Articles
Objective: to study an association of bone mineral density (BMD) with the expression of genes associated with the proliferation, survival, and differentiation of osteocytes in the peripheral blood of postmenopausal women with osteoporosis (OP).
Subjects and methods. Twenty-eight postmenopausal women with OP and 17 age-matched healthy women were examined. BMD was measured by X-ray absorptionmetry. Alkaline phosphatase activity and calcium and phosphorus levels in the blood were determined by conventional methods. RNA was isolated from the peripheral blood and used to estimate the gene expression, by using real-time polymerase chain reaction (RT-PCR).
Results. The postmenopausal women with OP were observed to have a significant increase in the expression of ATG1 (serine-threonine kinase that is responsible for the generation of autophagic vacuoles) as compared to the healthy controls, which suggests that autophagy develops in the blood cells of these patients. This was attended by a considerable reduction in the expression of the mTOR (the mammalian target of rapamycin) gene, a regulator of protein synthesis and cell proliferation, and in that of the genes associated with the differentiation of osteoblasts: transforming growth factor β1 (TGF-β1), Runx 2 (Runt-related transcription factor 2) and total alkaline phosphatase (TAP), and the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β). The expression of mTOR, TGF- β1, Runx2, and IL-1β genes was positively correlated with BMD in individual areas of the hip. On the contrary, that of ATG1 and TAP was correlated negatively with BMD in this area and positively with that in the spine. Although the expression of the genes in question was not correlated with the serum levels of phosphorus and calcium, that of TGF-β1 was positively related to TAP activity in postmenopausal women with OP.
Conclusion. In postmenopausal women with OP, bone loss is accompanied by a significant increase in the expression of the autophagy marker ATG1 and by a reduction in that of mTOR, which may be indicative of the inhibition of protein biosynthesis and cell proliferation and the suppression of the expression of the genes associated with the differentiation of osteoblasts and the proinflammatory cytokines TNF- α and IL-1β. The obtained data on gene expression may be used to search for new disease markers tested in peripheral blood.
Objective: to estimate the frequency of prescription for antiosteoporotic agents in real clinical practice and treatment adherence within a year after experienced low-trauma osteoporotic fracture (LOF).
Subjects and methods. A questionnaire survey was made in 192 subjects aged over 50 years (mean age 66±8 years) who had sustained fractures at different sites after a fall from standing height. Therapy and its compliance were assessed 4 and 12 months after LOF.
Results. One hundred and five (55%) patients received therapy, including 80 (73%) took only calcium preparations and vitamin D; 9 (8%), 15 (14%), and 5 (5%) patients had calcitonin, bisphosphonates, and strontium ranelate, respectively. At the same time, 87 (45%) subjects were given no antiosteoporotic drugs for a year after fracture. Throughout the follow-up, 42% of the respondents received treat- ment; 18% interrupted it within the first 4 months after fracture, and 40% started therapy 4 months or later (mean 6.5 months) after it. The reason for the absence of treatment was no recommendations by a traumatologist or primary care specialists in 49% of cases. Among those taking the drugs, treatment was recommended by the specialists of the Osteoporosis Center, Research Institute of Rheumatology, Russian Academy of Medical Sciences, in 89% of cases and by primary care specialists in only 11%.
Conclusion. The study indicated that after LOF, the patients did not receive adequate antiosteoporotic therapy, at the same time 49% had no respective recommendations made by traumatologists or primary care physicians. The frequency of prescription for pathogenic agents for the treatment of osteoporosis was considerably increased during patient observation in a specialized osteoporosis center.
Objective: to assess the course of osteoarthrosis associated with obesity, by examining the secretion of hormones produced by adipose tissue, as well as that of proinflammatory cytokines.
Subjects and methods. Eighty-one patients aged 47 to 73 years, who had been diagnosed as having osteoarthrosis in accordance with the criteria developed by R. Altman, were examined. Anthropometric characteristics, the duration of the disease, the degree of functional fail- ure, and the levels of adipocytokines (adiponectin, interleukins (IL) 4 and 6) were estimated and X-ray study of the joints was conducted in all the patients. The impact of altered adipokine secretion on the course of osteoarthrosis and the degree of pain was evaluated.
Results and discussion. The elevated level of proinflammatory interleukin (IL-6) was associated with severer X-ray changes, higher func- tional failure, the presence of synovitis, and evident pain syndrome. At the same time, IL-4 and adiponectin were decreased in severe osteoarthrosis. Thus, the change in the level of the above adipokines is associated with the poor course of osteoarthrosis.
