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ID PMID Title PublicationDate abstract
27512186 Heat Shock Protein-70 Expression in Vitiligo and its Relation to the Disease Activity. 2016 Jul BACKGROUND: Vitiligo is a progressive depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. The etiopathogenesis of vitiligo is still unclear. Heat shock proteins (HSPs) are prime candidates to connect stress to the skin. HSPs were found to be implicated in autoimmune diseases such as rheumatoid arthritis and other skin disorders as psoriasis. AIM AND OBJECTIVES: The aim of this study was to map the level of HSP-70 in vitiligo lesions to declare its role in the pathogenesis and activity of vitiligo. MATERIALS AND METHODS: The study included thirty patients with vitiligo and 30 age- and sex-matched healthy controls. Vitiligo patients were divided as regards to the disease activity into highly active, moderately active, and inactive vitiligo groups. Skin biopsies were taken from the lesional and nonlesional skin of patients and from the normal skin of the controls. HSP-70 messenger RNA (mRNA) expression was estimated using quantitative real-time polymerase chain reaction. RESULTS: Our analysis revealed a significantly higher expression of HSP-70 mRNA in lesional skin biopsies from vitiligo patients compared to nonlesional skin biopsies from vitiligo patients (P < 0.001) and compared to skin biopsies from healthy controls (P < 0.001). The level of HSP-70 was not found to be correlated with age, sex, or disease duration. The expression of HSP-70 was correlated with the disease activity and patients with active vitiligo showed higher mean HSP-70 level compared to those with inactive disease. CONCLUSIONS: HSP-70 plays a role in the pathogenesis of vitiligo and may enhance the immune response in active disease.
27345162 Human Diversity in a Cell Surface Receptor that Inhibits Autophagy. 2016 Jul 25 Mutations in genes encoding autophagy proteins have been associated with human autoimmune diseases, suggesting that diversity in autophagy responses could be associated with disease susceptibility or severity. A cellular genome-wide association study (GWAS) screen was performed to explore normal human diversity in responses to rapamycin, a microbial product that induces autophagy. Cells from several human populations demonstrated variability in expression of a cell surface receptor, CD244 (SlamF4, 2B4), that correlated with changes in rapamycin-induced autophagy. High expression of CD244 and receptor activation with its endogenous ligand CD48 inhibited starvation- and rapamycin-induced autophagy by promoting association of CD244 with the autophagy complex proteins Vps34 and Beclin-1. The association of CD244 with this complex reduced Vps34 lipid kinase activity. Lack of CD244 is associated with auto-antibody production in mice, and lower expression of human CD244 has previously been implicated in severity of human rheumatoid arthritis and systemic lupus erythematosus, indicating that increased autophagy as a result of low levels of CD244 may alter disease outcomes.
27325143 Increased Cumulative Incidence of Dermatomyositis in Ulcerative Colitis: a Nationwide Coho 2016 Jun 21 On a molecular level, two autoimmune diseases: ulcerative colitis (UC) and dermatomyositis share common genetic determinants. On a clinical level, case reports evidenced the co-occurrence of these two diseases. We therefore hypothesize that UC is potentially associated with increased cumulative incidence of dermatomyositis. The goals of this retrospective cohort study were to evaluate whether UC is associated with increased cumulative incidence of dermatomyositis independent of sex and age. For comparison, we also assessed the cumulative incidence of polymyositis in UC and control subjects. The study enrolled 3,133 UC subjects and 14,726 control subjects. The cumulative incidence of dermatomyositis was significantly higher in UC than that of control subjects (p = 0.026), but the cumulative incidence of polymyositis was comparable between UC and control subjects (p = 0.596). UC was independently associated with the increased incident dermatomyositis (hazard ratio: 6.19, 95% confidence interval = 1.77-21.59, p = 0.004) after adjusting for sex, age, and concomitant rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. Similar trends of increased dermatomyositis in UC were observed when patients were stratified based on sex and age. In conclusion, our findings suggest that UC is probably associated with increased cumulative incidence of dermatomyositis, independent of sex, age, and concomitant autoimmune diseases.
