Eight per cent leakage of Lyman continuum photons from a compact, star-forming dwarf galaxy.

One of the key questions in observational cosmology is the identification of the sources responsible for ionization of the Universe after the cosmic 'Dark Ages', when the baryonic matter was neutral. The currently identified distant galaxies are insufficient to fully reionize the Universe by redshift z ≈ 6 (refs 1-3), but low-mass, star-forming galaxies are thought to be responsible for the bulk of the ionizing radiation. As direct observations at high redshift are difficult for a variety of reasons, one solution is to identify local proxies of this galaxy population. Starburst galaxies at low redshifts, however, generally are opaque to Lyman continuum photons. Small escape fractions of about 1 to 3 per cent, insufficient to ionize much surrounding gas, have been detected only in three low-redshift galaxies. Here we report far-ultraviolet observations of the nearby low-mass star-forming galaxy J0925+1403. The galaxy is leaking ionizing radiation with an escape fraction of about 8 per cent. The total number of photons emitted during the starburst phase is sufficient to ionize intergalactic medium material that is about 40 times as massive as the stellar mass of the galaxy.

[Overlap syndromes in rheumatology].

Overlap syndromes in rheumatology present a challenging problem reflecting clinical and immunogenetic heterogeneity of rheumatic disorders. Current statistics refers 25% of the connective tissue diseases to "overlap syndromes". There are three main groups of them, viz. (1) overlap forms of systemic connective tissue diseases, (2) mixed connective tissue disease (Sharp's syndrome), (3) undifferentiated rheumatic disease. Characteristics of these groups are presented based on the published studies and the original data on 100 patients with the most frequent forms of systemic connective tissue pathologies, such as systemic sclerodermias with polymyositis/dermatomyositis (68 patients) and rheumatoid arthritis (32 patients).

[Endothelial dysfunction in scleroderma systematica: clinicopathogenetic correlations].

AIM: To evaluate disturbances of vascular tonicity regulation in scleroderma systematica (SS) patients using laser Doppler flowmetry (LDF) with calculation of amplitude-frequency blood flow fluctuations (variability) basing on the mathematical model wavelet-transformation. MATERIAL AND METHODS: The trial included 101 patients with verified SS aged 21-60 years (mean 52.3 years, 97 females). In addition, 15 and 10 patients with primary and secondary Raynaud syndrome diagnosed by ACR criteria, respectively, entered the trial. The control group consisted of 20 healthy subjects. Cardiovascular patients were not included in the study. Microcirculation was investigated with laser analyzer of capillary circulation in the tip of left hand finger III and external surface of the left arm. Endothelial motor function was studied in the tests with reactive hyperemia and nitroglycerin. RESULTS: SS patients were found to have a significantly higher variability and endothelial rhythm amplitude index in arm skin, reduced microcirculation, the variation index and high neurogenic tonicity in the hand finger tip. A direct correlation was found between severity and area of skin lesion (of the arm, in particular) and their amplitude of endothelial fluctuations (r = 0.38, p = 0.03) of circulation in the arm skin. Persistent correlations between skin count and LDF values were not registered. There was a significant regression of flow-dependent dilation of the brachial artery in SS patients independent of classic cardiovascular risk factors. CONCLUSION: SS patients have defects in regulation of vascular tonicity both in microcirculation and middle-caliber arteries. Vasomotor activity of the middle-caliber vessels is low in the absence of conventional cardiovascular disease risk factors. LDF detects changes in local regulation in cardiovascular patients confirming the role of neuroendothelial disorders in its pathogenesis. The trend to systemic DE in cardiovascular patients is associated with both disease-mediated vascular lesions (ulcers of finger tips, pulmonary hypertension) and cardiovascular disease markers.

[Significance of bone marrow endothelial progenitor cells in disturbance of angiogenesis and endothelial dysfunction in systemic scleroderma].

The study is aimed to investigate the process of endothelial repair related to endothelial progenitor cells (EPC) in systemic sclerosis (SS), and analyze the role of EPC abnormalities in endothelial dysfunction and impaired angiogenesis. Correlation between EPC circulating levels, measured by flowcytometry, and peripheral vascular manifestations, cardiac involvement, carotid artery disease, Framingham risk factor score, endothelial function and morphological signs of microangiopathy is explored. Our data demonstrate, that EPC reduction with disease progression is closely linked with endothelial dysfunction and destructive microangiopathy, and significantly contribute into development of severe cardiac disease and pulmonary hypertension in SS patients.

