Immunopathology of exercise-induced bronchoconstriction in athletes — A new modified inflammatory hypothesis

Elite athletes have a higher prevalence of exercise-induced bronchoconstriction than the general population. The pathogenesis of exercise-induced bronchoconstriction is not fully elucidated. Increasing evidence suggests that airway inflammation plays a major role in the immunopathogenesis of exercise-induced bronchoconstriction. The aim of our review is to discuss existing evidence and to present a new, modified inflammatory hypothesis of exercise-induced bronchoconstriction. Exercise alters the number and function of circulating immune cells. Episodes of upper respiratory symptoms in elite athletes do not follow the usual seasonal patterns. Moreover, they have an unusual short-term duration, which suggests a non-infectious etiology. If the pro-inflammatory response to exercise has the potential to induce symptoms that mimic respiratory tract infection, it definitely up-regulates pro-inflammatory cytokine expression in the airways. We can conclude that exercise up-regulates airway cytokine expression in a way that favors inflammation and allergic reactions in bronchi and lowers the threshold for bronchoconstriction to different stimuli like cool, dry air, allergens, and pollutants.     

Similarities and differences in interactions of thyroid stimulating and blocking autoantibodies with the TSH receptor

Binding of a new thyroid-stimulating human monoclonal autoantibody (MAb) K1-18 to the TSH receptor (TSHR) leucine-rich domain (LRD) was predicted using charge-charge interaction mapping based on unique complementarities between the TSHR in interactions with the thyroid-stimulating human MAb M22 or the thyroid-blocking human MAb K1-70. The interactions of K1-18 with the TSHR LRD were compared with the interactions in the crystal structures of the M22-TSHR LRD and K1-70-TSHR LRD complexes. Furthermore, the predicted position of K1-18 on the TSHR was validated by the effects of TSHR mutations on the stimulating activity of K1-18. A similar approach was adopted for predicting binding of a mouse thyroid-blocking MAb RSR-B2 to the TSHR. K1-18 is predicted to bind to the TSHR LRD in a similar way as TSH and M22. The binding analysis suggests that K1-18 light chain (LC) mimics binding of the TSH-α chain and the heavy chain (HC) mimics binding of the TSH-β chain. By contrast, M22 HC mimics the interactions of TSH-α while M22 LC mimics TSH-β in interactions with the TSHR. The observed interactions in the M22-TSHR LRD and K1-70-TSHR LRD complexes (crystal structures) with TSH-TSHR LRD (comparative model) and K1-18-TSHR LRD (predictive binding) suggest that K1-18 and M22 interactions with the receptor may reflect interaction of thyroid-stimulating autoantibodies in general. Furthermore, K1-70 and RSR-B2 interactions with the TSHR LRD may reflect binding of TSHR-blocking autoantibodies in general. Interactions involving the C-terminal part of the TSHR LRD may be important for receptor activation by autoantibodies.     

Complete surgical resection of lung tumor decreases exhalation of mutated KRAS oncogene

Exhaled breath condensate (EBC) contains extracellular DNA that may originate from pathological lesions of the respiratory tract and can be a genetic marker of pulmonary malignancy. We tested whether complete surgical excision of lung cancer will decrease exhalation of mutated KRAS oncogene. Fifty seven patients with clinical diagnosis of lung cancer and detectable KRAS mutations in pre-surgery EBC-DNA were qualified for surgical treatment. Point mutations at codon 12 of KRAS oncogene were detected using mutant-enriched PCR technique in DNA from pre-surgery blood, EBC collected before, 7 and 30 days after surgery and from specimens of resected tumor and normal pulmonary parenchyma. The ratio of mutated to wild type KRAS DNA (R mut/wild KRAS) was calculated for each specimen after electrophoresis and densitometry of the final amplification and digestion product. In 46 patients non-small cell lung cancer (NSCLC) and in 11 benign lesion (BL) were confirmed. All blood and tumor specimens were positive for KRAS mutations, while 41 specimens of normal pulmonary parenchyma were negative. In NSCLC patients pre-surgery EBC R mut/wild KRAS of 0.20?±?0.03 decreased by 1.3- and 3.7-times (p?相似文献   

Aggregation and deformability of erythrocytes in primary open-angle glaucoma (POAG); the assessment of arterial hypertension

