Are diet and exercise associated with depression in rheumatoid arthritis patients?

Background: Although depression is a common comorbidity of rheumatoid arthritis (RA), little is known about a potential treatment strategy. Current studies of dietary improvement for depression have recently emerged in the general population, but have hardly any coverage in RA. Also, less exercise increases the number of people experiencing depression, and current studies showed that most RA patients are physically inactive. Thus, our study aimed to identify the potential factors associated with depression in RA patients.Methods: We included 157 RA patients (84.7% female; mean age 56.43±13.9 years; mean disease duration 19.53±9.54 years). All participants completed the General Health Questionnaire - 28, the Visual Analogue Scale Pain, the 36-item Short Form Health Survey, the Physical Activity Scale, and the Food Frequency Questionnaire. Correlations and multiple linear regressions were used to analyse the data.Results: Bivariate analyses showed a significant association between disease activity (.25; p ≤ 0.01), functional disability (.22; p ≤ 0.01), pain (.35; p ≤ 0.001), fatigue (-.45; p ≤ 0.001), physical inactivity (-.19; p ≤ 0.05), frequent consumption of fried foods (-.22; p ≤ 0.01) and depression. No other foods were associated with depression in RA. The multiple regression analyses showed that disease activity, fatigue, and fried foods consumption were significantly associated with depression in the final model. However, the association between physical activity and depression was no longer significant using multivariate models. Explained variance in the final regression model was 27.6%.Conclusions: It appears that frequent consumption of fried foods is associated with depression in RA when controlled for sociodemographic and clinical variables. Further research on specific dietary habits and underlying mechanisms in the gut-brain axis may help to develop treatment options for the prevention of psychological distress in RA. (Grant: VEGA: 1/0748/22; APVV-15-0719

Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis in methotrexate-naive patients: the RESPOND study

Objective: To compare the efficacy and safety of treatment with infliximab plus methotrexate with methotrexate alone in methotrexate-naive patients with active psoriatic arthritis (PsA). Methods: In this open-label study, patients 18 years and older with active PsA who were naive to methotrexate and not receiving disease-modifying therapy (N=115) were randomly assigned (1:1) to receive either infliximab (5 mg/kg) at weeks 0, 2, 6 and 14 plus methotrexate (15 mg/week); or methotrexate (15 mg/week) alone. The primary assessment was American College of Rheumatology (ACR) 20 response at week 16. Secondary outcome measures included psoriasis area and severity index (PASI), disease activity score in 28 joints (DAS28) and dactylitis and enthesitis assessments. Results: At week 16, 86.3% of patients receiving infliximab plus methotrexate and 66.7% of those receiving methotrexate alone achieved an ACR20 response (p<0.02). Of patients whose baseline PASI was 2.5 or greater, 97.1% receiving infliximab plus methotrexate compared with 54.3% receiving methotrexate alone experienced a 75% or greater improvement in PASI (p<0.0001). Improvements in C-reactive protein levels, DAS28 response and remission rates, dactylitis, fatigue and morning stiffness duration were also significantly greater in the group receiving infliximab. In the infliximab plus methotrexate group, 46% (26/57) had treatment-related adverse events (AE) and two patients had serious AE, compared with 24% with AE (13/54) and no serious AE in the methotrexate-alone group. Conclusions: Treatment with infliximab plus methotrexate in methotrexate-naive patients with active PsA demonstrated significantly greater ACR20 response rates and PASI75 improvement compared with methotrexate alone and was generally well tolerated. This trial is registered in the US National Institutes of Health clinicaltrials.gov database, identifier NCT00367237

Steroid receptor coactivator 1 deficiency increases MMTV-neu mediated tumor latency and differentiation specific gene expression, decreases metastasis, and inhibits response to PPAR ligands