[Characteristics of clinical symptoms and course of systemic scleroderma depending on sex and age of onset]. / Osobennosti klinicheskikh proiavlenii i techeniia sistemnoi sklerodermii v zavisimosti ot pola i vozrasta nachala bolezni.

AIM: To define clinical features of systemic sclerosis (SS) in age and sex aspects. MATERIAL AND METHODS: The study covered 100 patients aged 15 to 83 years with SS (24 males and 76 females) lasting for 1-15 years (mean 6.2 +/- 4.1 years). Groups of females and males, with disease onset age under 50 years (32 years) and over 50 years were compared. RESULTS: Males had a prevalent diffuse clinical form of SS with advanced skin syndrome, primarily indurative alterations, marked disturbances of microcirculation, abnormal heart rhythm and conduction, interstitial pulmonary fibrosis with development of pulmonary hypertension. The patients with late SS onset are characterized by development of visceral pathology within the first 3 years of the disease. CONCLUSION: In making SS diagnosis and in the disease treatment it is necessary to consider the patients' sex and age, peculiarities of the debut, clinical picture, course and prognosis.

[Level of soluble tumor necrosis factor receptor type I in patients with systemic scleroderma]. / Uroven' rastvorimogo retseptora I tipa faktora nekroza opukholi u bol'nykh sistemnoi sklerodermiei.

AIM: To study content and clinical correlations of sTNF-RI in patients with systemic sclerosis (SS). MATERIAL AND METHODS: Thirty nine SS patients were examined with enzyme immunoassay for serum levels of sTNF-RI and soluble adhesion molecules (sSAM) sVSAM-1, sISAM-1 and sR-selectine using R&D System kits (USA). The control group consisted of 14 healthy subjects (donors). Content of sTNF-RI and sSAM was considered as elevated if it exceeded relevant mean values by 1SD. RESULTS: sTNF-RI content was significantly higher in the patients than in the controls (p = 0.0001) and was similar in patients with diffuse and limited forms of the disease. A rise in sTNF-RI correlated with a rise in pulmonary artery pressure. In patients with pulmonary hypertension or restrictive pulmonary affection sTNF-RI was higher than in patients free of pulmonary hypertension or impaired external respiration function. A marked correlation was found between sTNF-RI and sVSAM-1. Patients with high CRP had significantly higher sTNF-RI level than patients with normal CRP. CONCLUSION: SS is characterized by elevated content of sTNF-RI. This content may serve a diagnostic marker of the disease progression.

[Morphological characteristics of sclerodermic angiopathy]. / Morfologicheskaia kharakteristika sklerodermicheskoi angiopatii.

Capillaroscopic study of the nail bed of patients with scleroderma systematica (SS) detects avascular regions and neoangiogenesis signs, but the data on the morphological substrate of these changes are lacking. Positive correlation is established between the degree of inflammation and fibroblast number in the skin biopsies on the one hand and expression of the avascular foci, their total surface and sclerodermic processes activity, on the other. Vascular lesions in SS manifested with sclerodermic vasculopathy which in some patients is comorbid with vasculitis of microcirculatory vessels. A wide spectrum of morphological vascular lesions reflects clinical heterogeneity of SS. Vascular lesions is an obligatory component, are manifest at early stages of SS and their transformation reflects the disease evolution.

[Clinical value of soluble adhesion molecules in systemic scleroderma]. / Klinicheskoe znachenie rastvorimykh molekul adgezii pri sistemnoi sklerodermii.

The aim of the trial was to study clinical significance of estimation of cell adhesion soluble molecules (CASM) in scleroderma systematica (SS). Quantitation of CASM VCAM-1, ICAM-1 and R-selectin was made with enzyme-immunoassay (R&D System kits, USA) in 38 patients with SS (11 with limited SS and 27 with diffuse SS). The levels of VCAM-1, ICAM-1 and R-selectin was elevated in 30 (79%), 17 (45%) and 20 (53%) patients, respectively. Mean values of VCAM-1 and ICAM-1 in patients were significantly higher than in healthy donors. R-selectin was also higher but insignificantly. A mean CASM level and a relative number of patients with elevated count of CASM in patients with diffuse and limited forms of SS did not differ. In 15 patients with active (progressive) course of the disease the level of VCAM-1 was significantly higher than in patients with chronic (non-progressive) course of SS while concentrations of ICAM-1 and R-selectine were almost the same. Thus, SS patients have elevated levels of CASM. CASM VCAM-1 concentration is the most sensitive marker of SS activity compared to other CASM.

