Inactive Stage Research Articles

Patients with chronic hepatitis B treated with oral antiviral therapy retain a higher risk for HCC compared with patients with inactive stage disease

BackgroundIt is generally stated that oral antiviral therapy in patients with chronic hepatitis B (CHB) decreases the risk of developing hepatocellular carcinoma (HCC). Although oral nucleos(t)ide analogues (NUCs) may induce...

Mean platelet volume as an indicator of disease activity in juvenile SLE

The aim of the study was to assess mean platelet volume (MPV) in children with systemic lupus erythematosus (SLE) at the active and inactive stages. Twenty children with SLE and 30 age- and gender-matched controls were enrolled. Demographic data, SLE disease activity index (SLEDAI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), MPV, complement 3 (C3), complement 4 (C4), urine protein (Up), and urine creatinine (Ucr) values upon reactivation and remission phases were recorded. MPV was statistically higher in patients than in controls and significantly increased in active phase compared to inactive phase (p = 0.001). A MPV level of 8.4fL was determined as predictive cutoff value of activation of SLE (sensitivity 75%, specificity 90%). MPV was positively correlated with SLEDAI (p = 0.01, r = 0.55), ESR (p = 0.01, r = 0.45), CRP (p = 0.04, r = 0.24), and Up/Ucr (p = 0.01, r = 0.45) and negatively correlated with C3 (p = 0.02, r = -0.36), albumin (p = 0.01, r = -0.63), and Hb (p = 0.01, r = -0.48). There was not any significant association between MPV and the histological classification of lupus nephritis (p = 0.65). MPV might be used as an early indicator of reactivation in children with SLE. MPV seemed to be more accurate than ESR, CRP, and C3 for monitoring the disease activity in SLE.

Integrating Successional Ecology and the Delta Lobe Cycle in Wetland Research and Restoration

Inactive deltas are more extensive than active deltas in most deltaic landscapes; thus, the subsurface generally is dominated by mineral sediments that rapidly accreted at different times, whereas the landscape at any one time generally is dominated by ephemeral emergent wetlands that are slowly accreting via vegetative growth. Subsidence is slow enough in most deltas that emergent wetlands, although ephemeral, can persist for millennia but accelerating global sea level rise probably will slow wetland creation in active deltas and accelerate the loss of existing wetlands in inactive deltas this century worldwide. A recent publication created confusion regarding the effects of river management on coastal Louisiana, where spatially variable subsidence is great enough in some areas to mimic extremely rapid sea level rise. I show how integrating Successional Ecology with the Delta Lobe Cycle, and correcting some omissions and errors in recent publications, clarifies the effects of river management in coastal Louisiana and provides a framework for predicting deltaic landscape dynamics worldwide. Successional Ecology provides a framework for understanding changes in natural and managed environments worldwide, whereas the Delta Lobe Cycle provides a framework for understanding river-dominated deltas worldwide. Sediment diversions are a form of river management that removes artificial barriers to river flow and are designed to mimic hydrologic conditions during the active delta stage of the Delta Lobe Cycle by focusing rapid mineral sedimentation in open water and thus creating new emergent wetlands. Freshwater diversions are another form of river management that also removes artificial barriers to river flow but are designed to mimic hydrologic conditions during the inactive stages of the Delta Lobe Cycle by reducing salinity stress over large areas of emergent wetlands and thus promoting marsh vertical accretion via vegetative growth. The Delta Lobe Cycle and both types of river diversions also create salinity gradients that simultaneously increase the sensitivity of emergent wetlands to disturbance while increasing the ability of emergent wetlands to recover from disturbance. Freshwater diversions only slow the loss of existing wetlands because the natural Delta Lobe Cycle, artificial channels that increase salinity stress, artificial ridges that increase flooding stress, and repeated disturbances eventually will cause vertical accretion via vegetative growth to become inadequate. Formally integrating these concepts might advance research and restoration in deltaic landscapes worldwide especially in the majority of deltas where inactive deltas are more extensive than active deltas.

