constructs penetrated the zona pellucida and accumulated in the blastomere perinuclear space. The percentage of blastocysts formed was about 70% after incubation of zygotes and two-cell embryos with the constructs. Foreign DNA was detected after 51 hr in 80% of rabbit embryos and after 96 hr in 73% of mouse embryos. Inclusion of various adenoviruses into the construct improved foreign DNA preservation in early embryos. Blot hybridization revealed genome-integrated foreign DNA in 12- and 15-day mouse embryos and in a newborn. Thus, the ligand-mediated mechanism can be employed for introducing foreign genetic material into early mammalian embryos; insulin provides for delivery inside the cell and to the nucleus, while adenoviruses ensure release from endosomes.

[Scientific bases of medical examinations of patients with rheumatic diseases]. / Nauchnye osnovy dispanserizatsii bol'nykh revmaticheskimi zabolevaniiami.

The 40-year experience of the Institute of Rheumatology has shown that follow-up in rheumatic diseases is the necessary method of management of patients with rheumatic diseases since it is the method that makes it possible to control the progression of disease and provide long-term safe treatment with glucocorticoids, cytotoxics, and other antirheumatic drugs which are now widely used in rheumatological care. Medical examination mainly made in rheumatism caused a substantial reduction in the number of relapses. Since the 1960s, intensive and scientifically grounded studies in medical examinations for other rheumatic diseases have promoted more prolonged longevity and better working fitness in the vast majority of patients. Thus, a long-term follow-up of over 600 patients with exanthematous lupus erythematosus made it possible to detail its clinical picture and to develop the therapeutical programmes that control the progression of the disease in 93% of the patients who had been incurable before. In rheumatoid arthritis, the follow-up of large groups of patients by using the computer database has enabled the researchers to develop a mathematically accurate method for prediction of the progression of disease by employing the integral parameter--the index of severity, as well as to reveal a number of important regularities of treatment. A follow-up of patients with reactive arthritis, Bekhterev's disease, systemic scleroderma, and other rheumatic diseases is shown to be of great importance.

[Comparative study of DNA-repair ability of lymphocytes from systemic lupus erythematosus and rheumatoid arthritis patients]. / Sravnitel'noe issledovanie DNA-repariruiushchei sposobnosti limfotsitov bol'nykh sistemnoi krasnoi volchankoi i revmatoidnym artritom.

Induction of DNA breaks with 4-NQO and their resynthesis in the cultivated lymphocytes of peripheral blood of 23 patients with systemic lupus erythematosus (SLE) and 12 patients with rheumatoid arthritis (RA) were studied by the method of hydroxyapatite column chromatography of cell lysates. The number of spontaneous DNA breaks was shown to increase in 48% of patients with SLE and in 42% of patients with RA, compared to that in the control. Inhibition of the repair process was observed in 35% of patients with SLE and in 17% of patients with RA. Complete repair of DNA breaks was observed in 67% of patients with RA and only in 26% of patients with SLE.

[Active forms of oxygen and pathogenesis of rheumatoid arthritis and systemic lupus erythematosus]. / Aktivnye formy kisloroda i patogenez revmatoidnogo artrita i sistemnoi krasnoi volchanki.

In this paper the authors underline the significance of studies into the body's free radical oxidation, analyze the involvement of free radical reactions in the maintenance of homeostasis. They indicate that free radical metabolic changes leading to oxidative stress play a role in the pathogenesis of many human diseases. Particular emphasis is laid on the contribution of active forms of oxygen (AFO) in the development of autoimmune diseases, including rheumatic diseases. The history of this problem is outlined. There are examples that confirm the enhancement of free radical processes and the inhibition of the antioxidative system in rheumatic arthritis (RA) and some other rheumatic diseases. The essential drugs used in the treatment of RA patients are demonstrated to also act due to the inhibited "respiratory outbreak" of phagocytes. The key point of the paper is the role of free radical reactions in the pathogenesis of systemic lupus erythematosus (SLE). There is evidence suggesting that there is a reduction in antioxidative defense and a rise in neutrophilic production of AFO in SLE patients. Consideration is also given to the possible participation of AFO in the formation of DNA antibodies, the effects of AFO on the immune system, atherogenesis in SLE. Taking into account a possible contribution of AFO in the pathogenesis of SLE, it is expedient to include antiradical agents into the multimodality therapy for this disease and promising to continue investigations in this field.

[The long-term parenteral use of cyclophosphane in treating patients with systemic lupus erythematosus and central nervous system involvement]. / Dlitel'noe parenteral'noe primenenie tsiklofosfana v lechenii bol'nykh sistemnoi krasnoi volchankoi s porazheniem tsentral'noi nervnoi sistemy.

In the treatment of systemic lupus erythematosus (SLE) with acute CNS affections good results may be obtained with intravenous cyclophosphamide (CP) + methylprednisolone followed with long-term parenteral CP administration. CNS abnormalities in SLE patients can be effectively managed by parenteral CP in combination with minimal-dose glucocorticoids given for 5-7 years.

[Corticosteroid therapy and aseptic bone necrosis in patients with rheumatoid arthritis]. / Kortikosteroidnaia terapiia i asepticheskie nekrozy kostei u bol'nykh revmatoidnym artritom.

Two groups of RA patients were compared: 102 patients with osteonecrosis of the head of the femur (group 1) and 50 patients free of it (group 2). Group 1 patients had bilateral lesion of the hip joints (28% of cases), unilateral osteonecrosis of knee joint in 14.5% and bilateral in 2.9% of the patients. Unilateral humeral osteonecrosis occurred in 17.6%, bilateral in 4.9% of patients. Extra-articular manifestations of RA (lymphadenopathy, renal lesions and Cushing's syndrome) were diagnosed more frequently in group 1. Progression of osteonecrosis is related to a mean maximal day dose of prednisolone in the first month of therapy.