scholarly journals Determination of PFOR gene expression in strains of G. intestinalis with different inhibitory concentrations of metronidazole

2015 ◽  
Vol 9 (05) ◽  
pp. 519-523 ◽  
Author(s):  
Rozalia Begaydarova ◽  
Yekaterina Yukhnevich ◽  
Dmitry Babenko ◽  
Sholpan Kaliyeva ◽  
Iliya Azizov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Software Tool ◽  
Giardia Intestinalis ◽  
Gene Expressions ◽  
Development Of Resistance ◽  
Metronidazole Resistance ◽  
Significant Difference ◽  
The Difference ◽  
Specific Pair

Introduction: Giardia intestinalis is the most important and common diarrhea-causing parasitic protozoa worldwide with growing clinical relevance in public health. There are many documented cases of G. intestinalis resistance to metronidazole (MZ). Pyruvate: ferredoxin oxidoreductase (PFOR), the membrane-localized enzyme, plays a key role in the development of resistance to drugs. The aim of the present study was to evaluate the difference in the levels of PFOR gene expression between MZ-resistant and MZ-susceptible strains of G. intestinatlis. Methodology: From 159 samples with G. intestinalis cysts, 48 strains were successfully cultivated. Using specific pair primers, PFOR gene expressions were estimated in different groups of Giardia. The polymerase chain reaction (PCR) data were analyzed with Bayesian analysis of qRT-PCR data using MCMC.qpcr package, with relative expression software tool (REST) and quantitative PCR CopyCount web source. Results: In the group of Giardia with minimum inhibitory concentration (MIC) of 6.3 µM, the level of PFOR gene expression was downregulated and compared with controls, differed by 1.5 to 2.8 times. At the same time, there was no significant difference in PFOR gene expression between the control (susceptible) group and the group with MIC of 3.2 µM. Conclusions: Though there is association between PFOR gene expression and metronidazole resistance of Giardia intestinalis, the level of PFOR gene expression cannot be a strong genetic marker to predict level of resistance to metronidazole based on MICs.

scholarly journals EXPRESSION OF micro RNAs (miRNAs) IN MYELODYSPLASTIC SYNDROME (MDS)

2019 ◽  
Vol 141 (7-8) ◽  
pp. 226-232
Keyword(s):  
Gene Expression ◽  
Myelodysplastic Syndrome ◽  
Healthy Volunteers ◽  
Myelogenous Leukemia ◽  
University Hospital ◽  
Gene Expressions ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Micro Rnas ◽  
Significant Difference

Myelodisplasia or myelodysplastic syndrome (MDS) is the name for a group of heterogeneous clonal hematological disorders of hematopoietic stem cells followed by ineffective hematopoesis of one or more cell lines and the emergence of consequent cytopenias with increased risk of progression to acute myelogenous leukemia (AML). Micro Messenger Ribonucleic Acids (miRNAs) are short, non-coding RNA molecules that, apart from contributing to MDS pathogenesis, act as regulators of epigenetic mechanisms and also are recognized as potential prognostic markers for early diagnosis and classification of MDS. The aim of the study was to examine the levels of gene expression of specific miRNAs (hsa-miR-125a, hsa-miR-99b, hsa-miR-126 and hsa-miR-125b) in healthy volunteers plasma and MDS diagnosed patients. Gene expressions of miRNAs were determined at the Clinical Institute of Medical Biochemistry and Laboratory Medicine, Merkur University Hospital, accredited according to EN ISO 15189:2012, in plasma samples of four healthy volunteers and 33 MDS patients diagnosed at the Institute of Hematology of the Clinic for Internal Diseases of Merkur University Hospital, Reference Center of the Ministry of Health of the Republic of Croatia for Diagnosis and Treatment of MDS. Statistically significant difference in gene expression of miRNA in healthy volunteers compared to the MDS patients was not found (P [hsa-miR-125a] = 0.398; P [hsa-miR-99b] = 0.134; P [hsa- miR-126] = 0.305; P [hsa-miR-125b] = 0.079). MiRNA ratios of hsa-miR-125a and hsa-miR-99b in MDS patients were almost twice as high compared to normalized levels of gene expression in healthy volunteers (2.30 versus 1.90), and the level of change of miRNAs hsa-miR-125 and hsa-miR-99b was more than two times higher than the level of change of miRNA hsa-miR-125b. Finally, the results of the research indicate that the gene expression of miRNAs hsa-miR-125a and hsa-miR-99b could be regulated by the same mechanism and could be clinically relevant in MDS patients.

