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ID PMID Title PublicationDate abstract
25198906 Real-time emission factor measurements of isocyanic acid from light duty gasoline vehicles 2014 Oct 7 Exposure to gas-phase isocyanic acid (HNCO) has been previously shown to be associated with the development of atherosclerosis, cataracts and rheumatoid arthritis. As such, accurate emission inventories for HNCO are critical for modeling the spatial and temporal distribution of HNCO on a regional and global scale. To date, HNCO emission rates from light duty gasoline vehicles, operated under driving conditions, have not been determined. Here, we present the first measurements of real-time emission factors of isocyanic acid from a fleet of eight light duty gasoline-powered vehicles (LDGVs) tested on a chassis dynamometer using the Unified Driving Cycle (UC) at the California Air Resources Board (CARB) Haagen-Smit test facility, all of which were equipped with three-way catalytic converters. HNCO emissions were observed from all vehicles, in contrast to the idealized laboratory measurements. We report the tested fleet averaged HNCO emission factors, which depend strongly on the phase of the drive cycle; ranging from 0.46 ± 0.13 mg kg fuel(-1) during engine start to 1.70 ± 1.77 mg kg fuel(-1) during hard acceleration after the engine and catalytic converter were warm. The tested eight-car fleet average fuel based HNCO emission factor was 0.91 ± 0.58 mg kg fuel(-1), within the range previously estimated for light duty diesel-powered vehicles (0.21-3.96 mg kg fuel(-1)). Our results suggest that HNCO emissions from LDGVs represent a significant emission source in urban areas that should be accounted for in global and regional models.
25591677 Endoscopic decompression of cervical spondylotic myelopathy using posterior approach. 2014 Nov BACKGROUND: Cervical spondylotic myelopathy, radiculopathy and myeloradiculopathy can be managed by laminoforaminotomy, or bilateral decompression using posterior approach in single or multilevel compression. Posterior endoscopic techniques allow preservation of motion segment and neural decompression without fusion. MATERIALS AND METHODS: A prospective study of 50 patients of cervical compressive myelopathy with primarily posterior lesion or multilevel anterior compression with acceptable preoperative lordosis was undertaken. Any instability, significant anterior compression, and cervical myelopathy secondary to tumor, trauma, severe ossification of posterior longitudinal ligament, rheumatoid arthritis, pyogenic spondylitis, and destructive spondylo-arthropathy were excluded from the study. There were 5, 23, 12, 10 patients with 2, 3, 4, 5 vertebral body level pathologies, respectively. RESULTS: There were 2, 4, 7, 32, and 5 patients in preoperative Nurick grade 0, 1, 2, 3, and 4, respectively with an average of 2.6 grades. All the patients improved in post-operative grading with 10, 34, and 6 patients in 0, 1, and 2 grades (average 0.92), respectively. Better outcome was observed in patients with good preoperative grade and in short segment compression on cord. There was no change in cervical Cobb angle after surgery. Follow-up ranged from 6 to 24 months (averages 19 months). There was small dural tear, minor bleeding from muscles or epidural vessels and temporary C 5 root injury in 1, 3, and 2 patients, respectively. CONCLUSION: Endoscopic decompression of cervical spondylotic myelopathy is a safe and an effective alternative treatment option in selected patients when pathologic changes are primarily posterior or multi level anterior lesions with acceptable preoperative lordosis.