27268469 Repurposing auranofin as an antifungal: In vitro activity against a variety of medically i 2017 Feb 17 Repositioning old drugs can significantly decrease the time and effort that it takes to develop novel antifungal therapeutics, which represents a pressing and unmet clinical need due to the devastating nature of fungal infections. We have previously described the activity of auranofin, a gold thiol compound used to treat rheumatoid arthritis, against Candida albicans biofilms. Here we evaluate its antifungal spectrum of action and describe its activity against a variety of medically important fungi.
26997366 Modulation of human monocyte/macrophage activity by tocilizumab, abatacept and etanercept: 2016 Jun 5 Tocilizumab, etanercept and abatacept are biological drugs used in the therapy of Rheumatoid Arthritis (RA). Their mechanism of action is well documented but their direct effects on human monocytes/macrophages have not been fully investigated. The objective of this study was to evaluate in vitro the influence of these drugs on monocytes/macrophages from healthy volunteers. Human monocytes were isolated from healthy anonymous volunteers and cultured as such or differentiated to monocyte-derived macrophages (MDMs). The effect of tocilizumab, etanercept and abatacept (at concentrations similar to those in plasma of patients) on superoxide anion production, matrix metalloproteinase-9 (MMP-9) gene expression and activity, Peroxisome Proliferator-Activated Receptor (PPAR)γ expression and cell phenotype was evaluated. Exposure of monocytes/macrophages to tocilizumab, etanercept or abatacept resulted in a significant decrease of the PMA-induced superoxide anion production. Interestingly, the expression of PPARγ was significantly increased only by tocilizumab, while etanercept was the only one able to significantly reduce MMP-9 gene expression and inhibit the LPS-induced MMP-9 activity in monocytes. When etanercept and abatacept were added to the differentiating medium, both significantly reduced the amount of CD206(+)MDM. This study demonstrates that etanercept, abatacept and tocilizumab affect differently human monocytes/macrophages. In particular, the IL-6 antagonist tocilizumab seems to be more effective in inducing an anti-inflammatory phenotype of monocytes/macrophages compared to etanercept and abatacept, also in light of the up-regulation of PPARγ whose anti-inflammatory effects are well recognised.
26776881 Auranofin-loaded nanoparticles as a new therapeutic tool to fight streptococcal infections 2016 Jan 18 Drug-loaded nanoparticles (NPs) can improve infection treatment by ensuring drug concentration at the right place within the therapeutic window. Poly(lactic-co-glycolic acid) (PLGA) NPs are able to enhance drug localization in target site and to sustainably release the entrapped molecule, reducing the secondary effects caused by systemic antibiotic administration. We have loaded auranofin, a gold compound traditionally used for treatment of rheumatoid arthritis, into PLGA NPs and their efficiency as antibacterial agent against two Gram-positive pathogens, Streptococcus pneumoniae and Streptococcus pyogenes was evaluated. Auranofin-PLGA NPs showed a strong bactericidal effect as cultures of multiresistant pneumococcal strains were practically sterilized after 6 h of treatment with such auranofin-NPs at 0.25 μM. Moreover, this potent bactericidal effect was also observed in S. pneumoniae and S. pyogenes biofilms, where the same concentration of auranofin-NPs was capable of decreasing the bacterial population about 4 logs more than free auranofin. These results were validated using a zebrafish embryo model demonstrating that treatment with auranofin loaded into NPs achieved a noticeable survival against pneumococcal infections. All these approaches displayed a clear superiority of loaded auranofin PLGA nanocarriers compared to free administration of the drug, which supports their potential application for the treatment of streptococcal infections.
