PURPOSE: To compare the recurrence rates and complications associated with instillation of topical mitomycin C, cyclosporine, and bevacizumab after primary pterygium surgery. METHODS: Between July 2013 and June 2014, we performed surgery using the bare sclera method on 132 eyes (132 patients) with primary pterygium. We randomly selected 33 eyes (33 patients) and treated them with artificial tears four times a day for three months, 29 eyes (29 patients) were treated with topical 0.02% mitomycin C four times a day for five days, 34 eyes (34 patients) were treated with topical 0.05% cyclosporine four times a day for three months, and 36 eyes (36 patients) were treated with topical 2.5% bevacizumab four times a day for three months after surgery. We prospectively determined the recurrence rates of pterygium and complications at the six-month follow-up examination. RESULTS: At six months after surgery, the recurrence rates in each group were as follows: 45.5% (15 eyes) in the control group, 10.3% (three eyes) in the mitomycin C group, 20.6% (seven eyes) in the cyclosporine group, and 41.7% (15 eyes) in the bevacizumab group (p = 0.004). No serious complications, except subconjunctival hemorrhages, were observed in any group. CONCLUSIONS: Groups receiving topical 0.02% mitomycin C and 0.05% cyclosporine after surgery showed lower recurrence rates than the control group; however, no difference in recurrence rate was observed between the control group and the group receiving topical 2.5% bevacizumab after surgery.
Administration, Topical ; Aged ; Aged, 80 and over ; Alkylating Agents/administration & dosage ; Angiogenesis Inhibitors/administration & dosage ; Bevacizumab/*administration & dosage ; Cell Count ; Combined Modality Therapy ; Cyclosporine/*administration & dosage ; Double-Blind Method ; Endothelium, Corneal/pathology ; Female ; Humans ; Immunosuppressive Agents/administration & dosage ; Male ; Middle Aged ; Mitomycin/*administration & dosage ; Ophthalmic Solutions ; Ophthalmologic Surgical Procedures ; Prospective Studies ; Pterygium/diagnosis/*drug therapy/*surgery ; Recurrence ; Vascular Endothelial Growth Factor A/antagonists & inhibitors

No abstract available.
Crohn Disease/*drug therapy ; Female ; Humans ; Immunosuppressive Agents/*administration & dosage ; Male ; Oligonucleotides/*administration & dosage ; Smad7 Protein/*antagonists & inhibitors

Autophagy acts as an important homoeostatic mechanism by degradation of cytosolic constituents and plays roles in many physiological processes. Recent studies demonstrated that autophagy can also regulate the production and secretion of the proinflammatory cytokine interleukin-1β (IL-1β), which plays a critical role in the development and maintenance of neuropathic pain. In the present study, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were significantly decreased after spinal nerve ligation (SNL), and the changes were accompanied by inhibited autophagy in the spinal microglia and increased mRNA and protein levels of IL-1β in the ipsilateral spinal cord. We then investigated the antinociceptive effect of rapamycin, a widely used autopahgy inducer, on SNL-induced neuropathic pain in rats and found that treatment with intrathecal rapamycin significantly attenuated the mechanical allodynia and thermal hyperalgesia. Moreover, rapamycin significantly enhanced autophagy in the spinal microglia, whereas it reduced the mRNA and protein levels of IL-1β in the ipsilateral spinal cord. Our results showed that rapamycin could ameliorate neuropathic pain by activating autophagy and inhibiting IL-1β in the spinal cord.
Animals ; Autophagy ; drug effects ; Immunosuppressive Agents ; Interleukin-1beta ; antagonists & inhibitors ; metabolism ; Male ; Neuralgia ; drug therapy ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sirolimus ; pharmacology ; Spine ; metabolism ; pathology

BACKGROUND/AIMS: Our aim was to assess whether short-term treatment with soluble tumor necrosis factor (TNF) receptor affects circulating markers of bone metabolism in rheumatoid arthritis (RA) patients. METHODS: Thirty-three active RA patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum levels of bone metabolism markers were compared among patients treated with DMARDs at baseline and after etanercept treatment, normal controls and naive RA patients not previously treated with DMARDs (both age- and gender-matched). RESULTS: Bone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)-1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin levels increased. In patients whose DAS28 improved, the sclerostin level increased from 1.67 +/- 2.12 pg/mL at baseline to 2.51 +/- 3.03 pg/mL, which was statistically significant (p = 0.021). Increases in sclerostin levels after etanercept treatment were positively correlated with those of serum CTX-1 (r = 0.775), as were those of BSALP (r = 0.755). CONCLUSIONS: RA patients treated with DMARDs showed depressed bone metabolism compared to naive RA patients. Increases in serum CTX-1 and sclerostin levels after short-term etanercept treatment suggest reconstitution of bone metabolism homeostasis.
Adult ; Alkaline Phosphatase/blood ; Arthritis, Rheumatoid/blood/diagnosis/*drug therapy ; Biological Markers/blood ; Bone Morphogenetic Proteins/blood ; Bone Remodeling/*drug effects ; Collagen Type I/blood ; Female ; Genetic Markers ; Homeostasis ; Humans ; Immunoglobulin G/*administration & dosage ; Immunosuppressive Agents/*administration & dosage ; Inflammation Mediators/blood ; Male ; Middle Aged ; Peptides/blood ; Receptors, Tumor Necrosis Factor/*administration & dosage ; Time Factors ; Treatment Outcome ; Tumor Necrosis Factor-alpha/antagonists & inhibitors

