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Chanloung W, Kasitanon N, Wichainun R, Louthrenoo W. Thrombotic risk assessment in patients with systemic lupus erythematosus: Validation of the adjusted-Global Antiphospholipid Syndrome Score (aGAPSS) in Thai patients. Int J Rheum Dis 2021; 24:1510-1519. [PMID: 34716670 DOI: 10.1111/1756-185x.14230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 10/13/2021] [Accepted: 10/14/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND The adjusted-Global Antiphospholipid Syndrome Score (aGAPSS) has been validated and used to predict antiphospholipid antibodies (aPL) related to vascular thrombosis (VT). OBJECTIVE To validate aGAPSS for predicted aPL-related VT and pregnancy complications (PC) in Thai systemic lupus erythematosus (SLE) patients. METHODS A cross-sectional study was performed among Thai SLE patients with clinical manifestations; history of VT and PC, cardiovascular risk factors, and aPL profiles were collected. The aGAPSS was calculated from the sum of the risk factors (hyperlipidemia = 3.0, arterial hypertension = 1.0, anti-cardiolipin antibody = 5.0, anti-b2 glycoprotein I antibody = 4.0, and lupus anticoagulant = 4.0). RESULTS Of 132 SLE patients, 12 (9.1%) had VT and 5 (4.1%) had PC. When comparing the aGAPSS (median; interquartile range [IQR]) of patients with events (VT and/or PC) (6.5; IQR 3.3-9.0), VT (8.0; IQR 4.0-9.0), arterial thrombosis (3.5; IQR 1.0-5.8), and PC (9.0; IQR 8.0-11.5), and the aGAPSS of patients without an event (3.0; IQR 0-4.0), aGAPSS of patients with events was significantly higher, except in patients with arterial thrombosis. An aGAPSS of 4.5 or more was associated with risk of aPL-related VT (sensitivity 71.4%, specificity 76.7%), and an aGAPSS of 6.0 or more was associated with risk of aPL-PC (sensitivity 100%, specificity 84.0%). CONCLUSION The aGAPSS could predict the risk of aPL-PC and aPL-related VT in Thai SLE patients.
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Affiliation(s)
- Wanitcha Chanloung
- Faculty of Medicine, Division of Rheumatology, Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Nuntana Kasitanon
- Faculty of Medicine, Division of Rheumatology, Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Ramjai Wichainun
- Faculty of Medicine, Division of Rheumatology, Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Worawit Louthrenoo
- Faculty of Medicine, Division of Rheumatology, Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand
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Baker SA, Jin J, Pfaffroth C, Vu T, Zehnder JL. DOAC-Stop in lupus anticoagulant testing: Direct oral anticoagulant interference removed in most samples. Res Pract Thromb Haemost 2021; 5:314-325. [PMID: 33733031 PMCID: PMC7938630 DOI: 10.1002/rth2.12472] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 11/14/2020] [Accepted: 11/20/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The use of direct oral anticoagulants (DOACs) is a convenient therapeutic option for patients at risk of thrombosis. DOACs interfere with clot-based testing for the identification of lupus anticoagulant antibodies (LACs) in patients with antiphospholipid syndrome (APS), a common cause of acquired thrombotic disease. OBJECTIVES To evaluate a commercially available reagent DOAC-Stop for the removal of DOAC interference encountered in LAC testing. PATIENTS/METHODS We collected a cohort of 73 test samples from patients on DOAC therapy identified at a large institutional coagulation laboratory from March to December 2019, along with samples from 40 LAC positive and negative control patients not on therapy. Samples were treated with DOAC-Stop and tested for anti-Xa activity and thrombin time for the removal of apixaban, rivaroxaban, argatroban, and dabigatran activity from patient samples. Treated and untreated samples were tested using the activated partial thromboplastin time, silica clotting time, and dilute Russell's viper venom time to evaluate the reliability and utility of DOAC-Stop. RESULTS DOAC-Stop markedly reduced DOAC interference from test samples (P < .05). DOAC-Stop had no effect on LAC testing in the absence of DOAC therapy, permitting the identification of all LAC positive and negative controls. DOAC-Stop removed false positives and false negatives resulting from DOAC interference and allows the identification of patients meeting criteria for the diagnosis of APS by LAC testing, as well as the detection of patients on rivaroxaban who are triple positive for APS. CONCLUSIONS DOAC-Stop is an effective adjunct for the clinical laboratory faced with DOAC interference in LAC testing.
