Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
30847766 Determination of Elements in Gymnema inodorum Lour by Particle Induced X-Ray Emission (PIX 2019 Dec At present, Thailand uses medicinal plants to treat various diseases. Alternative medicine utilizes Gymnema inodorum Lour for antipyretic and anti-allergic purposes. There are also other research studies to treat diabetes mellitus, coronary artery disease, cataract, rheumatoid arthritis, gout, liver cancer, and stomach cancer. This study used particle-induced X-ray emission (PIXE) technique to analyze the elements in this plant. The advantage of this technique over other methods is the multi-elemental analysis and high sensitivity. The objective of this study was to determine the elemental compositions and to develop new standard methods for analyzing plant elemental compositions in Thailand. A 2-MeV proton beam was used to identify and characterize major and minor elements namely Mg, Al, Si, P, S, Cl, K, Ca, Ti, Mn, Fe, and Zn in Gymnema Inodorum Lour. Results have shown that these elements are present in varying concentrations in the selected parts: roots, stems, and leaves. The data of elemental analysis, applied in recommended quantities that are harmful to the body, describe the relationship between elements and efficacy of this plant in alternative medicine.
30733703 Do Th17 Lymphocytes and IL-17 Contribute to Parkinson's Disease? A Systematic Review of Av 2019 Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons, appearance of Lewy bodies and presence of neuroinflammation. No treatments currently exist to prevent PD or delay its progression, and dopaminergic substitution treatments just relieve the consequences of dopaminergic neuron loss. Increasing evidence points to peripheral T lymphocytes as key players in PD, and recently there has been growing interest into the specific role of T helper (Th) 17 lymphocytes. Th17 are a proinflammatory CD4+ T cell lineage named after interleukin (IL)-17, the main cytokine produced by these cells. Th17 are involved in immune-related disease such as psoriasis, rheumatoid arthritis and inflammatory bowel disease, and drugs targeting Th17/IL-17 are currently approved for clinical use in such disease. In the present paper, we first summarized current knowledge about contribution of the peripheral immune system in PD, as well as about the physiopharmacology of Th17 and IL-17 together with its therapeutic relevance. Thereafter, we systematically retrieved and evaluated published evidence about Th17 and IL-17 in PD, to help assessing Th17/IL-17-targeting drugs as potentially novel antiparkinson agents. Critical appraisal of the evidence did not allow to reach definite conclusions: both animal as well as clinical studies are limited, just a few provide mechanistic evidence and none of them investigates the eventual relationship between Th17/IL-17 and clinically relevant endpoints such as disease progression, disability scores, intensity of dopaminergic substitution treatment. Careful assessment of Th17 in PD is anyway a priority, as Th17/IL-17-targeting therapeutics might represent a straightforward opportunity for the unmet needs of PD patients.
29500302 Oral Therapies for Multiple Sclerosis. 2019 Jan 2 Multiple sclerosis treatment faces tremendous changes owing to the approval of new medications, some of which are available as oral formulations. Until now, the four orally available medications, fingolimod, dimethylfumarate (BG-12), teriflunomide, and cladribine have received market authorization, whereas laquinimod is still under development. Fingolimod is a sphingosine-1-phosphate inhibitor, which is typically used as escalation therapy and leads to up to 60% reduction of the annualized relapse rate, but might also have neuroprotective properties. In addition, there are three more specific S1P agonists in late stages of development: siponimod, ponesimod, and ozanimod. Dimethylfumarate has immunomodulatory and cytoprotective functions and is used as baseline therapy. Teriflunomide, the active metabolite of the rheumatoid arthritis medication leflunomide, targets the dihydroorotate dehydrogenase, thus inhibiting the proliferation of lymphocytes by depletion of pyrimidines. Here we will review the mechanisms of action, clinical trial data, as well as data about safety and tolerability of the compounds.