Distant activity of Comet C/2002 VQ94 (LINEAR): Optical spectrophotometric monitoring between 8.4 and 16.8 au from the Sun

Spectrophotometric monitoring of distant Comet C/2002 VQ94 (LINEAR) was performed with the 6-m telescope of SAO RAS (Special Astrophysical Observatory of Russian Academy of Sciences) and with the 2.5-m Nordic Optical Telescope (Observatory del Roque de los Muchachos, Canarias, Spain) between 2008 and 2013. During this period the comet was on the outbound segment of its orbit, between heliocentric distances of 8.36au and 16.84au. Analysis of the spectra revealed the presence of the CO+ and N2+ emissions in the cometary coma at a distance of 8.36au from the Sun. This distance is larger than ionic emissions have been detected in any previous objects. Only continuum, with no traces of emissions, was detected in the spectrum obtained in 2009 when the comet was at a distance of 9.86au. From the spectra obtained in 2008, average column densities of 2.04×109molcm−2 for N2+ and 3.26×1010molcm−2 for CO+ were measured in the cometary coma. The derived values correspond to N2+/CO+=0.06 within the projected slit. Images obtained through a red continuum filter in 2008 showed a bright, dust coma, indicating a high level of physical activity. A considerably lower level of activity was observed in 2009 and 2011 at distances of 9.86au and 13.40au respectively. No noticeable activity was detected in 2013 at a heliocentric distance of 16.84au. The Afρ parameter, which is used as an indicator of cometary activity, was measured as 2000cm in 2008, and 800cm in 2009 and 2011. The Afρ values correspond to dust production rates between 10–20kgs−1, 4–6kgs−1 and 3–5kgs−1 at 8.36, 9.86, and 13.40au respectively. There is an obvious correlation between the decrease of the dust production rate of the nucleus and the disappearance of the emissions in the spectrum of C/2002 VQ94 (LINEAR) at heliocentric distances greater than 9au. The colors and size of the nucleus of C/2002 VQ94 (LINEAR) were estimated from the images obtained during the late stage at a heliocentric distance of 16.84au, when the activity had probable ceased. The B–V and V–R colors were estimated to be 1.07±0.05 and 0.54±0.03 respectively. The effective nucleus radius of 48±2km is in agreement with the previously published results, obtained from the observations of the comet during its early inactive stage (Jewitt, D. [2005]. Astron. J. 129, 530–538; Weiler, M., Rauer, H., Sterken, C. [2011]. Icarus 212, 351–366).

ЭФФЕКТИВНОЕ ПРИМЕНЕНИЕ МОНОКЛОНАЛЬНЫХ АНТИТЕЛ К TNF Α — АДАЛИМУМАБА — КАК ПРЕПАРАТА ПЕРЕКЛЮЧЕНИЯ У ПАЦИЕНТА С ЮВЕНИЛЬНЫМ ИДИОПАТИЧЕСКИМ ПОЛИАРТРИТОМ И УВЕИТОМ

The article presents a case of severe juvenile idiopathic arthritis associated uveitis in a patient who contracted the disease at the age of 10 year. Uveitis developed 9 months after manifestation of the articular syndrome in the event of etanercept therapy. Switch to adalimumab induced remission of the articular syndrome and uveitis. By the 8th week of treatment, an inactive disease stage (6 months) was diagnosed in a child.

Association of human leukocyte antigen DQB1 and DRB1 alleles with chronic hepatitis B.

To investigate the effect of human leukocyte antigen (HLA) DRB1 and DQB1 alleles on the inactive and advanced stages of chronic hepatitis B. Patient records at a single institution's hepatology clinic were reviewed. Demographic data, laboratory results, endoscopy results, virological parameters, biopsy scores and treatment statuses were recorded. In total, 355 patients were eligible for the study, of whom 226 (63.7%) were male. Overall, 82 (23.1%) were hepatitis B early antigen (HBeAg) positive, 87 (24.5%) had cirrhosis, and 66 (18.6%) had inactive disease. The presence of DQB1 and DRB1 alleles was determined by polymerase chain reaction with sequence-specific primers. The distribution of the genotyped alleles among patients with cirrhosis and patients with chronic active hepatitis was analyzed. The most frequent HLA DQB1 allele was DQB1*03:01 (48.2%), and the most frequent HLA DRB1 allele was DRB1*13/14 (51.8%). DQB1*05:01 was more frequent in patients with active disease than in inactive patients (27% vs 9.1%; P = 0.002, Pc = 0.026). DRB1*07 was rare in patients with cirrhosis compared with non-cirrhotics (3.4% vs 16%; P = 0.002, Pc = 0.022). Older age (P < 0.001) and male gender (P = 0.008) were the other factors that affected the presence of cirrhosis. In a multivariate logistic regression analysis, DRB1*07 remained a significant negative predictor of cirrhosis (P = 0.015). A bioinformatics analysis revealed that a polymorphic amino acid sequence in DRB1*07 may alter interaction with the T-cell recognition site. This study demonstrates that HLA alleles may influence cirrhosis development and disease activity in Turkish chronic hepatitis B patients.

