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ID PMID Title PublicationDate abstract
27355450 Origin of B-Cell Neoplasms in Autoimmune Disease. 2016 Autoimmune diseases (ADs) are associated with a number of B-cell neoplasms but the associations are selective in regard to the type of neoplasm and the conferred risks are variable. So far no mechanistic bases for these differential associations have been demonstrated. We speculate that developmental origin of B-cells might propose a mechanistic rationale for their carcinogenic response to autoimmune stimuli and tested the hypothesis on our previous studies on the risks of B-cell neoplasms after any of 33 ADs. We found that predominantly germinal center (GC)-derived B-cells showed multiple associations with ADs: diffuse large B cell lymphoma associated with 15 ADs, follicular lymphoma with 7 ADs and Hodgkin lymphoma with 11 ADs. Notably, these neoplasms shared significant associations with 5 ADs (immune thrombocytopenic purpura, polymyositis/dermatomyositis, rheumatoid arthritis, Sjogren syndrome and systemic lupus erythematosis). By contrast, primarily non-GC neoplasms, acute lymphocytic leukemia, chronic lymphocytic leukemia and myeloma associated with 2 ADs only and mantle cell lymphoma with 1 AD. None of the neoplasms shared associated ADs. These data may suggest that autoimmune stimulation critically interferes with the rapid cell division, somatic hypermutation, class switch recombination and immunological selection of maturing B-cell in the GC and delivers damage contributing to transformation.
27261633 Computer tomography navigation for the transoral anterior release of a complex cranioverte 2016 INTRODUCTION: The surgical correction of deformities of the craniovertebral junction (CVJ) remains a challenge due to its complex anatomy. Despite the well-known usefulness of computed tomography (CT) navigation in posterior spinal surgery, it is applied far less frequently in anterior spinal surgery, mainly due to registration difficulties. PRESENTATION OF THE CASE: Case 1 was a 68-year-old female with rheumatoid arthritis, with a complaint of neck pain, motor weakness, and dysesthesia in the upper extremities. Case 2 was a 61-year-old male with Chiari malformation, with a complaint of neck pain and gait disturbance after a fall. Magnetic resonance imaging (MRI) showed severe atlantoaxial dislocation and multilevel cervical spinal cord compression in both patients. Continuous halo traction failed to reduce atlantoaxial dislocation, even under general anesthesia, and they were treated with combined anterior release and posterior decompression and fixation using CT navigation. Occipitocervical assimilation, which was present in both patients, enabled precise registration for navigation. DISCUSSION: The lack of anatomically characteristic landmarks on the vertebral surface makes obtaining accurate registration difficult in anterior CVJ surgery using CT navigation. The remaining mobility in the occipitocervical joint precludes the use of facial or cranial landmarks. However, occipitocervical assimilation, which is not uncommon in patients with CVJ deformities, enables accurate navigation during transoral surgery. CONCLUSION: Transoral anterior release using CT navigation is an effective treatment option for rigid complex CVJ deformities. The accurate identification of the patients' anatomical features such as occipitoatlantal assimilation, is crucial for the conducting accurate preoperative CT-based navigation during transoral surgery.
27020302 Hit-to-lead evaluation of a novel class of sphingosine 1-phosphate lyase inhibitors. 2016 May 1 Inhibition of sphingosine-1-phosphate lyase has recently been proposed as a potential treatment option for inflammatory disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. In this report we describe our hit-to-lead evaluation of the isoxazolecarboxamide 6, a high-throughput screening hit (in vitro IC50=1.0 μM, cell IC50=1.8 μM), as a novel S1P lyase inhibitor. We were able to establish basic structure-activity relationships around 6 and succeeded in obtaining X-ray structural information which enabled structure-based design. With the discovery of 28, enzyme activity was quickly improved to IC50=120 nM and cell potency to IC50=230 nM. The main liability in the established isoxazolecarboxamide hit series was determined to be metabolic stability. In particular we identified that future lead-optimization efforts to overcome this problem should focus on blocking the N-dealkylation on the secondary amine.
