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ID PMID Title PublicationDate abstract
34030995 Oral hairy leukoplakia: a series of 45 cases in immunocompetent patients. 2021 Aug OBJECTIVE: Oral hairy leukoplakia (OHL) is a benign Epstein-Barr virus infection typically presenting as a white lesion on the lateral border of the tongue. Historically, OHL was described in patients who are severely immunocompromised, such as those with HIV/AIDS and organ transplant patients. OHL is increasingly seen in patients who are not severely immunocompromised. This study reviews 45 cases of OHL in a single institution and characterizes the clinical features of these relatively immunocompetent patients. STUDY DESIGN: Retrospective study. RESULTS: There were 45 cases with 23 male patients (51.1%) and a median age of 64 (range, 24-100 years). The lateral/ventral tongue was the affected site in 41 cases (91.1%), and 5 cases presented bilaterally. A review of the medical history and medications showed the most common conditions were hypertension (53.3%), hyperlipidemia (42.2%), and chronic respiratory conditions (33.3%); 8 patients (17.8%) had diabetes mellitus, and 1 had rheumatoid arthritis. Eleven cases (24.4%) reported no underlying medical conditions or history of medications. The most frequently reported medications included antihypertensive drugs (21.0%), steroid inhalers (14.6%), and cholesterol-lowering drugs (11.0%). CONCLUSIONS: OHL is not exclusively seen in profoundly immunocompromised patients. Localized immunosuppression (from steroid inhalers) and immunosenescence (aging) are possible contributing factors.
34012869 Ayurvedic Balarista ameliorate anti-arthritic activity in adjuvant induced arthritic rats 2021 May BACKGROUND AND AIM: Balarista is a fermented ayurvedic liquid preparation recommended as a good therapy for the treatment of rheumatoid arthritis. In the present investigation, the anti-arthritic activity of in-house Balarista formulation and marketed M1, M2, M3 and M4 Balarista formulations at the dose of 2.31 ml/kg were studied on Complete Freund's adjuvant-induced arthritic rat model. EXPERIMENTAL PROCEDURE: Measurement of paw diameter, arthritic index, arthritic score, and body weight were made to assess the anti-arthritic activity. Alterations in hematological and biochemical parameters were carried out to ascertain the disease progression. The inflammatory mediators (TNF-α, IL-1β, and IL-6) were measured by the ELISA method. The oxidative stress parameters were evaluated in tissues of joint, liver, spleen and kidney. The histological and radiological changes in the ankle joint of rats were also studied. RESULTS AND CONCLUSION: Administration of in-house and marketed formulations exhibited significant anti-arthritic activity by reducing all the arthritic parameters. The anomalous alterations in hematological and biochemical parameters were remarkably restored. The expression level of serum pro-inflammatory cytokines was significantly suppressed in treated animals. The oxidative stress, indicated by an increase in lipid peroxidation, decreased in antioxidant enzyme i.e. superoxide dismutase and catalase along with non-enzymatic reduced glutathione in tissues, were strongly counteracted by the formulation. Abnormal changes in arthritic ankle joints shown by X-ray and histological examination were significantly protected by the formulation. The present study suggests that the administration of in-house and marketed Balarista formulations have produced a significant anti-arthritic effect by inhibiting free radicals and inflammatory cytokines.
33492451 Cyclophilin A: a key player for etiological agent infection. 2021 Feb Cyclophilin A (CypA), a key member of the immunophilin family, is the most abundantly expressed isozyme of the 18 known human cyclophilins. Besides acting as an intracellular receptor for cyclosporine A, CypA plays a vital role in microorganismal infections, cardiovascular diseases, liver diseases, kidney diseases, neurodegeneration, cancer, rheumatoid arthritis, periodontitis, sepsis, asthma, and aging. This review focuses on the pivotal roles of CypA in the infection of etiological agents, which manifests mainly in promoting or inhibiting viral replication based on the host cell type and viral species. CypA can interact with viral proteins and thus regulate the replication cycle of the virus. CypA is involved in pathogenic bacterial infections by regulating the formation of host actin skeleton or membrane translocation of bacterial toxins, or mediated the adhesion of Mycoplasma genitalium during the infection processes by acting as a cellular receptor of M. genitalium. CypA also plays a critical role in infection or the life cycle of certain parasites or host immune regulation. Moreover, we summarized the current understanding of CypA inhibitors acting as host-targeting antiviral agents, thus opening an avenue for the treatment of multiple viral infections due to their broad antiviral effects and ability to effectively prevent drug resistance. Therefore, the antiviral effect of CypA has the potential to promote CypA inhibitors as host-targeting drugs to CypA-involved etiological agent infections and human diseases. KEY POINTS: • CypA is involved in the replication and infection of several viruses, pathogenic bacteria, mycoplasma, and parasites. • CypA inhibitors are in a strong position to inhibit the infection of viruses, bacterial, and mycoplasma.