Primary open-angle glaucoma (POAG) is one of the most common types of glaucoma. Glaucoma is a progressive neuropathy of the optic nerve with characteristic visual area disorders. The aim of this study was to assess the correlations between rheological parameters of blood and other parameters such as: intraocular pressure, visual acuity, angular breadth of the aqueous fluid eluvium, visual area and arterial hypertension. The examined group was comprised of 54 patients with POAG. Out of this group two subgroups was separated: I subgroup of 24 patients without hypertensive and II subgroup of 30 patients with chronic hypertensive disease. The control group was comprised of 40 healthy subjects. Erythrocyte aggregation and deformability analysis were determined using LORCA. From the results we concluded that rheological disorders such as enhanced erythrocyte aggregation or significantly decreased erythrocyte deformability occur in patients with POAG. Additionally, it revealed a significant relation between the duration of hypertension and an increased erythrocyte aggregation index (r = +0.27 p < 0.005) along with decreased deformability (r = -0.37 p < 0.001), where the decrease in deformability correlated with the severity of hypertonic retinal angiopathy (r = -0.30 p < 0.05). All these disorders may result in decreased blood flow to the optic nerve, which contributes towards the development of neuropathy.     

LNA units present in [RP-PS]-(DNA#LNA) chimeras enhance the thermal stability of parallel duplexes and triplexes formed with (2′-OMe)-RNA strands

The results of CD measurements indicate that 2-4 LNA units distributed along 12 nt P-stereodefined phosphorothioate [R_P-PS]-(DNA#LNA) chimeras impose a C3′-endo conformation on the 2′-deoxyribonucleosides. Under neutral and slightly acidic conditions homopurine [R_p-PS]-(DNA#LNA) hybridizes with 9–12 nt Hoogsteen-paired (2′-OMe)-RNA strands to form parallel duplexes, which are thermally more stable than the reported earlier analogous complexes containing LNA-free [R_P-PS]-DNA oligomers (ΔT_m = 7 °C per LNA unit at pH 5.4). Upon addition of the corresponding Watson–Crick-paired (2′-OMe)-RNA strands, parallel triplexes are formed with further increased thermal stability.

3′-O-(2-Thio-1,3,2-oxathiaphospholane) derivatives of 5′-O-DMT-LNA-nucleosides were used to prepare P-stereodefined (R_P-PS)-DNA#LNA chimeras, which form thermally stable parallel complexes with (2′-OMe)-RNA matrices.     

Hydrophilic nanofibers in fog collectors for increased water harvesting efficiency

The water crisis is a big social problem and one of the solutions are the Fog Water Collectors (FWCs) that are placed in areas, where the use of conventional methods to collect water is impossible or inadequate. The most common fog collecting medium in FWC is Raschel mesh, which in our study is modified with electrospun polyamide 6 (PA6) nanofibers. The hydrophilic PA6 nanofibers were directly deposited on Raschel meshes to create the hierarchical structure that increases the effective surface area which enhances the ability to catch water droplets from fog. The meshes and the wetting behavior were investigated using a scanning electron microscope (SEM) and environmental SEM (ESEM). We performed the fog water collection experiments on various configurations of Raschel meshes with hydrophilic PA6 nanofibers. The addition of hydrophilic nanofibers allowed us to obtain 3 times higher water collection rate of collecting water from fog. Within this study, we show the innovative and straightforward way to modify the existing technology that improves water collection by changing the mechanisms of droplet formation on the mesh.

Modification of Raschel meshes used for fog water collectors with PA6 nanofibers allow to obtain 300% higher water collection rate in collecting water from fog.     

Major liver resection results in early exacerbation of insulin resistance, and may be a risk factor of developing overt diabetes in the future

Purpose

This single center prospective cohort study evaluated the influence of hemihepatectomy on glucose homeostasis.

Methods

The study included 30 patients undergoing hemihepatectomy. All patients underwent an oral 75 g glucose tolerance test before (baseline), 1 week and 1 month after the surgery. Plasma glucose, insulin and glucagon were measured in the OGTT samples, and the HOMA index was calculated. The fasting levels of interleukin 6 and 1β, tumor necrosis factor and adiponectin were assessed.

Results

The fasting plasma and 120-min post-challenge mean glucose level increased during the study from 89.6 to 103.5 mg/dl (by 15.5 %) and from 136.4 to 162.2 (by 18.9 %; p = 0.51), respectively, accompanied by an increase in fasting glucagon (from 3.2 to 5.9 ng/mL; p = 0.043) and insulin (from 14.6 to 19.3 IU/mL) and by a decrease in plasma insulin at 60 min of OGTT (p = 0.34). An increase of IL-6 (p = 0.015) and TNF (from 49.7 to 53 pg/mL), and decrease of plasma APO (7658 to 5152 ng/mL) and exacerbation of insulin resistance (p = 0.007) were noted.

Conclusion

Hemihepatectomy resulted in moderate disturbances in glucose homeostasis, in a majority of patients that was likely to be of minor clinical relevance. However, the patients might be at higher risk of developing overt diabetes following long-term survival.