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ID PMID Title PublicationDate abstract
32344736 Enigmatic Histamine Receptor H(4) for Potential Treatment of Multiple Inflammatory, Autoim 2020 Apr 24 The histamine H(4) receptor, belonging to the family of G-protein coupled receptors, is an increasingly attractive drug target. It plays an indispensable role in many cellular pathways, and numerous H(4)R ligands are being studied for the treatment of several inflammatory, allergic, and autoimmune disorders, including pulmonary fibrosis. Activation of H(4)R is involved in cytokine production and mediates mast cell activation and eosinophil chemotaxis. The importance of this receptor has also been shown in inflammatory models: peritonitis, respiratory tract inflammation, colitis, osteoarthritis, and rheumatoid arthritis. Recent studies suggest that H(4)R acts as a modulator in cancer, neuropathic pain, vestibular disorders, and type-2 diabetes, however, its role is still not fully understood.
33258019 [Prospective monitoring of a university rheumatology outpatient clinic throughout the fir 2021 Jun BACKGROUND: In March 2020 the SARS-CoV‑2 pandemic disseminated initially especially in Bavaria. At that time data on patients with rheumatic diseases and immunomodulatory treatment was lacking. OBJECTIVE: The aim was to analyze the influence of the SARS-CoV‑2 pandemic on the clinical treatment strategy. MATERIAL AND METHODS: Between 16 March and 31 July 2020 all patients who consecutively presented at the rheumatology outpatient clinic of the Klinikum rechts der Isar of the Technical University of Munich were included in the study. Individual treatment adjustments were based on clinical judgment and the recommendations for action of the German Society for Rheumatology (DGRh). RESULTS: A total of 322 patients were included. The most frequent diagnosis was rheumatoid arthritis with 17%, ANCA-associated vasculitis (AAV) with 14% and SLE with 12%. Of the patients 262 were on DMARD treatment and 77 received oral glucocorticoids. There were 5 cases of suspected SARS-CoV‑2 infection; however, no patient verifiably became ill due to COVID-19. In 40 patients, treatment adjustments were done due to the pandemic, whereby 3 patients developed a flare of the underlying disease. In retrospect, treatment de-escalation occurred most frequently in AAV, IgG4-related disease, immunosuppressive treatment with rituximab and the simultaneous presence of malignant diseases. CONCLUSION: The total lack of confirmed SARS-CoV‑2 infections in an otherwise strongly affected region could indicate that the infection risk for SARS-CoV‑2 is not substantially increased for patients with inflammatory rheumatic diseases. A continuation of most immunosuppressive medications therefore seems reasonable during the ongoing pandemic.
33181479 Syntheses and anti-HIV and human cluster of differentiation 4 (CD4) down-modulating potenc 2020 Dec 15 CADA compounds selectively down-modulate human cell-surface CD4 protein and are of interest as HIV entry inhibitors and as drugs for asthma, rheumatoid arthritis, diabetes and some cancers. Postulating that fusing a pyridine ring bearing hydrophobic substituents into the macrocyclic scaffold of CADA compounds may lead to potent compounds with improved properties, 17 macrocycles were synthesized, 14 with 12-membered rings having an isobutylene head group, two arenesulfonyl side arms, and fused pyridine rings bearing a para substituent. The analogs display a wide range of CD4 down-modulating and anti-HIV potencies, including some with greater potency than CADA, proving that a highly basic nitrogen atom in the 12-membered ring is not required for potency and that hydrophobic substituents enhance potency of pyridine-fused CADA compounds. Cytotoxicities of the new compounds compared favorably with those of CADA, showing that incorporation of a pyridine ring into the macrocyclic scaffold can produce selective compounds for potently down-modulating proteins of medicinal interest.
32635226 Identification of Novel Molecular Markers of Human Th17 Cells. 2020 Jul 3 Th17 cells are important players in host defense against pathogens such as Staphylococcus aureus, Candida albicans, and Bacillus anthracis. Th17 cell-mediated inflammation, under certain conditions in which balance in the immune system is disrupted, is the underlying pathogenic mechanism of certain autoimmune disorders, e.g., rheumatoid arthritis, Graves' disease, multiple sclerosis, and psoriasis. In the present study, using transcriptomic profiling, we selected genes and analyzed the expression of these genes to find potential novel markers of Th17 lymphocytes. We found that APOD (apolipoprotein D); C1QL1 (complement component 1, Q subcomponent-like protein 1); and CTSL (cathepsin L) are expressed at significantly higher mRNA and protein levels in Th17 cells than in the Th1, Th2, and Treg subtypes. Interestingly, these genes and the proteins they encode are well associated with the function of Th17 cells, as these cells produce inflammation, which is linked with atherosclerosis and angiogenesis. Furthermore, we found that high expression of these genes in Th17 cells is associated with the acetylation of H2BK12 within their promoters. Thus, our results provide new information regarding this cell type. Based on these results, we also hope to better identify pathological conditions of clinical significance caused by Th17 cells.
