EGFR blocker lapatinib inhibits the synthesis of matrix metalloproteinases from synovial fibroblasts.

BACKGROUND: Epidermal growth factor receptor (EGFR) family members and their associated ligands may be related to bone and joint destruction in rheumatoid arthritis. Matrix metalloproteinases are responsible for joint and bone tissue degradation. This study is intended to investigate the effect of epidermal growth factor receptor inhibition by lapatinib on the synthesis of matrix metalloproteinases in in vitro. METHODS: Synovial fibroblast cell culture was obtained from a patient with rheumatoid arthritis who underwent knee arthroplasty. Interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were added to the cell culture to stimulate synovial fibroblast cells and create an inflammatory character. Understimulated and nonstimulated conditions, lapatinib was applied to the culture in four different concentrations of 25, 50, 100, and 200 µmol. Then, matrix metalloproteinase -1, -3, and, -13 levels were assessed. RESULTS: When stimulated with IL-1ß and TNF-α, the synthesis of matrix metalloproteinases from synovial fibroblast was increased significantly. When lapatinib is added to the stimulated synovial fibroblasts, matrix metalloproteinases synthesis is significantly suppressed. DISCUSSION: Inhibition of the EGFR pathway with lapatinib suppresses matrix metalloproteinases synthesis. Our results suggest EGFR pathway inhibition may be a promising option to prevent joint destruction in the treatment of rheumatoid arthritis.

Molecularly imprinted polymers in toxicology: a literature survey for the last 5 years.

The science of toxicology dates back almost to the beginning of human history. Toxic chemicals, which are encountered in different forms, are always among the chemicals that should be investigated in criminal field, environmental application, pharmaceutic, and even industry, where many researches have been carried out studies for years. Almost all of not only drugs but also industrial dyes have toxic side and direct effects. Environmental micropollutants accumulate in the tissues of all living things, especially plants, and show short- or long-term toxic symptoms. Chemicals in forensic science can be known by detecting the effect they cause to the body with the similar mechanism. It is clear that the best tracking tool among analysis methods is molecularly printed polymer-based analytical setups. Different polymeric combinations of molecularly imprinted polymers allow further study on detection or extraction using chromatographic and spectroscopic instruments. In particular, methods used in forensic medicine can detect trace amounts of poison or biological residues on the scene. Molecularly imprinted polymers are still in their infancy and have many variables that need to be developed. In this review, we summarized how molecular imprinted polymers and toxicology intersect and what has been done about molecular imprinted polymers in toxicology by looking at the studies conducted in the last 5 years.

Efficacy of anti-interleukin-1 treatment in colchicine-resistant arthritis in patients with familial Mediterranean fever.

OBJECTIVE: In the familial Mediterranean fever (FMF) clinic, arthritis is among the most common symptoms, and it generally responds well to colchicine treatment. However, cases of patients with chronic prolonged colchicine-resistant arthritis have been reported, and there are inadequate studies on the treatments to be used for such patients. METHODS: This study included 18 patients diagnosed with FMF who had colchicine-resistant chronic arthritis and received anti-interleukin (IL)-1 treatment for at least 1 year. The clinical and laboratory data of the patients were retrospectively retrieved from the database of our hospital. RESULTS: Remission was achieved in arthritis attacks in 16 of 18 patients who started anti-IL-1 therapy because of colchicine-resistant chronic arthritis. The clinical and laboratory values of the other 2 patients improved, but complete remission could not be achieved. The treatment dose of colchicine was reduced with anti-IL-1 therapy. In addition to the improvement in arthritis symptoms, remission was achieved in other clinical findings of FMF by anti-IL-1 therapy. In this study, with an average follow-up time of 33 months, no adverse effects requiring discontinuation were observed in any patient. CONCLUSION: Anti-IL-1 therapy is effective and reliable in the treatment of colchicine-resistant chronic FMF arthritis. The efficacy of anti-IL-1 therapy was realized without concomitant disease-modifying antirheumatic drug therapy, despite the reduction in colchicine dose.

