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ID PMID Title PublicationDate abstract
32707043 Subchronic administration of auranofin reduced amyloid-β plaque pathology in a transgenic 2020 Nov 1 Alzheimer's disease (AD) is the most common cause of dementia. Neuropathological processes, including the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles, and neuroinflammation, lead to cognitive impairment at middle and eventually later stages of AD progression. Over the last decade, focused efforts have explored repurposed drug approaches for AD pathophysiological mechanisms. Recently, auranofin, an anti-inflammatory drug, was shown to have therapeutic potential in a number of diseases in addition to rheumatoid arthritis. Surprisingly, no data regarding the effects of auranofin on cognitive deficits in AD mice or the influence of auranofin on Aβ pathology and neuroinflammatory processes are available. In the present study, we used 14-month-old transgenic male APP(NL-G-F/NL-G-F) mice to assess the effects of subchronic administration of auranofin at low doses (1 and 5 mg/kg, intraperitoneal) on spatial memory, Aβ pathology and the expression of cortical and hippocampal proteins (glial fibrillary acidic protein (GFAP), ionized calcium binding adaptor molecule-1 (Iba-1)) and proteins related to synaptic plasticity (glutamic acid decarboxylase 67 (GAD67), homer proteins homologue-1 (Homer-1)). The data demonstrated that auranofin significantly decreased Aβ deposition in the hippocampus and the number of Aβ plaques in the cingulate cortex, but it did not have memory-enhancing effects or induce changes in the expression of the studied proteins. Our current results highlight the importance of considering further pre-clinical research to investigate the possible beneficial effects of auranofin on the other pathological aspects of AD.
32509417 The effects of B cell depletion on immune related adverse events associated with immune ch 2020 This letter describes the potential effect of B cell depletion on immune related adverse events associated with immune checkpoint inhibition. B cell depleting agents such as rituximab reduce B cell to plasma cell differentiation and antibody production. This treatment strategy is used in several immune mediated inflammatory diseases such as rheumatoid arthritis and small vessel vasculitis. The immune related adverse events associated with immune checkpoint inhibition resemble immune mediated inflammatory diseases. Here, we report a lower incidence of hypothyroidism in a trial of combined B cell depletion and immune checkpoint inhibitor treatment compared with studies of immune checkpoint inhibitor monotherapy. This letter aims to increase awareness of the immune related adverse events associated with immune checkpoint inhibition in future clinical trials of immune checkpoint inhibition together with B cell depletion (primarily trials of B cell lymphomas). Hopefully, observations from these clinical trials can guide future treatment strategies to treat or prevent immune related adverse events associated with immune checkpoint inhibition.
32401672 Lung-resident mesenchymal stromal cells are tissue-specific regulators of lung homeostasis 2020 Aug 1 Until recently, data supporting the tissue-resident status of mesenchymal stromal cells (MSC) has been ambiguous since their discovery in the 1950-60s. These progenitor cells were first discovered as bone marrow-derived adult multipotent cells and believed to migrate to sites of injury, opposing the notion that they are residents of all tissue types. In recent years, however, it has been demonstrated that MSC can be found in all tissues and MSC from different tissues represent distinct populations with differential protein expression unique to each tissue type. Importantly, these cells are efficient mediators of tissue repair, regeneration, and prove to be targets for therapeutics, demonstrated by clinical trials (phase 1-4) for MSC-derived therapies for diseases like graft-versus-host-disease, multiple sclerosis, rheumatoid arthritis, and Crohn's disease. The tissue-resident status of MSC found in the lung is a key feature of their importance in the context of disease and injuries of the respiratory system, since these cells could be instrumental to providing more specific and targeted therapies. Currently, bone marrow-derived MSC have been established in the treatment of disease, including diseases of the lung. However, with lung-resident MSC representing a unique population with a different phenotypic and gene expression pattern than MSC derived from other tissues, their role in remediating lung inflammation and injury could provide enhanced efficacy over bone marrow-derived MSC methods. Through this review, lung-resident MSC will be characterized, using previously published data, by surface markers, gene expression patterns, and compared with bone-marrow MSC to highlight similarities and, importantly, differences in these cell types.