33450164 A Randomized Double-Masked Phase 2a Trial to Evaluate Activity and Safety of Topical Ocula 2021 May Purpose: To determine whether reproxalap, a novel reactive aldehyde species (RASP) inhibitor, is safe and effective for the treatment of the signs and symptoms of dry eye disease (DED). Methods: In a randomized double-masked parallel-group Phase 2a trial of 3 topical ocular reproxalap formulations (0.1% ophthalmic solution, 0.5% ophthalmic solution, and 0.5% lipid ophthalmic solution), 51 patients with DED were randomly assigned 1:1:1 at a single US site. Eyes were treated bilaterally 4 times daily for 28 days, and standard DED signs and symptoms were assessed at baseline and after 7 and 28 days of dosing. Tear RASP levels were assessed at baseline and at day 28. Results: The effect of treatment on DED signs and symptoms was similar across the treatment arms, and pooled data from the 28-day treatment period demonstrated significant improvement from baseline in Symptom Assessment in Dry Eye Disease score (P = 0.003), Ocular Discomfort Scale score (P < 0.0001), Ocular Discomfort Score and 4-Symptom Questionnaire overall score (P = 0.0004), Schirmer's test (P = 0.008), tear osmolarity (P = 0.003), and lissamine green total staining score (P = 0.002). Improvements in DED symptoms were evident within 1 week of therapy, and effect sizes generally approached or exceeded 0.5. No significant changes in safety measures were observed. Conclusion: The results suggest that the novel RASP inhibitor reproxalap has the potential to mitigate the signs and symptoms of DED, and may represent a new, rapidly and broadly active treatment approach for DED (NCT03162783).
33975174 Polymorphisms in TNFAIP3, but not in STAT4, BANK1, BLK, and TNFSF4, are associated with su 2021 Jul BACKGROUND: Takayasu arteritis (TAK) is considered a rare disease characterized by nonspecific inflammation of the large arteries, especially the aorta and its major branches. Because TAK is an autoimmune disease (AD), it could share susceptibility loci with other pathologies such as systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), among others. Widely explored polymorphisms in non-HLA genes, including TNFAIP3, STAT4, TNFSF4, BANK1, and BLK have been consistently associated with both SLE and RA, but they have not been evaluated in TAK. OBJECTIVE: The aim of our study was to investigate whether TNFAIP3, STAT4, BANK1, BLK, and TNFSF4 polymorphisms are associated with susceptibility to TAK. METHODS: The TNFAIP3 rs2230926T/G and rs5029924C/T, STAT4 rs7574865G/T, BANK1 10516487G/A, BLK rs2736340T/C, rs13277113A/G, and TNFS4 rs2205960G/T polymorphisms were genotyped in 101 cases and 276 controls by using a TaqMan SNP genotyping assay. An association analysis was performed. RESULTS: The TNFAIP3 rs2230926T/G and rs5029924C/T polymorphisms were in complete linkage disequilibrium and turned out to be risk factors for TAK (OR = 4.88, p = 0.0001). The STAT4, BANK1, BLK, and TNFSF4 polymorphisms were not associated with the disease. CONCLUSIONS: This is the first study documenting an association of TNFAIP3 rs2230926T/G and rs5029924C/T with TAK. Our results provide new information on the genetic bases of TAK.