35240760 Reducing the risk of infection after total joint arthroplasty: preoperative optimization. 2019 Aug 1 Total joint arthroplasty (TJA) is one of the most commonly performed procedures in orthopedic surgery, and as the demand for TJA increases over time, the number of concurrent complications such as surgical infection will also increase. There are multiple risk factors that independently increase the risk of surgical site infection (SSI) and periprosthetic joint infection (PJI) after surgery. These modifiable risk factors can be identified in preoperative clinic screening visits that gives physicians the opportunity to provide specific intervention that can decrease patient infection risk. The risk factors that are known to significantly increase the risk of PJI and/or SSI include MSSA/MRSA colonization, rheumatoid arthritis, cardiovascular and renal disease, obesity, diabetes mellitus, hyperglycemia, anemia, malnutrition, tobacco use, alcohol consumption, depression, and anxiety. Patients who present with one or more of these risk factors require intervention with a multidisciplinary approach including patient education, counseling, and follow-up. Preoperative patient optimization for high risk TJA patients can significantly decrease PJI and SSI risk while improving surgical outcomes and patient care.
32051778 Osteochondral Autograft Transplant (Mosaicplasty) for Knee Articular Cartilage Defects. 2019 Oct Osteochondral autograft transplant (mosaicplasty) is a cartilage repair procedure for patients with knee articular cartilage lesions of a substantial size (>3 cm(2)). Patient selection is key to a successful result; patients with established osteoarthritis or systematic disorders such as rheumatoid arthritis should not undergo surgery. An exercise program involving neuromuscular training for a minimum of 3 months should be attempted before proceeding to osteochondral autograft transplant. The procedure can, in many cases, be performed arthroscopically. Patients should, however, provide consent for a mini-arthrotomy as this might be needed to achieve optimal access for graft harvesting and insertion. The procedure, in general, consists of 4 major steps. (1) At the initial arthroscopic examination, the size and localization of the defect are assessed after a proper debridement has been performed. The number and size of autografts needed can thereafter be assessed. (2) Graft harvesting is then performed from the periphery of the non-weight-bearing trochlea. (3) To prepare for graft insertion at the recipient site, a drill guide is inserted perpendicular to the joint surface in the defect to allow graft sockets to be reamed. (4) Grafts should be spaced approximately 3 mm apart to avoid confluence of tunnels and weakening of condyles. The orientation and depth of insertion of the grafts are key to mimic the native curvature of the affected joint surface. After an initial phase of non-weight-bearing focusing on range of motion, a gradual increase in neuromuscular exercises is recommended. Patients are typically advised to delay their return to sports until 6 months at the earliest. Results after mosaicplasty have shown that the procedure improves subjective outcomes, compared with baseline function, for up to 10 years after surgery. The additional effect over traditional microfracture treatment is, however, reduced over time. A study evaluating early factors affecting outcomes after cartilage repair procedures (including mosaicplasty) found that a series of factors, such as the time from the onset of symptoms to surgery, number and size of lesions, location and quality of surrounding cartilage, as well as concomitant meniscal injuries, were important(3).
31579534 The Isometric Quadriceps Contraction Method for Intra-Articular Knee Injection. 2019 Jun 26 The intra-articular injection is the most important technique for treating not only rheumatoid arthritis but also osteoarthritis of the knee. However, 1 problem is that the drug is often inaccurately injected outside of the joint, especially when no effusion is present. According to a previous systematic review by Maricar et al., the use of a superolateral patellar approach without ultrasonography had a higher success rate (87%) than both a medial midpatellar approach (64%) and an anterolateral joint-line approach (70%). For knees with little effusion, we devised a method of intra-articular injection in which the needle is inserted into the suprapatellar pouch while the patient maintains isometric contraction of the quadriceps. This method, which we call the isometric quadriceps contraction (IQC) method, is based on the concept that isometric contraction of the quadriceps induces contraction of the articularis genus muscle complex, thus expanding the volume of the suprapatellar pouch. The major steps of the procedure are (1) patient positioning and knee placement, (2) finding the puncture point, (3) isometric quadriceps contraction, and (4) needle approach to the suprapatellar pouch and injection. We also show the ultrasound evaluation of the suprapatellar pouch expansion under IQC and the accuracy of the IQC method compared with that of the non-activated quadriceps method. The results of this injection method indicate that the suprapatellar pouch is likely to expand during IQC, improving the probability of successful intra-articular injections. We believe that the IQC method is therapeutically effective and achieved a success rate of 93.3% despite the presence of little effusion and no use of ultrasonography.