scholarly journals Pengaruh Penerapan Model Pembelajaran Kooperatif Tipe Course Review Horay (CRH) Terhadap Keaktifan Belajar dan Hasil Belajar Ekonomi

2019 ◽  
Vol 1 (1) ◽  
pp. 1
Author(s):  
Aisyah Aisyah
Keyword(s):  
Learning Outcomes ◽  
Sampling Method ◽  
Learning Model ◽  
Positive Influence ◽  
Learning Activity ◽  
Economic Study ◽  
Purposive Sampling ◽  
Significant Difference ◽  
The Difference

This research is experimental research on students class XI of MIPA in SMA Negeri 3 Purwokerto. This research takes the title of "The Influence of the Application of the Cooperative Learning Model Type Course Review Horay (CRH) Against the Liveliness of learning and the Results of the Economic Study (study on the Grade XI MIPA in SMA Negeri 3 Purwokerto)". The purpose of this research is to know the difference in learning outcomes and learning activity between the learning model Course Review Horay (CRH) with conventional learning model, to know the influence of learning model Course Review Horay (CRH) against the learning outcomes and learning activity, as well as to know the influence of the liveliness of the learning results of learning. The population of this research is the grade XI MIPA in SMA Negeri 3 Purwokerto. The number of samples taken in this study is 72 i.e. 2 Class XI of MIPA which each class amounted to 36 students. Purposive Sampling Method used in the determination of the sample. Based on the results of the research and the anallisis data indicate that (1) there is a significant difference between the model of learning learning activeness cooperative Course Review Horay (CRH) and conventional learning model on economics. (2) there are significant differences between the learning outcomes learning model cooperative Course Review Horay (CRH) and conventional learning model on economi. (3) there is a positive influence learning model cooperative Course Review Horay (CRH) against the liveliness of the study on economic. (4) there is a positive influence learning model cooperative Course Review Horay (CRH) against the results of the study on economic. (5) there is no positive influence between the liveliness of student learning against the results of the study on economic. Penelitian ini adalah penelitian eksperimen pada siswa kelas XI MIPA di SMA Negeri 3 Purwokerto. Penelitian ini mengambil judul “Pengaruh Penerapan Model Pembelajaran Kooperatif Tipe Course Review Horay (CRH) terhadap Keaktifan Belajar dan Hasil Belajar Ekonomi (Studi pada Siswa Kelas XI MIPA di SMA Negeri 3 Purwokerto)”.        Tujuan dari penelitian ini adalah untuk mengetahui perbedaan keaktifan belajar dan hasil belajar antara model pembelajaran Course Review Horay (CRH) dengan model pembelajaran konvensional, untuk mengetahui pengaruh model pembelajaran Course Review Horay (CRH) terhadap keaktifan belajar dan hasil belajar, serta untuk mengetahui pengaruh keaktifan belajar terhadap hasil belajar. Populasi penelitian ini adalah siswa kelas XI MIPA di SMA Negeri 3 Purwokerto. Jumlah sample yang diambil dalam penelitian ini adalah 72 yaitu 2 kelas XI MIPA yang masing-masing kelas berjumlah 36 siswa. Purposive Sampling Method digunakan dalam penentuan sample. Berdasarkan hasil penelitian dan anallisis data menunjukkan bahwa (1) Terdapat perbedaan signifikan keaktifan belajar antara model pembelajaran kooperatif Course Review Horay (CRH) dengan model pembelajaran konvensional pada mata pelajaran ekonomi. (2) Terdapat perbedaan signifikan hasil belajar antara model pembelajaran kooperatif Course Review Horay (CRH)  dengan model pembelajaran konvensional pada mata pelajaran ekonomi. (3) Terdapat pengaruh positif model pembelajaran kooperatif Course Review Horay (CRH)  terhadap keaktifan belajar pada mata pelajaran ekonomi. (4) Terdapat pengaruh positif model pembelajaran kooperatif Course Review Horay (CRH)  terhadap hasil belajar pada mata pelajaran ekonomi. (5) Tidak terdapat pengaruh positif antara keaktifan belajar siswa terhadap hasil belajar pada mata pelajaran ekonomi.  