Терапия генно-инженерными биологическими препаратами: эффективность и безопасность переключения

Aim : to assess efficacy and safety of «changeover» to the second genetically engineered biological agent (GEBA) in patients with juvenile idiopathic arthritis (JIA) with resistance or intolerability to the first GEBA. Patients and methods : the results of retrospective observational research of efficacy and safety of «changeover» to the second GEBA in 136 patients with various variants of JIA aged from 1 to 17 years old with primary resistance, partial effect or loss of efficacy to other biological agents are shown in this article. Among those 41 patient have systemic and 95 — JIA without extra-articular involvement. In 32 patients with JIA without extra-articular involvement the efficacy and safety of etanercept were assessed; in 63 — of adalimumab; in 22 patients with JIA and active extra-articular involvement — of tocilizumab, in 5 — of rituximab; in 14 patients with JIA without extra-articular involvement and active arthritis — of tumor necrosis factor (TNF) α inhibitors — adalimumab and etanercept. JIA was diagnosed according to the ILAR criteria. Results : in 6 and 12 months of treatment with the second GEBA inactive stage of disease / remission was detected in 65 and 84% of patients, respectively. In 13/22 patients with JIA and insufficient efficacy of rituximab remission was achieved in 24 weeks of follow-up after switching to the treatment with interleukin (IL) 6 receptors inhibitor, in 2/5 patients with resistance to tocilizumab — after switching to rituximab. In a year of treatment with etanercept as the second GEBA non-active stage / remission was induced in 100% of children with JIA without extra-articular involvement, in 85% — after switching to adalimumab, and in 100% of patients with JIA without extra-articular involvement — after administration of anti-TNF α-therapy. Conclusions : changeover to the second GEBA in patients with primary and secondary resistance or intolerability to the first GEBA allowed achieving of remission of systemic manifestations in patients with JIA and contributed to almost complete restoration of function in the joints in patients with JIA without extra-articular involvement and articular forms of JIA. Along with its high clinical efficacy the second GEBA was characterized by good tolerability and comparable safety profile.

Gomphina (Macridiscus) veneriformis (Lamark, 1818) (Bivalvia: Veneridae) in the East Sea of Korea

Gonad development, the reproductive cycle, first sexual maturty and size at 50% of group sexual maturity (the biological minimum size) of Gomphina (Macridiscus) veneriformis were investigated for clams collected from the coastal waters of Donghae City, the East Sea of Korea by histological, and morphometric analysis. Monthly variations of the gonad index showed a pattern similar to that of the reproductive cycle. The reproductive cycle with the gonad developmental stages in female and male G. (M.) veneriformis can be classified into five successive stages: early active stage (December to March), late active stage (March to June), ripe stage (June to July), partially spawned stage (June to August), and spent / inactive stage (September to December). The spawning period continued from June to August, with a peak between July and August when the seawater temperature exceeds . The percentages of first sexual maturities of female and male clams ranging from 25.1 to 30.0 mm were 56.3% in females and 61.1% in males, and for clams over 30.1 mm shell length, it was 100%. Shell lengths at 50% of group sexual maturity (biological minimum size, ) were 27.71 mm in females and 26.31 mm in males. Because harvesting clams

Ex vivo immunomodulatory effect of all-trans-retinoic acid during Behçet’s disease: a study in Algerian patients