33949620 Association of TYK2 polymorphisms with autoimmune diseases: A comprehensive and updated sy 2021 Autoimmune diseases are characterized by the loss of self-tolerance, leading to immune-mediated tissue destruction and chronic inflammation. Tyrosine kinase 2 (TYK2) protein plays a key role in immunity and apoptosis pathways. Studies have reported associations between single nucleotide polymorphisms (SNPs) in the TYK2 gene and autoimmune diseases; however, results are still inconclusive. Thus, we conducted a systematic review followed by meta-analysis. A literature search was performed to find studies that investigated associations between TYK2 SNPs and autoimmune diseases (multiple sclerosis, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, psoriasis, rheumatoid arthritis, type 1 diabetes, and inflammatory bowel disease). Pooled odds ratios (OR) with 95 % CI were calculated using random (REM) or fixed (FEM) effects models in the Stata 11.0 Software. Thirty-four articles were eligible for inclusion in the meta-analyses, comprising 9 different SNPs: rs280496, rs280500, rs280523, rs280519, rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800. Meta-analysis results showed the minor alleles of rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800 SNPs were associated with protection against autoimmune diseases. Moreover, the A allele of the rs280519 SNP was associated with risk for systemic lupus erythematosus. Our meta-analyses demonstrated that the rs2304256, rs12720270, rs12720356, rs34536443, rs35018800, and rs280519 SNPs in the TYK2 gene are associated with different autoimmune diseases.
33935453 I-Kappa-B-Zeta Regulates Interleukin-17A/Tumor Necrosis Factor-Alpha Mediated Synergistic 2021 Apr BACKGROUND: Interleukin (IL)-19 and IL-20 are important members of the IL-10 cytokine family, which are known to play a role in inflammatory processes. Both anti-IL-19 and -IL-20 targeting drugs have been suggested in the treatment of inflammatory diseases such as psoriasis and rheumatoid arthritis. Recently, we presented I-kappa-B-zeta (IκBζ) as a key player in psoriasis by identifying IκBζ as a regulator of IL-17/tumor necrosis factor (TNF)α-inducible psoriasis-associated genes and proteins. Some of these genes were synergistically regulated by IL-17/TNFα. OBJECTIVE: The purpose of this study was to explore the role of IκBζ in the regulation of IL-17A/TNFα-mediated induction of IL-19 and IL-20 expression in human keratinocytes. METHODS: In vitro experiments with cultured primary humane keratinocytes were conducted and investigated by quantitative polymerase chain reaction (qPCR), Western blotting, ELISA and EMSA. For statistics, a one- or two- way repeated-measures analysis of variance (RM ANOVA) or the Friedman test (a nonparametric equivalent to the RM ANOVA) were conducted. RESULTS: We demonstrated that IL-19 and IL-20 mRNA and protein expressions were synergistically induced by IL-17A and TNFα, whereas IL-17A and TNFα alone had only a minor effect on the IL-19 and IL-20 expression. Moreover, we demonstrated IκBζ to be a regulator of this synergistic induction of IL-19 and IL-20. Finally, the IL-17A/TNFα-induced synergistic induction of IL-19 and IL-20 expression was found to be mediated by a p38 MAPK-, NF-κB- and JNK1/2-dependent mechanism. CONCLUSION: This study demonstrates that IκBζ plays a role in the IL-17A/TNFα-mediated synergistic induction of IL-19 and IL-20 in humane keratinocytes.
33860447 Inflammation-responsive delivery systems for the treatment of chronic inflammatory disease 2021 Aug Inflammation is the biological response of immune system to protect living organisms from injurious factors. However, excessive and uncontrolled inflammation is implicated in a variety of devastating chronic diseases including atherosclerosis, inflammatory bowel disease (IBD), and rheumatoid arthritis (RA). Improved understanding of inflammatory response has unveiled a rich assortment of anti-inflammatory therapeutics for the treatment and management of relevant chronic diseases. Notwithstanding these successes, clinical outcomes are variable among patients and serious adverse effects are often observed. Moreover, there exist some limitations for clinical anti-inflammatory therapeutics such as aqueous insolubility, low bioavailability, off-target effects, and poor accessibility to subcellular compartments. To address these challenges, the rational design of inflammation-specific drug delivery systems (DDSs) holds significant promise. Moreover, as compared to normal tissues, inflamed tissue-associated pathological milieu (e.g., oxidative stress, acidic pH, and overexpressed enzymes) provides vital biochemical stimuli for triggered delivery of anti-inflammatory agents in a spatiotemporally controlled manner. In this review, we summarize recent advances in the development of anti-inflammatory DDSs with built-in pathological inflammation-specific responsiveness for the treatment of chronic inflammatory diseases.