26767111 Comparison of Pap Smear and Colposcopy in Screening for Cervical Cancer in Patients with S 2015 Nov INTRODUCTION: Cervical cancer is the second most common cancer among women worldwide. The sensitivity of conventional Pap smear in detecting cervical lesions before cervical cancer is 51%, which means the false negative value is 49%. The aim of this study was to compare two methods for screening for cervical cancer in patients with secondary immunodeficiency, i.e., the conventional Pap smear and colposcopy. METHODS: This cross-sectional study was conducted on 101 immunodeficient patients who were referred to the Gynecologic Clinic at Shahid Sadughi Hospital in Yazd from March 2011 to August 2012. All patients underwent the Pap test, a colposcopy, and a cervical biopsy, with the latter being considered as the gold-standard test. RESULTS: The most frequency of immunodeficiency was noted among patients with rheumatoid arthritis (53.3%), and this was followed by patients who were undergoing chemotherapy (30.7%), patients with lupus erythematosus (12.9%), and patients with AIDS (3%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the Pap smear were 18.2, 98.5, 85.5, 71.3, and 72.2%, respectively. The respective values for colposcopy were 66.7, 98.94, 80, 97.9, and 97%, respectively. CONCLUSION: In this study the accuracy, sensitivity, specificity, and negative predictive values of colposcopy were higher than those for the Pap smear in detecting high-grade, cervical, pre-malignant lesions (cervical intraepithelial neoplasia: CIN ≥ 2). Therefore, an annual colposcopy is advised for secondary immunodeficient patients instead of a Pap smear.
26752990 Transdermal iontophoretic delivery of celecoxib from gel formulation. 2015 Sep Celecoxib is used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, joint inflammation and sport injuries. Long term administration of the drug results in such complications as gastrointestinaland renal disturbances and cardio-vascular complications. The main objective of the present study was to investigate the feasibility of delivering celecoxib incorporated in gel formulations by iontophoresis. Sodium alginate, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose (HPMC) and carbopol 934P were used to develop topical gel formulations of celecoxib. The gel formulations were evaluated for macroscopic and microscopic properties, pH determination, spreadability, rheological behaviour, and drug release characteristics both in vitro and ex vivo. Drug release was evaluated in the presence of iontophoresis field (0.1 to 0.5 mA/cm(2)) or without electrical current (passive diffusion) and celecoxib was measured spectrophotometrically at 252 nm. Most gel formulations showed acceptable physicochemical properties. Amongst formulations, gel formulation containing HPMC K4M which indicated greater performance in drug release behaviour was selected for further in vivo studies. The cumulative percent of drug released in vitro at the end of each experiment was 36%, 63%, and 89.7% for passive diffusion, direct electric current (DC) current density of 0.3 mA/cm(2), and 0.5 mA/cm(2), respectively. The findings of ex vivo drug transport across rat skin also showed a significantly higher release of celecoxib compared to passive flux for both AC and DC currents. A 0.5 mA/cm(2) of DC current increased drug flux to 73% compared to 41.5% of passive diffusion. It can be concluded from the results of this study that the application of iontophoresis enhances the flux of celecoxib, as compared to the passive diffusion.
26701644 Personal Authentication Analysis Using Finger-Vein Patterns in Patients with Connective Ti 2015 OBJECTIVE: To examine how connective tissue diseases affect finger-vein pattern authentication. METHODS: The finger-vein patterns of 68 patients with connective tissue diseases and 24 healthy volunteers were acquired. Captured as CCD (charge-coupled device) images by transmitting near-infrared light through fingers, they were followed up in once in each season for one year. The similarity of the follow-up patterns and the initial one was evaluated in terms of their normalized cross-correlation C. RESULTS: The mean C values calculated for patients tended to be lower than those calculated for healthy volunteers. In midwinter (February in Japan) they showed statistically significant reduction both as compared with patients in other seasons and as compared with season-matched healthy controls, whereas the values calculated for healthy controls showed no significant seasonal changes. Values calculated for patients with systemic sclerosis (SSc) or mixed connective tissue disease (MCTD) showed major reductions in November and, especially, February. Patients with rheumatoid arthritis (RA) and patients with dermatomyositis or polymyositis (DM/PM) did not show statistically significant seasonal changes in C values. CONCLUSIONS: Finger-vein patterns can be used throughout the year to identify patients with connective tissue diseases, but some attention is needed for patients with advanced disease such as SSc.