26967987 Transdiscal mid- and upper thoracic vertebroplasty: first description of 2 exemplary cases 2016 Aug Kyphoplasty and vertebroplasty are established treatment methods to reinforce fractured vertebral bodies. In cases of previous pedicle screw instrumentation, vertebral body cannulation may be challenging. The authors describe, for the first time, an approach through the adjacent inferior vertebra and disc space in the thoracic spine for cement augmentation. A 78-year-old woman underwent posterior fusion with pedicle screws after vertebrectomy and reconstruction with cement and Steinmann pins for a pathological T-7 fracture. Two months later she developed a compression fracture of the vertebral body at the lower part of the construct, and a vertebroplasty was performed. Because a standard transpedicular route was not available, an inferior transdiscal trajectory was used for the cement injection. A 73-year-old man with a history of rheumatoid arthritis underwent cervicothoracic fusion posteriorly for subluxation. He developed pain in the upper thoracic area, and the authors performed a transdiscal vertebroplasty at T-2. The standard transpedicular route was not possible. The vertebral body was satisfactorily filled up with cement. Clinically both patients benefited significantly in terms of back pain and showed an uneventful follow-up of 3 months. Transdiscal vertebroplasty can achieve good results in the mid- and upper thoracic spine when a standard transpedicular trajectory is not possible, and can therefore be a good alternative in select cases.
26830007 Targeting autophagy as a potential therapeutic approach for immune thrombocytopenia therap 2016 Apr Autophagy involves the sequestration and lysosomal degradation of various cytoplasmic structures, including damaged organelles and invading microorganisms. Autophagy is not only an essential cell-intrinsic mechanism for protecting against internal and external stress conditions but is also key in the cellular response against microbes, in antigen processing for major histocompatibility complex (MHC) presentation, and in lymphocyte development, survival, and proliferation. In recent years, perturbations in autophagy have been implicated in a number of diseases, including autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). Immune thrombocytopenia (ITP) is a multifactorial disease characterized by autoimmune responses to self-platelet membrane proteins. Recently, our unpublished original data demonstrated aberrant expression of molecules in the autophagy pathway in ITP patients compared with controls, and we found a close correlation between the pathogenesis of ITP and the autophagy pathway. The potential of targeting the autophagy pathway in ITP as a novel therapeutic approach has been discussed.
26660186 Quantification of Hydroxychloroquine in Blood Using Turbulent Flow Liquid Chromatography-T 2016 Hydroxychloroquine (HQ) is used routinely in the treatment of autoimmune disorders such as rheumatoid arthritis and lupus erythematosus. Issues such as marked pharmacokinetic variability and patient non-compliance make therapeutic drug monitoring of HQ a useful tool for management of patients taking this drug. Quantitative measurements of HQ may aid in identifying poor efficacy as well as provide reliable information to distinguish patient non-compliance from refractory disease. We describe a rapid 7-min assay for the accurate and precise measurement of HQ concentrations in 100 μL samples of human blood using turbulent flow liquid chromatography coupled to tandem mass spectrometry. HQ is isolated from EDTA whole blood after a simple extraction with its deuterated analog, hydroxychloroquine-d4, in 0.33 M perchloric acid. Samples are then centrifuged and injected onto the TFLC-MS/MS system. Quantification is performed using a nine-point calibration curve that is linear over a wide range (15.7-4000 ng/mL) with precisions of <5 %.