33812255 Daphnetin ameliorated GM-induced renal injury through the suppression of oxidative stress 2021 Jul Gentamicin (GM), an aminoglycoside antibiotic, is one of the most effective drugs used in the treatment of various types of bacterial infections, but the major adverse effect and drug-induced nephrotoxicity of GM limit its clinical applications. Daphnetin (Daph) is a natural coumarin derivative that is clinically used to treat rheumatoid arthritis and coagulopathy and exhibits antioxidant effects. However, the effect of Daph on GM-induced nephrotoxicity has not yet been elucidated. This study investigated Daph-mediated protection against GM-induced nephrotoxicity in mice and explored the underlying mechanisms of GM-induced renal dysfunction in mice. We found that Daph treatment significantly reduced GM-induced nephrotoxicity mainly by ameliorating renal injury in mice and attenuating cell damage in vitro. Mechanistically, we found that Daph upregulated the expression level of Nrf2 and its regulated antioxidant enzymes HO-1, NQO1, GCLC and GCLM in vivo and in vitro. GM upregulated the expression levels of NOX4, cleaved Caspase-3 and p53 and the BAX/BCL2 ratio in vivo to stimulate oxidative stress and apoptosis. However, Daph treatment significantly improved the oxidative stress and apoptosis caused by GM, thereby exerting antioxidative and antiapoptotic effects. Our study was the first to suggest that the natural product Daph protects against GM-induced nephrotoxicity through the activation of Nrf2 which regulates oxidative stress and apoptosis. The pharmacological activation of Nrf2 may be useful as a novel therapy to prevent renal injury.
33655922 Prevalence of anti-dense fine speckled 70 antibodies in healthy individuals and patients w 2021 Mar 5 Previous studies from various countries have reported anti-dense fine speckled pattern (DFS)70 antibody prevalence but few studies have been from Asia. We investigated the prevalence of anti-DFS70 autoantibodies in a Japanese cohort of healthy individuals (HI) and patients with antinuclear antibody-associated autoimmune rheumatic diseases (AARD).Enzyme-linked immunosorbent assay and indirect immunofluorescence were performed using samples from 250 HI and 276 AARD patients.The overall anti-DFS70 antibody prevalence in HI was 16.4%, with 12.8% for males and 20.0% for females (sex difference; P = .12). In AARD patients, the anti-DFS70 antibody prevalence in systemic lupus erythematosus, mixed connective tissue disease, systemic sclerosis, dermatomyositis and polymyositis (DM/PM), Sjögren syndrome, and rheumatoid arthritis (RA) was 22.1%, 14.3%, 14.3%, 3.0%, 21.3%, and 18.1%, respectively (no significant difference between AARD patients except DM/PM and HI). The prevalence of isolated anti-DFS70 antibody in HI and all AARD patients excluding RA was 14.8% (37/250) and 4.4% (9/204), respectively (P  < .01 vs HI). Among anti-DFS70 antibody-positive cases, 63.4% (26/41) were DFS pattern by IIF and 23.5% (8/34) were HI and AARD patients excluding RA, respectively.The anti-DFS70 antibody prevalence in HI and AARD patients in Japan was similar. Furthermore, the anti-DFS70 antibody prevalence in HI and AARD in Japan is higher than in HI and AARD in regions other than Asia. This makes AARD differential diagnosis by antinuclear antibody screening difficult.