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Affiliation(s)
| | - Jing Jin
- Department of Special Coagulation Clinical LaboratoryStanford Health CarePalo AltoCAUSA
| | - Christopher Pfaffroth
- Department of Special Coagulation Clinical LaboratoryStanford Health CarePalo AltoCAUSA
| | - Trang Vu
- Department of Special Coagulation Clinical LaboratoryStanford Health CarePalo AltoCAUSA
| | - James L. Zehnder
- Department of PathologyStanford University School of MedicineStanfordCAUSA
- Division of HematologyStanford University School of MedicineStanfordCAUSA
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Radin M, Cecchi I, Foddai SG, Rubini E, Barinotti A, Ramirez C, Seaman A, Roccatello D, Mahler M, Sciascia S. Validation of the Particle-Based Multi-Analyte Technology for Detection of Anti-PhosphatidylSerine/Prothrombin Antibodies. Biomedicines 2020; 8:biomedicines8120622. [PMID: 33348782 PMCID: PMC7766094 DOI: 10.3390/biomedicines8120622] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 12/11/2020] [Accepted: 12/14/2020] [Indexed: 11/16/2022] Open
Abstract
Among “extra-criteria” antiphospholipid (aPL) antibodies, anti-phosphatidylserine/prothrombin (aPS/PT) antibodies, are considered a part of risk assessment strategies when investigating patients suspected of having antiphospholipid syndrome (APS). aPL detection is currently performed by solid-phase assays to identify anti-cardiolipin (aCL), anti-β2glycoprotein I (aβ2GPI) and aPS/PT antibodies, but new techniques are emerging. Among these, particle-based multi-analyte technology (PMAT), which allows the full automation and simultaneous digital detection of autoantibodies and proteins, including IgG, IgA and IgM isotypes of aCL, aβ2GPI and aPS/PT. The aim of this study was to investigate the agreement of aPS/PT testing between enzyme-linked immunosorbent assay (ELISA) and the PMAT platform. A total of 94 patients were enrolled in the study, including 71 patients with confirmed APS and 23 “aPL carriers”. aPS/PT IgG showed a moderate binomial agreement between ELISA and PMAT (k = 0.57, 95% CI 0.45–0.75), and aPS/PT IgM showed a moderate agreement (k = 0.60, 95% CI 0.45–0.75). Moreover, when considering the continuous agreement, both aPS/PT IgG and IgM showed a statistically significant correlation between ELISA and PMAT (Spearman’s correlation = 0.69, p < 0.001 and 0.72, p < 0.001, respectively). This study demonstrates that PMAT technology is a reliable method for aPS/PT IgG and IgM testing when compared to the available commercial ELISA kit.
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Affiliation(s)
- Massimo Radin
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, 10154 Turin, Italy; (M.R.); (I.C.); (S.G.F.); (E.R.); (A.B.); (D.R.)
| | - Irene Cecchi
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, 10154 Turin, Italy; (M.R.); (I.C.); (S.G.F.); (E.R.); (A.B.); (D.R.)
| | - Silvia Grazietta Foddai
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, 10154 Turin, Italy; (M.R.); (I.C.); (S.G.F.); (E.R.); (A.B.); (D.R.)