26523229 Elevated anthranilic acid plasma concentrations in type 1 but not type 2 diabetes mellitus 2015 Experimental data suggested involvement of tryptophan (Trp) - kynurenine (Kyn) pathway (TKP) in mechanisms of autoimmune, type 1 (T1D), and metabolic, type 2 (T2D), diabetes. However, clinical evaluations of TKP metabolites were limited to T2D. We assessed Trp, Kyn and TKP metabolites: anthranilic (AA), kynurenic (KYNA) and xanthurenic (XA) acids, in plasma samples of fifteen T1D, thirty T2D patients and twenty eight non-diabetic subjects by HPLC-mass spectrometry. Trp concentrations were higher in T1D than in T2D and controls while Kyn concentrations were not changed suggesting down-regulation of indoleamine-2,3-dioxygenase (IDO), a rate-limiting enzyme of TKP, in T1D. AA concentrations were 2.3-fold higher in T1D than in T2D and in controls. KYNA and XA concentrations were higher in T1D than in controls, and in previously reported T2D. AA elevation might be a specific feature of T1D. TKP shift towards AA formation in T1D may result from riboflavin deficiency, that increases AA in rats and baboons, and is highly associated with T1D but not T2D. AA augments autoimmune-induced apoptosis of pancreatic cells (PC) by increasing formation of antibodies to PC auto-antigen. Marked increase of AA was reported in rheumatoid arthritis, another autoimmune disorder. Trp, an essential amino acid for humans, is synthesized from AA by diabetogenic intestinal microbiome. AA down-regulates IDO by inhibition of Trp entry into cells. Resulting elevation of Trp attenuates Trp depletion-induced protection of PC against autoimmunity. Further studies of TKP might offer new tools for prevention and treatment of T1D and other autoimmune disorders.
26258058 Microspheres and tablet in capsule system: A novel chronotherapeutic system of ketorolac t 2015 Jul The objective of the present work was to develop a novel delivery system of ketorolac tromethamine (KT) for dual pulse release based on microspheres and tablet in capsule system (MATICS) as a treatment modality for rheumatoid arthritis. The design consisted of an impermeable hard gelatin capsule body, in which a core tablet was (second pulse) placed in the bottom and sealed with a hydrogel plug (HP2). The body was locked with enteric coated cap filled with KT microspheres (first pulse). The microspheres for first pulse were selected by screening the formulations (M1-M6), and M1 with least particle size of 96.38 ± 0.05 μm, highest drug loading of 25.10% ± 0.28% and maximum CDR of 89.32% ± 0.21% was adjudged as the best formulation. The HP2 tablet was selected based on its capability for maintaining a lag period of 6 h. The selection criterion of the second pulse (core tablet: T3) was its disintegration time of 4.02 ± 0.53 min and CDR of 99.10% ± 0.32% in 30 min. All the optimized formulations were assembled in accordance with the proposed design to form pulsatile MATICS and evaluated for in vitro release. MATICS displayed delayed sustained CDR of 80.15% in 8 h from the first pulse (microspheres) after a lag time of 2 h, followed by 97.05% KT release from second pulse (core tablet) in simulated colonic fluid within 10 h. Conclusively, in vitro pulsatile release was a rational combination of delayed sustained and immediate release of KT that has the potential to combat the pain at night and morning stiffness. Incorporation of two pulses in one system offers a reduction in dose frequency and better pain management.
27800220 Effect of Systemic Infliximab Therapy in Patients with Sjögren's Syndrome. 2015 Aug OBJECTIVES: To investigate the effect of systemic infliximab therapy on tear function tests and the ocular surface in patients with Sjögren's syndrome secondary to various autoimmune diseases. MA­TE­RI­ALS AND MET­HODS: This prospective study included 22 eyes of 22 patients with Sjögren's syndrome who began treatment with systemic infliximab. Tear film break-up time (TBUT), anesthetized Schirmer's 1 test, fluorescein staining test, and Ocular Surface Disease Index (OSDI) scores were recorded before treatment and in the 3rd and 6th months of treatment. RE­SULTS: In the 3rd month of infliximab therapy, no significant changes were observed in Schirmer's values, TBUT, fluorescein staining, or OSDI scores (p=0.260, p=0.357, p=0.190 and p=0.07, respectively). In the 6th month of infliximab therapy, no significant changes were observed in TBUT, fluorescein staining, Schirmer's value or OSDI scores (p=0.510, p=0.320, p=0.220 and p=0.344, respectively). CONCLUSION: Infliximab therapy, which is commonly used in systemic autoimmune diseases such as rheumatoid arthritis, Crohn's disease, ulcerative colitis, and ankylosing spondylitis, did not show a positive effect on ocular surface and tear function tests.