33553436 Th17 Cells in Inflammatory Bowel Disease: Cytokines, Plasticity, and Therapies. 2021 Autoimmune diseases (such as rheumatoid arthritis, asthma, autoimmune bowel disease) are a complex disease. Improper activation of the immune system or imbalance of immune cells can cause the immune system to transform into a proinflammatory state, leading to autoimmune pathological damage. Recent studies have shown that autoimmune diseases are closely related to CD4+ T helper cells (Th). The original CD4 T cells will differentiate into different T helper (Th) subgroups after activation. According to their cytokines, the types of Th cells are different to produce lineage-specific cytokines, which play a role in autoimmune homeostasis. When Th differentiation and its cytokines are not regulated, it will induce autoimmune inflammation. Autoimmune bowel disease (IBD) is an autoimmune disease of unknown cause. Current research shows that its pathogenesis is closely related to Th17 cells. This article reviews the role and plasticity of the upstream and downstream cytokines and signaling pathways of Th17 cells in the occurrence and development of autoimmune bowel disease and summarizes the new progress of IBD immunotherapy.
33128728 Massive Demodicosis of the Eyes in a Patient with Sjögren Syndrome: A Case Report. 2021 Jun PURPOSE: Demodex mites infestation, typically asymptomatic, is a problem for patients with weakened immune systems because it often takes the form of symptomatic, massive infection. The Demodex mites play an important role in the occurrence of a range of eye surface diseases such as Demodex blepharitis, Meibomian gland dysfunctions, conjunctivitis and corneal changes. The ocular infection is closely related to the systemic invasion. Our goal was to minimize infestation and alleviate the symptoms of massive demodicosis so as to prevent further damage to the cornea. METHODS: Our research note involves a 61-year old woman diagnosed with secondary Sjögren syndrome due to rheumatoid arthritis. On the background of the autoimmune disease, corneal perforation of the left eye occurred that was cured by surgery. Then during the follow-up visit the patient was found (microscopically) massively infected with Demodex mites and the developed symptoms were particularly severe. RESULTS: Adequate dry eye syndrome and massive demodicosis therapy significantly reduced the number of Demodex mites and improved the patient's condition. CONCLUSION: We would like to draw the attention of the physicians of different specialties that special care should be taken with respect to the therapy of dry eye syndrome and ocular demodicosis in patients with immunological disorders to achieve therapeutic success and avoid particularly dangerous consequences of these diseases.
33091639 Musculoskeletal morbidity following spinal cord injury: A longitudinal cohort study of pri 2021 Jan BACKGROUND: People living with spinal cord injuries (SCIs) experience motor, sensory and autonomic impairments that cause musculoskeletal disorders following the injury and that progress throughout lifetime. The range and severity of issues are largely dependent on level and completeness of the injury and preserved function. OBJECTIVE: High risk of developing musculoskeletal morbidities among individuals after sustaining a traumatic SCI is well known in the clinical setting, however, there is a severe lack of evidence in literature. The objective of this study was to compare the incidence of and adjusted hazards for musculoskeletal morbidities among adults with and without SCIs. METHODS: Privately-insured beneficiaries were included if they had an ICD-9-CM diagnostic code for SCI (n = 9081). Adults without SCI were also included (n = 1,474,232). Incidence estimates of common musculoskeletal morbidities (e.g., osteoporosis, sarcopenia, osteoarthritis, fractures, etc.) were compared at 5-years of enrollment. Survival models were used to quantify unadjusted and adjusted hazard ratios for incident musculoskeletal morbidities. RESULTS: Adults living with traumatic SCIs had a higher incidence of any musculoskeletal morbidities (82.4% vs. 47.5%) as compared to adults without SCI, and differences were to a clinically meaningful extent. Survival models demonstrated that adults with SCI had a greater fully-adjusted hazard for any musculoskeletal morbidity (Hazard Ratio [HR]: 2.41; 95%CI: 2.30, 2.52), and all musculoskeletal disorders, and ranged from HR: 1.26 (1.14, 1.39) for rheumatoid arthritis to HR: 7.02 (6.58, 7.49) for pathologic fracture. CONCLUSIONS: Adults with SCIs have a significantly higher incidence of and risk for common musculoskeletal morbidities, as compared to adults without SCIs. Efforts are needed to facilitate the development of improved clinical screening algorithms and early interventions to reduce risk of musculoskeletal disease onset/progression in this higher risk population.