- School of Specialization of Clinical Pathology, Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy
| | - Elena Rubini
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, 10154 Turin, Italy; (M.R.); (I.C.); (S.G.F.); (E.R.); (A.B.); (D.R.)
| | - Alice Barinotti
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, 10154 Turin, Italy; (M.R.); (I.C.); (S.G.F.); (E.R.); (A.B.); (D.R.)
| | - Carlos Ramirez
- Inova Diagnostics, San Diego, CA 92131, USA; (C.R.); (A.S.); (M.M.)
| | - Andrea Seaman
- Inova Diagnostics, San Diego, CA 92131, USA; (C.R.); (A.S.); (M.M.)
| | - Dario Roccatello
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, 10154 Turin, Italy; (M.R.); (I.C.); (S.G.F.); (E.R.); (A.B.); (D.R.)
- Nephrology and Dialysis, Department of Clinical and Biological Sciences, S. Giovanni Bosco Hospital, University of Turin, 10154 Turin, Italy
| | - Michael Mahler
- Inova Diagnostics, San Diego, CA 92131, USA; (C.R.); (A.S.); (M.M.)
| | - Savino Sciascia
- Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, Department of Clinical and Biological Sciences, University of Turin, 10154 Turin, Italy; (M.R.); (I.C.); (S.G.F.); (E.R.); (A.B.); (D.R.)
- Nephrology and Dialysis, Department of Clinical and Biological Sciences, S. Giovanni Bosco Hospital, University of Turin, 10154 Turin, Italy
- Correspondence: mail
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Abd-Rabou AA, Bharali DJ, Mousa SA. Viramidine-Loaded Galactosylated Nanoparticles Induce Hepatic Cancer Cell Apoptosis and Inhibit Angiogenesis. Appl Biochem Biotechnol 2019; 190:305-324. [PMID: 31346920 DOI: 10.1007/s12010-019-03090-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 07/05/2019] [Indexed: 01/19/2023]
Abstract
Current estimates indicate that hepatocarcinoma is the leading cause of death globally. There is interest in utilizing nanomedicine for cancer therapy to overcome side effects of chemo-interventions. Ribavirin, an antiviral nucleoside inhibitor, accumulates inside red blood cells, causing anemia. Its analog, viramidine, can concentrate within hepatocytes and spare red blood cells, thus limiting anemia. Hepatocarcinoma cells have a large number of asialoglycoprotein receptors on their membranes that can bind galactosyl-terminating solid lipid nanoparticles (Gal-SLN) and internalize them. Here, viramidine, 5-fluorouracil, and paclitaxel-loaded Gal-SLN were characterized inside cells. Cytotoxicities of free-drug, nano-void, and drug-loaded Gal-SLN were evaluated using HepG2 cells; over 3 days, cell viability was measured. To test the mechanistic pathway, we investigated in vitro apoptosis using flow cytometry and in ovo angiogenesis using the CAM assay. Results showed that 1 and 2 μM of the viramidine-encapsulated Gal-SLN had the highest cytotoxic effect, achieving 80% cell death with a steady increase over 3 days, with induction of apoptosis and reduction of necrosis and angiogenesis, compared to free-drugs. Gal-SLN application on breast cancer MCF-7 cells confirmed its specificity against liver cancer HepG2 cells. We conclude that viramidine-encapsulated Gal-SLN has anticancer and anti-angiogenic activities against hepatocarcinoma.
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Affiliation(s)
- Ahmed A Abd-Rabou
- Hormones Department, Medical Research Division, National Research Centre, Giza, 12622, Egypt.,Stem Cell Laboratory, Center of Excellence for Advanced Science, National Research Centre, Giza, 12622, Egypt
| | - Dhruba J Bharali
- The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, NY, 12144, USA
| | - Shaker A Mousa
- The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 1 Discovery Drive, Rensselaer, NY, 12144, USA.