scholarly journals Study on the Distribution Characteristics and Influencing Factors of Homocysteine in the Physical Examination Population

2021 ◽  
Author(s):  
Fang Bao ◽  
Ming Cui ◽  
Xiuying Shi ◽  
Shaoqing Ju ◽  
Hui Cong
Keyword(s):  
Blood Pressure ◽  
Physical Examination ◽  
Large Scale ◽  
Kidney Injury ◽  
Scientific Basis ◽  
Cerebrovascular Diseases ◽  
Health Examination ◽  
Significant Difference ◽  
The Difference

Abstract Background: Homocysteine (Hcy) is considered to be an independent risk factor for cardiovascular and cerebrovascular diseases. No study has evaluated the distribution of Hcy on a large-scale health examination. Accordingly, this study aimed to investigate the level and distribution of Hcy in the healthy physical examination population and the correlation with other biomarkers, and analyzed for cardiovascular and other diseases. The prevention provides an important scientific basis.Methods: From February 2017 to April 2020, 8063 medical examination populations were selected for analysis. Determination of serum Hcy, TC, TG, LDL-c, HDL-c, ALT, ALP, γ-GT, TBIL, GLU, urea, Cr, UA and related metabolic risk factors. According to the multivariate regression model of age, gender, smoking, drinking, body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP), the relationship between Hcy and other biochemical indicators was evaluated. Results: Among 8063 cases, the age, BMI, SBP and DBP of the high-Hcy group were higher than those of the low-Hcy group, the difference was statistically significant (P<0.05), and the proportion of males, smoking and drinking were higher than the low In the Hcy group, the difference was statistically significant (P<0.05); the ALT, ALP, γ-GT, TBIL, Urea, Cr, UA, and TG in the high Hcy group were higher than those in the low Hcy group, and the difference was statistically significant (P<0.05 ); HDL-c in the high-Hcy group was lower than that in the low-Hcy group, and the difference was statistically significant (P<0.05). There was no statistically significant difference in TC, LDL-c, and GLU between the high- and low-Hcy groups (P>0.05). In multivariate analysis, lnHDL-C was negatively correlated with lnHcy (β=-0.038, SE=0.016, P<0.05), lnCr was positively correlated with lnHcy (β=0.055, SE=0.016, P<0.05), lnUA and lnHcy were positive correlation (β=0.043, SE=0.019, P<0.05). Conclusion: Hcy is closely related to HDL-c, Cr and UA, which indicates that Hcy may affect the metabolism of HDL-c and UA, and can also be used as an auxiliary diagnostic index for kidney injury.

Pyridine Extraction Method for Determination of Bacitracin in Feeds: Collaborative Evaluation

1979 ◽  
Vol 62 (3) ◽  
pp. 662-670
Author(s):  
Hussein S Ragheb
Keyword(s):  
High Temperature ◽  
Extraction Method ◽  
Main Difficulty ◽  
Coefficients Of Variation ◽  
Significant Difference ◽  
The Difference ◽  
Zinc Bacitracin ◽  
Collaborative Evaluation

Abstract Seventeen laboratories evaluated the pyridine extraction method and neomycin-sensitized agar for the determination of zinc and MD bacitracin in swine and broiler rations at 10 and 100 g/ton. The method was also applied to the analysis of 2 premixes labeled 50 g/lb (MD bacitracin) and 40 g/lb (zinc bacitracin). Bacitracin activity was determined on each of 2 days with 2 dilutions on each day. No significant difference was found between dilutions within a day or between days for each sample. The type of bacitracin or type of feed did not significantly affect results. The difference in results between MD and zinc bacitracin in premixes approached significance. The large coefficients of variation for premixes (ca 13%) and complete feeds (ca 15–30%) indicate operational problems. The main difficulty was evaporation of pyridine. Some laboratories were not able to evaporate it completely, whereas others lost bacitracin activity, probably due to high temperature of drying. The pyridine extraction method as in 42.200 and 42.204 should be discontinued.