31448336 Poor communication by health care professionals may lead to life-threatening complications 2019 We report two cases which highlight the fact how poor communication leads to dangerously poor health outcome. We present the case of a 50-year-old woman recently diagnosed with rheumatoid arthritis from Southern Nepal presented to Patan hospital with multiple episodes of vomiting and oral ulcers following the intake of methotrexate every day for 11 days, who was managed in the intensive care unit. Similarly, we present a 40-year-old man with ileo-caecal tuberculosis who was prescribed with anti-tubercular therapy (ATT) and prednisolone, who failed to take ATT due to poor communication and presented to Patan Hospital with features of disseminated tuberculosis following intake of 2 weeks of prednisolone alone. These were events that could have been easily prevented with proper communication skills. Improvement of communication between doctors and patients is paramount so that life-threatening events like these could be avoided.
31352871 Menopausal symptoms and related factors among Cambodian women. 2020 Apr This study analyzed the prevalence and severity of menopausal symptoms and associated factors among Cambodian women. A cross-sectional study was performed with 200 women aged 40-60 years in three provinces and one urban area in Cambodia from July 2017 to August 2017. Three symptom categories: somatic, psychological, and urogenital symptoms (totaling 11 symptoms) related to menopause were assessed using the Khmer version of Menopause Rating Scale (MRS). Over one-fifth (21.5%) of the participants were premenopausal; 22.5% were perimenopausal, and 56% were postmenopausal. Somatic and psychological symptoms occurred more frequently than urogenital symptoms in all three statuses. The three most prevalent symptoms for all women were physical and mental exhaustion (88.1%), irritability (85.9%), and sleep problems (82.5%). The average MRS score was 12.22 ± 5.37 (range 0-44). Postmenopausal women had significantly higher rates of menopausal symptoms than pre- and perimenopausal women. Increased severity of menopausal symptoms was associated with less personal income (≤100 US$), higher parity (>4 children), abortion(s), use of calcium supplements, and history of heart disease and rheumatoid arthritis. This study demonstrated a high prevalence of menopausal symptoms among Cambodian women in Cambodia. A multidisciplinary approach is needed to deal with independent factors associated with these symptoms.
31217209 Eosinophilic granulomatosis with polyangiitis in a Nigerian woman. 2019 Jun 18 Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss Syndrome, is a systemic autoimmune disease that is usually associated with asthma and eosinophilia. It is a rare condition associated with antineutrophil cytoplasmic antibodies (ANCA). We report a case of a 52-year-old Nigerian woman who presented with bilateral leg swelling with multiple ulcers, background history of allergic rhinitis and chronic sinusitis since adolescence. There were also associated symptoms of peripheral neuropathy, weight loss, peripheral blood eosinophilia and positive perinuclear ANCA and she was previously managed for rheumatoid arthritis and asthma. She fulfilled the American College of Rheumatology criteria for EGPA and was treated with glucocorticoids and methotrexate which led to significant improvement of her symptoms.
31160225 Contraception in autoimmune diseases. 2019 Oct Autoimmune diseases (AIDs) affect women and men with a 2:1 ratio, which suggests that hormonal contraceptives play a role in their clinical course. Combined oral contraceptives have complex, sometimes contradictory, effects on AIDs; they can worsen the situation in women with systemic lupus erythematosus and with anti-phospholipid syndrome, conditions in which they are contraindicated. Early studies indicated a positive effect on rheumatoid arthritis (RA), whereas more recent trials failed to do so, possibly because of the lowering of oestrogen content. Evidence of effects on multiple sclerosis (MS) is conflicting: risk may vary depending on the progestin used. Minor adverse effects may exist on inflammatory bowel diseases, and no significant effect was found on autoimmune thyroid diseases. Women can become sensitised to sex hormones. Progestin-only contraceptives may be used, although copper-releasing intra-uterine devices represent the best option. Finally, several organisations have issued guidelines for contraceptive use in women with AIDs.