32531188 The effect of astaxanthin on inflammation in hyperosmolarity of experimental dry eye model 2020 Aug Hyperosmolarity is pro-inflammatory stress to the ocular surface epithelium associated with dry eye disease (DED). Astaxanthin (AST) is a kind of carotene, which exists in seafood and plays important roles in the amelioration of inflammatory diseases like arteriosclerosis, inflammatory bowel disease, sepsis, rheumatoid arthritis, gastric inflammation, brain inflammatory diseases. The aim of this study was to characterize the protective effect and potential mechanism of AST on DED in vitro and in vivo. Mouse models and human corneal epithelial cell (HCEC) cultures were exposed to hyperosmotic saline solution (HOSS) in in vitro and in vivo experiments, respectively. Experimental subjects were first pretreated with AST, and then the effect of the compound was assessed with clinical evaluation, real-time PCR (RT-PCR), western blot and immunofluorescent staining. We further investigated the possible mechanism of AST in DED by pre-treating with phosphoinositide 3-kinase inhibitor (LY294002). The addition of AST significantly reduced the expression of High-mobility group box 1 (HMGB1), as well as significantly inhibited the increases of TNF-α, IL-1β in a dose-dependent manner, but promoted the expression of phospho-Akt (p-Akt). BALB/c mice in DE group pretreated with AST showed significantly decreased corneal fluorescein staining scores. Moreover, pretreatment with LY294002 could eliminate the effects of AST preconditioning on the decrease of HMGB1. Our study provides evidence that AST could ameliorate DED which may be related to the inhibition of HMGB1, TNF-α, IL-1β, while PI3K/Akt signaling pathway may be involved in the expression of HMGB1 and the protective effect of AST preconditioning.
32521607 Beyond Macrophages and T Cells: B Cells and Immunoglobulins Determine the Fate of the Athe 2020 Jun 8 Atherosclerosis (AS) leading to myocardial infarction and stroke remains worldwide the main cause for mortality. Vulnerable atherosclerotic plaques are responsible for these life-threatening clinical endpoints. Atherosclerosis is a chronic, complex, inflammatory disease with interactions between metabolic dysfunction, dyslipidemia, disturbed microbiome, infectious triggers, vascular, and immune cells. Undoubtedly, the immune response is a most important piece of the pathological puzzle in AS. Although macrophages and T cells have been the focus of research in recent years, B cells producing antibodies and regulating T and natural killer (NKT) cell activation are more important than formerly thought. New results show that the B cells exert a prominent role with atherogenic and protective facets mediated by distinct B cell subsets and different immunoglobulin effects. These new insights come, amongst others, from observations of the effects of innovative B cell targeted therapies in autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). These diseases associate with AS, and the beneficial side effects of B cell subset depleting (modifying) therapies on atherosclerotic concomitant disease, have been observed. Moreover, the CANTOS study (NCT01327846) showed impressive results of immune-mediated inflammation as a new promising target of action for the fight against atherosclerotic endpoints. This review will reflect the putative role of B cells in AS in an attempt to connect observations from animal models with the small spectrum of the thus far available human data. We will also discuss the clinical therapeutic potency of B cell modulations on the process of AS.