Inverse alterations of BCKA dehydrogenase activity in cardiac and skeletal muscles of diabetic rats

1999 ◽  
Vol 277 (4) ◽  
pp. E685-E692 ◽  
Author(s):  
Yolanda B. Lombardo ◽  
Cynthia Serdikoff ◽  
Manikkavasagar Thamotharan ◽  
Harbhajan S. Paul ◽  
Siamak A. Adibi
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Protein Expression ◽  
Cardiac Muscle ◽  
Dehydrogenase Activity ◽  
Skeletal Muscles ◽  
Diabetic Rats ◽  
Gene Expressions ◽  
The Difference ◽  
Activity State

Rat cardiac and skeletal muscles, which have been used as model tissues for studies of regulation of branched-chain α-keto acid (BCKA) oxidation, vary greatly in the activity state of their BCKA dehydrogenase. In the present experiment, we have investigated whether they also vary in response of their BCKA dehydrogenase to a metabolic alteration such as diabetes and, if so, to investigate the mechanism that underlies the difference. Diabetes was produced by depriving streptozotocin-treated rats of insulin administration for 96 h. The investigation of BCKA dehydrogenase in the skeletal muscle (gastrocnemius) showed that diabetes 1) increased its activity, 2) increased the protein and gene expressions of all of its subunits (E1α, E1β, E2), 3) increased its activity state, 4) decreased the rate of its inactivation, and 5) decreased the protein expression of its associated kinase (BCKAD kinase) without affecting its gene expression. In sharp contrast, the investigation of BCKA dehydrogenase in the cardiac muscle showed that diabetes 1) decreased its activity, 2) had no effect on either protein or gene expression of any of its subunits, 3) decreased its activity state, 4) increased its rate of inactivation, and 5) increased both the protein and gene expressions of its associated kinase. In conclusion, our data suggest that, in diabetes, the protein expression of BCKAD kinase is downregulated posttranscriptionally in the skeletal muscle, whereas it is upregulated pretranslationally in the cardiac muscle, causing inverse alterations of BCKA dehydrogenase activity in these muscles.

scholarly journals Gender Differences of B Cell Signature in Healthy Subjects Underlie Disparities in Incidence and Course of SLE Related to Estrogen

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Hongye Fan ◽  
Guanjun Dong ◽  
Guangfeng Zhao ◽  
Fei Liu ◽  
Genghong Yao ◽  
...  
Keyword(s):  
Gender Differences ◽  
B Cells ◽  
Global Gene Expression ◽  
Gene Expressions ◽  
Significant Difference ◽  
Healthy Female ◽  
Nonsignificant Difference ◽  
Differential Gene ◽  
The Difference ◽  
Healthy Females

The aim of the present study was to investigate mechanism of the gender differences of B cells. The results showed that 358 differential gene expressions (DEGs) were displayed between healthy females and males. Compared with male, 226 and 132 genes were found to be up- and downregulated in the female. 116 genes displayed possible correlation with estrogen. Moreover, the upregulated DEGs (Cav1, CD200R1, TNFRSF17, and CXCR3) and downregulated DEGs (EIF1AY and DDX3Y) in healthy female may be involved in gender predominance of some immune diseases. Furthermore, signaling pathway analysis for estrogen-relevant DEGs showed that only 26 genes were downregulated in SLE female versus SLE male, of which expressions of 8 genes had significant difference between SLE females and SLE males but are having nonsignificant difference between healthy females and healthy males. Except for the 5 Y-chromosome-related genes or varients, only 3 DEGs (LTF, CAMP, and DEFA4) were selected and qRT-PCR confirmed that the expressions of LTF and CAMP decreased significantly in B cells from female SLE patients. These data indicated that the gender differences were existent in global gene expression of B cells and the difference may be related to estrogen.