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Dai ZW, Wang H, Xu WJ, Wang ZH, Xu SQ, Wang B, Ye DQ. Diagnostic accuracy of miRNAs as potential biomarkers for systemic lupus erythematosus: a meta-analysis. Clin Rheumatol 2018; 37:2999-3007. [PMID: 29980876 DOI: 10.1007/s10067-018-4189-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 05/30/2018] [Accepted: 06/24/2018] [Indexed: 02/01/2023]
Abstract
To systematically evaluate the diagnostic accuracy of miRNAs as potential biomarkers for systemic lupus erythematosus (SLE). Studies were searched in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and China Biology Medicine (CBM) disc database, and languages were limited in English and Chinese. QUADAS-2 tool was applied to assess the quality of eligible studies. Random-effect model was applied to calculate pooled effects of miRNAs on diagnosing SLE. Subgroup analysis was used to explore the sources of heterogeneity. All data were calculated and analyzed by Meta-Disc 1.4 and RevMan 5.3 software. Six eligible studies were included in this meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio of miRNAs were 0.75(95% CI 0.71-0.79), 0.72(95% CI 0.66-0.78), and 8.79(95% CI 4.91-15.73), respectively. The pooled positive likelihood ratio was 2.71(95% CI 2.20-3.33) and negative likelihood ratio was 0.34(95% CI 0.24-0.48). The area under the curve was 0.787. The subgroup analysis showed that the number of healthy controls might be the sources of heterogeneity. MiRNAs in blood have moderate accuracy and influence on diagnosing SLE, and the exact diagnostic value should be confirmed by further studies.
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Affiliation(s)
- Zi-Wei Dai
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Hong Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Wen-Juan Xu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Zhi-Hui Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Sheng-Qian Xu
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, Anhui, China
| | - Bin Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, 230032, Anhui, China.
| | - Dong-Qing Ye
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, 230032, Anhui, China.
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Ahluwalia J, Sreedharanunni S, Kumar N, Masih J, Bose SK, Varma N, Varma S, Singh S. Thrombotic Primary Antiphospholipid Syndrome: the profile of antibody positivity in patients from North India. Int J Rheum Dis 2014; 19:903-12. [PMID: 25292011 DOI: 10.1111/1756-185x.12479] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Jasmina Ahluwalia
- Department of Hematology; Postgraduate Institute of Medical Education & Research; Chandigarh India
| | - Sreejesh Sreedharanunni
- Department of Hematology; Postgraduate Institute of Medical Education & Research; Chandigarh India
| | - Narender Kumar
- Department of Hematology; Postgraduate Institute of Medical Education & Research; Chandigarh India
| | - Joseph Masih
- Department of Hematology; Postgraduate Institute of Medical Education & Research; Chandigarh India
| | - Sunil Kumar Bose
- Department of Hematology; Postgraduate Institute of Medical Education & Research; Chandigarh India
| | - Neelam Varma
- Department of Hematology; Postgraduate Institute of Medical Education & Research; Chandigarh India
| | - Subhash Varma
- Department of Internal Medicine; Postgraduate Institute of Medical Education & Research; Chandigarh India
| | - Surjit Singh
- Department of Pediatrics; Postgraduate Institute of Medical Education & Research; Chandigarh India
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Khogeer H, Alfattani A, Al Kaff M, Al shehri T, Khojah O, Owaidah T. Antiphosphatidylserine antibodies as diagnostic indicators of antiphospholipid syndrome. Lupus 2014; 24:186-90. [DOI: 10.1177/0961203314552462] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Background Antiphospholipid syndrome (APS) is an autoimmune condition that is diagnosed by the presence of at least one of the clinical manifestations (thrombosis and/or pregnancy failure) and one of antiphospholipid antibodies (aPL) laboratory tests. The most relevant aPL are lupus anticoagulant (LA), anti-beta2 glycoprotein I (aβ2GPI) and anticardiolipin (aCL). The clinical significance of other antibodies like anti-phosphatidylserine antibodies (aPS) is still under investigation. Objectives The aim of the study was to assess the diagnostic value of aPS antibodies, and to compare their utility to that of other aPL antibodies. Methods We conducted a prospective observational study consisting of 212 patients with suspected thrombosis, pregnancy failure, or unexplained, prolonged clotting time. Data on demography, clinical presentation and autoantibody levels were assessed. Descriptive analysis, accuracy analysis, sensitivity, specificity, predictive value and likelihood ratio were calculated for aPS in comparison to other aPL. Results The diagnostic value of aPS versus other aPL antibodies revealed the high specificity of aPS (87%), with 70% of aPS-positive patients being confirmed APS. When the aPS test was used as a single test, it was effective for detection of confirmed APS cases ( p < 0.01). Among 28 confirmed primary APS cases, 75% of patients were positive for aPS ( p < 0.003). Moreover, by using aPS we detected three additional confirmed APS cases and another three probable cases. Conclusion Our findings reveal a significant association between aPS and APS, especially when used to diagnosis clinical cases with other negative aPL tests. There is an independent association between aPS and primary APS. In addition, these results demonstrated the advantages of using aPS as a diagnostic test for APS.