31091976 Treatment of Neurodegenerative Diseases with Bioactive Components of Tripterygium wilfordi 2019 Tripterygium wilfordii Hook F. (TWHF), a traditional Chinese medicine, has been widely used to treat autoimmune and inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus and dermatomyositis in China. Recently, studies have demonstrated that the bioactive components of TWHF have effective therapeutic potential for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and Multiple Sclerosis. In this paper, we summarize the research progress of triptolide and celastrol (the two major TWHF components) as well as their analogues in the treatment of neurodegenerative diseases. In addition, we review and discuss the molecular mechanisms and structure features of those two bioactive TWHF components, highlighting their therapeutic promise in neurodegenerative diseases.
30994012 Multiplexed immunoassay approach to characterize antidrug antibody like specific reactivit 2019 Apr Aim: Characterization of antidrug antibody (ADA)-like reactivity has emerged as critical element of bioanalytical design and assessment of compound immunogenicity risk. Materials & methods: Multiplex immunoassay was applied to detect and characterize ADA like reactivity using Photonic Ring Immunoassay platform (Genalyte). Specific binding to human IgE or human recombinant IL21-receptor-Fc fusion using exogenous reagents as surrogates for drug-specific reactivity was investigated. Results: Multiplexed assay format allowed identification of spiked antihuman IgE reactivity as murine IgG1 and endogenous antihuman recombinant IL21-receptor-Fc reactivity in rheumatoid arthritis sera as antihuman Fc-specific binding. Conclusion: The ability of a multiplex immunoassay platform to identify isotype and domain specificity of antidrug immunoglobulins was shown to be effective and should be considered when screening and characterizing pre- and post-dose ADA reactivity.
30875506 Modeling caspase-1 inhibition: Implications for catalytic mechanism and drug design. 2019 May 1 The metabolic product of caspase-1, IL-1β, is an important mediator in inflammation and pyroptosis cell death process. Alzheimer's disease, septic shock and rheumatoid arthritis are IL-1β mediated diseases, making the caspase-1 an interesting target of pharmacological value. Many inhibitors have been developed until now, most of them are peptidomimetic with improved potency. In the present study, all-atom molecular dynamics simulations and the MM/GBSA method were employed to reproduce and interpret the results obtained by in vitro experiments for a series of inhibitors. The analysis shows that the tautomeric state of the catalytic His237 impact significantly the performance of the prediction protocol, providing evidence for a His237 tautomeric state different to the proposed in the putative mechanism. Additionally, analysis of inhibitor-enzyme interactions indicates that the differences in the inhibitory potency of the tested ligands can be explained mainly by the interaction of the inhibitors with the S2-S4 protein region. These results provide guidelines for subsequent studies of caspase-1 catalytic reaction mechanism and for the design of novel inhibitors.
30788072 A case of Loeffler's endocarditis after initiation of adalimumab. 2019 Tumor necrosis factor antagonists (anti-TNF) are increasingly prescribed as maintenance therapy for a variety of autoimmune conditions. Therefore, frequent monitoring and awareness of side effects are of the utmost importance. Adalimumab is known to cause peripheral eosinophilia, but there are few reports of more severe adverse events. Loeffler's endocarditis is a rare and fatal disease characterized by eosinophilic infiltration of the endomyocardium leading to fibrosis and restrictive cardiomyopathy. Herein we describe a 72 year old female on adalimumab therapy for two years for rheumatoid arthritis presenting with Loeffler's endocarditis. This case represents a rare case of Loeffler's endocarditis diagnosed rapidly and without myocardial biopsy. Early intervention is crucial in the prevention of permanent fibrosis and mortality in Loeffler's endocarditis. This case demonstrates the need for close monitoring and early recognition in patients on anti-TNF therapy. Abbreviations: tumor necrosis factor (TNF), hypereosinophilic syndrome (HES).
