Kombinirani učinci smjenskog rada i faktora okoline (vrućina, buka, toksični agensi)

The paper deals with the results of studies or discussions concerning the problem of nightwork combined with other adverse working conditions. Special emphasis is laid on the untoward effect of high temperature during nightwork, as well as on noise and exposure to chemicals. It is shown that there is no substantial influence of heat stress on the circadian rhythm of adrenaline excretion under sitting working conditions with the subject performing a difficult mental task at warm climates up to 30 °C BET. Shiftwork and noise induce independent different effects which can be explained in terms of activation for shiftwork and in terms of tension for noise. The combination of both adverse exposures is therefore partly subtractive but partly additive as night work and noise negatively affect daysleep. Practical experience in the field of combined effects of shiftwork and chemical agents is lacking, but theoretical speculations lead to the conclusion that there may exist a time of day dependence of some chemicals, used at workplaces.U radu su prikazani rezultati istraživanja i iznesena je teorijska rasprava o problemu smjenskog rada povezanim s drugim nepovoljnim uvjetima rada. Naročito je naglašeno moguće negativno djelovanje visoke temperature za vrijeme smjenskog rada, kao i utjecaj buke i izloženost kemikalijama. Nađeno je da nema značajnog utjecaja toplinskog stresa na dnevni ritam izlučivanja adrenalina pri sjedećem teškom mentalnom radu sve dok temperatura ne pređe 30 ° BET. Smjenski rad i buka imaju neovisno djelovanje koje se može razjasniti aktivnošću u smjenskom radu i napetošću uzrokovanom bukom. Stoga je djelovanje ovih dvaju negativnih utjecaja djelomično suprotno, a djelomično aditivna, budući da noćni rad i buka negativno utiču na san slijedećeg dana. Nedostaju iskustva o kombiniranom djelovanju smjenskog rada i kemijskih spojeva u radnoj okolini, no teorijske pretpostavke dovode do zaključka da bi mogle postojati razlike u toksičnosti pojedinih kemikalija s obzirom na doba dana

Exposure to Mimivirus collagen promotes arthritis

Collagens, the most abundant proteins in animals, also occur in some recently described nucleocytoplasmic large DNA viruses such as Mimiviridae, which replicate in amoebae. To clarify the impact of viral collagens on the immune response of animals exposed to Mimiviridae, we have investigated the localization of collagens in Acanthamoeba polyphaga mimivirus particles and the response of mice to immunization with mimivirus particles. Using protein biotinylation, we have first shown that viral collagen encoded by the ORF L71 is present at the surface of mimivirus particles. Exposure to mimivirus collagens elicited the production of anti-collagen antibodies in DBA/1 mice immunized intra-dermally with mimivirus protein extracts. This antibody response also targeted mouse collagen type II and was accompanied by T-cell reactivity to collagen and joint inflammation as observed in collagen-induced arthritis following immunization of mice with bovine collagen type II. The broad distribution of nucleocytoplasmic large DNA viruses in the environment suggests that humans are constantly exposed to such large virus particles. A survey of blood sera from human healthy subjects and from rheumatoid arthritis patients indeed demonstrated that 30% of healthy subject and 36% of rheumatoid arthritis sera recognized the major mimivirus capsid protein L425. Moreover, whereas 6% of healthy subject sera recognized the mimivirus collagen protein L71, 22% of rheumatoid arthritis sera were positive for mimivirus L71. Accordingly, our study shows that environmental exposure to mimivirus represents a risk factor in triggering autoimmunity to collagens

Fatal anaphylactoid response to protamine after percutaneous transluminal coronary angioplasty

A generalized skin erythema and severe hypotension developed following administration of protamine for the reversal of heparin anticoagulation after an unsuccessful attempt at percutaneous transluminal angioplasty in a patient who had never been exposed to protamines before. Evidence of classical pathway complement activation was present indicating that this reaction could have been triggered by a non-immunological mechanism. The patient could not adequately be resuscitated because of the presence of severe coronary artery diseas

Diversity of new Martian crater clusters informs meteoroid atmospheric interactions

We investigated 634 crater clusters on Mars detected between 2007 and 2021, which represent more than half of all impacts discovered in this period. Crater clusters form when meteoroids in the 10 kg to 10 ton mass range break-up in Mars' atmosphere to produce a few to a few hundred fragments that hit the ground. The properties of the clusters can inform our understanding of meteoroid properties and the processes that govern their fragmentation. We mapped individual craters $>$1 m within each cluster and defined a range of cluster properties based on the spatial and size distributions of the craters. The large data set, with over eight times more cluster observations than previous work, provides a more robust statistical investigation of crater cluster parameters and their correlations. Trends in size, dispersion and large crater fraction with elevation support weak atmospheric filtering of material. The diversity in the number of individual craters within a cluster, and their size-frequency distributions, may reflect either a diversity in fragmentation style, fragility or internal particle sizes.Comment: 12 pages, 12 figures at the en

Metastasis-inducing S100A4 protein is associated with the disease activity of rheumatoid arthritis

Objectives. To evaluate the association between metastasis-inducing protein S100A4 and disease activity in patients with RA, and to demonstrate the effect of TNF-alpha blocking therapy on plasma levels of S100A4 in these patients. Methods. Plasma levels of the S100A4 protein were analysed in 40 anti-TNF-alpha naive patients with active RA. Of the 40 patients, 25 were treated with adalimumab and monitored over time. The conformational form of S100A4 was analysed using size-exclusion gel chromatography. TNF-alpha mRNA expression and protein synthesis were analysed by RT-PCR and ELISA, respectively. Results. Baseline levels of S100A4 were significantly correlated with disease activity in RA patients (r = 0.41; P < 0.01). After 12 weeks of treatment with adalimumab, there was an obvious shift in the conformations of S100A4 from the multimeric to the dimeric forms, whereas the total levels of the S100A4 protein remained unchanged. This suggests that the bioactive (multimer) S100A4 may decline in response to successful treatment with adalimumab. In addition, we showed significant up-regulation of TNF-alpha mRNA (P < 0.01), and protein release to the cell culture medium of monocytes stimulated with the S100A4 multimer compared with those treated with the dimer and to the unstimulated monocytes (P < 0.001). Conclusions. This is the first study to show that the levels of the S100A4 protein are correlated with RA disease activity. Furthermore, only the bioactive form, but not the total amount of S100A4, decreases after successful TNF-alpha blocking therapy in patients with RA. These data support an important role for the S100A4 multimer in the pathogenesis of R

Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study

Aims Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive. Methods and results Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051). This difference between study groups was significant [estimated treatment effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F2t-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo. Conclusion This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT0064175

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research