Uveitis, recurrent oral and genital ulcerations associated with skin lesions are the major symptoms of a chronic multisystemic inflammatory disorder known as Behçet’s disease (BD). High prevalence of this dreaded disease has been observed in the Mediterranean basin, including Algeria and along the Silk Road. Although the etiologic agent of this disease remains uncertain, many hypotheses have been advanced in its pathogenesis. Our team has previously reported high levels of nitric oxide (NO) in sera of BD patients, suggesting its deleterious effect during chronic inflammation. In our current study, the aim is to investigate the ex vivo immunomodulatory effect of all-trans-retinoic acid (ATRA) on NO pathway in Algerian BD patients. First, peripheral blood mononuclear cells isolated from active and inactive BD patients and healthy controls were cultured with different concentrations of ATRA. NO production was estimated with the Griess method. To elucidate the underlying mechanisms of ATRA effect on NO production, we analyze inducible nitric oxide synthase expression and nuclear factor-κB (NF-κB) activity by immunofluorescence test. Our results revealed a higher production of NO in active BD compared with the inactive stage and healthy controls. We observed that ATRA inhibits NO production in BD both in active and inactive stages and inhibits NF-κB translocation. In conclusion, we report a relationship between NO production and the disease activity. ATRA down-regulates NO production in BD patients. This immunomodulatory effect seems to be mediated through NF-κB pathway. All these findings suggest that ATRA could be considered as a promising therapy for BD.

Immunoblotting with Human Native Antigen Shows Stage-Related Sensitivity in the Serodiagnosis of Hepatic Cystic Echinococcosis

The diagnosis of hepatic cystic echinococcosis is based on ultrasonography and confirmed by serology. However, no biological marker of cyst viability is currently available implying years-long patient follow-up, which is not always feasible in endemic areas. We characterized the performance of an immunoblotting test based on human hydatid cyst fluid with particular regard to its ability to distinguish between cyst stages. Sera from patients with cysts in different stages showed distinctive band pattern recognition. Most importantly, the test discriminated in 80% of cases CE3a from CE3b transitional cysts, known to have different viability profiles. Interestingly, we observed a rapid change in band pattern recognition of sera from one patient at time points when his cyst passed from active to transitional to inactive stages. Further identification of different antigens expressed by different cyst stages will support the development of diagnostic tools that could early define cyst viability, to guide clinical decision making, and shorten patient follow-up.

한국 진해만 해역에 분포하는 개조개, Saxidomus purpuratus의 재생산 연구 : 산란 및 군성숙각장

This study investigated purplish Washington clam, Saxidomus purpuratus on its gonadal development, reproductive cycle and shell length (age) at 50% female group maturity from January to December 2011 in Jinhae Bay, Korea. This species is dioecious. The gonad index (GI) began to increase in January, reached the maximum value in May and to decrease in June, reached the minimum value in September then to increase slowly in October again. The reproductive cycle of the clams can be divided into five successive stages: the early active stage (Ea, from February to March), the late active stage (La, from January to March and October to December), the ripe stage (R, from January to May), the spawning stage (S, from June to December) and the degenerative and inactive stage (Ia, from January to February and November to December). The spawning periods were from June to December and the main spawning periods were from July to October. The shell length at 50% female group maturity (SL50) was estimated to be 63.6 mm, which can be converted as sexual maturity age of 2.2 year.

Update endokrine Orbitopathie

Graves' orbitopathy is an autoimmune disease of the ocular adnex connective tissue and most commonly occurs together with Grave's hyperthyroidism. Anti-TSH receptor antibodies are specific for Graves' disease and are related to both the course of thyroid and orbital diseases. An active inflammatory disease stage is followed by an inactive stage of incomplete remission in most patients. Periorbital swelling, proptosis, diplopia and lid retraction severely impair the patients' quality of life. In the active state anti-inflammatory treatment consists of i.v. steroids, off-label use of immunomodulatory medication, selenium and in emergency cases orbital decompression. Fortunately, defects in inactive stable Graves' orbitopathy can be successfully treated by surgery and involve decompression for proptosis reduction, muscle recession to correct diplopia and (finally) lid surgery.

CLINICAL CASE OF CANAKINUMAB USE IN A PATIENT WITH SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS

The article presents a case of successful use of therapeutic monoclonal antibodies to interleukin 1 (canakinumab) at severe systemic juvenile idiopathic arthritis. Canakinumab treatment promptly provided reduction in clinical and laboratory disease activity indicators, increase in life quality, development of inactive disease stage and allowed avoiding prescription of glucocorticoids.

