Adjuvant benefit of a peptide-rich marine biology formula (LD-1227) in rheumatoid arthritis: a randomized, double-blind, controlled study

Introduction. There is a growing interest on non-chemical therapies among patients suffering from rheumatoid arthritis (RA), although safety, efficacy and properly designed studies are often lacking. Objective. The aim of the present investigation was to explore the clinical effectiveness of a marine nutraceutical, LD-1227, endowed by fine molecular biology studies, in the management of RA. Methods. The study design was a 12-week, randomized, double-blind study involving forty patients with stable longstanding RA who were randomized to receive either LD-1227 (n = 20) or Omega-3 (n = 20) on top of their established maintenance therapy. Results. At study recruitment and after 12 weeks of treatment, their Health Assessment Questionnaire (HAQ), erythrocyte sedimentation rate (ESR), visual analogue scale (VAS), and Disease Activity Score (DAS) 28, anxiety and depression analysis, C-reactive protein (CRP) levels, CXCL1, several pro-inflammatory interleukins levels and related gene expression, were compared between the two groups. Primary end point was the proportion of patients with response at weeks 12 as from the 20 % to 50% improvement criteria of the American College of Rheumatology (ACR20). At 12 weeks, ACR20 beneficial response was 81.0 % in LD-1227 group and 44 % in omega-3 group, (p< 0.01). The superiority of LD-1227 appeared also when considering the ACR50 response at 12 weeks (62% in LD-1227 group as compared to 31 % in omega-3 group, p< 0.01). The LD-1227-treated group displayed a significant improvement of VAS scale, HAQ score, morning stiffness and tender points (p < 0.01 vs control and p < 0.05 vs omega-3, respectively). From the biochemical viewpoint, patients in the LD-1227 group showed a lower level of CRP, IL-6, TNF-α, IL-1β, CXCL1, IFNγ, IL-15 and IP-10 and significant downregulation of related gene expressions. Unlike what observed in LD-1227 group, in the omega-3 group, CRP and DAS28 did not reach statistical difference. A substantial reduction of extra pain killer use was noted under LD-1227 treatment. Conclusion. One can conclude that LD-1227 may play a significant role on the management of RA and with a specrum and mechanisms of actions distinct from the canonical omega-3 while being devoid of any side effect or tolerability issues

An Investigation of Products of (n, ƒ), (n, ɣ) and (ɣ, ƒ), (ɣ, xn, p) Reactions on Samples of Uranium and Bismuth using the Phasotron and LINAС-200 Accelerators at JINR: Experiments and Calculations

The paper presents the results of physical experiments with 238U and 209Bi samples at the Nuclotron, Phasotron and LINAC-200 accelerators of the Joint Institute for Nuclear Research, with the results processed using the FLUKA, GEANT4 and MCNP programs

Structure of the archaeal pab87 peptidase reveals a novel self-compartmentalizing protease family.

Self-compartmentalizing proteases orchestrate protein turnover through an original architecture characterized by a central catalytic chamber. Here we report the first structure of an archaeal member of a new self-compartmentalizing protease family forming a cubic-shaped octamer with D(4) symmetry and referred to as CubicO. We solved the structure of the Pyrococcus abyssi Pab87 protein at 2.2 A resolution using the anomalous signal of the high-phasing-power lanthanide derivative Lu-HPDO3A. A 20 A wide channel runs through this supramolecular assembly of 0.4 MDa, giving access to a 60 A wide central chamber holding the eight active sites. Surprisingly, activity assays revealed that Pab87 degrades specifically d-amino acid containing peptides, which have never been observed in archaea. Genomic context of the Pab87 gene showed that it is surrounded by genes involved in the amino acid/peptide transport or metabolism. We propose that CubicO proteases are involved in the processing of d-peptides from environmental origins

Palliation of Metastatic Bone Pain with Radiolabeled Phosphonates

This chapter reviews the role of various radiolabeled phosphonates in the palliation of bone pain from osteoblastic metastatic and primary bone disease. Various radiophosphonates are available for this purpose. These include Samarium-153 ethylenediaminetetramethylenephosphonate (Samarium-153 EDTMP), Rhenium-188 hydroxyethylidenediphosphonate (Rhenium-188 HEDP), and Lutetium-177 ethylenediaminetetramethylene phosphonic acid (Lutetium-177 EDTMP). They generally have comparatively short physical half-lives and high dose rates and can be administered as either monotherapy or fractionated therapy with low toxicity. They also can be imaged to both assess efficacy and conduct dosimetry studies. One agent that has been studied extensively and approved for bone palliation in a variety of cancers, including prostrate, breast, lung, and other primary cancers, is Samarium-153 EDTMP. It has been shown to be effective with single-dose treatment in 65–85% of patients, with pain relief seen within 4–6 weeks of treatment. Initial positive responses have been sustainable over longer periods, with significant reduction in opioid and other analgesic needs, overall improvement in quality of life, and survival benefits with minimal short- and long-term adverse events. Additionally, more recent studies have demonstrated that it can be safe to combine Samarium-153 EDTMP with chemotherapy, external beam radiation therapy, and nonradioactive bisphosphonates, to palliate metastatic bone pain and provide an antitumor strategy especially for metastatic castration-resistant prostate cancer. More recently, studies have shown that Rhenium-188 HEDP holds promise because it appears to be effective in rapidly relieving pain and improving overall survival in patients with prostate cancer when given as repeated therapy, it is readily available from a generator, and it is cost-effective