The importance of Mediterranean fever gene in familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease characterized by recurrent serositis attacks and fever. The discovery of the Mediterranean fever (MEFV) gene has been a milestone in FMF etiopathogenesis. Our knowledge about the relationship between the MEFV gene and FMF phenotype increases each day. This study aims to investigate the relationship between MEFV gene mutations and the FMF clinical findings of a single-center FMF cohort. METHODS: Gender, age, age at symptom onset, age at diagnosis, clinical characteristics, and MEFV gene analysis of the patients were recorded. RESULTS: A total of 837 FMF patients were included in this study. There were 515 females and 322 males. The age at symptom onset was 18.3±10.9 years, while the age at diagnosis was 24.4±10.9 years. The most common symptom that accompanied fever was peritonitis (91.1%), while the other common clinical findings were pleuritis (45%), myalgia (44%), and arthritis (36%). A total of 47 patients developed amyloidosis. A total of 553 (66%) FMF patients had M694V mutation, 221 (26%) of which were homozygous, while 332 (40%) were heterozygous. Exon 10 mutation frequency was 759 (91%), while the non-exon 10 mutation frequency was 78 (9%). There was no wild type among the patients. CONCLUSION: In conclusion, the fact that a vast majority of the disease burden was constituted by the exon 10, especially M694V mutations and that none of the 837 patients from our cohort had a wild-type FMF proved the significance of MEFV gene mutation analysis. Therefore, we speculate that it is necessary to examine the MEFV gene mutations in each FMF suspected case. It seems plausible to re-evaluate the FMF diagnosis for cases in which a wild type MEFV gene mutation occurs.

Effectiveness of Methotrexate in Idiopathic Granulomatous Mastitis Treatment.

BACKGROUND: Idiopathic granulomatous mastitis is a rare inflammatory disease of the breast, for which there is a lack of consensus on the treatment protocol; it requires long-term follow-up and is associated with a high rate of relapse after surgical treatment. In this study, we report on the largest single-center cohort of idiopathic granulomatous mastitis treated with steroids + methotrexate. METHODS: We retrospectively examined the data of 33 patients histopathologically diagnosed with idiopathic granulomatous mastitis who were evaluated by our Rheumatology or General Surgery Clinics between 2013 and 2016. RESULTS: Of the 33 female patients (age: 38.64 ± 6.9 years), 24 were admitted with an initial diagnosis of idiopathic granulomatous mastitis, whereas 9 were admitted after surgical treatment. Remission was achieved in 87.9% of patients with steroid + methotrexate treatment, and there were no relapses during the 24-months follow-up period. CONCLUSIONS: Steroid + methotrexate treatment is an effective and reliable method for ensuring long-term remission in patients with idiopathic granulomatous mastitis diagnosis.

Infliximab treatment in refractory vascular Behcet's disease: A single-center experience.

OBJECTIVE: This study aims to investigate the efficacy and reliability of infliximab treatment in Behcet's disease with vascular involvement. METHODS: This single-center retrospective study included a total of 18 patients diagnosed with Behcet's disease with vascular involvement who were initiated infliximab treatment after exhibiting resistance to conventional immunosuppressive treatments. RESULTS: Seventeen patients achieved remission with infliximab treatment. While 18 patients were receiving a median of 50 (IQR: 20-61) mg/day equivalent of methylprednisolone before infliximab treatment, after infliximab treatment, only four patients were receiving 4 mg/day equivalent of methylprednisolone (p < 0.001). Only 4 patients were receiving oral anticoagulant treatment during infliximab treatment, and compared to the patients who were not receiving oral anticoagulants, there was no significant difference between the two groups according to occurrence of new vascular events. CONCLUSION: Infliximab seems to be an effective and reliable treatment in Behcet's disease with vascular involvement and may also allow reduced dosage or even the discontinuation of corticosteroids. The results of our study suggest that oral anticoagulant use is unnecessary in Behcet's disease with vascular involvement. However, further long-term randomized controlled studies are needed to investigate the length of infliximab regimen, whether or not it should be discontinued, and if so, whether or not immunosuppressants should be given as maintenance after discontinuation.

Chronic cough and tachycardia-induced cardiomyopathy in a patient with idiopathic frequent, monomorphic premature ventricular contractions.

A 70-year-old woman presented with a 1-year history of dry cough. Extensive work-up ruled out common causes of chronic cough. She was found to have very frequent, monomorphic premature ventricular contractions (PVCs) and mild-to-moderate left ventricular systolic dysfunction. Propafenone 450 mg/day resulted in complete resolution of her cough and disappearance of PVCs within 24 hours of initiation. One month after the initiation of propafenone therapy, left ventricular ejection fraction normalized and her chronic cough resolved completely.