Disease Activity in Graves' Ophthalmopathy: Diagnosis with Orbital MR Imaging and Correlation with Clinical Score

In Graves' ophthalmopathy (GO) it is important to distinguish acute inflammation at an early stage, responsive to immunosuppressive treatment, from inactive fibrotic end stage disease, unresponsive to the same treatment. The purpose of this study was to identify the most relevant signal intensities on orbital MR imaging with contrast administration both to classify patients according to their clinical activity score (defined by a cut-off value of 3) and to make a prediction of patient's CAS. Such threshold was considered as widely used in literature. Sixteen consecutive patients with a diagnosis of GO in different phases of thyroid disease based on clinical and orbital MR imaging signs, and six normal volunteers were examined. Orbital MR imaging was performed on a 1.5 Tesla MR Unit. MR scans were assessed by an experienced neuroradiologist, blinded to the clinical examinations. We found a statistical correlation between CAS and both STIR and contrast enhanced T1-weighted sequences. There was also a statistically significant correlation between STIR and contrast-enhanced T1 images disclosing the possibility of avoiding the injection of contrast medium. Our study proved that signal intensity values on STIR sequence increase in the inflammatory oedematous phase of disease. We confirmed the correlation between signal intensities on this sequence and CAS, showing an increase in signal intensity proportional to the CAS value. So we validated MRI use to establish the activity phase of disease more sensitively than CAS alone.

Elevated Serum Levels of Interleukin-17A in Uveitis Patients

Purpose: T helper 17 cells (Th17) are one of the main pathogenic effectors in autoimmune uveitis, and IL-17A is the signature cytokine of Th17 cells. This study aims to assess serum IL-17A levels in patients with autoimmune uveitis and evaluate associations between IL-17A levels and disease characteristics.Methods: Serum IL-17A levels from 87 autoimmune uveitis patients and 60 healthy controls were assessed using an enzyme-linked immunosorbent assay. Among this cohort, 9 patients were followed longitudinally for IL-17A levels during active and inactive stages of their disease.Results: Median serum IL-17A levels were higher among uveitis patients compared to controls (p < 0.0001). Moreover, IL-17A levels were elevated among uveitis patients with active disease compared to those with inactive disease (p = 0.0202). Among the 9 patients followed longitudinally, IL-17A levels were elevated during active disease compared to the inactive stage (p = 0.0078).Conclusions: Serum IL-17A levels are elevated in uveitis patients, particularly in active uveitis.

19: B cell activation during Behçet disease: Possible BAFF involvement in pathogenesis

Behcet disease (BD) is a systemic inflammatory disorder with uncertain etiology. This disease is frequent in Algeria. Several studies reported the presence of auto-antibodies during Behcet disease. In this study, we evaluated the production of IL-6 and BAFF during Behcet disease and their effect on B cell responses in vitro . 26 patients with BD during active ( n = 16) or inactive ( n = 10) stage were included in our study. Plasma were obtained from patients and controls peripheral blood. BAFF and IL-6 were assessed by ELISA tests while total IgG, IgA and IgM were measured by nephelometry. Control Peripheral B lymphocytes (PBL) were purified and cultured in RPMI 1640 complemented by 10% FBS and antibiotics in presence or absence or patients’ plasma (20%). After 24 h, cells’ activation and/or differentiation markers were analyzed by flow cytometry (CD19, CD5, IgD, CD38). The comparison of the groups tested was performed by Mann–Whitney U test for soluble factors while markers’ expression was compared by Student T test. Our results showed a significant IL-6 and BAFF production increase during BD in comparison to controls ( p p p