32395171 Acute Inflammatory Optic Neuritis Associated with a Self-Taper of Oral Prednisone in a Pat 2020 Jun Therapies, such as adalimumab, aimed at inhibiting the pro-inflammatory cytokine "tumour necrosis factor" (TNF) are effective and are frequently used in combination with non-biologic disease-modifying anti-rheumatic drugs to treat rheumatoid arthritis (RA) and other autoimmune diseases. Some reports indicate that, rarely, demyelinating CNS disorders such as optic neuritis can present in association with therapy initiation, whilst others suggest that there is no association between the two. Oral corticosteroids such as prednisone, though similarly effective in the treatment of inflammatory or auto-immune conditions, can be associated with adverse effects upon their discontinuation or tapering. We present a patient who developed an acute inflammatory optic neuropathy shortly after a self-taper of oral prednisone while being treated with adalimumab for RA, and discuss the challenge of deciding whether or not to halt anti-TNF therapy.
30335143 Disease gene identification based on generic and disease-specific genome networks. 2019 Jun 1 SUMMARY: Immune diseases have a strong genetic component with Mendelian patterns of inheritance. While the tight association has been a major understanding in the underlying pathophysiology for the category of immune diseases, the common features of these diseases remain unclear. Based on the potential commonality among immune genes, we design Gene Ranker for key gene identification. Gene Ranker is a network-based gene scoring algorithm that initially constructs a backbone network based on protein interactions. Patient gene expression networks are added into the network. An add-on process screens the networks of weighted gene co-expression network analysis (WGCNA) on the samples of immune patients. Gene Ranker is disease-specific; however, any WGCNA network that passes the screening procedure can be added on. With the constructed network, it employs the semi-supervised learning for gene scoring. RESULTS: The proposed method was applied to immune diseases. Based on the resulting scores, Gene Ranker identified potential key genes in immune diseases. In scoring validation, an average area under the receiver operating characteristic curve of 0.82 was achieved, which is a significant increase from the reference average of 0.76. Highly ranked genes were verified through retrieval and review of 27 million PubMed literatures. As a typical case, 20 potential key genes in rheumatoid arthritis were identified: 10 were de facto genes and the remaining were novel. AVAILABILITY AND IMPLEMENTATION: Gene Ranker is available at http://www.alphaminers.net/GeneRanker/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
30176059 Simultaneous determination of tiopronin and its primary metabolite in plasma and ocular ti 2019 Feb Tiopronin, formally 2-mercaptopropionylglycine (MPG), is currently prescribed to treat cystinuria and rheumatoid arthritis, and its antioxidant properties have led to its investigation as a treatment for cataracts, a condition in which oxidative stress is strongly implicated. To study its accumulation in the eye, a reliable, isocratic HPLC method was developed for the determination of MPG and its primary metabolite 2-mercaptopropionic acid (MPA) in plasma and relevant ocular tissues. This method utilizes pre-column derivatization and fluorescence detection. The 3.5 min separation enables high-throughput analysis, and validation experiments demonstrated that this method is suitable for evaluating ocular accumulation of MPG and MPA at concentrations as low as 66 and 33 nm, respectively. Excellent linearity was achieved over the working concentration range with R(2)  > 0.997. Extraction recovery was reproducible within each matrix and exceeded 97%. Accuracy was within 13.3% relative error, and intra- and inter-day precisions were within 6% CV and 7% CV, respectively. Sample stability was demonstrated under various storage conditions, and the use of an internal standard conferred exceptional ruggedness. This method has been successfully applied for the determination of MPG and MPA in plasma, cornea, lens and retina following intraperitoneal administration of the drug in Wistar rats.