25440726 Non-anti-infective effects of antimicrobials and their clinical applications: a review. 2015 Jan Antimicrobial agents are undoubtedly one of the key advances in the history of modern medicine and infectious diseases, improving the clinical outcomes of infection owing to their inhibitory effects on microbial growth. However, many antimicrobial agents also have biological activities stemming from their interactions with host receptors and effects on host inflammatory responses and other human or bacterial cellular biological pathways. These result in clinical uses of antimicrobial drugs that are distinct from their direct bacteriostatic or bactericidal properties. We reviewed the published literature regarding non-anti-infective therapeutic properties and proposed clinical applications of selected antimicrobials, specifically, macrolides, tetracyclines, sulfonamides, and ketoconazole. The clinical applications reviewed were varied, and we focused on uses that were clinically relevant (in terms of importance and burden of disease) and where published evidence exists. Such uses include chronic inflammatory pulmonary and skin disorders, chronic periodontitis, gastrointestinal dysmotility, rheumatoid arthritis, and cancer. Most of these potential therapeutic uses are not Food and Drug Administration approved. Clinicians need to weigh the use of antimicrobial agents for their non-anti-infective benefits, considering potential adverse effects and long-term effect on microbial resistance.
25400448 Interplay between intestinal alkaline phosphatase, diet, gut microbes and immunity. 2014 Nov 14 Intestinal alkaline phosphatase (IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP's role in the intestine is to dephosphorylate toxic microbial ligands such as lipopolysaccharides, unmethylated cytosine-guanosine dinucleotides and flagellin as well as extracellular nucleotides such as uridine diphosphate. IAP's ability to detoxify these ligands is essential in protecting the host from sepsis during acute inflammation and chronic inflammatory conditions such as inflammatory bowel disease. Also important in these complications is IAP's ability to regulate the microbial ecosystem by forming a complex relationship between microbiota, diet and the intestinal mucosal surface. Evidence reveals that diet alters IAP expression and activity and this in turn can influence the gut microbiota and homeostasis. IAP's ability to maintain a healthy gastrointestinal tract has accelerated research on its potential use as a therapeutic agent against a multitude of diseases. Exogenous IAP has been shown to have beneficial effects when administered during ulcerative colitis, coronary bypass surgery and sepsis. There are currently a handful of human clinical trials underway investigating the effects of exogenous IAP during sepsis, rheumatoid arthritis and heart surgery. In light of these findings IAP has been marked as a novel agent to help treat a variety of other inflammatory and infectious diseases. The purpose of this review is to highlight the essential characteristics of IAP in protection and maintenance of intestinal homeostasis while addressing the intricate interplay between IAP, diet, microbiota and the intestinal epithelium.
25381969 Management of patients with psoriasis treated with biological drugs needing a surgical tre 2014 Nov Tumor necrosis factor alpha (TNF-α) is a cytokine that plays a critical role in inflammatory and immune processes and in the control of infections and sepsis. Data on the perioperative management of patients treated with biologic drugs are limited and mainly in patients with rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). This retrospective study assesses variations in the incidence of side effects between psoriatic patients who temporarily discontinue or continue biological therapy before surgical treatment. Despite the immunosuppressive risk, our results suggest that postoperative complications are not influenced by the suspension of biologic therapies. As TNF-α plays a role in promoting collagen synthesis and wound healing, we suggest that anti-TNFs should be discontinued before major surgery, whereas for minor surgery, the lower rates of infections favor anti-TNF-α continuation, particularly since suspending anti-TNF therapy is known to induce psoriasis relapse.
25271379 Characteristics of hip fracture patients with and without muscle atrophy/weakness: predict 2015 Jan OBJECTIVE: Hip fractures have negative humanistic and economic consequences. Predictors and sub-groups of negative post-fracture outcomes (high costs and extensive healthcare utilization) were identified in patients with and without muscle atrophy/weakness (MAW). METHODS: Truven Health MarketScan data identified patients ≥50 years old with inpatient hospitalizations for hip fracture. Patients had ≥12 months of continuous healthcare insurance prior to and following index hospitalization and no hip fracture diagnoses between 7 days and 1 year prior to admission. Predictors and sub-groups of negative outcomes were identified via multiple logistic regression analyses and classification and regression tree (CART) analyses, respectively. RESULTS: Post-fracture 1-year all-cause healthcare costs (USD$31,430) were higher than costs for the prior year ($18,091; p < 0.0001). Patients with MAW had greater post-fracture healthcare utilization and costs than those without MAW (p < 0.05). Greater post-fracture costs were associated with a higher number of prior hospitalizations and emergency room visits, length of index hospitalization, Charlson Comorbidity Index (CCI), and discharge status; diagnosis of rheumatoid arthritis, osteoarthritis, or osteoporosis; and prior use of antidepressants, anticonvulsants, muscle relaxants, benzodiazepines, opioids, and oral corticosteroids (all p < 0.009). High-cost patient sub-groups included those with MAW and high CCI scores. CONCLUSIONS: Negative post-fracture outcomes were associated with MAW vs no MAW, prior hospitalizations, comorbidities, and medications.