26639475 Simultaneous quantitation of Ofloxacin, Fexofenadine HCl and Diclofenac Potassium in affix 2015 Nov A high-pressure liquid chromatography (HPLC-UV) based simple and specific method for simultaneous quantitative determination of Ofloxacin, Fexofenadine HCl and Diclofenac Potassium has been developed and validated according to ICH guidelines. Chromatographic separation of the three drugs was carried out on 4.6 x 250 mm x 5 µ Licrospher RP Select B Column, using mobile phase constituted of methanol and phosphate buffer pH 3.5 (650: 350), pH adjusted to 3.5 ± 0.05 with dilute ortho-phosphoric acid and delivered at a flow rate of 1 ml/min. The eluents were detected at UV wavelength of 220 nm and the retention times for Ofloxacin, Fexofenadine HCl and Diclofenac Potassium were 2.5 minutes, 4 minutes and 11.5 minutes, respectively. This method is suitable and specific for the three drugs and was found to be linear (R² > 0.996), accurate, specific, reproducible and robust over a concentration range of 0.05 to 0.15 mg/ml for Ofloxacin, 0.015 to 0.045 mg/ml for Fexofenadine HCl and 0.0125 to 0.0375 mg/ml for Diclofenac Potassium. The proposed method is simple and convenient, hence easily utilized for the characterization and quantitation of the three drugs in a single formulation for combination therapy of rheumatoid arthritis, sepsis, infection with fever and flu.
26276169 Protective effect of soft contact lenses after Boston keratoprosthesis. 2016 Apr PURPOSE: To evaluate associations between preoperative diagnosis, soft contact lens (SCL) retention and complications. METHODS: A retrospective chart review was conducted of 92 adult patients (103 eyes) who received a Boston keratoprosthesis type I at the Massachusetts's Eye and Ear Infirmary or the Flaum Eye Institute. Records were reviewed for preoperative diagnosis, SCL retention and subsequent complications. Preoperative categories included 16 autoimmune (Stevens-Johnson syndrome, ocular cicatricial pemphigoid, rheumatoid arthritis and uveitis), 9 chemical injury and 67 'other' (aniridia, postoperative infection, dystrophies, keratopathies) patients. RESULTS: 50% of the lenses had been lost the first time after about a year. A subset (n=17) experienced more than 2 SCL losses per year; this group is comprised of 1 patient with autoimmune diseases, 2 patients with chemical injuries and 14 patients with 'other' diseases. The preoperative diagnosis was not predictive of contact lens retention. However, multivariate analysis demonstrated that the absence of a contact lens was an independent risk factor for postoperative complications, such as corneal melts with or without aqueous humour leak/extrusion and infections. CONCLUSIONS: Presence of a contact lens after Boston keratoprosthesis implantation decreases the risk of postoperative complications; this has been clinically experienced by ophthalmologists, but never before has the benefit of contact lens use in this patient population been statistically documented.
26264895 Readmissions Following Gastric Bypass Surgery. 2016 Feb BACKGROUND: Interest is growing in preventing readmissions as payers start to link reimbursement to readmission rates. The purpose of this study was to assess factors contributing to 30-day readmission for patients undergoing gastric bypass (GB) and determine whether these readmissions may be preventable. METHODS: Data were from the Pennsylvania Health Care Cost Containment Council (PHC4) and included all patients undergoing elective GB for obesity in 2011 (n = 4427). The outcomes measured were length of stay (LOS) and 30-day readmission. Univariate comparisons between characteristics of readmitted (n = 298) and non-readmitted (n = 4133) patients were performed. Readmission was modeled using multivariate logistic regression; LOS was modeled using linear regression. RESULTS: Of the 298 (6.6%) patients who were readmitted, the most common causes for readmission were bleeding (11.84%), infection (8.88%), and abdominal pain (7.89%). In multivariate analyses, black race, open GB, and history of myocardial infarction or rheumatoid arthritis were associated with increased odds of readmission. Longer LOS was also predictive of readmission (OR 1.10, p = <0.0001). Patients who were >50 years old and those with history of congestive heart failure, peripheral vascular, and kidney diseases were more likely to have longer LOS. Black race, open surgery, and discharge to an extended care facility were also predictive of prolonged LOS. CONCLUSIONS: The most common causes of readmission following elective GB were bleeding, infection, and abdominal pain. Since several patient-specific factors were associated with higher odds of readmission and longer LOS, there are opportunities to design interventions to prevent readmissions and decrease LOS in this patient population.