26165557 Nonsteroidal Anti-Inflammatory Drugs Cause Inhibition of the Growth Plate in Cultured Rat 2016 Jan 13 BACKGROUND: Little is known presently about the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the longitudinal bone growth occurring in the growth plate. We have examined the effects of administration of different types of NSAIDs on the longitudinal growth of the growth plate using a fetal rat metatarsal bone culture model. METHODS: Cultured fetal rat metatarsal bones were used to study the effect of nonselective (indomethacin) and selective cyclooxygenase-2 (COX-2, celecoxib) NSAIDs on longitudinal bone growth. The effect of NSAIDs on proliferation and apoptosis of growth plate chondrocytes were analyzed by BrdU incorporation and a TUNEL assay. Prostaglandin E2 (PGE2) production was measured by an ELISA kit. We also examined the effect of exogenous PGE2 on the growth plate. RESULTS: NSAIDs caused a dose-dependent growth retardation of cultured metatarsal bones. Both nonselective and COX-2 selective NSAIDs inhibit longitudinal bone growth. We found that NSAIDs suppressed the proliferation of chondrocytes and production of PGE2, and increased the apoptosis of chondrocytes. Supplemental PGE2 could not reverse the effects of NSAIDs on the growth plate. CONCLUSIONS: Our data show that NSAIDs induce a dose-dependent growth retardation of cultured rat metatarsal bones. A detailed analysis revealed decreased proliferation and increased apoptosis of chondrocytes in the growth plate, indicating that COX-2 is responsible for PGE2 production in growth plate chondrocytes. CLINICAL RELEVANCE: The data from the present study suggest that deleterious effects on the growth plate by chronic NSAIDs use should be considered for children who have chronic inflammatory diseases, such as juvenile rheumatoid arthritis.
25961655 Masitinib for the treatment of mild to moderate Alzheimer's disease. 2015 Jun Alzheimer's disease (AD) is a degenerative neurological disorder that is the most common cause of dementia and disability in older patients. Available treatments are symptomatic in nature and are only sufficient to improve the quality of life of AD patients temporarily. A potential strategy, currently under investigation, is to target cell-signaling pathways associated with neurodegeneration, in order to decrease neuroinflammation, excitotoxicity, and to improve cognitive functions. Current review centers on the role of neuroinflammation and the specific contribution of mast cells to AD pathophysiology. The authors look at masitinib therapy and the evidence presented through preclinical and clinical trials. Dual actions of masitinib as an inhibitor of mast cell-glia axis and a Fyn kinase blocker are discussed in the context of AD pathology. Masitinib is in Phase III clinical trials for the treatment of malignant melanoma, mastocytosis, multiple myeloma, gastrointestinal cancer and pancreatic cancer. It is also in Phase II/III clinical trials for the treatment of multiple sclerosis, rheumatoid arthritis and AD. Additional research is warranted to better investigate the potential effects of masitinib in combination with other drugs employed in AD treatment.