32498083 TNFα and Reactive Oxygen Signaling in Vascular Smooth Muscle Cells in Hypertension and At 2020 Oct 21 Hypertension and atherosclerosis, the predecessors of stroke and myocardial infarction, are chronic vascular inflammatory reactions. Tumor necrosis factor alpha (TNFα), the "master" proinflammatory cytokine, contributes to both the initiation and maintenance of vascular inflammation. TNFα induces reactive oxygen species (ROS) production which drives the redox reactions that constitute "ROS signaling." However, these ROS may also cause oxidative stress which contributes to vascular dysfunction. Mice lacking TNFα or its receptors are protected against both acute and chronic cardiovascular injury. Humans suffering from TNFα-driven inflammatory conditions such as rheumatoid arthritis and psoriasis are at increased cardiovascular risk. When treated with highly specific biologic agents that target TNFα signaling (Etanercept, etc.) they display marked reductions in that risk. The ability of TNFα to induce endothelial dysfunction, often the first step in a progression toward serious vasculopathy, is well recognized and has been reviewed elsewhere. However, TNFα also has profound effects on vascular smooth muscle cells (VSMCs) including a fundamental change from a contractile to a secretory phenotype. This "phenotypic switching" promotes proliferation and production of extracellular matrix proteins which are associated with medial hypertrophy. Additionally, it promotes lipid storage and enhanced motility, changes that support the contribution of VSMCs to neointima and atherosclerotic plaque formation. This review focuses on the role of TNFα in driving the inflammatory changes in VSMC biology that contribute to cardiovascular disease. Special attention is given to the mechanisms by which TNFα promotes ROS production at specific subcellular locations, and the contribution of these ROS to TNFα signaling.
32021394 The Pain Paradox of Borderline Personality and Total Knee Arthroplasty (TKA): Recruiting B 2020 BACKGROUND: TKA is a common treatment for arthropathies of the knee; however, its results are compromised by psychosocial equivalents of pain: prior research suggests persistent pain and dysfunction after TKA not only to be linked to psychological symptoms such as depression or anxiety but also to psychodynamic determinants of borderline personality, namely borderline personality organization. Osteoarthritis (OA) and Rheumatoid arthritis (RA), the main indications for TKA, are themselves linked to personality factors and disorders, e.g. borderline. The present study investigates the influence of borderline personality organization (BPO) on the outcomes of TKA one year postoperatively. METHODS: We studied 144 patients scheduled for primary TKA before and after the operation using the IPO-16 and the WOMAC for the assessment of knee pain and function. RESULTS: Non-parametric correlations were found between primitive defenses and knee-pain, not function. Linear regression showed prediction of knee pain and knee function by the preoperative WOMAC scores (p<0.01), whereas there was additional prediction of knee-pain by gender (p=0.03) and primitive defenses (p=0.04). DISCUSSION: The results suggest a psychodynamic mechanism of maladaptation after TKA apparently representing the bodily manifestations of fundamental psychic defenses.
31694754 Algorithm for antinuclear antibodies in subjects with clinical suspicion of autoimmune dis 2020 Jul OBJECTIVES: Antinuclear antibodies (ANA) are fundamental in the diagnosis of systemic autoimmune rheumatic diseases (SARDs). Different assays for ANA screening are available, such as indirect immunofluorescence (IIF) on HEp-2 cells and Multiplex fluorescent immunoassay (MFI). This study aimed to clarify the importance of ANA detected only by IIF in the future development of SARDs and to recommend a laboratory algorithm that integrates the available diagnostic approaches to optimise the diagnosis of ANA IIF+MFI- subjects. METHODS: A total of 9,291 subjects with clinical suspicion of SARDs were evaluated for ANA by IIF and MFI. One hundred and ninety-eight subjects (2.1%) were ANA IIF+MFI-, who were followed up for 2 years. ANA were evaluated using IIF on HEp-2 cells and MFI on the BioPlex 2200. RESULTS: The ANA IIF+MFI- cohort included 106 subjects with SARDs, 26 subject with other autoimmune diseases (not-SARDs) and 66 subjects with minor symptoms or ANA requested in check-ups. Only 94 subjects underwent re-evaluation. After a 2-year follow-up, most re-evaluated subjects (51 patients) became ANA negative for both assays (mainly rheumatoid arthritis, polymyalgia and inflammatory bowel disease patients) and 35 subjects remained ANA IIF+MFI- (principally systemic sclerosis and systemic lupus erythematosus patients). A new algorithm for ANA evaluation was suggested. CONCLUSIONS: According to the proposed algorithm, ANA IIF+MFI- subjects should be screened by an alternative solid-phase assay such as line-immunoassay or ELISA.