33052444 Menorrhagia due to uterine amyloidosis in familial Mediterranean fever: case-based review. 2021 Jan Amyloidosis is described by the deposition of misfolded proteins in the tissues. Amyloidoses are classified into two as systemic and localized. Out of the systemic forms, AL (light chain) amyloidosis is the most prevalent type; however, amyloid A (AA) amyloidosis is more frequently encountered in the rheumatology practice. AA amyloidosis stands out as a major complication of familial Mediterranean fever (FMF). Splenic and renal involvement is more likely in FMF-associated systemic amyloidosis. The involvement of thyroid and adrenal glands has also been described, although infrequently. Amyloidoses have a heterogeneous plethora of clinical manifestations, with certain phenotypes associated with specific amyloid forms. Gynecological amyloidosis is a rare condition. Uterine involvement may occur in a localized fashion or may also arise as a part of systemic involvement, albeit at a lesser ratio. Several cases of uterine AL amyloidosis have been documented so far as an organ involvement in systemic AL amyloidosis. On the other hand, uterine amyloidosis associated with AA amyloidosis has been described merely in one case with rheumatoid arthritis (RA). Here, we presented a 40-year-old female patient with FMF known for 38 years who underwent splenectomy and hysterectomy due to massive splenomegaly, deep anemia, and persistent menometrorrhagia. Histological examinations of materials revealed uterine and splenic AA amyloidosis. This case report is first-of-its-kind to describe FMF-associated uterine AA amyloidosis and also provides a discussion of possible mechanisms of amyloidosis-induced uterine bleeding.
34912017 Effects of sub-threshold transcutaneous auricular vagus nerve stimulation on cerebral bloo 2021 Dec 15 Transcutaneous auricular vagus nerve stimulation (taVNS) has shown promise as a non-invasive alternative to vagus nerve stimulation (VNS) with implantable devices, which has been used to treat drug-resistant epilepsy and treatment-resistant depression. Prior work has used functional MRI to investigate the brain response to taVNS, and more recent work has also demonstrated potential therapeutic effects of high-frequency sub-threshold taVNS in rheumatoid arthritis. However, no studies to date have measured the effects of high-frequency sub-threshold taVNS on cerebral blood flow (CBF). The objective of this study was to determine whether high-frequency (20 kHz) sub-threshold taVNS induces significant changes in CBF, a promising metric for the assessment of the sustained effects of taVNS. Arterial spin labeling (ASL) MRI scans were performed on 20 healthy subjects in a single-blind placebo-controlled repeated measures experimental design. The ASL scans were performed before and after 15 min of either sub-threshold taVNS treatment or a sham control. taVNS induced significant changes in CBF in the superior posterior cerebellum that were largely localized to bilateral Crus I and Crus II. Post hoc analyses showed that the changes were driven by a treatment-related decrease in CBF. Fifteen minutes of high-frequency sub-threshold taVNS can induce sustained CBF decreases in the bilateral posterior cerebellum in a cohort of healthy subjects. This study lays the foundation for future studies in clinical populations, and also supports the use of ASL measures of CBF for the assessment of the sustained effects of taVNS.