32361977 Safety, Tolerability and Pharmacokinetics of Vidofludimus calcium (IMU-838) After Single a 2020 Oct BACKGROUND AND OBJECTIVE: Vidofludimus is a potent and selective inhibitor of human mitochondrial enzyme dihydroorotate dehydrogenase (DHODH). The clinical efficacy and safety profile of vidofludimus has been analyzed in patients suffering from rheumatoid arthritis and Crohn's disease and ulcerative colitis. In previous sudies, hematuria at higher doses occurred in close temporal relationship to vidofludimus administration and appeared to be dose related. The present report describes the results from two phase 1 studies conducted in healthy male subjects to investigate the safety, tolerability and pharmacokinetics after single and multiple ascending (SAD and MAD) oral doses of IMU-838 (vidofludimus calcium, tablets containing a specific polymorph). The effect of food on the pharmacokinetics of IMU-838 was also assessed in the SAD study. METHODS: In the SAD study, 12 subjects received single doses of IMU-838 under fasting (10-40 mg) or fed (10 mg) condition in an open-label, partial parallel group design. In the MAD study, 52 subjects received multiple doses of IMU-838 (30-50 mg) in a double-blind, placebo-controlled, parallel group design. RESULTS: IMU-838 showed dose-proportional pharmacokinetics after single and multiple oral dosing in both SAD and MAD studies. IMU-838 was well absorbed after single daily doses. Food did not impact the pharmacokinetics of IMU-838. The accumulation factor for multiple daily dosing was approximately 2. Steady-state concentrations were reached within about 6-8 days for 30-50 mg groups. The geometric mean plasma half-life of IMU-838 at steady state was approximately 30 h, which supports its use for once-daily dosing regimen. Single and multiple oral doses of IMU-838 were safe and well tolerated. CONCLUSION: Overall, oral IMU-838 was generally well tolerated in SAD and MAD studies in healthy subjects over a wide dose range of 10-50 mg. IMU-838 was well absorbed after single daily doses. IMU-838 showed dose proportional pharmacokinetics after single and multiple oral dosing.
32210952 The Role of Calcium-Calcineurin-NFAT Signaling Pathway in Health and Autoimmune Diseases. 2020 Calcium (Ca(2+)) is an essential signaling molecule that controls a wide range of biological functions. In the immune system, calcium signals play a central role in a variety of cellular functions such as proliferation, differentiation, apoptosis, and numerous gene transcriptions. During an immune response, the engagement of T-cell and B-cell antigen receptors induces a decrease in the intracellular Ca(2+) store and then activates store-operated Ca(2+) entry (SOCE) to raise the intracellular Ca(2+) concentration, which is mediated by the Ca(2+) release-activated Ca(2+) (CRAC) channels. Recently, identification of the two critical regulators of the CRAC channel, stromal interaction molecule (STIM) and Orai1, has broadened our understanding of the regulatory mechanisms of Ca(2+) signaling in lymphocytes. Repetitive or prolonged increase in intracellular Ca(2+) is required for the calcineurin-mediated dephosphorylation of the nuclear factor of an activated T cell (NFAT). Recent data indicate that Ca(2+)-calcineurin-NFAT1 to 4 pathways are dysregulated in autoimmune diseases. Therefore, calcineurin inhibitors, cyclosporine and tacrolimus, have been used for the treatment of such autoimmune diseases as systemic lupus erythematosus and rheumatoid arthritis. Here, we review the role of the Ca(2+)-calcineurin-NFAT signaling pathway in health and diseases, focusing on the STIM and Orai1, and discuss the deregulated calcium-mediated calcineurin-NFAT pathway in autoimmune diseases.