31663542 Tannic acid-based nanogel as an efficient anti-inflammatory agent. 2020 Feb 21 Biologically produced reactive oxygen species (ROS) are important signaling molecules in the human body. Despite their importance under normal conditions, abnormal overproduction of ROS under unbalanced or irregular homeostasis can cause severe inflammatory diseases. Various antioxidants have been developed in the biomedical field to resolve high levels of ROS; however, high doses of natural antioxidants such as polyphenol can induce side effects on health. Further, synthetic antioxidants are still controversial in regards to their safety and their complicated synthesis. Inspired from our previous work, a nitric oxide-scavenging nanogel designed for treating rheumatoid arthritis, we report herein a biocompatible tannic acid (TA)-based nanogel as an effective ROS scavenger. A polymeric phenylboronic acid-tannic acid nanogel (PTNG) was prepared by simply mixing through to the formation of phenylboronic ester bonds between polymeric phenylboronate and TA. We focused on the reaction of phenylboronic ester with H(2)O(2), which readily consumes H(2)O(2) molecules, and applied it as an antioxidant. In addition, TA is a well-known antioxidant, specifically a free radical scavenger; thus, we expected combinatory ROS scavenging effects for PTNG. Various ROS scavenging assays revealed the significant antioxidant effects of PTNG. Under an induced inflammation model in vitro, our PTNG showed high biocompatibility as well as strong anti-inflammatory effects. Furthermore, in the zymosan-induced peritonitis mouse model, a representative acute inflammation model in vivo, PTNG reduced significant neutrophil recruitment and pro-inflammatory cytokines, indicating successful alleviation of inflammation. On the basis of these results, we suggest that PTNG has great potential as an antioxidant and should find application in the treatment of further ROS-overproducing inflammatory diseases.
33348582 An Ultrahigh Sensitive Paper-Based Pressure Sensor with Intelligent Thermotherapy for Skin 2020 Dec 17 Porous microstructure pressure sensors that are highly sensitive, reliable, low-cost, and environment-friendly have aroused wide attention in intelligent biomedical diagnostics, human-machine interactions, and soft robots. Here, an all-tissue-based piezoresistive pressure sensor with ultrahigh sensitivity and reliability based on the bottom interdigitated tissue electrode and the top bridge of a microporous tissue/carbon nanotube composite was proposed. Such pressure sensors exhibited ultrahigh sensitivity (≈1911.4 kPa(-1)), fast response time (<5 ms), low fatigue of over 2000 loading/unloading cycles, and robust environmental degradability. These enabled sensors can not only monitor the critical physiological signals of the human body but also realize electrothermal conversion at a specific voltage, which enhances the possibility of creating wearable thermotherapy electronics for protecting against rheumatoid arthritis and cervical spondylosis. Furthermore, the sensor successfully transmitted wireless signals to smartphones via Bluetooth, indicating its potential as reliable skin-integrated electronics. This work provides a highly feasible strategy for promoting high-performance wearable thermotherapy electronics for the next-generation artificial skin.
33343914 The experience of living with a chronic disease in pediatrics from the mothers' narratives 2020 Jul The Clinical Interview on the Sense of Grip on Chronic Disease has been administered to 68 mothers of children affected by Hereditary Angioedema (C1-Inh HAE), Type 1 Diabetes (T1D), Juvenile Rheumatoid Arthritis (JRA). The objectives are to detect general features of the experience of parenting children with chronic illness as well as the specificities of this experience related to the different conditions. Four Profiles of Sense of Grip were identified: Adempitive, Controlling, Reactive, Dynamic. The Sense of Grip Interview is an effective clinical tool for understanding the characteristics of the disease in daily life, which can help clinicians to encourage family adjustment to disease.
33317935 The Effects of Psychological Interventions on Diabetic Peripheral Neuropathy: A Systematic 2021 Jun BACKGROUND: Psychological interventions are effective at ameliorating the experience of pain in conditions such as rheumatoid arthritis and chronic back pain. However, their effect on diabetic peripheral neuropathy (DPN) pain has yet to be established AIM: To assess the effectiveness of psychological interventions on pain and related outcomes in adults with DPN. DESIGN: Systematic review. SETTINGS: Community, hospital in-patient and out-patient. PARTICIPANTS/SUBJECTS: Adults with diabetic peripheral neuropathy. METHODS: Medline, Embase, PsychInfo, and CINAHL databases together with grey literature and trial registers were searched. A meta-analysis and narrative synthesis of included studies were undertaken. RESULTS: Nine studies were selected from 1610 citations. At short-term follow-up psychological therapies showed a large effect on pain severity (SMD = -0.94, 95%CI [-1.50, -0.37], p = .001), a small effect on pain interference (SMD = -0.39, 95%CI [-0.73, -0.05], p = .02), and a moderate effect on depressive symptoms (SMD = -0.58, 95%CI [-0.95, -0.21], p = .002). Quality of life significantly improved in experimental subjects, (MD = -2.35, 95%CI [-3.99, -0.71], p = .005). At medium-term follow-up there was a large effect on pain severity (SMD = -1.26, 95%CI [-1.76, -0.77], p < .00001) and on pain interference (SMD = -0.91, 95%CI [-1.61, -0.21], p = .01) and a moderate effect on depressive symptoms (SMD = -0.76, 95%CI [-1.48, -0.05], p = .04). At long-term follow-up, improvements in pain interference, mood, and self-care behaviors were reported. CONCLUSIONS: These findings demonstrate that the relationship between pain and perceived control identified in other groups who experience chronic pain may also be replicated in the DPN population. This is an important outcome that can guide further research and associated service developments.