34748054 Comparison study of patient demographics and risk factors for infections following primary 2021 Nov 8 INTRODUCTION: While studies have shown favorable outcomes in the treatment of femoral neck fractures with the utilization of total hip arthroplasty (THA), adverse events, such as infections, can still occur. Therefore, the aims of this study were to 1) compare baseline demographics and 2) identify risk factors associated with developing either surgical site infections (SSIs) or peri-prosthetic joint infections (PJIs). MATERIALS AND METHODS: A retrospective analysis of patients who underwent primary THA for femoral neck fractures were queried from the Medicare database. The inclusion criteria consisted of patients developing SSIs within 90 days or PJIs within 3 years following the index procedure. The query yielded 2502 patients who developed infections in the form of either SSIs (n = 987) or PJIs (n = 1515) out of 57,191 patients treated for femoral neck fractures with primary THA. Primary endpoints were to compare baseline demographic profiles and determine risk factors associated with developing infections. Multivariate binomial logistic regression analyses were performed to determine the odds (OR) of developing infections. A p value less than 0.001 was considered to be statistically significant. RESULTS: Patients who developed either infections were found to be significantly different when compared to patients who did not develop infections. SSI (10 vs. 8, p < 0.0001) and PJI (9 vs. 5, p < 0.0001) patients both had significantly higher mean Elixhauser Comorbidity Index (ECI) scores compared to their counterparts. The regression model found the greatest risks for developing SSIs included hypertension (OR 1.63, p = 0.001), pathologic weight loss (OR 1.58, p < 0.0001), and iron deficiency anemia (IDA) (OR 1.48, p < 0.0001), whereas IDA (OR 2.14, p < 0.0001), pathologic weight loss (OR 1.75, p < 0.0001), and rheumatoid arthritis (OR 1.57, p < 0.0001) increased the odds for PJIs. CONCLUSION: This study can be utilized by orthopedic surgeons and other healthcare professionals to adequately educate these patients of the complications which may occur following their surgery.
34666667 [Two Case of Rhino-Orbito-Cerebral Mucormicosis Developed After COVID-19 Infection]. 2021 Oct Coronavirus 2019 (COVID-19) infection causes excessive cytokine response and a decrease in cellular immune response and this increases susceptibility to fungal co-infections. Mucormycosis is a rare, lifethreatening invasive fungal infection. In this report, two cases who developed rhino-orbito-cerebral mucormycosis shortly after having COVID-19 infection were presented. The first case was a 68-year old woman who admitted to our clinic with orbital cellulitis in her left eye and had a known diagnosis of asthma and rheumatoid arthritis. She was diagnosed with COVID-19 pneumonia 40 days ago, stayed in the intensive care unit for a long time, and received pulse steroid (1000 mg methylprednisolone), interleukin-1 (IL-1) inhibitor (anakinra) and broad-spectrum antibiotic treatments together with antiviral therapy during this period. The second case was a 63-year-old male patient with known diabetes mellitus, hypertension and retinitis pigmentosa, with a history of hospitalization in the intensive care unit due to COVID-19 pneumonia 20 days ago and received pulse steroid therapy during this period. He admitted to our clinic with the complaints of droopy right eyelid, swelling, nausea and vomiting. In both cases, paranasal sinus tomography findings were consistent with invasive sinusitis. Functional endoscopic sinus surgery was performed immediately in less than 16 hours from the first admission in both cases. Histopathological examination of the both cases revealed results consistent with mucormycosis. Mucorales spp. was isolated in sinus tissue culture of the second case taken during the operation. Both of the patients received liposomal amphotericin B. First case died on the 19th day of the treatment. Second case was discharged with full recovery after nine weeks of treatment. The suppression of cellular immunity during the COVID-19 infection, and the use of steroids and interleukin inhibitors in the treatment of severe cases may increase secondary invasive fungal infections. Therefore, clinicians should more frequently consider possible fungal infections in patients with COVID-19.
34603768 Modern Imaging Technologies of Mast Cells for Biology and Medicine (Review). 2021 Mast cells play an important role in the body defense against allergens, pathogens, and parasites by participating in inflammation development. However, there is evidence for their contributing to the pathogenesis of a number of atopic, autoimmune, as well as cardiovascular, oncologic, neurologic, and other diseases (allergy, asthma, eczema, rhinitis, anaphylaxis, mastocytosis, multiple sclerosis, rheumatoid arthritis, inflammatory gastrointestinal and pulmonary diseases, migraine, etc.). The diagnosis of many diseases and the study of mast cell functions in health and disease require their identification; so, the knowledge on adequate imaging techniques for mast cells in humans and different species of animals is of particular importance. The present review summarizes the data on major methods of mast cell imaging: enzyme histochemistry, immunohistochemistry, as well as histochemistry using histological stains. The main histological stains bind to heparin and other acidic mucopolysaccharides contained in mast cells and stain them metachromatically. Among these are toluidine blue, methylene blue (including that contained in May-Grünwald-Giemsa stain), thionin, pinacyanol, and others. Safranin and fluorescent dyes: berberine and avidin - also bind to heparin. Longer staining with histological dyes or alcian blue staining is needed to label mucosal and immature mast cells. Advanced techniques - enzyme histochemistry and especially immunohistochemistry - enable to detect mast cells high-selectively using a reaction to tryptases and chymases (specific proteases of these cells). In the immunohistochemical study of tryptases and chymases, species-specific differences in the distribution of the proteases in mast cells of humans and animals should be taken into account for their adequate detection. The immunohistochemical reaction to immunoglobulin E receptor (FcεRI) and c-kit receptor is not specific to mast cells, although the latter is important to demonstrate their proliferation in normal and malignant growth. Correct fixation of biological material is also discussed in the review as it is of great significance for histochemical and immunohistochemical mast cell detection. Fluorescent methods of immunohistochemistry and a multimarker analysis in combination with confocal microscopy are reported to be new technological approaches currently used to study various mast cell populations.