32005854 Evaluation of the effect of GM-CSF blocking on the phenotype and function of human monocyt 2020 Jan 31 Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multipotent cytokine that prompts the proliferation of bone marrow-derived macrophages and granulocytes. In addition to its effects as a growth factor, GM-CSF plays an important role in chronic inflammatory autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Reports have identified monocytes as the primary target of GM-CSF; however, its effect on monocyte activation has been under-estimated. Here, using flow cytometry and ELISA we show that GM-CSF induces an inflammatory profile in human monocytes, which includes an upregulated expression of HLA-DR and CD86 molecules and increased production of TNF-α and IL-1β. Conversely, blockage of endogenous GM-CSF with antibody treatment not only inhibited the inflammatory profile of these cells, but also induced an immunomodulatory one, as shown by increased IL-10 production by monocytes. Further analysis with qPCR, flow cytometry and ELISA experiments revealed that GM-CSF blockage in monocytes stimulated production of the chemokine CXCL-11, which suppressed T cell proliferation. Blockade of CXCL-11 abrogated anti-GM-CSF treatment and induced inflammatory monocytes. Our findings show that anti-GM-CSF treatment induces modulatory monocytes that act in a CXCL-11-dependent manner, a mechanism that can be used in the development of novel approaches to treat chronic inflammatory autoimmune diseases.
31945049 Murphy's law in force: sequential adverse events encountered during the treatment of Pneum 2020 Jan 17 Methotrexate monotherapy is a common management strategy in rheumatoid arthritis (RA). Treatment with immunosuppression can lead to opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). The treatment options for PJP include cotrimoxazole, clindamycin-primaquine and dapsone. Though these drugs are generally well tolerated, they can result in potentially severe adverse effects. Sometimes several undesired events may occur in a single patient, reminding us of Murphy's law. Herein, we report a case which exemplifies this adage. A 50-year-old female developed PJP, while on methotrexate therapy for RA and was treated with cotrimoxazole. The latter resulted in painful peripheral neuropathy, which improved after cotrimoxazole was stopped. Salvage therapy for PJP with primaquine-clindamycin, lead to another serious adverse event, methemoglobinemia. Withdrawing the offending drug resulted in dramatic improvement.
31375267 Cortical hypointensity in T2-weighted gradient-echo sequences in patients with progressive 2020 Jan INTRODUCTION: Progressive multifocal leukoencephalopathy is a demyelinating disease of the central nervous system caused by the reactivation of the JC virus. This opportunistic encephalopathy mainly affects immunodepressed patients with stage III HIV infection, although in recent years it has also been found in association with treatment with immunosuppressors such as natalizumab. MRI plays an important role in both the early diagnosis and follow-up of this disease. Recently, it has been reported that hypointensities in U-fibers and cortex adjacent to white-matter lesions characteristic of the disease can be identified on T2-weighted gradient-echo and susceptibility-weighted sequences in patients with progressive multifocal leukoencephalopathy. OBJECTIVE: We aimed to analyze the presence and usefulness of cortical hypointensity on T2-weighted gradient-echo sequences in relation to the diagnosis of progressive multifocal leukoencephalopathy and to review the literature on the topic. MATERIAL AND METHODS: We analyze three cases of progressive multifocal leukoencephalopathy seen at our center in three patients with immunosuppression of different origins: one with stage III HIV infection, one with multiple sclerosis being treated with natalizumab, and one with rheumatoid arthritis being treated with rituximab. RESULTS: In all three cases MRI showed the cortical hypointensity adjacent to the white-matter lesion in the T2-weighted gradient-echo sequence. In the patient with multiple sclerosis, this sign appeared earlier than the abnormal signal in the white matter. The patient being treated with rituximab was diagnosed postmortem and the pathology findings correlated with the MRI findings. CONCLUSION: The finding of cortical hypointensity on T2-weighted gradient-echo MRI sequences seems to support the diagnosis of progressive multifocal leukoencephalopathy, regardless of the type of immunosuppression, so this finding should routinely assessed in patients suspected of having this disease.