Objective: to define the clinical value of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) in early psori- atic arthritis (PA).
Subjects and methods. Fifty-six patients (32 females and 24 males) with early PA with a mean duration of 12±6.7 months were studied. The examinees' age ranged from 18 to 76 years (mean age 44±15.5 years). Mean psoriasis duration was 12.5±2.2 years. RF IgM was determined using a high-sensitive nephelometric method on a BN Pro-Spec analyzer (Siemens, Germany) and serum anti-CCP concentra- tions were measured by immunochemiluminescence on a COBAS e411 analyzer (Roche, Switzerland). Group 1 included 10 patients with anti-CCP and/or RF (a study group); Group 2 comprised 46 patients without anti-CCP and RF (a control group).
Results. There was anti-CCP in 7 (12.5%) of the patients with early PA, RF in 8 (14.3%), both of them in 5 (9%). The study group had a severer course of PA accompanied by polyarthritis, inflamed distal interphalangeal joints, axial arthritis, dactylitis, enthesitis, and, in some cases spondylitis and sacroiliitis. In groups 1 and 2, the number of tender joints was 17.6±4 and 10±1.5, respectively (p = 0.04); that of swollen ones, 12.6±1.5 and 7.0±1.1 (p = 0.02); DAS28 index, 5.9±1.7 and 4.5±1.5 (p = 0.02); ESR, 34.5±5.9 and 22±2.3 (p = 0.04), high-sensitive C reactive protein, 70±25.3 and 24.9±5.0 (p = 0.06); and Sharp ratio, 68.7±14.3 and 21.3±3.8 (p < 0.004).
Conclusion. In patients with early PA, anti-CCP and RF were encountered with an approximately equal frequency; at the same time, they were associated with polyarthritis, high disease activity, and an erosive process.
Objective: to analyze the incidence of giant-cell arteritis (GCA) in the Khabarovsk Territory.
Subjects and methods. Ten (11.6%) cases of GCA identified during a 20-year prospective follow-up and treatment of 89 patients with polymyalgia rheumatica (PR) and GCA were analyzed. The rate of some criteria for the diagnosis of GCA was estimated; its onset and paraclinical data were described. The study enrolled women aged 67.3±2.1 years (range 59 to 76 years).
Results and discussion. GCA concurrent with PR was observed in 70% of cases. In addition to temporal arteritis, there was a clinical picture of involvements of the parietal (50%), ocular (30%), occipital (30%), and coronary (10%) arteries. Scalp involvement with necrosis in the parietal area was found in one case. The diagnosis was established after an average of 71±1.6 months. All had elevated ESR, up to 110.2±3.1 on average after Westergren. Seven patients were treated with prednisolone 1.0 mg/kg body weight; due to contraindications,
6 patients had 0.5 mg/kg in combination with pulse therapy with cyclophosphanum 1000 mg intravenously, dropwise once monthly. One female patient died from stroke 4 months later. The late period was marked by the development of osteoporosis with fractures in 2 cases, diabetes mellitus and hypertension in 2, and cancer of the cervix uteri (successfully cured) in one case. Vision loss was seen in one patient whose diagnosis was made 1.5 years later.
Objective: to analyze disease activity, functional state, quality of life (QL), and the frequency of infectious complications in methotrexate (MT) – or leflunomide (LF)-treated patients with rheumatoid arthritis (RA) who had undergone endoprosthetic replacement of the large joints of the lower limbs.
Subjects and methods. One hundred and fourteen patients with RA who had undergone endoprosthetic replacement of the knee and hip joints were divided into 3 groups: 1) 36 patients who continuously received MT or LF in the perioperative period; 2) 42 patients who dis- continued MT or LF 2 and 4 weeks, respectively, prior to surgery; 3) 36 patients who took no disease-modifying anti-rheumatic drugs (DMARDs) within 12 months before surgery. Disease activity was estimated by the DAS28 index. QL was determined using the EQ-5D questionnaire and functional capacity was estimated by the HAQ index.