[Vascular pathology in systemic scleroderma]. / Patologiia sosudov pri sistemnoi sklerodermii.

The mechanisms of vascular lesions in systemic scleroderma (SSC) are still little studied with the current comprehensive investigations being focused on this issue. The results of a study dealing with the structural-and-morphological and molecular reasons of sclerodermic micro-angiopathy as compared with the variations and pattern of the clinical disease course are summarized in the article. The structural capillary changes were evaluated on the basis of the results of a wide-field video-capillaroscopy of the nail bed (CNB). The level of soluble adhesion molecules VCAN-1, ICAM-1 and P-selectine determined by the quantitative immune-enzyme assay described the vascular endothelium condition. Morphological examinations of dermal samplings included an identification of the lymphocytic composition of infiltrates by applying the mononuclear antibodies to markers T (CD3, CD4, CD8) and B (CD20) of lymphocytes and detection of the endothelial activation by applying the mononuclear antibodies to intercellular adhesion-1 molecule (ICAM-1). The conducted investigations revealed the structural capillary changes in all SSC patients; the nature of such changes is closely related with a clinical variation and course of the disease. The morphological signs of micro-angiopathy were detected in 98% of patients including at the early disease stage. A more pronounced perivascular infiltration with predominance of CD4+ T-lymphocytes was observed and expression of ICAM-1 to the endothelial cells was registered more often in an active disease course. Higher levels of VCAM-1, ICAM-1 and P-selective in blood were found in 80%, 45% and 48% of patients, respectively. Correlations of VCAM-1 with an activity and a progressing disease course were established. Therefore, the serological and morphological signs of vascular lesions reflect an intensity degree of sclerodermic micro-angiopathy and correlate with an SSC clinical course.

[Effect of vazaprostan on microcirculation in patients with scleroderma systematic]. / Vliianie vazaprostana na mikrotsirkuliatsiiu u bol'nykh sistemnoi sklerodermiei.

AIM: To investigate the effect of vazaprostan (alprostadil) on skin blood flow in patients with sclerodermia systematica (SS). MATERIAL AND METHODS: A total of 51 patients with SS aged 33-70 years were included in the study. 33 of them received a 3-hour infusion of vazaprostan at the standard dose for 20 consecutive days. The rest 18 patients received low molecular dextran solution. Before and at the end of the treatment digital skin microcirculation was measured with a laser Doppler flowmeter. The laser probe was attached to the distal pad of the ring finger on the left hand. Baseline blood flow and vascular reactivity in the tests with sympathetic stimulation, local heating and during orthostasis were evaluated. RESULTS: Baseline blood flow and vascular response to functional tests were significantly reduced in all the patients. At the end of the treatment the flow increased only in patients treated with vazaprostan. Vascular reactivity was not changed after the treatment in both groups of patients. CONCLUSION: Vazaprostan increases baseline blood flow and contributes to the improvement of microcirculation in patients with SS.

Investigation of sialic acids and sialyltransferase activity in blood of patients with systemic scleroderma.

Systemic scleroderma (SSd) is a connective tissue disorder accompanied by generalized fibrosis. A disturbance of the synthesis and production of matrix glycoproteins, such as collagens, fibronectin, and proteoglycans, by connective tissue cells is typical for this disease. We previously demonstrated a decrease in the ganglioside content of cultured skin fibroblasts from patients with SSd. In this work the contents of sialoglycoproteins and sialoglycolipids in blood sera of patients with SSd were estimated. Simultaneously, the level of asialofetuin-sialyltransferase activity in blood plasma of three groups of patients--those with SSd, Raynaud's phenomenon, and with localized scleroderma--was investigated. CMP-5-acetamido-9-deoxy-9-fluoresceinylthioureidoneuraminic acid was used as a substrate for the enzyme assay. It was shown that the concentration of total sialic acid was increased and the concentration of lipid-bound sialic acid was slightly decreased in the blood sera of patients with SSd. A correlation between the lipid-bound sialic acid level and the severity of disease was observed; there was no correlation between severity of disease and total sialic acid. Sialyltransferase assay showed a decrease in the activity level in all three groups of patients. The greatest decrease (2-fold) of this activity was observed in patients with Raynaud's phenomenon. Our data suggest that in SSd and similar diseases the process of glycoconjugate sialylation is disturbed. These changes may considerably affect the mechanisms of regulation of metabolism and cellular interactions.