25116951 Post-translational modifications of integrin ligands as pathogenic mechanisms in disease. 2014 Nov Protein post-translational modifications like glycation, carbamylation and citrullination increase the functional diversity of the proteome but in disease situations might do more harm than good. Post-translational modifications of ECM proteins are thus appearing as mechanisms, which contribute to tissue dysfunction in chronic kidney disease, in diabetes and in various inflammatory diseases. In chronic renal failure, carbamylation could lead to kidney fibrosis. In diabetes, high glucose levels lead to non-enzymatic glycation and cross-linking of collagens, which contribute to tissue stiffening with consequences for cardiovascular and renal functions. In inflammatory diseases, citrullination deiminates arginine residues with possible consequences for integrin-mediated cell adhesion to RGD- and GFOGER sequences in ECM proteins. Citrullination of fibronectin was in one study suggested to affect cell adhesion by modifying the heparin-binding site and not the RGD site. In a recent publication citrullination of GFOGER sequences in collagen II was demonstrated to selectively affect α10β1 and α11β1 integrin-mediated cell adhesion to collagen II, with consequences for synovial fibroblast and stem cell adhesion and migration. The implications of citrullination affecting integrin binding in disease open up a new area of study and might have implications for the pathogenesis of inflammatory diseases like rheumatoid arthritis and periodontitis.
25100747 Is Alzheimer's Disease Autoimmune Inflammation of the Brain That Can be Treated With Nasal 2015 May The Alzheimer's Association recently reported that a woman's estimated lifetime risk of developing Alzheimer's at age 65 is 1 in 6, compared to nearly 1 in 11 for a man (ie, female to male ratio 1.8). Based on female to male ratio, Alzheimer's disease could well be an autoimmune disorder. Like Alzheimer's, multiple sclerosis, an autoimmune inflammation of the central nervous system, has a female to male ratio of 2.3. Also based on female to male ratio, Alzheimer's resembles the autoimmune inflammatory disease rheumatoid arthritis, which has a female to male ratio of 2.7. The reasons for the female preponderance in autoimmune disease are unclear, but nonsteroidal anti-inflammatory drugs (NSAIDs) are widely and successfully employed to treat autoimmune anti-inflammatory disease and dramatically relieve symptoms. Moreover, oral NSAIDs consistently reduce the risk of Alzheimer's disease, although they have been totally ineffective as a treatment in multiple failed clinical trials. A basis for this failure might well be that the brain dose after oral administration is too small and not sufficiently early in the pathogenesis of the disorder. But NSAID brain dose could be significantly increased by delivering the NSAIDs intranasally.