34756393 Biomechanics of the effect of subaxial cervical spine degeneration on atlantoaxial complex 2020 Oct 16 OBJECTIVES: Retro-odontoid pseudotumor (ROP), with no rheumatoid arthritis, atlantoaxial instability, or other primary diseases, is defined as idiopathic retro-odontoid pseudotumor (IROP). Cervical spine degeneration is associated with IROP development. This study aims to evaluate the effect of cervical spine degeneration on the atlantoaxial complex and find the possible biomechanical mechanism of IROP development. METHODS: This study was performed using a three-dimensional (3D) finite element (FE) analysis. A degenerated FE model (FEM) and five operation FEMs (C1-C2 fusion, C0-C2 fusion, C0-C3 fusion, C0-C4 fusion, and C1 posterior arch resection) were established based on a normal 3D FEM of the cervical spine including C0-T1 with the main ligaments and muscles. The parameters, including the C1-C2 range of motions (ROMs) and odontoid-related ligaments' stresses in degenerated and operation FEMs, were obtained and compared with those in normal FEM. RESULTS: Compared to normal FEM, degenerated FEM had reduced C3-C7 ROMs and increased C1-C2 ROMs and odontoid-related ligaments' stresses. After internal fixation, C1-C2 ROMs and most odontoid-related ligaments' stresses were greatly decreased, but with no significant differences among C0-C2, C0-C3, C0-C4, and C1-C2 fusion models. For the C1 posterior arch resection model, C1-C2 ROMs and most odontoid-related ligaments' stresses increased, compared with normal FEM. CONCLUSIONS: Cervical spine degeneration plays an important part in IROP development in biomechanics. Atlantoaxial complex compensates for cervical spine degeneration, with increased C1-C2 ROMs and odontoid-related ligaments' stresses. Atlantoaxial fusion or short segmental occipitocervical fusion can effectively reduce the stress and should be considered in IROP treatment.
33359266 A 13-week subchronic toxicity study of a Dioscorea Rhizome water extract in rats. 2021 Mar Dioscorea Rhizome is widely used as a traditional herbal medicine to treat asthma, diarrhea, cough, bronchitis, spermatorrhea, leukorrhea, and rheumatoid arthritis. This study investigated the potential subchronic toxicity of a D. Rhizome water extract (DRWE) after repeated oral administration at 0, 800, 2000, and 5000 mg/kg/day in rats for 13 weeks. During the study period, clinical signs, mortality, body weight, food consumption, water consumption, urinalysis, ophthalmoscopy, hematology, serum biochemistry, gross pathology, organ weights, and histopathology were examined. The 13-week repeated oral administration of DRWE to rats resulted in an increased incidence of zona glomerulosa hypertrophy and hyperplasia in the adrenal gland at dose levels of ≥2000 mg/kg/day in both sexes. However, these findings are considered as non-adverse adaptive changes because of minimal histological changes in the lesions, which were not accompanied by any corresponding alterations in serum electrolytes and adrenal gland weight. No treatment-related adverse effects on clinical signs, body weight, food and water consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, and organ weights were observed at any dose tested. Under the present experimental conditions, the no-observed-adverse-effect level of the DRWE was considered to be 5000 mg/kg/day in both sexes, and no target organs were identified.
33103382 Reduction in flippase activity contributes to surface presentation of phosphatidylserine i 2020 Dec Mature human erythrocytes circulate in blood for approximately 120 days, and senescent erythrocytes are removed by splenic macrophages. During this process, the cell membranes of senescent erythrocytes express phosphatidylserine, which is recognized as a signal for phagocytosis by macrophages. However, the mechanisms underlying phosphatidylserine exposure in senescent erythrocytes remain unclear. To clarify these mechanisms, we isolated senescent erythrocytes using density gradient centrifugation and applied fluorescence-labelled lipids to investigate the flippase and scramblase activities. Senescent erythrocytes showed a decrease in flippase activity but not scramblase activity. Intracellular ATP and K(+) , the known influential factors on flippase activity, were altered in senescent erythrocytes. Furthermore, quantification by immunoblotting showed that the main flippase molecule in erythrocytes, ATP11C, was partially lost in the senescent cells. Collectively, these results suggest that multiple factors, including altered intracellular substances and reduced ATP11C levels, contribute to decreased flippase activity in senescent erythrocytes in turn to, present phosphatidylserine on their cell membrane. The present study may enable the identification of novel therapeutic approaches for anaemic states, such as those in inflammatory diseases, rheumatoid arthritis, or renal anaemia, resulting from the abnormally shortened lifespan of erythrocytes.