Results and discussion. In all the groups, there was a preponderance of patients with moderate RA activity (more than 60%). In Groups 1 and 2, the mean dose of MT was about 10 mg weekly and that of LF was 20 mg daily. The use duration of glucocorticoids (GC) and their doses were comparable in all the groups. Twelve months after surgery, DAS28 significantly reduced from 4.22±1.08 to 3.58±1.07 months in Group 1 (p = 0.01); in Group 2, the decrease was insignificant: from 4.17±1.17 to 3.80±1.15 (p > 005); in Group 3, RA activity remained as before. All the groups achieved 50% functional improvement; better results were obtained in the group of patients who continued to use DMARDs in the perioperative period (∆HAQ=-0.67). The difference in the Eq-5D index corresponded to a moderate QL improvement: ∆EQ-5D = 0.28, 0.29, and 0.31 in Groups 1, 2, and 3, respectively (p < 0.05). There were no significant group differences. Deep infection in the endoprosthetic replacement area was detected in 2.8, 2.4, and 8.3% of cases, respectively (p > 005).
Conclusion. Continuous use of MT and LF leads to a reduction in total disease activity and to functional improvement in patients with RA after endoprosthetic joint replacement, without increasing the frequency of infectious complications.
Along with its basic activity in removing B-lymphocytes, rituximab (RTM) causes depletion of a population of CD20+ T cells that can pro- duce a variety of immunoregulatory and proinflammatory cytokines and chemokines.
Objective: to define a role of multiplex cytokine analysis in the evaluation of the efficiency of using RMT in rheumatoid arthritis (RA).
Subjects and methods. Thirty-four patients with the valid diagnosis of RA according to the ACR criteria of 1987 were examined. The con- centrations of cytokines were measured using the xMAP technology (27-plex).
Results and discussion. In the group of patients with a clinical response to therapy with the gene engineering biological agent, there was a decrease in the concentrations of interleukins (IL) 1β, 1ra, 2, 4, 6, 9, and 13, granulocyte macrophage colony-stimulating factor (GM- CSF), γ-interferon (IFN-γ), monocyte chemoattractant 1 at week 8 of therapy; that in IL 1β, 1ra, 2, 5, 6, 9, 10, 12, 13, and 15, fibroblast growth factor 2 (FGF-2), GM-CSF, IFN-γ, and tumor necrosis factor-α at week 24, and that in IL-9 at week 40. The no-clinical response group showed a reduction in GM-CSF at week 8 and in IL-2 and macrophage inflammatory protein 1β (MIP-1β) at week 40, and an increase in IL-8 at week 8. At week 8 after drug infusion, the elevated levels of IL-17 and MIP-1β can be identified as possible early pre- dictors of a response (at week 40). Comparison of the baseline cytokine levels in the groups with different clinical response demonstrated a more than three-fold increase in the concentrations of IL 4, 5, 7, 8, 10, 12, 13, 15, 17, IFN-γ, and vascular endothelial growth factor, and IL-8 at weeks 8 and 40, respectively.
Objective: to estimate the advantages and disadvantages of using the injectable formulation of methotrexate (MT) (Methoject (MTJ)) in rheumatoid arthritis (RA) in clinical practice.
Subjects and methods. A 24-week open-label controlled randomized comparative study evaluated the therapeutic and side effects of MTJ and methotrexate tablets in RA and clarified whether MTJ treatment might be continued if its tabletted formulation was discontinued because of adverse reactions.
Results and discussion. MTJ was found to be more effective than the tabletted formulation of MT and as a whole; and following 3-month therapy, more patients receiving MTJ achieved an ACR20 response. The advantage of MTJ was also retained 6 months after therapy. Higher transaminase levels were noted in 2 patients, one in each group. Switching from MT to MTJ noticeably reduced the number of adverse reactions in the majority of patients from an additional group.
Conclusion. As compared to MT, MTJ used in RA patients is more effective when given in an equivalent dose, exerts a therapeutic effect more rapidly, and induces adverse gastrointestinal reactions less frequently.
Nekhodzhkinskie limfomy (NKhL), predstavlyayushchie soboi geterogennuyu gruppu opukholei iz limfoidnoi tkani, naibolee chasto (>90%) imeyut V-kletochnoe proiskhozhdenie. Vozmozhno, etot fakt obuslovlen osobennostyami V- kletochnogo immunnogo otveta. Tak, neobkhodimoe porazitel'noe raznoobrazie immunoglobulinov (Ig) po spetsifichnosti tsentrov svyazyvaniya s antigenom obespechivaetsya razlichnymi mekhanizmami, vklyuchayushchimi somaticheskii mutagenez, gennuyu konversiyu, rekombinatsiyu ryada gennykh segmentov, obrazuyushchikh polnyi V-gen (variabel'noi oblasti molekuly Ig).
ISSN 1995-4492 (Online)