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Affiliation(s)
- H Khogeer
- Section of Hematology, Department of Pathology and Laboratory Medicine (DPLM), King Faisal Specialist Hospital and Research Center (KFSH & RC), Riyadh, Kingdom of Saudi Arabia
| | - A Alfattani
- Section of Hematology, Department of Pathology and Laboratory Medicine (DPLM), King Faisal Specialist Hospital and Research Center (KFSH & RC), Riyadh, Kingdom of Saudi Arabia
| | - M Al Kaff
- Section of Hematology, Department of Pathology and Laboratory Medicine (DPLM), King Faisal Specialist Hospital and Research Center (KFSH & RC), Riyadh, Kingdom of Saudi Arabia
| | - T Al shehri
- Research Unit, Department of Pediatric, KFCH & RC, Riyadh, Kingdom of Saudi Arabia
| | - O Khojah
- Pathology Department, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - T Owaidah
- Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center (KFSH & RC), Riyadh, Kingdom of Saudi Arabia
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Plavsic A, Miskovic R, Raskovic S, Bogic M, Bonaci Nikolic B. Systemic Lupus Erythematosus and Antiphospholipid Syndrome. Open Access Maced J Med Sci 2014. [DOI: 10.3889/oamjms.2014.098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Antiphospholipid syndrome is an autoimmune disorder defined as association of vascular thrombosis and/or pregnancy complications with presence of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin and anti-β2 glycoprotein I). It is the most common cause of acquired thrombophilia, and can occur as an independent entity or in relation with other diseases, especially systemic lupus erythematosus. Presence of antiphospholipid syndrome in systemic lupus erythematosus is additional vaso occlusive factor in already present inflammation, bringing further risk for thrombotic events. Clinical and serological manifestations of antiphospholipid syndrome and systemic lupus erythematosus are very similar, so possible connection for these two autoimmune disorders is assumed.
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Cheng MR, Li Q, Wan T, He B, Han J, Chen HX, Yang FX, Wang W, Xu HZ, Ye T, Zha BB. Galactosylated chitosan/5-fluorouracil nanoparticles inhibit mouse hepatic cancer growth and its side effects. World J Gastroenterol 2012; 18:6076-87. [PMID: 23155336 PMCID: PMC3496884 DOI: 10.3748/wjg.v18.i42.6076] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2012] [Revised: 07/18/2012] [Accepted: 07/28/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To observe the curative effect of galactosylated chitosan (GC)/5-fluorouracil (5-FU) nanoparticles in liver caner mice and its side effects.
METHODS: The GC/5-FU nanoparticle is a nanomaterial made by coupling GC and 5-FU. The release experiment was performed in vitro. The orthotropic liver cancer mouse models were established and divided into control, GC, 5-FU and GC/5-FU groups. Mice in the control and GC group received an intravenous injection of 200 μL saline and GC, respectively. Mice in the 5-FU and GC/5-FU groups received 200 μL (containing 0.371 mg 5-FU) 5-FU and GC/5-FU, respectively. The tumor weight and survival time were observed. The cell cycle and apoptosis in tumor tissues were monitored by flow cytometry. The expression of p53, Bax, Bcl-2, caspase-3 and poly adenosine 50-diphosphate-ribose polymerase 1 (PARP-1) was detected by immunohistochemistry, reverse transcription-polymerase chain reaction and Western blot. The serum blood biochemical parameters and cytotoxic activity of natural killer (NK) cell and cytotoxicity T lymphocyte (CTL) were measured.