24965722 Assessment of thyroid disorders and autoimmunity in patients with rheumatic diseases. 2014 We investigated whether there was a significant increase in thyroid autoimmunity, and disorders in patients with rheumatic diseases (RDs). We enrolled 201 patients with RDs (41 with ankylosing spondylitis, 15 with systemic lupus erythematosus, 80 with rheumatoid arthritis [RA], 65 with familial Mediterranean fever), and 122 healthy controls. Serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), C-reactive protein, and thyroid autoantibodies (anti-thyroglobulin and anti-thyroid peroxidase) were measured in all participants. There were no significant differences between the ages of the patients and controls. The mean TSH values of the patients with RDs and the controls were 3.1 ± 2.68 mIU/L and 1.9 ± 0.83 mIU/L, respectively (P = 0.004). The mean fT4 value of the patients with RDs was 1.43 ± 0.67 ng/dL whereas that of the controls was 1.58 ± 0.68 ng/dL (P <0.001). Subclinical hypothyroidism was detected in 24 patients with RDs. Thyroid antibodies were detected in 16 of 201 (8%) patients with RDs. Three of these patients had subclinical hypothyroidism, while the others were euthyroid. Thyroid autoantibodies were significantly higher in patients with RDs (P <0.001). Additionally, thyroid disorders were observed more frequently in patients with RDs than in the healthy controls. Based on our findings, we recommend that thyroid function tests should better be included in the clinical evaluation of patients with RDs.
24831789 Development of an HTS-compatible assay for the discovery of ASK1 signalosome inhibitors us 2014 May Genetic target validation studies have demonstrated that the apoptosis signal-regulating kinase 1 (ASK1) represents an important target for the treatment of rheumatoid arthritis, cardiac diseases, and several neurodegenerative disorders. To identify small-molecule inhibitors of ASK1, we have developed a high-throughput screening-compatible, homogenous, biochemical assay using AlphaScreen technology. This novel assay design utilizes purified stress-activated ASK1 signalosome complex, and it monitors phosphorylation of its full-length native substrate, MKK6. The assay has been optimized in a 384-well format and validated by screening the Sigma LOPAC library. The results presented here demonstrate that the assay is sensitive and robust with a Z' factor value of 0.88±0.04 and a signal-to-background ratio of 11, indicating that this assay can be used to screen large chemical libraries to discover novel inhibitors of ASK1.
24790673 Extended exposure in difficult total knee arthroplasty using tibial tubercle osteotomy. 2013 Sep OBJECTIVES: In some total knee arthroplasty cases, the usual medial parapatellar approach does not allow the appropriate patellar eversion and the desired exposure of the knee joint. Partial disinsertion of the patellar tendon doesn't substantially improve the surgical exposure and can lead to extensor apparatus weakening and complete secondary ruptures, while the V-Y quadricipital plasty leads to post-op immobilization of the knee, which delays the functional rehabilitation, with negative impact on the range of motion. The tibial tubercle osteotomy, however, allows an extension of the approach in total knee arthroplasty, without endangering the quadricipital extensor apparatus. MATERIAL AND METHODS: In this study we analysed the post-operative results of 11 cases of primary total knee arthroplasty in which a frontal plane osteotomy of the tibial tubercle was performed in addition to the standard medial parapatellar approach, as a result of the patients associated conditions, like rheumatoid arthritis with an extension deficit higher than 150, previous knee synovectomy by arthrotomy, progressive genu varum with more than 150 deviation, varus deviation of the lower limb with previous closing wedge proximal tibial osteotomy or patellar fractures with vicious consolidation. OUTCOMES: Overall, the results were more than satisfactory with a significant increase in the patients mean range of motion and Knee Society Score. There were some post-op issues in some of the patients, but they were adressed accordingly, having no long-term impact on the results. CONCLUSIONS: . We could thus conclude that, in special cases, the frontal plane tibial tubercle osteotomy is an effective technique which can provide a wide approach with appropriate protection of the knee extensor apparatus.
24559124 The risk of progressive multifocal leukoencephalopathy under biological agents used in the 2014 Biological agents such as monoclonal antibodies and soluble cytokine receptors have taken on an expanding role in the treatment of chronic immune mediated diseases. Progressive multifocal leukoencephalopathy (PML) is a rare central neurological disease caused by JC virus infection that has been described in the setting of conditions with severe impairment of immune surveillance, such as haematological malignancies, stem cell or solid organ transplantation and AIDS. This serious demyelinating disease has recently been described in patients receiving monoclonal antibodies for chronic inflammatory diseases such as multiple sclerosis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus or psoriasis. We review here the disease of PML, the different biological agents used in chronic inflammatory diseases that are associated with an increased risk of PML (natalizumab, rituximab, efalizumab and alemtuzumab), and the potential mechanisms that may explain the development of PML. Based on current knowledge of the biology of the JC virus and on the mechanisms of action of these biological agents, we discuss currently available tools that may be helpful in evaluating the risk of PML in this patient population.