ANALISI DAMPAK BENDUNGAN PANDANDURI TERHADAP USAHATANI PADI SAWAH DI KECAMATAN SAKRA BARAT KABUPATEN LOMBOK TIMUR

2021 ◽  
Vol 1 (2) ◽  
pp. 18-26
Author(s):  
Abdur Rahim
Keyword(s):  
Rice Paddy ◽  
Lowland Rice ◽  
Rice Farming ◽  
Productivity Level ◽  
Significant Difference ◽  
Survey Technique ◽  
The Difference ◽  
The Impact ◽  
The Village

This study aims to determine the impact of the Pandan Duri dam on changes in the Crop Index (IP) and changes in the productivity level of rice paddy farming in West Sakra District, East Lombok Regency. The method in this research is descriptive, data collection is done by survey technique. Determination of the number of samples as many as 30 people is done by sampling quota and taking farmers in each village is done by proportional random sampling and determining the village as a sample is done by purposive sampling. The results showed that: 1) The total planting index (IP) of lowland rice before the Pandan Duri dam in West Sakra District was 1.39 and after 2.12. This means that the existence of the Pandan Duri dam can have an impact on the difference in the Crop Index (IP) of lowland rice farming in Sakra District and, 2) The average productivity of rice before the Pandan Duri dam in West Sakra District was 49,682 Kw/Ha while after the Pandan Duri dam was 57,267 Kw/Ha and there was a significant difference at the alpha 5% (0,05) level.or in the other word, that the existence of Pandan Duri development has real/significant impact on the productivity of lowland rice farming in West Sakra District, East Lombok Regency

Association of Gene Expression Profiling, Interim PET, EBV Status and PD-L1 Expression in Classical Hodgkin Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1437-1437
Author(s):  
Ralph Schwiebert ◽  
Sharon Barrans ◽  
Jan Taylor ◽  
Andrew S Jack ◽  
Cathy H Burton
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Hodgkin Lymphoma ◽  
Expression Profiling ◽  
B Cell Lymphoma ◽  
Classical Hodgkin Lymphoma ◽  
Treatment Needs ◽  
Gene Signatures ◽  
Significant Difference ◽  
The Difference

Abstract Introduction A challenge in the management of classical Hodgkin lymphoma (CHL) is selecting treatment which will maximise success while minimising treatment side effects. The international Response Adapted Therapy in Hodgkin Lymphoma (RATHL) trial (NCT00678327) demonstrated that treatment may be successfully adapted based on positron emission tomography (PET-CT) scan results after 2 cycles (PET2) of ABVD chemotherapy in advanced CHL. This approach however delays risk stratification meaning some patients may be over or under treated and therefore a baseline predictor is highly desirable. A gene expression-based model performed on RNA from formalin-fixed paraffin-embedded tissue (FFPET) biopsies on the Nanostring platform (Scott et al, J Clin Oncol 2013; 31:692-700) has been published. In addition Steidl et al used gene expression profiling (GEP) to correlate tumour-associated macrophages with survival in CHL (Steidl et al, NEJM 2010; 10:875-885). In order to explore whether GEP at baseline could be used in combination with PET2 results to predict outcome, these published gene signatures were explored on the DASL platform in a series of CHL cases and correlated with PET2 response. Recently, PD-1 ligand (PD-L1) on the cell surface of Reed-Sternberg cells (the hallmark cells of CHL) has been demonstrated to co-opt the PD-1 pathway allowing immune evasion (Green et al, Blood 2010;116:3268-77). Therefore this was also performed by immunohistochemistry (IHC) and GEP as well as assessment of EBV status. Methods 50 patients with CHL were identified, with at least 2 years of follow up, diagnosed between 2008 and 2013. Deauville scores at PET2 were determined. IHC consistent with CHL, including: CD3, CD19, CD20, CD30, CD79, BOB-1, OCT-2, MUM1 and TARC was performed on 3mm FFPET lymph node sections, and reported by two independent observers. Latent Epstein-Barr virus (EBV) infection was determined by IHC for LMP-1 expression and in-situ hybridisation using fluorescein-labelled peptide nucleic acid probes (Dako, K5201). PD-L1 expression was determined by IHC using a rabbit monoclonal antibody (Cell Signaling Technology, E1L3N, #13684). Three to five 5mm sections of FFPET were used for RNA extraction using the Ambion RecoverAll™ kit standard protocol. GEP was quantified using Illumina's whole genome cDNA-mediated annealing, selection, extension, and ligation Assay (WG-DASL). 61 genes of interest were analysed for significance in the difference in gene expression between groups and included genes from the two recently reported GEP predictor tools in CHL (Steidl et al, 2010, Scott et al 2013) as well as PD-1 and PD-L1. The Mann-Whitney test was used to assess the significance in the difference between means (significant if p<0.05). Results A statistically significant difference in EBV status was found between PET negative (Deauville scores 1-3) and PET positive (Deauville scores 4-5) groups (Fisher's exact test: P-Value = 0.028). All patients who were EBV positive had a negative PET2 scan. GEP using WG-DASL revealed that only 2 genes of those reported in recent predictor models (Steidl et al 2010, Scott et al 2013) were expressed at significantly different levels between PET negative and PET positive patients (GLUL, RNF144B), both with increased expression in the PET2 positive group. There was no significant difference between PD-L1 expression and PET scores, CD274 gene expression and outcome. Assessment as to whether samples would cluster into groups according to PET positivity or PD-L1 expression status by unsupervised cluster analysis using four recently reported B cell lymphoma gene signatures (Monti et al, Blood 2005; 5:1851-61, Care et al, PloS one 2013; 2: e55895) was performed, but no significant grouping was found. Conclusion GEP on the DASL platform was not able to predict PET response. The original models were trained on outcome and therefore retraining of the GEP model based on PET response is likely to be required. EBV status was found to be predictive of PET response but this could not be correlated with other biomarkers to predict outcome. Although PD-1 and PD-L1 targeted therapy has shown exciting results in patients with CHL, PD-L1 IHC expression and CD274 gene expression, did not correlate with PET2 response or outcome. Baseline biomarkers capable of identifying patients likely to benefit from targeted treatment needs to be further investigated in proposed clinical trials. Disclosures No relevant conflicts of interest to declare.