RESULTS: The GC/5-FU nanoparticle is a sustained release system. The drug loading was 6.12% ± 1.36%, the encapsulation efficiency was 81.82% ± 5.32%, and the Zeta potential was 10.34 ± 1.43 mV. The tumor weight in the GC/5-FU group (0.4361 ± 0.1153 g vs 1.5801 ± 0.2821 g, P < 0.001) and the 5-FU (0.7932 ± 0.1283 g vs 1.5801 ± 0.2821 g, P < 0.001) was significantly lower than that in the control group; GC/5-FU treatment can significantly lower the tumor weight (0.4361 ± 0.1153 g vs 0.7932 ± 0.1283 g, P < 0.001), and the longest median survival time was seen in the GC/5-FU group, compared with the control (12 d vs 30 d, P < 0.001), GC (13 d vs 30 d, P < 0.001) and 5-FU groups (17 d vs 30 d, P < 0.001). Flow cytometry revealed that compared with the control, GC/5-FU caused a higher rate of G0-G1 arrest (52.79% ± 13.42% vs 23.92% ± 9.09%, P = 0.014 ) and apoptosis (2.55% ± 1.10% vs 11.13% ± 11.73%, P < 0.001) in hepatic cancer cells. Analysis of the apoptosis pathways showed that GC/5-FU upregulated the expression of p53 at both the protein and the mRNA levels, which in turn lowered the ratio of Bcl-2/Bax expression; this led to the release of cytochrome C into the cytosol from the mitochondria and the subsequent activation of caspase-3. Upregulation of caspase-3 expression decreased the PARP-1 at both the mRNA and the protein levels, which contributed to apoptosis. 5-FU increased the levels of aspartate aminotransferase and alanine aminotransferase, and decreased the numbers of platelet, white blood cell and lymphocyte and cytotoxic activities of CTL and NK cells, however, there were no such side effects in the GC/5-FU group.
CONCLUSION: GC/5-FU nanoparticles can significantly inhibit the growth of liver cancer in mice via the p53 apoptosis pathway, and relieve the side effects and immunosuppression of 5-FU.
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Borchers AT, Naguwa SM, Keen CL, Gershwin ME. The implications of autoimmunity and pregnancy. J Autoimmun 2009; 34:J287-99. [PMID: 20031371 DOI: 10.1016/j.jaut.2009.11.015] [Citation(s) in RCA: 132] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
There are multiple epidemiological studies that document the potential adverse affects of autoimmunity on nearly every aspect of reproduction, even in the absence of clinically manifest autoimmune disease. Two decades ago, it was suggested that women with autoimmune diseases avoid pregnancy due to inordinate risks to the mother and the child. In contrast, newer epidemiological data demonstrated that advances in the treatment of autoimmune diseases and the management of pregnant women with these diseases have similarly improved the prognosis for mother and child. In particular, if pregnancy is planned during periods of inactive or stable disease, the result often is giving birth to healthy full-term babies without increased risks of pregnancy complications. Nonetheless, pregnancies in most autoimmune diseases are still classified as high risk because of the potential for major complications. These complications include disease exacerbations during gestation and increased perinatal mortality and morbidity in most autoimmune diseases, whereas fetal mortality is characteristic of the anti-phospholipid syndrome (APS). In this review, we will discuss these topics, including issues of hormones, along with potential long-term effects of the microchimerism phenomenon. With respect to pregnancy and autoimmune diseases, epidemiological studies have attempted to address the following questions: 1) Is it safe for the mother to become pregnant or are there acute or chronic effects of pregnancy on the course of the disease? 2) Does the disease alter the course and/or the outcome of a pregnancy and thereby represent an inordinate risk for the fetus and infant? And do new therapeutic and management approaches improve the pregnancy outcomes in women with autoimmune diseases? 3) Does passage of maternal autoantibodies represent a risk to the child? 4) Do pregnancy, parity, or other factors influencing hormonal status explain the female predominance of many autoimmune diseases, and is the pregnancy effect related to microchimerism? Answering these questions has taken on additional importance in recent decades as women in western countries now frequently choose to delay pregnancies and have some or all of their pregnancies after disease onset. In this paper, we primarily focus on APS, systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), and type 1 diabetes (T1D).