<p>Abstract</p> <p>Background</p> <p>The peroxisome proliferator activated receptor (PPAR) subgroup of the nuclear hormone receptor superfamily is activated by a variety of natural and synthetic ligands. PPARs can heterodimerize with retinoid X receptors, which have homology to other members of the nuclear receptor superfamily. Ligand binding to PPAR/RXRs results in recruitment of transcriptional coactivator proteins such as steroid receptor coactivator 1 (SRC-1) and CREB binding protein (CBP). Both SRC-1 and CBP are histone acetyltransferases, which by modifying nucleosomal histones, produce more open chromatin structure and increase transcriptional activity. Nuclear hormone receptors can recruit limiting amounts of coactivators from other transcription factor binding sites such as AP-1, thereby inhibiting the activity of AP-1 target genes. PPAR and RXR ligands have been used in experimental breast cancer therapy. The role of coactivator expression in mammary tumorigenesis and response to drug therapy has been the subject of recent studies.</p> <p>Methods</p> <p>We examined the effects of loss of SRC-1 on MMTV-neu mediated mammary tumorigenesis.</p> <p>Results</p> <p>SRC-1 null mutation in mammary tumor prone mice increased the tumor latency period, reduced tumor proliferation index and metastasis, inhibited response to PPAR and RXR ligands, and induced genes involved in mammary gland differentiation. We also examined human breast cancer cell lines overexpressing SRC-1 or CBP. Coactivator overexpression increased cellular proliferation with resistance to PPAR and RXR ligands and remodeled chromatin of the proximal epidermal growth factor receptor promoter.</p> <p>Conclusions</p> <p>These results indicate that histone acetyltransferases play key roles in mammary tumorigenesis and response to anti-proliferative therapies.</p

Abstract P5-05-09: Extract ERr731® does not mimic estrogen stimulated growth of MNU-induced breast cancer in ovariectomized Sprague-Dawley rats

Abstract Background: ERr731® (trade names Phyto-Strol® or femi-loges®), an extract isolated from the roots of the Siberian rhubarb (Rheum rhaponticum), is used as an alternative treatment option for menopausal complaints. In addition, it is regularly used for the treatment of oligomenorrhoea or amenorrhea. The efficacy of the extract on treatment of menopausal complaints was shown in clinical trials and follow-up studies. Although clinical trials did not show changes of mammographic density, we addressed the question whether ERr731 is capable to stimulate experimental breast cancer in an estrogen dependent manner. Objective: The aim of the study was to assess whether or not the special extract ERr731® in a dosage relevant to human applications is capable to stimulate the growth of methyl-nitroso-urea (MNU) induced experimental breast cancer in ovariectomized Sprague-Dawley (SD) rats. Experimentals: 32 female SD rats were obtained at the age of postnatal day (PND) 40. On PND 49 and 56 all animals received an intra peritoneal MNU injection of 50 mg/kg body weight (BW). 28 days after the second injection 24 animals were ovariectomized (OvEx) and randomly allocated to 3 experimental groups, 8 animals were SHAM operated and served as positive control. SHAM operated animals (first positive control) and one group of OvEX animals (negative control) were fed a (phyto)estrogen-free diet. A second positive control group of OvEx animals received the phytoestrogen-free diet supplemented with 10 mg/kg diet of estradiol-benzoate. To mimic human exposure, ERr731®, in a dose of 0.067 mg/kg BW/d was chosen which is equivalent to 2.5 mg of the extract/kg chow. The experiment was terminated 25 weeks after MNU injection. Tumor-specific parameters, as well as uterine wet weights (UWW) were assessed. Results: Ovariectomy reduced the UWW &amp;gt; 6fold. Estradiol-benzoate restored UWW almost completely, whereas ERr731® did not lead to an increase in UWW. Tumor incidence in estrogenized animals was 62.5% (5/8 animals) in the SHAM group and 50% (4/8 animals) in the estradiol-benzoate treated group. No tumors were detected in OvEx negative controls and OvEx animals supplemented with the human relevant dose of ERr731®. The total numbers of tumors were 17 in the group of SHAM operated animals and 5 in the estradiol-benzoate treatment group. Conclusions: The human dose of ERr731® did neither exhibit estrogenic properties in the uterotrophic assay nor did it stimulate growth of MNU-induced breast cancers in OvEx SD rats, whereas estradiol supplementation at a low dose as well as estradiol levels in animals with a regular estrus cycle significantly promoted tumor growth. In this experimental model the used human dosage of ERr731® therefore appears safe regarding estrogen dependent growth stimulation of experimental MNU breast cancers. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-05-09.</jats:p