Rheumatoid Arthritis research studies for holistic treatments

OBJECTIVE:
Stinging nettle leaf extracts are registered in Germany for adjuvant therapy of rheumatic s. In a whole blood culture system the nettle extract IDS 23 (Rheuma-Hek) inhibited lipopolysaccharide stimulated monocyte cytokine expression, indicating an immunomodulating effect. We investigated the immunomodulating effects of IDS 23 on phytohemagglutinin (PHA) stimulated peripheral blood mononuclear cells (PBMC) in vitro.
METHODS:
Using commercial immunoassays the distinct cytokine patterns of Th1 and Th2 cells were determined. Interleukin 2 (IL-2) and interferon-gamma (IFN-gamma) mRNA expression was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) with PHA stimulated PBMC.
Results:
IDS 23 inhibited PHA stimulated production of Th1-specific IL-2 and IFN-gamma in PBMC culture (n = 10) in a dose dependent manner up to 50+/-32% and 77+/-14%, respectively. In contrast, IDS 23 stimulated the secretion of Th2-specific IL-4. The dose dependent inhibiting effect on IL-2 and IFN-gamma expression was also detected with RT-PCR, while the amount of actin-specific mRNA transcript was not modified by IDS 23.
Conclusion:
Our results suggest the effective ingredient of IDS 23 acts by mediating a switch in T helper cell derived cytokine patterns. IDS 23 may inhibit the inflammatory cascade in autoimmune s like rheumatoid arthritis.

Arthritis and other rheumatic conditions (AORC) are the leading cause of disability, are associated with poor quality of life and incur considerable direct and indirect costs. It is considered that the instance of AORC will continue to increase. To assess the effectiveness, safety and tolerability of Harpagophytum (Bioforce) in the treatment of AORC, a single group open study of 8 weeks duration (259 patients) was performed in the United Kingdom. Effectiveness was assessed by numeric rating scales, the Western Ontario and McMasters Universities Osteoarthritis (WOMAC) Index and the Algofunctional Hand Osteoarthritis Index. Tolerance was measured by a numeric rating scale and safety by self-reporting, blood analysis and liver function tests. Quality of life was measured by SF-12 questionnaire. There were statistically significant (p < 0.0001) improvements in patient assessment of global pain, stiffness and function. There were also statistically significant reductions in mean pain scores for hand, wrist, elbow, shoulder, hip, knee and back pain. Quality of life measurements (SF-12) were significantly increased from baseline and 60% patients either reduced or stopped concomitant pain medication. Harpagophytum is an effective and well-tolerated serious treatment option for mild to moderate degenerative rheumatic disorders providing improved quality of life measure. Copyright (c) 2007 John Wiley & Sons, Ltd.

OBJECTIVE:
To evaluate the effects of oral nonsteroidal antiinflammatory drugs (NSAIDs) on C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients, with a prespecified focus on the different NSAIDs.
METHODS:
We performed a systematic search in Medline via PubMed, the Cochrane Central Register of Controlled Trials, EMBase via OVID, the Institute for Scientific Information Web of Science, and other sources. Eligible trials were parallel-group, randomized, placebo-controlled trials of oral NSAID therapy in RA patients for which there were extractable CRP data. Standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated from the differences in means of CRP levels between groups (active treatment minus placebo) divided by the pooled SDs. For the meta-analysis, a random-effects model was used to estimate the overall change in CRP level, and stratified analysis was used to examine differences among NSAIDs.
Results:
We included 19 trials of 10 different NSAIDs. Overall, NSAIDs showed no effect on the CRP level (SMD 0.01 [95% CI -0.03, 0.06], P = 0.62). However, the prespecified stratified analysis indicated varying effects on the CRP level according to the different NSAIDs; lumiracoxib caused a statistically significant and consistent (I(2) = 0%) increase in the CRP level (SMD 0.13 [95% CI 0.01, 0.25], P = 0.037), whereas naproxen caused a statistically significant and consistent (I(2) = 0%) decrease in the CRP level (SMD -0.11 [95% CI -0.20, -0.02], P = 0.022).
Conclusion:
Overall, NSAIDs have no effect on the CRP level. However, the nonselective NSAID naproxen was associated with a significant decrease in the CRP level, whereas the cyclooxygenase 2-selective NSAID lumiracoxib was associated with a significant increase in the CRP level. This finding is interesting considering the suspected influence of NSAIDs on cardiovascular complications.