24416448 TL1A induces TCR independent IL-6 and TNF-α production and growth of PLZF⁺ leukocytes. 2014 An elevated level of the cytokine TL1A is known to be associated with several autoimmune diseases, e.g. rheumatoid arthritis and inflammatory bowel disease. However, the mode of action of TL1A remains elusive. In this study, we investigated the role of TL1A in a pro-inflammatory setting, using human leukocytes purified from healthy donors. We show that TL1A, together with IL-12, IL-15 and IL-18, directly induces the production of IL-6 and TNF-α from leukocytes. Interestingly, TL1A-induced IL-6 was not produced by CD14⁺ monocytes. We further show that the produced IL-6 is fully functional, as measured by its ability to signal through the IL-6 receptor, and that the induction of IL-6 is independent of TCR stimulation. Furthermore, the transcription factor PLZF was induced in stimulated cells. These results offer a substantial explanation for the role of TL1A, since TNF-α and IL-6 are directly responsible for much of the inflammatory state in many autoimmune diseases. Our study suggests that TL1A is a possible target for the treatment of autoimmune diseases.
24357414 Synthesis, characterization and biodistribution studies of (125)I-radioiodinated di-PEGyla 2014 May PURPOSE: The objective of this study was to prepare a bisphosphonate (BP) mediated bone targeting di-PEGylated salmon calcitonin analogue sCT-2(PEG-BP) as a novel bone targeting pharmaceutical. METHODS: HPLC was used for isolation of sCT-2(PEG-BP) from the reaction mixture, followed by determination of possible PEGylation sites by trypsin digestion. Stability of the compound over time, bone mineral affinity using hydroxyapatite, and biodistribution in normal rats after radiolabeling of sCT-2(PEG-BP) or control sCT with (125)I was evaluated. RESULTS: PEGylated sCT analogues were synthesized, and sCT-2(PEG-BP) was isolated by HPLC and confirmed by MALDI-TOF and ICP-MS. MALDI-TOF analysis of trypsinized fragments suggested Cys(1) (or Lys(11)) and Lys(18) to be the two PEGylation sites. Bone mineral affinity test showed sCT-2(PEG-BP) or (125)I-sCT-2(PEG-BP) exhibited significantly increased bone mineral affinity over sCT or (125)I-sCT, respectively. sCT-2(PEG-BP) remained stable for at least 1 month. In vivo biodistribution study showed significantly increased bone retention and prolonged plasma circulation time for sCT-2(PEG-BP) compared to the control sCT. CONCLUSION: Those results support sCT-2(PEG-BP) as a promising new drug candidate for the treatment of resorptive and/or maladaptive bone conditions, such as Osteoporosis, Osteoarthritis, Rheumatoid Arthritis, Paget's disease and bone cancers.