33209380 Type 2 diabetes is associated with failure of non-operative treatment for sternoclavicular 2020 Oct BACKGROUND: A standardized treatment algorithm for sternoclavicular joint infection management is lacking in the literature. While major risk factors for sternoclavicular joint infection, including immunosuppression, rheumatoid arthritis, type 2 diabetes, indwelling catheters, and intravenous drug use have been identified, clear association with treatment outcome has not been established. As our safety net hospital treats a patient population with high incidence of intravenous drug use, we sought to identify risk factors associated with failure of non-operative management of sternoclavicular joint infection. METHODS: We conducted a retrospective cohort study, reviewing charts of patients diagnosed with sternoclavicular joint infection between January 2001 and December 2017 to collect demographic information as well as clinical risk factors and treatment patterns. A chi-square test was performed to determine any association between clinical variables and management, as well as relation to treatment outcome. RESULTS: The study cohort consisted of 35 patients with diagnosis of sternoclavicular joint infection and complete follow-up. Intravenous drug use was prevalent, seen in 45.6% (16/35) of subjects, though there was no association with failure of non-operative management (P=0.50). Operative management was the initial treatment for 25.7% (9/35) of subjects and was associated with abscess on presentation (P=0.03). Failure of non-operative management was seen in 26.9% (7/26). Type 2 diabetes was associated with failed initial non-operative management, present in 42.9% (3/7) of patients (P=0.03) experiencing failure. CONCLUSIONS: This study constitutes the largest series of sternoclavicular joint infection with intravenous drug use. While intravenous drug use was not associated with failure of non-operative management, we observed that type 2 diabetes is associated with failure of non-operative management and could be considered in determining management of sternoclavicular joint infection patients.
33127561 A review of the traditional uses, phytochemistry, pharmacology and quality control of the 2021 Nov 15 ETHNOPHARMACOLOGICAL RELEVANCE: Persicaria orientalis (L.) Spach (syn. Polygonum orientale L.) is a potent medicinal herb widely used in many ethnic groups, such as the Han, Tibetan, Mongolian, Zhuang, Miao, Yao, Yi, Korean, Dong, Hani, Lisu, Naxi and She people in China. Aims of the review: This article aims to present the research progress on P. orientalis, which is helpful to understand the multi-purpose of Chinese herbal medicine (CHM) and prompt its medicinal value. MATERIALS AND METHODS: Information on P. orientalis was obtained from published materials, including monographs on medicinal plants, ancient and modern recorded classics, pharmacopoeias and electronic databases, such as Web of Science, Science Direct, Springer, AGRIS, Europe PMC, SCI Finder, PubMed, CNKI, Wanfang DATA, J-STAGE, classical treatises of modern pharmaceutical science and Flora Reipublicae Popularis Sinicae (FRPS). RESULTS: Clinical applications of traditional medicine of P. orientalis have therapeutic effects for dispelling rheumatism, promoting digestion, aiding diuresis and activating blood circulation. A total of 153 chemical constituents have been identified from P. orientalis, including flavonoids, carboxylic acids, phenolic acids, amino acids, hydrocarbons, chromones, lignans, volatile oils, amides and other components. Its active ingredients have a wide range of pharmacological effects, such as anti-oxidative, anti-aging, anti-inflammation, analgesia, anti-myocardial ischemia, anti-abortion, and anti-rheumatoid arthritis, as well as protective effects on cerebral ischemia and liver injury. By establishing stable detection methods, the quality standards of P. orientalis medicinal materials have been guaranteed, such as determination of the iconic components, harvesting periods and optimization of specific components extraction processes. CONCLUSIONS: P. orientalis has different pharmacological activities based on the diversity of chemical constituents. However, the existing reports mainly focus on the extracts, and these studies on its corresponding compounds are not clear enough. The information suggests that P. orientalis has good potential medicinal value, and more attention should be paid to further explore its bioactive components.