25921473 Muscular strength as a strong predictor of mortality: A narrative review. 2015 Jun Muscular strength, an important component of physical fitness, has an independent role in the prevention of chronic diseases whereas muscular weakness is strongly related to functional limitations and physical disability. Our purpose was to investigate the role of muscular strength as a predictor of mortality in health and disease. We conducted a systematic search in EMBASE and MEDLINE (1980-2014) looking for the association between muscular strength and mortality risk (all-cause and cause-specific mortality). Selected publications included 23 papers (15 epidemiological and 8 clinical studies). Muscular strength was inversely and independently associated with all-cause mortality even after adjusting for several confounders including the levels of physical activity or even cardiorespiratory fitness. The same pattern was observed for cardiovascular mortality; however more research is needed due to the few available data. The existed studies failed to show that low muscular strength is predictive of cancer mortality. Furthermore, a strong and inverse association of muscular strength with all-cause mortality has also been confirmed in several clinical populations such as cardiovascular disease, peripheral artery disease, cancer, renal failure, chronic obstructive pulmonary disease, rheumatoid arthritis and patients with critical illness. However, future studies are needed to further establish the current evidence and to explore the exact independent mechanisms of muscular strength in relation to mortality. Muscular strength as a modifiable risk factor would be of great interest from a public health perspective.
25786537 Restless legs syndrome in psoriasis: an unexpected comorbidity. 2015 May BACKGROUND: Restless legs syndrome (RLS) is characterized by unpleasant sensations in the legs and an uncontrollable urge to move them in order to gain relief. Higher frequencies of RLS have been reported in systemic lupus, multiple sclerosis, rheumatoid arthritis and atopic dermatitis. OBJECTIVES: Since the disease-related stress present in psoriasis is similar to the stress of those diseases, we aimed to study the frequency of RLS in a German cohort of patients with psoriasis. METHODS: 300 patients with psoriasis and 300 healthy controls were evaluated for RLS symptoms in this study. RESULTS: While 17% (n = 51) of patients with psoriasis reported symptoms of RLS, only 4% (n = 12) of individuals without psoriasis suffered from RLS symptoms (95% confidence interval: 0.08 - 0.18, p<0.01). In patients with psoriasis and RLS the average RLS score was 16.0 ± 9.2 whereas individuals with RLS in the control group had an average RLS score of 13.5 ± 7.1. CONCLUSIONS: Our findings indicate an increased frequency of RLS in patients with psoriasis, suggesting screening patients with psoriasis for the presence of RLS as a well-treatable co-morbidity.
25745909 Unlinked total elbow arthroplasty. 2015 For more than 60 years, total elbow arthroplasty (TEA) has been successfully used to treat a variety of elbow conditions. Although first designed to treat older patients with rheumatoid arthritis, the indications have expanded to include younger, higher-demand patients with a broad range of elbow pathology. Two groups of TEA currently exist. The first group includes linked or semiconstrained elbows with a mechanical connection between the humeral and ulnar components that prevents disassociation. These implants do not rely on muscular or ligamentous tissues for stability. The second group includes unlinked implants that have no physical connection between the humeral and ulnar components. They rely on bearing surface architecture as well as soft-tissue integrity for elbow stability. Critical to the success of unlinked implants is a thorough preoperative evaluation of elbow stability, including bone stock, collateral ligament integrity, and periarticular muscle function. Unlinked implants should apply less strain to the bone-cement-implant interfaces, which may theoretically decrease rates of bearing wear and aseptic loosening. For this reason, some surgeons prefer unlinked implants for younger, higher-demand patients. To date, unlinked implants have not been clinically shown to improve survivorship compared with linked devices. No prospective randomized trials comparing linked and unlinked TEAs are currently available. Historically, unlinked implants have had higher revision rates, mostly caused by instability and early design flaws. More recent series have shown no significant differences in outcomes compared with linked devices. Unlinked TEA provides reliable pain relief and improved range of motion for patients with a variety of elbow disorders. Diligent patient selection and careful surgical technique are of utmost importance when considering an unlinked TEA as a treatment option. The recent development of convertible implants now allows surgeons to make intraoperative decisions regarding elbow stability and convert to a linked implant without revising the stems.