24325804 Interleukin-6: from basic biology to selective blockade of pro-inflammatory activities. 2014 Feb Cytokines receptors exist in membrane bound and soluble form. A soluble form of the human IL-6R is generated by limited proteolysis and alternative splicing. The complex of IL-6 and soluble IL-6R stimulates target cells not stimulated by IL-6 alone, since they do not express the membrane bound IL-6R. We have named this process trans-signaling. Soluble gp130 is the natural inhibitor of IL-6/soluble IL-6R complex responses. Recombinant soluble gp130 protein is a molecular tool to discriminate between gp130 responses via membrane bound and soluble IL-6R responses. Neutralizing monoclonal antibodies for global blockade of IL-6 signaling and the sgp130Fc protein for selective blockade of IL-6 trans-signaling have been used in several animal models of human diseases. Using the sgp130Fc protein or sgp130Fc transgenic mice we demonstrate in models of inflammatory bowel disease, peritonitis, rheumatoid arthritis, atherosclerosis pancreatitis, colon cancer, ovarian cancer and pancreatic cancer, that IL-6 trans-signaling via the soluble IL-6R is the crucial step in the development and the progression of the disease. Therefore, sgp130Fc is a novel therapeutic agent for the treatment of chronic inflammatory diseases and cancer and it undergoes phase I clinical trials as an anti-inflammatory drug since June 2013.
24255778 Effects of leflunomide on inflamation and fibrosis in bleomycine induced pulmonary fibrosi 2013 Oct PURPOSES: Pulmonary fibrosis is a rare and progressive lung disease with a high mortality rate. The treatment regimens still fail to recover the disease. Leflunomide (LEF) is an immunomodulatory agent with antiproliferative activity that is used for the treatment of rheumatoid arthritis. The purpose of the study is to investigate the potential therapeutic efficacy of LEF in bleomycin (BLM) induced pulmonary fibrosis. METHODS: A total of 21 male, adult wistar albino rats were used. The animals were divided into three groups as control, BLM and BLM plus LEF groups (n=7). In BLM group, mice were treated with intratracheal instillation of BLM (2.5 U/kg). Control group received the same volume of saline instead of BLM. In LEF group, in addition to BLM, LEF (10 mg/kg, daily) was administrated by oral gavage. The effect of LEF on pulmonary inflammation and fibrosis was studied by measurements of serum clara cell protein-16 (CC-16), thiobarbituric acid reactive substance levels (TBARS), superoxide dismutase (SOD) and advanced oxidation protein products (AOPP) levels and lung tissue contents of IL-6, TNF-α and NF-κB by immunhistochemical examinations. RESULTS: LEF significantly increased the level of CC-16 and decreased the level of AOPP (P=0.042 and P=0.003 respectively). Lung tissue contents of IL-6, TNF-α and NF-κB significantly decreased in LEF group compared to BLM group by immunhistochemical examinations (P<0.001). CONCLUSIONS: LEF reduces oxidative stress factors, alveolar inflammation and attenuates lung injury and fibrosis.
24120697 Disturbed sleep in bipolar disorder is related to an elevation of IL-6 in peripheral monoc 2013 Dec Bipolar disorder is a severe psychiatric disorder that is associated with persistent changes in the quality, duration and architecture of sleep. Currently there is no unifying hypothesis explaining the alterations in sleep observable in patients with bipolar disorder and management is often difficult though vital. Sleep is modified by various cytokines including IL-6. Elevated levels of IL-6 are associated with a poorer quality of sleep and changes in the architecture of sleep similar to those observed in bipolar disorder. Therapeutic administration of Interferon causes elevations of intrathecal IL-6 concentrations and appears to provoke a deteriorating quality of sleep. The blockade of IL-6 with tocilizumab in rheumatoid arthritis is associated with improvements in the quality of sleep. Bipolar disorder is associated with elevated levels of IL-6 and in particular elevated levels of mRNA coding for IL-6 in peripheral monocytes. We propose that the changes observed in the sleep of patients with bipolar disorder are related to the elevation of IL-6 and that this correlates with an elevated expression of mRNA coding for IL-6 expression in peripheral monocytes.