33090621 Anti-inflammatory effects of cordycepin: A review. 2020 Oct 8 Cordycepin is the major bioactive component extracted from Cordyceps militaris. In recent years, cordycepin has received increasing attention owing to its multiple pharmacological activities. This study reviews recent researches on the anti-inflammatory effects and the related activities of cordycepin. The results from our review indicate that cordycepin exerts protective effects against inflammatory injury for many diseases including acute lung injury (ALI), asthma, rheumatoid arthritis, Parkinson's disease (PD), hepatitis, atherosclerosis, and atopic dermatitis. Cordycepin regulates the NF-κB, RIP2/Caspase-1, Akt/GSK-3β/p70S6K, TGF-β/Smads, and Nrf2/HO-1 signaling pathways among others. Several studies focusing on cordycepin derivatives were reviewed and found to down metabolic velocity of cordycepin and increase its bioavailability. Moreover, cordycepin enhanced immunity, inhibited the proliferation of viral RNA, and suppressed cytokine storms, thereby suggesting its potential to treat COVID-19 and other viral infections. From the collected and reviewed information, this article provides the theoretical basis for the clinical applications of cordycepin and discusses the path for future studies focusing on expanding the medicinal use of cordycepin. Taken together, cordycepin and its analogs show great potential as the next new class of anti-inflammatory agents.
32952489 Nicotine Dependence in US Military Veterans: Results from the National Health and Resilien 2020 BACKGROUND: Veterans are a unique population that may be at increased risk of tobacco use disorder and nicotine dependence (ND). We analyzed data from the National Health and Resilience in Veterans Study (NHRVS), a large nationally representative sample of US veterans, in order to more fully understand the prevalence and correlates of lifetime ND in US Veterans. METHODS: Descriptive statistics were conducted to summarize health and functioning/quality of life characteristics among veterans with and without lifetime ND. Hierarchical binary logistic regression analyses were conducted to evaluate the relationship between ND and psychiatric and physical health variables. RESULTS: Compared with veterans without lifetime ND, veterans with lifetime ND were more likely to screen positive for several lifetime psychiatric disorders including current alcohol use disorder (odds ratio [OR] 2.79 [95% confidence interval [CI] 2.23, 3.49]), depression (OR 1.86 [1.38, 2.50]), and PTSD (OR 1.68 [1.14, 2.47]). From a medical standpoint, they were more likely to endorse having kidney disease (OR 4.18 [2.55, 6.86]), heart attack (OR 2.09 [1.51, 2.89]), and rheumatoid arthritis (1.90 [1.20, 3.00]) in addition to other conditions. They scored lower in overall physical functioning and higher in somatization symptoms. CONCLUSIONS: Veterans with lifetime ND in the NHRVS survey were more likely to have psychiatric and medical conditions and lower physical functioning compared with Veterans without lifetime ND. Veterans with lifetime ND may therefore require a comprehensive and integrated approach to care that includes attention to co-morbid illness in addition to drug addiction.
32849554 Circadian Control of Inflammasome Pathways: Implications for Circadian Medicine. 2020 The innate immune system senses "non-self" molecules derived from pathogens (PAMPs) as well as endogenous damage-associated molecular patterns (DAMPs) and promotes sterile inflammation that is necessary for injury resolution, tissue repair/regeneration, and homeostasis. The NOD-, LRR- and pyrin domain containing protein 3 (NLRP3) is an innate immune signaling complex whose assembly and activation can be triggered by various signals ranging from microbial molecules to ATP or the abnormal accumulation of crystals, thus leading to IL-1β and IL-18 maturation and secretion. Deregulation of the NLRP3 signaling cascade is associated with numerous inflammatory and metabolic diseases including rheumatoid arthritis, gout, atherosclerosis or type 2 diabetes. Interestingly, the circadian clock controls numerous inflammatory processes while clock disruption leads to or exacerbates inflammation. Recently, the biological clock was demonstrated to control NLRP3 expression and activation, thereby controlling IL-1β and IL-18 secretion in diverse tissues and immune cells, particularly macrophages. Circadian oscillations of NLRP3 signaling is lost in models of clock disruption, contributing to the development of peritonitis, hepatitis, or colitis. Sterile inflammation is also an important driver of atherosclerosis, and targeting the production of IL-1β has proven to be a promising approach for atherosclerosis management in humans. Interestingly, the extent of injury after fulminant hepatitis or myocardial infarction is time-of-day dependent under the control of the clock, and chronotherapy represents a promising approach for the management of pathologies involving deregulation of NLRP3 signaling.