scholarly journals Vitamin D and Vitamin D Receptor in Scleroderma Subtypes

2020 ◽  
pp. 19-24
Author(s):  
Kocak Ayse
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Mrna Levels ◽  
Diffuse Type ◽  
Gene Expressions ◽  
Vdr Gene ◽  
Vitamin D Levels ◽  
Significant Difference ◽  
Tgf Β1

Vitamin D Receptor (VDR) is a member of the nuclear hormone receptor family. 1,25(OH)2D, a form of metabolically active vitamin D3 form, is the ligand of VDR. When VDR and 1,25(OH)2D are connected, many genes start to molecular interaction reactions that will modulate the transcription. VDR has been shown to be a negative regulator of the transforming growth factor beta-1 / Smad (TGF-β1 / Smad) signalling pathway. TGF-β1 / Smad signalling is important in the pathogenesis of scleroderma (SSc). Vitamin D has pleiotropic effects including immunomodulatory and antifibrotic properties in scleroderma pathogenesis. The aim of this study was to investigate the expression of VDR and the levels of vitamin D in scleroderma subtypes and study the possible correlation between the two parameters. 28 SSc patients and 30 healthy controls were included in the study and they were classified according to the 2013 ACR / EULAR criteria and Rodnan Scores were calculated. 14 were of the limited type and 14 were of the diffuse type of scleroderma. Vitamin D levels were determined in serum. Vitamin D level was measured by chemiluminescence immunometric assay. VDR gene expression was determined by quantitative PCR in isolated RNAs from the blood. Changes in mRNA levels were analysed and beta-actin was used as the housekeeping gene. Also, TGF-β1 gene expressions were determined. VDR gene expressions in diffuse type scleroderma patients were significantly decreased compared to the control. TGF-β1 gene expressions were increased in diffuse type scleroderma. It was found that VDR gene expression in limited type scleroderma patients did not show any significant difference when compared to control. Vitamin D levels and VDR gene expressions showed no correlation in scleroderma subtypes. VDR gene expression decreased in patients with diffuse type scleroderma and showed negative correlation with the Rodnan score and TGF-β1 gene expressions. There was no significant difference between vitamin D and VDR levels.