퇴조개, Coecella chinensis (Mesodesmatidae: Bivalvia)의 생식주기

한국 남해안 남해 연안에서 채집한 퇴조개 (Coecella chinensis) 를 대상으로 생식주기, 생식소지수, 비만도지수 및 성비를 조직학적 분석 및 형태 계량학적 자료에 의해 조사하였다. 생식소지수 및 비만도지수의 월별 변화는 생식주기의 월별 변화와 유사한 양상을 보였다. 암컷과 수컷 퇴조개의 생식주기는 초기활성기 (4월), 후기활성기 (5월), 완숙기 (6월), 부분산란기/방정기 (6-8월), 퇴화기 (8월) 및 비활성기 (9-3월) 의 연속적인 6기 (stages) 로 구분할 수 있었다. 본 종의 산란기는 6-8월 이었으나, 주산란기는 수온이 약 <TEX>$24.5^{\circ}C$</TEX>인 7-8월이었다. 난경모드 조사에서, 6월에는 특히 70 <TEX>${\mu}m$</TEX> 정도의 난모세포가 다수 출현하였으나, 7-8월에는 평균 50 <TEX>${\mu}m$</TEX> 전후의 난모세포가 약 80% 정도 출현하는 대신, 60-70 <TEX>${\mu}m$</TEX> 전후의 완숙 난모세포는 감소하였다. 암 수 개체들의 성비는 1:1로 유의하게 다르지 않았으며 (<TEX>${\chi}^2$</TEX>=1.20, p>0.05), 자웅동체는 발견되지 않았다. The reproductive cycle, gonad index, condition index, and the sex ratio in female and male Coecella chinensis, which were collected from the coastal waters of Namhae, the South Coast of Korea, were investigated by histological analysis and morphometric data. Monthly variations of the gonad index and condition index of this species showed similar patterns to that of the reproductive cycle. The reproductive cycle in female and male C. chinensis can be classified into six successive stages: early active stage (April), late active stage (May), ripe stage (June), partially spawned/spent stage (June to August), degeneration stage (August) and inactive stage (September to March). According to monthly changes in relative frequency distributions of ovarian egg diameters of this species, in particular, a number of ripe eggs ranging about 70 <TEX>${\mu}m$</TEX> appear in June, however, in July and August, although the mode of egg diameters ranging about 50 <TEX>${\mu}m$</TEX> appear about 80%, these ripe eggs ranging from 60 <TEX>${\mu}m$</TEX> to 70 <TEX>${\mu}m$</TEX> are gradually decreased during the period from June to August. Therefore, the spawning period of this species is continued from June to August with a peak between July and August when the seawater temperature exceeds about <TEX>$24.5^{\circ}C$</TEX>. The sex ratio of female and male individuals was not significantly different from 1:1 (<TEX>${\chi}^2$</TEX>=1.20, p>0.05). No hermaphrodites were found.

FRI0398 Derailed b cell homeostasis in patients with mixed connective tissue disease

BackgroundMixed connective tissue disease (MCTD) is a systemic autoimmune disorder, characterized by the presence of antibodies to U1-RNP protein. Although the exact pathogenesis of MCTD is still unknown, B cell...

SAT0457 Efficacy and Safety of Etanercept in Combination with Methotrexate in the Patients with Early and Late Juvenile Idiopathic Arthritis

BackgroundThe use of biological products in the therapy of juvenile idiopathic arthritis (JIA) enables to achieve sustained remission of the disease and to improve the prognosis.ObjectivesTo assess efficacy and safety...

Cellular Composition of Induced Sputum in Sarcoidosis

The aim of this study was to evaluate the cellular composition of induced sputum (IS) in sarcoidosis and its role in assessing the disease activity. The safety of the procedure was also determined. Sputum induction by inhalation of hypertonic saline was performed. Twenty-one samples from the healthy controls, 32 from patients with active disease, and 33 from subjects with inactive disease were analysed. The percentage of lymphocytes in IS was significantly higher in active sarcoidosis than in inactive disease and the control group (9.7% vs. 3.1% vs. 2.9%), and was the highest in the patients with parenchymal changes and active disease (13.3%). The percentage of macrophages was significantly lower in active sarcoidosis than in normal subjects (76.8% vs. 83.4%). It was also significantly lower in IS in active disease and stages II and III than in both subgroups with active and inactive stage I of sarcoidosis. There were no significant differences in the IS cell percentages between the whole sarcoidosis group and the controls. Sputum induction was well tolerated and stopped only four times, two of them because of dyspnoea or the decrease of PEF. The symptoms were well reversible after administering salbutamol. Sputum induction by inhalation of hypertonic saline is safe, but the evaluation of IS differential cell counts is not useful in sarcoidosis diagnosing. However, it could be used in assessing the activity of the disease, especially in patients with interstitial lung changes.