32847008 Biosensing Cytokine IL-6: A Comparative Analysis of Natural and Synthetic Receptors. 2020 Aug 24 Cytokines are a family of proteins which play a major role in the regulation of the immune system and the development of several diseases, from rheumatoid arthritis to cancer and, more recently, COVID-19. Therefore, many efforts are currently being developed to improve therapy and diagnosis, as well as to produce inhibitory drugs and biosensors for a rapid, minimally invasive, and effective detection. In this regard, even more efficient cytokine receptors are under investigation. In this paper we analyze a set of IL-6 cytokine receptors, investigating their topological features by means of a theoretical approach. Our results suggest a topological indicator that may help in the identification of those receptors having the highest complementarity with the protein, a feature expected to ensure a stable binding. Furthermore, we propose and discuss the use of these receptors in an idealized experimental setup.
32808463 Microarray-based transcriptional profiling of a mouse model of autoimmune hepatitis. 2020 Oct Long noncoding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that do not typically code for a protein. lncRNAs have regulatory roles in many physiological processes, and their dysregulation can contribute to cancer, cardiovascular and neurodegenerative diseases, as well as the onset of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. However, lncRNA expression changes in autoimmune hepatitis (AIH), a form of inflammation induced by immunological tolerance disorders, are poorly understood. Here, for the first time to our knowledge, we used microarrays to profile 1161 differentially expressed lncRNAs (DELs; 608 up- and 553 down-regulated) and 11 512 differentially expressed mRNAs (DEMs; 5189 up- and 6323 down- regulated) in a concanavalin A-induced AIH mouse model. We used quantitative real-time PCR to confirm the expression of eight DELs and DEMs, and analyzed the coexpression relationship between them. Potential biological functions of screened DELs and DEMs were predicted with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. DEL-DEM interaction networks were also constructed. Our study revealed the roles of DELs and DEMs in the pathogenesis of AIH. We also provided potential candidate biomarkers that may have potential for future development into possible diagnostics or as a treatment for this disorder.
32415419 Smooth or Risky Revisit of an Old Malaria Drug for COVID-19? 2020 Jun Hydroxychloroquine (HCQ) is an old medication for malaria. In addition to handling this parasitic disease, HCQ is also used to treat a number of autoimmune disorders including rheumatoid arthritis and systemic lupus erythematosus when other medications are not effective. Recently a new viral infection (COVID-19) is rocking the entire world so much that it has already taken more than 200,000 lives throughout the world within the last two months and the World Health Organization was forced to declare it as a pandemic on March 11, 2020. Interestingly, some reports indicate that this wonder drug may be also beneficial for COVID-19 and accordingly, many clinical trials have begun. Here, we discuss different modes of action (anti-inflammatory, antioxidant, inhibition of endosomal acidification, suppression of angiotensin-converting enzyme 2 or ACE2 glycosylation, etc.) of HCQ that might be responsible for its possible anti-COVID-19 effect. On the other hand, this review also makes an honest attempt to delineate mechanisms (increase in vasoconstriction, inhibition of autophagy, depletion of T cells, etc.) indicating how it may aggravate certain conditions and why caution should be taken before granting widespread repurposing of HCQ for COVID-19. Graphical Abstract.
32380297 Laboratory and clinical correlates of brain atrophy in Neuro-Behçet's disease. 2020 Jul 15 BACKGROUND: Diagnostic evaluation of patients with parenchymal Neuro-Behçet's disease (NBD) requires magnetic resonance imaging (MRI), neuro-ophthalmologic, and neuropsychological evaluation. In this study, we aimed to find out the ideal diagnostic method that most closely reflects the progress in cognitive disability and brain atrophy in NBD. METHODS: In this matched case-control study, we included patients with parenchymal NBD, Behçet's disease without neurological involvement (BD), rheumatoid arthritis, and healthy controls. Detailed ophthalmological examination, pattern-reversal visual evoked potentials (prVEP) test, optical coherence tomography (OCT), brain MRI volumetry and cognitive evaluation tests were performed. Disability status was assessed by revised EDSS. RESULTS: Sixty-eight individuals (35 female, 33 male) were recruited. Mean ACE-R scores were significantly lower in the NBD group (NBD vs. healthy, 80±14.4, 93±4.9, p=0.002). prVEP values were similar across groups, but retinal nerve fiber layer thickness (RNFLT) were more frequently abnormal in the NBD group. We found considerable volume reduction in the brainstem, cerebellum, hippocampus, and thalamus in the NBD group. Regarding prVEP, 120 minutes P100 amplitude (p<0.001, r=0.97) and 60 minutes P100 amplitude values (p=0.006, r=0.90) were positively correlated with the total cerebral white matter volume. CONCLUSION: Our results confirmed previous observations on cognitive dysfunction in patients with NBD. We reported MRI volumetry data of patients with parenchymal neuro-Behçet's disease for the first time and elucidated novel brain regions with atrophy. Clinically determined scores and OCT failed to predict the status of brain atrophy. prVEP P100 amplitude may be used as a surrogate marker of cerebral white matter involvement in NBD.
