Complementary alternative medicine in rheumatic diseases: Causes, choices, and outcomes according to patients.

OBJECTIVE: The knowledge of physicians about complementary and alternative medicine (CAM) applications is limited. However, especially in chronic diseases, patients and their relatives can often refer to CAM applications. Rheumatic diseases are chronic in nature presenting with a wide clinical spectrum. Despite developing treatment options, achieving treatment goals may not always be possible. For this reason, patients seek different treatment and use traditional and complementary medicine. The aim of this study was to investigate causes, consequences, and the frequency of applying to CAM in rheumatic diseases. METHODS: Ninety-five patients admitted to the rheumatology outpatient clinic were enrolled in the study. Health assessment questionnaire and short-form-36 were used to determine the quality of life of patients. Anxiety and depression symptoms were screened by the Hospital Anxiety and Depression scale, a questionnaire that was filled-in by the patients themselves. Also, patients were questioned about their place of residence, level of education, diagnosis, CAM modality types, application reasons, and outcomes. Chi-square test was used to analyze categorical data. Parametric data were analyzed using Student t-test, and nonparametric data were analyzed using Mann-Whitney U test. RESULTS: Thirty-two of our patients had applied to CAM modalities (phytotherapy [34.45%], cupping therapy [21.8%], acupuncture [12.5%], hirudotherapy [12.5%], food supplement [12.5%], and ozone treatment [6.25%]). Only 31.3% of the patients informed their doctors about CAM applications. 47.8% of fibromyalgia patients and 29.2% of patients with inflammatory rheumatic diseases had applied to CAM. Gender, working status, income level, smoking, and alcohol habits were not associated with the application to CAM. However, none of the residents of the village, 14.3% of the residents of the district center, and 41.1% of the residents of the city center had applied to CAM modality. The rate of applying to CAM was 18.2% for those who cannot read and write. The application ratio of CAM is over 40% among secondary school, high school, and university graduates. CONCLUSION: Among patients with rheumatic diseases, application to CAM is quite common. Very few patients inform their physicians about applying to CAM. Contrary to what is presumed, the rate of applying CAM applications is lower among those living in rural areas and with low education levels.

Tofacitinib and metformin reduce the dermal thickness and fibrosis in mouse model of systemic sclerosis.

Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is important in the process of inflammation and fibrosis. The adenosine 5'-monophosphate-activated protein kinase (AMPK) enzyme can affect JAK/STAT pathway. Tofacitinib is a pan-JAK inhibitör. Metformin activates AMPK enzyme. We aimed to investigate the therapeutic efficacy of tofacitinib and metformin on IL-17 and TGF-ß cytokines, skin fibrosis and inflammation in mouse model of systemic sclerosis (SSc). 40 Balb/c female mice were divided into 4 groups: (control, sham (BLM), tofacitinib and metformin). The mice in the tofacitinib group received oral tofacitinib (20 mg/kg/daily) and mice in the metformin group received oral metformin (50 mg/kg/day) for 28 days. At the end of 4th week, all groups of mice were decapitated and tissue samples were taken for analysis. Histopathological analysis of skin tissue was performed, and mRNA expressions of collagen 3A, IL-17 and TGF-ß were assessed by real-time PCR and ELISA. Repeated BLM injections had induced dermal fibrosis. Moreover, the tissue levels of collagen 3A, IL-17 and TGF-ß were elevated in the BLM group. Tofacitinib and metformin mitigated dermal fibrosis. They reduced dermal thickness and tissue collagen 3A, IL-17 and TGF-ß levels. Tofacitinib and metformin demonstrated anti-inflammatory and anti-fibrotic effects in the mouse model of SSc.

Secukinumab and metformin ameliorate dermal fibrosis by decreasing tissue interleukin-17 levels in bleomycin-induced dermal fibrosis.

Although the pathogenesis of systemic sclerosis is not exactly known, it is thought that immune activation has prominent roles in pathogenesis. Secukinumab is a monoclonal antibody against interleukin (IL)-17A. Metformin, a widely used antidiabetic medication, has anti-proliferative, immunomodulating and anti-fibrotic activities. The purpose of our study is to determine the therapeutic efficacy of secukinumab and metformin on bleomycin (BLM) induced dermal fibrosis. Fifty Balb/c female mice were divided into 5 groups: (group 1 control, 2 sham, 3 secukinumab, 4 metformin and 5 secukinumab + metformin). The mice in the control group received 100 µL phosphate-buffered saline (PBS), while the mice in other groups received 100 µL (100 µg) BLM in PBS subcutaneously (sc) every day for 4 weeks. In addition, mice in groups 3 and 5 received secukinumab at a dose of 10 mg/kg/wk sc, and mice in the groups 4 and 5 received oral metformin 50 mg/kg/d for 28 days. All groups of mice were sacrificed at the end of the 4th week and tissue samples were taken for analysis. In addition to histopathological analysis, skin tissue messenger RNA (mRNA) expressions of IL-17 and collagen 3A were measured by real-time polymerase chain reaction. Repeated BLM injections had caused dermal fibrosis. In addition, the mRNA expressions of IL-17 and collagen 3A were increased in the BLM group. Secukinumab and metformin ameliorated dermal fibrosis. They decreased dermal thickness and tissue IL-17A and collagen 3A mRNA levels. Secukinumab and metformin exhibit anti-fibrotic effects in the BLM-induced dermal fibrosis.