25738173 The in vitro modulatory effect of TNFα on the mRNA expression and protein levels of zinc 2015 We have shown before that the expression of ZNF334 gene, coding for a newly described zinc finger protein of as yet unknown function, is extremely reduced in CD4(+) lymphocytes of rheumatoid arthritis (RA) patients regardless of their age, and thus can be considered a new molecular marker of the disease. Based on the promoter sequence of the gene we speculated that it might be regulated by TNFα. Here we have tested that hypothesis, studying the in vitro influence of TNFα on the ZNF334 gene expression and protein levels in resting and stimulated CD4(+) cells of healthy volunteers. We have confirmed that treatment with TNFα modifies the levels of ZNF334 expression in the CD4(+) cells ex vivo; however, the effect varied for different individuals and reduction of expression was seen only for those cell samples that initially exhibited high transcriptional activity of the gene, while for those exhibiting initially very low expression, some increase in the transcriptional activity was observed. Incubation with TNFα significantly reduced the amounts of two isoforms of ZNF334 protein (initially high in all subjects) in parallel to the reduced transcription. Finally, the expression of ZNF334 in CD4(+) lymphocytes isolated after various periods of anti-CD3 stimulation generally increased with longer culture times, and the effect of TNFα treatment was negligible. Concluding, our results obtained in vitro for helper lymphocytes of healthy individuals seem to mimic the regulatory effect of TNFα on the expression of ZNF334 in the cells of RA patients.
25698371 MRI findings of the shoulder and hip joint in patients with polymyalgia rheumatica. 2015 Sep OBJECTIVES: The purpose of this study is to evaluate magnetic resonance imaging (MRI) findings of the shoulder and hip joint in patients with polymyalgia rheumatica (PMR). METHODS: MR images of a total of 25 PMR patients (23 shoulders and 6 hips), 43 rheumatoid arthritis (RA) patients (22 shoulders and 22 hips), and 50 control patients (25 shoulders and 25 hips) were examined. The following MRI findings were evaluated: In the shoulder, thickness and abnormalities of the supraspinatus tendon, effusion around the glenohumeral joint, subacromial-subdeltoid bursa, and the biceps tendon; In the hip, effusion around the acetabulofemoral joint, iliopsoas bursa, and trochanteric bursa. Periarticular soft-tissue edema and bone findings were also analyzed. RESULTS: The supraspinatus tendon was significantly thicker in PMR patients than in RA patients and control patients (p < 0.05). Severe rotator cuff tendinopathy was frequently observed in PMR patients (p = 0.002). The scores for the amount of effusions (joint, bursa, and tendon sheath in the shoulder and bursa in the hip) were much higher in PMR patients (p < 0.05). Periarticular soft tissue edema was detected more frequently in PMR patients than in RA patients and control patients (p < 0.05). CONCLUSIONS: Thick supraspinatus tendon, severe rotator cuff tendinopathy, effusion around the joints, and periarticular soft tissue edema can be good indicators for the diagnosis of PMR.
25394310 Neutrophilic dermatosis: disease mechanism and treatment. 2015 Jan PURPOSE OF REVIEW: The purpose of this review is to describe the physiopathological and therapeutic aspects of neutrophilic dermatosis, taking into account their most frequent associated conditions. RECENT FINDINGS: In autoinflammatory syndromes featuring neutrophilic dermatosis, the role of interleukin-1 and tumor necrosis factor (TNF)-α cytokines in the immunopathogenesis of neutrophilic dermatosis has supported their classification as autoinflammatory diseases. In malignancy-associated neutrophilic dermatosis, the role of the malignant clone in myeloid neoplasms and the role of the monoclonal gammopathy and/or of the malignant plasmocyte clone in myeloma have been underlined. SUMMARY: Recent insights into neutrophilic dermatosis' pathophysiology have encouraged the use of targeted biological therapies for their treatment. Although systemic glucocorticoids remain the mainstay of treatment for Sweet's syndrome and pyoderma gangrenosum, anti-TNF-α is becoming the preferred treatment when pyoderma gangrenosum is accompanied by inflammatory bowel disease or rheumatoid arthritis. Interleukin-1 receptor inhibitor anakinra is a promising therapeutic alternative for refractory Sweet's syndrome.