26015667 Aggressive periodontitis: An appraisal of systemic effects on its etiology-genetic aspect. 2015 Mar BACKGROUND: Myeloperoxidase (MPO) is a lysosomal enzyme found in the azurophilic granules of polymorphonuclear leukocytes and is able to mediate inflammatory tissue destruction in aggressive and chronic periodontitis (CP). Human telomerase is a multi subunit ribonucleoprotein enzyme concerned with telomeric lengthening and homeostasis in man and has been found to be elevated in inflammatory conditions such as rheumatoid arthritis and periodontitis. The aim of this study was to explore in aggressive periodontitis (AP) subjects: (i) The role of MPO-463G/A gene polymorphism and (ii) the level of telomerase expression. These parameters have been compared with the subjects of CP and that of the healthy controls. MATERIALS AND METHODS: A total of 45 subjects of the age group 20-50 years and free from any known systemic disease were included in the study. They were divided into three groups - Group I-periodontally healthy control (n = 15), Group II-CP (n = 15) and Group III-AP (n = 15). Peripheral blood samples and gingival tissue samples were collected for MPO gene polymorphism and telomerase expression, respectively, for detection by reverse transcriptase polymerase chain reaction. RESULTS: The frequencies of AG and AA genotypes in the MPO gene polymorphism were more common in the AP subjects when compared to the controls. The m-RNA expression of human telomerase reverse transcriptase (hTERT) was undetectable in the gingival tissue of the control group. Its expression in AP subjects was significantly higher than that of CP group (83.61 ± 2.94 in CP and 104.27 ± 6.06 in AP) (P < 0.0001). CONCLUSIONS: Our data suggest that MPO-463G/A may be associated with increased risk of AP. The level of tissue hTERT was elevated in AP subjects as compared to CP and healthy control groups.
25993011 Toddaculin, Isolated from of Toddalia asiatica (L.) Lam., Inhibited Osteoclastogenesis in 2015 Osteoporosis with bone loss is widely recognized as a major health problem. Bone homeostasis is maintained by balancing bone formation and bone resorption. The imbalance caused by increased bone resorption over bone formation can lead to various bone-related diseases such as osteoporosis and rheumatoid arthritis. Osteoclasts are the principal cells responsible for bone resorption and the main targets of anti-resorptive therapies. However, excessive inhibition of osteoclast differentiation may lead to inhibition of osteoblast differentiation. Therefore, it is important to screen for new compounds capable of inhibiting bone resorption and enhancing bone formation. Toddalia asiatica (L.) Lam. has been utilized traditionally for medicinal purposes such as the treatment of rheumatism. Currently, the extract is considered to be a good source of pharmacological agents for the treatment of bone-related diseases, but the active compounds have yet to be identified. We investigated whether toddaculin, derived from Toddalia asiatica (L.) Lam., affects both processes by inhibiting bone resorption and enhancing bone formation. Towards this end, we used pre-osteoclastic RAW 264 cells and pre-osteoblastic MC3T3-E1 cells. We found that toddaculin not only inhibited the differentiation of osteoclasts via activation of the NF-κB, ERK 1/2, and p38 MAPK signaling pathways, but it also induced differentiation and mineralization of osteoblasts by regulating differentiation factors. Thus, toddaculin might be beneficial for the prevention and treatment of osteoporosis.
25973441 Assessment of physicochemical properties of rituximab related to its immunomodulatory acti 2015 Rituximab is a chimeric monoclonal antibody employed for the treatment of CD20-positive B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis. It binds specifically to the CD20 antigen expressed on pre-B and consequently on mature B-lymphocytes of both normal and malignant cells, inhibiting their proliferation through apoptosis, CDC, and ADCC mechanisms. The immunomodulatory activity of rituximab is closely related to critical quality attributes that characterize its chemical composition and spatial configuration, which determine the recognition of CD20 and the binding to receptors or factors involved in its effector functions, while regulating the potential immunogenic response. Herein, we present a physicochemical and biological characterization followed by a pharmacodynamics and immunogenicity study to demonstrate comparability between two products containing rituximab. The physicochemical and biological characterization revealed that both products fit within the same response intervals exhibiting the same degree of variability. With regard to clinical response, both products depleted CD20+ B-cells until posttreatment recovery and no meaningful differences were found in their pharmacodynamic profiles. The evaluation of anti-chimeric antibodies did not show differential immunogenicity among products. Overall, these data confirm that similarity of critical quality attributes results in a comparable immunomodulatory activity.