[Clinical and laboratory characteristics of patients with Sjogren's disease lasting from young age]. / Kliniko-laboratornaia kharakteristika bol'nykh bolezn'iu Shegrena s nachalom zabolevaniia v molodom vozraste.

AIM: Characterization of Sjogren's disease (SD) with onset at early age basing on the comparison of two patient groups--with the disease onset at the age under 30 and over 50. MATERIALS AND METHODS: Clinical, ophthalmological and stomatological examinations were performed in 31 SD patients who developed the disease at the age under 30 (group 1) and over 50 (group 2). RESULTS: In group 1 the disease started with parotitis in 42.8% of cases, dysfunction of secreting epithelial glands was rare, functional activity of exocrine glands was normal, dysproteinemia (high total protein levels, hypergammaglobulinemia, hypoalbuminemia) and immunological defects (high levels of circulating immune complexes, rheumatoid factor, antinuclear factor) were more pronounced. At retrospective analysis not only a decline of functional activity of the salivary and lacrimal glands but also appearance of systemic symptoms were registered. CONCLUSION: Development of systemic SD symptoms at young age necessitates early pathogenetic therapy employing corticosteroid, cytostatic and other drugs.

[Madecassol treatment of systemic and localized scleroderma]. / Lechenie madekassolom sistemnoi i ochagovoi sklerodermii.

AIM: The trial of efficacy of 6-month therapy with madecassol (tablets, ointment, powder) of patients with systemic and focal scleroderma (SS and FS). MATERIALS AND METHODS: 54 patients (49 females and 5 males) aged 15 to 70 years with scleroderma running from 3 months to 15 years entered the study. 30 patients had typical SS, 24 patients had FS. Tablets were given to 18 patients, ointment was applied in 42 patients, powder in 3 and tablets + ointment in 9 patients. Madecassol 10 mg tablets were taken 3 times a day by patients with SS and advanced FS. The ointment was preferred in ulcers and scars on fingers and toes in SS and vascular trophic lesions in FS. In active focal scleroderma the ointment was applied to the skin lesions. The ointment was used 2 times a day (in the morning and evening) for 1-6 months. Madecassol powder was employed rarely, primarily of anal and vulval lesions. RESULTS: 6-month oral course (30 mg/day) in 12 SS patients brought about a decrease of indurative lesions, hyperpigmentation (8), vascular trophic disorders (6) and improvement of general condition (5). Subjective response was good in 10 patients and corresponded to absence of progression. In progressive disease and diffuse skin lesions the drug was ineffective. The best response was obtained in local application of madecassol ointment on digital ulcers in SS. CONCLUSION: Madecassol is effective and well tolerated and therefore recommended for oral and local use in combined treatment of SS adn FS. Indications for per os utelization are: chronic or subchronic SS with limited skin involvement, advanced and/or prone to progression FS in which combined administration of the tablets and ointment is proposed.

[Forty years study of systemic scleroderma (data of Institute of Rheumatology, Russian Academy of Medical Sciences)]. / 40 let izucheniia sistemnoi sklerodermii (po dannym Instituta revmatologii RAMN).

The basic stages and the results of 40-year studies of systemic scleroderma (SSD) at the Institute of Rheumatology, Russia Academy of Medical Sciences, are given. The goal-oriented studies of the systemic, peripheral, and visceral manifestations of the disease, which were undertaken in the 1960s basically altered our insight into the disease. Subsequently the diagnostic signs of the disease were developed, which substantially improved the diagnosis of SSD. Long-term studies examined the evolution of SSD and identified three major types of its course: acute, subacute, and chronic, which differ in the rapidity of progression of a pathological process, the pattern of clinical and morphological manifestations and prognosis, as evidenced by survival rates. The identified types of the course (n = 3) and clinical forms (n = 5) formed the basis for the Russia classification of SSD. Studying the pathogenesis of the disease mainly in the context of the mechanisms of formation of fibrosis and impaired microcirculation, as well as its clinical heterogeneity served as the basis for developing pathogenetic therapy regimens by differentially using disease-modifying agents and other therapeutical complexes. At present, the Institute of Rheumatology has accumulated unique experience in studying and following over 1500 patients with SSD and related diseases. There is a rise in the sclerodermal group of diseases, cross-over and combined forms of SSD along with great progress in the diagnosis and treatment, which enhances the quality of life of patients with SSD and prognosis in them.