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Affiliation(s)
- Andrea T Borchers
- Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, 451 Health Sciences Drive, Suite 6510, Davis, CA 95616, USA
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Bibliography. Current world literature. Systemic lupus erythematosus and Sjögren's syndrome. Curr Opin Rheumatol 2008; 20:631-2. [PMID: 18698190 DOI: 10.1097/bor.0b013e3283110091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Baker WF, Bick RL. The clinical spectrum of antiphospholipid syndrome. Hematol Oncol Clin North Am 2008; 22:33-52, v-vi. [PMID: 18207064 DOI: 10.1016/j.hoc.2007.10.007] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Antiphospholipid syndrome (APS) is a disorder characterized by a wide variety of clinical manifestations. Virtually any organ system or tissue may be affected by the consequences of large- or small-vessel thrombosis. There is a broad spectrum of disease among individuals with antiphospholipid antibodies (aPL). Patients may exhibit clinical features suggesting APS but not fulfill the International Criteria for a "definite" diagnosis. Seronegative APS patients demonstrate typical idiopathic thromboses but aPL are not initially detected. Patients defined with definite APS demonstrate nearly identical sites of venous and arterial thrombosis, regardless of the presence or absence of systemic lupus erythematosus. Microangiopathic APS may present with isolated tissue and organ injury or as the overwhelming "thrombotic storm" observed in catastrophic APS.
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Affiliation(s)
- William F Baker
- David Geffen School of Medicine, Center for Health Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
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Angchaisuksiri P, Atichartakarn V, Aryurachai K, Archararit N, Rachakom B, Atamasirikul K, Tiraganjana A. Risk factors of venous thromboembolism in thai patients. Int J Hematol 2008; 86:397-402. [PMID: 18192106 DOI: 10.1007/bf02983995] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Venous thromboembolism (VTE) has been reported to be less common among Thais than Caucasians. Whether this observation reflects genetic or environmental factors, or both, is uncertain. To identify genetic and acquired risk factors of Thai patients with VTE, we enrolled in the study 105 consecutive Thai patients (34 men, 71 women) who had an objectively confirmed history of VTE. A complete clinical summary was obtained from each patient, with emphasis on personal and family history of VTE, as well as circumstantial vascular risk factors (surgery, immobilization, pregnancy, postpartum condition, trauma, oral contraceptive use, and malignancy). Of the 105 patients, 19% were found to have a malignancy. The mean age at the time of the first thrombotic episode was 52.1 years (range, 29-76 years), compared with 42.6 years (range, 17-82 years) for the patients without malignancy. Of the 85 patients without malignancy, 12.3% had protein S deficiency, 8.9% had protein C deficiency, 4.7% had antithrombin deficiency, 10.4% had antiphospholipid antibody, 30.4% had an elevated factor VIII level, 26.8% had an elevated factor XI level, 5.3% had hyperhomocysteinemia, and 16.5% were on oral contraceptives before the thrombotic episode. Factor V Leiden, the G20210A prothrombin gene mutation, and homozygosity for the C677T methylenetetrahydrofolate reductase (MTHFR) gene variant were not found. The VTE in 7.1% of the patients was considered to be secondary to recent surgery, trauma, and/or immobilization. Compared with studies of Caucasian patients, there were significant differences in the risk factors for VTE, with protein S deficiency and protein C deficiency being more common in the Thai patients. In contrast, factor V Leiden, the G20210A prothrombin gene mutation, and the C677T MTHFR gene mutation are not genetic risk factors among Thai patients with VTE. Malignancy and the use of oral contraceptives were the most common acquired risk factors for VTE in the Thai patients.
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Affiliation(s)
- Pantep Angchaisuksiri
- Division of Hematology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
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