25760632 Specific management of post-chikungunya rheumatic disorders: a retrospective study of 159 2015 Mar BACKGROUND: Since 2003, the tropical arthritogenic chikungunya (CHIK) virus has become an increasingly medical and economic burden in affected areas as it can often result in long-term disabilities. The clinical spectrum of post-CHIK (pCHIK) rheumatic disorders is wide. Evidence-based recommendations are needed to help physicians manage the treatment of afflicted patients. PATIENTS AND METHODS: We conducted a 6-year case series retrospective study in Reunion Island of patients referred to a rheumatologist due to continuous rheumatic or musculoskeletal pains that persisted following CHIK infection. These various disorders were documented in terms of their clinical and therapeutic courses. Post-CHIK de novo chronic inflammatory rheumatisms (CIRs) were identified according to validated criteria. RESULTS: We reviewed 159 patient medical files. Ninety-four patients (59%) who were free of any articular disorder prior to CHIK met the CIR criteria: rheumatoid arthritis (n=40), spondyloarthritis (n=33), undifferentiated polyarthritis (n=21). Bone lesions detectable by radiography occurred in half of the patients (median time: 3.5 years pCHIK). A positive therapeutic response was achieved in 54 out of the 72 patients (75%) who were treated with methotrexate (MTX). Twelve out of the 92 patients (13%) received immunomodulatory biologic agents due to failure of contra-indication of MTX treatment. Other patients mainly presented with mechanical shoulder or knee disorders, bilateral distal polyarthralgia that was frequently associated with oedema at the extremities and tunnel syndromes. These pCHIK musculoskeletal disorders (MSDs) were managed with pain-killers, local and/or general anti-inflammatory drugs, and physiotherapy. CONCLUSION: Rheumatologists in Reunion Island managed CHIK rheumatic disorders in a pragmatic manner following the outbreak in 2006. This retrospective study describes the common mechanical and inflammatory pCHIK disorders. We provide a diagnostic and therapeutic algorithm to help physicians deal with chronic patients, and to limit both functional and economic impacts. The therapeutic indication of MTX in pCHIK CIR could be approved in future efficacy trials.
25699629 Modified Protocol Decreases Surgical Site Infections after Total Knee Arthroplasty. 2015 Oct We investigate the effectiveness of a comprehensive aseptic protocol in reducing surgical site infection (SSI) after knee arthroplasty in a single medical center with a high prevalence of MRSA. A database of all patients in a single center undergoing primary knee arthroplasty between 2005 and 2011 was reviewed for SSI using Centers for Disease Control criteria and AAOS guidelines. All patients were treated with an aseptic protocol consisting of the following: preoperative 2% mupirocin nasal ointment and 0.4% chlorhexidine surgical site wipes, modified instrument care, perioperative prophylactic vancomycin and cefazolin, and surgical site skin preparation with chlorhexidine, alcohol, and iodophor. We compare our protocol total knee arthroplasty SSI rate to our institutional historical control (2001-2004) and to contemporary literature. Among 1,224 patients, 70% were ASA class >2 and 64% had a body mass index (BMI) > 30 kg/m(2). We found an overall 0.49% infection rate, significantly lower than that of our institutional historical control (0.49 vs. 2.24%, p < 0.001; odds ratio [OR], 0.21; number needed to treat [NNT], 145) and seven recently published reports (p < 0.001-0.042; OR, 0.07-0.42). Compared with these reports, significantly more of our patients were ASA class > 2, BMI > 30 kg/m(2), immunosuppressed, or had rheumatoid arthritis. Our aseptic protocol decreases SSI in a high-risk population undergoing knee arthroplasty in a medical center and community with a high prevalence of MRSA.