There is no consensus on whether it is safe to re-administer tumor necrosis factor-alpha (TNFalpha) inhibitors in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) flared after withdrawal of TNFalpha inhibitors due to active tuberculosis (TB). We evaluated the safety of restarting anti-TNFalpha therapy in patients with TNFalpha-associated TB. We used data of 1,012 patients with RA or AS treated with TNFalpha inhibitors at Seoul St. Mary's Hospital between January 2003 and July 2013 to identify patients who developed active TB. Demographic and clinical data including the results of tuberculin skin tests (TST) and interferon-gamma releasing assays (IGRA) were collected. Fifteen patients developed active TB. Five cases were occurred in RA and 10 cases in AS. Nine of 15 patients had a negative TST or IGRA and 6 TST-positive patients had received prophylaxis prior to initiating anti-TNFalpha therapy. All patients discontinued TNFalpha inhibitors with starting the treatment of TB. Eight patients were re-administered TNFalpha inhibitors due to disease flares and promptly improved without recurrence of TB. TNFalpha inhibitors could be safely resumed after starting anti-TB regimen in patients with RA or AS.
Adult ; Aged ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects/therapeutic use ; Antibodies, Monoclonal/adverse effects/therapeutic use ; Antibodies, Monoclonal, Humanized/adverse effects/therapeutic use ; Antirheumatic Agents/adverse effects/therapeutic use ; Arthritis, Rheumatoid/*drug therapy ; Enzyme Inhibitors/adverse effects/therapeutic use ; Female ; Humans ; Hydroxychloroquine/adverse effects/therapeutic use ; Immunoglobulin G/adverse effects/therapeutic use ; Immunosuppressive Agents/adverse effects/*therapeutic use ; Interferon-gamma Release Tests ; Male ; Methotrexate/adverse effects/therapeutic use ; Middle Aged ; Mycobacterium tuberculosis/isolation & purification ; Receptors, Tumor Necrosis Factor/therapeutic use ; Retrospective Studies ; Spondylitis, Ankylosing/*drug therapy ; Tuberculin Test ; Tuberculosis/*chemically induced/microbiology ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

BACKGROUND/AIMS: Individuals being treated with tumor necrosis factor (TNF)-alpha inhibitors are at increased risk of developing tuberculosis (TB). We determined the clinical characteristics and treatment response of patients who developed TB after using TNF-alpha inhibitors. METHODS: Patients with TB detected within 12 months of the initiation of TNF-alpha inhibitor treatment were included, if seen from January 1, 2000 to August 31, 2011. We retrospectively reviewed the clinical records, results of bacteriological examinations, and radiographs of the included patients and the response to anti-TB treatment. RESULTS: We indentified seven cases of TB in 457 patients treated with TNF-alpha inhibitors during the study period. TB developed a median of 123 days (range, 48 to 331) after the first dose of TNF-alpha inhibitor. Pulmonary TB, including TB pleuritis, was diagnosed in three patients and extrapulmonary TB in four. Favorable treatment outcomes were achieved in six of seven patients. CONCLUSIONS: Among the TNF-alpha inhibitor users who contracted TB, extrapulmonary sites were common and the treatment response was satisfactory.
Adult ; Aged ; Antitubercular Agents/therapeutic use ; Female ; Humans ; *Immunocompromised Host ; Immunosuppressive Agents/*adverse effects ; Interferon-gamma Release Tests ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; Tuberculin Test ; Tuberculosis/diagnosis/drug therapy/*immunology/microbiology ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

No abstract available.
Female ; Humans ; *Immunocompromised Host ; Immunosuppressive Agents/*adverse effects ; Male ; Tuberculosis/*immunology ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

Understanding of the pathophysiology of inflammatory bowel disease (IBD) is constantly evolving and, recently, a number of biologic agents have been developed. They selectively target specific molecule or pathways and correct the imbalance of the gut immune system. Among them, antibody to tumor necrosis factor (anti-TNF-alpha) is the first developed drugs, and it dramatically improved the IBD management. However, more than one-third of the patients do not respond to the drugs due to antibody formation. To increase treatment efficacy, enormous effort to develop novel anti-cytokines which can be an alternative to anti-TNF-alpha has been made. They are anti CD4+ T cell cytokine including interleukin (IL)-12/23 and IL-17 blockers, selective anti-adhesion molecule known as natalizumab, vedolizumab and alicaforsen, T-cell proliferation inhibitor, anti-inflammatory cytokine, immune stimulator, growth factor, and mitogen-activated protein kinase inhibitor. The efficacy and safety of each drugs are under investigation. Some drugs reported very promising data, however, others showed disappointing and different results. In addition, most of the trials were done in a very small number of patients, and there is no trial comparing to anti-TNF-alpha. The present paper reviews the action mechanism, short or long term efficacy and safety of variable drugs other than anti-TNF-alpha in IBD.
Antibodies, Monoclonal/therapeutic use ; Cell Migration Inhibition ; Colony-Stimulating Factors/therapeutic use ; Cytokines/antagonists & inhibitors ; Gene Therapy ; Humans ; Immunosuppressive Agents/therapeutic use ; Inflammatory Bowel Diseases/drug therapy/*therapy ; Intercellular Signaling Peptides and Proteins/therapeutic use ; Mitogen-Activated Protein Kinases/antagonists & inhibitors ; Stem Cell Transplantation ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors/immunology