32363574 Alcohol use and the development of periodontal pockets: An 11-year follow-up study. 2020 Dec BACKGROUND: This study investigates whether alcohol use predicts the periodontal pocket development over an 11-year follow-up period. METHODS: The study participants' periodontal condition was examined both in the Health 2000 and 2011 Surveys (BRIF8901). Participants were aged 30 to 65 years, dentate, periodontally healthy, and did not have diabetes or rheumatoid arthritis in 2000. Periodontal outcome measures in 2011 were the number of teeth with deepened (≥4 mm) periodontal pockets and the presence of deepened periodontal pockets. The exposure in 2000 was alcohol use (amount [g/week], frequency [any alcohol or different beverages]). Incidence rate ratios (IRRs) with 95% confidence intervals (CI) were estimated using negative binomial regression model and Poisson regression model with a robust variance estimator. RESULTS: Overall, the amount of alcohol use or use over the risk limit in 2000 was inconsistently associated with the development of periodontal pockets (IRRs varied from 0.6 to 1.0). The frequency of alcohol use (any alcohol or different beverages) had an inconsistent association with the presence of periodontal pockets (IRRs varied from 0.5 to 1.2) while there was an inverse association with the number of teeth with periodontal pockets. Among smokers, there were no clear associations between any of the exposures and either of the outcomes. The same was found among non-smokers except an inverse association was found between frequency of alcohol use and the number of teeth with periodontal pockets. CONCLUSION: Alcohol use was not consistently associated with the periodontal pocket development over a period of 11 years.
32605504 A case of asthma with Behcet's disease: successful treatment with omalizumab and its effec 2020 Aug CONTEXT: Monoclonal antibody therapies have revolutionized the treatment of autoinflammatory-immune/genetic disease including spondylarthritis, asthma and rheumatoid arthritis. Behcet's disease (BD) is a multi-systemic vasculitis, which is generally recurrent aphthous lesions (RAL) as well as ocular and skin lesions. Today, the immunohistopathogenesis of BD is mostly unknown. METHOD: Omalizumab (Anti-IgE humanized monoclonal antibody) therapy is given for severe persistent allergic asthma, and unintentionally it had effect on RAL. Our patient has received omalizumab treatment for 3 years. The steroid treatment was completely discontinued a month later and the systemic-steroid dependent diabetes mellitus was healed. The IL-1 β, IL-6, IL-8, IL-33, IL-25, IL-10, IL-23, and IL-17A levels were measured using an Enzyme-Linked Immunosorbent Assay (ELISA) kit. RESULTS: After a long-term omalizumab treatment administered, the levels of WBC, d-dimer, IL-33, IL-6, IL-25 and IL-1 β decreased. The patient's hsCRP decreased from 3 to 0.1 and Eosinophil Cationic Protein (ECP) levels decreased from 78 to 21. A significant improvement was noticed in the RAL, the asthma symptoms (cough, shortness of breath), the number of emergency admissions, and the average length of stay of the patient within the days following the initiation of the omalizumab treatment. CONCLUSIONS: Here, for the first time, we introduce omalizumab treatment of a patient diagnosed with BD and the examination of the treatment for the clinical manifestations and the cytokines/coagulant protein levels. A significant improvement is observed in the patient's RAL following the initiation of omalizumab. There is strong evidence that the serum proinflammatory cytokines/coagulant factors could also play an important role in the relationship between RAL and IgE-dependent vascular autoinflammation.