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

Photonuclear reactions on the stable isotopes of selenium at bremsstrahlung end-point energies of 10-23 MeV

The experiments were performed at bremsstrahlung end-point energies of 10-23 MeV with the beam from the MT-25 microtron with the use of the {\gamma}-activation technique. The experimental values of relative yields were compared with theoretical results obtained on the basis of TALYS with the standard parameters and the combined model of photonucleon reactions. Including isospin splitting in the combined model of photonucleon reactions allows to describe experimental data on reactions with proton escape in energies range from 10 to 23 MeV. Therefore, taking into account isospin splitting is necessary for a correct description of the decay of the GDR.Comment: 22 pages, 8 figure

ВОЗМОЖНОСТИ ЛЕЧЕНИЯ БОЛЬНЫХ РАКОМ ЖЕЛУДКА С МЕТАСТАЗАМИ В КОСТИ СКЕЛЕТА

The results of treatment of 14 patients with gastric cancer with metastases to the bones of the skeleton  were analized, which was conducted by the stabilization of metastatic spine vertebroplasty, systemic  radionuclide therapy with  samarium-153 oksabifor and  intravenous infusion  by Zolendronic  acid 4 mg 1 time in 28 days. When applying this method decreased by stabilizing vertebral  pain occurred in the first 12 hours after vertebroplasty (cf. value 4.8±1,2 hours, from 30 minutes to 12 hours), the average pain intensity decreased to 4.5 ±0,6 (from 2 to 6). After the treatment of bone  metastases with samarium-153 oksa bifor,  pain intensity  decreased by 3,9 ± 0,3 days (range from 2 to 6) and reached the level of 0,9 ± 0,5 (from 0 to 2). Value pain scores before and after treatment was significantly different, and was P <0,0001. Thus,  the  combination of  vertebroplasty, radionuclide therapy  with  samarium-153 oksabifor and  systemic  therapy with bisphosphonates (Zolendronic acid)  in patients with gastric  cancer  with bone  metastases can be treated in the  presence or threat of vertebral fractures, which gives an opportunity to expand the  indications for palliative radionuclide therapy and improve efficiency treatment of severe category of patients with multiple bone metastases and pain. The proposed approach allows us to quickly achieve durable  and pronounced reduction in pain intensity, significantly  reduce the need for analgesics.Анализированы результаты лечения  14 больных  раком  желудка  с метастазами в кости скелета,  которым  проводилась стабилизация метастатических позвонков путем вертебропластики, системная радионуклидная терапия Самарием – 153 оксабифором и внутривенные инфузии Золендроновой кислоты 4 мг 1 раз в 28 дней. При применении данной методики отмечено снижение боли вследствие стабилизации позвонков, наступившее в первые 12 часов после вертебропластики (ср. значение 4,8±1,2 часа: от 30 минут до 12 часов), среднее значение интенсивности боли  снизилось до 4,5±0,6 (от 2 до 6). После  терапии  костных  метастазов  Самарием-153  оксабифором  интенсивность болевого  синдрома  снизилась  через  3,9±0,3  дней  (от  2  до  6)  и  достигла  уровня 0,9±0,5(от 0 до 2). Значение по болевой шкале до и после лечения  статистически достоверно отличалось и составило P< 0,0001.Таким образом, комбинация вертебропластики, радионуклидной терапии самарием-153 оксабифором и системной терапии бисфосфонатами (Золендроновая кислота) у больных   раком  желудка  с метастазами в кости позволяет проводить лечение при наличии  или угрозе переломов позвонков, что дает возможность расширить показания для паллиативной радионуклидной терапии и повысить  эффективность лечения тяжелой категории больных с множественными метастазами в кости и болевым синдромом. Предложенный подход  позволяет быстро  достичь  стойкого  и выраженного снижения интенсивности болевого синдрома, существенно снизить потребность в анальгетиках