30030862 Application of an electrochemiluminescence assay for quantification of E6011, an antifract 2019 Jan BACKGROUND: E6011, a humanized antifractalkine monoclonal antibody, is under development for the treatment of various inflammatory diseases, such as rheumatoid arthritis. A reproducible assay method has been developed for the determination of E6011 in monkey and human serum by electrochemiluminescence (ECL) assay. METHODS: E6011 in serum was captured by fractalkine and detected by ruthenium-labeled rabbit anti-E6011 Fab polyclonal antibodies for ECL detection. E6011 in serum was quantifiable from 0.02 and 0.1 μg/mL in monkey and human serum, respectively, with minimum required dilution of 500. The method was then validated in accordance with bioanalytical guidelines. RESULTS: Accuracy and precision of quality control samples at five concentrations in intra- and interbatch reproducibility demonstrated that relative error and relative standard deviation were within acceptable criteria. Recovery of E6011 was 92.9%-121.7% and 85.0%-109.3% in humans and monkeys. Dilution integrity, no prozone effects, and no impacts by antigen were also ensured. Parallelism was also confirmed using incurred clinical sample analysis. Various types of stability were assessed, which confirmed that E6011 in serum was stable for 367 and 735 days in monkey and human sera, respectively, under frozen conditions. CONCLUSION: The developed method was successfully applied supporting pharmacokinetic studies in monkeys and humans.
30907775 Guidelines for Cervical Cancer Screening in Immunosuppressed Women Without HIV Infection. 2019 Apr EXECUTIVE SUMMARY: The risk of cervical cancer (CC) among women immunosuppressed for a variety of reasons is well documented in the literature. Although there is improved organ function, quality of life and life expectancy gained through use of immunosuppressant therapy, there may be increased long-term risk of cervical neoplasia and cancer and the need for more intense screening, surveillance, and management. Although guidance for CC screening among HIV-infected women (see Table 1) has been supported by evidence from retrospective and prospective studies, recommendations for CC screening among non-HIV immunosuppressed women remains limited because quality evidence is lacking. Moreover, CC screening guidelines for HIV-infected women have changed because better treatments evolved and resulted in longer life expectancy.The objective of this report was to summarize current knowledge of CC, squamous intraepithelial lesions, and human papillomavirus (HPV) infection in non-HIV immunocompromised women to determine best practices for CC surveillance in this population and provide recommendations for screening. We evaluated those with solid organ transplant, hematopoietic stem cell transplant, and a number of autoimmune diseases.A panel of health care professionals involved in CC research and care was assembled to review and discuss existing literature on the subject and come to conclusions about screening based on available evidence and expert opinion. Literature searches were performed using key words such as CC, cervical dysplasia/squamous intraepithelial lesion, HPV, and type of immunosuppression resulting in an initial group of 346 articles. Additional publications were identified from review of citations in these articles. All generated abstracts were reviewed to identify relevant articles. Articles published within 10 years were considered priority for review. Reviews of the literature were summarized with relevant statistical comparisons. Recommendations for screening generated from each group were largely based on expert opinion. Adherence to screening, health benefits and risks, and available clinical expertise were all considered in formulating the recommendations to the degree that information was available. RESULTS: Solid Organ Transplant: Evidence specific for renal, heart/lung, liver, and pancreas transplants show a consistent increase in risk of cervical neoplasia and invasive CC, demonstrating the importance of long-term surveillance and treatment. Reports demonstrate continued risk long after transplantation, emphasizing the need for screening throughout a woman's lifetime.Hematopoietic Stem Cell Transplant: Although there is some evidence for an increase in CC in large cohort studies of these patients, conflicting results may reflect that many patients did not survive long enough to evaluate the incidence of slow-growing or delayed-onset cancers. Furthermore, history of cervical screening or previous hysterectomy was not included in registry study analysis, possibly leading to underestimation of CC incidence rates.Genital or chronic graft versus host disease is associated with an increase in high-grade cervical neoplasia and posttransplant HPV positivity.Inflammatory Bowel Disease: There is no strong evidence to support that inflammatory bowel disease alone increases cervical neoplasia or cancer risk. In