26448173 Potential Application of Biological Products for the Treatment of Ocular Surface Inflammat 2015 Nov Various biological products have been introduced for the treatment of autoimmune diseases. The injection of tocilizumab [anti-interleukin (IL)-6R antibody] and a tumor necrosis factor receptor fusion protein (TNFR-Fc) has been approved for the treatment of rheumatoid arthritis. We investigated the effect of the anti-IL-6R antibody and TNFR-Fc on corneal inflammation. Topical instillation of the anti-IL-6R antibody (MR16-1, 2 μg/μL; anti-IL-6R group) or TNFR1-Fc (100 μg/mL; TNFR1 group) was performed after corneal wounds were induced in BALB/c mice by alkali burns. The injured eye was analyzed on day 14 or 28 after injury, and topical instillation was performed until day 14 or day 28. Corneal stromal sections were made using a laser capture microdissection system, and total RNA from the specimens was subjected to quantitative polymerase chain reaction array analysis. Topical instillation of phosphate-buffered saline (PBS) served as a control. The vascularized area was significantly reduced in the anti-IL-6R (day 14) and TNFR1 groups (day 28) compared with that in the PBS group. In the anti-IL-6R group, the expression levels of matrix metalloproteinase-13, monocyte chemotactic protein-1, and C-C motif ligand-22 were downregulated compared with those in the PBS group. In the TNFR1 group, expression of mitogen-activated protein kinase 8 was downregulated. These results indicate the possible application of biological products for topical instillation for the treatment of corneal inflammation.
26427728 Comparison of immune manifestations between refractory cytopenia of childhood and aplastic 2015 Dec This retrospective single-center study assessed the incidence and clinical features of immune manifestations of refractory cytopenia of childhood (RCC) and childhood aplastic anemia (AA). We evaluated 72 children with RCC and 123 with AA between February 2008 and March 2013. RCC was associated with autoimmune disease in 4 children, including 1 case each with autoimmune hemolytic anemia, rheumatoid arthritis, systemic lupus erythematosus, and anaphylactoid purpura. No children with AA were diagnosed with autoimmune diseases. Immune abnormalities were common in both RCC and AA; the most significant reductions were in the relative numbers of CD3-CD56+ subsets found in RCC. Despite the many similar immunologic abnormalities in AA and RCC, the rate of autoimmune disease was significantly lower in childhood AA than RCC (p=0.008, χ2=6.976). The relative numbers of natural killer cells were significantly lower in RCC patients than AA patients. By month 6, there was no significant difference in autoimmune manifestations between RCC and AA in relation to the response to immunosuppressive therapy (p=0.907, χ2=0.014). The large overlap of analogous immunologic abnormalities indicates that RCC and childhood AA may share the same pathogenesis.
26190800 Methotrexate influx via folate transporters into alveolar epithelial cell line A549. 2015 Aug Methotrexate (MTX), a drug used for the treatment of certain cancers as well as rheumatoid arthritis, sometimes induces serious interstitial lung injury. Although lung toxicity of MTX is related to its accumulation, the information concerning MTX transport in the lungs is lacking. In this study, we investigated the mechanisms underlying MTX influx into human alveolar epithelial cell line A549. MTX influx into A549 cells was time-, pH-, and temperature-dependent and showed saturation kinetics. The influx was inhibited by folic acid with IC50 values of 256.1 μM at pH 7.4 and 1.6 μM at pH 5.5, indicating that the mechanisms underlying MTX influx would be different at these pHs. We then examined the role of two folate transporters in MTX influx, reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT). The expression of RFC and PCFT mRNAs in A549 cells was confirmed by reverse transcription polymerase chain reaction. In addition, MTX influx was inhibited by thiamine monophosphate, an RFC inhibitor, at pH 7.4, and by sulfasalazine, a PCFT inhibitor, at pH 5.5. These results indicated that RFC and PCFT are predominantly involved in MTX influx into A549 cells at pH 7.4 and pH 5.5, respectively.