Relationship Between Anti-DFS70 Autoantibodies and Oxidative Stress

Background: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. Methods: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. Results: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH (P =.038) and 11% lower concentration of UA (P =.005). TOS was 20% lower (P =.014). The activity of SOD was up to 5% higher (P =.037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. Conclusion: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes

High-intensity interval training and moderate-intensity continuous training in adults with Crohn’s disease: a pilot randomised controlled trial

Background: This study assessed the feasibility and acceptability of two common types of exercise training—high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT)—in adults with Crohn’s disease (CD). Methods: In this mixed-methods pilot trial, participants with quiescent or mildly-active CD were randomly assigned 1:1:1 to HIIT, MICT or usual care control, and followed up for 6 months. The HIIT and MICT groups were offered three exercise sessions per week for the first 12 weeks. Feasibility outcomes included rates of recruitment, retention, outcome completion, and exercise attendance. Data were collected on cardiorespiratory fitness (e.g., peak oxygen uptake), disease activity, fatigue, quality of life, adverse events, and intervention acceptability (via interviews). Results: Over 17 months, 53 patients were assessed for eligibility and 36 (68%) were randomised (47% male; mean age 36.9 [SD 11.2] years); 13 to HIIT, 12 to MICT, and 11 to control. The exercise session attendance rate was 62% for HIIT (288/465) and 75% for MICT (320/429), with 62% of HIIT participants (8/13) and 67% of MICT participants (8/12) completing at least 24 of 36 sessions. One participant was lost to follow-up. Outcome completion rates ranged from 89 to 97%. The mean increase in peak oxygen uptake, relative to control, was greater following HIIT than MICT (2.4 vs. 0.7 mL/kg/min). There were three non-serious exercise-related adverse events, and two exercise participants experienced disease relapse during follow-up. Conclusions: The findings support the feasibility and acceptability of the exercise programmes and trial procedures. A definitive trial is warranted. Physical exercise remains a potentially useful adjunct therapy in CD

Antagonism of receptors for gastrin, cholecystokinin and GRP/bombesin in postprandial stimulation of exocrine pancreas in dogs

Postprandial pancreatic secretion results from the interaction of neural and hormonal factors such as cholecystokinin (CCK), gastrin and gastrin releasing peptide (GRP), but their contribution to the net secretion is not established. Recent description of highly specific and potent hormonal receptor antagonists allows the determination of the physiological role of CCK, gastrin and GRP. In six dogs with chronic pancreatic fistulas, the blockade of CCK receptors by L-364, 718, gastrin receptors by L-365, 260 or GRP/bombesin receptors by nonapeptide RC-3095 failed to affect basal or sham-feeding induced pancreatic secretion indicating that none of these hormonal peptides plays a major role in this secretion. In contrast, the pancreatic response to ordinary feeding (which includes cephalic, gastric and intestinal phases), that was accompanied by a significant increment in plasma CCK and gastrin levels, was strongly inhibited (by over 50%) by L-364, 718 and slightly (by 20-30%) by L-365, 260 but not by RC-3095. Each antagonist was given at a dose that eliminated the secretory response to CCK, gastrin or GRP, respectively. We conclude that specific receptor antagonists are useful tools in assessing the physiological role of gut hormones in the control of pancreatic secretion and that none of the peptides tested appears to be involved in the cephalic phase. However, CCK plays a major role in the postprandial stimulation of pancreatic secretion

The Effects of Isopropyl Methylphosphono-Fluoridate (IMPF) Poisoning on Tumor Growth and Angiogenesis in BALB/C Mice

International audienceBackground Acetylcholinesterase (AChE) and cholinergic receptors have an important role in the immune system and angiogenesis. This work evaluated the effects of isopropyl methylphosphonofluoridate (IMPF), an irreversible inhibitor of AChE, on tumor growth and selected parameters associated with tumor angiogenesis. Material/Methods Experiments were performed on male BALB/c mice exposed to IMPF (study group) or saline buffer (control group) and inoculated with L-1 sarcoma; the number of new blood vessels (TIA test) and the level of avb3 integrin (131I-MAb-antib3 assay) were analyzed at seven, 14, or 21 days after implantation of the tumor cells. Results The IMPF poisoning affected tumor angiogenesis (TIA test). There was a statistically significant increase in the number of newly forming blood vessels in the group subjected to IMPF and inoculated with tumor cells. Conclusions This study showed that IMPF had a significant effect on the regulation of lymphocyte-induced angiogenesis and the modulation of angiogenic and pro-inflammatory cytokines secretion. The observed effects suggest involvement of neuronal and/or non-neuronal cholinergic signaling pathway

Human model MATROSHKA for radiation exposure determination of astronauts

The exploration of space as seen in specific projects from the European Space Agency (ESA) acts as groundwork for human long-duration space missions. One of the main constraints for long-duration human missions is radiation. The radiation load on space travellers is a factor of ~100 higher than the natural radiation exposure on Earth and it might further increase due to solar particle events should humans travel to Mars. In preparation for long-duration space missions, it is important to evaluate the impact of space radiation in order to secure the safety of astronauts and minimize their radiation risks. To determine the radiation risks on humans one has to measure the radiation doses to vital organs of the human body. One way to realize this is the utilization of the ESA facility MATROSHKA (MTR), which houses a human phantom and is operated under the scientific project lead of the German Aerospace Center (DLR). The facility was launched in January 2004 and is just performing its fourth experimental phase - now inside the Japanese Experiment Module (JEM). The MATROSHKA project is dedicated determining the radiation load on astronauts when staying within or outside the International Space Station (ISS). The MTR phantom is equipped with over 6,000 radiation detectors to determine the depth dose and organ dose distribution in the body. It is the largest international research initiative ever performed in the field of space dosimetry and combines the expertise of leading research institutions around the world, thereby generating a huge pool of data of potentially immense value for research. Aiming at optimal scientific exploitation, the FP7 project HAMLET intends to process and compile the data acquired individually by the participating laboratories of the MATROSHKA experiment. Based on experimental input from the MATROSHKA experiment phases as well as radiation transport calculations, a three-dimensional model for the distribution of radiation dose in an astronaut´s body will be set up. Based on a solid experimental and theoretical basis the model is essential for realistic radiation risk estimates for future human interplanetary space exploration. Data received up to now from the MTR experimental phases (MTR-1, -2A and -2B) are already implemented in the database along with relevant experimental and scientific background data. DOI: 10.2769/154