Fingolimod Alters Tissue Distribution and Cytokine Production of Human and Murine Innate Lymphoid Cells

Sphingosine-1 phosphate receptor 1 (S1PR1) is expressed by lymphocytes and regulates their egress from secondary lymphoid organs. Innate lymphoid cell (ILC) family has been expanded with the discovery of group 1, 2 and 3 ILCs, namely ILC1, ILC2 and ILC3. ILC3 and ILC1 have remarkable similarity to CD4+ helper T cell lineage members Th17 and Th1, respectively, which are important in the pathology of multiple sclerosis (MS). Whether human ILC subsets express S1PR1 or respond to its ligands have not been studied. In this study, we used peripheral blood/cord blood and tonsil lymphocytes as a source of human ILCs. We show that human ILCs express S1PR1 mRNA and protein and migrate toward S1P receptor ligands. Comparison of peripheral blood ILC numbers between fingolimod-receiving and treatment-free MS patients revealed that, in vivo, ILCs respond to fingolimod, an S1PR1 agonist, resulting in ILC-penia in circulation. Similarly, murine ILCs responded to fingolimod by exiting blood and accumulating in the secondary lymph nodes. Importantly, ex vivo exposure of ILC3 and ILC1 to fingolimod or SEW2871, another S1PR1 antagonist, reduced production of ILC3- and ILC1- associated cytokines GM-CSF, IL-22, IL-17, and IFN-γ, respectively. Surprisingly, despite reduced number of lamina propria-resident ILC3s in the long-term fingolimod-treated mice, ILC3-associated IL-22, IL-17A, GM-CSF and antimicrobial peptides were high in the gut compared to controls, suggesting that its long term use may not compromise mucosal barrier function. To our knowledge, this is the first study to investigate the impact of fingolimod on human ILC subsets in vivo and ex vivo, and provides insight into the impact of long term fingolimod use on ILC populations

Investigation of genotoxic effect of ultrasound in cases receiving therapeutic ultrasound by using micronucleus method

In 1991, Miller et al. (1991) reported that therapeutic ultrasound (US) did not induce sister chromatid exchanges (SCEs) in patients whereas, in 1984, Stella et al. (1984) reported that each of 10 patients exposed to therapeutic US had a statistically significant increase in SCEs. The present study was planned to investigate if there was chromosomal damage resulting from therapeutic US by using a micronucleus (MN) method, and to counter the lack of reports in this area over the past 10 years. A total of 20 female volunteers were included in the study; 10 of them with low back pain (mechanical low back pain and facet syndrome) were treated with US and 10 healthy cases constituted the control group. Patients with low back pain received 10 sessions of US therapy at an intensity of 2 W/cm(2) and a frequency of 1 MHz for 10 min and patients in the control group received sham US therapy for 10 min. Peripheral blood taken before and after the fifth and tenth applications of US therapy was cultured for MN frequencies both for the treatment and the control groups. The scores of MN assessed before the therapy were compared with those at the end of the fifth session and the end of the tenth session in the treatment and the control groups. Pretreatment, end of the fifth session and end of the tenth session MN frequencies were compared between the treatment and the control groups. There was no statistically significant difference in MN frequencies between pretreatment and fifth session or pretreatment and tenth session in both groups. Nor was there any significant difference in the MN frequencies of the treatment and control groups between pretreatment, fifth session and tenth session evaluations. In conclusion, we observed that therapeutic US did not induce increases in MN frequency, which are a sign of cytogenetic damage. (E-mail: [email protected]) (C) 2004 World Federation for Ultrasound in Medicine Biology

Increased Chromosomal and Oxidative DNA Damage in Patients with Multinodular Goiter and Their Association with Cancer

WOS: 000398311000001PubMed: 28373882Thyroid nodules are a common clinical problem worldwide. Although thyroid cancer accounts for a small percentage of thyroid nodules, the majority are benign. 8-Hydroxy-2 '-deoxyguanosine (8-OHdG) levels are a marker of oxidative stress and play a key role in the initiation and development of a range of diseases and cancer types. This study evaluates cytokinesis-block micronucleus cytome (CBMN-cyt) assay parameters and plasma 8-OHdG levels and their association with thyroid nodule size and thyroid hormones in patients with multinodular goiter. The study included 32 patients with multinodular goiter and 18 age-and sex-matched healthy controls. CBMN-cyt assay parameters in peripheral blood lymphocytes of patients with multinodular goiter and controls were evaluated, and plasma 8-OHdG levels were measured. The micronucleus (MN) frequency (chromosomal DNA damage), apoptotic and necrotic cells (cytotoxicity), and plasma 8-OHdG levels (oxidative DNA damage) were significantly higher among patients with multinodular goiter. Our study is the first report of increased chromosomal and oxidative DNA damage in patients with multinodular goiter, which may predict an increased risk of thyroid cancer in these patients. MN frequency and plasma 8-OHdG levels may be markers of the carcinogenic potential of multinodular goiters and could be used for early detection of different cancer types, including thyroid cancer.Erciyes University Scientific Research Projects Units [TSA-10-3285]This work was supported by Erciyes University Scientific Research Projects Units (Project no.: TSA-10-3285)