33091150 Association between atopic dermatitis and autoimmune diseases: a population-based case-con 2021 Aug BACKGROUND: Atopic dermatitis (AD) is a common chronic skin disorder and is well known to be associated with other atopic conditions. There is increasing evidence for an association also with nonatopic conditions, including autoimmune diseases, but data are limited about several autoimmune diagnoses. OBJECTIVES: To investigate the association between AD and autoimmune diseases. METHODS: This case-control study used Swedish national healthcare registers. The source population comprised the entire Swedish population aged ≥ 15 years from 1968 to 2016. Cases, including all those with an inpatient diagnosis of AD (from 1968) and/or a specialist outpatient diagnosis of AD (from 2001), were matched by sex and age to healthy controls (104 832 cases of AD, 1 022 435 controls). RESULTS: AD was significantly associated with one or more autoimmune diseases compared with controls - adjusted odds ratio (aOR) 1·97, 95% confidence interval (CI) 1·93-2·01 - and this association was significantly stronger in the presence of multiple autoimmune diseases compared with only one. The association was strongest for autoimmune disorders involving the skin (aOR 3·10, 95% CI 3·02-3·18), the gastrointestinal tract (aOR 1·75, 95% CI 1·69-1·82) or connective tissue (aOR 1·50, 95% CI 1·42-1·58). In the overall analysis, men with AD had a stronger association with rheumatoid arthritis and coeliac disease than did women with AD. In subanalyses, the findings remained stable in multivariable analyses after adjustment for smoking and parental autoimmune disease. CONCLUSIONS: This large population-based study indicates significant autoimmune comorbidity of adults with AD, especially between AD and autoimmune dermatological, gastrointestinal and rheumatological diseases. Having multiple autoimmune diseases resulted in a stronger association with AD than having only one autoimmune disease.
33023542 Does the IOFix implant improve union rates? 2020 Oct 6 BACKGROUND: First metatarso-phalangeal joint fusion is the current gold standard for severe hallux rigidus. Data regarding the union rate and the re-operation rate when IOFix (an Intra-osseous fixation device, Extremity medical, New Jersey, USA) is used for hallux rigidus fusion is limited but promising. The aim of this study was to review our outcomes with the IOFix implant. METHODS: We have conducted a retrospective chart review, following the approval of the hospital IRB committee. Exclusion criteria included bilateral operations on the same patient, multiple surgeries, charcot foot or other structural foot abnormalities (except hallux valgus), rheumatoid arthritis and a recent foot trauma. We collected demographic data, physical examination documentation, functional score evaluations (AOFAS), and Plain radiographic studies. RESULTS: Thirty patients were included in the study. The mean age was 60.36 ± 9.12 (range 36 to 77) years, 18 (60%) female patients and 12 (40%) male. Fourteen (53.33%) were left side pathologies. The average follow up period was 36.2 ± 12.31 (range 12 to 54) months. Union was obtained in 28 (93.33%) patients, of whom none had requested a hardware removal due to a prominent hardware during a minimum of 2 year follow up period. The mean postoperative AOFAS score was 80.5 ± 10.87 (range 35 to 90). A more stringent inclusion criteria and fusion definitions would have led to an exclusion of two more patients and a dropout of two patients from the "fused" group, which would have led to a fusion rate of 85.71%. CONCLUSIONS: This is the largest series of hallux rigidus patients that were operated with an IOFix device. The rates of fusion and hardware removal in MTPJ1 arthrodesis performed with an IOFix implant were found to be similar at most when compared to previously described rates that were obtained with other cheaper and more simple fixation devices. LEVEL OF EVIDENCE: 4.