Menaquinones (MKs) have been reported to induce apoptosis in rheumatoid arthritis (RA) synovial cells. Recently, menaquinone-4 (MK-4) was proven as a new potential agent for the treatment of RA. However, menaquinone-7 (MK-7) has greater bioavailability and efficacy than MK-4 after oral administration. Yet, the therapeutic benefits of MK-7 in the management of patients with RA have never been addressed. This study was designed to clarify the therapeutic role of MK-7 added to normal therapeutic regimen of RA in patients with different stages of the with a clinical follow up through a randomized clinical trial. In a cross sectional study, 84 RA patients (24 male, 60 female) (average age=47.2 years) were enrolled in this study. The patients were divided into MK-7 treated group (n=42) and MK-7 naïve group (n=42). MK-7 capsules were administered in a dose of 100µg/day for three months in the first group without changing in other medications. The clinical and biochemical markers on RA patients treated with MK-7 and naïve group were assessed. In MK-7 treated group, serum concentrations of MK-7 were monitored before and after three months of MK-7 administration. In the cross sectional study, a significant decrease in MK-7 treated group for the levels of undercarboxylated osteocalcin (ucOC), erythrocyte sedimentation rate (ESR), activity score assessing 28 joints with ESR (DAS28-ESR), C-reactive protein (CRP) and matrix metalloproteinase (MMP-3) was found. In MK-7 treated group, a marked decrease in RA clinical and biochemical markers for moderate and good response compared to non-responders was observed in ucOC, ESR and DAS28-ESR. A marked increase in the levels of MK-7 for the moderate and good responders compared to non-responders was observed. The results suggest that MK-7 improves activity in RA patients. Therefore, MK-7 represents a new promising agent for RA in combination therapy with other modifying antirheumatic drugs.

OBJECTIVES:
Our study sought to evaluate the effects of silibinin in patients with active rheumatoid arthritis (RA) treated with methotrexate (MTX).
METHODS:
We conducted a randomized multi-center, double-blind, placebo-controlled clinical trial over a 16-week treatment period at the Al-Sader and Baghdad Teaching Hospitals in Najaf and Baghdad, respectively. A total of 60 patients (30 of each sex) with active RA, already maintained on 12 mg MTX weekly for at least three consecutive months, were included in the study. Patients were randomly allocated to receive either 120 mg silibinin twice daily or a placebo, combined with their regular MTX regimen. The patients were evaluated by measuring activity score using the 28-joint Activity Score, Simple Activity Index, and Health Assessment Questionnaire-Disability Index scores at the start and end of the study. Blood samples were evaluated for the erythrocyte sedimentation rate (ESR), hemoglobin (Hb), high-sensitivity C-reactive protein (hs-CRP), creatine kinase (CK), anti-cyclic citrullinated peptide (CCP), and the serum cytokine levels of tumor necrosis factor (TNF)-?, interleukin (IL)-6, IL-8, IL-10, and IL-2.
Results:
Silibinin significantly decreases the already elevated clinical scores compared to placebo treatment. ESR, IL-8, IL-6, TNF-?, anti-CCP, hs-CRP levels were significantly reduced. Additionally, the use of silibinin significantly increases Hb, IL-10, and IL-2 levels.
Conclusion:
Silibinin may improve the effects of MTX on certain biochemical and clinical markers of patients with active RA.

Resveratrol is a polyphenolic phyto-estrogen that has been shown to exhibit potent anti-oxidant, anti-inflammatory and anti-catabolic properties. Increased osteoclastic and decreased osteoblastic activity result in bone resorption and loss of bone mass. These changes have been implicated in pathological processes in rheumatoid arthritis (RA) and osteoporosis. Receptor activator of NF-kappaB ligand (RANKL), a member of the TNF superfamily, is a major mediator of bone loss. In this study we investigated the effects of resveratrol on RANKL during bone morphogenesis in high-density bone cultures in vitro. Untreated bone-derived cell cultures produced well-organized bone-like structures with a bone specific matrix. Treatment with RANKL induced formation of TRAP positive multinucleated cells that exhibited morphological features of osteoclasts. RANKL induced NF-kappaB activation, whereas pre-treatment with resveratrol completely inhibited this activation, suppressed the activation of IkappaB? kinase, IkappaB? phosphorylation and degradation. RANKL up-regulated p300 (a histone acetyltransferase) expression, which, in turn, promoted acetylation of NF-kappaB. Resveratrol inhibited RANKL-induced acetylation and nuclear translocation of NF-kappaB in a time and concentration dependent manner. In addition, activation of Sirt-1 (a histone deacetylase) by resveratrol induced Sirt-1-p300 association in bone-derived and pre-osteoblastic cells, leading to deacetylation of RANKL-induced NF-kappaB, inhibition of NF-kappaB transcriptional activation and osteoclastogenesis. Co-treatment with resveratrol activated the bone transcription factor Cbfa-1, Sirt-1 and induced the formation of Sirt-1/Cbfa-1-complexes. Overall, these results demonstrate that resveratrol-activated Sirt-1 plays pivotal roles in regulating the balance between osteoclastic versus osteoblastic activity result in boneformation in vitro thereby highlighting its therapeutic potential for treating osteoporosis and RA-related bone loss.