scholarly journals Hydroxychloroquine Therapy and Netosis Regulators Expression in Patients with Primary Antiphospholipid Syndrome

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5049-5049
Author(s):  
Bruna M Mazetto ◽  
Bidossessi Wilfried Hounkpe ◽  
Sabrina Saraiva ◽  
Joyce Maria Annichino Bizzacchi ◽  
Erich Vinicius De Paula ◽  
...  
Keyword(s):  
Gene Expression ◽  
Treatment Period ◽  
Antiphospholipid Syndrome ◽  
Primary Antiphospholipid Syndrome ◽  
Gene Expressions ◽  
The Mean ◽  
The Difference ◽  
Mean Differences ◽  
Relative Gene

Abstract Introduction: Primary antiphospholipid syndrome (PAPS) is an autoimmune pro-thrombotic condition that affects different vascular beds, with no detectable underlying diseases. Immunothrombosis is at the basis of thrombosis development in PAPS and neutrophil activation and generation of neutrophil extracellular traps (termed NETosis) have been described as part of the immunological process. NETosis involves the orchestrated participation of several proteins such as peptidyl arginine deaminase (PADI4), neutrophil elastase (ELANE) and myeloperoxidase (MPO). PADI4 mediates histone citrullination, so that inhibition of PADI4 could be considered a potential therapeutic strategy to prevent NETosis. Hydroxychloroquine (HCQ) is an anti-malarial drug prescribed for patients with autoimmune diseases as complementary treatment for prevention of immune activation and thrombosis. Whether HCQ treatment affects the NETosis process is not known. Objective: The aim of this study was to evaluate whether HCQ use is associated with the expression of NETosis regulators proteins PADI4, ELANE, and MPO in patients with PAPS. Methods: This is a cross-over study in which patients with PAPS were selected to receive HCQ at 400mg per day for 6 months and then discontinue the drug. The study had two periods of follow-up: 6 months of HCQ treatment and 6 months of no HCQ treatment. A wash-out period of 6 months between the two study periods was allowed. The mean gene expression and 95% confidence intervals (95% CI) of PADI4, ELANE, and MPO were calculated at baseline and at the end of the study periods. The within periods change in gene expression from baseline to the end of the treatment and the difference in gene expression between periods at the end of the follow-up were determined. Results: The study comprised 20 patients. Mean age was 45 years, 70% were women. In HCQ treatment period, mean relative gene expressions of PADI4, ELANE, and MPO were respectively: 1.0 (SD=0.6), 0.5 (SD=0.7) and 0.6 (SD=0.7) at baseline and 0.8 (SD=0.3), 0.9 (SD=1.5) and 0.6 (SD=0.9) at the end of the period. The mean changes in PADI4, ELANE, and MPO relative gene expressions during HCQ treatment period were: -0.1 (95%CI:-0.4;0.1), 0.4 (95%CI: -0.5;1.4), 0 (95%CI: -0.6;0.5), respectively. In the period when HCQ was not used, mean relative gene expressions of PADI4, ELANE, and MPO were respectively: 1.2 (SD=0.6), 0.6 (SD=1.4) and 0.8 (SD=1.3) at baseline and 0.8 (SD=0.4), 0.4 (SD=0.9) and 0.6 (SD=0.6) at the end of the period. The mean changes in PADI4, ELANE, and MPO relative gene expressions during period of no treatment were: -0.4 (95%CI:-0.6;-0.2), -0.2 (95%CI:-0.5;0.1) and -0.2 (95%CI -0.5;0), respectively. In comparison with no treatment period, treatment with HCQ had no effect on the relative gene expressions of PADI4, ELANE, and MPO. The mean differences in PADI4 ELANE, and MPO relative gene expression between HCQ treatment and no treatment at the end of the periods were 0.1 (95%CI:-0.1; 0.3), 0.5 (95%CI:-0.2; 1.3) and 0.1 (95%CI:-0.3; 0.5), respectively. Conclusion: The results suggest that HCQ treatment has no effect on NETosis process, as measured by the gene expression of NETosis regulators proteins, in patients with PAPS. Disclosures De Paula: Hematology and Transfusion Medicine Center, University of Campinas: Employment.

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