32881511 Epitope Identification and Affinity Determination of an Inhibiting Human Antibody to Inter 2020 Jan 2 The polypeptide chemokine Interleukin-8 (IL8) plays a crucial role in inflammatory processes in humans. IL8 is involved in chronic inflammatory lung diseases, rheumatoid arthritis, and cancer. Previous studies have shown that the interaction of IL8 with its natural receptors CXCR1 and CXCR2 is critical in these diseases. Antibodies have been used to study the receptor interaction of IL8; however, the binding epitopes were hitherto unknown. Identification of the antibody epitope(s) could lead to a molecular understanding of the inhibiting mechanism and development of improved inhibitors. Here, we report the epitope identification and the affinity characterization of IL8 to a monoclonal anti-human IL8 antibody inhibiting the receptor binding by a combination of surface plasmon resonance (SPR) biosensor analysis and MALDI-mass spectrometry. SPR determination of IL8 with the immobilized antibody revealed high affinity (K(D), 82.2 nM). Epitope identification of IL-8 was obtained by proteolytic epitope-extraction mass spectrometry of the peptide fragments upon high pressure trypsin digestion, using an affinity microcolumn with immobilized anti-IL-8 antibody. MALDI-MS of the affinity-bound peptide elution fraction revealed an assembled (discontinuous) epitope comprising two specific peptides, IL8 [12-20] and IL8 [55-60]. Identical epitope peptides were identified by direct MALDI-MS of the eluted epitope fraction from the immobilized anti-IL8 antibody on the SPR chip. SPR determination of the synthetic epitope peptides provided high affinities confirming their binding specificity. The previously reported finding that the anti-Il8 antibody is inhibiting the IL8-CXCR1 interaction is well consistent with the overlapping region of epitope interactions identified in the present study.
32763298 Molecular effects and retinopathy induced by hydroxychloroquine during SARS-CoV-2 therapy: 2020 Nov 5 Antimalaria drugs such as chloroquine (CQ) and hydroxychloroquine (HCQ) have been administered to several inflammatory diseases including rheumatoid arthritis and systemic lupus erythematosus, and infectious diseases such as acquired immune deficiency syndrome and influenza. Recently, several patients infected with novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were given HCQ, and showed a discrepant response. HCQ inhibits SARS-CoV-2 cell entry, and inflammatory cascade by interfering with lysosomal and endosomal activities, and autophagy, impeding virus-membrane fusion, and inhibiting cytokine production resulted from inflammatory pathways activation. Despite ongoing administration of HCQ in a wide spectrum of disorders, there are some reports about several side effects, especially retinopathy in some patients treated with HCQ. Cytochrome P450 (CYP450) and its isoforms are the main metabolizers of HCQ and CQ. Pharmacokinetic properties of CYP enzymes are influenced by CYP polymorphism, non-coding RNAs, and epigenetic mechanisms such as DNA methylation, and histone acetylation. Accumulating evidence about side effects of HCQ in some patients raise the possibility that different response of patients to HCQ might be due to difference in their genome. Therefore, CYP450 genotyping especially for CYP2D6 might be helpful to refine HCQ dosage. Also, regular control of retina should be considered for patients under HCQ treatment. The major focus of the present review is to discuss about the pharmacokinetic and pharmacodynamic properties of CQ and HCQ that may be influenced by epigenetic mechanisms, and consequently cause several side effects especially retinopathy during SARS-CoV-2 therapy.
32634079 The Role of Chloroquine and Hydroxychloroquine in Immune Regulation and Diseases. 2020 Chloroquine (CQ) and hydroxychloroquine (HCQ) are derivatives of the heterocyclic aromatic compound quinoline. These economical compounds have been used as antimalarial agents for many years. Currently, they are used as monotherapy or in conjunction with other therapies for the treatment of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS) and antiphospholipid antibody syndrome (APS). Based on its effects on the modulation of the autophagy process, various clinical studies suggest that CQ and HCQ could be used in combination with other chemotherapeutics for the treatment of various types of cancer. Furthermore, the antiviral effects showed against Zika, Chikungunya, and HIV are due to the annulation of endosomal/lysosomal acidification. Recently, CQ and HCQ were approved for the U.S. Food and Drug Administration (FDA) for the treatment of infected patients with the coronavirus SARSCoV- 2, causing the disease originated in December 2019, namely COVID-2019. Several mechanisms have been proposed to explain the pharmacological effects of these drugs: 1) disruption of lysosomal and endosomal pH, 2) inhibition of protein secretion/expression, 3) inhibition of antigen presentation, 4) decrease of proinflammatory cytokines, 5) inhibition of autophagy, 6) induction of apoptosis and 7) inhibition of ion channels activation. Thus, evidence has shown that these structures are leading molecules that can be modified or combined with other therapeutic agents. In this review, we will discuss the most recent findings in the mechanisms of action of CQ and HCQ in the immune system, and the use of these antimalarial drugs on diseases.