Resveratrol inhibits Src tyrosine kinase, STAT3, and Wnt signaling pathway in collagen induced arthritis model.

Resveratrol, a phytochemical, acts several cellular signaling pathways and has anti-inflammatory potentials. The purpose of this study is to research the therapeutic effect of resveratrol in collagen-induced arthritis (CIA) model in rats and whether resveratrol affects the activities of signaling pathways those are potent pathogenic actors of rheumatoid arthritis. Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant in Wistar albino rats. One day after the onset of arthritis (day 14), resveratrol (20 mg/kg/day) was given via oral gavage, until day 29. The paws of the rats were obtained for further analysis. Tissue Wnt5a, mitogen-activated protein kinase (MAPK), Src tyrosine kinase and signal transducer, and activator of transcription-3 (STAT3) mRNA expressions were determined by real-time polymerase chain reaction. Resveratrol ameliorated the clinical and histopathological (perisynovial inflammation and cartilage-bone destruction) findings of inflammatory arthritis. The tissue mRNA expressions of Wnt5a, MAPK3, Src kinase, and STAT3 were increased in the sham group compared to the control group. Resveratrol supplement decreased their expressions. The present study shows that Src kinase, STAT3, and Wnt signaling pathway are active in the CIA model. Resveratrol inhibits these signaling pathways and ameliorates inflammatory arthritis. © 2018 BioFactors, 45(1):69-74, 2019.

Serum GDF-15 level in Behçet's disease: relationships between disease activity and clinical parameters.

Growth differentiation factor-15 (GDF-15), a member of the transforming growth factor-ß superfamily of cytokines, plays an important role in cell growth, signal transduction, and apoptosis regulation. The aim of this study was to evaluate serum GDF-15 levels and their relationships with disease-related variables in patients with Behçet's disease (BD). Forty-six patients diagnosed with BD and 30 demographically matched healthy control subjects participated in the study. GDF-15 levels were measured in blood samples from patients and controls. The Behçet's Disease Current Activity Form (BDCAF) was used to evaluate the disease activity of BD. There were no significant differences between the two groups in C-reactive protein (CRP) level, mean erythrocyte sedimentation rate (ESR), age, body mass index, and mean GDF-15 levels (P > 0.05). Serum GDF-15 levels were positively correlated with findings for peripheral arthritis and CRP, and with BDCAF erythema nodosum, BDCAF arthralgia, and BDCAF arthritis scores. Patients with BD were divided into two groups according to the presence of peripheral arthritis; nine subjects (20%) were positive for peripheral arthritis. Serum ESR, CRP, white blood cell counts, and GDF-15 levels were significantly higher in the group that was positive for peripheral arthritis (P < 0.05). GDF-15 may play a role in the progression and pathway of Behçet's joint involvement and erythema nodosum that is independent of classic inflammatory response measures.

Comorbidities in patients with psoriatic arthritis: a comparison with rheumatoid arthritis and psoriasis.

AIM: Psoriatic arthritis (PsA) is a chronic, inflammatory disease. The purpose of this study was to examine the association between PsA and comorbid conditions. This is the first study to investigate comorbid diseases in PsA in Turkey. METHODS: This study was performed under the auspices of the Anatolian Group for the Assessment in Rheumatic Diseases (ANGARD) and involved participation by six university research hospitals. Patients diagnosed with and treated for PsA on the basis of clinical, radiological and laboratory findings and expert opinion were monitored using standardized examination methods and jointly prepared forms. Clinical status, accompanying systemic diseases and surgical history were recorded. RESULTS: One hundred and seventy-three patients with PsA (75 male, 98 female, mean age 41.8) and 138 patients with rheumatoid arthritis (RA) (17 male, 121 female, mean age 48.6) and 67 with psoriasis (PsO) (43 male, 24 female, mean age 36.1) were included in the study. No accompanying disease was determined in 72.8% of PsA, 50.0% of RA and 80.6% of PsO groups. In regression analysis, patients with PsA had higher risk for cataract/glaucoma surgery (odds ratio [OR] = 11.99; 95% CI 1.36-105.4, P = 0.025) compared to patients with RA, and higher risk for hypertension (HT) (OR = 4.26; 95% CI 1.27-14.23, P = 0.018) compared to the patients with PsO. CONCLUSION: Patients with PsA have relatively lower frequency of comorbidities like diabetes mellitus, HT and cataract/glaucoma surgery compared to the patients with RA. The increased risk for having cataract/glaucoma surgery in RA compared to PsA may be particularly attributed to the more prevalent glucocorticoid use in RA.