24111584 Childhood psoriasis--an analysis of German health insurance data. 2014 Jan This study explored the epidemiology, treatment, and comorbidities of juvenile psoriasis in Germany using health insurance data. Psoriasis is a chronic inflammatory skin condition that affects approximately 2% to 3% of the world's population. Data were obtained from a database of approximately 6.7 million individuals registered with health insurance organizations throughout Germany. The analysis considered all individuals age 18 years and younger with psoriasis who were registered in 2007. Comorbidities were identified using software based on a morbidity-based risk adjustment model. A total of 138,338 patients with a diagnosis of psoriasis were identified in the database, yielding a prevalence of 2.1%. Within this group there were 4,499 children and adolescents (≤ 18 years of age), a prevalence of 0.4%. The prevalence ranged from 0.1% at the age of 1 year to 0.8% at the age of 18 years. Most of the patients were treated with topical corticosteroids (72.2%) and antipsoriatics (e.g., tars, psoralen; 20.0%). Immunosuppressants were used in 3.3% of the cases. Juvenile psoriasis was associated with numerous significant comorbidities such as rheumatoid arthritis and inflammation (2.1%); delirium, psychosis, and psychotic and dissociative disorder (1.1%); and heart disease (0.6%). Our study demonstrated that psoriasis is more prevalent in children and adolescents than some older international investigations have documented. Analysis of the health insurance data showed that juvenile psoriasis is associated with a range of comorbidities. The data also may suggest an unrecognized burden of mental health problems in young persons with psoriasis.
24029260 Incidence and clinical outcome of renal amyloidosis: a retrospective study. 2013 Sep The kidneys are affected in almost all patients with amyloid A in secondary amyloidosis (AA) amyloidosis but less frequently in immunoglobulin light chains in primary systemic amyloidosis (AL) amyloidosis. In this study, we present the incidence, etiology, clinical manifestations, biochemical features and clinical course of renal amyloidosis. We conducted a retrospective study on a group of 40 cases with renal biopsy-proven amyloidosis. They constituted 2.5% of the total cases of renal biopsies performed in the Theodor Bilharz Research Institute, Cairo, Egypt, during the period from February 2003 to May 2009. The mean age (30 males, ten females) was 36.51 ± 10.32 years. Thirty-two of the cases had secondary AA amyloidosis and eight cases had primary AL amyloidosis. The causes of secondary amyloidosis were as follows: 12 (30%) familial Mediterranean fever (FMF), eight (20%) pulmonary tuberculosis, four (10%) chronic osteomyelitis, four (10%) bronchiectasis, three (7%) rheumatoid arthritis and one (2%) rheumatic heart disease. The eight cases of primary AL amyloidosis comprised of five cases that were associated with myloma (13%) and three (8%) cases that were idiopathic. Among the 23 patients with AA amyloidosis, after six months of treatment with colchicine, the proteinuria improved, serum albumin level increased and edema disappeared in 13 patients. In four cases of AA amyloidosis who were clinically and biochemically normal after cholchicine therapy, a second renal biopsy disclosed decreased amyloid deposition compared with the first biopsy. In the three renal transplanted patients who had amyloidosis secondary to FMF and were treated with colchicines, AA amyloidosis did not recur in the transplanted kidney. It might be possible that in AL amyloidosis, treatment with methotrexate, melphalan and prednisolone may improve survival. The incidence of renal amyloidosis is increasing and colchicine can be used in secondary amyloidosis as it may have an effect on reducing the production of the amyloid precursor proteins and in reducing proteinuria.
23983404 Off-label uses of anti-TNF therapy in three frequent disorders: Behçet's disease, sarcoid 2013 Tumoral necrosis factor α plays a central role in both the inflammatory response and that of the immune system. Thus, its blockade with the so-called anti-TNF agents (infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab) has turned into the most important tool in the management of a variety of disorders, such as rheumatoid arthritis, spondyloarthropatties, inflammatory bowel disease, and psoriasis. Nonetheless, theoretically, some other autoimmune disorders may benefit from these agents. Our aim is to review these off-label uses of anti-TNF blockers in three common conditions: Behçet's disease, sarcoidosis, and noninfectious uveitis. Due to the insufficient number of adequate clinical trials and consequently to their lower prevalence compared to other immune disorders, this review is mainly based on case reports and case series.