25245056 The protocol for the isolation and cryopreservation of osteoclast precursors from mouse bo 2016 Jan Osteoclasts are responsible for physiological bone remodeling as well as pathological bone destruction in osteoporosis, periodontitis and rheumatoid arthritis, and thus represent a pharmacological target for drug development. We aimed to characterize and compare the cytokine-induced osteoclastogenesis of bone marrow and spleen precursors. Established protocols used to generate osteoclasts from bone marrow were modified to examine osteoclastogenesis of the spleen cells of healthy mice. Osteoclast formation was successfully induced from spleen precursors using receptor activator of nuclear factor κB ligand (50 ng/ml) and macrophage colony stimulating factor (50 ng/ml). Compared to bone marrow cultures, differentiation from spleen required a longer cultivation time (9 days for spleen, as compared to 5 days for marrow cultures) and a higher plating density of non-adherent cells (75,000/cm(2) for spleen, as compared to 50,000/cm(2) for bone marrow). Osteoclasts generated from spleen precursors expressed osteoclast marker genes calcitonin receptor, cathepsin K and matrix metalloproteinase 9 and were capable of resorbing hydroxyapatite. The differentiation capacity of spleen and bone marrow precursors was comparable for BALB/c, C57BL/6 and FVB mice. We also developed and tested a cryopreservation protocol for the osteoclast precursors. While 70-80 % of cells were lost during the first week of freezing, during the subsequent 5 weeks the losses were within 2-5 % per week. Osteoclastogenesis from the recovered bone marrow precursors was successful up to 5 weeks after freezing. Spleen precursors retained their osteoclastogenic capacity for 1 week after freezing, but not thereafter. The described protocol is useful for the studies of genetically modified animals as well as for screening new osteoclast-targeting therapeutics.
30208732 A Viewpoint on the Leaky Gut Syndrome to Treat Allergic Asthma: A Novel Opinion. 2017 Jul Asthma is a common respiratory disease characterized by airway inflammation, airway hyperreactivity, and reversible airflow obstruction. Despite current treatments, the prevalence of asthma has increased markedly over decades. According to the theories proposed to explain the pathophysiology of autoimmune diseases in integrative medicine, leaky gut syndrome is a phenomenon of increased intestinal permeability due to the disruption of tight junctions and is thought to be related to many chronic diseases, such as food intolerance, inflammatory bowel disease, rheumatoid arthritis, asthma, and other autoimmune disease. One of the classical approaches used by integrative physicians to treat leaky gut syndrome is to repair intestinal permeability to prevent allergic cascade. Due to several mechanisms that have been mentioned in the protective effects of plant gums and plantain family seeds on the intestinal epithelium, we can propose an effective management for leaky gut syndrome to treat asthma.
26493510 [A Case of Crohn's Disease Showing Favorable Response to Induction and Maintenance Therapy 2015 Oct Thanks to the introduction of immumomodulators and biologics, therapeutic approaches in Crohn's disease have changed significantly during the past decade. Although new biologic therapy has dramatically improved the treatment of Crohn's disease, a substantial number of patients are refractory to these therapies or lose their initial response. Methotrexate (MTX) is a structural analogue of folic acid that can competitively inhibit the binding of dihydrofolic acid to the enzyme dihydrofolate reductase and has been widely used as immunomodulator in rheumatology area for patients with rheumatoid arthritis and psoriasis. Although MTX has also been shown to be an effective agent for remission induction and maintenance of remission in Crohn's disease, the use of MTX in Crohn's disease has not yet been reported in Korea. Herein, we report a case of Crohn's disease patient who was successfully treated with MTX after treatment failure with thiopurine and anti-tumor necrosis factor.