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

Scientific Research Methods of Medicinal Plants and Their Cultivation

Nowadays, stocks of naturally growing medicinal plants are declining under human influence. In order to compensate for this and meet the needs of our people, it would be expedient to increase the number of medicinal plants and plant them in irrigated areas, taking into account the soil and climatic conditions of Uzbekistan. In order to provide the pharmaceutical industry in Uzbekistan with raw materials for medicinal plants, it would be expedient to establish and increase the number of farms and specialized farms growing medicinal plants in the coming year

THE POSSIBILITY OF TREATING PATIENTS WITH GASTRIC CANCER WITH METASTASES TO THE BONES OF THE SKELETON

The results of treatment of 14 patients with gastric cancer with metastases to the bones of the skeleton  were analized, which was conducted by the stabilization of metastatic spine vertebroplasty, systemic  radionuclide therapy with  samarium-153 oksabifor and  intravenous infusion  by Zolendronic  acid 4 mg 1 time in 28 days. When applying this method decreased by stabilizing vertebral  pain occurred in the first 12 hours after vertebroplasty (cf. value 4.8±1,2 hours, from 30 minutes to 12 hours), the average pain intensity decreased to 4.5 ±0,6 (from 2 to 6). After the treatment of bone  metastases with samarium-153 oksa bifor,  pain intensity  decreased by 3,9 ± 0,3 days (range from 2 to 6) and reached the level of 0,9 ± 0,5 (from 0 to 2). Value pain scores before and after treatment was significantly different, and was P <0,0001. Thus,  the  combination of  vertebroplasty, radionuclide therapy  with  samarium-153 oksabifor and  systemic  therapy with bisphosphonates (Zolendronic acid)  in patients with gastric  cancer  with bone  metastases can be treated in the  presence or threat of vertebral fractures, which gives an opportunity to expand the  indications for palliative radionuclide therapy and improve efficiency treatment of severe category of patients with multiple bone metastases and pain. The proposed approach allows us to quickly achieve durable  and pronounced reduction in pain intensity, significantly  reduce the need for analgesics

Strategy for Bone Metastases Treatment in Patients with Impending Cord Compression or Vertebral Fractures: A Pilot Study

Impending spinal cord compression and vertebral fractures are considered contraindications for radionuclide bone pain palliation therapy. However, most of the patients with widespread bone metastases already have weakened vertebral segments that may be broken. Therefore, local field external-beam radiotherapy or percutaneous vertebroplasty (VP) should be considered to improve the patient's quality of life and to institute subsequent appropriate treatment, including radionuclide therapy for bone pain palliation. The objective of this study was to develop a strategy for an effective treatment of bone metastases in patients with widespread bone metastases and intolerable pain, associated with impending cord compression or vertebral fractures. Eleven patients (5 females and 6 males, aged 32-62 years; mean age 53.8 ± 2.7 years) with multiple skeletal metastases from carcinomas of prostate (n = 3), breast (n = 3) and lung (n = 5) were studied. Their mean pain score measured on a visual analogue scale of 10 was found to be 8.64 ± 0.15 (range 8-9) and the mean number of levels with impending cord compression or vertebral fracture was 2.64 ± 0.34 (range 1–4). All patients underwent vertebroplasty and after 3–7 days received Sm-153 ethylene diamine tetra methylene phosphonic acid (EDTMP) therapy. Sm-153 EDTMP was administered according to the recommended standard bone palliation dose of 37 MBq/kg body weight. Whole body (WB) bone scan, computed tomography and magnetic resonance imaging (MRI) were performed before and after treatment in all patients. Pain relief due to stabilization of vertebrae after VP occurred within the first 12 hours (mean 4.8 ± 1.2 hours; range 0.5–12 hours), and the mean pain score was reduced to 4.36 ± 0.39 (range 2–6). Subsequent to Sm-153 EDTMP treatment, further pain relief occurred after 3.91 ± 0.39 days (range 2-6 days) and the pain score decreased to 0.55 ± 0.21 (range 0–2). The responses to treatment were found to be statistically significant (P < 0.0001). Based on the results on this limited patient population, we conclude that spinal stabilization using VP in patients with widespread bone metastases and impending cord compression is an effective way to decrease disability with pain and to facilitate subsequent systemic palliation of painful skeletal metastases by Sm-153 EDTMP therapy

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