Evaluation of chromosomal DNA damage, cytotoxicity, cytostasis, oxidative DNA damage and their relationship with endocrine hormones in patients with acute organophosphate poisoning

WOS: 000423001300001PubMed: 29307370Pesticides are commonly used compounds in agriculture. Especially, organophosphates (OPs) are among the extensively used pesticides. Therefore, OPs poisoning is common, especially in underdeveloped and developing countries. Primary aim of this study was to research the effects of acute OPs poisoning on genome instability in the individuals' lymphocytes with acute OPs poisoning both by using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay to examine chromosome/genome damage, cell proliferation index and cell death rate and by using the plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels to determine oxidative DNA damage. Secondary aim of this study was also to assess whether a relation exists between endocrine hormones and the genome damage in acute OPs poisoning. In the study, blood samples were analysed of 13 patients before and after treatment admitted to the Department of Intensive Care Unit with acute OPs poisoning and of 13 healthy subjects of similar age and sex. The present study demonstrates that genome damage (micronucleus; MN and nucleoplasmic bridges; NPBs frequencies), apoptotic and necrotic cell frequencies increased in lymphocytes of patients with acute OPs poisoning before treatment and decreased after treatment. The present study also show that CBMN cyt assay parameters and 8-OHdG levels could be affected by some endocrine hormones such as E2, fT3, fT4, GH, IGF-1, FSH, LH, TSH, PRL, but not be related to ACTH and tT levels in acute OPs poisoning. In conclusion, it is believed that this is the first study to evaluate the chromosomal/oxidative DNA damage, cell proliferation, cell death and their associations with endocrine hormones in acute OPs poisoning. These preliminary findings need to be supported by further studies with larger sample sizes.Research Fund of the Erciyes University [TSA-12-3792]This work was supported by Research Fund of the Erciyes University (Project number: TSA-12-3792)

Gut barrier protein levels in serial blood samples from critically ill trauma patients during and after intensive care unit stay

Purpose In an efort to better manage critically ill patients hospitalised in the intensive care unit (ICU) after experiencing multiple traumas, the present study aimed to assess whether plasma levels of intestinal epithelial cell barrier proteins, including occludin, claudin-1, junctional adhesion molecule (JAM-1), tricellulin and zonulin, could be used as novel biomarkers. Additional potential markers such as intestinal fatty acid-binding protein (I-FABP), d-lactate, lipopolysaccharide (LPS) and citrulline were also evaluated. We also aimed to determine the possible relationships between the clinical, laboratory, and nutritional status of patients and the measured marker levels. Methods Plasma samples from 29 patients (frst, second, ffth and tenth days in the ICU and on days 7, 30 and 60 after hospital discharge) and 23 controls were subjected to commercial enzyme-linked immunosorbent assay (ELISA) testing. Results On frst day (admission) and on the second day, plasma I-FABP, d-lactate, citrulline, occludin, claudin-1, tricellulin and zonulin levels were high in trauma patients and positively correlated with lactate, C-reactive protein (CRP), number of days of ICU hospitalisation, Acute Physiology and Chronic Health Evaluation II (APACHE II) score and daily Sequential Organ Failure Assessment (SOFA) scores (P<0.05–P<0.01). Conclusion The results of the present study showed that occludin, claudin-1, tricellulin and zonulin proteins, as well as I-FABP, d-lactate and citrulline, may be used as promising biomarkers for the evaluation of disease severity in critically ill trauma patients, despite the complexity of the analysis of various barrier markers. However, our results should be supported by future studies

TEDAVİ ALMAMIŞ NÖROENDOKRİN TÜMÖR TANILI HASTALARDA DNA HASARININ ARAŞTIRILMASI

Nanodielectrics have been extensively researched in recent years with the expectation that they may enhance electrical performance. In this paper we have studied the electrical conduction processes in linear low density polyethylene (LLDPE) filled with nano alumina particles. The electrical conduction was measured at various applied electric fields. It has been found that the conduction current shows a minimum at a 1% b.w. concentration nano alumina particles. To aid an understanding of conduction processes in the nanodielectric, differential scanning calorimetry (DSC) was used to analyse the interaction between nano alumina particles and the host matrix. Initial findings suggest that there is an interaction zone around the nano alumina particles. Neighbouring interaction zones are expected to overlap when the percentage of nano alumina particles exceeds 5% in LLDPE