contrast, immunosuppressant therapy does seem to increase the risk, although results of observational studies are conflicting regarding which type of immunosuppressant medication increases risk. Moreover, misclassification of cases may underestimate CC risk in this population. Recently published preventive care guidelines for women with inflammatory bowel disease taking immunosuppressive therapy recommend a need for continued long-term CC screening.Systemic Lupus Erythematosus and Rheumatoid Arthritis: The risk of cervical high-grade neoplasia and cancer was higher among women with systemic lupus erythematosus than those with rheumatoid arthritis (RA), although studies were limited by size, inclusion of women with low-grade neoplasia in main outcomes, and variability of disease severity or exposure to immunosuppressants. In studies designed to look specifically at immunosuppressant use, however, there did seem to be an increase in risk, identified mostly in women with RA. Although the strength of the evidence is limited, the increase in risk is consistent across studies.Type 1 DM: There is a paucity of evidence-based reports associating type 1 DM with an increased risk of cervical neoplasia and cancer. RECOMMENDATIONS: The panel proposed that CC screening guidelines for non-HIV immunocompromised women follow either the (1) guidelines for the general population or (2) current center for disease control guidelines for HIV-infected women. The following are the summaries for each group reviewed, and more details are noted in accompanying table:Solid Organ Transplant: The transplant population reflects a greater risk of CC than the general population and guidelines for HIV-infected women are a reasonable approach for screening and surveillance.Hematopoietic Stem Cell Transplant: These women have a greater risk of CC than the general population and guidelines for HIV-infected women are a reasonable approach for screening. A new diagnosis of genital or chronic graft versus host disease in a woman post-stem cell transplant results in a greater risk of CC than in the general population and should result in more intensive screening and surveillance.Inflammatory Bowel Disease: Women with inflammatory bowel disease being treated with immunosuppressive drugs are at greater risk of cervical neoplasia and cancer than the general population and guidelines for HIV-infected women are a reasonable approach for screening and surveillance. Those women with inflammatory bowel disease not on immunosuppressive therapy are not at an increased risk and should follow screening guidelines for the general population.Systemic Lupus Erythematosus and Rheumatoid Arthritis: All women with systemic lupus erythematosus, whether on immunosuppressant therapy or not and those women with RA on immunosuppressant therapy have a greater risk of cervical neoplasia and cancer than the general population and should follow CC screening guidelines for HIV-infected women. Women with RA not on immunosuppressant therapy should follow CC screening guidelines for the general population.Type 1 Diabetes Mellitus: Because of a lack of evidence of increased risk of cervical neoplasia and cancer among women with type 1 DM, these women should follow the screening guidelines for the general population.
30328549 Compound GDC, an Isocoumarin Glycoside, Protects against LPS-Induced Inflammation and Pote 2019 Apr Compound 3R-(4'-hydroxyl-3'-O-β-D-glucopyranosyl phenyl)-dihydro isocoumarin (GDC) is a natural isocoumarin, recently isolated from the stems of H. paniculiflorum. However, we know little about the effects of GDC on rheumatoid arthritis (RA). This study aims to investigate the protective effects and potential mechanisms of GDC against LPS-induced inflammation in vitro. Fibroblast-like synoviocytes (FLSs) obtained from synovial tissue of rats were induced by lipopolysaccharide (LPS) and treated with GDC. Cell viability was determined by mitochondrial-respiration-dependent3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. Secretion of various inflammatory mediators was analyzed by ELISA and RayBio® Rat Cytokine Antibody Array. Potential mechanisms that are associated with anti-inflammatory effect were examined by Western blot. Results showed that GDC significantly inhibited the production of tumor necrosis factor alpha (TNF-α) and interleukin- (IL-) 6 induced by LPS. GDC also reduced the expression of inducible nitric oxide synthase (iNOS), TNF-α, IL-6, and IL-1β, as well as proinflammatory cytokines such as activin A, ciliary neurotrophic factor (CNTF), fractalkine, IFN-γ, IL-4, and TIMP-1. Moreover, GDC inhibited LPS-induced phosphorylation of extracellular regulated protein kinases (ERK1/2), p38 mitogen-activated protein kinases (p38), c-Jun N-terminal kinase (JNK), and IκB. And GDC also blocked NF-κBp65 nuclear translocation. All the results suggested that the protective effects of GDC against LPS-induced inflammation in vitro may be related with NF-κB and JNK signaling pathway.