34479036 Synthetically-tailored and nature-derived dual COX-2/5-LOX inhibitors: Structural aspects 2021 Dec 5 Inflammation is a most complex pathological process that gives birth to different diseases. Different inflammatory mediators are released during an inflammation responsible for acute pain and chronic inflammatory diseases like cancer, asthma, rheumatoid arthritis, osteoarthritis, neurodegenerative diseases, metabolic and cardiovascular disorders. The arachidonic acid pathway, which results in the production of inflammatory mediators, provides several targets for anti-inflammatory intervention. The most popularly used medications for inflammation are non-steroidal anti-inflammatory agents (NSAIDs) but it has some limitations, in particular traditional NSAIDs which inhibit the COX pathway non-selectively, producing gastrointestinal side effects, and other adverse effects like stroke and renal failure. On the other hand, selective COX-2 inhibitors commonly known as 'coxibs' produce cardiovascular side effects. Frequent inhibition of either cyclooxygenase or lipoxygenase enzyme switches the metabolism of arachidonic acid from one to another which could lead to serious consequences. Therefore, a need to develop novel, effective and safe anti-inflammatory agents which can inhibit the release of both prostaglandins and leukotrienes from the respective cyclooxygenase and lipoxygenase pathways has emerged. This resulted in the discovery of new anti-inflammatory agents derived from natural and synthetic sources as dual COX-2/5-LOX inhibitors. To further contribute towards the discovery in this field, we have attempted to summarize structural features and pharmacological activities of heterocyclic scaffolds and natural products explored as dual COX-2/5-LOX inhibitors. We have emphasized the designing of the dual inhibitors inspired by the previously reported COX-2 and 5-LOX inhibitors. This outline could render us to identify the best pharmacophores catering to dual COX-2/5-LOX inhibitory activity while improving their efficiency as anti-inflammatory agents.
34305402 Effect of Leptin on Chronic Inflammatory Disorders: Insights to Therapeutic Target to Prev 2021 In response to obesity-associated chronic inflammatory disorders, adipose tissue releases a biologically active peptide known as leptin. Leptin activates the secretion of chemical mediators, which contribute to the pathogenesis of chronic inflammatory disorders, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and psoriasis. Conversely, adiposity and obesity are the major aggravating risk factors in the pathogenesis of metabolic syndrome (MetS), including type II diabetes mellitus and obesity-associated hypertension. Elevated level of leptin in obesity-associated hypertension causes an increase in the production of aldosterone, which also results in elevation of arterial blood pressure. Hyperleptinemia is associated with the progress of the atherosclerosis through secretion of pro-inflammatory cytokines, like interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), IL-17, and other cytokines to promote inflammation. The release of those cytokines leads to chronic inflammatory disorders and obesity-associated MetS. Thus, the aberrant leptin level in both MetS and chronic inflammatory disorders also leads to the complication of cardiovascular diseases (CVD). Therapeutic target of leptin regarding its pro-inflammatory effect and dysregulated sympathetic nervous system activity may prevent further cardiovascular complication. This review mainly assesses the mechanism of leptin on the pathogenesis and further cardiovascular risk complication of chronic inflammatory disorders.