This report presents the case of a patient demonstrating multicentric Castleman's disease (MCD) with a lung lesion that was successfully treated with an anti-interleukin-6 receptor antibody, tocilizumab in combination with corticosteroid and tacrolimus. A 43-yr-old female with abnormal shadows on a chest X-ray was referred to the hospital for further examination. She was diagnosed as having MCD based on the characteristic pathology of inguinal lymph node, lung lesions, laboratory data, and undifferentiated arthritis. Corticosteroid and rituximab therapy did not fully ameliorate the symptoms; thus, the therapeutic regimen was changed to include tocilizumab, oral corticosteroid and tacrolimus. This regimen resulted in clinical remission and the dose of tocilizumab and corticosteroid could be tapered. Tocilizumab in combination with corticosteroid and tacrolimus may therefore be a beneficial treatment regimen for lung lesions associated with MCD.
Adrenal Cortex Hormones/therapeutic use ; Adult ; Antibodies, Monoclonal/*therapeutic use ; Drug Therapy, Combination ; Female ; Giant Lymph Node Hyperplasia/*diagnosis/drug therapy/radiography ; Humans ; Immunosuppressive Agents/therapeutic use ; Lung Diseases, Interstitial/*drug therapy/pathology ; Lymph Nodes/pathology ; Receptors, Interleukin-6/antagonists & inhibitors ; Tacrolimus/therapeutic use ; Tomography, X-Ray Computed

OBJECTIVENeuroinflammation with microglial activation has been implicated to have a strong association with the progressive dopaminergic neuronal loss in Parkinson's disease (PD). The present study was undertaken to evaluate the activation profile of microglia in 1-methyl-4-phenyl pyridinium (MPP+)-induced hemiparkinsonian rats. Triptolide, a potent immunosuppressant and microglia inhibitor, was then examined for its efficacy in protecting dopaminergic neurons from injury and ameliorating behavioral disabilities induced by MPP+.

METHODSThe rat model of PD was established by intranigral microinjection of MPP+. At baseline and on day 1, 3, 7, 14, 21 following MPP+ injection, the degree of microglial activation was examined by detecting the immunodensity of OX-42 (microglia marker) in the substantia nigra (SN). The number of viable dopaminergic neurons was determined by measuring tyrosine hydroxylase (TH) positive neurons in the SN. Behavioral performances were evaluated by counting the number of rotations induced by apomorphine, calculating scores of forelimb akinesia and vibrissae-elicited forelimb placing asymmetry.

RESULTSIntranigral injection of MPP+ resulted in robust activation of microglia, progressive depletion of dopaminergic neurons, and ongoing aggravation of behavioral disabilities in rats. Triptolide significantly inhibited microglial activation, partially prevented dopaminergic cells from death and improved behavioral performances.

CONCLUSIONThese data demonstrated for the first time a neuroprotective effect of triptolide on dopaminergic neurons in MPP+-induced hemiparkinsonian rats. The protective effect of triptolide may, at least partially, be related to the inhibition of MPP+-induced microglial activation. Our results lend strong support to the use of immunosuppressive agents in the management of PD.

1-Methyl-4-phenylpyridinium ; antagonists & inhibitors ; toxicity ; Animals ; Biomarkers ; metabolism ; CD11b Antigen ; analysis ; metabolism ; Cell Count ; Cell Survival ; drug effects ; physiology ; Disability Evaluation ; Diterpenes ; pharmacology ; therapeutic use ; Dopamine ; metabolism ; Encephalitis ; drug therapy ; immunology ; prevention & control ; Epoxy Compounds ; pharmacology ; therapeutic use ; Gliosis ; drug therapy ; immunology ; prevention & control ; Herbicides ; antagonists & inhibitors ; toxicity ; Immunosuppression ; methods ; Immunosuppressive Agents ; pharmacology ; therapeutic use ; Male ; Microglia ; drug effects ; immunology ; Neurons ; drug effects ; immunology ; pathology ; Parkinsonian Disorders ; drug therapy ; immunology ; physiopathology ; Phenanthrenes ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; drug effects ; immunology ; physiopathology ; Treatment Outcome ; Tyrosine 3-Monooxygenase ; analysis ; metabolism